Maternal immunoglobulin G affects brain development of mouse offspring.

Maternal immunoglobulin (Ig)G is present in breast milk and has been shown to contribute to the development of the immune system in infants. In contrast, maternal IgG has no known effect on early childhood brain development. We found maternal IgG immunoreactivity in microglia, which are resident macrophages of the central nervous system of the pup brain, peaking at postnatal one week. Strong IgG immunoreactivity was observed in microglia in the corpus callosum and cerebellar white matter. IgG stimulation of primary cultured microglia activated the type I interferon feedback loop by Syk. Analysis of neonatal Fc receptor knockout (FcRn KO) mice that could not take up IgG from their mothers revealed abnormalities in the proliferation and/or survival of microglia, oligodendrocytes, and some types of interneurons. Moreover, FcRn KO mice also exhibited abnormalities in social behavior and lower locomotor activity in their home cages. Thus, changes in the mother-derived IgG levels affect brain development in offsprings.

Neuronal SAM68 differentially regulates alternative last exon splicing and ensures proper synapse development and function.

Alternative splicing in the 3'UTR of mammalian genes plays a crucial role in diverse biological processes, including cell differentiation and development. SAM68 is a key splicing regulator that controls the diversity of 3'UTR isoforms through alternative last exon (ALE) selection. However, the tissue/cell type-specific mechanisms underlying the splicing control at the 3' end and its functional significance remain unclear. Here, we show that SAM68 regulates ALE splicing in a dose-dependent manner and the neuronal splicing is differentially regulated depending on the characteristics of the target transcript. Specifically, we found that SAM68 regulates interleukin-1 receptor-associated protein splicing through the interaction with U1 small nuclear ribonucleoprotein. In contrast, the ALE splicing of protocadherin-15 (Pcdh15), a gene implicated in several neuropsychiatric disorders, is independent of U1 small nuclear ribonucleoprotein but modulated by the calcium/calmodulin-dependent protein kinase signaling pathway. We found that the aberrant ALE selection of Pcdh15 led to a conversion from a membrane-bound to a soluble isoform and consequently disrupted its localization into excitatory and inhibitory synapses. Notably, the neuronal expression of the soluble form of PCDH15 preferentially affected the number of inhibitory synapses. Moreover, the soluble form of PCDH15 interacted physically with α-neurexins and further disrupted neuroligin-2-induced inhibitory synapses in artificial synapse formation assays. Our findings provide novel insights into the role of neuron-specific alternative 3'UTR isoform selections in synapse development.

ROS1 as a possible prognostic biomarker of cervical adenocarcinoma: An exploratory analysis with next-generation sequencing.

OBJECTIVES: Given the differences in clinical and biological characteristics between cervical adenocarcinoma and squamous cell carcinoma, this study aimed to conduct an exploratory analysis to examine the molecular characteristics of cervical adenocarcinoma in a Japanese population. METHODS: This study explored the simultaneous testing of multiple mutations targeting cervical adenocarcinoma using next-generation sequencing (NGS). The following genes were analyzed: BCAR4, CD274, PDCD1LG2, KRAS, ARID1A, PTEN, ALK, EGFR, ROS1, BRAF, PIK3CA, EP300, EBXW7, SHCBP1, TGFBR2, SMAD4, ERBB2, ERBB3, and KLF5. Tumor tissue and blood samples were obtained at the time of primary treatment. The NGS-based molecular profiles obtained from Tokai University (49 specimens) were compared with the registered data in The Cancer Genome Atlas (TCGA) database (133 specimens). RESULTS: The study cohort had higher rates of adenocarcinoma than the TCGA cohort (44.9% vs. 18.0%; P = 0.001). The adenocarcinomas in the study cohort had more alterations in ROS1, EGFR, EP300, SHCBP1, ALK, and PIK3CA than those in the TCGA cohort. Among them, ROS1 had the highest number of gene alterations (median, 7.00 ± 2.63). In the study cohort, patients with a high number of ROS1 alterations had a significantly higher recurrence rate (5-year recurrence rate, 48.8% vs. 14.6%; hazard ratio [HR], 4.32; 95% confidence interval [CI], 1.20-15.50; P = 0.014) and lower overall survival than those with low alterations (5-year survival rate, 70.7% vs. 93.1%; HR, 7.15; 95% CI, 1.08-58.22; P = 0.032). CONCLUSION: The current exploratory analysis suggests that ROS1 gene alteration may be a prognostic biomarker in cervical adenocarcinoma in Japanese patients.

Middle-aged and older people with urgent, unaware, and unmet mental health care needs: Practitioners' viewpoints from outside the formal mental health care system.

BACKGROUND: Mental health challenges are highly significant among older individuals. However, the non-utilization of mental health services increases with age. Although universal health coverage (UHC) was reported to reduce unmet health care needs, it might not be sufficient to reduce unmet mental health care needs from a clinical perspective. Despite the existence of UHC in Japan, this study aimed to explore the factors related to the non-utilization of formal mental health care systems among middle-aged and older people with urgent, unaware, and unmet mental health care needs. METHODS: Purposeful sampling was used as the sampling method in this study by combining snowball sampling and a specific criterion. The interviewees were nine practitioners from four sectors outside the mental health care system, including long-term care, the public and private sector, as well as general hospitals in one area of Tokyo, where we had conducted community-based participatory research for five years. The interviews were conducted by an interdisciplinary team, which comprised a psychiatrist, a public health nurse from a non-profit organization, and a Buddhist priest as well as a social researcher to cover the broader unmet health care needs, such as physical, psychosocial, and spiritual needs. The basic characteristics of the interviewees were enquired, followed by whether the interviewees had case of middle-aged or older individuals with urgent, unaware, and unmet mental health care needs. If the answer was yes, we asked the interviewees to describe the details. The interviews pertinent to this study were conducted between October 2021 and November 2021. In this study, we adopted a qualitative descriptive approach. First, we created a summary of each case. Next, we explored the factors related to the non-utilization of formal mental health care systems by conducting a thematic analysis to identify the themes in the data collected. RESULTS: The over-arching category involving "the factors related to an individual person" included two categories, as follows: 1) "Individual intrinsic factors," which comprised two sub-categories, including "difficulty in seeking help" and "delusional disorders," and 2) "family factors," which comprised "discord between family members," "denial of service engagement," "multiple cases in one family," and "families' difficulty in seeking help." The over-arching category "the factors related to the systems" included four categories, as follows: 1) "Physical health system-related factors," which comprised "the indifference of physical healthcare providers regarding mental health" and "the discontinuation of physical health conditions," 2) "mental health system-related factors," which comprised "irresponsive mental health care systems" and "uncomfortable experiences in previous visits to clinics," and 3) "social service system-related factors," which comprised "the lack of time to provide care," "social service not allowed without diagnosis," and "no appropriate service in the community," as well as 4) " the lack of integration between the systems." Apart from the aforementioned factors, "the community people-related factor" and "factors related to inter-regional movements" also emerged in this study. CONCLUSIONS: The results of this study suggest a specific intervention target, and they provide further directions for research and policy implementation. The suggested solutions to the issues pertinent to this study are as follows: the recognition of the ways in which older people may inadequately understand their health or be unaware of available services, the building of a therapeutic alliance for "the individual intrinsic factors." Regarding the "family factors," the solutions include the provision of particularly intensive care for families with family discords, families with multiple cases, and families who find it difficult to seek help, as well as making intensive efforts for ensuring early involvement after contact with health care services. Regarding the "the factors related to the systems," the solutions include the implementation of mental health education campaigns aimed at enhancing mental health knowledge among non-mental health professionals, as well as formulating and implementing reforms ensuring that such professionals are increasingly responsible especially with regard to emergency inpatient care. It also include listening without ageism in clinical practice, the expansion of social services regarding human resources and the flexibility of use which increases the breadth of the types of care, as well as facilitating the integration between the associated health care systems. Further suggestions include encouraging community residents to join social security systems as well as the provision of particularly intensive care for people who have just moved in.

Meaning of death among care workers of geriatric institutions in a death-avoidant culture: Qualitative descriptive analyses of in-depth interviews by Buddhist priests.

OBJECTIVE: Care workers' views of clients' death have not been explored in Japan because of a cultural tendency to avoid talking openly about death. However, given the arising problems in end-of-life care settings, such as abuse and burnout, understanding care workers' views regarding death is essential for designing effective interventions. We had two main research questions: Do care workers in Japan have their own ideas about death after working in the landscape of dying and death? Do these ideas influence care workers' professional lives? METHODS: We recruited interviewees based on a quantitative survey of care workers at 10 geriatric institutions in Tokyo. Among the 323 respondents, 23 survey respondents were willing to participate in an interview. After the scheduling process, nine individuals were able to participate in an in-depth interview. To overwhelm cultural avoidance regarding death that prevents care workers from talking openly about death, Buddhist priests conducted interviews in the current study. Physicians and researchers assisted the interviews. Because this was exploratory studies in which little is known about the topic in question, we adapted a qualitative descriptive approach. FINDINGS: Thematic analysis revealed that: 1) care workers had clear views about conditions of clients' good death after working in the field of dying and death; 2) care workers were motivated by past experiences of being close to dying themselves; and 3) care workers regarded their care for the dying as an experience that enriched their lives. In addition, the results revealed that the concept of spiritual care in Japan is still its infancy among care workers because of its vague definition. CONCLUSIONS: Care workers were willing to work for dying people with their view of death, and regarded their jobs as important opportunities for personal growth through caring for the dying.

Reflections of Buddhist priests who started a dementia carers' café in Japan.

AIM: Faith-based organizations are a potential global resource; however, details of their activities have not been fully explored in the academic literature. In Japan, little is known about delivering support for dementia caregivers in a faith-based setting. In this study, we spoke with priests who started carers' cafés to support people who have dementia and people who care for them. These "carers' cafés" are set up in temples and this movement is slowly expanding. The aim of this study was to (1) provide a detailed description of a carers' café and (2) report the reflections of the Buddhist priests who have been involved in the project from the beginning. METHODS: We conducted in-depth interviews with five Buddhist priests who pioneered the carers' café movement, and conducted a thematic analysis of the transcripts using a qualitative descriptive approach. RESULTS: Six prominent themes were identified: "A carers' café aligns with Buddhist doctrine," "...reveals the strengths of Buddhism and its temples," "...facilitates priests' personal growth," and "...introduces viewpoints from outside of Buddhism." CONCLUSIONS: Carers' cafés set up in temples have a positive impact on the Buddhist priests who are involved and on the visitors. One possible reason for this is that the relationship between the temple and the local residents has a long history and thus provides a sense of security for those who are suffering from the realities related to dementia. To create a more inclusive society, it is necessary for secular entities to support this new movement.

Use of universal primers for the 18S ribosomal RNA gene and whole soil DNAs to reveal the taxonomic structures of soil nematodes by high-throughput amplicon sequencing.

Nematodes are abundant metazoans that play crucial roles in nutrient recycle in the pedosphere. Although high-throughput amplicon sequencing is a powerful tool for the taxonomic profiling of soil nematodes, polymerase chain reaction (PCR) primers for amplification of the 18S ribosomal RNA (SSU) gene and preparation of template DNAs have not been sufficiently evaluated. We investigated nematode community structure in copse soil using four nematode-specific (regions 1-4) and two universal (regions U1 and U2) primer sets for the SSU gene regions with two DNAs prepared from copse-derived mixed nematodes and whole soil. The major nematode-derived sequence variants (SVs) identified in each region was detected in both template DNAs. Order level taxonomy and feeding type of identified nematode-derived SVs were distantly related between the two DNA preparations, and the region U2 was closely related to region 4 in the non-metric multidimensional scaling (NMDS) based on Bray-Curtis dissimilarity. Thus, the universal primers for region U2 could be used to analyze soil nematode communities. We further applied this method to analyze the nematodes living in two sampling sites of a sweet potato-cultivated field, where the plants were differently growing. The structure of nematode-derived SVs from the two sites was distantly related in the principal coordinate analysis (PCoA) with weighted unifrac distances, suggesting their distinct soil environments. The resultant ecophysiological status of the nematode communities in the copse and field on the basis of feeding behavior and maturity indices was fairly consistent with those of the copse- and the cultivated house garden-derived nematodes in prior studies. These findings will be useful for the DNA metabarcoding of soil eukaryotes, including nematodes, using soil DNAs.

[Conflicts in the end-of-life care: Interviews with care staff by Buddhist priests and researchers].

AIM: Interprofessional communication and collaboration is essential for a better end-of-life and death, where individual dying people are respected and their satisfaction is the goal. The aim of this study is to explore 1) ethical conflicts viewed by care staff of geriatric institutions, 2) their views about geriatric medicine, and 3) their views about religion in the context of institutional end-of-life care. METHODS: Semi-structured interviews were conducted by Buddhist priests and researchers with nine care workers who worked in nursing homes or long-stay geriatric hospitals. This interview was conducted as part of a research project that investigated the feasibility of the engagement of religious workers in the geriatric care setting. RESULTS: Regarding ethical conflicts, six themes were merged: difficulty in knowing the will of the person being cared for, dissonance with the family, older person's wish to die, losing the purpose for living, staff not being used to death, and families not being used to death. Regarding geriatric medicine, eight themes were merged: gratitude for cooperation, persuasive explanation, not accepting death, not allowing patients to share a peer's death, cold attitude, being drug therapy centered, not being person-centered, and heavy burden for patients. Regarding religion, five themes were merged: expectation for salvation, barrier to hospitals, already involved in nursing homes, explicit religious traits are acceptable, and favorable character of religious workers in institutions. CONCLUSIONS: Communication between geriatric physicians, care staff, and mainstream religious workers, with the aim of providing a better quality of end-of-life and death, is beneficial in a super-aged society.

A positive attitude towards provision of end-of-life care may protect against burnout: Burnout and religion in a super-aging society.

AIM: The aim of our study was to investigate factors associated with burnout of nurses and care workers in nursing homes and geriatric hospitals in Japan. The use of Buddhist priests, the major religion in Japan, was also explored. METHODS: Questionnaires for nurses and care workers were sent to 10 care facilities. The survey questions included basic demographic information, the Japanese Burnout Index and the Japanese version of the Frommelt Attitude Toward Care Of Dying Scale Form B. They also asked questions about use of Buddhist priests for tasks such as helping to manage the anxiety or distress of patients, families, and staff, or providing sutra chanting. RESULTS: In total, 323 questionnaires were returned, of which 260 were used for analysis. Only 18 (6.9%) answered that they had any religious beliefs, which was relatively low compared to 27% from governmental survey data. In total, however, 71% expressed a need for Buddhist priests to help with anxiety or distress among patients. A positive attitude towards providing end-of-life care was a protective factor against depersonalization. It was, however, also related to lower feelings of personal accomplishment. CONCLUSION: Care homes and geriatric hospitals may want to consider calling more on religious resources as a support for staff and patients.