Haruo Takeshita

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.

NAC1, a transcription regulator protein associated with cancer, is highly expressed in several tumor types, including ovarian cancer. However, it remains unclear how NAC1 is involved in carcinogenesis. Our previous studies demonstrated that the knockdown of NAC1 in ovarian clear cell carcinoma (OCCC) cell lines induces apoptosis and restores their sensitivity to chemotherapy, suggesting NAC1 as a potential therapeutic target. The present study aimed to identify molecular pathways through which NAC1 is involved in the development of endometriosis-related ovarian neoplasms (ERONs). Immunohistochemistry was performed to clarify the relationship between NAC1 and the potential target protein ACOX2 in surgical specimens of ERONs. Reporter assays were conducted to determine the interaction of NAC1 with the specific cis-element on the ACOX2 promoter. Subsequently, a ChIP assay was performed to investigate the in vivo interaction of NAC1 with the ACOX2 promoter. There was an inverse relationship between NAC1 and ACOX2 expressions in the tumor specimens of ERONs. High NAC1/low ACOX2 expression was found to be a worse prognostic marker for patient survival. Reporter assays demonstrated that NAC1 negatively regulated the ACOX2 promoter via the proximal CATG site. ChIP assays confirmed in vivo binding of NAC1 to the promoter. The present study implicated that NAC1 may contribute to the development of ERONs as a transcriptional repressor by regulating ACOX2 expression via specific binding sites on the promoter, providing a novel insight into the NAC1/ACOX2 axis as a potential therapeutic target of this tumor type.

Background: Murder is one of the most serious societal problems. Risk factors for murder and indices of societal phenomena that are likely to increase the incidence of murder should be ascertained, and preventive measures based on definitive evidence require discussion for implementation. Objective: We speculated that unemployment may be strongly related to emotions that stimulate people to commit murder. Materials and Methods: Herein, we researched the relationship between murders and unemployment in the Republic of Kazakhstan, which became an independent country in December 1991 and has rapidly modernized since then. This relationship has rarely been discussed in the Republic of Kazakhstan. We examined the annual murder rate (per 100,000 population) and the annual unemployment rate (%) published by the International Labor Organization (ILO) and International Monetary Fund(IMF) in the Republic of Kazakhstan that occurred over the 29-year period from 1992 to 2020. The relationship between the murder rate and the unemployment rate was analyzed statistically. Results: The annual murder rate in the Republic of Kazakhstan was significantly related to the country's annual unemployment rate (according to the ILO and IMF). An increase in the unemployment rate is likely to be related to an increase in murders. Conclusions: Personnel and organizations in areas dealing with unemployment and with murders should work together to prevent each to the greatest extent possible. Changes in a country's unemployment rate should also be continuously monitored by the identification of both momentary and continued increases in that rate, in part toward the prevention of murders. Актуальность. Убийство остаётся одной из наиболее серьёзных социальных проблем. Необходимо выявлять факторы риска и социальные показатели, способствующие росту числа убийств, а также обсуждать профилактические меры, основанные на достоверных доказательствах. Цель. Изучение показателей безработицы, которая может значительно усиливать эмоциональные состояния, побуждающие людей к совершению убийств. Материалы и методы. В настоящем исследовании рассмотрена взаимосвязь между убийствами и безработицей в Республике Казахстан, ставшей независимым государством в декабре 1991 года и переживающей быстрые процессы модернизации. Такая взаимосвязь до сих пор практически не обсуждалась в Казахстане. Мы проанализировали годовой уровень убийств (на 100 000 населения) и годовой уровень безработицы (%) за 29-летний период с 1992 по 2020 гг., опубликованные Международной организацией труда (МОТ) и Международным валютным фондом (МВФ). Корреляция между показателями оценивалась статистически. Результаты. В Казахстане годовой уровень убийств достоверно коррелировал с годовым уровнем безработицы (по данным МОТ и МВФ). Повышение безработицы, вероятно, связано с увеличением числа убийств. Выводы. Службам, занимающимся вопросами безработицы и расследованием убийств, следует максимально тесно сотрудничать в целях их профилактики. Изменения уровня безработицы необходимо непрерывно мониторировать, уделяя внимание как кратковременным, так и устойчивым тенденциям роста, что позволит частично предупредить убийства. Негіздеме. Кісі өлтіру — қоғамдағы ең өзекті қылмыстардың бірі. Кісі өлтіруге итермелейтін қауіп-қатер факторларын және осы көрсеткіштің өсуіне ықпал ететін әлеуметтік жағдайларды анықтау, сол деректерге негізделген алдын алу шараларын талқылау маңызды. Мақсат. Жұмыссыздық кісі өлтіруге итермелейтін эмоцияларды күшейтуі мүмкін болжамын ұсыну. Материалдар мен әдістер. 1991 жылдың желтоқсанында тәуелсіздік алғаннан кейін қарқынды жаңғырып келе жатқан Қазақстан Республикасында кісі өлтірулер мен жұмыссыздық арасындағы байланыс сирек зерттелген. Біз 1992–2020 жылдар аралығындағы 29 жылдық кезеңде Халықаралық еңбек ұйымы (ХЕҰ) мен Халықаралық валюта қоры (ХВҚ) жариялаған деректерді қолданып, жылдық кісі өлтіру коэффициентін (100 000 тұрғынға шаққанда) және жылдық жұмыссыздық деңгейін (%) талдадық. Көрсеткіштер арасындағы...

Genetic variants, such as single nucleotide polymorphisms (SNPs), in the deoxyribonuclease I (DNase I) gene which remarkably reduce or abolish the activity are assumed to be substantially responsible for the genetic backgrounds determining susceptibility to autoimmune dysfunction. Here, we evaluated many genetic variants, including missense and nonsense SNPs, and indel (inframe) variants in the gene, potentially implicated in autoimmune diseases as functional variants resulting in altered activity levels. Eighteen missense and 7 nonsense SNPs, and 9 indel (inframe) variants were found to result in loss of function and disappearance of DNase I activity. Furthermore, considering the positions in the DNase I protein corresponding to the various nonsense SNPs, all of the other nonsense SNPs and frameshift variants registered in the Ensembl database (https://asia.ensembl.org) appear likely to exert a pathogenetic effect through loss of the activity. Accordingly, a total of 60 genetic variants in the DNase 1 gene (DNASE1) inducing abolishment or marked reduction of the DNase I activity could be identified as genetic risk factors for autoimmunity, irrespective of how sparsely they were distributed in the population. It was noteworthy that SNP p.Gln244Arg, reportedly associated with autoimmunity and reducing the activity to about half of that of the wild type, and SNP p.Arg107Gly, abolishing the activity completely, were distributed worldwide and in African populations at the polymorphic level, respectively. On the other hand, with regard to copy number variations in DNASE1 where loss of copy leads to a reduction of the in vivo enzyme activity, only 2 diploid copy numbers were distributed in Japanese and German populations, demonstrating no loss of copy. These exhaustive data for genetic variants in DNASE1 resulting in loss or marked reduction of the DNase I activity are highly informative when considering genetic predisposition leading to autoimmune dysfunction.

Deoxyribonucleases (DNases) might play a role in prevention of autoimmune conditions such as systemic lupus erythematosus through clearance of cell debris resulting from apoptosis and/or necrosis. Previous studies have suggested that variations in the in vivo activities of DNases I-like 3(1L3) and II have an impact on autoimmune-related conditions. The genes for these DNases are known to show copy number variations (CNVs) whereby copy loss leads to a reduction of the in vivo activities of the enzymes, thereby possibly affecting the pathophysiological background of autoimmune diseases. Using a simple newly developed quantitative real-time PCR method, we investigated the distributions of the CNVs for DNASE1L3 and DNASE2 in Japanese and German populations. It was found that only 2 diploid copy numbers for all of these DNASE CNVs was distributed in both of the study populations; no copy loss or gain was evident for any of the autoimmune-related DNase genes. Therefore, it was demonstrated that these human autoimmune-related DNase genes show low genetic diversity of CNVs resulting in alterations of the in vivo levels of DNase activity.

Dysfunction of DNase I-like 2 (DNase 1L2) has been assumed to play a role in the etiology of parakeratosis through incomplete degradation of DNA in the epidermis. However, the pathogenetic background factor for such pathophysiologic conditions remains unknown. In this context, non-synonymous single-nucleotide polymorphisms (SNPs) in DNASE1L2 that would potentially result in loss of in vivo DNase 1L2 activity might serve as a genetic risk factor for such pathophysiologic conditions. Our aim was to effectively survey the non-synonymous SNPs of DNASE1L2 that would produce a loss-of-function variant of the enzyme together with a genetic distribution in the various populations. Here, the effects of all of the SNPs predicted by PolyPhen-2 analysis to be “probably damaging” (score = 1.000), and derived from frameshift/nonsense mutations, on the activity of DNase 1L2 were examined using the corresponding DNase 1L2 variants expressed in COS-7 cells. Genotyping of these SNPs was also performed in three ethnic groups including 14 different populations. Among the 28 SNPs examined, the minor allele of 23 SNPs was defined as a loss-of-function variant resulting in loss of DNase 1L2 function, indicating that Polyphen-2 analysis could be effective for surveys of at least non-synonymous SNPs resulting in loss of function. On the other hand, these minor alleles were not distributed worldwide, thereby avoiding any marked reduction of the enzyme activity in human populations. Furthermore, all of the 19 SNPs originating from frameshift/ nonsense mutations found in DNASE1L2 resulted in loss of function of the enzyme. Thus, the present findings suggest that each of the minor alleles for these SNPs may serve as one of genetic risk factors for parakeratotic skin diseases such as psoriasis, even though they lack a worldwide genetic distribution.

Postmortem computed tomography (PMCT) has recently become important to clarify the cause of death in forensic medicine. It has also been proven to be useful for in-hospital deaths to a certain extent when interpreted by radiologists. However, accuracy of the interpretations of PMCT by non-radiologists remains to be elucidated. Nevertheless, they are often required to write death certificates based on the findings of PMCT in the absence of radiologists in Japan. We compared the interpretations of postmortem head CT (PMCT-H) by non-radiologists with the autopsy findings. This study included 13 patients who underwent both brain dissection at autopsy and PMCT between June 2011 and December 2014. All cases were non-traumatic in-hospital deaths. Interpretation of PMCT was performed by the clinicians in charge of the patients, not by radiology experts. The patients were first examined with PMCT and then autopsies were performed. Ten out of 13 cases were confirmed to have no lesions in the cranial cavity by both PMCT-H and autopsy. Two cases were diagnosed with intracranial hemorrhage (intracerebral and/or subarachnoid hemorrhage) and one with recurrent malignant lymphoma by both the clinicians and the pathologists. Intracranial hemorrhages were thought to be the direct causes of mortality of the two patients, and recurrent malignant lymphoma was considered to be one of the cardinal findings of the cancer death. There were no discrepancies between PMCT-H and autopsy findings. The interpretations of PMCT-H by non-radiologists were completely the same as the autopsy findings regarding the non-traumatic in-hospital deaths in this study. It is premature to draw a definitive conclusion at present, but PMCT-H might be as effective as autopsy not only for those lesions described above but also for no remarkable changes in the brain. There has been no report on such a comparison. We believe further verification of the validity of interpretation of PMCT by non-radiologists is worthwhile in terms of death certificates made out in the absence of radiology experts and pathologists.