3D Printer-Assisted Layered Fabrication of a Novel Appliance for Oral Myofunctional Therapy and Functional Evaluation of Its Effects on Orofacial Muscles During Wear.

Aim Balanced function of the orofacial muscles is important for normal occlusion and dentition; however, patients with malocclusion often present with myofunctional disorder (MFD). Myofunctional therapy (MFT) has received much attention as a method for reducing MFD. Moreover, prefabricated functional appliances (PFAs) have been developed as a method to eliminate abnormal muscle pressure and guide the tongue into the correct position. However, PFAs have disadvantages, such as poor intraoral retention, limited usage time due to discomfort and poor patient compliance, and changes in the axis of the mandibular anterior teeth. Therefore, this study aimed to develop a new custom-made splint-type orthodontic appliance with CAD/CAM technology. Moreover, we evaluated the characteristics of the appliance and conducted functional tests to determine the effects of the appliance on the orofacial muscles and the discomfort associated with its use. Materials and methods Twenty-five volunteers (nine females and 16 males; mean age 28.4 ± 3.4 years) with normal swallowing function were included in the study. Lip-closing strength (LCS), electromyogram during swallowing, oxygen saturation, and pulse rate were measured and compared when the appliance was not worn and when it was worn. In addition, tongue habits were evaluated, and the maximum tongue pressure was measured when the appliance was not worn. The subjects were asked to answer a questionnaire using a numerical rating scale (NRS) regarding discomfort when wearing the appliance. The evaluation items were swallowing difficulty, speaking difficulty, and breathlessness, which were rated on an 11-point scale ranging from 0 to 10. Statistical tests were conducted using IBM SPSS version 28.0.1 (IBM, Armonk, NY, USA) with the Shapiro-Wilk and Levene's test, followed by the Wilcoxon signed rank sum test. The significance level was set at α = 0.05. The measurement error for each measurement item was evaluated using an intraclass correlation coefficient. Results A new custom-made splint-type orthodontic appliance was fabricated for each subject. The fit and retention of the appliance in the mouth were good when fitted, and a comparison of the functional test measurements of 25 subjects with and without the appliance showed that the LCS decreased significantly (p<0.05) before and after wearing the appliance. However, no statistically significant differences were found for the other items. The Mann-Whitney U test regarding the effects of sex, previous orthodontic treatment, or MFT, and oral habits did not statistically significantly influence the effects of wearing the device. In the NRS results, "difficulty swallowing" was observed in half of the subjects, "difficulty breathing" was rarely observed, and "difficulty speaking" was observed in all subjects. Conclusions A novel custom-made splint-type orthodontic appliance was designed and fabricated using digital workflow and 3D printing technology. This appliance was designed to correct oral habits and was made from a new material classified as a class II medical appliance according to the international harmonized classification.

Roles of Visiting Nurses in Supporting Medically Dependent Children Living at Home.

The purpose of this study was to identify the fundamental roles of visiting nurses as a foundation for creating effective educational programs for nurses of medically dependent (MD) children being treated at home. The relationship among the statements representing 3 types of roles was analyzed using structural equation modeling. There were 296 participants involved in performing home-visit nursing for MD children. Their structural roles related to home-visit nursing systems and skills were strongly correlated with the interpersonal roles related to support for MD children and their families, arrangements for whole families, and interprofessional collaborations. The correlations between these roles and the role determination process demonstrated that their future vision and selfgrowth were weak. This study makes the following recommendations: the development of specialized approaches to nursing practices; training in interprofessional collaboration; the realization of professional self-growth; and the creation of educational programs to assist visiting nurses in improving the home-visit nursing systems.

Effects of work-family life support program on the work-family interface and mental health among Japanese dual-earner couples with a preschool child: A randomized controlled trial.

OBJECTIVES: This study examined the effectiveness of a newly developed work-family life support program on the work-family interface and mental health indicators among Japanese dual-earner couples with a preschool child(/ren) using a randomized controlled trial with a waitlist. METHODS: Participants who met the inclusion criteria were randomly allocated to the intervention or the control groups (n = 79 and n = 85, respectively). The program comprised two 3-h sessions with a 1-month interval between them and provided comprehensive skills by including self-management, couple management, and parenting management components. The program sessions were conducted on weekends in a community center room with 3-10 participants. Outcomes were assessed at baseline, 1-month, and 3-month follow-ups. Primary outcomes were work-family balance self-efficacy (WFBSE), four types of work-family spillovers (i.e., work-to-family conflict, family-to-work conflict, work-to-family facilitation, and family-to-work facilitation), psychological distress, and work engagement reported by the participants. RESULTS: The program had significantly pooled intervention effects on WFBSE (P = .031) and psychological distress (P = .014). The effect sizes (Cohen's d) were small, with values of 0.22 at the 1-month follow-up and 0.24 at the 3-month follow-up for WFBSE, and -0.36 at the 3-month follow-up for psychological distress. However, the program had nonsignificant pooled effects on four types of work-family spillovers and work engagement. CONCLUSIONS: The program effectively increased WFBSE and decreased psychological distress among Japanese dual-earner couples with a preschool child(/ren).

Whole-brain afferent input mapping to functionally distinct brainstem noradrenaline cell types.

The locus coeruleus (LC) is a small region in the pons and the main source of noradrenaline (NA) to the forebrain. While traditional models suggested that all LC-NA neurons project indiscriminately throughout the brain, accumulating evidence indicates that these cells can be heterogeneous based on their anatomical connectivity and behavioral functionality and exhibit distinct coding modes. How LC-NA neuronal subpopulations are endowed with unique functional properties is unclear. Here, we used a viral-genetic approach for mapping anatomical connectivity at different levels of organization based on inputs and outputs of defined cell classes. Specifically, we studied the whole-brain afferent inputs onto two functionally distinct LC-NA neuronal subpopulations which project to amygdala or medial prefrontal cortex (mPFC). We found that the global input distribution is similar for both LC-NA neuronal subpopulations. However, finer analysis demonstrated important differences in inputs from specific brain regions. Moreover, sex related differences were apparent, but only in inputs to amygdala-projecting LC-NA neurons. These findings reveal a cell type and sex specific afferent input organization which could allow for context dependent and target specific control of NA outflow to forebrain structures involved in emotional control and decision making.

Mental status is significantly associated with low back pain: a survey-based cross-sectional study among Japanese women.

OBJECTIVE: Low back pain (LBP) is a highly prevalent condition that poses significant patient burden. This cross-sectional study identified factors associated with LBP occurrence and developed a strategy to identify, prevent, and reduce LBP-related burden on patient health. A web-based questionnaire-answering system was used to assess the potential effects of LBP on mental health, assessing five domains (physical features, demographics, lifestyle, diet, and mental status) conceptually associated with hie, a common disease state traditionally described in the Japanese culture as a chilly sensation. RESULTS: Of 1000 women, 354 had and 646 did not have LBP. The Chi test identified 21 factors, and subsequent multivariate logistic regression indicated eight factors significantly associated with LBP: age, history of physician consultation regarding anemia, history of analgesic agents, dietary limitations, nocturia, sauna use, hie, and fatigue. Furthermore, women with LBP exhibited a significantly lower body temperature (BT) in the axilla/on the forehead than women without LBP. LBP and hie are subjective and potentially affected by patient mental status. Stress reduces blood circulation, causing hypothermia and possibly worsening LBP. Therefore, mental-health support is important for patients with LBP to reduce physiological stress. Hyperthermia therapy, a traditionally prescribed intervention, is a potential intervention for future studies.

Association between CA 15­3 and progression of interstitial lung disease in a case of coexisting systemic sclerosis and recurrent breast cancer: A case report.

Carbohydrate antigen 15-3 (CA 15-3) is known as a specific tumor marker for breast cancer, the main use of which is monitoring therapy in patients with advanced breast cancer. Either systemic sclerosis (SSc)-interstitial lung disease (ILD) or pulmonary arterial hypertension is currently the leading cause of disease-related morbidity and mortality in patients with scleroderma. Although CA 15-3 has been investigated as a biomarker in SSc-ILD, its role remains unclear. The current report presented a case of recurrent breast cancer diagnosed with SSc-ILD during treatment. The patient, at 63 years old, experienced shortness of breath with minimal exertion after four cycles of perutuzumab, trastuzumab and weekly paclitaxel. Computed tomography (CT) revealed ground-glass opacities and linear shadows in the peripheral lower lobes of both lungs. Although the development of lung involvement associated with breast cancer, such as carcinomatous lymphangitis, was initially suspected, because of the increase in CA 15-3, skin biopsies were taken from the left index finger base and extension side of the left elbow, which demonstrated increased thickness of the dermis, leading to a diagnosis of SSc-ILD. The findings in this case suggested the importance of considering a differential diagnosis, including ILD, concurrently while screening for the progression of recurrent breast cancer when encountering patients with breast cancer and elevated levels of CA 15-3.

Enhanced synchronization between prelimbic and infralimbic cortices during fear extinction learning.

The ability to extinguish aversive memories when they are no longer associated with danger is critical for balancing survival with competing adaptive demands. Previous studies demonstrated that the infralimbic cortex (IL) is essential for extinction of learned fear, while neural activity in the prelimbic cortex (PL) facilitates fear responding and is negatively correlated with the strength of extinction memories. Though these adjacent regions in the prefrontal cortex maintain mutual synaptic connectivity, it has been unclear whether PL and IL interact functionally with each other during fear extinction learning. Here we addressed this question by recording local field potentials (LFPs) simultaneously from PL and IL of awake behaving rats during extinction of auditory fear memories. We found that LFP power in the fast gamma frequency (100-200 Hz) in both PL and IL regions increased during extinction learning. In addition, coherency analysis showed that synchronization between PL and IL in the fast gamma frequency was enhanced over the course of extinction. These findings support the hypothesis that interregional interactions between PL and IL increase as animals extinguish aversive memories.

Qualitative analysis of actual Standard for Exchange of Nonclinical Data (SEND) datasets for Data Domains: Proposition from Japan Pharmaceutical Manufacturers Association SEND Taskforce Team on standardization of nonclinical data.

The Standard for Exchange of Nonclinical Data (SEND) has been adopted by the US FDA, which has required pharmaceutical companies who are developing new drugs for the US market to implement SEND. The Japan Pharmaceutical Manufacturers Association (JPMA) SEND Taskforce Team responded to this situation by starting a project to better understand the contents of SEND datasets. The project focused on domains generally included in the SEND domains for single- and repeat-dose general toxicology studies, and surveyed what kind of information are populated in which domains and in what way. The qualitative analysis of the results indicated that variations exist based on whether or not an individual variable was populated and on how the variable was populated. The Taskforce Team recommends reducing variations not only in the SEND datasets but also in the descriptions in the study protocol and/or final study report. Reduction of such variations should lead to higher quality datasets with powerful and increased searchability so that accumulated SEND datasets should become more valuable. These efforts would provide regulatory agencies with easier review of SEND datasets, which contributes to efficient development of new drug candidates.

Spontaneous regression of breast cancer with immune response: a case report.

BACKGROUND: Spontaneous regression (SR) is a rare phenomenon in which a cancer disappears or remits without treatment. We report a case of breast cancer that showed spontaneous tumor regression in the surgical specimen after core needle biopsy. CASE PRESENTATION: A 59-year-old woman came to our hospital complaining of a painful lump in the right breast. In the upper-outer quadrant of the right breast, a tumor with an unclear boundary, 30 mm in diameter, was palpable. In pathological findings from needle biopsy, the tumor was diagnosed as solid-type invasive ductal breast carcinoma. Partial coagulation necrosis was generated in estrogen receptor-negative, HER2-negative, and AE1/AE3-positive ductal carcinoma without infiltration of lymphocytes. Surgery for right breast cancer was then performed. Histological examination of the surgical specimen revealed the tumor was invasive ductal carcinoma with lymphocyte infiltration, coagulation necrosis, and fibrous tissue with hemosiderin. The tumor formed a solid nest, 3 mm in diameter, suggesting the possibility of SR. CONCLUSIONS: Immune responses, infection, hormones, surgical stress, and ischemia have been reported as mechanisms of SR. The findings in this case strongly suggest that SR of breast cancer is associated with anti-tumor immune responses.

Influence of electroacupuncture stimulation on skin temperature, skin blood flow, muscle blood volume and pupil diameter.

OBJECTIVE: To examine the effect of electroacupuncture (EA) stimulation on multiple physiological indices and to evaluate both local and systemic physiological responses induced by the stimulation. METHODS: 15 healthy male college students participated in an experimental crossover study. They received two kinds of interventions: one with EA stimulation and one without EA stimulation on different days. Two disposable acupuncture needles were inserted at two traditional acupuncture points (ST36 and ST38), located along the anterior tibialis muscle. EA stimulation was administered for 10 min. Skin temperature (ST), skin blood flow (SBF) and muscle blood volume (MBV) were recorded near the stimulation sites, while the pupil diameter (PD) was measured before, during and after the interventions. RESULTS: ST, SBF and MBV increased significantly following EA stimulation. PD of the right and left eyes decreased significantly following EA stimulation. There was a significant difference in ST responses between the groups (P=0.001). For SBF, MBV and PD, no significant differences were demonstrated between the groups. CONCLUSIONS: Our study showed that 10 min of EA stimulation increased ST, SBF and MBV, and decreased PD, compared to baseline, while no significant change was observed in the control group. This suggests that EA stimulation alters local blood flow and ST, and these responses are likely mediated via segmental spinal reflexes, supraspinal reflexes involving parasympathetic activation, and other mechanisms.

Subtypes of overtime work and nurses' fatigue, mental status, and work engagement: A latent class analysis of Japanese hospital nurses.

AIMS: To clarify the subgroups of overtime work motivations and to determine how fatigue, mental status, and work engagement differ among the subgroups. DESIGN: Cross-sectional. METHODS: Questionnaires were distributed to 1,075 full-time nurses working in four hospitals in Japan from October 2015 - February 2016. Nurses were categorized into subgroups of overtime work motivation by latent class analysis. An analysis of covariance was conducted to examine how fatigue, mental status, and work engagement differ among subgroups. RESULTS/FINDINGS: We identified five types of overtime workers differing greatly in fatigue, mental status, and work engagement. CONCLUSIONS: Even when nurses worked approximately the same work hours, the difference in motivation corresponded to different degrees of fatigue, mental status, and work engagement. When introducing policies to reduce overtime work, managers should consider the different groups of overtime workers, as effective measures may differ.

Emotional Effects on Factors Associated with Chronic Low Back Pain.

PURPOSE: Although chronic low back pain (CLBP) has profound effects on patients, society, and economy, its causes are difficult to identify. Psychogenic effects or social stress is known to affect CLBP; hence, investigation of its underlying causes requires a multifactorial approach. We determined the factors associated with CLBP by using an Internet-based survey. To prevent CLBP, we need to understand its cause and background. PATIENTS AND METHODS: A total of 1000 participants either with (+) or without (-) CLBP answered the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), which assesses five domains of CLBP: low back pain, lumbar function, walking ability, social life function and mental health. We also administered a new questionnaire for participants, that comprised five different domains: Body, Lifestyle, Emotion, Diet, and Social. To evaluate psychogenic effects on CLBP, we added two original factors, namely outshout and HIE, which have not yet been studied. HIE is a traditional concept (sense) of "feeling cold" or "chilly." All participants completed both questionnaires. RESULTS: Multivariate logistic regression analysis extracted four factors (sleep, room temperature, outshout, and HIE) that were associated with CLBP. The mental health domain was assessed using the JOABPEQ for each of these factors. The factors outshout and HIE differed between CLBP (+) and CLBP (-) patients. CLBP (-) participants also showed a difference in Sleep and HIE factors. CONCLUSION: Among psychogenic effects, Emotion was common to all the four extracted factors. There was no common physical divisor. Therefore, we hypothesized that acute low back pain might develop into CLBP in the presence of psychological stress or other emotional factors such as outshout or HIE. Hence, we need to consider both physical and psychogenic effects in the prevention and treatment of CLBP. Furthermore, appropriate evaluation and treatment of psychological stress may be effective in reducing CLBP.

Progressive Encephalomyelitis with Rigidity and Myoclonus Resolving after Thymectomy with Subsequent Anasarca: An Autopsy Case.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is an autoimmune disorder involving the brainstem and spinal cord and is sometimes associated with thymoma. We encountered a 75-year-old woman with typical PERM features, glycine receptor antibody, and thymoma. Her neurologic symptoms improved after thymectomy, but she unexpectedly developed anasarca with massive pleural effusions and hypoalbuminemia and finally succumbed to death. The autopsy showed edema and mononuclear infiltration in the pleura but no neuropathological findings typical of PERM. Effective treatment of PERM can reverse the neuropathological signs of encephalomyelitis. The autoimmune nature of anasarca is possible but not proven.

Effect of Different Dosages of ST36 Indirect Moxibustion on the Skin Temperature of the Lower Legs and Feet.

Background: Indirect moxibustion (IM) has been previously performed between the spinous process while recording skin temperature of the trunk. However, moxibustion is often applied not only to acupuncture points on the back, but also to points located on the limbs. Thus, there is a need to investigate skin temperature (ST) responses following IM applied to the limbs. Methods: In Experiment 1 (Exp 1), subjects were randomly assigned to three groups: the left IM stimulation, right IM stimulation and control groups. In Experiment 2 (Exp 2), the subjects underwent two experimental sessions consisting of a single stimulation of IM or triple stimulations of IM. The IM stimulation was administered to the ST36 acupuncture point. A thermograph was used to obtain the ST on the lower limbs. Results: In Exp 1, the ST of the lower limbs increased in the stimulation groups whereas there was no increase in the non-stimulation group. In Exp 2, no significant response occurred between the single and triple stimulation of IM groups for all observed sites except for the left ankle ST. Conclusions: Lower limb ST increased following IM application to the ST36 point. No difference was observed between the dosage of the stimulation and ST responses.

The effect of quality of overtime work on nurses' mental health and work engagement.

AIM AND BACKGROUND: Recent research has suggested that the reasons why nurses work overtime hours exert differential effects on the overall impact of the work. This study aimed to clarify why nurses work overtime, and whether well-being effects differed by reason, at both the ward and individual level. METHODS: Participants were 1,075 permanent nurses from 54 wards. Overtime reasons' distribution and impact on nurses were examined by a multilevel structural equation modelling approach. RESULTS: Nurses typically worked overtime due to a pressure to conform, high workload and to enhance self-development. Involuntary overtime work demonstrated a detrimental effect on mental health and work engagement at both the ward and individual level, whereas voluntary overtime work exerted a beneficial effect on well-being. CONCLUSIONS: The distribution and impact of overtime work differed by the reasons for working the overtime. IMPLICATIONS FOR NURSING MANAGEMENT: These results suggest the importance of assessing the reasons for overtime, aside from the length of overtime hours. When trying to reduce overtime work, hospital managers and nurse managers need to advance the plan by ward as a whole, and also carefully assess the reasons for overtime.

Structural connectivity in spatial attention network: reconstruction from left hemispatial neglect.

Left hemispatial neglect (neglect) is an impaired state of spatial attention. We aimed to reconstruct structural connectivity in the spatial attention network and to identify disconnection patterns underlying neglect. We enrolled 59 right-handed patients who had their first-ever infarction in the right hemisphere and classified them into neglect group (34 patients with neglect) and control group (25 patients without neglect). The neglect group was further subcategorized into 6 subgroups based on infarcted vascular territories. Diffusion tensor imaging data were obtained from all patients. Fractional anisotropy maps were compared between neglect group/subgroups and the control group by using non-parametric voxel-based analysis, generating a lesion path mask. Probabilistic tractography analysis using the lesion path mask reconstructed the following structural connectivity in the spatial attention network, which is specifically damaged in neglect patients: (1) superior longitudinal fasciculus (SLF) I connecting the superior parietal lobule/intraparietal sulcus with the superior frontal gyrus/frontal eye field (SFG/FEF) (dorsal attention network); (2) SLF III/the arcuate fasciculus (AF) and the extreme capsule/inferior fronto-occipital fasciculus (IFOF) connecting the right inferior parietal lobule/temporoparietal junction/superior temporal gyrus (IPL/TPJ/STG) with the middle frontal gyrus/inferior frontal gyrus (ventral attention network); (3) the thalamic radiations to the spatial attention-related cortices; and (4) SLF II and IFOF interconnecting dorsal and ventral attention networks. Individual analysis indicated that isolated damage in SLF I, SLF II, SLF III/AF or the thalamic radiations to IPL/TPJ/STG due to posterior cerebral artery infarction, or simultaneous damage in four thalamic radiations due to anterior choroidal artery infarction, underlies different phenotypes of neglect.

A novel scoring system to predict delirium and its relationship with the clinical course in patients with acute decompensated heart failure.

BACKGROUND: Delirium is known to be a poor prognostic factor in patients with acute decompensated heart failure (ADHF). The purpose of this study was to determine predictors of delirium on admission of ADHF patients, and to establish a scoring formula to identify patients at high risk for delirium. METHODS AND RESULTS: We recorded the Intensive Care Delirium Screening Checklist (ICDSC) score in 120 ADHF patients during their stay in the coronary care unit (CCU). Patients with a highest ICDSC score of 4 or more were diagnosed with delirium. We examined independent candidate predictors of delirium using multivariate logistic regression analysis and developed the following scoring formula, the delirium prediction score (DPS), using independent predictors of delirium and their regression coefficients: DPS=inferior vena cava diameter+C-reactive protein (and additionally +10 for patients with a history of cerebral infarction). Receiver operating curve analysis indicated that evaluation using this scoring system at the time of admission was able to predict delirium with high accuracy (C-statistic: 0.885). In addition, the calculated scores had significantly positive correlations with duration of CCU stay and overall length of hospital stay. CONCLUSIONS: We established a novel scoring system to predict on admission the likelihood of development of delirium in ADHF patients; this system also predicts prolongation of intensive care and hospital stay.

Dysregulation of aversive signaling pathways: a novel circuit endophenotype for pain and anxiety disorders.

Aversive experiences activate dedicated neural instructive pathways which trigger memory formation and change behavior. The strength of these aversive memories and the degree to which they alter behavior is proportional to the intensity of the aversive experience. Dysregulation of aversive learning circuits can lead to psychiatric pathology. Here we review recent findings elucidating aversive instructive signaling circuits for fear conditioning. We then examine how chronic pain as well as stress and anxiety disrupt these circuits and the implications this has for understanding and treating psychiatric disease. Together this review synthesizes current work on aversive instructive signaling circuits in health and disease and suggests a novel circuit based framework for understanding pain and anxiety syndromes.

The impact of job and family demands on partner's fatigue: A study of Japanese dual-earner parents.

OBJECTIVES: This study of Japanese dual-earner couples examined the impact of family and job demands on one's own and one's partner's fatigue as well as gender differences in these effects. METHODS: A total of 2,502 parents (1,251 couples) were surveyed using a self-administered questionnaire. A crossover model was tested using structural equation modeling. RESULTS: The results of structural equation modeling analyses showed that both job and family demands independently exacerbated fatigue. There was an indirect effect of job and family demands on partner fatigue through one's own fatigue only from husbands to wives. An indirect effect of job demands on partner fatigue through partner's family demands was identified only from wives to husbands. Furthermore, there were gender differences in the crossover of fatigue. CONCLUSIONS: This study shows that job and family demands influence family circumstances. When considering means to reduce employees' fatigue, gender differences in the mechanism of fatigue need to be taken into account.

Psychosocial Factors of Overtime Work in Relation to Work-Nonwork Balance: a Multilevel Structural Equation Modeling Analysis of Nurses Working in Hospitals.

PURPOSE: Few studies have investigated the impact of psychosocial factors on overwork and employee well-being while taking into account the complex relationships between such factors and the effect of workplace. The present study aimed to examine the association between psychosocial factors of overtime work and work-nonwork balance using a multilevel structural equation modeling (SEM) technique. METHODS: A survey was conducted among nurses working in three hospitals (n = 603) in Japan. After confirming the constructs of the factors by confirmatory factor analysis (CFA) and exploratory factor analysis (EFA), a multilevel SEM was conducted to investigate the direct and indirect effects of involuntary and voluntary overtime work on work-nonwork balance at both individual and workplace levels. RESULTS: Both involuntary and voluntary overtime work factors were further differentiated into two factors (four factors in total). Involuntary overtime work directly decreased work-nonwork balance on both levels; voluntary overtime work had a direct positive effect. However, voluntary overtime work had a negative indirect effect on work-nonwork balance satisfaction. CONCLUSIONS: The use of multilevel SEM techniques to evaluate the association of clinical factors with work-nonwork balance demonstrated that involuntary overtime work has a negative effect on work-nonwork balance and voluntary overtime work had a positive direct effect but a negative indirect effect.