Bone mass and density response to a 12-month trial of calcium and vitamin D supplement in preadolescent girls.
Maximal bone acquisition in adolescent girls through dietary and lifestyle practices is advocated to prevent or minimize the development of osteoporosis and its associated complications in later life. Longitudinal investigations of bone acquisition in children and adolescents have utilized areal bone mineral density (BMD, mg/cm(2)) as a measure of bone mass and strength. Peripheral quantitative computed tomography (pQCT), which provides a three-dimensional display of data, separate analyses of bone compartments, and bone mass in terms of volumetric BMD (vBMD, mg/cm(3)), has recently been introduced for clinical use. To assess the impact of a 12-month daily calcium supplement on total and trabecular bone acquisition as measured by pQCT in preadolescent girls. Early adolescent Caucasian girls (aged 12 years, Tanner Stage 2) were enrolled in a randomized trial of daily calcium supplement (TX, 800 mg calcium carbonate and 400 IU vitamin D) or placebo (C). Body weight, height, and distal tibia measurements by pQCT were obtained at enrollment, 6 and 12 months. Pubertal status and physical activity records were assessed at baseline and 12 months. Three-day food intake records were completed every three months. Seventy-one girls completed the 12-month trial (TX=35, C=36). No differences were found for age, weight, height, body mass index, pubertal maturation, or reported physical activity at enrollment or during the study. Average intakes during the study were 1524 mg calcium and 496 IU vitamin D (TX) versus 865 mg calcium and 160 IU vitamin D (C) per day. Baseline total bone values were similar, however, trabecular values were greater in TX girls despite randomization. Percent changes were calculated to adjust for baseline differences. Because of the small cortical thickness at the 10% site (mean values < 1.6 mm), cortical mass and density were not analyzed. The percent changes for trabecular bone mineral content (BMC, mg) and vBMD were significantly greater in TX girls (+4.1% BMC and +1.0% vBMD TX versus -1.6% BMC and -2.0% vBMD C, p<0.006; ANCOVA) after 12 months of supplement. Trabecular bone area (BA, cm(2)) and total bone change, however, did not differ between groups. Daily calcium and vitamin D supplementation promotes greater trabecular BMC and vBMD acquisition in preadolescent girls. The single site selected for pQCT evaluation in this study did not allow evaluation of the cortical bone compartment. Future studies that utilize the pQCT technique need to incorporate multiple measurement sites to better assess total, cortical, and trabecular bone.


The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production.
Neuropathological hallmarks of Alzheimer's disease are neurofibrillary tangles composed of tau and neuritic plaques comprising amyloid-beta peptides (Abeta) derived from amyloid precursor protein (APP), but their exact relationship remains elusive. Phosphorylation of tau and APP on certain serine or threonine residues preceding proline affects tangle formation and Abeta production in vitro. Phosphorylated Ser/Thr-Pro motifs in peptides can exist in cis or trans conformations, the conversion of which is catalysed by the Pin1 prolyl isomerase. Pin1 has been proposed to regulate protein function by accelerating conformational changes, but such activity has never been visualized and the biological and pathological significance of Pin1 substrate conformations is unknown. Notably, Pin1 is downregulated and/or inhibited by oxidation in Alzheimer's disease neurons, Pin1 knockout causes tauopathy and neurodegeneration, and Pin1 promoter polymorphisms appear to associate with reduced Pin1 levels and increased risk for late-onset Alzheimer's disease. However, the role of Pin1 in APP processing and Abeta production is unknown. Here we show that Pin1 has profound effects on APP processing and Abeta production. We find that Pin1 binds to the phosphorylated Thr 668-Pro motif in APP and accelerates its isomerization by over 1,000-fold, regulating the APP intracellular domain between two conformations, as visualized by NMR. Whereas Pin1 overexpression reduces Abeta secretion from cell cultures, knockout of Pin1 increases its secretion. Pin1 knockout alone or in combination with overexpression of mutant APP in mice increases amyloidogenic APP processing and selectively elevates insoluble Abeta42 (a major toxic species) in brains in an age-dependent manner, with Abeta42 being prominently localized to multivesicular bodies of neurons, as shown in Alzheimer's disease before plaque pathology. Thus, Pin1-catalysed prolyl isomerization is a novel mechanism to regulate APP processing and Abeta production, and its deregulation may link both tangle and plaque pathologies. These findings provide new insight into the pathogenesis and treatment of Alzheimer's disease.


Skin and brain: itch and psychiatric disorders.
Skin diseases (atopic eczema, psoriasis, idiopathic urticaria), systemic diseases (chronic hepatic or renal failure, morbus Hodgkin, diabetes mellitus) and psychiatric disorders (obsessive compulsive disorders, depression, delusions of parasitosis) can occur with itching. The aim of this review is to clarify the link between pruritus and psychiatric morbidity and emphasize the importance of a psychiatric consultation for patients with a chronic itching, without a skin disease. In the last years, there is a growing awareness regarding psychogenic itch, although these types of itch are significantly less studied in comparison to other types of pruritus. Psychogenic pruritus is usually a diagnosis of exclusion. There are not controlled studies about treatment of psychogenic itch, but the same drugs prescribed for neuropathic pain, depression, and anxiety are used. There is a strong association between pruritus and psyche; so, it is important that the dermatologist evaluates psychosomatic dimension. According to the analysis of scientific literature and our clinical experience, pruritus seems to be a rather common phenomenon in patients suffering from depression. Future works should explain the basis of psychopathology of chronic itching thanks to studies of selected groups of patients with a particular type of chronic itching, highlighting the clinical features to establish appropriate and individual targeted care, based on the several types of pruritus. Some questions still unanswered could be clarified in this way. It is really important to decrease the symptoms "itching", because the quality of life of the patient will be improved, but the goal is to identify the underlying mechanisms of itch and establish a targeted therapy, depending on the biological changes and the underlying disease.


[Modern trends in the treatment of the obturated colonic ileus].
The results of treatment of 365 patients with obturated colonic ileus, caused by tumor, for the period from 1979 to 2000 years were analyzed. Till 1987 year in clinic were applied proximal colostomy, excision of tumor, restorative stage--in 3-4 months. From 1987 year using the method of intraoperative colonic lavage we performed simultaneous intervention with formation of primary anastomosis.


Vertical oviposition and Lambornella clarki (Ciliophora: Tetrahymenidae) dispersal by Aedes sierrensis (Diptera: Culicidae) in California.
Vertical stratification of treeholes used by mosquitoes may reflect resource quality or result from interspecific competition. Mosquitoes able to monopolize treeholes with optimal resources may be over-represented in the community. Aedes sierrensis, which is well adapted for the Mediterranean climate of California, has evolved in the absence of interspecific competition, so oviposition should reflect resource quality to a large extent. Artificial oviposition traps mounted at four canopy heights facing north or south on trees in a mixed-oak forest at four elevations of the Pacific Coastal Range were used to assess vertical ovipositional preferences by the western treehole mosquito. Natural dispersal of the ciliated protozoan parasite Lambornella clarki was similarly monitored. Gravid Ae. sierrensis showed no vertical stratification during egg laying in traps. Lambornella clarki were naturally dispersed at relatively low frequency into traps and persisted unless eliminated by larval predation. Aedes sierrensis is not currently constrained into occupying a subset of treeholes. However, invasion of its native range by competitive species may alter oviposition patterns.


The protozoan parasite Toxoplasma gondii targets proteins to dense granules and the vacuolar space using both conserved and unusual mechanisms.
All known proteins that accumulate in the vacuolar space surrounding the obligate intracellular protozoan parasite Toxoplasma gondii are derived from parasite dense granules. To determine if constitutive secretory vesicles could also mediate delivery to the vacuolar space, T. gondii was stably transfected with soluble Escherichia coli alkaline phosphatase and E. coli beta-lactamase. Surprisingly, both foreign secretory reporters were delivered quantitatively into parasite dense granules and efficiently secreted into the vacuolar space. Addition of a glycosylphosphatidylinositol membrane anchor rerouted alkaline phosphatase to the parasite surface. Alkaline phosphatase fused to the transmembrane domain and cytoplasmic tail from the endogenous dense granule protein GRA4 localized to dense granules. The protein was secreted into a tuboreticular network in the vacuolar space, in a fashion dependent upon the cytoplasmic tail, but not upon a tyrosine-based motif within the tail. Alkaline phosphatase fused to the vesicular stomatitis virus G protein transmembrane domain and cytoplasmic tail localized primarily to the Golgi, although staining of dense granules and the intravacuolar network was also detected; truncating the cytoplasmic tail decreased Golgi staining and increased delivery to dense granules but blocked delivery to the intravacuolar network. Targeting of secreted proteins to T. gondii dense granules and the plasma membrane uses general mechanisms identified in higher eukaryotic cells but is simplified and exaggerated in scope, while targeting of secreted proteins beyond the boundaries of the parasite involves unusual sorting events.


Low-dose dexamethasone-supplemented fluid resuscitation reverses endotoxin-induced acute renal failure and prevents cortical microvascular hypoxia.
There is growing evidence that impairment in intrarenal oxygenation and hypoxic injury might contribute to the pathogenesis of septic renal failure. An important molecule known to act on the renal microvascular tone and therefore consequently being involved in the regulation of intrarenal oxygen supply is NO. The main production of NO under septic conditions derives from iNOS, an enzyme that can be blocked by dexamethasone (DEX). In an animal model of endotoxin-induced renal failure, we tested the hypothesis that inhibition of iNOS by low-dose DEX would improve an impaired intrarenal oxygenation and kidney function. Twenty-two male Wistar rats received a 30-min intravenous infusion of LPS (2.5 mg/kg) and consecutively developed endotoxemic shock. Two hours later, in 12 animals, fluid resuscitation was initiated. Six rats did not receive resuscitation; four animals served as time control. In addition to the fluid, six animals received a bolus of low-dose DEX (0.1 mg/kg). In these animals, the renal iNOS mRNA expression was significantly suppressed 3 h later. Dexamethasone prevented the appearance of cortical microcirculatory hypoxic areas, improved renal oxygen delivery, and significantly restored oxygen consumption. Besides a significant increase in MAP and renal blood flow, DEX restored kidney function and tubular sodium reabsorption to baseline values. In conclusion, treatment with low-dose DEX in addition to fluid resuscitation reversed endotoxin-induced renal failure associated by an improvement in intrarenal microvascular oxygenation. Therefore, low-dose DEX might have potential application in the prevention of septic acute renal failure.


Contagious bovine pleuropneumonia vaccines: the need for improvements.
Contagious bovine pleuropneumonia (CBPP) vaccines are routinely used only in Africa. The vaccines are usually produced from one of two strains (T1/44 and KH3J), each of which has a streptomycin-resistant variant. The necessity for a 'master seed strain' is evident. At least one manufacturer in Africa produces a broth culture vaccine, while others produce a freeze-dried product. A standardised manufacturing protocol needs to be developed, together with in-process and final product quality control procedures. Some CBPP vaccine manufacturing procedures do not allow sufficient leeway for the execution of typical quality control practices. For example, it is difficult to perform batch testing on broth culture vaccine, as the vaccine is produced in its final container. Quality control test results from the Pan African Veterinary Vaccine Centre (PANVAC) are analysed in terms of causes of batch failure and indicators for process development. Taking potency as an example, most vaccine batches tested by PANVAC pass only at the limit of the OIE minimum requirement of 10(7) colony-forming units per dose. To improve the titre of the vaccine, it will be necessary to modify the manufacturing process, either by increasing mycoplasma yield during the culture phase or by minimising losses during downstream processes, especially freeze-drying. Data on inactivated vaccines are scarce. Duration of the immunity achieved with live CBPP vaccines is relatively short, in comparison with other live vaccines. Data may be required on the molecular basis of virulence and immunogenicity, as well as on the molecular immunology of CBPP, to enable the development of improved vaccines.


Comparison between rheumatoid arthritis with malignant lymphoma and other malignancies: Analysis of a National Database of Rheumatic Disease in Japan.
The background status and the current treatment options of patients with rheumatoid arthritis (RA) who develop malignant lymphoma (ML) and other malignancies are unclear. This study investigated the differences in background factors between ML and other malignancies that occur in RA patients and post-malignancy treatment. We identified 935 RA patients with new-onset malignancies among 110,571 person-years registered in the National Database of Rheumatic Disease in Japan from 2012 to 2018. Analysis cohorts 1 and 2 included 597 and 490 patients with available data for 1 year before and after the development of malignancies, respectively. Factors associated with the development of ML were longitudinally evaluated by multiple logistic regression analyses. Of the 935 patients (mean age 70.5, standard deviation 9.9), 15.5% had ML; this was comparable to the rate of lung cancer (14.3%). In cohort 1, methotrexate (MTX), biological disease-modifying anti-rheumatic drugs (bDMARDs), and non-steroidal anti-inflammatory drugs (NSAIDs) were used in 74.4%, 23.4%, and 56.7% of ML and in 56.8%, 25.4%, and 35.3% of other malignancies 1 year before the occurrence of malignancies. Clinical disease activity index (CDAI) and C-reactive protein were similar between the two groups. Multivariable analysis showed that MTX use (odds ratio [OR]: 2.22, 95% CI [confidence interval]: 1.32-3.73, p=0.003) and NSAID use (OR: 2.51, 95% CI: 1.58-3.98, p <0.001) were significantly associated with the development of ML versus other malignancies. However, this association was not observed with bDMARDs. In cohort 2, one year after the development of malignancies, MTX was used in none of ML and 41.8% of patients who developed other malignancies. In both malignancy groups, approximately 15% of patients received bDMARDs and 50% received glucocorticoids. IL-6 inhibitors were preferentially prescribed in patients with ML versus those with other malignancies. At year 1, CDAI remission was achieved in 37.3% and 31.1% of patients in the ML and other malignancy groups, respectively. Patients receiving long-term treatment with MTX and NSAIDs may be at a relatively high risk of developing ML. The treatment landscape after developing malignancies differed considerably between patients with ML and other malignancies, and different treatment strategies should be established.


Lesion growth and degeneration patterns measured using diffusion tensor 9.4-T magnetic resonance imaging in rat spinal cord injury.
Using diffusion tensor MR imaging, the authors conducted a study to explore lesion growth and degeneration patterns, from the acute through chronic stages of spinal cord injury (SCI), in an experimental animal model. In vivo and ex vivo diffusion tensor imaging was performed using a 9.4-T MR imaging system in rats allowed to recover from traumatic contusion SCI from 2 weeks through 25 weeks postinjury, mimicking progression of human SCI from the acute through chronic stages. Results showed significant growth of the traumatic lesion up to 15 weeks postinjury, where both the size and mean diffusivity (MD) reached a maximum that was maintained through the remainder of recovery. Mean diffusivity was sensitive to overall spinal cord integrity, whereas fractional anisotropy showed specificity to sites of cavity formation. The use of an MD contour map for in vivo data and a 3D surface map for ex vivo data, showing MD as a function of rostral-caudal distance and recovery time, allowed documentation of rostral and caudal spreading of the lesion. Results from this study demonstrate changes in both lesion morphology and diffusivity beyond previously reported time points and provide a unique perspective on the process of cavity formation and degeneration following traumatic SCI. Additionally, results suggest that MD more accurately defines regions of histological damage than do regions of T2 signal hyperintensity. This could have significant clinical implications in the detection and potential treatment of posttraumatic syringes in SCI.


Retinoic acid-mediated G1 arrest is associated with induction of p27(Kip1) and inhibition of cyclin-dependent kinase 3 in human lung squamous carcinoma CH27 cells.
Retinoids are promising agents for the prevention and treatment of several human malignancies including lung cancer. In this study, the effect of retinoic acid (RA) on cell growth and the mechanism of growth modulation were examined in human lung squamous carcinoma CH27 cells. Here we report that RA mediated the dose- and time-dependent growth arrest in G1 phase, accompanied by the up-regulation of p27(Kip1) and the down-regulation of the cyclin-dependent kinase 3 (Cdk3) and p21(CIP1/Waf1) proteins. Furthermore, RA-induced growth arrest of CH27 cells was also associated with increased retinoic acid receptor beta (RARbeta) and reduced c-Myc expression. However, RA had no effect on the levels of cyclins A, D1, D3, E, or H, or on Cdk2, Cdk4, Cdk5, CDk6, Cdk7, p16(Ink4A), p15(Ink4B), p53, or pRb proteins in CH27 cells. Evaluation of the kinase activity of cyclin-Cdk complexes showed that RA increases p27(Kip1) expression in CH27 cells leading to markedly reduced cyclin A/Cdk2 kinase activity and slightly reduced cyclin E/Cdk2 kinase activity, with no effect on cyclin D/Cdk4 and cyclin D/Cdk6 activities. Moreover, coincident with the decrease in kinase activity was a drastic increase in cyclin A-bound p27(Kip1). These results suggest that increases in the levels of p27(Kip1) and its binding to cyclin A, as well as reduction of Cdk3 protein expression, are strong candidates for the cell cycle regulator that prevents the entry into the S phase in RA-treated CH27 cells, with prolongation of G1 phase and inhibition of DNA synthesis.


Characterization of focal liver masses using acoustic radiation force impulse elastography.
To investigate the diagnostic performance of acoustic radiation force impulse (ARFI) elastography for characterizing focal liver mass by quantifying their stiffness. This prospective study included 62 patients with a focal liver mass that was well visualized on conventional ultrasonography performed in our institution from February 2011 to November 2011. Among them, 12 patients were excluded for ARFI measurement failure due to a lesion that was smaller than the region of the interest and at an inaccessible location (deeper than 8 cm) (n = 7) or poor compliance to hold their breath as required (n = 5). Finally, 50 patients with valid ARFI measurements were enrolled. If a patient had multiple liver masses, only one mass of interest was chosen. The masses were diagnosed by histological examination or clinical diagnostic criteria. During ultrasonographic evaluation, stiffness, expressed as velocity, was checked 10 times per focal liver mass and the surrounding liver parenchyma. After further excluding three masses that were non-diagnostic on biopsy, a total of 47 focal mass lesions were tested, including 39 (83.0%) malignant masses [24 hepatocellular carcinomas (HCC), seven cholangiocellular carcinomas (CCC), and eight liver metastases] and eight (17.0%) benign masses (five hemangiomas and three focal nodular hyperplasias, FNH). Thirty-seven (74.0%) masses were confirmed by histological examination. The mean velocity was 2.48 m/s in HCCs, 1.65 m/s in CCCs, 2.35 m/s in metastases, 1.83 m/s in hemangiomas, and 0.97 m/s in FNHs. Although considerable overlap was still noted between malignant and benign masses, significant differences in ARFI values were observed between malignant and benign masses (mean 2.31 m/s vs 1.51 m/s, P = 0.047), as well as between HCCs and benign masses (mean 2.48 m/s vs 1.51 m/s, P = 0.006). The areas under the receiver operating characteristics curves (AUROC) for discriminating the malignant masses from benign masses was 0.724 (95%CI, 0.566-0.883, P = 0.048), and the AUROC for discriminating HCCs from benign masses was 0.813 (95%CI, 0.649-0.976, P = 0.008). To maximize the sum of sensitivity and specificity, an ARFI value of 1.82 m/s was selected as the cutoff value to differentiate malignant from benign liver masses. Furthermore, the cutoff value for distinguishing HCCs from benign masses was also determined to be 1.82 m/s. The diagnostic performance of the sum of the ARFI values for focal liver masses and the surrounding liver parenchyma to differentiate liver masses improved (AUROC = 0.853; 95%CI, 0.745-0.960; P = 0.002 in malignant liver masses vs benign ones and AUROC = 0.948; 95%CI, 0.896-0.992, P < 0.001 in HCCs vs benign masses). ARFI elastography provides additional information for the differential diagnosis of liver masses. However, our results should be interpreted in clinical context, because considerable overlap in ARFI values existed among liver masses.


Regional body composition changes in women after 6 months of periodized physical training.
Data are lacking regarding regional morphological changes among women after prolonged physical training. This study employed dual-energy X-ray absorptiometry to assess changes in whole body and regional (i.e., trunk, legs, arms) fat mass, lean mass, and bone mineral content body composition adaptations in 31 healthy women pre-, mid-, and post-6 mo of periodized physical training. These results were compared with those of 1) a control group of women who had not undergone the training program and were assessed pre- and post-6 mo and 2) a group of 18 men that was tested only once. Additionally, magnetic resonance imaging was used to assess changes in muscle morphology of the thigh in a subset of 11 members of the training group. Physical training consisted of a combination of aerobic and resistance exercise in which the subjects engaged for 5 days/wk for 24 wk. Overall, the training group experienced a 2.2% decrease, a 10% decrease, and a 2.2% increase for body mass, fat mass, and soft tissue lean mass, respectively. No changes in bone mineral content were detected. The women had less of their soft tissue lean mass distributed in their arms than did the men, both before and after the women were trained. Novel to this study were the striking differences in the responses in the tissue composition of the arms (31% loss in fat mass but no change in lean mass) compared with the legs (5.5% gain in lean mass but no change in fat mass). There was a 12% fat loss in the trunk with no change in soft tissue lean mass. Dual-energy X-ray absorptiometry and magnetic resonance imaging fat mass measurements showed good agreement (r = 0. 72-0.92); their lean mass measurements were similar as well, showing approximately 5.5% increases in leg lean tissue. These findings show the importance of considering regional body composition changes, rather than whole body changes alone when assessing the effects of a periodized physical training program.


Portal ductopathy: clinical importance and nomenclature.
Non-cirrhotic portal hypertension (PHT) accounts for about 20% of all PHT cases, portal vein thrombosis (PVT) resulting in cavernous transformation being the most common cause. All known complications of PHT may be encountered in patients with chronic PVT. However, the effect of this entity on the biliary tree and pancreatic duct has not yet been fully established. Additionally, a dispute remains regarding the nomenclature of common bile duct abnormalities which occur as a result of chronic PVT. Although many clinical reports have focused on biliary abnormalities, only a few have evaluated both the biliary and pancreatic ductal systems. In this review the relevant literature evaluating the effect of PVT on both ductal systems is discussed, and findings are considered with reference to results of a prominent center in Turkey, from which the term "portal ductopathy" has been put forth to replace "portal biliopathy".


Mitochondrial H2S donor AP39 induces stomatal closure by modulating guard cell mitochondrial activity.
Hydrogen sulfide (H2S) is a gaseous signaling molecule involved in numerous physiological processes in plants, including gas exchange with the environment through the regulation of stomatal pore width. Guard cells (GCs) are pairs of specialized epidermal cells that delimit stomatal pores and have a higher mitochondrial density and metabolic activity than their neighboring cells. However, there is no clear evidence on the role of mitochondrial activity in stomatal closure induction. In this work, we showed that the mitochondrial-targeted H2S donor AP39 induces stomatal closure in a dose-dependent manner. Experiments using inhibitors of the mitochondrial electron transport chain (mETC) or insertional mutants in cytochrome c (CYTc) indicated that the activity of mitochondrial CYTc and/or complex IV are required for AP39-dependent stomatal closure. By using fluorescent probes and genetically encoded biosensors we reported that AP39 hyperpolarized the mitochondrial inner potential (Δψm) and increased cytosolic ATP, cytosolic hydrogen peroxide levels, and oxidation of the glutathione pool in GCs. These findings showed that mitochondrial-targeted H2S donors induce stomatal closure, modulate guard cell mETC activity, the cytosolic energetic and oxidative status, pointing to an interplay between mitochondrial H2S, mitochondrial activity, and stomatal closure.


Quantifying the Urban Food-Energy-Water Nexus: The Case of the Detroit Metropolitan Area.
The efficient provision of food, energy, and water (FEW) resources to cities is challenging around the world. Because of the complex interdependence of urban FEW systems, changing components of one system may lead to ripple effects on other systems. However, the inputs, intersectoral flows, stocks, and outputs of these FEW resources from the perspective of an integrated urban FEW system have not been synthetically characterized. Therefore, a standardized and specific accounting method to describe this system is needed to sustainably manage these FEW resources. Using the Detroit Metropolitan Area (DMA) as a case, this study developed such an accounting method by using material and energy flow analysis to quantify this urban FEW nexus. Our results help identify key processes for improving FEW resource efficiencies of the DMA. These include (1) optimizing the dietary habits of households to improve phosphorus use efficiency, (2) improving effluent-disposal standards for nitrogen removal to reduce nitrogen emission levels, (3) promoting adequate fertilization, and (4) enhancing the maintenance of wastewater collection pipelines. With respect to water use, better efficiency of thermoelectric power plants can help reduce water withdrawals. The method used in this study lays the ground for future urban FEW analyses and modeling.


Bone tissue-specific transcription of the osteocalcin gene: role of an activator osteoblast-specific complex and suppressor hox proteins that bind the OC box.
Bone-specific expression of the osteocalcin gene is transcriptionally controlled. Deletion analysis of osteocalcin promoter sequences by transient transfection of osseous (ROS 17/2.8) and nonosseous (R2 fibroblast) cells revealed that the most proximal 108 nucleotides are sufficient to confer tissue-specific expression. By gel mobility shift assays with wild-type and mutated oligonucleotides and nuclear extracts from several different cell lines we identified a novel transcription factor complex which exhibits sequence-specific interactions with the primary transcriptional element, the OC box (nt -99 to -76). This OC box binding protein (OCBP) is present only in osteoblast-like cells. Methylation interference demonstrated association of the factor with OC box sequences overlapping the Msx homeodomain consensus binding site. By assaying several mutations of the OC box, both in gel shift and transient transfection studies using ROS 17/2.8, we show the following. First, binding of OCBP correlates with osteocalcin promoter activity in ROS 17/2.8 cells. Increased binding leads to a 2-3-fold increase in transcription, while decreased binding results in transcription 30-40% of control. Second, homeodomain protein binding suppresses transcription. However, Msx expression is critical for full development of the bone phenotype as determined by antisense studies. Last, we show that one of the mutations of the OC box permits expression of osteocalcin in non-osseous cell lines. In summary, we demonstrate association of at least two classes of tissue-restricted transcription factors with the OC box element, the OCBP and Msx proteins, supporting the concept that these sequences contribute to defining tissue specificity.


Iris phenotypes and pigment dispersion caused by genes influencing pigmentation.
Spontaneous mutations altering mouse coat colors have been a classic resource for discovery of numerous molecular pathways. Although often overlooked, the mouse iris is also densely pigmented and easily observed, thus representing a similarly powerful opportunity for studying pigment cell biology. Here, we present an analysis of iris phenotypes among 16 mouse strains with mutations influencing melanosomes. Many of these strains exhibit biologically and medically relevant phenotypes, including pigment dispersion, a common feature of several human ocular diseases. Pigment dispersion was identified in several strains with mutant alleles known to influence melanosomes, including beige, light, and vitiligo. Pigment dispersion was also detected in the recently arising spontaneous coat color variant, nm2798. We have identified the nm2798 mutation as a missense mutation in the Dct gene, an identical re-occurrence of the slaty light mutation. These results suggest that dysregulated events of melanosomes can be potent contributors to the pigment dispersion phenotype. Combined, these findings illustrate the utility of studying iris phenotypes as a means of discovering new pathways, and re-linking old ones, to processes of pigmented cells in health and disease.


Contributing to the debate on categorising shared sanitation facilities as 'unimproved': An account based on field researchers' observations and householders' opinions in three regions, Tanzania.
Health risks associated with poor sanitation behaviours continue to be reported mostly from low-income countries (LICs). Reports show that various factors limit many people from accessing and using improved latrines, forcing some to opt for sharing latrines with neighbours, others practicing open defecation. Meanwhile, debate prevails on whether shared latrines should be categorised as unimproved according to WHO/UNICEF-JMP criteria. We contribute to this debate based on results from a study undertaken in three regions, Tanzania. Data were collected through observations in 1,751 households with latrines, coupled with collection of opinions from heads of such households regarding the latrine-sharing practices. Bivariate and multivariate logistic regression analyses were performed to assess associations between the outcome and possible predictor variables. Of all 1,751 latrines, 14.6% were shared. Among the shared latrines, 74.2% were found being generally clean as compared to 69.2% of the non-shared ones. Comparing the shared and non-shared latrines, the non-shared latrines were significantly less likely to be found with floors built with permanent materials (OR = 0.73, 95% CI: 0.55, 0.98); washable floors (OR = 0.69; 95% CI: 0.51, 0.93); and lockable doors (OR = 0.73; 95% CI: 0.56, 0.95). Shared latrines were less likely to have floors with faecal matter, functional handwashing facilities (HWFs), HWFs with running water, and roofs; albeit the differences in all these scenarios were not statistically significant. Respondents expressed desire for improved latrines, but also did not find it wrong to share latrines if cleanliness was maintained. Having an 'improved' latrine remains important as JMP recommends, but based on our study findings, we argue that possessing a non-shared latrine neither guarantees safety to its users nor its categorisation as 'improved'. Instead, the state of the latrine, the construction technology used and the behaviours of the users may be more important.


Effect of acute peppermint oil administration on gastric sensorimotor function and nutrient tolerance in health.
Menthol reduces intestinal motility in animal studies, an effect that is probably mediated by transient receptor potential channels. Peppermint oil (PO), with menthol as a major constituent, is widely used as a spasmolytic agent in irritable bowel syndrome. In the current study, we investigated the effect of acute PO administration on intragastric pressure (IGP) profiles and gastric sensorimotor functions in health. Healthy volunteers underwent IGP measurement before and during continuous intragastric infusion of a nutrient drink (n = 13), and gastric barostat studies (n = 13). A single capsule of PO (182 mg) or placebo was administered during the studies in a randomized controlled crossover design. Throughout the studies, healthy volunteers scored 11 epigastric symptoms on a visual analogue scale (VAS); satiation was scored on a 6-point Likert scale during intragastric infusion. During fasting, IGP and motility index (MI) of the proximal stomach decreased significantly after PO administration compared with placebo (P < 0.0001 and <0.05, respectively). In contrast, during intragastric infusion of the nutrient drink, no significant differences were detected between PO and placebo in IGP profiles, MI, satiation scores, and epigastric symptoms. The maximum infused volume, gastric compliance or sensitivity to balloon distention did not differ between both treatment arms. However, reduced appetite scores were seen during fasting after PO treatment, as compared with placebo (P = 0.01). Postprandial VAS scores were similar between PO and placebo. Peppermint oil reduces IGP, proximal phasic contractility, and appetite, with negligible effects on gastric sensitivity, tone, accommodation, and nutrient tolerance in health.


Comparison of Recruitment Strategy Outcomes in the National Children's Study.
In 2000, the US Congress authorized the National Institutes of Health to conduct a prospective national longitudinal study of environmental influences on children's health and development from birth through 21 years. Several recruitment methodologies were piloted to determine the optimal strategy for a main National Children's Study. After an initial pilot recruitment that used a household enumeration strategy performed poorly, the National Children's Study Vanguard Study developed and evaluated the feasibility, acceptability, and cost of 4 alternate strategies to recruit a large prospective national probability sample of pregnant women and their newborn children. We compare household-based recruitment, provider-based recruitment, direct outreach, and provider-based sampling (PBS) strategies with respect to overall recruitment success, efficiency, cost, and fulfillment of scientific requirements. Although all 5 strategies achieved similar enrollment rates (63%-81%) among eligible women, PBS achieved the highest recruitment success as measured by the ratio of observed-to-expected newborn enrollees per year of 0.99, exceeding those of the other strategies (range: 0.35-0.48). Because PBS could reach the enrollment target through sampling of high volume obstetric provider offices and birth hospitals, it achieved the lowest ratio of women screened to women enrolled and was also the least costly strategy. With the exception of direct outreach, all strategies enrolled a cohort of women whose demographics were similar to county natality data. PBS demonstrated the optimal combination of recruitment success, efficiency, cost, and population representativeness and serves as a model for the assembly of future prospective probability-based birth cohorts.


Feedback based simultaneous correction of imaging artifacts due to geometrical and mechanical cross-talk and tip-sample stick in atomic force microscopy.
This paper presents a feedback scheme that simultaneously corrects, in real time, for the imaging artifacts caused by cantilever and photosensor misalignments as well as misinterpretations in relative lateral position of the tip with respect to the sample due to the tip-sample stick in atomic force microscopy (AFM). The optical beam bounce method, typically used in AFM for imaging, is sensitive to inaccuracies of cantilever geometry and the relative misalignment of the laser source, cantilever, and the laser sensitive diode from the intended design. These inaccuracies, which contribute to the geometrical cross-talk between the normal and the lateral signals, become prominent at the atomic and subnanometer scales, and thereby impede high resolution imaging studies. The feedback scheme accounts for these artifacts and makes imaging insensitive to, in fact, practically independent of these inaccuracies. This scheme counteracts the lateral twisting dynamics of the cantilever, and as a result, it avoids the misinterpretation problem of the relative lateral position of the cantilever tip from the sample and thereby avoids the corresponding imaging artifacts that are typically prominent in contact mode friction force microscopy (FFM). The feedback scheme consists of simultaneously regulating the normal as well as the lateral cantilever deflection signal at their respective set points. This not only removes the imaging artifacts due to geometrical misalignments, mechanical cross-talk, and irregular sliding but also the corresponding compensatory control signal gives a more accurate real time measure of the lateral interaction force between the sample and the cantilever as compared to the lateral deflection signal used in FFM. Experimental results show significant improvement, and in some cases, practical elimination of the artifacts. The design and implementation of a split piezoassembly needed for the lateral actuation for the feedback scheme are also presented.


Expression Profiling along the Murine Intestine: Different Mucosal Protection Systems and Alterations in Tff1-Deficient Animals.
Tff1 is a typical gastric peptide secreted together with the mucin, Muc5ac. Tff1-deficient (Tff1KO) mice are well known for their prominent gastric phenotype and represent a recognized model for antral tumorigenesis. Notably, intestinal abnormalities have also been reported in the past in these animals. Here, we have compared the expression of selected genes in Tff1KO mice and their corresponding wild-type littermates (RT-PCR analyses), focusing on different mucosal protection systems along the murine intestine. As hallmarks, genes were identified with maximum expression in the proximal colon and/or the duodenum: Agr2, Muc6/A4gnt/Tff2, Tff1, Fut2, Gkn2, Gkn3, Duox2/Lpo, Nox1. This is indicative of different protection systems such as Tff2/Muc6, Tff1-Fcgbp, gastrokines, fucosylation, and reactive oxygen species (ROS) in the proximal colon and/or duodenum. Few significant transcriptional changes were observed in the intestine of Tff1KO mice when compared with wild-type littermates, Clca1 (Gob5), Gkn1, Gkn2, Nox1, Tff2. We also analyzed the expression of Tff1, Tff2, and Tff3 in the pancreas, liver, and lung of Tff1KO and wild-type animals, indicating a cross-regulation of Tff gene expression. Furthermore, on the protein level, heteromeric Tff1-Fcgbp and various monomeric Tff1 forms were identified in the duodenum and a high-molecular-mass Tff2/Muc6 complex was identified in the proximal colon (FPLC, proteomics).


MR imaging and ultrasound of fetal cervical cystic lymphangioma: utility in antepartum treatment planning.
We present a case of fetal cystic lymphangioma that was initially diagnosed by ultrasonography and further evaluated by prenatal MR imaging. MR imaging findings aided in improved delineation of the neck mass. T2-weighted MR images revealed partial compression of the airway by the neck mass. This information was useful in the decision to use ex utero intrapartum treatment (EXIT) and helped surgeons in planning their approach to establish airway control during delivery.


Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial.
Uveitis associated with juvenile idiopathic arthritis is a cause of major ocular morbidity. A substantial proportion of children are refractory to systemic methotrexate and TNF inhibitors. Our aim was to study the safety and efficacy of tocilizumab in children with juvenile idiopathic arthritis-associated uveitis refractory to both methotrexate and TNF inhibitors. This multicentre, single-arm, phase 2 trial was done following a Simon's two-stage design at seven tertiary hospital sites in the UK. Patients aged 2-18 years with active juvenile idiopathic arthritis-associated uveitis were eligible. All patients had been on a stable dose of methotrexate for at least 12 weeks and had not responded to treatment with a TNF inhibitor. Patients weighing 30 kg or more were treated with 162 mg subcutaneous tocilizumab every 2 weeks for 24 weeks, and participants weighing less than 30 kg were treated with 162 mg every 3 weeks for 24 weeks. The primary outcome was treatment response defined as a two-step decrease, or decrease to zero, from baseline in the level of inflammation (anterior chamber cells) at week 12, per the standardisation of uveitis nomenclature criteria. A phase 3 trial would be justified if more than seven patients responded to treatment. An interim analysis was planned to assess whether the trial would be stopped for futility, with futility defined as two or fewer treatment responses among ten participants. Adverse events were collected up to 30 calendar days after treatment cessation. The primary analysis was done in the intention-to-treat population and the safety analysis was done in all patients who started the treatment. This trial is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN95363507) and EU Clinical Trials Register (EudraCT 2015-001323-23). 22 participants were enrolled to the trial between Dec 3, 2015, and March 9, 2018, and 21 participants received treatment. One participant was found to be ineligible immediately after enrolment and was therefore withdrawn. Seven of 21 (median unbiased estimate of proportion 34% [95% CI 25-57]) responded to treatment (p=0·11). Safety results were consistent with the known safety profile of tocilizumab. The primary endpoint was not met, and thus the results do not support a phase 3 trial of tocilizumab in patients with juvenile idiopathic arthritis-associated uveitis. Importantly, data on the use of tocilizumab in clinical practice is now captured in national registries. Despite this trial not meeting the threshold required to justify a larger phase 3 trial, several patients responded to treatment; as such, tocilzumab might still be a therapeutic option in some children with uveitis refractory to anti-TNF drugs, given the absence of other treatment options. Versus Arthritis and the National Institute for Health Research Clinical Research Network: Children.


Differential gene expression during substrate probing in larvae of the Caribbean coral Porites astreoides.
The transition from larva to adult is a critical step in the life history strategy of most marine animals. However, the genetic basis of this life history change remains poorly understood in many taxa, including most coral species. Recent evidence suggests that coral planula larvae undergo significant changes at the physiological and molecular levels throughout the development. To investigate this, we characterized differential gene expression (DGE) during the transition from planula to adult polyp in the abundant Caribbean reef-building coral Porites astreoides, that is from nonprobing to actively substrate-probing larva, a stage required for colony initiation. This period is crucial for the coral, because it demonstrates preparedness to locate appropriate substrata for settlement based on vital environmental cues. Through RNA-Seq, we identified 860 differentially expressed holobiont genes between probing and nonprobing larvae (p ≤ .01), the majority of which were upregulated in probing larvae. Surprisingly, differentially expressed genes of endosymbiotic dinoflagellate origin greatly outnumbered coral genes, compared with a nearly 1:1 ratio of coral-to-dinoflagellate gene representation in the holobiont transcriptome. This unanticipated result suggests that dinoflagellate endosymbionts may play a significant role in the transition from nonprobing to probing behaviour in dinoflagellate-rich larvae. Putative holobiont genes were largely involved in protein and nucleotide binding, metabolism and transport. Genes were also linked to environmental sensing and response and integral signalling pathways. Our results thus provide detailed insight into molecular changes prior to larval settlement and highlight the complex physiological and biochemical changes that occur in early transition stages from pelagic to benthic stages in corals, and perhaps more importantly, in their endosymbionts.


Leg design in hexapedal runners.
Many-legged animals, such as crabs and cockroaches, utilize whole-body mechanics similar to that observed for running bipeds and trotting quadrupedal mammals. Despite the diversity in morphology, two legs in a quadrupedal mammal, three legs in an insect and four legs in a crab can function in the same way as one leg of a biped during ground contact. To explain how diverse leg designs can result in common whole-body dynamics, we used a miniature force platform to measure the ground reaction forces produced by individual legs of the cockroach Blaberus discoidalis. Hexapedal runners were not like quadrupeds with an additional set of legs. In trotting quadrupedal mammals each leg develops a similar ground reaction force pattern that sums to produce the whole-body pattern. At a constant average velocity, each leg pair of the cockroach was characterized by a unique ground reaction force pattern. The first leg decelerated the center of mass in the horizontal direction, whereas the third leg was used to accelerate the body. The second leg did both, much like legs in bipedal runners and quadrupedal trotters. Vertical force peaks for each leg were equal in magnitude. In general, peak ground reaction force vectors minimized joint moments and muscle forces by being oriented towards the coxal joints, which articulate with the body. Locomotion with a sprawled posture does not necessarily result in large moments around joints. Calculations on B. discoidalis showed that deviations from the minimum moments may be explained by considering the minimization of the summed muscle forces in more than one leg. Production of horizontal forces that account for most of the mechanical energy generated during locomotion can actually reduce total muscle force by directing the ground reaction forces through the leg joints. Whole-body dynamics common to two-, four-, six- and eight-legged runners is produced in six-legged runners by three pairs of legs that differ in orientation with respect to the body, generate unique ground reaction force patterns, but combine to function in the same way as one leg of a biped.


Second-harmonic imaging microscopy of normal human and keratoconus cornea.
The purpose of this study was to evaluate the ability of second-harmonic imaging to identify differences in corneal stromal collagen organization between normal human and keratoconus corneas. Six normal corneas from eye bank donors and 13 corneas of patients with keratoconus, obtained after penetrating keratoplasty were examined. A femtosecond titanium-sapphire laser with 800-nm output was used to generate second-harmonic signals collected at 400 nm from central and paracentral corneal tissue blocks. Three-dimensional (3-D) data sets were collected and reconstructed to evaluate the location and orientation of stromal collagen lamellae. Imaging of second-harmonic signals combined with 3-D reconstruction of the normal cornea identified a high degree of lamellar interweaving, particularly in the anterior cornea. Of note was the detection of lamellae that inserted into Bowman's layer and were oriented transverse to the corneal surface, penetrating posteriorly approximately 120 mum. In keratoconus corneas, imaging second-harmonic signals identified less lamellar interweaving and a marked reduction or loss of lamellae inserting into Bowman's layer in 12 of 13 cases, particularly in regions associated with cone development without breaks in Bowman's layer or scarring. Compared with normal adult corneas, marked abnormalities were detected in the organization of the anterior corneal collagen lamellae of keratoconus corneas by second harmonic imaging. These structural abnormalities are consistent with the known changes in collagen organization and biomechanical strength of keratoconus.


Validity evidence for procedural competency in virtual reality robotic simulation, establishing a credible pass/fail standard for the vaginal cuff closure procedure.
The use of robotic surgery for minimally invasive procedures has increased considerably over the last decade. Robotic surgery has potential advantages compared to laparoscopic surgery but also requires new skills. Using virtual reality (VR) simulation to facilitate the acquisition of these new skills could potentially benefit training of robotic surgical skills and also be a crucial step in developing a robotic surgical training curriculum. The study's objective was to establish validity evidence for a simulation-based test for procedural competency for the vaginal cuff closure procedure that can be used in a future simulation-based, mastery learning training curriculum. Eleven novice gynaecological surgeons without prior robotic experience and 11 experienced gynaecological robotic surgeons (> 30 robotic procedures) were recruited. After familiarization with the VR simulator, participants completed the module 'Guided Vaginal Cuff Closure' six times. Validity evidence was investigated for 18 preselected simulator metrics. The internal consistency was assessed using Cronbach's alpha and a composite score was calculated based on metrics with significant discriminative ability between the two groups. Finally, a pass/fail standard was established using the contrasting groups' method. The experienced surgeons significantly outperformed the novice surgeons on 6 of the 18 metrics. The internal consistency was 0.58 (Cronbach's alpha). The experienced surgeons' mean composite score for all six repetitions were significantly better than the novice surgeons' (76.1 vs. 63.0, respectively, p < 0.001). A pass/fail standard of 75/100 was established. Four novice surgeons passed this standard (false positives) and three experienced surgeons failed (false negatives). Our study has gathered validity evidence for a simulation-based test for procedural robotic surgical competency in the vaginal cuff closure procedure and established a credible pass/fail standard for future proficiency-based training.


Major complications of acute and chronic liver disease.
Many advances have been made in the understanding, diagnosis, and management of severe complications of liver disease. The pathogenesis of hepatic encephalopathy remains a challenge. Several toxins including ammonia, mercaptans, short-chain fatty acids, benzodiazepine-like substances, GABA-like substances, and impaired glutamatergic neurotransmission are at the top of the list of candidates. Use of the benzodiazepine antagonists is an experimental but promising new therapy in patients with hepatic encephalopathy. In patients with cirrhosis, spontaneous bacterial peritonitis (SBP) remains a common and highly lethal complication. The diagnosis of SBP is based on the polymorphonuclear cell count in the ascites and confirmed by culture of ascitic fluid. Early diagnosis and aggressive treatment has reduced mortality of SBP from greater than 90 per cent to 30 to 50 per cent. The appearance of cerebral edema in severe acute hepatocellular failure is associated with high mortality and conventional neurologic signs may be unreliable indicators of brain swelling. Current management of cerebral edema in fulminant hepatocellular failure may include early placement of an extradural sensor for continuous monitoring of intracranial pressure, so that short-term measures can be instituted making later liver transplantation safer. Coagulopathy remains a serious problem in patients with liver disease. Exchange plasmapheresis is a promising short-term adjuvant therapy. However, liver transplantation should be considered the definitive treatment for fulminant hepatocellular failure. The gastroenterologist often encounters multiorgan failure in patients with severe liver disease. Liver transplantation is now an important therapeutic consideration in almost every patient with severe, irreversible liver disease. Efforts should be targeted to early diagnosis of irreversible disease and coordination of patient care with a liver transplant center.


NYSDA Membership Survey. How the components stack up.
There are many similarities and differences between the demographic characteristics of dentists, their practice arrangements, business activities, income and other factors, which do not follow the purported "downstate-upstate" dichotomy. In each district society, most respondents are sole proprietors, and 26+ years is the most frequently reported period of time in practice. A great majority of dentists in most component societies work 32+ hours per week, and average 50 to 56 scheduled and six to nine emergency visits per week. $175,000+ was reported most frequently as the net income of dentists in eight component societies. A small percent of practitioners belong to IPAs and capitation plans. A small percent accepts Medicaid patients. A somewhat larger percent belongs to DR plans. A much greater percent belongs to PPO arrangements. Approximately 25% of respondents expect that their primary occupation will change in the next 10 years, with the vast majority anticipating no longer being in dental practice.


Correlation of lip patterns, gender, and blood group in North Kerala population: A study of over 800 individuals.
With the ever-changing field of criminal justice, the constant revision of criteria for acceptable evidence by the judiciary poses new challenges in forensic investigation. The applicability of cheiloscopy in individual identification is an area of extensive research in recent years. The aim of the present study was to determine the distribution of different lip print patterns in North Kerala population, to assess any sexual dimorphism in lip patterns, and to correlate lip print patterns with ABO and Rh blood groups. A total of 858 students, 471 males and 387 females, from different colleges in the district of Kozhikode in North Kerala were included in the study. Lip prints were obtained using lipstick and cello tape and transferred onto white papers. Blood group of the participants was noted. The most predominant pattern observed was Type I (48.3%), followed by Type II, Type III, Type IV, Type I', and Type V. We also observed that the lower lip exhibited an overwhelming predominance of Type I pattern in the North Kerala population while the upper lip showed a more even distribution. Gender-wise difference was observed with Type II being the most common in males and Type IV being the predominant pattern in females. No correlation was obtained between the blood groups and lip patterns. The potential usefulness of cheiloscopy in forensic medicine still remains largely untapped and under-recognized. Similar studies in different populations with large sample sizes will allow a more definite picture of lip print patterns to emerge.


Idiopathic Orbital Inflammatory Disease Attack Associated with Large Serous Detachment Without Anterior and Posterior Segment Inflammation.
Idiopathic orbital inflammatory disease is a benign, non-infectious, and non-neoplastic space-occupying orbital and peri-orbital inflammation with no identifiable local or systemic causes. Patients usually present with eyelid and periorbital erythema and edema, proptosis, and decreased eye movements. In this report, a case of large serous retinal detachment accompanying a unilateral idiopathic orbital inflammatory disease attack is discussed. It demonstrates that very extensive and highly serous retinal detachment may accompany idiopathic orbital inflammatory disease attacks. Dramatic improvement in clinical findings and imaging can be observed with high-dose steroid treatment in a short time.


Thymic epithelial tumours: histopathological classification and differential diagnosis.
The epithelial and lymphoid compartments of the thymus can give rise to a wide variety of tumours, including thymomas, thymic carcinomas, lymphoreticular proliferations, germ cell tumours, and sarcomas. While some of these have close similarity to their counterparts in other organs, both in terms of histology and immunohistochemistry, as well as molecular features, others are unique to the thymus. The epithelial tumours, which can develop in the thymus, will be discussed in this review, with a particular emphasis on resolving differential diagnosis by means of morphology, immunohistochemical profiles, and molecular diagnostics.


Closing the Gap in Direct Admissions: A Quality Improvement Project.
Direct admissions (DAs) are nonemergent admissions to the inpatient unit that bypass the emergency department. Our institution lacked a standardized DA process, which resulted in postponement of prompt patient care. The purpose of the present study was to review and modify the existing DA process and to decrease the time between patient arrival for DA and placement of initial clinician orders. A team was assembled and tasked with using quality improvement tools (eg, Define-Measure-Analyze-Improve-Control, fishbone diagrams, process mapping) to streamline the DA process to decrease average time between patient arrival for DA and initial clinician orders, from 84.4 minutes in July 2018 to 60 minutes or less by June 2019, without negatively affecting patient admission loyalty questionnaire scores. In a standardized and streamlined DA process, average time between patient arrival and provider order placement decreased to less than 60 minutes. This reduction was achieved without substantially affecting patient loyalty questionnaire scores. By using a quality improvement methodology, we developed a standardized DA process that resulted in prompt care for patients without decreasing admission loyalty scores.


[Return to work following work-related orthopaedic rehabilitation: a cluster randomized trial].
Since the 1990s work-related programmes became more important in orthopaedic rehabilitation. However, in Germany orthopaedic rehabilitation initially focussed on improvements in evaluating functional capacity and on the development of appropriate modules of exercise therapy while psychosocial work demands have been less considered in the rehabilitation process so far. Aims of the study were implementation and efficacy evaluation of an intensified multimodal work-related programme following a cognitive behavioural approach. Participants were patients with substantial work-related problems. Included patients were randomized in groups either to the work-related programme or to the common orthopaedic rehabilitation (cluster randomization). Primary outcome was return to work. Analyses were based on post-treatment data and data after six months. 236 (86.8%) patients consented to participate. Questionnaires at post-treatment were completed by 155 (65.7%) persons and after six months by 169 (71.6%) persons. The medical performance evaluation given in the discharge letters documented a better performance of the intervention group (positive capacity: p=0.037; negative capacity: p=0.016). This evaluation was also reflected by the patients' evaluation at post-treatment. Participants of the intervention group reported higher work-related self-efficacy (p<0.001) and felt that they are better prepared for the time after their rehabilitation (p=0.006). After six months participants of the intervention group had a 2.4-fold higher chance (p=0.007) of returning to work, reported a better mental condition (HADS depression: p=0.014; SF-36 Mental Health Index: p=0.026) and a more salutary work-related behaviour (AVEM striving for perfection: p=0.012). Regarding physical outcomes both groups achieved moderate to high effects. Results of the trial confirm that an intensified work-related programme with a well-defined multimodal composition like the one presented here is able to enhance the chances of participation in working life for patients with substantial work-related problems.


Molecular photothermal effects on time-resolved IR spectroscopy.
Time-resolved IR pump-probe (IR-PP) and two-dimensional IR (2D-IR) spectroscopy are valuable techniques for studying various ultrafast chemical and biological processes in solutions. The time-dependent changes of nonlinear IR signals reflecting fast molecular processes such as vibrational energy transfer and chemical exchange provide invaluable information on the rates and mechanisms of solvation dynamics and structural transitions of multispecies vibrationally interacting molecular systems. However, due to the intrinsic difficulties in distinguishing the contributions of molecule-specific processes to the time-resolved IR signals from those resulting from local heating, it becomes challenging to interpret time-resolved IR-PP and 2D-IR spectra exhibiting transient growing-in spectral components and cross-peaks unambiguously. Here, theoretical considerations of various effects of vibrational coupling, energy transfer, chemical exchange, the generation of hot ground states, molecular photothermal process, and their combinations on the line shapes and time-dependent intensities of IR-PP spectra and 2D-IR diagonal peaks and cross-peaks are presented. We anticipate that the present work will help researchers using IR pump-probe and 2D-IR techniques to distinguish local heating-induced photothermal signals from genuine nonlinear IR signals.


Effect of rare-earth component of the RE/Ni catalyst on the formation and nanostructure of single-walled carbon nanotubes.
A systematic experimental study has been carried out on the efficiency of bimetallic catalysts based on Ni and the rare-earth elements Y, La, Ce, Nd, Gd, Tb, Dy, Ho, Er, and Lu (group A) and Eu, Sm, Yb, and Tm (group B) in the synthesis of single-walled carbon nanotubes (SWNTs). The two groups give quite different results when analyzed by a combination of SEM/TEM and Raman and UV-NIR spectroscopies. The elements in group A have an obvious catalytic effect and increase the yield of SWNTs dramatically, whereas those in group B are not efficient catalysts. The diameter distribution of the synthesized SWNTs was also affected by the rare-earth element used. For group A metals, there is a tendency that the fraction of small-diameter tubes decreases with decreasing ionic radius of the rare-earth element used. EDX and X-ray analyses indicate that group A metals deposit on the cathode deposits and form rare-earth carbides, whereas no group B metals are found in cathode deposits, except for a small amount of Tm present in the form of thulium carbide. Further analysis indicates that there is a very strong correlation between the ability to form rare-earth carbides and the catalytic efficiency for the formation of SWNTs.


The last vial. What it means to (aspiring) parents to use the same sperm donor for siblings.
Introduction: A lot of attention has been given to the quest of parents, children and donors to find donor siblings (= half siblings who share the same donor gametes but who are born in different families). However, literature is scarce about the use of the same sperm donor for subsequent children in the same family.Methods: This study included 68 lesbian and heterosexual (aspiring) parents, recruited at the Department of Reproductive Medicine of Ghent University Hospital (Belgium). The in-depth semi-structured couple interviews were performed between October 2012 and October 2013. Data were analyzed through step-by-step inductive thematic analysis.Results: The couples showed a clear preference to use the same sperm donor for their children. The most common reasons for this preference were related to the family or sibling relationships and medical reasons. Uncertainty about the availability of the same donor over time seeped through in their stories. Most lesbian aspiring parents decided that both partners should have a genetic link with at least one child.Conclusion: The use of the same sperm donor for subsequent conceptions appeared quasi unambiguously in the interviews of the lesbian and heterosexual (aspiring) parents in our study.


Levofloxacin: a review of its use in the treatment of bacterial infections in the United States.
Levofloxacin (Levaquin) is a fluoroquinolone antibacterial agent with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and atypical respiratory pathogens. It is active against both penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae. The prevalence of S. pneumoniae resistance to levofloxacin is <1% overall in the US.A number of randomised comparative trials in the US have demonstrated the efficacy of levofloxacin in the treatment of infections of the respiratory tract, genitourinary tract, skin and skin structures. Sequential intravenous to oral levofloxacin 750mg once daily for 7-14 days was as effective in the treatment of nosocomial pneumonia as intravenous imipenem/cilastatin 500-1000mg every 6-8 hours followed by oral ciprofloxacin 750mg twice daily in one study. In patients with mild to severe community-acquired pneumonia (CAP), intravenous and/or oral levofloxacin 500mg once daily for 7-14 days achieved clinical and bacteriological response rates similar to those with comparator agents, including amoxicillin/clavulanic acid, clarithromycin, azithromycin, ceftriaxone and/or cefuroxime axetil and gatifloxacin. A recent study indicates that intravenous or oral levofloxacin 750mg once daily for 5 days is as effective as 500mg once daily for 10 days, in the treatment of mild to severe CAP. Exacerbations of chronic bronchitis and acute maxillary sinusitis respond well to treatment with oral levofloxacin 500mg once daily for 7 and 10-14 days, respectively. Oral levofloxacin was as effective as ofloxacin in uncomplicated urinary tract infections and ciprofloxacin or lomefloxacin in complicated urinary tract infections. In men with chronic bacterial prostatitis treated for 28 days, oral levofloxacin 500mg once daily achieved similar clinical and bacteriological response rates to oral ciprofloxacin 500mg twice daily. Uncomplicated skin infections responded well to oral levofloxacin 500mg once daily for 7-10 days, while in complicated skin infections intravenous and/or oral levofloxacin 750mg for 7-14 days was at least as effective as intravenous ticarcillin/clavulanic acid (+/- switch to oral amoxicillin/clavulanic acid) administered for the same duration. Levofloxacin is generally well tolerated, with the most frequently reported adverse events being nausea and diarrhoea; in comparison with some other quinolones it has a low photosensitising potential and clinically significant cardiac and hepatic adverse events are rare. Levofloxacin is a broad-spectrum antibacterial agent with activity against a range of Gram-positive and Gram-negative bacteria and atypical organisms. It provides clinical and bacteriological efficacy in a range of infections, including those caused by both penicillin-susceptible and -resistant strains of S. pneumoniae. Levofloxacin is well tolerated, and is associated with few of the phototoxic, cardiac or hepatic adverse events seen with some other quinolones. It also has a pharmacokinetic profile that is compatible with once-daily administration and allows for sequential intravenous to oral therapy. The recent approvals in the US for use in the treatment of nosocomial pneumonia and chronic bacterial prostatitis, and the introduction of a short-course, high-dose regimen for use in CAP, further extend the role of levofloxacin in treating bacterial infections.


Investigating ethnic variations in reporting of psychotic symptoms: a multiple-group confirmatory factor analysis of the Psychosis Screening Questionnaire.
Epidemiological evidence suggests risk for psychosis varies with ethnicity in Western countries. However, there is little evidence to date on the cross-cultural validity of screening instruments used for such comparisons. Combining two existing UK population-based cohorts, we examined risk for reporting psychotic symptoms across White British (n = 3467), White Irish (n = 851), Caribbean (n = 1899), Indian (n = 2590), Pakistani (n = 1956) and Bangladeshi groups (n = 1248). We assessed the psychometric properties of the Psychosis Screening Questionnaire (PSQ) with a multiple-group confirmatory factor analysis, assessing the equivalence of factor loadings, response thresholds and residual variances in an analysis of measurement non-invariance. Compared with prevalence among British Whites (5.4%), the prevalence of self-reported psychotic symptoms was greater in the Caribbean group (12.7%, adjusted OR = 2.38 [95% CI 1.84-3.07]). Prevalence was also increased among Pakistani individuals (8.3%, adjusted OR = 1.36 [1.01-1.84]) although this difference was driven by a greater likelihood of reporting paranoid symptoms. PSQ items for thought interference, strange experience and hallucination were measured in equivalent ways across ethnic groups. However, our measurement models suggested that paranoid symptoms were measured less reliably among ethnic minorities than among British Whites and appeared to exaggerate latent differences between Pakistani and White British groups when measurement non-invariance was not accounted for. Notwithstanding evidence for measurement non-invariance, the greater risk for reporting psychotic symptoms among Caribbean individuals is unlikely to be an artefact of measurement. Greater residual variance in the recording of paranoid symptoms among ethnic minority respondents warrants caution in using this item to investigate ethnic variation in psychosis risk.


Insulin-resistance and associated risk factors for coronary heart disease as seen in families.
Recent reports have shown that resistance to insulin-stimulated glucose uptake, increased plasma glucose and insulin response to oral glucose, and hypertriglyceridemia can be seen in first degree relatives of patients with type 2 diabetes. We have recently shown that very similar metabolic changes can be seen in hyperinsulinemic individuals who have either normal or impaired glucose tolerance (IGT). Given these data, we thought it would be of interest to compare the plasma glucose and insulin response to an oral glucose challenge, plasma lipid concentrations, and blood pressure in offspring of parents with IGT as compared to offspring of parents with normal glucose tolerance. Parents with IGT had higher plasma insulin and triglyceride levels and blood pressure than those with normal glucose tolerance. The two groups of offspring were young, non-obese and similar in terms of age, gender distribution and body mass index. Statistically significant increases in plasma insulin response to oral glucose and in systolic and diastolic blood pressure were present in the offspring of parents with IGT. Demonstration of similar abnormalities in plasma insulin response to glucose and blood pressure regulation in patients with IGT and in their offspring is consistent with the view that individual differences in insulin metabolism and blood pressure are modulated by genetic factors and that both may be related to variations in insulin-stimulated glucose uptake and/or plasma insulin concentration.


Thinking about the idea of consent in data science genomics: How 'informed' is it?
In this paper we argue that 'informed' consent in Big Data genomic biobanking is frequently less than optimally informative. This is due to the particular features of genomic biobanking research which render it ethically problematic. We discuss these features together with details of consent models aimed to address them. Using insights from consent theory, we provide a detailed analysis of the essential components of informed consent which includes recommendations to improve consent performance. In addition, and using insights from philosophy of mind and language and psycholinguistics we support our analyses by identifying the nature and function of concepts (ideas) operational in human cognition and language together with an implicit coding/decoding model of human communication. We identify this model as the source of patients/participants poor understanding. We suggest an alternative, explicit model of human communication, namely, that of relevance-theoretic inference which obviates the limitations of the code model. We suggest practical strategies to assist health service professionals to ensure that the specific information they provide concerning the proposed treatment or research is used to inform participants' decision to consent. We do not prescribe a standard, formal approach to decision-making where boxes are ticked; rather, we aim to focus attention towards the sorts of considerations and questions that might usefully be borne in mind in any consent situation. We hope that our theorising will be of real practical benefit to nurses and midwives working on the clinical and research front-line of genomic science.


CHD5, a tumor suppressor gene deleted from 1p36.31 in neuroblastomas.
Neuroblastomas are characterized by hemizygous 1p deletions, suggesting that a tumor suppressor gene resides in this region. We previously mapped the smallest region of consistent deletion to a 2-Mb region of 1p36.31 that encodes 23 genes. Based on mutation analysis, expression pattern, and putative function, we identified CHD5 as the best tumor suppressor gene candidate. We determined the methylation status of the CHD5 gene promoter in NLF and IMR5 (with 1p deletion) and SK-N-SH and SK-N-FI neuroblastoma cell lines using methylation-specific sequencing and measured CHD5 mRNA expression by reverse transcription polymerase chain reaction in cells treated with or without 5-aza-2-deoxycytidine, an inhibitor of DNA methylation. We transfected the cells with CHD5 and antisense (AS) CHD5 DNA to assess the effect of CHD5 overexpression and suppression, respectively, on colony formation in soft agar and growth of xenograft tumors in athymic mice. We also analyzed the association of CDH5 expression with outcomes of 99 neuroblastoma patients. Statistical tests were two-sided. CHD5 expression was very low or absent in neuroblastoma cell lines. The CHD5 promoter was highly methylated in NLF and IMR5 lines, and CHD5 expression increased after treatment with 5-aza-2-deoxycytidine. Clonogenicity and tumor growth were abrogated in NLF and IMR5 cells overexpressing CHD5 compared with antisense CHD5 (clonogenicity: mean no. of colonies per plate, NLF-CHD5, 43 colonies, 95% confidence interval [CI] = 35 to 51 colonies, vs NLF-CHD5-AS, 74 colonies, 95% CI = 62 to 86 colonies, P < .001; IMR5-CHD5, 11 colonies, 95% CI = 2 to 20 colonies, vs IMR5-CHD5-AS, 39 colonies, 95% CI = 17 to 60 colonies, P = .01; tumor growth, n = 10 mice per group: mean tumor size at 5 weeks, NLF-CHD5, 0.36 cm(3), 95% CI = 0.17 to 0.44 cm(3), vs NLF-CHD5-AS, 1.65 cm(3), 95% CI = 0.83 to 2.46 cm(3), P = .002; IMR5-CHD5, 0.28 cm(3), 95% CI = 0.18 to 0.38 cm(3), vs IMR5-CHD5-AS, 1.15 cm(3), 95% CI = 0.43 to 1.87 cm(3); P = .01). High CHD5 expression was strongly associated with favorable event-free and overall survival (P < .001), even after correction for MYCN amplification and 1p deletion (P = .027). CHD5 is the strongest candidate tumor suppressor gene that is deleted from 1p36.31 in neuroblastomas, and inactivation of the second allele may occur by an epigenetic mechanism.


Doppler study of splanchnic hemodynamics in Hirschsprung's disease.
Doppler studies of splanchnic vessels have demonstrated alteration in blood flow in bowel obstruction and strangulation. The aim of this study was to evaluate hemodynamic changes in celiac artery (CA), superior mesenteric artery (SMA) and inferior mesenteric artery (IMA) using pulsed Doppler sonography (PDS) in Hirschsprung's disease. Fasting splanchnic flowmetry of CA, SMA, and IMA arteries was performed using PDS preoperatively in 13 patients with Hirschsprung's disease and 13 healthy age- and sex-matched controls. Diagnostic workup for Hirschsprung's disease included a barium enema and a rectal biopsy. A primary transanal pull through was performed if the transition zone was at rectosigmoid or midsigmoid. Doppler studies were repeated on the 1st and 7th postoperative day under similar conditions. Mean flow velocity (V(mean)) and the pulsatility index (PI) of the three major vessels was measured. Patients with Hirschsprung's disease showed increased blood flow velocities in CA, SMA, and IMA (p < 0.001), an increased resistance to blood flow in IMA (p < 0.001) and a decreased resistance to blood flow in CA and SMA (p < 0.005 and p < 0.001, respectively). The blood flow velocity for IMA normalized after resection of the aganglionic segment (r = 0.41, p < 0.005, 95% CI: 45.4-52.7). Hirschsprung's diseaseis associated with alterations in splanchnic vessel hemodynamics which are reversible after corrective surgery. Doppler studies may play an important role in the assessment of bowel function after surgery.


Synchrotron Fourier transform infrared (FTIR) analysis of single living cells progressing through the cell cycle.
The application of FTIR spectroscopy to disease diagnosis requires a thorough knowledge of the spectroscopy associated with the cell cycle to discern disease markers from normal cellular events. We have applied synchrotron FTIR spectroscopy to monitor cells at different phases of the cell cycle namely G1, S and G2 phases. By applying Principal component analysis (PCA) from three independent trials we show clustering on a 2-dimensional scores plots (PC1 versus PC2) from cell spectra only two hours apart within the cell cycle. The corresponding PCA Loadings Plots indicate the clustering is primarily based on changes to the overall concentration of nucleic acids, proteins and lipids. During the first ten hours post mitosis, cells are observed to increase in protein and decrease in both lipid and nucleic acid concentration. During the synthesis phase, (beginning 9-11 hours post-mitosis) the PCA Loadings Plots show the accumulation of lipids within the cell as well the duplication of the genome as evidenced by strong DNA contributions. In the 4-6 hours following the synthesis phase, the cells once again accumulate protein while the relative nucleic acid and lipid concentrations decrease. These results, in comparison to previous studies on dehydrated cells, show previously unresolvable biochemical information as well as highlighting the advantages of FTIR spectroscopy applied to single living cells.


Electrostatic airborne ultrasonic transducers: modeling and characterization.
An a priori theoretical model for electrostatic airborne ultrasonic transducers has been developed. The historical development of transducer modeling is briefly reviewed. This paper applies the plate-on-air-spring model to establish a mathematical formulation for the transducer behavior in terms of the characterized impedance parameters. It is clarified that such an electrostatic transducer is a capacitive-type device and obeys the reciprocity principle in the same way as a piezoelectric device. The accurate prediction of multiple resonant frequencies and transmitting responses for a typical V-grooved backplate transducer serve to substantiate the theoretical model.


Field trials with chlorproguanil in the prophylaxis of malaria in Ghana.
Chlorproguanil is one of the antimalarial drugs developed in recent years which have shown promise for field use in malaria eradication campaigns. It has been demonstrated to possess properties similar to those of proguanil but with a more persistent action. The author reports the results obtained in four field trials with this drug in Ghana.Chlorproguanil was shown to have a rapid action on asymptomatic parasitaemias of P. falciparum and P. malariae (exclusive of crescents) in Ghanaian schoolchildren. In weekly doses of 20 mg it protected a group of children from reinfection for four weeks, but thereafter irregular dosage was associated with a small number of break-throughs by P. falciparum. By the end of six months there was strong evidence of P. falciparum resistance to the drug. Evidence was also found in P. falciparum infections of cross-resistance between chlorproguanil and pyrimethamine.Unlike pyrimethamine, chlorproguanil was not secreted in the maternal milk in sufficient quantity to be of therapeutic value to young, wholly breast-fed infants.The author considers that, while this drug might serve as an effective weekly prophylactic in households where the regimen would be strictly followed, it would not be suitable for long-term community use in rural tropical Africa.


Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase.
Cbl is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface. The evolutionarily conserved amino-terminal region of Cbl (Cbl-N) binds to phosphorylated tyrosine residues and has cell-transforming activity. Point mutations in Cbl that disrupt its recognition of phosphotyrosine also interfere with its negative regulatory function and, in the case of v-cbl, with its oncogenic potential. In T cells, Cbl-N binds to the tyrosine-phosphorylated inhibitory site of the protein tyrosine kinase ZAP-70. Here we describe the crystal structure of Cbl-N, both alone and in complex with a phosphopeptide that represents its binding site in ZAP-70. The structures show that Cbl-N is composed of three interacting domains: a four-helix bundle (4H), an EF-hand calcium-binding domain, and a divergent SH2 domain that was not recognizable from the amino-acid sequence of the protein. The calcium-bound EF hand wedges between the 4H and SH2 domains and roughly determines their relative orientation. In the ligand-occupied structure, the 4H domain packs against the SH2 domain and completes its phosphotyrosine-recognition pocket. Disruption of this binding to ZAP-70 as a result of structure-based mutations in the 4H, EF-hand and SH2 domains confirms that the three domains together form an integrated phosphoprotein-recognition module.


TGF-β/SMAD/GLI2 signaling axis in cancer progression and metastasis.
The Hedgehog (HH) and TGF-β signaling pathways represent essential regulators of cell proliferation and differentiation during embryogenesis. Pathway deregulation is a characteristic of various cancers. Recently, evidence for a convergence of these pathways at the level of the GLI2 transcription factor in the context of tumor initiation and progression to metastasis has emerged. This short review summarizes recent knowledge about GLI2 function and mechanisms of action downstream of TGF-β in cancer.


Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance.
Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.


Traumatic rupture of a hydatid cyst of the liver presenting with skin lesions.
The hydatid cyst is the evolution of a parasitic infection caused by Echinococcus granulosus and is an endemic disease in Turkey. The hydatid cysts of the liver can give origin to several complications and the rupture is one of them. Rupture can occur spontaneously or as a result of external trauma. The presentation with skin lesions is very rare. We present a 20-year-old male patient who presented himself after a car accident, and was diagnosed with a rupture of traumatic hydatid cysts due to hives rash. In the operation, a scolicidal gent was administered to the cyst, the cyst wall was partially excised and the germinative membranes were removed. Medical treatment with albendazole was started. The postoperative period was quiet. The intraperitoneal traumatic rupture of a hydatid cyst is rare, but it can cause severe anaphylactic reactions and biliary peritonitis. Although a rare and broken hydatid cyst due to trauma may present with skin lesions in a patient in an endemic region, it should be considered in the differential diagnosis. KEY WORDS: Primary hydatid cyst, Trauma, Urticaria.


Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake.
Plasma and adipose tissue concentrations of carotenoids are thought to reflect short- and long-term intakes of carotenoids, respectively. The ability of adipose tissue carotenoid concentrations to reflect dietary intake in population studies is unknown. We examined the relation between intakes of the major dietary carotenoids and their concentrations in plasma and adipose tissue. A blood sample and an adipose tissue biopsy sample were collected from 115 women and 344 men in Costa Rica after they had fasted overnight, and a dietary interview based on a 135-item food-frequency questionnaire was administered. After carotenoid intake was adjusted for total energy intake and plasma concentrations were adjusted for HDL-, LDL-, and VLDL-cholesterol concentrations, we calculated partial Spearman correlation coefficients that were adjusted for age, sex, smoking, and body mass index. In women, the correlations (r) between intakes and concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, and lutein+zeaxanthin were 0.25, 0.29, 0.44, and 0.17, respectively (P < 0.05 for r > or = 0.19), in adipose tissue and 0.26, 0.13, 0.55, and 0.22 in plasma. In men, these values were 0.04, 0.07, 0.23, and 0.06 in adipose tissue and 0.24, 0.22, 0.44, and 0.20 in plasma. In women and men, correlations for lycopene were higher in plasma (r = 0.19 and 0.35, respectively) than in adipose tissue (r = 0.14 and 0.26). The relative abundance of each carotenoid in the diet was similar to its distribution in plasma but not in adipose tissue. The usefulness of adipose tissue and plasma carotenoids as biomarkers of intake is similar, although correlations for individual carotenoids vary substantially.


Surgery for lung abscess in immunocompetent and immunocompromised children.
The aim of this study was to evaluate the surgical management results of lung abscess in immunocompetent and immunocompromised children. Surgery was performed on 30 children with lung abscess or necrotizing pneumonia refractory to medical treatment in a 12-year period. Of them, 23 were immunocompetent, and 7 were immunocompromised. Pulmonary resection was performed including unilateral lung in 28, bilateral in 2, and 2 lobes in 6. Concomitant decortication was performed in 18 (78.2%) immunocompetent patients. Increased incidence of surgery for lung abscess was caused mainly by drug-resistant and fungal infection. Surgery was performed commonly for bacterial lung abscess on patients less than 5 years old and fungal lung abscess on adolescence. A multiple small abscess was the predominant type of abscess in immunocompetent patients, whereas 2-lobe involvement tended to occur in immunocompromised patients. Fungal lung abscess tended to occur on left lung and in female patients. Left lower lobe was involved most commonly in both groups of patients in which majority need lobectomy. Immunocompromised patients required a more extensive pulmonary resection. There were 3 postoperative complications (morbidity of 10.2%) with no postoperative mortality. Length of postoperative hospital stay ranged from 6 to 85 days with average of 18.4 days. The incidence and pattern of lung abscess that required surgery between immunocompetent and immunocompromised children were different. A more aggressive, extensive surgical procedure is preferable for immunocompromised patients, and the surgical results were comparatively excellent to immunocompetent patients. However, the prognosis of immunocompromised children depends on their underlying disease process.


The treatment of osteomyelitis of the tibia with sodium salicylate. An experimental study in rabbits.
Osteomyelitis was induced in the tibiae of rabbits by injecting a suspension of Staphylococcus aureus and sodium tetradecylsulphate, a sclerosing agent. These rabbits were then divided into two groups: one group remained untreated and the other was fed a diet containing sodium salicylate. Two and four weeks after induction of osteomyelitis the tibiae taken from untreated rabbits with osteomyelitis and incubated in vitro released significantly more prostaglandin E and F than the control uninjected or uninfected tibiae. Tibiae taken from rabbits treated with sodium salicylate showed minimal radiographic changes and a significantly decreased release of prostaglandin E and F compared to the untreated rabbits. Prostaglandins are known to be potent bone resorbing agents and the results of this study suggest that they may also be involved in the destruction of bone which is characteristic of osteomyelitis. The treatment of rabbits with osteomyelitis using anti-inflammatory drugs, which block synthesis of prostaglandins, in addition to antibiotics, may prevent the destruction of bone and possible sequestration thereby decreasing the risk of chronic disease.


Tyrosine hydroxylase gene associated with depressive symptomatology in mood disorder.
Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of dopamine and norepinephrine. It may be involved in the pathophysiology of psychiatric disorders and positive associations have been reported for TH gene markers in mood disorders. While most replications failed to confirm the initial findings, other papers suggested a potential role of this gene in the etiology of mood disorders. Among the many different reasons for a lack of consistent replications, a critical role is played by the "correct" phenotype identification. Actually, up to now the only classification criteria has been the psychiatric diagnosis, but within the same psychiatric diagnoses the symptomatologic presentation may vary dramatically depending upon severity, presence of psychotic features or other psychopathologic traits. Thus, the aim of our study is to evaluate a possible association for TH gene with symptomatology in a sample of subjects affected by mood disorders. We have developed a phenotype definition based on the observed symptomatology divided into the four factors "Excitement," "Depression," "Delusion," and "Disorganization." Our sample includes 46 mood disorder subjects, investigated by the OPCRIT (operational criteria checklist for psychotic illness) checklist for their symptomatological pattern and typed for TH variants by polymerase chain reaction (PCR) amplification. Depressive factor was associated with TH variants (F = 4.79, df = 4, 87, P = 0.006), with TH*2 subjects presenting lower depressive scores. Subjects with genotype TH*2/2 were the only ones in the sample to report mild depressive episodes. TH variants may be related with depressive symptomatology in subjects affected by mood disorders.


Role of pentraxin 3 in shaping arthritogenic alphaviral disease: from enhanced viral replication to immunomodulation.
The rising prevalence of arthritogenic alphavirus infections, including chikungunya virus (CHIKV) and Ross River virus (RRV), and the lack of antiviral treatments highlight the potential threat of a global alphavirus pandemic. The immune responses underlying alphavirus virulence remain enigmatic. We found that pentraxin 3 (PTX3) was highly expressed in CHIKV and RRV patients during acute disease. Overt expression of PTX3 in CHIKV patients was associated with increased viral load and disease severity. PTX3-deficient (PTX3(-/-)) mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Furthermore, binding of the N-terminal domain of PTX3 to RRV facilitated viral entry and replication. Thus, our study demonstrates the pivotal role of PTX3 in shaping alphavirus-triggered immunity and disease and provides new insights into alphavirus pathogenesis.


Addressing the practicalities of anodic stripping voltammetry for heavy metal detection: a tutorial review.
Anodic Stripping Voltammetry (ASV) has the capability to detect heavy metals at sub ppb-level with portable and cheap instrumentation making it ideal for in the field (at the source) analysis, however, commercial activity is surprisingly limited. The more commonly used liquid mercury electrodes are now obsolete due to toxicity concerns, and replacements are all based around solid electrodes, which come with their own challenges. This tutorial review aims to discuss the experimental practicalities of ASV, providing a clear overview of the issues for consideration, which can serve as a guide for anyone wanting to undertake analytical ASV. Choice of electrode material (with or without subsequent modification) and solution composition (pH, electrolyte, buffer) are important parameters, as well as an understanding of pH dependent metal speciation and possible intermetallic effects. Measurements made on model solutions often differ from those made on environmental samples with the latter containing organic matter, biological and inorganic species, which themselves can adsorb metal ions. Consideration should also be given to the method of solution collection and the sample container utilised. ASV can be a powerful tool to an analytical chemist, however optimisation for the application of interest is essential, which this review aims to help guide.


Assessment of vectorial total variation penalties on realistic dual-energy CT data.
Vectorial extensions of total variation have recently been developed for regularizing the reconstruction and denoising of multi-channel images, such as those arising in spectral computed tomography. Early studies have focused mainly on simulated, piecewise-constant images whose structure may favor total-variation penalties. In the current manuscript, we apply vectorial total variation to real dual-energy CT data of a whole turkey in order to determine if the same benefits can be observed in more complex images with anatomically realistic textures. We consider the total nuclear variation ([Formula: see text]) as well as another vectorial total variation based on the Frobenius norm ([Formula: see text]) and standard channel-by-channel total variation ([Formula: see text]). We performed a series of 3D TV denoising experiments comparing the three TV variants across a wide range of smoothness parameter settings, optimizing each regularizer according to a very-high-dose 'ground truth' image. Consistent with the simulation studies, we find that both vectorial TV variants achieve a lower error than the channel-by-channel TV and are better able to suppress noise while preserving actual image features. In this real data study, the advantages are subtler than in the previous simulation study, although the [Formula: see text] penalty is found to have clear advantages over either [Formula: see text] or [Formula: see text] when comparing material images formed from linear combinations of the denoised energy images.