Inhaled corticosteroids (ICSs) are an effective drug commonly used in asthma treatment. It is known that osteoporotic changes can occur secondary to steroid usage, depending on dosage and duration. The aim of this study was to compare radiomorphometric indices and fractal dimension on panoramic images of patients with asthma using ICSs and healthy controls. A total of 66 dental panoramic radiographs (DPRs) taken from 32 patients with asthma using ICSs and 34 healthy individuals were evaluated in this retrospective study. Panoramic mandibular index inferior and superior , mandibular cortical width (MCW), gonial index (GI), antegonial index (AI), mandibular cortical index (MCI), and fractal dimension analysis (FDA) were measured on DPRs.p=0.02), MCW (p<0.001), GI (p<0.001) and AI (p<0.001) values were significantly lower in the group of the asthma using ICSs than control group. However, the PMI-i (p ˃0.05) measurement, the MCI (p ˃0.05) and FDA values distribution were similar in both groups. PMI-s ( The use of ICSs in asthma patients can affect bone quality. The evaluation of PMI-s, MCW, GI, and AI on DPR can help determine the effect of this drug on the jawbones in the early period and select dental and surgical treatment plans appropriately. Key words:Asthma, corticosteroids, osteoporosis, radiomorphometric indices, fractal dimension. Asthma is a respiratory disease characterized by reversible airflow obstruction with airway inflammation and hypersensitivity. Asthma is a common chronic disease affecting from 1% to 20% of the population depending on the country and an estimated 300 million people worldwide. Although it is more common in women and individuals of low socioeconomic status, asthma can affect people of all ages and has a high mortality rate in elderly individuals  are the most effective anti-inflammatory drug used in the treatment of some chronic obstructive pulmonary diseases and asthma. ICSs improve lung function, symptoms and quality of life as well as reduce exacerbations and mortality in patients with asthma . Long-teThe most effective method for determining low BMD is dual-energy X-ray absorptiometry (DEXA). It is an expensive measurement tool that is easy to use in the clinic but not easily accessible for all patients. In addition, the most important disadvantages of the DEXA method are that it cannot distinguish between cortical and trabecular bone and it can elicit false-positive results . Dental Fractal dimension analysis (FDA), a statistical tissue analysis and it can be used to evaluate the microarchitecture of the mandibular bone mass and trabecular bone . AlthougThe present study aimed to evaluate the effects of ICSs commonly used in asthma treatment on BMD of mandibular bone using radiomorphometric measurements and FDA performed on DPRs.Materials and Methods- Study DesignIn the study, subjects who had applied to the Oral and Maxillofacial Radiology Department of Akdeniz University, Faculty of Dentistry between January 2017 and December 2018 for various reasons and underwent DPR for any reason were retrospectively evaluated. The study of two groups: the patients with asthma using ICSs and the healthy control group. A total of 66 dental panoramic radiographs (DPRs) taken from 32 patients with asthma using ICSs and 34 healthy individuals were evaluated in this retrospective study. This study was limited to individuals between the ages of 18 and 45 years. Because endocrine changes specific to the onset of perimenopause have been shown to begin near the age of 45, this age was considered the age cut-off point.The patient group subjects were formed from those who use ICSs twice a day for maintenance treatment for at least one year according to the previous medical records and who did not have an acute asthma attack for the last one year.Inclusion criteria for the study group were the absence of any systemic disease, pathology, or drug use that could affect bone metabolism except asthma in the patients in the entire study group, and the absence of any disease, including asthma, in the control group. Radiographs of adequate radiographic quality were selected and the inferior mandibular border and one or both mental foramen should be visible on the DPR.Exclusion criteria for the study group were intrinsic artifacts and patient positioning errors on DPR, history of diseases that affect bone metabolism, history of malignancy or a benign lesion in the mandible, a documented history of consumption of any drugs affecting bone metabolism, history of maxillofacial trauma, and history of pathological fracture.- Obtaining RadiographsAll DPRs had been obtained using the same panoramic devices  with the same exposure parameters: . The Frankfurt plane of the patients was positioned parallel to the floor and the right-hand plane was parallel to the vertical plane of the device. All dental panoramic radiographs were recorded in DICOM image processing software.- Radiomorphometric MeasurementsPanoramic mandibular index (PMI), mandibular cortical width (MCW), GI , antegonial index (AI), mandibular cortical index (MCI), and FDA were measured on DPRs.Inferior panoramic mandibular index (PMI-i) and superior panoramic mandibular index (PMI-s) were calculated as the ratio of the mandibular cortical thickness in the mental region over the distance between the lower border of the mandible and either the inferior or the superior border of the mental foramen  Fig. 1)1). MCW iMCI is a method based on visual morphological evaluation of the mandibular cortex distal to the mental foramen on DPR. The types of MCI are as: C1, the endosteal margin of the mandibular cortex is continuous and sharp; C2, the endosteal margin of the mandibular cortex appears as semi-lunar defect or endosteal cortical residues; C3, the cortical layer is highly endosteal cortical residues and clearly porous  For the FDA, all the images were analyzed using ImageJ version 1.3 . ImageJ was used to measure linear distance and calculate fractal dimension by using the box-counting method recommended by White and Rudolph . RegionsAll DPRs were saved in TIFF format. After ROI was selected, the image was cropped and duplicated. Gaussian filter was applied to the duplicated image. The resulting images were extracted from the original images, and 128 shades of gray were added to each pixel. Bone trabeculae were distinguished to distinctively visualize the spaces between trabeculae. After the images were converted to black and white with the threshold option, the noise was reduced with the ‘erode’ and ‘dilate’ options. After applying the ‘invert’, ‘skeletonize’, and ‘analyze’ functions, FDA was calculated Fig. .In order to minimize the margin of error for the evaluator, all measurements on the DPRs were evaluated in the early hours of the day and in a dimly lit environment with no more than 10 patients per day. All radiomorphometric measurements were investigated in the DPR of all the subjects by an oral radiologist (S.G.Y.) with 10 years of experience who were blinded to the subject category. The radiomorphometric indices were Figured out bilaterally on the mandibular bone, and mean values were recorded. The measurements were done and the mean value was recorded for statistical analysis for PMI-i, PMI-s, MCW, GI, AI, and FDA. Regarding MCI, the opinion of a more experienced second investigator was sought for DPRs which cannot be decided.- Evaluation of Intraobserver ReliabilityThe radiographic measurements were performed by one of the authors. To test within-observer reliability, all measurements on 20 DPRs images (10 DPRs from each group) were re-evaluated one month later. The intra-observer correlation coefficient for qualitative data and kappa statistical tests for categorical data were used ,13. The - Statistical Analysisp ˂ 0.05.All statistical analysis was made using SPSS-version 22 for Windows . Basic descriptive statistical analysis and normality tests of all variables were performed. The normality test of the distribution was evaluated using the Kolmogorov-Smirnov method. Age, GI, AI, and FDA measurements were showed normal distribution but gender, PM-Ii, PMI-s, MCW, and MCI were nonparametrically distributed. To compare the results of the asthma patients using ICSs and healthy controls, Chi-square test was used to evaluate gender and MCI. Age, GI, AI, and FDA measurements distribution between the groups were evaluated with the Student t-test, and PMI-i, PMI-s, and MCW were evaluated with the Mann-Whitney U test. Statistical significance level was considered as the value of n = 66), the mean age of the patient group (n = 32) was 32.84 ± 9.11 years and the mean age of the control group was 34.88 ± 9.58 years. The age distribution of both groups was similar, with no statistically significant difference between them (p = 0.38)  .p = 0.14). PMI-s values were significantly lower in the patient group than in the control group (p = 0.02) (p < 0.001) (p < 0.001) (p = 0.32). There was no statistically significant difference between the groups in the distribution of MCI types (p = 0.24).  . When th< 0.001) . Both GI< 0.001) . There w= 0.24). . In all = 0.24). .Intraobserver reliability was ranged from good to excellent, for PMI-s, MCW, GI, AI, and FDA measurements. The weighted Cohen kappa coefficient was almost perfect for MCI with a 0.92 value. Intraobserver reliability value was obtained as a result of ICC analysis for qualitative data of radiometric indices are presented in This study found significantly lower PMI-s, MCW, GI and AI scores in patients with asthma using ICSs for more than one year compared to healthy controls. These results suggested that ICSs may cause osteoporotic changes in jawbone. While a previous study  has evalThe link between systemic steroids and osteoporosis is well established . In a pret al. (Han et al. , using tet al. . Providiet al. .DEXA is the gold standard for examining changes in bone structure in the general population . HoweverSeveral studies have evaluated BMD in different conditions and diseases using mandibular radiomorphometric indices ,11,23. Cet al. (et al. (The PMI index has been evaluated in many studies to detection of osteoporotic changes. Dagistan et al.  found a  (et al.  found a et al. (et al. (Dagistan et al.  reported (et al.  found th (et al.  also shoet al. (et al. (In light of the findings of previous studies, a low MCW score has been presented as a reliable indicator of osteoporosis ,23. Carmet al. , and patet al. , compare (et al.  performeet al. (In studies comparing patient groups with poorly controlled type 1 diabetes mellitus , and chret al.  found thet al. (et al. (AI is the measurement of the cortical width in the region anterior to the gonion at a point identified by extending a line of best fit on the anterior border of the ascending ramus down to the lower border of the mandible. It provides an important panoramic view of osteoporotic changes. Dagistan et al.  evaluate (et al.  also fouMCI calculated on DPRs has been reported in some studies as a repeaTable and reliable indicator of mandibular bone changes and low BMD . On the et al. (In the literature, there are studies in which FDA was used in the evaluation of trabecular bone structure in patients with different systemic diseases ,11,16,26The present study has several limitations that warrant mentioning. First, it had a single-center, retrospective and cross-sectional design. Cross-sectional investigations lack the power to show true-negative results and bias can be introduced if the case and control groups are not properly matched. Second, the study had a small sample, decreasing the likelihood of finding significant differences and increasing the risk of missing real differences. Third, the DEXA measurement values of the entire study group were not available. Fourth, the osteoportic changes in the mandibular bone could not be evaluated in patient group with asthma who did not use any medication.In the present study, it was shown that ICSs cause osteoporotic changes in the mandibular bone. Professionals in dental and oral surgical practices should consider that these side effects of ICSs, which are widely used for the treatment of individuals with asthma, increase the risk for dental health complications.Future studies evaluating the pre-treatment and post-treatment radiographs of patients with asthma who have received the same dose and duration of ICSs compared with a control group of similar age with no additional systemic diseases can contribute to the literature by supporting our results with clinical and laboratory parameters.


Ventricular septal rupture (VSR) is a serious complication occurring after myocardial infarction (MI). Cardiogenic shock (CS) is a common complication of VSR and an important factor affecting its prognosis. CS can occur in either an immediate or delayed manner after VSR; however, studies on the risk factors associated with immediate or delayed CS are scarce.We retrospectively studied patients diagnosed with VSR after MI and admitted to the West China Hospital between September 2009 and August 2023. Demographic data, medical history, physical examination results, electrocardiograms, and echocardiographic and hematological data were extracted from electronic medical records or archived records. CS was defined as hypotension (<90 mmHg) and/or the requirement for catecholamines, pulmonary congestion, and signs of end-organ failure. The CS onset time was defined as the time at which catecholamines were initiated.A total of 88 patients with VSR after MI, including 49 males (55.7%), were enrolled. The average age was 70.2 years. Of these patients, 32 (36.4%) who already had CS at the time of VSR discovery were defined as immediate CS, and 28 (31.8%) who developed CS within 2 weeks after VSR discovery were defined as delayed CS. A smaller left ventricular end-diastolic diameter (LVEDD) and VSR discovered after admission were independent risk factors for immediate CS. Elevated heart rate and higher levels of creatine kinase-MB isoenzyme on admission were independent risk factors for delayed CS in patients without immediate CS after VSR.The occurrence of CS in patients with VSR after MI has an evident time course. Thus, an early identification of patients at risk of immediate or delayed CS and optimization of treatment procedures may help improve the prognosis. Ventricular septal rupture (VSR) is a serious complication occurring after myocardial infarction (MI), with a reported incidence rate of 0.2%–0.3% in the era of thrombolysis and primary percutaneous coronary intervention (PCI) , 2. RepaWe retrospectively studied patients diagnosed with VSR after MI who were admitted to the West China Hospital between September 2009 and August 2023. All patients with discharge diagnose, including MI and VSR, were included in the study. Patients with ventricular septal defects due to endocarditis, congenital heart disease, or trauma were excluded. Data were extracted from electronic medical or archived records. History of smoking, height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate were obtained from the admission records. Hypertension, diabetes mellitus, history of coronary heart disease, and pneumonia were derived from the discharge diagnose. CS was defined as hypotension (<90 mmHg) and/or the requirement for catecholamines, pulmonary congestion, and signs of end-organ failure , 12. TheP < 0.05.Continuous variables were presented as means and standard deviations or as medians and quartiles, as appropriate. Categorical variables were presented as frequencies and percentages. One-way analysis of variance (ANOVA) or Wilcoxon rank-sum test was used to compare categorical variables among the three groups, and the least significant difference (LSD) test was used for pairwise comparisons between groups in ANOVA analysis. Categorical variables were compared using Pearson's chi-square test or Fisher's exact test. Univariate and multivariate logistic regression analyses (forward: LR) were used to compare odds ratios (ORs) with 95% confidence intervals (CIs) to assess the independent risk factors for immediate CS in patients with VSR after MI compared with patients without immediate CS and for delayed CS in patients without immediate CS after VSR compared with patients in the non-CS group. Age, sex, and variables with a statistical correlation with immediate or delayed CS in the univariate logistic regression analysis were included in the multivariable logistic regression analysis. The SPSS software package  was used for statistical analysis. Statistical significance was defined as Of the 119 patients with VSR after MI in our hospital, 88 were included in the analysis . The aveThe characteristics of the patients in the immediate CS, delayed CS, and non-CS groups are shown in Cardiogenic shock is a common complication of VSR after MI and an important risk factor for poor prognosis of VSR , 9, 10. The LVEDD is usually obtained in the parasternal long-axis section. It is a simple index commonly used to evaluate the size of the left ventricle (LV). The size of LVEDD in adults is affected by age, sex, height, weight, and heart disease status , 17. LV For patients who develop CS immediately after VSR discovery, the treatment should be aggressive, including vasoactive medications, IABP, and other MCS when necessary, to prolong the waiting time prior to repair , 10–12. Elevated heart rate is an important risk factor for poor prognosis after MI . Both anCK-MB level is a specific and sensitive indicator of myocardial injury . It can Our study had several limitations. First, this was a retrospective study from a single center, which is not always the first hospital to treat patients with acute chest pain, leading to selection bias. This may not fully reflect the overall occurrence of CS in all patients with VSR after MI, and the promotion of research results needs to be performed with caution. However, this study may reflect the basic characteristics of such patients in tertiary hospitals and provide references for management strategies. Second, owing to the limitations of retrospective studies, we were unable to determine the exact time at which CS occurred. Instead, the occurrence of CS was determined by two experienced physicians based on the BP, clinical manifestations, lactate levels, and medication use in medical records. The CS onset time was defined as the time at which catecholamines were initiated. Although there may be deviations, it can reflect the onset time of CS as judged by physicians at that time. Third, we may not have been able to find VSR at the first time when it occurred, and the chronological sequence of CS and VSR could not be definitively defined in patients in the immediate CS group. To avoid bias, we excluded patients who did not have VSR at the time of CS occurred but develop VSR subsequently, and those patients who were found to have VSR at the time of CS occurred were included in the immediate CS group.Our study indicates that the occurrence of CS in patients with VSR after MI has an evident time course. Smaller LVEDD and VSR discovered after admission are independent risk factors for immediate CS. In addition, elevated heart rate and higher CK-MB levels on admission are independent risk factors for delayed CS in patients without immediate CS after VSR. An early identification of patients at risk of immediate CS or delayed CS and optimization of treatment procedures may help improve the prognosis. Prospective cohort studies with larger sample sizes are required to verify our conclusions.


Autism spectrum disorders (ASDs) impair many aspects of everyday life and may prevent access to dental care, often limiting it to emergencies. Impaired oral health has long-lasting negative consequences on health status and on the acquisition of oral habits  or competencies . Children with ASD may be scared in the dental setting, which is rich in sensory stimuli and requires physical contact. Due to their behavioral manifestations, they represent a challenge for dentists and hygienists. We created a dedicated pathway with behavioral support for children with ASD to allow dental care and possibly limit the use of general anesthesia.n = 84) was visited every 2 months for 3 years and received additional support . A control group, matched for age and sex, was visited at least twice a year or more, if needed, according to standard healthcare guidelines.We evaluated the effects of behavioral support in a quasi-experimental design by comparing two groups of children with ASD. The first group (Compliance with the schedule was high throughout the 3 years. The degree of collaboration significantly improved after 1 year in the supported group, while the control group did not change. At the end of the study, collaboration remained significantly higher than at the beginning in the supported group. Half of dental treatments were possible without general anesthesia in supported children. No adverse effect was apparent on collaboration due to COVID-19 restrictions.Behavioral techniques improved the compliance of ASD children to regular dentistry visits and treatment. Furthermore, oral hygiene at home was similarly improved, addressing oral health from a lifelong perspective. The prevalence of autism spectrum disorders (ASDs) is increasing with similar prevalence worldwide, reaching 1 in 100 children . The onsAt variance with many other fields in health sciences, most articles on dentistry for ASD children come from a variety of countries from all over the world, underlining the spread of this issue throughout human cultures. Sadly enough, even recent studies sustain the use of physical restraint for persons with intellectual disabilities or general anesthesia as the other option . HoweverSince the literature on the efficacy of psychological techniques for the dental management of autistic patients is scarce , mostly Moreover, most of the available data come from surveys completed by parents/caregivers and suggest great difficulty for caregivers and dentists in dealing with ASD patients . As a reBehavioral interventions are highly effective in improving a variety of social deficits  and reprN = 86; two quit the project after the first visit), according to the following inclusion criteria: They were 4 to 13 years old at the beginning of the treatment, formally diagnosed and recognized as having autistic spectrum disorder (ASD), in some cases in the frame of genetic syndromes, or pervasive developmental disorder—not otherwise specified (PDD-NOS), a diagnosis present in the Diagnostic and Statistical Manual of Mental Disorders—DSM4—later merged to ASD in DSM5. Exclusion criteria were as follows: age outside the selected range, additional diseases, in particular those preventing autonomous oral hygiene , familiarity with dental treatments, and good acceptance of dental treatments. Selected patients were not yet regularly seen by dentists, but in some cases, they had received some dental treatment for urgencies before the beginning of the study.This study was approved by the Ethical Committee of the Province of Padova, CESC Code 4578/U6/18, according to Italian law. It was carried out at the Community Dentistry Department  of the “N = 84) served as a control. They were matched 1:1 for age, sex, and diagnosis to the abovementioned group. They were selected for matching the characteristics (age and sex) of the first group on a patient-to-patient basis, among the patients meeting the inclusion criteria of the study, but whose caregivers were not available to adhere to the strict 2-month visit schedule. Patients in this control group were asked to visit at least twice every year, or more if needed, but without a fixed 1-h duration of the visit, visual pedagogy instruments, or parent training. Some children from both groups were scheduled for treatments under general anesthesia when needed from a clinical point of view, without difference in their group affiliation.A second group of ASD patients . Caregivers decided whether to stay on the usual treatment (visits every 6 months) or comply with the study requirements. In this case, a map with the pathway from the parking place to the operating room was sent via e-mail, including details of the building  to familiarize children with the environment. The first physical meeting was devoted to detailed explanations about the project and the signature of informed consent; a weekly diary was also given to take notes about oral hygiene habits; and a plastic mirror was given to be used at home. An anamnestic interview was carried out by the dentist in charge of the case on clinical history, information on therapies  and preferred activities, and the use of positive or negative reinforcers for shaping behavior. The child was set free to explore the environment unless he/she was already cooperative and free to sit in the dentist's chair.From the second visit, the protocol was adapted to the needs of every child. It included visual pedagogy (if needed) to show the steps for oral hygiene to be tried first in the dental office and then at home. The images  were alsThe primary outcome was the degree of collaboration assessed by the dentists  at the end of each visit, measured on the Frankl scale , from 0 *Power 3.1.9.6  and Latent GOLD for hierarchical clustering  modeling, which allowed us to identify homogeneous groups of visits similar in the attitude of patients and groups of patients similar in their composition of types of visits. Multilevel LC (MLLC) models perform clustering at both levels of the data, taking into account between- and within-group heterogeneity , 36.Latent class (LC) analysis assumes that one or more latent variables exist and that these variables can be measured through their relationship with observed variables, also known as indicators. LC analysis takes into account the categorical  nature of these variables.LC analysis can be seen as a model-based method for clustering. It is an interesting alternative to k-means clustering as it is very flexible. It was originally designed for categorical variables, but it can also treat continuous ones; it deals very easily with mixed-scale observed variables. Model specifications and assumptions on parameters can be tested with rigorous statistical tests . In the The study has been described and reported using the TREND guidelines , 38.n = 18). Hence, in these 84 children with ASD, a total of 342 dental treatments were done, 49.7% of which were in the dentist's chair, in order to cure 37.23% of teeth (a single tooth could receive more than one treatment).Of the 86 patients initially enrolled  to follon = 93), in the caregivers' arm (n = 20), or in the pushchair (n = 3)  . Once th (n = 3) , while t (n = 3) . The airThe degree of collaboration at each appointment is shown in N = 73, 87.95% of patients; see p < 0.0001, Wilcoxon test), mean difference (0.671), and CI (0.489–0.854).We first asked whether there was a difference in collaboration between the first visit and the last visit. As the total number of visits varied because of possible missing visits or increased frequency for clinical reasons, we chose visit 15 because of possible delays, meaning 5 visits/year and representing an advanced stage in the program that was reached by most of the patients . Compared with the first visit, the degree of collaboration was significantly higher from visit 9 onward (Dunn's multiple comparisons test). From visit 7 onward, there was no statistically significant difference in collaboration with subsequent visits, suggesting that the improvement in collaboration was reached during the first six visits, which encompasses the first year of treatment. Already at visit 6, the mean value for collaboration was 1.466 (CI 1.300–1.631), while the median improved from 1 at the first visit to 2 at the sixth visit, indicating that 50% of the children reached a good degree of collaboration . However, during the second and third years of the project, the COVID-19 pandemic posed a great threat to autistic persons, possibly delaying or impeding any further possible improvement in collaboration. Nevertheless, it is noteworthy that the achievements of the 1st year were neither lost nor impaired, despite the increased difficulties in accessing the hospital and the department.Actually, the degree of collaboration varied among the first 15 visits , as children with a diagnosis of ASD are less collaborative. The association between collaboration and age can be in part biased by the fact that during the 3-year project, children were growing older and improving their collaboration as a result of their participation in the project. Concerning diagnosis, the older PDD-NOS  diagnosis was usually used for symptoms milder than those for autism diagnosis and was often used in toddlers/young children before releasing a clear diagnosis of autism. Hence, it is conceivable that the ASD group includes more severe, and hence less collaborative, cases compared with PDD-NOS.Collaboration was associated with sex (Somers' D: 0.132), being slightly but significantly higher in male participants , indicating that collaboration is not operator-dependent in the present setting. We expected that hygiene could be less invasive than dentist visits. However, when looking at the type of visit, whether hygiene or dental, a similar trend was observed. By summing all the positive responses to all the variables that described the phases of the visits , the mean number of accepted actions increased with the number of visits for both hygiene and dentist visits, as shown by simple linear regression  are as follows: 0.2432 (0.049), 0.1122 (0.358), and 0.3518 (0.045), respectively, and they are significantly different . During professional hygiene visits, the increase in the number of accepted actions was significantly different from zero for welcome and dentist procedures , but not for hygiene treatments . For dentist visits, the fitted regression model for the welcome procedure was Y = 0.1491*X + 2.747, R2 = 0.7382; for hygiene procedures, the model was Y = 0.07274*X + 0.2143, R2 = 0.9476; and for dentist procedures, Y = 0.1209*X + 3.416, R2 = 0.9237. The three slopes (standard error) are as follows: 0.1491 (0.023), 0.0727 (0.004), and 0.1209 (0.009), respectively; and they are significantly different . During dentist visits, the increase in the number of accepted actions was significantly different from zero for welcome procedures, F = 39.49, p < 0.0001; for hygiene procedures, F = 252.90, p < 0.0001; and for dental treatments, F = 169.5, p < 0.0001.Collaboration was not significantly associated with the type of visit (hygiene or dentistry)  allowed for the identification of four groups of visits, clustered by patients' behavior and groups of similar patients. The classification of visits  does notp = 0.032), with older patients being more collaborative. The effect of age may include developmental issues and the effect of more visits received during the project.Subsequently, each patient was assigned to one of the four groups according to their behavior during each visit . The behp = 0.149, Mann–Whitney test), the experimental group experienced a significant improvement in collaboration , while the control group did not . Notably, positive collaboration degrees 2 or 3, which allow easy treatment at the dentist chair, changed from 9.52 to 50% in the experimental group but only from 29.41 to 33% in the control group [chi-square 13.942, p < 0.0002 . While no difference in collaboration was apparent at the first visit between the groups  and professional oral hygiene in all patients were performed without the need for sedation or general anesthesia.p = 0.638, Mann–Whitney test). In detail, 71 children maintained the same level, 8 improved by one level, and only 4 worsened by one level.Finally, we asked whether the lockdown experience for COVID-19 (from 8 March 2020 to 28 May 2020 in our country) influenced the collaboration degree. The last appointment before the lockdown was compared with the first after the lockdown (between May and June 2020): Out of 83 patients for which the comparison was possible, no significant change was detected . Hence, we underline the strength of the achievements, which appear resilient to the changed regulations for hospital access and use of personal protective equipment. This is relevant considering the lifelong management of ASD patients in the dental setting, which may improve and maintain their overall health.Professionals should be aware of the conditions shown by each patient and of the most powerful techniques for managing them. Dentists may ask for support from other healthcare workers  to instruct caregivers and patients themselves to maintain proper oral hygiene . Some baThe original contributions presented in the study are included in the article/The studies involving humans were approved by Ethical Committee of the Province of Padova, CESC Code 4578/U6/18. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants' legal guardians/next of kin.IP: Conceptualization, Investigation, Writing—review & editing. EB: Investigation, Writing—review & editing. GM: Investigation, Writing—review & editing. FB: Writing—review & editing, Formal analysis, Validation. CG: Writing—review & editing, Conceptualization, Funding acquisition, Supervision. CM-C: Conceptualization, Supervision, Data curation, Formal analysis, Methodology, Visualization, Writing—original draft.


Mycobacterium avium keratitis, first detected in the laboratory, which is from an 81-year-old female patient with a 13-year history of recurrent keratitis after eye injuries. This patient underwent anterior chamber irrigation of the right eye, and autologous conjunctival flap covering plus medication, and the corneal ulcer healed. She recovered well after continuing with the medication for half a year. The patient was not immune-compromised. Complex eye diseases such as blurred vision and cataracts caused by advanced age, delayed symptoms caused by slow growth of Mycobacterium avium and low-grade inflammation, difficulty with laboratory culture, repeated medication use, and repeated illnesses were the main reasons for the prolonged failure to clarify the etiology of this case. Morphological examination provided important clues for the initial discovery of pathogenic bacteria. Remind to pay attention to the morphology of Mycobacterium under Gram staining and Rui’s Giemsa staining. Acid fast staining and Deoxyribonucleic Acid(DNA) microarray chip method can be used as indicators for rapid diagnosis of Mycobacterium species.We report a case of  Mycobacterium avium complex (MAC) are the main members of non-tuberculous Mycobacteria (NTM), and they are the mycobacteria with the most new species and subspecies discovered. They are opportunistic pathogens that are ubiquitous in the environment. Infection rates have been rising in recent decades, and people with weakened immune systems are susceptible. Infection can affect a variety of tissues and organs, especially in the lungs, lymph nodes, skin, and soft tissue and in the form of disseminated disease and osteomyelitis. Eye infection is rarely reported. Ophthalmia is an inflammatory reaction that occurs inside and around the eyes which can be caused by both infectious and non-infectious factors. Infectious factors are associated with microbial infections, such as bacterial, viral, fungal and Rickettsia, chlamydia and so on. Non-infectious factors are usually caused by external stimuli such as smoke, dust, ultraviolet, trauma, acid-base burn. Part of ophthalmia are related to autoimmunity. The disseminated infections caused by MAC include ophthalmia in immunocompromised populations, such as those with acquired immunodeficiency syndrome, those positive for neutralizing antibodies for serum anti-interferon-γ (Mycobacterium avium intracellulare (MAI) keratitis is rare, and trauma and surgery are major risk factors , and she did not seek treatment. In May 2009, she first visited the doctor because of recurrent redness and pain in the right eye with blurred vision. The Best Corrected Visual Acuity(BCVA) vision was finger count for 50cm in 2009.The clinical diagnosis was keratitis in the right eye, complicated by cataract. Levofloxacin eye drops, Tobradex eye drops, Ganciclovir eye drops, and recombinant basic fibroblast growth factor eye drops alleviated the symptoms. In 2012, she went to the hospital again because the symptoms of red, pain, blurred vision in her right eye relapsed. At that time, the BCVA was 0.01. The clinical diagnosis were keratitis in the right eye, dry eye and cataract in both eyes. Cyclosporine eye drops, Tobradex eye drops, and Eyprotor eye gel eased her symptoms. After that, she was treated several times for recurring illnesses and came to our hospital with worsening illnesses 2 months ago. Eye examination showed light perception in positioning accuracy in the right eye and BCVA 0.12 in the left eye. Intraocular pressure: right 11.2 mmHg, left 13.5 mmHg . The nasal conjunctiva of the left eye and its underlying connective tissue had abnormal hyperplasia, invading the corneal limbus for approximately 2 mm. Accord to Lens Opacities Classification System II(LOCS II), the lens wasC2N2P1. and the rest was normal. The conjunctiva of the right eye had mixed congestion, and the nasal conjunctiva and its underlying connective tissue had abnormal hyperplasia and invaded the corneal limbus by approximately 2 mm. The cornea was edematous and opaque, and the Descemets folds.A round ulcer was seen in the center of the pupil, with a size of approximately 4 mm×4 mm, and the local corneal tissue in the center of the lesion was defective, thin, with gray and white opacities around it and at its base Figure 1Mycobacterium avium infection. Moxifloxacin eye drops were administered for once an hour, sodium hyaluronate eye drops were given for twice an hour, and rifapentine 0.45 twice daily, ethambutol 0.75 once daily, moxifloxacin 0.4 once daily, and clarithromycin 0.5 once daily were given orally. After 10 days of treatment, the patient’s vision wasn’t change, the eye pain and photophobia were relieved, and the size of the ulcer was the same as before.Due to the patient’s long course of disease and repeated disease, the corneal ulcer was grey and turbid focus in appearance, so fungal keratitis was likely. Empirical antifungal (customized voriconazole drops 0.02%) treatment was administered first, while corneal scrapings were sent for examination, all of which were negative. After several days of treatment, the patient’s symptoms were not alleviated but even worsened, suggesting that the clinical judgment was wrong, so the corneal scraping was sent again for examination, and the Gram stain was negative for fungi. Unstained rod-shaped microorganisms were seen in the background : slight chronic inflammation in both lungs. No congenital or acquired immunodeficiency, no MAC infection found in other areas.Mycobacterium avium keratitis usually has a long time from infection to onset, with reported cases of 21 months  microarray chip method can be used as indicators for rapid diagnosis of Mycobacterium species.In conclusion, we report a case of The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Written informed consent was obtained from the individuals for the publication of any potentially identifiable images or data included in this article. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.XC: Data curation, Writing – original draft. HW: Writing – review & editing. KW: Methodology. SL: Resources. BL: Investigation. ML: Validation.


One in three women of reproductive age is obese. The mainstay treatment for obesity is bariatric surgery, and the following weight reduction results in a decrease in pregnancy adverse effects, including gestational diabetes mellitus, pregnancy-induced hypertension, and macrosomia. However, nutritional and vitamin deficiencies due to changes in the gastrointestinal tract after bariatric surgery are associated with an increase in the risk of fetal growth retardation and small for gestational-age neonates. The purpose of this review was to analyze the available recent literature on the subject of the management of pregnancy after bariatric surgery. We searched for available articles from 2007 to 2023 and chose articles of the greatest scientific and clinical value. Micronutrient, vitamin, and protein supplementation is recommended in the prenatal period and throughout the pregnancy. It is advised that pregnant women with a history of bariatric surgery should be provided with regular specialist dietary care. There is still a lack of recommendations about the optimum gestational weight gain after different types of bariatric surgery and for patients of different metabolic statuses. Women of reproductive age undergoing bariatric procedures should be provided with appropriate counseling about adequate contraception, the recommended time-to-conception interval, and the positive and negative influence of bariatric surgery on perinatal outcomes. Obesity is an important health problem worldwide, and the number of obese patients has doubled over the last two decades, being present in one in three women of childbearing age. Obesity is associated with numerous co-morbidities, including diabetes mellitus, hypertension, and obstructive sleep apnea, but also negatively influences fertility in both sexes and maternal and fetal outcomes. Obesity in pregnancy increases the risk of gestational diabetes mellitus (GDM), pregnancy-induced hypertension  infants . ObesityAlthough the positive impact of BS on weight is undeniable, bariatric procedures influence dietary and nutritional intake . BS leadThe purpose of our study was to present available up-to-date guidelines for the management of pregnancy after bariatric surgery, with special recognition of recommendations for nutrition and dietary supplementation.The PubMed MEDLINE, Scopus, and Cochrane scientific databases were searched for original articles on the subject of management of pregnancy after bariatric surgery that had been published between 2007 and 2023. The research was performed by three independent researchers under the supervision of two senior researchers, and articles were retrieved using Google Scholar. The terms that were searched for were: “nutrition in pregnancy after bariatric surgery”, “supplementation in pregnancy after bariatric surgery”, “vitamin deficiencies in pregnancy after bariatric surgery”, “diabetes mellitus in pregnancy after bariatric surgery”, and “surgical complications in pregnancy after bariatric surgery”. Additional manual searches were conducted for the lists of references found according to the article’s novelty, quality, and clinical relevance. The review was divided into chapters, including the most common nutrient, micronutrient, and vitamin deficiencies, dietary supplementation, optimum time-to-conception after bariatric surgery, gestational weight gain, diagnosis of diabetes mellitus, pregnancy outcomes, and surgical complications.Coupaye et al. analyzed 123 s-trimester pregnancies and found disparities in the distribution of micronutrient and vitamin deficiencies after different types of BS. The caloric intake did not differ between SG and RYGB groups, but the protein intake was lower after SG. Women after RYGB were more likely to take multivitamins and other dietary supplements. Hemoglobin, calcium, and vitamin E levels were lower in the RYGB group, and there was a higher risk of vitamin B12 deficiency. Additionally, the RYGB group had higher levels of parathyroid hormone. There were no differences found between the groups in the serum albumin levels and urea excretion; the selenium and iron deficits were similar in both groups. Low protein and iron levels were correlated with impaired intrauterine fetal growth .Rottenstreich et al. performed a systematic review of 27 articles that comprised 2056 pregnancies after BS. The reported deficiencies were common and included vitamins A, B1, B6, B12, C, D, and K, iron, calcium, selenium, and phosphorous. The adverse effects reported in the studies were anemia due to iron and B12 deficiency, urinary tract infections due to vitamin deficiencies, and night blindness due to vitamin deficiency. Iron, folate, and vitamins B1, B12, and D are found both after restrictive and malabsorptive procedures, while vitamins A, K, and E, calcium, zinc, and copper deficiencies are found mostly after malabsorptive procedures. The prevalence of anemia in pregnant post-bariatric patients differed between the studies, from 17% up to 77% of patients. A total of 10% to 16% of patients had to be treated with intravenous iron supplementation throughout pregnancy, and 3% to 17% required blood transfusion. A higher prevalence of anemia was correlated with a longer time-to-conception (TTC) interval. Vitamin A deficiency was found in up to 90% of post-bariatric pregnant patients, and night blindness was found in 57% up to 87% of patients [Anemia in pregnant patients after BS mostly results from vitamin B12, iron, or folate deficiency, but unexplained anemia that is not treated by classic supplementation should be investigated, as it can be a symptom of copper or zinc deficiency . As zincMicronutrients and vitamin deficiencies after BS do not diminish the importance of breastfeeding. Women after BS should receive appropriate supplementation and should be encouraged to breastfeed . MineralMultivitamin and mineral supplementation prior to conception and throughout pregnancy is recommended by all international guidelines considering pregnancy after BS . The mulFolic acid supplementation after BS is still being discussed. For pregnant women who remain obese after BS, the recommended daily dose of folic acid before conception and in the first trimester is 4–5 mg. However, it is not recommended for the whole population after BS because folic acid deficiency is less common than vitamin B12, especially in patients after MS, and over-supplementation of folic acid can mask the symptoms of vitamin B12 deficiency despite augmenting neurological defects. Most studies do not show a higher prevalence of folate deficiency in pregnant patients after BS than in the general pregnant population . Some stIron deficiency anemia is defined by hemoglobin levels below 105 g/L and ferritin levels below 30 μg/L. The minimum recommended daily dosage of iron is 45 mg of elemental iron (18 mg after AGB); however, it has to be adjusted according to the patient’s ferritin and hemoglobin levels . IntraveThe retinol form of vitamin A is teratogenic and, therefore, should be avoided during pregnancy. Vitamin D should be maintained at a level of at least 50 nmol/L (or 75 nmol/L depending on different recommendations), and the serum parathyroid hormone should be within normal limits, with a possible additional supplementation of calcium. Other studies recommend supplementation of calcium in all pregnant patients after BS . There iThe serum levels of the following parameters should be checked at least once a trimester: full blood count, including hemoglobin, ferritin, transferrin, folate, vitamin B12, vitamin D, calcium, magnesium, phosphate, and parathyroid hormone, followed by vitamin A, prothrombin time, INR, vitamin K1, protein, albumin, and renal and liver function tests. If any deficiencies are found, the intensity of exams should be adjusted for the optimum monitoring .The diet of pregnant women should be planned with a bariatric dietitian and specialistic dietary care should be maintained throughout the pregnancy. The diet should be prepared individually based on the type of BS, TTC, pre-pregnancy body mass index (BMI), gestational weight gain (GWG), physical activity, and individual food preference and tolerance. General rules include small but frequent meals, long chewing, drinking between (not during) meals, and avoiding simple carbohydrates. According to some studies, pregnant patients who have had BS may require an additional 200 kcal per day . GWG is International guidelines clearly state that it is not recommended to begin pregnancy in a period of rapid weight loss after BS. The length of the catabolism period differs between the patients, depending mostly on the pre-surgery BMI and the type of surgery. In most patients, weight stabilization is achieved a year after surgery. Conception is recommended after at least 2 months of plateau of body weight. The recommended TTC differs between guidelines from 1 to 2 years after BS p = 0.002) and lower birth weight and inadequate GWG (p = 0.03); however, the study showed no significant correlation between TTC and PIH, and GDM and neonatal outcomes [p = 0.04) [During the rapid weight loss period, there is a high risk of nutritional deficiencies and, subsequently, the impairment of fetal growth or spontaneous abortion. Different studies confirm that pregnancies started under 12 months after BS are associated with a higher risk of inadequate gestational weight gain (GWG), which, in consequence, can negatively influence fetal growth ,27,28. Aoutcomes . In a re = 0.04) .p = 0.02), with no differences between groups with a TTC interval of 12 and 24 months and >24 months [However, there are studies contraindicating the necessity of maintaining a TTC interval after BS. Froylich et al. analyzed 95 pregnancies after laparoscopic sleeve gastrectomy (LSG), comparing three groups with TTC intervals of < 12 months, 12–24 months, and >24 months. They found no significant differences in pregnancy course or complications and the neonates’ weight. The possible bias of the study was the size of the groups and the history of only one type of BS, but the results are interesting and to be further studied . The stu4 months .A study in a cohort of 1464 patients after BS who gave birth in the United States between 2011 and 2017 found that more than 85% of births occurred within 21 months after BS. Chao et al. found that delivery during the 2 years after BS was not associated with an increased risk of surgical reinterventions . AdditioGestational weight gain is positively associated with the fetal growth ,36. Therp = 0.002) [In a study by Heusschen et al., GWG was analyzed in correlation with time to conception after BS. Patients were divided into three groups: early (less than 12 months after BS), middle (12 to 24 months after BS), and late (more than 24 months after BS). Pregnancy in the early group was associated with lower gestational weight gain and lower neonatal birth weight. Inadequate gestational weight gain was associated with lower gestational age at delivery  . These rThe incidence of GDM in pregnancies following BS has been shown to be lower, with one reason being the improvement in insulin resistance. The risk of developing GDM remains higher in women who remain obese after BS. An oral glucose tolerance test (OGTT) is not recommended in pregnancies after BS because there is concern about its tolerability, safety, and accuracy . Fast inAccording to recent studies, there is a correlation between hypoglycemic events in pregnancies after BS and decreased birth weight of neonates. Women who had hypoglycemia during OGTT had a higher risk of repetitive hypoglycemic events in pregnancy and, therefore, intrauterine growth retardation (IUGR), and there was an association found between the maternal glucose nadir during OGTT and fetal growth restriction . The altAccording to most studies, patients after BS have a reduced risk of fetal macrosomia, PIH, preeclampsia, and GDM, whereas the risk of IUGR and SGA is increased ,46,47. Ip = 0.031), congenital anomalies , preterm birth , and NICU admission . After RYGB, but not AGB, odd ratios for SGA were higher , and for LGA, ratios were lower . The incidence of post-term birth was decreased after BS . The birth weight of neonates born to mothers after BS  was more than 200 g lower than that of those born to mothers without prior BS  [A systematic review and meta-analysis by Zakhter et al. analyzed adverse perinatal outcomes of 14,880 pregnancies after BS. A history of BS  increased the risk of perinatal mortality  .BS is known to be associated with a higher risk of IUGR. There is a correlation between maternal protein deficiency, more common after BS than in the general population, and the rate of incidence of IUGR and small for gestational age (SGA) neonates. The risk of IUGR in most studies is higher in patients after MS . There ip = 0.018) and SGA infants (p < 0.001) [Most studies indicate a 2–3-fold decrease in the incidence of GDM after BS, with reduced insulin resistance as an explanation . There a< 0.001) .p <0.001) [p = 0.006) [There are conflicting findings about the rate of CS, though most studies indicate an increase in the rate of CS after BS. In a cohort of 53,950 pregnant patients after BS, Youssefzadeh et al. found that the rate of CS was higher in women with a history of CS than in women without prior BS  . However= 0.006) .There are only case series and small cohort studies available on the subject of surgical complications after BS. The risk of serious complications that require surgical intervention during pregnancy is incomparably higher after RYGB than after SG. Pregnancy can increase the risk of internal herniation due to an increase in intra-abdominal pressure and displacement of the small intestine as the pregnant uterus grows. Internal herniation can lead to obstruction of the small intestine and the following necrosis that can be avoided only with early surgical intervention. The rate of incidence of internal herniation after RYGB is reported as 2–12% .Clinical presentation of internal herniation can be mistaken for typical symptoms in pregnancy: abdominal pain, in most cases, postprandial, nausea, and vomiting. It is of extreme importance to increase patients’ awareness of the risk of this complication. A patient with the symptoms mentioned above that appear in pregnancy after BS should report herself immediately to an emergency ward, as there is a risk of maternal and fetal death, especially more than 48 h after the beginning of symptoms. The patient should report to a center with both bariatric care and maternal and neonatal care, as it can reduce the rate of both maternal and neonatal mortality to 0% . In any Another type of surgical complication in pregnancy after BS is gastric band slippage, which can take place in up to 12% of pregnancies after gastric banding. The intra-abdominal pressure is increased by the pregnancy itself and can be aggravated by vomiting, the result of which can be gastric band slippage.p < 0.001) [Rapid and sustained weight loss after BS can lead to a sudden increase in fertility. A pregnancy is unadvised during the period of weight loss after BS for at least a year. Therefore, a female patient of reproductive age should receive contraceptive advice before and after BS. There is a low level of contraception counseling. A recent survey by Graham et al. asked 382 bariatric surgeons if they provided adequate information about contraception to reproductive-aged bariatric surgical patients. The response rate was low, at 17%; only 7% of bariatric surgeons reported having provided information about contraception to their patients . Mengesh< 0.001) .There is also a need to inform women about the positive and negative influence of BS on perinatal outcomes. Patients should be informed about the possible nutritional deficiencies, the importance of adequate diet and supplementation, and their influence on fetal growth, as patient compliance is crucial to optimum pregnancy care. In a study by Assaf et al., conducted in a group of 183 women after BS, aged 15–49, more than half of the participants were not aware of the influence of BS on perinatal outcomes .One of the main limitations of this study was that there were different lifestyle factors of the participants associated with their nationality, culture, religion, sociodemographic conditions, and their influence on patients’ nutrition. Additionally, there was no data considering the diet of the participants, and only a few studies presented information about the characteristics of the supplementation received by the participants. It is also impossible to determine the patient’s compliance, both according to diet and supplementation. Apart from the information about the possible masking of vitamin B12 anemia symptoms by overdosage of folic acid, we have not found any information about the risks and adverse effects of supplementation.Some questions remain unanswered. It is still to be established whether the minimum TTC interval of 12 months after BS to avoid adverse perinatal outcomes is necessary in all patients and after all types of surgeries, as the results differ between the studies. Most include more patients after RYGB, whereas SG is the most common bariatric procedure in Europe and leads to fewer micronutrients and vitamin deficiencies. As sleeve gastrectomy is associated with a lower risk of nutritional deficiencies and its consequences, including different types of deficiency, as well as surgical complications, we suggest it should be considered as the procedure of choice for women of childbearing age.There is still a lack of recommendations about the optimum gestational weight gain after different types of BS and within different TTC intervals and BMI. More prospective studies in large groups are necessary to establish the prevalence of various micronutrient deficiencies after different types of surgeries and in different populations. There is a lack of adequate pre-surgery counseling about optimum contraception and the positive and negative influence of BS on perinatal outcomes for reproductive-age women considering both surgery and procreation.


Eggs and their products are commonly consumed in food products worldwide, and in addition to dietary consumption, egg components are widely used in the food industry for their antimicrobial, cooking, and other functional properties. Globally, eggs are the second most common allergenic food after milk. However, current research on egg allergy primarily focuses on egg white allergens, while research on egg yolk allergens is not comprehensive enough. Therefore, summarizing and analyzing the important allergen α-livetin in egg yolk is significant in elucidating the mechanism of egg allergy and exploring effective desensitization methods. This paper discusses the incidence, underlying mechanism, and clinical symptoms of egg allergy. This article provides a comprehensive summary and analysis of the current research status concerning the molecular structural properties, epitopes, and immune cross-reactivity of the egg yolk allergen, Gal d 5. Additionally, it examines the effects of various processing methods on egg allergens. The article also offers suggestions and outlines potential future research directions and ideas in this field. In the past few decades, the number of patients with food allergies and the incidence of food allergies has been gradually rising. The prevalence of food-induced asthma and allergic rhinitis has increased significantly, and it is now considered a serious public health problem in developed countries. In the United States, it affects about 8% of children (corresponding to >5.6 million United States children), 10.8% of adults (corresponding to >26 million United States adults) .In theory, any food protein can be considered a potential allergen. However, the most common allergenic foods include milk, eggs, wheat, soy, peanuts, tree nuts, fish, and seafood . Most foEggs and their derivative products are commonly consumed worldwide . Due to The incidence rate of egg allergy is higher in infants and young children, in a recent evaluation of anaphylaxis in infants younger than 12 months of age, eggs were found to be the most common food trigger . However2.Lianto et al.  found th3.Egg allergens are concentrated in egg white and egg yolk. Of them, egg white allergens have been more extensively studied. Four egg white proteins have been identified as egg allergens. These four proteins are ovomucoid (OVM), which is named Gal d 1 according to the naming convention of the Allergen Nomenclature Sub-Committee of the World Health Organization/International Union of Immunological Societies (WHO/IUIS); ovalbumin (OVA), named Gal d 2; ovotransferrin (OVT), named Gal d 3; and lysozyme (Lys), named Gal d 4 . However3060H4818N826O936S55, an instability index of 45.12, and a grand average hydropathicity (GRAVY) of −0.347. The secondary structure of the protein was predicted using Garnier-Robson and Cho-Fasman methods, and the secondary structure of Gal d 5 was analyzed using SOPMA and DNAstar software. Their analysis revealed that α-helices, extended chains, β-sheets, and irregular curls accounted for 66.18, 4.23, 2.93, and 26.67% of the Gal d 5 sary structure, respectively.α-livetin was the first allergen discovered in egg yolk. It is a water-soluble 69-kDa globular glycoprotein, accounting for approximately 7% of egg yolk proteins. Huang et al.  analyzed4.Epitopes serve as the foundation for allergy research. In food allergic reactions, allergenic proteins directly interact with antibodies through allergenic epitopes . TherefoAt present, the understanding of food allergen epitopes remains in its early stages; however, relevant data on milk, peanut, and egg allergen epitopes have been obtained. The findings from later-stage research are anticipated to be applied in medical clinical diagnosis and treatment, playing a crucial role in the food industry , 43. ComResearch on epitopes of egg white allergens is far more extensive than that on epitopes of egg yolk allergens. For example, as early as 1992, the key B-cell epitopes of ovalbumin (OVA) were determined to be between positions 41–172 and 301–385 through peptide membrane and dot blot assays . Later, Bioinformatics plays an important role in revealing the structural information of Gal d 5. Our research team, led by Wang Guangyu, searched for a homologous model of the egg allergen based on the SWISS-MODEL homology modeling results . Wang GuIn addition to predicting linear and conformational epitopes, Huang et al.  used the5.Food cross-reactivity allergy can occur when a person consumes two or more different food products, they are allergic to , 52. SomAccording to the evaluation strategy recommended by FAO/WHO (2001), the criteria for determining cross-reactivity between a test protein and a known allergen are >35% homology or at least six consecutive identical amino acids. However, relying solely on the criterion of six consecutive identical amino acids can easily result in false positive outcomes due to the random arrangement and combination of amino acids in natural protein sequences. Consequently, in 2003, Codex Alimentarius Commission (CAC) revised these criteria to consider potential cross-allergenicity if any 80 amino acid sequences exhibit more than 35% homology or if eight consecutive amino acids are identical. Nevertheless, amino acid sequence homology should not be the only criterion for determining the potential allergenicity of proteins. Therefore, combining experimental testing with clinical diagnosis is an effective method for confirming the existence of cross-reactivity.in vivo and in vitro, and strong mutual cross-inhibition is noted between bird feather extracts and egg yolk but not between feather extracts and egg white  of the children exhibited allergic reactions to at least one type of egg . Mitomorgg white . In birdWang Guangyu  of our r6.in vivo tolerance response-ability for egg allergy is of considerable significance. Hypoallergenic egg products have been reported to be unresponsive to a significant proportion of egg-allergic patients  and prevent health risks caused by cross-reactive allergens in food. WJ is responsible for article retrieval and writing. CY is responsible for the arrangement and revision of the content of the article and the writing of the outlook of the article. All authors contributed to the article and approved the submitted version.This work was supported by National Science and Technology Major Project of China  and National Natural Science Foundation of China .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.


To our knowledge, this is the first study to address both sleep duration and psychological stress in association with GC risk. Long sleep was associated with gastric cancer, and its subsites and histological types, and stress increased the risk of noncardia cancer in particular. The two exposures exerted an independent effect on GC. These findings contribute to providing evidence for the role of sleep and stress in gastric cancer epidemiology.p for heterogeneity = 0.02 and <0.001, respectively). In conclusion, long sleep duration (≥9 h) was associated with GC and its subtype categories. Stress linearly increased the risk of GC and was related to noncardia GC.The association between sleep and stress and cancer is underinvestigated. We evaluated these factors in association with gastric cancer (GC). Five case-control studies from the Stomach Cancer Pooling (StoP) Project were included. We calculated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for sleep duration and stress level in association with GC through multiple logistic regression models adjusted for several lifestyle factors. The analysis included 1293 cases and 4439 controls, 215 cardia and 919 noncardia GC, and 353 diffuse and 619 intestinal types. Sleep duration of ≥9 h was associated with GC  compared to 8 h. This was confirmed when stratifying by subsite  and histological type . Stress was associated with GC . This relationship was selectively related to noncardia GC . The risk of diffuse  and intestinal type  were higher when stress was reported. Results for the association between increasing level of stress and GC were heterogeneous by smoking and socioeconomic status ( Helicobacter pylori (Hp), the improved level of hygiene and sanitation, and the decrease in tobacco smoking are among the reasons likely explaining this declining trend, together with better preservation and storage of foods and increased intake of fruits and vegetables [Hp, and of low socioeconomic status (SES) [Gastric cancer (GC) is one of the neoplasms that has shown large changes in incidence during recent decades . The idegetables ,3. A higus (SES) ,5,6,7. Gus (SES) . Based ous (SES) . The disus (SES) ,11,12,13us (SES) ,15,16,17Among potential lifestyle risk factors for cancer, sleep duration and level of stress remain underinvestigated. The meta-analysis by Chen et al. found no particular pattern of risk related to sleep duration, except from a positive relationship between short sleep and cancer in Asians and between long sleep and colorectal cancer . ConcernGiven that few studies investigated sleep duration and psychological stress in relation to GC risk, and given their physiological role in daily life, we aimed at describing the contribution of each of these two factors in the risk of GC and its subtypes through a pooled-analysis of five studies from the Stomach Cancer Pooling (StoP) Project Consortium.http://www.stop-project.org/ accessed on 15 May 2023) [This study is based on the StoP Project Consortium ay 2023) , which i , which 2).We excluded 29 studies, mostly due to lack of information on sleep duration and stress, or because >25% of missing values were present on the exposures or main confounders . Subjects with >10% missing data in the variable in the main regression model were excluded. Five individuals with extreme body mass index (BMI) were also excluded  and histological type  were available for all studies.Self-reported sleep duration was assessed based on the number of hours of night sleep—excluding daily naps. We consequently categorized sleep hours into 4 groups: ≤6, 7, 8, and ≥9 h. We used 8 h of sleep as reference based on the US National Sleep Foundation recommendation . PsycholHp status was not included in the analysis given the high number of missing values. For stress level, we estimated the odds ratios (OR) of GC for increasing psychological stress; concerning sleep duration, it could not be treated as a continuous variable because of the lack of linearity in the dose–response relationship (the reference was 8 h of sleep per night).The final regression models included terms for study, sex, age , smoking status , socioeconomic status , alcohol drinking , salt consumption , and vegetable and fruit intake . We conducted stratified analyses by sex, smoking status, SES, anatomical subsite (cardia vs. noncardia), and histological type . We also considered a potential interaction between sleep and stress.The effect of race/ethnicity (Caucasian/Black/Asian/Hispanic or Latin/others) and family history of GC in first-grade families (yes vs. no) were also explored, but they did not affect the results and were not included in the final models. Similarly, the main model was additionally adjusted for BMI to explore its potential confounding role.To assess the contribution of individual studies to the overall results, we repeated the pooled analysis within each single study, and excluding one study at the time.p-value lower than 0.05 was considered significant.All the statistical analyses were performed on STATA, version 16.1  . A two-tThe analysis included 5732 individuals, comprising 1293 GC cases and 4439 controls. The case group included 215 cardia and 919 noncardia GC, along with 353 diffuse and 619 intestinal types. p = 0.16 among controls), while a negative correlation was found with long sleep duration (p = 0.01).There was no correlation between stress level and short sleep duration . No difference was found by smoking status (p for heterogeneity = 0.622). Last, no difference was observed by SES (p for heterogeneity = 0.794), despite we observed only a significant association between ≥9 h of sleep and GC in individuals from low level .Results stratified by anatomical subsite within the stomach and histological type are reported in When considering stress levels, we included 843 GC cases and 976 controls.p = 0.01). The risk of diffuse GC increased in individuals reporting high levels of stress compared to low levels , with an OR for the continuous analysis equal to 1.32 (95% CI = 1.11–1.58); similar results were found for intestinal type  in subjects with high level of stress; OR for the continuous analysis equal to 1.23 .Results of the multivariable analysis are reported in p for heterogeneity = 0.651). No difference was found by age groups (p for heterogeneity = 0.684), while stress effect resulted to be slightly more pronounced among current smokers . Also, a significant heterogeneity was revealed for stress and GC by level of socioeconomic status .Despite the different distribution of stress levels in men and women, the stratified analysis did not reveal an effect modification by sex , suggesting that the normal/short-sleep pattern is overall more favourable.These results were confirmed for both major histological GC types, being slightly stronger for the diffuse type. In terms of anatomical subsite, as compared to cardia, noncardia GC showed a stronger association with both sleep duration and stress level.Stratification analyses showed a stronger effect of sleep duration in women and individuals aged 65 or older; concerning sex and age, no difference was found in the effect exerted by stress, while we observed a particularly increased GC risk in current smokers. Additionally, the effect of stress (but not that of sleep duration) on GC risk in low-socioeconomic-status vs. high-socioeconomic-status individuals showed opposite directions. Subjects from less affluent groups of the population may experience different economic and psychosocial problems than subjects from high social class. While this may explain at least in part the mechanism of reverse causality under the association between stress and GC which we found, this difference was not observed for sleep duration. Regardless, we suggest using this information with caution rather than considering it as definite findings, for which further studies specifically developed to investigate these exposures are needed.The interaction between sleep duration and stress level were consistent with a multiplicative model, suggesting independent effects on GC risk.p < 0.001).Sleep is fundamental in the biochemical and hormonal homeostasis in humans ,31. QualA nationwide case-control study conducted in Taiwan on data from 2001–2011 identified a significantly higher cancer risk in individuals with sleep disorders, and specifically breast cancer being linked to insomnia, parasomnia, and obstructive sleep apnea, this latter also causing nasal and prostate cancer in a range of risk between 1.70 and 6.00 .Few studies are available to compare our results on GC. To our knowledge, our findings are consistent with current literature on the topic, despite the relationship between sleep duration and GC is elsewhere described through a U-shaped curve that we do not observe . U-shapeSleep is a complex vital function that can take different shapes in an individual’s course of life, primarily based on age . CircadiIn our analysis, high stress level was almost three times more likely to be observed in cases than in controls, with a significant trend in risk. This relationship appeared to be independent from that with sleep duration and GC.Stress response is accompanied by emotional and physical signs and symptoms, also affecting many GI functions by stimulating secretion and colonic transit, delaying gastric emptying time, increasing intestinal permeability and visceral sensitivity, and modifying intestinal microbiota .Stress response is physiological in human life and occurs every time a person faces an event that disrupts his or her balance, and constitutes a menace . Stress The exposure investigated in the present analysis addresses psychological stress, combining both intensity and frequency; the resulting variable was operationalized in three categories of increasing stress, ranging from low level  to high level (most frequently reported and with highest intensity).To our best knowledge, this is the first study that simultaneously analyzed the risk of GC in association with both sleep and stress. We performed several sensitivity analyses that confirmed the main results, consistently showing an increased risk of GC in individuals with long sleep duration and high level of stress. These effects appeared not to depend on reciprocal confounding or effect modification. Based on our knowledge, this analysis is the first that tried to unravel the effects of sleep from that of psychological stress on GC.The disease can have partially influenced the two exposures. That is, GC cases may have more often experienced altered sleep duration and high level of stress compared with controls because of potential symptoms. Indeed, GC patients are often burdened by sleep disorders, poor quality of sleep, and high levels of anxiety. This finds confirmation in a recent case-control study, where sleep disorder and risk of GC were significantly associated only within 1 year prior to cancer diagnosis and not when sleep disorders were documented earlier. In our pooled analysis, the information collected with questionnaires referred to the year before cancer diagnosis/interview, i.e., to a period when GC patients were likely to be asymptomatic.This analysis is impaired by some limitations. The main problem concerns the possibility of reverse causation when examining the two exposures we investigated. Indeed, the case-control design of the included studies could not eliminate the possibility of selection bias and recall bias, and that of reverse causation, despite the cases were asked about their previous (at least 1 year before diagnosis) sleep behaviors. The data reported may be affected by recall bias, given the time lag between the requested exposure and the questionnaire administration. Moreover, we cannot exclude that altered sleep or psychological stress presented as early symptoms of GC in this timeframe. As pointed out in previous studies , exposurHp status was not considered in this analysis because of missing values in the participating studies. This is a potential limitation when focusing on stress levels, as far as Hp can cause gastric and extra-gastric symptoms which may have a psychological burden. Thus, stress can mediate part of the Hp effect. Four out of five of the studies included in this analysis were hospital-based, impairing the generalizability of the data and implying the collected information on sleep and stress, which are largely dependent on condition of the subject, may have been affected by selection bias and recall bias. Despite this, the questions referred to usual habits, thus outside the hospitalization period.The included studies were not designed to investigate these exposures. Also, The large sample size of our analysis, the detailed sociodemographic and lifestyle information available for study subjects, and the pathologic confirmation of case diagnoses are strengths of our study.Our study provides evidence for a positive association of GC with both long hours of sleep and high stress levels. The two exposures resulted to be independently related to GC. These associations were confirmed for both intestinal and diffuse types, and cardia and noncardia subsites of GC. Neuropsychological factors such as sleep characteristics and stress level would need more investigation in relation to neoplastic disease and specifically GC. Prospective studies designed to investigate these exposures would be warranted to clarify their role in cancer epidemiology and specifically GC epidemiology.


Recent information on the occurrence of bovine hypodermosis in Kazakhstan is limited to the results of a few clinical studies in the northern and eastern regions. A first serological study aimed to obtain more data on its geographical distribution and to estimate the prevalence in this country.Hypoderma spp. first-stage larval antigen using a commercially available enzyme-linked immunosorbent assay (IDEXX Bovine Hypodermosis Serum Antibody Test).Serum samples collected from 891 dairy cows on 30 dairy farms in eight Kazakh provinces during the winter season 2015/2016 were examined for antibodies to Hypoderma, and antibody-positive cows were found in 28 of 30 farms and in seven of eight provinces.Overall, 73.6%  of the cows sampled were seropositive for The results suggest a high prevalence of bovine hypodermosis in Kazakhstan, for which the socioeconomic changes in agriculture and village life following the country’s independence are considered to be responsible. Hypoderma species (“warble flies”): Hypoderma bovis , Hypoderma lineatum , and Hypoderma sinense  [Hypoderma spp. have an annual life cycle: Adult flies deposit eggs on the hair of hosts in summer, first-stage larvae hatch from the eggs, burrow through the host’s skin, and migrate to the spinal canal (H. bovis) or esophagus tissue  to overwinter. The following spring, the larvae reach the subcutaneous tissue of the back and develop into the second and third larval stages, forming characteristic subcutaneous bumps called “warbles” [Hypodermosis in cattle and other bovine species  is caused by the larval stages of three warbles” , and loswarbles” . HypoderClinical studies showed that bovine hypodermosis still occurs in many regions of Central Asia, for example, in mountainous areas of South-west Siberia  and in TOur first serological study aimed to obtain more data on the geographical distribution and to estimate the prevalence of this parasitosis in Kazakhstan, the largest Central Asian country.No ethical approval was necessary for this study because the blood samples used were collected during official surveillance.Serum samples used were routinely collected from all adult female cattle on each farm for the official surveillance of infectious bovine rhinotracheitis and bovine leukosis in Kazakhstan during the winter season of 2015/2016. For this study, the National Reference Center for Veterinary Medicine in Astana kindly provided 891 serum samples from 2 to 6-year-old dairy cows from 30 private households and small farms in eight oblasts ; the numHypoderma spp. first-stage larval antigen using a commercially available enzyme-linked immunosorbent assay kit  according to the manufacturer’s instructions. In brief, test sera, as well as positive and negative controls, were diluted 1:20, given into antigen-coated (purified extract of H. lineatum first-stage larvae) wells and incubated at 37°C for 1 h. After three washes, anti-bovine IgG, peroxidase conjugate was added in a dilution of 1:100, the plates were incubated at 37°C for 30 min and washed thrice. The enzyme-substrate  solution was added, and the plates were incubated in the dark at 20°C for 20 min, the stop solution was added, and the optical density (OD) was measured at 450 nm. Finally, a corrected OD value was calculated for each test serum, considering that the positive control had a minimal OD value of 0.350 and the ratio of positive and negative OD values was at least 3.5. The result was given as a percentage; test sera with ≥ 55% were considered positive.All serum samples were stored at –20°C until use. They were examined for immunoglobulin G (IgG) antibodies to Data analysis was performed using the commercially available statistical software BIAS for Windows . The seroprevalence, including its 95% confidence interval (CI), was calculated as the quotient of the number of seropositive animals and the total number of animals examined.Hypoderma-seropositive dairy cows were found in 28 (93%) of the 30 farms surveyed and in seven of eight provinces. In total, 656  of the 891 cows tested were seropositive  is much higher than the prevalence of warbles in adult cattle previously reported from clinical studies in North or East Kazakhstan (8% [3.6% is mreatment . Therefoth century, bovine hypodermosis had been controlled and reduced, but not eradicated, with state support in the former Soviet Union, including its Central Asian regions [Hypoderma spp. in the country.The high seroprevalence can be explained by the history of livestock farming in the country. In the last decades of the 20 regions , 11. Aft regions . This al regions . There h regions . After i regions . The num regions . Today,  regions . However regions , and mosHypoderma first-stage larvae [However, bovine hypodermosis can be successfully controlled and eradicated from an area. If the control is mandatory or coordinated at a regional level, and appropriate compounds are used strictly for all cattle on all farms, eradication would be possible within a few years . Therefoe larvae , 17. A pe larvae . Given tA limitation of the study is the examination of cattle from a small number of farms. However, our serological results from several regions in Kazakhstan suggest a high prevalence of bovine hypodermosis, which may be a consequence of the socioeconomic changes in agriculture and village life following the country’s independence. Based on this assumption, the relevant authorities should initiate province-wide campaigns to eradicate this parasitosis by means of appropriate control measures. In addition, cattle from all farms in an affected region should be tested after the grazing period to obtain an accurate assessment of both the prevalence of the parasitosis and the effectiveness of the control measures implemented.CB: Planned the study and drafted and revised the manuscript. MK, LAL, DMS, and ZAS: Performed the serological examinations and analyzed the data. All authors have read, reviewed, and approved the final manuscript.