The harmful effects of air pollution can cause various diseases. Most research on the hazards of air pollution focuses on lung and cardiovascular diseases. In contrast, the impact of air pollution on neurological disorders is not widely recognized. Air pollution can cause various neurological conditions and diseases, such as neural inflammation, neurodegeneration, and cerebrovascular barrier disorder; however, the mechanisms underlying the neurological diseases induced by various components of air pollutants remain unclear. The present paper summarizes the effects of different components of air pollutants, including particulate matter, ozone, sulfur oxides, carbon oxides, nitrogen oxides, and heavy metals, on the nervous system and describes the impact of various air pollutants on neurological disorders, providing ideas for follow-up research. Air pollution is a major global public health problem. Most people breathe clean air every day, whereas others live in areas with air pollution all their lives. Air quality is closely related to our quality of life, so the study of air pollutants is of great importance. According to the Global Burden of Disease report, air pollution is associated with the occurrence of many acute and chronic diseases. Air pollution was responsible for 6.5 million deaths worldwide in 2015. According to World Health Organization statistics of (3), sulfur oxides, carbon oxides, nitrogen oxides (NOx), and heavy metals. These pollutants can directly or indirectly cause damage to human health, and their chemical composition changes with geographical location, seasonal changes, and alterations in the source; thus, the toxic effect also differs. A growing body of research suggests that living in areas with high levels of air pollution is associated with neurodegenerative diseases , the Cochrane Library, SinoMed, China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI) database, and Wanfang Data Knowledge Service Platform, were searched from their inception to December 2021 by two reviewers for original research articles.All the search results were imported into the literature management software (Note Express V.3.4) for further screening. Two independent reviewers  conducted two rounds of literature screening. First, the reviewers read the title and abstract for preliminary screening, downloaded the full text of the papers that had passed the preliminary screening, and made a final judgment after reading the full text. After determining the literature that would be included in the final analysis, specific features of these articles were extracted using data extraction table.2.5 correlates with CVD. PM2.5, or fine particles, have an aerodynamic diameter of 2.5 microns or less and are a major component of particles in the air. PM2.5 is the result of natural and human factors, mainly wood combustion, coal combustion, fuel combustion, and vehicle emissions. PM2.5 is small in volume, abundant in quantity, large on the surface, high in activity, and slow in sedimentation, and therefore, provides a medium for a variety of chemicals, bacteria, and viruses. Given its lightweight, it remains in the atmosphere for a long time and can be deposited in the alveoli through breathing  = 1.878, 95% confidence interval (CI): 1.363–2.560] -17 expression, primarily in hippocampal neurons, along with chronic neurodegenerative changes associated with activation of hippocampal astrocytes similar to those observed in human AD  , indicating that SO2 has a negative impact on neurocognitive performance  and/or protein kinase C (PKC)-mediated signaling pathways  can impair spatial learning and memory and lead to abnormal expression of apoptosis-related genes   . Another of rats . Howeverpocampus . In addiproteins . SO2 is CO, which is tasteless, colorless, and insoluble in water, accounts for a large proportion of air pollutants. According to statistics, the world emits ~26 Mt of CO into the atmosphere every year, 60% of which is derived from human activities. Anthropogenic CO emissions are mainly produced by incomplete combustion of carbon materials, most of which are emitted by gasoline engine vehicles. Other common emission sources include waste incineration and coal-fired power generation.CO has 200 times the affinity for hemoglobin than oxygen, and a reduction in oxygen's binding ability leads to a reduction in the amount of oxygen reaching surrounding tissues, including the brain. Acute CO exposure can cause tissue hypoxic ischemia, heart damage, and shock, which may further aggravate hypoxia of the central nervous system, leading to nervous system damage , 32.Nakamura et al. reported that chronic CO exposure led to elevated serum carboxyhemoglobin levels in two elderly patients with cognitive impairment. On their initial visit, both patients had cognitive impairment and brain magnetic resonance imaging findings consistent with the diagnosis of AD. However, when patients stopped using their charcoal heaters, their serum carboxyhemoglobin levels returned to normal, their physical symptoms disappeared, and their cognitive function improved slightly, suggesting that CO exposure may have temporarily exacerbated the patients' cognitive impairment . Chang ex into the atmosphere every year. As the main form of NOx, NO2 is an important target of air pollution and environmental quality. NO2 enters through the respiratory tract, corrodes and irritates the respiratory tract, and causes respiratory tract damage. After entering the body, NO2 first targets the lungs. When the lungs exchange gas, NO2 enters the blood and then reaches the tissues and organs of the organism through the circulation of body fluids. Brain tissue is the most important part of the central nervous system of the organism. The brain is also the hub of the nervous system. The learning, memory, and cognitive functions of the organism are closely related to brain function. Therefore, brain damage caused by NO2 and its transformed derivatives in living organisms are of great concern.According to statistics, human industrial production and social activities emit 52 million tons of NO2 was associated with an increased incidence of dementia from 2001 to 2013   mechanisms that induce neuronal excitation in normal and stroke rat models were elucidated  and correlated detailed daily air pollution data from January 1, 1998, to December 31, 2010. We calculated the date from baseline to the onset of dementia, patient withdrawal, or study end along with the average annual pollutant concentration. We segmented or classified the distribution of these data by quartiles and concluded that exposure to high levels of NO2 or CO increases the risk of AD in Taiwan, China  accumulation, and promote pathological abnormalities and cognitive deficits associated with AD  . Crous-Bpocampus . Li et aucidated . Molton ucidated . Chang en, China . In anim with AD . NO2 mayasticity .x affects the human body through respiration.Nitrogen oxide compounds exclusively consist of nitrogen and oxygen and include a variety of compounds. Most of the anthropogenic nitrogen oxide emissions are derived from the combustion of fossil fuels, such as automobiles, airplanes, internal combustion engines, and industrial furnaces. Nitrogen oxide is also derived from the process of producing and using nitric acid, such as nitrogen fertilizer in plants, organic intermediate plants, and non-ferrous and ferrous metal smelters. There are some reports indicating that NOx exposure to the development of AD. Cerza et al. recruited 350,844 subjects aged 65–100 years without dementia and followed them for 12 years to assess the association between long-term exposure to air pollution and first-time hospitalization for dementia. NOx exposure was positively associated with hospitalization for dementia  ]. NOx, a common marker of traffic-related air pollution, has also been linked to higher rates of AD in longitudinal studies in Sweden and China (Studies have linked NO0 μg/m3) . Oudin end China , 44.Manganese is a trace metal commonly found in the environment and a component of urban air pollution with concentrations varying based on geography, season, and source . The maiExposure to manganese is typically higher in an occupational manganese environment compared with a normal environment. People with occupational exposure have been reported to have deficits in attention and concentration, memory, visuospatial function, language, executive function, and other cognitive functions, and a dose–response relationship is noted between blood manganese levels and cognitive function . After e2.5 undergo morphological changes, suggesting that microglia may participate in PM-induced neuronal damage   . These searly PD .3 is one of the risk factors. Based on the 2001 Canadian Census Health and Environment Cohort, including a total of 3.5 million people, scientists found that long-term exposure to O3 is positively correlated with PD mortality. For each unit increase in O3 (10.1 PPB), the risk of PD mortality increased 1.09-fold   (3 and PD risk in some regions during the warm season (April to November) , but no significant association was reported between year-round O3 exposure and PD risk , inducible nitric oxide synthase (iNOS), and superoxide dismutase (SOD) correlated with O3 after repeated exposure. These changes indicate that O3 induced oxidative damage to the substantia nigra and striatum in rats   . Hu et a00–1.02) . Kirrane PD risk . In anim in mice , 71. A d in rats . In addi2 (2.97 MCG/m3), the risk of PD increased by 9%  in downtown Vancouver, Canada, and investigated the relationship between air pollution exposure and PD. They found that air pollutants were associated with the incidence of PD, and every quartile increased the NO2 concentration with a PD hazard ratio of 1.12 (1.05–1.20)  . It has reported . Althougpatients . A recenients  and PD. For each 7.1 μg/m3 increase in NOx concentration, the risk of PD increased by 1.06 (95% CI = 1.02–1.11)  for PD in NOx above the 75th percentile compared to the lowest percentile in the multipollutant model. This finding suggests that exposure to ambient air pollution, particularly traffic-related pollutants, such as NOx, increases the risk of PD . A case–02–1.11) . In a sy02–1.11) .Excessive accumulation of manganese in the central nervous system can cause neurotoxicity, leading to a disease called manganese intoxication, which is characterized by early psychotic symptoms and often accompanied by chronic symptoms similar to idiopathic PD . This coSeveral epidemiological studies have assessed the association between manganese exposure and PD. In a cohort study of 886 US workers, a dose-dependent relationship was noted between exposure to manganese-containing welding fumes and the progression of PD . Similarin vivo, and epidemiological studies support the role of inflammation in the pathogenesis of PD  . Severalce of MS . In a por for MS . Elgabsir for MS . Furtherr for MS . Howeverr for MS . Bai et rt study . At pres3 in the pathogenesis of MS is limited. Jeanjean et al. investigated the short-term association between O3 exposure and the recurrence rate of MS in 424 patients living in the Strasbourg region of France between 2000 and 2009  and found a significant correlation between the recurrence rate of MS and O3 exposure. Interestingly, these correlations are seasonal. Using the multipollutant model, only O3 was significantly associated with the probability of relapse during the “hot” season    . Moghada < 0.01) . A meta- with MS . Given t2 are limited. Heydarpour et al. analyzed the spatial distribution of MS epidemics and their relationship to spatial patterns of air pollution. A regression model was used to estimate long-term exposure to SO2 in MS patients, and the results showed a clustered pattern of MS epidemics. The study revealed the potential role of long-term exposure to air pollutants as an environmental risk factor for MS . These correlations are seasonal. For example, a one-quarter-fold increase in NO2 exposure was associated with the incidence of MS recurrence  in the “cold” season (October–March)  . Howeverollow-up . Tang et with MS .x and MS is limited. Heydarpour et al. analyzed the spatial distribution of MS prevalence and its relationship with spatial patterns of air pollution. By collecting records of 2,188 patients who met the criteria for a definite diagnosis of MS from 2003 to 2013, we used a regression model to estimate long-term exposure to NOx in MS patients. The results revealed a cluster of MS epidemic cases in Tehran, and the spatial distribution of NOx exposure was significantly different from that of MS epidemic cases (P < 0.001), demonstrating the potential role of long-term exposure to NOx as an environmental risk factor for MS  for every 10 μg/m3 increase in SO2 , Guangdong Basic and Applied Basic Research Foundation (2021B1515140032), Discipline Construction Project of Guangdong Medical University, Discipline Construction Project of Guangdong Medical University (4SG22021G), the Fund for Ph.D., Researchers of Dongguan People's Hospital (K202001), and Science Foundation of Traditional Chinese (20222104).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.


Stigmatizing attitude toward patients with severe mental disorders is one of the main obstacles of improving the mental health of societies. Media plays an important role in how the public views mental health issues. Thus, we have performed this study to investigate the Iranian theater artists' mental health status, and their view toward patients with severe mental disorders.via an online anonymous survey including the Social Distance Scale and the Dangerousness Scale measuring the attitude of participants toward patients with severe mental disorders, and the 28-item General Health Questionnaire (GHQ-28). It was disseminated to artists who had the experience of working in theater in the past year in Iran.This cross-sectional study was performed Our survey was responded by 104 artists. Social Distance Scale scores' mean was 10.67 (scores can range from 0 to 21) and the Dangerousness Scale scores' mean was 28.87 (scores can range from 8 to 56); higher scores indicate worse discrimination. Our participants' strongest fears were to let someone with a severe mental disorder to take care of their children, and for these groups of patients to obtain a hunting license. Twenty-six (25%) participants were at risk of moderate to severe anxiety, and 18 (17.3%) participants were at risk of moderate to severe depression.By and large, our participants did not have a positive attitude toward patients with severe mental disorders. Providing the knowledge of mental health issues can help the general public to be more tolerant of the mentally ill and specifically, theater can be employed to fight stigmatizing mental health issues by educating its audience. Stigma is defined as disapproval of an individual or group based on their distinguishing characteristics. Stigmatizing mental health issues exists on three levels: individual, interpersonal, and institutional. It stems from misconception and prompts falsely applied stereotypes, prejudice, and discrimination , 2.Discrimination takes different forms and may emerge as social disapproval and exclusion. It may lead to decline in social status, worsening the illness, aggression, interpersonal conflicts, and isolation. Furthermore, stigma may encourage substance abuse and reluctance toward treatment. Consequently, people with mental health issues do not just have to carry the burden of their symptoms but also deal with reduced quality of life –3.Previous studies have reported that stigma invigorates the general public to withhold help from minorities . ProtestMedia plays a vital role in how the public views mental health issues, and its imprecise representation in television and films has been reinforcing the negative stereotypes. It has been portraying the mentally ill as potentially dangerous people to society .As theater creatively interacts with its audience, it can either be used to fight mental disorders stigma or prompt the negative attitude toward patients with severe mental disorders. Several studies indicated the theater's positive effects on reducing stigma among teenagers and young adults –19. TherPrevious studies have reported that significant rates of moderate to severe mental health issues exist among artists in different fields –21 whichvia an online anonymous survey including the Persian versions of three questionnaires: the Social Distance Scale, the Dangerousness Scale, and the 28-item General Health Questionnaire (GHQ-28).This cross-sectional study was performed via email and chat applications). We used the snowball sampling method, starting at art centers and art schools based in Tehran. Thereafter artists across the country were contacted. The sample size was calculated with CI = 95% , p = 0.24 (population proportion) (d = 0.09 (sampling error). The inclusion criteria were being over the age of 18, and having the experience of working in theater in the past year.The survey was open from June of 2021 until June of 2022, and was disseminated to 340 artists through social media (portion)  and d = The Social Distance Scale (first developed by Link) and the Dangerousness Scale (first developed by Park) both present cases of patients with severe mental disorders and measure the attitude toward the target person. The Social Distance consists of seven questions and uses the Likert scale as “definitely willing/ probably willing/ probably not willing/ definitely not willing.” The Dangerousness Scale consists of eight questions and uses the Likert scale as “strongly agree, rather agree, agree, nor agree or disagree, disagree, rather disagree, and strongly disagree”. Higher scores indicate worse discrimination . RanjbarThe 28-item General Health Questionnaire (GHQ-28) includes 28 questions in four subsections measuring the somatic symptoms, anxiety and insomnia, social dysfunction, and depression. Ebrahimi et al. assessed and determined the validity and reliability of the Persian version of the GHQ-28. Its Cronbach's alpha and split reliability co-efficient were 0.78, 0.97 and 0.90 respectively .Participants responded to our survey voluntarily and anonymously. Our study was approved by the Institutional Review Board of Iran University of Medical Sciences (Reference: IR.IUMS.FMD.REC.1400.362).Data were analyzed by IBM SPSS Statistics (v. 25.0). To report the frequencies and percentages of categorical variables, descriptive statistics were used, and only valid percentages are reported. The demographic data and the GHQ subscales were compared with the variables of the Social Distance Scale and the Dangerousness Scale, through Chi-Square Test.N = 62) of them were male. A total of 104 artists, within the age range of 18-56, responded to our survey, and more than half , and the Dangerousness Scale scores' mean was 28.87 (±10.291). We found no significant correlation between the demographic data and the Social Distance Scale scores and the Dangerousness Scale scores, probably due to our small sample size. However, previous studies have reported that older age and marital status (being married) were indicators of negative attitude, and younger age, being female, and higher education were indicators of positive attitude toward patients with severe mental disorders .What do you think about someone like that person taking care of your children for an hour or two?” received the most negative feedback. This result was unexpected as there has been no substantial report of child abuse by patients with severe mental disorders over the past years. Notwithstanding that prevention of any type of child abuse or assault is a critical issue among all societies, no rationale supports this fear, and it seems to stem from general attitudes. Besides, previous studies have reported that most child abuse perpetrators are among the families or acquaintances  participants were at risk of moderate to severe anxiety, and 18 (17.3%) participants were at risk of moderate to severe depression. In total, 15 (12.6%) participants were at risk of having moderate to severe mental disorders. Whereas, in a study conducted by Noorbala et al. among Iranian general population, using the same cut-offs, it was reported that 29.50% were at risk of anxiety, and 10.39% were at risk of depression. In total, 23.44% of the general population were suspected of moderate to severe mental disorders  and 51.6We did not find any significant correlation between our participants' mental health status and their attitude toward patients with psychiatric disorders. However, a study conducted in Finland, reported that dealing with depressive symptoms, leads to a positive attitude toward people with depression .To the best of our knowledge, this is the first study in Iran to investigate the view of the artists working in theater on mental disorders. Our study is limited by a small sample size, social-desirability bias, and participation bias . Probably due to our small sample size, no significant correlation was found between the demographic data, the GHQ subscales' scores, the Social Distance Scale scores, and the Dangerousness Scale scores.Most anti-stigma interventions and campaigns have been conceptualized using knowledge-attitude-behavior paradigm , i.e., eFurther investigations should be done among artists, and if needed, we can provide them with anti-stigma activities and interventions, i.e., workshops, screening films or performing plays about mental disorders, and discussion classes that have been suggested by previous studies for other groups –18.We concluded that all in all, our participants do not have a positive attitude toward patients with severe mental disorders. However, we found no significant correlation between the demographic data, the GHQ-28 scores, the Social Distance Scale scores and the Dangerousness Scale scores, which was probably due to our small sample size. Twenty-five percent of the participants were at risk of moderate to severe anxiety, and 17.3% of the participants were at risk of moderate to severe depression. Our participants' strongest fears were to let patients with severe mental disorders take care of their children, and obtain a hunting license. As reported before, providing knowledge of mental health issues can help the general public to be more tolerant of patients with severe mental disorders. Thus, theater can be employed to fight stigmatizing mental health issues by educating its audience through its creative ways.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 Institutional Review Board of Iran University of Medical Sciences (Reference: IR.IUMS.FMD.REC.1400.362). The patients/participants provided their written informed consent to participate in this study.Conceptualization and design: NE, ZA, ES, and MS. Data collection: NE, ZA, RA, MB, AA-D, AG, and MS. Data analyses: NE and HM. Initial draft preparation: NE and MS. All authors contributed to the article, editing and review, 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.


To evaluate the immunogenicity of COVID-19 vaccines in patients with diabetes mellitus (DM) through a systematic approach.A comprehensive search was conducted in PubMed, Scopus, and Web of Science with no time restrictions. The search was based on the three main concepts: Covid-19, Vaccine immunogenicity and Diabetes Mellitus.After excluding irrelevant studies, 16 studies remained for the quantitative assay. Among the sixteen studies, eleven had controls. Type of diabetes was specifically mentioned in six studies . Twelve of the included studies were conducted on the immunogenicity of vaccines that included mRNA vaccines (i.e. BNT162b2 and mRNA-1273) in DM, five studies included vector-based vaccines (i.e. Ad5-nCoV and ChAdOx1-S), and five studies assessed the immunogenicity of vaccines in DM, including inactivated vaccines . Most of the current studies indicate lower antibody response in patients with DM compared to individuals without DM, after the second dose of vaccine and irrespective of vaccine type. Several studies have shown that higher age and higher BMI are associated with lower antibody response, while optimum glycemic control and higher GFR are associated with higher antibody response among patients with DM.Immunogenicity of the vaccines has mostly been reported to be lower among patients with DM compared to healthy controls. There are also few studies assessing variables that significantly affect this association, including age, type of diabetes, BMI, glycemic control and eGFR. Investigating these associations could help us provide the most advantageous condition for patients with DM before, during and after vaccination for optimum antibody response. Many unresolved issues concerning potential factors affecting vaccine immunogenicity, including type of vaccine, numbers of administered doses, re-vaccination intervals and hyperglycemia in patients with DM need to be addressed through future research. Diabetes mellitus (DM) is a major concern in healthcare worldwide, with high morbidity and mortality. Underlying DM is a significant risk factor for higher susceptibility to coronavirus disease 2019 (COVID-19) with a more severe condition, worse outcomes, and higher mortality  were determined .PubMed, Scopus, and Web of Science were searched for relevant articles published up to April 27, 2022, matching the PICO question using the following keywords: [(COVID-19) OR (SARS-CoV-2) OR (novel coronavirus) OR (2019-nCoV)] AND [(vaccine) OR (vaccination) OR (vaccinated) OR (immunization)] AND [(Diabetes Mellitus) OR ((Diabetes) AND (Mellitus)) OR (Diabetic)]. English original articles that assessed the immunogenicity of COVID-19 vaccines in patients with DM were included. No limitation was determined for the date or status  of the publication. Moreover, the reference lists were screened for remaining relevant studies and included in case of eligibility. Two reviewers independently performed the literature search, and any disagreement was resolved according to the consensus.The studies that assessed vaccination in patients with DM were eligible for inclusion. The inclusion criteria were as follows: 1) Population: articles on human subjects; with participants with DM; whose diagnosis of DM was established by an endocrinologist based on ADA criteria , 2) InteEligible studies were evaluated by two experts independently. The following data were extracted from each included publication: title, author, time of publication, country of origin, study design, number of participants at baseline and follow-up, if applicable, clinical subgroups, mean age and male to female ratio of the participants, type of DM, complications of DM, type of COVID-19 vaccination, the immunogenicity of the administered vaccine. Any conflicts in data extraction were discussed or consulted by a third expert and resolved.For the quality assessment, we used the National Institutes of Health (NIH) quality assessment tool to evaluate the included studies. The scores of 0–5, 6–10, and 11–14 were considered poor, fair, and good, respectively . The stuDatabase search resulted in 3932 records, of which 3490 were primarily excluded based on title and abstract. The remaining 181 articles were thoroughly studied and the articles that met the inclusion criteria were extracted, leaving us with 16 studies. The remaining articles were carefully evaluated for qualitative assay. Included studies dated from 2021 to 2022. Sample sizes of the studies varied from 86 to 56261. The mean age of the participants ranged from 29 to 70.38. The proportion of males ranged from 27.8% to 65.9% in the studies. The number of patients with DM was mentioned in 15 of the articles and ranged from two to 4626 , 37–42. Quality assessment of the included studies is presented in vs. 138 ± 59.4 BAU/ml) and neutralizing antibodies (87.1 ± 11.6 vs. 79.7 ± 19.5%) were significantly lower in patients with T2DM. Another study by Nomura et al. , whereas the humoral response was not significantly associated with DM(p=0.135) . In contSeveral studies have been conducted on vector based vaccines, most of which showed significantly lower antibody response among patients with DM compared to those without , 35, 40 Inactivated vaccines have lower immunogenicity in DM patients than those without , 34, 39.The immunogenicity outcomes of the included studies are detailed in vs. patient without DM  and antibody response in patients with DM thout DM , 38, 43.A study by Marfella et al.  with a pThree studies have assessed the association between age, gender, and BMI with antibody response in DM patients , 38, 43.Type of diabetes management and insulin therapy and how they affect the antibody response in patients with DM were assessed in two studies , 35. In Duration of diabetes and its association with antibody response was assessed among patients with DM in three studies, none of which showed any significant association , 35, 38.Since the emergence of COVID-19 pandemic and the development of vaccines against the virus, immunogenicity has gained increasing attention as an indicator of vaccine effectiveness . ImmunogSeveral studies illustrated that the immune process might be inadequate in people with diabetes . NumerouIn this systematic review, most of the studies showed a significantly lower antibody response in patients with DM than those without. In one prospective observational study, 17% of participants with DM had an inadequate humoral immune response to SARS-CoV-2 BNT162b2 Vaccine after the first dose; however, after the second dose, both participants with and without DM developed high and similar seroconversion . One stuIn another study, Sourij et al. have observed high immune response in patients with T1DM compared to patients with T2DM and healthy controls, according to the unadjusted analyses. They also extracted relevant variables, including the patients’ mean age, sex, BMI, estimated glomerular filtration rate (eGFR), and other comorbidities. It has been found that among patients with type 1 or 2 diabetes, age and eGFR directly affected anti-SARS-CoV-2 S antibody response, whereas baseline HbA1c levels or its changes during the follow up did not. In addition, BMI of patients with DM had a weak negative correlation with antibody response . AlthougNevertheless, the majority of studies in this systematic review confirm the effect of diabetes on vaccine immunogenicity. In one study, no significant difference was found in antibody titers between people with diabetes and those without. Guzmán and his collogues also reported no statistically significant association between S1 IgG antibodies generation and diabetes . This reFurthermore, the number of diabetic patients included in these studies was low. For instance, Watanabe et al. include only two participants with diabetes . Hence tNevertheless, it remains unclear whether the reduced response to the vaccine in diabetics results from a quantitatively lower immune reaction or is associated with poor clinical efficacy. Studies have shown an inherently interrelated relationship between immunity and metabolism. Therefore, diabetes, as an ingredient of metabolic disorders, induces immune defects . It appeOf note, Alqassieh et al. compared the effectiveness of two SARS- CoV-2 vaccines that are widely available, Sinpharm (the inactivated CoronaVac vaccine) and PfizereBioNTech’s (the mRNA BNT162b2 vaccine), among the adult population in Jordan. This study showed that after six weeks of the second dose, there was lower seropositivity among DM patients given the Sinpharm vaccine than Pfizer- BioNTech’s vaccine . In anotAltogether, most studies show their acceptable efficacy in immunizing patients with DM against COVID-19. Although the heterogeneity of the outcome measures (some presented as mean and some others as percentages) has made the comparison difficult, but all together when pooling the conclusions from these thirteen studies, it could be inferred that despite the lower seroconversion in DM patients, there was still a considerable amount of antibody response to vaccines in patients with DM. However, due to its lower immunogenicity in DM compared to healthy subjects, a third or even fourth dose may be considered necessary for patients with DM to reach the same level of immunity as those without diabetes. This still remains a controversy and further research is warranted.This study has some strengths. To the best of our knowledge, this is the first study to systematically review the immunogenicity of COVID-19 vaccines in patients with DM. Our data could help investigate the necessity of booster doses in this population to build successful vaccination strategies in the future. Additionally, this study provides important data about how glycemic control affects vaccine immunogenicity and other factors that could be considered before administering vaccines or during vaccination for people with diabetes.This study has several limitations. Firstly, we could not perform meta-analysis due to the low number of included studies and the heterogeneity of the outcome measures. Secondly, we assessed the immunogenicity mostly based on the antibody response, which depends on the humoral immunity. While, cellular immunity is also involved in immunization after COVID-19 vaccination . Since tvs. vector-based vs. inactivated vaccines) is warranted. Thirdly, it is noteworthy that most of the studies have discussed all types of diabetes without differentiation. However, DM consists of different types with different pathophysiology and a wide range of symptoms and management strategies. Similar approach to different types of diabetes for making healthcare policies may not be cost-effective; thus, we recommend future research to assess and compare the immunogenicity of COVID-19 vaccines in different subgroups of DM. Lastly, it is noteworthy that based on our systematic literature search, there has not been any published original article evaluating the immunogenicity of the third dose of COVID-19 vaccines in patients with DM. Research in this regard is strongly recommended.This systematic review revealed some literature gaps that could be addressed in the future. Firstly, there has been plenty of research on COVID-19 disease and vaccination in patients with DM, but there are limited studies on the immunogenicity of the vaccines in this group of high risk patients. We recommend further research focusing on seroconversion after COVID-19 vaccination in patients with DM. Secondly, most of the studies have used different types of vaccines without differentiating and comparing their immunogenicity, specifically in patients with DM. Further research on comparing different vaccine types (mRNA In conclusion, vaccination reduces mortality and morbidity related to COVID-19, especially in high-risk groups like people with diabetes. Studies have elucidated that people with diabetes had lower antibody levels after two doses of vaccination, irrespective of the vaccine type. Furthermore, management of diabetes and glycemic control could be associated with antibody responses. On the contrary, some studies have found no significant difference in vaccine immunogenicity between patients with DM and the control groups. Hence, further studies are required to evaluate the immune response following COVID-19 vaccination in patients with diabetes and investigate whether booster shots are required to achieve a sufficient level of immunity in this specific population.The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding author.Conceptualization: AB and MF; methodology: FK and AS; validation: LG; data curation: PK; writing—original draft preparation: DN; writing—review and editing: all. All authors contributed to the article and approved the submitted version.Authors wish to thank all who helped in drafting this manuscript.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.


Body mass index (kg/m2) and nutritional status were not predictors of cognitiveperformance. Interestingly, among the GFFI tasks, muscle strength influenced thetest execution time, both in upper and lower limbs . Ourfindings showed that: 1) women performed the Stroop test faster than men; 2) theolder the person, the lower was the cognitive performance; 3) the higher theeducation, the better the test execution time; and 4) higher scores in the GFFIwere associated with a better performance in the Stroop test. Therefore, gender,age, education, and functional fitness and capacity were predictors of cognitiveperformance in the elderly.Aging is related to a decrease in physiological abilities, especially cognitivefunctions. To unravel further evidence of age-related cognitive decline, weanalyzed which physical and functional variables are predictors of cognitiveperformance in a sample of 498 Brazilian elderly (67.26% women). To do so, weused the Stroop test as a tool to evaluate executive functions and the Generalfunctional fitness index (GFFI) to evaluate the functional fitness of theparticipants. A linear regression analysis revealed that female sex (β=-0.097; The world is facing a significant increase in the elderly population. The WorldHealth Organization (WHO) estimates a population of 2 billion elderly people in theworld by 2050, which will represent 22% of the global population, 80% of which willlive in developing countries . In BrazOne of the major concerns of aging is the decline in functional capacity such asmuscle strength, gait, balance, cognition, among others. In the elderly, loss ofcognitive ability is associated with neurodegenerative diseases, which directlyaffect quality of life . Both loStudies have highlighted the importance of preserving cognitive function duringaging, especially executive function ,7. ExecuSeveral studies have shown that the older the age, the worse the score on cognitivetasks ,8,9. AmoWe conducted a cross-sectional study with a convenience and non-probabilisticsampling that was approved by the Ethics committee of the Federal University of SãoPaulo (CEP/UNIFESP - CAAE 57307016.9.0000.5505). To be included in the study,participants had to sign the informed consent form (466/2012-CNS/CONEP) and have amedical consent (issued up to 1 year) to perform physical tests (requirement ofelderly centers). Those who presented musculoskeletal and/or neurological diseasesthat made it impossible to perform the functional capacity tests or were beingtreated for cognitive, psychological, or psychiatric illnesses and alcoholism wereexcluded. A total of 756 elderly people of both sexes were recruited from elderlycenters in the Alto Tiete region of São Paulo state. Of these, 154 did not meet theinclusion criterion and 104 met the exclusion criterion, leaving a final sample of498 participants .post hoc analysis; http://g-power.apponic.com),adopting an effect size of 25%, a 5% probability of error (P<0.05), a sample sizeof 498 volunteers, and 9 predictors, resulting in a power of 100%.With the selected participants, the power of the study was calculated using thesoftware G*Power version 3.1.7  wasdetermined by the following equation: BMI = Weight / (Height)The GFFI was initially adapted as proposed in the Senior Fit Test ,17. The The Stroop test was used to evaluate cognitive function. Because the studiedsample contained illiterate participants, we used the validated model by Kulaifand Valle  with numX2.The data of the Stroop test, educational level, nutritional status, functionalcapacities, and respective GFFI were analyzed with the general linear model(GLM) or chi-squared test. Results of GLM are reported as mean and standarddeviation followed by the Fisher (F) value. The chi-squared test was conditionedto the interpretation of residuals  andof the adjusted residuals (AR). The residual analysis is necessary to show whichcategory has a significant value  and the adjusted residual determinesthe significance level for the excess of occurrences. P values were consideredsignificant when higher than 1.96. Added to this interpretation is the value ofX2 distances between the categories of the studied variables. Thesymmetric projection was used, which allows the simultaneous examination of therelationships between rows and columns in the contingency table, that is, therelationships between all categories of both variables. Categories close to theflat projection have a stronger relationship than categories separated bygreater distances. Any category, represented as a point in the projection plane,can be analyzed separately and characterized according to the proximity of theprojections of all other categories, on a line that links its characteristicpoint to the origin of the axes of the projection plane. When categories of thesame variable are found in close positions on the map of the correspondenceanalysis, this suggests that, regardless of their semantic content, they can beconsidered equal in terms of the mass distribution of the total observationsmade. When categories of contingent variables are projected close together, anassociation between the events they represent is suggested, although nothing isconsidered statistically significant. For statistical analysis, it is necessaryto interpret adjusted residuals, as already described.Correspondence analysis was also used. This analysis consists of a graphicalrepresentation in a flat projection of multidimensional relations oft andsignificance values from the Student's t-test. In addition, theinterpretation of collinearity of variables is offered. If an independentvariable presented more than one category, one of them was fixed to be used asreference. For example, for gender, the woman category was fixed and for theother independent variables, the last category was fixed. For all statisticaltests, a level of significance lower than 5% was adopted.To analyze the predictive factors of the Stroop test (dependent variable - timeof card 3), linear regression (stepwise model - forward) was used with thefollowing independent variables: gender, age, nutritional status, education, andGFFI. For the analysis of which GFFI tests are predictors of the Stroop testtime, linear regression  was performed with the following independent variables: gender, elbowflexion, sit-to-stand, TUG, and 6-min walk tests. Thus, the analysis of themodels adopted was done by the interpretation of the standardized and adjustedcoefficient (β), followed by the analysis of the vs 32.73%; X2=59.406; P<0.0001). Non-significant differences between men and womenwere found for age , BMI , and nutritionalstatus .X2=18.038; P<0.0001) in the following categories: 9 to 11 years ofstudy (30.7 vs 18.8%) and >12 years of study (19.0vs 11.9%), while in women, the observed frequency was higherthan expected in the illiterate category .The observed frequency in men was significantly higher than expected compared towomen . However, the observed frequency in men washigher than expected in the categories very weak compared to women , while women participants had a higher than expectedfrequency in the weak classification compared to men . When adding up the percentage of weak and regularclassifications, 70.7% of the participants were in these categories.X2=553.888; P<0.0001), indicating the maintenance of strength.Nonetheless, a significant difference between genders  was found, with the observed value in men being higherthan in women.The observed value for the good and very good categories for strength of upper limbsassessed by the elbow flexion test was higher than expected . However, in gender comparison, the observedfrequency in men was higher than expected for the good classification , while the observed frequency in women was higher inthe very weak classification . These findings showed that men presented ideal valuesfor this functional capacity while women presented values below the recommendedlevel.As for strength of lower limbs, measured by the sit-to-stand chair test, the observedfrequencies of weak, regular, and good classifications were higher than expected. There was nosignificant difference between gender for this test (P=0.058). It is possible toconclude that this functional capacity was worse than the recommendation in oursample.In the TUG test, observed values were higher than expected in the categories veryweak and weak . However, no significant difference was observedbetween genders , indicating that the aerobic capacity in men and womenwas below the regular, presenting an unsatisfactory result.Finally, in the 6-min walk test, the observed values were higher than expected in thecategories very weak, weak, and regular . Women had fewer errors incard 2 than men .No significant difference between genders was found for card 3 (Stroop effect), card4, and interference neither for time nor for error counting. Yet, a significantdifference was found between genders for both average time spent in card 3 comparedto card 1 and error counts .Thus, the Stroop effect was not significantly different between genders, but genderdifference was evident between different cards.t=-2.286; P=0.023). Regarding age,each year of life added 0.205 s in task execution . In addition, the higher the education, the less the time required tofinish the test, 0.28 s faster . Finally,the higher the GFFI, the less the time required to complete the task, 0.10 s faster. Nutritional status was excluded from themodel for not being a predictor for the Stroop test performance in the studypopulation. In brief, these findings show that gender (women), age (younger),schooling (higher), and GFFI (higher) were predictors for better performance in theStroop test.t=-4.672; P<0.0001) for elbow flexion and 0.125 s faster for the sit-to-stand test. Gender andfunctional capacities tests  were excluded from the model fornot being predictors of Stroop test performance. Finally, our findings suggestedthat muscle strength (both in upper and lower limbs) was a predictor of Stroop testperformance.Since the GFFI is composed of four distinct tests, and these combined with gendercontribute to the composition of the index, we enlightened the concept of functionalcapacities and gender being predictors of performance in the Stroop test . Elbow fAging is associated with a decrease in physiological capacities, especiallyfunctional and cognitive abilities. In the present study, we aimed to analyzepredictive factors for cognitive performance in a Brazilian elderly sample using theStroop test as a tool to evaluate selective attention and executive functions. Ourresults indicated that gender (women), age (younger), education (higher), and GFFI(higher) were predictive factors for the Stroop test performance. Moreover, amongthe tests of the GFFI, only muscle strength was a potential predictor for Strooptest performance.In the social context, the current findings suggested that age and educational levelwere crucial factors when planning programs for cognitive rehabilitation.Furthermore, the more the years of education, the greater the gain in cognitivefunction. Our results were consistent with other studies . In the Another predictor of cognitive function was functional fitness. Other studies showsimilar results, where physically active elderly women showed better executivefunction compared to men ,23. In aAmong the functional capacities, upper limb strength was preserved in both genders inour sample. Data regarding this subject are controversial. For instance, our datadiffer from the study by dos Santos et al.  in whichAs for lower limb strength, elderly men had better than expected values, while morewomen were included in the very weak category. The association between lower limbstrength and the probability of hospitalization has been reported, showing thatparticipants with weaker legs have a higher prevalence of hospital admission .Participants of both sexes were classified as very weak and weak in the TUG test. TheTUG test has been widely used in clinical practice and in research for theevaluation of sarcopenia, survival, functional mobility, and risk of falls in theelderly community . ElderliThe results of the 6-min walk test showed that the aerobic capacity of participantsof both sexes was unsatisfactory. Similar to TUG, the 6-min walk test has beenwidely used as a scientific instrument because of its high correlation withmorbidity/mortality . CahalinSince GFFI was a predictor of executive functions, we sought to verify which of theGFFI tests was contributing to the result. Muscle strength was the only factorassociated with performance in the Stroop test. Unlike our results, the literatureshows that both acute aerobic and strength exercises improve executive functions,32. HoweSeveral studies have found that sarcopenia is associated with decreased cognitiveability ,36. In aFinally, the majority of studies address levels of physical fitness throughquestionnaires (a subjective assessment) or isolated functional capacity tests,rather than through an index. In this study, we used an index and the classificationproposed by Rikli and Jones ,17, as mThe limitations of our study should be mentioned to guide future investigations.First, there were no tools to equalize the initial cognitive status of participantsor even factors that could interfere with their cognitive function. Second, there isa lack of instruments available for cognitive assessment, and it would beinteresting to associate multiple tests to assess executive cognitive function ortasks for other cognitive domains . However, due to thenumber of participants and research volunteers that worked in this study, we wereunable to perform further cognitive analyses. The average time spent applying thetests was 60 min per person, with 30% of this time used for the Stroop test.Nevertheless, our results showed that GFFI was a predictor of executive capacity asmeasured by the Stroop test. We also observed that muscle strength played animportant role in executive function. This information adds to the existingliterature and reinforces the attention that should be paid to the reduction ofmuscle mass and especially muscle strength in the elderly, as they are much moreprone to sarcopenia. In this sense, the present study indicated an interestingassociation between muscle strength and cognitive capacity. These findings are alsorelevant for healthcare professionals, since they indicate the importance ofmaintaining functional capacities  for the maintenanceof cognitive function in the elderly. Improving executive functions can be avaluable asset in the quality of life of older adults. Once predictors of cognitiveperformance are known, the scientific and medical communities will have moreaccurate subsidies for the treatment/prevention of cognitive decline.


As the world population is progressively ageing, more and more elderly patients will require cancer surgery. Although curative surgery is the treatment of choice for resectable colorectal cancer (CRC), it is still debated whether elderly frail patients should undergo major cancer surgery due to the increased risk of postoperative and long-term mortality. The aim of this retrospective study was to evaluate the impact of age and comorbidities on postoperative mortality/morbidity and long-term outcomes, looking for potential age-related survival differences.A total of 1,482 patients operated for CRC at our institution between January 2005 and October 2020 were analysed. The independent effect of age and comorbidities on postoperative complications was assessed by a logistic model, while the effect on overall survival (OS) and cancer-related survival (CRS) was estimated by a Cox regression model.The median age in the cohort was 67.8 years. Postoperative mortality was very low in the whole cohort (0.8%) and contained even in older age groups . The cumulative incidence of postoperative complications was doubled in patients with comorbidities . With regard to OS, as expected, it exponentially decreased with advancing age. Conversely, differences in CRS were less pronounced between age groups and absent in patients with stage 0–I CRC. Analysis of all causes and cancer-related mortality revealed a peak within 2 years from surgery, suggesting a prolonged impact of surgery. In patients aged 75 years and above, all-cause mortality showed a steep increase 1 year after surgery, while cancer-related mortality plateaued at about 4 years after surgery. On multivariable analysis, OS, but not CRS, was significantly influenced by age.Although acceptable results of surgery in elderly patients, OS is strongly dependent on age: older people die more from competing causes than cancer-related treatments compared to younger age classes. The preoperative identification of risk factors for low OS may help the selection of those elderly patients who would benefit from curative CRC surgery. Colorectal cancer (CRC) is one of the most common tumours worldwide, and its incidence increases with age, with a median age at diagnosis of 67 years . As the The aim of this retrospective study was to evaluate the impact of age and comorbidities on postoperative mortality/morbidity and long-term outcomes on a large cohort of surgically treated CRC patients, and to evaluate the opportunity to submit elderly and frail patients to surgery.The initial cohort of patients included 1,645 patients who had surgery for CRC at the Division of General and Hepatobiliary Surgery, University of Verona Hospital Trust, between January 2005 and October 2020. All elective and urgent surgeries and stage 0–IV, potentially curative (R0–1), and palliative (R2) procedures were included. Patients below the age of 30 and above the age of 90 were excluded, as the numbers in those age categories were very exiguous. Patients with missing follow-up data were also excluded. After application of inclusion criteria, 1,482 patients were analysed Figure 1https://demo.istat.it/tvm2016). p-values below 0.05 were considered statistically significant. The statistical analysis was performed using STATA software, release 17.0 .The primary outcome variables were postoperative mortality and long-term OS and CRS. The main predictors considered in the present study were age, coded as <65, 65–69, 70–74, 75–79, 80–84, and 85–89 years, stage , gender , comorbidities , tumour location , type of surgery , neoadjuvant therapy (yes versus no), adjuvant therapy (yes versus no), radicality of surgery (R0–1 versus R2), postoperative complications , and number of analysed lymph nodes . Significance of the association between age class and postoperative mortality was evaluated by Fisher’s exact test, and results are presented as n (%). Survival curves were estimated using the Kaplan–Meier method, and the log-rank test was used to evaluate the significance of differences among curves. To plot the estimated hazard function, a kernel smoother was used with a bandwidth of 0.2 years. The independent effect of age class on overall or cancer-related survival was evaluated by a Cox regression model, adjusting for gender, stage, comorbidity, and neoadjuvant and adjuvant chemotherapy. To test whether the prognostic significance of the main risk factors changed over time, the proportional hazards assumption of the Cox model was tested on the basis of Schoenfeld residuals. Life expectancy was compared between the CRC cohort and the general population from Verona. The comparison was restricted to patients undergoing R0–R1 surgery and to the age class 80–84 years, where median and mean survival could be computed for the CRC cohort. Life expectancy of the CRC cohort was extrapolated, as some patients were still alive at the end of follow-up, while life expectancy in the Verona general population was yielded by the Italian National Institute of Statistics . Thirty-day postoperative mortality in the whole cohort was low and within acceptable ranges in all age groups (0.8%). Patients aged 80 years and above presented the highest postoperative mortality . Only patients with at least one comorbidity died in the postoperative period (12/928 = 1.3%). Finally, postoperative complications occurred more often in elderly patients , and its occurrence was strictly associated with the presence of comorbidities . Similarly to neoadjuvant treatment, adjuvant therapy was most frequently adopted in younger patients .There was a non-linear relationship between stage and age. Stage 0–I and IV were more frequent in the youngest age group, where older patients presented a higher proportion of stage II and III CRC (p < 0.001). The radicality of surgery did not differ significantly between age groups as demonstrated by the similar proportions of potentially curative resections (R0–1).As expected, OS markedly differed among the six age classes  and furthermore in stage IV patients . Life expectancy in stage II patients was affected by gender, as it was similar to that of the general population in men (7.4 years) and substantially reduced in women (5.7 years).The primary aim of the present study was to determine the long-term outcomes of elderly patients undergoing CRC surgery and to evaluate whether all age groups benefit from surgery. The treatment of CRC in elderly patients represents a contemporary dilemma as the world population is progressively ageing , and CRCDespite poorer OS in elderly patients, postoperative mortality was very low in the whole cohort (0.8%), and within acceptable ranges even in octogenarian patients (3%–4%). These data are in line with the current literature –27 and sIn line with previous reports, we observed a higher proportion of advanced and early stages of CRC in younger patients . ConversIn our cohort, OS differed significantly between age classes, as expected. On multivariable analysis, age remained a statistically relevant risk factor for OS, together with stage, presence of comorbidities, occurrence of postoperative complications, non-curative resection, inadequate lymphadenectomy, and neoadjuvant treatment. On the other hand, whereas CRS was lower in older patients Figure 2Interestingly, life expectancy at 80–84 years of age was similar between stage 0–I CRC patients and the general population of Verona , suggesting a low impact of surgical treatment. However, life expectancy of stage III and stage IV CRC was markedly reduced in both sexes. These data suggest that curative surgery can be safely performed also in elderly patients with CRC, with important benefits on OS if they do not die of competing causes and they present with resectable and early-stage disease. Palliative surgery or extensive resections for stage IV CRC, however, do not provide survival benefits.From the results of our study and from current literature, we could conclude that elderly CRC patients should not be undertreated just because of their chronological age. A careful preoperative evaluation should select elderly fit patients for low-risk surgery. Frail and comorbid patients should otherwise be directed towards medical optimization and prehabilitation before surgery –33. The Despite including a large number of patients with a long follow-up time, our study presents some limitations. Due to its retrospective nature, it was not possible to retrieve complete data on some variables, including the administration of neoadjuvant/adjuvant therapy and the complications related to perioperative oncological treatment. Also, retrieval of the cause of the death was sometimes limited by the possibility to directly contact the patients or their relatives.In conclusion, CRC surgery may be offered even to elderly patients with acceptable postoperative mortality. However, it should be considered that there is a more pronounced increase in 2-year all-cause mortality in elderly patients, suggesting a prolonged impact of surgery.corrado.pedrazzani@univr.it.The dataset will be available on reasonable request at the corresponding author. Requests to access the datasets should be directed to All methods used in this study were performed in accordance with the relevant ethical guidelines and regulations of the University Hospital of Verona, where the investigation was carried out. Informed consent was obtained from all patients and the study protocol was approved by the local ethical committee (ID: 1560 CESC).GT, GC, CC, GV, and CP contributed to conception and design of the study. GT, GC, and LM organized the database. GC, LM, and GV performed the statistical analysis. GT, GC, CC, LM, EG, CP, and GV wrote the first draft of the manuscript. AR, AG, GV, and CP contributed to interpretation of the results and critical revision. 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.


Proximal humeral fractures (PHFs) are rare in children. Currently, the recommended surgical methods for severely displaced PHFs are closed reduction and percutaneous fixation using K-wires or intramedullary nailing, which can't provide firm internal fixation, especially for older and high-weight children. This study aimed to introduce a novel surgical approach, pediatric physeal slide-traction plate fixation (PPSP), for Neer–Horwitz grade IV PHFs in children.A 9-year-old boy presented with left shoulder pain and swelling due to a car accident. Physical examination revealed a positive shoulder deformity and local tenderness. On physical examination, we palpated bone friction without vascular and nerve damage. Based on imaging findings, we diagnosed Neer-Horwitz grade IV PHF. In view of the patient's condition, we performed PPSP after careful communication with the patient's parents. After 22 months of follow-up, the patient's left shoulder function was satisfactory, and there was no restriction of activities.According to previous studies, PPSP is only used for femur fractures. To the best of our knowledge, this is the first in the treatment for PHFs. Given the satisfactory outcomes, it is a safe and effective method and may provide a reference to cure analogous patients in the future. Proximal humeral fractures (PHFs) are relatively rare, accounting for approximately 3% of all pediatric fractures . It is mThe epiphyseal plate  is particularly important during the growth and development of children. It is more susceptible to damage than tendons, ligaments, and joint capsules and its injury is more common in long bones. The epiphyseal plate is the growth and development site of bone during the growth period and functions in longitudinal and transverse growth. Only normal cell function, orderly band arrangement, and complete blood supply are important for maintaining the physiological function of the epiphyseal plate. The epiphysis of the proximal humerus is responsible for 80% of humeral length growth . When PHThere is a great potential for bone healing and spontaneous remodelling after PHF in children. Some people believe that patients aged >12 years with obvious displacement need surgical treatment , whereasIn previous clinical and animal studies, pediatric physeal slide-traction plate fixation (PPSP) was only used in the lower limb fractures and not in upper limb fractures. Therefore, we proposed this procedure for Neer–Horwitz grade IV PHF in children. In this case, PPSP can be prolonged with proximal humeral growth, which provides reliable internal fixation without affecting epiphyseal growth.A 9-year-old boy experienced painful swelling and limited movement of his left shoulder after a car accident. On physical examination, we palpated bone friction without vascular and nerve damage. There was no associated neurovascular injury.X-ray films showed discontinuity of the left proximal humerus cortical bone, belonging to the type of complete dislocation. Based oWe used a 3.5-mm pediatric sliding locking plate from Double Medical Company, which is made of titanium alloy and consists of a barrel and sliding. The head and body of the plate are used to fix the epiphysis and metaphysis/diaphysis of the distal femur respectively, bypassing the growth plate. The plate was used following the same principles for fixation of the proximal humerual fracture in our case. The head of the plate is 80 mm long, 13 mm wide, and 4 mm thick. The body of the plate is 60–120 mm long, 9.3 mm wide, and 2.6 mm thick. The hole spacing is 10.0 mm. The outer diameter of the screw is 3.5 mm. The plate head has the shape of a drawer, which allows for slide traction of the body part .A deltopectoral approach to the proximal humerus was utilised and the fracture was exposed. A proximal humeral sliding plate was placed after the fracture was reduced. We screwed one screw each at the proximal and distal ends of the PPSP to provide temporary fixation. Fluoroscopy showed that the plate screw and fracture end were in a good position, and the remaining screws were inserted . FixatioNo splint or abduction brace was used after surgery, and active shoulder and elbow exercises were started on the second postoperative day. The sliding length of the PPSP was measured using anteroposterior and lateral radiographs. At the last follow-up, three-dimensional computed tomography of the affected limb was performed to measure humeral length. In addition, we recorded any complications associated with the surgery.The total postoperative hospital stay was 5 days. Radiography was performed at 6 weeks and 3 and 6 months after surgery to evaluate the sliding distance of the sliding plate, which were 3.67, 6.16, and 12.35 mm respectively . At 6 moIn children with displaced and unstable PHF, the optimal outcome is to maintain normal limb function and limb force line to the fracture end. Meanwhile, the growth and development of the epiphyseal plate don't be affected so that to ensure its normal transverse and longitudinal growth. Therefore, effective internal fixation and postoperative avoidance of secondary epiphyseal injuries are important factors.Percutaneous Kirschner wire internal fixation is a common clinical treatment with less intraoperative trauma, shorter operative time, and reasonable cost and is favored by many clinicians. However, it is prone to the risk of humeral head perforation . The fleConsequently, the conventional treatment of pediatric PHF may result in unreliable fixation and secondary epiphyseal plate injury, such as epiphyseal penetration injury, longitudinal growth inhibition, and other complications. The best surgery should depend on the patient's remodeling potential, amount of deformity, and functional needs. In view of the patient's grade IV, large angular malformation, and failure of closed reduction, open reduction was adopted. We designed a PPSP that slides along with the growth of the epiphyseal plate while providing reliable fixation for the fracture.The PPSP system was first proposed by Lin et al. . In previn vitro experiments by Lian et al.  this is just a case report and nededs more cases to confirm efficacy, (2) short follow-up period, (3) lack of follow-up of suppressed epiphysis, and (4) use of a single surgeon and the lack of a multicenter study, (5) this is an off-label use of this plate which is designed for the distal femur and we need to apply for a patent in this regard. In conclusion, we should further establish a multicenter trial with a larger sample size and long-term follow-up.Here, we report a new method for treating PHF using PPSP. After 22 months of follow-up, the patient's shoulder range of motion was normal, and there was no residual limb deformity. Imaging results show that PPSP can be effectively prolonged with the growth of the epiphyseal plate. Therefore, this method provides a feasible new approach for the treatment of severely displaced and unstable PHF in children.


The children with Henoch-Schönlein purpura (HSP) may suffer from renal insufficiency, which seriously affects the life and health of the children. This study aims to construct a prediction model of Henoch-Schönlein purpura nephritis (HSPN).  A total of 240 children with HSP treated in dermatology and pediatrics in our hospital were selected. The general information, patients' clinical symptoms, and laboratory examination indicators were collected for feature selection, and the XGBoost algorithm prediction model was built. β-D-aminoglucosidase, urinary retinol-binding protein, IgA, age, recurrence of purpura, purpura area, abdominal pain, 24-h urinary protein quantification, percentage of neutrophils, and serum albumin. The areas under the curves of the training set  and test set  models were similar.  According to the input feature indexes, the top ten crucial feature indicators output by the XGBoost model were urine N-acetyl- The prediction model based on XGBoost is used to predict HSP renal damage based on clinical data of children, which can reduce the harm caused by invasive examination for patients. Henoch-Schönlein purpura (HSP) is one of the most common systemic vasculitides in childhood, a common vascular allergic disease. It mainly affects the skin, kidneys, intestines, joints, and other body parts . In receEpidemiology suggests that HSP patients develop HSPN at a rate as high as 30% to 50% . AlthougMachine learning can use clinical data to build a prediction model and verify its predictive efficiency –12. In r2), it is considered as renal insufficiency.A total of 240 children with HSP treated in dermatology and pediatrics in our hospital from October 2019 to December 2021 were selected, of which 153 were complicated with HSPN. According to the European Union Against Rheumatism , HSP is The indicators tested in this study mainly include general information, clinical symptoms, and laboratory indicators. General information includes sex, age, and season of onset. Clinical signs and symptoms include joint swelling, abdominal pain and gastrointestinal bleeding, purpura of the upper body skin, and recurrence of purpura. Laboratory indicators include blood routine tests, urine routine tests, and biochemical tests.The machine learning used in this study is the integrated machine learning XGBoost algorithm based on a classification and regression tree . XGBoostK base models:ft is k basis models and ith sample.XGBoost is an ensemble learning algorithm based on gradient boosting. Its principle is to achieve an accurate classification effect through the iterative calculation of a weak classifier . It is aΩ that inhibits the complexity of the model. Thus, the objective function can be expressed asThe model's deviation and variance jointly determine the model's prediction accuracy, and the variation of the model is embodied as the loss function. Therefore, the objective function is composed of the model's loss function and the regular term According to the calculation method of the Taylor formula, the above objective function can be written asft = wq(x), x is a certain text, q (x) represents the leaf node where the sample is located, and wq represents the value of the leaf node w. Therefore, wq(x) represents the value of w of each sample . The regular term of the objective function can be defined asThe CRT is defined as Gradient enhancement generates a series of CRTs in the training process. The corresponding value of the leaf node of the CRT is an actual score, and the cumulative score of each CRT is the final predicted value. We test the accuracy of the algorithm using the 5-fold crossover method. The data set was divided into five parts, 4 of which were taken as the training set and the other as the test set. The accuracy of each experiment was obtained, and the average accuracy of the 5 results was taken as the estimation of the algorithm's accuracy. The specific modeling process is shown in χ2 test. Measurement data were expressed by mean ± standard deviation and t test was adopted. P < 0.05 means the difference is statistically significant.Counting data were counted by P > 0.05).Among the 240 children with HSP, there were 126 males and 114 females. The onset age was 2-16 years old, with an average age of 9.03 ± 2.68 years old. Among them, 62 cases (25.8%) occurred in winter, 102 cases (42.5%) had joint swelling and pain, 128 cases (53.3%) had abdominal pain and gastrointestinal bleeding, and 38 cases (15.8%) had upper body skin purpura. There were 153 cases of HSPN children and 87 cases without renal damage. There was no significant difference between the training group and the test group in gender, onset season, joint swelling and pain, abdominal pain, purpura of the upper body, and HSPN (P < 0.05)  .P > 0.05) (β-D-aminoglucosidase (NAG), and 24-h urinary protein quantification were significantly correlated with HSPN (P < 0.05).The correlation of HSPN occurrence was predicted according to laboratory indexes such as biochemical tests, among which there was no significant difference in HSPN in platelet count, C-reactive protein, total cholesterol, IgM, and D-dimer ( > 0.05) . HoweverThe XGBoost model automatically calculates features. According to the input feature indexes, the top ten important feature indicators output by the XGBoost model are as follows : NAG, RBIn the training set, the area under the curve of the XGBoost model was 0.895 (95% CI: 0.827-0.963). In the test set, the area under the curve of the model was 0.870 (95% CI: 0.799-0.941). The XGBoost prediction model has good sensitivity and specificity. The receiver operation characteristic curves of XGBoost algorithm model is shown in HSP is a kind of systemic vasculitis, which mainly involves the skin, joints, gastrointestinal tract, capillaries, and small blood vessels of the kidney, accompanied by significant deposition of IgA . ClinicaThe XGBoost model can automatically obtain the importance score of each attribute, thus effectively filtering features. Our study screened children for general information, clinical symptoms, and laboratory test indicators. The top 3 indicators based on the XGBoost model are NAG, RBP, and IGA. Our results are consistent with Karadag et al. , who belSerum IgA is the main component of the body's mucosal defense system. It is widely distributed in milk, saliva, and mucosal secretions of the gastrointestinal tract, respiratory tract, and urogenital tract. Therefore, it plays a vital role in the first line of defense against infection, especially in the respiratory tract and intestinal tract. This is also an essential indicator in the prediction model of this paper. NAG is a lysosomal enzyme that occurs in the urinary system and is usually found in very low levels of urine. When the tubular cells are damaged, many NAG is released from the tubular epithelial cells into the urine, where NAG levels are elevated. RBP is the third important feature in the prediction model in our study. Liu et al. believed that the RBP has an important predictive value for delayed renal involvement in children with HSP .In this study, the prediction model constructed based on the XGBoost algorithm can effectively reduce the overfitting problem and automatically specify the default branch direction for missing values, thus improving the algorithm's efficiency , 27. TheThere are several limitations to our study. It was a single-center retrospective study with a small sample size and no external validation. Secondly, due to the limitation of data sources, although this study included many predictive variables for screening, it was still not comprehensive. There may be potential predictive variables that were not included. In addition, this will further limit the advantage of the XGBoost algorithm. The next study will increase the sample size and expand the prediction index.Based on the XGBoost prediction model, we can preliminarily predict HSP renal damage according to clinical test data in dermatological outpatient work. This can reduce the harm caused by invasive examination of children. It provides a new idea for the prognosis of children with Henoch-Schönlein purpura in the first diagnosis of dermatology. In future work, we will improve the shortcomings, starting from clinical needs, to better serve the clinical application.


In addition, it was found that an increase in the total DASH score was associated with a lower risk of MetS . In the correlation analysis of the total population, a better-quality diet (higher DASH score) was positively correlated with high-density lipoprotein cholesterol (HDL-c), and negatively correlated with triglyceride (TG) concentration and waist circumference. It was also found that an increase in the total DASH score was associated with a lower risk of abdominal obesity . The results from the analyzed data highlight the potential benefits of following a healthy diet such as DASH.The current study was designed to examine the relationship between diet quality, as measured by the Dietary Approaches to Stop Hypertension (DASH) score, and the prevalence of metabolic syndrome (MetS) and its components. The study was cross-sectional in design and enrolled 535 people, including 215 with MetS and 320 without MetS. Using a validated food frequency questionnaire, the DASH diet quality score was counted. The mean age of the MetS group and control subjects was 58.48 ± 14.65 and 58.33 ± 9.26 years, respectively. The study showed that the MetS group had a significantly lower mean total DASH score than the control group (23.13 ± 5.44 vs. 24.62 ± 5.07,  There is no single established dietary pattern for patients with metabolic syndrome (MetS) due to the varied components of the MetS in individual patients. Studies have used various diets and nutritional practices for MetS diet therapy, including low- and very low-fat diets (<30% or <10% energy from dietary fat), and low- and very low-carbohydrate diets (26–45% or <26% energy from dietary carbohydrates), as well as the Mediterranean diet (MD), DASH diet (Dietary Approaches to Stop Hypertension), MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay), portfolio diet, vegan diet, vegetarian diet, Zone diet and Nordic diet [The benefits of a given dietary pattern must be combined with calorie restriction in the diet , as exceThe DASH diet is considered one of the healthiest diets in the world and was initially only used in patients with arterial hypertension and for preventing the development of arterial hypertension ,10. The Many scientific studies have found following the DASH diet to be associated with a lower risk of colorectal cancer , heart dMeanwhile, many studies have found an inverse relationship between adherence to the DASH diet and the prevalence and progression of MetS ,24,25, tThis study aimed to assess the cross-sectional association between adherence to the DASH diet and the prevalence of MetS and its individual components. The study investigated whether higher diet quality, as measured by the DASH score, was associated with a lower risk of MetS and its components. In addition, the study evaluated the correlations between the total DASH score, its components, and MetS components. Specifically, the research questioned if diet quality differed in patients with MetS compared to those in the control group. In addition, whether the content of individual components of the DASH score significantly differed in patients with MetS compared to those in the control group was assessed.This study was a cross-sectional study in design, and the study group consisted of patients with MetS (the MetS group). They were recruited from the Clinical Department of Internal Diseases and the Clinical Department of Endocrinology in the 4th Military Hospital of Wroclaw. Nutrition interviews were collected from the MetS group between 2013 to 2017. The initial MetS group consisted of 222 patients, but 7 patients were excluded from the study . This left a final MetS group that included 215 patients, of whom 127 were women and 88 were men. The MetS group had three or more components of MetS, according to the criteria defined by the American Heart Association (AHA), the National Heart, Lung, and Blood Institute (NHLBI), and the International Diabetes Federation (IDF) ,29. The The study was approved by the Bioethics Committee of Wroclaw Medical University (no. KB-306/2018).The eating habits of both groups were assessed using a 154-item semi-quantitative food frequency questionnaire (FFQ) that had been validated for the Polish population . The valThe DASH score was calculated for each person in the study based on the information collected through the FFQ. To neutralize the effect of energy intake on the eight DASH score components, each food group and food ingredient was calculated per 1000 kcal . The DASInformation on TGs, HDL-C, and fasting glucose (FG) was collected from the results of the biochemical test, and information on medications taken was derived from the medical history of patients with MetS during hospitalization. For the control group, blood was drawn for biochemical tests, and BP and anthropometric measurements were taken during the PURE study. FG, TGs and HDL-c concentrations were measured in venous blood samples. TGs and HDL-c concentrations were measured using the SPRINREACT enzymatic assay , while FG levels were tested using the Ascensia Entrust Glucometer .In both groups, BP was measured in a sitting and relaxed position after a 5-minute rest, using a certified digital sphygmomanometer . The mean BP values included in the analyses were derived from two measurements from each participant.2). The study and data collection details had been published previously [WC was measured at the midpoint between the lower marginal edge and the iliac crest, and measurements are expressed in centimeters with an accuracy of 0.5 cm. Body weight was measured with an accuracy of 0.1 kg and body height was measured with an accuracy of 0.5 cm. The body mass index (BMI) was calculated for both groups using the weight and height measurements (BMI = weight (kg)/height (m)eviously .The criteria for the clinical diagnosis of MetS used in the study were standardized in 2009 by representatives of the IDF, NHLBI, AHA, WHF (World Heart Federation), IAS , and IASO  . The WC t-test was used to compare means for normally distributed data.The study assessed descriptive features depending on gender and the presence of MetS. The descriptive data are presented as mean and standard deviation for numeric variables. The normality of the distribution of continuous variables was assessed using graphical (a histogram) and analytical methods (the Shapiro-Wilk test). The Mann–Whitney U test was used to analyze subgroups of non-normally distributed variables, and Student’s Multivariate logistic regression analysis was performed to find significant determinants of the prevalence of Mets and its components, and included total DASH score, age, gender, BMI, the daily energy intake, and the taking of drugs to lower TGs, as independent variables (model I-VI). In the model in which the relationship of certain independent variables with low HDL-c and high TGs was examined, the use of drugs to lower TGs was not taken into account. Before building the logistic regression models, it was determined if the response variable was binary, whether there was a lack of collinearity among the explanatory variables using a correlation matrix, and whether there was a linear relationship between the continuous explanatory variables and the logit of the response variable. Only independent variables that met these assumptions were selected for the multivariate logistic regression model.The relationships between the components of the DASH score expressed in grams or mg per 1000 kcal and the MetS components in the total population and within each gender group were analyzed using Kendall’s tau correlation.p < 0.05. The analyses were performed using Statistica v.13.3. .The level of statistical significance was set at p < 0.0001; BMI – OR = 1.27, 95% CI = 1.21–1.33, p < 0.0001). It was also found that an increase in the total DASH score was significantly associated with a lower risk of MetS prevalence .p < 0.0001). However, an increase in the total DASH score was shown to reduce the risk of this MetS component, but the result was not statistically significant. It was also found that the risk of abnormally elevated TG values was significantly higher in men than in women . On the other hand, an increase in BMI was significantly associated with a higher risk of abnormal FG levels . Meanwhile, the risk of abdominal obesity substantially increased with an increase in BMI  and significantly reduced with an increase in total DASH score . An increased risk of high BP was strongly associated with taking drugs to lower TGs , the male sex , and an increase in BMI .A better diet quality (a higher DASH score) was positively correlated with HDL-c and negatively correlated with TGs and WC in women. However, no correlation was found between the total DASH score and the individual MetS components in men. Among the DASH score components, a higher consumption of total fruits, nuts and legumes, and whole grains, was positively correlated with HDL-c in women. In contrast, a higher intake of sodium and red and processed meat was negatively correlated with HDL-c in women. Higher consumption of nuts and legumes was correlated positively with HDL-c and negatively with WC in men, while it was negatively correlated with TGs and WC in women. A higher consumption of total fruits was also negatively correlated with TGs and WC in women, although a higher consumption of vegetables correlated positively with WC. A higher consumption of whole grains was correlated negatively with WC and DBP in men, while a higher consumption of low-fat dairy products correlated positively with TGs. It was found in women that a higher sodium intake was correlated positively with TGs and WC. On the other hand, a higher consumption of red and processed meat was positively correlated with WC in women and with FG and WC in men. All significant correlations were weak and the highest r value was 0.168.This study assessed the relationship between diet quality measured using the DASH score and the prevalence of MetS and its components in 535 participants (215 patients with MetS and 320 without MetS) to determine if a diet similar to DASH was associated with a lower risk of MetS and its components.The study found no significant difference in the energy value of daily food rations in the group of women with MetS compared to women without MetS. Similar statistically insignificant results were obtained in the group of men. The most effective intervention in people with MetS is limiting the energy intake of their diet. Indeed, changing nutrition to achieve a 7–10% weight loss is appropriate for people with prediabetes unless additional weight loss is desired for other purposes [One of the proposed nutritional interventions for MetS is the DASH diet. The DASH diet emphasizes greater consumption of fruits, vegetables, nuts, legumes, whole-grain cereals, and reduced-fat dairy products. Furthermore, it limits the consumption of red meat, sweetened beverages, sugar, total fats, and saturated fatty acids . This stDiet can contribute to reducing the risk of prevalence and the deterioration of MetS and its components ,35. Dietp < 0.001). Also, after adjusting the model for energy intake, socioeconomic status, and BMI, participants in the highest tertile of DASH scores were 72% less likely to have MetS compared to the lowest tertile of DASH scores . In addition, Ghorabi et al. [p < 0.001), elevated serum TGs  and reduced HDL-c . In their adjusted model, adherence to the DASH diet was inversely related to elevated BP , while the results for high TGs  and low serum HDL-C  were at the limit of statistical significance. However, they did not find a relationship between adherence to the DASH diet and abdominal obesity. Furthermore, in their fully adjusted model, there was no significant association between adherence to the DASH diet and elevated FG. Piment et al. [p = 0.083). However, analyses by tertile of alcohol consumption showed that greater adherence to the DASH diet was inversely related to the risk of MetS in people with low alcohol consumption .This study found that an increase in the total DASH score significantly reduced the risk of MetS and was associated with a lower risk of abdominal obesity. In a study by Ghorabi et al. , an invei et al.  found tht et al.  also assp < 0.001), large LDL , total HDL-c , large HDL-c  and medium HDL-c . On the other hand, it was negatively correlated with TGs , total triglyceride-rich lipoprotein (TRL) , large very low-density lipoprotein (VLDL) , medium VLDL , total low-density lipoprotein (LDL) , intermediate-density lipoprotein (IDL) , small LDL  and small HDL . The study also found that lipoprotein concentrations were more strongly correlated with the DASH diet than the HEI-2015, MD, or E-DII™ scores.In the current study, a higher DASH score was positively correlated with HDL-c concentration, while it was negatively correlated with TG concentration. WC. Millar et al.  assessedp = 0.006; HEI-2015 − β = −0.052, p = 0.037), TGs  and LDL-c  [In the study by Millar et al. , linear = 0.033) . However= 0.033) . Further= 0.033) .p < 0.05), and WC (p < 0.001), as well as lower levels of tumor necrosis factor-alpha , interleukin 6 (IL-6), and plasminogen activator inhibitor-1 (PAI-1) (p < 0.01), a lower white blood cell count (WBC) (p < 0.01) and reduced insulin resistance (p < 0.05). In addition, individuals in the highest DASH quartile were 54% and 48% less likely to develop central obesity and MetS, respectively, than those in the lowest quartile (p < 0.05).In a study by Philips et al. , the relStudies have proposed the mechanisms behind the beneficial effects of a higher adherence to the DASH diet on MetS risk, although they are not yet clearly understood . Higher Although the DASH diet was first introduced more than 20 years ago, it is still the subject of numerous scientific studies, and the use of the DASH diet is still relevant and reasonable ,42. In aThis study found that higher diet quality was associated with a lower risk of MetS and visceral obesity, and was positively correlated with HDL-c and inversely correlated with TGs and WC. This cross-sectional study may provide a basis for designing longitudinal studies to examine these associations in the Polish population. In clinical practice, the DASH diet can be proposed as one of the most important components of lifestyle change for the prevention of MetS in at-risk individuals as well as patients with MetS. The need for the study stemmed from the fact that there are only a few scientific studies on the diet quality of patients with MetS in Poland. Patients with MetS are at risk of CVD and CVD-related death. Therefore, increasing the awareness of clinicians in Poland about a holistic approach to diet and the implementation of dietary changes for patients with MetS, as well as monitoring the quality of their diet, could significantly improve the quality of life of these patients.This study had several strengths. As far as we know, this is the first study to compare the DASH score with the prevalence of MetS and its components in the Polish population. Research based on a specific indicator of dietary quality is important from a public health perspective as it provides greater insight into the causes of chronic diseases and MetS.The study also had several limitations similar to those described in our previous study . The stuAssessment of the whole diet takes into account the interactions of nutrients and their synergistic effects on the risk of chronic diseases and MetS. The results of this study suggest that higher diet quality, measured by the DASH score, is associated with a lower risk of MetS and one of its components, visceral obesity. The results from the analyzed data highlight the potential benefits of following a healthy diet such as DASH.