Unusual ocular manifestations of ethomoidal mucocele: a case report.
A 42-year-old female patient had vision loss and chronic epiphora in her left eye. Her best-corrected visual acuity was 10/10 in the right eye and 0.3/10 in the left eye. The anterior segment examination results were normal. In fundus examination, choroidal folds were detected. Optical coherence tomography showed elevation on the macula and choroidal folds. Ultrasonography revealed a T-sign. Magnetic resonance imaging revealed an ethmoidal mucocele that compresses the orbital tissues. Surgical treatment was performed in the otorhinolaryngology department. Postoperatively, choroidal folds recovered, and the best-corrected visual acuity improved, but subretinal fluid accumulated. During the follow-up period without any treatment, subretinal fluid totally disappeared.


Paediatric critical incident analysis: lessons learnt on analysis, recommendations and implementation.
The objectives of this study were to identify causal and contributing factors of serious patient safety incidents in a paediatric university hospital, to report on ensuing recommendations and to assess the extent of implementation of the recommendations. The possible causal and contributing factors identified in 17 incidents were classified by a system devised by Vincent et al. Proposed recommendations were classified by the same system, and degrees of implementation were established. A median of 5 causal and contributing factors per incident were identified. Twenty-two percent of all factors were related to teamwork and 22 % to task factors. A median of 5 recommendations per analysis were formulated. Most recommendations were related to task factors (36 %). The time load of each analysis was a mean of 27 h. One third of the recommendations have been acted upon, mostly those related to task and team factors. Incident analysis is time-consuming but yields indispensable information on causal and contributing factors, presenting numerous opportunities for quality improvement. The value of these analyses could be improved by appointing responsibilities and setting up time frames for implementation. A bottom-up approach with managerial support appears to be a key to turning incident analysis and quality improvement into an ongoing process.


Analysis of dose distribution in organs at risk in patients with prostate cancer treated with the intensity-modulated radiation therapy and arc technique.
This study describes a comparative analysis of treatment plans in 48 patients with prostate cancer treated with ionizing radiation. Each patient was subjected to the intensity-modulated radiation therapy (IMRT) and arc technique. In each treatment plan, the organs at risk were assessed: the urinary bladder, rectum and heads of the femur, as well as the volume of normal tissue. The following features were compared: treatment time, conformity indices for the planning target volume, mean doses and standard deviation in organs at risk, and organ volumes for each particular dose. The treatment period in the arc technique is 13.7% shorter than in the IMRT technique. Comparing the results of the IMRT and arc techniques (arc vs. IMRT), the mean values were 29.21 ± 12.91 Gy versus 28.36 ± 13.79 Gy for the bladder, 20.36 ± 3.16 Gy versus 18.17 ± 5.11 Gy for the right femoral head, and 18.98 ± 3.28 Gy versus 16.67 ± 5.15 Gy for the left femoral head. For the rectum, lower values were obtained after application of the arc technique, not the IMRT technique: 35.84 ± 12.28 Gy versus 35.90 ± 13.05 Gy. The results indicate that the applied therapy has a statistically significant influence on the volume for a particular dose with regard to the urinary bladder. It is advisable to apply the IMRT technique to patients who need the femur heads and urinary bladder protected by exposing them to low irradiation doses.


Evaluating a measure of tanning abuse and dependence.
To evaluate the Structured Interview for Tanning Abuse and Dependence (SITAD). Longitudinal survey. College campus. A total of 296 adults. The SITAD modified items from the Structured Clinical Interview for DSM-IV Axis I Disorders that focus on opiate abuse and dependence. Indoor tanning (IT) behavioral patterns and opiate-like reactions to tanning were measured, and IT behavior was measured 6 months later. Of 296 participants, 32 (10.8%) met the SITAD criteria for tanning abuse (maladaptive pattern of tanning as manifested by failure to fulfill role obligations, physically hazardous tanning, legal problems, or persistent social or interpersonal problems) and 16 (5.4%) for tanning dependence as defined by 3 or more of the following: loss of control, cut down, time, social problems, physical or psychological problems, tolerance, and withdrawal. The IT frequency in dependent tanners was more than 10 times the rate in participants who do not meet the SITAD criteria for tanning abuse or dependence. Tanning-dependent participants were more likely to report being regular tanners (75%; odds ratio, 7.0). Dependent tanners scored higher on the opiate-like reactions to tanning scale than did abuse tanners, who scored higher than those with no diagnosis. The SITAD demonstrated some evidence of validity, with tanning-dependent participants reporting regular IT, higher IT frequency, and higher scores on an opiate-like reactions to tanning scale. A valid tanning dependence screening tool is essential for researchers and physicians as a tanning-dependent diagnosis may facilitate a better understanding of tanning motivations and aid in the development of efficacious intervention programs.


Weirdest Martensite: Smectic Liquid Crystal Microstructure and Weyl-Poincaré Invariance.
Smectic liquid crystals are remarkable, beautiful examples of materials microstructure, with ordered patterns of geometrically perfect ellipses and hyperbolas. The solution of the complex problem of filling three-dimensional space with domains of focal conics under constraining boundary conditions yields a set of strict rules, which are similar to the compatibility conditions in a martensitic crystal. Here we present the rules giving compatible conditions for the concentric circle domains found at two-dimensional smectic interfaces with planar boundary conditions. Using configurations generated by numerical simulations, we develop a clustering algorithm to decompose the planar boundaries into domains. The interfaces between different domains agree well with the smectic compatibility conditions. We also discuss generalizations of our approach to describe the full three-dimensional smectic domains, where the variant symmetry group is the Weyl-Poincaré group of Lorentz boosts, translations, rotations, and dilatations.


Permanent work disability before and after ischaemic heart disease or stroke event: a nationwide population-based cohort study in Sweden.
We examined the risk of disability pension before and after ischaemic heart disease (IHD) or stroke event, the burden of stroke compared with IHD and which factors predicted disability pension after either event. A population-based cohort study with follow-up 5 years before and after the event. Register data were analysed with general linear modelling with binary and Poisson distributions including interaction tests for event type (IHD/stroke). All people living in Sweden, aged 25‒60 years at the first event year, who had been living in Sweden for 5 years before the event and had no indication of IHD or stroke prior to the index event in 2006‒2008 were included, except for cases in which death occurred within 30 days of the event. People with both IHD and stroke were excluded, resulting in 18 480 cases of IHD (65%) and 9750 stroke cases (35%). Disability pension. Of those going to suffer IHD or stroke event, 25% were already on disability pension a year before the event. The adjusted OR for disability pension at first postevent year was 2.64-fold (95% CI 2.25 to 3.11) for people with stroke compared with IHD. Economic inactivity predicted disability pension regardless of event type (OR=3.40; 95% CI 2.85 to 4.04). Comorbid mental disorder was associated with the greatest risk (OR=3.60; 95% CI 2.69 to 4.83) after an IHD event. Regarding stroke, medical procedure, a proxy for event severity, was the largest contributor (OR=2.27, 95% CI 1.43 to 3.60). While IHD event was more common, stroke involved more permanent work disability. Demographic, socioeconomic and comorbidity-related factors were associated with disability pension both before and after the event. The results help occupational and other healthcare professionals to identify vulnerable groups at risk for permanent labour market exclusion after such an event.


Restrained Terminal Differentiation and Sustained Stemness in Neonatal Skin by Ha-Ras and Bcl-2.
Nonmelanoma skin cancer is the most frequently diagnosed cancer in the United States. Deregulation of bcl-2 and ras family members is commonly observed in nonmelanoma skin cancer. It has been previously demonstrated that simultaneous bcl-2 and Ha-ras gene expression in keratinocytes results in resistance to cell death induced by ultraviolet radiation and enhanced multistep skin carcinogenesis. In this study, we aimed to elucidate the central roles of Ha-Ras and Bcl-2 in maintaining epidermal homeostasis. To assess the effect of deregulated Ha-Ras and Bcl-2 on skin differentiation, we have generated skin-specific transgenic mouse model constitutively expressing both oncogenic Ha-Ras and Bcl-2. Ectopic expression of Ha-Ras and Bcl-2 in newborn double transgenic epidermal keratinocytes induced abnormal epidermal differentiation accompanied by increased cell proliferation and suppressed apoptotic cell death, which resulted in thickened and wrinkled skin morphology in neonate skins. Expression of epidermal differentiation marker cytokeratin 1 was decreased. Expression of other differentiation markers loricrin and filaggrin was also decreased and delayed to be detected only in the upper stratum granulosum, whereas the proliferative markers cytokeratin 14 and cytokeratin 6, which are expressed in constitutively proliferative basal layer and stem cell niches such as hair follicles or neoplastic lesions, respectively, were highly expressed. The abnormal expression of epidermal cytokeratins suggests that Ha-Ras and Bcl-2 suppress the terminal differentiation and sustain the stem cell-like features in epidermal keratinocytes.


A qualitative evaluation of racial disparities in glucose control.
Type 2 diabetes is more prevalent and severe among African Americans than among Whites. To elucidate barriers to glucose control that are unique to African Americans with poor glucose control we conducted a qualitative study among veterans with diabetes in an academic Veterans Affairs medical center. We enrolled African American and White veterans with diabetes; participants' glucose control was described as well controlled or poorly controlled, and groups were organized on the basis of ethnicity and glucose control. Discussions were conducted by using modified nominal group technique to define factors that aided or hindered glucose control. Well-controlled groups similarly reported that self-care, health care, and psychosocial factors were important in controlling glucose. Although poorly controlled African Americans cited self-care as important, they also noted difficulty following self-care practices and the interference of psychosocial factors with glucose control. Poorly controlled Whites were similar. Uniquely, poorly controlled African Americans were less likely to report positive healthcare experiences; their barriers were related to poor access and poor relationships with providers. Poorly controlled African Americans endorsed healthy self-care behaviors but found it difficult to follow through. Interventions targeting the management of stress, depression, mood, and temptation, as well as improved access to and communication with providers may help these patients better manage their glucose and minimize disparities in diabetes outcomes. (Ethn Dis. 2009; 19:121-127)


There is no relation between the occurrence of proliferative vitreoretinopathy and the location of the donor site after transplantation of a free autologous retinal pigment epithelium-choroid graft.
A free autologous retinal pigment epithelium (RPE)-choroid graft can be harvested during transplantation surgery from a 6 or 12 o'clock site in the midperiphery. This study evaluated whether proliferative vitreoretinopathy (PVR) occurs more frequently in patients with an inferior donor site retinotomy, which is not closed by the tamponade and is in contact with the hydrophilic, pro-inflammatory and fibrotic environment, than in patients with a superior donor site retinotomy. Retrospective analysis of a prospective cohort of 246 patients with exudative age-related macular degeneration treated with an RPE-choroid graft transplantation and a lighter-than-water, 5000 centistoke silicone oil endotamponade. The location of the donor site, the presence or absence of PVR development and the location of PVR were noted. The two-tailed Fisher's exact test was used for statistical analysis. Thirty-nine of 246 (15.9%) patients developed PVR, of whom 35 had a superior donor site and four an inferior donor site. Of the 209 patients without PVR, 155 had a superior donor site and 25 had an inferior one. For 27 patients, no donor site location was explicitly documented in the patient files. We found no difference between the groups with a superior or inferior donor site and the occurrence of PVR (p=0.8). Shifting the inflammatory aqueous milieu away from the graft donor site does not prevent the occurrence of PVR.


Acute Acetabular Protrusion: the Hardinge Approach for Implant Removal and One-stage Hip Reconstruction.
Acute penetration of a total hip arthroplasty into the pelvic cavity is a grave and potentially catastrophic scenario. Fortunately, this complication is uncommon and rarely encountered during a surgical career. Currently, a two-stage procedure is favoured by most surgeons, but the evidence for this is unconvincing and may expose the patient to unnecessary risks. Furthermore, a two-stage approach may be more suitable for the more common chronic migration of a loose acetabular shell, which fundamentally differs from acute pelvic penetration. We present the case of a 76-year-old man referred to our institution for reconstructive surgery following acute pelvic penetration of the acetabular shell during total hip arthroplasty. We used a single-stage Hardinge approach to retrieve the shell and successfully reconstruct the acetabulum. Specific indications for using this method are proposed. In carefully selected cases of intrapelvic implants, a single-stage method can improve patient outcomes while minimising unnecessary risks associated with the conventional two-stage approach.


Intravenous conscious sedation in children.
More and more children undergoing both invasive and noninvasive procedures are receiving intravenous conscious sedation (IVCS). Medications including midazolam and fentanyl are used to provide both anxiety and pain relief, whereas barbiturates such as pentobarbital induce sleep for more sensitive studies including diagnostic imaging. An emphasis on proper staff education regarding airway management, medication delivery, patient assessment, and monitoring is essential for safe administration and care. In addition, planning should include preparation time for the patient and family. Adequate patient education as well as proficiency of the clinician enables IVCS to be delivered safely and effectively to achieve the desired outcome with limited risk to the patient.


Be good to your patient: how the therapeutic relationship in the treatment of patients admitted to assertive outreach affects rehospitalization.
We investigated whether the quality of the therapeutic relationship (TR) between patient and clinician predicts rehospitalization in patients in assertive outreach treatment. Analyses were conducted on 332 "established" (equal to in care for > or =3 months) and 150 "new" (equal to in care for <3 months) patients with severe mental illness sampled from 24 assertive outreach teams in London, England. TR was assessed at baseline using the clinician version of the Helping Alliance Scale. Rehospitalization was assessed over a 9-month follow-up period. Controlling for other predictors, a more positive TR was found to predict fewer hospitalizations in new patients but not in established ones.


STUDIES ON THE PATHOGENESIS OF FEVER. 13. THE EFFECT OF PHAGOCYTOSIS ON THE RELEASE OF ENDOGENOUS PYROGEN BY POLYMORPHONUCLEAR LEUKOCYTES.
1. Phagocytosis promotes the release of endogenous pyrogen from polymorphonuclear leucocytes. 2. The release of pyrogen, though initiated by the phagocytic event, is not synchronous with it. 3. The postphagocytic release mechanism is not inhibited by sodium fluoride and, therefore, appears not to require continued production of energy by the cell. 4. The release process, on the other hand, is inhibited by arsenite, suggesting the participation of one or more sulfhydryl-dependent enzymes in the over-all reaction. 5. Particle for particle, the ingestion of heat-killed rough pneumococci causes the release of approximately 100 times as much pyrogen as the ingestion of polystyrene beads of the same size. 6. The pyrogen release mechanism of polymorphonuclear leucocytes separated directly from blood, unlike that of granulocytes in acute inflammatory exudates, is not readily activated by incubation of the cells in K-free saline. Despite this difference, both blood and exudate leucocytes following phagocytosis release large amounts of pyrogen, even in the presence of K(+). The fact that the postphagocytic reaction is uninhibited by the concentrations of K(+) which are present in plasma and extracellular fluids, suggests that this mechanism of pyrogen release may well operate in vivo. 7. As might be expected from the foregoing observations, the intravenous injection of a sufficiently large number of heat-killed pneumococci causes fever in the intact host. Intravenously injected polystyrene beads, on the other hand, are significantly less pyrogenic. Evidence is presented to support the conclusion that the fever in both instances is caused by pyrogen released from the circulating leucocytes which have phagocyted the injected particles. 8. The possible relationships of these findings to the pathogenesis of fevers caused by acute bacterial infections are discussed.


Post-discharge venous thromboembolism after cancer surgery: extending the case for extended prophylaxis.
To (1) define the frequency of overall and postdischarge venous thromboembolism (VTE) after cancer surgery, (2) identify VTE risk for individual cancer operations, and (3) assess mortality rates in patients who experienced a VTE. Cancer is a known risk factor for VTE but less is known about VTE risk after specific cancer operations. Moreover, most cancer patients routinely receive VTE prophylaxis postoperatively while in the hospital, but few receive prolonged prophylaxis despite strong evidence it reduces postdischarge events. From 211 ACS NSQIP hospitals, 44,656 patients undergoing surgery for 9 cancers were identified (2006-2008). The frequency of VTE within 30-days of surgery was evaluated by cancer site and categorized as occurring before or after discharge. Multivariable logistic regression models were constructed to assess risk factors associated with VTE. VTE occurred in 1.6% of all patients, most frequently after esophagogastric (4.2%) and hepatopancreaticobiliary (3.6%) surgery. Overall, 33.4% of VTEs occurred postdischarge (from 17.9% for esophagogastric to 100% for endocrine operations). Factors associated with VTE were age (≥65 years), cancer/procedure type, metastatic disease, congestive heart failure, body mass index (BMI; ≥25 kg/m(2)), ascites, thrombocytosis (>400,000 cells/mm(3)), albumin (<3.0 g/dL), and operation duration (>2 hours; all P < 0.001). Overall VTE was significantly more likely after gastrointestinal, lung, prostate, and ovarian/uterine operations (all P < 0.001). In those experiencing a VTE, mortality increased over 6-fold (8.0% vs. 1.3%; P < 0.001). One-third of VTE events in cancer surgery patients occurred postdischarge. Postoperative VTE was associated with operation type. Routine postdischarge VTE prophylaxis should be considered for high-risk patients.


Inhibition of adhesion of Clostridium difficile to Caco-2 cells.
For many microorganisms, including Clostridium difficile, mucosal association is an important factor influencing intestinal colonisation and subsequent infection. Inhibition of adhesion of C. difficile to intestinal mucosa could be a new promising strategy for prevention and treatment of antibiotic-associated diarrhoea. We investigated the possibilities of influencing the adhesion of C. difficile by xylitol and bovine colostrum whey. Caco-2 cells and C. difficile cells were incubated with 1%, 5% and 10% solutions of xylitol and colostrum. Our study revealed that both xylitol and colostrum inhibited the adhesion of C. difficile to Caco-2 cells. Inhibition by xylitol was dose-dependent. When compared to the control, the count of adherent C. difficile decreased 3.4 times when treated with 1% xylitol, 12 times when 5% xylitol was applied, and 18.7 times when treated with 10% xylitol. The inhibition of adherence by colostrum was partially dose-dependent: 3.1 times in the case of 1%, and 5.5 times in the cases of 5% and 10% colostrum. Further experimental and clinical studies are needed for the application of xylitol and colostrum in the treatment and prophylaxis of pseudomembraneous colitis.


From Spark to Flame -- Radical Innovations from Cataclysmic Events in Medical Education.
This article was migrated. The article was marked as recommended. We all knew it was coming. We just didn't realize it would all come at once. No, we are not talking about the zombie apocalypse, but rather the emergence of virtual teaching and virtual healthcare delivery pervading every aspect of life as we now know it. In the context of COVID-19 and marked shifts in how and where we teach medical learners, the staggering number of new ideas, adaptations, and innovations has been inspiring. This game-changing pandemic is a spark, a lightning bolt if you will, that has created solutions, where previous barriers may have been in virtual teaching and healthcare provision. It is impossible to even consider going "back to normal", as they say. We believe the torrent of ideas and possibilities for medical education, brought by COVID-19, cannot and should not be stopped. We explore the nuances of virtual teaching and virtual care and seek readers to consider what their actionable frameshift can mean for medical education in their teaching realm moving forward. We believe that this is the time to innovate: the time to radically change our traditional medical education practices. To sustain these innovations, institutional support, participant buy-in, and assessment and outcome data will be invaluable to harness these new opportunities.


Expression of serum amyloid A in uterine cervical cancer.
As an acute-phase protein, serum amyloid A (SAA) is expressed primarily in the liver. However, its expression in extrahepatic tissues, especially in tumor tissues, was also demonstrated recently. In our study, we investigated the expression of SAA in uterine cervical carcinomas, and our results suggested its potential as a serum biomarker. Quantitative real-time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the SAA gene and protein expression levels in the tissues and sera of patients with non-neoplastic lesions (NNLs), cervical intraepithelial neoplasia (CIN) and cervical carcinoma (CC). Compared with NNLs, the SAA gene (SAA1 and SAA4) expression levels were significantly higher in uterine CC (mean copy numbers: 138.7 vs. 5.01, P < 0.000; and 1.8 vs. 0.079, P = 0.001, respectively) by real-time PCR. IHC revealed cytoplasmic SAA protein staining in tissues from adenocarcinoma and squamous cell carcinoma of the cervix. The median serum concentrations (μg/ml) of SAA were 6.02 in patients with NNLs and 10.98 in patients with CIN (P = 0.31). In contrast, the median serum SAA concentration was 23.7 μg/ml in uterine CC patients, which was significantly higher than the SAA concentrations of the NNL group (P = 0.002) and the CIN group (P = 0.024). Our data suggested that SAA might be a uterine CC cell product. High SAA concentrations in the serum of CC patients may have a role in monitoring disease occurrence and could have therapeutic applications. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1433263219102962.


Aids and orthoses in patients with stroke consequences.
The presence of alterations in the muscular tone and in the normal motorial synergies at an articular level causes interferences in the functional recovery of patients with stroke consequences. In the rehabilitative field there are some aids that are useful to replace the compromised functions and to make the patient as autonomous as possible in the common movements of the everyday life. The orthoses are used mainly in two cases: to prevent and/or to contain myofascial retractions (spasticity passive component) and to improve the neuromuscolar control of movement through integration of a partially or totally insufficient function. Hemiparesis patients mainly show synergy alteration of the heel muscles and especially of the peroneus, with the consequent tendency of equinism-supination deviation. Analysis of literature shows a scientific validation especially in the use of dynamic orthoses of legs, the most known being the ankle-foot-orthoses.


Stanford School of Medicine. I. Problems over more than money.
Since World War II the American medical school has become a highly complex institution and, like other American institutions today, the medical school is being challenged to respond to diverse and often conflicting demands. In part the pressure comes from activists who insist that the medical school more fully meet the needs of the community by reforming both training and the delivery of medical care. But another sort of pressure is exerted as a result of changes in internal relationships that have occurred in the last two decades in large measure because of the federal support of biomedical research. As in most institutional conflicts the dispute is expressed in contests over power and money, but, at a more fundamental level, what is involved is the value and reward system of academic medicine and the question of how the medical school is to be governed. This is the first of three articles which will attempt to discuss these issues in the context of the development of one medical school-Stanford's. The first article will describe the pattern and policies of expansion since World War II, and the other two will examine the effects of internal and external pressures for change.


Is 48 hours enough for Obstetrics and Gynaecology training in Europe?
The European Working Time Directive, implemented by the European Union (EU) in 1993, was adopted in the medical profession to improve patient safety as well as the working lives of doctors. The Directive reduced the average amount of hours trainee doctors worked to 48 hours per week. However, its adoption has varied throughout the EU. Its potential effect on both the quality and total amount of hours of -training has caused concern. This monograph presents data on Obstetrics and Gynaecology training in Europe obtained from several of the European Network of Trainees in Obstetrics & Gynaecology's (ENTOG) surveys. The monograph demonstrates large variations in training and explains the difficulties in ascertaining whether 48 hours of training a week is sufficient to become an Obstetrics and Gynaecology specialist in Europe.


Metacontrast and saccadic suppression.
A vertical slit of light illuminated during horizontal saccadic eye movements appeared as a horizontally extended smear when stimulation was terminated before the saccade ended. However, on trials for which duration of illumination of the slit was extended into the period after the saccade, the smear appeared shorter and dimmer, and a clear image of the slit was seen. With further increases in duration, no smears were seen at the highest luminance of the slit employed, although smears were more than 2 log units above threshold when flashes were brief. This saccadic suppression is discussed in terms of metacontrast, with the accumulated luminance in the period after the saccade primarily responsible for masking the effects of the stimulation received during the movement of the eye.


Novel Genetic Locus Influencing Retinal Venular Tortuosity Is Also Associated With Risk of Coronary Artery Disease.
The retina may provide readily accessible imaging biomarkers of global cardiovascular health. Increasing evidence suggests variation in retinal vascular traits is highly heritable. This study aimed to identify the genetic determinants of retinal vascular traits. Approach and Results: We conducted a meta-analysis of genome-wide association studies for quantitative retinal vascular traits derived using semi-automatic image analysis of digital retinal photographs from the GoDARTS (Genetics of Diabetes Audit and Research in Tayside; N=1736) and ORCADES (Orkney Complex Disease Study; N=1358) cohorts. We identified a novel genome-wide significant locus at 19q13 (ACTN4/CAPN12) for retinal venular tortuosity (TortV), and one at 13q34 (COL4A2) for retinal arteriolar tortuosity (TortA); these 2 loci were subsequently confirmed in 3 independent cohorts (Ntotal=1413). In the combined analysis of discovery and replication cohorts, the lead single-nucleotide polymorphism in ACTN4/CAPN12 was rs1808382 (βs.d.=-0.109; SE=0.015; P=2.39×10-13) and in COL4A2 was rs7991229 (βs.d.=0.103; SE=0.015; P=4.66×10-12). Notably, the ACTN4/CAPN12 locus associated with TortV is also associated with coronary artery disease, heart rate, and atrial fibrillation. Genetic determinants of retinal vascular tortuosity are also linked to cardiovascular health. These findings provide a molecular pathophysiological foundation for the use of retinal vascular traits as biomarkers for cardiovascular diseases.


Developmental changes in the type I procollagen processing pathway in chick-embryo cornea.
Type I procollagen processing in chick-embryo corneas was studied at days 12, 14 and 17 of development. Pulse-chase experiments and electrophoretic analysis of salt-soluble extracts showed developmental changes in the processing pathway. A kinetic model was fitted to the data to determine rate constants for processing of both N- and C-propeptides. Data for pro alpha 1(I)-chain processing and pro alpha 2(I)-chain processing were fitted separately (where pro means procollagen). Between days 12 and 17 the relative flux through the pC-collagen (procollagen chain lacking the N-propeptide) and pN-collagen (procollagen chain lacking the C-propeptide) pathways increased approx. 4-fold. Pro alpha 1(I) chains and pro alpha 2(I) chains were processed by slightly different routes. Variations in the rate constants were compared with electron-microscopic measurements of collagen fibril diameters at each stage of development. Diameters increased by less than 10% over the period from 12 to 17 days. It was concluded that fibril diameters are relatively insensitive to the pathway of procollagen processing in the salt-soluble pool.


Simulation fails to replicate stress in trainees performing a technical procedure in the clinical environment.
Simulation-based training (SBT) has become an increasingly important method by which doctors learn. Stress has an impact upon learning, performance, technical, and non-technical skills. However, there are currently no studies that compare stress in the clinical and simulated environment. We aimed to compare objective (heart rate variability, HRV) and subjective (state trait anxiety inventory, STAI) measures of stress theatre with a simulated environment. HRV recordings were obtained from eight anesthetic trainees performing an uncomplicated rapid sequence induction at pre-determined procedural steps using a wireless Polar RS800CX monitor © in an emergency theatre setting. This was repeated in the simulated environment. Participants completed an STAI before and after the procedure. Eight trainees completed the study. The theatre environment caused an increase in objective stress vs baseline (p = .004). There was no significant difference between average objective stress levels across all time points (p = .20) between environments. However, there was a significant interaction between the variables of objective stress and environment (p = .045). There was no significant difference in subjective stress (p = .27) between environments. Simulation was unable to accurately replicate the stress of the technical procedure. This is the first study that compares the stress during SBT with the theatre environment and has implications for the assessment of simulated environments for use in examinations, rating of technical and non-technical skills, and stress management training.


Solid Organ Cool-tip Radiofrequency Ablation: An Experimental Study with Clinicopathological Correlations.
Radiofrequency ablation (RFA) with internally cooled electrodes is a technique for the in situ treatment of solid tumors, inducing characteristic pathological changes with limited clinical complications. Our purpose was to assess RFA-induced histological alterations and correlate them with clinical complications. Using a porcine model, the pathology of RFA-induced kidney, liver and spleen lesions was associated with the postoperative course and clinical complications recorded. Complications and relevant histological lesions, including abscess formation, hemorrhage and bile or urinary leakage, were limited or absent. The majority of RFA-induced necrotic tissue exhibited preserved architecture, with relatively limited inflammatory reaction, associated with sealing of blood/bile vessels or urinary tubules along the periphery of the lesions. The preserved architecture of RFA-induced necrotic tissue, its slow clearance, the relatively limited inflammation and the ability of RFA to seal blood/bile/urinary vessels are probably responsible for the minimal complications observed.


Left ventricular assist device performance with long-term circulatory support: lessons from the REMATCH trial.
Left ventricular assist device (LVAD) failure and malfunction rates are critical gauges for establishing LVADs as a long-term therapy for end-stage heart failure patients. These device performance measures, however, have been inadequately characterized in the bridge-to-transplantation literature. REMATCH is a randomized trial that compares optimal medical management with LVAD implantation for patients with end-stage heart failure. An independent committee adjudicated patient outcomes. The primary endpoint--survival--was analyzed by intention to treat using the log-rank statistic. Frequency of event occurrence was analyzed by Poisson regression. The time to first event was analyzed by the product limit method. Device performance was disaggregated into confirmed malfunctions and system failures. The latter were events in which patients could not be rescued with backup circulatory support measures. The 1-year survival rate was 52% (95% confidence limit [CL]; 40%-63%) for LVAD patients versus 28% (95% CL; 17%-39%) for medical patients and the 2-year survival rate was 29% (95% CL; 19%-40%) for LVAD patients versus 13% (95% CL; 5%-22%) for medical patients. System failure was 0.13 per patient per year and the confirmed LVAD malfunction rate was 0.90. Freedom from device replacement was 87% at 1 year and 37% at 2 years. Despite the observed rates of device malfunction and replacement, LVAD implantation confers clinically significant improvement with regard to survival as compared with medical management. Device modifications and innovations for infection management exhibit great promise of improving device performance in the near future.


[Various data concerning the ultrastructure of Proteus spheroplasts].
Spheroplasts were obtained under the action of penicillin on the same medium which was later used to obtain the L-forms. Spheroplast formation started 15 to 20 minutes after the addition of penicillin and reached the maximum in 2 hours. The first dividing forms were revealed at that time, and this division continued for at least 24 hours. The majority of the cells represented spheroplasts surrounded by outer and cytoplasmic membrane, and only some--true protoplasts--had cytoplasmic membrane alone. Division was anomalous in comparison with the bacterial forms with the cell wall: it was noted that either both daughter cells were surrounded by a common outer membrane, or one daughter cell had two membranes serving as a spheroplast and the other--one membrane, serving as a true protoplast. Individual vesicles and myelin-like structures were found to be extruded into the periplasmic space or directly into the surrounding environment. In the latter case pearl-like structures described by Ryter in the formation of protoplasts in bacilli were observed. However, in the Proteus such structures were largely formed by the material of the plastic layer of the cell wall, and to a lesser extent--by the lipoproteid membrane.


Electrical Stimulation of Visual Cortex: Relevance for the Development of Visual Cortical Prosthetics.
Electrical stimulation of the cerebral cortex is a powerful tool for exploring cortical function. Stimulation of early visual cortical areas is easily detected by subjects and produces simple visual percepts known as phosphenes. A device implanted in visual cortex that generates patterns of phosphenes could be used as a substitute for natural vision in blind patients. We review the possibilities and limitations of such a device, termed a visual cortical prosthetic. Currently, we can predict the location and size of phosphenes produced by stimulation of single electrodes. A functional prosthetic, however, must produce spatial temporal patterns of activity that will result in the perception of complex visual objects. Although stimulation of later visual cortical areas alone usually does not lead to a visual percept, it can alter visual perception and the performance of visual behaviors, and training subjects to use signals injected into these areas may be possible.


Longitudinal survey of Staphylococcus aureus in cystic fibrosis patients using a multiple-locus variable-number of tandem-repeats analysis method.
Staphylococcus aureus infection in patients with cystic fibrosis (CF) is frequent and may be due to colonization by a few pathogenic lineages. Systematic genotyping of all isolates, methicillin-susceptible S. aureus (MSSA) as well as methicillin-resistant S. aureus (MRSA) is necessary to identify such lineages and follow their evolution in patients. Multiple-locus variable-number tandem repeat analysis (MLVA/VNTR) was used to survey S. aureus clinical isolates in a French paediatric CF centre. During a 30 months period, 108 patients, aged 2 to 21 years, regularly followed up at the centre, provided sputum for culture. From 79 patients, a total of 278 isolates were genotyped by MLVA, resolving into 110 genotypes and 19 clonal complexes (CC) composed of similar or closely related isolates. 71% of the strains were distributed into four main CCs, in term of number of isolates and number of genotypes. Spa (Staphylococcus protein A) typing was performed on representative samples, showing an excellent concordance with MLVA. In 17 patients, strains from two to four different CCs were recovered over time. On six occasions, S. aureus isolates with the same genotype were shared by 2 different patients and they belonged to one of the four main clusters. Methicillin-resistance was observed in 60% of the isolates, 90% of which belonged to the main clonal complexes CC8, CC45 and CC5. In 5 patients, methicillin-resistance of S. aureus isolates was not associated with the mecA gene: for four patients, it was due to overproduction of beta-lactamase, leading to BOR-SA (borderline S. aureus) isolates, while a strain showing probably a new modified penicillin-binding capacity (MOD-SA) was observed from one patient. Systematic genotyping of S. aureus isolates recovered from sputum of CF children allows a thorough analysis of the strains responsible for sporadic as well as chronic colonization and the follow up of their evolution over time. We show here that more than 70% of these strains belong to 4 major CCs. MSSA as well as MRSA, BOR-SA and MOD-SA isolates can persist over several years, despite antibiotic treatments.


Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses.
Natural killer (NK) cells provide early defense against viral infections by killing infected cells and producing cytokines that inhibit viral replication. NK cells also interact with dendritic cells (DCs) and this reciprocal interaction regulates both innate and adaptive immunity. Genetic studies have suggested that NK cell activity is a determinant of HCV infectious outcome but a functional correlation has not been established. We hypothesized that increased NK cell activity during acute HCV infection correlates with spontaneous viral clearance. We used multiparametric flow cytometry to monitor longitudinally the phenotype and the activity of NK cells in a cohort of intravenous drug users following HCV exposure. Three groups were studied: acute HCV with chronic evolution (n = 13), acute resolving HCV (n = 11), and exposed un-infected individuals (n = 10). We examined the expression of several NK cell-activating and -inhibiting receptors, IFN-γ production and CD107a degranulation upon stimulation, and the kinetics of NK cell responses relative to T cell responses. We observed decreased expression of the inhibitory NKG2A receptor in NK cells following spontaneous HCV clearance. In addition, we observed increased NK cell degranulation during acute HCV irrespective of infectious outcome. NK cell peak responses preceded or coincided with peak T cell responses. Furthermore, NK cell degranulation correlated with the magnitude of HCV-specific T cells. Our results demonstrate that NK cells are activated during acute HCV regardless of infection outcome and may play an indirect role through induction and priming of T cell responses.


The Neighborhood Social Environment and Objective Measures of Sleep in the Multi-Ethnic Study of Atherosclerosis.
To investigate cross-sectional associations of neighborhood social environment (social cohesion, safety) with objective measures of sleep duration, timing, and disturbances. A racially/ethnically diverse population of men and women (N = 1949) aged 54 to 93 years participating in the Multi-Ethnic Study of Atherosclerosis Sleep and Neighborhood Ancillary studies. Participants underwent 1-week actigraphy between 2010 and 2013. Measures of sleep duration, timing, and disruption were averaged over all days. Neighborhood characteristics were assessed via questionnaires administered to participants and an independent sample within the same neighborhood and aggregated at the neighborhood (census tract, N = 783) level using empirical Bayes estimation. Multilevel linear regression models were used to assess the association between the neighborhood social environment and each sleep outcome. Neighborhood social environment characterized by higher levels of social cohesion and safety were associated with longer sleep duration and earlier sleep midpoint. Each 1 standard deviation higher neighborhood social environment score was associated with 6.1 minutes longer [95% confidence interval (CI): 2.0, 10.2] sleep duration and 6.4 minutes earlier (CI: 2.2, 10.6) sleep midpoint after adjustment for age, sex, race, socioeconomic status, and marital status. These associations persisted after adjustment for other risk factors. Neighborhood social factors were not associated with sleep efficiency or sleep fragmentation index. A more favorable neighborhood social environment is associated with longer objectively measured sleep duration and earlier sleep timing. Intervening on the neighborhood environment may improve sleep and subsequent health outcomes.


Association of arterial blood pressure and CPR quality in a child using three different compression techniques, a case report.
A 2-year-old boy found in cardiac arrest secondary to drowning received standard CPR for 35 minutes and was transported to a tertiary hospital for rewarming from hypothermia. Chest compressions in hospital were started using two-thumb encircling hands technique. Subsequently two-thumbs direct sternal compression technique and after sternal force/depth sensor placement, chest compression with classic one-hand technique were done. By using CPR recording/feedback defibrillator, quantitative CPR quality data and invasive arterial pressures were available for analyses for 5 hours and 35 minutes. 316 compressions with the two-thumb encircling hands technique provided a mean (SD) systolic arterial pressure (SAP) of 24 (4) mmHg, mean arterial pressure (MAP) 18 (3) and diastolic arterial pressure (DAP) of 15 (3) mmHg. ~6000 compressions with the two thumbs direct compression technique created a mean SAP of 45 (7) mmHg, MAP 35 (4) mmHg and DAP of 30 (3) mmHg. ~20,000 compressions with the sternal accelerometer in place produced SAP 50 (10) mmHg, MAP 32 (5) mmHg and DAP 24 (4) mmHg. Restoration of spontaneous circulation (ROSC) was achieved at the point when the child achieved normothermia by using peritoneal dialysis. Unfortunately, the child died ten hours after ROSC without any signs of neurological recovery. This case demonstrates improved hemodynamic parameters with classic one-handed technique with real-time quantitative quality of CPR feedback compared to either the two-thumbs encircling hands or two-thumbs direct sternal compression techniques. We speculate that the improved arterial pressures were related to improved chest compression depth when a real-time CPR recording/feedback device was deployed. ClinicalTrials.gov: NCT00951704.


Patient-Specific Precision Injury Signatures to Optimize Orthopaedic Interventions in Multiply Injured Patients (PRECISE STUDY).
Optimal timing and procedure selection that define staged treatment strategies can affect outcomes dramatically and remain an area of major debate in the treatment of multiply injured orthopaedic trauma patients. Decisions regarding timing and choice of orthopaedic procedure(s) are currently based on the physiologic condition of the patient, resource availability, and the expected magnitude of the intervention. Surgical decision-making algorithms rarely rely on precision-type data that account for demographics, magnitude of injury, and the physiologic/immunologic response to injury on a patient-specific basis. This study is a multicenter prospective investigation that will work toward developing a precision medicine approach to managing multiply injured patients by incorporating patient-specific indices that quantify (1) mechanical tissue damage volume; (2) cumulative hypoperfusion; (3) immunologic response; and (4) demographics. These indices will formulate a precision injury signature, unique to each patient, which will be explored for correspondence to outcomes and response to surgical interventions. The impact of the timing and magnitude of initial and staged surgical interventions on patient-specific physiologic and immunologic responses will be evaluated and described. The primary goal of the study will be the development of data-driven models that will inform clinical decision-making tools that can be used to predict outcomes and guide intervention decisions.


Perceived parenting behaviours predict young adolescents' nutritional intake and body fatness.
This study investigated whether perceptions of parenting behaviours predict young adolescents' nutritional intake and body fatness. The randomly selected study sample consisted of 106 13-15 years olds from Houston Metropolitan Statistical Area. Parenting style variables were created by cluster analysis and factor analysis. A two-cluster solution for both maternal and paternal parenting style represented authoritative vs. non-authoritative parenting. Two parenting dimension factors derived were maternal/paternal nurturing and control. For adolescents' energy and nutrient intake, greater maternal nurturing appeared to be most beneficial given its association with lower consumption of total kilocalorie and lower saturated fat intake. Paternal nurturing was associated with lower sodium intake, whereas paternal control predicted lower percentage of kilocalories from carbohydrate and percentage Dietary Reference Intake for dietary fibre, and greater percentage of kilocalories from total fat. Maternal authoritative parenting and lower maternal control over their adolescents may have protective effects against having heavier and fatter adolescents given their associations with adolescents' body weight, sub-scapular skinfold, waist circumference, body mass index, and the tendencies of being at risk of overweight and being overweight. None of paternal parenting styles or dimensions appeared to be significantly related to adolescents' body fatness.


The Gal4-Type Transcription Factor Pro1 Integrates Inputs from Two Different MAPK Cascades to Regulate Development in the Fungal Pathogen Fusarium oxysporum.
Mitogen-activated protein kinase (MAPK) signaling pathways control fundamental aspects of growth and development in fungi. In the soil-inhabiting ascomycete Fusarium oxysporum, which causes vascular wilt disease in more than a hundred crops, the MAPKs Fmk1 and Mpk1 regulate an array of developmental and virulence-related processes. The downstream components mediating these disparate functions are largely unknown. Here we find that the GATA-type transcription factor Pro1 integrates signals from both MAPK pathways to control a subset of functions, including quorum sensing, hyphal fusion and chemotropism. By contrast, Pro1 is dispensable for other downstream processes such as invasive hyphal growth and virulence, or response to cell wall stress. We further show that regulation of Pro1 activity by these upstream pathways occurs at least in part at the level of transcription. Besides the MAPK pathways, upstream regulators of Pro1 transcription also include the Velvet regulatory complex, the signaling protein Soft (Fso1) and the transcription factor Ste12 which was previously shown to act downstream of Fmk1. Collectively, our results reveal a role of Pro1 in integrating the outputs from different signaling pathways of F. oxysporum thereby mediating key developmental decisions in this important fungal pathogen.


A role for the orphan nuclear receptor TLX in the interaction between neural precursor cells and microglia.
Microglia are an essential component of the neurogenic niche in the adult hippocampus and are involved in the control of neural precursor cell (NPC) proliferation, differentiation and the survival and integration of newborn neurons in hippocampal circuitry. Microglial and neuronal cross-talk is mediated in part by the chemokine fractalkine/chemokine (C-X3-C motif) ligand 1 (CX3CL1) released from neurons, and its receptor CX3C chemokine receptor 1 (CX3CR1) which is expressed on microglia. A disruption in this pathway has been associated with impaired neurogenesis yet the specific molecular mechanisms by which this interaction occurs remain unclear. The orphan nuclear receptor TLX (Nr2e1; homologue of the Drosophila tailless gene) is a key regulator of hippocampal neurogenesis, and we have shown that in its absence microglia exhibit a pro-inflammatory activation phenotype. However, it is unclear whether a disturbance in CX3CL1/CX3CR1 communication mediates an impairment in TLX-related pathways which may have subsequent effects on neurogenesis. To this end, we assessed miRNA expression of up- and down-stream signalling molecules of TLX in the hippocampus of mice lacking CX3CR1. Our results demonstrate that a lack of CX3CR1 is associated with altered expression of TLX and its downstream targets in the hippocampus without significantly affecting upstream regulators of TLX. Thus, TLX may be a potential participant in neural stem cell (NSC)-microglial cross-talk and may be an important target in understanding inflammatory-associated impairments in neurogenesis.


Synthetic, spectroscopic, computational and structural studies of some 13-vertex ruthenacarboranes.
Reduction of 1,2-closo-C2B10H12 followed by treatment with [RuCl2(p-cymene)]2(p-cymene = C6H4MeiPr-1,4) affords the 13-vertex ruthenacarborane 4-(p-cymene)-4,1,6-closo-RuC2B10H12, characterised both spectroscopically and, in two crystalline forms, crystallographically. Although asymmetric in the solid state, having a docosahedral cage architecture with cage C atoms at vertices 1 and 6, this species clearly has Cs symmetry on the NMR timescale at room temperature. However, the fluctional process in operation can be arrested at low temperature, and an activation energy of 43.1 kJ mol(-1) is estimated. A computational study of the related species 4-(eta-C6H6)-4,1,6-closo-RuC2B10H12 reveals that the fluctionality is due to a double diamond-square-diamond process, first suggested by Hawthorne et al for the analogous CpCo species. These calculations yield an activation energy of 40.4 kJ mol(-1), in excellent agreement with that derived from experiment. Reduction of 1,2-Ph(2)-1,2-closo-C2B10H10 followed by treatment with [RuCl2(eta-C6H6)]2 or [RuCl2(p-cymene)]2 yields the analogous species 1,6-Ph2-4-(eta-C6H6)-4,1,6-closo-RuC2B10H10 and 1,6-Ph2-4-(p-cymene)-4,1,6-closo-RuC2B10H10, respectively. These C,C-diphenyl compounds were again studied spectroscopically and crystallographically, the p-cymene species again showing two crystalline modifications. In contrast to their CpCo and Cp*Co analogues all three ruthenacarboranes do not undergo isomerisation in refluxing toluene.


Comparing the Halogen Bond to the Hydrogen Bond by Solid-State NMR Spectroscopy: Anion Coordinated Dimers from 2- and 3-Iodoethynylpyridine Salts.
Halogen bonding is an increasingly important tool in crystal engineering, and measuring its influence on the local chemical and electronic environment is necessary to fully understand this interaction. Here, we present a systematic crystallographic and solid-state NMR study of self-complementary halogen-bonded frameworks built from the halide salts (HCl, HBr, HI, HI3 ) of 2-iodoethynylpyridine and 3-iodoethynylpyridine. A series of single crystal X-ray structures reveals the formation of discrete charged dimers in the solid state, directed by simultaneous X- ⋅⋅⋅H-N+ hydrogen bonds and C-I⋅⋅⋅X- halogen bonds (X=Cl, Br, I). Each compound was studied using multinuclear solid-state magnetic resonance spectroscopy, observing 1 H to investigate the hydrogen bonds and 13 C, 35 Cl, and 79/81 Br to investigate the halogen bonds. A natural localized molecular orbital analysis was employed to help interpret the experimental results. 1 H SSNMR spectroscopy reveals a decrease in the chemical shift of the proton participating in the hydrogen bond as the halogen increases in size, whereas the 13 C SSNMR reveals an increased 13 C chemical shift of the C-I carbon for C-I⋅⋅⋅X- relative to C-I⋅⋅⋅N halogen bonds. Additionally, 35 Cl and 79/81 Br SSNMR, along with computational results, have allowed us to compare the C-I⋅⋅⋅X- halogen bond involving each halide in terms of NMR observables. Due to the isostructural nature of these compounds, they are ideal cases for experimentally assessing the impact of different halogen bond acceptors on the solid-state NMR response.


Miscarriage after sonographic confirmation of an ongoing pregnancy in women with moderate and severe obesity.
To compare the incidence of spontaneous miscarriage in women with moderate to severe obesity to that in women with a normal BMI after sonographic confirmation of the foetal heart rate in the first trimester. Women were enrolled in a prospective observational study at their convenience in the first trimester after an ultrasound confirmed an ongoing singleton pregnancy with foetal heart activity present. Maternal height and weight were measured digitally and BMI was calculated. In the 3,000 women enrolled, the miscarriage rate overall was 3.9% (n = 117). The mean gestational age at enrolment was 11.1 weeks. In the class 2-3 (BMI > 34.9 kg/m(2)) obese primigravidas the miscarriage rate was 11.3% (n = 8) compared with 2.7% (n = 24) in the normal BMI category (p = 0.003), and 3.7% (n = 5) in the class 1 obese category (not significant). In multigravidas, there was no increased rate of miscarriage among class 2-3 obese women compared with multigravidas in the normal BMI category. The mean body composition values showed that primigravidas who miscarried had both increased fat and fat-free masses compared with those who did not, but multigravidas who miscarried had a similar fat mass and fat-free mass with those who did not. In women with sonographic evidence of foetal heart activity in the first trimester, the rate of spontaneous miscarriage is low. It was increased in moderate to severely obese primigravidas, but was not increased in other obese women compared to women in the normal BMI category.


Gas-liquid chromatographic determination of alachlor (2-chloro-2', 6'-diethyl-N-(methoxymethyl)-acetanilide) herbicide residues in corn and soybeans.
A method has been developed for the extraction and determination of alachlor (2-chloro-2',6'-diethyl-N- (methoxymethyl)-acetanilide) residues in green corn and soybeans. Residues are extracted with acetonitrile and cleaned up on a Florisil column. The methylene chloride extract is sufficiently clean for electron capture gas-liquid chromatographic analysis and for verification by thin layer chromatography. Average recoveries of spiked samples (0.2 ppm) were 69 and 82% for corn and soybeans, respectively. This procedure could be useful for the detection of the parent compound in these crops soon after field application, but it does not detect metabolites.


Digital Receptor Occupancy Assay in Quantifying On- and Off-Target Binding Affinities of Therapeutic Antibodies.
While monoclonal antibodies are the fastest-growing class of therapeutic agents, we lack a method that can directly quantify the on- and off-target binding affinities of newly developed therapeutic antibodies in crude cell lysates. As a result, some therapeutic antibody candidates could have a moderate on-target binding affinity but a high off-target binding affinity, which not only gives a reduced efficacy but triggers unwanted side effects. Here, we report a single-molecule counting method that precisely quantifies antibody-bound receptors, free receptors, and unbound antibodies in crude cell lysates, termed digital receptor occupancy assay (DRO). Compared to the traditional flow cytometry-based binding assay, DRO assay enables direct and digital quantification of the three molecular species in solution without the additional antibodies for competitive binding. When characterizing the therapeutic antibody, cetuximab, using DRO assay, we found the on-target binding ratio to be 65% and the binding constant (Kd) to be 2.4 nM, while the off-target binding causes the binding constant to decrease by 0.3 nM. Other than cultured cells, the DRO assay can be performed on tumor mouse xenograft models. Thus, DRO is a simple and highly quantitative method for cell-based antibody binding analysis which can be broadly applied to screen and validate new therapeutic antibodies.


[Asymmetry in the structure of average and large neurons of the ganglion layer of the frog retina].
Morphometric analysis of the symmetry of middle and large ganglionic cells was performed on silver-impregnated retinal wholemounts of the frog. The nucleolus and the axis passing through the nucleolus in direction to optic disk were chosen as elements of symmetry characterizing the radial symmetry and bilateral one, respectively. It is demonstrated that the dendritic ramification angles of all cell types are smaller than 360 degrees and the angles of middle-type-GC are smaller than 180 degrees. In addition, their somata do not lie in the centre of the dendritic field, thus ganglionic cells have no radial symmetry. Directions of the axon and dendrites are opposite each other in the most of ganglionic cells, the terminals of dendrites being oriented from retinal centre to periphery in all quadrants of the retinal map. For estimation of bilateral symmetry the distance from the greatest remoted dendritic terminals to cell axis on the left and on the right from it was measured. Besides, the numbers of ramification knots and basal dendrites were counted. Most of ganglionic cells are asymmetrical in 2-3 mentioned structural parameters. Thus, the asymmetry in the structure of frog retinal neurons is rather norm than exception. Correlation between the asymmetry in ganglionic cell structure and functional asymmetry of their receptive fields is discussed.


The Quality of Mobile Apps Used for the Identification of Pressure Ulcers in Adults: Systematic Survey and Review of Apps in App Stores.
The increasing global use of smartphones has contributed to the growing use of apps for various health conditions, showing promising results. Through mobile apps, it is possible to perform chronological and iconographic follow-up of wounds, such as pressure ulcers, using a simple and practical tool. However, numerous surveys have pointed out issues related to the functionality, design, safety, and veracity of app information. The objective of this study was to perform a systematic review of published studies regarding mobile apps and a systematic survey in app stores looking for apps developed to identify, evaluate, treat, and/or prevent pressure ulcers in adults, and to evaluate those apps based on software quality characteristics. This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The main bibliographic databases were searched between January 1, 2007 and October 15, 2018, and an app survey was performed in app stores. The selected studies were evaluated according to software quality characteristics by the International Organization for Standardization/International Electrotechnical Commission (ie, ISO/IEC 25010:2011) that involve functionality, efficiency, compatibility, usability, reliability, safety, maintenance, and portability. The search in databases and web-based app stores returned a total of 2075 studies. After removal of duplicates and screening of titles and abstracts, 48 complete articles were evaluated for eligibility, and among these, six were included for qualitative synthesis. In this review, it was observed that all studies involved the initial phase of app development or improvement, and therefore, the apps still need to be evaluated using different software quality characteristics, so that in the future, a gold standard can be approached. Therefore, the prescription of an app for the identification, evaluation, treatment, and/or prevention of pressure ulcers in adults is currently limited. However, the evaluated studies provided important insights for future research. It is of utmost importance that future surveys develop apps jointly with users, using collaborative and cocreative processes and assess patients in real-world situations across different service settings, and they should consider different ethnicities, so that apps are useful to end users, such as patients, family members, health professionals, and students, in the health area. In addition, it is necessary for studies to describe the methodological course of app development in a clear and objective way in order to ensure reproducibility of the study and to offer inputs to allow future research to approach the development of ideal apps that are geared to positively impact the health of end users. PROSPERO CRD42018114137; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=114137.


Effects of carvedilol on ventriculo-arterial coupling in patients with heart failure.
Ventriculo-arterial coupling, defined as the ratio of the effective afterload (Ea) to contractility (Ees), reflects the mechano-energetic performance of the heart and is increased in chronic heart failure (CHF); the aim of treatment is to reduce its value. We studied the effect of carvedilol on the Ea/Ees ratio in patients with CHF treated with ACE-inhibitors, diuretics, and digoxin. Between November 1999 and October 2001, 36 consecutive ambulatory patients (aged 31 to 76 years) with stable CHF and idiopathic or hypertensive cardiomyopathy, in sinus rhythm and with a left ventricular ejection fraction < or = 40%, were started on carvedilol and the dose was increased to the maximum tolerated. Ees was calculated as the left ventricular systolic pressure--taken as the systolic arterial pressure measured using the cuff manometer simultaneously with two-dimensional echocardiographic recordings--divided by the left ventricular end-systolic volume. Ea was measured as the ratio of the left ventricular systolic pressure to the stroke volume. All patients were investigated prospectively after 6 and 12 months of treatment. Out of 36 patients, 4 did not tolerate the drug and were dropped out. At 6.35 +/- 1 months, the daily dosage of carvedilol was 49.7 +/- 21 mg. The NYHA functional class improved from 1.52 +/- 0.67 to 1.29 +/- 0.53 (p = 0.017), the heart rate markedly diminished from 73.6 +/- 13.3 to 60.8 +/- 10.8 b/min (p < 0.001) and so did Ea (3.35 +/- 0.91 to 2.84 +/- 0.93, p = 0.001). Peripheral resistances and Ees did not change. Therefore, the decrease in the Ea/Ees ratio (2.61 +/- 0.78 vs 2.19 +/- 0.89, p = 0.004) and the related increase in left ventricular ejection fraction (28.8 +/- 5.68 vs 33.3 +/- 7.5%, p < 0.001) were due to the decrease in Ea, while Ees did not vary significantly. Moreover, the Ea reduction was related linearly to the decrease in heart rate (r = 0.46, p = 0.001). There was no change in diuretic or ACE-inhibitor dosing during carvedilol titration. At 14.7 +/- 2 months of follow-up, no further variation occurred, short of a trend toward a slight increase in Ees (1.38 +/- 0.49 to 1.58 +/- 0.65, p = 0.07). Carvedilol, added to the conventional therapy of CHF, improves left ventricular performance and reduces the Ea/Ees ratio by decreasing Ea, mainly through a reduction in heart rate. This effect is already evident at 6 months and persists later on, while only after 12 months does Ees tend to increase slightly.


The M-phase-promoting factor modulates the sensitivity of the Ca2+ stores to inositol 1,4,5-trisphosphate via the actin cytoskeleton.
The resumption of the meiotic cycle (maturation) induced by 1-methyladenine in prophase-arrested starfish oocytes is indicated by the breakdown of the germinal vesicle and is characterized by the increased sensitivity of the Ca2+ stores to inositol 1,4,5-trisphosphate (InsP3) to InsP3 starting at the animal hemisphere (where the germinal vesicle was originally located) and propagating along the animal/vegetal axis of the oocyte. This initiates Ca2+ signals around the germinal vesicle before nuclear envelope breakdown. Previous studies have suggested that the final activation of the maturation-promoting factor (MPF), a cyclin-dependent kinase, which is the major element controlling the entry of eukaryotic cells into the M phase, occurs in the nucleus. MPF is then exported to the cytoplasm where its activity is autocatalytically amplified following a similar animal/vegetal spatial pattern. We have investigated whether activated MPF was involved in the increased sensitivity of the Ca2+ response to InsP3. We have found that the development of increased sensitivity of the Ca2+ stores to InsP3 receptors together with the Ca2+ signals in the perinuclear region was blocked in oocytes treated with the specific MPF inhibitor roscovitine. That the nuclear MPF activation is indeed required for changes of the InsP3 receptors sensitivity was shown by enucleating or by dissecting oocytes into vegetal and animal hemispheres prior to the addition of 1-MA. MPF activity 50 min after 1-methyladenine addition was much lower in the enucleated oocytes and in the vegetal hemisphere, which did not contain the germinal vesicle, as compared with the animal hemisphere, which did contain it. The Ca2+ increase induced by InsP3 under these experimental conditions correlated with the changes in actin cytoskeleton induced by MPF.


Defects in gliding motility in mutants of Cytophaga johnsonae lacking a high-molecular-weight cell surface polysaccharide.
We previously observed (W. Godchaux, L. Gorski, and E.R. Leadbetter, J. Bacteriol. 172:1250-1255, 1990) that two mutants (strains 21 and NS-1) of the gliding bacterium Cytophaga johnsonae that were totally deficient in motility-dependent colony spreading, movement of rafts (groups) of cells as observed with a microscope, and movement of polystyrene-latex spheres that attached to the cell surface (observed in wet mounts) were also deficient in a high-molecular-weight cell surface polysaccharide (HMPS) and suggested a role for that substance in gliding motility. Antisera have been prepared against the purified HMPS, and these were used to select mutants specifically and highly deficient in the polysaccharide. All five such mutants had rates of colony spreading and raft movement that were much lower than those of the parent strain, but the rate of increase in colony diameter was higher than that found for strains NS-1 and 21 (which do not undergo raft movement at all). Unlike these latter two strains, the HMPS mutants retained the ability to move polystyrene-latex spheres over their surfaces. Hence, HMPS deficiency results in defective motility but not nonmotility, and the HMPS deficiency cannot fully explain the phenotype of mutants 21 and NS-1; in these strains, gliding must be affected by additional biochemical lesions. The HMPS may, nonetheless, be advantageous in that it supports greater gliding speeds.


E3 ubiquitin ligase ZBTB25 suppresses beta coronavirus infection through ubiquitination of the main viral protease MPro.
The main protease of severe acute respiratory syndrome coronavirus 2, Mpro, is a key viral protein essential for viral infection and replication. Mpro has been the target of many pharmacological efforts; however, the host-specific regulation of Mpro protein remains unclear. Here, we report the ubiquitin-proteasome-dependent degradation of Mpro protein in human cells, facilitated by the human E3 ubiquitin ligase ZBTB25. We demonstrate that Mpro has a short half-life that is prolonged via proteasomal inhibition, with its Lys-100 residue serving as a potential ubiquitin acceptor. Using in vitro binding assays, we observed ZBTB25 and Mpro bind to each other in vitro, and using progressive deletional mapping, we further uncovered the required domains for this interaction. Finally, we used an orthologous beta-coronavirus infection model and observed that genetic ablation of ZBTB25 resulted in a more highly infective virus, an effect lost upon reconstitution of ZBTB25 to deleted cells. In conclusion, these data suggest a new mechanism of Mpro protein regulation as well as identify ZBTB25 as an anticoronaviral E3 ubiquitin ligase.


Orthostatic Hypotension Is Associated With Cognitive Decline in Parkinson Disease.
Introduction: Cognitive impairment and orthostatic hypotension (OH) are common, disabling Parkinson disease (PD) symptoms that are strongly correlated. Whether the relationship is causative or associative remains unknown. OH may occur without classic orthostatic symptoms of cerebral hypoperfusion (i.e., lightheadedness or dizziness). Whether longitudinal differences in cognition occur between symptomatic and asymptomatic OH patients has not been explored. Objectives: We characterized the prevalence of OH, orthostatic symptoms, and cognitive impairment among PD patients and compared cognition between patients with and without OH, and between patients with symptomatic and asymptomatic OH. Methods: Our cross-sectional, retrospective, observational study included 226 clinically diagnosed PD patients who underwent repeated standardized evaluations. Among these, 62 had longitudinal follow-up of > 3.5 years. We compared longitudinal Montreal Cognitive Assessment (MoCA) scores between patients remaining OH-free (n = 14) and those without baseline OH that developed OH (n = 28), matched for age, sex, education, and PD duration. We also compared MoCA scores between groups with asymptomatic OH (n = 13) and symptomatic OH (n = 13) matched for the same factors. Results: In the cross-sectional analysis, OH patients had worse cognition. In the longitudinal analysis (mean follow-up = 5.3 years), OH patients had worse cognitive decline (p = 0.027). Cognitive impairment was similar between asymptomatic and symptomatic OH patients in the cross-sectional and longitudinal analyses. Conclusions: OH is associated with cognitive impairment in PD. Further studies are needed in larger cohorts to expand our findings and to determine whether treating OH can prevent or delay cognitive dysfunction.


NAA10 p.(N101K) disrupts N-terminal acetyltransferase complex NatA and is associated with developmental delay and hemihypertrophy.
Nearly half of all human proteins are acetylated at their N-termini by the NatA N-terminal acetyltransferase complex. NAA10 is evolutionarily conserved as the catalytic subunit of NatA in complex with NAA15, but may also have NatA-independent functions. Several NAA10 variants are associated with genetic disorders. The phenotypic spectrum includes developmental delay, intellectual disability, and cardiac abnormalities. Here, we have identified the previously undescribed NAA10 c.303C>A and c.303C>G p.(N101K) variants in two unrelated girls. These girls have developmental delay, but they both also display hemihypertrophy a feature normally not observed or registered among these cases. Functional studies revealed that NAA10 p.(N101K) is completely impaired in its ability to bind NAA15 and to form an enzymatically active NatA complex. In contrast, the integrity of NAA10 p.(N101K) as a monomeric acetyltransferase is intact. Thus, this NAA10 variant may represent the best example of the impact of NatA mediated N-terminal acetylation, isolated from other potential NAA10-mediated cellular functions and may provide important insights into the phenotypes observed in individuals expressing pathogenic NAA10 variants.


The autoactivation of factor XII (Hageman factor) induced by low-Mr heparin and dextran sulphate. The effect of the Mr of the activating polyanion.
Human Factor XII is known to undergo autoactivation in the presence of dextran sulphate of Mr 500,000. We have now studied the dependence of this reaction on the Mr of the dextran sulphate by using fractions resolved by gel filtration. We have found that autoactivation can be induced by dextran sulphate fractions with Mr as low as 3000, and there is a marked dependence of the rate constant of autoactivation on the Mr value. Fractions with Mr below 8000 gave very low rates of autoactivation; there was a sharp increase in the rate obtained when the Mr of the dextran sulphate was greater than 10,000. Various preparations of heparin were also able to support the autoactivation of Factor XII and gave a very similar relationship between molecular size and reaction rate. The data provide support for the hypothesis that the mechanism by which the 'surface' acts in contact activation involves the presence, on the same particle, of multiple binding sites for the proteins.


Macronutrient intake and food sources in the very old: analysis of the Newcastle 85+ Study.
Food and nutrient intake data are scarce in very old adults (85 years and older) - one of the fastest growing age segments of Western societies, including the UK. Our primary objective was to assess energy and macronutrient intakes and respective food sources in 793 85-year-olds (302 men and 491 women) living in North-East England and participating in the Newcastle 85+ cohort Study. Dietary information was collected using a repeated multiple-pass recall (2×24 h recalls). Energy, macronutrient and NSP intakes were estimated, and the contribution (%) of food groups to nutrient intake was calculated. The median energy intake was 6·65 (interquartile ranges (IQR) 5·49-8·16) MJ/d - 46·8 % was from carbohydrates, 36·8 % from fats and 15·7 % from proteins. NSP intake was 10·2 g/d (IQR 7·3-13·7). NSP intake was higher in non-institutionalised, more educated, from higher social class and more physically active 85-year-olds. Cereals and cereal products were the top contributors to intakes of energy and most macronutrients (carbohydrates, non-milk extrinsic sugars, NSP and fat), followed by meat and meat products. The median intakes of energy and NSP were much lower than the estimated average requirement for energy (9·6 MJ/d for men and 7·7 MJ/d for women) and the dietary reference value (DRV) for NSP (≥18 g/d). The median SFA intake was higher than the DRV (≤11 % of dietary energy). This study highlights the paucity of data on dietary intake and the uncertainties about DRV for this age group.


A digital decision support system (selfBACK) for improved self-management of low back pain: a pilot study with 6-week follow-up.
Very few of the publicly available apps directed towards self-management of low back pain (LBP) have been rigorously tested and their theoretical underpinnings seldom described. The selfBACK app was developed in collaboration with end-users and clinicians and its content is supported by best evidence on self-management of LBP. The objectives of this pilot study were to investigate the basis for recruitment and screening procedures for the subsequent randomized controlled trial (RCT), to test the inclusion process in relation to questionnaires and app installation, and finally to investigate the change in primary outcome over time. This single-armed pilot study enrolled 51 participants who had sought help for LBP of any duration from primary care (physiotherapy, chiropractic, or general practice) within the past 8 weeks. Participants were screened for eligibility using the PROMIS-Physical-Function-4a questionnaire. Participants were asked to use the selfBACK app for 6 weeks. The app provided weekly tailored self-management plans targeting physical activity, strength and flexibility exercises, and education. The construction of the self-management plans was achieved using case-based reasoning (CBR) methodology to capture and reuse information from previous successful cases. Participants completed the primary outcome pain-related disability (Roland-Morris Disability Questionnaire [RMDQ]) at baseline and 6-week follow-up along with a range of secondary outcomes. Metrics of app use were collected throughout the intervention period. Follow-up data at 6 weeks was obtained for 43 participants. The recruitment procedures were feasible, and the number needed to screen was acceptable (i.e., 1.6:1). The screening questionnaire was altered during the pilot study. The inclusion process, answering questionnaires and app installation, were feasible. The primary outcome (RMDQ) improved from 8.6 (SD 5.1) at baseline to 5.9 (SD 4.0) at 6-week follow-up (change score 1.8, 95% CI 0.7 to 2.9). Participants spent on average 134 min (range 0-889 min) using the app during the 6-week period. The recruitment, screening, and inclusion procedures were feasible for the subsequent RCT with a small adjustment. The improvement on the RMDQ from baseline to follow-up was small. Time pattern of app usage varied considerably between the participants. NCT03697759. Registered on August 10, 2018. https://clinicaltrials.gov/ct2/show/NCT03697759.


Possible functional proximity of various organisms based on the bioinformatics analysis of their taste receptors.
Taste is one of the essential senses in providing the organism a faithful representation of the external world. Taste perception is responsible for basic food and drink appraisal and bestows the organism with valuable discriminatory power. Umami and sweet are "good" tastes that promote consumption of nutritive food, whereas bitter and sour are "bad" tastes that alert the organism to toxins and low pH, promoting rejection of foods containing harmful substances. Not every animal has the same sense of taste as humans. Variation in the taste receptor genes contributes to inter and intra organism differences of taste (sweet/bitter) sensation and preferences. Therefore a deeper understanding was needed to comprehend taste perception by various vertebrates and accordingly elucidate a possible proximity among them. In this study, a total 20 Type-1 (sweet) and 189 Type-2 (bitter) taste receptor complete-amino acid sequences were taken from the 20 vertebrate organisms (18 mammalian, 1 Aves, and 1 amphibian). Among 10 primates, 8 including humans were very close based on genomics of taste receptors and rodent organisms viz. the rat and mouse were away from them. This investigation throws light on the similitude and dissimilitude of perception of sweet and bitter taste among 20 different organisms, steered by quantitative analysis of their genomic data. Furthermore, it enlightened that ligand binding affinity of sweet/bitter taste molecules in the taste receptors of any proximal pair of organisms would be similar.


Amyloid-β reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNFα from neuronal protection to death.
The brains of patients with Alzheimer's disease (AD) present elevated levels of tumor necrosis factor-α (TNFα), a cytokine that has a dual function in neuronal cells. On one hand, TNFα can activate neuronal apoptosis, and on the other hand, it can protect these cells against amyloid-β (Aβ) toxicity. Given the dual behavior of this molecule, there is some controversy regarding its contribution to the pathogenesis of AD. Here we examined the relevance of the long form of Fas apoptotic inhibitory molecule (FAIM) protein, FAIM-L, in regulating the dual function of TNFα. We detected that FAIM-L was reduced in the hippocampi of patients with AD. We also observed that the entorhinal and hippocampal cortex of a mouse model of AD (PS1(M146L)xAPP(751sl)) showed a reduction in this protein before the onset of neurodegeneration. Notably, cultured neurons treated with the cortical soluble fractions of these animals showed a decrease in endogenous FAIM-L, an effect that is mimicked by the treatment with Aβ-derived diffusible ligands (ADDLs). The reduction in the expression of FAIM-L is associated with the progression of the neurodegeneration by changing the inflammatory response mediated by TNFα in neurons. In this sense, we also demonstrate that the protection afforded by TNFα against Aβ toxicity ceases when endogenous FAIM-L is reduced by short hairpin RNA (shRNA) or by treatment with ADDLs. All together, these results support the notion that levels of FAIM-L contribute to determine the protective or deleterious effect of TNFα in neuronal cells.


Transfer impedance of microperforated materials with tapered holes.
It has been previously shown that relatively simple computational fluid dynamics (CFD) models can be used to calculate the transfer impedances, including the associated end corrections, of microperforated panels. The impedance is estimated by first calculating the pressure difference across a single hole when a transient input velocity is imposed, and then Fourier transforming the result to obtain the impedance as a function of frequency. Since the size of the hole and the dimensions of the inlet and outlet channels are very small compared to a wavelength, the flow through the hole can be modeled as incompressible. By using those procedures, Bolton and Kim extended Maa's classical theory to include a resistive end correction for sharp-edged cylindrical holes which differs from those previously proposed by the inclusion of a static component. Here it is shown that CFD models can also be used to compute end corrections for tapered holes. Since practical experimental characterization of perforated materials often involves measurement of the static flow resistance, a closed form empirical equation for that quantity has been developed. Finally, it is shown that configurations having equivalent static flow resistances can yield different acoustic absorptions.


Inhalation toxicity of potassium octatitanate fibers (TISMO) in rats following 13 weeks of aerosol exposure.
One hundred and forty male and 140 female rats were divided into 1 control and 3 test groups of 35 rats each, per sex, and exposed by whole-body inhalation to test compound at target concentrations of 0, 1 mg/m(3) (1700 fibers/cm(3), 123 WHO fibers/cm(3)), 10 mg/m(3) (5900 fibers/cm(3), 952 WHO fibers/cm(3)), and 100 mg/m(3) (112,700 fibers/cm(3), 7440 WHO fibers/cm(3)) for 6 h/day, 5 days/wk for 13 wk. Ten rats from each group were killed after 13 wk of exposure and 13 wk of recovery, respectively, for histopathological evaluation. The other 15 rats from each group were killed to study lung clearance after 91 days of exposure, and approximately 1.5 and 3 mo of recovery following the end of the 13 wk of exposure. The mean fiber length of the chamber atmosphere was 2.8, 2.7, and 2.8 microm, while the mean fiber width was 0.48, 0.48, and 0.45 microm for the 1-, 10-, and 100-mg/m(3) chambers, respectively. In the 1-mg/m(3) (123 WHO fibers/cm(3)) exposure group, inhaled particles were mostly retained in a few fiber-laden alveolar macrophages (AMs) within the alveoli adjacent to alveolar ducts without any adverse tissue response throughout 13 wk of exposure and following 13 wk of recovery. This exposure concentration was considered to be a no-observable-adverse-effect level (NOAEL), since the alveoli containing fiber-laden AMs preserved normal structure. After 13 wk of exposure to 10 mg/m(3) (952 WHO fibers/cm(3)), fiber-laden AMs were mainly retained at the alveoli adjacent to the alveolar ducts. Infrequently, slight fibrotic thickening was observed in the alveolar ducts and adjoining alveoli, with proliferating fibroblasts and hyperplastic Type II pneumocytes, and microgranulomas. Occasionally, trace amounts of collagenous material were deposited in the thickened alveolar ducts and adjoining alveolar walls. In addition, minimal alveolar bronchiolarization was occasionally found in the alveoli adjacent to the terminal bronchioles. The peribronchial lymphoid tissue and thymic lymph nodes contained migrated fiber-laden AMs. After 13 wk of recovery, fiber-laden AMs had mostly disappeared from alveoli located in the peripheral acini, but they localized in the alveolar ducts region, suggesting there was active lung clearance of fibers by the AMs via airways. Thickened alveolar ducts and adjacent alveoli were decreased in thickness, a reversible change manifested by reduction of proliferating Type II pneumocytes and fibroblasts. Collagenized fibrosis was slightly more pronounced in the thickened alveolar ducts and adjoining alveoli. The lung response following 13 wk of exposure to 100 mg/m(3) (7440 WHO fibers/cm(3)) and after 13 wk of recovery was similar to those findings of the 952 WHO fibers/cm(3) group but more pronounced, demonstrating a clear concentration-related response. Alveolar ducts and adjoining alveolar walls in the central acini were irregularly thickened with more frequent evidence of minimal collagenized fibrosis. The lung burden and clearance of fibers were estimated by measuring the total content of titanium (Ti) in the lungs, but high variability of Ti content in control and exposed groups prevented meaningful lung clearance analysis.


[Clinical symptoms of vascular laryngeal tumors in children depending on their location].
To study peculiarities of clinical symptoms of laryngeal angiomas in children, 71 case histories for children with vascular tumor aged 27 days to 14 years have been analysed. The cases were divided into two groups by location of the tumor: group 1--with hemangioma located in the subvocal larynx (45 children admitted to hospital at the age of 27 days to 2 years); group 2--with laryngeal vascular tumor located in the vocal or supravocal larynx (26 children admitted to hospital at the age of 3 months to 14 years). It was established that the age of the first angioma symptoms and the symptoms manifestation depend on the tumor location. Subvocal hemangioma should be considered an independent nosological unit of the disease.


If control of Neospora caninum infection is technically feasible does it make economic sense?
Recent work on Neospora caninum, a protozoan parasite that causes abortions in dairy cattle has focused on a number of different control options. Modelling has suggested the most effective options for control but the present paper argues that the most effective option might not necessarily be optimal from an economic point of view. Decision trees, using published quantitative data, were constructed to choose between four different control strategies. The costs of these interventions, such as 'test and cull', therapeutic treatment with a pharmaceutical, vaccination or "doing nothing" were compared, and modelled, in the first instance, on the New Zealand and Australian dairy situation. It is argued however, that the relative costs in other countries might be similar and that only the availability of a registered vaccine will change the decision tree outcomes, as does the within-herd prevalence of N. caninum infection. To "do nothing" emerged as the optimal economic choice for N. caninum infections/abortions up to a within-herd prevalence of 18%, when viewed over a 1-year horizon, or 21% when costs were calculated over a 5 years horizon. For a higher (>or=21%) within-herd prevalence of N. caninum infection vaccination provided the best (i.e. most economic) strategy. Despite being the most efficacious solutions, 'test and cull' or therapeutic treatment never provided a viable economic alternative to vaccination or "doing nothing". Decision tree analysis thus provided clear outcomes in terms of economically optimal strategies. The same approach is likely to be applicable to other countries and the beef industry, with only minor changes expected in the relationships of decisions versus within-herd prevalence of N. caninum infection.


Adult haemoglobin in developmentally retarded tadpoles of Xenopus laevis.
Tadpoles of Xenopus laevis reared in water containing 0-01% propylthiouracil continue to grow but fail to develop or metamorphose. The haemoglobin of such tadpoles has been extracted in buffer, converted to a cyanmet form, and run on polyacrylamide gels. The developmentally retarded tadpoles are found to possess adult-type haemoglobin rather than the tadpole type which normally characterizes their developmental stage.


Tumor necrosis factor-alpha and tumor growth factor-beta1 genotype: partial association with intragraft gene expression in two cases of long-term peripheral tolerance to a kidney transplant.
Genomic DNA was obtained from peripheral blood samples of patients JB and DS each of whom received a kidney transplant at 16 years of age from a serologically HLA-DR matched and HLA-class I -mismatched donor. Both patients discontinued immunosuppression after 1-2 years and retained good renal function for an additional 5 years or more. DNA was analyzed for genetic polymorphisms in the tumor necrosis factor-alpha (TNFalpha) and tumor growth factor-beta1 (TGFbeta1) loci. Biopsy samples obtained during stable function (DS, JB) and during rejection (JB) were analyzed by RT/PCR for cytokine gene expression. Both patients had a high responder genotype for TGFbeta1. DS had a low responder TNFalpha genotype, while JB and his donor were both genotypically TNFalpha intermediate responders. DS had a high TGFbeta1: TNFalpha mRNA ratio in two biopsies obtained during tolerance, while JB, who eventually lost his graft, had more TNFalpha than TGFbeta1 mRNA. The results suggest a possible role for cytokine immunogenetics in the stability of peripheral tolerance.


MiR-200-3p Is Potentially Involved in Cell Cycle Arrest by Regulating Cyclin A during Aestivation in Apostichopus japonicus.
The sea cucumber (Apostichopus japonicus) has become a good model organism for studying environmentally induced aestivation in marine invertebrates. We hypothesized that mechanisms that arrest energy-expensive cell cycle activity would contribute significantly to establishing the hypometabolic state during aestivation. Cyclin A is a core and particularly interesting cell cycle regulator that functions in both the S phase and in mitosis. In the present study, negative relationships between miR-200-3p and AjCA expressions were detected at both the transcriptional and the translational levels during aestivation in A. japonicus. Dual-luciferase reporter assays confirmed the targeted location of the miR-200-3p binding site within the AjCA gene transcript. Furthermore, gain- and loss-of-function experiments were conducted in vivo with sea cucumbers to verify the interaction between miR-200-3p and AjCA in intestine tissue by qRT-PCR and Western blotting. The results show that the overexpression of miR-200-3p mimics suppressed AjCA transcript levels and translated protein production, whereas transfection with a miR-200-3p inhibitor enhanced both AjCA mRNA and AjCA protein in A. japonicus intestine. Our findings suggested a potential mechanism that reversibly arrests cell cycle progression during aestivation, which may center on miR-200-3p inhibitory control over the translation of cyclin A mRNA transcripts.


Large-scale seaweed cultivation diverges water and sediment microbial communities in the coast of Nan'ao Island, South China Sea.
Seaweed cultivation not only provides economy benefits, but also remediates the environment contaminated by mariculture of animals (e.g., fish, shrimps). However, the response of microbial communities to seaweed cultivation is poorly understood. In this study, we analyzed the diversity, composition, and structure of water and sediment microbial communities at a seaweed, Gracilaria lemaneiformis, cultivation zone and a control zone near Nan'ao Island, South China Sea by MiSeq sequencing of 16S rRNA gene amplicons. We found that large-scale cultivation of G. lemaneiformis increased dissolved oxygen (DO) and pH but decreased inorganic nutrients, possibly due to nutrient uptake, photosynthesis and other physiological processes of G. lemaneiformis. These environmental changes significantly (adonis, P<0.05) shifted the microbial community composition and structure of both water column and sediment samples in the G. lemaneiformis cultivation zone, compared to the control zone. Also, certain microbial taxa associated with seaweed, such as Arenibacter, Croceitalea, Glaciecola, Leucothrix and Maribacter were enriched at the cultivation zone. In addition, we have proposed a conceptual model to summarize the results in this study and guide future studies on relationships among seaweed processes, microbial communities and their environments. Thus, this study not only provides new insights into our understanding the effect of G. lemaneiformis cultivation on microbial communities, but also guides future studies on coastal ecosystems.


Purification and characterization of PLUNC from human tracheobronchial secretions.
To study proteins secreted into the airway, we used secretions from primary human airway epithelial cells, re-differentiated at the air-liquid interface, and from patients intubated during surgery. A major protein of the cultured cell secretions was ethanol soluble. This protein was purified, analyzed by Edman degradation, matrix-assisted laser-desorption ionization time-of-flight mass spectroscopy of tryptic digests, and Western blots of two-dimensional electrophoresis gels using antisera against the purified preparation. The protein was identified as palate, lung, nasal epithelium clone protein (PLUNC). The protein had multiple truncated molecules, a pattern also seen in tracheal aspirates. PLUNC was poorly soluble in water (50 microg/ml) or in 50 mM NaCl but was more soluble in 75% ethanol (> 380 microg/ml). PLUNC secretion dramatically increased during the second week in air-liquid interface culture and continued to increase over time. Immunohistochemistry showed that PLUNC was expressed in human airway epithelium and submucosal glands. Although PLUNC is in the lipopolysaccharide (LPS)-binding protein (LBP) and bactericidal/permeability-increasing protein family of antibacterial host defense proteins, purified PLUNC failed to compete with LBP for the binding of LPS, whereas polymyxin B, a known inhibitor of LPS-LBP binding, did interfere with binding. This study showed that plunc gene product is expressed both in vivo and in vitro, detailed a method for its purification and provided basic information on its biochemical properties in secretions.


Distinguishing features of self-limiting adult small-bowel intussusception identified at CT.
To determine if clinical or computed tomographic (CT) findings can be used to distinguish self-limiting cases of adult small-bowel intussusception from those requiring surgery. Thirty-seven cases of adult small-bowel intussusception were identified by a retrospective computerized search of 69,040 abdominopelvic CT examinations performed over a 4-year period. Two independent readers recorded CT features. Clinical findings and outcomes were determined by review of all available medical records. Outcome was classified as either surgical or self-limiting. Association between predictive variables and outcome was assessed by the Fisher exact test and logistic regression models. A multivariate, stepwise, logistic regression model was used to determine the best predictors of outcome. Six patients (16%) underwent surgery, and all had lead-point tumors. Thirty-one patients were cared for conservatively (84%) and none required surgery at a mean follow-up of 5.2 months (range, 0-46 months). Multivariate, stepwise, logistic regression analysis showed intussusception length was the only variable that was independently predictive of outcome. All 20 patients with an intussusception length of 3.5 cm or less, as measured by either reader, had cases that were self-limiting. Seventeen patients had an intussusception length greater than 3.5 cm, as measured by either reader. Eleven patients had an intussusception that was self-limiting, and six patients had an intussusception that required surgery. Intussusception length is the main factor in distinguishing the majority of small-bowel intussusceptions detected at CT that are self-limiting from the minority that require surgery. An intussusception that is shorter than 3.5 cm is likely to be self-limiting.