Socioeconomic differences in sickness absence are well known, but previous studies have tended to focus on wage earners only. This study examined incidence and length of sickness absence comparing the employee groups of upper and lower non-manual employees and manual workers, but also entrepreneurs, the unemployed and other non-wage-earners. The study utilized register data on a nationally representative 70% sample of Finns aged 25–62 at the end of year 2012 . Sickness absence spells compensated by sickness allowance and initiated during 2013 were retrieved from the register of the Social Insurance Institution of Finland (SIIF) and followed until the end of each episode and linked to socio-demographic covariates collected from the registers of the SIIF and of Statistics Finland. Zero-inflated negative binomial regression was used in multivariate models. After adjusting for age, marital status, region and income, there were clear differences in the occurrence and length of sickness absence across socioeconomic groups. Compared to upper non-manual employees, lower non-manual employees and especially manual workers had higher cumulative annual incidence of sickness absence among both men and women, but the entrepreneurs, the unemployed and other non-wage-earners had a clearly higher expected number of sickness absence days. Results varied by diagnostic group. The results highlight the importance of different types of preventive measures for reducing the occurrence of sickness absence and for preventing prolongations of sickness absence spells in different socioeconomic groups. Sickness absence incurs significant costs for the employers, for the individuals and their families and for the society as a whole in terms of lost productivity, lost income, and payments of sickness benefits ,2. In FiSeveral previous studies conducted in different countries have generally shown that socioeconomic status is associated with the risk of sickness absence: those in a lower occupational class have more sickness absence than those in a higher occupational class ,21,22,23However, previous studies on the socioeconomic gradient of sickness absence have mainly focused on wage earners only. This is understandable since most data sets used in sickness absence studies are based on employed cohorts. However, also groups not in a wage earner position within the working-age populations are susceptible to poor work ability and, in consequence, to sickness absence. In many benefit systems, such as in the Scandinavian welfare states of Finland and Sweden, also the entrepreneurs may be listed as sickness absent and receive sickness benefits if their poor work ability prevents them from working. The unemployed may receive sickness benefits if their poor work ability prevents them from seeking and accepting employment. Furthermore, also other groups in non-wage-earner positions may be eligible to receive sickness allowances. Thus, in addition to the hierarchical occupational classes that have most often been studied , sickness absence research is needed also concerning the non-wage-earners in the working-age populations, and especially concerning the groups of entrepreneurs and unemployed. The entrepreneurs are often seen as the backbone of the society in terms of creating jobs, and thus monitoring their work ability is crucial. The unemployed, in turn, are an important labor reserve, and maintaining and monitoring also their work ability is justified. Previous studies have shown that the self-employed may have a higher risk of transitioning to sickness absence compared to the wage earners overall . It is aIn addition to focusing on employed populations only, previous studies have often concentrated on limited measures of sickness absence, most often measuring annual proportions of persons with sickness absence spells. In order to deepen previous knowledge, the aim of this study was to examine both the incidence of sickness absence and the length of absence spells using nationally representative register-based data on the Finnish working-age population. Sickness absence was examined both among hierarchical occupational classes  and among the entrepreneurs and the unemployed, as well as among the remaining group of other non-retired working-age persons, i.e., the rest of the non-wage-earners. In addition to all-cause sickness absence, sickness absences in the two largest diagnostic groups, i.e., musculoskeletal diseases and mental disorders, were assessed separately.The study population was retrieved from the population data file of the Social Insurance Institution of Finland and consists of a 70% random sample of the Finnish population between ages 25 and 62 at the end of year 2012 . The lower age limit was set at 25 years in order to measure socioeconomic status more reliably than would be possible among younger adults. Furthermore, since measurement of sickness absence is meaningful and relevant only concerning those not retired and old age retirement was possible at age 63, the upper age limit was set at 62. Those who were retirees at the end of 2012  were removed from the analyses since the retired (disability pensioners and old-age pensioners) are not eligible for sickness allowance, our measure for sickness absence  and of the register of occupational class from Statistics Finland (permission TK-53-1106-15). The data were linked at the Social Insurance Institution of Finland, using the personal identity codes assigned to every Finnish citizen, after which the personal identity codes were removed from the data set. The researchers only had access to pseudonymized data. As the study used only secondary data retrieved from registers and no human subjects were contacted to collect the data, no ethics approval was required according to Finnish law and practices . ConventSickness absence was measured through recipiency of sickness allowance. The Social Insurance Institution of Finland can pay sickness allowance to an individual whose disease or injury has caused reduced work capacity for more than 10 working days . Thus, since sickness absence was measured through receipt of sickness allowance, all sickness absence episodes that were included in this study were rather long-term, at least 12 calendar days long absences. A physician’s certificate is required to obtain the benefit. If the person is employed, the employers compensate the first days through sick pay . SicknesRegister data was used on all new sickness allowance episodes that started during 2013, with their beginning and end dates as well as diagnoses. Overlapping and consecutive episodes of sickness absence in the original data were combined. Diagnosis of each sickness absence episode was recorded based on the International Classification of Diseases, 10th revision (ICD-10) . In addiThe length of each separate sickness absence episode was first calculated from the beginning date to the end date of the absence episode. Then, the total number of sickness absence days of an individual was calculated as a sum of length of all episodes and separately for the two diagnostic groups of musculoskeletal and mental diagnoses. Full information on the length was used also of those sickness absence episodes that extended until year 2014. Thus, if an absence episode started in 2013 but ended in 2014, we included also the absence days in year 2014 in the calculation of the length of that episode.Working-age persons are eligible for sickness allowance only if they have not already accumulated the maximum amount of payable allowance days, totaling to approximately one year, but a one-year consecutive period of non-use of allowance resets the counter. Thus, some absence spells in 2013 may have been cut short because the allowance days had already mostly been used up during the previous year. In order to overcome this problem and to focus on the incidence of truly new sickness absence episodes among previously healthy persons, the analyses were restricted to those who had received no prior sickness allowance during one year’s time before the onset of their first absence episode in 2013. For persons who had no new sickness absence spells in 2013, the one year’s healthy period was assessed from 1 July 2013 backwards. The same requirement of one healthy year was applied irrespective of the diagnosis of the first occurring sickness absence episode. After including only those with no prior sickness allowance in the recent history, 125,203 persons were dropped, and the final sample used in the analyses included 1,615,352 persons .The variable of main interest in the analyses was occupational class. Information on occupational class at the end of 2012 was retrieved from the register of Statistics Finland. The persons were classified into six groups according to the classification of Statistics Finland : first, In addition, several individual-level socio-demographic covariates were retrieved from the registers of the Social Insurance Institution of Finland. The covariates included gender, age , marital status  and region of residence (four large regions based on geographic location) at the end of 2012, and taxable yearly income during 2012 . These covariates were taken into account since various socio-demographic variables are important predictors of sickness absence and may also confound the association between occupational class and disability ,14,21.The outcomes of the study were (1) the incidence of at least one new sickness absence episode in the study population during 2013, corresponding to the cumulative incidence measure suggested by Hensing  and (2) When linked to population data, the data on the number of sickness absence days in our data have an excess number of zeros and are severely over-dispersed: a large proportion of persons are not sickness absent at all so that they would receive sickness allowance, while among those who are, the distribution is strongly right-skewed. Partly, not being absent may be related to never being ill. Additionally, not being absent may be related to other reasons, such as sickness presenteeism i.e., being at work while sick, non-willingness to get medical treatment and get a doctor’s certificate for sickness absence, or some other reasons. Both the excess number of zeros and the overdispersion need to be taken into account in the analytic strategy. Main options for modeling this type of count data are a simple Poisson model, a simple negative binomial model, a zero-inflated Poisson model, and a zero-inflated negative binomial (ZINB) model ,33. AccoThe ZINB models allow for modeling separately the excess zeros and the number of days among the non-zero group. Thus, the results are divided into two parts. The first part (the logit part) predicts the probability of having/not having sickness absence , expressed as odds ratios (OR) with their 95% confidence intervals (CI). For easier interpretation of the results, the odds ratios were reversed to denote the relative odds of belonging to the non-zero group instead of being in the always zero group. This reparameterization is mathematically equivalent with the original model . The secRobust standard errors were used to control for omitted individual heterogeneity . Models The distributions of the individual-level variables are shown in The associations of the socio-demographic covariates with all-cause sickness absence are presented in Differences in sickness absence in terms of occupational class were large. While 5% of men and 8% of women in the group of upper non-manual employees had new sickness absence spells in 2013, the proportions were 10% and 14% among male and female manual workers, respectively. The proportion was also relatively high (12%) among female lower non-manual employees. In the groups of entrepreneurs and the unemployed, cumulative incidence of sickness absence was at a similar, somewhat lower than average, level. The occupational class of other non-wage-earners showed low cumulative incidence of sickness absence. However, differences in the average number of sickness absence days per one person with incident spells showed quite different associations with occupational class than the incidence of sickness absence did . GeneralConcerning all-cause sickness absence , the employee groups showed a consistent socioeconomic gradient: compared to upper non-manual employees, lower non-manual employees had almost 50% higher odds of having any sickness absence . The odds of manual workers were even higher, especially among men . Thus, manual workers showed highest probability of sickness absence also adjusted for covariates. Concerning the non-employee groups, among men, also the entrepreneurs and the unemployed showed about 26–27% higher odds of sickness absence compared to upper non-manual employees. Among women, in contrast, the group of other non-wage-earners had 21% lower odds of sickness absence compared to the upper non-manual employees but the incidence among the entrepreneurs and the unemployed did not differ from that of upper non-manual employees.In all-cause sickness absence, the negative binomial parts of the ZINB models showed associations partly of different magnitude and partly in the opposite direction. The expected number of sickness absence days were not statistically significantly different when comparing lower non-manuals to upper non-manuals. Among manual workers, the expected number of days was only rather moderately, although statistically significantly, higher than among upper non-manuals . However, the entrepreneurs and especially the unemployed showed larger differences compared to upper non-manuals in the expected number of days than in the probability of sickness absence. Among unemployed men, the expected number of sickness absence days was 82% higher compared to upper non-manual employees, and 71% higher among unemployed women, respectively. The group of other non-wage-earners also showed high expected numbers of sickness absence days even though the adjusted odds of having any sickness absence were relatively low in this group.The association of occupational class with the incidence of sickness absence due to musculoskeletal diseases was stronger than the association with all-cause sickness absence. Both among men and women, the differences in odds in almost all other occupational classes compared to upper non-manual employees were larger than in all-cause sickness absence. Manual workers had 3.46-fold (men) and 2.96-fold (women) odds of sickness absence due to musculoskeletal diseases compared to upper non-manuals. In this disease group, also female entrepreneurs and female unemployed had statistically significantly higher odds of sickness absence than upper non-manuals. Additionally the IRR:s, denoting the differences in expected number of sickness absence days compared to upper non-manuals, were generally higher in musculoskeletal diseases than in all-cause sickness absence among men. Among women, the IRRs were of similar magnitude as in all-cause sickness absence.Incidence of sickness absence due to mental disorders showed clearly different results than all-cause sickness absence or sickness absence due to musculoskeletal diseases. While lower non-manual employees had 18–19% increased odds of sickness absence compared to upper non-manuals, the odds were not higher among manual workers in this disease group. Entrepreneurs, on the other hand, had clearly lower odds of sickness absence compared to upper non-manuals . Compared to upper non-manuals, unemployed women had slightly higher odds of sickness absence due to mental disorders, but not unemployed men. Finally, concerning the expected number of sickness absence days due to mental disorders, the results were more similar to the results concerning all-cause sickness absence and sickness absence due to musculoskeletal diseases. Differences in length were small between the three employee groups, but the expected number of days was high in the remaining three groups of entrepreneurs, the unemployed and other non-wage-earners. The unemployed had the highest IRRs compared to the reference group .Our analyses focused on the incidence and length of new sickness absence spells that started in year 2013 among persons who had not had previous sickness absence compensated by sickness allowance during a one-year retrospective time frame. We conducted the analyses also without this restriction, thus including also persons with prior sickness absence. These supplementary analyses yielded very similar results as those presented above. In these analyses, the proportions of persons having sickness absence were somewhat higher than when focusing the analyses on persons with no prior sickness absence, but the results concerning the associations of occupational class with incidence and length of sickness absence were nearly identical.Utilizing large-scale national register-based data on 1.6 million working-aged Finns, this study examined both cumulative incidence and length of sickness absences that started in 2013, looking at the full spectrum of occupational classes. The study included also the entrepreneurs and the unemployed as well as other non-wage-earners in the analyses alongside the hierarchical occupational classes of upper and lower non-manual employees and manual workers.The main findings of the study can be summarized as follows: (1) Compared to upper non-manual employees, lower non-manual employees and especially manual workers had higher incidence of sickness absence. The incidence was somewhat higher also among male but not female entrepreneurs and unemployed. (2) Among those with any sickness absence spells, especially not being in a wage-earner position was associated with longer sickness absence spells. The unemployed and the entrepreneurs as well as others outside employment had relatively long spells. In addition, manual workers had longer sickness absence spells than upper non-manual employees. (3) The magnitude of the relative differences between occupational classes varied between different diagnoses and between the two measures of sickness absence. Musculoskeletal diseases showed largely similar results as all-cause sickness absence, but the differences between occupational classes were even more pronounced. Relative differences between the wage earner groups of upper non-manual employees, lower non-manual employees and manual workers were smaller in mental disorders than in musculoskeletal diseases or all-cause sickness absence, and lower non-manual employees showed higher incidence. In sickness absence due to mental disorders, entrepreneurs showed smallest incidence, but their spells were long, as were the spells of the unemployed and of other non-wage-earners.Our findings largely corroborate earlier findings on the differences in sickness absence between the occupational classes in the employed population, i.e., that upper non-manual employees have lowest incidence and generally lowest number of absence days, and that lower occupational class in the wage earner population is associated with higher incidence and longer duration of absence ,21,22,23Our results concerning different diagnostic groups were also in line with previous studies: there is a strong socioeconomic gradient in sickness absence due to musculoskeletal diseases so that compared to upper non-manual employees, manual workers have a higher incidence and length of sickness absence, and the results concerning lower non-manuals are in between these two groups ,21,23. IWe obtained also novel results on sickness absence among the entrepreneurs, the unemployed, and other non-wage-earners in comparison to the traditional hierarchical occupational groups of upper and lower non-manual employees and manual workers. We are not aware of previous nationally representative studies that would have included the entrepreneurs and the unemployed in the same analyses with the wage-earner groups and that would have compared the full spectrum of occupational classes in the working-age population. This is largely because most previous studies have utilized data on employed cohorts only.Concerning entrepreneurs—a group including both self-employed and owners of companies with salaried employees—our results showed that male entrepreneurs had a higher incidence of sickness absence than upper non-manual employees, but the incidence was lower than among lower non-manual employees or manual workers. Among women, entrepreneurs had a similar level of low incidence as upper non-manual employees. The result was nearly similar in musculoskeletal disorders, but in sickness absence due to mental disorders, both male and female entrepreneurs had a clearly lower risk of sickness absence than any of the other studied groups—lower than even upper non-manual employees. Our results are in contrast to those obtained by a Danish study  that fouOn the other hand, the sickness absence spells among the entrepreneurs were long compared to the employee population. Thus, health of the entrepreneurs seems to be polarized: on average, they have a rather low incidence of sickness absence but among those who have sickness absence, the diseases tend to be long-term. This seems to be the case especially concerning mental disorders both among male and female entrepreneurs: while the entrepreneurs have a lower incidence than the employee groups, their sickness absence spells are clearly longer than in any of the employee groups. Because of the responsibilities towards their companies and running their businesses, and due to fear of losses of productivity of the company , workingThe unemployed, on the other hand, are known to be in poorer health than the employed population . FurtherHowever, when analyzing the length of sickness absence spells, the results concerning the unemployed were quite similar as concerning the entrepreneurs. The expected number of sickness absence days was higher among the unemployed than in any other group in all-cause sickness absence and in sickness absence due to musculoskeletal diseases and in mental disorders, both among men and women. The reasons may be partly similar as among entrepreneurs. The unemployed do not have access to occupational health care and thus monitoring of their work ability may be inadequate. On the other hand, there are indications that since sickness insurance benefits tend to be higher than unemployment benefits, the unemployed may have an incentive to stay longer on sickness absence . FurtherWe also included in the analyses the remaining group of other non-wage-earners who could not be classified into the above-mentioned groups. This group is very heterogeneous, including, for example, students, those taking care of the household, and other persons for whom a clear socioeconomic status could not be defined. Thus, also the factors determining their sickness absence are varied. In many aspects, however, they are close to the other non-employee groups of unemployed and entrepreneurs, especially in terms of prolongation of sickness absence spells. Moreover, in this group of other non-wage-earners, the explanations for long spells may be related, for example, to lack of support for work ability.Our analyses focused on new sickness allowance episodes among persons who had not had previous episodes during a one-year retrospective time frame. We conducted the analyses also without this restriction and found that the results were very similar. Thus, our conclusions are not dependent on this definition of the study cohort.Our study had various strengths. A key strength was that we were able to utilize a large-scale, fully representative register-based data set that comprised 70% of working-age Finns, including 1.6 million persons. National registers are deemed to be highly reliable and objective, data quality is high, and there is very little missing information. Also, there is no self-report bias and no loss to follow-up in register data. We were able to measure sickness absence spells very precisely, including their beginning and end dates and diagnoses certified by a physician. Our study aimed to give a comprehensive picture of the socioeconomic differences in sickness absence, and thus both incidence and length of absence were analyzed simultaneously. Another strength was that in contrast to most previous studies, we examined the total working-age population susceptible to sickness absence and sickness allowance, i.e., also the classes of self-employed and unemployed and others without employment. The results may be generalized with some caution also to other countries with a roughly similar social security system, such as Sweden.The study also had some limitations. The definition of sickness absence in this study is based on receipt of sickness allowance and, hence, refers to rather long-term absence episodes lasting more than 10 working days. Consequently, sickness absences measured in this study tended to be rather long, since shortest spells lasting up to 10 working days could not be observed in the data. Unfortunately, there is no national register data in Finland on shorter sickness absence spells, i.e., spells shorter than 10 working days that do not entitle to sickness allowance. Another limitation of the study is the observational cross-sectional design; thus, no causal effects can be established. Health-related selection into the occupational classes may explain part of the results. Additionally, due to limitations in the availability of different measures in register data, we had no information on several factors that could partly explain the association between socioeconomic class and sickness absence, such as differences in health and functional capacity, different physical and psychosocial working conditions, living conditions, health behavior and use of health services. Previous studies have shown that some of these factors may contribute to the occupational class differences in sickness absence ,17,43 alReducing sickness absence entails two steps: first, preventing the occurrence of absence episodes, and second, preventing the prolongation of episodes that have already started. Especially long sickness absence is a strong predictor of permanently leaving the work force through disability retirement ,9,10,11.Reducing sickness absence may necessitate actions related to, for example, promoting good health and beneficial health behavior, improving physical and psychosocial working conditions and facilitating access to health care. In order to reduce occurrence of sickness absence due to musculoskeletal diseases, preventive measures should be targeted particularly at manual workers’ working conditions that often include heavy physical work tasks. On the other hand, psychosocial working conditions—particularly of lower non-manual employees—should be improved in order to decrease sickness absence due to mental disorders.In terms of prolongation of absences, the unemployed and the entrepreneurs should be under special focus. Maintaining and improving work ability of the unemployed persons is crucial since they constitute an important labor reserve in the era of a worsening economic dependency ratio. On the other hand, supportive measures should be targeted also at the entrepreneurs. They are often seen to constitute the economic basis of the economy in terms of creating jobs and welfare, and thus also need work ability related support. While employers in Finland are obliged by law to organize occupational health care for employees, the proportion of self-employed that organize occupational health care for themselves is low . IncreasFurther research should focus on better understanding the mechanisms that contribute to social inequalities in sickness absence and focus more specifically on different diagnoses. Some previous research exists on factors that could explain differences between the occupational classes in employed populations ,16,17,43Furthermore, more research on sickness absence among both the wage-earner and non-wage-earner groups is needed from other countries, such as from the Scandinavian welfare states having roughly similar social security systems and data sources available for research. Later research needs to ascertain whether the results observed in this study hold also in other countries.There were large differences between upper and lower non-manual employees, manual workers, entrepreneurs, the unemployed and other non-wage-earners in both the cumulative incidence and length of sickness absence. The magnitude of differences varied according to diagnostic group and measure of sickness absence. In order to curb costs and harms related to sickness absence, actions are needed to reduce occurrence of sickness absence, on the one hand, and to prevent prolongation of absence spells, on the other. While manual workers were the group with highest cumulative incidence of sickness absence in general, the unemployed and entrepreneurs, as well as other non-wage-earners, stood out as groups with a high risk or prolongation of sickness absence spells. Further research is needed on the explanations for the observed differences and of potential intervention strategies to reduce both occurrence and prolongation of absences. It is important to understand different patterns of sickness absence in different socioeconomic groups to be able to target effective preventive measures accordingly. Diverse measures are needed in order to reduce the overall burden of sickness absence in the working-age population and to narrow differences between the occupational classes. Different socioeconomic groups may benefit from different policies and preventive measures, notably since those in employment may utilize occupational health care. Special efforts should be targeted to maintaining work ability also in non-wage-earner groups, such as the unemployed and entrepreneurs, who are often not subject to specific work ability monitoring and support by occupational health care to prevent unnecessary prolongation of sickness absence spells. Preventing the accumulation of sickness absence days is crucial also in reducing disability retirement and permanent early withdrawal from the labor market. Measures are needed to combat both the incidence and prolongation of sick leave in order to save costs and prevent the loss of potential labor input.


Nasal mucosa injury can be caused by trauma, radiotherapy, chronic infection such as sinusitis, and post sinus surgery. The rate of healing and its treatment are important in the recovery of patients especially in post sinus surgery, which introduces new injuries. In this review, the current knowledge in terms of the mechanism underlying nasal wound healing was initially discussed. The currently available treatment options for enhancement of wound healing following sinus surgery were discussed and these had included intravenous antibiotics or steroids, various nasal sprays, and nasal packing. In addition, emerging alternative therapies in nasal mucosa wound healing such as herbal medicine and the advancement of regenerative medicine therapies such as stem cells and their byproducts were also discussed. Despite the various available treatment options for wound healing in nasal mucosa, rigorous strong evidence of their efficacy is gravely warranted in order to recommend them as part of the treatment modality. Nasal diseases, particularly as a result of chronic inflammation and infection such as rhinosinusitis, significantly affect the quality of life of the patient . RhinosiHowever, mucosal damage is inevitable in this intervention and these damages may lead to serious known complications such as synechia, osteitis, or fibrosis, especially for difficult areas such as the frontal recess . This caThe significance of ESS in otorhinolaryngology practice lead to an interest in understanding the post-surgical wound healing of the nasal mucosa. Unfortunately, to date, the majority of our knowledge is available in terms of wound healing, which concerns the repair of wounded skin or cornea . In termThe nasal epithelium is made of a continuous layer of pseudostratified columnar epithelial cells that are separated from the lamina propria by a continuous basement membrane. Within the epithelium, four distinctive cell types can be found, which are the basal, goblet, ciliated, and non-ciliated columnar cells. In intact mucosa, nasal epithelial cell functions include mucus production and transport, resorption of surface fluid, homeostasis, and immune responses in concert with the underlying lymphatic and vascular tissue . Damage Following ESS, normal wound healing in nasal mucosa consists of four clinical different stages of the healing process, i.e., the stage of immediate cleaning of the operative cavity, mucosal transition, complete epithelialization, and tissue remodeling . PhysiolInjury to the nasal mucosa causes hemorrhage. Hence, the first agenda of wound healing is to seal the leakage through the formation of a fibrin plug via the activation of the coagulation cascade . ImmediaFollowing the hemostasis phase is the inflammatory phase. The key aim of this phase is to clear infection at the wound site . In humaUpon the clearance of pathogenic materials and dead immune cells, the proliferation phase follows . The cleThe last phase of wound healing is tissue remodeling. In the nasal mucosa, this phase involves the differentiation of nasal epithelial into the specialized cells, goblet cells, and ciliated cells. In humans, changes in the subepithelial mucosa could be noted up to six months following the surgery . In a raESS is a technique that utilizes endoscopic vision to enable the surgeon to reach the paranasal sinuses with minimal damage to the surrounding tissue . It is oFollowing the introduction of surgical injury, bleeding is anticipated due to the fact that the nasal cavity is rich with blood supply derived from the external and internal carotid arteries in this region . PostopeAnother common complication following ESS is tissue adhesion, which is also known as nasal synechiae. Nasal synechiae form when two moist, opposite surfaces inside the nose heal together, forming fused fibrous tissue that may block the normal airflow through the nose . Due to There is also a subgroup of patients with recurring chronic rhinosinusitis who have presented bone thickening known as osteitis. Osteitis is the thickening of the bone due to inflammation. Diseased mucosal can affect the viability of the bone underneath it. Over time, this poor viability can develop into bony inflammation that finally leads to the bone thickening. Little is known about post-surgical osteitis and the strategy to treat this condition .Hence, major objectives of postoperative management of nasal wound healing aim to control postoperative bleeding, preventing adhesions, and expedite the healing process .A multitude of topical interventions and dressings has been used to facilitate the nasal mucosa wound healing following invasive sinus surgery. Interventions that have been used include intravenous antibiotics or steroids, nasal douching, and nasal packing to prevent infection and attenuate prolonged inflammation, thus collectively improving the nasal mucosa healing process.Post-surgical management with systemic drugs involves the oral or intravenous delivery of steroids and antibiotics that are used to reduce the inflammation and infection that halts the progression of the wound healing following sinus surgery .Among corticosteroids that were being used post-surgically were oral betamethasone  and oralDespite having most of the patients benefiting from systemic steroids in terms of wound recurrence prevention, a significant proportion of patients still experienced wound recurrence even in the immediate postoperative period . FurtherThere was little evidence to support the use of antibiotics in post-FESS patients . A threeClinicalTrials.gov: NCT02194062) that determine two types of intranasal steroid spray (fluticasone and budesonide) to reduce the incidence of polyposis in post-FESS chronic rhinosinusitis patients. Budesonide was observed to be superior  and Lund–Kennedy scores) than fluticasone [Nasal spray is a method of delivering drugs, mainly steroids, into the intranasal space using an aerosol spray bottle. The main objective of post-surgical management with nasal spray is to modulate the inflammation phase of the nasal wound healing ,25. It iticasone .Topical antibiotic and antifungal delivery using nasal spray were once considered to be the cornerstone of post-surgery management following ESS. This is due to the old paradigm that postulated that the inflammation seen in post-surgical nasal is a result of a microorganism infection in the sinus. In the age of the antibiotic-resistant microorganism, both therapies have generally fallen out of favor in terms of post-surgery management following ESS .As the technology has developed, nasal spray is used to deliver bioactive compounds such as ECM component or coagulation cascade component. In the in vitro skin wound healing model, the ECM protein hyaluronan has been shown to enhance re-epithelialization . NebulizThe idea of delivering coagulation cascade component into the nasal cavity centers around resolving the hemostasis phase to allow wound healing to progress . A prospSimultaneous to the development of nasal spray is the use of biomaterials as a nasal packing. A major goal of nasal packing is to enhance postoperative wound healing by expediting the healing process, preventing adhesions, and control postoperative bleeding. Massey and Singh have published a thorough review of the biomaterials used in nasal packing . Nasal pThe non-absorbable packing has been used in sinus surgery for decades before the emergence of its absorbable variant . Nasal pIn terms of absorbable nasal packing, several materials have been known to be used to fabricate them. In general, they can be divided into three categories: ECM protein, coagulation agent, and biopolymer. Such materials include gelatin, hyaluronan, fibrin, chitosan, cellulose, potato starch, carboxymethyl cellulose, polyurethane, and polyethylene glycol . They haThe earliest form of absorbable nasal packing is in the form of gelatin film  or foam Hyaluronan is one of the major components of the extracellular matrix that is known to enhance re-epithelialization in vitro . HyaluroIn terms of other biomaterials, two materials, fibrin  and chitAs the field progresses, the postoperative management of nasal wound healing has shifted into the paradigm of a functional nasal pack. In this paradigm, biomaterials that were fabricated into an absorbable nasal packing were used as a delivery vehicle for known medications for wound healing such as steroids and antibiotics.® is a registered nasal packing that is made from silver sucrose octasulfate in association with potassium sucrose octasulfate, sodium hyaluronate, propylene glycol, carbomer, and water [® were reported to have performed better at the Sino-Nasal Outcome Test 22 (SNOT22) scale compared to the placebo group. Better mucosal integration has also been observed in the Silsos gel® group endoscopically. The placebo contains the gel (carbopol and propylene glycol) without the silver. The study has successfully shown the efficacy of silver in nasal mucosa wound healing [Silsos gelnd water . Silver  healing .SinuBandFP is a 2 cm × 2 cm bi-layered thin film that is made up of fibrinogen and is fortified with a total of 160 µg fluticasone propionate. After application of SinuBandFP in the nasal cavity, the corticosteroid fluticasone propionate will be released over time. In a randomized controlled trial to investigate its safety and efficacy, the SinuBandFP group had demonstrated local safety, ocular safety, and no significant changes in urine cortisol after 24 h when compared to the SinuBand without the corticosteroid. In terms of efficacy, the SinuBandFP group did better in terms of polyp score, adhesion occurrence, and general pain .® is a bioabsorbable nasal packing that is made of a fragmentable poly (DL-lactide-co-E-caprolactone) urethane. In a randomized, placebo-controlled study, Grzeskowiak and colleagues compared the efficacy of the Nasopore® packing impregnated with either steroid (betamethasone) or antibiotics (ciprofloxacin) [® impregnated with saline was used as a placebo. The study indicated a significant improvement with both steroid-eluting and antibiotic-eluting bioabsorbable packing on the postoperative healing process and patient satisfaction as compared to saline-soaked packing. Nasoporeloxacin) ; NasoporManagement of nasal injury has been described in many cultural and religious records in the past. Due to the intimate relationship between the nasal mucosa and the external environment through the air that is breathed in, herbal medicine plays a large role in the management of the many nasal injury occurrences within different cultures .jala neti, also known as the practice of nasal irrigation [The ancient Hindu practice of Ayurveda provides the earliest record of nasal irrigation . The Ayurigation . Accordirigation . In moderigation .The precise mechanisms are still unknown but most experts think that it is due to the direct cleansing of the nasal mucosa, independent of the solution composition used . This caNasal irrigation with the addition of ions such as sodium and chloride can promote the integrity and function of epithelial cells. Moreover, the addition of magnesium will reduce eicosanoid metabolism by directly inhibiting the 5-lipoxygenase enzyme, encouraging cell repair, and limiting inflammation . MagnesiIn Chinese medicine, herbal formulations are created to balance the “Yin-Yang”, which is based on traditional Chinese medicine (TCM) theory. The occurrence of diseases is thought to be the result of imbalance within the theory. In Asian countries such as China, nasal steroids and oral antibiotics are used along with herbs as an adjuvant treatment for post-ESS care. A study was done to investigate the safety and effectiveness of Zhu-Yuan decoction (ZYD) in the postoperative care of patients for FESS. In TCM theory, ZYD is used to treat Chinese medicine symptoms (phlegm and heat obstructing the sinus). The study has shown that ZYD administration has produced significant results that have similar safety and efficacy as intranasal cortisone. However, the study was short-term (lasting 12 weeks) and required the study of long-term effects and further study to elucidate the underlying mechanisms of ZYD .Propolis is the material used by bees to build their hives. Synthesized by bees from plant resin, it has been demonstrated to have anti-inflammatory activity . A studyAmong the spices, the medicinal properties of turmeric have been reported substantially . In cutaTissue engineering is a branch of regenerative medicine that employs a multidisciplinary approach to achieve tissue repair and regeneration through the combination of three elements: stem cells, biomimetic scaffolds, and bioactive molecules. In the context of nasal mucosa regeneration, tissue engineering is promising in reaching the goals of regeneration.Stem cells have been the subject of interest in regenerative medicine since the dawn of the 20th century. In terms of wound healing, there were reports on its efficacy with skin  and cornAnother study has attempted to utilize the aerosol delivery technique to deliver regenerative cells onto the injured tissue such as the works of Kardia and colleagues . They suIn many surgical interventions, autologous tissue graft is considered as the gold standard. This can be observed in burn wounds , ligamenTissue scaffolds serve as a template that provides support to cells in engineered tissue. Scaffolds are fabricated in a way that resembles the native tissue, either through structural networks and geometries or biochemical compositions.The biomaterial that is used to construct a scaffold can be of natural or synthetic origin. One of the types of natural tissue scaffolds is the decellularized matrix of native tissue. Decellularized tracheal extracellular matrix has been shown to positively influence the migration, differentiation, and function of respiratory epithelium in the mouse model of orthotopic tracheal transplantation .Collagen and hyaluronan are two commonly used natural biomaterials for the ciliary differentiation of human respiratory epithelial cells . In combTissue-engineered scaffolds can also be of synthetic origin. Fabrication of bi-layered trachea using autologous nasal respiratory epithelial cells and fibroblast seeded on titanium scaffold has successfully induced re-epithelialization within the sheep trachea . On top As an alternative to the stem cell differentiation hypothesis, the effect of stem cells on wound healing has also been hypothesized to be through the secretion of cytokines and growth hormones that activates resident cells in the tissue to regenerate. In the laboratory, cell-secreted factors can be found in the medium where the stem cells are cultured. Hence, upon collection, this medium is termed as conditioned medium.As a result, the healing properties of the conditioned medium of stem cells have also been the subject of interest in regenerative medicine. Delivery of airway epithelium into the respiratory tract has been proven to improve its regeneration . The secFibroblasts are the cells of the connective tissue that play supporting roles in the tissue where they reside, one of such is the synthesis of the extracellular matrix . Nasal fMesenchymal stem cells and their secretory factors are also a subject of interest in the context of tissue regeneration. Conditioned medium from umbilical cord-derived mesenchymal stem cells has been shown to improve nasal epithelium healing both in vivo and in vitro . In a stTo support the notion for clinical application of human bone marrow-derived mesenchymal stem cell (MSC) secretome in regeneration for the treatment of idiopathic pulmonary fibrosis and other fibrotic lung disorders, Akram et al. tested the MSC conditioned medium (MSC-CM) with the human type II alveolar epithelial cell line A549 cells (AEC) and primary human small airway epithelial cells (SAEC) using an in vitro scratch wound repair model. They found that the MSC-CM in their study contained fibronectin, lumican, periostin, and IGFBP-7. They also demonstrated that the MSC-CM facilitated AEC and SAEC wound repair through stimulation of cell migration .Recombinant protein technology has enabled scientists to synthesize individual growth factors. As a result, the study on the effect of individual growth factors in many of the human diseases has been made possible. The hepatocyte growth factor (HGF), which has been initially discovered as a mitogen for hepatocyte, is mainly produced by the mesenchymal cells . It is aNerve growth factor (NGF) has also been reported to enhance epithelial healing following surgery . An air-Insulin-like growth factor (IGF-I) is a hormone that has a similar molecular structure as insulin. Mainly secreted by the liver, IGF-I is important for both the regulation of normal physiology and several pathological states . In vitrResearchers have expanded their interest in studying plasma effect in medicine as some of the literature have suggested its beneficial effects including anti-inflammatory, anti-cancer, anti-microbial, and even tissue regeneration. Plasma is considered as the fourth state of matter, which is made up of partially ionized gas that contains electrons, radicals, energetic photons, and ions.More importantly, the application of plasma therapy has been documented recently by Won et al. (2018)  by studyFurthermore, an in vitro study revealed that NTS also enhanced the matrix-metalloproteinase (MMP)-2/MMP-9 activities, which functioned to induce cell migration during wound healing. To provide more evidence on its efficacy, they tested NTS on rats by performing NTS-treated saline irrigation toward the nasal mucosa after the introduction of a wound at the right nasal septal mucosa. Epithelial thickness index (ETI) and sub-epithelial index (STI) were used to obtain the ratio of the average height of newly formed tissue in the treated group compared to the height of the control group. Histopathological analysis revealed that NTS significantly increased ETI, suggesting an increased epithelial proliferation while significantly decreasing STI, which translated into decreased edematous changes of the tissue. Furthermore, the NTS-treated group has less inflammatory cell infiltration compared to the control group. Taken together, this report has documented the potential efficacy of plasma therapy in enhancing the wound healing of nasal mucosa .Over the past decades, many interventions in the post-trauma management of nasal mucosa healing have been innovated. With the advancement of medicine, a favorable outcome of sinus mucosa wound healing can be achieved. Besides the conservative treatment, stem cells and other regenerative medicine strategies offer great potential in airway epithelium regeneration. However, rigorous clinical trials need to be conducted to bring them to the mainstream treatment modality.


Methodology: We carried out a systematic review based on international scientific literature, in which only peer-reviewed papers were included. To identify reviews, we carried out an electronic search of the Cochrane Database Reviews, ERIC, Web of Science, PubMed, Medline, Scopus and PsycINFO. This paper provides a narrative review of reviews of the literature from 2015 to 2020. Results: 20 reviews met the inclusion criteria : they focused mainly on reducing risk behaviors , whilst obviating themes such as desire and pleasure, which were not included in outcome evaluations. The reviews with the lowest risk of bias are those carried out in school settings and are the ones that most question the effectiveness of sex education programs. Whilst the reviews of digital platforms and blended learning show greater effectiveness in terms of promoting sexual and reproductive health in adolescents (ASRH), they nevertheless also include greater risks of bias. Conclusion: A more rigorous assessment of the effectiveness of sexual education programs is necessary, especially regarding the opportunities offered by new technologies, which may lead to more cost-effective interventions than with in-person programs. Moreover, blended learning programs offer a promising way forward, as they combine the best of face-to-face and digital interventions, and may provide an excellent tool in the new context of the COVID-19 pandemic.Adolescence, a period of physical, social, cognitive and emotional development, represents a target population for sexual health promotion and education when it comes to achieving the 2030 Agenda goals for sustainable and equitable societies. The aim of this study is to provide an overview of what is known about the dissemination and effectiveness of sex education programs and thereby to inform better public policy making in this area.  Adolescence is a period of transition, growth, exploration and opportunities that the World Health Organization defines as referring to individuals between 10 years and 19 years of age . Sexual In high-income countries, sexual debut usually occurs during adolescence , though Sexual education can be defined as any combination of learning experiences aimed at facilitating voluntary behavior conducive to sexual health. Sex education during adolescence has centered on the delivery of content (abstinence-only vs. comprehensive instruction) by teachers, parents, health professionals or community educators, and on the context (within school and beyond) of such delivery . As regaWith regard to context, sexual education may occur in different settings. School settings are key sites for implementing sexual education and for promoting adolescent sexual health , but todThanks to the ubiquity and popularity of technologies, digital media interventions for sexual education offer a promising way forward, both via the internet  and via mobile phones , given the privacy and anonymity they afford, especially for young people. Digital interventions in school—both inside and outside the classroom—offer interesting possibilities, because of their greater flexibility with regard to a variety of learning needs and benefits in comparison with traditional, face-to-face interventions, and because they offer ample opportunities for customization, interactivity as well as a safe, controlled, and familiar environment for transmitting sexual health knowledge and skills . As GarzThe present study sets out to research the dissemination and effectiveness in different settings  of sex education programs that promote healthy and positive relationships and the reduction of risk behaviors, so as to make current sexual health interventions more effective . NumerouThe decision to conduct a review of reviews (RoR), assessing the quality and summarizing the findings of existing systematic reviews, rather than working directly with primary intervention studies, addresses the need to include as wide a range of topics covered within the field of sex education as possible . As Scha(1) To systematically review existing reviews of Sex Education (SE) of school-based (face-to-face), digital platforms and blended learning programs for adolescent populations in high-income countries.(2) To summarize evidence relating to effectiveness.The review is structured in accordance with the PRISMA checklist  see , and theThis systematic review is based on international scientific literature and only peer- reviewed papers have been included. Only meta-analyses (publications that combine results from different studies) and systematic reviews  were used for this review. Findings from reviews of reviews were not analyzed. To identify reviews, we electronically searched the Cochrane Database Reviews, ERIC, Web of Science, PubMed, Medline, Scopus and PsycINFO. After the list was completed the duplicated papers were automatically removed. Two reviewers working independently applied inclusion criteria in screening citations by titles, abstracts, and keywords to identify records for full-text review. A third reviewer reconciled any disagreement. The same procedure was carried out in screening the full text of studies selected after the title and abstract screening phase. Two reviewers then examined the full text of each article to determine which satisfied inclusion criteria. Data extraction was carried out independently by the first and second reviewer. The extracted data included specific details about the interventions, populations, study methods and outcomes significant to the review question and objective. Any discrepancies were discussed until consensus was reached. Search terms are included in This RoR included the reviews published since 2015, when the United Nations decided on new Global Sustainable Development Goals, until December 2020. The 2030 Agenda for Sustainable Development  takes inWe extracted data using a “Population, Intervention, Comparison, Outcome” structure, PICO .Population: Reviews of interventions targeting adolescents (aged 10–19 years), school-setting, digital platforms or blended learning education were eligible for inclusion. Reviews in which studies of interventions targeted youth and adults were eligible if the primary studies included people between the ages of 10–19 years.Intervention: Reviews of interventions developed in school-setting (school-based), digital  or blended learning programs were included. Interventions based on multiple settings or targeted multiple health-related issues were only considered for inclusion if any primary studies were linked to school-based, digital or blended learning interventions, as well as targeting Sexual and Reproductive Health (SRH).Comparison groups: Randomized controlled trials (RCTs) and studies using a quasi-experimental design . Single group, pre- and post-test research designs, group exposed to sexual education (SE) program  compared with non-exposed control group or another intervention.Outcomes: Primary outcomes: (1) Sexual behavior and (2) Health and social outcomes related to sexual health. Secondary outcomes: (1) Knowledge and understanding of sexual health and relationship issues and (2) Attitudes, values and skills.Their primary focus was adult people and adolescents were not included.Their primary focus was sexual-health screening, sexual abuse or assault or prevention of sexual abuse or rape.The studies targeted specific populations .The interventions focused on low- and middle-income countries or if high income countries were not included in the study.Recipients were professionals, teachers, parents or a combination of the latter.Reviews were excluded if:Review quality was assessed by the first author using the AMSTAR II checklist . This isAfter manually coding the papers and extracting relevant data, we used a narrative/descriptive approach for data synthesis to summarize characteristics of the studies included. Considering the heterogeneity of outcomes, their measures and research designs, meta-analysis of all the studies included was not carried out. Two researchers were involved in data synthesis. Discrepancies were resolved through discussion, and a third researcher was consulted to resolve any remaining discrepancies. For the classification of the information and presentation of the effects of the interventions reported, data was separated  and structured around population, intervention, comparison, and outcome. To address the main review questions, data was synthesized in two phases. Phase 1 addressed the first question, the description of sex education/sexual health interventions. Phase 2 addressed the second question, the effectiveness and benefit of the interventions; studies with a low risk of bias were highlighted, so as to strengthen the reliability of findings (AMSTAR II) .Our searches yielded 1476 unique citations. After excluding 776 records based on title and abstract screening, we reviewed 217 full-text articles for eligibility, of which 20 ultimately met inclusion criteria, and proceeded to data extraction. Of the 197 studies that we excluded after full-text review, 82 were carried out in low- and middle-income countries, 47 targeted exclusively adults, 56 dealt with minority groups, and 12 targeted exclusively pre-teen students.According to the AMSTAR II quality assessment tool’s developers  scores mKey information regarding the 20 reviews included is shown in Ten studies 50%) dealt with school-based interventions % dealt w,53,54,55The targeted age for reviews in school settings, as shown in All the studies included in this review of reviews used randomized controlled trials (RCTs), non-randomized controlled trials (non-RCT), and a quasi-experimental design or a pre-test/post-test design to examine program effects.The term “sexual outcomes” refers to the attitudes, behaviors, and experiences of adolescents consequent to their sex education  (p. 1), Of the 10 reviews of interventions in school settings, the authors are from the USA in 7 reviews ,53,54,55The studies cited in the reviews that met the inclusion criteria for this review were published over a wide range of years (between 1981–2019), although only one , with arAll reviews include more than 2 tools to carry out the search, in a range of 3–12, and in 7 of them the review of gray literature was included.All reviews from school settings are multicenter, except that of Mirzazadeh et al. , which iAs for the number of reviews that carry out a meta-analysis, there are 8 in total: 4 in school settings ,48,49,55Half of the reviews conclude that interventions are not effective in promoting healthy sexual behaviors and/or reducing risks ,48,49,50In contrast to these negative results in terms of the effectiveness of the programs implemented in the school environment (identified in 5 of the 10 reviews included), 3 of the 10 reviews concluded that the programs evaluated were mostly effective in promoting knowledge, attitudes and/or in reducing risk behaviors ,52,53 whFinally, the review by Haberland et al. , which fThe reviews included show a very diverse panorama of digital platforms used to carry out educational interventions , which makes it difficult to compare the results. Of the 9 reviews of studies included, only one—in which the effects of TCCMD (Targeted Client Communication delivered via Mobile Devices) are evaluated —meets thWhen compared with more conventional approaches, interventions that use TCCMD may increase sexual health knowledge (low certainty evidence), and may modestly increase contraception use (low certainty evidence) while the effect on condom use remains unclear given the very low certainty evidence. Additionally, when compared with digital non-targeted communication, the effects TCCMD on sexual health knowledge, condom and contraceptive use are also unclear, again given the very low-certainty evidence. The review finds evidence of a modest beneficial intervention effect on contraceptive use among adolescent (and adult) populations, but that there was insufficient evidence to demonstrate that this translated into a reduction in contraception.Most of the reviews included refer to changes to a greater or lesser extent ,60,62,63The review by L´Engle et al.  assessesThe review by Widman et al.  reveals n = 9) suggest that the digital interventions carried out with the adolescents generally had a positive effect on health-promoting behaviors. However, in another study focused on fostering HIV prevention [The review by Bailey et al.  (p. 5) aevention , there wIn the review by DeSmet et al. , no signn = 20) while online social networks were the second most favored medium (n = 13), mostly via Facebook (n = 8). The programs under review favored online interaction, principally amongst peers (n = 23) but also with professionals (n = 16). The review concludes that ASHR programs promoting these kinds of online participation interventions have demonstrated feasibility, practical interest, and attractiveness, though their effectiveness has yet to be determined, given that they are still in the early stages of design and evaluation.Finally, in the review by Martin et al.  60 studiIn the only blended learning review included in our study , the autThe present review of reviews assesses, for the first time jointly to our knowledge, the effectiveness of sexual education programs for the adolescent population (ASRH) developed in school settings, digital platforms and blended learning. Of the twenty reviews included , ten correspond to reviews of programs implemented in school settings, nine to those dealing with interventions via digital platforms and only one deals with studies relating to blended learning. Twelve (60%) of the reviews included  have been published in the last 3 years (between 2018 and 2020). Thus, the present study constitutes the most up-to-date and recent review of reviews incorporating several contemporary studies not covered by earlier reviews ,37,38,39The interventions included in the reviews covered by our study were largely focused on reducing risk behaviors , and envisaging sex as a problem behavior. Programs reviewed often focused on the physical and biological aspects of sex, including pregnancy, STIs, frequency of sexual intercourse, use of condom, and reducing adolescents´ number of sexual partners. One exception is Golfard’s et al.  review aAs for more positive views of sexuality, only on rare occasions do interventions address issues such as sexual pleasure, desire and healthy relationships. Desire and pleasure were not included in the outcome evaluations for school settings, nor for digital and blended learning programs included in this review: again this is in line with the position of other authors cited in the present study, who advocate the need to also embrace the more positive aspects of sexuality ,56. SpecPleasure and desire are largely absent within sex and relationship education  and, wheThe absence of desire and pleasure in the outcomes of the evaluated reviews is connected with the absence of gender-related outcomes. Only one of the reviews addresses the issue of gender and power in sexuality programs , illustrThe International Guidance on Sexuality Education , and theFurthermore, sexual education that privileges heterosexuality reinforces hegemonic attributes of femininity and masculinity, and ignores identities that distance themselves from these patterns. Our collective heteronormative legacy marginalizes and harms LGB families  and LGBTThis present review of reviews shows a variety of types of sexual health promotion initiatives across the three settings , with inconsistent results. The reviews with lower risk of bias are those carried out in school settings and those that are most critical regarding the effectiveness of programs promoting ASRH, both in the prevention of pregnancies and of HIV/STIs. Reviews dealing with digital platforms and blended learning show greater effectiveness in terms of promoting adolescent sexual health: however, these are also the studies that incorporate the highest risks of bias. Specifically, in digital platforms programs the great variety of alternatives makes comparability difficult. Moreover, these programs, along with blended learning, are in a more incipient state of evaluation, compared to school-setting evaluations, and present greater risks of lower quality than reviews in school settings.The results of the present RoR are in line with those of previous RoRs ,32. The However, although in our RoR the higher quality/lower bias studies—in keeping with the findings of previous reviews ,33—fail With regard to school settings, Peterson et al.  concludeHowever, “despite clear and compelling evidence for the benefits of high-quality curriculum-based CSE, few children and young people receive preparation for their lives that empowers them to take control and make informed decisions about their sexuality and relationships freely and responsibly”  (p. 12),This study represents the first review of reviews, as far as we are aware, in which the effectiveness of sex education programs in different settings  is evaluated, using a rich methodology and providing interesting conclusions. However, the present review of reviews is not without its limitations.While systematic reviews and reviews of reviews can offer a way synthesizing large amounts of data, the great heterogeneity and diversity of measured outcomes make it difficult to establish a synthesis of the results, even more so in cases where it is not possible to apply meta-analysis. Furthermore, the quality of reviews of reviews is limited by that of the reviews they include and RoRs do not necessarily represent the leading edge research in the field.In addition, although we searched for a wide range of keywords on the most commonly used databases in the field of health  to identify relevant papers, it is possible that the choice of keywords and database may have resulted in our omitting some relevant studies. Moreover, our review has focused on articles in international journals published in English, allowing us access to the most rigorous peer-reviewed studies and to those with greater international diffusion, given that English is the most frequently used language in the scientific environment: notwithstanding, this has also limited the scope of our review by precluding research published in other languages and contexts. Nor have documents that could have been found in the gray literature been included, given that only peer-reviewed studies have been considered for inclusion.It is worth remembering moreover that most of the data on the outcomes of the studies included are self-reported, with mention of only occasional biological outcomes, which may limit the reliability of the effectiveness results. This represents another interesting reflection on the way in which the evaluation of the effectiveness of programs on sexual education is being carried out, and alerts us to the need for change.Finally, it should be noted that this review of reviews is focused on adolescents from high-income countries, and our results show that studies carried out in the United States are largely overrepresented, since it is the country that provides the highest number of samples, especially in school settings: this may give rise to bias when it comes to generalizing from these results. Once again, this raises another necessary reflection on the capitalization that studies focused on American samples are having in the construction of the body of scientific knowledge on sexual and reproductive behavior, when in reality sexuality is conditioned by socio-economic variables that require a far-more multicultural and world-centric approach.This review of reviews is the first to assess jointly the effectiveness of school-based, digital and blended learning interventions in ASRH in high-income countries. The effectiveness of the sex education programs reviewed mostly focused on the reduction of risky behaviors  as public health outcomes; however, pleasure, desire and healthy relationships are outcomes that are mostly conspicuous by their absence in the reviews we have covered. Nonetheless, the broad range of studies included in this RoR, with their diversity of settings and methods, populations and objectives, precludes any easily drawn comparisons or conclusions. The inconsistent results and the high risk of bias reduce the conclusiveness of this review, so a more rigorous assessment of the effectivity of sexual education programs is pending and action needs to be taken to guarantee better and more rigorous evaluations, with sufficient human and financial resources. Schools and organizations need technical assistance to build the capacity for rigorous program planning, implementation and evaluation . To thisThe extent of the risks of bias identified in the reviews and studies covered by this RoR points to an important conclusion, allowing us to highlight the precariousness that characterizes the evaluation of sexual education programs and the consequent undermining of public policy oriented to promoting ASRH. Public policies that promote ASRH are of vital importance when it comes to minimizing risks related to sexual behavior, and maximizing healthy relations and sexual well-being for the youngest members of our society.Above all it is important to recognize the opportunities afforded by new technologies, so ubiquitous in the lives of young people, since they allow for programs that are far more cost-effective than traditional, in-person interventions. Finally, blended learning programs are perhaps even more promising, given their combination of the best of face-to-face and digital interventions, meaning they provide an excellent educative tool in the new context of the COVID-19 pandemic, and may even become the dominant teaching model in the future.


There has been a recent surge in the use of cryo and/or vacuum specimen preparation and transfer systems to broaden the scope of research enabled by the microscopy technique of atom probe tomography. This is driven by the fact that, as for many microscopes, the application of atom probes to air- and temperature-sensitive materials or wet biological specimens has previously been limited by transfer through air at room temperature. Here we provide an overview of areas of research that benefit from these new transfer and analysis protocols, as well as a review of current advances in transfer devices, environmental cells, and glove boxes for controlled specimen manipulation. This includes the study of catalysis and corrosion, biological samples, liquid-solid interfaces, natural aging, and the distribution of hydrogen in materials. However, many of the highest resolution microscopes require high-vacuum environments, limiting their application to materials that remain stable in a vacuum and ruling out hydrated samples such as soft biological matter unless it is fixed or cryogenically prepared. Moreover, modern microscopy workflows typically involve the examination of a specimen in several different microscopes, or the preparation of a specimen in one type of instrument and analysis in another. Transfer through air thus creates further challenges for the study of air-sensitive or cryo-frozen materials.Atom probe tomography (APT) is a powerful microscopy technique that provides detailed three-dimensional 3D) maps showing the arrangement of atoms within nanoscale volumes of matter. APT has contributed to major advances in materials science, from alloy design  to the dD maps shE. coli) ., 97.96, Using the ETH, Schreiber et al.  have devOther environmentally protected specimen transfer systems exist at a number of different universities, including at Erlangen/ Nurnberg , Univers4.The composition of surfaces during chemical interactions or reactionsMeasurement of the arrangement of molecules at hydrated surfaces (ligands)Compositional mapping across liquid-solid interfacesObservation of the position of hydrogen atoms by using deuterium as a tracerAtomic-scale mapping of ions or molecules in vitrified biological materialsDirect observation of the arrangement of ions in vitrified liquidsThe analysis of highly reactive samples that are sensitive to air, such as battery or nuclear materialsIn some cases, successful FIB preparation of specimen that are affected by the ion beam at room temperatureVacuum and cryogenic preparation and transfer tools for microscopy are evolving rapidly and it is now possible to apply these methods to the preparation of specimen for APT. This has the potential to allow a number of exciting new experiments that were not previously possible:Effective protocols for cryogenic specimen preparation, gas exposure, deuteration, and/or vitrification and fabrication into the required needle-shaped samplesReliable transfer tools to ensure the pressure and temperature requirements are maintained throughout all steps from specimen preparation, transfer, and analysisOptimization of atom probe acquisition parameters and an understanding of how they affect the data, especially in systems that contain materials of vastly different evaporation fieldsProtocols for the interpretation of atom probe data from materials with little existing literature New reconstruction algorithms that can account for molecular ions (i.e. fragments)For many of these examples, successful experiments will require substantial developments in both the experimental setup and the available tools for data treatment and analysis. The workflows required will involve the following:In materials science, considering current interest in the field, it is reasonable to expect that deuterium labeling might become a standard method for measuring the distribution of hydrogen within materials. Hydrogen-free instruments, if successfully developed, may still require cryogenic transfer systems to ensure that hydrogen from charging remains within alloys. Cryo FIB instruments may prove useful to minimize FIB-induced damage and vacuum/cryo transfer to both atom probe and TEM is highly likely to become commonplace to avoid exposure of specimen to air.We are likely to see the continued use of ancillary environmental chambers to study corrosion and catalysis. These are sociogenically important problems. Corrosion has an enormous economic impact. Evolving cryogenic specimen preparation and environmental transfer strategies will continue to allow APT analysis of corrosion product and across the liquid-solid interface , allowinThere is scope for vacuum-based transfer methods to enable transformational research into battery materials, such as Li-based anode materials , and earIt is difficult to predict the impact that atomic-scale imaging may have on life sciences. FIB-based site-specific specimen preparation and correlative light electron microscopy  might al


Autoinflammatory diseases are characterized by recurrent fevers and clinical findings of impaired natural immunity and can involve various organ systems. The concept of autoinflammatory disease emerged after the definition of familial Mediterranean fever and tumor necrosis factor receptor-associated periodic syndrome. This new disease group was considered to differ from the standard concept of autoimmune diseases, which is relatively better known in terms of basic features, such as defects in innate immunity and the absence of antibodies. A better understanding has been achieved regarding the genetic and pathogenetic mechanisms of this relatively new disease group over the past 20 years since they were first diagnosed, which have led to some changes in the concept of autoinflammatory diseases. The recent definition classifies autoinflammatory disease to be a wide range of diseases with different clinical features, mainly accompanied by changes in innate immune and rarely in humoral immunity. The spectrum of autoinflammatory diseases is rapidly expanding owing to recent developments in molecular sciences and genetics. This review article discusses the clinical features, classification criteria, treatment options, and long-term prognosis of periodic fever, aphthous stomatitis, pharyngitis, adenitis syndrome, and other common autoinflammatory diseases in the light of current literature. Autoinflammatory diseases are a group of diseases that occur because of the dysfunction or dysregulation of innate immunity and can cause serious morbidity and mortality by affecting multiple organ systems. This new group differs from the standard concept of autoimmune diseases, which is relatively better known in terms of basic features, such as defects in innate immunity and the absence of antibodies circulating in the bloodstream. The concept of autoinflammatory disease emerged after the definition of familial Mediterranean fever (FMF). Notably, the spectrum of autoinflammatory diseases is rapidly expanding owing to recent developments in molecular sciences and genetics.Until date, several definitions have been proposed to describe this group of rare diseases . The terThe changes in the definition of the disease reflect the expansion of the spectrum and the classification of new diseases under this group. The recent definition of autoinflammatory disease classifies it as a wide range of diseases exhibiting different clinical features, mainly accompanied by changes in innate immune and rarely in humoral immunity. Diseases classified presently under the group of autoinflammatory diseases are summarized in Fever is one of the most common reasons for hospital admission during childhood, with infections being the leading cause of fever in children. The initial step in the evaluation of a child with fever is the definition of fever and its characteristics. It should be kept in mind that parents can subjectively exaggerate the symptoms, and if parents complain regarding recurrent fevers, a fever diary that is filled objectively should be requested. Fever diary is a useful tool in confirming the fever and identifying fever patterns like periodic, recurrent, or prolonged.In the case of recurrent or periodic fever, a detailed medical history of the patient and family should be obtained, and cautious physical examination should be performed. Nonetheless, considering the rarity of autoinflammatory diseases, other possible reasons for periodic or recurrent fever should be considered, such as recurrent infections, malignancies, immunodeficiencies like cyclic neutropenia. Moreover, fever can be a sign of Munchausen syndrome by proxy, and accordingly, physicians should be vigilant regarding every child with recurrent fever. While developmental delay, growth restriction, and history of hospitalization for severe infections primarily suggest possible immunodeficiency, night sweats, night pains, weight loss, generalized lymphadenopathy, or hepatosplenomegaly may indicate malignancies. On the other hand, indications suggestive of autoinflammatory diseases are normal growth and development patterns, asymptomatic between episodes, positive family history, and history of similar episodes. A diagnostic approach algorithm is presented in PFAPA syndrome is one of the most common periodic fever syndromes observed during childhood . HoweverMEFV) gene mutations in patients with PFAPA syndrome. The frequency of the MEFV mutations in patients with PFAPA syndrome is reported to be 8%-66%  therapy, and tonsillectomy are the recommended treatment options for the disease . Althoug studies ,14,15. T studies . BecauseFMF is the most common hereditary autoinflammatory disease with an autosomal recessive inheritance pattern, characterized by recurrent fever attacks and polyserositis ,25. The MEFV encoding pyrin protein is the causative gene of the disease . Th. ThMEFV criteria  reportedThe primary aim of FMF treatment is to prevent amyloidosis—the most critical complication of the disease. Notably, colchicine is the mainstay of FMF treatment. Colchicine was first shown to be effective in FMF by Ozkan et al.  and thenMVK gene that encodes mevalonate kinase, an enzyme that plays a crucial role in cholesterol biosynthesis , it is below 1% . Ep. EpMVK efections . The frefections . Contrarfections . On the fections . In addifections .MVK variants (homozygous or in trans compound heterozygous) and at least one of the following symptoms are needed for diagnosis: gastrointestinal symptoms, cervical lymphadenitis, and aphthous stomatitis  omatitis   that is located on chromosome 12  is an autoinflammatory disease with the following three distinct subtypes: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and chronic infantile neurological, cutaneous, and articular (CINCA) or neonatal-onset multisystem inflammatory disease (NOMID) . These tsubtypes ,80.NLRP3 (CIAS1) gene encoding cryopyrin protein are responsible for CAPS  . Most ofThe most recently proposed classification criteria for CAPS are the Eurofever/PRINTO criteria  Table 6Table 6. Like in all the other autoinflammatory diseases, the primary purpose of treatment is to urgently control the disease activity, to resolve the illness, prevent treatment-related damages, and increase the quality of life of patients .Because an increase in IL-1 cytokine level plays a crucial role in the pathogenesis of the disease, the appropriate treatment approach is to antagonize the effect of IL-1 ,80,82. VIn conclusion, the number of autoinflammatory diseases is increasing every day. Therefore, these diseases should be considered in the presence of skin and musculoskeletal system findings with accompanying periodic or recurrent fever during childhood. The diagnostic algorithm for suspected autoinflammatory diseases according to clinical findings is summarized in


Nowadays, the biomolecular assay platforms built-up based on bead counting technologies have emerged to be powerful tools for the sensitive and high-throughput detection of disease biomarkers. In this mini-review, we classified the bead counting technologies into statistical counting platforms and digital counting platforms. The design principles, the readout strategies, as well as the pros and cons of these platforms are introduced in detail. Finally, we point out that the digital bead counting technologies will lead the future trend for the absolute quantification of critical biomarkers, and the integration of new signal amplification approaches and routine optical/clinical instruments may provide new opportunities in building-up easily accessible digital assay platforms. Motivated by the growing demand for rapid and precise analysis of critical biomarkers , particle-based biomolecular assays and particle counting technologies have significantly enlarged the toolbox for bioanalysis , where each microhole was designed to trap a single bead that functionalized with probe antibodies    is a template-independent DNA polymerase that catalyzes the repetitive sequential addition of deoxynucleotides (dNTP) at the 3′-OH group of a DNA  is the most mature digital counting bioassay, which has already been commercialized (Hindson et al., Another prominent digital platform is the Simoa, which was firstly proposed by the Walt group (Rissin et al., As a conclusion, the ultrahigh sensitive quantification of disease-biomolecules can be achieved by introducing bead-based digital counting strategies, which is with great promise to offer even the absolute number of target molecules in complex biological samples. Therefore, compared with the statistical counting strategies, the bead-based digital counting strategies are more precise and sensitive.Although the digital assay strategies, including ddPCR, BEAMing, and Simoa have shown the future trend of biomarker analysis, we anticipate that the development of new bead-based digital platforms with commonly accessible equipment, simple operation, and wide applicability is of great significance for the prevalence of digital assays. Considering the advantages of bead-based approaches and the superior of digital counting assays, our group has developed a new digital platform based on the single molecule-initiated signal amplification that can illuminate a single bead for the ultrasensitive detection of biomolecules (dFlowSeim, Fan et al., In this mini-review, a series of bead counting strategies, including statistical counting and digital counting for the analysis of disease-related biomolecules have been summarized. The design principles and advantages of the most popular bead counting-based assays have been described and discussed in detail. Finally, we point out that the digital assay will lead the future trend of the bead counting-based bioassays and the integration of routine instruments and emerging on-bead signal amplification technologies will broaden the way of digital assays.WF and DL wrote and revised the manuscript. WR supervised and revised the manuscript. WR and CL were in charge of the whole manuscript. CL put forward the central idea of the manuscript and gives final modification. All authors contributed to the article and approved the submitted version.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.


Staphylococcus aureus (S. aureus) is a very common human pathogenic microorganism that can trigger a variety of infectious diseases, such as skin and soft tissue infections, endocarditis, osteomyelitis, bacteremia, and lethal pneumonia. Moreover, according to the sensitivity to antibiotic drugs, S. aureus can be divided into methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). In recent decades, due to the evolution of bacteria and the abuse of antibiotics, the drug resistance of S. aureus has gradually increased, the infection rate of MRSA has increased worldwide, and the clinical anti-infective treatment for MRSA has become more difficult. Accumulating evidence has demonstrated that the resistance mechanisms of S. aureus are very complex, especially for MRSA, which is resistant to many kinds of antibiotics. Therefore, understanding the drug resistance of MRSA in a timely manner and elucidating its drug resistance mechanism at the molecular level are of great significance for the treatment of S. aureus infection. A large number of researchers believe that analyzing the molecular characteristics of S. aureus can help provide a basis for designing effective prevention and treatment measures against hospital infections caused by S. aureus and further monitor the evolution of S. aureus. This paper reviews the research status of MSSA and MRSA, the detailed mechanisms of the intrinsic antibiotic resistance and the acquired antibiotic resistance, the advanced research on anti-MRSA antibiotics and novel therapeutic strategies for MRSA treatment.Infectious diseases are the second most important cause of human death worldwide;  Staphylococcus aureus (S. aureus) is one of main pathogens in hospital and community infections and can cause many infectious diseases, such as mild skin and soft tissue infections infective endocarditis, osteomyelitis, bacteremia, and fatal pneumonia , is encoded by bacterial chromosomal genes, and is transferable , vancomycin-intermediate Staphylococcus aureus (VISA) and heterologous vancomycin resistant Staphylococcus aureus (hetero-VRSA)  enters the cell. Finally, the drug is released inside the cell, thereby exerting antibacterial action  Phages only begin to proliferate when the bacteria reach a certain density. Phages may be inoculated prematurely or at inappropriate doses, and may be eliminated by the body before they begin to proliferate. Therefore, determining the optimal inoculation time and dose will become a major difficulty in phage treatment. The above are common problems in phage therapy. Therefore, these problems also exist in the course of Staphylococcus aureus treatment.At the beginning of their discovery, phage were used by the former Soviet Union and Eastern European medical communities to treat bacterial infections (Cisek et al., Escherichia coli and S. aureus (Li M. et al., Nanotechnology refers to the preparation, research and industrialization of substances at the nanoscale, as well as comprehensive technical systems for cross-research and industrialization using nanoscale materials (Wu et al., Staphylococcus aureus is a bacterium that is ubiquitous in the environment and is common in the human body on the surface of the skin and in the upper respiratory tract mucosa (Lowy, S. aureus, and most people do not show clinical symptoms; however S. aureus is still an important pathogen of humans (Humphreys, S. aureus can cause infections in hospitals and communities, and has become the leading pathogen in hospitals worldwide (Edwards and Massey, S. aureus infection (Gardete and Tomasz, sa Lowy, . ApproxiYW designed the concept. YG and GS drafted the manuscript. MS collected and analyzed the literature. JW edited the manuscript and revised the language.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.


Megalagus turgidus, from the Orella Member of the Brule Formation, early Oligocene, Nebraska, USA. The specimen represents one of the oldest nearly complete lagomorph skulls known. Primitive aspects of the endocranial morphology in Megalagus include large olfactory bulbs, exposure of the midbrain, a small neocortex and a relatively low encephalization quotient. Overall, this suggests a brain morphology closer to that of other basal members of Euarchontoglires (e.g. plesiadapiforms and ischyromyid rodents) than to that of living lagomorphs. However, the well-developed petrosal lobules in Megalagus, comparable to the condition in modern lagomorphs, suggest early specialization in that order for the stabilization of eye movements necessary for accurate visual tracking. Our study sheds new light on the reconstructed morphology of the ancestral brain in Euarchontoglires and fills a critical gap in the understanding of palaeoneuroanatomy of this major group of placental mammals.Early lagomorphs are central to our understanding of how the brain evolved in Glires  from basal members of Euarchontoglires . Here, we report the first virtual endocast of the fossil lagomorph  Previouadiation ,20 of foTribosphenomys and other Alagomyidae; see ::Tribosphdae; see ,23). For2.Megalagus turgidus was extracted  from high-resolution X-ray CT data of an almost complete (only the zygomatic arches are missing), undistorted skull Megalagus turgidus . The hypophyseal fossa is not clearly demarcated, with the relevant region actually being concave rather than convex on the endocast .The brainstem is well preserved , thus the more posterior vascular foramina and casts of some cranial nerves can be reconstructed. The casts of the passageways for cranial nerves VII  and VIII (vestibulocochlear) are visible on both sides, located rostral to the petrosal lobules . Similar3.Megalagus can be interpreted to exhibit an array of primitive and derived characters, the latter mostly in a nascent form, representing features developed further in crown lagomorphs. The primitive characters displayed by Megalagus include large olfactory bulbs that are separated from the cerebrum by a wide circular fissure, partly exposed midbrain, and generally much less expanded cerebral hemispheres, in comparison with recent lagomorphs and archaeolagines , the endocast morphology of gure S3, ).Megalagus  shows a greater similarity to leporids (and to exclusively fossil archaeolagines) than to ochotonids. As in leporids, the cerebral hemispheres are round rather than triangular in outline, which contrasts with the shape of the hemispheres in extant ochotonids , reflecting the arched profile of the cranium, also characteristic of leporids  cerebrum, which resembles more closely that of Ochotona .Compared to extant lagomorphs, the endocast of hotonids . Additiorch (see ). The loMegalagus are larger in terms of their volume relative to the endocranial volume and their width relative to the cerebrum maximal width than those of all extant lagomorphs for which data are currently available . In terms of the length of the olfactory bulbs relative to the endocast length  and it is close to the archaeolagine Hypolagus brachygnathus and fossil ochotonid Prolagus meyeri, for which the relative length of the olfactory bulbs is ca. 20% ; tagus (c) –39, but agus (c) ,32.Megalagus  and Microsyops displaying proportionally the longest cerebrum (54.0%). This primitive brain architecture shared by Megalagus with Ischyromyidae and Plesiadapiformes is in contrast with more derived modern lineages of Glires Cedromus)oryctes) . WhetherMegalagus, the anterior extremities of its olfactory bulbs reach the area over M1; thus, they are more posteriorly located in the cranium compared to modern lagomorphs  and rodents (up to the diastema) [Megalagus is similar to the middle-to-late Eocene ischyromyids (Rapamys and Ischyromys) [Ignacius [Cedromus) [et al. [In iastema) . With rehyromys) ,36, and Ignacius , and so edromus) . Silcox  [et al.  suggesteAsioryctes, Barunlestes, Kennalestes and Zalambdalestes [Megalagus is likely to be an archaic (plesiomorphic) feature, comprising part of the morphotype of early Euarchontoglires.In all Palaeogene taxa studied herein the midbrain is exposed, although to varying degrees. The relatively well-exposed midbrain, which is partially visible between the posteriorly diverging and relatively long cerebral hemispheres, was characteristic of stem placentals, such as dalestes ,45. As sPlesiadapis to the early Oligocene Megalagus suggest that this general architecture remained relatively stable, especially in Lagomorpha. In that context, the endocast structure of Me. turgidus fills the gap in our knowledge of the primitive brain morphology for Lagomorpha, arguably the most basal branch of Glires, and as such it gives us an insight into the ancestral brain architecture of Euarchontoglires.In summary, the stem groups of Euarchontoglires share features that include relatively large olfactory bulbs, an at least partially exposed midbrain, the cerebellum with relatively large petrosal lobes, low EQ and a small neocortex. The similarities in taxa that range from the late early Palaeocene


Worldwide, the burden of musculoskeletal disorders is increasing with great variations between-countries, which makes it difficult for policymakers to provide resources and adequate interventions in order to provide for their appropriate management . Thus, mIndeed, nutrients and biological biomarkers play a key role in the prognosis, diagnosis and health status of patients suffering from musculoskeletal conditions, being the main indicators for understanding biological processes as well as tailoring therapeutic interventions and nutritional programs in patients with musculoskeletal disorders .Thus, the purpose of this Special Issue was to provide an update on the state of the art, through current reviews as well as new insights and interventions, about the main role of nutrients and biomarkers in patients who suffer from musculoskeletal conditions from a multidisciplinary point of view. According to the aim of this Special Issue, a total of six papers summarized in Among these publications, three papers were reviews providing an update of various topics including the current metabolic impact of COVID-19 pandemic confinement secondary to diet modifications and the reduction of physical activity ; the infIn addition, three papers were original research studies supporting key information from a multidisciplinary approach about the effects of curcumin and resveratrol on satellite cells as well as biomarkers for muscle regeneration process ; the fatThe main characteristics of the reviews provided in this Special Issue are presented in Firstly, Martínez-Ferran et al.  provided12, C and K, calcium, folic acid, magnesium, phosphorus, zinc, sodium, selenium and copper were implicated in bone mass formation. These patients seemed to commonly consume inadequate amounts of these vitamins and minerals, impairing absorption and disturbing nutritional status with an increase in the risk of osteoporosis. Therefore, the authors also encouraged researchers to develop nutritional guidelines for patients suffering from inflammatory bowel diseases to prevent osteoporosis.Secondly, Ratajczak et al.  reviewedLastly, the review carried out by Li et al.  highlighThe principal characteristics of the original research reports published in this Special Issue are presented in First, Mañas-García et al.  carried Second, Gimenez-Donoso et al.  performeFinally, Parsanathan et al.  performer = 0.73) with the vascular area at histological level, linked to the cellular profile and pro-inflammatory cytokines, which provided considerable validity for using these measurements as objective assessments of synovial inflammation in clinical practice [r = 0.81) that allowed a non-invasive assessment of muscle glycogen [Future studies should address the role of ultrasound imaging as a promising tool for nutrient and biomarker status in musculoskeletal disorders . The anapractice . In addipractice . Finallyglycogen ,15.In conclusion, the main findings of this Special Issue summarize the current scientific evidence available about nutrients and biomarkers in musculoskeletal diseases related to the metabolic impairment secondary to COVID-19 confinement, the prevention of osteoporosis for patients suffering from inflammatory bowel diseases, and nutritional issues in patients who suffer from spinal muscular atrophy, as well as new insights from experimental animal models on pharmacological agents to enhance muscle tissue regeneration, spontaneous acetylcholine release in the neuromuscular junction of mice by hypercaloric diet supplementation increasing spontaneous neurotransmission and the consequent activation of myofascial trigger points to originate myofascial pain syndrome, and the improvement of myogenic biomarkers of musculoskeletal conditions and gene expression due to vitamin D and L-cysteine cosupplementation. Future studies should investigate the role of ultrasound imaging as a promising tool for nutrient and biomarker status in musculoskeletal disorders.