Addressing Perinatal Opioid Use at a Local Health Department in Florida.

PURPOSE: Perinatal substance use disorders (SUDs) remain an urgent public health concern in the United States and are associated with increased maternal and infant morbidity and mortality. Establishing holistic prenatal care among this population allows for engaging or re-engaging the pregnant population in appropriate medical care, including treatment for SUD. DESCRIPTION: The Florida Department of Health in Citrus County (DOH-Citrus) noticed an increase in SUD among their pregnant population and developed a pilot program that incorporates Medication for Opioid Use Disorder (MOUD) and mental health services during routine prenatal care appointments. ASSESSMENT: Since the launch of the pilot program, DOH-Citrus has provided prenatal programs with buprenorphine assistance to 23 members of the community. CONCLUSION: A growing number of local health departments (LHDs) provide harm reduction supplies, overdose prevention education, and local resources for treatment and other life-saving services. In many communities, LHDs are typically the most accessible sources of public health information and health care services. By framing the pilot program as a prenatal care center that incorporates SUD treatment as the prescribed standard of care, DOH-Citrus has implemented a holistic model for treating SUD and reducing barriers while improving continuity of care. LHDs are uniquely positioned to implement harm reduction strategies that address perinatal SUDs, treatment, and recovery within maternal and child health populations. As a health department located in a state without expanded Medicaid and with high rates of uninsured people, this pilot program has the potential to be replicated in other states facing similar challenges.

[Successful second allogeneic hematopoietic stem cell transplantation with azacitidine as bridging therapy for relapsed juvenile myelomonocytic leukemia].

Hematopoietic cell transplantation (HCT) is the only curative therapy for juvenile myelomonocytic leukemia (JMML). Meanwhile, an established conventional chemotherapy before HCT remains unavailable. Studies have shown that azacitidine (AZA), which is a DNA methyltransferase inhibitor, is clinically effective for JMML as a bridging therapy for HCT; a prospective clinical trial in Japan is ongoing. Herein, we present a case of a patient with JMML who was administered AZA as bridging therapy for both first and second HCT. A 3-year-old boy with neurofibromatosis type 1 was administered with intravenous AZA (75 mg/m2/day for 7 days, intervals of 28 days, and four cycles) and received myeloablative HCT (unrelated bone marrow). When relapse occurred on day 123, four additional AZA therapy cycles were administered, and the patient received a second nonmyeloablative HCT (cord blood). After seven AZA therapy cycles as post HCT consolidation, hematological remission was sustained for 16 months after the second HCT. No severe adverse events occurred. AZA is effective for JMML as a bridging therapy for HCT and has robust cytoreductive potential despite the risk of relapse.

Structure and mechanism of the mammalian fructose transporter GLUT5.

The altered activity of the fructose transporter GLUT5, an isoform of the facilitated-diffusion glucose transporter family, has been linked to disorders such as type 2 diabetes and obesity. GLUT5 is also overexpressed in certain tumour cells, and inhibitors are potential drugs for these conditions. Here we describe the crystal structures of GLUT5 from Rattus norvegicus and Bos taurus in open outward- and open inward-facing conformations, respectively. GLUT5 has a major facilitator superfamily fold like other homologous monosaccharide transporters. On the basis of a comparison of the inward-facing structures of GLUT5 and human GLUT1, a ubiquitous glucose transporter, we show that a single point mutation is enough to switch the substrate-binding preference of GLUT5 from fructose to glucose. A comparison of the substrate-free structures of GLUT5 with occluded substrate-bound structures of Escherichia coli XylE suggests that, in addition to global rocker-switch-like re-orientation of the bundles, local asymmetric rearrangements of carboxy-terminal transmembrane bundle helices TM7 and TM10 underlie a 'gated-pore' transport mechanism in such monosaccharide transporters.

Epigenetic regulation of Kiss1 gene expression mediating estrogen-positive feedback action in the mouse brain.

This study aims to determine the epigenetic mechanism regulating Kiss1 gene expression in the anteroventral periventricular nucleus (AVPV) to understand the mechanism underlying estrogen-positive feedback action on gonadotropin-releasing hormone/gonadotropin surge. We investigated estrogen regulation of the epigenetic status of the mouse AVPV Kiss1 gene locus in comparison with the arcuate nucleus (ARC), in which Kiss1 expression is down-regulated by estrogen. Histone of AVPV Kiss1 promoter region was highly acetylated, and estrogen receptor α was highly recruited at the region by estrogen. In contrast, the histone of ARC Kiss1 promoter region was deacetylated by estrogen. Inhibition of histone deacetylation up-regulated in vitro Kiss1 expression in a hypothalamic non-Kiss1-expressing cell line. Gene conformation analysis indicated that estrogen induced formation of a chromatin loop between Kiss1 promoter and the 3' intergenic region, suggesting that the intergenic region serves to enhance estrogen-dependent Kiss1 expression in the AVPV. This notion was proved, because transgenic reporter mice with a complete Kiss1 locus sequence showed kisspeptin neuron-specific GFP expression in both the AVPV and ARC, but the deletion of the 3' region resulted in greatly reduced GFP expression only in the AVPV. Taken together, these results demonstrate that estrogen induces recruitment of estrogen receptor α and histone acetylation in the Kiss1 promoter region of the AVPV and consequently enhances chromatin loop formation of Kiss1 promoter and Kiss1 gene enhancer, resulting in an increase in AVPV-specific Kiss1 gene expression. These results indicate that epigenetic regulation of the Kiss1 gene is involved in estrogen-positive feedback to generate the gonadotropin-releasing hormone/gonadotropin surge.

[Features and evaluations of organizational support provided by occupational health nurses in private practice for the implementation of sustainable health and productivity management in medium-sized enterprises].

OBJECTIVES: This study aimed to clarify the features and evaluations of the organizational support provided by occupational health nurses (OHNs) in private practice to promote sustainable health and productivity management (HPM) in medium-sized enterprises. METHODS: Corporate managers and employees of four enterprises with fewer than 300 employees received support from an experienced OHN in private practice through five support sessions per company, primarily targeting company managers. The OHNs documented their support steps and evaluations. After completing the support process, we conducted semi-structured interviews with company managers and OHNs to evaluate the support provided by the OHNs. The support processes were organized for each company according to an analytical framework based on the consolidated framework for implementation research; the support features of OHNs were extracted. The evaluations of the support provided by OHNs from the perspective of company personnel were categorized using content analysis. RESULTS: Six features of support by OHNs for the promotion of HPM were extracted, including clarifying corporate needs while focusing on relationships of trust with company representatives, providing appropriate health information, and introducing external resources to facilitate independent and continuous efforts in the company to promote sustainable HPM. The managers' evaluations of the support provided by the OHNs included the following six categories: 1) identified and recognized current internal health issues; 2) received specific assistance tailored to the company; 3) gained an opportunity to work on health promotion measures; 4) considered the development and continuation of future health promotion measures; 5) learned about the existence of OHNs as easy to consult with; and 6) identified aspects of support from OHNs that were different from what they expected. CONCLUSIONS: This study clarified the features and evaluations of the support provided by OHNs in private practice in medium-sized enterprises for the promotion of HPM. Our findings suggest that the involvement of OHNs in private practice may increase the number of medium-sized enterprises that can autonomously commit themselves to HPM in a sustainable manner.

Effectiveness of a support program for balancing treatment and work in small and medium-sized enterprises promoted by occupational health nurses using a web meeting system: A cluster randomized controlled trial.

OBJECTIVES: In this study, we conducted a cluster randomized control trial to verify the effectiveness of a treatment work balance support (TWBS) program promoted by occupational health nurses (OHNs) in small and medium-sized enterprises (SMEs) using a web meeting system. METHODS: We analyzed data from 64 managers (32 each in the control and intervention groups) and 541 workers (246 and 295 in the control and intervention groups, respectively) from 22 SMEs (11 in each group) with less than 200 workers. The TWBS program comprised online consultations for managers and seminars for workers by an OHN. TWBS leaflets were distributed among both groups. The "Recognition and Attitude Scale toward TWBS" was administered and workplace climate, psychological safety (PS), and work engagement (WE) scores were measured at baseline and endpoint. The increase in scores of each group was analyzed using a linear mixed-effects model. RESULTS: Increases in managers' scores on all three recognition and attitude subscales were significantly greater in the intervention than in the control group (P = .048, .003, and .032, respectively). Workers' score increases were significantly higher on two subscales-recognition of workplace initiatives and understanding of professionals' roles-in the intervention than in the control group (P = .043 and .001, respectively). There was no difference between the two groups in the amount of increase in PS and WE, as perceived by managers and workers. CONCLUSIONS: The TWBS program by OHNs increased recognition and attitude among SME managers and workers, indicating the usability of promoting TWBS in SMEs.

[Initiatives, outcomes, and facilitating factors to changing workplace environments in small- and medium-sized enterprises due to the COVID-19 pandemic: Interviews with employers and human resource managers].

OBJECTIVES: This study identified changes in the work environment due to the COVID-19 pandemic, subsequent initiatives and outcomes, and facilitating factors from the perspective of company officials in small- and medium-sized enterprises (SMEs). METHODS: In 2021, semi-structured interviews were conducted with employers or human resource managers of SMEs with less than 300 employees regarding changes in the work environment due to the pandemic, initiatives, outcomes, and facilitating factors. Thereafter, codes were extracted from verbatim transcripts or interview notes and categorized based on similarities in content. RESULTS: Based on interviews with 16 companies, the following four major categories of changes in the work environment were identified: "conflict and anxiety about infection when employees were forced to attend work despite the rapid transmission of the infection," "unfamiliarity and loneliness with the new working style that was suddenly imposed on them," "loss of emotional ties with workmates and opportunities for mood changes," and "future anxiety, feelings of alienation, and mental illness." The following seven initiatives were implemented to address these issues: "a hands-on approach to infection prevention and physical healthcare," "urgent introduction of telework for business continuity," "development and promotion of online information sharing," "establishment of a place and opportunity to maintain emotional connections within the company," "economic and management measures to protect employees and ensure company continuity," "support for employees for health maintenance," and "measures to respond to employees' needs and ideas, and support the continuation of activities." Four major categories of outcomes were: "increased efficiency of information sharing and enhanced performance," "maintenance and promotion of emotional ties and a sense of solidarity," "increased independence and sense of health among employees," and "adaptation of employees to novel situations." The initiatives were facilitated by factors classified into the following three major categories: "workplace culture wherein employees shared opinions and helped each other," "management's attitude and philosophy of valuing employees," and "proactive attitude toward information acquisition and resource utilization." CONCLUSIONS: The rapid introduction of teleworking as a new working style in response to the need to balance infection control and business continuity resulted in increased loneliness and other associated stressors. Many SMEs stated that they could maintain a sense of solidarity in the workplace and improve employee autonomy through their efforts to incorporate employees' opinions and maintain human connections.

PCR-based profiling of transcription factor activity in vivo by a virus-based reporter battery.

Understanding the molecular mechanisms of gene regulation is pivotal for understanding how cells establish and modify their identities and functions. Multiple transcription factors (TFs) coordinate to alter gene expression in cells; however, a method to quantitatively analyze the activity of each TF is lacking, particularly in vivo. Here, we introduce a viral-vector-based TF reporter battery that can be used to simultaneously analyze the activity of multiple TFs, visualized as the TF activity profile (TFAP) obtained by qPCR. We show that the cells possess distinct TFAPs that dynamically change according to experimental manipulation or physiological activity. We report a practical method to obtain the TFAP of a defined cell population and their experience-dependent changes in the mouse brain in vivo. The TFAP obtained by our method will help bridge the information gap between the genome and transcriptome and aid the multi-omics view of understanding the gene regulation system.

[Institutional measures and desired supports regarding COVID-19 pandemic among small and medium-sized enterprises: An interview study in Japan].

OBJECTIVES: Owing to the spread of COVID-19, many companies are likely to experience a significant impact on not only the safety and health of employees, but also on their businesses. The impact may be more severe for small and medium-sized enterprises (SMEs) than large enterprises, given their limited management resources. This study aims to clarify the good practices of institutional measures, the challenges in implementing these measures, and the required supports among SMEs. METHODS: The authors conducted an interview survey in August-October 2020 covering 27 SMEs in Japan regarding the infection control measures implemented and the desired supports in the future. Based on the content analysis, four researchers, comprising two occupational physicians and occupational health nurses each, extracted small categories by focusing on the commonality of codes, and gradually increased the degree of abstraction, subsequently extracting large categories. RESULTS: The study consolidated the implemented institutional measures into four categories: "making immediate decisions," "obtaining accurate information and sharing it with all employees," "strengthening infection control measures," and " launching efforts to continue business." In addition, challenges in implementing institutional measures were classified into five categories: "information gathering," "counter measures against unknown virus," "poor accessibility to Polymerase Chain Reaction (PCR) test," "consensus building," and "balancing business continuity and infection control." Furthermore, desired support in the future was classified into three categories: "information gathering," "accessibility to PCR test," and "compensation and subsidy." CONCLUSIONS: With taking the advantage of the characteristics of SMEs, not a few companies implemented the four categories of institutional measures. Therefore, it is imperative for SMEs to provide accurate information to employers for appropriately recognizing the risks. Accordingly, it is desirable for occupational health professionals at SMEs to provide support to employers to help them identify appropriate information.

[Competencies required for occupational health professionals in disaster management based on their personal experiences of workplaces damaged by the Kumamoto earthquakes].

OBJECTIVES: This study aimed to clarify the competencies required for occupational health professionals in disaster management based on their personal experiences of workplaces damaged by the Kumamoto earthquakes. METHODS: This study adopted a qualitative descriptive design using semi-structured interviews. The study participants included eight occupational health professionals who had been engaged in occupational health practice at workplaces affected by the Kumamoto earthquakes and subsequently employed at the same workplace. Data analyses were performed using a qualitative data analysis method. The researcher read transcripts of the interviews verbatim and extracted subcategories and categories, seeking points of commonality among homogeneous and heterogeneous elements while identifying content related to the competencies of the professionals during a disaster. RESULTS: Nine categories and 29 subcategories were extracted. The following competencies were identified as skills required for occupational health professionals when a disaster occurred: "perceiving the essentials of the situation through a comprehensive understanding of the health impacts caused by disasters," "prioritizing tasks while appropriately understanding a situation that is changing over time," "starting from what one can do while ensuring one's own health and safety," "continuing occupational health practice by devising efficient approaches while flexibly responding to the situation," "creating an environment that enables each occupational health team member to fulfill their role," and "adjusting the positions of occupational health departments within organizations to utilize networks." The following competencies were identified as skills required for occupational health professionals' disaster response and preparedness: "having the essential personal qualities of occupational health professionals," "establishing relationships of trust with employees and companies," and "linking one's experience of a disaster to future occupational health practice." CONCLUSIONS: The competencies required for occupational health professionals in disaster management are disaster response and preparedness. Moreover, these aspects in disaster response and preparedness suggest that occupational health professionals are required to have strategic and creative thinking skills including organizational approaches such as boosting networking in the workplace and establishing employer-employee relationships based on multifaceted assessment and situational flexibility.

Identification of hypothalamic arcuate nucleus-specific enhancer region of Kiss1 gene in mice.

Pulsatile secretion of GnRH plays a pivotal role in follicular development via stimulating tonic gonadotropin secretion in mammals. Kisspeptin neurons, located in the arcuate nucleus (ARC), are considered to be an intrinsic source of the GnRH pulse generator. The present study aimed to determine ARC-specific enhancer(s) of the Kiss1 gene by an in vivo reporter assay. Three green fluorescent protein (GFP) reporter constructs (long, medium length, and short) were generated by insertion of GFP cDNA at the Kiss1 locus. Transgenic female mice bearing the long and medium-length constructs showed apparent GFP signals in kisspeptin-immunoreactive cells in both the ARC and anteroventral periventricular nucleus, in which another population of kisspeptin neurons are located. On the other hand, transgenic mice bearing 5'-truncated short construct showed few GFP signals in the ARC kisspeptin-immunoreactive cells, whereas they showed colocalization of GFP- and kisspeptin-immunoreactivities in the anteroventral periventricular nucleus. In addition, chromatin immunoprecipitation and chromosome conformation capture assays revealed recruitment of unoccupied estrogen receptor-α in the 5'-upstream region and intricate chromatin loop formation between the 5'-upstream and promoter regions of Kiss1 locus in the ARC. Taken together, the present results indicate that 5'-upstream region of Kiss1 locus plays a critical role in Kiss1 gene expression in an ARC-specific manner and that the recruitment of estrogen receptor-α and formation of a chromatin loop between the Kiss1 promoter and the 5' enhancer region may be required for the induction of ARC-specific Kiss1 gene expression. These results suggest that the 5'-upstream region of Kiss1 locus functions as an enhancer for ARC Kiss1 gene expression in mice.

Proteoliposome-based selection of a recombinant antibody fragment against the human M2 muscarinic acetylcholine receptor.

The development of antibodies against human G-protein-coupled receptors (GPCRs) has achieved limited success, which has mainly been attributed to their low stability in a detergent-solubilized state. We herein describe a method that can generally be applied to the selection of phage display libraries with human GPCRs reconstituted in liposomes. A key feature of this approach is the production of biotinylated proteoliposomes that can be immobilized on the surface of streptavidin-coupled microplates or paramagnetic beads and used as a binding target for antibodies. As an example, we isolated a single chain Fv fragment from an immune phage library that specifically binds to the human M2 muscarinic acetylcholine receptor with nanomolar affinity. The selected antibody fragment recognized the GPCR in both detergent-solubilized and membrane-embedded forms, which suggests that it may be a potentially valuable tool for structural and functional studies of the GPCR. The use of proteoliposomes as immunogens and screening bait will facilitate the application of phage display to this difficult class of membrane proteins.