Clinical significance of integrin αV and ß superfamily members and focal adhesion kinase activity in oral squamous cell carcinoma: a retrospective observational study.

Objectives: Integrins are heterodimeric transmembrane plasma membrane proteins composed of α- and ß-chains. They bind to extracellular matrix (ECM) and cytoskeletal proteins as ECM protein receptors. Upon ECM protein binding, integrins activate focal adhesion kinase (FAK) and transduce various signals. Despite their importance, integrin and FAK expression in oral squamous cell carcinoma (OSCC) tissue and the prognosis of patients with OSCC remains elusive. Methods: In a retrospective observational study, we immunohistochemically evaluated integrin αV, ß1, ß3, ß5, ß6, FAK, and phosphorylated-FAK (pFAK) expressions as prognostic predictors in 96 patients with OSCC. Patients were classified as positive or negative based on staining intensity, and clinicopathologic characteristics and survival rates of the two groups were compared. The association between above integrin-related proteins and PD-1 or PD-L1 in OSCC tissues was investigated. Results: We observed immunohistochemical integrin αV, ß1, ß6, ß8, and FAK expressions in the cell membrane and cytoplasm but not integrin ß3 and ß5 in the OSCC tissues. pFAK was expressed in the cytoplasm of OSCC cells. The overall survival rate significantly decreased in pFAK-positive OSCC patients compared to the negative group, and cervical lymph node metastasis significantly increased in integrin ß8-positive patients with OSCC (p < 0.05). No association between integrin-related proteins and PD-1 or PD-L1 in OSCC tissues was observed. Conclusion: Our results indicate that pFAK and integrin ß8 are prognostic factors for OSCC. Therefore, pFAK- and integrin ß8-targeting new oral cancer diagnostic and therapeutic methods hold a promising potential.

Interaction of Integrin αvß8 With Type I Collagen Promotes Squamous Cell Carcinoma Cell Motility via RAC1 Activation.

BACKGROUND/AIM: The interaction of integrin αvß8 with type I collagen was shown to promote oral squamous cell carcinoma (SCC) cell proliferation via the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. However, the role of integrin αvß8 in SCC progression remains poorly understood. In this study, the role of integrin αvß8 in oral SCC progression was therefore investigated. MATERIALS AND METHODS: Integrin αv and ß8 protein expression in oral SCC cells was examined by western blotting. Oral SCC cell motility was investigated using modified Boyden chamber assays. Behavior of oral SCC cells was examined in three-dimensional culture using type I collagen gel. Ras homolog family member A (RHOA), Ras-related C3 botulinum toxin substrate 1 (RAC1), and cell division control protein 42 homolog (CDC42) activity of oral SCC cells was analyzed by pull-down assays. RESULTS: SCC cells with high integrin αvß8 expression levels had a high ability to migrate on type I collagen and exhibited enhanced invasion into type I collagen gel. In SCC cells with high integrin αvß8 expression level, cultivation on type I collagen induced RAC1 activation. Treatment with RAC1 inhibitor reduced type I collagen-induced motility of SCC cells. Down-regulation of integrin ß8 by specific antisense oligonucleotide reduced type I collagen-induced RAC1 activation and suppressed cell motility and invasion into type I collagen gel. CONCLUSION: The interaction of integrin αvß8 with type I collagen facilitates SCC cell motility and invasion via RAC1 activation. Therefore, integrin αvß8 and RAC1 may represent new targets for inhibiting metastasis and invasion in patients with oral SCC.

Descending thoracic aortic repair outcomes for chronic aortic dissection: a single-centre experience.

OBJECTIVES: Thoracic endovascular aortic repair is a widely accepted treatment for chronic aortic dissection because of good early results compared to open surgical repair. We provide early and long-term results of descending thoracic aortic repair for chronic aortic dissection. METHODS: Patients who underwent descending thoracic aortic repair for chronic aortic dissection between January 2012 and December 2020 at Kawasaki Aortic Centre were included in this analysis. RESULTS: Four hundred ninety-two patients (median age, 64 years; interquartile range, 52-75 years) were included. The median duration of follow-up was 3.2 years (interquartile range, 1.5-5.2 years). The early mortality rate was 2.0% (n = 10); strokes occurred in 17 patients (3.5%); and spinal cord injuries occurred in 30 patients (6.1%). Early major adverse events including early death, stroke, spinal cord injury, tracheostomy and haemodialysis at the time of discharge occurred in 62 patients. Multivariable analysis indicated that age > 70 years and non-elective surgery were predictors of early major adverse events. Among patients without both risk factors (i.e. low-risk patients), 1 early death (0.4%), 3 strokes (1.5%) and 1 spinal cord injury (0.4%) were observed, 2 tracheostomies were performed (0.8%) and no patients required haemodialysis at the time of hospital discharge. The 5-year survival rate was 87.2%. The cumulative incidence of chronic aortic dissection-related aortic reintervention at 5 years was 7.9%. CONCLUSIONS: Descending thoracic aortic repair for chronic aortic dissection resulted in good early and long-term results, and it can serve as the gold standard for low-risk patients.

Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020.

The prevalence of sleep disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared in order to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Because sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021.

Therapeutic effect of laparoscopic sleeve gastrectomy on obstructive sleep apnea and relationship of type 2 diabetes in Japanese patients with severe obesity.

AIMS/INTRODUCTION: Obstructive sleep apnea (OSA) is among the most important obesity-related diseases, and offers the potential for accelerated the early onset and progression of type 2 diabetes. The aim of the present study was to clarify the therapeutic effect of laparoscopic sleeve gastrectomy on OSA in severely obese Japanese patients, and to find correlations between OSA improvements and ß-cell function (BCF). MATERIALS AND METHODS: Between September 2013 and December 2019, 61 patients who underwent laparoscopic sleeve gastrectomy were enrolled. The apnea-hypopnea index (AHI) was used to diagnose OSA. The tongue area, uvula area and other parameters were measured using cone-beam computed tomography. Regarding BCF parameters, the homeostasis model assessment of ß-cell function, insulinogenic, Matsuda and disposition indexes were used to evaluate the improvement in BCF. Improvement of OSA was defined as AHI <15. RESULTS: The improvement rate of OSA was 51.8% (29/56). The change in AHI was significantly correlated with the excess weight loss percentage (ρ = 0.501), changes in tongue area (ρ = 0.350) and uvula area (ρ = 0.341). Multivariate analysis showed that preoperative AHI and postoperative hemoglobin A1c were independent prognostic factors of OSA non-improvement. The homeostasis model assessment of ß-cell function (P < 0.001), the insulinogenic index (P < 0.001) and the disposition index (P = 0.019) of patients with AHI of <15 were significantly higher than those in patients with AHI of ≥15. CONCLUSIONS: Laparoscopic sleeve gastrectomy is a promising procedure for severely obese patients with OSA. BCF recovery was found to be significantly higher in patients with OSA improvement.

Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020.

The prevalence of sleep-disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Since sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021.

False-positive cases in multiple sleep latency test by accumulated sleep debt.

PURPOSE: Multiple sleep latency test (MSLT) is performed as objective assessment of sleepiness, on the following day after polysomnography (PSG). In most clinics, patients are required to stay for 2 days. However, if patients have chronic sleep debt before the examination, even if they get adequate nocturnal sleep during the initial PSG, their sleep debt would not be fully resolved, affecting MSLT results. This may lead to improper administration of psycho-stimulant medication. To clarify the sleep debt for the patients who showed short sleep latencies, we compared the mean sleep latencies of MSLTs. METHODS: Twelve hypersomnolent males, who underwent MSLTs (1st MSLT with 1 night and 2nd MSLT with more than 3 nights), were enrolled. We selected these cases based on the longer total sleep time on PSG night compared to the mean total sleep time on pre-examination sleep logs and shortened sleep latencies on PSG. To evaluate the effect of the sleep debt for the patients who showed short sleep latencies, we extended their hospitalization or re-hospitalized them. RESULTS: The mean sleep latency of 1st MSLT was 5.8 minutes and that of 2nd was 13.9 minutes (P < .001). Among these 12 cases, 5 cases altered from short to normal sleep latencies at the 2nd MSLT. These 5 cases were prevented from over-diagnoses by the extension of evaluations. CONCLUSIONS: The sleep debt may produce false-positive results when patients are examined by standard PSG and MSLT. Accumulation of sleep debt will cause shortened sleep latencies in the following nights. Patients should be advised to extend their hospitalization before PSG and MSLT to reduce the chronic sleep debt for accurate diagnosis of hypersomnia.

Left Ventricular Hypertrophy Is More Prevalent in Type B than Type A Aortic Dissection.

OBJECTIVES: Several factors determining differences between types A and B aortic dissection (AD) have been reported; however, little data exist examining their differences in left ventricular hypertrophy (LVH). We compared the prevalence of LVH in patients with types A and B AD. METHODS: We retrospectively analyzed 334 patients with acute AD (227 type A; 107 type B). Concentric hypertrophy (CH; increased left ventricular mass index [LVMI] and relative wall thickness [RWT]) is one of four types of left ventricular (LV) geometry thought to be most associated with hypertension. We compared LVMI and the prevalence of CH in patients with types A or B AD. Multivariate logistic regression analyses of variables associated with type B AD were performed. RESULTS: Comparing type A and B AD, LVMI (95 ± 26 vs.107 ± 28, p <0.001) and prevalence of CH (26% vs. 44%, p = 0.001) were higher in type B AD. In multivariate analysis, CH was an independent factor associated with type B AD (odds ratio: 2.62, confidence interval: 1.54-4.47, p <0.001). CONCLUSIONS: Our data suggested LVH was more prevalent in type B than in type A AD. Considering LVH usually results from hypertension, patients with type B AD may be more affected by hypertension than those with type A.

Oral squamous cell carcinoma of the tongue dorsum with multiple cancer-associated mutations in the TP53 gene.

OBJECTIVES: Squamous cell carcinoma (SCC) of the tongue is one of the most common oral cancers, tongue dorsum being a site of low incidence of primary SCC. We report a rare case of SCC of the tongue dorsum in a 69-year-old man having a history of multiple cancers, including esophageal cancer, gastric cancer, and renal cell carcinoma. We discuss the findings in relation to past reports. MATERIALS AND METHODS: TP53 was PCR amplified using the genomic DNA extracted from peripheral blood mononuclear cells and formalin-fixed, paraffin-embedded tissue sections from the tumor site of the patient, and was sequenced. RESULTS: Physical examination revealed an elastic hard mass on the tongue dorsum, with a size of 22 × 15 mm. There were no palpable enlarged lymph nodes in the cervical and submandibular region. An incisional biopsy was performed. The diagnosis was well-differentiated SCC of tongue, T2N0M0, Stage II, and was treated through surgery. Surgical specimen of the deep ulcer area showed increased expression of p16 protein with no expression of p53 protein. He had a heterozygous gene polymorphism (c.215C > G: p.Pro72Arg) and a germline mutation (c.838A > T: p.Arg280*) of the TP53. However, there has been no recurrence or metastasis of the tongue carcinoma through the follow-up for 3 years. CONCLUSION: Germline TP53 mutation and codon 72 polymorphism are risk factors for uncontrolled cell proliferation, possibly leading to the patient's clinical phenotype. Therefore, strict follow-up is required when treating those who are at a higher risk of cancer due to a TP53 mutation.

Diabetes care providers' manual for disaster diabetes care.

To ensure that experiences and lessons learned from the unprecedented 2011 Great East Japan Earthquake are used to improve future disaster planning, the Japan Diabetes Society (JDS) launched the "Research and Survey Committee for Establishing Disaster Diabetes Care Systems Based on Relevant Findings from the Great East Japan Earthquake" under the supervision of the Chairman of the JDS. The Committee conducted a questionnaire survey among patients with diabetes, physicians, disaster medical assistance teams (DMATs), nurses, pharmacists, and nutritionists in disaster areas about the events they saw happening, the situations they found difficult to handle, and the needs that they felt required to be met during the 2011 Great East Japan Earthquake. A total of 3,481 completed questionnaires were received. Based on these and other experiences and lessons reported following the 2011 Great East Japan Earthquake and the 2004 Niigata-Chuetsu Earthquakes, the current "Manual for Disaster Diabetes Care" has been developed by the members of the Committee and other invited authors from relevant specialties. To our knowledge, the current Manual is the world's first to focus on emergency diabetes care, with this digest English version translated from the Japanese original. It is sincerely hoped that patients with diabetes and healthcare providers around the world will find this manual helpful in promoting disaster preparedness and implementing disaster relief.

Pregnancy rate after emergency contraception with single-dose oral levonorgestrel in Japanese women.

AIM: To evaluate the pregnancy rate in Japanese women treated with levonorgestrel for emergency contraception. METHODS: This retrospective record-based medical study included 1000 women who visited our clinic for emergency contraceptive treatment with 1.5 mg single-dose oral levonorgestrel, followed by 50 µg hormonal oral contraceptive from May 2011 to December 2017. The outcomes of the emergency contraceptive treatment were recorded at a follow-up visit, and descriptive statistics were obtained. RESULTS: The number of women treated with levonorgestrel at the clinic increased from 2011 to 2015, but there was no subsequent increase thereafter. Most women were in their 20s (57.4%), followed by their 30s (19.3%) and teens (18.3%). Of the 1000 women treated with levonorgestrel, 659 were followed up. Among the 659 women with follow-up data, 16 were pregnant (2.4%), of whom 11 underwent abortions, three had miscarriages, and two delivered at term. The timing of unprotected sexual intercourse relative to the estimated ovulation date among the pregnant women ranged from -3 to 23 days. The most commonly used contraceptive method before the emergency contraceptive visit was condoms (89.3%, 887/993). No new safety concerns were identified throughout the study period. CONCLUSION: The pregnancy rate after levonorgestrel treatment in Japanese women was low, and similar to that reported in previous studies. Information on contraceptive methods and emergency contraception with levonorgestrel needs to be better disseminated among women of childbearing age.

Diabetes Care Providers' Manual for Disaster Diabetes Care.

To ensure that experiences and lessons learned from the unprecedented 2011 Great East Japan Earthquake are used to improve future disaster planning, the Japan Diabetes Society (JDS) launched the "Research and Survey Committee for Establishing Disaster Diabetes Care Systems Based on Relevant Findings from the Great East Japan Earthquake" under the supervision of the Chairman of the JDS. The Committee conducted a questionnaire survey among patients with diabetes, physicians, disaster medical assistance teams (DMATs), nurses, pharmacists, and nutritionists in disaster areas about the events they saw happening, the situations they found difficult to handle, and the needs that they felt required to be met during the 2011 Great East Japan Earthquake. A total of 3,481 completed questionnaires were received. Based on these and other experiences and lessons reported following the 2011 Great East Japan Earthquake and the 2004 Niigata-Chuetsu Earthquakes, the current "Manual for Disaster Diabetes Care" has been developed by the members of the Committee and other invited authors from relevant specialties. To our knowledge, the current Manual is the world's first to focus on emergency diabetes care, with this digest English version translated from the Japanese original. It is sincerely hoped that patients with diabetes and healthcare providers around the world will find this manual helpful in promoting disaster preparedness and implementing disaster relief.

Open Thoracoabdominal Aortic Aneurysm Repair: Contemporary Outcomes for 393 Elective Cases.

BACKGROUND: The purpose of this study was to reveal the midterm and long-term mortality rates among patients with thoracoabdominal aortic aneurysm (TAAA) after open TAAA repair and to clarify the effect of aneurysm type on mortality. METHODS: We retrospectively analyzed data for 393 patients (290 men; age, 63.2 ± 12.7 years) who underwent open TAAA repair of elective Crawford extent I, II, or III TAAAs (62, 197, and 134 patients, respectively) between June 2003 and December 2015. The overall survival probability and differences according to aneurysm type were assessed using the Kaplan-Meier product limit method. Also, the effect of aneurysm type on mortality was assessed using the hazard ratio and Cox proportional hazards regression. RESULTS: The overall survival probabilities at 3 months, 1 year, 5 years, and 10 years were 90%, 84%, 78%, and 75%, respectively. The age-adjusted relative mortality rate was significantly higher for patients with dissecting aneurysms than for those with nondissecting aneurysms (relative risk, 1.62; 95% confidence interval, 1.03 to 2.55). In the multivariate Cox proportional hazard regression model, the hazard ratio for all-cause mortality did not differ between patients with dissecting and those with nondissecting aneurysms. However, those with dissecting aneurysms had increased mortality rates as their percentage vital capacity decreased (hazard ratio, 0.7; 95% confidence interval, 0.5 to 1.0); a similar trend was not observed for those with nondissecting aneurysms. CONCLUSIONS: Open TAAA repair can be safely performed with acceptable midterm and long-term results. Poor pulmonary function can impair the survival outcome of patients with dissecting aneurysms.

Decrease of Plasma Soluble (Pro)renin Receptor by Bariatric Surgery in Patients with Obstructive Sleep Apnea and Morbid Obesity.

BACKGROUND: Plasma concentrations of soluble (pro)renin receptor [s(P)RR], which are elevated in patients with obstructive sleep apnea (OSA), have not been studied in morbid obesity. The aim of this study is to clarify effects of bariatric surgery on plasma s(P)RR concentrations and identify associated factors for their changes in OSA patients with morbid obesity. METHODS: Twenty-three patients with OSA complicated by morbid obesity (10 men and 13 women; body mass index, 40.7 ± 6.16 kg/m2) without chronic kidney disease were followed up after bariatric surgery. Overnight polysomnography (PSG) was performed before surgery, and 4 and 24 weeks after surgery. Plasma s(P)RR concentrations were measured each morning after PSG. RESULTS: Preoperative plasma s(P)RR concentrations showed significant positive correlations with serum creatinine (P < 0.05), arousal index (P < 0.01), apnea-hypopnea index (AHI) (P < 0.05), apnea index (P < 0.005), and desaturation index (P < 0.05), and a significant inverse correlation with an estimated glomerular filtration rate (P < 0.05). With the improvement of these PSG parameters, plasma s(P)RR concentrations significantly decreased from 15.3 ± 3.6 to 12.5 ± 2.7 ng/mL 4 weeks after surgery, which further decreased to 11.4 ± 2.4 ng/mL 24 weeks after surgery. The association observed before surgery between plasma s(P)RR concentrations and the PSG parameters was not seen after surgery. CONCLUSIONS: Bariatric surgery in patients with OSA complicated by morbid obesity decreased plasma s(P)RR concentrations. The most associated factors for their changes were arousal index, AHI, apnea index, and desaturation index.

Surgical outcomes of aortic repair via transapical cannulation and the adventitial inversion technique for acute Type A aortic dissection.

OBJECTIVES: To evaluate the surgical outcomes of aortic repair via transapical cannulation and the adventitial inversion technique for acute Type A aortic dissection. METHODS: Between 2008 and 2015, a total of 300 patients with acute Type A aortic dissection underwent emergency surgery, consisting of 271 hemiarch repairs and 29 total aortic arch replacements, using transapical cannulation and the adventitial inversion technique at a distal anastomosis. The mean follow-up periods were 31.7 ± 25.2 months. Overall, 18% (54/300) of the patients were octogenarians, and 21.7% (65/300) had cardiac tamponade; 25% (75/300) had preoperative malperfusion. RESULTS: The in-hospital and 30-day mortality rates were 8.3% (25/300) and 6.7% (20/300), respectively. The 30-day mortality rate was 2.7% (6/225) among patients without preoperative malperfusion and 18.7% (14/75) among patients with malperfusion (P < 0.0001), 7.4% (4/54) among octogenarians and 6.5% (16/246) among patients aged less than 80 years (P = 0.81), and 6.3% (17/271) among patients treated with hemiarch repair and 10.3% (3/29) among patients treated with total aortic arch replacement (P = 0.403). Preoperative malperfusion was an independent predictor of perioperative mortality in a multivariable analysis. During the follow-up period, distal reintervention was performed in 11% (33/300) of the patients. The rates of freedom from reintervention at 1, 3 and 5 years were 95.9%, 88.9% and 80.0%, respectively. The overall survival rates at 1, 3 and 5 years were 88.7%, 86.7% and 82.0%, respectively. The in-hospital mortality rate for elective reintervention was 3.0% (1/33). CONCLUSIONS: Aortic repair via transapical cannulation and the adventitial inversion technique for acute Type A aortic dissection provides good early and mid-term results. The safety of elective distal reintervention can be guaranteed. To obtain better operative outcomes, effective treatment for cases with malperfusion is mandatory.

Soluble (Pro)renin Receptor and Obstructive Sleep Apnea Syndrome: Oxidative Stress in Brain?

(Pro)renin receptor ((P)RR) is a multi-functional molecule that is related to both the renin-angiotensin system (RAS) and vacuolar H⁺-ATPase (v-ATPase), an ATP-dependent multi-subunit proton pump. Soluble (P)RR (s(P)RR), which consists of the extracellular domain of (P)RR, is present in blood and urine. Elevated plasma s(P)RR concentrations are reported in patients with chronic kidney disease and pregnant women with hypertension or diabetes mellitus. In addition, we have shown that plasma s(P)RR concentrations are elevated in patients with obstructive sleep apnea syndrome (OSAS). Interestingly, the levels are elevated in parallel with the severity of OSAS, but are not related to the presence of hypertension or the status of the circulating RAS in OSAS. It is known that v-ATPase activity protects cells from endogenous oxidative stress, and loss of v-ATPase activity results in chronic oxidative stress. We hypothesize that hypoxia and subsequent oxidative stress, perhaps in the brain, may be one of the factors that elevate plasma s(P)RR levels in OSAS.

[Epidemiological Survey of the Extended-spectrum ß-lactamase-producing Bacteria in Hospitals and Nursing Homes in Morioka Secondary Medical Area Zone of Iwate Prefecture].

The spread of ESBL-producing bacteria (ESBLs) in local communities is a crucially important issue related to infection control. We investigated the relevance of isolation of ESBLs and the risk factors influencing the isolation rates of these organisms at medical facilities (4 rural hospitals, A-D; 4 nursing homes, a-d) located in the Morioka medical area. The isolation rates of ESBLs at 4 hospitals were estimated from the patient medical records from April 2013 to March 2014. Also, ESBLs were isolated from stool samples from residents in 4 nursing homes during almost the same period, and were analyzed to ascertain their genotypes. Furthermore, we compared the isolation rates of ESBLs among four hospitals to determine the influence of use of third-generation cephalosporins and alcohol-based hand rubs, and also among four nursing homes to identify the clinical backgrounds of the nursing home residents influencing the isolation rates. The isolation rates of ESBLs in hospitals and nursing homes were 13.3% (3.6-25.0%) and 9.3% (3.4-21.0%), respectively. Hospital B, which had the highest isolation rate of ESBLs, showed the highest rate of use of third-generation cephalosporins. On the other hand, Hospital A, with a lower isolation rate of ESBLs, showed the highest frequency of use of alcohol rubs. The rate of use of enteral nutrition was significantly higher in the nursing homes with higher isolation rate of ESBLs than those with lower isolation rates (odds ratio 2.71, p < 0.05). Nursing home c, with a significantly higher isolation rate of ESBLs, showed higher usage of adult diapers as well as higher rates of residents with recent hospitalization and high-level care. All ESBLs (13 Escherichia coli) isolated from nursing home c showed the same genotype: CTX-M-3. Although numerous ESBLs were isolated from the hospitals and nursing homes investigated in this study, the isolation rates of ESBLs and the clinical backgrounds of the patients differed greatly among the medical facilities in the same area. Furthermore, as patients and residents were transferred reciprocally among the hospitals and nursing homes, it was suggested that infection control for ESBLs at any individual facility alone was not sufficient and also that cooperative education and information sharing on ESBLs among facilities in the same area might be important.

Elevated Plasma Levels of Soluble (Pro)Renin Receptor in Patients with Obstructive Sleep Apnea Syndrome in Parallel with the Disease Severity.

(Pro)renin receptor ((P)RR), a receptor for renin and prorenin, is implicated in the pathophysiology of diabetes mellitus, hypertension and their complications. Soluble (P)RR (s(P)RR) is composed of extracellular domain of (P)RR and thus exists in blood. We have reported that plasma concentrations of s(P)RR were elevated in male patients with obstructive sleep apnea syndrome (OSAS). The aim of the present study was to clarify the difference in plasma s(P)RR concentrations between male and female OSAS patients. Plasma s(P)RR concentrations were studied in 289 subjects (206 males and 83 females) consisting of 259 OSAS patients and 30 non-OSAS control subjects. The 259 OSAS patients were classified into mild (5 ≤ apnea hypopnea index (AHI) < 15 events/h), moderate (15 ≤ AHI < 30), and severe OSAS (AHI ≥ 30). Plasma s(P)RR levels were significantly elevated in all three OSAS groups compared to non-OSAS control subjects (AHI < 5) in the entire cohort and male subjects, whereas in female subjects, the significant elevation was found only in severe OSAS. Plasma s(P)RR levels were significantly correlated with AHI in both sexes, with a higher r value found in male subjects (male r = 0.413, p < 0.0001; female r = 0.263, p < 0.05). Importantly, when OSAS patients (26 males and 15 females) with AHI ≥ 20 underwent continuous positive airway pressure treatment, plasma s(P)RR levels were significantly decreased. In conclusion, plasma s(P)RR levels are elevated in both male and female OSAS patients in parallel with the disease severity.

Overexpression of integrin αv facilitates proliferation and invasion of oral squamous cell carcinoma cells via MEK/ERK signaling pathway that is activated by interaction of integrin αvß8 with type â collagen.

To examine the role of integrin αv subunit in the progression of squamous cell carcinoma (SCC), oral SCC cells were stably transfected with integrin αv cDNA. Integrin αv transfectants exhibited the enhancement of proliferation on type Ⅰ collagen, and seemed to have a high ability to invade type Ⅰ collagen gel. Overexpression of integrin αv led to rapid phosphorylation of focal adhesion kinase (FAK), mitogen­activated protein kinase kinase 1/2 (MEK1/2) and extracellular signal­regulated kinase 1/2 (ERK1/2) in SCC cells on type Ⅰ collagen. The downregulation of integrin ß8 in integrin αv transfectants by its specific antisense oligonucleotide led to a decrease in type Ⅰ collagen­stimulated activation of FAK and the MEK/ERK signaling pathway, and also suppressed the proliferation on type Ⅰ collagen and the invasiveness into type Ⅰ collagen gel. Moreover, the expression of integrin ß8 was induced following transfection with integrin αv cDNA. These results indicated that the overexpression of integrin αv induces integrin αvß8 heterodimer formation and the binding of integrin αvß8 to type Ⅰ collagen might enhance the proliferation and invasion of SCC cells via the activation of the MEK/ERK signaling pathway.