Neutrophil extracellular traps (NETs) are essential components of antimicrobial defense, but excessive or persistent NET accumulation can promote inflammation, tissue injury, thrombosis, and disease progression. DNase I is a major extracellular nuclease involved in the degradation of NETs and extracellular DNA, thereby contributing to immune homeostasis. Genetic variation in DNASE1 may influence this clearance capacity. Among DNASE1 polymorphisms, the Q222R substitution, designated DNASE1*2, is a common functional variant associated with reduced DNase I enzymatic activity. This reduction may limit NET degradation under conditions of increased extracellular DNA burden, such as inflammation and malignancy. Clinical studies have linked DNASE1*2 or DNase I phenotype 2 with myocardial infarction, adverse cardiovascular outcomes, and several malignancies. This review summarizes current evidence supporting DNASE1*2 as a potential genetic modifier of DNase I activity, NET clearance, and disease susceptibility. The review also discusses the possible clinical relevance of DNASE1*2 in disease risk, prognosis, and future genotype-informed therapeutic strategies, which require further validation.

Background: Depression is a major global health burden, requiring culturally appropriate assessment instruments, but no validated Kazakh-language version of the Patient Health Questionnaire-9 (PHQ-9) is available. This study aimed to translate, culturally adapt, and evaluate the psychometric properties of the Kazakh PHQ-9 in a community-based, non-clinical sample. Methods: This cross-sectional study included 503 Kazakh-speaking adults (mean age = 24.0 years, SD = 10.1; 51.3% women and 48.7% men) who completed the Kazakh PHQ-9 and Generalized Anxiety Disorder-7 (GAD-7) questionnaires. Internal consistency, structural validity, measurement invariance across genders, and convergent validity were assessed. Results: Internal consistency was excellent (Cronbach’s α = 0.91), and both one-factor and correlated two-factor models showed excellent fit (CFI = 0.998; TLI = 0.997–0.998; RMSEA = 0.046–0.048; SRMR = 0.050–0.052), with a slightly better fit for the latter. Measurement invariance across genders was supported, and PHQ-9 and GAD-7 scores were strongly correlated (r = 0.68, p < 0.001). Conclusions: The Kazakh PHQ-9 demonstrated excellent internal consistency and structural validity, measurement invariance across genders, and strong convergent validity in this non-clinical sample. These findings support its use for assessing depressive symptoms in Kazakh-speaking adults. Clinical validation is needed to establish diagnostic validity and screening performance.

Background: In the Republic of Kazakhstan, informal caregivers remain the main source of patient support. Caregivers of individuals with dementia experience an increased caregiver burden and significantly higher levels of stress. We investigated the levels of caregiver burden, depression, anxiety, and stress among informal dementia caregivers and assessed the relationships between these indicators and the caregivers’ socio-demographic characteristics. Methods: With the cooperation of two regional mental health centers and three polyclinics in Kazakhstan, we conducted a cross-sectional study of 174 informal caregivers of dementia patients. The caregiver burden was assessed using the Zarit Burden Interview, and psychological distress was measured with the Depression Anxiety Stress Scale-21. The caregivers’ sociodemographic data were collected and analyzed. The adjusted odds ratios and 95%CIs were calculated using logistic and ordinal regressions. Results: Overall, 75.9% of the caregivers reported experiencing at least a mild burden, and the levels of depression, anxiety, and stress among the caregivers were higher than expected. Spousal caregivers had higher odds of abnormal depression (p = 0.022) and anxiety (p = 0.020); in severity models, spouses more often had a severe burden (p = 0.042) and anxiety (p = 0.006). Conclusions: Caregiver burden and psychological distress are highly prevalent among informal dementia caregivers in Kazakhstan, particularly among spouses. It is especially important to provide support for spouse caregivers. Culturally tailored psychoeducation, support groups, and respite services are urgently needed to mitigate the mental health risks faced by dementia caregivers in Kazakhstan.

Deoxyribonucleases (DNases) are essential enzymes involved in DNA metabolism, playing critical roles in replication, repair, recombination, and the degradation of apoptotic DNA. They are primarily classified into two families: DNase I and DNase II, each exhibiting distinct catalytic properties and tissue-specific functions. Dysregulated DNase activity is implicated in various diseases. This review synthesizes current knowledge on the biochemical properties, gene structures, tissue distributions, and clinical significance of DNases. It explores their roles in disease mechanisms, the impact of genetic polymorphisms on enzyme activity, and their potential as biomarkers for early disease detection. While considerable progress has been made in elucidating the physiological functions of endogenous DNases, increasing attention is being directed toward the therapeutic applications of exogenous DNases. Beyond their established role in cystic fibrosis treatment, DNases show promise in addressing conditions such as cancer, acute kidney injury, sepsis, traumatic brain injury, and diabetic wound healing by modulating inflammation and clearing extracellular DNA. By providing a comprehensive overview of DNase families, this review highlights their functional diversity and clinical relevance, paving the way for future research, therapeutic advancements, and novel approaches to disease management. Therefore, this article contributes valuable insights not only to the field of legal medicine but also to broader areas of basic and clinical medical sciences.

The number of suicides by children in Japan has increased over the past few years. We conducted this descriptive epidemiological study to identify aspects of this situation that must be improved. We summarize the observations based on our findings and describe effective approaches to decrease the number of suicides among children. We investigated and calculated the number of suicides and the percentage of 'unknown' causes of/motives for suicide among the categories of causes of/motives for suicide among Japanese elementary, junior high school, and high school students (including separate analyses for male and female students) during the 3-year period 2022-2024 based on the numerical data published by Japan's Ministry of Health, Labour and Welfare and the National Police Agency. The current problems with suicide statistics are explained, and potential approaches to dealing with these statistics are described. During the 3-year study period, 1,556 suicides by elementary, junior high school, and high school students were recorded in Japan. 'Unknown' causes of/motives for suicide accounted for 11.8% of the suicides by the students overall during the 3-year period; the yearly percentage for these unknown causes was 10.1%-12.9%. Since Japan's Status of Suicide report was revised in 2022, care is required when comparing suicide data with the data obtained before 2022. These issues must be addressed in collaborations by legal medicine and public health experts.

This review comprehensively explores the molecular characterization, genetic insights, and functional implications of human DNase II, an enzyme crucial for DNA hydrolysis under acidic conditions. We discuss its purification, identification, and characterization, emphasizing the importance of highly purified samples for accurate analyses as well as for understanding the biochemical properties. The discovery and analysis of DNase II’s cDNA and gene have provided crucial insights into its genetic regulation and chromosomal location. Genetic polymorphism in DNase II activity levels, characterized by distinct alleles, provides valuable information on the diversity of enzyme function among individuals. Tissue distribution studies reveal its widespread presence across human tissues, hinting at potential endocrine connections. Clinical implications of DNase II variants, including therapeutic strategies targeting the JAK1 pathway, offering insights into disease mechanisms and potential treatments. Overall, this review serves as a valuable resource for advancing our knowledge of DNase II and its impact on human health and disease.

Smartphone ownership and social media use are increasing worldwide, and children are not exempt from these trends. Past studies on this issue have mainly focused on educational campaigns to prevent the prolonged use of smartphones, social media, and video games. Recently, harm to children from engagement with bad actors through social media has become a major problem in Japan, and preventive measures need to be based on close analysis of the facts. The present study was performed descriptive epidemiology and comparison between two groups. This study investigated the number of children in Japan who fell victim to criminal offense through their use of social media, categorized by level of schooling, type of offense, and means of accessing social media over the 8year period from 2016 to 2023. The 8-year period was divided into 2016-2019 (4 years prior to the COVID-19 pandemic) and 2020-2023 (4 years during the pandemic). Statistical analysis was conducted to compare these periods. The number of elementary school students victimized by criminal offense through social media in Japan increased significantly in 4 years during the pandemic. Furthermore, in 4 years during the pandemic, there was also a notable rise in felony-related incidents, and an increase in the number of victims accessing social media via smartphones. Schools, parents/guardians, and personnel and organizations in relevant fields need to collaborate in addressing and educating students about the proper use of smartphones and the risks of social media starting at the elementary school age.

Background: The COVID-19 pandemic had profound impacts worldwide on individuals with mental and behavioral disorders, including disorders due to psychoactive substance use. We investigated how the COVID-19 pandemic affected the trends in these disorders in the Republic of Kazakhstan. Methods: We researched and compared ICD-10 data on mental and behavioral disorders due to substance use in Kazakhstan that were diagnosed in 2018–2019 (pre-pandemic) versus 2020–2021 (the pandemic period). Results: The data for the pandemic period were significantly different from those of the pre-pandemic in that (i) ‘other stimulant-related disorders (F15)’ and ‘other psychoactive substance-related disorders (F19)’ were increased in the younger age groups, (ii) the risk of ‘opioid-related disorders (F11)’ was decreased in the 30-year-old group in both males and females, and (iii) the risk of ‘alcohol-related disorders (F10)’ was increased in the 30-year-old group and decreased in the 20- and 50-year-old groups. In only the males, (iv) the risk of ‘other psychoactive substance-related disorders (F19)’ was increased in almost all of the age groups, and (v) the risk of ‘cannabis-related disorders (F12)’ was increased in the ≥50-year-olds. The pre-pandemic and pandemic periods thus involved changes due to COVID-19 in both males and females that were especially notable in males. Conclusions: These results indicate that further measures designed to prevent mental and behavioral disorders due to psychoactive substances are necessary at the primary, secondary, and tertiary levels, and personnel in medicine/nursing, the government, private organizations, and the public need to collaborate to devise such measures.

Investigations of suicide in countries of the former Soviet Union, which broke into 15 different countries in the early 1990s, require examinations of a combination of economic, social, and health factors. It is important to address these factors individually and to examine the various composite indicators for each. Moreover, it would be worthwhile to explore the potential applicability of a comprehensive worldwide index. We analyzed data from nine of the former Soviet countries for which both the annual suicide rate and the Global Competitiveness Index (GCI) were available for the years 2006-2017. We determined the precise relationships between the suicide rate and the GCI during this period in these nine countries as well as in nine countries with high suicide rates in Europe and Asia. The results indicated the following: (i) In six of the nine former Soviet countries with complete data, the suicide rate showed a relationship with the GCI. Notably, this relationship was inverse in all but one country. (ii) Among the nine European and Asian countries with high suicide rates, three exhibited a correlation between the suicide rate and the GCI. Measures to prevent suicide should be devised especially in countries of the former Soviet Union through collaboration among multiple fields and organizations, as necessary, with particular attention paid to countries with worse or worsening GCI values.

Abstract Aim We conducted a 12‐week double‐blind, placebo‐controlled, multicenter study to evaluate the efficacy and safety of yokukansan in patients with schizophrenia. Methods Patients with schizophrenia resistant to antipsychotics whose Positive and Negative Syndrome Scale (PANSS) scores were stable within five points were enrolled and assigned to the yokukansan or placebo group. Fifty‐three of the 61 consenting patients were allocated to the yokukansan (n = 27) and placebo (n = 26) groups. Results The changes in total and positive PANSS scores at 12 weeks were significantly greater in the yokukansan group than in the placebo group. There were no significant changes in other psychiatric symptom rating scores in either group. Adverse reactions were reported in six of 27 patients (22.2%) in the yokukansan group and five of 26 patients (19.2%) in the placebo group, all of which were nonserious. Conclusion Yokukansan is very safe and has clinical potential as a treatment for schizophrenia in combination with Western medicine.

Background: Periodontitis is one of the most common chronic inflammatory disorders in adults. Although clinical studies have suggested a causal relationship between periodontitis and major depression (MD), the biological mechanisms by which periodontitis instigates MD are unknown. We investigated whether a systemic administration of lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg), a major Gram-negative pathogen of periodontitis, causes depressive-like behavior and glial activation in the hippocampus and the prefrontal cortex (PFC), which are MD-related brain regions. Materials and Methods: Eight-week-old male Sprague Dawley rats were randomly divided into a behavioral test group and an immunohistochemistry group. The rats in each group were further assigned to the sham injection (saline) and Porphyromonas gingivalis-lipopolysaccharide (Pg-LPS) injection protocols. The rats received an intraperitoneal injection of saline or Pg-LPS with gradually increasing doses (day 1: 0.5, day 2: 0.5, day 3: 0.75, day 4: 0.75, day 5: 1.0, day 6: 1.0, and day 7: 1.0 mg/kg of body weight) for seven consecutive days. After the systemic administration, the behavior test group underwent the forced swimming test (FST) and Y-maze test. For the immunohistochemistry group, we quantified the immunoreactivity for microglial Iba-1 (ionized calcium-binding adapter molecule 1) and astrocytic glial fibrillary acidic protein (GFAP) in the hippocampus (dentate gyrus [DG], cornu ammonis [CA1 and CA3]) and PFC (prelimbic [PrL] and the infralimbic [IL]) areas. Results: The FST immobility time in the Pg-LPS group was significantly longer than that in the sham group. In the Y-maze test, a significant decline in spontaneous alternation behavior was observed in the Pg-LPS group compared to the sham group. The peripheral administration of Pg-LPS significantly increased the immunoreactivity for Iba-1 in the CA3 and PrL. Pg-LPS injection significantly increased the immunoreactivity for GFAP in the DG, CA1, and CA3. Conclusions: The major result of this study is that a repeated systemic administration of Pg-LPS caused depressive-like behavior and both microglial and astrocytic activation in rats. This finding may comprise biological evidence of a causal relationship between periodontitis and MD.