Suffering of patients developing lymphedema following gynecological cancer surgery.

Objective: Lymphedema developing in the lower extremities following gynecological cancer surgery (LE-GCS) produces various kinds of sufferings, including impacts on quality of life (QOL) and body image. This research will serve as a basic resource for the care of patients with this type of lymphedema (LE). Patients and Methods: A qualitative discursive research method: Thirteen patients suffering from LE-GCS were interviewed in a semi-organized manner. Analysis involved extracting and codifying from transcripts and expressions related to the suffering of LE. Next, these codes were arranged into categories and subcategories under the supervision of qualitative researchers. Furthermore, this study was conducted with the approval of the Research Ethics Review Specialist Committee, which targets individuals affiliated with the public university corporation of Shiga Prefectural University. Results: Based on the interviews with 13 patients aged 47-79 (median age 62), two core categories were created: 1). Suffering of LE Developing in Lower Extremities (570 codes, seven categories, 23 subcategories); and 2). Supports that Allow Patients to Face Suffering of LE (254 codes, four categories, 14 subcategories). Conclusion: Patients with LE-GCS live with the fear that LE exacerbation will produce adverse life changes, and this may exceed the fear of cancer itself. The aggravation of their condition results in immense pain as well as reduced mobility, change in appearance, and loss of self-worth. The symptoms fluctuate, and may lead to chronic misery, which does not manifest, but occasionally flares-up because of both, worsening physical disability as well as ordinary events. Additionally, every patient subjectively described the strength they found within themselves to face the suffering. They cited the support of family and friends, existence of compassionate therapists and doctors, acquisition of knowledge, and self-care.

A Histogram Analysis of the Pixel Grayscale (Luminous Intensity) of B-Mode Ultrasound Images of the Subcutaneous Layer Predicts the Grade of Leg Edema in Pregnant Women.

The technique most widely used to quantitatively measure leg edema is only a pitting edema method. It has recently become possible to digitize B-mode ultrasound images and accurately quantify their brightness using an image-analysis software program. The purpose of this study was to find new indices of the grade of leg skin, to study whether or not analyses of the subcutaneous layer of leg skin on ultrasound images using image-editing software program can be used to evaluate it and to digitize it. Images of 282 subcutaneous layers of leg skin in 141 pregnant women were obtained using a B-scan portable ultrasound device. Rectangular photographs (vertical: skin thickness; horizontal: width of probe) were obtained using an image-editing program, and the luminous intensity (pixel grayscale: 0-255) and thickness of the skin were calculated using a histogram. We investigated the correlation between these parameters and the grade of pitting edema (0-3). There was a significant positive correlation between the grade of pitting edema and the average luminous intensity value, its standard deviation, and the skin thickness (ρ = 0.36, ρ = 0.22, ρ = 0.51, p < 0.0001, respectively). In particular, there was strong positive correlation between the grade of pitting edema and both the total number of pixels in a rectangle × (multiplied by) the average luminous intensity value and the total number of pixels in a rectangle × the standard deviation of the average luminous intensity value (ρ = 0.58 and ρ = 0.59, p < 0.0001, respectively). We could quantitatively evaluate the grade of leg edema by analyzing ultrasound photographs of the subcutaneous layer of the leg skin using an image-editing software program and found new indices to digitize it.

Measurement of Skin Thickness Using Ultrasonography to Test the Usefulness of Elastic Compression Stockings for Leg Edema in Pregnant Women.

Background: One of the most common treatments for leg edema during pregnancy is the use of compression stockings. The purpose of this study was to evaluate the objective effectiveness in pregnant women, by measuring the changes of skin thickness using ultrasonography. Methods: Pregnant women were diagnosed with leg edema using the pitting edema method at 36 weeks of gestation. Twenty-four pregnant women (48 legs) with leg edema spent time without wearing elastic stockings at 36−37 weeks of gestation. Then, they wore elastic stockings for one week at 37−38 weeks of gestation. We measured the grade of edema (from 0 to 3) and the skin thickness of the lower leg by portable ultrasonography at 36, 37, and 38 weeks of gestation (a before-and-after study). Results: In 24 pregnant women, thigh edema was not detected in any of the 48 legs before or after the use of elastic stockings. All 48 legs in 24 pregnant women had physiological lower leg edema, but not thigh edema. The average grade of pitting edema in each lower leg significantly decreased after using the stockings (36 weeks, 1.77 ± 0.85; 37 weeks, 1.79 ± 0.77; 38 weeks, 1.04 ± 0.74, p < 0.0001). In addition, the skin thickness of the lower legs was significantly decreased after the use of elastic stockings (36 weeks, 7.47 ± 2.45 mm; 37 weeks, 7.93 ± 2.83 mm; 38 weeks, 7.15 ± 2.35 mm, p < 0.0001). Conclusions: The wearing of elastic compression stockings on the lower legs is objectively effective for improving leg edema in pregnant women.

Novel electron microscopic staining method using traditional dye, hematoxylin.

Uranyl acetate (UA) has been routinely used as a staining solution for ultrathin sections used in biological electron microscopy. As a radioactive nuclear material, UA is subject to strict international regulations. To develop an alternative and easy-to-use staining method for ultrathin sections, we examined various commercial light microscopic dyes. We found that Mayer's hematoxylin followed by Reynold's lead citrate solution showed staining results comparable to UA and Reynold's lead citrate solution, and this method is therefore suggested as a reliable and promising alternative to UA staining.

[A protective effect of acetaminophen on ibuprofen-induced small intestinal damage in rats via the suppression of MMP-13].

BACKGROUND & AIMS: Capsule endoscopy has revealed that nonsteroidal anti-inflammatory drugs may cause damage not only to the stomach but also to the small intestine, which has become one of the most serious issues in gastroenterology. However, few studies have reported the effect of ibuprofen (IBP), which is widely prescribed worldwide, on the small intestine, and it remains unclear whether IBP can cause small intestinal damage. We have previously shown that acetaminophen (APAP), which is used as an antipyretic/analgesic drug, inhibits IBP-induced gastric damage by suppressing matrix metalloprotease-13 (MMP-13) gene expression. In this study, we investigated the ability of IBP to induce small intestinal damage and the efficacy of APAP against IBP-induced small intestinal damage in rats. MAIN METHODS: Nonfasted male Sprague-Dawley rats were orally administered with IBP (200mg/kg) and then euthanized at various time points (0, 4, 8, 16, and 24h) after the administration. The small intestine, jejunum, and ileum were removed, and intestinal lesions were measured. To elucidate the efficacy of APAP against IBP-induced small intestinal damage, the rats were treated with IBP (200mg/kg) with or without APAP (200mg/kg), and small intestinal damage was evaluated 24h after the administration. Moreover, the expression levels of GAPDH, TNFα, iNOS, and MMP-13 genes were determined at various time points (8, 16, and 24h) by RT-qPCR. KEY FINDINGS: The oral administration of IBP induced obvious small intestinal damage, which was found to be significant at 24h (p<0.05 vs 0h, Dunnett's test). The coadministration of APAP significantly prevented IBP-induced damage (p<0.05, Student's t-test). In addition, the expression levels of TNFα and iNOS genes were significantly increased by IBP (p<0.01 and p<0.05 vs. vehicle, respectively, Tukey-Kramer test), whereas the cotreatment with APAP suppressed the increases at 8h. Moreover, compared with the vehicle, the IBP treatment significantly increased the expression level of the MMP-13 gene (p<0.01) at each time point (8, 16, and 24h, Tukey-Kramer test), whereas the APAP cotreatment significantly suppressed the increase (p<0.01 vs. IBP at 8h, p<0.05 vs. IBP at 16 and 24h, Tukey-Kramer test). CONCLUSIONS: This study suggested that a single administration of IBP was associated with the risk of inducing small intestinal ulcers in rats, and APAP could prevent IBP-induced small intestinal damage by suppressing the MMP-13 gene expression.

Early recovery of basic mobility under femoral nerve block after hip fracture surgery - A propensity score matched pilot study.

BACKGROUND: Previous studies have shown better pain reduction utilizing femoral nerve block (FNB) in patients who underwent hip fracture surgery. However, few studies have focused on the recovery of physical function after FNB, and most studies excluded patients with dementia. We investigated the association between FNB performed in the operating room and the recovery of physical function after hip fracture surgery, including patients with dementia. METHODS: A total of 103 patients with a mean age of 87.4 years who underwent hip fracture surgery under spinal anesthesia between July 2015 and December 2017 (46 patients receiving a single injection of FNB and 57 standard care) were enrolled. Patients with FNB versus standard care were matched by a propensity score to adjust for patient characteristics. An anesthesiologist performed FNB with 20ml of 0.2% ropivacaine, and the standard care group received intravenous 1000 mg acetaminophen or 50mg flurbiprofen once after surgery. After matching, 78 patients were analyzed. Our primary outcome was 3-day cumulated ambulation score (CAS, 0-18 points) and secondary outcomes were 1-day CAS on postoperative day 1-3 and length of hospital stay. We also stratified patient groups based on the presence of dementia and fracture type. RESULTS: Patients undergoing FNB had significantly better 3-day CAS compared to standard care (mean [SD], 8.72 [3.42] vs 7.33 [2.62]; mean difference, 1.38 [95%CI; 0.03 - 2.74]; p = 0.048) and 1-day CAS on postoperative day two (mean [SD], 3.10 [1.39] vs 2.56 [0.94]; mean difference, 0.54 [0.01 - 1.07]; p = 0.049). Length of hospital stay did not significantly differ among the two groups (p = 0.65). Larger positive effect was likely to be seen for patients with a femoral neck fractures and for those without dementia. CONCLUSIONS: Patients who underwent surgery with spinal anesthesia plus FNB had better ambulatory status early after hip fracture surgery compared to patients not offered FNB. The beneficial association between FNB and ambulatory status was likely to be observed especially in patients with femoral neck fracture and without dementia.

The Preventive Effect of Dietary Antioxidants on Cervical Cancer Development.

Cervical cancer results from a continuous process, starting from a normal cervical epithelium after human papillomavirus (HPV) infection and progressing to cervical intraepithelial neoplasia (CIN), before finally developing into invasive squamous carcinoma (ISC). In recent decades, dietary antioxidants, such as vitamins, have received much attention in relation to cancer prevention. We reviewed the relevant literature to investigate the dietary and nutrient intake on cervical cancer. The intake of vitamins A and D and carotenoids may inhibit early cervical cancer development. The intake of folate may prevent or inhibit HPV infection rom progressing to various grades of CIN. The intake of vitamins C and E may widely inhibit the process of cervical cancer development. Polyphenols are often used in cases of cervical cancer in combination chemotherapy and radiation therapy. Regarding nutrients, different antioxidants may have differing abilities to intervene in the natural history of cervical diseases associated with HPV infection. Regarding foods, the intake of both vegetables and fruits containing multiple vitamins may widely suppress cervical cancer development. Most previous papers have described epidemiological studies. Thus, further research using in vitro and in vivo approaches will be needed to clarify the effects of the dietary and nutrient intake in detail.

Mechanism of aspirin-induced inhibition on the secondary hyperalgesia in osteoarthritis model rats.

AIMS: The daily activity of osteoarthritis (OA) patients is limited by chronic pain and central sensitization. Although non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are the first-line drugs for the treatment of OA-related pain, their efficacy on central sensitization remains unclear. In the present study, we evaluated the effect of acetylsalicylic acid (ASA, Aspirin) using an OA model induced by monosodium iodoacetate (MIA), which has a similar disease progression to human OA. MAIN METHODS: Secondary hyperalgesia was assessed at the plantar surface of the hind paw by Von Frey test. We evaluated the expression of acid-sensing ion channel 3 (ASIC3) in dorsal root ganglia and that of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in the spinal cord, which may cause secondary hyperalgesia in OA, by immunohistochemical analysis and real-time qPCR. KEY FINDINGS: The administration of ASA attenuated secondary hyperalgesia at 1-3 weeks after MIA, while celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, failed to attenuate secondary hyperalgesia at week 2 after MIA injection, suggesting that ASA exerts its analgesic effect through a COX-2-independent pathway. Immunohistochemical analysis of the dorsal root ganglia indicated that ASA reduced the expression of ASIC3 during OA progression. Expression of TNF-α mRNA, but not IL-1ß mRNA, in the spinal cord following MIA injection was suppressed by ASA administration. SIGNIFICANCE: These findings suggest that ASA may have the ability to attenuate secondary hyperalgesia through suppression of ASIC3 and/or TNF-α expression. ASA is therefore a clinically useful analgesic drug for treatment of secondary hyperalgesia in OA.

[My Story of Recovery from Brain Damage].

The author (hereafter referred to as I) is a speech-language-hearing pathologist and former professor of neuropsychology at Kobe University, who had been engaged in neuropsychological rehabilitation and research of conditions, such as aphasia and unilateral spatial neglect, for 37 years. In July 2009, I experienced right hemispheric infarction in Kobe City, and developed left-sided hemiparesis and various symptoms of cognitive dysfunctions, which was previously my field of expertise. As a neuropsychological rehabilitation expert, I focused my efforts on recovery and I have recovered the majority of my cognitive and neurologic functions. This is my story of recovery from stroke, in which functional magnetic resonance imaging (fMRI) studies of my arithmetic ability are described. I had been an excellent abacus user with brilliant achievements since elementary school. Premorbidly, I could use the right hemisphere of my brain to visualize a clear image of an abacus. However, my ability to visualize the abacus disappeared following the stroke. Two experiments were conducted involving calculation and digit memory tasks using fMRI. This may be the most important aspect of my story. My recovery process for other cognitive deficits is also delineated here.

[The Analgesic Effect of Aspirin on Inflammatory Pain in Rats Is Affected by Pain Intensity and Administration Timing].

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely known as painkillers. The analgesic action of NSAIDs is attributable to the inhibition of prostaglandin synthesis that occurs in response to blocking cyclooxygenase activity. The effective dose of NSAIDs can vary depending on pain intensity and administration timing; however, there are few studies on this. This study aimed to elucidate whether the analgesic effect of NSAIDs changes depending on the situation in which they are taken and we focused on the NSAID, aspirin (ASP). In a rat model of brewer's yeast-induced inflammation, pain caused by 20% (w/v) brewer's yeast-treatment was defined as "strong pain" and that caused by 2.5% (w/v) was defined as "weak pain". The analgesic effect of ASP (low-dose; 44 mg/kg or high-dose; 66 mg/kg) against strong pain was dose-dependent, but that against weak pain was the same. Furthermore, we defined drug administration after 3 h of brewer's yeast-treatment as "late administration" and that after 20 min as "early administration". In the case of strong pain, the analgesic effect of "late ASP administration" was dose-dependent, but that of "early ASP administration" was the same. These results suggest that low-dose NSAIDs have an analgesic effect against weak pain or when taken early.

Development and Themes of Diagnostic and Treatment Procedures for Secondary Leg Lymphedema in Patients with Gynecologic Cancers.

Patients with leg lymphedema sometimes suffer under constraint feeling leg heaviness and pain, requiring lifelong treatment and psychosocial support after surgeries or radiation therapies for gynecologic cancers. We herein review the current issues (a review of the relevant literature) associated with recently developed diagnostic procedures and treatments for secondary leg lymphedema, and discuss how to better manage leg lymphedema. Among the currently available diagnostic tools, indocyanine green lymphography (ICG-LG) can detect dermal lymph backflow in asymptomatic legs at stage 0. Therefore, ICG-LG is considered the most sensitive and useful tool. At symptomatic stage ≥1, ultrasonography, magnetic resonance imaging-lymphography/computed tomography-lymphography (MRI-LG/CT-LG) and lymphosintiography are also useful. For the treatment of lymphedema, complex decongestive physiotherapy (CDP) including manual lymphatic drainage (MLD), compression therapy, exercise and skin care, is generally performed. In recent years, CDP has often required effective multi-layer lymph edema bandaging (MLLB) or advanced pneumatic compression devices (APCDs). If CDP is not effective, microsurgical procedures can be performed. At stage 1-2, when lymphaticovenous anastomosis (LVA) is performed, lymphaticovenous side-to-side anastomosis (LVSEA) is principally recommended. At stage 2-3, vascularized lymph node transfer (VLNT) is useful. These ingenious procedures can help maintain the patient's quality of life (QOL) but unfortunately cannot cure lymphedema. The most important concern is the prevention of secondary lymphedema, which is achieved through approaches such as skin care, weight control, gentle limb exercises, avoiding sun and heat, and elevation of the affected leg.

Development of a cognitive function test using virtual reality technology: examination in healthy participants.

We developed a virtual reality test to assess the cognitive function of Japanese people in near-daily-life environment, namely, a virtual shopping test (VST). In this test, participants were asked to execute shopping tasks using touch panel operations in a "virtual shopping mall." We examined differences in VST performances among healthy participants of different ages and correlations between VST and screening tests, such as the Mini-Mental State Examination (MMSE) and Everyday Memory Checklist (EMC). We included 285 healthy participants between 20 and 86 years of age in seven age groups. Therefore, each VST index tended to decrease with advancing age; differences among age groups were significant. Most VST indices had a significantly negative correlation with MMSE and significantly positive correlation with EMC. VST may be useful for assessing general cognitive decline; effects of age must be considered for proper interpretation of the VST scores.

Role of LRP1 and ERK and cAMP Signaling Pathways in Lactoferrin-Induced Lipolysis in Mature Rat Adipocytes.

Lactoferrin (LF) is a multifunctional glycoprotein present in milk. A clinical study showed that enteric-coated bovine LF tablets decrease visceral fat accumulation. Furthermore, animal studies revealed that ingested LF is partially delivered to mesenteric fat, and in vitro studies showed that LF promotes lipolysis in mature adipocytes. The aim of the present study was to determine the mechanism underlying the induction of lipolysis in mature adipocytes that is induced by LF. To address this question, we used proteomics techniques to analyze protein expression profiles. Mature adipocytes from primary cultures of rat mesenteric fat were collected at various times after exposure to LF. Proteomic analysis revealed that the expression levels of hormone-sensitive lipase (HSL), which catalyzes the rate-limiting step of lipolysis, were upregulated and that HSL was activated by protein kinase A within 15 min after the cells were treated with LF. We previously reported that LF increases the intracellular concentration of cyclic adenosine monophosphate (cAMP), suggesting that LF activates the cAMP signaling pathway. In this study, we show that the expression level and the activity of the components of the extracellular signal-regulated kinase (ERK) signaling pathway were upregulated. Moreover, LF increased the activity of the transcription factor cAMP response element binding protein (CREB), which acts downstream in the cAMP and ERK signaling pathways and regulates the expression levels of adenylyl cyclase and HSL. Moreover, silencing of the putative LF receptor low-density lipoprotein receptor-related protein 1 (LRP1) attenuated lipolysis in LF-treated adipocytes. These results suggest that LF promoted lipolysis in mature adipocytes by regulating the expression levels of proteins involved in lipolysis through controlling the activity of cAMP/ERK signaling pathways via LRP1.

Influence of p53 status on the effects of boron neutron capture therapy in glioblastoma.

BACKGROUND/AIM: The tumor suppressor gene p53 is mutated in glioblastoma. We studied the relationship between the p53 gene and the biological effects of boron neutron capture therapy (BNCT). MATERIALS AND METHODS: The human glioblastoma cells; A172, expressing wild-type p53, and T98G, with mutant p53, were irradiated by the Kyoto University Research Reactor (KUR). The biological effects after neutron irradiation were evaluated by the cell killing effect, 53BP1 foci assay and apoptosis induction. RESULTS: The survival-fraction data revealed that A172 was more radiosensitive than T98G, but the difference was reduced when boronophenylalanine (BPA) was present. Both cell lines exhibited similar numbers of foci, suggesting that the initial levels of DNA damage did not depend on p53 function. Detection of apoptosis revealed a lower rate of apoptosis in the T98G. CONCLUSION: BNCT causes cell death in glioblastoma cells, regardless of p53 mutation status. In T98G cells, cell killing and apoptosis occurred effectively following BNCT.

A virtual shopping test for realistic assessment of cognitive function.

BACKGROUND: Cognitive dysfunction caused by brain injury often prevents a patient from achieving a healthy and high quality of life. By now, each cognitive function is assessed precisely by neuropsychological tests. However, it is also important to provide an overall assessment of the patients' ability in their everyday life. We have developed a Virtual Shopping Test (VST) using virtual reality technology. The objective of this study was to clarify 1) the significance of VST by comparing VST with other conventional tests, 2) the applicability of VST to brain-damaged patients, and 3) the performance of VST in relation to age differences. METHODS: The participants included 10 patients with brain damage, 10 age-matched healthy subjects for controls, 10 old healthy subjects, and 10 young healthy subjects. VST and neuropsychological tests/questionnaires about attention, memory and executive function were conducted on the patients, while VST and the Mini-Mental State Examination (MMSE) were conducted on the controls and healthy subjects. Within the VST, the participants were asked to buy four items in the virtual shopping mall quickly in a rational way. The score for evaluation included the number of items bought correctly, the number of times to refer to hints, the number of movements between shops, and the total time spent to complete the shopping. RESULTS: Some variables on VST correlated with the scores of conventional assessment about attention and everyday memory. The mean number of times referring to hints and the mean number of movements were significantly larger for the patients with brain damage, and the mean total time was significantly longer for the patients than for the controls. In addition, the mean total time was significantly longer for the old than for the young. CONCLUSIONS: The results suggest that VST is able to evaluate the ability of attention and everyday memory in patients with brain damage. The time of VST is increased by age.

Abacus in the brain: a longitudinal functional MRI study of a skilled abacus user with a right hemispheric lesion.

The abacus, a traditional physical calculation device, is still widely used in Asian countries. Previous behavioral work has shown that skilled abacus users perform rapid and precise mental arithmetic by manipulating a mental representation of an abacus, which is based on visual imagery. However, its neurophysiological basis remains unclear. Here, we report the case of a patient who was a good abacus user, but transiently lost her "mental abacus" and superior arithmetic performance after a stroke owing to a right hemispheric lesion including the dorsal premotor cortex (PMd) and inferior parietal lobule (IPL). Functional magnetic resonance imaging experiments were conducted 6 and 13 months after her stroke. In the mental calculation task, her brain activity was shifted from the language-related areas, including Broca's area and the left dorsolateral prefrontal and IPLs, to the visuospatial-related brain areas including the left superior parietal lobule (SPL), according to the recovery of her arithmetic abilities. In the digit memory task, activities in the bilateral SPL, and right visual association cortex were also observed after recovery. The shift of brain activities was consistent with her subjective report that she was able to shift the calculation strategy from linguistic to visuospatial as her mental abacus became stable again. In a behavioral experiment using an interference paradigm, a visual presentation of an abacus picture, but not a human face picture, interfered with the performance of her digit memory, confirming her use of the mental abacus after recovery. This is the first case report on the impairment of the mental abacus by a brain lesion and on recovery-related brain activity. We named this rare case "abacus-based acalculia." Together with previous neuroimaging studies, the present result suggests an important role for the PMd and parietal cortex in the superior arithmetic ability of abacus users.

Cultural adaptation and validating a Japanese version of the readiness for interprofessional learning scale (RIPLS).

Readiness for interprofessional education (IPE) can be an important factor to evaluate because of the influences of attitudes toward the outcomes of interprofessional learning activities. However, a dearth of Japanese evaluation tools hinders its evaluation. The readiness for interprofessional learning scale (RIPLS) was selected, because it has been validated in different countries and its items reflected our local situation best. This research aimed to develop and validate a Japanese version of the original 19-item RIPLS. We developed a Japanese RIPLS employing forward/backward translation. Reliability of the Japanese version was studied using classical test theory and structural equation modeling to construct a model to inform curriculum development. We obtained a 0.74 Cronbach's α, which indicates adequacy. Subscales of "interprofessional education opportunities" (α = 0.90) and "uniqueness of profession" (α = 0.60) have relatively little weight compared to "teamwork and collaboration" (α = 0.92). A one-way structure suggests that readiness for interprofessional learning starts with "teamwork & collaboration" followed by changes in "learning opportunities" and subsequently "uniqueness of profession" (root mean square error of approximation = 0.06, comparative fit index = 0.93). This Japanese RIPLS can be used in undergraduate health sciences students with appropriate caution. Further development of the subscales and a client-centered subscale would be beneficial to fully achieve its potential. The need for further research into its reliability and validity is identified. Recommendations are provided for cross-cultural adaptation and for establishing validity across different contexts.

Role of fibronectin-binding proteins A and B in in vitro cellular infections and in vivo septic infections by Staphylococcus aureus.

Fibronectin-binding protein A (FnBPA) and FnBPB are important adhesins for Staphylococcus aureus infection. We constructed fnbA and/or fnbB mutant strains from S. aureus SH1000, which possesses intact rsbU, and studied the role of these adhesins in in vitro and in vivo infections. In intravenous infection, all fnb mutants caused a remarkable reduction in the colonization rate in kidneys and the mortality rate of mice. fnbB mutant caused a more severe decrease in body weight than that caused by fnbA mutant. Serum levels of interleukin-6 and nuclear factor κB (NF-κB) activation in spleen cells were remarkably reduced in fnbA or fnbA fnbB mutant infections; however, there was no significant reduction in fnbB mutant infections. In in vitro cellular infection, FnBPA was shown to be indispensable for adhesion to and internalization by nonprofessional phagocytic cells upon ingestion by inflammatory macrophages and NF-κB activation. However, both FnBPs were required for efficient cellular responses. The results showed that FnBPA is more important for in vitro and in vivo infections; however, cooperation between FnBPA and FnBPB is indispensable for the induction of severe infection resulting in septic death.

Enhancement of precise hand movement by transcranial direct current stimulation.

The effect of transcranial direct current stimulation (tDCS) on the precise nondominant hand movement was investigated by applying anodal stimulation over the right primary motor cortex. We recruited 14 healthy participants for this single-blind, sham-controlled crossover trial. A circle-drawing task was performed before, immediately after, and at 30 min after 20 min of 1 mA anodal or sham tDCS. Anodal tDCS, compared with sham stimulation, significantly improved the circle-drawing task compared with sham stimulation. The deviation area and path length of the task were significantly decreased after anodal tDCS application and were further enhanced at 30 min after stimulation. These results suggest that anodal tDCS over the primary motor cortex enhances the precise movement of the nondominant hand for 30 min in healthy participants.

Inhibition of endothelial interleukin-8 production and neutrophil transmigration by Staphylococcus aureus beta-hemolysin.

Neutrophils play a crucial role in the host response to infection with Staphylococcus aureus, which is a major human pathogen capable of causing life-threatening disease. Interleukin-8 (IL-8) is a potent chemoattractant and activator of neutrophils. We previously reported that S. aureus secretes a factor that suppresses IL-8 production by human endothelial cells. Here we isolated an inhibitor of IL-8 production from the supernatant and identified it as staphylococcal beta-hemolysin. Beta-hemolysin reduced IL-8 production without cytotoxicity to endothelial cells. Pretreatment with beta-hemolysin decreased the expression of both IL-8 mRNA and protein induced by tumor necrosis factor alpha (TNF-alpha). Migration of neutrophils across TNF-alpha-activated endothelium was also inhibited by beta-hemolysin. In contrast, beta-hemolysin had no effect on intercellular adhesive molecule 1 expression in activated endothelial cells. These results showed that beta-hemolysin produced by S. aureus interferes with inflammatory signaling in endothelial cells and may help S. aureus evade the host immune response.