Aggression and alcohol use disorder were correlated in Group3 (r = 0.31), Group4 (r = 0.34), and Group5 (r = 0.32), and aggression and smartphone addiction were correlated in Group2 (r = 0.39) and Group4 (r = 0.31). Problem gambling was correlated with aggression in Group5 (r = 0.39). A negative relationship between quality of life and alcohol use disorder occurred in Group1 (r = −0.36). According to the occupation group, the relationships between addiction problems, aggression, and quality of life were different. These findings suggest that addiction management for adults should be implemented in consideration of occupation groups.Addiction is related to aggression and quality of life. This study examined the relationship between these three factors according to occupation group in a mixed urban/rural area to better understand adult addiction problems. This study was a secondary data analysis of cross-sectional data collected by a 2017 regional survey of adults living in Gunsan City, South Korea. The survey included 500 people split into the unemployed (Group1), full-time homemakers (Group2), and primary (Group3), secondary (Group4), and tertiary (Group5) industry workers. Addiction problems and aggression were positively correlated ( Substance misuse and behavioral addiction are serious health problems. Approximately three million people die each year because of harmful use of alcohol . The burAddiction is not only a health problem but also a factor associated with aggression  and violMoreover, people with addiction problems have lower quality of life (QOL) . QOL is There is a relationship between occupation engagement, health, and well-being . OccupatIn a few studies, differences in alcohol misuse, smartphone addiction, and problem gambling were reported according to occupation groups ,19,20,21It is necessary to determine whether there are differences in addiction problems and related variables depending on an individual’s occupation and determine how the relationships vary according to occupation group. Therefore, this study was concerned with understanding addiction problems, aggression, and QOL of residents in mixed urban/rural areas by occupation. The objectives of the research were to (1) determine the differences between alcohol use disorder, smartphone addiction, problem gambling, aggression, and QOL according to occupation groups, (2) identify the relationships between alcohol use disorder, smartphone addiction, gambling problem, aggression, and QOL by occupation group.This study was based on data from surveys conducted by the Addiction Management Center (AMC) in Gunsan City. We received approval to use this survey data in our analysis. Gunsan City is a mixed urban/rural area with a population of 267,987, located in Jeollabuk-do, South Korea . Data weThis study used the Korean version of the World Health Organization (WHO) Alcohol Use Disorders Identification Test (AUDIT)  in KoreaThe Adult Smartphone Addiction Proneness (ASAP) scale , developThe Korean version of the Problem Gambling Severity Index (KPGSI)  was usedA Korean adaption of Buss and Perry’s Aggression Questionnaire (AQ) ,30 was uThe Korean version of the WHO Quality of Life Assessment Scale  was used2) in the analysis. We used the Bonferroni method as a post hoc test after ANCOVA, and the relationship between the variables was analyzed using the Pearson correlation coefficient. In order to detect a Pearson’s correlation coefficient of r = 0.30 with 80% power , G*Power 3.1.9.4. suggested we would need 84 participants [Data were analyzed using SPSS version 24.0. Descriptive statistics were used to assess participants’ general characteristics. Differences in variables were analyzed according to occupation using one-way analysis of variance (ANOVA). Age is a variable related to addiction and behavior. Therefore, we repeated the analysis of covariance (ANCOVA), which treats age as a covariate. ANCOVA was performed after confirming normality, homogeneity of variances, and homogeneity of regression slopes, and we included significance level and effect size .n = 254) were female and 49.2% (n = 246) were male. Their average age was 47.3 ± 16.53 years, and 41–50 years old was the most common age range . A total of 68.0% (n = 340) were residents in urban areas and 25.8% (n = 129) were residents in rural areas.The general characteristics of the participants are shown in p = 0.006, partial η2 = 0.03), smartphone addiction , overall QOL , psychological health , social relationships , and environment  among the QOL domains.The differences between groups of each variable were significant for alcohol use disorder  [ > 0.30)  or highep < 0.001). In Group2, smartphone addiction was positively correlated with aggression  and problem gambling . QOL was negatively correlated with aggression .In Group1, there was a negative correlation between QOL and alcohol use disorder  and problem gambling  in Group3. In Group4, aggression was positively correlated with alcohol use disorder  and smartphone addiction . QOL was negatively correlated with aggression . In Group5, aggression was positively correlated with alcohol use disorder  and problem gambling .Alcohol use disorder was positively correlated with aggression  and lowest in Group3 (adjusted M = 49.27), but there was no statistically significant difference. Addiction problems and aggression were positively correlated. Alcohol use disorder and aggression were significantly correlated only in Group3, Group4, and Group5, and smartphone addiction was significantly correlated in Group2 and Group4. Problem gambling was correlated with aggression only in Group5. In Group1, which had the highest level of aggression, there was no correlation between aggression and addiction problems.There was a significant difference in QOL between groups, and overall QOL was lowest in Group1 (adjusted M = 3.24) and highest in Group3 (adjusted M = 3.48). In the case of Group1, the score was the lowest for all four subdomains of QOL, and there were significant differences in psychological health, social relationships, and environment. Results of the post-test showed that all three domains were significantly lower than in Group3, and psychological health was significantly lower than in Group3, Group4, and Group5. Regarding the correlation between QOL and addiction problems, only Group1 showed a significant negative relationship between QOL and alcohol use disorder.Group1 comprised unemployed people and college students who do not engage in economic activities. They had lower QOL and a higher level of smartphone addiction than other groups. However, QOL was only significantly correlated with alcohol use disorder. Increasing poverty increases alcohol use and alcohol problems, and recent unemployment reduces alcohol use, while long-term unemployment increases alcohol use . TherefoGroup2 included full-time homemakers, mostly women and three men. This group’s results showed smartphone addiction scores second to those of Group1; aggression was positively correlated with smartphone addiction, and QOL was not correlated with addiction problems. These results were similar to those of Group3, Group4, and Group5, but not the unemployed group. Socially, “full-time homemakers” tend to be regarded as “people without a job or housewives”, but when it comes to addiction management, they should be regarded as “people who perform housework as their occupation”. However, they often spend their days at home, and the QOL of social relationships was relatively good, so programs using community organizations or individual support groups will be more effective for this group than workplace-based programs. Because smartphone functionality can vary with regard to information, entertainment, and communication , additioResults for Group3 (workers in primary industries), Group4 (workers in secondary industries), and Group5 (workers in tertiary industries) showed that aggression was positively correlated with alcohol use disorder and QOL was not correlated with addictions. Therefore, an intervention program that reflects self-control for aggression and alcohol misuse should be implemented for workers in all occupation groups. Roman  suggesteThe relationship between aggression and problem gambling was significant in Group5. Excessive gambling can induce a broad range of physical, social, and economic problems at the individual and family level . Unlike Summarizing the results of this study, Group1 showed a correlation between QOL and alcohol misuse. Group2, Group3, Group4, and Group5 showed significant results in the relationships between alcohol misuse and aggression, Group2 and Group4 in the relationships between smartphone addiction and aggression, and Group5 in the relationship between problem gambling and aggression. Therefore, unlike other occupation groups, Group1 related QOL, rather than aggression, to an addiction problem, and addiction problems and aggression were related in all other groups. Based on these results, future research directions are suggested as follows: Since this study analyzed data from only one mixed urban/rural area, further studies will be needed to collect data from various communities and compare the results. In addition, since there may be differences in drinking patterns between urban and rural workers in mixed urban/rural areas , addictiHowever, since only one part of AMC survey data in one mixed urban/rural area was analyzed, there are limitations as follows: (1) Non-evaluation and exclusion of participants’ mental disorders may have biased the results in aggression and QOL. (2) College students were included in the unemployed group; although students do not work, they may be involved in activities that require more time.Substance misuse and behavioral addiction are serious problems related to mental health and QOL. This study analyzed secondary data collected by a regional survey of adults living in a mixed urban/rural area in South Korea to confirm the relationship between addiction problems, aggression, and QOL by occupation status. There were differences in the degree of alcohol use disorder, smartphone addiction, and QOL between unemployed, full-time homemaker, and primary, secondary, and tertiary industrial worker groups. The relationships between the variables were different for each group. The results could be used as basic data for developing adult workplace-based programs among addiction management projects to be implemented in the community. Therefore, it is suggested that addiction management programs should be planned and implemented in consideration of occupation groups.In addition, since only one part of AMC survey data in one area was analyzed, there are limitations to the generalizability of these results; various communities should be researched in the future and the results should be compared to those found in this study.


Background: Hepatocellular carcinoma (HCC) is a male-predominant cancer. However, the relationship between 5α-dihydrotestosterone (DHT), the active form of testosterone, and HCC risk has not been established yet.Methods: We performed a serum epidemiological study in the Chinese population. From 2010 to 2012, 106 male HCC patients and 318 age-matched controls were detected for their serum DHT and estradiol (E2). The odds ratios (ORs) and 95% confidence interval (CI) were estimated by logistic regression analysis with adjustment for potential risk factors. Bivariate Pearson correlations between hormone concentrations and liver function index were investigated.Results: Serum DHT levels were lower (to 1/3 of control), and E2 levels were higher (to 1.5-fold of control) in HCC patients. Compared with the low DHT level, men with a medium level had an adjusted multiple OR of 0.15 , and men with a high level had an OR of 0.05 . Notably, DHT concentration, but not E2, is correlated with liver injury.Conclusion: The data suggest that serum DHT is closely associated with HCC risk, providing a reference in order to accurately predict liver cancer and study the pathogenesis of this disease. Hepatocellular carcinoma (HCC) is one of the most common fatal cancers in the world –4. NotabAlthough the serum E2 to testosterone ratio is reported higher in individuals with HCC , experimLiver cancer incidence varies substantially among different races , 4, 17. In the present work, focusing on Chinese men, we conducted a serum epidemiological case-control study to analyze the potential effects of serum DHT levels associated with HCC risk.We carried out a serum epidemiological study of HCC in Changchun, one of the biggest cities in the northeast of China. From 2010 to 2012, 106 HCC male cases diagnosed newly, aged 32 to 81, were selected from China-Japan Union Hospital, Jilin University. HCC was diagnosed on the basis of histological findings or an elevated level of serum α-fetoprotein more than 20 ng/ml combined with at least one positive image from angiography, sonography, and/or computed tomography. The 318 control subjects were randomly selected from healthy men who took part in regular health examinations in the same hospital. The controls were matched to 106 cases by age (±3 years) with a ratio of 3:1.All the men received an initial baseline examination, including routine blood tests, urine tests, etiology analyses, conventional liver function tests, and an in-person interview conducted by trained research assistants using a structured questionnaire on demographic and anthropometric characteristics, lifetime habits of alcohol, and tobacco use, dietary pattern, as well as personal and family histories of major chronic diseases. A blood specimen also was collected.Serum samples were divided into 100-μl shares and frozen at −80°C until tested for hormonal measurements. Serum DHT and E2 were measured by enzyme-linked immunosorbent assay (ELISA). The DHT ELISA kits were purchased from DRG International USA, and the E2 ELISA kits were purchased from DRG Instruments GmbH, Germany –24. The t-tests were used to compare clinical and demographic features, which involved age, height, weight, body mass index (BMI), history of cigarettes, and alcohol, eight serum liver function indexes of albumin (ALB), globulin (GLB), total bilirubin (T-BIL), cholinesterase (CHE), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT), and serum hormone concentrations. Pearson correlations were calculated between hormone and liver function index to investigate their relationships to liver injury.Student In the serum case-control study, subjects were divided into three groups for each sex hormone with cutoff for DHT of 500 and 1,255 pg/ml; for E2, 32.7 and 43.6 pg/ml. Odds ratios (ORs) and 95% confidence intervals (CIs) from binary logistic regression models, adjusted for age , BMI , smoking , and alcohol consumption , were used to assess serum hormone concentrations associated with the HCC risk.In further studies, we deepened our research using three models. First, we divided all the participants into two parts by age (<65 or ≥65) and analyzed as the method above. Second, we divided the 106 cases by etiology and compared those with or without viral [hepatitis B virus (HBV) or hepatitis C virus (HCV)] infection to all the controls. Finally, we divided the 106 cases by alcohol/alcohol intake (ever or never) and compared them to the controls. ORs and 95% CIs from the binary logistic regression models were analyzed individually. All statistical analyses were calculated using SPSS 17.0 .p < 0.01; 41.27 ± 76.191 vs. 19.77 ± 37.053 g per day), suggesting alcohol consumption as a risk factor for HCC.The average age of subjects in this study was 62 years, and there was no significant difference in height, weight, or BMI . Of the p < 0.01). Meanwhile, the E2 was significantly higher . Further, a good linear trend of DHT and E2 was observed in healthy men  but disappeared in HCC patients, suggesting the unbalance.Since testosterone is the intermediate to both DHT and E2, it is better to measure directly their association to HCC. Using ELISA kits, we tested the serum DHT and E2 concentrations of all men . The resp-values were calculated via dividing the patients into three groups by DHT level   . First, p trend. For the older men, the highest DHT levels had a similar multivariate 0.03 (95% CI 0.01–0.16) with p trend < 0.01. Thus, age does not play a pivotal role in the relationship between the low DHT level and the high HCC risk.By dividing the subjects by the median age of 65 years, the effect of age on the association between DHT and HCC risk was assessed. For the younger men, highest serum DHT concentration had lower multivariate ORs of 0.02 (95% CI 0.01–0.07) with a significant p < 0.01) in HCC patients with HBV or HCV infection and 0.11  in HCC patients without viral infection. For lifestyle factors , the OR values for the highest vs. lowest DHT concentration were 0.15  in the smoking group and 0.11  in the no smoking group; 0.15  in the alcohol intake group and 0.13  in the no alcohol intake group. These results demonstrated that the serum DHT is inversely associated with HCC risk, irrelevant to age, viral infection, smoking, or alcohol consumption. Interestingly, we found that the link between DHT and HCC risk seems to have disappeared in overweight males. However, the accurate evaluation between sex hormones and HCC risk among obese people needs a further confirmation based on the small sample size.For virus infection factor, here, we showed that the OR values for the highest vs. lowest DHT concentration were 0.14  and positive correlation with CHE  suggest the potentially important role of DHT in hepatic synthetic function.Interestingly, almost all the liver function indexes showed a significant correlation with serum DHT , rather In this study, we performed a serum epidemiological case-control study setting Chinese men as subjects to assess the significance of sex hormones for HCC. The data displayed that the Chinese HCC males show extremely low serum DHT and higher E2 levels compared with the control group. The results of logistic regression analysis showed that the serum DHT and E2 were significantly negatively or positively correlated with HCC risk, respectively. For further study, we found that serum DHT rather than E2 is closely related to the liver injury.HCC patients with cirrhosis have significantly lower plasma DHT concentrations than those with cirrhosis alone , and theIn vitro, AA exposure induced hepatoma in a dose-dependent manner in mice, including HCC and intrahepatic cholangiocarcinoma  . Among tarcinoma . The eviarcinoma , 32. In arcinoma  have ideLifestyle and chronic HBV/HCV infection are another two important risk factors for HCC –36. MarrA higher increase in serum E2 levels was found in cases according to our study , consistAlpha fetoprotein (AFP) is a specific marker for the diagnosis of HCC, with a positive rate of about 70%, which is not sufficient to predict the occurrence of HCC. Since the incidence of HCC in men is higher than that in women, more studies have concentrated on the relationship between testosterone and the pathogenesis of HCC, but the results are contradictory –16. Prevvia various statistical methods. Due to the small sample size, there is a certain degree of deviation in the strength of their correlation in the logistic stratified analysis. Especially in the analysis of the relationship between E2 and HCC, it is doubtful whether the OR and CI values obtained in this study are able to reflect the true correlation between them due to the limitation of sample size. In order to solve this problem, more HCC patients and a larger sample size are supposed to be included in the study. Therefore, for the further work, more observation objects will be collected to conduct a thorough and comprehensive investigation regarding the relationship between sex hormones (not limited to DHT and E2) and HCC risk.In this study, we preliminarily determined the association of sex hormones (DHT and E2) with HCC risk In this work, the DHT and E2 levels of 106 HCC patients and 318 age-matched controls were investigated among Chinese men. Compared with healthy people, HCC patients showed lower DHT and higher E2 concentrations, respectively. The results of logistic regression analysis suggested that both the serum DHT and E2 levels are closely related to HCC risk. Further studies indicated that DHT instead of E2 is associated with liver injury. Our study illustrates that serum DHT has the potential to be a better predictor of HCC compared to testosterone. For further work, we will expand the sample size to accurately determine the association of DHT with HCC risk. Moreover, the causal relationship between DHT and HCC will be explored through prospective experiments.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by Animal Experiment Ethics Committee of Northeast Normal University. The patients/participants provided their written informed consent to participate in this study.LW, ZL, AR, and XL contributed to conception and design. LW and ZL contributed to acquisition of data. LW and YP contributed to analysis and interpretation of data. LW and XL contributed to drafting of the manuscript. LW, WW, JL, and XL contributed to critical revision of the manuscript for important intellectual content. LW, ZL, and XL contributed to statistical analysis. JL and XL contributed to administrative support and study supervision. LW, AR, JL, and XL contributed to final approval of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Cardiovascular diseases (CVDs) incidence is becoming higher. This fact is promoted by metabolic disorders such as obesity, and aging. Atherosclerosis is the underlying cause of most of these pathologies. It is a chronic inflammatory disease that begins with the progressive accumulation of lipids and fibrotic materials in the blood-vessel wall, which leads to massive leukocyte recruitment. Rupture of the fibrous cap of the atherogenic cusps is responsible for tissue ischemic events, among them myocardial infarction. Extramedullary hematopoiesis (EMH), or blood cell production outside the bone marrow (BM), occurs when the normal production of these cells is impaired  or is altered by metabolic disorders, such as hypercholesterolemia, or after myocardial infarction. Recent studies indicate that the main EMH tissues  complement the hematopoietic function of the BM, producing circulating inflammatory cells that infiltrate into the atheroma. Indeed, the spleen, which is a secondary lymphopoietic organ with high metabolic activity, contains a reservoir of myeloid progenitors and monocytes, constituting an important source of inflammatory cells to the atherosclerotic lesion. Furthermore, the spleen also plays an important role in lipid homeostasis and immune-cell selection. Interestingly, clinical evidence from splenectomized subjects shows that they are more susceptible to developing pathologies, such as dyslipidemia and atherosclerosis due to the loss of immune selection. Although CVDs represent the leading cause of death worldwide, the mechanisms involving the spleen-atherosclerosis-heart axis cross-talk remain poorly characterized. Hematopoiesis is the process by which blood cellular components are formed. It occurs from embryonic development to adulthood in order to produce and replenish the blood system. Hematopoietic stem and progenitor cells (HSPCs), with self-renewal and differentiation properties, can be employed as a model system to understand tissue stem cells´ fate and their role in aging, inflammation, atherogenesis and cancer –7.2 and CO2, while megakaryocytes generate platelets for blood clotting and wound healing. In fact, blood is one of the most regenerative and plastic tissues . It occurs when there is an insufficient or irregular production of blood cells from the BM , 21–23. The anatomical sites commonly involved in EMH include the spleen, liver, lymph nodes and paravertebral regions, although other organs and tissues may participate  , 34, 35.+ cells continues for at least 24 days after challenge (The establishment of HSPCs in hematopoietic locations is mediated by the expression of CXCL12 and vascular cell adhesion molecule-1 (VCAM-1), which bind to CXCR4 and to very late antigen-4 (VLA-4), respectively , 38–41. hallenge . Convershallenge .ca. 13 cm long , and platelets. In rodents, it is a place of EMH , 23, 61.+ T cells, although small amounts of CD8+ T cells are also present, as well as interdigital DCs and migrating B cells. The external PALS is formed by B and T lymphocytes, macrophages and, after antigenic stimulation, newly formed plasma cells. The follicles are continuous in the PALS and are mainly composed of B cells with a smaller number of follicular DCs and CD4+ T cells, but usually do not contain CD8+ T cells. They contain germinal centers, which are formed after antigenic stimulation and contain macrophages and apoptotic B cells.The spleen contains almost a quarter of the body’s lymphocytes and initiates immune responses to blood antigens, especially in the WP, which surrounds the central arterioles and is subdivided into the periarteriolar lymphoid sheath (PALS), the follicles and the MZ , 58. It +, the sinus-coated endothelial cells. Peripheral to the marginal sinus, is the thick outer ring of the MZ, with reticular fibroblasts, macrophages, DCs and B cells. Macrophages of the MZ are another population of splenic macrophages that are selectively characterized by the expression of scavenger receptor MARCO and by SIGN-R1 lectin   –69. Althntibody) , 58. (Cardiovascular diseases (CVDs) are the main cause of mortality worldwide, being atherosclerosis one of the underlying agents of these pathologies. The deposition of cholesterol-rich lipoproteins in the arterial wall initiates the atherosclerotic process, triggering leukocyte recruitment and chronic inflammation. Aforetime, atherosclerosis was thought to be only the consequence of the progressive lipid accumulation in the blood vessels. The current view is that it is a much more complex process involving both lipids and immune cells  , 70–72.  , 71, 73. , 75. The , 76.high monocytes to the growing atheroma layer. These monocytes express pro-inflammatory interleukins (such as pro-IL1) and have proteolytic capacity, contributing to the remodeling of the atheroma and favoring plaque instability. In addition to this, they exhibit increased production of reactive oxygen species, promoting the oxidation of LDL, which results in macrophages loaded with lipids (foam cells)  , 80. Regm cells) , 78, 81., which is more common in lesions than Ly-6Clo monocytes. Ly-6Chi monocyte subset is thought to differentiate into an inflammatory phenotype  show a dramatic increase in HSPCs and EMH  coupled with cholesterol dysregulation which increases HSPC proliferation and skewing of leukocyte production towards monocytes and neutrophils . Many mechanisms modulate the distribution and composition of lipid rafts, but efficient cholesterol efflux is the most important one and, consistently, cholesterol pathways contribute to hematopoiesis homeostasis  led to the degradation of the BM niche and the subsequent mobilization of HSPCs to other tissues, such as the spleen. In addition, this nervous system activation induces the release of proteases by neutrophils which cleave the CXCR4 receptor on HSPCs  and express proinflammatory factors, including reactive oxygen species and proteases .Acute infections or a large accumulation of pus with abscess in the spleen.Thrombosis in the blood vessels of the spleen or cirrhosis in the liver.e.g. chronic lymphocytic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, myeloproliferative dysplasia and hairy cell leukemia).Certain types of cancers  and EMH appears to be a key issue in the development of new therapeutic strategies against atherosclerosis by focusing on specific targets.VF-G wrote the paper, designed the figures and revised the manuscript. SG-R, PM-S, and AC provided intellectual input. SG-R also revised the manuscript. LB provided funding and intellectual input and discussed the information. The authors thank Mr Adrián Povo-Retana for the review and critical comments on the manuscript. All authors contributed to the article and approved the submitted version.The review was written by authors that work in a laboratory where projects are supported by: Ministerio de Economía, Industria y Competitividad, Ministerio de Ciencia, Investigación y Universidades, and Agencia Estatal de Investigación , Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CB16/11/00222), Fundación Ramón Areces (CIVP18A3864), Consorcio de Investigación en Red de la Comunidad de Madrid, S2017/BMD-3686 and Fondo Europeo de Desarrollo Regional.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.


Neonatal thrombocytopenia is a common hematological abnormality that occurs in 20–35% of all newborns in the neonatal intensive care unit. Platelet transfusion is the only known treatment; however, it is the critical point to identify neonates who are really at risk of bleeding and benefit from platelet transfusion as it also has various potential harmful effects.To investigate the prevalence and risk factors of neonatal thrombocytopenia and its relationship to intraventricular hemorrhage in the neonatal intensive care unit and to determine whether the use of platelet mass index-based criteria could reduce the rate of platelet transfusion.Retrospective cohort study.9/L between January 2013 and July 2016 were analyzed.This study was conducted in the neonatal intensive care unit of a tertiary university hospital. The medical records of neonates in the neonatal intensive care unit with platelet counts <150×10During the study period, 2,667 patients were admitted to the neonatal intensive care unit, and 395 (14%) had thrombocytopenia during hospitalization. The rate of intraventricular hemorrhage was 7.3%. Multiple logistic regression analysis showed that although lower platelet counts were associated with a higher intraventricular hemorrhage rate, the effects of respiratory distress syndrome, sepsis, and patent ductus arteriosus were more prominent than the degree of thrombocytopenia. Thirty patients (7%) received platelet transfusion, and these patients showed a significantly higher mortality rate than their non-platelet transfusion counterparts (p<0.001). In addition, it was found that the use of platelet mass index-based criteria for platelet transfusion in our patients would reduce the rate of platelet transfusion by 9.5% (2/21).Neonatal thrombocytopenia is usually mild and often resolves without treatment. As platelet transfusion is associated with an increased mortality rate, its risks and benefits should be weighed carefully. The use of platelet mass index-based criteria may reduce platelet transfusion rates in the neonatal intensive care unit, but additional data from prospective studies are required. It is the critical point to identify and discriminate neonates who are really at risk of bleeding and benefit from PT as PT has also various potential harmful effects. Among these harmful effects, infectious, inflammatory, and hemodynamic risks are widely known , which is among the most significant problems in neonates due to its association with a poor long-term prognosis ,15. We a9/L between January 2013 and July 2016 were analyzed. Thrombocytopenia was confirmed with peripheral blood smear, and patients with pseudothrombocytopenia were excluded.This study was conducted retrospectively in the NICU of a tertiary university hospital. The medical records of neonates in the NICU with platelet counts <150×10th minute Apgar score below 7 was considered , sepsis, respiratory distress syndrome (RDS), patent ductus arteriosus (PDA), necrotizing enterocolitis , IVH, indirect hyperbilirubinemia (IHB), phototherapy treatment, and total parenteral nutrition (TPN) use were recorded from the medical files and blood bank records. For the low Apgar score, the 5nsidered . Placentr damage . Sepsis r damage . “Suspecr damage . For ther damage . Cranialr damage . As a roPostmenstrual ages of all infants were within the neonatal time frame for the data “age at the onset of thrombocytopenia,” “lowest platelet day,” and “transfusion day.”The patients were grouped according to the onset of thrombocytopenia. Thrombocytopenia before 72 h was defined as early-onset thrombocytopenia and after 72 h as late-onset thrombocytopenia .9/L; moderate, 50-100×109/L; and severe thrombocytopenia, <50×109/L.To evaluate associated risk factors for severe thrombocytopenia, we divided the patients into the following categories based on their lowest platelet counts: mild, 100-150×109/L if the infant is stable; a platelet count of 20-50×109/L if the infant is unstable and/or had a birth weight of <1000 g and/or had previous major bleeding, and/or after an exchange transfusion and/or before a planned surgery, and/or a rapid decrease in the platelet level; a platelet count of 50-100×109/L in an infant with active bleeding, and/or at the beginning of an exchange transfusion  with ethylenediaminetetraacetic acid-anticoagulated blood samples.The study was approved by the local institutional review board (18-KAEK-014).Statistical Package for the Social Sciences (SPSS) for Windows version 18.0  was used for all statistical analyses. The data are expressed as percentage, median, or mean ± standard deviation. Continuous variables were compared using the two-tailed t-test for parametrically distributed data or the Mann–Whitney U test for nonparametrically distributed data. Categorical variables were analyzed using the chi-square test. A multivariate logistic regression model was implemented to determine the relationships between the selected variables and IVH, and enter model was used. Variables that were significant in the univariate model and clinically thought to be effective on IVH were included in the model. The rate of IVH in thrombocytopenic neonates in NICU is reported as 4.5–33% ,12. If t9/L. Of these thrombocytopenic neonates, 176 (44.6%) were girls, and 224 (58%) were preterm. The median birth weight was 2,322 g . The demographic characteristics, perinatal features, and postnatal event rates in the study population are given in During the study period, 2,667 patients were admitted to the NICU. After excluding the patients with pseudothrombocytopenia (n=25), there were 395 patients (14%) with at least one recorded platelet count <150×109/L (8–149×109/L), and the median age at the lowest platelet count was 3 days (1–81 days). The mean and median values for postmenstrual ages of the infants at the onset of thrombocytopenia were 35.2±4.4 and 36.1 (22–44) weeks, respectively. Thrombocytopenia was present in 254 (64%) of the infants before they were 72 h old (early-onset thrombocytopenia) and in 141 (36%) after 72 h (late-onset thrombocytopenia). The median time for resolution of thrombocytopenia was 3 days (1–31 days). Comparison of early-onset and late-onset thrombocytopenia groups according to the demographic and clinical features revealed that the following factors were associated with late-onset thrombocytopenia: gestational age, birth weight, sepsis, IVH, PDA, NEC, IHB, phototherapy treatment, and TPN use (The median age of the patients at the onset of thrombocytopenia was 2 days old (1–78 days). The median lowest platelet count was 101×10 TPN use .Of the thrombocytopenic neonates, 74 (18.7%) had severe thrombocytopenia, 119 (30%) had moderate thrombocytopenia, and 202 (51.3%) had mild thrombocytopenia. The rate of severe thrombocytopenia among all of the neonates in the NICU during the study period was 2.7%. To elucidate the risk factors for severe thrombocytopenia, the clinical features of these three groups were compared. The following factors were associated with severe thrombocytopenia: low Apgar score, IUGR, sepsis, IVH, PDA, RDS, TPN use, PT, and mortality .Among the 395 thrombocytopenic patients, 30 (7%) received PT. A comparison of these patients with those who did not receive PT is shown in As thrombocyte transfusion was based on the platelet count, we also investigated whether these transfusions would have been indicated if PMI-based criteria had been considered. As these criteria are mostly for prophylactic PT, three patients who received transfusions because of active bleeding were excluded. The data of PMI were available for 21 of the remaining 27 patients with PT. These patients included the two who received transfusion based on the platelet count criteria, although no indications were present if PMI-based criteria were considered. Thus, for our patients, the use of PMI-based criteria would decrease the PT rate by 9.5% (2/21).Twenty-nine of the total patient population had IVH; 6 infants had grade 4 IVH, 6 had grade 3, 3 had grade 2, and 14 had grade 1 IVH. As IVH is commonly encountered during neonatal care and is important in the long-term prognosis, we documented the relationships between patient characteristics, thrombocytopenia, and IVH. Significant associations were observed between IVH and gestational age, birth weight, age at onset of thrombocytopenia, lowest platelet count, lowest platelet count day, sepsis, PDA, RDS, and PT . In thisMultiple logistic regression analysis indicated that gestational age, lowest platelet count, sepsis, PDA, and RDS were associated with the development of IVH in thrombocytopenic neonates, with sepsis showing the greatest effect .This study showed that although NT was encountered commonly in the NICU (14%), most cases were mild and resolved quickly without treatment (93%). Although lower platelet counts were associated with a higher IVH rate in the NICU, the effects of sepsis, RDS, and PDA were more prominent than the degree of thrombocytopenia. We also found that the use of PMI-based criteria for PT in neonates instead of platelet count-based criteria would decrease the PT rate by 9.5%.The thrombocytopenia rate in the NICU has been reported to be 20–35%; this wide range is probably due to the differences between patient populations ,2. The lIn our study, 64% of the neonates exhibited thrombocytopenia within 72 h after birth as early-onset thrombocytopenia. In general, early-onset thrombocytopenia is usually mild and resolves without treatment . In the 9/L and found that IVH was not significantly related to the level of the lowest platelet count. Andrew et al.  preterm infants and reported no difference in the incidence of bleeding between groups with and without PT; they concluded that prophylactic PT is not necessary (9/L) for PT in NICU were investigated, and it showed that the rates of both mortality and major hemorrhagic events were higher in the higher threshold group (In this study, the PT rates among all of the NICU patients and the thrombocytopenic neonates in the NICU were 1.1% and 7%, respectively. However, rates of up to 10% for all NICU patients have been reported in the literature . This loecessary . In anotecessary . Moreoveecessary ,30,36. Fecessary  reportedld group , but docld group ,5. Apartld group ,38. OtheAlthough the number of patients in the transfused group in our study was small, our observations indicated that the rate of transfusions may be further decreased by 9.5% using PMI-based criteria. Since the 1970s, it has been known that larger platelets function better in plug formation, and PMI-based criteria were established because of the idea that bleeding risk is not related solely to platelet count but also platelet size and function ,39,40. PThis study has some limitations, mainly due to its retrospective nature. For example, we did not know the exact diagnoses and etiologies of NT in all of the patients. On the other hand, a relatively large sample size is the strength of the study. Also, this study is among the rare studies in literature regarding the use of PMI-based criteria in thrombocytopenic neonates. Prospective studies are needed, and these will provide more accurate information.Based on the results of this study, we conclude that NT was usually mild and often resolved without treatment. Moreover, PT was associated with a higher mortality and IVH rate. Considering these findings, the risks and benefits should be weighed carefully before administering PT to neonates in the NICU. Prospective studies regarding the use of PMI-based criteria to decrease PT rates are required.


Mikulicz's disease is a unique condition involving the enlargement of the lacrimal and salivary glands, similar to that observed in Sjogren's syndrome; however, Mikulicz's disease is clinically characterized by infrequent autoimmune reactions and responsiveness to glucocorticoid treatment. The ultrasound features of the lacrimal and salivary glands in patients with IgG4-Mikulicz's disease were characterized by multiple hypoechoic areas of varying sizes within the enlarged glands. IgG4 serum level was also elevated, in contrast to the detection of normal levels in Sjogren's syndrome. In this article, we intended to illustrate a case of Mikulicz's disease with clinical and imaging features. IgG4-related disease (IGG4-RD) is a chronic inflammatory disease, characterized by swollen and thickened lesions of the affected organs, such as lacrimal glands, salivary glands, or pancreas, with high serum concentrations of IgG4, and marked IgG4-positive plasma cell infiltrations of the affected tissues. Inflammation can extend to multiple organs, including the biliary tree and kidney, during long-term follow-up. Therefore, IgG4-RD is generally regarded as a systemic disease. Diseases involving lacrimal and major salivary glands have often been referred to as “Mikulicz´s disease” or “Mikulicz´s syndrome” in the past . Since tA 32-year-old female patient was admitted to hospital with bilateral, symmetrical, painless swelling of the lacrimal, submandibular glands, with no history of dry eyes or mouth. The symptoms appeared since the first pregnancy and lasted for a period of longer than 3 years. Although she attended medical check-ups several times, she did not receive any definitive diagnosis or treatment.Imaging findings: on ultrasound examination of the patient´s orbit and neck, the diffuse enlargement of the lacrimal and submandibular glands was observed, in addition to hypervascularity and multiple hypoechoic areas (ic areas . Facial ic areas .Pathology: the patient underwent a biopsy of the lacrimal gland. The microscopic images showed lymphoplasmacytic infiltration and fibrotic areas. The immunohistochemical findings revealed CD138-positive cells (ve cells  and the ve cells .Serum IgG4: serum IgG4 levels were as high as 5,012 mg/L before the administration of steroid therapy, compared with the normal range of less than 1,350 mg/L [350 mg/L .Treatment: the patient was treated with 40 mg/day prednisolone for 4 weeks, after which the dose decreased by 5 mg/week until it reached 5 mg/day. After 9 months of treatment with corticoids, the serum IgG4 level was markedly decreased, returning to within the normal range, at 798 mg/L, accompanied by decreased gland sizes.During the past 2 decades, significant advancements have been made toward understanding MD. The association between the enlargement of lacrimal and salivary glands and elevated IgG4 serum levels was first reported in 2004  and was The 2019 American College of Rheumatology/ European League Against Rheumatism classification criteria for IgG4-RD is recommended for diagnosis. If the inclusion criteria are met, no exclusion criteria are present, and the total score is ≥20, then a diagnosis of IgG4-RD could be established . AlternaSystemic corticosteroid is the first-line treatment for MD, in most of the cases. The majority of patients respond well to glucocorticoid therapy within weeks, typically with reductions in mass sizes and improved symptoms, often associated with a significant drop in serum IgG4 levels . IntraorMD is a benign disease of unknown etiology, characterized by the bilateral enlargement of the lacrimal and salivary glands. The symptoms could be expected to improve following steroid therapy. We presented a case report of MD with a focus on the imaging. In our article, the association between lacrimal biopsy tissues, IgG4 serum levels, and treatment response were consistent with IgG4-RD. Ultrasound imaging may be a useful procedure for monitoring the efficacy of corticosteroid therapy in these patients.


In this study based on a large nationally representative sample of Korean adults, we investigated the potential associations of the body mass index (BMI) and waist circumference (WC) with mortality in patients undergoing hemodialysis. We obtained the data of 18,699 participants >20 years of age who were followed up with for 4 years and for whom BMI and WC information were available, using a nationally representative dataset from the Korean National Health Insurance System. Patients were stratified into five levels by their baseline BMI and into six levels by their WC (5-cm increments). A total of 4975 deaths occurred during a median follow-up period of 48.2 months. Participants with a higher BMI had a lower mortality rate than those with a lower BMI. In a fully adjusted Cox regression analysis, being overweight and obese was associated with a significantly lower relative risk of all-cause mortality relative to the reference group. Conversely, the mortality rate was higher among participants with a high WC than among those with a low WC. Participants with the highest WC had a higher risk of mortality, while those with the lowest WC level had a significantly lower risk of mortality. In conclusion, all-cause mortality was positively associated with WC, a measure of abdominal obesity, and inversely associated with BMI, a measure of body volume, in patients undergoing hemodialysis.  Increases in the prevalence of obesity during the past half-century have led to worldwide health concerns. Obesity particularly increases the risks of several other diseases, including cardiovascular diseases, diabetes, cancer, and chronic kidney disease (CKD) ,2. MoreoGenerally, the body mass index (BMI), an internationally accepted standard anthropomorphic measurement, is used to define obesity in research settings . HoweverPreviously, measures of central or abdominal obesity, which is defined by a high waist circumference (WC) and waist-hip ratio, have also been used as predictors of cardiovascular and all-cause mortality . MultiplThe data used in this study were obtained from a national health insurance claims database established by the Korean NHIS. This database includes all claims data provided by the NHIS and Medical Aid programs. The Korean NHIS is a compulsory social insurance scheme that covers approximately 97% of the Korean population; the remaining 3% are covered by the Medical Aid program . TherefoThe study protocol was approved by the Institutional Review Board (IRB) of Chonnam National University Hospital (CNUH-EXP-2020-009) and the NHIS (NHIS-2018-1-109). The patients’ identification numbers were anonymized to protect individual privacy. Because only anonymized and de-identified information was used for analysis, the IRB waived the requirement for informed consent. n = 71,510) and those with missing covariate data (n = 2915), the study population finally comprised 18,699 subjects. A flowchart of the study participant selection process is shown in This study included the data of 93,124 hemodialysis patients older than 20 years who underwent at least 1 health examination between 2009 and 2015. Hemodialysis patients were identified using a combination of the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes  and a special code . The Korean Health Insurance Review and Assessment Service database can be used for the reimbursement of medical expenses for dialysis. Moreover, dialysis patients are registered as special Medical Aid program beneficiaries. Therefore, we were able to use this combination of information to identify every hemodialysis patient in the South Korean population for inclusion in our study. After excluding participants who had not participated in a health checkup within 1 year after hemodialysis initiation (2). We defined obesity as a BMI ≥ 25 kg/m2. The participants were then classified into the following categories according to the World Health Organization recommendations for Asian populations: underweight (BMI < 18.5 kg/m2), normal (≥18.5 to <23 kg/ m2), overweight (≥23 to <25 kg/m2), stage 1 obesity (≥25 to 30 kg/m2), or stage 2 obesity (≥30 kg/m2) [For each participant, the BMI was calculated by dividing the weight (in kg) by the square of the height (in m0 kg/m2) . The WC of each participant was also measured at the midpoint between the rib cage and the iliac crest by a trained examiner. The patients were divided into 6 categories based on 5-cm WC increments: <80 cm in men and <75 cm in women, 80–85 cm in men and 75–80 cm in women, 85–90 cm in men and 80–85 cm in women (reference group), 90–95 cm in men and 85–90 cm in women, 95–100 cm in men and 90–95 cm in women, and ≥100 cm in men and ≥95 cm in women. Abdominal obesity was defined as WC ≥90 cm in men and ≥85 cm in women according to the definition of the Korean Society for the Study of Obesity . 2 and was calculated using the Modification of Diet in Renal Disease formula [The analysis included comorbidities, such as hypertension, diabetes, dyslipidemia, cardiovascular disease, and cancer; and health behavioral factors, such as physical activity, alcohol consumption, and smoking, which are known to be associated with mortality. Hypertension was defined as a previous hypertension diagnosis  and a history of taking at least 1 antihypertensive drug, or a recorded systolic blood pressure of ≥140 mmHg or diastolic blood pressure of ≥90 mmHg in the health examination database. Diabetes was defined as a previous clinical diagnosis (ICD-10 codes E11–14) and a medical history of diabetes, or a recorded fasting serum glucose concentration of ≥126 mg/dL in the health examination database. Dyslipidemia was identified using the appropriate diagnostic code (E78) and a history of lipid-lowering drug use, or a total serum cholesterol concentration of ≥240 mg/dL in the health examination database. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m formula . CardiovParticipants were additionally categorized into 3 groups according to their smoking status  and into 3 categories according to alcohol consumption ). Participation in regular exercise was defined by the response to the following question: “Did you exercise moderately for >30 min until you were substantially short of breath on more than 5 days during the last week?” Residence in an urban area was also determined.Finally, the participants were divided into the income quartiles (Q) of Q1 (lowest), Q2, Q3, and Q4 (highest) to assess the effects of socio-economic status. A low income was defined as classification into Q1 or the receipt of Medical Aid benefits. For all participants, the incidence of all-cause mortality between January 1, 2009 and December 31, 2017, was evaluated, and the total number of person-years of follow-up was calculated. A total of 4975 deaths occurred during a median follow-up period of 48.2 months.The data are presented as numbers or proportions for categorical variables and as means ± standard deviations for continuous variables. Non-normally distributed variables are presented as geometric means . To compare the characteristics of interest between cohorts, Student’s t-test was applied to continuous variables, and the Chi-square test was used to assess binary and categorical variables. The mortality rate was calculated per 100 person-years. 2) and obesity (BMI ≥25 kg/m2) or abdominal obesity (WC ≥90 cm in men and ≥85 cm in women) with all-cause mortality with respect to the 5 BMI groups and 6 WC groups, respectively. The cumulative incidence probability of all-cause mortality was estimated using the Kaplan–Meier method, and between-group comparisons of the resulting curves were subjected to a univariate analysis via the log-rank test. Multivariable Cox proportional hazard models were developed to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations between the 5 BMI categories and 6 WC categories with all-cause mortality. In model 1, these calculations were adjusted for age and sex. Model 2 was additionally adjusted for smoking, alcohol consumption, regular exercise, a low income, and previous histories of diabetes, hypertension, dyslipidemia, cardiovascular disease, and cancer. Model 3 included all covariates from model 2 plus the BMI or WC, according to the independent variable, with the intent to reduce the confounding effects of either latter variable. Smooth HR curves of the BMI or WC were plotted after adjusting for all covariates. Finally, the adjusted Cox model (model 2) was used to examine the associations of overweight .All statistical tests were two-tailed. A We similarly evaluated the associations of the WC with various factors. Notably, an increase in the WC was associated with a higher BMI, worse a lipid profile, and a higher prevalence of diabetes, dyslipidemia, and cardiovascular disease. The associations of WC with the proportions of female subjects, subjects with cancer, a low income, or non-regular exercise habits, and non-smokers also yielded U-shaped curves.The Kaplan–Meier estimations of the incidence probability of all-cause mortality according to the BMI or WC category are shown in Conversely, the adjusted HRs for all-cause mortality increased linearly as the WC increased. In the BMI-adjusted Cox model (model 3), participants with the highest WC values had a higher risk of all-cause mortality than those in the reference group, while those in the lowest WC group had a significantly lower risk of all-cause mortality than those in the reference group . These associations were confirmed by smooth HR curve analyses performed after the adjustment of all covariates . SpecifiWe further explored the associations between all-cause mortality and obesity and abdominal obesity after stratifying patients into the five BMI categories and six WC categories. Notably, an increased mortality rate was observed among patients with a lower BMI and higher WC, whereas a decreased mortality rate was observed in the higher BMI and lower WC groups. However, the highest or lowest BMI and WC groups were excluded from these trends .P for the interaction, 0.928). Next, we evaluated the association between abdominal obesity, as defined by the WC, and all-cause mortality in the five BMI subgroups to investigate the adverse effect of this variable when modified by BMI A. In theWe also analyzed the association of overweight and obesity, as defined by the BMI, with all-cause mortality in the six WC subgroups. Conversely, we observed lower adjusted HRs for all-cause mortality in patients with an overweight or obese BMI across all WC subgroups B,C. TherIn our large Korean population-based study of patients undergoing hemodialysis, we identified associations of a low BMI and a 5-cm increase in WC with an increased risk of all-cause mortality. These observed linear associations of the BMI and WC with mortality remained significant, even after adjusting for the WC or BMI, respectively. Moreover, abdominal obesity was associated with an increased risk of mortality  among normal weight or obese patients receiving hemodialysis. Conversely, an obese BMI was associated with a lower risk of mortality, regardless of the WC. These associations persisted even after adjusting for multiple confounding variables, including smoking status, alcohol consumption, exercise habits, and various comorbidities. Previous studies reported associations of obesity or abdominal obesity with mortality and decreased renal function in both the general population ,18,19,202 increase in the BMI was associated with a 5% decrease in the risk of all-cause mortality [2) relative to that of normal weight patients receiving hemodialysis. Our findings are consistent with recently published data from a Korean hemodialysis registry, which reported an association of overweight (BMI ≥30 kg/m2) with a reduced risk of mortality in patients older than 40 years [Several factors and mechanisms have been proposed to explain the inverse relationship between BMI and all-cause mortality in patients with CKD. For example, Ladhani et al., suggested that obese patients with CKD have survived the traditional factors associated with obesity, such as hypertension, diabetes mellitus, and cardiovascular disease . Moreoveortality . We simi40 years . Recent studies have suggested that metabolically unhealthy obesity and a visceral pattern of body fat deposition ,29 are mOur results suggest that patients with a low BMI and high WC should have the highest risk of mortality, as observed in the CREDIT study . HoweverThis study has several limitations. First, we were unable to determine the causes of death and variables related to comorbidities , the type of vascular access and dialysis technique, inflammatory markers, and nutrition factors due to the limitations of the database ,39,40,41In conclusion, our findings indicate that abdominal obesity, measured according to the WC, is associated with all-cause mortality in Korean patients undergoing hemodialysis. In contrast, body volume, as measured by BMI, exhibited an inverse relationship with all-cause mortality. Our results suggest that the routine measurement of both BMI and WC would provide useful information about the risk of mortality faced by patients undergoing hemodialysis. Although no Korean guideline currently provides recommendations for obesity management in patients undergoing hemodialysis, we suggest that a therapeutic intervention intended to preserve muscle mass while reducing abdominal body fat would ultimately improve patients’ outcomes.


Recently, biocompatible energy harvesting devices have received a great deal of attention for biomedical applications. Among various biomaterials, viruses are expected to be very promising biomaterials for the fabrication of functional devices due to their unique characteristics. While other natural biomaterials have limitations in mass-production, low piezoelectric properties, and surface modification, M13 bacteriophages (phages), which is one type of virus, are likely to overcome these issues with their mass-amplification, self-assembled structure, and genetic modification. Based on these advantages, many researchers have started to develop virus-based energy harvesting devices exhibiting superior properties to previous biomaterial-based devices. To enhance the power of these devices, researchers have tried to modify the surface properties of M13 phages, form biomimetic hierarchical structures, control the dipole alignments, and more. These methods for fabricating virus-based energy harvesting devices can form a powerful strategy to develop high-performance biocompatible energy devices for a wide range of practical applications in the future. In this review, we discuss all these issues in detail. Recently, energy harvesting from biomechanical movement has attracted a great deal of interest in wearable, sustainable, and biomedical technologies ,2,3. Esp3) [3) [3) [3) [xTi1−x]O3) O3) , and etci1−x]O3) . For thie Bi4Ti3O, quartz,z, etc.) ,14 and oz, etc.) ,16 were z, etc.) .Otherwise, biomaterials have been regarded as promising alternative materials due to their good biocompatibility, non-toxicity, and environmental friendliness. After the first discovery of the piezoelectric effect of bone, the piezoelectric properties of diverse natural biomaterials such as wood, bone, hair, dentin, tendon, and collage were investigated ,21,22,23In this short review, we provide an overview of M13 bacteriophages (phages) as superior biopiezoelectric materials for piezoelectric energy harvesting applications. In addition, we discuss in detail the piezoelectric properties of M13 phages and the fabrication of M13 phage-based piezoelectric energy harvesting devices. It is expected that this review will inspire the design of novel biomaterials and the development of functional devices for energy harvesting, sensing, biomedical applications, and other applications.Due to their unique structural, biological, and physical properties, the M13 phage is the most attractive candidate in biomaterials for mimicking natural structures and developing novel piezoelectric energy harvesting devices. Especially, from the engineering point of view, M13 phages have several advantages, such as (1) structural similarity with collagens; (2) mass-producibility by bacteria infection and mass-amplification; (3) surface tunability through genetic engineering; (4) possibility of forming a highly-ordered structure via self-assembly; and (5) superior piezoelectric properties.The M13 phage is a filamentous bacteriophage composed of circular single-stranded deoxyribonucleic acid (ssDNA) and capsid proteins. ssDNA is encapsulated in approximately 2700 copies of the helically arranged major coat protein pVIII, and five to seven copies of two different minor coat proteins  on the ends a. The diRecent advances in genetic engineering make it possible to modulate the peptide sequence of phage proteins as desired. By using the recombinant DNA technique and M13mp phage vectors, we can design the molecular structures of surfaces according to the required properties and easily display the related peptide motif on the coat proteins of M13 phages c. This aIn addition, M13 phages exhibit a lyotropic liquid crystalline phase due to their helical structure, nanofibrous shape, monodispersity, and expressed functional motifs d. AccordLastly, recent studies have shown that M13 phages have excellent piezoelectric properties, which are larger than other natural biomaterials . This maPiezoelectricity is a phenomenon of coupling between the electrical and mechanical states of a material by crystal deformation. When piezoelectric materials are mechanically stressed and deformed, the positive and negative charge centers shift in the materials, which then results in an external electrical field and a current flow. The opposite can also happen. When an electrical field is applied to the materials, the piezoelectric materials are stretched or compressed a.This direct piezoelectric effect was first discovered in 1880 by Paul-Jacques Curie, Pierre, and Marie Curie. They combined the knowledge of pyroelectricity with their understanding of crystal structures and behavior, and demonstrated the first piezoelectric effect by using crystals of quartz and Rochelle salt. Since then, many researchers have discovered and reported the piezoelectric properties of organic ,16, inorThese piezoelectric characteristics originate from the deformation of the crystal structure and charge rearrangement within the material. In the equilibrium state, the arrangement of charges within the material lattice is neutral. However, there will be a charge redistribution within the unit cell and this induces net charges on the faces of the unit cell under the mechanical stress, which results in a net dipole moment. The sum of these dipole moments from all the unit cells leads to charge separation and generates electrical polarization in piezoelectric materials b. The moFortunately, M13 phages have structural properties that can make them suitable for piezoelectric properties. M13 phages are composed of ssDNA and capsid proteins, and each capsid protein has a dipole moment because these capsid proteins are made up of three parts—a positively charged area, a neutral charged area, and a negatively charged area. Especially, 2700 pVIII major coat proteins, which are the body-coat proteins, are assembled on the ssDNA with a 20° tilt angle with respect to the phage long axis and are arranged in right-handed helical structures. These major coat proteins form a pentagonal structure, which means that M13 phages have five-fold rotational symmetry, two-fold screw symmetry, and no inversion center c 46,47],4746,47]One of the great advantages of M13 phages as functional materials is the possibility of surface modification through genetic engineering. The most frequently used and well-established method to modify the genes of phages is recombinant DNA technology, which involves the insertion of foreign genes into the bacterial plasmids. Especially, M13mp phage vectors are usually used for engineering M13 phages. By incorporating foreign DNA, converting certain DNA into foreign DNA, and deleting specific DNA with enzymes, a high density of functional peptides and proteins can be simultaneously displayed on the M13 phage’s coat proteins . This teThese genetic modifications are also very useful in fabricating energy harvesting devices. Most energy harvesting devices  have a direct correlation to surface charges and dipole moments. Therefore, the number of charges on the outer surfaces of M13 phages should be increased to improve the power of energy generators. For this purpose, B. Y. Lee et al. expressed AEGDP (1E), AEEGDP (2E), AEEEGDP (3E), and AEEEEDP (4E) peptide sequences on the outer surfaces of the pVIII major coat protein of M13 phages a 28]. I. I28]. ILikewise, we can improve the physical and chemical properties and extend the range of applications through genetic molecular design. In the future, we expect that chemical modification  as well as genetic modification will be used for the further improvement of physical properties.effd) of the wild-type phage was 0.30 ± 0.03 pm V−1. The coefficients of 1E, 2E, 3E, and 4E phages were 0.14 ± 0.03 pm V−1, 0.35 ± 0.03 pm V−1, 0.55 ± 0.03 pm V−1, and 0.70 ± 0.05 pm V−1, respectively. This indicates that the coefficients improve as the surface charges of phages increase . T. T29]. TAlthough the power of phage-based energy generators is improving with diverse strategies, the power of the devices is still too low. For practical applications of these devices, many ways for enhancing electrical properties and developing mass-production methods should be contrived.Because these methods are to prepare the M13 phage film by self-assembly, the performance of the devices may be reduced when they are used for a long time. Fortunately, laterally assembled structures are very stable and robust, allowing the devices to run reliably for a long time ,30. HoweEscherichia coli bacteria, not human cells [As this technique is at an early stage of research, studies of the devices’ ideal operating conditions and toxicity issues have not been adequately carried out. However, by inferring from previous research based on M13 phages, the characteristics of these device can be predicted. Because the M13 phage is a biological material, optimized conditions for operating these devices will be room temperature (30 °C–70 °C) and low humidity . Howeveran cells ,52,53. RSince these technologies are still in their early stages of research, it is too early to discuss mass-production for practical applications. Most of the techniques discussed here are not suitable for mass production, because they use new process methods rather than conventional fabrication techniques. However, because these novel fabrication processes are very simple and facile, there is a strong possibility of mass-production and scale-up in the future. Although one of the main issues for scale-up is mass-production of the M13 phages, we can solve this problem using huge fermenters in the factories, like with biosimilar drug and alcohol manufacturing. Although the manufacturing cost of these devices is more expensive than existing devices, the M13 phage-based devices have several strong advantages which are very important in the biomedical fields. The M13 phage has very high piezoelectric coefficient compared to other biomaterials and their surfaces can be easily modified by genetic engineering. Further, it is also possible to mass-produce them.Even though the piezoelectric properties of biomaterials are lower than other inorganic materials, it is very important to design novel piezoelectric biomaterials and develop functional devices because of their specific applications in biomedical field. In particular, M13 bacteriophages are very attractive materials due to their unique features which distinguish them from other materials, such as their similar structures with collagens, mass-amplification, genetic modification, liquid-crystalline phase transition, and excellent piezoelectric properties. Recently, taking advantage of these characteristics, many researchers have made a great deal of efforts to fabricate M13 phage-based piezoelectric energy harvesting devices. Among these devices, vertically aligned phage films exhibited the highest performance—a peak voltage of 2.8 V and a peak current of 120 nA .However, it is still a challenge to develop high-performance piezoelectric energy generators based on M13 phages owing to the limitations of surface modification, structural, and dipole alignment control. Thus, the novel design of phage structures through genetic and chemical modification may improve the performance of devices. Further, fabricating triboelectric devices based on M13 phages will also be an effective way to enhance the power of devices.Another strategy for enhancing the power of devices is to develop composite structures composed of organic and inorganic biomaterials. Recently, novel methods for coating inorganic materials on biomaterial surfaces are attracting the attention of many researchers because of their various applications in biomedical field. For example, some researchers have reported effective methods to coat the inorganic materials on M13 bacteriophage surfaces via biomineralization ,55,56, wHigh-performance energy harvesting devices based on biomaterials can be used in various fields, such as chemical/bio-sensors, artificial skin, bioimplantable energy devices, flexible electronics, soft robotics, and more . Especia


Background: Red and processed meat intake have been associated with increased risk of morbidity and mortality, and a restricted intake is encouraged in patients with cardiovascular disease. However, evidence on the association between total meat intake and clinical outcomes in this patient group is lacking.Objectives: To investigate the association between total meat intake and risk of all-cause mortality, acute myocardial infarction, cancer, and gastrointestinal cancer in patients with stable angina pectoris. We also investigated whether age modified these associations.Materials and Methods: This prospective cohort study consisted of 1,929 patients  with stable angina pectoris from the Western Norway B-Vitamin Intervention Trial. Dietary assessment was performed by the administration of a semi-quantitative food frequency questionnaire. Cox proportional hazards models were used to investigate the association between a relative increase in total meat intake and the outcomes of interest.Results: The association per 50 g/1,000 kcal higher intake of total meat with morbidity and mortality were generally inconclusive but indicated an increased risk of acute myocardial infarction [HR: 1.26 ] and gastrointestinal cancer [1.23 ]. However, we observed a clear effect modification by age, where total meat intake was associated with an increased risk of mortality and acute myocardial infarction among younger individuals, but an attenuation, and even reversal of the risk association with increasing age.Conclusion: Our findings support the current dietary guidelines emphasizing a restricted meat intake in cardiovascular disease patients but highlights the need for further research on the association between meat intake and health outcomes in elderly populations. Future studies should investigate different types of meat separately in other CVD-cohorts, in different age-groups, as well as in the general population. Meat consumption has increased considerably worldwide in the last decades . Meat isCurrent dietary guidelines to reduce the risk of CVD also emphasize reduced intake of dietary sources of trans- and saturated fatty acids, including red and processed meat . Howevern = 2,573). We excluded patients with missing (n = 485) or incomplete  dietary data, and implausible reporters using simple criteria (n = 27). We also excluded patients with a very high reported alcohol intake , leaving a total of 1,929 patients eligible for analyses. A flowchart illustrating the inclusion process is provided in The population under study consisted of 1,929 patients  who were participating in the Western Norway B-vitamin Intervention Trial . A total of 3,090 patients were included in WENBIT, which was a randomized, double-blind, placebo-controlled trial conducted between 1999 and 2004 investigating the effect of treatment of homocysteine-lowering B-vitamins on mortality and cardiovascular outcomes. Inclusion criteria for participation in the trial were males and females >18 years with suspected stable angina pectoris who were undergoing coronary angiography at Haukeland University Hospital  or Stavanger University Hospital . Exclusion criteria were unavailability for follow-up, participation in other trials, known alcohol abuse, severe mental illness, or cancer. The trial has been described in detail elsewhere , 15. Forcriteria  , which was given at the first visit and returned at the 1-month follow-up visit, or by mail. The FFQ was designed to capture the habitual Norwegian diet and consisted of 169 food items grouped according to Norwegian meal patterns. Patients were asked to answer the questionnaire based on their food habits the year before the study. The data were converted from portion sizes and household measures into grams per day. Nutrient intake was calculated by using “Kostberegningssystemet” version 3.2, developed by the Department of Nutrition, University of Oslo, Norway.The study was carried out according to the Declaration of Helsinki and was approved by The Regional Committee for Health Research Ethics and The Norwegian Data Inspectorate. All patients provided written informed consent.Due to the FFQ used for dietary assessment, it was not possible to distinguish between different types of meat. Accordingly, the exposure in this study was total meat intake. For cold cuts, the frequency of consumption was given as times per week, and portion sizes were given as per slice of bread. For meat products used in dishes, the frequency was given as time per month, and portion sizes as slices, pieces, or by volume.All-cause mortality, AMI, cancer, and GI-cancer were chosen as primary outcomes of interest. AMI included both fatal- and non-fatal AMI -10 codes: I21, I22, I46.1, R96, R98). Cancer covered malignant neoplasms of all sites (ICD-10 codes: C00–C97), whereas GI-cancer included malignant neoplasms in the GI-tract, and accessory organs of digestion, including liver, gallbladder, and pancreas (ICD-10 codes: C15–C26). Information on mortality was obtained from the Cause of Death Registry at the Norwegian Institute of Public Health , informadplyr, tidyr, broom, purrr, stringr, rlang, and ggplot2) . The same models were applied to all outcomes. The analyses were also conducted for males and females separately and presented in All statistical analyses were performed using R, version 4.0.2 , and the packages within the Tidyverse (ggplot2) , skimr, approach . To estiapproach . The maiTo explore potential non-linear relationships, meat intake was modeled as a penalized spline in a model adjusted for Model 1  and Modep-values  and food groups , and their associations with meat intake are provided in A total of 572 (29.8%) patients died after a median follow-up of 14.1  years. In Model 1, we observed a 9% reduced risk of all-cause mortality [HR: 0.91 ] per 50 g/1,000 kcal higher intake of meat, but the data was compatible with both 25% reduced risk and 10% increased risk. Further adjustments did not have any pronounced impact on the result , but theDuring the follow-up of 7.8  years, 309 (16.0%) incident cases of AMI were reported. In Model 1, meat intake was associated with a 26% increased risk of AMI [1.26 ], per 50 g/1,000 kcal higher intake of meat . The relIn total, 213 (11.0%) patients were diagnosed with cancer during the follow-up of 8.0  years. In Model 1, meat intake was associated with a 4% increased risk of cancer per 50 g/1,000 kcal higher intake of meat per day. However, the low precision rendered the data inconclusive [1.04 ]. Further adjustments did not appreciably affect the results . ContinuA total of 61 (3.2%) patients were diagnosed with GI-cancer during follow-up of 8.1  years. In Model 1, we observed a 23% increased risk of GI-cancer per 50 g/1,000 kcal higher intake of meat [1.23 ], but the data was compatible both with 30% reduced risk and 116% increased risk of GI-cancer. Including BMI as a covariate in Model 2 and Model 4 slightly attenuated the association . The assIn this study, the association of a higher meat intake with morbidity and mortality were generally inconclusive but indicated an increased risk of AMI and GI-cancer. However, we observed a clear effect modification by age, where total meat intake was associated with an increased risk of mortality and AMI at younger ages, but an attenuation and even reversal of the risk association observed with increasing age.Our findings on AMI and GI-cancer are supported by previously reported findings on red and processed meat in the existing literature based on initially healthy populations , 25, andSeveral underlying mechanisms have been suggested to explain the observed association between higher meat intake and increased risk of cancer and coronary heart disease (CHD) in the existing literature. For cancer, the exact mechanisms are not known but might be attributable to the formation of the mutagenic compounds polycyclic aromatic hydrocarbons (PAHs), heterocyclic amines (HCAs), and N-nitroso compounds (NOCs). PAHs and HCAs are formed during cooking of meat at high temperatures , and NOCIt has been suggested that the content of fats in meat may be an explanation for the observed risk of CHD, but the total evidence suggests that other components of meat that are most relevant for cardiometabolic effects . The higThe large sample size and long follow-up are some of the main strengths of the current study. The study population consisted of patients in Western-Norway with established coronary artery disease, and it has previously been reported that the participants in WENBIT are comparable to samples of patients with verified coronary artery disease in Europe . HoweverIn conclusion, in patients with stable angina pectoris, the association of a higher total meat intake with mortality and morbidity were in general inconclusive but indicated an increased risk of AMI and gastrointestinal cancer, particularly at higher meat intakes. The associations with all-cause mortality and AMI differed across ages, with increased risk observed at younger ages, but an attenuation, and even reversal of the risk association with increasing age. The findings from this study support the current dietary guidelines emphasizing a restricted meat intake in patients with CVD but highlight the need for more research on the association between meat intake and health outcomes in elderly populations. Future studies should investigate different types of meat separately in other CVD-cohorts, in different age-groups, as well as in the general population.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 Regional Committee for Health Research Ethics and the Norwegian Data Inspectorate. The patients/participants provided their written informed consent to participate in this study.ÅM and VL analyzed data. ÅM had primary responsibility for final content and wrote the paper. AV, TO, TH, CB, ON, JD, and VL reviewed and edited the manuscript. All authors have read and approved the final version of the 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.


The Coronavirus Disease 2019 (COVID-19) pandemic has been posing a substantial challenge to human survival and well-being, which rely on the actions and behaviors of individuals. It is essential that accurate information is distributed; however, misinformation has been spread via social media. Consequently, the resulting panic has to be addressed while putting essential public health measures in place. It is also important to explore the link between the social media exposure and well-being. Therefore, in the current study, we aimed to identify the levels of anxiety, depression, and social isolation among individuals during the COVID-19 pandemic. Additionally, we explored the relationship between exposure to misleading social media news and anxiety, depression, and social isolation. A cross sectional design was employed to collect data from 371 Saudi participants (aged 16–60 years), using the Generalized Anxiety Disorder-7, Centre for Epidemiological Studies Depression Scale, and de Jong Gierveld Loneliness Scale. Results showed that the prevalence of anxiety, depression, and social isolation was 47.82%, 47.57%, and 46.42%, respectively. Further, more than 83% of the participants reported using social media frequently during the pandemic. We found that exposure to misinformation via social media has a significant positive relationship with anxiety, depression, and social isolation. However, Due to the cross-sectional nature of this study it cannot be determined whether social media causes negative mental health outcomes, or if individuals experiencing greater depression, anxiety and social isolation turn to social media more than others, or if some third variable might explain both. Based on our findings, we present specific suggestions related to the COVID-19 pandemic to the government of Saudi Arabia. Minoring and filtering out misleading information with the cooperation of the World Health Organization (WHO) can promote the spread of accurate news in Saudi Arabia. False information amplifies the challenges that humanity faces, such as the Coronavirus Disease 2019 (COVID-19) pandemic , 4. ThisThe dissemination of misleading and false information via social media has many negative psychological and social consequences for community members , 11. In Social media has unprecedented dominance and power throughout the world, allowing the spread of misinformation and rumors that are often presented as facts by fearful citizens looking for a sense of security . Times oIn the last few years, studies have been conducted, which indicated that social media exposure had little effect on mental health –26; thusTherefore, public health measures should focus on limiting not only the spread of the COVID-19 pandemic but also the social media panic pandemic . We needThe effective panic caused by social media can also be contained by disseminating the right information and supporting public health through social media. During the bans which were imposed due to the spread of COVID-19 in China, social media was used widely, and some governments monitored the information that was spread through such modes . In thisIn Saudi Arabia, the society has witnessed a rise in social media sites, especially due to the increasing use of modern communication technologies. By January 2020, approximately 4.54 billion, 3.8 billion, and 5.19 billion people globally were using the internet, social networking sites, and mobile phones, respectively. Moreover, 2.78 billion individuals used their phones to surf social networking sites. Saudi Arabia ranks 17th in the rate of internet usage globally , and is Considering the psychological, social, and behavioral effects of social media on the society during the COVID-19 pandemic, many countries, including Saudi Arabia, have implemented procedures such as taking legal action to counter the spread of rumors and misinformation. The Kingdom’s public prosecution has warned against spreading news from unknown sources and rumors through social media, especially those linked to the COVID-19 crisis; anyone who provides misleading information is subject to penal accountability .The mere fact that social media is used widely in Saudi Arabia makes it necessary to identify the exact impact of misleading information on its citizens’ psychological and social well-being, in particular, on their levels of anxiety, depression, and social isolation. Similar research has not yet been undertaken in the Saudi society in relation to the pandemic. Therefore, we aimed to identify the level of generalized anxiety, depression, and social isolation among participants during COVID-19. Additionally, we examined the relationship of exposure to misleading information through social media with psychological and social well-being during the pandemic. We explored the following research questions:What is the level of generalized anxiety, depression, and social isolation among participants during COVID-19?Q1: Is exposure to misleading news in social media related to the level of generalized anxiety, depression, and social isolation?Q2: Three hundred seventy-one participants  participated in this cross-sectional study in Najran, Saudi Arabia. Participants were invited to complete an online questionnaire one month after the spread of COVID-19 in Najran. The timeline of this study was concurrent with the lifting of restrictions applied nationally. Also, participants were randomly selected using the simple random sampling to provide equal and independent opportunity of selection for the sample.This cross-sectional study was online conducted over six days (May 10–15 May 2020) after cases in Saudi Arabia reached almost two thousand and while curfew and social distancing measures were implemented by Government authorities. We obtained approval for our quantitative study from the Dean of Scientific Research at Najran University. The department of public ration’s and university media at Najran University has contacted the ministry of health in Saudi Arabia to distribute the survey link to all Saudi citizens. The ministry of health send messages with the survey link to Saudi citizens over six days. All participants completed the voluntary consent section in the questionnaire and were assured confidentiality. They completed the questionnaire on the website. The authors expected to obtain 450 responses within six days, but only 386 questionnaires were returned, of which 15 were excluded because they did not follow the questionnaire instructions. Consequently, the total number of questionnaires used for analysis was 371.We administered the following three reliable scales with minor adaptions: the Generalized Anxiety Disorder-7 (GAD-7) , Centre Not at all,” “Several days,” “More than half the days,” and “Almost every day” and are recorded as 0, 1, 2, and 3, respectively. Therefore, GAD-7 scores range from 0 to 21, with scores of 5, 10, and 15 representing mild, moderate, and severe anxiety symptoms, respectively. The scale has demonstrated excellent internal consistency (Cronbach α = .92) and reliability (intraclass correlation = .83) [The GAD-7 is a seven-item questionnaire created to identify possible causes of generalized anxiety disorder and to measure the severity of the symptoms . It assen = .83) . Severaln = .83) –53. For n = .83) , 54.rarely or none of the time” (0) to “all the time” (3). Moreover, Item 5 and 8 are reverse scored as they are worded positively. Total scores range from 0 to 30, with higher scores indicating a greater severity of symptoms.The CES-D-10 is a 10-item Likert scale questionnaire that measures the occurrence of depressive symptoms over the week preceding the assessment . It inclFor the present study, the scale was translated (English to Arabic) and subsequently back-translated. We presented it to specialists in English and Arabic linguistics to ensure the accuracy of the translation and linguistic formulation. In the present study, the Saudi version showed adequate reliability and viability, with good internal consistency (Cronbach α = .81).there are many people I can completely trust”) and emotional  aspects of isolation between individuals, with three elements each. Response options are presented on a four-point Likert scale ranging from 1 (Strongly Disagree) to 5 (Strongly Agree). The original version’s Cronbach α was 0.76, which was consistent with many previous studies [α = .78).The six-item DJGLS aims to assess the social , age , educational level , Living area, self-rated health .We applied descriptive and inferential statistics to analyze the data. The descriptive statistics included frequency, percentage, average and standard deviation; these were analyzed using SPSS 21 . To addrWe conducted univariate analyses to compare the variation among participants’ characteristics based on their exposure to social media. Social media exposure was higher among women (77.77%) than men (73.16%), and higher among married (71.23%) than unmarried (51.97%) participants. Moreover, middle-aged (aged 36–50 years) had higher social media exposure than older (aged 50–60 years) and younger (aged 26–35 years) individuals. Furthermore, participants with lower levels of education (middle and high school) had less exposure to social media than did those with higher education (undergraduate and graduate). Finally, participants from rural areas (87.37%) reported a higher rate of social media exposure than did those from urban areas (64.64%). Healthy participants (72%) were significantly more likely than others to have exposure to social media.To find the relationship between the social media exposure and anxiety, depression and social isolation, we used regression analysis and The results of simple linear regression analysis showed that the regression model was significant between the independent variable and the dependent variables. The level of significance for the P-value was less than (0.05). social media exposure has a variance ratio of (0.135), (0.126), (0.117), and this can also be deducted from the value of t and its significance on anxiety, depression, and social isolation.The last national survey in Saudi Arabia indicated a prevalence of 23%, 6%, and 5.6% for anxiety, depression, and social isolation, respectively . In compSocial media has been one of the primary sources of up-to-date COVID-19 information , 70; a sFindings of single studies related to the effects of social media on mental health in reality were contradictory . It is pOur findings showed a significant prevalence of mental health problems within the Saudi society due to the COVID-19 pandemic; moreover, these issues are positively associated with the significant and frequent exposure to social media during the outbreak. Our results indicated that the Saudi Arabian government should pay more attention to the general population’s mental health during the COVID-19 pandemic. The Saudi government was the first to implement precautionary measures to protect its citizens, which contributed significantly to the low levels of active cases or mortality as compared to several other developed countries. Moreover, the Saudi government has been providing mental health services through various channels, including electronic applications, hotlines, online counseling and courses, and outpatient consultation.  However,Our study has a few limitations. First, it is a cross-sectional study, which presents challenges in terms of clarifying the causal relationships between social media exposure and mental health. This can be addressed in future longitudinal studies, including case studies and cross-control studies. Furthermore, this is an intermediate sample; the survey was conducted online, which enabled rapid assessment. However, the bias created by the limited representation of elderly citizens could have affected our results. Finally, the study’s findings can only be generalized to similar sample populations and societies.S1 File(ENL)Click here for additional data file.