Non-randomized controlled trial examining the effects of livestock on motivation and anxiety in patients with chronic psychiatric disorders.

Objectives: Patients with chronic schizophrenia exhibit negative symptoms, including decreased work motivation. Animal-assisted therapy programs have been reported to benefit such patients; hence, there is a possibility that sheep-rearing, rather than conventional employment training, may motivate these patients. Therefore, we investigated the effects of a one-day experiential learning program of sheep-rearing on the work motivation and anxiety of patients with chronic schizophrenia. Methods: Fourteen patients were included in a non-randomized controlled trial conducted between August 2018 and October 2018. The patients' participation in the sheep-rearing experiential learning (one day; intervention day) and normal day care (one day; control day) programs were compared. The salivary cortisol and testosterone levels and State-Trait Anxiety Inventory (STAI) scores of the patients were analyzed. Results: The patients' salivary testosterone was significantly higher on the intervention day (p = 0.04) than on the control day (p = 0.02). Their salivary cortisol was lower on the control day than on the intervention day, although the difference was not significant. Regression analysis was performed based on the change in salivary cortisol levels and STAI-Trait scores (p = 0.006), and a regression equation was established. Conclusions: The study revealed that participation in sheep-rearing may have promoted the testosterone production but did not increase anxiety in patients with schizophrenia. Additionally, regression equations for salivary cortisol levels in such patients may provide information on individual differences in anxiety levels.

Detection of residual disease in chronic myeloid leukemia utilizing genomic next generation sequencing reveals persistence of differentiated Ph+ B cells but not bone marrow stem/progenitors.

Persistence of leukemic stem cells (LSCs) results in the recurrence of chronic myeloid leukemia (CML) after the administration of tyrosine kinase inhibitors (TKIs). Thus, the detection of minimal residual disease (MRD) with LSC potential can improve prognosis. Here, we analyzed 115 CML patients and found that CD25 was preferentially expressed on the phenotypic stem and progenitor cells (SPCs), and TKI therapy decreased the number of CD25-positive cells in the SPC fraction. To detect MRD harboring BCR-ABL1 fusion DNA, we developed a highly-sensitive method using patient-specific primers and next-generation sequencing. By using this method, we identified that in patients who achieved molecular remission, almost all residual CD25-positive SPCs were BCR-ABL1-negative. Moreover, in some patients BCR-ABL1 was detectable in peripheral B cells but not in SPCs. We conclude that CD25 marks LSCs at diagnosis but does not mark MRD following TKI treatment and that analysis of peripheral B cells can allow sensitive detection of MRD.

Assessment of in vitro effects of direct thrombin inhibitors and activated factor X inhibitors through clot waveform analysis.

AIMS: Clot waveform analysis (CWA) has been reported to extend the interpretation of clotting time measurement. The parameters obtained from successive derivatives of the clotting reaction curves reflect the rates of activation of individual coagulation factors, theoretically dissecting the cascade pathway. This study aims to assess the in vitro effects of direct thrombin inhibitors (DTIs) and activated factor X (FXa) inhibitors. METHODS: CWA was applied to the activated partial thromboplastin time (APTT) assay of plasma samples spiked with each drug. For CWA of APTT measurement curves (APTT-CWA), the positive mode of clotting reaction curves was defined as the direction towards fibrin generation. RESULTS: All the maximum positive values in the successive derivatives were decreased dependently on the concentrations of each drug. Moreover, the negative values in the second and third derivatives appeared putatively due to consumption of thrombin and factor FXa, respectively, to form complexes with plasma serine protease inhibitors. The decrease of the maximum negative values observed dependently on the concentrations of each drug appeared to be consistent with the decreased generation of thrombin and factor FXa. The analysis of Hill coefficients of each drug in the dose-response of changes in the APTT-CWA parameters revealed a difference in anticoagulant cooperativity between DTIs versus FXa inhibitors. CONCLUSIONS: The APTT-CWA demonstrated evidence for the blockade of thrombin-positive feedback by DTIs and FXa inhibitors and that for the differences in anticoagulant cooperativity between them. The results demonstrate the usability of CWA for assessment of anticoagulation and provide insights into direct anticoagulants.

Effects of movement music therapy with a percussion instrument on physical and frontal lobe function in older adults with mild cognitive impairment: a randomized controlled trial.

OBJECTIVES: We tested the hypothesis that performing a rhythmic physical task accompanied by a cognitive task, such as multitask movement music therapy (MMT) involving repetitive rhythmic movement with a musical instrument (the Naruko clapper), may improve pre-frontal cortex (PFC) function and cognitive performance. METHOD: Forty-five older adult participants with MCI (74.62 ± 5.05 years) participated in this randomized, controlled, single-blind intervention trial. 35 were assigned to the MMT group and 10 to the control STT group. Before and after the 12-week exercise program, we administered six physical function tests, the Frontal Assessment Battery (FAB), and measured relative oxyhemoglobin concentrations using 45-multichannel functional near-infrared spectroscopy as a reflection of hemodynamic responses in the PFC. RESULTS: We observed significant improvements in FAB scores only in the MMT group. Cerebral blood flow (CBF) in the PFC during the exercise was significantly increased in the MMT group compared with the STT group. The CBF increase was significantly correlated among various channels in the MMT group. CONCLUSIONS: The MMT program appeared to stimulate the PFC and improve cognitive performance in our older adult participants with MCI, suggesting that the repetitive, rhythmic movements of MMT can activate the prefrontal area in older adults. TRIAL REGISTRATION: Clinical Trial Registry Numbers: R000026130, UMIN000022671 (2016/06/08) [(University Hospital Medical Information Network (UMIN) Center] retrospectively registered.

An interactive sports video game as an intervention for rehabilitation of community-living patients with schizophrenia: A controlled, single-blind, crossover study.

Hypofrontality is a state of decreased cerebral blood flow in the prefrontal cortex during executive function performance; it is commonly observed in patients with schizophrenia. Cognitive dysfunction, as well as the psychological symptoms of schizophrenia, influences the ability of patients to reintegrate into society. The current study investigated the effects of an interactive sports video game (IVG; Nintendo Wii™ Sports Resort) on frontal lobe function of patients with schizophrenia. A sample of eight patients (6 male and 2 female; mean age = 46.7 years, standard deviation (SD) = 13.7) engaged in an IVG every week for 3 months in a controlled, single-blind, crossover study. Before and after the intervention we examined frontal lobe blood-flow volume using functional near-infrared spectroscopy (fNIRS), and assessed functional changes using the Frontal Assessment Battery, Health-Related Quality of Life scale, and behaviorally-assessed physical function tests. fNIRS revealed that prefrontal activity during IVG performance significantly increased in the IVG period compared with the control period. Furthermore, significant correlations between cerebral blood flow changes in different channels were observed during IVG performance. In addition, we observed intervention-related improvement in health-related quality of life following IVG. IVG intervention was associated with increased prefrontal cortex activation and improved health-related quality of life performance in patients with schizophrenia. Patients with chronic schizophrenia are characterized by withdrawal and a lack of social responsiveness or interest in others. Interventions using IVG may provide a useful low-cost rehabilitation method for such patients, without the need for specialized equipment.

Effects of movement music therapy with the Naruko clapper on psychological, physical and physiological indices among elderly females: a randomized controlled trial.

BACKGROUND: Recent interventional studies have indicated that some exercise programs have beneficial physical and immunological effects for older people. Some evidence suggests that exercise programs involving music and/or a rhythmic movement component may be particularly beneficial. OBJECTIVE: To assess the effects of a new type of movement music therapy (MMT) on physical, immunological, hormonal and psychosocial health parameters among older adults. METHODS: 112 elderly female subjects (average age 73.62 ± 5.50 years) who performed little habitual exercise participated in this randomized, controlled, single-blinded intervention trial. The subjects were divided into two groups which participated in different exercise programs (experimental group: MMT; control group: simple exercise program). We assessed a comprehensive range of indices before and after the interventions, which lasted a total of 8 weeks. These indices included (1) the Philadelphia Geriatric Center morale scale, (2) self-rated health status, (3) physical function tests (e.g. blood pressure, pulmonary function, body balance, gait ability, muscle endurance, muscle-strength, and functional mobility), and (4) saliva analysis for physiological function indices (e.g. secretory immunoglobulin A (SIgA), chromogranin A, cortisol, and total protein). RESULTS: In comparisons between the MMT and control interventions in younger elderly subjects (≤74 years old), systolic blood pressure decreased (p = 0.02), pulmonary function improved (p = 0.05) and body balance improved (p = 0.04) in the MMT group, but not in the control group. The SIgA secretion rate of the experimental group remained significantly elevated (p = 0.02) 15 min after exercise compared with before exercise. There were no significant differences between interventions in psychosocial indices. In contrast, no significant differences were detected between interventions in any measures in the older elderly group (≥75 years old). CONCLUSION: These results indicate that the MMT, even with a short (8-week) intervention period, improves physical and physiological functions to a significantly greater extent in younger elderly individuals compared with a control intervention without music.

[B-cell acute lymphoblastic leukemia developed 5 years after autologous stem cell transplantation for multiple myeloma].

A 61-year-old female was diagnosed with multiple myeloma (MM) in 2001. After treatment with chemotherapy containing alkylating agents and thalidomide, she underwent autologous stem cell transplantation in 2003, with high-dose melphalan as a conditioning regimen. Thalidomide was also given after the transplant from July 2003 to November 2005 for residual disease and she remained in partial remission. In October 2008, she developed pancytopenia. Bone marrow examination confirmed the diagnosis of acute B lymphoblastic leukemia (B-ALL). We performed IgH gene rearrangement studies on genomic DNA which revealed the MM, and ALL seemed to be derived from different clones. The development of MM and ALL in the same patient is a very rare event. Further accumulation of the cases to understand the mechanism underlying this event is warranted.

Dietary whey protein hydrolysate suppresses development of atopic dermatitis-like skin lesions induced by mite antigen in NC/Nga mice.

BACKGROUND: Oral administration of enzymatic hydrolysate of cow's milk whey protein (WPH) has been reported to produce an anti-inflammatory effect. Since inflammation plays a role in dermatitis of allergic disease, we examined the influence of WPH on the development of atopic dermatitis (AD)-like skin lesions, induced in NC/Nga mice by the mite antigen Dermatophagoides pteronyssinus (Dp). METHODS: AD-like skin lesions were induced on the pinnae and backs of NC/Nga mice by daily application of Dp for 4 weeks. Mice were fed cow's milk casein (control), WPH or casein protein hydrolysate (CPH) diets for 2 weeks prior to Dp application. Clinical skin conditions were evaluated periodically by a clinical severity score, total serum IgE and soluble E-selectin levels were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: WPH-fed mice showed significantly less AD-like skin lesions than those fed casein diets at 2 and 4 weeks after Dp application. In contrast, CPH-fed mice had manifestations in a similar manner as casein-fed mice did, and did not show an inhibitory effect. Serum soluble E-selectin levels, known as a marker of disease activity in AD patients, were significantly lower in the WPH diet group. CONCLUSIONS: Our results suggest that in addition to its hypoallergenicity an anti-inflammatory function, dietary WPH might be useful for reducing the severity of AD-like skin lesions.

Orally tolerized T cells can form conjugates with APCs but are defective in immunological synapse formation.

Oral tolerance is systemic immune hyporesponsiveness induced by the oral administration of soluble Ags. Hyporesponsiveness of Ag-specific CD4 T cells is responsible for this phenomenon. However, the molecular mechanisms underlying the hyporesponsive state of these T cells are not fully understood. In the present study, we investigated the ability of orally tolerized T cells to form conjugates with Ag-bearing APCs and to translocate TCR, protein kinase C-theta (PKC-theta), and lipid rafts into the interface between T cells and APCs. Orally tolerized T cells were prepared from the spleens of OVA-fed DO11.10 mice. Interestingly, the orally tolerized T cells did not show any impairment in the formation of conjugates with APCs. The conjugates were formed in a LFA-1-dependent manner. Upon antigenic stimulation, the tolerized T cells could indeed activate Rap1, which is critical for LFA-1 activation and thus cell adhesion. However, orally tolerized T cells showed defects in the translocation of TCR, PKC-theta, and lipid rafts into the interface between T cells and APCs. Translocation of TCR and PKC-theta to lipid raft fractions upon antigenic stimulation was also impaired in the tolerized T cells. Ag-induced activation of Vav, Rac1, and cdc42, which are essential for immunological synapse and raft aggregation, were down-regulated in orally tolerized T cells. These results demonstrate that orally tolerized T cells can respond to specific Ags in terms of conjugate formation but not with appropriate immunological synapse formation. This may account for the hyporesponsive state of orally tolerized T cells.