This review aims to explore the role and value of serology testing in the context of COVID-19 immunization policies in Latin American countries and the barriers and challenges to the adequate use and uptake of this tool. It builds on a review of the academic literature, evidence, and existing policies, and includes a multistage process of discussion and feedback by a group of five experts. Regional and country-level evidence and resources from five focus countries—Argentina, Brazil, Chile, Colombia, and Mexico—were collected and analyzed. This review contains an overview of (1) the impact of the SARS-CoV-2 pandemic, the variants of concern and current testing strategies, (2) the introduction of COVID-19 vaccination, (3) the potential use of serology testing to support immunization initiatives, (4) the current frameworks for the use of serology testing in the region, and (5) the barriers and challenges to implementing serology testing in the context of COVID-19 immunization policies, including a discussion on the potential actions required to address these barriers and facilitate the uptake of this strategy in the region. Stakeholders can use elements of this document to guide timely decision-making, raise awareness, and inspire further studies. Methodologically, this paper builds on a review of literature and policies and a multistage process of discussion, validation, and feedback with a group of five experts from Latin America (LATAM). These experts were selected based on academic merit in various areas of knowledge such as microbiology, epidemiology, public health, pharmacology, and infectiology. An in-depth understanding of serology testing, immunization policies, and the current COVID-19 pandemic was deemed essential. Experience in seroprevalence, seroepidemiology, and post-marketing vaccine effectiveness studies was considered an asset.This review was inspired by a similar project conducted in Europe , adoptinEvidence on the epidemiological impact was retrieved from well-known monitoring databases, paying particular attention to the countries of interest. Evidence on the socioeconomic impact of the pandemic and the policy frameworks and recommendations for the use of serology testing were extracted from reports of leading international organizations, such as the Organization for Economic Co-Operation and Development, Inter-American Development Bank, International Monetary Fund, Americas Society, Economic Commission for Latin America and the Caribbean, World Health Organization (WHO), Pan-American Health Organization (PAHO), United States Food and Drug Administration (FDA), and Centers for Disease Control and Prevention (CDC). Evidence on the characteristics of serology tests and the use of serology testing in various immunization programs were retrieved from academic publications in peer-reviewed journals (where possible). The national COVID-19 vaccination policies and policies for the use of serology testing of focus countries were retrieved from the official government portals. Finally, the barriers and challenges were identified using all the reviewed sources.Scientific perspectives on SARS-CoV-2 testing strategies, including challenges and opportunities;The health and socioeconomic impact of the pandemic in the region;The current position, guidelines, and recommendations on the use of serology testing from key international organizations and focus countries;Progress on COVID-19 immunization roll-out and coverage in countries of focus; andThe national COVID-19 immunization plans and/or strategies of the focus countries.Regional and country-level evidence, policies, and guidelines from five focus countries—Argentina, Brazil, Chile, Colombia, and Mexico—were collected and analyzed. Resources were prioritized using the following inclusion criteria:The information gathered was synthetized and organized, creating a working document. This document served as the basis for the discussion, validation, and feedback provided by all experts during three online panel sessions and rounds of offline review. The working document was edited until the experts reached a consensus.On 31 December 2019, the Chinese authorities reported a novel coronavirus causing a cluster of pneumonia-like cases in Wuhan in Hubei Province of China. The virus was later named SARS-CoV-2, and the disease caused by this new virus was named COVID-19 [As of 28 October 2021, WHO has reported 244,897,177 confirmed cases of COVID-19, leading to 4,970,429 deaths worldwide . Within Based on cumulative deaths as of 28 October 2021, the worst affected countries in the region are Brazil 606,679), Mexico , Peru , and Colombia  [06,679, MNevertheless, it is important to emphasize that as challenges related to the detection and reporting of cases and deaths across the region arise, many have expressed concerns regarding the accuracy of these numbers to reflect the real impact of the pandemic, which considerably limits efforts to compare impact across countries. These challenges include differences in how cases are defined and considerable delays in reporting cases and deaths.Besides the direct human impact of COVID-19, the pandemic has also severely affected health systems and population health. LATAM countries have experienced severe shortages of essential medicines and equipment to treat COVID-19, personal protective equipment, and health care personnel throughout the pandemic ,12. MoreThe pandemic has also created socio-political externalities. In many cases, pre-existing social unrest has challenged governments’ capacity to respond to the pandemic comprehensively ,22. ConcMeasures to combat the pandemic have affected the most vulnerable sectors of society to a larger extent. Reports estimate that approximately 40% of formal workers and 65% of informal workers have no social safety net, including health care coverage ,24. In mGender inequalities have also soared during the pandemic. Women, representing 70% of health workers in the region, have been disproportionally exposed to the virus . This haDuring the first year of the pandemic, most countries in the region responded with severe containment measures, such as declaring states of emergency and instituting national quarantines between March and October 2020. Evidence suggests that federal states, such as Mexico and Brazil, experienced a delay in implementing such restrictions due in part to the decentralized nature of their governments. Similarly, a closer look at non-pharmaceutical interventions enforced in the countries of focus reveals that, compared to centralized states, federal states enforced fewer restrictions through the central government. In these scenarios, most policies were eventually adopted and adapted by subnational governments .Nevertheless, various non-pharmaceutical interventions, varying substantially in nature and stringency, have been implemented across countries. These interventions include containment and closure policies to reduce the spread of the virus, health system policies to reinforce capacity to manage the pandemic, immunization policies, and economic policies to support vulnerable households and affected sectors of the economy .While all LATAM countries applied containment and closure measures to reduce the spread of the virus, few governments implemented economic policies to protect individuals and businesses and furthermore support adherence to these restrictions. Countries such as Mexico and Paraguay are currently enforcing looser restrictions than Argentina, Chile, Colombia, and Peru . HoweverImplementing non-pharmaceutical interventions that limit mobility and the regular functioning of businesses has sparked fear of an economic crisis. Decisions regarding how to reduce the effects of the pandemic on mortality without compromising the economy any further will continue to be challenging. To date, evidence has shown that measures have negatively affected the supply and demand chain of products and services across economic sectors ,35,36, pReducing the impact of the pandemic on the economy and people’s health and wellbeing requires effective policies that can help accelerate the return to normalcy. Vaccination has long been perceived as one of the main strategies to respond to the pandemic, triggering a massive effort to develop COVID-19 vaccines in record time. Governments of LATAM introduced COVID-19 vaccines in December 2020. With limited availability of resources and vaccine doses in many LATAM countries, tools that can help vaccination campaigns be carried out in the most effective and efficient way possible are extremely valuable. SARS-CoV-2 serology testing can provide important information to support decision-making regarding the containment and mitigation of COVID-19. According to information from other vaccine preventable diseases, within COVID-19 immunization policies, serology testing might play an important role in ensuring the effective planning, implementation and monitoring of immunization programs, as well as support endeavors to monitor and study the effectiveness of vaccines during immunization roll-out. This review will introduce the key aspects that shape the current pandemic scenario (the impact of virus mutations and the introduction of vaccination) while exploring potential avenues for the use of serology testing, based on current policy frameworks and available evidence.This review has three goals: (1) to provide an overview of the role and value of serology testing as a tool to support COVID-19 immunization policies in LATAM, (2) to identify the barriers and challenges to the use and uptake of this tool in the current pandemic scenario, and (3) to provide an overview of the potential actions required to address these barriers and facilitate the uptake of this strategy in the region. International, national, and local health policy decision-makers involved in planning COVID-19 vaccination programs and strategies, the academic community, medical societies, as well as other stakeholders can use elements of this document to inspire further studies and build the necessary partnerships and alliances for collaborative actions.According to the WHO, as of October 2021, four variants of SARS-CoV-2 are classified as ‘variants of concern’ (VOC)—Alpha, Beta, Gamma, and Delta—first identified in the United Kingdom, South Africa, Brazil, and India, respectively . AccordiThe emergence of virus mutations has been accompanied by concerns regarding their effect on transmissibility, severity of disease, immunity, and effectiveness of diagnostic methods. Evidence suggests an increased transmissibility of all VOC ,45,46,47Evidence on the impact that VOC may have on immunity suggests a potential increased risk of reinfection for all VOC ,60,61,62Regarding the impact on vaccines effectiveness, it is worth noting that the evidence varies greatly depending on the VOC and the type of vaccine being studied. Having said that, evidence from a number of retrospective studies on periods of high incidence of the VOC and studies conducted in outbreak prompt settings indicates that vaccines grant similar protection against infection from Alpha ,73,74 anWHO, PAHO, and the FDA have expressed concern regarding the potential loss of test performance as new variants emerge ,84,85. AThere are currently two primary types of tests for COVID-19: (1) those used to diagnose acute infection through the direct detection of genetic material of the virus or specific viral antigens  and (2) those used to evaluate the antibody response (serology tests). Serology tests can provide essential information and evidence for research and policy-making purposes. Given the scope of this document, we will introduce the main characteristics of serology tests in this section.Serology tests are designed to detect antibodies in the serum within days to weeks following acute infection ,87. The Serology tests vary depending on the choice of antibodies. Serology tests can measure three types of antibodies: immunoglobulin M (IgM), immunoglobulin G (IgG), and immunoglobulin A (IgA). However, the most commonly used are IgM and IgG, which are the two main isotypes of antibodies . The speSerological tests also vary according to the viral antigens measured. Spike proteins (S) and nucleocapsid proteins (N) are the viral antigens used to detect antibodies for SARS-CoV-2. While testing positive for antibodies against either N, S, or receptor binding domains (RBD) can accurately indicate prior infection , recent In most cases, infection with SARS-CoV-2 initiates an adaptive antiviral humoral and cellular immune response, including B and T cell-mediated immunity ,99,100. Notably, the neutralization assay, a lab-based test, is the gold standard for determining potential protective immunity, although a correlation with protection has not been established. This test can help (1) to increase understanding of immunity and potentially evaluate vaccine efficacy, (2) to determine the real number of infections by enhancing the serological diagnosis of asymptomatic infections, and (3) to identify eligible donors for a possibly beneficial convalescent plasma therapy . NeverthAn alternative that has received recent attention is the use of pseudovirus neutralization assays. Pseudovirus neutralization assays are a great alterative for highly pathogenic viruses such as SARS-CoV-2. A pseudovirus neutralization assay is a laboratory method used to study the effect of antibodies or drugs in preventing infection. This method uses a vector (pseudovirus) that has a similar conformational structure of the surface proteins and the ability to enter cells using the same mechanisms and receptors to that of the native virus. Pseudoviruses are, however, much safer to handle, since they cannot replicate, requiring only biosafety level 2 laboratories. Pseudovirus neutralization can be automated and standardized in laboratories across the world, as has been done for the human immunodeficiency virus .This method has the potential for improving SARS-CoV-2 immunization policies, by providing an easy and accessible approach to classical serum neutralization assays, that can also easily be adapted to different SARS-CoV-2 variants and maintain a similar sensitivity and quantitative reliability . SeveralSerological tests can be performed through laboratory-based assays and rapid diagnostic tests (RDT). While laboratory-based assays can generate more accurate results and provide qualitative and quantitative data, they have an increased turnaround time, higher cost, and require laboratory capacity . ContrarThe pandemic has triggered a massive effort to develop COVID-19 vaccines in record time. Today, the general public perceives COVID-19 immunization as the most critical means of reducing the burden of disease, hospitalizations, and deaths, contributing to the return of normalcy and economic recovery. Nonetheless, immunization alone might not be sufficient to put a full stop to the pandemic and reach endemic status. Governments introduced COVID-19 vaccines in LATAM countries starting in December 2020. Unlike other regions of the world, countries in LATAM have proceeded independently regarding the procurement of doses and the principles that organize immunization rollout.Launched in April 2020, COVID-19 Vaccines Global Access (COVAX) is a global platform to support the development, manufacturing, and distribution of COVID-19 vaccines ,111, proEither through COVAX or independent agreements, countries in the region had contracted doses from 11 providers so far: AstraZeneca-Oxford, Janssen-Cilag, Moderna, Pfizer-BioNTech, Sputnik V, CanSino BIO, Sinopharm, Sinovac, Covishield, CureVac, and Novavax ,116. As Given the limited supply of doses worldwide and the logistical challenge to immunize the whole population, countries have proceeded with immunization rollouts prioritizing different population groups. Most countries worldwide, including in LATAM, started vaccinating single groups, such as health care personnel and essential workers, and later proceeded to larger segments of the population based on different vulnerability parameters . The criConcerns regarding the safety of vaccines for service users have also accompanied immunization rollout in LATAM. While PAHO has recognized the need to strengthen national regulatory mechanisms to ensure that the introduced vaccines are safe and effective , the senAccess disparities between and within countries are another source of concern. From a regional perspective, vaccination campaigns in LATAM have stalled due to unequal global access to vaccines and challenges surrounding vaccine production, distribution, and delivery ,125,126,Delayed economic recovery is a particular source of apprehension, as evidence suggests that many LATAM countries will not reach full immunization of the eligible population until 2023 . As of 2Using serology tests and seroepidemiological data to support immunization policies and strategies across vaccine-preventable diseases is well-documented . AccordiIn the context of post-marketing vaccine surveillance, serology tests have been used to (1) determine the duration of immunity after the primary series, (2) evaluate the need for and timing of booster doses, (3) evaluate dosing strategies, and (4) study the efficacy of vaccines across different population groups for vaccines with well-established correlates of protection ,133,134.Finally, stakeholders have also used seroepidemiological data to evaluate the effectiveness of immunization policies. Conducting this type of assessment requires evaluating the impact of immunization campaigns by monitoring population immunity over time. This activity is critical when there are recurrent outbreaks despite high immunization coverage. In the past, serology testing has helped in investigating possible causes of infection resurgence, such as those attributed to changes in vaccination schedule or formulation, and monitor progress towards elimination in due time ,132.Since the evidence gathered on the use of serosurveys and seroepidemiological data is limited to vaccine campaigns that target specific population groups, extrapolating these findings must be done carefully. In the current scenario, governments must administer COVID-19 vaccines to broader  segments of the population; thus, implementing serology testing as a policy within the pandemic should be assessed considering the conditions of each country and the cost–benefits of implementing this strategy in each context. Nonetheless, and as we will see in the next section, serology testing in the current pandemic scenario, could be used by the government to support the monitoring of infection and disease, including the middle- and long-term effects of COVID-19 on patients. Endeavoring to monitor population immunity over time can help researchers to investigate infection outbreaks and evaluate the progress of control measures, such as immunization. This information should be used to inform immunization policies, ensuring that resources are used in the most effective and efficient way. Targeted immunization activities and changes to immunization schedules can help to channel vaccine doses to where they are needed the most.From an international perspective, WHO, PAHO, FDA, and CDC have all provided statements and recommendations on the use of serology testing in the context of the COVID-19 pandemic. WHO has recommended against the use of serology testing for so-called “immunity passports” ,136. TheSerology testing can also contribute to accurately forecasting the spread of COVID-19, providing essential evidence for optimal public policy measures. Different frameworks have been proposed for modeling the spread of COVID-19, including compartmental models, differential equation model, and branching point process models. The compartmental model Susceptible Exposed Infectious Removed (SEIR) is currently the most widely used model to forecast epidemic diseases such as COVID-19, despite the fact that it has been found to be less accurate than the Hawkes model (a branching point process model) . AlthougIn a statement, the WHO’s Director-General, Dr. Tedros Adhanom, recommended conducting seroprevalence studies to help understand the duration of immunity following both natural infection and vaccination and to evaluate the extension of the infection across different population groups . The FDAAt the regional level, the Argentinian Consensus on the Use of Diagnostic Tests for SARS-CoV-2  recommenWhen analyzing the countries of focus, it is worth noting that none have included serology testing in their national immunization plans. However, in Argentina , Brazil Finally, while Argentina  and ColoSeveral international organizations and the academic community have voiced their concerns regarding the challenges and barriers to the use of serology testing in the context of immunization policies and the broader response to the COVID-19 pandemic. These challenges can be categorized into two main groups. The first group includes the intrinsic limitations of serology testing. The second group points to the challenges surrounding the use of serology testing in the context of immunization policies, surveillance and monitoring activities, and epidemiology studies.Some researchers observed considerable variations in the results of SARS-CoV-2 seroprevalence studies. Studies may underestimate the prevalence of SARS-CoV-2 for several reasons. The first and perhaps more apparent reason results from the choice of assay . Not onlCross-reactivity has been a source of concern regarding the use of certain serology tests in prevalence studies . While eFinally, while the use of serologic testing to identify, evaluate and understand the immune response from natural infection is well accepted, many argue that serology tests are not entirely validated to assess the level of protection provided by COVID-19 vaccination ,146. MorUsing serology testing to support immunization policies is primarily limited by gaps in the knowledge and understanding of (1) the immune response triggered by infection and vaccination and (2) the subsequently conferred immunity. How long antibodies against SARS-CoV-2 persist in the body, the titers of protection and the conditions that lead to protection remain unknown. While some studies indicate that IgG antibodies, including IgG against the S and N proteins, persist for at least nine to ten months after infection in most cases , other sDetermining if infection or vaccination confers an antibody response that grants immunity essentially depends on whether correlates of protection are available. A correlate of protection is an immunological measurement (an immune marker) used to predict protection against disease or infection reliably ,172. DetNonetheless, in recent months, significant evidence has been developed on correlates of protection. Although there are documented cases of reinfection ,177, sevWhile evidence of this nature supports the argument that post-immunization antibody levels might be used as the basis for a correlate of protection, the necessary next steps toward achieving consensus on this measurement include: (1) establishing comparable antibody measurements across laboratories, (2) agreeing on a neutralization assay to serve as the gold standard, (3) calculating, where possible, the protective threshold in Phase III studies, (4) convening stakeholders to reach a consensus despite discrepancies between studies, and (5) verifying that the correlate of protection will apply to new variants using appropriately adapted assays .Given the discrepancies in the antibody response across populations, the absence of consensus on clinical markers of correlation, and the lack of knowledge of the impact of emerging variants on immunity, additional studies are required to provide sound correlates of protection. There is a strong need for standardized processes and more extensive longitudinal and multicenter studies that include different population groups. Efforts to address knowledge gaps should emphasize the adequacy of the study design and its standardized implementation to ensure the comparability of data across countries. While the WHO has taken the first steps to standardize the different assays available in the market by suggesting the use of a single measurement unit (BAU/mL), urging different in vitro diagnostic companies to standardize their assays , there iOnce correlates of protection are available, in partnership with research institutes, governments could conduct serosurveys on vaccinated individuals from specific population groups and the general public to determine the duration of immunity and the need and timing of booster doses. In addition, serosurveys could help us to assess the effectiveness of different vaccine formulations as they become available and are being introduced in different epidemiological scenarios, including those with new virus variants. The implementation of serosurveys to evaluate and monitor vaccine effectiveness should be considered as a complementary tool to infection studies and carefully considering the prevalence of infection in the community when interpreting data.Besides the presented knowledge gaps, implementing serosurveys also faces challenges related to time, technology, logistical, and financial constraints . These cFinally, as multiple vaccines, diverse in both manufacturer and type, are currently being introduced to individuals who may or may not have had prior infection, studying and evaluating antibody production and vaccine-induced immunity becomes exceptionally complicated. Research institutes and the academic community must pay particular attention to studies that can help to identify and understand potential differences in the kinetics of the immune response and antibody dynamics against SARS-CoV-2 and vaccination.Evidence and current national and international guidelines and recommendations highlight the potential benefits of using serology testing as a strategy to support COVID-19 immunization policies and the broader policy response to the pandemic. Serology tests have successfully helped to develop evidence and provide critical information for decision-making in the past. While considerable financial and logistical constraints characterize the current scenario, the benefits of using serology testing might outweigh the medium- to long-term costs.Serology tests are a valuable tool to help us understand the antibody response triggered by natural infection and vaccines, as well as to provide the necessary evidence to design better and more effective immunization policies. With a concerning shortage of vaccines in many LATAM countries and the widely accepted notion that immunization is vital for the control of the pandemic and the return to normalcy, information that can contribute to implementing effective immunization strategies is particularly critical to safeguard the economic recovery of countries and prevent soaring inequalities in the region.Nevertheless, the full use of serology tests in this context requires developing the necessary evidence to address critical knowledge gaps. For this purpose, the commitment and collaboration of both private and public stakeholders and the academic and international communities are of utmost importance.


BackgroundOn March 24, 2020, the Government of India declared a nationwide lockdown and a series of measures aimed at limiting the spread of the coronavirus disease 2019 (COVID-19) infection. This led to dynamic changes in patient inflow and management in the emergency department.This study aims to evaluate the impact of the pre-lockdown and lockdown periods on the demography of trauma in a tertiary care teaching hospitaland to compare it with the homologous period of 2019.MethodsThe trauma caseloads between March 25, 2020, and April 14, 2020, and that of the homologous period of 2019 were thoroughly analyzed and compared retrospectively.ResultsThere was an overall decrease in trauma patients. Elderly male patients had an increased incidence of injury during the lockdown period with a significant p-value (0.0009). There was a significant increase in the number of minor orthopedic procedures while there was a significant decrease in the number of major orthopedic procedures. Fractures of the proximal femur were significantly increased during the lockdown period  and fractures of the femur and tibia shaft were significantly decreased during the lockdown period . Fractures of the distal radius were significantly increased during the lockdown period  and fractures of the shaft of humerus, radius, and ulna were significantly decreased during the lockdown period . Injuries following fall, trivial trauma, and animal-induced trauma were significantly increased , whereas injuries following sports and motor vehicle accidents were significantly decreased . The number of patients reaching within the golden hour (<1 hour) was significantly increased . The total number of patients presenting under the influence of alcohol during the lockdown period was significantly decreased . The use of government-sponsored ambulances for transport to the hospital was significantly increased during the lockdown period (p <0.0001).ConclusionStrict administrative measures had a high impact on the number and epidemiology of trauma with remarkable changes. There was a decreased number of trauma cases but the mechanism, type, and management of these cases were significantly altered from the homologous period of the previous year. The novel coronavirus disease 2019 (COVID-19) first reported in China in December 2019 has rapidly spread across the entire world. The first case of COVID-19 was detected in India on January 30, 2020. The World Health Organization (WHO) declared the COVID-19 outbreak as a global pandemic on March 11, 2020. The Government of India invoked the Epidemic Disease Act, 1987, and declared COVID-19 an epidemic of serious concern. On March 24, 2020, the Government of India declared a nationwide lockdownand a series of measures, including stoppage of vehicular movements, aimed at limiting the spread of the COVID-19 infection [The plethora of measures initiated to arrest the spread of the virus included restricting all non-essential travel, prohibiting the sale of alcohol, closure of workplaces for nonessential services, and restricting social gatherings. Consequently, all vehicular movement, schools, construction work, industries, and national highways were shut down.Essential food supplies and medical needs were arranged without much movement outside.Many people have altered their daily routines in response to the novel coronavirus outbreaks, and these changes had brought about atypical trends in injuries related to trauma. There has been a sharp and noticeable decline in the number of acute trauma referrals, admissions, operations, and aerosolizing anesthetic procedures in the emergency department . As a reDespite the restriction on mobility of people and vehicles, sporadic trauma cases continued to arrive at most emergency departments, in small numbers. This study brings a comparative analysis of the effect of this complete lockdown on the pattern of orthopedic workload and trauma with similar, normal periods in previous years. There is little clinical data available in our country about the patterns and volumes of injury that can impact hospital resources and manpower during periods of strict community lockdowns. This being a unique and new situation, hospital administratorscontinueto be baffled regarding the optimum utilization of resources in managing non-COVID trauma patients requiring acute care . Little The aim of this study was to understand the effect of the lockdown and reduced vehicular and industrial activity on the pattern and number of orthopedic trauma cases. The secondary objective was to study epidemiology, patterns of injuries, mechanisms, and causes of the same. The study may help predict the pattern of orthopedic injuries that may arise in the future, in a post-pandemic world where there will be a change in the way we all live.This study was conducted at an 1100-bedded tertiary care multispecialty teaching hospital. This was a retrospective observational study conducted in the department of emergency medicine after obtaining institutional ethics committee approval (IEC number- 102/20). All hemodynamically stable trauma patients, from five years to 80 years, visiting our emergency during the national lockdown-1 period  were included.Pregnant patients and patients with major life-threatening co-morbidities were excluded from our study.Data from records and case sheets of trauma patients during this period and the same period of the previous year  were obtained. Epidemiological data were collected, including age, sex, mode of injury, alcohol status, and time of injury, time delay in presentation to the emergency, mode of transfer . Data regarding the type and location of the fracture and bony and soft tissue procedures performed were also collected and tabulated. Detailed tabulation of data was done and appropriate statistical analysis was performed.Data analysisContinuous data were analyzed as mean standard deviation. Categorical data were reported as numbers and percentages and were analyzed using the Chi-square test or Fishers exact test as appropriate. The value p<0.05 was considered statistically significant.In our series, the total number of patients reporting to the emergency department in the pre-lockdown time frame was 278, with 173 (62.2%) being males and 105 (37.8%) being females. During the lockdown period, the total number of patients presenting was 216, with 121 (56%) being males and 95 (44%) being females. Elderly male patients had an increased incidence of injury during the lockdown period with a significant p-value (0.0009). The rest of the age groups showed no significant difference in presentation  were major cases and 36 (28%) were minor cases. During the lockdown period, the total number of orthopedic procedures performed was 70, with 17 (24%) being major and 53 (76%) being minor.This difference was significant with p-values of <0.0001. There was a significant increase in the number of minor procedures while there was a significant decrease in the number of major procedures  and fractures of the femur and tibia shaft were significantly decreased during the lockdown period . The rest of the lower limb fractures did not show a significant change. Fractures sustained in the upper limb were divided into subgroups of fractures of the clavicle, scapula, and proximal humerus, fractures around the elbow, fractures of the shaft of the humerus, radius and ulna, fractures of the distal radius, and fractures of the wrist and hand. The total number of upper limb fractures presenting pre-lockdown was 73 and during lockdown were 68. Among the subgroups, fractures of the distal radius were significantly increased during the lockdown period  and fractures of the shaft of the humerus, radius, and ulna were significantly decreased during the lockdown period . The rest of the upper limb fractures did not show a significant change. Fractures sustained in the spine and pelvis were divided into subgroups of cervical spine fractures, fractures of the dorsolumbar spine, andfractures of the pelvis and acetabulum. The total number of spine and pelvic fractures presenting pre-lockdown was 21 and 10 during the lockdown. Among the subgroups, cervical spine, dorsolumbar spine, and pelvis and acetabulum fractures did not show a significant change. Pediatric fractures including both upper and lower limbs did not show any significant change during the lockdown period  Table .The mechanism of injury of cases presenting pre- and during lockdown was subdivided into fall, sports injuries, motor vehicle accidents, gunshot injuries, animal-induced, and injuries following trivial trauma. Injuries following fall, trivial trauma, and animal-induced trauma were significantly increased , whereas injuries following sports and motor vehicle accidents were significantly decreased . Injuries following a gunshot wound were nonsignificantly decreased   was significantly increased . The total number of patients presenting under the influence of alcohol during the lockdown period was significantly decreased . The use of government-sponsored ambulances for transport to the hospital was significantly increased during the lockdown period (p <0.0001) Table .The total number of trauma cases presenting during the lockdown period was significantly decreased, similar to findings by Hazra et al. . ElderlyFractures around the hip and fractures of the distal radius, which are fragility fractures encountered in the elderly, were found to be significantly increased . This maFractures of long bones, including the femur, tibia, humerus, radius, and ulna, were significantly decreased. This may be explained by the fact that these injuries usually occur following high-velocity trauma in the form of motor vehicle accidents . Due to Fractures of the axial skeleton, including spine and pelvis injuries, usually occur following high-velocity injuries or following fall from heights. Although road traffic accidents were decreased, injuries following a fall were significantly increased in our series. This led to a nonsignificant difference in the number of these fractures during the lockdown.Injuries following motor vehicle accidents and sports injuries were decreased due to lack of traffic and vehicular movements and complete stoppage of outdoor sports activities. Injuries following falls and trivial trauma were significantly increased. This may be explained by a longer stay at home and exposure to unaccustomed household chores. Animal-induced trauma was also found to be significantly increased. In our society, stray dogs and animals usually feed themselves from food wastes and dustbins. During the lockdown period, there was a complete stoppage of the availability of food wasteon the roads. This may have led to aggressive behavior and unprovoked attacks of these strays, causing trauma. This was in contrast to a study by Morris et al. who reported no change in dog bites and other animal-induced trauma .There was a non-significant decrease in episodes of firearm injury. This was probably due to the implementation of a curfew-like situation and strict vigilance by the administration and police personnel. This was in contrast to reports by Abdallah et al. who reported increased firearm injury during the pandemic lockdown .Due to the involvement of people in new and unfamiliar types of work, there was an increase in soft tissue injuries requiring minor soft tissue operative procedures.Males involved in kitchen work, gardening, use of sharp instruments for repairing minor household appliances, and involvement of factory workers in farming at their hometown are a few examples of unaccustomed work. There was an increase in minor orthopedic procedures due to the same reasons mentioned above. However, there was a significant decrease in major orthopedic and elective orthopedic procedures during the lockdown period. This was probably due to a decrease in overall trauma and fractures requiring surgical interventions. Elective procedures were postponed due to safety protocols as per COVID guidelines, as well as the redistribution of health personnel for the care of COVID patients. These findings were similar to the study by Ribau et al. .The use of government-sponsored ambulances was significantly increased due to the lack of availability of private vehicles, as well as the difficulty in obtaining clearance for road travel across borders. Also, there was excellent availability of ambulances due to administrative vigilance. Maximum patients reached emergency within one hour of trauma. This was possible due to the complete lack of traffic on the roads and the use of government ambulances. Government ambulances also have the advantage of being Global Positioning System (GPS) enabled and drivers are experienced regarding the type of services offered by hospitals .Alcohol intake promotes risk-taking behavior and predisposes to accidents . PatientThe COVID-19 pandemic has had a significant impact on trauma and emergency caseloadsand services. The administrative measures during the lockdown significantly affected the epidemiology and the total number of trauma patients. There was a reduction of accidental, work-related, and sports-related trauma but there was an increase in fragility fractures. The vigilant administrative efforts, however, led to quicker response to the trauma patients and a significant decrease in injuries under the influence of alcohol. These findings will not only serve as a record of this particular pandemic lockdown but, with deeper analysis and more extensive studies, may help in developing injury prevention and prompt emergency management strategies.


Social and behavioural change strategies are crucial to facilitating the adoption of preventive behaviours during the COVID-19 pandemic. For the success of such social and behavioural changes, the community should be aware of the interventions and willing to adhere to health advice. This letter details the strategies employed in Tanzania to accelerate the adoption of preventive behaviour and contain the spread of COVID-19. Dear Editor-in-Chief,Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is transmitted from human to human via droplets, contact, airborne aerosols and fomites . There iTo contain the spread of COVID-19, the World Health Organization (WHO) has recommended a series of preventive behavioural measures, including regular handwashing with water and soap (HWWS) or alcohol-based sanitisers, physical distancing, wearing masks, avoiding crowds and coughing into a bent elbow or tissue , 6. For In Tanzania, the first COVID-19 case was confirmed on 16 March 2020. Social and behavioural strategies were subsequently employed to limit the spread of the disease to other regions. Behavioural change strategies included the following:The government launched health promotion campaigns focusing on education and training to raise awareness of COVID-19 transmission and prevention. These included information on the benefits of preventive behaviours. The health promotion programme aimed to motivate people to adopt new behaviours and was accompanied by the installation of handwashing facilities in all public areas and the distribution of masks and hygienic kits to communities. Posters and banners emphasising the necessity and benefits of preventive measures were placed in all public areas.Digital communication tools were used to encourage preventive behaviours and promote new social norms. Citizens received daily reminders of the importance of HWWS, wearing masks, and physical distancing via short massage services and social media. Mass media were consistently used to provide correct information on the pandemic and to eliminate threat perceptions and panic arising from misinformation.A restriction strategy was implemented to influence the process of behavioural change by establishing social rules on what was and was not acceptable during the pandemic. The government set restrictions on public gatherings. Public events such as funerals were restricted to family members only, while religious activities were conducted with careful observation of preventive measures such as mask-wearing, handwashing, maintaining distances between individuals, and decontamination of surfaces, such as benches and chairs. Although it was undoubtedly difficult to adhere to such unfamiliar regulations at first, people increasingly recognised the value of the strategy when the number of new cases started to decline.An environmental control strategy was employed to accelerate the process of behavioural change. This strategy consisted in controlling environments that could facilitate the transmission of the disease. Events that could foster transmission, such as weddings, sports events, musical events, and political gatherings, were banned, and schools and universities were closed. This strategy helped to further control the spread of COVID-19.A modelling strategy was also employed to promote behavioural change. Government officials, religious leaders and celebrities served as role models of preventive behaviour in health promotion campaigns. For example, government officials were seen wearing masks, washing their hands, and bumping elbows or tapping feet instead of shaking hands. This facilitated the adoption of such behaviours by most citizens.The implementation of behavioural change strategies has contributed to the containment of the spread of COVID-19 in Tanzania. The implemented strategies have motivated people to adopt recommended preventive behaviours, controlled environments to support behavioural change and helped change traditional social norms.In conclusion, the social and behavioural change strategies employed in Tanzania have confirmed the importance of preventive behaviours for containing the transmission of COVID-19. The lessons learned from these strategies are that the mobilisation of financial and human resources, governmental support, community awareness and willingness to change are key to the success of behavioural change interventions.


The coronavirus pandemic (COVID-19) has affected the delivery of healthcare services and posed enormous challenges to medical and dental care across the world. This article sought to explore various challenges implicated in the provision, access, and utilization of oral healthcare services in Sudan and to describe the current situation amid COVID-19. The oral health sector in Sudan has been experiencing multiple challenges in the delivery of dental care, and the current pandemic of COVID-19 has aggravated and multiplied the existing challenges. Conflict, economic meltdown, and political instability have disrupted all medical and dental services in many parts of Sudan. Furthermore, the oral health sector in Sudan suffers a lack of essential instruments, materials, and supplies, a shortage of health workers, and poor infection control practices, which present major threats to dental care in the region. The COVID-19 pandemic has contributed to further scarcity of essential materials and supplies. Moreover, the frequent closure of dental hospitals and clinics either due to civil disobedience or COVID-19 lockdown has limited accessibility and utilization of oral services. There is an urgent need to address challenges identified to ensure adequate provision of oral healthcare in Sudan. The coronavirus pandemic COVID-19) has impacted the delivery of healthcare globally, posing enormous challenges to medical and dental care across the world, and Sudan is not an exception. As of December 20, 2021, the total number of COVID-19 cases in Sudan reached 45,112 with 3,252 confirmed deaths [9 has impAccording to the World Health Organization (WHO), oral health is considered a key indicator for overall health, well-being, and quality of life . FollowiPrompt utilization of oral services is critical for the prevention and treatment of oral diseases. However, due to the COVID-19 pandemic, dental health providers around the globe have been experiencing multiple challenges in providing oral care to their patients. Their special working conditions including proximity to patients, routine exposure to patients' airways, and performance of aerosol-generating procedures put them at increased risk of contracting COVID-19 . TherefoSeveral articles have explored the status of oral care during the COVID-19 pandemic in different parts around the world, however, the situation in Sudan remains unclear. In this commentary, we aimed to highlight various challenges implicated in the provision, access, and utilization of oral healthcare services in Sudan and share the country's experience with COVID-19. This is important to identify existing challenges, summarize lessons learned and inform relevant interventions by policymakers to improve on policy and practices to ensure adequate provision of oral healthcare in Sudan.Overview of the oral health sector in Sudan: dental services in Sudan are provided through public dental hospitals, dental departments in public hospitals, and private dental clinics. They are regulated by the oral health directorates under the state ministries of health in different states of Sudan. However, most of the hospitals and clinics are located in Khartoum State, the capital of Sudan. The Oral Health Directorate (OHD) is one of the Curative Medicine sectors at the Ministry of Health in Khartoum State. It is responsible for all public dental hospitals and clinics in Khartoum state. OHD has 163 public dental hospitals and outpatient clinics spread over the seven districts of Khartoum state [um state .Challenges to the provision of oral healthcare in Sudan: oral health sector in Sudan has been experiencing multiple challenges in the delivery of dental care summarized in Conflict, economic and political instability: the decades of war and civilian conflicts had affected the sustainable development and healthcare services in Sudan, collapsing healthcare infrastructure and poor health outcomes are some effects of the war [ the war . The cur the war . The lacMaterials and Supplies shortage: Sudan is solely dependent on imported medical and dental supplies. The economic meltdown and decreasing financial indicators hinder the production of dental materials in the country and most dental needs  are being imported from outside Sudan. Additionally, the high inflation rate in the country has led to increased prices and a lack of technical equipment in many dental hospitals and clinics. The COVID-19 restrictions have aggravated the scarcity of dental material and resulted in the disruption of many essential oral services. Furthermore, unpaved roads throughout Sudan and floods impede movements and transportation especially through rainy reasons causing difficulties in the delivery of medicines and other essential needs for dental hospitals and clinics at peripheral States of Sudan [of Sudan , 11, theHealth workforce shortage: availability of a qualified and trained health workforce is essential to the effective provision of health services. Yet before the COVID-19 pandemic, there was already a severe shortage of dental practitioners, because of the migration of qualified dental staff and recent graduates seeking overseas training. This is because a trainee in Sudan has to wait for several years after graduation to enrol in the post-graduation internship program. The main reason for this is that the number of dental colleges continues to expand, but the number of teaching hospitals and training centres available for training is not growing proportionally. Furthermore, the lack of dental materials and continuous increase in their prices is among the contributing factors, making the enrolment of graduate dentists in the internship immediately after graduation more challenging. Additionally, the scarcity of opportunities for dental speciality training, and the absence of a Sudanese dental syndicate add to the problem. More importantly, the low salaries for dental practitioners led to severe migration of qualified personnel to Arab-Gulf countries. Currently, the number of registered dentists in Sudan is 8,492 as per the latest records of Sudan Medical Council, with a 1: 33,000 dentist-to-patient ratio [nt ratio . The issnt ratio .Poor infection control practices: dental procedures and instrumentation require specific strategies directed at the prevention of transmission of diseases among oral health care workers and their patients, especially during the pandemic of COVID-19. On April 18, 2020, the emergency committee in Sudan adopted precautionary preventive measures and imposed a national lockdown for 21 days. During this period all the public dental hospitals were only considering the emergency cases and private dental clinics were closed. This had resulted in a lack of accessibility to dental care services. Even after the lockdown was lifted on July 8, 2020, by the High Commission for Health Emergencies; the fear of acquiring nosocomial infection has prevented utilization of dental care by the general population due to their perceived poor infection control in dental hospitals in Sudan [in Sudan .A recent study has reported that adherence to eye protection and the use of personal protective equipment (PPE), except gloves, is below the current recommendations for a dental practice in Sudan . The vasRecommendations: in Sudan, as is the case in most developing countries, financial constraints often lead to compromised quality of care. Therefore, health authorities should invest more in preparing the public hospitals and ensure adequate supply of all the necessary materials and instruments. Additionally, training barriers should be removed, for instance, the number of equipped dental facilities should be increased to accommodate the number of recently graduated dentists. The Medical Specialization Board should allow numerous dentists to be selected for enrolment in the speciality training programs by making use of the public centres, private and university hospitals as training centres.The statistical report of WHO shows that until December 13, 2021, a total of 3,103,997 COVID-19 vaccine doses have been administered. Only 2% of the population were fully vaccinated due to high rates of vaccination hesitancy and other vaccination challenges in the region. It´s crucial to implement urgent measures to increase public acceptance of COVID-19 vaccines and overcome other vaccination challenges. Together with pre-existing precautionary measures, this will help to end this global pandemic and consequently mitigate the reduced access to oral healthcare services due to COVID-19.Adherence to standards and guidelines for safe practice, and prevention of cross-infection in the dental environment, is the responsibility of all parties involved in dental treatment. The use of PPE, proper sterilization and disinfection, and following social distancing guidelines should strictly be imposed to break the chain of infection in one or more links and ensure these guidelines are following the principles of universal precautions. Tele-screening of cases and triaging should be explored as a feasible alternative, as it will help in minimizing the time of patients´ exposure to dental clinic environments, hence decreasing the risk of getting SARS-CoV-2 infection for both patients and dental healthcare workers .Conclusion: the health system in Sudan is not equipped to handle the current circumstances of the COVID-19 pandemic. Dental public hospitals need extra supplies and instruments, moreover, there is an obvious shortage of health workers and basic protective equipment. With no compliance with preventive and infection control measures against COVID-19 infection; dental hospitals and clinics will be places for spreading the virus. Health authorities should work to improve access to health services through optimal coverage and a comprehensive and equitable geographical distribution, as well as improving the quality of health services.


As one of the most frequently occurring injuries, thoracic trauma is a significant public health burden occurring in road traffic crashes, sports accidents, and military events. The biomechanics of the human thorax under impact loading can be investigated by computational finite element (FE) models, which are capable of predicting complex thoracic responses and injury outcomes quantitatively. One of the key challenges for developing a biofidelic FE model involves model evaluation and validation. In this work, the biofidelity of a mid-sized male thorax model has been evaluated and enhanced by a multi-level, hierarchical strategy of validation, focusing on injury characteristics, and model improvement of the thoracic musculoskeletal system. At the component level, the biomechanical responses of several major thoracic load-bearing structures were validated against different relevant experimental cases in the literature, including the thoracic intervertebral joints, costovertebral joints, clavicle, sternum, and costal cartilages. As an example, the thoracic spine was improved by accurate representation of the components, material properties, and ligament failure features at tissue level then validated based on the quasi-static response at the segment level, flexion bending response at the functional spinal unit level, and extension angle of the whole thoracic spine. At ribcage and full thorax levels, the thorax model with validated bony components was evaluated by a series of experimental testing cases. The validation responses were rated above 0.76, as assessed by the CORA evaluation system, indicating the model exhibited overall good biofidelity. At both component and full thorax levels, the model showed good computational stability, and reasonable agreement with the experimental data both qualitatively and quantitatively. It is expected that our validated thorax model can predict thorax behavior with high biofidelity to assess injury risk and investigate injury mechanisms of the thoracic musculoskeletal system in various impact scenarios. The relevant validation cases established in this study shall be directly used for future evaluation of other thorax models, and the validation approach and process presented here may provide an insightful framework toward multi-level validating of human body models. The human thorax is a fairly complex body region with musculoskeletal structures (ribcage) and soft tissue organs in the thoracic cavity. The ribcage consists of 12 thoracic vertebrae (T1–T12), 12 pairs of ribs, costal cartilages, sternum, scapulae, and clavicles. In automobile crashes, thoracic injury is one of the most prevalent injuries, and ranks second only to head injury with reference to the number of fatalities and serious injury outcomes . AccordiTo investigate MVC related human injuries and enhance vehicle safety designs, surrogates of occupants have been used, including post mortem human surrogates (PMHSs), anthropomorphic test devices (ATDs), and volunteers. They each have their strengths and limitations, but their common feature is that they provide a similar response to that of the living human body during a crash and are studied to assess MVC injuries and develop or improve design for automotive safety systems . Over thA considerable number of thorax FE models have been developed to simulate chest behaviors under complex kinematics during various impact loading conditions. The goal of this study was to report on the hierarchical improvement, evaluation, and validation of the GHBMC M50 thorax model, focusing on the biofidelity of the thoracic MSK system at multi-levels. Specifically, this study focuses on improvements and validations to the thoracic spine, clavicle, sternum, costal cartilage, etc. To our knowledge, FE models for thoracic spine (T-spine) are fewer compared to cervical and lumbar spines. Detailed T-spine models with proper verifications and validations (V&V) using experimental studies are relatively rare, especially for impact scenarios. To evaluate the biofidelity of the whole thorax model, body regional level and full thorax or torso level validation tests were conducted across different loading conditions. These tests contained point loading of the eviscerated ribcage, frontal pendulum impacts, shoulder pendulum impact and table-top belt loading tests. The biomechanical response of the thorax was overall deemed biofidelic and the model was found to be in good agreement with the experimental data using both qualitative and quantitative assessments. The validated thorax model, as demonstrated in this study, was able to serve as a valuable tool for safety researchers and automobile designers to predict, prevent, and mitigate thoracic injuries of vehicle occupants. Additionally, this study describes a multi-level, hierarchical evaluation and validation strategy to enhance the biofidelity of other human body models for injury risk prediction and prevention.The GHBMC 50th percentile male (M50) detailed seated occupant (v4.5) FBM was the basis for the improvement, development, and validation in this study. The model was developed for use with the LS-DYNA solver, a commercial non-linear explicit finite element analysis (FEA) program . The anatomical geometry of the body was reconstructed based on the anthropometric data scanned from a 50th percentile male volunteer . The hig∗MAT_Piecewise_Linear_Plasticity) in LS-DYNA, including cortical and trabecular bones of the ribs, sternum, and clavicles. The thoracic vertebrae were represented by rigid bodies, and the costal cartilages were modeled as an elastic material. For each thoracic intervertebral disc, the annulus and nucleus pulposus was modeled as a highly compressible Hill foam , and a graphical overview of the steps of the study can be found in the The T-spine was enhanced and improved by accurate representation of the components, material properties, and ligament failure properties at tissue level. For the intervertebral discs (IVDs), the nucleus pulposus and annulus fibrosus ground substance were modeled using solid elements. For each IVD, four pairs of concentric quadrilateral layers  were created to represent the annulus fibrosus fiber laminae , which wInitial quasi-static evaluations of the model were conducted for adjacent vertebrae and the intervertebral disc between them (motion segment) to ensure a valid tissue-level response , includiThe costovertebral joints were evaluated at component level using the method outlined in The clavicle model was evaluated at the component level using experimental testing results in The sternum fracture was evaluated under a dynamic three-point bending test . The tesThe costal cartilage model was evaluated at the component level using experimental testing data from After validating the MSK structures at the component level, the components were integrated into the thorax model in FBM. The overall mechanical response of the chest, which included the contribution of these MSK soft and hard tissues, could be evaluated against a number of loading cases at ribcage or full thorax level. Here four experimental cases were selected based on their relevance, the availability of data, and the large range of structural levels they represented.The quasi-static point loading of the ribcage was simulated using the experimental testing approach reported in The frontal pendulum impact testing was designed to quantify the thoracic response and injury tolerance along the anteroposterior direction under midsternal blunt impact. The PMHS used in the experiments was placed in a seated upright position, and compressed on the frontal chest by a 23.4 kg cylindrical impactor with an initial impact velocity of 4.3 m/s and a diameter of 152 mm centered with the sternum at the level of the 4th intercostal space. In the simulation, the FBM was seated on a rigid plate and the impactor positioned at the same mid-sternum level as in the PMHS testing . The oveThe lateral impact on the shoulder provided response characteristics and injury tolerance of the shoulder and upper thorax along the lateral direction. Based on the investigation of the force-deflection response of the thorax under dynamic, non-impact, restraint-like loading at a non-injurious level, To quantitatively evaluate the model performance, the outputs between model simulations and the experimental testing were compared by a widely used objective rating tool known as CORelation and Analysis or CORA . The CORThe simulation results of component level validations were presented in the The simulation results of adjacent vertebrae to quasi-static external loads  produced reasonable responses see  comparedFollowing the FSU validation, a validation case involving a hub impact to the spine was simulated and a deformed configuration was shown in The results for all simulated costovertebral joints under each loading direction were summarized and provided in The experiment testing reported reaction forces  against the deflection, and the peak bone surface strain against the forces. To evaluate the clavicle response, the simulation results were compared to the response obtained from three-point bending tests and axial compression tests, including the force versus the deflection and the peak cortical bone strain versus the force. It was noted that the response of the base model was softer when compared to the testing data. After a parametric study of the material properties, the elastic modulus of cortical clavicle bone was updated from 9 to 18 GPa, and the yield strength was increased from 0.08 to 0.16 GPa. The force-deflection response and peak strain-force response obtained from updated cortical bone model were plotted, which were reasonable compared to testing data see .For the three-point bending test of the sternum, the vertical reaction force was measured from the two supporting posts, which were associated with the proximal and distal ends of the sternum. The vertical force response obtained from the base model showed much higher peak force than the experiments. After performing parametric studies of material properties on cortical bone, the cortical sternum bone modulus was reduced from 14 to 4 GPa, and reducing yield strength from 0.09 to 0.035 GPa. The 2% MPS threshold was adopted to represent the strain based failure feature of cortical sternum bone. The vertical reaction force response on each post was plotted and compared with the experimental data see . The peaE = 12.5 MPa for the solid cartilage and E = 55 MPa for the fabric perichondrium shell layer) were compared to the results of the experimental data  from each of the perichondrium-removed tests were normalized by dividing them by the peak forces of the matching perichondrium-intact tests. The simulation results of the model with optimized material parameters  was provided in In In In this study, a hierarchical process was presented to evaluate, validate, and improve the musculoskeletal modeling of a mid-sized male thorax for impact scenarios. At the component level, the modeling enhancement and improvement for major bony structures of the thorax was introduced, including the thoracic intervertebral joints, costovertebral joints, clavicle, sternum and costal cartilages. At ribcage and full thorax levels, the thorax model with validated components was quantitatively evaluated by four types of experimental testing.Most published thoracic spine models for impact analysis were part of thoracic or whole body models with oversimplified model features . For exaThe simulation of the costovertebral joints under quasi-static ventral-dorsal flexion and cranial-caudal flexion predicted fair to good results compared to For clavicle and sternal validation and improvement, the material parameters were determined based on parametric studies of material properties. The adjusted material properties can compensate for missing model details or geometry deficiencies , aiming Once the presented body components were enhanced by adding more biofidelic details or adjusting material properties, and validated by adopted experimental loading cases, these components were integrated into the thorax in the FBM. To check the stability and biomechanical responses of thorax model, validations were conducted under a wide variety of loading scenarios at ribcage or full thorax level.In this study, the validated sternum, costal cartilages, and thoracic spine were integrated into the thorax model. The geometry and material properties of the ribs in the current thorax model were not changed since they were already validated in previous studies . The quaIn summary, to develop a credible thorax FE model, there is a need for a computational approach that can evaluate and validate model response for the sake of achieving high biofidelity. This work presented a hierarchical approach to validate and enhance thorax model biofidelity. Based on relevance and necessity to improve the current GHBMC thorax model, as well as the availability of experimental data, the aforementioned test cases were selected for validation at both component and whole thorax or torso levels. Overall, the model responses showed good or close agreement with the experimental data both qualitatively and quantitatively.Detailed human thorax body models can provide insights to investigate injury mechanisms and tolerances by qualitative assessment and quantitative evaluation of thoracic response at tissue level. However, similar to developing other human body models, there are some limitations of this work which may or may not affect the model biofidelity. First, there were a paucity of available experimental data or missing technical details regarding specific aspects of model verifications or validations. Unfortunately, most experimental data were not developed or presented for the purposes of computational modeling studies . Also, sSecond, there were some model simplifications due to insufficient representation of anatomical details or material properties. For example, all ligaments related to the thoracic intervertebral joints and costovertebral joints were modeled using 1D elements, rather than a faithful representation of the 3D geometry. Also, the regional differences in cortical bone thickness were not considered in this thorax model, except for the ribs.Third, the model presented in the current study was not able to accurately predict local strains of the thoracic skeleton. At the component level validation, the strain-force response of the clavicle was compared between simulation and experimental results, since the data was available. However, reliable experimental data is needed to evaluate the strain distribution elsewhere within the whole ribcage. Even though a model can be validated against global impact responses, the local strains of most parts at tissue level are not able to be validated since cortical strain was relatively insensitive to the model inputs  in a fulFinally, the current model was created based on a single mid-sized subject, which is not a real population-averaged model. The medical images for CAD data of this model were collected from a young (26-year-old) living male volunteer . Age-relThis work presented a comprehensive evaluation and validation procedure to hierarchically improve and enhance the MSK system of a mid-sized male thorax FE model. The material characteristics of relevant thoracic bony structures and ligaments were either improved by parametric study or determined based on available literature. To achieve high biofidelity, new model features were developed and incorporated into the chest components, such as thoracic intervertebral joints and costal cartilage. For the sake of accurately predicting injury risk at both component and whole thorax levels, a multi-level validation process was presented in this study to maximize the capability of FE model-predicted impact responses. The whole ribcage or thorax model was evaluated against a wide range of loads and different modes of loading. Compared with those corresponding experimental data sets, the CORA ratings of the model ranged from 0.76 to 0.99, indicating the model provides good predictions of the overall biomechanical responses of the whole thorax. This validated, highly biofidelic thorax model has been integrated into the newest generation of GHBMC models to represent the state-of-the-art computational human body models for crash injury prediction and prevention. Future studies will focus on tissue-level injury predictions based on reliable experimental data, as well as extending the framework of accurate modeling and multi-level validation procedure for different population groups including age- and gender-based computational models.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.All authors contributed to the conception, design, and interpretation of results presented in this study, and are accountable for all aspects of this work.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.


Electrospinning technology, which was previously known as a scientific interdisciplinary research approach, is now ready to move towards a practice-based interdisciplinary approach in a variety of fields, progressively. Electrospun nanofiber-applied products are made directly from a nonwoven fabric-based membranes prepared from polymeric liquids involving the application of sufficiently high voltages during electrospinning. Today, electrospun nanofiber-based materials are of remarkable interest across multiple fields of applications, such as in electronics, sensors, functional garments, sound proofing, filters, wound dressing and scaffolds. This article presents such a review for summarizing the current progress on the manufacturing scalability of electrospun nanofibers and the commercialization of electrospun nanofiber products by dedicated companies globally. Despite the clear potential and limitless possibilities for electrospun nanofiber applications, the uptake of electrospinning by the industry is still limited due to the challenges in the manufacturing and turning of electrospun nanofibers into physical products. The recent developments in the field of electrospinning, such as the prominent nonwoven technology, personal views and the potential path forward for the growth of commercially applied products based on electrospun nanofibers, are also highlighted. Nanotechnology is a fast-growing interdisciplinary technology that is concerned with the novel changes and drastic improvements in the properties of materials conjugated to their nanosized structures . The proElectrospun nanofibers are derived from electrospinning technology, with exceptional characteristics such as a high surface-to-volume ratio, interconnected ultrafine fibrous structure, high tortuosity, high permeability and lightweight materials. Electrospun nanofibers with diameters as low as 100 nm have continuously attracted broad attention from worldwide researchers, who are ready to move towards a practice-based interdisciplinary approach in a variety of fields ,7,8,9,10Electrospinning is a versatile technique and is evidenced by the accessibility to tailor electrospun fiber production into a rich variety of fiber morphologies. These electrospun nanofibers can be designed into various morphological structures, such as core shell hollow, porous, deposited in the aligned or a random orientation of nanofiber mesh, using a single or blended copolymer, with the incorporation of additive materials, subjectively . The verThe growing interest in electrospinning technology has paved the way to their advanced development by offering the controllable inclusion of the nanoparticles into these nanosized fibers through the blending of the nanoparticles-polymer solution prior to the spinning process. The simplicity, high efficiency, low cost and high reproducibility of nanofibers have categorized electrospinning as the potent fabrication technique of fibrous structured materials in nanometer sized ,23. In lSolution variables: concentration, degree of polymerization, viscosity and surface tension of the polymer.Needle variables: mono-axial, co-axial, tri-axial and needle-free.Collector variables: stationary collector, drum rotary collector and rotational speed.Electrospinning variables: voltage, feed rate, distance, temperature and humidity.Electrospinning has been acknowledged as an ancient nanotechnology rediscovered for modern demands, being intensely practiced in both laboratories and industries around the whole world. In order to be able to manufacture nanofiber-based fabrics from electrospun nanofibers in mass production, the need for proper control over the electrospinning processing is very crucial. Electrospinning involves a very simple and cost-effective method, yet is an intricate process that crucially depends on several main processing and technical parameters ,39,40,41An optimized concentration of polymer solution is needed in order to control the formation of electrospun fibers, to be free from defectiveness such as beaded fibers or sprayed droplets. It is mentioned that as below the optimized spinning solution concentration was prepared, the polymer chain entanglements are insufficient to stabilize the Coulombic repulsion within the ejected jet, leading to the formation of sprayed droplets ,43. WhilAnother important concern in regard to ecological impact is related to the use of organic solvents in electrospinning. The importance of this factor not only denoted the safety during the spinning handling but also the quality of produced nanofibers due to the entrapped of residual solvent. A precise monitoring to minimize residual solvents is vital for clinical medicine studies as compared to other applications. The use of safe, environmentally benign solvents in the electrospinning should be developed, to decrease the large consumption of volatile organic solvents.Besides, the formation of uniform diameter sizes of electrospun nanofibers is driven by the surface tension properties of polymer solution. Zhang (2011) clarified that by using a smaller internal diameter of a needle, the size of the charged droplet at the tip is reduced, consequently increases the surface tension of the charged droplet. As the surface tension is increased, extra energy is required to overcome the force. As a result, the decrease in the acceleration of the jet will give more time for the droplet to be stretched into a smaller size of fibrous form before deposited on the collector . On the While electrospinning technology offers an exciting insight in the fabrication of distinctive nanofiber-based materials, a significant hurdle has remained. Current innovative applications and the spinnable fluid limitation are still restricted significantly owing to the inconsistency and instability of electrospinning to assure reliability in processing nanofibers. These existing hurdles boost a robust urge in improving manufacturing efficiency, in order to deal with the related limitation issues involving macro-scale production, process stability and reproducibility in the manufacturing steps of electrospinning as described ,37. The Based on previous studies, it is largely demonstrated that environmental conditions are an essential stimulus to the outcome of charged dispersed fibers jets. It is reported that a substantial variation in the fiber properties is directly affected by the minor changes in the environment. To resolve the matter, a great improvement of electrospinning systems has been proposed to incorporate the proprietary climate-controlled electrospinning systems with promising temperature and humidity regulators. For instance, IME Technologies provides a laboratory-scale system consisting of an electrospinning compartment and a control cabinet inclusive of the ventilation system, water filtration and regulator with specific temperature and relative humidity accuracy ,59.4 as the foaming agent in expanding 2D electrospun polycaprolactone (PCL) nanofibers. A higher concentration of foaming agent was found to significantly increase the thickness of the scaffold. This post-treated method was able to produce 3D scaffolds and reduce the risk of breaking the interconnected fibers structure ..146].2 exhibited the best nanoparticle uniformity and optimal ethylene photo-degradation activity as compared to the control sample  with the aim of producing a nanofiber-based film to enhance the photocatalytic activity of ethylene degradation and deceleration the ripening of banana has been demonstrated . Their sl sample b,c. Thisarticles ,149,150.Staphylococcus aureus and Escherichia coli. It is reported that the control (unpacked strawberry) had started bruises and decayed on the 4th day. The strawberries packed with PVA/CEO/β-CD nanofibrous film showed no sign of decay even on the 6th day. The use of PVA/CEO/β-CD nanofibrous film has practically prolonged the shelf-life of packed strawberries by preventing water losses and delaying the degradation of the cell wall, thus, holding the firmness of the packed fruits during storage [Apart from nanoparticles, a number of works on the use of antibacterial substances have been studied. Vega-Lugo et al. (2009) fabricated electrospun fibers from soy protein isolate (SPI) in poly (ethylene oxide) (PEO) and poly (lactic acid) (PLA) for the controlled release of a naturally occurring antimicrobial compound, allyl isothiocyanate (AITC). AITC is mostly found in mustard oil, and is effective against cheese-related fungi. Through this work, it is found that the concentration of AITC has significantly affected the fiber morphology, whereas it is reported that the AITC release was negligible under dry conditions but increased drastically as the relative humidity increased. It can be concluded that the AITC release is directly triggered by any change in the relative humidity. Aside from SPI and AITC, the application of cinnamon essential oil (CEO) embedded electrospun nanofibers also has been tested. According to Wen et al. (2016), the PVA nanofibrous packaging film containing CEO exhibited excellent antimicrobial activity against both  storage ,152,153. storage .Electrospinning has the potential for use in various cosmetic applications for example facial masks, perfumes, deodorants and antiperspirants. A common feature of these applications is that they can be used in the form of a membrane which can be easily fabricated by electrospinning. The conceivable of incorporating active ingredients into electrospun nanofibers also makes this spinning process feasible for cosmetic applications. Yet, the application in the cosmetics product from nanofibers textiles material is relatively new. A reported study conducted by Fathi-Azarbayjani et al. (2010) indicated that electrospun fiber materials are influential to replace the conventional materials used in the current cosmetic facial masks. Their work demonstrated an anti-wrinkle nanofiber face mask incorporating collagen, novel vitamin and gold nanoparticles, with a control polymer degradation to discharge the active ingredients once contact with premoistened skin. The study reported that the high surface area to-volume ratio of the nanofiber mask will ensure maximum contact with the skin surface and help to enhance the skin permeation to restore its healthy appearance. The dry nature of face masks increases both the structural stability and their shelf lives when compared to premoistened cotton masks available in the market .Another research study that utilized emulsion electrospinning to fabricate membranes containing volatile fragrance through poly (PVA) fibrous matrix to release encapsulated (R)-(+)-limonene for 15 days under ambient temperatures has been demonstrated . The relTo shift the electrospun nanofibers from their prototyping to finished products is quite challenging. In contempt of the full potent ideas, electrospinning technology is facing several challenges in establishing its own position in the market and also substituting the current commercialized technologies. Researchers have been intent on evolving these materials, fabricating nanofibers from electrospinning over the past decade and transforming them into downstream and upstream products. The commercial usage of the electrospun nanofiber-based products is across various fields such as filtration and biomedical applications. ® in 1981. The nanofibers presence did show a promise in reducing operating costs and improved efficiency as reported by Balamurugan et al. (2011) [TM, the recent technology in the world that enables nanofiber production for performance apparel on an industrial scale [The first technology enabling the production of nanofibers appeared on the global market in the 1980s. Donaldson, one of the leading companies in nanofiber-based applications brought out the nanofibers first time for advanced commercial applications namely as air filtration technology–Ultra-Web. (2011) . Until tal scale . Since tThe rising popularity of an advanced product made of electrospun nanofiber-based materials is the primary factors that drive the growth of this market. Currently, the global nanofibers market is valued at USD 927 million in 2018 and is estimated to hit USD 4.3 billion by 2023 with an expected compound annual growth rate (CAGR) of 36.2% during the forecast period. The global market report done by PR Newswire is further analyzed by the following projected end-use application segments such as in packaging, automotive, electronics and semiconductors, aerospace, coatings and energy in segmented leading countries such as USA, Canada, China, Japan, Europe, North America and Asia regions. A research report by Global Industry Analysts Inc. entitled “Nanofibers: A Global Strategic Business Report” also has provided comprehensive reviews of the nanofibers market trends. As stated by the report, Asia–Pacific is the largest and the fastest growing market worldwide over the analysis period was conducted as a result of the strong public and private investments in nanotechnology. This is attributed to the high demand for nanofibers in performance apparel applications whereby their unique properties of high surface area, small fiber diameter, filtration properties, layer thinness, high permeability, and low basis weight, contribute to an outstanding product functionality . Given bThe review presented here collectively highlighted the development of the scaling-up method in electrospinning technologies, current progress on the manufacturing scalability of electrospun nanofibers materials and the commercialization of electrospun nanofiber-based products. We started with a brief opening related to the history of electrospinning, followed by a detailed literature review of its genesis principle and typical apparatus. The discussion narrowed into their revolution as a potent technology for the production of nanoscale dimension materials with diversified compositions, and their properties and applications were revealed. The potential for the commercialization applications of electrospun nanofiber-based materials opened up a new avenue towards economically extending and enlightening the values of electrospinning products. Through electrospinning nanotechnology, ultra-strong, durable and specific function-oriented nanofiber-based fabrics have been now tested for a number of consumer product applications, such as filtration, defense and protection garments, medical dressings, home furnishings, food packaging and, also, in cosmetics. As mentioned, nanotechnology has overcome the limitations of applying conventional methods to impart certain properties to electrospun nanofiber-based materials. Electrospinning techniques have facilitated the fabrication of nonwoven fibers in nano-sized scale dimensions, which now has become possible for highly effective modern performance products. Thus, there is no doubt that, in the next incoming years, nanotechnology through electrospinning will penetrate every area of the functional textiles industry for more innovative product applications.Yet, there are other concerns about the electrospinning technology that need to be addressed by the manufacturer, as well as the researchers. The issues are the hazardous vapors emitting from electrospinning solutions while forming nanofiber webs that need to be recovered or disposed of in an environmentally friendly manner. This will definitely involve additional equipment and cost. Another issue is the raised concern over possible health hazards to humans due to the inhalation of fibers, which needs to be taken into another, future study. From the authors’ point of view, the functionality of electrospun nanofibers has been greatly improved and proven to have abilities in various fields of application. However, the shelf-life issue of electrospun nanofibers fabrics prior to laundering and restoration is certainly limited, and insufficient work has been reported. The fabric should have both appropriate mechanical properties and the durability to withstand the physical and chemical stresses of laundering. The importance of the lifespan of electrospun nanofibers products should be thoroughly evaluated before actual industrial production begins. Finally, this review article offered the readers with interesting perspectives regarding applied products of electrospun nanofibers. We strongly believe that all the difficulties and constraints faced in the manufacturing, research and development, as well as processing, of electrospun nanofibers will be clearly resolved throughout advanced research exploration in the coming future.


Exosomes are nanoscale membrane vesicles, which carry biologically active substances of their cell of origin and play an important role in signal transduction and intercellular communication. At present, exosomes have been identified as a promising non-invasive liquid biopsy biomarker in the tissues and circulating blood of nasopharyngeal carcinoma (NPC) and found to participate in regulating pathophysiological process of the tumor. We here review recent insights gained into the molecular mechanisms of exosome-induced cell growth, angiogenesis, metastasis, immunosuppression, radiation resistance and chemotherapy resistance in the development and progression of NPC, as well as the clinical application of exosomes as diagnostic biomarkers and therapeutic agents. We also discuss the limitations and challenges in exosome application. We hope this review may provide some references for the use of exosomes in clinical intervention. NPC is a squamous cell carcinoma arising from the epithelial cells of the nasopharyngeal mucosa. Epstein-Barr virus (EBV) infection is one of the essential factors leading to NPC Exosomes are cell vesicles with a diameter of 40-100 nm, secreted by various types of cells outside the cell by fusing with the plasma membrane. The plasma membrane buds inward to form early endosomes, which then mature into late endosomes and multivesicular bodies (MVBs) with intraluminal vesicles. When late MVBs fuse with the plasma membrane, exosomes are released The poor prognosis of NPC is mainly attributed to insufficient consciousness of the prominent symptoms of the disease, the limited detections and therapeutic options Exosomes related to NPC have definite significance for the occurrence and progression of NPC. Exosomes carry cancer-aggravating or oppressing molecules that act on NPC or other stromal cells, which exert influence on different stages of NPC development and progression.in vitro, covering promoting cell growth, protecting cells from apoptosis and enhancing cell motility The onset of NPC is etiologically associated with EBV infection. The establishment of EBV latent infection in pre-invasive nasopharyngeal epithelium is considered to be an early stage of NPC pathogenesis. A mass of viral products are expressed during the latent phase of infection, including EB virus nuclear antigen (EBNA) 1, EB virus-encoded latent membrane proteins (LMP) 1 and 2, EB virus-encoded RNA (EBER), BamH Ⅰ A rightward transcripts (BART), and some incubation period mRNA, with which EBV-related exosomes coexist Figure 1). Quantitative proteomic analysis have demonstrated that the expression of angiogenic proteins, ICAM-1 and CD44v5, is up-regulated in the exosomes of NPC, while the expression of angiostatin TSP-1 is down-regulated Angiogenesis is the process by which new blood vessels form. The formation of tumor blood vessels can enhance tumor growth, invasiveness and metastasis, leading to poor prognosis NPC frequently metastasizes beyond the nasopharynx through additional blood vessels and lymph nodes, which is the most common reason for poor prognosis. EMT is a process by which the epithelial cells are transformed into quasi-mesenchymal cells. During this process, the interaction and interference between the cells and the extracellular matrix are reshaped with increased invasive and metastatic properties, resulting in separation of epithelial cells from each other and the basement membrane. Recent studies have revealed that EMT can enhance the mobility and invasiveness of the cell to gain greater metastatic potential, which prompts tumor metastasis and progression Figure 2).The salient feature of NPC is the infiltration of a large number of non-malignant white blood cells in the primary tumor, mainly consisting of T lymphocytes and a small number of B cells, macrophages and dendritic cells, etc. However, this leukocyte infiltration has been found to disappear in the process of metastasis, replaced by rapidly and massively proliferated malignant cells with obvious anti-tumor immune feature Radiotherapy is the major treatment for NPC, but radiation resistance seems inevitable in this process in some patients. Treatment failure of local radiotherapy accompanied with local recurrence or distant metastasis continues to be a severe challenge for NPC management in vitro, accompanied by decreased sensitivity of the tumor cells to cisplatin, and exosomes can transfer this DDP resistance to untreated cells to induce resistance in vitro through upregulating MDR1 In lung cancer exosomes, abnormal expression of some miRNAs and mRNAs regarding to cisplatin (DDP) sensitivity has been discovered Figure 3), and have been widely used, especially in clinical application for NPC diagnosis and treatment.Some exosomal molecules have multiple functions in the progression of NPC, such as LMP1  in NPC, which achieves excellent lysosomal escape ability, strong stability and high sensitivity, better than the traditional non-biological materials for NPC detection Although the incidence of NPC has declined to a certain extent, its early detection is still a challenge due to its atypical symptoms and hidden location. Many NPC patients are already at an advanced stage at the time of diagnosis, worsening the outcome of the disease. Early diagnosis and interference are very important for NPC prognosis. Given that EBV is an influential issue for NPC, various EBV assays aiming at EBV-DNA and the relative antibody detection have been developed, but their sensitivity and specificity cannot satisfy the needs of the clinic in vitro or in vivo. A research team has worked to incorporate antagomiR targeting BART10-5p and miR-18a (which are intended to promote angiogenesis) into iRGD-tagged exosomes, resulting in preferentially suppressed angiogenesis and growth of NPC Exosomes can provide protection for their contents against proteolytic digestion or drug action, which may be one of the causes for the failure of drug effect on NPC treatment, as exosomal cancer-promoting molecules move from the cancerous cells to the recipient cells. Increasingly, exosomes are being recognized as alternative therapeutics for NPC for their ability to induce potent cellular responses. For instance, targeting exosomal EBV-LMP1 transfer and miR-203 expression have positive significance for EBV-targeted therapy by aspirin in invasive NPC Although researches on NPC exosomes have achieved certain accomplishments, there are also challenges and limitations in the application process.The first lies in the means of detection. Despite the fact that tumor exosomes are attractive biomarkers for tumor diagnosis, their early detection for clinical use is still challenging. Some researchers have established a creative exosome detection method with high sensitivity and specificity, which refers to recombinase polymerase amplification triggered by adjacent ligation and transcription-mediated amplification (PAL-RPA-TMA) The second involves the selective exosomal cargo loading mechanism driving biomolecules sorting into exosomes. Despite the entry of exosomes into recipient cells is non-specific, the exosome uptake mechanism depends on the recipient cells A study comparing the effect of conventional doxorubicin chemotherapy with the replacement therapy of Ag-TiO2-catalyzed reactive oxygen species generation in the treatment of 5-8F NPC cells has pointed out that beyond the classic chemotherapeutic agent, Ag-TiO2 in the photo-catalytic process also exhibits cytostatic activity; tumor cell damage induced by cytostatic treatment enormously changes the number of released exosomes and leads to the predominance of tumor inhibitors in the exosomal miRNA profile There are also limitations in exosome application. Due to the characteristics of stability, permeability, biocompatibility and extremely small size, exosomes can deliver drugs and nucleic acids as carriers With the improvement of diagnostic methods and treatment strategies, the incidence and prognosis of NPC have been improved, however, the mechanism of the tumor's development and progression is unclear, and problems emerge in practical treatment. The exosomes secreted from different types of NPC cells contain a variety of biomolecules, which participate in the circulation of body fluids, and affect the growth, angiogenesis, metastasis, immune response, radiation and chemotherapy sensitivity of NPC. As a promising non-invasive liquid biopsy biomarker, exosomes are highlighted in developing new diagnostic and treatment methods of NPC, but there are challenges in their clinical application. Conclusively, this article reviews the molecular mechanisms of NPC-related exosome-induced tumor progression in NPC and the potential clinical application of exosomes, which we hope may provide some references for the use of exosomes in clinical intervention.