[A Multicenter randomized comparative study of dementia nursing practice skills development programs for nurses in acute care hospitals: A Comparison of person-centered care and dementia-type-specific programs].

PURPOSE: The present multicenter randomized controlled trial explored the effectiveness of a person-centered care program (intervention group) and a dementia-type-specific program (control group) for nurses in acute-care hospitals. METHODS: Seven hospitals in Prefecture A were randomly allocated to two groups (an intervention group and a control group), and a study of these groups was conducted from July 2021 to January 2022. RESULTS: A total of 158 participants were included in the study: 58 in the control group and 100 in the intervention group. In a comparison of assessment values immediately after the course, three months later, and six months later for both the intervention and control groups, "expertise in dementia nursing," "medical expertise in dementia, " and "confidence in nursing older people with dementia" were all significantly higher than before the course. Significant improvements in the intervention group's "knowledge of dementia" and "sense of dignity" on the ethical sensitivity scale were found immediately after the course compared to baseline, three months later, and six months later and were also significantly greater than the control group in terms of the amount of change. In the control group's "unique care tailored to cognitive function and the person," there were significant improvements in the ratings immediately after the course and three and six months after the course compared to baseline, with significantly greater amounts of change than in the intervention group. CONCLUSION: The person-centered care program for nurses led to improvements in the knowledge about dementia and awareness of the dignity of ethical sensitivity. In addition, the type of dementia program had a significant influence on medical knowledge and unique care tailored to the cognitive function and the individual patient. Further outcome evaluations of physical restraint rates as a quality of care in nursing practice are needed.

Investigation of anti-adhesion ability of 8-arm PEGNHS-modified porcine pericardium.

In post-adhesion surgery, there is a clinical need for anti-adhesion membranes specifically designed for the liver, given the limited efficacy of current commercial products. To address this demand, we present a membrane suitable for liver surgery applications, fabricated through the modification of decellularized porcine pericardium with 20 KDa hexaglycerol octa (succinimidyloxyglutaryl) polyoxyethylene (8-arm PEGNHS). We also developed an optimized modification procedure to produce a high-performance anti-adhesion barrier. The modified membrane significantly inhibited fibroblast cell adherence while maintaining minimal levels of inflammation. By optimizing the modification ratio, we successfully controlled post-adhesion formation. Notably, the 8-arm PEG-modified pericardium with a molar ratio of 5 exhibited the ability to effectively prevent post-adhesion formation on the liver compared to both the control and Seprafilm®, with a low adhesion score of 0.5 out of 3.0. Histological analysis further confirmed its potential for easy separation. Furthermore, the membrane demonstrated regenerative capabilities, as evidenced by the proliferation of mesothelial cells on its surface, endowing anti-adhesion properties between the abdominal wall and liver. These findings highlight the membrane's potential as a reliable barrier for repeated liver resection procedures that require the removal of the membrane multiple times.

Effect of multi arm-PEG-NHS (polyethylene glycol n-hydroxysuccinimide) branching on cell adhesion to modified decellularized bovine and porcine pericardium.

Implanting physical barrier materials to separate wounds from their surroundings is a promising strategy for preventing postoperative adhesions. Herein, we develop a material that switches from an anti-adhesive surface to an adhesive surface, preventing adhesion in the early stage of transplantation and then promoting recellularization. In this study, 2-arm, 4-arm, and 8-arm poly(ethylene glycol) succinimidyl glutarate (2-, 4-, 8-arm PEG-NHS) were used to modify the surface of decellularized porcine and bovine pericardium. The number of free amines on the surface of each material significantly decreased following modification regardless of the reaction molar ratio of NH2 and NHS, the number of PEG molecule branches, and the animal species of the decellularized tissue. The structure and mechanical properties of the pericardium were maintained after modification with PEG molecules. The time taken for the PEG molecules to detach through hydrolysis of the ester bonds differed between the samples, which resulted in different cell repulsion periods. By adjusting the reaction molar ratio, the number of PEG molecule branches, and the animal species of the decellularized pericardium, the duration of cell repulsion can be controlled and is expected to provide an anti-adhesion material for a variety of surgical procedures.

Evaluation of mycophenolic acid exposure in a patient with immune-related hepatotoxicity caused by nivolumab and ipilimumab therapy for malignant melanoma: a case report.

BACKGROUND: Guidelines such as the National Comprehensive Cancer Network recommend mycophenolate mofetil (MMF) for the treatment of severe steroid-refractory immune-related hepatotoxicity. Mycophenolic acid (MPA) is an active form of MMF that suppresses T- and B-lymphocyte proliferation and immune-related adverse events caused by immune checkpoint inhibitors. MPA has a narrow therapeutic range (37-70 µg·h/mL) and overexposure increases the risk of leukopenia in transplantation. However, the optimal use of MMF in oncology has not yet been established; thus, monitoring plasma MPA concentrations is necessary to avoid excessive immunosuppression in oncology practice. CASE PRESENTATION: We evaluated plasma MPA concentration in a 75-year-old man with immune-related hepatotoxicity following nivolumab and ipilimumab combination therapy for malignant melanoma. The patient developed severe hepatotoxicity after immunotherapy, and immunosuppressant therapy with corticosteroids was initiated. The patient then developed steroid-refractory immune-related hepatotoxicity; therefore, MMF (1,000 mg twice daily) was co-administered. Seven days after the administration of MMF, the plasma MPA concentration was measured using an enzyme multiplied immunoassay technique. The area under the plasma concentration-time curve for MPA from 0 to 12 h was 41.0 µg·h/mL, and the same dose of MMF was continued. Grade 2 lymphocytopenia, which could be attributed to MMF, was observed during the administration period. Unfortunately, the patient was infected with SARS-CoV-2 and died from respiratory failure. CONCLUSION: Our patient did not exceed the upper limit of MPA levels as an index of the onset of side effects of kidney transplantation and achieved rapid improvement in liver function. Prompt initiation of MMF after assessment of the steroid effect leads to adequate MPA exposure. Therapeutic drug monitoring should be considered when MMF is administered, to avoid overexposure.

Preparation of Cholesterol-Modified Hyaluronic Acid Nanogel-Based Hydrogel and the Inflammatory Evaluation Using Macrophage-like Cells.

Nanogels are candidate biomaterials for tissue engineering and drug delivery. In the present study, a cholesterol-hyaluronic acid hydrogel was developed, and the pro-inflammatory response of macrophages to the hydrogel was investigated to determine its use in biomedical applications. Hyaluronic acid modified with cholesterol (modification rate: 0-15%) and maleimide (Chol-HA) was synthesized. The Chol-HA nanogel was formed through self-assembly via hydrophobic cholesterol interactions in aqueous solution. The Chol-HA hydrogel was formed through chemical crosslinking of the Chol-HA nanogel via a Michael addition reaction between the maleimide and thiol groups of 4arm-PEGSH. We found that the Chol-HA hydrogels with 5, 10, and 15% cholesterol inhibited the pro-inflammatory response of HiBiT-THP-1 cells, suggesting that the cholesterol contributed to the macrophage response. Furthermore, Interleukin 4 (IL-4) encapsulated in the hydrogel of the Chol-HA nanogel enhanced the inhibition of the inflammatory response in HiBiT-THP-1 cells. These results provide useful insights into the biomedical applications of hydrogels.

One-pot Syntheses of Benzo- and Benzofuran-fused Iridaoxabenzenes via CH Bond Activations of Alkyl-bridged Diphenol Derivatives.

One-pot syntheses of new π-extended metallaaromatic compounds have been developed by utilizing Ir-mediated CH bond activation of ethylene- or ethylidene-bridged diphenol derivatives. Depending on the bridging alkyl groups, two types of iridaoxabenzenes, both of which are doubly fused with benzo and benzofuran units, have been obtained. Studies on their structures and electronic characters indicate that both complexes have an aromatic character on the iridaoxacycles, and their π-conjugated systems are fully delocalized over the whole molecular skeletons. These novel metallaaromatic complexes exhibited some reactivities which are distinct from those reported for the non-fused metallaaromatic compounds.

Preparation of mineralized pericardium by alternative soaking for soft-hard interregional tissue application.

Recent applications of decellularized tissues include the ectopic use of sheets and powders for three-dimensional (3D) tissue reconstruction. Decellularized tissues are modified (or fabricated) with the desired functions for application to the target (transplanted or used) tissue, including soft-hard interregional tissues, such as ligaments, tendons, and periodontal ligaments. This study aimed to prepare a mineralized decellularized pericardium to construct a soft-hard interregional tissue by 3D fabrication of decellularized pericardium, for example, rolling up to a cylindrical form. The decellularized pericardial tissue was prepared using the high hydrostatic pressurization (HHP) and surfactants method. The pericardium consisted of bundles of aligned fibers, and the bundles were slightly disordered when prepared with the surfactant decellularization method compared with that prepared using the HHP decellularization method. Mineralization of the decellularized pericardium was performed using an alternate soaking process with various cycles. The surface of the decellularized pericardium was covered with calcium phosphate precipitates, which accumulated on the surface with an increasing number of soaking cycles. The inside of the HHP decellularized pericardium was mineralized uniformly, whereas the mineralization of the decellularized pericardium decreased toward the interior. These findings suggest that the decellularization method strongly affects the structure and mineralized parts of the decellularized pericardium. The mineralized decellularized pericardium could be a candidate material for reconstructing alternative interregional tissues, such as ligaments and tendons.

In Vitro Tissue Reconstruction Using Decellularized Pericardium Cultured with Cells for Ligament Regeneration.

Recent applications of decellularized tissues have included the ectopic use of their sheets and powders for three-dimensional (3D) tissue reconstruction. Decellularized tissues are fabricated with the desired functions to employ them to a target tissue. The aim of this study was to develop a 3D reconstruction method using a recellularized pericardium to overcome the difficulties in cell infiltration into tight and dense tissues, such as ligament and tendon tissues. Decellularized pericardial tissues were prepared using the high hydrostatic pressurization (HHP) and surfactant methods. The pericardium consisted of bundles of aligned fibers. The bundles were slightly disordered in the surfactant decellularization method compared to the HHP decellularization method. The mechanical properties of the pericardium were maintained after the HHP and surfactant decellularizations. The HHP-decellularized pericardium was rolled up into a cylindrical formation. Its mechanical behavior was similar to that of a porcine anterior cruciate ligament in tensile testing. NIH3T3, C2C12, and mesenchymal stem cells were adhered with elongation and alignment on the HHP- and surfactant-decellularized pericardia, with dependences on the cell type and decellularization method. When the recellularized pericardium was rolled up into a cylinder formation and cultured by hanging circulation for 2 days, the cylinder formation and cellular elongation and alignment were maintained on the decellularized pericardium, resulting in a layer structure of cells in a cross-section. According to these results, the 3D-reconstructed decellularized pericardium with cells has the potential to be an attractive alternative to living tissues, such as ligament and tendon tissues.

Effects of capacitive and resistive electric transfer therapy on pain and lumbar muscle stiffness and activity in patients with chronic low back pain.

[Purpose] In this study, we investigated the therapeutic effects of capacitive and resistive electric transfer therapy in patients with chronic low back pain. [Participants and Methods] The study included 24 patients with chronic low back pain (12 patients each in the intervention and sham groups). Pain intensity, superficial and deep lumbar multifidus stiffness and maximum forward trunk flexion and associated activation level of the iliocostalis (thoracic and lumbar component) and lumbar multifidus muscles were measured. [Results] Post-intervention pain intensity and muscle stiffness were significantly lower than pre-intervention measurements in the intervention group. However, no between-group difference was observed in the muscle activation level at the end-point of standing trunk flexion. [Conclusion] Our findings highlight a significant therapeutic benefit of capacitive and resistive electric transfer therapy in patients with chronic low back pain and muscle stiffness.

Standards of Conducts for Biostatisticians and Stem Cell Researchers: A Call for Self-formulated Aspirational Ethics Over Built-in Prohibitive Ethics.

We proposed the Standards of Conducts to provide a general framework that will serve as the basis for guiding each biostatistician and stem cell researcher to formulate their personal standards, rather than as rules with which they are required to comply. Given the responsibility and characteristics of their work, they are expected to maintain independence and work autonomously as professionals. Each of the Standards of Conducts comprises a preamble, mission and values to uphold, Standards of Conducts (10 items), and background. When one internalizes "self-formulated" standards, to make excuses for oneself would be akin to a self-betrayal; responsible actions can be anticipated. If one begins and continues to consider "who I am and what do I work for," this will become their inner energy, and a source of motivation and pride to inspire oneself. In addition, this aspirational style might help citizens to recognize the autonomous stance of the professional body and that they share the same values.

[Questionnaire Survey on Adoption and Prescription of Biosimilars (Antibody and Its-related Products) by Medical Doctors in Japan].

Biosimilars are less expensive than their originators, and Japanese government policies call for their development and promotion. However, the adoption and prescription of some biosimilars, especially antibody/its-related ones, have been delayed for use in Japan, possibly due to concerns on the differences in quality attributes such as glycan structures between the originators and their biosimilars, and that clinical efficacy/safety studies are conducted for usually one disease and its results extrapolated to other indications. We conducted a questionnaire survey among physicians in four disease areas (hematology, medical oncology, rheumatoid arthritis, and inflammatory bowel disease), where biosimilars of antibody/its-related drugs have been approved, regarding their thoughts on the adoption and prescription of biosimilars in Japan from January to April 2020. We received totally 1024 responses. When adopting biosimilars and explaining them to patients, physicians requested specific information including the comparative results of phase III clinical trials and quality characteristics between biosimilars and their originators; the results of clinical studies on switching from originators to their biosimilars; and a comparison of the estimated cost on patients in consideration of the high medical cost payment system. Priority differed depending on the studied disease areas. In terms of post-marketing information, physicians requested a variety of information. When explaining biosimilars to the patients, physicians would like to use general material from government describing the comparability between originators and their biosimilars. These results suggest that physicians sought more comparative information on the quality, efficacy, and patients' cost between originators and their biosimilars when adopting or prescribing biosimilars.

Changes in the awareness and understanding of trunk muscle training in high school athletes.

[Purpose] This study aimed to compare the results of two questionnaires administered in 2013 and 2020, on the level of awareness and understanding of trunk muscle training. [Participants and Methods] In total, 238 soccer club members in high schools responded to our questionnaire regarding trunk muscle training. Two teams were recruited from the top (top 4), middle (top 16), and bottom levels (first-round losers), according to the prefectural tournament's results in 2019. This questionnaire comprised questions divided into four parts: 1. Prevalence of trunk muscle training; 2. Knowledge of the classification of trunk muscles (local and global); 3. Consciousness of local and global muscles during trunk muscle training; and 4. Knowledge of the role of each muscle. These results were compared to those obtained from the survey in 2013. [Results] A significant difference was observed only in the responses to question 2. Regarding question 2 in 2020, several student-athletes in the top-level teams were aware of muscle classification compared to those in the middle- and lower-level teams. [Conclusion] The number of athletes who understood the classification of trunk muscles increased significantly in 2020. Therefore, in the future, we would need to better educate young athletes concerning the purpose of trunk muscle training and the role of each muscle.

Relationship between gait speed and trunk muscles in frail elderly individuals.

[Purpose] The external and internal abdominal muscles may be related to gait speed; however, this has not yet been elucidated. In this study, we aimed to clarify the relationship between gait speed and trunk muscle thickness in elderly individuals. [Participants and Methods] The participants were 12 elderly individuals (4 males and 8 females, mean age 83.4 years old, SD ± 0.5) that attend a day service center. We measured the 5 m free gait speed, the 5 m fastest gait speed, and the thickness of five trunk muscles (the rectus abdominis [divided into three parts: upper, central, and lower], external oblique, internal oblique, transverse abdominis, and iliopsoas muscles). [Results] There were positive correlations between the free gait speed and the thickness of the lower rectus abdominis, internal oblique, and transverse abdominis muscles. There were also positive correlations between the fastest gait speed and the thickness of the lower rectus abdominis, internal oblique, and transverse abdominis muscles. [Conclusion] Incorporating muscle strength training of the lower rectus abdominis, internal oblique, and transverse abdominis muscles into existing lower limb muscle training protocols is important to effectively maintain the gait speed of elderly individuals.

Is the diaphragm thickness related to gait speed in patients with hemiplegia caused by cerebrovascular accident?

[Purpose] We aimed to determine the relationship between gait speed and diaphragm thickness in community-residing patients with hemiplegia caused by cerebrovascular accidents. [Participants and Methods] We recruited 11 elderly participants (six male and five female, mean age 71.1 ± 13.6 years) from an outpatient rehabilitation unit. The inclusion criteria were as follows: patients with hemiplegia caused by cerebrovascular accidents, those able to walk without assistance, and those able to understand our instructions. We measured the diaphragm thickness on both the paretic and non-paretic sides in each participant during maximum exhalation and inhalation during three laboured breaths by ultrasonography with a 7.5-MHz linear scanner. The liner scanner was placed on the eighth or ninth rib between the anterior and middle axillary lines. And their gait speed was measured during a 10 m walk. [Results] There was a strong positive correlation between gait speed and the ratio of diaphragm thickness between the paretic and the non-paretic sides during maximal inspiration. The other measured parameters did not show significant correlation with gait speed. [Conclusion] The symmetrical thickness of the diaphragm is a key factor in increasing gait speed in patients with hemiplegia. These findings may contribute to the development of trunk muscle strength-training programs that improve trunk function and gait speed in patients with hemiplegia.

Effect of low back pain on the muscles controlling the sitting posture.

[Purpose] The purpose of the current study was to reveal the association between posture control and muscle activity by measuring the trunk and hip joint muscle activities in the upright and slump sitting positions in both the healthy participants and patients with recurrent lower back pain. [Participants and Methods] We recruited eleven patients of recurrent lower back pain and ten healthy participants. During the maintenance of the two types of posture, upright and slump, we collected the surface electromyography data. We assessed the following muscles: rectus abdominis, external oblique, thoracic erector spinae, lumbar erector spinae, internal oblique, lumbar multifidus, iliacus, serratus anterior, rectus femoris, tensor fascia latae, and gluteus maximus. We studied the differences in spinal-pelvic curvature and muscle activity between the upright and slump positions in each group. [Results] In the healthy group, comparison of the muscle activity in upright and slump positions for both the trunk (external oblique, internal oblique, lumbar erector spinae, and lumbar multifidus), and the hip muscles (iliacus and gluteus maximus) showed a significant decrease in activity in the slump position. In the group with recurrent lower back pain, although the external oblique, lumbar erector spinae and lumbar multifidus showed reduced activity in slump position, these values were smaller when compared to those in the healthy group. [Conclusion] This study aimed to clarify the relationship between posture (upright and slump) and the activity of the trunk and hip joint muscles in the healthy participants and the patients with recurrent lower back pain. The results indicated that postural changes caused by recurrent lower back pain significantly affected the activity of the muscles involved in controlling the posture.

Chronic retinoic acid treatment induces differentiation and changes in the metabolite levels of brown (pre)adipocytes.

Dietary vitamin A status affects energy metabolism. The present study explored the effect of all-trans retinoic acid (ATRA) on the expression levels of molecules and metabolites of brown adipocytes. Chronic ATRA treatment was initiated during the early stage (days 0-8) or late stage (days 8-12) of adipogenesis. Treatment with ATRA during the early and late stage of adipogenesis resulted in an increase in the expression level of Ucp1 and Cidea, genes highly expressed in brown adipocytes, on day 8 and day 12, respectively, whereas expression of Pgc-1α, another gene expressed during brown adipogenesis, was unaffected by ATRA. Non-targeted metabolomic analyses indicated that the pathways related to the glucose metabolism were affected by ATRA, irrespective of the differentiation stage. Cellular levels of glucose 6-phosphate, fructose 6-phosphate, citric acid, and succinic acid decreased after ATRA treatment on days 8 and 12. In contrast, glucose level was higher in ATRA-treated cells on day 8, but it was lower on day 12. ATRA decreased the cellular level of aconitic acid, fumaric acid, and malic acid on day 12 but not on day 8. Furthermore, ATRA increased the expression level of Hxk2 and downregulated the expressions of G6pdh and Pfkl/Pfkp on day 8 but not on day 12. Together, the results indicate that the chronic treatment with ATRA stimulated the formation of activated brown adipocytes, eventually leading to alterations in the levels of cellular metabolites related to glucose metabolism. SIGNIFICANCE OF THE STUDY: Significance of the study treatment with all-trans retinoic acid (ATRA) during the early and late stage of adipogenesis increased the expression of Ucp1 and Cidea, genes highly expressed in brown adipocytes, on day 8 and day 12. Cellular levels of glucose 6-phosphate, fructose 6-phosphate, citric acid, and succinic acid decreased after ATRA treatment on days 8 and 12. In contrast, glucose level was higher in ATRA-treated cells on day 8, but it was lower on day 12. The present results indicate that ATRA stimulated the formation of activated brown adipocytes, eventually leading to alterations in the levels of cellular metabolites related to glucose metabolism.

Simultaneous Measurements of Structure and Water Permeability in an Isolated Human Skin Stratum Corneum Sheet.

Stratum corneum (SC), the outermost layer of human skin, acts as an intelligent physicochemical interface between the inside and the outside of our body. To make clear the relationship between structure and physical barrier properties of SC, we developed a method that enables us to simultaneously acquire X-ray diffraction (XD) patterns and transepidermal water loss (TEWL) values using a spread SC sheet isolated from human skin. The synchrotron X-ray was incident on the SC sheet surface at an angle of 45° to avoid interference between the two kinds of measurements. Detailed comparison between XD and TEWL data suggested that the thermal behavior of water permeability is closely related to the thermal expansion of the lattice spacings of the hexagonal phases above 40 °C and to the existence ratio of the orthorhombic phase below 40 °C. Thus, the new method we developed can give useful information on the mechanism of water permeation in SC without ambiguity caused by separate measurements of structure and water permeability with different samples.

Role of estradiol and testosterone in Ucp1 expression in brown/beige adipocytes.

Activity of brown/beige adipocytes is higher in women than in men. The expression level of uncoupling protein 1 (UCP1) is largely consistent with the thermogenic activity in brown/beige adipocytes. The present study examined the direct effects of sex hormones on Ucp1 expression in brown adipocytes and beige adipocytes, which were differentiated from HB2 brown preadipocytes and 3T3-L1 white preadipocytes, respectively; treatment with estradiol or testosterone was used during the early (days 0-8) or late stage (days 8-12) of brown adipogenesis and beige adipogenesis. On day 8 or day 12, cells were treated with or without isoproterenol (Iso), an agonist for the ß-adrenergic receptor, for 4 hours. Furthermore, the sex of cells was examined; the sex-determining region y gene, which is located on the y chromosome, was present in HB2 cells, but not in 3T3-L1 cells, suggesting that HB2 cells and 3T3-L1 cells are male and female cells, respectively. Treatment with 17ß-estradiol during the early stage of brown adipogenesis enhanced the responsiveness to Iso on Ucp1 induction, whereas treatment during the late stage of brown adipogenesis decreased Ucp1 expression in unstimulated brown adipocytes. Estradiol decreased Iso-induced Ucp1 expression during the early stage of beige adipogenesis. Treatment with testosterone during the early stage of brown adipogenesis did not affect Ucp1 expression but increased the responsiveness to Iso on Ucp1 induction by the treatment during the late stage of brown adipogenesis. The present results suggest that sex hormones modulate the expression level of Ucp1 in brown/beige adipocytes in a stage-dependent manner. Direct effects of sex hormones in brown/beige adipogenesis were evaluated. Treatment with 17ß-estradiol during the early stage of brown adipogenesis enhanced the responsiveness to isoproterenol (Iso), an agonist for the ß-adrenergic receptor, on Ucp1 induction, whereas treatment during the late stage of brown adipogenesis decreased Ucp1 expression in unstimulated brown adipocytes. Estradiol decreased Iso-induced Ucp1 expression during the early stage of beige adipogenesis. Testosterone during the late stage of brown adipogenesis increased the responsiveness to Iso on Ucp1 induction. Sex hormones modulate the expression level of Ucp1 in brown/beige adipocytes in a stage-dependent manner.

Effects of Products Containing Bacillus subtilis var. natto on Healthy Subjects with Neck and Shoulder Stiffness, a Double-Blind, Placebo-Controlled, Randomized Crossover Study.

Neck and shoulder stiffness is a typical subjective symptom in developed countries. This stiffness is caused by factors such as muscle tension and poor blood flow, leading to reduce work efficiency and diminish QOL. NKCP®, a natto-derived dietary food supplement whose main component is bacillopeptidase F, has antithrombotic, fibrinolytic, and blood viscosity-lowering effects. Here, we investigated the effect of NKCP® on neck and shoulder stiffness in a double-blind placebo-controlled randomized crossover study. Thirty subjects with neck and shoulder stiffness were randomly divided into 2 groups and ingested 250 mg of NKCP® or placebo daily for 4 weeks. Headache score significantly improved in the NKCP® group compared to the placebo group. Moreover, NKCP® significantly improved the score of visual analogue scale for neck and shoulder stiffness and pain, reduced muscle stiffness of the neck, and increased the skin surface temperature of neck and shoulders, compared to before ingestion. No adverse effects were observed during this study. These results suggest that NKCP® may alleviate headaches and chronic neck and shoulder stiffness and pain.

Switch from ambient to focal processing mode explains the dynamics of free viewing eye movements.

Previous studies have reported that humans employ ambient and focal modes of visual exploration while they freely view natural scenes. These two modes have been characterized based on eye movement parameters such as saccade amplitude and fixation duration, but not by any visual features of the viewed scenes. Here we propose a new characterization of eye movements during free viewing based on how eyes are moved from and to objects in a visual scene. We applied this characterization to data obtained from freely-viewing macaque monkeys. We show that the analysis based on this characterization gives a direct indication of a behavioral shift from ambient to focal processing mode along the course of free viewing exploration. We further propose a stochastic model of saccade sequence generation incorporating a switch between the two processing modes, which quantitatively reproduces the behavioral features observed in the data.