Ziltivekimab for anemia and atherosclerosis in chronic kidney disease: a new hope?

Anemia of chronic kidney disease is a multifactorial condition secondary to various etiologies, including nutritional deficiencies, chronic inflammation, erythropoietin deficiency or resistance, bone marrow suppression, iron deficiency and adverse drug effects. The major therapeutic intervention for anemia among chronic kidney disease patients is erythropoiesis-stimulating agents. However, a limitation of erythropoiesis-stimulating agents is the risk for thromboembolic events, hypertension, seizures, solid organ malignancies and hyporesponsiveness. A novel interleukin-6 monoclonal antibody, ziltivekimab, has been evaluated for managing anemia in chronic kidney disease patients in pilot clinical trials with promising outcomes, including an improvement in hemoglobin levels and reduction of inflammatory parameters. These trials have shown that ziltivekimab does not increase the risk for cytopenia or infectious complications as has been described for other interleukin-6-targeting monoclonal antibodies, like tocilizumab. Furthermore, potentially beneficial effects on serum lipid profile have been reported, leading to the hypothesis of a favorable impact of the drug on atherosclerotic complications. In addition, ziltivekimab has shown efficacy in improving anemia parameters, including hemoglobin levels and iron studies. Ziltivekimab deserves full scale clinical development, and to this aim, large-scale clinical trials are under way.

The Turkish Version of the Sexual Interest and Desire Inventory-Female (SIDI-F): Examination of the Validity, Reliability and Factorial Structure.

The aim of this study is to investigate the validity and reliability of the Turkish version of the Sexual Interest and Desire Inventory-Female (SIDI-F). This methodological study was conducted with 268 women who met the sampling criteria between January and February 2024. Validity analysis was performed using the content validity index, convergent and divergent validity, exploratory factor analysis, and confirmatory factor analysis. Pearson product-moment correlation and Cronbach Alpha reliability coefficients were used for reliability analysis. To evaluate invariance of the inventory over time, test-retest measurements were conducted three weeks apart and showed no difference in mean scores (p > .05). Corrected item-total score correlations ranged from 0.303 to 0.846 in the positive direction and were statistically highly significant. Adjusted goodness-of-fit index > 0.85 and comparative fit index > 0.90 confirmed the construct validity of the Turkish SIDI-F. The Cronbach Alpha was found to be .88, indicating high internal consistency. The Turkish version of SIDI-F can be used as a measurement tool to determine the level of sexual interest and arousal.

Validity and reliability of the Turkish version of the Self-Efficacy Tool for the Ability to Support Breastfeeding Mothers.

AIM: The aim of the study is to investigate the validity and reliability of the Turkish version of the Self-Efficacy Tool for the Ability to Support Breastfeeding Mothers. METHODS: In the current methodological study, research data were collected using a Descriptive Information Form and the Self-Efficacy Tool for the Ability to Support Breastfeeding Mothers. Validity analysis was conducted using the content validity index, exploratory factor analysis, and confirmatory factor analysis. The Pearson product-moment correlation and Cronbach alpha reliability coefficients were performed for reliability analysis. High scores indicate a higher ability to support breastfeeding mothers. RESULTS: To evaluate the tool's invariance over time, test-retest measurements were made at an interval of at least two weeks and showed no difference in mean scores (p > 0.05). Corrected item-total score correlations varied between 0.43 and 0.77. The Cronbach alpha value was determined to be 0.97, which indicated high internal consistency. CONCLUSION: The results of the present study show that the Turkish version of the Self-Efficacy Tool for the Ability to Support Breastfeeding Mothers is valid and reliable. It can be utilised as a measurement tool to determine the degree of self-efficacy in the ability to support breastfeeding mothers.

Do adverse childhood experiences increase the risk of postpartum traumatic stress and depression?

AIM: This study was conducted to determine the effect of childhood adverse experiences on the risk of postpartum posttraumatic stress disorder (PP-PTSD) and postpartum depression (PPD). METHODS: This descriptive study was conducted with 417 mothers between 1 March and 30 April 2022. Data were collected using a demographic and obstetric information form, the Adverse Childhood Experiences Questionnaire (ACE), City Birth Trauma Scale (CityBiTS) and Edinburgh Postpartum Depression Scale (EPDS) through the Google Forms platform. RESULTS: The mothers participating in the study had a mean age of 30.47 ± 4.21 years, 65.9% (n = 275) had at least one ACE, 10.3% (n = 43) met all of the DSM-5 PTSD criteria according to the CityBiTS, and 91.8% (n = 383) had at least one traumatic stress symptom. Correlation analysis revealed weak positive associations between number of ACEs and CityBiTS score (p < 0.001, r = 0.328) and EPDS score (p < 0.001, r = 0.291) and a moderate positive association between CityBiTS and EPDS scores (p < 0.001, r = 0.601). PP-PTSD was found to be a partial mediator variable between ACE and PPD. CONCLUSION: The presence of ACE in mothers was found to increase the risk of developing PPD, both alone and when combined with traumatic birth experience. Therefore, we believe that screening for a history of ACE during pregnancy, investigating traumatic birth experiences in the postpartum period, closer follow-up of mothers with both ACE and traumatic birth experiences and increasing support systems will be beneficial in the prevention and early diagnosis of PPD.

Management of cytomegalovirus infection after liver transplantation.

Cytomegalovirus (CMV) infection is one of the primary causes of morbidity and mortality following liver transplantation (LT). Based on current worldwide guidelines, the most effective strategies for avoiding post-transplant CMV infection are antiviral prophylaxis and pre-emptive treatment. CMV- IgG serology is the established technique for pretransplant screening of both donors and recipients. The clinical presentation of CMV infection and disease exhibits variability, prompting clinicians to consistently consider this possibility, particularly within the first year post-transplantation or subsequent to heightened immunosuppression. At annual symposia to discuss CMV prevention and how treatment outcomes can be improved, evidence on the incorporation of immune functional tests into clinical practice is presented, and the results of studies with new antiviral treatments are evaluated. Although there are ongoing studies on the use of letermovir and maribavir in solid organ transplantation, a consensus reflected in the guidelines has not been formed. Determining the most appropriate strategy at the individual level appears to be the key to enhancing outcomes. Although prevention strategies reduce the risk of CMV disease, the disease can still occur in up to 50% of high-risk patients. A balance between the risk of infection and disease development and the use of immunosuppressants must be considered when talking about the proper management of CMV in solid organ transplant recipients. The objective of this study was to establish a comprehensive framework for the management of CMV in patients who have had LT.

Investigation of the Effectiveness of an Algorithm as an Auxiliary Method in Intraoperative Consultations of Central Nervous System Tumors.

OBJECTIVE: One of the most difficult areas in a surgical pathology practice is intraoperative consultation. In a previous study, we proposed an algorithm that provides a systematic approach to intraoperative consultation for central nervous system tumors. Our aim was to demonstrate the effectiveness of this algorithm. MATERIAL AND METHODS: 102 cases were selected from intraoperative consultation procedures performed at our institution between 2012 and 2020. The algorithm was tested by five observers. The observers examined the smears and frozen sections without the algorithm, and then with the algorithm. RESULTS: The percentage change in the rate of correct diagnoses made by the four observers (O) increased after using the algorithm (O2: 8%, O3: 5%, O4: 8% and O5: 13%), but decreased for only one observer (O1) (5%). The most common error made by the four observers was `grading of glial tumors` (O1: 40%; O2: 23%; O4: 40% and O5: 27.5%), and this group of errors was mostly corrected by using the algorithm (O1: 33%; O2: 3.8%; O4: 23% and O5: 10%). For two observers (O2 and O5), a statistically significant change in diagnostic levels was observed after using the algorithm (p=0.024 and p=0.040; respectively). In addition, thanks to the use of the algorithm, a high degree of agreement was found between the observers` diagnoses (77.7%, p < 0.001). CONCLUSION: In the intraoperative consultation of central nervous system lesions, algorithms can help to increase the accuracy of the diagnosis and reduce interobserver variability. This study demonstrates that an algorithmic approach is an effective method for pathologists in intraoperative consultation procedures.

Prophylactic third molar removal: are oral surgeons and orthodontists aligned in preventive approaches?

BACKGROUND: There is a general consensus among dental professionals regarding the extraction of impacted third molars in the presence of clinical symptoms. However, there is less agreement on the management of asymptomatic third molars. The objective of this study is to compare the perspectives of oral surgeons and orthodontists regarding the indications for the extraction of asymptomatic third molars. It is possible that healthcare professionals from different specialties may approach the extraction of these teeth in different ways. METHODS: In this cross-sectional study, a web-based questionnaire has been employed to collect data by inquiring about the reasons why participants prefer the extraction of asymptomatic third molars. Descriptive statistics were employed to evaluate the data obtained. The level of significance was set at P < 0.05. RESULTS: Prophylactic extraction of partially impacted molars was more favored among the participants (P < 0.05). The orthodontists preferred prophylactic extraction due to the risk of late anterior dental crowding (LADC); however, the oral surgeons preferred pre-pregnancy extractions (P < 0.05). The extraction decision for partial impaction was higher in females when the risk of distal caries was considered. For fully impacted ones, it was higher in males when the risk of caries and pericoronitis were considered (P < 0.05). CONCLUSIONS: Orthodontists preferred extraction because of the risk of LADC and caries, while oral surgeons focused on preventing pericoronitis, pathology, focal infection, and symptoms during pregnancy. This divergence between the participants may inform the guidelines for prophylactic management of third molars. These findings may be pertinent in gender medicine. CLINICAL RELEVANCE: This study has been enlightening for departments to consult each other before the extraction of a patient's asymptomatic third molar.

Descriptives and genetic correlates of eating disorder diagnostic transitions and presumed remission in the Danish registry.

Objective: Eating disorders (EDs) are serious psychiatric disorders with an estimated 3.3 million healthy life-years lost worldwide yearly. Understanding the course of illness, diagnostic transitions and remission, and their associated genetic correlates could inform both ED etiology and treatment. The authors investigated occurrences of ED transitions and presumed remission and their genetic correlates as captured by polygenic scores (PGSs) in a large Danish register-based cohort. Methods: The sample compromised of 10,565 individuals with a diagnosis of anorexia nervosa (AN), bulimia nervosa (BN), or eating disorder not otherwise specified (EDNOS) with at least two registered hospital contacts between 1995 and 2018. Based on medical records, occurrence of diagnostic transitions and periods of presumed remission were identified. Associations between 422 PGS and diagnostic transitions and presumed remission were evaluated using Cox proportional hazard models. Results: A minority of ED cases (14.1%-23.1%) experienced a diagnostic transition. Presumed remission ranged between 86.9%-89.8%. Higher (one SD increase) PGS for major depressive disorder and multisite chronic pain were positively associated with transitioning from AN to either BN or EDNOS. Higher PGS on a measure of body fat percentage and financial difficulties were positively associated with presumed remission from AN. Higher PGS for mood swings was positively associated with presumed remission from EDNOS whereas higher PGS for health rating showed the opposite. Conclusions: The authors found that most ED patients did not experience diagnostic transitions but were more likely to experience a period of presumed remission. Both diagnostic transitions and presumed remission have significant polygenic component.

Traumatic brain injury-induced peripheral damage: The dynamics of the inflammatory and autophagy pathway from acute to chronic stages.

INTRODUCTION: Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide, and brings a huge burden on the quality of life of patients with TBI and the country's healthcare system. Peripheral organs, especially the kidney, and liver, may be affected by the onset of molecular responses following brain tissue damage. While secondary injury responses post TBI has been well studied in the brain, the effect/consequences of these responses in the peripheral organs have not yet been fully elucidated. Thus, our study aimed to investigate the immunoreactivity of these responses, particularly via proinflammatory cytokines and autophagy markers in the kidney and liver post-acute and chronic TBI. MATERIAL AND METHODS: Mild TBI (mTBI) and repetitive mTBI (r-mTBI) were induced in male and female 2-month-old Balb/c mice via the Marmarou weight-drop model. Liver and kidney tissues were sampled at 24 hours (acute) and 30 days (chronic) post TBI and subjected to histopathological and immunoreactivity analysis. RESULTS: Interleukin (IL)-6 levels were significantly increased in the male liver and kidney tissues in both TBI groups compared to the control group but were seen to be decreased in the female r-mTBI chronic liver and r-mTBI acute kidney. Tumor necrosis factor a (TNF-a) levels were found to increase only in the female r-mTBI chronic kidney tissue and mTBI chronic liver tissue. IL-1b levels were increased in the male and female r-mTBI liver tissues but decreased in the female mTBI kidney tissue. Inducible nitric oxide synthase (iNOS) levels were found to be significantly increased in the female mTBI acute and r-mTBI chronic kidney tissue and mTBI liver tissue, but decreased in the r-mTBI acute kidney and r-mTBI liver tissues. Beclin-1 levels were increased in male mTBI chronic and r-mTBI acute liver tissue but decreased in the r-mTBI chronic group. LC3A/B and P62/SQSTM1 levels were significantly increased in the female mTBI chronic and male r-mTBI chronic liver tissues but decreased in the male r-mTBI and female r-mTBI acute kidney tissues. Significant histopathological changes were also observed in the liver and kidney tissue which were dependent on the TBI severity, gender, and time post TBI. CONCLUSIONS: The results showed that TBI may elicit peripheral molecular responses, particularly in terms of alteration in the levels of inflammatory cytokines and autophagy markers, which were gender- and time-dependent. This suggests that TBI may have a significant role in the cellular damage of the kidney and liver in both the acute and chronic phases post TBI, thus ensuring that the effects of TBI may not be confined to the brain.

Importance of In Vitro Embryo Model Procedure Standardization.

In vivo studies offer a detailed understanding of organism functioning, surpassing the insights provided by in vitro studies. These experiments are crucial for comprehending disease emergence, progression, and associated mechanisms in humans, as well as for developing treatments. When choosing experimental models, factors such as genomic similarity, physiological relevance, ethical appropriateness, and economic feasibility must be considered. Standardized protocols enhance the reliability, and reproducibility of scientific methods, promoting the assessment of research in the scientific literature. Researchers conducting embryo studies should establish and document standardized protocols for increased data comparability. Standardization is vital for scientific validity, reproducibility, and comparability in both in vivo and in vitro studies, ensuring the accuracy and reliability of experimental results and advancing scientific knowledge.

Diagnosed eating disorders in Danish registers - incidence, prevalence, mortality, and polygenic risk.

Eating disorders are a group of severe and potentially enduring psychiatric disorders associated with increased mortality. Compared to other severe mental illnesses, they have received relatively limited research attention. Epidemiological studies often only report relative measures despite these being difficult to interpret having limited practical use. The aims of this study were to evaluate the incidence and prevalence of diagnosed anorexia nervosa (AN), bulimia nervosa, and eating disorder not otherwise specified recorded in Danish hospital registers and estimate both relative and absolute measures of subsequent mortality - both all-cause and cause-specific in a general nationwide population of 1,667,374 individuals. In a smaller, genetically informed case-cohort sample, the prediction of polygenic scores for AN, body fat percentage, and body mass index on AN prevalence and severity was estimated. Despite males being less likely to be diagnosed with an eating disorder, those that do have significantly increased rates of mortality. AN prevalence was highest for individuals with high AN and low body fat percentage/body mass index polygenic scores.

Comparison of Microsatellite Instability With Clinicopathologic Data in Patients With Colon Adenocarcinoma.

Background Microsatellite instability (MSI) is a genetic condition caused by errors in DNA repair genes that cause colorectal cancer (CRC). The literature contradicts the frequency of MSI in sporadic CRCs and its effect on prognosis. This study investigated the distribution of clinicopathologic features and the relationship between MSI and survival outcomes. Methodology This is a retrospective study of 101 consecutive cases of CRC and immunohistochemical studies. All cases were retrospectively reviewed and reevaluated by histological grade, lymphovascular invasion, perineural invasion, tumor borders, dirty necrosis, tumor-infiltrating lymphocytes (TILs), Crohn's-like lymphoid reaction, mucinous and medullary differentiation, and tumoral budding from pathological slides. An immunohistochemical study was performed in appropriate blocks for using MLH-1, MSH-2, MSH-6, and PMS-2. We collected the clinical stage, pathological tumor stage, lymph node metastasis, age, sex, tumor diameter, distant metastasis, localization, and survival information from patients' clinical data. Results There was no statistically significant difference between the two groups regarding age, gender, tumor diameter, histological grade, tumor border, dirty necrosis, TILs, N and M stage, perineural and lymphovascular invasion, mucinous differentiation, medullary differentiation, and tumor budding characteristics of the patients. The MSI-H group was more frequently located in the right colon and transverse colon (p < 0.001), and the T stage was higher among them than in the MSI-L group (p = 0.014). Upon multivariate regression analysis, MSI status had no significant effect on survival time. Age and stage N and M were independent prognostic factors for colon cancer prognosis. Conclusions Our study presented the distribution of clinicopathological features and their relationship with MSI for 101 regional CRC patients. MSI status was detected by immunohistochemistry. Identifying MSI in CRCs may help personalize therapy planning. As the distribution of the features may vary from population to population, further investigations are needed on this topic.

A comprehensive analysis of age of onset and cumulative incidence of mental disorders: A Danish register study.

BACKGROUND: The age of onset (AOO), incidence and cumulative incidence of mental disorders are critical epidemiological measures, providing essential insights into the development and course of these disorders across the lifespan. This study aims to provide up-to-date estimates of the AOO, age-specific incidence, and cumulative incidence for a comprehensive range of mental disorders using data from Danish registers. METHODS: We conducted a follow-up study encompassing all Danish residents from January 1, 2004, to December 31, 2021, totaling 91,613,465 person-years. Data were sourced from the Danish Psychiatric Central Research Register, identifying individuals treated for various mental disorders in psychiatric hospitals, outpatient departments, and accident/emergency departments, that is, treated in secondary care settings. We investigated specific categories of mental disorders, including substance abuse disorders, schizophrenia, mood disorders, anxiety, eating disorders, borderline personality disorders, intellectual disabilities, pervasive developmental disorders, and behavioral and emotional disorders. Age-sex-specific incidence rates were estimated using Poisson generalized linear models, and cumulative incidence was calculated using Aalen-Johansen's competing risks model. The study provides estimates of AOO, incidence, and cumulative incidence for various mental disorders, including their age and sex distributions. RESULTS: The cumulative incidence by age 80 years for any mental disorder was 30.72% (95% confidence interval: 30.62%-30.83%) for males and 34.46% (34.35%-34.57%) for females. The most common types of mental disorders were anxiety-related disorders 16.27% (16.19%-16.36%) for males and 23.39% (23.29%-23.50%) for females, and followed by mood disorder 10.34% (10.27%-10.41%) for males and 16.67% (16.58%-16.77%) for females. For those who develop mental disorder, half will have developed their disorder by approximately age 22 years (median and interquartile range: males 21.37 (11.85-36.00); females 22.55 (16.31-36.08)). CONCLUSIONS: Approximately one in three individuals will seek treatment for at least one mental disorder in a secondary care setting by age 80. Given that half of these individuals develop mental disorders before age 22, it is crucial to tailor service planning to meet the specific needs of young individuals. Web-based interactive data-visualization tools are provided for clinical utility.

The Turkish version of the Postpartum Bonding Questionnaire (PBQ): Examination of the validity and reliability and scale structure.

PURPOSE: The aim of this study is to investigate the validity and reliability of the Turkish version of the Postpartum Bonding Questionnaire (PBQ). DESIGN AND METHODS: This methodological study was conducted with 250 women who presented to three family health centers in Istanbul/Turkey between April and June 2022 and met the sampling criteria. Validity analysis was performed using the content validity index, exploratory factor analysis, and confirmatory factor analysis. Pearson product-moment correlation and Cronbach Alpha reliability coefficients were used for reliability analysis. RESULTS: To evaluate invariance of the instrument over time, test-retest measurements were conducted at least two weeks apart and showed no difference in mean scores (p > .05). Adjusted goodness-of-fit index >0.97 and comparative fit index >0.98 confirmed the construct validity of the Turkish PBQ. Each item had a content validity index of 96%. Corrected item-total score correlations ranged from 0.50 to 0.93. The Cronbach Alpha was found to be 0.96, indicating high internal consistency. CONCLUSION: The results of this study show that the Turkish version of the PBQ is valid and reliable. It can be used as a measurement tool to determine the degree of maternal bonding in the postpartum period.

The role of anticomplement therapy in the management of the kidney allograft.

As the number of patients living with kidney failure grows, the need also grows for kidney transplantation, the gold standard kidney replacement therapy that provides a survival advantage. This may result in an increased rate of transplantation from HLA-mismatched donors that increases the rate of antibody-mediated rejection (AMR), which already is the leading cause of allograft failure. Plasmapheresis, intravenous immunoglobulin therapy, anti-CD20 therapies (i.e., rituximab), bortezomib and splenectomy have been used over the years to treat AMR as well as to prevent AMR in high-risk sensitized kidney transplant recipients. Eculizumab and ravulizumab are monoclonal antibodies targeting the C5 protein of the complement pathway and part of the expanding field of anticomplement therapies, which is not limited to kidney transplant recipients, and also includes complement-mediated microangiopathic hemolytic anemia, paroxysmal nocturnal hemoglobinuria, and ANCA-vasculitis. In this narrative review, we summarize the current knowledge concerning the pathophysiological background and use of anti-C5 strategies (eculizumab and ravulizumab) and C1-esterase inhibitor in AMR, either to prevent AMR in high-risk desensitized patients or to treat AMR as first-line or rescue therapy and also to treat de novo thrombotic microangiopathy in kidney transplant recipients.

Interplay of polygenic liability with birth-related, somatic, and psychosocial factors in anorexia nervosa risk: a nationwide study.

BACKGROUND: Although several types of risk factors for anorexia nervosa (AN) have been identified, including birth-related factors, somatic, and psychosocial risk factors, their interplay with genetic susceptibility remains unclear. Genetic and epidemiological interplay in AN risk were examined using data from Danish nationwide registers. AN polygenic risk score (PRS) and risk factor associations, confounding from AN PRS and/or parental psychiatric history on the association between the risk factors and AN risk, and interactions between AN PRS and each level of target risk factor on AN risk were estimated. METHODS: Participants were individuals born in Denmark between 1981 and 2008 including nationwide-representative data from the iPSYCH2015, and Danish AN cases from the Anorexia Nervosa Genetics Initiative and Eating Disorder Genetics Initiative cohorts. A total of 7003 individuals with AN and 45 229 individuals without a registered AN diagnosis were included. We included 22 AN risk factors from Danish registers. RESULTS: Risk factors showing association with PRS for AN included urbanicity, parental ages, genitourinary tract infection, and parental socioeconomic factors. Risk factors showed the expected association to AN risk, and this association was only slightly attenuated when adjusted for parental history of psychiatric disorders or/and for the AN PRS. The interaction analyses revealed a differential effect of AN PRS according to the level of the following risk factors: sex, maternal age, genitourinary tract infection, C-section, parental socioeconomic factors and psychiatric history. CONCLUSIONS: Our findings provide evidence for interactions between AN PRS and certain risk-factors, illustrating potential diverse risk pathways to AN diagnosis.

Inpatient admissions and mortality of anorexia nervosa patients according to their preceding psychiatric and somatic diagnoses.

OBJECTIVE: Anorexia nervosa (AN) is associated with increased risk of mortality, but little is known about the risk of inpatient admissions and mortality outcomes in individuals with diagnoses of both AN and other psychiatric and somatic conditions. We aimed to investigate the inpatient admissions and mortality among people with AN and other diagnosed conditions using Danish national registers. METHOD: This retrospective cohort study included individuals diagnosed with AN in Denmark, born 1977-2010. We identified other mental and somatic conditions in this population. We used Cox proportional hazards regression to estimate the risk of inpatient admission and mortality, focusing on (i) the number of other diagnosed conditions, and (ii) specific combinations of conditions diagnosed prior to the AN diagnosis. Categories of inpatient admissions considered were due to: (i) AN, (ii) any psychiatric disorder, and (iii) any somatic disorder. Additionally, competing risks survival analysis was used to calculate the cumulative incidence of inpatient admission and all-cause mortality over the follow-up period. RESULTS: The study population included 11,489 individuals. The most common conditions individuals had prior to their AN diagnosis were other eating disorders (34.5%) and anxiety disorders (32.7%). During the follow-up, 3184 (27.7%), 4604 (40.1%), and 6636 (57.8%) individuals were admitted for AN, any psychiatric disorder, and any somatic disorder, respectively; and in total 106 (0.9%) died. The risk of all outcomes was highest among those who had received a higher number of other diagnoses. For most combinations, the risks of admission and mortality were increased. DISCUSSION: Our study presents the prevalence of other conditions in patients with AN in Denmark and elucidates their association with higher rates of inpatient admission and mortality. Our findings highlight the need for comprehensive, multidisciplinary care of patients with AN considering the spectrum of other diagnosed conditions to improve health outcomes.

Partners in Pain, Two Sides of a Zipper - Midwives' Experiences With Stillbirth: A Qualitative Study.

This study was conducted to explore and understand the experiences of midwives who care for women experiencing stillbirth and the challenges they face in this process. A qualitative study was conducted with 11 midwives using the phenomenological method. Descriptive analysis of the data revealed four main themes: 1) Silent screams in the face of despair (women's reactions to stillbirth), 2) Being a partner in pain, "two sides of a zipper" (midwives' experience of stillbirth), 3) Efforts to cope with the pain, and 4) Just two words: "if only." The impact of stillbirths on midwives should not be disregarded. Emotions such as shock, horror, fear, guilt, and anger experienced by midwives following a stillbirth can adversely affect their mental health. The guilt experienced by midwives can also negatively impact their health and quality of life, as well as cause burnout and distancing from the profession.

Polygenic Risk of Mental Disorders and Subject-Specific School Grades.

BACKGROUND: Education is essential for socioeconomic security and long-term mental health; however, mental disorders are often detrimental to the educational trajectory. Genetic correlations between mental disorders and educational attainment do not always align with corresponding phenotypic associations, implying heterogeneity in the genetic overlap. METHODS: We unraveled this heterogeneity by investigating associations between polygenic risk scores for 6 mental disorders and fine-grained school outcomes: school grades in language and mathematics in ninth grade and high school, as well as educational attainment by age 25, using nationwide-representative data from established cohorts (N = 79,489). RESULTS: High polygenic liability of attention-deficit/hyperactivity disorder was associated with lower grades in language and mathematics, whereas high polygenic risk of anorexia nervosa or bipolar disorder was associated with higher grades in language and mathematics. Associations between polygenic risk and school grades were mixed for schizophrenia and major depressive disorder and neutral for autism spectrum disorder. CONCLUSIONS: Polygenic risk scores for mental disorders are differentially associated with language and mathematics school grades.

Evaluation of the therapeutic effects of arbutin on cisplatin-induced ovarian toxicity in rats through endoplasmic reticulum stress and Nrf2 pathway.

Arbutin (ARB) is a glycosylated hydroquinone with potent antioxidant effects. Although cisplatin (CP) is widely used in chemotherapy, its toxicity in healthy tissues, including ovotoxicity, is an insurmountable problem. This study aimed to evaluate the therapeutic effect of ARB against CP-related ovototoxicity by including nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in rats for the first time. Rats treated one dose of CP (5 mg/kg) on the first day, followed by ARB (5 and 10 mg/kg) for three days. Serum reproductive hormone levels were determined using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers in ovarian tissue were also determined colorimetrically. In addition, how CP affects Nrf2 pathway and the effect of ARB on this situation were also addressed. ARB treatment reduced the levels of markers of OS, inflammation, ERS and apoptosis in ovarian tissue of CP-stimulated animals. ARB regenerated the depleted antioxidant system by triggering Nrf2 pathway in the ovarian tissues of animals stimulated by CP. Histological findings also supported the therapeutic efficacy of ARB. The results indicate that ARB may have therapeutic effects against CP-induced reproductive toxicity with its Nrf2 activator potential. ARB should be tested in more extensive studies as a new generation chemopreventive candidate molecule.