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This study examined the relationship between skin physiological indices and pressure ulcers in elderly people. The subjects were 55 bedridden elderly Japanese patients with a median age of 85 years. The following parame-ters were measured using non-invasive devices: skin surface temperature, moisture content in the stratum corneum, moisture content in the dermis, transepidermal water loss as an index of skin barrier function, skin erythema and skin elasticity. The sacral and 2 heel areas were observed as sites predisposed to pressure ulcers. Within one month after measuring the skin physiological indices, we confirmed pressure ulcers of National Pressure Ulcer Advisory Panel classification Stage II or worse based on medical records. Among the 55 patients, 4 (7.3%) prospectively developed a total of 5 pressure ulcers within 16 days. Only the skin erythema score was significantly higher with than without pressure ulcers (p < 0.001). We performed a binary logistic regression analysis and confirmed a significant relationship between pressure-ulcer development and the level of erythema (odds ratio = 1.026; 95% confidence interval: 1.011-1.042). Skin erythema increased before the development of pressure ulcers. Taken together, our results show that the high skin erythema score can be a predictive indicator of pressure ulcers.

Background: Previous studies have not specifically measured skin characteristics at common sites of pressure ulcers in high-risk elderly patients. Therefore, this study aimed to clarify the physiological skin characteristics at common pressure ulcer sites and their relationship with pressure ulcer risk and demographic/laboratory data in bedridden elderly Japanese patients. Methods: This study involved 55 elderly Japanese patients in a long-term care hospital and 25 female Japanese university students. Skin surface temperature, epidermal water content, transepidermal water loss, skin erythema/redness, skin elasticity, and skin thickness were measured using noninvasive devices. The sacral and both heel areas (sites predisposed to pressure ulcers) and mid-to-lower back area (control site) were observed. Results: Elderly patients showed a low epidermal water content at both heels (right heel, 14.8 ± 9.1 arbitrary units, AU.; left heel, 14.4 ± 8.3 AU). Transepidermal water loss remained acceptable at all sites in older patients despite the presence of dry skin (back, 7.1 ± 1.8 g/hm2; sacrum, 7.4 ± 3.0 g/hm2; right heel, 17.7 ± 7.1 g/hm2; left heel, 19.4 ± 8.1 g/hm2). Back (0.61 ± 0.13 AU) and sacral (0.67 ± 0.11 AU) skin elasticity and sacral skin thickness (0.97 ± 0.56 cm) were significantly lower than those of healthy young people (0.86 ± 0.04 AU, 0.87 ± 0.05 AU, and 2.27 ± 0.84 cm, respectively; p p p < 0.001) in older patients. Conclusions: Our findings showed that skin thickness and elasticity should be prioritized when evaluating pressure ulcer risk at the sacral region in bedridden elderly Japanese patients. Moreover, skin moisturization should be considered to minimize the risk at the heels in such patients.

Unhealthy diet can lead to the development of metabolic disorders, and studies have shown strong associations between those conditions and biomarkers, such as c-reactive protein (CRP) and adiponectin. Recently, marine algal biomaterials have been investigated extensively due to their health benefits. We report on associations between metabolic markers and bioactive nutrients from diet and Sujiaonori algal biomaterial (SBM), a natural adiponectin modulation inducer (NAMI) containing 60% of ulvan-rich fiber, in a sample of Japanese women. The study comprised dietary survey and intervention conducted in Kochi, Japan (2016-2017), involving 31 women who completed a dietary survey and provided biospecimen for CRP and adiponectin measurement using ELISA. Sixteen women received 3g SBM daily for one month and 15 others (controls) received 3g of corn starch. In SBM group, mean age was 23.06 (2.21) years [vs. 23.06 (1.55)], BMI was 21.11 (0.59) kg/m2 [vs. 21.43 (0.60) in controls], and daily intake of n3-PUFA [3.83 (0.24) vs. 2.21 (0.33) mg/day; p=0.042] and total fiber [364.12 (2.45) vs. 48.13 (1.57) mg/day in controls; p=0.000] were markedly higher. Furthermore, CRP was inversely associated with total fiber, total n3-PUFA, SBM-n3PUFA, vitamin D and vitamin B6, whereas adiponectin was strongly and positively associated with SBM-fiber and total n3-PUFA. Thus ulvan-rich SBM supplement, which contains ulvan-rich fiber and n3-PUFA, might be beneficial in reducing metabolic risk.

Background Malaria is one of the most severe public health issues that result in massive morbidity and mortality in most countries of the sub-Saharan Africa (SSA). This study aimed to determine the scope of household, accessibility to malaria care and factors associated with household malaria in the Democratic Republic of Congo (DRC). Methods This was a community-based cross-sectional study conducted in an urban and a rural sites in which 152 households participated, including 82 urban and 70 rural households (1029 members in total). The ‘malaria indicator questionnaire’ (MIQ) was anonymously answered by household heads (respondents), reporting on malaria status of household members in the last 12 months. Results There were 67.8% of households using insecticide-treated bed nets (ITN) only, 14.0% used indoor residual spraying (IRS) only, 7.3% used ordinary bed nets (without insecticide treatment), 1.4% used mosquito repelling cream, 2.2% combined ITN and IRS, whereas 7.3% of households did not employ any preventive measure; p

Nurses are required to make quantitative, evidence-based observations when implementing diabetic foot care. This study aimed to clarify the characteristics of lower-limb ischemia in patients with type 2 diabetes using subjective and objective symptoms and physiological indicators and whether the physiological characteristics are established as predictive indicators of arterial obstruction. Fifty Japanese patients with type 2 diabetes (100 limbs) were classified into three groups using the ankle–brachial index (ABI). Patients with an ABI of ≤0.69 had subjective and objective symptoms of blood flow disturbance, such as pain at rest, cold sensation, pale skin, and imperceptibility to the dorsalis pedis artery. Blood flow in the first toe was the lowest. Binary logistic regression analysis established hallux perfusion as a predictive model for lower-limb arterial occlusion (odds ratio = 0.979, 95% confidence interval 0.900–0.999). Thus, when nurses perform diabetic foot care, it is necessary to evaluate not only subjective and objective symptoms, but also blood flow at the microcirculatory level of the great toe.

Background Malaria is one of the most prevalent and deadliest illnesses in sub-Saharan Africa. Despite recent gains made towards its control, many African countries still have endemic malaria transmission. This study aimed to assess malaria burden at household level in Kongo central province, Democratic Republic of Congo (DRC), and the impact of community participatory Water, Sanitation and Hygiene (WASH) Action programme. Methods Mixed method research was conducted in two semi-rural towns, Mbanza-Ngungu (a WASH action site) and Kasangulu (a WASH control site) in DRC between 1 January 2017 through March 2018, involving 625 households (3,712 household members). Baseline and post-intervention malaria surveys were conducted with the use of World Bank/WHO Malaria Indicator Questionnaire. An action research consisting of a six-month study was carried out which comprised two interventions: a community participatory WASH action programme aiming at eliminating mosquito breeding areas in the residential environment and a community anti-malaria education campaign. The latter was implemented at both study sites. In addition, baseline and post-intervention malaria rapid diagnostic test (RDT) was performed among the respondents. Furthermore, a six-month hospital-based epidemiological study was conducted at selected referral hospitals at each site from 1 January through June 2017 to determine malaria trend. Results Long-lasting insecticide-treated net (LLIN) was the most commonly used preventive measure (55%); 24% of households did not use any measures. Baseline malaria survey showed that 96% of respondents (heads of households) reported at least one episode occurring in the previous six months; of them only 66.5% received malaria care at a health setting. In the Action Research, mean incident household malaria cases decreased significantly at WASH action site (2.3 ± 2.2 cases vs. 1.2 ± 0.7 cases, respectively; p Conclusion This research showed high prevalence of positive malaria RDT among the responders and high household malaria incidence, which were reduced by a 6-month WASH intervention. DRC government should scale up malaria control strategy by integrating efficient indoor and outdoor preventive measures and improve malaria care accessibility.

Background Malaria is one of the most prevalent and deadliest illnesses in sub Saharan Africa. Despite recent gains made towards its control or elimination in past decades, many African countries still have endemic malaria transmission. Thus, the search for disease control strategies is indispensable. This study aimed to assess malaria burden at household level in Kongo central province, Democratic Republic of Congo (DRC), and the impact of community participatory water, sanitation and hygiene (WASH) action. Methods Mixed method research was conducted in two semi-rural towns, Mbanza-Ngungu (WASH action site) and Kasangulu (WASH control site) between 1 January 2017 through March 2018, involving 625 households (3,712 household members). Baseline and post-intervention malaria surveys focusing on malaria episodes and preventive measures in previous six-month period using the World Bank/WHO Malaria Indicator Questionnaire. An action research consisting of a six-month study was carried out which comprised two interventions: a community participatory WASH action aiming at eliminating mosquito breeding areas in the residential environment and a community anti-malaria education campaign. The latter was implemented at both the WASH action and Control sites. In addition, baseline and post-intervention malaria rapid diagnostic test (RDT) was performed among respondents. Furthermore, a six-month hospital-based epidemiological study was conducted from 1 January through June 2017. Medical records of patients admitted at selected referral hospitals (one hospital per study site) were used to determine malaria trend in the sites. Results Long-lasting insecticide-treated net (LLIN) was the most commonly used preventive measure (55%), followed by mosquito repellent (15%), indoor residual spraying (2%), LLIN and indoor residual spraying combination (2%); however, 24% of households did not use any measures. Baseline malaria survey showed that 96% of respondents (heads of households) have reported at least one malaria episode occurring in the previous six-month period (January-June 2017); of them only 66.5% of them received malaria care at a health setting. In the Action Research, at household level, mean number of self-reported incident malaria cases decreased at WASH action site (2.3±2.2 cases vs. 1.2±0.7 cases, respectively; p

Background: Previous studies have not specifically measured skin characteristics at common sites of pressure ulcers in high-risk older patients. Therefore, this study aimed to clarify the physiological skin characteristics at common pressure ulcer sites and their relationship with pressure ulcer risk and demographic/laboratory data in bedridden older Japanese patients. Methods: Fifty-five older patients (32 female) with a mean age of 82.4 ± 9.8 years (range, 61-103 years) in a long-term care facility and 25 female Japanese university students with a mean age of 21.4 ± 1.3 years (range, 20-22 years) were recruited for the study. Skin surface temperature, epidermal water content, transepidermal water loss (TEWL), skin erythema/redness, skin elasticity, and skin thickness were measured noninvasively and compared between age groups. The sacral and two heel areas were evaluated as they constitute sites predisposed to pressure ulcers, while the mid-to-lower back area was designated as the control site. Additionally, the correlation between demographic/laboratory data and skin physiological indices was determined. Results: Elderly patients showed a low epidermal water content at both heels (right heel, 14.8 ± 9.1 arbitrary units, AU.; left heel, 14.4 ± 8.3 AU). TEWL remained acceptable at all sites in older patients despite the presence of dry skin (back, 7.1 ± 1.8 g/hm2; sacrum, 7.4 ± 3.0 g/hm2; right heel, 17.7 ± 7.1 g/hm2; left heel, 19.4 ± 8.1 g/hm2). Back (0.61 ± 0.13 AU) and sacral (0.67 ± 0.11 AU) skin elasticity and sacral skin thickness (0.97 ± 0.56 cm) were significantly lower than those of healthy young people (0.86 ± 0.04 AU, 0.87 ± 0.05 AU, and 2.27 ± 0.84 cm, respectively; p < .001 for all sites). Moderate positive correlations were observed between back skin elasticity and serum albumin level (r = .445, p < .001), and between sacral skin thickness and BMI (r = .506, p < .001) in older patients. Conclusions: Older patients have a lower epidermal water content and skin elasticity and thickness but not higher TEWL at sites predisposed to pressure ulcers. Moderate correlations were found between skin characteristics and demographic/laboratory data.

Summary: Malaria is one of the most prevalent and deadliest illnesses in the Sub-Saharan Africa. Despite recent gains made towards its control or elimination in past decades, many African countries still have endemic malaria transmission. Therefore, the search for novel disease control strategies and approaches are in progress. This study aimed to evaluate household malaria burden in Kongo central province, Democratic Republic of Congo (DRC), and the impact of community participatory water, sanitation and hygiene (WASH) action. Methods: Mixed method study was conducted in two semi-rural towns, Mbanza-Ngungu (WASH action site) and Kasangulu (control site), involving 625 households (3,712 individuals). Baseline and post-intervention surveys were conducted; an action research consisting of six-month prospective study was carried out which comprised two interventions: (1) community participatory WASH action and (2) anti-malaria education campaign. The latter was implemented in both study sites. In addition, rapid diagnostic test (RDT) for malaria was performed in respondents. Findings: Prevalence of positive malaria RDT among respondents decreased (38% vs. 20%) at WASH-action site, whereas it increased at the control site but not significantly. Of 96% of respondents who reported at least one malaria event occurring in the previous six-month period, only 66.5% of them received malaria care at a health setting. At household level, long-lasting insecticide-treated net (LLIN) was the most commonly used preventive measure (55%), followed by mosquito repellent (15%), indoor residual spraying (IRS) (2%), LLIN-IRS combination (2%); however, 24% of households did not use any measures. Mean household malaria incidence decreased in WASH action site; 2.3±2.2 cases vs. 1.2±0.7 cases, whereas no significant change was noted in control site. Moreover, malaria incidence rate was highest (60.9%) among households living in proximity to grassy and stagnant water spots. Proximity to high risk area (grassy/stagnant water spots) for malaria (ORa=5.13; 95%CI: 2-29-8.07; p

Atopic dermatitis (AD) is a skin disorder characterized by filaggrin (FLG) defect. We evaluated sacran’s effects on dust-mite extracts (DME)-induced AD-like disease and also its effect on profilaggrin (proFLG) in a murine model of 2,4-dinitroflurobenze (DNFB)-induced contact hypersensitivity. In the murine AD-like disease model, allergic NC/Nga mice (N = 60) were randomly divided into five treatment groups of 12 animals each: 0.2% and 1%sacran; 0.1% Tacrolimus; Vaseline and buffer-treated controls. Blood samples were drawn and serum levels of representative Th-1, Th-2 and also Th-17 (IL-17A) cytokines were assayed by Cytometric Bead Array (CBA). In the contact hypersensitivity model, diseased NC/Nga mice (N = 20) were divided into four groups of five mice each [0.05%sacran, 0.05% chondroitin sulfate (CS), 0.5% prednisolone (PD), non-treated control group] and were treated for 14 days. Skin biopsies were performed for the measurement of proFLG-mRNA by real-time PCR. Sacran solutions and 0.1%Tacrolimus reduced disease severity, suppressed histological changes and decreased the serum Th-1 (IFN-γ, TNF-α, IL-2) and Th-2 (IL-4, IL-6, IL-10) cytokines in allergic mice (vs. controls). Additionally, a marked increase of proFLG-mRNA expression was observed in 0.05%sacran group (vs. control 0.05% CS and 0.5% PD groups). Thus, Sacran might be useful as a natural skin barrier enhancer and anti-allergic agent.

Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) can control massive postpartum hemorrhage. Case presentation A 41-year-old woman transferred to hospital following cesarean section presented in refractory hemorrhagic shock. REBOA was blindly performed in the emergency department. She immediately underwent hysterectomy and damage control surgery in the operating room. The aortic balloon, whose position was confirmed at zone II by postoperative X-ray, provided intermittent occlusion for 40 min during surgery. Hemodynamics were stabilized with these interventions, with massive transfusion required for severe coagulopathy perioperatively. She gradually recovered with intensive care but suffered ascending colon ischemia with perforation on day 16. She received a colostomy and was discharged without sequelae after 130 days. Amniotic fluid embolism was diagnosed according to clinical criteria and supplemental serum markers. Conclusions This patient suffered colonic ischemia possibly due to REBOA used to manage amniotic fluid embolism. REBOA requires careful consideration to avoid complications.

Objective Gastrointestinal dysmotility in critically ill patients is important as enteral nutrition is crucial. However, normal gut motility is impaired under conditions of critical illness subsequent to severe insult. Interstitial cells of Cajal (ICC) form an extensive network associated with the myenteric plexus in the enteric nervous system. There are few reports about ICC distribution in critically ill patients. The aim of this study was to evaluate ICC in critically ill patients. Methods Postmortem colon harvest was obtained from critically ill patients. Control specimens were obtained from patients without bowel movement problems who underwent hemicolectomy. The tissues were stained with c-Kit for ICC. The number of ICC was identified by counting from 10 high-power fields (HPFs). Results Specimens from six patients were analyzed and compared with those from six control patients. All patients had abnormalities of crypt architecture and inflammatory cell infiltrations. Mucosal thickness tended to be lower in the critically ill patients than in the controls (147 ± 47 versus 231 ± 127 μm; P = 0.15). Muscle layer thickness tended to be higher in the critically ill patients than in the controls (494 ± 163 versus 394 ± 258 μm; P = 0.44). ICC in the critically ill patients were almost depleted in the colon compared with those in the controls. Significantly fewer ICC were present in the critically ill patients than in the controls (0.45 versus 7.25 cells/HPF; P Conclusions Critical illness is associated with diminished numbers of ICC in the colon. This finding could have implications for dysmotility in critically ill patients.

Sepsis remains a major cause of death. Cytokines interact closely with each other and play a crucial role in the progression of sepsis. We focussed on the associations of a cytokine network with prognosis and disease severities in sepsis. This retrospective study included 31 patients with sepsis and 13 healthy controls. Blood samples were collected from patients on days 1, 2, 4, 6, 8, 11 and 15 and from healthy controls. Levels of PAI-1, IFN-α, IFN-γ, IL-1β, IL-6, IL-8, IL-12/IL-23p40, IL-17A, TNF-α, MCP-1, IL-4 and IL-10 were measured. SOFA, JAAM DIC and ISTH DIC scores were evaluated at the same times blood samples were taken. Network analysis revealed a network formed by PAI-1, IL-6, IL-8, MCP-1 and IL-10 on days 1, 2 and 4 throughout the acute phase of sepsis. There were positive correlations of each cytokine and the combined score (IL-6 + IL-8 + IL-10 + MCP-1) with the SOFA, JAAM DIC and ISTH DIC scores throughout the acute phase. A Cox proportional hazards model focussed on the acute phase showed that the above combined score was significantly related with patient prognosis, suggesting that the cytokine network of IL-6, IL-8, MCP-1 and IL-10 could play a pivotal role in the acute phase of sepsis.

Bacterial translocation is a major cause of multiple organ dysfunction syndrome in critical illness, and its management is an important therapeutic strategy. In this study, we focused on the key factors responsible for bacterial translocation including the intestinal microbiome and investigated the impact of molecular hydrogen therapy as a countermeasure against bacterial translocation in a murine model of sepsis. The experimental protocols were divided into the sham, saline treatment (control), and hydrogen treatment (H2) groups. In the H2 group, 15 mL/kg of hydrogen-rich saline (7 ppm) was gavaged daily for 7 days following cecal ligation and puncture (CLP). In the control group, normal saline was gavaged in the same way. In the results, the 7-day survival rate was significantly improved in the H2 group versus the control group (69% vs. 31%, P 0.05). The incidence of bacterial translocation at 24 h after CLP as assessed by cultivation of mesenteric lymph nodes and blood was significantly decreased in the H2 group versus the control group. Administration of hydrogen-rich saline also prevented the expansion of facultative anaerobic Enterobacteriaceae and ameliorated intestinal hyperpermeability at 24 h after CLP. Intestinal tissue levels of inflammatory mediators such as inducible nitric oxide synthases, tumor necrosis factor α, interleukin (IL)-1β, IL-6, and oxidative stress marker malondialdehyde at 6 h after CLP were down-regulated in the H2 group. These results suggest luminal administration of hydrogen-rich saline, which prevents intestinal dysbiosis, hyperpermeability, and bacterial translocation, could potentially be a new therapeutic strategy in critical illness.

Numerous environmental factors are incriminated in the occurrence of skin disorders. Here, we provide an overview on dermatitis caused by bacteria, Kawasaki disease (KD), and the association between silica-dust exposure and cutaneous autoimmune diseases. Common bacterial skin infections are caused by Staphylococcus (S. aureus, S. beta-hemolytic) and Streptococcus (S. pyogenes) species, and they include cellulitis, erysipelas, ecthyma, impetigo, and others. On the other hand, folliculitis is caused by a gram-negative bacteria known as Pseudomonas aeruginosa. Recently, reports have suggested the infectious origin of KD, and there have been several KD cases reported in Asia and western countries, and KD is considered as a leading cause of acquired heart disease in children population. Recent researchers have discovered KD-specific molecules that share the same structures with microbe-associated molecular patterns (MAMPs), suggesting that KD might have an infectious origin. In the acute phase, KD patients often present with fever, erythema, edema in the extremities and accompanied by pain, exanthema, cervical lymphadenopathy (mostly unilateral, nonsuppurative), conjunctival injection, and changes in the lips and tongue (strawberry tongue, a common sign in KD patients) and oropharyngeal mucosa. Occupational silica-dust exposure has been associated with the development of a number of autoimmune diseases, including scleroderma. Additionally, since the work by Erasmus, several case-control studies have demonstrated this association and provided clues on biomarkers (anti-centromeric proteins (anti-CNEP-B in particular), anti-Scl70) that can serve in the early diagnosis of systemic sclerosis or scleroderma as well as a screening tool among silica-dust-exposed workers.

Atopic dermatitis (AD) is a chronic relapsing, and severely pruritic skin disorder. AD is considered one of the major public health problems in the world, and its prevalence is increasing, especially in industrialized countries. This report contains updated knowledge on AD, its epidemiology, and current diagnostic and management approaches. There are approximately 10–20% of children and 1–3% of adult population affected worldwide. According to the International Study of Asthma and Allergies in Childhood (ISAAC), AD is most prevalent in developed and westernized countries. In most western countries, AD diagnosis is made by considering a number of clinical features (Fig. 3.1) and patient’s history, classified into two categories, major and minor criteria, a system developed by Hanifin and Rajka in the 1980s. Sometimes, AD diagnosis is challenging, given the similarities in clinical features with other conditions. The disease severity is estimated using a number of scoring systems, of whom SCORAD is the most commonly used. It takes into account the intensity of each of the five AD skin lesions (redness, swelling, oozing/crusting, scratch marks, lichenification), in addition to pruritus (itch) and sleeplessness, and also the area of affected body parts. With the rising AD incidence and its familial association, new prophylactic strategies are being investigated. Currently, emollient and probiotic preparations provide a new hope in AD prevention in individuals at risk. Bacterial (Staphylococcus aureus) and viral (herpes simplex) infections are the most prevalent in complications. These complications may justify the use of anti-allergic agent combined with an antibiotic or antiviral drug in some AD patients, in addition to conventional anti-allergic drugs. Finally, most commonly used conventional AD treatment agents are presented in this work.

The preventive association of synbiotics therapy has not been thoroughly clarified in mechanically ventilated patients. The purpose of this study was to evaluate whether synbiotics therapy has preventive association against septic complications in ventilated critically ill patients.Critically ill patients who were mechanically ventilated were included in this retrospective observational study. Patients who received synbiotics (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides) within 3 days after admission (denoted as synbiotics group) were compared with patients who did not receive synbiotics. The incidences of enteritis, pneumonia, and bacteremia were evaluated as clinical outcome. Enteritis was defined as an acute onset of diarrhea consisting of continuous liquid watery stools for more than 12 h. The confounding factors include APACHE II on admission, gender, the cause of admission and antibiotics.We included 179 patients in this study: 57 patients received synbiotics and 122 patients did not receive synbiotics. The incidences of enteritis were significantly lower in the synbiotics group compared with the control group (3.5% vs. 15.6%; p 0.05). The odds ratios for diarrhea-free days during the first 28 days for the synbiotics group as compared with the controls were 4.354 (95% confidence interval (CI), 2.407 to 7.877; p 0.001) in an ordinal logistic regression model with propensity scores. The odds ratios for pneumonia-free days during the first 28 days for the synbiotics group were 2.529 (95% CI, 1.715 to 3.731; p 0.001). The incidences of bacteremia did not have significant differences.Prophylactic synbiotics appeared to have preventive association on enteritis and pneumonia in mechanically ventilated critically ill patients.

Background Commensal microbiota deteriorate in critically ill patients. The preventive effects of probiotic/synbiotic therapy on microbiota and septic complications have not been thoroughly clarified in patients with sepsis. The objective of this study was to evaluate whether synbiotics have effects on gut microbiota and reduce complications in mechanically ventilated patients with sepsis. Methods Sepsis patients who were mechanically ventilated in the intensive care unit (ICU) were included in this randomized controlled study. Patients receiving daily synbiotics (Bifidobacterium breve strain Yakult, Lactobacillus casei strain Shirota, and galactooligosaccharides) initiated within 3 days after admission (the Synbiotics group) were compared with patients who did not receive synbiotics (the No-Synbiotics group). The primary outcome was infectious complications including enteritis, ventilator-associated pneumonia (VAP), and bacteremia within 4 weeks from admission. The secondary outcomes included mortality within 4 weeks, fecal bacterial counts, and organic acid concentration. Enteritis was defined as the acute onset of continuous liquid stools for more than 12 h. Results Seventy-two patients completed this trial; 35 patients received synbiotics and 37 patients did not receive synbiotics. The incidence of enteritis was significantly lower in the Synbiotics than the No-Synbiotics group (6.3% vs. 27.0%; p

Crush injury patients often have systemic inflammatory response syndrome that leads to multiple organ failure. Receptor for advanced glycation endproducts (RAGE) functions as a pattern recognition receptor that regulates inflammation. We evaluated the effects of anti-RAGE antibody in a crush injury model. Pressure was applied to both hindlimbs of rats for 6 h by 3.0-kg blocks and then released. Animals were randomly divided into the sham (RAGE-Sh) group, crush (RAGE-Ctrl) group or anti-RAGE antibody-treated crush (RAGE-Tx) group. Samples were collected at 3, 6 and 24 h after releasing pressure. In the RAGE-Ctrl group, fluorescent immunostaining in the lung showed upregulated RAGE expression at 3 h. The serum soluble RAGE (sRAGE) level, which reflects the amount of RAGE expression in systemic tissue, increased at 6 h. Serum interleukin 6 (IL-6; systemic inflammation marker) increased immediately at 3 h. Histological analysis revealed lung injury at 6 and 24 h. Administration of anti-RAGE antibody before releasing compression inhibited upregulated RAGE expression in the lung alveoli, suppressed RAGE-associated mediators sRAGE and IL6, attenuated the lung damage and improved the 7-day survival rate. Collectively, our results indicated that the use of anti-RAGE antibody before releasing compression is associated with a favourable prognosis following crush injury.

Purpose One of the pathophysiological processes in sepsis is endothelial dysfunction, which leads to disseminated intravascular coagulation (DIC). Syndecan-1 is a major structural component of the endothelium and plays a key role in endothelial function. The purpose of this study was to assess the value of syndecan-1 as a predictive marker for DIC in sepsis. Methods We performed a prospective observational study of patients with sepsis from February 2014 to July 2015. Serial change of hemostatic markers, anticoagulant and fibrinolytic markers (antithrombin, PAI-1), endothelial markers (syndecan-1, VCAM-1, E-selectin), and inflammatory markers (IL-1β, IL-6, IL-8, HMGB-1, histone-H3) were analyzed. Clinical data including APACHE II, SOFA, and DIC scores and 28-day mortality were also evaluated. Results During the study, 39 septic patients and 15 healthy controls were included. Syndecan-1 levels were significantly increased in the septic patients compared with the healthy controls. Of the septic patients, non-survivors had higher syndecan-1 levels than did the survivors on days 1, 2, and 4. Significant correlations on day 1 were found between syndecan-1 levels and APACHE II, SOFA, and DIC scores, hemostatic markers, IL-1β, IL-8, and PAI-1. Syndecan-1 levels on day 1 were also significantly higher in patients with than without DIC and had strong discriminative power for the prediction of both DIC development and subsequent mortality, with AUCs of 0.79 and 0.85, respectively. Conclusion Syndecan-1 levels were associated with not only the severity of illness and mortality but also DIC development in sepsis, suggesting that syndecan-1 could be a predictive marker of DIC.

Mowat-Wilson syndrome (MOWS) is a congenital disease caused by de novo heterozygous loss of function mutations or deletions of the ZEB2 gene. MOWS patients show multiple anomalies including intellectual disability, a distinctive facial appearance, microcephaly, congenital heart defects and Hirschsprung disease. However, the skin manifestation(s) of patients with MOWS has not been documented in detail. Here, we recognized that MOWS patients exhibit many Ehlers-Danlos syndrome (EDS)-like symptoms, such as skin hyperextensibility, atrophic scars and joint hypermobility. MOWS patients showed a thinner dermal thickness and electron microscopy revealed miniaturized collagen fibrils. Notably, mice with a mesoderm-specific deletion of the Zeb2 gene (Zeb2-cKO) demonstrated redundant skin, dermal hypoplasia and miniaturized collagen fibrils similar to those of MOWS patients. Dermal fibroblasts derived from Zeb2-cKO mice showed a decreased expression of extracellular matrix (ECM) molecules, such as collagens, whereas molecules involved in degradation of the ECM, such as matrix metalloproteinases (MMPs), were up-regulated. Furthermore, bleomycin-induced skin fibrosis was attenuated in Zeb2-cKO mice. We conclude that MOWS patients exhibit an EDS-like skin phenotype through alterations of collagen fibrillogenesis due to ZEB2 mutations or deletions.

Miura S, Satake M, Tamura Y, Ikeda M, Kawagoshi A, Sugawara K, Takahashi H, Homma M, Sakata S, Shioya T. Evaluation of walking time according to walking speed using a triaxial accelerometer system. Jpn J Compr Rehabil Sci 2013; 4: 73−79. Purpose: The primary purpose of this study was to quantify the walking time in daily life as slow and fast walking times using a newly improved triaxial accelerometer system. The secondary purpose was to study the slow and fast walking times of healthy young and elderly adults and stable patients with chronic obstructive pulmonary disease (COPD) using this system. Methods: Twenty-six healthy young subjects, 15 healthy elderly adults, and 11 stable COPD patients participated in this study. The subjects’ time spent walking, standing, sitting, and lying down were assessed using an activity monitoring and evaluation system (A-MESTM). We evaluated the slow and fast walking times according to changes in the detection threshold in the system’s software. Results: The distinguishing speed was found to be 2 km/h, and thus we divided the subjects’ walking time into slow (

The replenishment of adiponectin—an adipocyte-derived hormone with salutary health effects—has recently been proposed as a new approach to treat hypertension, also ameliorate cardiovascular and metabolic risks. We conducted a prospective placebo-controlled, non-randomized and investigator-blinded dietary intervention study to evaluate the health effects of dietary intake of Sujiaonori (Ulva/Enteromorpha prolifera Müller) algal biomaterial (SBM), especially on adiponectin production, blood pressure (BP), and body mass index (BMI) in human subjects. Participants (N = 32) were divided into two equally sized groups (n = 16 for each group): SBM group (subjects supplemented with 3 g SBM powder twice a day during meal) and the control group (subjects who took 3 g of a supplement made of 70% corn starch powder and 30% spinach twice a day) for four weeks. Two health survey questionnaires (dietary and current health questionnaires) were completed anonymously, saliva sampling was done for adiponectin measurement by ELISA, and blood pressure (BP) and anthropometric parameters were measured at baseline and four weeks later. Student paired t-test was performed to compare baseline and post-intervention data on outcome variables between the two study groups. Results showed a 2.24-fold increase in adiponectin level in SBM group (2.81 and 6.26 ng/mL at baseline and at the end of study, respectively) (p < 0.01); whereas no significant change was observed in controls (3.58 and 3.51 ng/mL, respectively) (p > 0.05). In SBM subjects, an improvement of BP profile was noted with a significant decrease in systolic BP (p < 0.01). A positive correlation was found between SBM supplementation and adiponectin level, whereas an inverse correlation was noted between SBM supplementation and blood pressure, and also BMI. These findings suggest that SBM-increased adiponectin level and improved BP in a sample of Japanese young adults, and has the potential to improve blood pressure in humans.

A 71-year-old female presented to our hospital with recent increase in diarrhea and body weight loss. Radiologic and endoscopic examinations revealed rectal adenocarcinoma with synchronous multiple liver metastases accompanied by widespread intrabiliary tumor thrombi. After primary tumor resection, systemic treatment using 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI), and panitumumab was given. The disease responded well to treatment and about two years after rectal surgery she underwent left hemihepatectomy with removal of tumor thrombi. Histological examination showed that intrahepatic bile dusts were filled with tumor thrombi indicative of a tubular adenocarcinoma resembling rectal adenocarcinoma. No tumor invasion was observed on the surgical margins. She received 5-fluorouracil and leucovorin as adjuvant treatment for six months, and she has not shown any evidence of recurrence for one year after hepatectomy.

45歳，女性。初診の3ヵ月前より両下腿に紅斑，紫斑，潰瘍が出現した。初診時，両下腿および内足縁に網状の紅斑，紫斑が散在し，一部に痂皮を付着する潰瘍を認めた。病理組織では真皮全層に小血管が増生し，内腔は拡張して好酸性無構造物質による閉塞像を認めた。臨床検査から単クローン性のI型クリオグロブリン血症による末梢循環障害および皮膚潰瘍と診断した。更に，骨髄およびリンパ節に濾胞構造と，IgM（＋），λ（＋）の大型のリンパ球を認め，濾胞性リンパ腫と診断した。化学療法によるリンパ腫の寛解に伴って，血中のクリオグロブリンは消失し，皮疹は軽快した。

〔目的〕本研究の目的は，片膝しゃがみ位で床面から重量物を持ち上げる際に，下肢の機能の左右の相違が床反力に与える影響について検討することである。〔対象〕対象者は，平均年齢20.5±3.6歳の学生30名である。〔方法〕ボールを蹴る側の脚を利き脚と規定し，利き脚と非利き脚の等尺性膝伸展筋力，利き脚を前にした場合と非利き脚を前にした場合の片膝しゃがみ位を開始肢位とし，床面から重量物を持ち上げる際の床反力を測定した。〔結果〕膝伸展筋力には，利き脚と非利き脚との間で有意差は認められなかった。利き脚と非利き脚をそれぞれ前に出した時の床反力には，Fz，Fx，Fyのいずれも有意差は認められなかった。FxおよびFyと左右の筋力の間には有意な相関は認められなかった。Fzについては，筋力との間に有意な相関が認められたが，利き脚を前にした場合の方が非利き脚を前にした場合よりも相関が比較的強かった。〔結語〕以上より，利き脚は動作を行う際に純粋に筋力を反映させることが可能な，いわば器用な脚と推察された。それに対して，非利き脚は純粋に筋力のみを動作に反映することはできず，巧緻性や協調性などの影響を受け運動を調節するために他の要素も必要となる，いわば器用さの劣る脚であると考えられた。

Drug reaction can be one of the triggering factors either for exacerbation of pre-existing psoriasis or precipitation of psoriasis de novo. Herein, we report a case with psoriasiform drug eruption due to pravastatin, but it relapsed after discontinuance of the drug. Serial investigation of the histopathology and immunohistochemistry with anti-signal transducer and activator of transcription 3 (STAT3) revealed drug reaction-associated lesions intermingled with psoriasiform changes, which later predominated, suggesting a conversion into psoriasis de novo.

49歳, 男性。体幹・四肢に自覚症状のない紅斑, 丘疹が生じ増加してきた。病理組織にてCD4陽性を示す異型細胞の浸潤, TCR遺伝子再構成を認め, 皮膚T細胞リンパ腫 (CTCL) と診断した。ステロイドパルス療法後, ステロイドと低用量MTX内服投与で治療していたが, 皮疹が再燃した。病理組織にて大型の異型リンパ球の密な浸潤を認め, CD4陽性を示す異型T細胞とCD20, CD79a陽性を示す異型B細胞が混在していた。免疫グロブリンH鎖に遺伝子再構成を認めた。EBERs陽性細胞を少数認め, 組織学的にEBV感染が証明できた。以上よりCTCL患者にメトトレキセート関連リンパ増殖性疾患 (MTX-LPD) が発症したと考えた。MTX中止のみでは軽快せず, フルダラビンによる化学療法を施行した。MTX-LPDについて原疾患, Epstein-Barr Virusとの関連など過去の報告例と比較検討した。MTX-LPDは重篤な医原性疾患の一つであると考え報告する。

症例は71歳，男性。当科初診の7ヵ月前に右耳朶後面に増殖性局面が出現し，3ヵ月後に自壊した。摘出したところ，2週間後に創は潰瘍化した。外科的処置を繰り返すたびに潰瘍が拡大し，耳朶が下垂した状態になった。増殖性局面の病理組織所見はpseudoepitheliomatous hyperplasiaの像を示し，真皮に好中球，単核球および形質細胞が浸潤していた。増殖性膿皮症と診断し，プレドニゾロン40mg/日を内服投与したところ，潰瘍は上皮化したが，漸減後中止した3日後に発熱とともに潰瘍が再出現した。シクロスポリン3mg/kg/日の内服投与により再び潰瘍の上皮化はすすみ，現在漸減中である。

ステロイドと低用量メソトレキセート (以下MTXと略す) の併用療法が奏功した未分化型大細胞リンパ腫 (Anaplastic large cell lymphoma; 以下ALCLと略す) の1例を経験したので報告する。症例は60歳, 女性。初診の4年前に下肢に出現した皮疹をALCLの診断のもと, 近医および当科でステロイド外用・内服, PUVA療法, IFN-γ注射, エトレチナート内服, 電子線照射などで治療されていたが軽快再発を繰り返していた。平成16年の再発時にCHOP療法施行後に本治療を開始したところ, CHOP療法後に残存していた病変はすべて速やかに消退した。以後38ヵ月間再発はみられない。本治療はCHOPなどの多剤併用化学療法施行前の, あるいは施行後の補助・維持療法として推奨される治療法であると考えられる。

6歳, 女児。4歳頃より右側腹部に腫瘤が出現し徐々に増大した。やがて中央が潰瘍化したため当科を受診した。中央が潰瘍化した直径18mmのドーム状に隆起する淡紅色腫瘤が右側腹部に単発性に認められ, 診断目的に単純摘出術を施行した。病理組織では胞体内に好酸性の顆粒を持つ細胞が真皮内に密に浸潤し, 被膜に取り囲まれた腫瘤を形成していた。腫瘍細胞はS-100蛋白, vimentin陽性で, 顆粒がPAS陽性であったことより, 顆粒細胞腫と診断した。臨床的に潰瘍がみられ, 紡錘形腫瘍細胞を混じていたこと, 一部に被膜外浸潤を認めたことから追加拡大切除を行った。再切除標本では腫瘍細胞の残存はなく, 1年後の現在まで再発を認めていない。本疾患は小児には稀な疾患であり, また臨床的および病理組織学的に悪性顆粒細胞腫との鑑別を要したので報告する。

76歳, 女性。外陰部から大腿に境界明瞭な紅斑と黒褐色斑と脱色素斑の混在を認め, 紅斑上に紅色結節を認めた。結節部の病理組織所見はPaget細胞が真皮全層に浸潤していた。右鼠径リンパ節を触知し, CTでは右鼠径と右外腸骨動脈領域のリンパ節腫大を認めた。CEAは正常範囲内であった。病変境界部から2cm離して拡大切除し, 両側浅深鼠径リンパ節と右外腸骨動脈領域リンパ節郭清術を施行した。右鼠径, および右外腸骨動脈領域リンパ節にPaget細胞の浸潤を認め, Stage III(T3N1M0)と診断した。手術5ヵ月後に腹部大動脈分岐部にリンパ節転移を認めた。ドセタキセル(タキソテール®)療法を開始したところ, 3ヵ月半後(9回投与後)には画像診断上complete responseを得た。治療開始13ヵ月後の現在, 再発および転移を認めていない。

Proteins destined for the peroxisome matrix or membrane possess distinct targeting signals that engage signal sequence receptors to drive their transport to their final subcellular destination. Peroxisomal targeting signal 1 (PTS1) and 2 (PTS2) are well characterized as signaling the import from the cytosol into the peroxisomal matrix of soluble peroxisomal enzymes. The expression vectors of the enhanced green fluorescent protein (eGFP)-tagged alanine:glyoxylate aminotransferase (AGT) and deletion mutants were introduced into HeLa cells to identify the peroxisomal targeting signal of the AGT. Two sites of the targeting signals into peroxisome, an amino acid sequence containing 59-66 a.a. (8 amino acids) and 389-392 a.a. (4 amino acids, KKKL, but not KKL) on the AGT were clarified. In a three-dimensional structural model, their sites were separately located on the surface of the AGT protein.

Background: The histological resemblance between extramammary Paget disease and Bowen disease has been described since Bowen’s original article was published in 1912. Methods: We herein describe a case of vulval primary extramammary Paget disease in a 61-year-old women with the histological features of Bowen disease. Results: Histological examination of a biopsy specimen showed acanthosis with full-thickness cellular atypia, focal hyperkeratosis and parakeratosis in the epidermis, and no characteristic Paget cells were observed. However, histological examination of an operative specimen revealed areas characteristic of Paget disease and Bowen disease. Overall, the areas characteristic of Bowen disease and Paget disease occupied 6% and 32% of the total operative specimen, respectively. The two areas were sharply separated. Immunohistochemical findings showed carcinoembryonic antigen to be expressed in areas containing Paget cells, but not in the areas characteristic of Bowen disease. Cytokeratin 7 (CK7) (OV-TL 12/30) and CK8 (35βH11) were strongly expressed in both of these areas. The staining for high-molecular-weight cytokeratins was negative in both of these areas. Conclusions: Our findings indicated that primary extramammary Paget disease and squamous cell carcinoma in situ arose multifocally from a common cell in the epidermis.