Bombyx mori, which surrounds and keeps together two fibroin filaments in silk thread used in the cocoon. The recovery and reuse of sericin usually discarded by the textile industry not only minimizes environmental issues but also has a high scientific and commercial value. The physicochemical properties of the molecule are responsible for numerous applications in biomedicine and are influenced by the extraction method and silkworm lineage, which can lead to variations in molecular weight and amino acid concentration of sericin. The presence of highly hydrophobic amino acids and its antioxidant potential make it possible for sericin to be applied in the food and cosmetic industry. The moisturizing power allows indications as a therapeutic agent for wound healing, stimulating cell proliferation, protection against ultraviolet radiation, and formulating creams and shampoos. The antioxidant activity associated with low digestibility of sericin that expands the application in the medical field, such as antitumour, antimicrobial and anti-inflammatory agent, anticoagulant, acts in colon health, improving constipation and protects the body from obesity through improved plasma lipid profile. In addition, the properties of sericin allow its application as a culture medium and cryopreservation, in tissue engineering and for drug delivery, demonstrating its effective use, as an important biomaterial.Silk sericin is a natural polymer produced by silkworm, Bombyx mori, a holometabolous insect belonging to the Lepidoptera order and Bombycidae family. B. mori, which produces a great amount of sericin to the end of fifth larval instar and together with the fibroin, form the silk thread used in the production of the cocoon, structure that provides the ideal conditions for the occurrence of larval metamorphosis to adults [Sericin is a protein produced by the silkworm,o adults .In the textile industry, the cocoon is processed and sericin is largely removed in a process called degumming. The fibroin is converted into raw silk and used in the production of many types of yarns and silk fabrics –3. The c B. mori is the main lepidopteran used in scientific research, a genetic resource capable of elucidating a wide range of biological problems [ B. mori and its main proteins, fibroin and sericin, have been the subject of research that has shown the potential use in the field of polymers, biomaterials, cosmetics, and food industry [In addition to its economic importance arising from applications in agribusiness,problems . Recentlindustry , 6.For a long time, sericin has been disregarded in the field of sericulture. It is estimated that it 400,000 tons of dry cocoons worldwide, producing 50,000 tons of sericin ; sericinThe sericin is a natural polymer, which acts as an adhesive joining two fibroin filaments in order to form silk yarn . The mol B. mori.Thus, the demand for biocompatible and biodegradable materials shows the growing interest in nontextile applications of silk protein in a vast field in science and medicine and justifies the present review, which has properties and biological applications of sericin polymer obtained from cocoons of B. mori, commonly called silk glands, a pair tubular organ extending lateroventrally to the digestive tract, beginning in the labial segment to the caudal region. In B. mori, the gland is rudimentary from 1st to 4th instar producing small amount of silk, which is secreted at the end of each instar and is used to fix the tegument to be discarded after moulting to the substrate. At 5th instar, the gland hypertrophy occurs, an increase in cell volume, high silk biosynthesis, and secretion, and weight estimated to be between 20% and 40% of the total weight of the insect [The sericin is synthesized in the labial gland ofe insect –14.The silk gland is a typical exocrine gland, and, due to morphological and functional differences along the length, it is divided into three regions: the anterior silk gland (ASG) that forms the excretory duct and has about 200 cells; the middle silk gland (MSG) which secretes three types of sericin and is about 7 cm in length and approximately 300 cells; and the posterior silk gland (PSG), secretory of fibroin, that is about 15 cm long and about 500 secreting cells –16. In FThe silk gland growth occurs during embryonic development and remains in the larval stage, during which cellular DNA replication occurs without mitosis process known as endomitosis .The glandular epithelium, which resembles morphologically the posterior and middle regions, is simple and relies on a continuous basal lamina that separates the hemocoel. The ultrastructure of the secretory cells reveals numerous nucleoli distributed in the ramified nucleus , which cDue to the specificities of the middle region of the silk gland, the posterior area secretes the inner layer of sericin, which immediately accumulates around the fibroin. Surrounding the inner layer is deposited a layer of more granular texture, less dense, for the posterior-middle area. The outermost layer of sericin is synthesized by the previous field, which contains the largest cells characterized by the presence of fat bodies . B. mori head during spinning also acts on the orientation of protein molecules in the silk thread, and as the silk proteins aggregate and crystallize, they become more hydrophobic, inducing the loss of water on the surface of the thread [Thus, in the silk thread, the sericin forms three layers around two fibroin filaments coming from each of the silk glands . The mece thread .The production of cocoon lasts about three days and occurs from outside in, where silk threads are “glued” using the glue property of the sericin. Cocoon is formed by a long silk thread, whose size ranges from 900 to 1500 meters and its evolution over millions of years provides optimum protection during metamorphosis to silk moth against adverse environmental conditions and attacks of biological agents such as birds, insects, and bacteria. Its main proteins, fibroin and sericin, make up 98% of the structure, besides the presence of the p25 protein and seroin which are probably responsible for the resistance to predators, fungi, and microorganisms, which are also secreted by the silk glands. Other substances such as fats and waxes (0.4 to 0.8%), inorganic salts (0.7%), and pigment (0.2%) are also present in the cocoon , 13, 21.Silk gland undergoes morphological and functional changes resulting from insect metamorphosis, degenerating completely 48 hours after the beginning of the pupal stage , 22.Sericin and fibroin are two distinct families of proteins. Fibroin fibre is a glycoprotein secreted into the lumen of the posterior glands as a molecular complex comprising a heavy (H) chain of approximately 350 kDa and a light chain (L) of 25 kDa and P25 with 27 kDa. The L and H genes are located on chromosomes 14 and 25, respectively . FibroinSericin is a family of glycoproteins generated by alternative splicing of sericin genes , 25, and Ser1, Ser2 and Ser3. The first discovered gene was Ser1, localized in chromosome 11, locus Src, that consists of a single copy with about 23 kb and 9 exons and encodes four major mRNAs  by alternative splicing [ Ser2 gene, which contained 13 exons that ranged in size from 28 to 2574 bp and encoded two mRNAs (3.1 and 5.0–6.4 kb) also by alternative splicing. Ser2 gene proved to be more complex and variable than any other known gene encoding silk proteins. Its gene organization resembled that of the Ser1 gene, especially the similar size of the first two exons encoding the signal peptides [ Ser3 gene, was discovered by Takasu et al. [ Src-2. This gene with size about 3.5 bp contains 3 exons and encodes a simple transcript of 4.5 kb [At least three genes are responsible for sericin synthesis:splicing –30. Michsplicing  discoverpeptides . The lasSericin belongs to a family of proteins of the type “gluelike” which is positioned around the protein core, keeping the fibroin filaments together . In the β-sheets. Changes in random coil structure for β-sheet easily occur in response to mechanical stretching properties, moisture absorption, and temperature, where the sol-gel transition occurs. In hot water, 50–60°C or higher, protein adopts its soluble form. At lower temperatures, the solubility is reduced and the random coil structure is converted into β-sheets, resulting in the formation of a gel [Structurally, sericin is a globular protein consisting of random coil and of a gel –35.Macromolecule of hydrophilic character is composed of 18 amino acids with strong polar groups such as hydroxyl, carboxyl, and amino groups , capableThe solubility and the molecular weight of sericin are properties that can be used as a classification standard. Shaw and Smith  classifi Ser1 gene and form the first and second sericin layers that involve the fibroin, respectively [ Ser2 gene expression is detected in the anterior area; it is rare in the middle area and not expressed in the posterior area. Your expression is detected until day 4 and disappeared after day 6 from fifth instar [ Ser3 gene encodes sericin A that occurs mainly in the floss and outer layer of the cocoon [ Ser3 transcript initiates on day 5 and increases in intensity until day 7 from 5th instar [Considering the molecular weight, Takasu et al.  classifiectively . Your trh instar . Ser3 gee cocoon  and is mh instar . Ser1 and Ser3 genes compose the sericin layers in B. mori cocoon, the proteins encoded by Ser2 gene are classified as noncocoon and are related with larval silk [While products ofval silk . A smallval silk . B. mori sericin contains two types of oligosaccharide units. One consists of several mannose residues and two N-acetylglucosamine residues, one of which is linked to asparagine residue of protein core. The other oligosaccharide unit consists of an isolated N-acetylgalactosamine or a disaccharide β-galactosyl (1→3)-N-acetylgalactosamine, linked to the protein core in the serine or threonine residue.Sinohara and Asano  isolated B. mori but can also be extracted from the silk gland. In the traditional process of degumming in silk manufacturing, there is a common use of soaps and detergents [Removal of sericin gum from crude silk is based entirely upon the solubility in water . The protergents , but thitergents . B. mori, four methods can be listed: high temperature, associated or not with high pressure by autoclaving; acidic, mainly citric acid solution; alkali, with sodium carbonate solution; and urea [With the objective of extracting and utilizing the sericin from cocoon ofand urea , 38. AllKodama  reportedTakasu et al.  use a saKurioka et al.  tested t B. mori were autoclaved at 120°C and 15 lbf/in2 for 60 min. For the preparation by acid- and alkali-degraded was added to the cocoons 1.25% citric acid solution or 0.5% sodium carbonate solution, respectively, and boiled for 30 min. Cocoons were soaked into aqueous 8 M urea solution for 30 min and then refluxed at 85°C for 30 min for degumming with urea solution. The authors concluded that the sericin extracted with high temperature and pressure and by urea solution had higher yields compared with the other methods. Moreover, the sericin extracted by urea solution appeared to give the most clearly distinguishable protein bands in SDS-PAGE. When obtained with high temperature and high pressure, the sericin shows an endothermic degradation at 220°C, higher temperature than those obtained from other methods (210°C), implying that the use of chemicals during the extraction process influences the thermal stability of sericin. Other tests results revealed that the extraction process of sericin could affect the chemical structure of protein and change the amino acid composition. Among the four methods used in this study, extraction with urea had the most significant impact on sericin conformation. Still, regarding the inhibition of tyrosinase, urea-extracted sericin showed the highest antityrosinase activity, while the alkali-degumming has a minor.Aramwit et al.  investigEnzyme extraction is also used by other authors –55. The  B. mori, provide different sizes for the protein, which can be seen by the change in amino acid composition . Even though sericin does not activate the immune system itself, it was found that when it covers the fibroin fibres, there is a strong macrophage in response to bacterial lipopolysaccharide. Thus, the authors confirm the low inflammatory potential of silk fibres, making them promising candidates for biomedical applications.However, subsequent studies have shown a differential immunological role for sericin. An interesting finding regarding the immunological responses to silk has been presented by Panilaitis et al.  that exa in vitro, as well as reducing the release of interferon gamma (IFN-γ), without having effects on the release of interleukin 10 (IL-10) and TNF-α, thus highlighting the applicability of sericin dermatologically, showing its anti-inflammatory role, related positively your biocompatibility, as well as protection against endogenous cells aggressions [In a study involving cocoons of different lines of silkworms, Chlapanidas et al.  found thressions .Sericin has been successfully added to the culture media of several cell lines and it does not promote any cytotoxicity, which indicates the safety of sericin to cells , 70. in vitro and in vivo. When the sericin was added to the culture media of mouse monocyte and alveolar macrophage cell lines, there was an increase in cell proliferation and the generation of TNF-α and interleukin-1 beta (IL-1β); however, this increase in cytokines does not activate other inflammatory cascades. In their in vivo assay, the authors used an 8% sericin cream, which was applied topically on wounds on the back of rats. After 7 days of treatment, there was a reduction of the expression of TNF-α and IL-1β in tissue and the overall wound healing was accelerated in treated animals. In this way, sericin promoted wound healing without exacerbating the inflammatory process.Aramwit et al.  investigβ and TNF-α, both in vitro and in vivo [Considering that a protein or new substance can be used as a biomaterial or a biomedical product, the immunological response is normally evaluated as an inflammatory reaction, with the expression or release of cytokines, especially IL-1 in vivo . Therefo in vivo , and it  B. mori. Kato et al. [ in vitro study, that sericin inhibits lipid peroxidation in rat brain homogenate. The lipid peroxides, derived from polyunsaturated fatty acids, are unstable and may decompose into malondialdehyde [Dietary antioxidants have been of great interest, especially due to the findings on the effect of free radicals in the body, which can have serious consequences if their products are not neutralized by an efficient antioxidant system . In thiso et al.  showed, aldehyde , 106; whaldehyde . Similaraldehyde , highlig B. mori can provide natural pigments typically flavonoids and carotenoids that accumulate in sericin layers [ B. mori and the method of extraction of sericin affect their physical and chemical properties, influencing the antioxidant activity. Sericin extracted by urea solution, with molecular weight ranging from 10 to 225 kDa, has had the highest degree of antityrosinase activity, whereas alkali-degraded sericin showed no inhibition of tyrosinase. The high amount of arginine and valine amino acids, which can be observed in extraction by urea solution, is perhaps responsible for the antityrosinase activity, since arginine-containing peptides are the most tyrosinase-binding in shorter peptides and valine-containing peptides are the highest tyrosinase-inhibitor. Chlapanidas et al. [ B. mori also demonstrated its influence on the antioxidant properties  of sericin.Cocoons ofn layers . These pn layers  demonstrs et al.  working  Antheraea mylitta, against ultraviolet light B (UVB) in irradiated human keratinocytes. The analysis in flow cytometry revealed that previous treatment with sericin inhibited apoptosis induced by UVB, by inhibiting the expression of proapoptotic protein bax and upregulation of bcl-2, and it prevents the activation of caspase-3. There was also the inhibition of hydrogen peroxide formation in keratinocytes treated with UVB, indicating a role of sericin in preventing mitochondrial damage. In addition to these effects, intracellular reactive oxygen species (ROS) and activation of poly-ADP-ribose polymerase enzyme (PARP) were also decreased, directly involved in DNA cleavage processes, their own apoptotic process. The authors conclude that sericin, for these purposes, is a potent antioxidant and antiapoptotic agent. Likewise, the sericin antioxidant potential, extracted from A. mylitta cocoon, was demonstrated in skin fibroblasts (cell line AH927) exposed to hydrogen peroxide for 24 hours, using catalase, lactate dehydrogenase, and malondialdehyde as indicators [Dash et al.  analyseddicators .In Takechi's et al.  study, tLi et al. , 72 obse B. mori and haemocytes from oxidative damage, probably by the ability of sericin to eliminate ROS.The sericin significantly reduces intracellular ROS detected by fluorescence. Micheal and Subramanyam  suggeste Antheraea assamensis, and Prasong [ Samia ricini with B. mori, concluded that the presence of polyphenols and flavonoids in sericin is responsible for its antioxidant role. Therefore, these studies suggest the use of sericin as a natural and safe ingredient for food and cosmetics industries.The antioxidant properties of sericin could be related to your high serine and threonine content, whose hydroxyl groups' act chelating trace elements such as copper and iron . Devi et Prasong , that coThe use of sericin in cosmetic formulation, such as creams and shampoos, leads to an increase in hydration, elasticity, cleaning with less irritation, and antiaging and antiwrinkle effects –118 and  in vivo moisturizing effect of sericin on human skin and found its action to decrease the impedance and increase in the level of hydroxyproline and hydration of the epidermal cells. The increase in hydration was attributed to the occlusive effect of sericin, which prevented the transepidermal water loss, responsible for skin dryness. The moisturizing power remained flat epidermal topography. The authors still argue that sericin has similar amino acid structure to filaggrin, present in the stratum corneum of the skin and acts in the natural hydration of the skin; and, thus, sericin itself is an important moisturizing agent.Padamwar et al.  studied γ), peptidylarginine deiminase-3 (PAD3), and caspase-14, molecules responsible for the increase in expression of profilaggrin and filaggrin degradation of free amino acids, that recover dry skin conditions. Therefore, sericin is presented as a potential alternative therapy as an adjunct in the treatment of dry skin conditions such as atopic dermatitis.The dryness is characteristic of a number of skin diseases such as atopic dermatitis and ictiosis, which lead to a decrease in free amino acids in the stratum corneum. Using silk proteins, fibroin and sericin, as treatment in an animal model of atopic dermatitis, Kim et al.  observedStudies in cell culture are often the first way to test new discoveries or technologies, particularly in research on cell therapy and regenerative medicine . Many ceSericin obtained from the cocoon was added alone or combined with BSA in the culture media of mammalian cell lines . The use of sericin with molecular weights between 6 and more than 67 kDa, known as small-sericin, increased cell proliferation in four lines, with positive results in concentrations from 0.01% to 0.1%, while higher concentrations (1%) were potentially dangerous. The sericin promoted an increase in cell viability, which became more pronounced when added to the BSA. Furthermore, the activity of the sericin did not change after autoclaving, showing its use as a supplement in culture media to stimulate cell proliferation .From the study described above, Terada et al.  used the B. mori together with PBS , 0.5% maltose, 0.3% proline, 0.3% glutamine, and 10% DMSO. These media showed the same cryoprotectant potential in P3U1 myeloma and Chinese-hamster ovary cells as the conventional medium of BSA containing 10% DMSO and were superior to all three commercial media. The media containing sericin also proved effective in cryopreservation of human, rat, and insect cell lines. Thus, the authors concluded that the use of supplemented media with small-sericin could act as universal media for cryopreservation of mammalian cells and insects.Sasaki et al.  developeMorikawa et al.  used serConsidering its antioxidant potential and the ability to eliminate free radicals, Kumar et al.  used difVerdanova et al.  used serSeveral studies provide evidence of the healing properties of sericin, since it operates in stimulating the migration, proliferation, and production of collagen –128. AraIn vitro test in model of injury (injury in monolayer cell with measurement of the expansion of cell population on surface) revealed that treatment with sericin (100 μg/mL) induced migration of fibroblasts L929 and the wound closure time was significantly less than control [ control . In the  control . Thus, t control , and ser control .In a clinical study, Aramwit et al.  used the B. mori cocoons, was also used to form an 8% sericin cream for topical application in the treatment of uremic pruritus in patients with end-stage renal disease, demonstrating a greater skin hydration and less irritation and skin pigmentation. These clinical changes led to lower sensation of pain reported by patients using the Visual Analogue Scale and, consequently, improved quality of life in treated patients [Sericin, with molecular weight ranging within 50–150 kDa, extracted frompatients .Nagai et al. , 134 andBesides injuries to the cornea, diabetes mellitus can cause degeneration in other tissues, especially on the central and peripheral nervous system. Song et al.  used a dThe chemotherapy used in cancer treatment presents high cytotoxicity, affecting both normal cells and neoplastic, which limits its clinical applications . In addiZhaorigetu et al.  studied In order to clarify the mechanism involved in the antitumour action of sericin in colon cancer, Zhaorigetu et al.  supplemeKaewkorn et al.  studied α)anthracene (DMBA). Topical application of 2.5 mg dose led to a delay in tumour appearance in 1 week when compared with untreated group with sericin, whereas the dose of 5 mg of sericin inhibited its appearance for 15 weeks, and a small tumour was observed at the end of the experiment at the 16th week. In addition to the inhibition of tumorigenesis, sericin led to a reduction in the number (cell proliferation) of skin tumours in mice. There was a marked decrease in inflammatory response, by a decrease in leukocyte infiltration by TPA, and epidermal hyperplasia. Topical application of sericin, prior to TPA, also reduced the expression of epidermal protooncogenes, c-fos and c-myc, and proinflammatory mediator cyclooxygenase-2 (COX-2). Thus, the chemoprotector effect of sericin of mouse skin tumour occurred for its action in reducing the oxidative stress, inflammatory response and TNF-α.Sericin was used for Zhaorigetu et al.  to test Functional gastrointestinal disorders are common clinical conditions, characterized by the presence of symptoms in the absence of organic, structural, or metabolic abnormalities . Conside in vitro assay, since this was not digested by pepsin and pancreatin, indicating a potential for resistance to proteases related probably to its high serine content [Sasaki et al.  tested t content .Okazaki et al.  supplemeBioactive peptides derived from dietary proteins are important in modulating physiological functions , and Ons B. mori using chlorosulfonic acid. They found that higher molecular fractions had higher anticoagulant activity, estimated to be 1/10 to 1/20 of heparin. Sano et al. [The anticoagulant potential of sericin was investigated by Tamada et al. . The auto et al.  investigConsidering the regulatory role of dietary protein in the immune system , Keawkor In vitro exposure of peripheral blood mononuclear cells to oligopeptide derived from sericin resulted in increased NK activity against K562 target cells, with a dose-dependent effect. The authors found that the effect on NK cells is indirect, due to induction of interleukin-2 (IL-2) and IFN-γ. In vivo, oral administration of oligopeptides derived from sericin in mice, also caused increased activity of NK cells and an increase in IL-2 concentrations. Thus, it is evident the possibility of application of oligopeptides derived from sericin in the treatment of tumours and infectious diseases.The effects of oligopeptide with molecular mass < 5 kDa derived from sericin on NK cells activity was verified by Jantaruk et al. . In vitrObesity, a worldwide epidemic, is characterized by an excessive body fat increase, accompanied by a number of comorbidities . ConsideOkazaki et al.  examined in vitro model with differentiated Caco-2 cells, thus resulting in reduction of plasmatic cholesterol, probably due to the effect of sericin in inhibition of cholesterol absorption and its solubilisation into micelles. According to Morita et al. [Limpeanchob et al.  reporteda et al. , there ia et al.  may infl B. mori for 45 days in hyperlipidemia and atherosclerotic mice. The treatment improved the lipid profile and reduced the extent of atherosclerotic lesions, which, according to the authors, is due to sericin, who acted beneficially in the clinical condition studied, probably by its amino acid content.Ali and Arumugam Sarasa  used a cβ-oxidation with concomitant reduction of lipogenic enzymes. Still, there was decrease of serum leptin, resistin, and TNF-α, adipokines related to inflammatory profile of obesity [Seo et al.  investig obesity  and elev obesity . Accordi obesity , which cThe tissue engineering normally uses biomaterials that are a suitable scaffold that possess the specific structure of the tissue it replaces and must be capable in turn of being replaced in time via the ingress of new cells , 160.Teramoto et al.  show tha A. mylitta cocoon and glutaraldehyde as crosslinking agent. The sericin/gelatin combination structure possessed uniform pore distribution and homogeneous morphology, improved mechanical strength, and have high swellability. In in vitro test, at where feline fibroblast cells (AH 927) were cultured, there were attachment and proliferation of the cells on sericin/gelatin blended 2D films and 3D scaffolds, which became toxic at higher concentrations of sericin. Nayak et al. [ A. mylitta cocoon crosslinking with glutaraldehyde and observed increase in physical properties, associated with a slow enzymatic degradation and enhanced fibroblast cell attachment and viability. This result provides a perspective of sericin as biomaterial.Mandal et al.  fabricatk et al.  also stu in vitro. Presence of involucrin, collagen IV, and fibroblast surface protein can be observed, associated with no significant amount of proinflammatory cytokines  production in macrophages grown on the sericin matrices. The biostability and good biocompatibility indicate 3D sericin matrices as skin equivalent tissue in wound repair.Nayak et al.  construcA sericin/collagen membrane using glutaraldehyde as crosslinking was studied by Akturk et al.  and testSiritientong et al.  tested tOther researches also study the sericin as a biomaterial and its use in regenerative medicine, wound dressing, and tissue engineering , 167–170Pure sericin films form a low profile of mechanical properties that impedes your utilization as bone tissue engineering; however, its mitogenic capacity can promote bone synthesis and induce the nucleation of bone-like hydroxyapatite (HA) . Zhang eA. mylitta) using glutaraldehyde as crosslinked. The authors show that the surface modification with sericin enhances the osseointegration and osteoconduction, proved by the growth and proliferation of mouse MG-63 osteoblasts, increase of alkaline phosphatase and osteocalcin, and absence of TNF-α, IL-1β, and nitric oxide production by RAW 264.7 murine macrophages and macrophage-osteoblast cells. Therefore, use of sericin is a promising strategy to influence the osseointegration of titanium implants and provides bone tissue engineering.Nayak et al.  investigγ2 overexpression, that upregulated expression of adipogenic markers, serving as a candidate for soft tissue reconstruction.Dinescu et al.  tested aAn optimal effect of the drug is achieved when its release profile is both reliable and controlled and, eventually, a delivery system that is compatible and presents an adjustable morphology is necessary for that to occur, as the silk proteins . SericinWang et al.  fabricat In vivo test, using rats as model, shows that film and gel are encapsulated in collagen-like material and have their size and weight decreased with the time. The drug remained for approximately 3 weeks in gel form and for more 6 weeks in the sericin film, and none form induced inflammation upon the implantation. Sericin forms are suitable for use as a drug-releasing biomaterial.Nishida et al.  used dif in vitro studies show an increase of 70% of absorbable amount of fenofibrate when incorporated into the synthesized nanoparticles, results that were confirmed in vivo, with an improved in plasmatic lipid levels and reduction in lipid accumulation in liver. So, sericin/poly(ethyl cyanoacrylate) nanospheres can be used as delivery system for poorly water-soluble drugs.Parisi et al.  used a s in vitro was 2.2 and 2.7 times more than bovine serum albumin/insulin conjugates and intact insulin, respectively, and your pharmacological activity in mice was over 4 times longer than that of the native insulin and not induced any antigenic response. The physicochemical and biological stability of insulin are improved with sericin conjugation.Zhang et al.  used silBesides the use of sericin to form bioconjugates and act as a drug delivery system, many authors have formulated microspheres, nanospheres, or particles with other composts with objective of improving the releasing of their own sericin, which has, by itself, great properties in biomedical application. Aramwit et al.  fabricat B. mori. Sericin is a water-soluble glycoprotein and comprises 25 to 30% of the cocoon weight; it is characterized by the presence of 18 amino acids, with strong polar side groups  and high content of serine, aspartic acid, and glycine, resulting in a hydrophilic protein. Sericin is splicing alternative product of genes Ser1, Ser2, and Ser3, which provides a high molecular heterogeneity, 20 to 400 kDa, and variation on amino acid molar percent. The physicochemical properties of sericin, which mainly depend on the method of sericin isolation and the lineages of the silkworm, affect its functional properties and make sericin a potential biocompatible material for biomedical applications.Silk protein sericin is a natural polymer produced and secreted by the silk gland insect


To evaluate the intra-observer reproducibility of Schatzker classification for tibial plateau fractures through smartphone applications. Radiographs were evaluated in two incidences (anteroposterior and profile) and CT slices  of 37 patients with tibial plateau fracture. Two evaluators, knee surgery experts, classified the cases by viewing the images of the isolated radiographs and then X-rays associated with CT slices in four different stages via smartphones and then presential assessment. Data were statistically analyzed with the Kappa coefficient (k). There was intra-observer agreement by comparing the two methods of evaluation: display or via smartphone, and the analysis made showed statistical significance. The use of smartphones did not affect the reliability of Schatzker classification. Level of Evidence III, Diagnostic Study - Investigating a Diagnostic Test. A number of classification systems have been proposed to categorize these types of fractures, in order to simplify communication in clinical practice, to provide guidelines for preoperative planning, and to allow comparison with the data presented in the literature. The three classification systems used in the assessment of tibial plateau fractures include the OTA/AO system, the Schatzker classification and Hohl's classification.X-rays images and CT scans are commonly and frequently shared through smartphone devices between orthopedic surgeons and fellow residents, a technological facility that allows the debate at any time with team members who are far away from each other. Obviously, it does not replace the presential assessment and care provided to the patient by a qualified professional.-Currently, there are numerous software applications that can be installed on smartphones. Health-related applications are increasingly being developed, with approximately 1,000 new applications launched every month and 142 million downloads annually, estimated by 2016. Its use is popular, with 85% of medical professionals using smartphones and 30-50% using applications in clinical practice. The range of applications available for smartphones has been reported in various specialties, including orthopedics, colorectal surgery, anesthesiology, radiology and microbiology.,,-The use of smartphones applications in orthopedics have been described in the literature, such as measuring the angular deviation in hallux valgusThe aim of this study is to evaluate the intra-observer reliability of the Schatzker classification for tibial plateau fractures using smartphones. We retrospectively evaluated 37 cases of tibial plateau fractures treated at the same hospital between 2011 and 2014. All patients had knee radiographs in anteroposterior (AP) and lateral (L) views supplemented with computed tomography (CT). All these tests were stored in digital media.The two evaluators were orthopedic surgeons, members of the Brazilian Society of Orthopedics and Traumatology (SBOT) and the Brazilian Society of Knee Surgery (SBCJ) with expertise in the treatment of tibial plateau fractures. They will be hereafter designated as evaluator 1 and evaluator 2.(r). Then, they applied the Schatzker classification and sent the evaluations to the examiner, which, in turn, sent the photos of other cases to the evaluators, successively, until completion of the 37 cases.In the first stage, all AP and L radiographs were photographed using a smartphone and sent, case by case, in random and independent order to smartphones of the two evaluators using the mobile application WhatsappThe second stage was carried out similarly to the first, in random and independent order, however, in addition to the X-rays, CT images in coronal, axial and sagittal views were added to each evaluated case.In the third and fourth steps, performed six months after the first, the same cases and images were rated by two evaluators in presential way, directly from the hospital's computer monitor. In the third stage, the examiner presented only the X-ray image, and in the fourth stage, X-rays and CT scans.(r) iPhone 5S model with 4-inch screen. Regarding the presential assessment, the images were displayed on a full HD 21.5-inch monitor (1920 x 1080 pixels), and the software DViewer was used to visualize the images. Both the computer as the smartphone software allowed magnification of the image on their screens.The smartphones used for both capturing and sending images and classifying images by the evaluators were AppleData were entered and manipulated in Excel charts, for further processing using the Statistical Package for Social Sciences (SPSS) for Windows (version 21.0).13For concordance analysis was used the Kappa test. The values of this index ranged from +1 (perfect agreement) through zero (fortuitous or chance agreement) up to -1 (no agreement). In general, values lower than 0.5 were considered unsatisfactory, values between 0.5 and 0.75 were satisfactory, and values higher than 0.75 are considered excelent.For all tests we used a 95% level of confidence, i.e., p<0.05 was considered statistically significant. This study, that dealt with analysis of medical records, did not require approval by the Ethics Committee.Both evaluators showed significant agreement, with Kappa above 0.7 and p <0.001, in X-ray only presential and smartphone intra-observer evaluations. p<0.001.  in inter-observer analysisThe use of images through smartphone devices did not interfere with the intra-observer agreement of Schatzker classification of tibial plateau fractures in this study. The same result was obtained to rank X-rays only and also X-rays combined with tomography scans.


The effects of revascularization by percutaneous coronary intervention (PCI) on cardiac function and clinical outcomes in patients with confirmed coronary artery disease (CAD) and heart failure (HF), on the basis of the optimal medical treatment recommended by current guidelines, remain to be determined.A cohort study was performed to evaluate the efficacy of PCI on the basis of optimal medical treatment in patients with CAD and HF. Patients who received PCI were subsequently grouped according to partial and complete revascularization (CR) depending on the PCI outcome. The primary outcome was defined as a composite outcome of major adverse cardiovascular events (MACEs). Changes in left ventricular ejection fraction (LVEF) also were compared.P < .001), but patients in the medical treatment group did not (P > .05) after 3 months of follow-up. MACEs occurred in 50% patients in the medical treatment group and 19.3% patients of the PCI group, with this difference almost reaching statistical significance (P = .06). Compared with patients who received medical therapy only, patients who received PCI experienced better survival (P = .02). Moreover, survival seemed to be better in patients who achieved CR with PCI of the coronary arteries than in those who had partial revascularization of the coronary arteries (P = .06).A total of 69 patients  were included. Patients in the PCI group showed significantly improved LVEF (PCI may be effective for improving survival in patients with CAD and HF. In China, more than half of HF cases were found to be complicated by CAD. Indeed, partial or complete obstruction of the coronary artery was suggested to lead to apoptosis and necrosis of cardiomyocytes in the ischemic zone of the myocardium, which may be the most important mechanism underlying cardiac systolic dysfunction associated with CAD. Moreover, the cardiomyocytes in the borderline zone of the ischemic myocardium may suffer from stunning or hibernation, which has also been considered as an alternative mechanism underlying the pathogenesis of ischemic cardiac dysfunction. With the improvement of medical skills for the management of acute coronary events, many patients survive conditions such as acute coronary syndrome (ACS), and these patients have been suggested to be at higher risk for development of HF. Therefore, the development of effective treatment strategies for patients with IHD is of important clinical significance for improving the prognosis of patients with CAD and subsequent HF.Despite significant improvements in medication and device-based treatments in recent decades, heart failure (HF) remains one of the most important causes of morbidity and mortality worldwide. angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), and aldosterone receptor antagonists, have been proven to be associated with significantly improved prognosis in patients with HF. These treatments also are recommended for patients with CAD and HF by current major clinical guidelines for HF treatment.–13 However, whether revascularization can improve clinical outcomes in patients with CAD and HF remains to be determined.,15 Currently, strategies for myocardial revascularization include coronary arterial bypass graft (CABG) and percutaneous coronary intervention (PCI). A recently published large-scale randomized controlled trial  including 1212 patients  with an ejection fraction <35% and CAD amenable to CABG found that CABG on the basis of optimal medical treatment for HF was associated with significantly improved all-cause mortality and the combination of all-cause mortality and cardiovascular hospitalization. Moreover, these clinical benefits of CABG seemed to be more remarkable in younger patients with IHD than in older patients. The results of the STICH study highlight the possibility that achievement of revascularization with the less invasive strategy, PCI, may also be associated with improved clinical outcomes in patients with CAD and HF. However, to the best of our knowledge, few RCTs have been published regarding the clinical benefits of PCI in patients with CAD and HF. Therefore, in this study, we explored the potential effects of PCI as an add-on therapy with optimal medical treatment in patients with CAD and HF, focusing on outcomes of cardiac systolic function and clinical outcomes.Administration of optimal medical treatments for patients with HF, including medications such as beta-adrenergic receptor blockers,2This study was a single-center prospective cohort study designed to evaluate the efficacy of PCI based on optimal medical treatment in patients with confirmed CAD and HF. Patient enrollment was performed from October 1, 2013 to June 11, 2014 in the Department of Cardiology of Guangdong General Hospital. The study protocol was approved by the local ethics committee before performance of the study, and all included patients provided written consent before enrollment.2.1Hospitalized patients were included in our study if they met all of the following criteria:Adult age but <85 yearsHad symptoms of angina pectoris for at least 6 monthsHad confirmed CAD with ≥50% stenosis of at least 1 major coronary artery on coronary angiography (CAG) or coronary computed tomography angiography (CCTA)Had symptoms of cardiac dysfunction as evaluated by the New York Heart Association (NYHA) functional class III or IVHad echocardiographic examination-confirmed cardiac systolic dysfunction of left ventricular ejection fraction (LVEF) of <50%.Patients with the following conditions were excluded.Acute myocardial infarction diagnosed within 1 month of enrolmentDocumented valvular heart diseases or congenital heart diseases for which a surgical or an interventional repair may be needed or malignant diseases  and those with a life expectancy of <3 months.2.2 and HF. Moreover, based on the previous findings of CAG or CCTA, some of the patients also underwent PCI therapy based on the judgments of an experienced attending cardiologist following the indications and recommendations of the AHA PCI guidelines. The PCI process was performed by an experienced interventional cardiologist, and the periprocedural treatment of the patients who underwent PCI was based on the recommendations of the above guidelines. The complexity of lesions was categorized according to 3 levels, mild, moderate, and complicated, according the SYNTAX score. The patients who received PCI were further assigned to the complete revascularization (CR) group and partial revascularization (PR) group, depending on whether all of the severe stenosis of the coronary artery was treated during the PCI process. We defined CR as residual stenosis <10%.Baseline evaluation of the patients was performed at admission and included physical examination, biochemical assessment of blood samples, electrocardiographic (ECG) examination, and echocardiographic measurements. All of the included patients were treated with optimal medical treatment according to the recommendations of the American Heart Association (AHA) guidelines for CAD2.3Patients were scheduled for a follow-up at 3 months from the date of enrollment. The follow-up was performed by an experienced cardiologist in the cardiovascular department, which included briefly obtaining the clinical manifestations and medical histories, serum biomedical assessment, ECG, and another echocardiographic examination. The primary outcome of the study was the change in cardiac systolic function as indicated by the LVEF via ECG. Moreover, the composite clinical outcome of major adverse cardiovascular events (MACEs) in the follow-up was also evaluated. The MACEs included all-cause death and cardiovascular death, nonfatal myocardial infarction, severe HF, recurrence of angina pectoris, rehospitalization due to the aforementioned reasons, and revascularization (CABG or coronary artery stenting).2.4P < .05, and all statistical tests were 2-tailed.Statistical analyses were performed using SPSS 19.0 software. Continuous variables are presented as means ± standard deviations (SDs), and categorical variables are represented as frequencies and percentages. Comparisons of continuous variables were performed with t-test between 2 groups and analysis of variance (ANOVA) among multiple groups. As for comparisons of categorical variables, the chi-square test or Fisher exact test was applied. Event-rate estimates and clinical benefits were calculated using the Kaplan–Meier method and statistically compared using the log-rank test. A statistically significant difference was considered if 33.1P = .06). The baseline characteristics of patients who experienced CR or PR of the coronary artery are presented in Table P = .03), while the other baseline characteristics were generally matched.Overall, 69 patients with confirmed IHD and HF were included in this study and followed for up to 3 months, and PCI was performed in 57 of these patients. The baseline characteristics of the patients according to whether PCI was performed are presented in Table 3.2P > .05). Interestingly, although LVEF was not significantly improved after 3 months of optimal medical treatment, LVEF was significantly improved in the PCI group (P < .001). Consistently, the LVEF at 3 months after enrollment was significantly larger in patients in the PCI group than in those in the medical treatment group . These results suggested that PCI may support greater improvement in cardiac systolic function compared with optimal medical treatment only in patients with CAD and HF.The changes in echocardiographic parameters in patients with CAD and HF following treatment with optimal medication treatment with or without PCI are presented in Table 3.3P = .06). The results of subsequent survival analyses based on Kaplan–Meier plots are presented in Figures P = .02, Fig. P = .06, Fig. P = .023) and LVEF  were significantly affected in the PR group. In the CR group, the LVDd was not significantly affected after treatment for 3 months, whereas the left ventricular end-systolic diameter (LVDs) and LVEF changed significantly after 3 months . However, there were no differences in the LVDd, LVDs, and LVEF between the PR and CR groups. Based on these results, it is unclear whether CR was associated with increased LVEF.During the follow-up of 3 months, MACEs occurred in 50% patients in the medical treatment group and 19.3% patients in the PCI group, and this difference was almost significant . This study included 29 patients with HF with reduced LVEF and CMRI evidence of viability and/or ischemia within the region supplied by the targeted artery and found that application of PCI was associated with improved cardiac function, reduced serum B-type natriuretic peptide, and clinical prognosis. Since improvement in LVEF has been proven to be a significant predictor of improvement in clinical outcome in patients with HF, these benefits of PCI for cardiac function may be associated with the potential benefits for clinical outcomes such as survival in these patients. Indeed, our study found that PCI based on optimal medical treatment was associated with improved survival within a 3-month follow-up period in patients with CAD and HF, and CR achieved by PCI seemed to confer more remarkable benefits on survival as compared with PR. These results were consistent with the previous findings from a retrospective cohort study of patients with non-ST segment elevated ACS in which revascularization via PCI significantly improved the prognosis of patients presenting with HF, but not of those without HF. Interestingly, a previous meta-analysis including 19 clinical studies found that although achievement of revascularization via PCI in patients with left ventricular systolic dysfunction led to similar clinical outcomes of hospitalization and mortality compared with CABG, neither PCI or CABG improved clinical outcomes beyond pharmacological therapy alone. Of note, most of the included studies in this meta-analysis were published before 2011, and improvements in devices and skills related to PCI- and CABG-mediated revascularization may be the potential reasons for the differing results between the previous meta-analysis and our study and the STICH trial.Since the recently published STICH trial indicated the potential benefits of CABG for clinical outcomes in patients with CAD and HF on the basis of optimal medical treatment, whether revascularization achieved by PCI is associated with similar additional benefits for cardiac function and survival in these patients again became an important research topic in the treatment of IHF. However, to the best of our knowledge, no RCTs have been published to date regarding the role of PCI in CAD patients with HF. Therefore, the results of prospective cohort studies on the topic may provide some evidence and rationale for RCTs regarding the role of PCI in IHF. Our study found that PCI on the basis of optimal medical treatment was associated with significantly improved cardiac systolic function as compared with optimal treatment alone. These results were consistent with the findings of some previous studies. A recently published retrospective cohort study of 2,229 consecutive HF patients with reduced LVEF found that revascularization by PCI was a significant determinant of LVEF improvement. Fourthly, since CABG has been proven to be effective for improving clinical outcomes in patients with CAD and HF, comparisons of clinical outcomes achieved with PCI and CABG in patients with CAD and HF already on the optimal medical treatment are needed in future studies. Finally, also due to the small size of the patient population, whether the PCI process provided additional benefits in particular subgroups of patients was difficult to evaluate. This is important for the identification of patients who may benefit from PCI, since the STICH study found that the clinical benefits of revascularization achieved by CABG may be more remarkable in younger patients with CAD and HF than in elderly patients.Our study has limitations that should be considered when interpreting the results. First, our study was a pilot prospective cohort study with a limited sample size, and the results may be confounded by some characteristics of the patients and interventions. Therefore, the results of our study should be confirmed by studies with larger sample sizes. Although the important baseline characteristics of the patients in the PCI group and the medical group were generally balanced, we cannot exclude the possibility that some other potential variables may not have been matched and subsequently affected the outcome of the study. For example, patients who underwent PCI may have had better cardiac function at baseline, with an almost significant difference detected. This imbalance may have contributed to the favorable outcomes in patients assigned to the PCI group. Thus, RCTs are needed to confirm our results. Secondly, the numbers of patients included in our study were relatively small. Some differences in outcomes, such as the components of the MACE outcome, may become significant if a larger sample size could be achieved for the study. Thirdly, decisions regarding the performance of PCI were made based on the decisions and judgments of the interventional cardiologists based on the results of angiography and CTA according to the PCI guidelines. These processes seemed to be somewhat subjective, and evaluation of myocardial viability was not performed prior to the PCI process. A test of myocardial ischemia and viability could provide guidance for the performance of PCI in these patients to achieve better functional and clinical outcomes. However, these tests were not performed in our study. In view of the fact that improvement of the perfusion of the hibernating myocardium is considered the most important mechanism underlying revascularization in patients with CAD and HF, future research should apply a myocardial viability assessment as guidance for performing the PCI process in these patients.5PCI-mediated revascularization may be effective for improving survival, but it did not improve the cardiac systolic function in patients with CAD and HF. Large-scale RCTs are warranted to confirm these findings and evaluate the role of myocardial viability assessment in patients with IHF by PCI-guided revascularization.Conceptualization: L. Jin, Z. Wang.Data curation: L. Jin, W. Zhou, Z. Wang.Formal analysis: D. Lei, J. Zheng, L. Jin, W. Zhou, Z. Wang.Funding acquisition: L. Jin, Z. Wang.Investigation: D. Lei, H. Wang, H. Yan, H. Yu, L. Jin, Y. Dai, Z. Wang.Methodology: H. Yan, L. Jin, Z. Wang.Project administration: L. Jin, Z. Wang.Resources: H. Yu, L. Jin, Z. Wang.Software: L. Jin, Z. Wang, Z. Zeng.Supervision: G. Zhu, L. Jin, Z. Wang.Validation: L. Jin, Z. Wang.Visualization: L. Jin, Z. Wang.Writing – original draft: L. Jin, Z. Wang.Writing – review & editing: L. Jin, Z. Wang.


Physical inactivity, low physical fitness, and perceived stress during adolescence are presumed to be risk factors for various disorders and subjective health complaints. On the other hand, physical activity and physical fitness, as well as mindfulness qualities, are regarded as prerequisites for health and well-being in children and adolescent, possibly by moderating the negative effects of stress and protecting against stress-related health complaints. Previous studies have suggested gender differences in the relationship between physical activity/physical fitness and psychological variables. The main objective in this study was to evaluate how physical fitness, along with mindfulness qualities (MAAS-A), pain, and BMI, relate to stress (PSQ) in adolescents. Secondary objectives were to explore the relationship between physical fitness, mindfulness (MAAS-A), and BMI more explicitly in the study sample, as well as to evaluate possible gender differences. The cross-sectional sample included 102 Norwegian pupils in 10th grade (15 or 16 years). Study measurements were four items from the Test of Physical Fitness (TPF), the Norwegian version of the four-factor Perceived Stress Questionnaire (PSQ), the Norwegian version of the Mindful Attention Awareness Scale-Adolescent (MAAS-A), and BMI (recorded in terms of self-reported height and weight). Additionally, pain was measured in terms of localization, number of pain sites, duration, and intensity . According to the regression analyses, physical fitness could not explain any variation in stress among the adolescents. Nevertheless, there were some negative associations between one stress factor (lack of joy) and components of physical fitness at a group level, possibly influenced by conditions not measured in this study. As opposed to physical fitness, mindfulness qualities, and to some degree gender, seemed to explain variation in stress among the adolescents. None of the physical fitness components were associated to mindfulness (MAAS-A), but some components seemed negatively related to BMI, particularly among the males. Among the females, higher physical fitness (in terms of endurance) seemed related to reduced number of pain sites. Of note, the cross-sectional design did not allow us to determine any causal direction among the variables. Physical inactivity, low physical fitness, and perceived stress during childhood and adolescence are presumed to be risk factors for various chronic conditions including cardiovascular diseases , recruited from a public school in the Trondheim municipality. The participating school was considered to be an “average” school regarding sociocultural- and economic conditions  of 0.30 in the population at the 5% level . This number was increased to 110 to allow for withdrawals. The total number that completed both questionnaires and physical fitness test were N = 102, giving an overall response rate of 92.7%. 62 (60.8%) females and 40 (39.2%) males were included. The data was collected autumn 2015.Sample size calculation  showed that 90 participants were required to have 84% power to significantly detect a correlation   with two hands as far as possible. The starting position is with the feet parallel to each other and shoulder width apart, with the ball held against the chest. The test item score (better of two attempts) is the distance achieved (measured in meters).Running 20 m as quickly as possible. The participant starts in a standing position. At signal, the participant runs as fast as possible toward the finish line. The test item score is the time in seconds needed to run the 20 m.Standing broad jump. The participant starts with the feet parallel and a shoulder width apart behind a starting line. At a signal, the participant swings his or her arms backward and forward and jumps with both feet simultaneously as far forward as possible. The test item score (the better of two attempts) is the distance (in centimeters) between the starting line and the landing position.Reduced Cooper Test. The participant runs or walks around a marked rectangle measuring 9 × 18 m  for 6 min. Running and walking are allowed. The test item score is the distance covered (in m) in 6 min.n = 102). The score of test item 2 (running 20 m as quickly as possible), which measured the time needed to accomplish the test item, was beforehand converted to 1/score, such that higher scores always indicated better performance than lower scores. The test items scores represent subcategories or “sub-variables” of physical fitness, involving different components of physical fitness. Higher z-scores indicate better performance on the tasks. A total test score was calculated to express the adolescent's overall performance on the four physical fitness measures, as a “sum-variable” of total physical fitness. The total test score for each participant was defined as the average z-score on all test items successfully performed by that individual. Fjørtoft et al. (All test item scores were transformed into standardized score (z-scores) from the mean of the whole sample , duration, and intensity. Pain site (0–6) was divided into six main categories, corresponding to the questionnaire in the Young-HUNT Study 2008 , The questions are addressing everyday experiences/situations. The physical fitness test contains well-known motor fitness tasks, commonly applied in school gymnastics. The assessment of the physical fitness took place in a sport hall during school hours, in line with previously applied protocols  was used to assess the associations between the continuous variables , also with a split file command with respect to gender. Linear regression analyses evaluated the probability that physical fitness, mindfulness, and pain (duration) in addition to gender and BMI could explain variation in stress (lack of joy), with the latter variable applied as the dependent variable. The linear regression model was developed backward, in order to minimize suppressor effects and to reduce the risk of making a Type II error  was used to assess the associations between the outcome variables, since not all (pain) variables were normally distributed (Table Spearman's rank correlation coefficient (ed Table . Tables p < 0.001) and strong negative associations between stress and mindfulness, both overall and separately for gender. Among the females, demands appeared to be strongest related (rs = −0.57) to mindfulness, while tension (rs = −0.51) appeared strongest related to mindfulness in males.Table p < 0.05) to physical fitness in terms of pushing a medicine ball (strength) and reduced Cooper test (endurance) in the overall sample (Table p < 0.05) to BMI.Joy (lack of) seemed negatively associated (le Table . Also inp < 0.05) to pain intensity (measured by VAS). Among the males in the study sample, several of the associations appeared reversed: Both total stress  and tension seemed positively associated (p < 0.05) to physical fitness in terms of pushing a medicine ball (strength). Additionally, joy (lack of) appeared negatively associated to pain sites and pain duration, while total stress , worries and joy (lack of) seemed negatively associated to pain intensity (VAS)  Table .p < 0.05) with BMI. Among the females, physical fitness, measured by the reduced Cooper test (endurance), was negatively associated (p < 0.005) to number of pain sites. Among the males, physical fitness in terms of running 20 m, standing broad jump and reduced Cooper, were negatively associated (p < 0.05) with BMI. There was no associations between physical fitness and mindfulness qualities measured by the MAAS-A (Table Table p < 0.001) and gender  explained some of the variation in the stress factor (Table R2 (0.263) and significant F-value  supported acceptable fit of the model. The adjusted R2 (0.214) indicated very sparse loss of power. A Durbin-Watson test value close to two (1.70) indicated independence of the residuals.The linear regression analysis with stress (lack of joy) as dependent variable, revealed that mindfulness measured by the MAAS-A  Table . Hence, p < 0.05) between higher physical fitness (strength and endurance) and lower stress (increased joy) at a group level  between higher stress in terms of worries and higher BMI (Table p < 0.05) with lower BMI, both in the overall sample and among the males , there seemed to be a weak association   Table . However5) Table . However5) Table .p < 0.05) with higher stress among the males, in terms of total PSQ and tension , and the findings probably needs to be confirmed in further studies.However, we also acknowledge several limitations. Neither the cross-sectional design nor the correlation analyses are entitled to determine any causal relationships between the variables. Furthermore, the inclusion of a physical fitness test might have caused a selection bias. Adolescents already confident and comfortable in physical performances possibly appreciated the invitation and easily accepted to participate in the study. Less fit adolescents possibly declined to participate at a higher rate than their more fit peers. Adolescents perceiving pain and health complaints probably also declined more frequently that their pain-free (or approximately pain-free) peers. The sudden withdrawals at the day of testing due to pain and other subjective health complaints (voluntarily reported), might indicate such dropout mechanisms. The non-normally distribution of the pain-variables might also be an indicator of this. However, this was not evaluated in more detail. Furthermore, the self-reported height and weight, from which the BMI-values were calculated, were possibly not entirely reliable. In order to explain stress, several other factors and variables are also relevant, such as adverse childhood experiences, coping strategies, and catastrophizing. However, those fall beyond the defined scope of this study. Finally, the sample size was not very large , pain and BMI in relation to stress (PSQ) in Norwegian adolescents. Additional physical fitness associations were also explored as well as gender differences. Analyses revealed that physical fitness did not explain any variation in stress among the adolescents. However, there were some negative associations between one of the stress factors (lack of joy) and physical fitness components at a group level, which might have been influenced by conditions not measured in this study. As opposed to physical fitness, mindfulness qualities (MAAS-A), and to some degree gender, seemed to explain variation in stress among the adolescents. Physical fitness was unrelated to mindfulness (MAAS-A) but seemed somewhat related to BMI, particularly in males. Among the females, higher physical fitness (in terms of endurance) seemed related to fewer pain sites. The cross-sectional design did not allow us to determine any causal direction among the variables. Further studies might be needed to confirm these findings.BØ has made substantial contributions to the conception and design of the work, the acquisition, analysis, and interpretation of data for the work. BØ has also drafted the work, revised it critically for important intellectual content, and approved the final version to be published. BØ agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. HS and MH has made contributions to the conception and design of the work, and has contributed in revising it, and given final approval of the version to be published. HS agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.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.


Japanese encephalitis (JE) is a major public health problem in Nepal. For the effective management and surveillance of JE, a clear understanding of its epidemiology is essential. Therefore, we conducted descriptive and spatial analyses to understand the spatio-temporal distribution of JE in human in Nepal. From 2007 to 2015, 1,823 JE cases were reported with a cumulative mean incidence of 0.735/100,000 population and a case fatality rate of 6.6%. The death rate in the up-to-24 years of age group was 74%. The JE cases were most commonly reported in the age group of 1–14 years. There is a strong seasonal pattern of JE occurrence in Nepal which peaked in August and declined by October each year, which corresponds to the monsoon season. The JE cases were reported in 63 of 75 districts (84%), expanding in the mountain and hill regions. There was a strong clustering of JE incidence in the south-western and south-eastern Terai region, which is endemic for JE. Therefore, the JE surveillance system should be improved to better understand the drivers of disease expansion in Nepal for instituting a control program. The transmission cycle typically involves Culex tritaeniorhynchus mosquitoes and similar species, with aquatic birds and pigs acting as reservoir and amplifying hosts, respectively. Humans are the incidental host and play no role in perpetuating the virus [Japanese encephalitis (JE) is a vector-borne viral disease caused by a he virus . The firhe virus ,2. Therehe virus . In recehe virus –6. Globahe virus . The cashe virus . Fundamehe virus ,8,9.In Nepal, JE was first confirmed in the Rupandehi district during 1978 . Since tC. tritaeniorrhynchus), a proven vector of JE in Nepal [Nepal is a landlocked mountainous country situated between China in the north and India in the south, east and west, with a human population of approximately 29 million . Topograin Nepal .Three epidemiological surveillance and reporting systems exist for JEV in Nepal. They are: a health management information system (HMIS); an early warning reporting and response system (EWARS); and a laboratory-based surveillance program to collect morbidity and mortality data of JE cases. Since May 2004, the WHO-IPD (Programme for Immunization Preventable Disease) has supported Nepal for the active surveillance of JE. The disease has been integrated with the acute flaccid paralysis (AFP) surveillance network and laboratory-based surveillance. Samples from patients suspected of an acute encephalitis syndrome (AES) were collected from 127 sentinel sites for JE diagnosis.For this study, confirmed JE cases (diagnosed using anti-JE IgM antibody capture ELISA), for the period from 2007 to 2015, were collected from the Acute Encephalitis Syndrome (AES) surveillance unit of the WHO/IPD. The data included the number of cases by year, months, district, and age of the patients. The cases were verified with the WHO-IPD fact sheet to check the reliability and consistency of the data, comprising all endemic cases recorded at the sentinel sites in Nepal. Geographical data were collected from the Department of Land Survey and the projected population data (2007 to 2015) were collected from the Department of Health Service, Government of Nepal. The use of these surveillance data for analysis and publications was approved by the Child Health Division, Ministry of Health, Government of Nepal (vide letter no 1427).A descriptive data analysis was performed using Microsoft excel 2007 . The morbidity rate  and case fatality rate (number of deaths/number of cases diagnosed per year) were estimated to understand the burden of JE in humans. The seasonal and annual trend of JE cases were also analyzed and represented using graphs. The reported JE cases were integrated with projected population data (2007–2015) to compute yearly-specific incidence for each district. Annualized JE incidence per 100,000 populations at risk were also analyzed. The JE incidence was mapped using an open source Quantum Geographic Information system (QGIS).A spatial interpolation analysis was performed, using the centroid of each district as a point layer, to estimate a continuous distribution of JE incidence. An inverse distance weighing (IDW) method  was used to interpolate JE incidence in humans. The IDW is a moving average or distance-weighted average method and assumes that each interpolation surface should be influenced the most by nearby points and the least by more distant points. The IDW assumes that each measured point has a local influence that diminishes with distance. For example, to predict a value for any unmeasured location, IDW uses the measured values surrounding the prediction location. The resulting interpolation was then displayed as a continuous, graduated color surface of the centroid of each district.Global spatial autocorrelation analysis was performed using Spatial Analyst extension in ArcGIS10.2.2 software . First, a contiguity-based spatial weight was constructed for each district by creating a first order rook contiguity weights file to define the spatial relationships using the JE incidence as the variable of interest. Moran's I spatial autocorrelation statistic was then calculated to determine if the JE incidence  at the district level was clustered, dispersed, or random. A value of Moran’s I close to 0 implies that JE incidence is distributed randomly in space. A positive value of Moran’s I indicates clustering whilst a value near -1 is indicative of dispersion. The significance of Moran’s I were assessed employing a z-statistic. The spatial correlation at the global level is significant (P = 0.05) when the Z-score is greater than 1.96 or less than -1.96. Since the global spatial autocorrelation was significant , the spatial distribution of JE incidence at the district level was further investigated for clustering and outliers using a local indicator of spatial association (LISA) Moran’s test. This test detects local spatial autocorrelation  and can also be used as a diagnostic test for outliers in global spatial patterns. The variable of interest in this analysis was the district level JE incidence . A rook contiguity weight file to define the spatial relationships using the JE incidence as the variable of interest was used in this analysis. The Local Moran’s Index and the z-score were used to assess the significance of observed spatial correlations and then visualized in the form of LISA cluster map. A high positive Z-score indicates that the surrounding areas have either similarly high JE incidence (High-High) or low JE incidence (Low-Low), while a low negative Z-score indicates a significant (P<0.05) spatial outlier (High-Low) or (Low-High) .From 2007 to 2015, 1,823 JE cases (mean of 202 cases/year) in humans were reported nationwide with a cumulative mean incidence of 0.735/100,000 population, ranging between 0.289/100,000 and 1.648/100,000. The case fatality due to JE was 13.8% during 2007 and the trend decreased until 2010 with no record of deaths between 2011 and 2013. The disease was reported again during 2014 and 2015, with an overall case fatality rate of 6.6% during the nine year period .The JE cases and fatality were more commonly reported in the age group of 1–14 years when compared to other age groups .The distribution of JE cases in Nepal demonstrates a clear seasonal pattern of occurrence. Although JE cases were reported throughout the year, cases build from June-July, peaked in August and declined by October each year  panel C.During the nine year period (2007–2015), JE was reported in 63 of 75 districts (84%). The cases were reported mostly from the southern Terai low plain area, bordering with India and in Central Nepal. The highest average incidence of 2.15/100,000 was reported in the Kailali district, followed by Kanchanpur , Surkhet , Morang , Kathmandu , Bhaktapur , Dang , Lalitpur , Parsa , Nawalparasi , Sunsari , Banke  and Bardiya . The lowest incidence was reported in the Achham district  (C. tritaeniorrhynchus), thus favoring geographical expansion of JE in Nepal [This study demonstrates that JE incidence is not distributed homogeneously in Nepal. Cases were clustered mostly in the southern Terai or low plain land. This might be due to high vector density, high intensity of cultivated paddy fields and favorable climatic factors for the JE vector. Terai is the grain basket of Nepal with high paddy cultivation and animal farming, including swine and birds. This ecological region has been reported as a JE prone area in the previous studies , 18, 19.in Nepal . In addiin Nepal , 31. Thein Nepal . Similarin Nepal . TherefoThe JE incidence in Nepal demonstrates a clear seasonal pattern. More cases were reported during the rainy season during June-July, peaking in August and declining by October (The JE case detection in Nepal shows a declining trend over the years, which may be due to effective intervention programs, including immunization, enhanced surveillance and case management, which are priority intervention measures of JE control in Nepal. In other countries, such as Japan, the Republic of Korea, Brunei, Australia, and Malaysia, a comprehensive immunization program has significantly reduced JE cases . The GovThe morbidity rate due to JE is high for the 1–14 year-age group in Nepal. In the absence of immunization programs, persistence of infection in the area helps in the development of naturally-acquired immunity in older age groups when compared to children, thus making them into a high risk group for the disease. Prior to the implementation of vaccination programs, children under 15 years were considered as the high-risk group for JE in China, India, Thailand, and Sri Lanka, whereas all age groups are considered at risk of JE infection in Burma and Nepal . In some


In this study, first we examined the effect of workplace romance on employee job performance, and the mediatory role of psychological wellbeing in the relationship between workplace romance and employee performance. Then we tested the moderating effects of gender and workplace romance type – lateral or hierarchical – on the indirect effect of workplace romance on employee performance. Based on a survey of 311 doctors from five government teaching hospitals in Pakistan, we used structural equation modeling and bootstrapping to test these relationships. This study reveals that psychological wellbeing significantly fully mediates the positive relationship between workplace romance and job performance. Moreover, multi-group analysis shows that gender moderates the indirect effect of workplace romance on employee performance, where the indirect effect of workplace romance on employee performance is stronger for male participants. This study carries important implications, particularly for the policy makers and managers of healthcare sector organizations. Workplace romance is understood as a mutually-welcomed  and commAdditionally, workplace romance discourse is characterized by a lack of consensus on the nature of its effects on employee work-related behaviors and performance outcomes. Literature on this topic suggests that workplace romance can have both destructive and constructive effects on employee behavior and performance . The comThe mixed theoretical perspectives also laud the workplace romance and employee performance relationship as being intricate in nature. The relationship can be mediated through, and affected by, a number of different behavioral and demographic aspects displayed by employees. For instance, workplace romance literature is indicative of the links between workplace romance and psychological wellbeing . We undeThus, one of the aims of this study is to first examine the effect of workplace romance on employee performance, and then test the mediatory role of psychological wellbeing in this relationship.Furthermore, the aforementioned debate on the nature of the effect of workplace romance is linked to a number of different factors including gender and the type of workplace romance; i.e., lateral or hierarchical . This stBased on a survey of 311 doctors from five Pakistani public sector hospitals operating in the Punjab province of Pakistan, we used structural equation modeling (SEM), multi-group analysis, and bootstrapping to test these relationships.This study is important in terms of theoretical contributions and practical implications. Studying workplace romance is imperative because of its effects on employee behavior and performance and the lack of consensus on the nature of these effects . Our intImportantly, we contextualized the relationship between workplace romance, wellbeing and performance in healthcare settings. The job of healthcare professionals and particularly that of doctors plays a key role in determining the quality of human life. Thus, understanding the factors that affect the performance of doctors carries important practical implications. Moreover, studies on the relationship between workplace romance and performance in Muslim countries, including Pakistan, are rare.Traditionally, blending work-life and personal boundaries and becoming involved in romance in the workplace are portrayed as risky matters for employees as well as organizations . WorkplaThe Quinn’s conceptualization of workplace romance has drawn in researchers from different disciplines to debate and empirically study the relationship between workplace romance and the different facets of work-related behaviors and attitudes such as burnout, job satisfaction, commitment, absenteeism, wellbeing, and turnover intentions .Literature has usually focussed on, and brought to the fore, several negative repercussions of workplace romance such as negative publicity, litigation and job withdrawals, hostility and cynicism . The litOn the contrary, we expect a positive relationship between workplace romance and employee performance. This expectation is built on the following arguments. First, the impression management hypothesis proposes that workplace participants work hard and demonstrate improved performance to create a favorable impression . The litSecond, workplace romance literature has usually focussed on sexual or romantic behavior and sexual relations while studying the workplace romance relationship with employee behavior and performance e.g., . ParticuFinally, the effects of workplace romance depend on the motive for engaging in the relationship. These may include committed love, ego satisfaction, financial rewards, adventure and sexual satisfaction . Pierce In essence, building on the constructive effects discourse of the workplace romance , the impHypothesis 1: Workplace romance will positively affect employee performance.The concept of employee wellbeing is complex . ScholarScholarship on wellbeing also suggests that wellbeing is more than the absence of illness and negative emotions. Rather, wellbeing is conceived as positive emotions, a positive mental state and personal growth . Third, Additionally, general romance literature suggests that romantic relations promote psychological wellbeing. For instance, research has shown that affectionate touch from the romance partner relieves stress and instills optimism . AffectiWorkplace romance literature also suggests that workplace romance has a positive relationship with employee wellbeing. For instance, Indeed, a number of studies suggest that workplace romance can reduce stress, anxiety and tension . MoreoveMoreover, clinical psychologists acknowledge the imperative role of the pleasantness (depression or happiness) facet of wellbeing for determining different individual outcomes. Hypothesis 2: Psychological wellbeing mediates the positive relationship between workplace romance and employee performance.Literature on workplace romance highlights both constructive and destructive effects of workplace romance on employee performance. The variations in the conceptualizations and findings of the relationship between workplace romance and employee performance can be linked to a number of different factors including gender and the type of workplace romance.Women are more cautious than men about their involvement in workplace romance . Men tenThe variations in the conceptualization of the effects of workplace romance on performance are also attributed to the romance type; i.e., lateral or hierarchical romances. Lateral workplace romance refers to a romantic relationship between peers – two employees working at the same level of an organization . HierarcHypothesis 3: Gender moderates the indirect effect of workplace romance on employee performance, where the indirect effect for males is stronger.Hypothesis 4: Workplace romance type  moderates the indirect effect of workplace romance on employee performance, where the effect for lateral romances is stronger.We collected survey data from 311 doctors  from five government teaching hospitals operating in the Punjab province of Pakistan. To reduce the common method bias, we collected data in two rounds with a lag time of 6 months between each round of data collection. In the first round, data about our independent variable, workplace romance (self-reported) was collected. Data about gender, age, experience, and the type of workplace romance  was also collected in the first round. In the second round, data about psychological wellbeing was collected, while data about the outcome variable, clinical performance of the doctors was collected from the respondents’ supervisors. Supervisors’ performance ratings are said to be more reliable than self-ratings . Data waThe lag time of 6 months reduces the common method bias, as employees do not usually remember their previous responses and cannot relate them to the current responses . AdditioBefore starting the data collection, consent forms were sent to 800 doctors . In the consent forms, the doctors were informed about the aims and nature of the study. The key constructs of the study such as workplace romance, hierarchical workplace romance and lateral workplace romance were also defined in the consent form. For example, we defined lateral workplace romance as a romantic relationship between two employees working at the same level of an organization, and hierarchical workplace romance as a boss-subordinate romantic relationship. They were also assured that their identity would not be revealed and that the data would only be used for academic purposes. The consent form also included the criteria for participation in the study. The criteria included ‘yes’ responses from the potential participants for the following two questions: (1) Are you currently involved in a romantic  relationship with a colleague in your workplace (Yes or No)? (2) Are you willing to participate in two data collection rounds, separated by a time lag of almost 6 months (Yes or No)?The conceptualization and measurement scale of workplace romance used in this study required data from respondents who could reflect on their workplace romance experiences, the level of commitment they enjoyed with their romance partners and how they envisaged their relationships would develop in the future. Therefore, we aimed to collect data from the doctors who were involved in workplace romances. After several reminders, requests and the assurance of anonymity, we were able to get a list of 406 doctors who showed consent to participate in our data collection. We could not contact six out of the 406 doctors, as they were either on leave or transferred to other locations. Therefore, in the first round, the questionnaires were distributed to 400 doctors.Three hundred and forty-three responses were received in the first round. Of the 343 respondents who responded in the first round, we were able to contact 325 in the second round. Of these 325 received responses, 14 responses had missing data. Thus, 311 responses  were included in the data analysis.Supervisors’ ratings were received from the respective line managers (the managers to whom the respondents of our study were directly reporting) of our respondents . The structure of the hospitals meant that doctors reporting to a single line manager ranged from one to six. In our study, for any given line manager, the number of respondents ranged from a minimum of one to a maximum of four. Specifically, a total of 102 line managers rated the performance of 311 respondents of this study. In order to match employees’ responses from the two rounds of data collection and match employees’ and supervisors’ responses, we placed a code on each questionnaire.The respondents’ average age was 41 years with an average of 11 years’ professional experience. Before starting the survey, the questionnaire was pilot tested with five academicians and 15 respondents. We used SEM, multi-group analysis and bootstrapping (AMOS 24.0) to test our hypotheses.Workplace romance as a consensual and committed relationship was measured using a modified seven-item scale (α = 0.91) from To measure psychological wellbeing, an eight-item scale (α = 0.87) was adopted and modified  from Table 1.We measured doctors’ performance using a four-item clinical performance measurement scale (α = 0.76) adopted from Data about the type of workplace romance was collected by asking the respondents whether they are involved in a lateral workplace romance (1) or in a hierarchical workplace romance (2). Data about homosexual and heterosexual romances was collected by asking the respondents whether they are involved in a homosexual workplace romance (1) or a heterosexual workplace romance (2).Homosexual and heterosexual workplace romances have been reported to have different effects on employees’ work-related behaviors and performance outcomes . Thus, wr = 0.89, p < 0.05) in our sample. Thus, we controlled for age, which we perceived to have more conceptual relevance to the relationship between workplace romance and performance.Age and work experience may confound the results . HoweverWe used confirmatory factor analysis (CFA) to test the fitness of our overall  measurement model with the data. Our model consisted of three latent constructs – workplace romance (WR), psychological wellbeing (PWB), and employee performance (JP) – and 19 observed variables. The items  that showed either suboptimal loading were dropped from the analysis. As the purpose of this study was also to test the moderating role of gender on the indirect effect of workplace romance on employee performance, we also performed CFA separately for both males and females. The observed variables, WR7, PWB4, and PWB8 demonstrated suboptimal loadings on either males or females, and were dropped.2 = 110.513, df = 41, χ2/df = 2.695 < 3, GFI = 0.979 > 0.90, IFI = 0.986, CFI = 0.986 and TLI = 0.981 > 0.95, and RMSEA = 0.043 < 0.06 show that the model has a good fit with the data.The fit indices of the measurement model, χTable 1. The values of α > 0.70 for all the variables (Table 2) showed a satisfactory level of internal consistency. The values of composite reliability (CR), maximum shared variance (MSV), average variance extracted (AVE), and average shared variance (ASV) of WR, PWB, and JP for overall model and males and females are presented in Table 2. The values of CR > 0.70 demonstrated a satisfactory level of reliability for overall model and male and female groups. Moreover, AVE > 0.50 and CR > AVE (Table 2) showed a satisfactory level of convergent validity.The items, their mean values, standard deviation (SD) and standardized outer loadings are presented in Table 2) are greater than their inter-construct correlations. Additionally, ASV, MSV < AVE. Thus, the scales we used to measure WR, JP, and PWB demonstrated an acceptable level of discriminant validity. The square root values of AVE are presented on the diagonal in the last three columns of Table 2, while all other values in the last three columns of Table 2 are the values of inter-construct relations.The square root values of AVE of WR, JP, and PWB (p = 0.000 < 0.001). The fit indices of this initial model (1), χ2 = 32.149, df = 13, χ2/df = 2.473, GFI = 0.981, IFI = 0.993, CFI = 0.993, TLI = 0.991 and RMSEA = 0.040 showed that the model has a good fit with the data. Thus, our hypothesis (1) is supported.To evaluate the structural model, first, the direct effect of workplace romance on employee performance was tested. The direct effect of workplace romance on employee performance was significant . The fit indices used for the evaluation of the model (2), χFigure 1. The results obtained using bootstrapping are shown in Table 3.The significance of psychological wellbeing as a mediator in the relationship between workplace romance and employee performance was tested using AMOS bootstrapping by specifying a sample of 2,000 at a 95% confidence interval. The model (2) is presented in Table 3 shows that the indirect effect of workplace romance on employee performance is significant. Moreover, the direct effect of workplace romance on employee performance is non-significant. The effect of the control variable, age , was non-significant. Thus, our hypothesis (2) is supported. That is, our results show that psychological wellbeing significantly mediates the positive relationship between workplace romance and employee performance.Figure 1, we used multi-group analysis, bootstrapping  techniques and χ2 difference test. Multi-group moderation involves the testing of structural model estimates  and constrained  models was significant . This suggests that gender moderates the indirect effect of workplace romance on employee performance.To test the moderation effect of gender on the mediation model presented in stimates . For thistimates . Finallyifferent . The mulFigure 2. The moderated mediation model (B) for the female group is presented in Figure 3. The bootstrapping results of model (A) and model (B) are presented in Table 3. The fit indices, χ2 = 209.506, df = 102, χ2/df = 2.054, GFI = 0.978, IFI = 0.986, CFI = 0.986, TLI = 0.982, and RMSEA = 0.034 showed that the model has a good fit with the data. Also, the fit indices demonstrate improvement when compared with the mediation model (2).The moderated mediation model (A) for the male group is presented in Table 3 show that the indirect effect of workplace romance on employee performance is significant for both males and females. Moreover, the direct effect of workplace romance on the performance is non-significant. That is, the results show that psychological wellbeing significantly fully mediates the relationship between workplace romance and employee performance for both males and females separately. The results of the heterogeneity test showed that the indirect effect  of WR on JP for males is significantly stronger  than the indirect effect  of WR on JP for females. Our hypothesis (3) predicted that gender moderates the indirect effect of workplace romance on employee performance, where the effect for males is stronger. Thus, our results support hypothesis (3).The bootstrapping results of models (A) and (B) presented in 2 difference test. For this purpose, the moderating variable was first categorized into two groups – lateral romance (1) and hierarchical (2). Second, the unconstrained model was estimated. Third, the constrained model was estimated by constraining the structural weights along the paths of interest to be equal between the groups. Finally, the χ2 values and degrees of freedom of the unconstrained and constrained models were compared to determine if the models are significantly different. The χ2 difference between the unconstrained  and constrained  models was non-significant . This suggests that the workplace romance type does not moderate the indirect effect of workplace romance on employee performance.Hypothesis (4) proposed that the workplace romance type  moderates the indirect effect of workplace romance on employee performance, where the relationship for lateral workplace romances is stronger. To test the moderation effect the workplace romance type on the mediation model, we used multi-group analysis, bootstrapping  techniques and χz = 1.418, p = 0.139 > 0.05) from the indirect effect  of hierarchical romances on employee performance. Therefore, the results do not support hypothesis (4).Bootstrapping results showed that psychological wellbeing mediated the relationship between workplace romance and performance for both lateral and hierarchical romances separately. The results of the heterogeneity test showed that the indirect effect  of WR on JP for lateral romances is not significantly different  from a profession, which is equally attractive to both males and females. Women make up almost half of the population of Pakistan. The cultural interpretation of Islam has confined women to the peripheral, domestic, and supportive roles to ascertain the male dominance in the central roles . NeverthAdditionally, we focused on intact workplace romances and our sample included participants who were involved in workplace romances. However, the literature suggests that a large percentage of workplace romances dissolve over time and result in negative repercussions in the form of emotional disorders, poor job performance, litigations and job loss . This suAnother limitation of our study is that we did not focus on workplace romances as extramarital affairs, which are posited as unethical and destructive for a number of stakeholders within and outside an organization . As extrFinally, we relied on self-reports for measuring workplace romance and this approach may be viewed as being problematic. Future studies may consider supervisors’ or colleagues’ reports, providing these do not violate privacy and other ethical standards.This study was carried out in accordance with the recommendations of the Ethical Principles of Psychologists and Code of Conduct by the American Psychological Association’s (APA). All participants gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the employee’s council of the participating organizations as well as the ethics committee of COMSATS Institute of Information Technology Lahore.Definition of research objectives, models, and hypotheses: MASK, DJ, and MU. The provision of materials : MASK and DJ. Data collection: MU and MA. Data analysis plan: MASK, MU, and MA. Data analysis: DJ. Principal article writing: MASK and MU. Article revision and proofreading: DJ and MA. Final approval: MASK, DJ, MU, and MA.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.