Signal recognition particle (SRP) is an RNA and protein complex that exists in all domains of life. It consists of one protein and one noncoding RNA in some bacteria. It is more complex in eukaryotes and consists of six proteins and one noncoding RNA in mammals. In the eukaryotic cytoplasm, SRP co-translationally targets proteins to the endoplasmic reticulum and prevents misfolding and aggregation of the secretory proteins in the cytoplasm. It was demonstrated recently that SRP also possesses an earlier unknown function, the protection of mRNAs of secretory proteins from degradation. In this review, we analyze the progress in studies of SRPs from different organisms, SRP biogenesis, its structure, and function in protein targeting and mRNA protection. The large binding pocket of SRP is lined by methionines, which allow for a variety of sizes and shapes to fit into the pocket .In bacteria, prokaryotic SRP (Ffh/4.5S RNA complex) does not target secretory proteins and targets mostly inner membrane proteins with multiple transmembrane domains (TMDs). Unlike eukaryotes, bacterial secretory proteins are targeted by SecA . BacteriEukaryotic SRP requires the N-terminal signal sequence for proper targeting of secreted proteins but also identifies TMDs regardless of location . SRP genThe signal recognition particle is found ubiquitously across all three domains of life, although there is considerable variability in its structure, subunit number, and composition. The majority of SRPs consist of protein and RNA subunits. However, exceptions without RNA components are also known. The simplest version of an SRP consists of only one protein and one RNA in some bacteria. The increasing complexity of SRP characterizes the evolution of SRP from a single, evolutionarily conserved SRP54 on a short RNA to the mammalian six-subunit complex arranged on the longer and more structured RNA.Escherichia coli consists of 4.5S RNA and just the single protein subunit, Ffh, a homolog of the eukaryotic SRP54 [E. coli, PilA in Neisseria gonorrhoeae) [Bacillus subtilis has a slightly different composition, containing longer RNA (6S RNA) and the HBSu protein, an Alu domain homolog, in addition to Ffh [Archaeoglobus fulgidus  ,52,53. Tn to Ffh . The arcfulgidus A containArabidopsis thaliana, contains a chloroplast-specific SRP (cpSRP) that does not contain an RNA backbone, has chloroplast-specific SRP54 (cpSRP54), and an additional subunit cpSRP43, which may serve the same function as the noncoding RNA  to the SRP receptor. Each species has its specific SRP receptor on the cytosolic side of the ER membrane in eukaryotes or FtsY on the cytosolic side of the plasma membrane in bacteria D. The euPlasmodium falciparum SRP54, which has approximately 48% identity with mammalian SRP [Mammalian SRP is a multi-subunit structure with complex organization. However, there are very limited studies devoted to the assembly of the framework of SRP. A potential model for the process is shown in lian SRP .After reaching the nucleus, the subunits bind to 7SL RNA in the following order: SRP19, SRP68/72, and SRP9/14, as shown in vitro ,107,108.Mammalian SRP68 and 72 cohere on the opposite side of 7SL at helices five, six, and eight B. It appNeither SRP9 nor SRP14 in mammals can bind 7SL RNA by itself; they heterodimerize before binding the RNA . The AluOnce the pre-SRP complex is exported out of the nucleus, it then associates with SRP54, the final component of the SRP. The survival motor neuron complex (SMN) is a cell factor required for SRP54 association with 7SL RNA in mammals . No otheTo conduct its function, SRP is involved in a series of events called the SRP cycle. The cycle can be divided into four major steps: (1) engaging with the ribosome and recognition of the signal sequence, (2) targeting to ER, (3) engagement with the translocon, and (4) GTP hydrolysis and SRP recycling . There aAfter recognition of the signal sequence by SRP54, SRP engages with the ribosome and temporally stalls elongation of the nascent polypeptide chain Step 1, . During Targeting the SRP receptor on the ER membrane is the next step in the SRP cycle Step 2, . SRP54 aOnce SRP has delivered its ribosomal cargo to the translocon, it enters a post-handover state Step 4, . There aH. sapiens by [The structure of the whole mammalian SRP complex associated with the ribosome was solved by cryo-EM ,129. Sevpiens by ,108,128.piens by ,142,143.piens by ,144. Usipiens by , we conspiens by , 1RY1 [1piens by , and theEukaryotic SRP is 230–240 Å in length as measured by scanning transmission electron microscopy and is not much smaller than the eukaryotic ribosome at 250–300 Å ,148. SinStructurally, SRP9 acts as a clamp on the 5′ and 3′ ends of 7SL RNA , shown iA central region of SRP9 and three regions of SRP14  are required for heterodimerization . SRP14, Less is known about the second heterodimer pair SRP68/SRP72, located in the linker/S domain region of SRP, as shown in SRP54 binds 7SL at the end of the S domain, shown in The G domain of SRP54 has five GTPase conserved elements—G1 through G5, as shown in The subunit SRP19, and the long, noncoding RNA backbone, 7SL RNA, indirectly assist the SRP cycle. Their function is related to the biogenesis of SRP, as described previously and as illustrated in Besides SRP’s role in co-translational targeting, there is accumulating evidence that SRP protects the mRNA transcripts of SRP-dependent proteins from degradation ,166,167.RAPP is functionally distinct from other protein quality control pathways, including endoplasmic reticulum-associated protein degradation (ERAD) and the unfolded protein response (UPR), reviewed in ,169. In SRP has evolved from a single protein subunit complex mediating the co-translational pathway in early forms of archaebacteria and eubacteria to a complex, six-subunit protein with a long, noncoding RNA backbone. SRP has multiple functions in prokaryotes and eukaryotes: from targeting polytopic membrane proteins only in prokaryotes to the targeting of membrane and secretory proteins in eukaryotes, and the recently discovered function of mRNA protection in eukaryotic SRP.mRNA protection is still relatively undefined in SRP; RAPP involves the lack of recognition by SRP54 and degradation of mRNA and the involvement of AGO2. However, each protein’s complete role in RAPP is still elusive. Structures of most of the SRP subunits have been resolved; however, SRP68 and SRP72 still have un-crystallized regions and have a poorly defined role in the SRP cycle. Overall, despite being discovered in 1980, SRP still has quite a few mysteries left to be resolved and has surpassed its originally defined function in co-translational targeting.


STAC3 gene has long been considered native American myopathy (NAM). In 2017, the first case of a non-Amerindian patient with this myopathy was described. Here, we report the first Russian patient with NAM. The patient is a 17-year-old female with compound-heterozygous single nucleotide variants in the STAC3 gene: c.862A>T, p.(Lys288Ter) and c.93del, p.(Lys32ArgfsTer78). She has a milder phenotype than the earlier described patients. To our knowledge, this is the first case of a patient who had both nonsense and frameshift variants. It is assumed that the frameshift variant with premature stop codon lead to nonsense-mediated RNA decay. However, there are two additional coding isoforms of the STAC3 gene, which are not affected by this frameshift variant. We can speculate that these isoforms may partially carry out the function, and possibly explain the milder phenotype of our patient.Congenital myopathy associated with pathogenic variants in the  STAC3 is associated with Native American myopathy (NAM), in which until 2017, is described only in patients from the Lumber River of North Carolina [Congenital myopathies (CM) are a clinically and genetically heterogenic group of muscle disorders, united by the early onset of muscle hypotonia and muscle weakness at birth or infancy. The group of CM constantly expands due to the revealing of new associations with new genes. A relatively new gene Carolina ,5.STAC3 gene [The first description of NAM was attributed to Bailey and Bloch, who in 1987 described this myopathy in a 3-month-old Indian baby with malignant hyperthermia . MalignaAC3 gene . In addiAC3 gene .STAC3 gene (ENST00000332782.7): c.862A>T, p.(Lys288Ter) and c.93del, p.(Lys32ArgfsTer78). Our patient demonstrated early developed muscle weakness, some facial features, and severe scoliosis, but a lack of peculiar features, such as short stature, palate anomalies, multiple joint contractures, and feeding difficulties in infancy, exhibiting a milder phenotype than in the earlier reported cases.Here, we present a non-Amerindian patient of Russian ancestry, with compound heterozygous single nucleotide variants (SNVs) in the The proband is a 17-year-old female with the chief complaint of proximal muscle weakness from early childhood. She is the second child of healthy nonconsanguineous Russian parents. The pregnancy and delivery were unremarkable. Her birth weight was 3.80 kg and length was 52 cm. On the third day of life, the girl was hospitalized with pneumonia due to aspiration. She required mechanical ventilation until the age of 4.5 months, and it was the only episode of respiratory disfunction in her life. The proband had motor development delay, she held her head from 7 months of age, sat from 16 months of age, walked from 21 months of age, and she always required support to stand up. In early childhood, it was noted that her mouth was slightly open in a vertical position. Phrasal speech developed by age. There was no history of any seizures. Vision and hearing were preserved. From the age of 9–10 years, the development of prominent scoliotic deformity of the spine was noted. A conservative treatment of scoliosis was carried out at the age of 12–14 years. At the age of 12, she underwent surgery for ankle tendon retraction without general anesthesia. In the last few years, the course of her disease has become slowly worse. In addition, she had additional marked gait disturbances and difficulties climbing the stairs, and she could not rise from the floor by herself. Her cognitive functions were normal, and currently she is studying at university.At the examination, her height was 167 cm and body weight was 62 kg. Among the phenotypic features, the proband has only micrognathia, with downturned corners of the mouth and clinodactyly of the fifth finger of the right hand .A neurological exam showed the atrophy of the pectoral muscles, proximal muscles, weakness of facial, neck, and limb-girdle muscles, positive Gowers’ sign, and asymmetric Trendelenburg’s gait. The patient showed kyphoscoliosis of the thoracic spine and lumbar hyperlordosis that led to a prominent asymmetric hip position . MoreoveCreatine kinase values were normal. A needle electromyography detected a myopathic pattern and a spontaneous activity was absent.SELENON, LMNA, TPM3, ACTA1, PLOD1, MYPN, ITGA7, STAC3, CNTN1, MYF6, CFL2, KBTBD13, TRIP4, CHST14, CCDC78, MYH2, FKRP, TNNT1, RYR1, DNM2, COL6A3, KLHL41, BIN1, ZAK, SPEG, COL5A2, COL6A1, COL6A2, CHKB, ITGA9, KLHL40, LMOD3, MTMR14, MEGF10, LAMA2, COL12A1, DSE, FKBP14, AEBP1, TPM2, FKTN, COL5A1, MTM1, and VMA21. The coverage of target variants for DNA was at least ×200. The detected variants were analyzed using an hg19 genome assembly, HGMD Professional Database v2020.2, and ACMG criteria for variant interpretation [STAC3 gene (ENST00000332782.7). The validation and segregation analyses of detected SNVs showed that each of the parents is a carrier of only one, which verifies the compound heterozygosity of SNVs in the proband. The healthy brother is a carrier of the heterozygous variant c.862A>T, p.(Lys288Ter).For diagnostic purposes, we performed a next-generation sequencing of the genes panel on DNA, which is extracted from the proband’s blood lymphocytes. The sample was analyzed by mass parallel sequencing using a new-generation Ion S5™ sequencer . The libraries for sequencing were prepared with ultramultiplex PCR (AmpliSeq™). The target panel based on Ion Ampliseq technology included the following genes: Herein, we reported a patient of Russian ancestry diagnosed with a rare form of congenital myopathy. Notably, our patient does not have a severe clinical picture and lacks some characteristic phenotypic features, as previously described in the literature .Patients with NAM present quite specific extra-muscular manifestations along with the common signs of congenital myopathy, such as the long myopathic face, palate and dental anomalies, short stature, and talipes equinovarus at birth . Apart fAn additional prominent manifestation of NAM is severe early-onset of progressive scoliosis, which often requires surgical correction ,5. Our pSTAC3 gene were revealed. One of the SNVs c.862A>T, p.(Lys288Ter) was previously reported in a patient of Turkish ancestry [Our patient was initially suspected of having some form of congenital myopathy due to the absence of a certain specific phenotype of NAM. Therefore, she was referred to the sequencing of genes associated with congenital myopathies. Two compound heterozygous SNVs in the ancestry . Anotherancestry .STAC3 gene encodes SH3 and cysteine-rich domain 3, a component of excitation-contraction coupling (ECC) in skeletal muscle [The l muscle . It is el muscle . Nelson l muscle .It is shown that STAC3 directly interacts with Cav1.1. In addition, the amino acid substitution of the STAC3 protein Trp284Ser, Phe295Leu, and Lys329Asn affects the ECC by violating the interaction with the II–III loop of Cav1.1 . All of It seems interesting that the phenotype of our proband is similar to the phenotype of the patient of Turkish ancestry with the same nonsense variant and splice donor site variant c.432+4A>T [STAC3 gene has seven isoforms, which are all expressed in muscle tissue at different levels, according to the GTEx data, and four are coding proteins (To our knowledge, we reported the first case of a patient who has both nonsense and frameshift SNVs. It is assumed that the frameshift variant and premature stop codon that lead to the nonsense-mediated RNA decay was followed by an absence of the protein product, which is supposed to result in a more severe clinical picture. However, our patient has a milder phenotype compared to the reported patients with frequent homozygous loss-of-function missense variant Trp284Ser. To the best of our knowledge, the proteins . The mosproteins . The freSimilar to the other non-Amerindian NAM cases previously described, our report shows that NAM should be considered in patients with congenital myopathy of any ancestry. Even though it is possible to mark the peculiar features of this myopathy, there may be a milder phenotype, which is difficult to distinguish from other congenital myopathies.


This study aims to investigate public response attitude, anxiety, practices and trust in the authorities’ mitigation plan during the first wave of COVID-19 pandemic. A national cross sectional phone survey was conducted among Saudi residents aged 16 years and above. A total of 90,421 (45.2%) individuals participated in the study. Of those, the overall rate of COVID-19 correct knowledge was 82% (mean: 9.84); social media was the most reported source of knowledge. Younger age, low levels of education and foreign residents were associated with poor knowledge. Overall, 49.5% scored 5 or more on the GAD-7 test, indicating anxiety symptoms, 19.2% of them scored 10 and above, suggesting moderate to severe anxiety. Majority of participants (>78%) trusted and supported the interventions implemented by the government to control COVID-19. Social distancing practices among participants was as following, 72.5% stayed at home and avoid going out for nonessential business and 49.5% avoided attending social events and family gatherings. Trust in authorities, being anxious, worry and levels of knowledge about the disease, were the most common factors affecting adoption of the recommended practices. Continuous evaluation of public response about COVID-19, and the effectiveness of protective measures is essential to better inform policy-makers and identify ways of encouraging behaviour change among public during pandemic. Coronavirus disease 2019 (COVID-19) is an emerging respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) .Saudi Arabia has adopted various national response strategies aiming to control the pandemic curve, starting with travel suspension, shutdown of schools, limiting workspace access and curfew . An addiWhile almost all countries around the globe have applied unique measures that have not been undertaken previously, no study have investigated whether trust on authorities control plan and actions can affect public behaviour and anxiety level during COVID pandemic or not. Understanding the public’s response and behaviour is vital in designing policies, control strategic plan and preventive measures. Moreover, it can also inform policy-makers and identify ways of encouraging behaviour change among public during the early stages of the pandemic. To this end, this study is intended to understand the public concerns and behaviours at the beginning of COVID-19 pandemic in Saudi Arabia. This study is a national cross-sectional survey conducted among a sample of Saudi residents aged 16 years and above. The study was conducted between 17 and 18 March 2020. The survey was developed using a web-based questionnaire, integrated with a recruitment system and secure database to store the collected data. Data were collected from 13 administrative regions in Saudi Arabia, including Al-Riyadh, Makkah, Al-Madinah, Al-Qaseem, Eastern Region, Aseer, Tabouk, Hail, Northern Borders, Jazan, Najran, Al-Baha and Aljouf.Non-proportional quota sampling (‘soft quotas’) divided by region and gender was used to ensure that respondents were demographically representative of the general population . The sample size was calculated for a β of 0.05 and a power (1 − α) of 0.80; we estimated a minimum sample size of 5004 participants. Due to the limited timeline and the special period of time during conducting this survey, we considered a 10% response rate from the total recruited sample of 50,040. However, since this was an online-based survey capturing public response and attitude, around 200,000 messages have been sent. We aimed to recruit as many participants as possible within the survey period, even after achieving the set sample size.Because of this exceptional time of the pandemic, household survey was not applicable, thus the study was carried out using phone survey. Based on a list of random mobile phone numbers generated from a governmental database and divided by regions and gender, participants were invited to take part in the study using random digital dialling (RDD). The individuals received a message containing a short description of the study and the survey link. Each user had a unique device identifier linked to the research database, so the user could not submit information more than once. As the data were obtained electronically, no user could submit responses that were missing vital information. Respondents were required to be 16 years or older, living in Saudi Arabia, Arabic speakers and to have heard of COVID-19.Data on socio-demographic characteristics of the respondents, including age, gender, education level, nationality and working status were collected.The second part of the survey focused on awareness regarding COVID-19 and understanding its risk, requiring true or false responses. These items were developed by the authors and selected according to previous research as well as frequent questions and myths about COVID-19 as reported on the Saudi Ministry of Health (MoH) and WHO websites ,12,13.To measure the knowledge among participants, the questionnaire had 12 knowledge questions among different aspects of COVIS-19; 4 regarding clinical presentations, 3 regarding transmission routes and 5 regarding prevention and control of COVID-19. Knowledge score was assessed by multiple choice answers, three possible answers were presented in each question, only one answer was correct. A correct answer was assigned 1 point and an incorrect/unknown answer was assigned 0 points. The total knowledge score ranged from 0 to 12, with a higher score indicating better knowledge of COVID-19 and lower score indicating insufficient/poor knowledge. Cronbach’s α scores were less than 0.6, which prevented us from creating a knowledge scale.The survey also assessed the level of trust among the public about the government’s ability to handle and control the COVID-19 pandemic. The scale contained 10 questions; 4 items were related to the public’s general perception of the government’s ability to control the disease within the coming months, while the other 6 items specifically asked about their agreement with the implemented measures, such as school closures, travel suspension and mall and restaurant closures. Items measuring trust in authorities were phrased as statements, with response options ranging from strongly agree to strongly disagree . Each answer was scored on a scale from 0 to 4 as following; (strongly agree (4), agree (3), neutral (0), disagree (2), strongly disagree (1). The total score ranged from 0 to 40, with high scores indicating greater agreement that the authorities are to be trusted in handling COVID-19. The Cronbach’s alpha coefficient of the questionnaire was 0.81, indicating high internal consistency.The survey measured COVID-19’s impact on the public level of anxiety using the Generalized Anxiety Disorder scale (GAD-7). The GAD-7 is the most commonly used diagnostic self-report scales for screening, and severity assessment of anxiety among general population . The scat-tests and Chi-square tests as appropriate. To identify the factors associated with knowledge, we conducted a multivariable linear regression analysis using all of the demographic variables as independent variables and knowledge and trust in authorities as the outcome variables. We used binary logistic regression analyses to identify the factors associated with the level of anxiety and concern among participants after adjusting for demographics and knowledge using a backward Wald method. We used regression coefficients, standard error and odds ratios (ORs), 95% confidence intervals (CIs) and p values to quantify the associations between variables and study outcomes. The statistical significance level was set at p < 0.05 (two-sided). The sample population was weighted to the regions and gender distribution of the Saudi adult population. The weighted and unweighted data change was between 1% and 5%, both results (weighted and unweighted) are presented in all tables. Data analyses were conducted with SPSS version 26.0 and SAS 9.13 statistical software.Participants’ demographics, knowledge and various attitudes and practices were described in numbers and percentages. Knowledge scores according to demographic characteristics were compared with independent-samples This study was reviewed and approved by the Human Research Ethics Committee at Saudi Food and Drug Authority .After the end of data collection period, 204,186 participants had been approached, about 90,421 (45.2%) individuals completed the survey. Of those, 68.8% were male, and mean age was 33.6  years. Majority (77.5%) had a university-level or higher qualification and 75.7% were employed. The weighted and unweighted characteristics of participants are presented in The mean COVID-19 knowledge score was 9.84 , and the overall rate of correct answers was 82% (9.84/12 × 100). Over half of participants (56.7%) reported that governmental institutions’ social media accounts were their main source of COVID-19 knowledge, and 84% of them spent up to 3 h a day following COVID-19 pandemic news .p < 0.001). Knowledge scores were higher in regions that reported the first COVID-19 cases  compared to other regions in Saudi Arabia , being non-Saudi , having an education level of high school or less , being unemployed/retired  and being students  were more likely to be associated with poor knowledge  were either ‘not concerned’ or ‘slightly concerned’ about catching the disease. They gave the following reasons for this: believing that they were under Allah’s (God’s) protection (78.9%), complying with preventive measures (67.1%) and the confidence that they would get the needed health care from the MoH (56%). On the other hand, 30.3% of respondents were highly or moderately concerned about COVID-19 for the following reasons: highly contagious disease (83.2%), high-risk occupation  or working in crowded places) (56.8%) and having family members or friends who returned recently from countries with a high rate of infection (48%). p < 0.001), non-Saudis , 49 or younger , had bachelor’s degrees or higher  and health care workers   .p < 0.001), non-Saudis , those 49 and younger , those holding high school degrees or lower , those with poor COVID-19 knowledge  and those concerned about catching the disease  were more likely to report moderate to high levels of anxiety ; 16% reported trust scores ≤34, 22% reported trust scores between 35 and 37 and 62% reported scores ≥38.p < 0.001), having moderate to severe anxiety  and higher concern levels  were significantly associated with low trust in authorities.Multiple linear regression results showed that being a health care worker , non-Saudis , those concerned with catching the disease , those with moderate anxiety , those with severe anxiety , those reporting higher knowledge scores , those reporting more trust in authorities  and younger participants  were significantly more likely to practice personal protective measures. Moreover, females , Saudi citizens , those concerned about catching the disease , those with higher knowledge scores , older participants , those with minimal anxiety  and those with more trust in authorities  were significantly more likely to practice social distancing measures  protection was found to be the main reason for being unconcerned. Other surveys involving the Saudi public during the MERS-CoV outbreak showed that religious faith led individuals to believe that they are at a lower risk against serious emerging infectious risks ,21. AnotNotably, less than half of participants (47.8%) showed anxiety symptoms; 21% of them were struggling from moderate to severe anxiety. The ramifications of mental disorders during pandemics were addressed among Chinese population during this pandemic . The uncIn this cross-sectional study, healthcare workers (compared to other workers) were more likely to be at higher risk of anxiety. Previous studies reported similar results during the 2003 severe acute respiratory syndrome (SARS) outbreak among health care workers ,28,29. PThe study showed that in terms of symptoms of anxiety and concern, the uptake of preventive measures varied with risk perception and anxiety levels. High anxiety and risk perception led to individuals taking preventive measures, such as avoiding crowded areas and maintenance of high hand hygiene standards. The effect of anxiety on protective behaviours among the public was proven in a study of 10,345 adults, which found that anxiety levels were strongly associated with adoption of protective behaviours during pandemics ,24,30.In this study, personal hygiene measures were adopted by a larger number of people than social distancing measures, which would require alterations to their social interactions. While handwashing and use of disinfectants were practiced by 90.4% and 67.1%, respectively, staying at home and avoiding social events and family gatherings were practiced at rates of 76.6% and 55%, respectively. These results are in contrast to the results of a recent study on a Chinese community, where about 90% avoided going to crowded places . Hence, There are some limitations to this study. First, this is a cross sectional study; no follow-up was conducted, and public perception assessed at a point of time may not be representative of consistent beliefs or practice. Second, the data were self-reported and may not reflect the actual behaviour. Also, the sample was selected using random mobile phone numbers that were generated from a government database which excluding households with landing phone; all these could limit the generalisability of the findings. Lastly, there were more males (68.8%) than females and younger age groups were moderately over-represented, but geographically the sample closely reflected the Saudi population distribution. Despite these limitations, this study is the first in-depth analysis of public response during the COVID-19 pandemic and has provided unique data on public perception, anxiety, trust in authorities and practices surrounding COVID-19. Also, because the study used an anonymous online survey, any bias originating from cultural, ethnical or religious factors is eradicated. Additionally, the weighted data by region and gender did not change the outcomes by less than 5% compared to the unweighted data.To conclude, this study highlights that Saudi residents are well aware of COVID-19 risk and its transmission routes. This knowledge is influenced by demographic factors of the participants; younger age groups, individuals with low levels of education and foreign residents were associated with poor knowledge of the disease. Moreover, personal protective measures, such as hand hygiene, were more likely to be adopted than social distancing measures. Trust in health authorities, worry, anxiety and levels of knowledge about the disease were related to greater likelihood of implementation of protective practices. Understanding these factors can help public health authorities design culturally appropriate health campaigns to reach the population according to their social-demographic characteristics. Also, our findings recommend that current policy-makers continue providing the public with clear, consistent information, focusing on the practical things that people can do to protect themselves from the disease. Continuous evaluation of public response, knowledge about COVID-19 and the effectiveness of protective measures is essential to better inform policy-makers and identify ways of encouraging behaviour change among public during the early stages of the pandemic.


Childhood cancer survivors (CCSs) who have undergone bone marrow transplantation with systemic chemotherapy and whole-body irradiation often experience impaired glucose tolerance with marked insulin resistance. Incomplete acquired diabetic lipodystrophy should be considered as a late complication of bone marrow transplantation. A 24-year-old Japanese female patient with incomplete acquired lipodystrophy, a CCS of acute lymphocytic leukemia at the age of 3 years, was treated for diabetes mellitus and dyslipidemia at our hospital. Administration of multiple daily insulin injections (70 units/day), and oral administration of 500 mg/day metformin, 15 mg/day pioglitazone, and 200 mg/day bezafibrate had proven ineffective for her metabolic disorders. Subcutaneous administration of metreleptin improved her insulin resistance and hypertriglyceridemia within a month; however, it failed to maintain adequate plasma glucose levels in the long term. When oral administration of 10 mg/day empagliflozin was added to the metreleptin supplementation, her HbA1c value  improved from 11% to 8%, which was maintained for an additional 18 months. This is the first case report of incomplete lipodystrophy that shows efficacy of a combination therapy with metreleptin and a sodium glucose cotransporter 2 (SGLT2) inhibitor for the treatment of diabetes and dyslipidemia. An SGLT2 inhibitor attenuates hyperglycemia through urinary glucose excretion and has been suggested to enhance lipid catabolism in the extra-adipose tissues, especially in the liver and skeletal muscles. Furthermore, metreleptin supplementation could enhance the action of the SGLT2 inhibitor by promoting satiety and lipolysis through the central nervous system. Combination therapy with metreleptin and an SGLT2 inhibitor was suggested to recover the volume of adipose tissue, possibly through improvement of insulin resistance in the adipose tissue. This report highlights the pathophysiological mechanism of an SGLT2 inhibitor in the improvement of glucose metabolism in non-healthy lean CCSs with insulin resistance. Administration of SGLT2 inhibitor, along with metreleptin supplementation, could be a good alternative therapy for diabetic lipodystrophy observed in CCSs.  Childhood cancer survivors (CCS) are at a high risk of cardiovascular events and mortality , 2, evenDisturbance in both white and brown adipose tissues has been suggested to occur during radiation therapy-related acquired incomplete lipodystrophy , althougWe present a case of acquired incomplete diabetic lipodystrophy wherein the patient was treated with a combination of metreleptin supplementation and an SGLT2 inhibitor. We have previously reported the effect of metreleptin administration on lipid and glucose metabolisms in this case . An addiA 24-year-old Japanese female patient presented to our endocrinology center with hyperglycemia, and a 13-year history of acquired incomplete diabetic lipodystrophy with hypertriglyceridemia and non-alcoholic fatty liver disease . Systemi2, respectively, before administration of metreleptin and empagliflozin, had reduced to 28.6 kg and 14.6 kg/m2, respectively, following 18 months from empagliflozin initiation and continuous metreleptin supplementation. The area under the curve and fluctuations in the daily plasma glucose, measured using a flash glucose monitoring (FGM) system, demonstrated significant improvements . Her glycemic control improved immediately, and the HbA1c level decreased to ~8% (NGSP). On physical examination, her bodyweight and body mass index of 30.5 kg and 15.6 kg/movements Figure 2ovements   for the publication of any potentially identifiable images or data included in this article.AN collected the data and wrote the first draft of the manuscript with the support of KA and MN. KA, YK, HT, and MN reviewed the manuscript. AN, KA, MW, KM, AS, YK, HT, SY, SI, JY, NH, SO, SM, and MN discussed the case and approved the final manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To downgrade BI-RADS 4A patients by constructing a nomogram using R software.A total of 1,717 patients were retrospectively analyzed who underwent preoperative ultrasound, mammography, and magnetic resonance examinations in our hospital from August 2019 to September 2020, and a total of 458 patients of category BI-RADS 4A  were included. Multivariable logistic regression was used to screen out the independent influencing parameters that affect the benign and malignant tumors, and the nomogram was constructed by R language to downgrade BI-RADS 4A patients to eligible category.Of 458 BI-RADS 4A patients, 273 (59.6%) were degraded to category 3. The malignancy rate of these 273 lesions is 1.5% (4/273) (<2%), and the sensitivity reduced to 99.6%, the specificity increased from 4.41% to 45.3%, and the accuracy increased from 63.4% to 78.8%.By constructing a nomogram, some patients can be downgraded to avoid unnecessary biopsy. According to statistics, the number of new cases of breast cancer among Chinese women reached 0.42 million in 2020, accounting for 18% of the global breast cancer rate. It ranks first in the incidence of female cancer, and the mortality rate ranks fourth in China , 4. The The main purpose of this study is to downgrade category 4A lesions to avoid unnecessary biopsy. Since BI-RADS 4B, 4C, and 5 patients are still within the puncture range even if they are degraded, the degrading factors of these patients are not considered in our study.n = 35), (b) incomplete clinical data (n = 26), (c) part of the images was unclear (n = 35), (d) the interval between the three imaging examinations was more than 1 month (n = 40), (e) patients who have been diagnosed with BI-RADS category 6 (n = 49), and (f) non-mass enhancement (n = 350). In the end, 1,717 patients constituted the study group. Among them, there are 458 patients in category 4A,  patient characteristics is shown in This retrospective study was approved by the Ethics Committee of the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. The consent to participate in the study for patients was waived due to the retrospective study and all identity data of patients are undistinguishable. The study was carried out in conformity to the Declaration of Helsinki (as revised in 2013). From August 2019 to September 2020, 6,312 patients underwent breast surgery or core needle biopsy and obtained clear pathological results, including 2,252 females who went through ultrasound, mammography, and magnetic resonance imaging examinations simultaneously. Among the 2,252 patients, 535 were excluded due to the following reasons: (a) the location of the lesions shown by the three imaging ways was inconsistent  and the head and tail position (CC position). If necessary, local compression magnified irradiation and special body position irradiation were given.2), T1-weighted fat-suppressed dynamic enhancement scan: 1 stage no enhancement 90 s + 5 stage enhancement (90 s × 5) after injection of 20 ml of gadolinium meglumine, and then the images were uploaded to the PACS system. Postprocessing included T1-weighted subtraction, T1-weighted maximum intensity projection, and subtracted sagittal reconstruction; the apparent diffusion coefficient (ADC) was measured; and the time–signal intensity curve (TIC) was obtained.All the breast MRI examinations were performed with a 1.5-T unit  with a dedicated 18-channel phased-array breast coil. The patient was in the prone position, and the breasts were naturally suspended in the breast coil. The scanning range included bilateral axillary and bilateral upper and lower boundaries of the breast. The protocol included axial T1-weighted, T2-weighted fat-suppressed, diffusion-weighted imaging  is converted to the SWE model when the longest axis view of the lesion is displayed on the 2D image, and the probe should be handled gently.The analyzed images were downloaded from the hospital’s PACS system in DICOM format. Two people engaged in breast research  are also proficient in ultrasound, mammography, and magnetic resonance diagnostic images. Radiologists, without knowing the pathological results, according to the fifth edition of the ACR BI-RADS lexicon, used the ultrasound images , magnetic resonance images , and mammography images for evaluation. When one of the three images shows an obvious mass, it is defined as masses; otherwise, it is classified as no mass enhancement.t-test or one-way ANOVA when normally distributed, or the Mann–Whitney U test when not normally distributed.Continuous variables are expressed as the mean ± standard deviation, and categorical variables are presented as frequencies and percentages. Univariable analyses are performed by Student’s p < 0.05 in univariable analysis were considered possible predictors and were entered in multivariable logistic regression. The independent influencing factors of benign and malignant tumors were screened out using multivariable logistic regression.For this study, based on the BI-RADS lexicon, the clinical indicators included the patient’s age, history of hormone therapy, the activity of the mass, the mass texture, family history of breast cancer, history of breast surgery, and whether there is tenderness. Variables showing -3 mm2/s, SWEmax is 72.61 KPa). Patients were divided into three groups based on their age according to the United States Cancer Screening Guidelines  of mucinous carcinoma. In addition, adenopathy, papilloma, fibroadenoma, benign phyllodes tumor, sclerosing adenopathy, and accompanied by ductal dilatation were the most common benign lesions.Of 458 patients, 44 are malignant, namely, 19 cases (43.2%) of invasive ductal carcinoma, 13 cases (29.5%) of ductal carcinoma in situ, 4 cases (9.1%) of papillary carcinoma, 1 case (2.3%) of malignant phyllodes tumor, 1 case (2.3%) of small B-cell lymphoma, 3 cases (6.8%) of invasive lobular carcinoma, 2 cases (4.5%) of lobular carcinoma p < 0.05 were entered into multivariable logistic regression. The results in p = 0.000), ADC value (p = 0.043), mass margin (p = 0.018), calcification morphology (p = 0.000), SWE max (p = 0.024), and age groups (p = 0.000) were independent variables for differentiating between benign and malignant tumors, and DWI signal is excluded in the multivariable logistic regression analysis, which may have a strong correlation with the ADC value. Display these independent predictors as a nomogram  were downgraded to BI-RADS 3. Only one case was wrongly degraded, and the pathological type was in situ solid papillary carcinoma. The overall accuracy, especially the specificity, can be significantly improved without significantly reducing the sensitivity.All patients with a final BI-RADS score of 4 or 5 received a diagnostic core needle biopsy or open surgery was performed to determine the histopathologic diagnosis, as recommended by the American College of Radiology. Previous studies showed how to downgrade BI-RADS 4A relatively safely, to have these patients followed up instead of undergoing an immediate biopsy. For example, Flowers et al.  proposedSelecting the malignant signs with the highest risk to construct a nomogram can help distinguish benign and malignant lesions and improve the diagnostic value. Among them, the TIC curve, ADC value, mass edge, calcification morphology, age, and SWEmax were identified as independent predictors of benign and malignant tumors, which are the same as the previous study –11. No mp < 0.001), which proves that older is an important risk factor for breast cancer. Our results were consistent with the above previous studies. There were currently a variety of breast cancer risk assessment models, and the existing risk prediction models were generally similar  have no significant difference between benign and malignant tumors. This may be due to the large proportion of benign lesions in patients with category 4A, the unobvious clinical manifestations, or the limited sample size. Research by Jagpreet  also con similar –20.This study has some limitations. First of all, this article only degrades the patients who are classified as BI-RADS category 4A. Because even if patients above category 4A are degraded, they are still within the scope of biopsy. Therefore, patients of categories 4B, 4C, and 5 are not considered in our study. Secondly, we did not evaluate the consistency between observers, but previous studies have shown that the feasibility of guidelines makes the results of the report not significantly different between junior and experienced radiologists . FinallyIn short, by combining the BI-RADS lexicon and clinical indicators to perform downgrading for BI-RADS 4A patients, a large number of patients can be prevented from undergoing invasive biopsy, and clinical resources can be saved.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.XZ, WZ, and WC contributed to conception and design of the study. YX performed the statistical analysis. YX wrote the first draft of the manuscript. SZ, SX, YZ, and XZ wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Although the incidence of “diabesity” (coexistence of type 2 diabetes and obesity) is alarmingly increasing in Algeria, the diet–diabesity link has not been well defined. This study aimed to explore the association between dietary diversity score (DDS) and obesity among Algerian type 2 diabetic patients. It was a cross-sectional observational study involving 390 type 2 diabetic patients. Anthropometric data were gathered, and dietary intake information was obtained through a 24-h dietary recall method, which was used to calculate DDS. Potential confounders such as age, sex, smoking, physical activity and energy intake were controlled for using multivariate logistic regression. A total of 160 patients (41.3%) were classified as obese. As expected, obese patients had a higher body mass index, waist circumference, hip circumference, body fat and fat mass index. Furthermore, obese patients more frequently met carbohydrate recommendations and had a higher intake of meat and protein. Female sex, hypertension, low physical activity and high meat and protein intake were positively associated with diabesity. Additionally, higher DDS was positively associated with diabesity after adjusting for confounders. Thus, a more diversified diet may be a risk factor for obesity among Algerian type 2 diabetic patients. Diabesity, defined as the coexistence of diabetes mellitus type 2 (T2DM) and obesity, was considered the pandemic of the 21st century up to March 2020 when the World Health Organization (WHO) announced coronavirus disease 2019 (COVID-19) as a pandemic ,4.The incidence and progression of T2DM are closely associated with body mass index (BMI) . In factSince most of the above-described studies have been conducted in general population samples, questions remain regarding the link between dietary patterns and obesity in type 2 diabetic patients, especially in the Algerian population who is experiencing accelerating industrialization, urbanization and a nutrition transition concomitant with a dramatic rise in the incidence of diabetes . Thus, a2) and waist-to-hip ratio as waist circumference in cm divided by hip circumference in cm. The WHO cut-offs were used to classify participants as normal weight, overweight, obese or abdominally obese [This was a cross-sectional observational study conducted among T2DM patients on follow-up at the diabetic clinic “Maison du Diabétique” of Mustapha Pacha University Hospital in Algiers (Algeria), from January to March 2019. A single population proportion formula with an assumption of 95% confidence level, a 5% degree of precision, 40.82% previous prevalence of obesity among T2DM patients from Algeria  were excly obese ,16. Percly obese ,18. PhysDietary assessment was carried out using a 24-h recall method. Although a single 24-h recall might not accurately reflect the usual intake, this method is considered the best approach for determining dietary diversity, since multiple 24-h dietary recalls result in a lack of accuracy . HoweverDDS was used to calculate dietary diversity by applying the procedures described by Kant et al. . Five fot-tests, Chi-square and Mann–Whitney U tests were used to assess differences between the two groups. The association between diabesity and demographic, clinical, anthropometric and physical activity variables, as well as DDS and food groups intake were evaluated using univariate and multivariate logistic regression. p < 0.05 was considered as significant. All statistical analyses were conducted using SPSS, version 25 .All data were verified for normality distribution using the Kolmogorov–Smirnov test. Independent Student 2, respectively. With regard to physical activity level, the percentage of patients who were categorized as having low physical activity was 61%, whereas 34.9% and 4.1% were categorized as having moderate and high physical activity, respectively.Three hundred and ninety patients with T2DM were enrolled in this study. Their basic characteristics are shown in p < 0.0001), hypertensive (p = 0.023), less physically active (p < 0.0001) and, as expected, their BMI, waist circumference, hip circumference, body fat and fat mass index were higher (p < 0.0001)  .The mean and distribution of DDS according to obesity status are shown in p < 0.05).The dietary intake of the study patients is indicated in p < 0.05). Protein provided, on average, 12.3 ± 5.6% of the total energy intake, and 54.4% of the patients reported a diet with the recommended level of protein intake (10–20%). However, obese patients consumed significantly more protein, expressed as g/d  and as a percentage of total energy intake , than non-obese patients. On average, fat provided 27.1 ± 10.2% of the total energy intake, and 77.2% of the patients met the recommended level of <35% of total energy intake.The daily energy and macronutrient intakes of the patients are presented in p < 0.05). This association remained significant after further adjustment for smoking and physical activity based on Model 1  and energy intake based on Model 2 . Moreover, in the crude model, higher meat intake was associated with statistically significant increases in the odds of being diabase . This association was strengthened in Model 1, which was adjusted for age and sex , after further adjustment for smoking and physical activity based on Model 1  and total energy intake based on Model 2 .Crude and multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association of DDS and food group intake with diabesity are presented in Diabesity constitutes an important risk factor for the occurrence of short-term and long-term medical complications , therefoIn the present study, female sex, hypertension and physical inactivity were significant predictors of diabesity. These findings are in line with the results of a report made by the Algerian Ministry of Health, Population and Hospital Reform in collaboration with WHO , which iThe current study is the first in Algeria to report that the majority of patients with T2DM had adequate dietary diversity. In addition, while obese and non-obese diabetic patients had similar raw DDS, after adjusting for covariates, the obese group had higher dietary diversity than the non-obese group. According to previous reports ,10,11,12This study found that higher meat intake was a significant independent predictor of diabesity, and this is consistent with the literature ,26. In fOur results regarding energy intake differ from those of Diaf et al.  who repoFinally, a set of limitations warrant acknowledgement. First, the cross-sectional design of the study establishes associations and not causality. Second, we did not consider biomarkers in our analysis. Third, it was practically difficult to estimate diversity within food groups because the Algerian diet is largely comprised of mixed dishes. Fourth, due to limited data on the micronutrient content of mixed dishes, we were unable to calculate the nutrient adequacy ratio and the mean adequacy ratio. Fifth, educational and economic status were not recorded, although differences in either status are negligible because most participants were retired (similar economic conditions) and had limited access to higher levels of formal education as they were born in the 1940s–1960s. Acknowledging these limitations, our study, to our knowledge, is the first to consider the relationship between DDS and diabesity. The enrollment conditions were well-defined, and various potential confounding factors were considered. The sample was homogeneous in the sense that all participants attended the same clinic and thus had received diabetes education from the same team. In addition, to reduce the effect of recall bias, standardized methods were used. In conclusion, the study shows that, overall, Algerian type 2 diabetic patients had adequate dietary diversity. When adjusting for confounding variables, obese T2D patients had significantly higher dietary diversity than their non-obese counterparts. As we found a medium association between DDS and energy intake, the consumption of a diversified diet should consider the controlling of total energy intake to combat weight gain and diabesity. Moreover, female sex, hypertension, low physical activity and high meat and protein intake were the factors that were found to be associated with diabesity. These findings are important for healthcare professionals and policy-makers to intervene early and effectively. A future study could explore the impact of other variables on the diet diversity of T2DM patients and validate DDS using biomarkers.


Aurelia coerulea is one of the most common jellyfish worldwide and is particularly abundant in sheltered coastal lagoons and marinas of the Mediterranean Sea, where it first appeared—as an alien species—in the last century, when Pacific oyster cultivation began. In the present study, the antioxidant and lysozyme antibacterial activities associated with extracts from different medusa compartments—namely the umbrella, oral arms, and secreted mucus—were investigated. Extracts from the oral arms of A. coerulea displayed significant antioxidant activity. Similarly, lysozyme-like activity was the highest in extracts from oral arms. These findings suggest that A. coerulea outbreaks may be used in the search for novel cytolytic and cytotoxic products against marine bacteria. The geographically wide occurrence and the seasonally high abundance of A. coerulea populations in coastal waters envisage and stimulate the search for biotechnological applications of jellyfish biomasses in the pharmaceutical, nutritional, and nutraceutical sectors.Marine invertebrates represent a vast, untapped source of bioactive compounds. Cnidarians are represented by nearly 10,000 species that contain a complex mixture of venoms, collagen, and other bioactive compounds, including enzymes, oligosaccharides, fatty acids, and lipophilic molecules. Due to their high abundance in coastal waters, several jellyfish taxa may be regarded as candidate targets for the discovery of novel lead molecules and biomaterials and as a potential source of food/feed ingredients. The moon jellyfish  Marine invertebrates represent a source of bioactive compounds that are generally used as defensive barriers against predators, parasites, and microbial pathogens or as messengers for intraspecific and interspecific communication. The enormous chemical diversity of marine invertebrate products guarantees an almost unlimited resource in the search for novel bioactive molecules  for pharRhopilema esculentum were shown to have both ACE inhibitory and antioxidant abilities [Cotylorhiza tuberculata, Rhizostoma pulmo, and Aureliacoerulea show notable antioxidant activities [R. pulmo show remarkable antioxidant activity that is inversely proportional to the peptide molecular weight (MW), with low MW peptides being effective against oxidative stress in human epidermal keratinocyte (HEKa) cell cultures [R. esculentum extracts are also responsible of an in vivo photoprotection ability [In Cnidaria, scyphozoan jellyfish (class Scyphozoa) are represented by nearly 220 species and can be found across all of the world’s oceans: although some occur in deep seas, most species live in shallow coastal habitats. Several scyphozoan jellyfish can reach conspicuous size and may seasonally undergo massive population outbreaks, resulting in large gelatinous biomasses being frequently detected in coastal waters, thus making these organisms ideal candidates for bioprospecting. In fact, several compounds with multiple biological properties have been isolated from the different body parts and components  of several scyphozoan jellyfish ,6,7. Forbilities ,9. Extrativities . Peptidecultures . The ant ability ,13.Aurelia spp., mucus cells are abundant within the gastric pouches and the inner margin of the gonads, where mucus creates a defensive barrier into which antimicrobial compounds are released [Bioactive compounds are present not only within jellyfish organs, tissues, and cells but also in secreted mucus. Indeed, jellyfish release considerable amount of mucus, an aqueous secretion, entangling a network of proteins and polysaccharides into a weak watery gel. As a dynamic external layer, mucus plays a variety of specialized functions across the animal kingdom , facilitreleased . Antimicreleased . Marine released ,21.Actinia equina [R. pulmo, presumably as defence against the surrounding pathogens [Among the best characterized antimicrobial enzymes, lysozyme is a lytic agent that is able to break the peptidoglycan of bacterial cell walls by hydrolysing the beta-1,4-glycosidic bond between N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) and by damaging the integrity of bacterial cells ,23. Lysoa equina  and in tathogens ,25,26. Aurelia coerulea von Lendenfeld, 1884, one of the most common jellyfish in coastal areas worldwide. It also occurs in the Mediterranean Sea, where it is particularly encountered in coastal lagoons, sheltered inlets, and artificial habitats, such as marinas [A. coerulea, C. tuberculate, and R. pulmo are increasingly considered valuable candidates for the exploitation of their biomasses and for the bioprospecting of compounds with pharmaceutical, nutritional, and nutraceutical value [A. coerulea, creating encouraging opportunities for the potential exploitation of non-indigenous species.In this framework, we explored the antimicrobial and antioxidant potential of extracts from the moon jellyfish  marinas ,28. The  marinas . Indeed, marinas ,31,32,33al value ,26,34,35al value . Here, wA. coerulea samples were evaluated, and the results are shown in The protein content in the A. coerulea samples was also evaluated and are showed in The phenolic compound content in the tissues of the Remarkable antioxidant activity, which could be measured as radical scavenging activity, was detected in all of the jellyfish samples, as shown in Proteins of the different jellyfish samples were analyzed by SDS-PAGE electrophoretic separation. In A. coerulea, showed natural lysozyme like activity  of the sample and of the reaction medium  is now regarded as a cosmopolitan jellyfish [Aurelia spp. blooms occur in the Mediterranean Sea, from Spanish to the North Adriatic coasts yearly, providing considerable biomass from large populations of jellyfish, which has so far been rarely investigated from a Blue Biotechnology perspective [A. coerulea, highlighting the occurrence of potent antioxidant and antibacterial (lysozyme-like) compounds that are associated with the jellyfish mucus, oral arms, and umbrella.Linked to the human-driven spread of the Pacific oyster worldwide, the moon jellyfish ellyfish . For morspective . HoweverA. coerulea is intriguing when considering that natural antioxidant compounds play an important role as health-protecting factors from free radicals and ROS (reactive oxygen species) effects. Compounds with antioxidant activity are predicted to have other bioactivities and health benefits that are directly or indirectly linked to antioxidant property, such as anti-inflammatory, anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes, obesity, and neurodegenerative diseases; all of the applications have a dysregulation of the oxidative balance at their base [Cassiopea andromeda [A. coerulea, we demonstrated that conspicuous antioxidant activity was exerted by oral arms and umbrella tissues; however, antioxidant compounds seem more concentrated in the oral arms despite the low content of both proteins and phenolic compounds. From these data, low molecular weight components—mainly present in the oral arms—seem to have the highest antioxidant activity. However, the SDS-PAGE (and the resulting separation of polypeptides) is only the first step in the analysis of the proteinaceous components, which is not necessarily predictive of any biological activity. Eventually, an in-depth analysis will be required for the identification of the proteins/peptides or other molecules that are responsible for the observed biological activities. We hypothesize that the compounds evidenced from A. coerulea may have biological activities linked to defensive mechanisms: however, on the basis of our data, no clear relationship between the antioxidant and antibacterial activities can be established, although several peptides and phenolic compounds are known to exert both activities [The evidence for bioactive compounds with antioxidant activity in eir base . Then, indromeda ,38,39,40ndromeda ,11. The ndromeda ,42,43 anndromeda ,11,38,40tivities .Many marine taxa, including cnidarians, are known to develop defence mechanisms and to synthesize an astonishing variety of bioactive compounds , includiMicrococcus luteus) comparatively detected from three different compartments of the same jellyfish species, namely Aurelia coerulea umbrella, oral arms, and mucus.The occurrence of lysozyme-like enzymes is known in diverse marine invertebrates ,50,51,52Micrococcus luteus, such as Escherichia coli and Pseudomonas aeruginosa.Lysozyme represents the best characterized enzyme that is involved in the self-defence from bacteria and has been suggested as a rudimentary molecular defence, especially in organisms without adaptive immunity ,54. Thiscoerulea detected by electrophoretic analysis indicates the occurrence of proteins ranging from 20 to 50 kDa. This is in agreement with the general multi-protein nature of other marine invertebrate body compartments and with the previous SDS-analysis of Aurelia jellyfish in Leone et al. [Chrysaora quinquecirrha, toxic proteins have been categorized as medium-sized cytolytic actinoporins (∼20 kDa), cardiostimulatory proteins (∼28 kDa), and cytolysin with or without phospholipase in both crude and fractionated proteins (∼40 kDa) [Chrysaora achlyos, major protein component venom was found at 55 kDa [A. coerulea in the present study could be ascribed to one the major protein bands evidenced by the electrophoretic analysis. Accordingly, research focused on the structure and function of lysozymes from several bivalve molluscs showed a molecular weight ranging from 11 to 22 kDa [A. coerulea compartments. In particular, in the A. coerulea umbrella and oral arms, the lysozyme had a maximum of activity when the pH of both the reaction medium and the sample was 6 and when the ionic strength was 0.175, as previously reported for the lysozyme present in the mucus and in the extract of the nematocysts of A. equina and for other lysozymes [A. equina nematocysts  is equal to 4.75 ± 0.7 mm, which is very close to the lysis diameter produced by the lysozyme-like activity evidenced in the homogenate of the A. coerulea oral arms and umbrella. Moreover, in the present study, the obtained results prove that the homogenate of oral arms had lysozyme-like activity that was higher than that of umbrella and mucus. This could represent a further support within jellyfish tentacles as defence mechanism that is constituted by millions of nematocysts that are ready to trigger when physical contact occurs [A. coerulea umbrella compared to the other body compartments, the potential exploitation of the entire jellyfish could be encouraged.Here, the protein pattern of the A. e et al. , indicat∼40 kDa) . In Chryt 55 kDa . The lyso 22 kDa ,57. In tt occurs ,59,60. HA. coerulea could be due to the self defence of the jellyfish and the secretion of lysozyme in this matrix or could be due to the release of lysozyme by bacteria hosted in the mucus. In this last case, this could explain the different characteristics of the lysozyme activity recorded in the umbrella and oral arms (with a maximum of activity at pH 6) and the activity observed in the mucus that showed a maximum of activity when the pH of the reaction medium and sample was 4 and when the ionic strength was 0.175. Indeed, feeding may not be the only activity involved in the association of microorganisms with the mucus since, as already observed in sponges and bryozoans, the bacterial symbionts present in the mucus may produce chemicals that protect their hosts against potential pathogenic bacteria [A. coerulea. indicates the role of this compartment in defending the jellyfish from bacterial attack, serving as a medium into which the antibacterial substances are exuded. The defensive role of mucus has already been evidenced in several marine invertebrates, including polychaetes, such as Sabella spallanzanii and Myxicola infundibulum [A. coerulea lives along the coastal lagoons and harbours where bacteria, which often include pathogens that are harmful to man and marine organisms, are copious. Although bacteria may colonize the jellyfish, our results suggest the presence of a powerful immune system that includes lysozyme-like activity.Regarding mucus in marine invertebrates, it has a wide range of attributes and functions, including defence against an array of environmental stressors such as predators, parasites, and pathogens ,61. As sbacteria ,65,66. Ibacteria ,68,69. Hndibulum ,71, and ndibulum . This roVibrio anguillarum and Edwardsiella piscicida have been proposed [A. coerulea could represent a new natural source of lysozyme-like compounds.In recent years, lysozyme has attracted the interest of researchers due to its potential applications in the pharmaceutical and aquaculture fields . Currentproposed . In thiscoerulea encourage the potential use of the jellyfish for lysozyme-based preparations that are also in the pharmaceutical field.Currently, lysozyme is also used for pharmaceutical preparations ,77,78. LActinia equina and Anemonia sulcata, which had important application perspectives for the discovery of new biocleaning or antifouling agents [A. coerulea may represent an additional source of compounds for the development of natural antifouling molecules. This is particularly important considering that, up to now, highly toxic biocides are used [Recently, a notable discovery of antimicrobial peptides and new thermo-stable proteases was achieved from the sea anemones g agents . We beliare used ,81,82,83A. coerulea (and other jellyfish species) for biotechnological applications due to the evidence of antioxidant and antibacterial activities. A metabolomic approach based on advanced technologies, such as NMR resonance spectroscopy, will rapidly allow the multicomponent detection of complex mixture obtained from A. coerulea different body compartments. In this framework, further studies will also be required to isolate molecules of the utmost biotechnological interest through the combination of different analytical techniques, such as the HPLC, GC–MS, and LC–MS methods.In conclusion, this study corroborates previous findings encouraging the possible exploitation of 2 and reaches a maximum depth in the central zone of 5 m. Here, a resident population of Aurelia coerulea was recorded throughout the year, with high densities of jellyfish being present in spring and summer months, when the population abundance was estimated to be 4.5 ind/m2 [Varano Lake  is located on the southern Adriatic Sea on the north side of the Gargano promontory  produced in controlled conditions was collected using a sterile Pasteur pipette and was stored at −80 °C for the lysozyme-like activity assays. Subsequently, during mucus collection, some jellyfish were dissected by separating the oral arms from the umbrella. Whole jellyfish (W), the oral arms (OA), and umbrellas (U) were either frozen in liquid nitrogen as subsequently described or were directly homogenized for 90 s at 16,000 rpm in a sterile Waring blender at 4 °C and employed for further analyses. Some specimens were frozen in liquid nitrogen and stored at −80 °C.Fifty specimens of g for 30 min at 4 °C. The supernatants, which contained soluble compounds, including soluble proteins, were separated from the insoluble material remaining in the pellet, which included insoluble proteins, such as fibrillar collagen, and other insoluble components. Both fractions were analysed for the protein content and phenolic compounds as well as for the antioxidant activity.Whole jellyfish (W) and the separated oral arm (OA) and umbrella (U) specimens were homogenized in a sterile Waring blender that had previously been refrigerated. The entire procedure was performed at 0–4 °C by keeping the samples on ice. Homogenate samples were poured in 50 mL sterile Falcons  and were centrifuged at 9000× Total protein content was estimated in each sample through the modified Bradford assay  using bovine serum albumin (BSA) as a standard.2CO3). After 2 h of incubation at room temperature in the dark, the absorbance was spectrophotometrically measured at 760 nm. Gallic acid, ranging from 25 to 200 μg/mL, was used as a standard. The results were expressed as gallic acid equivalents (GAE) per gram of dry extract.The total phenol content was evaluated in soluble and insoluble fractions of samples of whole (W) jellyfish as well as in separated umbrella (U) and oral arms (OA) samples by a modified Folin–Ciocalteu colorimetric method as described in Leone et al. . BrieflyThe total antioxidant activity was determined spectrophotometrically in each sample by using the Trolox Equivalent Antioxidant Capacity (TEAC) method, as described by Longo et al. . Brieflyw/v) of cold PBS by stirring and were then centrifuged at 9000× g for 30 min at 4 °C in order to eliminate any remaining salts. Proteins were solubilized in Laemli buffer 6× and were analysed by SDS-PAGE.Proteins from the lyophilized samples 100 mg) of total jellyfish, umbrella, and oral arms were analysed by SDS-PAGE as in Leone et al. [0 mg of tBriefly, polypeptides were separated by electrophoresis through 12% polyacrylamide gels containing SDS (SDS-PAGE), as described in Leone et al. . Twenty-Micrococcus luteus  were suspended in 7 mL of 0.05 M PB-agarose  and then spread on Petri dishes. Wells with 6.3 mm diameters were sunk in the agarose gel, and each well was filled with 30 µL of sample . The diameter of the cleared zone of at least five replicates was recorded after overnight incubation at 37 °C. Diameters of lysis were compared with those of reference obtained with known amounts of standard hen egg-white lysozyme . The effects of pH, ionic strength (I), and temperature were evaluated for each sample. The pH effect was established by dialyzing (7000-MW cut-off) the samples in PB 0.05 M, ionic strength, I = 0.175, which was adjusted at pH 4, 5, 6, 7, 8, and by dissolving agarose in PB at the same I and pH values. The ionic strength effect was tested in PB 0.05 M and was adjusted at I = 0.0175, 0.175, 1.75. Agarose was dissolved in PB at the same I values. The temperature effect was assessed by performing the Petri dish assays (in PB at I = 0.175 and pH 6.0 for OA and U and pH 4 for M) and by incubating the plates at 5, 15, 22, and 37 °C. The dose–response curve of lysozyme-like activity was produced using Petri dish assays  with different amounts of sample .The presence of lysozyme activity can be detected by several methods. In the present paper, the occurrence of lysozyme activity was detected using the standard assay on Petri dishes, as already recently performed in other studies on Cnidarians in order to compare the data obtained in different species ,28,85. DTo evidence significant differences in the amount of protein contents, phenol contents, and antioxidant activity, a T test was used. Randomization of the T test was chosen to cope with the possible problem of non-normality and the heteroscedasticity of the data. The comparisons were made both in the whole jellyfish tissue and in the separated body parts . Statistical analysis was conducted with the software R , using tp < 0.05) to verify the consistency of the differences among several different levels that were investigated. When the restricted number of unique permutations in the pairwise tests occurred, p values were obtained from Monte Carlo samplings. Differences were illustrated through multidimensional scaling (MDS) plots. The analyses were performed using the software PRIMER v. 6 [To test the effects of temperature, pH, and ionic strength on antibacterial activity of several body compartments, permutational analyses of variance (PERMANOVA) were performed based on Euclidean distances on untransformed data, using 9999 random permutations of the appropriate units ,90. ThreMER v. 6 .A. coerulea provided the first insights into the discovery of new compounds [A. coerulea. Usually considered a critical issue in coastal areas, this alien jellyfish may be differently valued under a Blue Growth perspective, as it is a potential novel source of antioxidant and lysozyme-like compounds with multiple potential applications in the biotechnological and drug discovery sectors.Further investigations will be required in order to isolate the potential molecules of interest that are responsible for the antibacterial and antioxidant activities of the investigated moon jellyfish. Recent studies on the composition profile of proteins and metabolites in the homogenate of ompounds . Our res


This study aimed to determine the estimated proportion of contraindications among women taking combined oral contraceptives (COCs) and to assess the risk factors associated with their contraindications. This study was cross-sectional. Reproductive-aged women (18–49 years) on any COCs between 2018 and 2020 were recruited from one obstetrics–gynaecology clinic in a university-affiliated hospital and were included. Contraindications were defined using the World Health Organization (WHO) Medical Eligibility Criteria (MEC) for Contraceptive Use. Data were collected from electronic medical records for all included women, as well as a standardised, pretested, structured survey for one-third of the women. In this cross-sectional study, 380 women using COCs were included. Their mean age was 31.645 ± 7.366 years. Among them, 131 (34.5%) participated via a survey and electronic records, while the other 249 (65.5%) participated via electronic records only. The majority of the participants had a Bachelor’s degree (59.0%) and were married (62.1%). The overall estimated proportion of patients with at least one contraindication to COCs according to category 3 (relative contraindications) or 4 (absolute contraindications) was 31.3% (95% CI 26.63–35.99). The most common contraindications observed were controlled hypertension, category 3 (12.1%); major surgery with prolonged immobilisation, category 4 (4.7%); migraine with aura at any age, category 4 (4.2%); breastfeeding from six weeks to less than six months postpartum, category 3 (4.0%); and diabetes mellitus with complications, category 4 (3.2%). Significant factors associated with contraindications to COCs were married women , those aged 35 years or more , and those with one or more live births . Ensuring proper assessment prior to prescribing and considering alternatives suitable for long-term use among women taking an oral contraceptive regularly is recommended. Combined oral contraceptives (COCs), also known as birth control pills, are a hormonal therapy that contain both oestrogen and progestin. They are used mainly for contraception, as well as for several non-contraceptive indications such as polycystic ovarian syndrome (PCOS)  and dysmDespite the benefits of COCs, due to the increasing risk of adverse effects in the profile of oestrogen and progestin combination therapy, there are some medical conditions considered as contraindications. Contraindications are a common prescribing error  and are In Saudi Arabia, women can only obtain COCs through prescription, whereas in some other countries  , COCs arMost of the studies conducted in Saudi Arabia have focused on attitude, use, and knowledge of oral contraceptives ,11,12,13This study manuscript followed the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) checklist and the reporting of studies conducted using observational routinely-collected health data (RECORD) statement ,20 Supp.Ethical approval was obtained from the Institutional Review Board (IRB) at King Saud University (KSU) (Research project no.: E-20-5243) . Every pA retrospective cross-sectional study was undertaken to measure the estimated proportion of contraindications to COCs among reproductive-aged women in an OB-GYN clinic.The data were collected from an OB-GYN clinic in a university-affiliated hospital in the central region of Saudi Arabia. The university-affiliated hospital is a 1200-bed multi-disciplinary facility with general and subspecialty medical services that provides primary, secondary, and tertiary care to its patients. In addition, it provides a designated outpatient and inpatient facility, state-of-the-art surgical services, a fully equipped and staffed laboratory, radiology, pharmacy services, a dedicated home healthcare programme, and other support services .Reproductive-aged women (18–49 years) on COCs with or without a known contraindication to the use of COCs were included in this study. In addition, women who used COCs for contraceptive or non-contraceptive health benefits such as to reduce heavy menstrual bleeding (HMB), menstrual pain, improve acne, endometriosis, hirsutism and menstrual irregularities, PCOS, and premenstrual syndrome (PMS) were included . Women w®) and drospirenone and ethinylestradiol (Yasmin®). Other COCs were obtained from outside the hospital, such as cyproterone acetate and ethinylestradiol (Diane®), drospirenone and ethinylestradiol (Midian®), and desogestrel and ethinylestradiol . These COCs were checked against the Saudi Food and Drug Authority (SFDA) list of human medications and were subsequently classified into prescription medications [The baseline variables included were age, body mass index (BMI), educational level, marital status, number of births, and type of COCs. Two types of COCs were available in the hospital formulary: drospirenone and oestradiol hemihydrate (Angeliqications .The WHO MEC contains four categories for contraceptive eligibility. Category 1 is a condition for which there is no restriction for the use of the contraceptive method . CategorThe relative contraindications are the following: postpartum for less than 21 days without other risk factors for venous thromboembolism (VTE) or postpartum between 21 and 42 days with other risk factors for VTE, breastfeeding between six weeks and six months postpartum (primarily breastfeeding), age 35 or older and smokes less than 15 cigarettes/day, history of hypertension where blood pressure cannot be evaluated (including hypertension in pregnancy), adequately controlled hypertension where blood pressure can be evaluated, systolic blood pressure of 140–159 mmHg or diastolic blood pressure of 90–99 mmHg, migraine headaches without aura at age ≥35 years, past and no evidence of current breast cancer for five years, past or current gall bladder disease, past COC-related cholestasis, anticonvulsant therapy , or antimicrobial (rifampicin or rifabutin) .The absolute contraindications are the following: postpartum for less than 21 days with other risk factors for VTE, breastfeeding from less than 6 weeks postpartum, age 35 or older and smokes ≥15 cigarettes/day, vascular disease, hypertension systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg, history or acute deep vein thrombosis/pulmonary embolism (DVT/PE), DVT/PE and established on anticoagulant therapy, major surgery with prolonged immobilisation, migraine headaches with aura (at any age), current breast cancer, severe (decompensated) cirrhosis, malignant liver tumours, hepatocellular adenoma, known thrombogenic mutation, current and history of ischemic heart disease, stroke, complicated valvular heart disease , or systemic lupus erythematosus (SLE) with positive (or unknown) antiphospholipid antibodies .The categories that should be assessed according to the severity of the condition are the following: (a) diabetes with nephropathy/retinopathy/neuropathy or with another vascular disease, diabetes of a >20-year duration and (b) acute liver disease or flare viral hepatitis .The risk factors associated with COC contraindications are age, BMI, educational level, marital status, and parity ,24. PariAll electronic medical records for those women who visited the OB-GYN clinics between 1 January 2018 and 15 December 2020 were requested. After removing duplicated records, each record was given a code number and the inclusion/exclusion criteria were applied until the required sample size was reached.Data were extracted from both electronic medical records and from a standardized, pretested, structured survey.2 were considered to have “normal” weight. The terms overweight, obese, and severely obese were reserved for those with a BMI of 25–29.9 kg/m2, 30–39.9 kg/m2, and ≥40 kg/m2, respectively [The data collected from the electronic medical records were age, educational level, marital status, past medical history, medication history, and height/weight, which were needed to calculate BMI. BMI is a measure of total body weight relative to height, and can provide a better assessment of total body fat than weight alone. Those with a BMI of 18.5–24.9 kg/mThe survey was developed by four pharmacists, considering its clarity and relevance to ensure content validity. The face validity was tested on a pilot of five women. The survey was conducted by two trained pharmacy research interns (M.A. and W.A.), under the supervision of the principal investigators (G.A.A. and M.A.M.), either by a phone call or online link via phone messages according to the most convenient method for the women after obtaining their agreement to participate in the study.The survey consisted of three sections: (a) the first section consisted of demographic information, (b) the second consisted of the COC type, and finally, (c) the third included a checklist to determine the presence/absence of category 3 or 4 contraindications to COCs according to the WHO MEC . The surThe survey was used to ensure that the all of the outcome variables of interest were available for the research, in case they were not available from the medical record or the record was not updated. For example, the date of the last delivery, breastfeeding status, smoking history, and pattern of migraine headaches.Non-response bias is common in survey research . To overThe sample size was based on the assumption that the proportion of reproductive-aged women with contraindications to combined oral contraceptives is 50%, due to the fact there were no previous similar studies from Saudi Arabia . The minN = sample size;Z = Z statistic ;P = expected prevalence ;d = precision ;N = 1.962 × 0.50 (1 − 0.50)/0.052.N = 380 reproductive-aged women.The continuous variables are presented as the mean ± standard deviation (SD), and the categorical variables as number and percentage. The association between the demographic variables such as age, BMI, educational level, marital status, and parity and the dependent variable (contraindications to COCs) was assessed using univariate logistic regression. The statistical analysis was conducted using STATA Software SE/14.0 .The Excel datasheet was checked for errors in data, outliers, and missing data.n = 90) had one contraindication (23.7%), 17 had two contraindications (4.5%), 7 had three contraindications (1.8%), 3 had four contraindications (0.8%), 1 had five contraindications (0.3%), and 1 had six contraindications (0.3%).Out of the 119 women with contraindications, the majority (The estimated proportion of women with at least one contraindication to COCs according to category 3 of the WHO MEC (relative contraindication) was 85/380 . The estimated proportion of women with at least one contraindication to COCs according to category 4 of the WHO MEC (absolute contraindication) was 57/380 .The most common contraindications observed for category 3 were controlled hypertension  and breastfeeding from six weeks to less than six months postpartum . The most common contraindications observed for category 4 were major surgery with prolonged immobilisation , migraine with aura at any age , and diabetes mellitus with complications .p < 0.001 and OR 2.19, 95% CI 1.38–3.46, p = 0.001, respectively). Married women were at an 82% greater risk of contraindications to COCs . There were no statistically significant associations between women with contraindication to COCs with regards to BMI and educational level.In this research, we aimed to determine the estimated proportion of contraindications to COCs among reproductive-aged women, as well as the risk factors associated with their contraindications. The overall estimated proportion of contraindications to COCs according to categories 3 and 4 of the WHO MEC was 119/380 . The risk factors associated with these contraindications were married women aged 35 years or more or women with one or more live births.Relative contraindications were found in 22.4% of women. In these cases, the risks of using COCs outweigh the benefits, especially if an alternative is not available or is unacceptable for the patient; thus, COCs can be prescribed with caution and follow-up to ensure the safety of its use. Absolute contraindications were found in 15.0% of the women, which represents an unacceptable health risk if the contraceptive method is used.The most common contraindications observed for category 3 were controlled hypertension  and breastfeeding from six weeks to less than six months postpartum . For category 4, they were major surgery with prolonged immobilisation , migraine with aura at any age , and diabetes mellitus with complications .One of the most common contraindications observed for category 3 was controlled hypertension (12.1%). This was expected, as the prevalence of hypertension in Saudi Arabia is high . AccordiEvidence has shown that the risk of cerebral thromboembolism increases significantly in women with diabetes mellitus, hypertension, migraine, and past thromboembolic events . If oralKnowledge of contraindications to COCs among young females in one city in Saudi Arabia was assessed by Alsulaiman et al. (2017). A total of 40.9% (174/426) of the women mentioned that they should not use COCs if they had severe hypertension, 42.5% mentioned that they must wait at least six weeks after giving birth before starting COCs, 38.0% said that COCs can cause clotting in the legs and lungs, and 50.9% were aware that they must stop using COCs if they developed migraines with aura . HoweverA recent systematic review looked at the available evidence on the prevalence of combined hormonal contraceptive (CHC) use among women with contraindications according to the WHO recommendations (2015) . The sysIn order to make comparisons with other studies possible, the studies need to have the same numerators and denominators as our study. In this study, the estimated proportion of contraindications was analysed as the prevalence of contraindications among women who used contraceptives. We were able to compare our results with two studies. The first study was conducted in Brazil to estimate the prevalence of contraindicated use of oral contraceptives using a survey . The stuThe second study was a prospective cohort study in North America. Women were asked about their desired methods of contraception and medical history . The proportion was lower than our results, as only 24 of 1010 women desiring CHC  were found to have true medical contraindications to CHCs using a chart review . HoweverOur study has several strengths. First, in this study, we investigated most of the contraindications to provide a better estimate of their prevalence. Second, we used the most updated WHO MEC for Contraceptive Use 2015  to inforThe limitations of this study include, first, that the study was conducted in one centre and the women included had mostly attended high school or had Bachelor’s degrees, which might be not representative of all women in Saudi Arabia and this makes generalising the results difficult. Second, we relied on self-reported blood pressure or one reading from an electronic medical record instead of taking the average of two blood pressure measurements. Third, there were other contraindications that we could not categorise according to the severity, such as liver disease, and this could have resulted in an underestimation in our findings, although we suspect that this contraindication is rare. Finally, this study did not examine the adverse effects on the involved women; therefore, we do not know what harmful effect, if any, that the contraindications had on these women.When prescribing contraceptives to women, physicians have a central role in screening COCs for contraindications, explaining the risks and potential side effects, weighing the risks versus benefits, as well as providing advice on the appropriate use of contraceptives.The physician who prescribes the COC or the pharmacist who dispenses could provide all women with a formal written risk assessment for contraindications. In addition, we should not ignore the role of self-care; women can self-screen using a checklist of contraindications . PromotiMore research could be conducted on the accuracy of contraindications by using different data collection methods, such as surveys, medical records, or self-screening, and more research could be carried out in different regions in Saudi Arabia to increase generalisability.The estimated proportion of contraindications to COCs was 31.3%. The significant factors associated with contraindications to COCs were married women aged 35 years or more or with one or more live births. Weighing the risks versus benefits and screening COCs for contraindications in order to ensure the safe use of COCs is recommended.


Iatrogenic pneumothoracis, barotraumas, and tracheoesophageal fistulae, especially after prolonged intubation, and tracheal stenosis are all entities involving thoracic surgeons' consultation and management. With the surge of COVID-19 cases particularly in the critical care settings, various types of complications have been observed that require intervention from thoracic surgeons.  A retrospective study was conducted in an academic healthcare institute in the Eastern Province of Saudi Arabia. We included all COVID-19 cases admitted to ICU in the period between March 15, 2020, and August 15, 2020, requiring thoracic surgery consultation and management. Non-COVID-19 critical cases and iatrogenic pneumothorax were excluded.  Of 122 patients who were admitted to ICU with COVID-19, 18 patients (14.75%) required thoracic surgery consultation and management. We discovered a significant association between the outcomes and reintubation rates and the rate of pneumothorax occurrence. The survival analysis showed improvement in patients who had thoracostomy tube insertion as a management than the group who were treated conservatively. On the other hand, there was a significant difference between the COVID ICU group who had thoracic complication and those who did not regarding the length of hospital stay.  Noniatrogenic pneumothorax, subcutaneous emphysema, and mediastinal emphysema are well-known thoracic entities, but their presence in the context of COVID-19 disease is a harbinger for worse prognosis and outcomes. The presence of pneumothorax may be associated with better prognosis and outcome compared to surgical and mediastinal emphysema. The thoracic surgery role in critical care setting is usually reserved for complications. These could be related to a specific disease process, infections, inflammations, neoplasms, or other entities. They could also result from interventions performed within the intensive care unit (ICU).Iatrogenic pneumothorax, barotraumas, and tracheoesophageal fistulae associated with prolonged intubations, and tracheal stenosis are all conditions involving thoracic surgery services in their management . With thThe literature demonstrates that the significance of those entities is proportionate to the patient's prognosis, length of stay, and required recovery time. The pathophysiology indicates that the disease pattern rather than the side effects of assisted ventilation is the main cause of complications, with varying results depending on the lung area most affected by the disease .We aimed to review and analyze COVID-19 critically ill patients requiring thoracic surgery consultation and management while in the ICU. Demography, patterns, predisposing factors, comorbidities, hospital stay, thoracic complications, lengths of stay, interventions, and outcomes were examined.This retrospective chart review study was conducted in an academic healthcare institute located in the Eastern Province of Saudi Arabia. The inclusion criteria comprised all COVID-19 cases admitted to the ICU in the period from March 15th to August 15th, requiring thoracic surgery consultation and management. Non-COVID-19 critically ill patients and cases of iatrogenic pneumothorax were excluded from this study.Patients' charts were reviewed, and demographic data, comorbidities, patterns of thoracic complications, management, length of stay, intubation, reintubation, ventilatory settings, intervention, outcome, and recovery were all analyzed. In cases of ME and SE, conservative management that included close follow-up clinically and radiologically was applied according to the clinical pathway for SE and ME . ThoracoOur study posed no physical, psychological, social, legal, or economic risks. The study protocol was approved by the Institutional Review Board (IRB) of Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.U test and Fisher exact test were used, and a significant level was considered at P < 0.05.An excel spreadsheet was established for the entry of data. Data analysis was carried out using SPSS, Version 22. Categorical variables were summarized as frequencies and percentages. To determine the significant association of variables, the Mann–Whitney In addition, multivariate correlation and regression were done. Moreover, the Kaplan–Meier test was done for analyzing the expected duration of time of death in our sample size.Finally, a comparison between our sample and the total number of COVID-19 patients who were admitted to the ICU regarding their outcome and total length of stay in the hospital was done by using the Kruskal–Wallis test.One hundred and twenty-two COVID-19 patients were admitted to the ICU between the period March 15, 2020, and July 15, 2020. Ninety-six patients (78.7%) were males and 26 (21.30%) were females, with a male : female ratio of 1 : 0.3.Eighteen 14.75%) patients required thoracic consultation and management; fifteen males and three females 1 : 0.2) have developed thoracic complications including pneumothorax, SE, and ME. Fourteen patients required thoracostomy tube insertion. A descriptive analysis of our patients' population is shown in Tables 4.75% pat have devThe most common presenting symptoms were shortness of breath in 16 patients (88.9%), fever in 12 patients (66.6%), and cough in 11 patients (61.1%). Two patients (11.1%) were asymptomatic, one was admitted following a motor vehicle accident (MVA) and the second following a syncopal episode. One presented with hemoptysis and one with anorexia as an associated symptom.During the hospital course, the mean of length of stay in the regular unit was 4.55 ± 26.94 days (ranging from zero to 21 days) and the mean of ICU length of stay was 24.11 ± 14.22 days (ranging from 6 to 52 days).2O (ranging from 10 to 18) and median FiO2 of 70% ± 19.64 (ranging from 40 to 100%). On average, the thoracic complications occurred on day 6 (±8.34 days) after intubation (ranging from 1 to 28 days).Most of the patients were on a maximum ventilation setting, and the mean duration of ventilatory support was 21.00 ± 14.9 days (ranging from 3 to 52 days). Two patients (11.1%) required reintubation, ventilatory setting programmed on pressure-regulated volume control (PRVC), with a median positive end-expiratory pressure (PEEP) of 14 ± 2.40 cmHFour patients (22.2%) developed pneumothorax , six patP values of 0.034 and 0.007, respectively. The patients who required reintubation and those who had pneumothorax tend to have better prognosis.There was a significant association between reintubation and the occurrence of pneumothorax and the outcome with P value 0.005), reintubation , outcome , and duration of ventilatory support . Pneumothorax showed significant associations with duration of ventilatory support  and outcome . A significant association between the duration of ventilatory support and reintubation was also noticed  and with outcome .Furthermore, multivariate correlation  revealedThe Kaplan–Meier test was performed for analyzing the expected time of death in our sample depending on the intervention . Insertion of the thoracostomy tube was associated with significantly better outcome and better survival rate . The surP value 0.026). However, it did not have an effect on the outcome  who developed SE and ME without pneumothorax, the conservative approach is well accepted . But, weA significant difference was observed between the total COVID-19 patients who were admitted in the ICU without development of thoracic complications and those who had thoracic complications in the total length of hospital stay, a reflection of the magnitude of these complications and their effect on patients.It seems that the disease process plays a strong role in the degree of lung parenchyma destruction and subsequent thoracic complications. The generalization of such complications is the result of barotrauma which is not accurate since the first SARS infection. It is a true marker for aggressive disease that required this index of suspicion and prompt intervention.Due to the retrospective nature of this study, small sample size, and the fact that there is no consensus of clinical pathway in the literatures for COVID-19 patients, further studies involving multiple centers and a greater number of patients are required to clarify more statistical benefits and associations.The COVID-19 pandemic has provided the medical world with multiple challenges. In terms of thoracic surgery, the occurrence of unusual thoracic entities and complications dictates the need to revisit some concepts. Noniatrogenic pneumothorax, subcutaneous emphysema, and mediastinal emphysema are well-known conditions, but their presence in the context of COVID-19 disease is a precursor for a dismal prognosis and outcome. The presence of pneumothorax may be associated with better prognosis and outcome compared to surgical and mediastinal emphysema. This would alert the critical care teams to have high clinical suspicion and to anticipate such complications.