Purpose To elucidate the normative values of whole body sagittal alignment and balance of a healthy population in the standing position; and to clarify the relationship among the alignment, balance, health-related quality of life (HRQOL), and age. Methods Healthy Japanese adult volunteers [n = 126, mean age 39.4 years (20-69), M/F = 30/96] with no history of spinal disease were enrolled in a cross-sectional cohort study. The Oswestry Disability Index (ODI) questionnaire was administered and subjects were scanned from the center of the acoustic meati (CAM) to the feet while standing on a force plate to determine the gravity line (GL), and the distance between CAM and GL (CAM-GL) was measured in the sagittal plane. Standard X-ray parameters were measured from the head to the lower extremities. ODI was compared among age groups stratified by decade. Correlations were investigated by simple linear regression analysis. Ideal lumbar lordosis was investigated using the least squares method. Results The present study yielded normative values for whole standing sagittal alignment including head and lower extremities in a cohort of 126 healthy adult volunteers, comparable to previous reports and thus a formula for ideal lumbar lordosis was deduced: LL = 32.9 ? 0.60 9 PI -0.23 9 age. There was a tendency of positive correlation between McGregor slope, thoracic kyphosis, PT, and age. SVA, T1 pelvic angle, sacrofemoral angle, knee flexion angle, and ankle flexion angle, but not CAM-GL, increased with age, suggesting that the spinopelvic alignment changes with age, but standing whole body alignment is compensated for to preserve a horizontal gaze. ODI tended to increase from the 40s in the domain of pain intensity, personal care, traveling, and total score. ODI weakly, but significantly positively correlated with age and PI-LL. Conclusion Whole body standing alignment even in healthy subjects gradually deteriorates with age, but is compensated to preserve a horizontal gaze. HRQOL is also affected by aging and spinopelvic malalignment.

Human beings stand upright with the chain of balance beginning at the feet, progressing to the lower limbs (ankles, knees, hip joints, pelvis), each of the spinal segments, and then ending at the cranium to achieve horizontal gaze and balance using minimum muscle activity. The details of the alignment and balance of the chain, however, are not clearly understood, due to the lack of information regarding the three‐dimensional (3D) orientation of all bony elements in relation to the gravity line (GL). We performed a clinical study to clarify the standing sagittal alignment of whole axial skeletons in reference to the GL using the EOS slot‐scanning 3D X‐ray imaging system with simultaneous force plate measurement in a healthy human population. The GL was defined as a vertical line drawn through the centre of vertical pressure measured by the force plate. The present study yielded a complete set of physiological alignment measurements of the standing axial skeleton from the database of 136 healthy subjects (a mean age of 39.7 years, 20–69 years; men: 40, women: 96). The mean offset of centre of the acoustic meati from the GL was 0.0 cm. The offset of the cervical and thoracic vertebrae was posterior to the GL with the apex of thoracic kyphosis at T7, 5.0 cm posterior to the GL. The sagittal alignment changed to lordosis at the level of L2. The apex of the lumbar lordosis was L4, 0.6 cm anterior to the GL, and the centre of the base of the sacrum (CBS) was just posterior to the GL. The hip axis (HA) was 1.4 cm anterior to the GL. The knee joint was 2.4 cm posterior and the ankle joint was 4.8 cm posterior to the GL. L4‐, L5‐ and the CBS‐offset in subjects in the age decades of 40s, 50s and 60s were significantly posterior to those of subjects in their 20s. The L5‐ and CBS‐offset in subjects in their 50s and 60s were also significantly posterior to those in subjects in their 30s. HA was never posterior to the GL. In the global alignment, there was a positive correlation between offset of C7 vertebra from the sagittal vertical axis (a vertical line drawn through the posterior superior corner of the sacrum in the sagittal plane) and age, but no correlation was detected between the centre of the acoustic meati‐GL offset and age. Cervical lordosis (CL), pelvic tilt (PT), pelvic incidence, hip extension, knee flexion and ankle dorsiflexion increased significantly with age. Our results revealed that aging induces trunk stooping, but the global alignment is compensated for by an increase in the CL, PT and knee flexion, with the main function of CL and PT to maintain a horizontal gaze in a healthy population.

The intestinal tract is considered the most important reservoir of Pseudomonas aeruginosa in intensive care units (ICUs). Gut colonization by P. aeruginosa underlies the development of invasive infections such as gut-derived sepsis. Intestinal colonization by P. aeruginosa is associated with higher ICU mortality rates. The translocation of endogenous P. aeruginosa from the colonized intestinal tract is an important pathogenic phenomenon. Here we identify bacterial and host proteins associated with bacterial penetration through the intestinal epithelial barrier. We first show by comparative genomic hybridization analysis that the exoS gene, encoding the type III effector protein, ExoS, was specifically detected in a clinical isolate that showed higher virulence in silkworms following midgut injection. We further show using a silkworm oral infection model that exoS is required both for virulence and for bacterial translocation from the midgut to the hemolymph. Using a bacterial two-hybrid screen, we show that the mammalian factor FXYD3, which colocalizes with and regulates the function of Na,K-ATPase, directly binds ExoS. A pulldown assay revealed that ExoS binds to the transmembrane domain of FXYD3, which also interacts with Na,K-ATPase. Na,K-ATPase controls the structure and barrier function of tight junctions in epithelial cells. Collectively, our results suggest that ExoS facilitates P. aeruginosa penetration through the intestinal epithelial barrier by binding to FXYD3 and thereby impairing the defense function of tight junctions against bacterial penetration.Pseudomonas aeruginosa is an opportunistic pathogen that is a major cause of infection-related mortality among individuals with compromised immune systems. Fatality rates among patients infected with P. aeruginosa are higher than those among patients infected with any other opportunistic Gram-negative bacterium (48, 51). The lungs are a major site of P. aeruginosa infection in ill patients; however, a considerable number of such infections occur through direct contamination of the lungs by gastrointestinal flora or through hematogenous spread from the intestine to the lungs (51). In particular, the presence of highly virulent strains of P. aeruginosa within the intestinal tract alone is the main source of sepsis and death among immunocompromised patients, even in the absence of established extraintestinal infection and bacteremia (34,41,51). Furthermore, the lethal effects of intestinal P. aeruginosa are dependent upon its ability to adhere to and disrupt the intestinal epithelial barrier (1).The intestinal tract is considered to be the most important reservoir of P. aeruginosa (2). The rate of mortality of patients in intensive care units (ICUs) suffering from intestinal colonization by P. aeruginosa is significantly higher than that of patients without such colonization (34). The notion that gut colonization by P. aeruginosa sets the stage for the underlying development of invasive infection is supported by reports demonstrating a reduction in rates of...

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Although the control of biliary ductular morphogenesis has received some attention particularly using isolated rat biliary epithelial cell models, the regulation of human bile duct formation is not well defined. In the present study, using a 3-dimensional culture model comprising primary human biliary epithelial cells (BECs) and coculture with primary human hepatocytes, we have sought to define the factors involved. We have shown that primary human BECs can be expanded on collagen gels in the absence of growth factors or serum. When plated in high density in double collagen gels, BECs established 3-dimensional structures that subsequently developed into well differentiated polarized luminal ducts. This morphogenic response occurred in the absence of hepatocyte growth factor (HGF) and epidermal growth factor. Strikingly, the addition of growth factors While the control of liver regeneration has focused on the factors that regulate the initiation of growth in primary hepatocytes (HCs) 1,2 since they are the first cell type in the liver to respond in the regenerative process, 3 less attention has been paid to the biliary epithelial cell (BEC) compartment. We know that in vivo, BECs respond to partial hepatectomy with a delay of approximately 24 hours 4 (together with the sinusoidal cell populations). Although some of the mitogenic signaling molecules have been identified, 1,3 the factors that induce biliary ductular morphogenesis, essential to the efficient regeneration of the bile drainage system, are not well characterized.Many rodent-based biliary epithelial cell studies have focused on the bile duct ligation model, which results in extensive hyperplasia of ductular epithelium and indeed is a chosen means of increasing the yield of BECs that can be isolated from liver tissue. [5][6][7] In rats, factors including epidermal growth factor (EGF), hepatocyte growth factor (HGF), somatostatin, bile acids, and cytokines have been implicated in the proliferative response 6-10 after bile duct ligation 6,7 or partial hepatectomy. 10 After bile duct ligation in mice, HGF receptors (cmet) are up-regulated and interleukin 6 (IL-6) receptors (gp-80) are induced on the proliferating ductular cells. 11 Studies on isolated intrahepatic BECs from normal rats have also proven productive. 8,12,13 Other investigators have used dissected rodent bile duct units to show that interactions of the periductal inflammatory stroma are the source of these factors 11 and to perform functional studies on intrahepatic biliary epithelium. 12,[14][15][16][17][18] Some work on the control of ductular morphogenesis in vitro has also been performed with BECs from bile ductligated rats 5,6,18 and normal rats, 15-17 but the important regulatory factors remain poorly characterized. In other systems, most notably during angiogenesis and mammary gland ductulogenesis, factors such as EGF and HGF have been shown to be the principal morphogenic factors. [19][20][21][22][23][24] Recent evidence from in vitro-based cell proliferation and motility assays has ...

BackgroundThe effect of cigarette smoking on the onset of nonalcoholic fatty liver disease (NAFLD) is unclear, especially that associated with drinking small amounts of alcohol. We conducted a longitudinal study to investigate the relationship between cigarette smoking and NAFLD onset, which was stratified according to the amount of alcohol consumed.MethodsWe enrolled 7,905 Japanese subjects who had received annual health checkups more than twice between April 2003 and August 2013, 4,045 of whom met at least one of the following exclusion criteria and were excluded: (a) fatty liver at baseline; (b) hepatitis B or hepatitis C; (c) alcohol consumption (men: ≥210 g/wk; women: ≥140 g/wk); (d) change in alcohol drinking status between baseline and the study’s endpoint; (e) change in cigarette smoking habits between baseline and the study’s endpoint; or (f) current treatment with antidiabetic agents, antihypertensive agents, and/or lipid-lowering agents. The remaining 3,860 subjects (1,512 men, 2,348 women) were divided into two groups based on average alcohol consumption.ResultsAfter adjusting for the variables associated with metabolic disease, smoking was associated with fatty liver disease onset compared with nonsmokers in nondrinkers (adjusted hazard ratio = 1.988, 95% confidence interval 1.057–3.595; p = 0.034). No association was found between smoking and fatty liver disease onset in the low alcohol consumption group (men: <210 g alcohol/week; women: <140 g alcohol/week). The fatty liver disease incidence increased significantly among the nondrinkers as the number of cigarettes smoked increased (p = 0.001).ConclusionsCigarette smoking may be a significant risk factor associated with NAFLD onset in nondrinkers. These results may help clinicians to identify patients who are at a high risk of developing NAFLD and to prevent the progression of NAFLD by promoting earlier interventions that help people discontinue unhealthy lifestyle habits.