Improving the role of echocardiography in studying the right ventricle of repaired tetralogy of Fallot patients: comparison with cardiac magnetic resonance.
Right ventricular (RV) evaluation represents one of the major clinical tasks in the follow-up of repaired tetralogy of Fallot patients (rToF) with pulmonary valve regurgitation, as both severe RV dilatation and dysfunction are key factors in defining the need of pulmonary valve replacement. The aim of our study was to report the diagnostic accuracy of echocardiography in the identification of rToF patients with severely dilated and/or depressed RV as compared to cardiac magnetic resonance (CMR). Among our patients with rToF, a subgroup of 95 (17.6 ± 6.8 years; 60% male), who underwent right ventricular qualitative and quantitative evaluation with CMR following echocardiographic suspicion of severe dilation/dysfunction, were included in the analysis. When comparing echocardiographic RV functional parameters to CMR findings, we found no association between CMR-ejection fraction (EF) and either tricuspid annulus plane systolic excursion (TAPSe) nor tissue Doppler systolic tricuspid excursion velocity (all p = ns). In contrast RVFAC was strongly associated with CMR-EF (r = 0.44; p < 0.01) as well as to longitudinal components of RV mechanics including tissue Doppler s' (r = 0.40; p < 0.01) and TAPSE (r = 0.36; p < 0.01). When comparing echocardiographic and CMR structural parameters of the RV, we found that CMR RV volume was strongly related to echocardiographic measurements of RV end diastolic area (from the 4 chamber apical view) and with proximal parasternal short axis right ventricle outflow-dimension. Accordingly a regression model was derived from multiple regression analysis, which allows a more accurate estimate of CMR RV volume from echocardiography (r2 = 0.59, p < 0.001). Our study demonstrates a significant, although imperfect, correlation between echocardiographic and CMR RV functional and geometrical parameters. Combining echocardiographic measures of RV inflow and RV outflow, we deliver a simple formula to estimate CMR-RV volume, improving the echocardiographic accuracy in RV volume quantification.


Central nervous system effects of cardiopulmonary bypass.
The spectrum of approaches to the issue of brain injury in cardiac surgical practice ranges from refusal to acknowledge that the problem exists to an overemphasis on cerebral risks that can unduly frighten patients. An appropriate approach to therapeutic and preventive strategies requires a fitting sense of proportion and an understanding of the mechanisms of cerebral injury. This article reviews the incidence and severity of cerebral injury during cardiopulmonary bypass, the identification of high-risk patients, and the mechanisms of injury, including hypoperfusion, microemboli, and inflammatory response. It discusses the influences of alpha-stat and pH-stat strategies on cerebral blood flow during cardiopulmonary bypass; the use of retinal angiography to image the retinal circulation, thus providing a window on the cerebral microcirculation during bypass; magnetic resonance imaging evidence of an inflammatory response in the brain during bypass; and current efforts to gain better understanding of the molecular mechanisms involved in the inflammatory response. The current incidence of stroke during cardiopulmonary bypass is somewhat lower than in the 1980s but still remains a significant problem. Levels of cognitive impairment also are unacceptably high. Recognized predictors enable us to identify patients at particularly high risk of stroke. Hypertensive patients are particularly susceptible to ischemic injury during bypass and should be perfused at mean perfusion pressures higher than those for normotensive patients. Under conditions of hypothermia, a pH-stat strategy causes loss of cerebral blood flow autoregulation, and the cerebral blood flow becomes pressure-passive. With both the pH-stat and alpha-stat strategies, cooling of the patient greatly increases the flow to metabolism ratio of the cerebral blood flow; however, this luxury perfusion brings to the brain not just an excess supply of oxygen but also an increased quantity of microemboli. Current investigative efforts are focused on the endothelial cell-leukocyte adhesion cascade, attempting to characterize beta2 and beta1 adhesion molecule expression in patients undergoing cardiac surgery. Hammersmith Hospital is about to complete a study of the effects of high-dose aprotinin on the inflammatory response pattern and on cerebral infarction. Further progress in the development of therapeutic and preventive strategies with respect to cerebral injury during cardiac bypass depends on an increase in the understanding of the mechanisms involved. Current strategies should include optimizing cerebral perfusion and minimizing macroembolic and microembolic damage. The possibility of modifying the systemic inflammatory response is the most interesting challenge of the next few years.


An ellagitannin, n-butyl gallate, two aryltetralin lignans, and an unprecedented diterpene ester from Pelargonium reniforme.
The structural diversity of the metabolic pool of Pelargonium reniforme was extended by the characterization of the 1C4-glucose based ellagitannin pelargoniin E, gallic acid n-butyl ester, (-)-4,4',9'-trihydroxy-3',5'-dimethoxy-2,7'-cyclolignan 9-O-beta-glucopyranoside and reniformin, a diterpene ester comprised of a diterpene acid with an uncommon -(CH2)(2)- bridging element linked to 2-(4-hydroxyphenyl)ethansulfonic acid. These metabolites were associated with the known (alpha,beta)-3,4-di-O-galloyl-glucopyranoside, 4,6-dihydroxy-2beta-glucopyranosyloxyacetophenone, 1-O-galloylglycerol, 6'-O-galloylsalidroside and (+)-isolariciresinol-9'-O-beta-glucopyranoside. All structures were established on the basis of spectroscopic methods.


γ-secretase promotes Drosophila postsynaptic development through the cleavage of a Wnt receptor.
Developing synapses mature through the recruitment of specific proteins that stabilize presynaptic and postsynaptic structure and function. Wnt ligands signaling via Frizzled (Fz) receptors play many crucial roles in neuronal and synaptic development, but whether and how Wnt and Fz influence synaptic maturation is incompletely understood. Here, we show that Fz2 receptor cleavage via the γ-secretase complex is required for postsynaptic development and maturation. In the absence of γ-secretase, Drosophila neuromuscular synapses fail to recruit postsynaptic scaffolding and cytoskeletal proteins, leading to behavioral deficits. Introducing presenilin mutations linked to familial early-onset Alzheimer's disease into flies leads to synaptic maturation phenotypes that are identical to those seen in null alleles. This conserved role for γ-secretase in synaptic maturation and postsynaptic development highlights the importance of Fz2 cleavage and suggests that receptor processing by proteins linked to neurodegeneration may be a shared mechanism with aspects of synaptic development.


Optimization of Radiation Shielding Considerations for Designing Halcyon Vault.
To determine the radiation shielding considerations for optimization of Halcyon vault shielding requirements. The primary and leakage workloads were estimated using actual clinical treatment planning and treatment delivery data acquired from three busy operational clinical Halcyon facilities. The effective use factor was determined based on a newer approach proposed in this paper using the percentage of patients treated with different treatment techniques. The transmission factor of the primary beam block, maximum head leakage, and patient scatter fractions around the Halcyon machine were experimentally determined. The first tenth-value layer (TVL1) and equilibrium tenth-value layer (TVLe) for 6 MV - flattening-filter-free (FFF) primary X-ray beam for ordinary concrete were measured. The primary and leakage workloads are estimated as 1 × 105 cGy/wk and 3.1 × 105 cGy/wk at 1 m respectively. The effective use factor is found as 0.114. The primary beam-block transmission factor is determined as 1.7 × 10-4 at 1 m distance from isocenter along the central beam axis. The maximum head leakage is noted as 6.23 × 10-4. The patient scatter fractions are reported for various planar angles around the Halcyon machine at a radial distance of 1 m in a horizontal plane passing through isocenter. The TVL1 and TVLe of 6 MV-FFF X-ray beam energy for ordinary concrete are found to be 33 and 29 cm, respectively. Using experimentally determined shielding considerations, the optimized vault shielding requirements for the Halcyon facility are calculated and a typical layout drawing is proposed.


Association of sarcopenia, pre-sarcopenia, and dynapenia with the onset and progression of locomotive syndrome in Japanese older adults: a cross-sectional study.
Sarcopenia commonly occurs in older adults with motor disorders requiring long-term care, and the clinical features of sarcopenia are associated with locomotive syndrome. Dynapenia is the age-related loss of muscle strength. However, the association of sarcopenia and dynapenia with the onset and progression of locomotive syndrome in older adults remains unknown. The current study aimed to determine the association of sarcopenia, pre-sarcopenia, and dynapenia with the onset and progression of locomotive syndrome in Japanese older adults. This study included older females (n = 264, 73.9 ± 5.8 years) and males (n = 92, 76.3 ± 6.1 years). Sarcopenia was defined as low muscle function and mass; pre-sarcopenia was defined as low muscle mass with normal muscle function; and dynapenia was defined as low muscle function without low muscle mass. Locomotive syndrome (stage 0-2) severity was determined using the stand-up test, the two-step test, and the 25-question geriatric locomotive function scale. Logistic regression analysis was performed to determine the relationship between sarcopenia category and locomotive syndrome stages. Age (1.208, 95% confidence interval (CI) 1.124-1.298), sex (2.455, 95% CI 1.241-4.856), and BMI (1.211, 95% CI 1.077-1.361) were significant variables for determining locomotive syndrome stage ≥ 1, whereas pre-sarcopenia (0.543, 95% CI 0.331-0.891) and sarcopenia (1.664, 95% CI 1.005-2.755) were significant variables for determining locomotive syndrome stage 2. Only sarcopenia was associated with locomotive syndrome progression, while low muscle mass or low muscle function was not associated with locomotive syndrome. Gaining muscle mass accompanied by an increased muscle function for older adults is warranted to prevent locomotive syndrome progression in the super-aged society.


An infrared spectroscopy method to detect ammonia in gastric juice.
Ammonia in gastric juice is considered a potential biomarker for Helicobacter pylori infection and as a factor contributing to gastric mucosal injury. High ammonia concentrations are also found in patients with chronic renal failure, peptic ulcer disease, and chronic gastritis. Rapid and specific methods for ammonia detection are urgently required by the medical community. Here we present a method to detect ammonia directly in gastric juice based on Fourier transform infrared spectroscopy. The ammonia dissolved in biological liquid samples as ammonium ion was released in air as a gas by the shifting of the pH equilibrium of the ammonium/ammonia reaction and was detected in line by a Fourier transform infrared spectroscopy system equipped with a gas cell for the quantification. The method developed provided high sensitivity and selectivity in ammonia detection both in pure standard solutions and in a simulated gastric juice matrix over the range of diagnostic concentrations tested. Preliminary analyses were also performed on real gastric juice samples from patients with gastric mucosal injury and with symptoms of H. pylori infection, and the results were in agreement with the clinicopathology information. The whole analysis, performed in less than 10 min, can be directly applied on the sample without extraction procedures and it ensures high specificity of detection because of the ammonia fingerprint absorption bands in the infrared spectrum. This method could be easily used with endoscopy instrumentation to provide information in real time and would enable the endoscopist to improve and integrate gastroscopic examinations.


Evaluating the adverse outcome of subtypes of heart failure with preserved ejection fraction defined by machine learning: A systematic review focused on defining high risk phenogroups.
The ability to distinguish clinically meaningful subtypes of heart failure with preserved ejection fraction (HFpEF) has recently been examined by machine learning techniques but studies appear to have produced discordant results. The objective of this study is to synthesize the types of HFpEF by examining their features and relating them to phenotypes with adverse prognosis. A systematic search was conducted using the search terms "Diastolic Heart Failure" OR "heart failure with preserved ejection fraction" OR "heart failure with normal ejection fraction" OR "HFpEF" AND "machine learning" OR "artificial intelligence" OR 'computational biology'. Ten studies were identified and they varied in their prevalence of ten clinical variables: age, sex, body mass index (BMI) or obesity, hypertension, diabetes mellitus, coronary artery disease, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease or symptom severity (NYHA class or BNP). The clinical findings associated with the different phenotypes in > 85 % of studies were age, hypertension, atrial fibrillation, chronic kidney disease and worse symptoms severity; an adverse outcome was in 65 % to 85 % of studies identified diabetes mellitus and female sex and in less than 65 % of studies was body mass index or obesity, and coronary artery disease. COPD was a relevant factor in only 33 % of studies. Adverse clinical outcome - death or admission to hospital (for heart failure) defined phenogroups with the worst outcome. Combining the 4 studies that calculated the MAGGIC score showed a significant (p<0.05) linear relationship between MAGGIC score and outcome, using the one-year event rate. A new score based on strength of the evidence of the HFpEF studies analyzed here, using 9 variables (eliminating COPD), showed a significant (p<0.009) linear relationship with one-year event rate. Three studies examined biomarkers in detail and the ones most prominently related to outcome or consistently found in the studies were GDF15, FABP4, FGF23, sST2, renin and TNF. The dominant factors that identified phenotypes of HFpEF with adverse outcome were hypertension, atrial fibrillation, chronic kidney disease and worse symptoms severity. A new simplified score, based on clinical factors, was proposed to assess prognosis in HFpEF. Several biomarkers were consistently elevated in phenogroups with adverse outcomes and may indicate the underlying mechanism or pathophysiology specific for phenotypes with an adverse prognosis.


Functional and structural amygdala - anterior cingulate connectivity correlates with attentional bias to masked fearful faces.
An attentional bias to threat has been causally related to anxiety. Recent research has linked nonconscious attentional bias to threat with variability in the integrity of the amygdala - anterior cingulate pathway, which sheds light on the neuroanatomical basis for a behavioral precursor to anxiety. However, the extent to which structural variability in amygdala - anterior cingulate integrity relates to the functional connectivity within this pathway and how such functional connectivity may relate to attention bias behavior, remain critical missing pieces of the puzzle. In 15 individuals we measured the structural integrity of the amygdala - prefrontal pathway with diffusion tensor-weighted MRI (magnetic resonance imaging), amygdala-seeded intrinsic functional connectivity to the anterior cingulate, and attentional bias toward backward masked fearful faces with a dot-probe task. We found that greater biases in attention to threat predicted greater levels of uncinate fasciculus integrity, greater positive amygdala - anterior cingulate functional connectivity, and greater amygdala coupling with a broader social perception network including the superior temporal sulcus, tempoparietal junction (TPJ), and somatosensory cortex. Additionally, greater levels of uncinate fasciculus integrity correlated with greater levels of amygdala - anterior cingulate intrinsic functional connectivity. Thus, high bias individuals displayed a heightened degree of amygdala - anterior cingulate connectivity during basal conditions, which we believe predisposes these individuals to focus their attention on signals of threat within their environment.


Costs and benefits of defense by tannins in a neotropical tree.
The costs and benefits of defense by tannins were investigated for a neotropical tree, Cecropia peltata L. (Moraceae). Seedlings of equal age were grown under uniform conditions in a greenhouse for 18 months. Within a plant, leaf tannin concentrations measured in different years were highly correlated. Tannin concentrations differed substantially among individuals; plants with high tannin content had lower damage levels in herbivory experiments. The effects of tannin on herbivory appeared to be dosage dependent. There was, however, a cost associated with tannin production in terms of reduced leaf production.


The inhibition of hyaluronan degradation reduced pro-inflammatory cytokines in mouse synovial fibroblasts subjected to collagen-induced arthritis.
Hyaluronan (HA) degradation produces small oligosaccharides that are able to increase pro-inflammatory cytokines in rheumatoid arthritis synovial fibroblasts (RASF) by activating both CD44 and the toll-like receptor 4 (TLR-4). CD44 and TLR-4 stimulation in turn activate the NF-kB that induces the production of pro-inflammatory cytokines. Degradation of HA occurs via two mechanisms: one exerted by reactive oxygen species (ROS) and one controlled by different enzymes in particular hyaluronidases (HYALs). We aimed to investigate the effects of inhibiting HA degradation (which prevents the formation of small HA fragments) on synovial fibroblasts obtained from normal DBA/J1 mice (NSF) and on synovial fibroblasts (RASF) obtained from mice subjected to collagen induced arthritis (CIA), both fibroblast types stimulated with tumor necrosis factor alpha (TNF-α). TNF-α stimulation produced high mRNA expression and the related protein production of CD44 and TLR-4 in both NSF and RASF, and activation of NF-kB was also found in all fibroblasts. TNF-α also up-regulated the inflammatory cytokines, interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), and other pro-inflammatory mediators, such as matrix metalloprotease-13 (MMP-13), inducible nitric oxide synthase (iNOS), as well as HA levels and small HA fragment production. Treatment of RASF with antioxidants and specific HYAL1, HYAL2, and HYAL3 small interference RNA (siRNAs) significantly reduced TLR-4 and CD44 increase in the mRNA expression and the related protein synthesis, as well as the release of inflammatory mediators up-regulated by TNF-α. These data suggest that the inhibition of HA degradation during arthritis may contribute to reducing TLR-4 and CD44 activation and the inflammatory mediators response.


Synthesis, antibacterial and antioxidant activities of Thiazole-based Schiff base derivatives: a combined experimental and computational study.
Thiazole-based Schiff base compounds display significant pharmacological potential with an ability to modulate the activity of many enzymes involved in metabolism. They also demonstrated to have antibacterial, antifungal, anti-inflammatory, antioxidant, and antiproliferative activities. In this work, conventional and green approaches using ZnO nanoparticles as catalyst were used to synthesize thiazole-based Schiff base compounds. Among the synthesized compounds, 11 showed good activities towards Gram-negative E. coli (14.40 ± 0.04), and Gram-positive S. aureus (15.00 ± 0.01 mm), respectively, at 200 μg/mL compared to amoxicillin (18.00 ± 0.01 mm and 17.00 ± 0.04). Compounds 7 and 9 displayed better DPPH radical scavenging potency with IC50 values of 3.6 and 3.65 μg/mL, respectively, compared to ascorbic acid (3.91 μg/mL). The binding affinity of the synthesized compounds against DNA gyrase B is within - 7.5 to - 6.0 kcal/mol, compared to amoxicillin (- 6.1 kcal/mol). The highest binding affinity was achieved for compounds 9 and 11 (- 6.9, and - 7.5 kcal/mol, respectively). Compounds 7 and 9 displayed the binding affinity values of - 5.3 to - 5.2 kcal/mol, respectively, against human peroxiredoxin 5. These values are higher than that of ascorbic acid (- 4.9 kcal/mol), in good agreement with the experimental findings. In silico cytotoxicity predictions showed that the synthesized compounds Lethal Dose (LD50) value are class three (50 ≤ LD50 ≤ 300), indicating that the compounds could be categorized under toxic class. Density functional theory calculations showed that the synthesized compounds have small band gap energies ranging from 1.795 to 2.242 eV, demonstrating that the compounds have good reactivities. The synthesized compounds showed moderate to high antibacterial and antioxidant activities. The in vitro antibacterial activity and molecular docking analysis showed that compound 11 is a promising antibacterial therapeutics agent against E. coli, whereas compounds 7 and 9 were found to be promising antioxidant agents. Moreover, the green synthesis approach using ZnO nanoparticles as catalyst was found to be a very efficient method to synthesize biologically active compounds compared to the conventional method.


Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy.
The matrix metalloproteinases (MMPs) mediate homeostasis of the extracellular environment. They have multiple signalling activities that are commonly altered during tumorigenesis and that might serve as intervention points for anticancer drugs. However, there are many criteria to consider in validating MMPs as drug targets and for the development of MMP inhibitors. The inhibition of some MMPs could have pro-tumorigenic effects (making them anti-targets), counterbalancing the benefits of target inhibition. These effects might partially account for the failure of MMP inhibitors in clinical trials. What are the major challenges in MMP target validation and MMP-inhibitor-drug development?


Emerging Approaches to Monitor and Modify Care in the Era of Cystic Fibrosis Transmembrane Conductance Regulators.
As we characterize the clinical benefits of highly effective modulator therapy (HEMT) in the cystic fibrosis (CF) population, our paradigm for treating and monitoring disease continues to evolve. More sensitive approaches are necessary to detect early disease and clinical progression. This article reviews evolving strategies to assess disease control and progression in the HEMT era. This article also explores developments in pulmonary function monitoring, advanced respiratory imaging, tools for the collection of patient-reported outcomes, and their application to profile individual responses, guide therapeutic decisions, and improve the quality of life of people with CF.


Kestenbaum's number as an indicator of pupillomotor input asymmetry.
We compared the direct light response of both eyes in 90 patients who had anterior visual pathway disease using two different testing methods. We measured Kestenbaum's number in millimeters of pupillary diameter. Kestenbaum's number (K) is the difference in the pupil size attained in each eye under direct illumination while the other eye is occluded. We then measured the relative afferent pupillary defect (RAPD) in log units using neutral density filters. The two tests gave similar results (K = 0.88 x RAPD). Kestenbaum's number is the less precise measure, but it can be quickly and cheaply estimated even in dark brown eyes. The filter test requires a set of filters and at least one well-innervated iris sphincter. Kestenbaum's number can be measured without filters, but the iris sphincter and dilator muscles in both eyes must be normally innervated.


Undifferentiated pleomorphic sarcoma of the lateral thigh with KRAS/NF1 co-mutation recurred after repetitive surgical resection: A case report and review of the literature.
Undifferentiated pleomorphic sarcoma (UPS), a rare soft tissue sarcoma subtype, mainly occurs in the deep parts of the limbs and trunk, observed as rapidly growing painless lumps, rarely located under the skin or protrudes from the skin surface. The risk of recurrence and metastasis is associated with multiple factors. Mutation of tumor gene, tumor occurrence, location and depth of invasion, and tumor size have great influence on prognosis. In this study, we described a case of UPS with KRAS/NF1 co-mutation. This case had undergone UPS extended resection for four times combined with chemotherapy in another hospital. The resection area was more than 3 cm, and tumor relapsed after all operations. This time, the tumor protruded from the left lateral surface with ulceration and infection. Due to multiple surgeries, the anatomy of the lateral femoral vessels has been seriously damaged. We performed expanded tumor resection and adjacent flap transfer repair; meanwhile, vacuum sealing drainage (VSD)-negative pressure closed the drainage, and the patient recovered well after surgery. After surgery, the patient was transferred to the Department of Oncology for chemotherapy. There was no recurrence after 6 months of follow-up. Gene mutation plays an important role in UPS recurrence and metastasis. At the same time, occurrence and location, depth, and size of UPS have great influence on the prognosis. Deeper exploration and expanded resection are important for the prognosis of UPS.


Hydatid disease of the soft tissues of the lower limb: findings in three cases.
Three cases of hydatid disease are reported, all presenting as soft tissue lesions in the lower extremities. All three cases were studied with ultrasound (US), two with computed tomography (CT), and two with magnetic resonance (MR) imaging techniques. Two patients presented with multivesicular lesions which were considered diagnostic of hydatid disease. The third patient showed a lesion with a predominantly solid pattern, closely mimicking a soft-tissue neoplasm. US was not diagnostic, but MR outlined vesicular structures and a fibrous pericyst. Hydatid disease presenting in the soft tissues can therefore be diagnosed with confidence when it shows multivesicular lesions but MR may be the most useful imaging technique when a complex or solid pattern is present.


Interferon binding: the first step in establishment of antiviral activity.
Chick cells incubated at 1 degrees C with interferon fail to develop antiviral activity, but this activity appears subsequent to a 7-hour incubation at 37 degrees C after removal of interferon by repeated washings. Treatment with actinomycin D blocks the development of the latter activity. Cells incubated with interferon at 1 degrees C for up to 1 hour and then washed and incubated for 2 hours at 37 degrees C develop a degree of antiviral activity proportional to the concentration of interferon at initial incubation; at any concentration, the antiviral activity increased with the duration of initial incubation at 1 degrees C, but a maximal response was reached at 10 or 20 minutes. Treatment with trypsin after incubation with interferon at 1 degrees C inhibited development of antiviral activity. Interferon is rapidly bound to a superficial cell site, and this binding is necessary for development of antiviral activity in chick cells.


Omnidirectional thermal-electric signatures of functional illusion device with anisotropic geometry.
The omnidirectional thermal-electric signatures induced by the anisotropic functional illusion device and the corresponding camouflage device are reported. We first theoretically derive the anisotropic effective parameters of confocal elliptical bilayer core-shell structure for constructing the functional illusion device. Then, the thermal-electric signatures of the functional illusion device with camouflage device are presented numerically. In addition, we further transform the monolayered structure of the camouflage device into an alternating multilayered one to enrich the omnidirectional illusion effects. The results show that the functional illusion device with monolayered structure could realize omnidirectional thermal-electric illusion effects perfectly. When the monolayered structure is replaced by the alternating multilayered one, the functional illusion device with alternating multilayered structure could achieve different illusion effects with different scattering signatures under different directional heat flux and electric current launching. This article may open a new avenue to realize omnidirectional illusion effects of functional device in multiphysical fields.


Association of MICA gene Exon-5 polymorphism in oral submucous fibrosis.
The present study was conducted to explore the allele frequencies of MICA gene Exon-5 transmembrane and to measure the circulatory MICA levels in various histologic grades of patients with oral submucous fibrosis (OSF) compared to healthy individuals. We enrolled a total of 595 patients for this cross-sectional study and divided them into 2 groups: healthy controls (n = 320) and patients with OSF (n = 275). Further, patients with OSF were subdivided based on their histologic gradings. The genomic DNA was extracted followed by a polymerase chain reaction and genotyping using the ABI Prism DNA Sequencer (ThermoFisher Scientific, Inc., Waltham, MA, USA). Our study showed that the A5 allele of the MICA gene in the Exon-5 region conferred significant risk for patients with OSF. With reference to the histologic gradings of OSF, we found that the MICA gene conferred statistically significant risk among patients with grade III OSF. On the other hand, the A8 allele of MICA gene in the Exon-5 region conferred significant protection among the overall OSF cohort and in the grade III of histologic grade. Finally, the circulatory human MICA levels were found to have a stepwise increase from grade I toward grade III in patients with OSF. Our results suggested that the A5 allele in MICA might confer risk for the progression of OSF among the South Indian ethnic population.


Does temperament influence language development? Evidence from preterm and full-term children.
The aims of this study are: (1) to describe language and temperament characteristics of one group of low risk preterm (PR) children and a group of full-term (FT) children and (2) to identify those factors which can predict language outcomes at 30 months of age, with special attention on temperament. There is evidence of differences between very or extremely PR and FT children in relation to characteristics of temperament and language development. However, not many studies have been carried out with healthy PR children. The participants were 142 low risk PR children (mean gestational age (GA): 32.60 weeks) and 49 FT children (mean GA 39.84 weeks). The temperament of the children was assessed at 10 months of age through the Infant Behavior Questionnaire-Revised (IBQ-R). At 22 months of age the cognitive development of the children was assessed through the Spanish adaptation of the Batelle Developmental Inventory (BDI). In order to assess the children's language development the Galician adaptation of the MacArthur-Bates CDI was applied at 30 months of age. In addition, socio-demographic information about the children and their families was gathered at birth. The results indicate that there were no significant differences in the language measures of interest (word production, MLU3, and sentence complexity) between groups. The only differences found between the PR and the FT children in the IBQ-R were restricted to the smiling and laughter and the fear subscales. Hierarchical regression analyses performed indicate that GA did not have any predictive effect on language measures taken at 30 months. Cognitive scores were an important predictor of language measures, although certain temperament subscales contributed in a significant way to the variance of language measures, particularly low intensity pleasure, approach, high intensity pleasure, sadness, and vocal reactivity. Therefore, extroverted (positive affectivity) temperament seems to be beneficial for language development.


Basion-Cartilaginous Dens Interval: An Imaging Parameter for Craniovertebral Junction Assessment in Children.
Widening of the basion-dens interval is an important sign of cranioverterbral junction injury. The current literature on basion-dens interval in children is sparse and based on bony measurements with variable values. Our goal was to establish the normal values of a recently described new imaging parameter, the basion-cartilaginous dens interval in children. Three hundred healthy pediatric patients (0-10 years of age) were selected retrospectively. These patients were divided into 3 different groups: A (0-3 years), B (3-6 years), and C (6-10 years). The basion-cartilaginous dens interval was calculated on the sagittal MPR image of cervical spine CT in a soft-tissue window. The mean, SD, and the upper limit of normal (mean +2 SDs) of the 3 groups were calculated, and statistical tests were used to check for significant differences of the basion-cartilaginous dens interval among these 3 groups. The upper limits of the basion-cartilaginous dens interval for the 3 groups were 5.34 mm in group A, 5.64 mm in group B, and 7.24 mm in group C. There were statistically significant differences in the basion-cartilaginous dens interval values among the 3 groups. There was no statistically significant difference in basion-cartilaginous dens interval values between groups A and B; however, values in group C were significantly different from those in both A and B. There was no statistically significant difference in the basion-cartilaginous dens interval values between males and females. The basion-cartilaginous dens interval is a novel imaging parameter to assess cranioverterbral junction integrity in children, which includes the nonossified cartilage in the measurement.


Molecular adaptation of Lactobacillus plantarum WCFS1 to gallic acid revealed by genome-scale transcriptomic signature and physiological analysis.
Gallic acid (GA) is a model hydroxybenzoic acid that occurs esterified in the lignocellulosic biomass of higher plants. GA displays relevant biological activities including anticancer properties. Owing to its antimicrobial and cellulase-inhibiting activities, GA also imposes constraints to the fermentability of lignocellulosic hydrolysates. In depth-knowledge of the mechanisms used by tolerant microorganisms to adapt to hydroxybenzoic acids would be a step forward to improve the bioavailability of GA or select/engineer production hosts with improved metabolic traits for the bioconversion of pretreated lignocellulosic biomass. Whole genome transcriptional profiling using DNA microarrays was used to characterize the molecular response of Lactobacillus plantarum WCFS1 to GA. Expression levels of 14 and 40 genes were differentially regulated at 1.5 and 15 mM GA, respectively. The transcriptomic analysis identified a marked induction of genes with confirmed or related roles to gastrointestinal survival, the repression of genes coding for certain ABC-type transporters and modulation of genes involved in the control of intracellular ammonia levels, among other responses. Most notably, a core set of genes dedicated to produce GA from polyphenols (tanB Lp ), decarboxylate GA to pyrogallol (lpdB, lpdC and lpdD) and transport functions (lp_2943) was highly overexpressed at both GA concentrations. Correspondingly, resting cells of strain WCFS1 induced by GA, but not their non-induced controls, produced pyrogallol. Gene expression and organization of genes involved in GA metabolism suggested a chemiosmotic mechanism of energy generation. Resting cells of L. plantarum induced by GA generated a membrane potential and a pH gradient across the membrane immediately upon addition of GA. Altogether, transcriptome profiling correlated with physiological observations indicating that a proton motive force could be generated during GA metabolism as a result of electrogenic GA uptake coupled with proton consumption by the intracellular gallate decarboxylase. The combination of transcriptome and physiological analyses revealed versatile molecular mechanisms involved in the adaptation of L. plantarum to GA. These data provide a platform to improve the survival of Lactobacillus in the gut. Our data may also guide the selection/engineering of microorganisms that better tolerate phenolic inhibitors present in pretreated lignocellulosic feedstocks.


The expression and role of protein kinase C in neonatal cardiac myocyte attachment, cell volume, and myofibril formation is dependent on the composition of the extracellular matrix.
The extracellular matrix (ECM) is a dynamic component of tissues that influences cellular phenotype and behavior. We sought to determine the role of specific ECM substrates in the regulation of protein kinase C (PKC) isozyme expression and function in cardiac myocyte attachment, cell volume, and myofibril formation. PKC isozyme expression was ECM substrate specific. Increasing concentrations of the PKC delta inhibitor rottlerin attenuated myocyte attachment to randomly organized collagen (1, 5, and 10 microM), laminin (5 and 10 microM), aligned collagen (5 and 10 microM), and fibronectin (10 microM). Rottlerin significantly decreased cell volume on laminin and randomly organized collagen, and inhibited myofibril formation on laminin. The PKC alpha inhibitor Gö 6976 inhibited attachment to randomly organized collagen at 6 nM but did not affect cell volume. The general PKC inhibitor Bisindolylmalemide I (10 and 30 microM) did not affect myocyte attachment; however, it significantly decreased cell volume on randomly organized collagen. Our data indicate that PKC isozymes are expressed and utilized by neonatal cardiac myocytes during attachment, cell growth, and myofibril formation. Specifically, it appears that PKC delta and/or its downstream effectors play an important role in the interaction between cardiac myocytes and laminin, providing further evidence that the ECM influences cardiac myocyte behavior.


Solubility factors established by gas-liquid chromatography. A balance sheet.
Dravnieks and Laffort first used a method based on gas-liquid chromatography for establishing solubility factors (or parameters) of solutes. This method has been developed and improved over ten years (1972-1982) and applied to quantitative structure-activity relationships in olfaction. The physico-chemical and biological implications of this approach are reappraised.


Predictive modelling of growth and enzyme production and activity by a cocktail of Pseudomonas spp., Shewanella putrefaciens and Acinetobacter sp.
The possibility was examined of developing a predictive model that combined microbial growth (increase in cellular number) with extracellular lipolytic and proteolytic enzyme activity of a cocktail of four strains of Pseudomonas spp. and one strain each of Acinetobacter sp. and Shewanella putrefaciens. Environmental conditions within the following matrix of conditions were examined: temperature 2-20 degrees C, pH value 4.0-7.5 and water activity (a(w)) 0.95-0.995 and a model was constructed, which predicted growth based on increase in cell number. Data on lipase production and protease activity were generated and will be available as a database, but no function could be identified, which was a good fit to these data, since most enzymatic production and activity occurred, as expected, during transition from exponential to stationary phase. Even at lower cell numbers, in more unfavourable conditions, hydrolysing effects were detectable, which made it difficult to construct a model combining both microbiological and enzymatic data.


Possible participation of IgG4 in the activation of complement in IgG4-related disease with hypocomplementemia.
To investigate which IgG subclasses contribute to the activation of the complement pathway in IgG4-related disease (IgG4RD) patients with hypocomplementemia. Sera of IgG4RD patients were analyzed for the binding ability of IgG subclasses to complement component 1q (C1q). Polyethylene glycol (PEG) precipitates containing immune complexes (ICs) in sera of IgG4RD patients were analyzed for IgG subclass composition by Western blotting. PEG precipitates containing ICs (PEG-ICs) in sera of patients were also analyzed for their ability to consume complement in normal human serum (NHS) using a total complement hemolytic (CH50) assay and a commercial kit to measure the complement capacity of all three individual complement pathways. The C1q binding assay revealed high serum levels of C1q-binding IgG4 in IgG4RD patients with hypocomplementemia. ICs in PEG precipitates were formed with IgG4 in IgG4RD patients, regardless of the presence or absence of hypocomplementemia. We observed a marked reduction of CH50 and reduced complement activity in the classical complement pathway as well as the mannan-binding lectin complement pathway in NHS incubated with PEG-IC isolated from IgG4RD patients with hypocomplementemia. Our results suggest that IgG4 may participate in the activation of complement in IgG4RD patients with hypocomplementemia.


Fine-needle aspiration diagnosis of intra-thoracic and intra-abdominal lesions: review of experience in the pediatric age group.
Review of fine-needle aspiration (FNA) smears from 121 pediatric patients with intra-thoracic and intra-abdominal lesions revealed 42 (34.7%) cases of neoplasms, 35 (28.9%) cases of tuberculosis, 12 (9.9%) cases of non-tuberculous inflammations, 4 (3.3%) cases of benign cystic lesions, and 28 (23.1%) inadequate/inconclusive cases. The age of the patients ranged from 20 days to 18 yr. Ultrasound and/or CT study done in 105 cases localized the lesions in following common sites: lungs (19 cases), mediastinum (22 cases), liver (14 cases), intestines (11 cases), and lymph nodes (17 cases). The neoplastic lesions consisted of 39 malignant, one suspicious, and two benign neoplasms. Among the neoplasms, the small round cell tumors were the most frequent (27 cases), followed by germ cell tumors (eight cases) and miscellaneous neoplasms (seven cases). The common small round cell tumors were non-Hodgkins lymphoma (eight cases), hepatoblastoma (seven cases), neuroblastoma (five cases), and nephroblastoma (three cases). A combined clinical, imaging, and FNA cytology approach was found to be useful in arriving at a tissue diagnosis.


Toward a Better Definition of Acute-on-Chronic Liver Failure.
Acute-on-chronic liver failure (ACLF) has been defined differently in the East and West. The definitions given by Asian Pacific association for the study of liver (APASL) and American association for the study of liver (AASLD) and European association for the study of liver (EASL) working group have fundamental deficiencies and contradictions and do not encompass all patients with ACLF seen in the East and West. Although the World Gastroenterology Organisation (WGO) working party attempted to provide an improved definition but this too is not appropriate. In this article, we have compared the various definitions of ACLF given by APASL, EASL-AASLD and WGO and suggest a comprehensive definition for prospective collection of data on ACLF.


Cerebral laterality and the study of alcoholism.
This paper suggests that the strategy of studying individuals at high risk to develop alcoholism by comparing, for example, sons of alcoholic fathers with sons of nonalcoholic fathers might not control for handedness or for patterns of cerebral laterality. In our sample of alcoholic men, at least 50% of the men left-handed or having a left-handed first-degree relative had an alcoholic father, versus only 26% of the right-handed men not having a left-handed first-degree relative. If generalized to nonalcoholic individuals, these data suggest that a larger proportion of the sons of alcoholic fathers either would be left-handed or would have a left-handed first-degree relative, and might have an anomalous pattern of cerebral dominance. Furthermore, several findings associated with being at high risk for alcoholism have also been associated with left-handedness or with left-hemisphere dysfunction.


An epidemiologic approach to the study of retinopathy: the Pittsburgh diabetic morbidity and retinopathy studies.
Diabetic retinopathy was studied in two cohorts of insulin-dependent diabetics (IDDs) from the Children's Hospital of Pittsburgh. The first cohort (n = 696) consisted of IDDs of long duration. Severe retinopathy was self-reported in 70% of this cohort by 30 years duration of diabetes. Associations between severe retinopathy, hypertension and smoking were observed. In order to examine the relationship between metabolic control and early diabetic retinopathy, a second cohort of adolescent IDDs (n = 58) were referred for standardized fluorescein angiography. Sixty-four percent had early retinopathy. None had proliferative changes. Significant differences in individual mean whole blood glycosylated hemoglobin (GHb), averaged over 3 years before angiography, were consistently seen between those with and without early retinopathy. Also, the number of microaneurysms was positively correlated with individual mean GHb. Before the advent of GHb testing, those IDDs who later had retinopathy were more likely to have experienced at least one hospitalization for diabetic ketoacidosis. These observations provide strong support that poor metabolic control preceded the development of diabetic retinopathy. Results are consistent with the hypothesis that improvement of metabolic control early in the course of IDDM may prevent or delay the development of the early changes of diabetic retinopathy.


Exosome-mediated miR-9-5p promotes proliferation and migration of renal cancer cells both in vitro and in vivo by targeting SOCS4.
Exosomes secreted by cancer cells play important roles in tumor progression by interacting with cell receptors. Renal cancer derived exosomes contain miRNAs which are associated with cell proliferation and invasion. Micro RNA 9-5 (miR-9-5) is highly expressed in the serum of renal cancer patients with advanced (tumor size - node - metastasis) TNM stage and Fuhrman grade. miR-9-5p is extensively expressed in exosomes derived from renal cancer cells. Overexpression of miR-9-5p promotes proliferation and invasion of A-704 (a cancer cell line of human kidney) cells via targeting and deregulating SOCS4 mRNA. Inhibition of the Janus kinase (JAK)/signaling transducer and activator of transcription (STAT) pathway by SOCS4 will be reduced, which leads to phosphorylation of STAT3 and JAK. Activated cytokine signaling promotes cell proliferation and invasion, and inhibits apoptosis. Moreover, overexpression of SOCS4 reduces miR-9-5p levels and plays an opposite role in cell. To conclude, exosomal miR-9-5p plays important roles in renal cancer both in vivo and in vitro, indicating it may be used as biomarker for diagnosis and for monitoring the efficacy if therapy.


Attentional bias to pain-relevant body locations: New methods, new challenges.
In a recent issue of Consciousness and Cognition, Filbrich, Torta, Vanderclausen, Azanon, and Legrain (2016) commented on a paper in which we used a tactile Temporal Order Judgment (TOJ) task to show that expecting pain on a specific body location biased attention to that location (Vanden Bulcke, Crombez, Durnez, & Van Damme, 2015). Their main criticism is that the effects are likely to reflect response bias rather than genuine attentional bias. We agree that the TOJ task used may be susceptible to response bias, and welcome the authors' methodological suggestions to control for such bias. However, we feel that certain aspects of our work are misrepresented in their paper. Most importantly, we contest their argument that our instructions made the threat location task-relevant, thereby increasing risk of response bias. Further, we reply to other methodological and theoretical issues raised by these authors.


In vitro ability of Fusarium keratoplasticum to form biofilms in venous catheter.
Fusarium keratoplasticum is a common specie in human infections and is responsible for many diseases affecting immunocompetent and immunocompromised patients. This study aimed to evaluate the ability of Fusarium keratoplasticum to form biofilm in venous catheters (VC), focusing on the development of maturation and dispersion over time (24, 48, 72, 96 and 120 h) and the evaluation amphotericin B (AB) susceptibility in planktonic cells and after 96 h of biofilm formation. F. keratoplasticum was able to form a biofilm in VC with maturation most likely between 48 and 72 h, according to colony count and total biomass results. The dispersion process supposedly occurred from 72 to 96 h, when we observed a decrease in the parameter's colony count, total biomass and mitochondrial metabolic activity. The planktonic cells of F. keratoplasticum were susceptible to AB, however, there was no inhibition of the F. keratoplasticum strain biofilm in any of the AB concentrations, with the growth of the fungus recovering after 48 h in contact with AB. Thus, our findings suggest that in addition to forming a biofilm on VC, F. keratoplasticum becomes AB-resistant, highlighting the concern of this fungus on medical devices.


Biochemical and histopathological changes of subacute cadmium intoxication in male rats.
Biochemical and histopathological effects of subacute intoxication of rats with cadmium (Cd) were studied in rats. Twenty adult healthy male albino rats were randomly divided into two duplicate groups (five rats in each cage); (1) control group where rats were provided with standard diet and water ad-libitum, (2) Cd group where rats were subjected to freshly prepared Cd chloride solution (CdCl2) 200 mg/l in drinking water daily for 8 weeks, the whole duration of experiment. Blood samples were obtained after 4 weeks, via retro-orbital bleeding for separation of serum. Five rats were killed, each sacrifice by decapitation for collection of kidneys and heart. Disturbed renal and cardiac functions were achieved after 4 weeks as indicated by the increase of most biochemical parameters measured in the serum, renal, and cardiac tissues. Histopathological examination of kidneys and hearts showed pathological alterations in Cd-intoxicated rats after 4 and 8 weeks with hematoxylin and eosin (H&E) and Masson trichrome stains. It was concluded that subacute exposure of rats to Cd (200 mg/l) in drinking water daily induced glomerular shrinkage, focal renal, and cardiac fibrosis at 4 and 8 weeks.


The surgical treatment of inflammatory and fibrous laryngotracheal stenosis.
Seventy-two patients with laryngeal or laryngo-tracheal stenotic lesions resulting from tracheal intubation or laryngo-tracheal injuries are reported. Prior to 1978, the method of surgical treatment consisted mainly of laryngoplasty supported by laryngeal stenting. Twenty-six patients were treated by this method with 2 mortalities. Twenty-one long term results were good and 3 were fair. After 1978, laryngo-tracheal resection was performed in 46 patients. Twenty-seven had a Pearson-type operation, 13 underwent total or subtotal cricoid plate resection and modelling, and the remaining 6 had modelling alone. Perfect results after resection depend on the treatment of infection and inflammation of the airway before surgery. Our preferred method is resection and end-to-end anastomosis whenever possible. In addition to the anatomical site of the lesion, the glottic opening has to be considered in planning the surgical operation since impairment necessitates enlargement of the glottis as part of the procedure.


The pattern of angiodysplasia of the gastrointestinal tract in a tropical country.
Angiodysplasia of the intestine was diagnosed by selective visceral angiography in ten of 30 patients from India with unexplained recurrent hemorrhage of the gastrointestinal tract. In contrast with the reports from the western literature, most of the instances involved the small intestine and occurred in the third decade of life.


Expression of cardiac neural crest and heart genes isolated by modified differential display.
The invasion of the cardiac neural crest (CNC) into the outflow tract (OFT) and subsequent outflow tract septation are critical events during vertebrate heart development. We have performed four modified differential display screens in the chick embryo to identify genes that may be involved in CNC, OFT, secondary heart field, and heart development. The screens included differential display of RNA isolated from three different axial segments containing premigratory cranial neural crest cells; of RNA from distal outflow tract, proximal outflow tract, and atrioventricular tissue of embryonic chick hearts; and of RNA isolated from left and right cranial tissues, including the early heart fields. These screens have resulted in the identification of the five cDNA clones presented here, which are expressed in the cardiac neural crest, outflow tract and developing heart in patterns that are unique in heart development.


Percutaneous placement of pedicle screws in overweight and obese patients.
In obese patients, placing pedicle screws percutaneously is a particular challenge. As the bulky and thick configuration of obese patients may produce fuzzier fluoroscopic view and longer passage of surgical instruments, the chances of misplacement might increase. This study was designed to evaluate the effect of patient's body habitus on the incidence of percutaneous pedicle screw misplacements. A retrospective study with prospectively collecting data. Three hundred seventy percutaneous pedicle screws for minimally invasive lumbar spinal fusion surgery were noted in 89 consecutive patients. The position and direction of screws to pedicle were evaluated using the findings in computed tomography (CT) scan with the following grading method: Grade A, completely in the range without pedicle cortex violation; Grade B, pedicle wall violation <2 mm; Grade C, pedicle wall violation 2 to 4 mm; and Grade D, pedicle wall violation >4 mm. The direction of violation was grouped as medial, lateral, cranial, and caudal. Two independent observers retrospectively examined all of the postoperative CT images. All screws were assigned into one of the following three groups along with patient's body mass index (BMI): 157 screws (38 patients) in normal weight (BMI<25) group; 124 (29) in overweight (25≤BMI<30) group; and 89 (22) in obese (BMI≥30) group. A pedicle screw was considered misplaced if the grade was defined as B, C, and D. Multivariate logistic regression analyses were performed to evaluate the association between screw misplacements and BMI. Sixty-two screws (16.8%) were misplaced with the majority of Grade B (72.6%, 45/62) and lateral direction (72.6%, 45/62). Twenty-eight screws (22.6%, 28/124) were misplaced in overweight group, 12 (13.5%, 12/89) in obese group, and 22 (14.0%, 22/157) in normal weight group. Two symptomatic pedicle violations were noted with Grade D: a caudal violation was found in overweight group, which happened in the third case of surgeon's series; a medial misplacement, which was occurred in the 29th case, was noticed in obese group. There was no statistically significant association of pedicle violations along with patient's BMI (odds ratio [OR]=1.00, 95% confidence interval [CI]=0.94-1.07, p=.99). Moreover, no other factors, such as patient's age, gender, preoperative diagnosis, number of the fused segments, and year of the surgery, had a statistically significant relationship with pedicle violations. On the contrary, pedicle violations observed approximately five times more frequently at the level of L3 (47.1%, 8/17) and L4 (28.8%, 36/125) rather than L5 (10.1%, 16/158) and S1 (2.9%, 2/70) (OR=4.95, 95% CI=2.62-9.33, p<.0001). Although symptomatic pedicle violations were noted in the earlier period of surgeon's learning curve and in overweight and obese patients, no statistical evidence could be found between patient's body habitus and percutaneous pedicle screw misplacement. Our data also suggest that greater caution should be exercised to avoid pedicle violations especially at L3 and L4.


Three dimensional left atrial volume index is correlated with P wave dispersion in elderly patients with sinus rhythm.
P wave dispersion is a noninvasive electrocardiographic predictor for atrial fibrillation. The aim of the study was to explore relation between left atrial volume index assessed by 3-dimensional echocardiography and P wave dispersion in elderly patients. Seventy-three consecutive patients over the age of 65 (mean age: 75 ± 7 years, 17 men) were included. P wave dispersion is calculated as the difference between maximum and minimum P wave durations. Left atrial volume index was measured by both 2-dimensional and 3-dimensional echocardiography and categorized as normal (≤ 34 mL/m(2)) or increased (mild, 35-41 mL/m(2); moderate, 42-48 mL/m(2); severe, ≥ 49 mL/m(2)). Thirty-one patients had normal left atrium while 24 patients had mildly enlarged, nine had moderately enlarged, and nine had severely enlarged left atrium. Prolongation of P wave dispersion was more prevalent in patients with dilated left atrium. P wave dispersion was significantly correlated with both 2-dimensional (r = 0.600, p < 0.001) and 3-dimensional left atrial volume index (r = 0.688, p < 0.001). Both left atrial volume indexes were associated with prolonged P wave dispersion when adjusted for age, sex, presence of hypertension, and left ventricular mass index. Receiver-operator characteristic (ROC) analysis revealed that a 3-dimensional left atrial volume index ≥ 25 mL/m(2) separated patients with prolonged P wave dispersion with a sensitivity of 82.2 %, specificity of 67.9 %, positive predictive value of 80.4 %, and negative predictive value of 70.4 %. In elderly patients, 3-dimensional left atrial volume index showed a better correlation with P wave dispersion and might be helpful in discriminating patients with prolonged P wave dispersion, who might be prone to atrial fibrillation.


An effective transplanting technique using shells for restoration of Zostera marina habitats.
Significant declines in seagrass coverage have occurred in many parts of the world. In recent decades, transplanting projects for seagrass restoration at die-off areas have been attempted, but most current seagrass transplanting techniques are cost and labor intensive. We have developed a new seagrass transplanting method in which oyster shells are used as an anchoring device, and does not require SCUBA diving for sub-tidal planting. Here, we tested the shell method for feasibility and efficiency in large-scale seagrass restoration. Planting units consisting of two Zostera marina shoots anchored to one oyster shell were dropped from a boat to settle on the sediment at the test site. Four transplanting trials were conducted throughout the experimental period (December 2003, January, February, and November 2004) in Koje Bay on the southern coast of Korea. Eelgrass shoots planted using the shell method successfully established at the test areas, and the survival rates of transplants were comparable to those obtained using other common planting techniques. The transplant shoot density declined during the first 2-3 months following transplantation due to the initial transplant shock, and then surviving shoots became established at the sites and produced new lateral shoots after these periods. Plant size and leaf productivity of transplants 7 months post-transplanting were similar to or exceeded those of pre-existed shoots, suggesting that the physiological status of transplants is similar to that of natural population after 7 months. Because the shell method did not require workers to be in the water, the method was cost and labor effective. Additionally, given that shells originate from marine environments, the shell method did not leave any hazardous materials in the transplanting areas after restoration.


Localization and functional characterization of metal-binding sites in phytochelatin synthases.
Metal-binding domains consisting of short, contiguous stretches of amino acids are found in many proteins mediating the transport, buffering, trafficking or detoxification of metal ions. Phytochelatin synthases are metal-activated enzymes that function in the detoxification of Cd(2+) and other toxic metal and metalloid ions. In order to localize Cd(2+)-binding sites, peptide libraries of two diverse phytochelatin synthases were synthesized and incubated with (109)Cd(2+). Distinct binding sites and binding motifs could be localized based on the patterns of Cd(2+)-binding. The number of binding sites was consistent with previous findings for recombinant protein. Positions of binding sites appeared to be conserved even among diverse phytochelatin synthases. Mutant peptide analysis was used to assess the contribution of exemplary amino acids to binding. Several binding motifs contain cysteines or glutamates. For cysteines a strong correlation was found between binding activity and degree of conservation among known phytochelatin synthases. These findings indicate the suitability of peptide scanning for the identification of metal-binding sites. The functional role of several cysteines was investigated by expression of hemagglutinin-tagged phytochelatin synthases in phytochelatin synthase-deficient, Cd(2+)-hypersensitive Schizosaccharomyces pombe cells. The data are consistent with a model suggesting functionally essential metal-binding activation sites in the N-terminal catalytic part of phytochelatin synthases and additional binding sites at the C-terminus not essential for activity.


Irradiation exposure modulates central opioid functions.
Exposure to low doses of gamma irradiation results in the modification of both the antinociceptive properties of morphine and the severity of naloxone-precipitated withdrawal in morphine-dependent rats. To better define the interactions between gamma irradiation and these opiate-mediated phenomena, dose-response studies were undertaken of the effect of irradiation on morphine-induced antinociception, and on the naloxone-precipitated withdrawal syndrome of morphine-dependent rats. In addition, electrophysiologic studies were conducted in rats after irradiation exposure and morphine treatment correlating with the behavioral studies. The observations obtained demonstrated that the antinociceptive effects of morphine as well as naloxone-precipitated withdrawal were modified in a dose-dependent manner by irradiation exposure. In addition, irradiation-induced changes in the evoked responses obtained from four different brain regions demonstrated transient alterations in both baseline and morphine-treated responses that may reflect the alterations observed in the behavioral paradigms. These results suggest that the effects of irradiation on opiate activities resulted from physiologic alterations of central endogenous opioid systems due to alterations manifested within peripheral targets.


Metabolic dysfunction-associated fatty liver disease and the risk of hepatocellular carcinoma.
The metabolic dysfunction-associated fatty liver disease (MAFLD) is a new inclusive term proposed to replace non-alcoholic fatty liver disease (NAFLD). We analysed whether hepatocellular carcinoma (HCC) risk differs by MAFLD or NAFLD status in a large sample of asymptomatic adults. A cohort comprising 73,691 adults were followed up for the development of HCC. NAFLD was diagnosed among participants without other liver diseases (n = 65,992). Participants with MAFLD showed higher incidence of HCC than those without MAFLD (0.37 and 0.24 per 1,000 person-years, respectively; p = 0.006). However, MAFLD was not an independent factor associated with HCC in multivariable adjusted analysis (hazard ratio [HR] 1.21; 95% CI 0.92-1.60). When stratified according to presence of other liver diseases, MAFLD was not associated with HCC in participants with other liver diseases. In participants without other liver diseases, both MAFLD (adjusted HR 1.84; 95% CI 1.09-3.11) and NAFLD (adjusted HR 1.71; 95% CI 1.01-2.90) were independent factors associated with HCC. When stratified according to NAFLD and MAFLD status, there was no HCC development among participants with NAFLD only during 8,936 person-years of follow-up, but this NAFLD-only group comprised 3.4%, and the majority of participants with hepatic steatosis fulfilled both NAFLD and MAFLD criteria. In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. For those without other chronic liver diseases, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC. This study investigated the usefulness of newly proposed nomenclature, metabolic dysfunction-associated fatty liver disease (MAFLD), over non-alcoholic fatty liver disease (NAFLD), in terms of predicting hepatocellular carcinoma. In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. However, for those without chronic liver disease, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC.


Recurrent overexpression of c-IAP2 in EBV-associated nasopharyngeal carcinomas: critical role in resistance to Toll-like receptor 3-mediated apoptosis.
The oncogenic process leading to nasopharyngeal carcinoma (NPC) requires the combination of genetic and epigenetic alterations, latent infection by the Epstein-Barr virus and local inflammation. A transcriptome analysis of NPC xenografts identified the gene encoding the cellular inhibitor of apoptosis protein 2 (c-IAP2) among the top five most intensely expressed. Consistently, the very high levels of the c-IAP2 protein were detected in 11 of 13 NPC biopsies. RMT 5265, a structural analog of second mitochondria-derived activator of caspase (SMAC), induced the rapid degradation of c-IAP2 in nasopharyngeal epithelial cells, whether malignant or not, but blocked clonal cell growth in NPC cells only. In short-term experiments, RMT 5265 induced apoptosis in a fraction of NPC cells, and this apoptosis was dramatically enhanced when RMT 5265 was combined with Toll-like receptor 3 (TLR3) stimulation. By contrast, the cooperative effect with tumor necrosis factor alpha was only marginal. The apoptosis induced by the combination of RMT 5265 and TLR3 stimulation was mediated by caspase-8 and associated with a decrease in the cellular content of the long isoform of FLICE-like inhibitory protein. Similar caspase-8 activation was obtained when siRNA knockdown of c-IAP2 was combined with TLR3 stimulation. In conclusion, c-IAP2 has a specific protective function in NPC cells challenged by TLR3 agonists. This protective function is probably important to make NPC cells tolerant to their own production of small viral RNAs, which are potential agonists of TLR3. Our data will help to design a rational use of IAP inhibitors in NPC patients.


Usefulness of ¹¹C-methionine positron emission tomography for treatment-decision making in cases of non-enhancing glioma-like brain lesions.
The present study evaluated usefulness of the positron emission tomography with (11)C-methionine for prediction of the clinical course and treatment decision-making in adult patients with newly diagnosed non-enhancing brain lesions mimicking low-grade gliomas. Retrospective analysis was done in 163 cases. In overall, 131 tumors underwent surgical resection, which in 34 cases was done after initial period of observation. Among the latter 5 patients were operated on after significant clinical deterioration. In overall, 3 resected neoplasms corresponded to WHO histopathological grade I, 87 to grade II, 39 to grade III, and 2 to grade IV. In all 163 cases the tumor/normal brain uptake ratio (T/N ratio) of (11)C-methionine ranged from 0.68 to 8.02 (mean 2.21 ± 1.16, median 1.81). Mean T/N ratios of non-operated lesions, low-grade and high-grade tumors were 1.60 ± 0.85, 2.27 ± 1.22, and 2.54 ± 1.09, respectively (P < 0.0001), but overlap between 3 groups was prominent. In patients who had clinical deterioration during the period of observation T/N ratios of the lesion varied from 1.49 to 3.38 (mean 2.23 ± 0.70, median 2.15). Comparison of the deterioration-free survival of patients with T/N ratios of the lesion above and below 1.90 revealed statistically significant difference (P < 0.0001). In conclusion, "wait-and-scan" strategy with delay of surgical treatment does not seem reasonable option if T/N ratio of (11)C-methionine in the non-enhancing glioma-like brain lesion constitutes ≥1.90, since it may be associated with significant risk of tumor progression and clinical deterioration during follow-up.


Cold plasma reactive species: Generation, properties, and interaction with food biomolecules.
Cold plasma- the fourth state of matter generated at room temperature is composed of several reactive species that account for chemical and physical changes in biological materials. Applications of plasma in food include but are not limited to maintaining safety, quality, and property modification. However, plasma application in the food sector lacks a detailed understanding of the cause of alteration in food. While several plasma reactive species could potentially be involved in biomolecular interactions, only a few reactive oxygen and nitrogen species (RONS) have been examined in detail. The lack of identifying reactive species with respect to the changes in process parameters leads to misconceptions about the actual chemical reaction. Therefore, this review explores the possibility of using different feed gases to alter species composition and emphasizes that all reactive species are equally involved in modifying food components, alongside the futuristic means of using molecular dynamics simulation to fill the knowledge gap.


Geographical differences in mortality of severely injured patients in Italy.
In Italy there are no accepted standards for trauma care nor dedicated programs for quality assessment on a national scale, like trauma registries. At the same time there seems to be a north-south gradient in the quality of health care. We hypothesized that geographical inequalities of health-care quality may affect trauma mortality. Retrospective comparison of hospital mortality by Cox regression in three main areas of Italy adjusted for age, Glasgow Coma Scale and source of admission. A leading national database on patients admitted to intensive care units (ICU) in the years 2002-2005 was used. 9162 adult trauma cases admitted to the ICU from the emergency department were included. There is a significant north-south gradient of risk. Compared to the north, the risk of death is about 60% higher in the south and about 30% higher in the central region. These figures are similar in both referral centres and other hospitals and both in the head-injured only and total injured cases. Despite the limitations of this study, mainly related to sampling issues, risk-adjustment and incomplete follow-up, the large geographic differences in mortality that we found highlight likely deficiencies in the quality of trauma care that deserve further accurate assessment.


Transurethral collagen therapy in women.
We evaluated our recent experience with transurethral collagen therapy in women. A series of 44 women with video urodynamic evidence of intrinsic sphincter deficiency were treated with transurethral collagen therapy using local anesthesia. Median patient age was 72 years (range 41 to 94). Mean duration of incontinence was 72 months. Incontinence was grade 3 in 42 patients. Mean abdominal leak point pressure before treatment was 56 cm. water. Patient response to treatment was evaluated by the change in the number of pads required to effect significant improvement. Median number of pads used was 5 pretreatment (range 3 to 12) and 3 posttreatment. A total of 20 patients was cured and 8 others required only 1 pad daily after treatment (63% cured or needing no pads daily). Of the cured patients 4 had used greater than 10 pads daily before collagen injection. One treatment was given to 22 patients and 7 have not improved of whom 2 underwent only 1 treatment. Mean volume of collagen used to effect a cure was 9.1 cc. Collagen injection is a useful treatment for the severely incontinent female patient with intrinsic sphincter deficiency.


Mechanism of Proarrhythmic Effects of Potassium Channel Blockers.
Any disturbance of electrical impulse formation in the heart and of impulse conduction or action potential (AP) repolarization can lead to rhythm disorders. Potassium (K(+)) channels play a prominent role in the AP repolarization process. In this review we describe the causes and mechanisms of proarrhythmic effects that arise as a response to blockers of cardiac K(+) channels. The largest and chemically most diverse groups of compound targets are Kv11.1 (hERG) and Kv7.1 (KvLQT1) channels. Finally, the proarrhythmic propensity of atrial-selective K(+) blockers inhibiting Kv1.5, Kir3.1/3.4, SK, and K2P channels is discussed.


Fracture resistance of endodontically treated molars restored with extensive composite resin restorations.
When cuspal coverage is required, there is no evidence that indirect composite resin restorations are superior to direct restorations in terms of biomechanical behavior. The purpose of this in vitro study was to compare the fracture resistance of cusp-replacing direct and indirect composite resin restorations in endodontically treated molars. Forty-five human mandibular molars were selected and divided into 3 groups (n=15): DIR specimens, restored with direct composite resin (Estelite Sigma) restorations; IND specimens, restored with indirect composite resin (Estelite Sigma) restorations, and control specimens, which remained intact. Endodontic treatment was performed using NiTi ProTaper rotary instruments, and teeth were filled using lateral condensation of gutta-percha and sealer. Extensive Class II MO cavities were prepared, and the 2 mesial cusps were reduced, allowing a 2-mm layer of composite resin. All teeth were prepared to the same dimensions, considering reasonable human variation. Specimens were loaded to failure and the fracture loads were recorded (N). The mode of fracture was determined using a stereomicroscope and classified as favorable or unfavorable failure. The data were subjected to a Kruskal-Wallis test, multiple-comparison Mann-Whitney test, and a chi-square test (alpha=.05). Significant differences (P<.001) were observed between the control group and both DIR and IND groups. However, no significant difference was found between the DIR and IND groups. The chi-square test did not show a significant difference in the frequencies of favorable/unfavorable failure modes among the 3 groups (P=.981). No significant difference was observed in the fracture resistance of endodontically treated molars restored to original contours with an extensive cusp-replacing direct or indirect composite resin restoration.


DHX9 Strengthens Atherosclerosis Progression By Promoting Inflammation in Macrophages.
Atherosclerosis (AS) is the main cause of cerebrovascular diseases, and macrophages play important roles in atherosclerosis. DExH-Box helicase 9 (DHX9), as a member of DExD/H-box RNA helicase superfamily II, is identified as an autoantigen in the sera of systemic lupus erythematosus patients to trigger inflammation. The aim of this study was to investigate whether DHX9 is involved in AS development, especially in macrophages-mediated-inflammatory responses. We find that DHX9 expression is significantly increased in oxLDL or interferon-γ-treated macrophages and peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Knockdown of DHX9 inhibits lipid uptake and pro-inflammatory factors expression in macrophages, and ameliorates TNF-α-mediated monocyte adhesion capacity. Furthermore, we find that oxLDL stimulation promotes DHX9 interaction with p65 in macrophages, and further enhances the transcriptional activity of DHX9-p65-RNA Polymerase II complex to produce inflammatory factors. Moreover, using ApoE -/- mice fed with western diet to establish AS model, we find that knockdown of DHX9 mediated by adeno-associated virus-Sh-DHX9 through tail vein injection evidently alleviates AS progression in vivo. Finally, we also find that knockdown of DHX9 inhibits p65 activation, inflammatory factors expression, and the transcriptional activity of p65-RNA Polymerase II complex in PBMCs from patients with CAD. Overall, these results indicate that DHX9 promotes AS progression by enhancing inflammation in macrophages, and suggest DHX9 as a potential target for developing therapeutic drug.


Human vaccine research and development: an overview.
One-fifth of global mortality, especially in children under the age of five is due to infectious diseases. Vaccines are effective at combating these diseases, as shown by the success of smallpox eradication, the impressive progress towards polio eradication, the significant achievements in measles mortality reduction and many others. New safe and effective vaccines must be developed for a variety of infections of public health importance against which no effective preventive intervention measure is either available or practical. In addition, appropriate mechanisms should be put in place to ensure access for all children to the needed vaccines. To meet these challenges, a new paradigm needs to be built among all stakeholders of immunization, including countries, industry, research institutions, foundations and international agencies like the World Health Organization (WHO) and the United Nations Children Fund (UNICEF). Importantly, developing countries should be empowered to participate actively in the development and introduction of new vaccines according to their national priorities.


Influence of Chlorella vulgaris on growth, digestibility and gut morphology and microbiota of weaned piglet.
The purpose of this study was to evaluate the impact of Chlorella vulgaris (5% in the diet), supplemented or not with two exogenous carbohydrase mixtures on piglets' performance, nutrient digestibility and gut morphology, fermentation products and microbiota. Forty-four male piglets weaned at 28 days of age, with 11.2 ± 0.46 kg of live weight, were used and assigned to 1 of 4 dietary treatments: cereal and soybean meal based-diet (control, n = 11), control diet with 5% of C. vulgaris (CH, n = 10), CH diet supplemented with 0.005% of Rovabio® Excel AP (CH + R, n = 10) and CH diet supplemented with 0.01% of a recombinant 4-carbohydrase mixture (CH + M, n = 11). Growth performance was not changed by the of C. vulgaris inclusion during 21 days of trial. However, total tract apparent digestibility of nutritional fractions was negatively impacted by the inclusion. In addition, the viscosity of duodenum plus jejunum contents slightly increased in all groups fed with the microalga. In contrast, dietary microalga increased duodenum villus height and promoted a healthier gut microbiota, with higher abundance of some specific bacterial taxa (Colidextribacter, Oscillospira and Lactobacillus). This study indicates that the dietary inclusion of 5% C. vulgaris improves piglets' gut health without impairing performance. Data also indicate that C. vulgaris reduces nutrient digestibility but promotes compensatory developments of gut mucosa and prebiotic effects. Dietary supplementation with exogenous carbohydrases does not seem to be necessary for this inclusion level. Therefore, the incorporation of CH as a sustainable feed ingredient in piglets' nutrition is a viable alternative approach.


An unusual location of the ansa cervicalis.
The ansa cervicalis (AC) is part of the cervical plexus and is formed by the ventral rami of spinal nerves C1-C3. It is usually formed by two roots that run parallel to each other and then form a loop anterior to the internal jugular vein. Herein, we report a rare case where the AC was found deep to the internal carotid artery and common carotid artery and had sympathetic contributions.


Alteration of 86Rb+ influx and efflux following depletion of membrane sterol in L-cells.
Ouabain-sensitive uptake of 86Rb+ (an analogue of K+) was enhanced in L-cells that had been treated with 25-hydroxycholesterol or 7-ketocholesterol in order to deplete their sterol concentration. Ouabain-insensitive Rb+ efflux also increased in the sterol-depleted cells and the intracellular concentration of K+ diminished while the concentration of Na+ increased. All of these effects of 25-hydroxycholesterol were counteracted by the addition of mevalonate to the culture medium. Despite the evidence for increased active Rb+ transport in the 25-hydroxycholesterol-treated cells, the level of sodium and potassium ion-activated adenosine triphosphatase ((Na+ + K+)-activated ATPase) activity measured in homogenates and plasma membrane preparations from the treated cells was not significantly different from the control values. Rb+ uptake was more sensitive to ouabain inhibition in sterol-depleted cells than in control cells, although ATPase activity in plasma membrane fractions isolated from treated cells was not more sensitive to ouabain inhibition than was that from control cells. It is possible that the ability of the oxygenated sterols to inhibit DNA synthesis and cell division (Kandutsch, A. A., and Chen, H. W. (1977) J. Biol. Chem. 252, 409-415) is related to their effects upon cellular ion transport.


Atractylodin alleviates nonalcoholic fatty liver disease by regulating Nrf2-mediated ferroptosis.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Oxidative stress is one of the main inducers of NAFLD. Atractylodin (ART), a major active ingredient of Atractylodes lancea, possesses potential antioxidant and anti-inflammatory activity in many types of disease. In the current study, the underlying mechanism by which ART alleviates the progression of NAFLD was explored. The function of ART in facilitating NAFLD was investigated in vitro and in vivo. Functionally, ART attenuated high-fat diet (HFD)-induced NAFLD in mice and palmitic acid (PA)-induced oxidative stress in HepG2 cells. Furthermore, our data verified that ART attenuated HFD-induced NAFLD by inhibiting ferroptosis of hepatocyte cells, as evidenced by decreased Fe2+ concentration, reactive oxygen species (ROS) level, malondialdehyde (MDA) content, and increased glutathione (GSH) content. The protective effect of ART on the cell viability of hepatocytes was blocked by a specific ferroptosis inhibitor (ferrostatin-1). Mechanistically, ART treatment promoted the translocation of nuclear factor erythroid 2-related Factor 2 (NFE2L2/NRF2) and thus increased glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11) expression. Taken together, ART alleviates NAFLD by regulating Nrf2-mediated ferroptosis.


The Double Trouble: A Case of Duplicated Extrahepatic Bile Duct with Choledochal Cyst.
Biliary tract shows a large number of anatomic variations and duplication of the bile duct is an extremely rare anomaly. It has been reported to be associated with other congenital conditions like Abnormal Pancreato Biliary Junction (APBJ), biliary atresia and choledochal cyst and may lead to complications like cholangitis, choledocholithiasis and malignancy. The clinical presentation may be with one of the above complications and the condition usually reveals itself only on imaging investigations, as a surprise to the radiologist and the surgeon. Its detection is important prior to any biliary tract surgery to prevent inadvertent bile duct injury. The authors report a case of a rare subtype of extrahepatic bile duct duplication with coexisting choledochal cyst.


Straw-derived biochar mitigates CO2 emission through changes in soil pore structure in a wheat-rice rotation system.
To better understand the relationships between soil pore structure features and soil CO2 emission and soil organic carbon (SOC) sequestration following different straw return modes, undisturbed soil cores (0-5 cm and 5-10 cm) were collected from a rice-wheat rotation system under 4 straw return treatments as (1) no straw return (CK), (2) straw direct return (DR), (3) straw biochar return (BR); (4) straw-pig manure fermentation return (FR) for six years. Pore structure parameters including pore size distribution, porosity, connectivity, anisotropy and fractal dimension (FD) were determined using X-ray computer tomography. Soil CO2 flux and concentrations of SOC, readily oxidable carbon and nutrients were also measured. The results showed that BR and FR had significantly higher SOC concentration than DR and CK. Porosity and number of >500 μm and 500-100 μm macropores, FD and connectivity were significantly highest under FR and was lowest under BR. FR and DR produced 28.1%-32.4% higher C-CO2 than CK and BR in wheat growing season, and 9.80%-16.9% higher in rice season. Soil CO2 emission and C concentrations were significantly related to soil pore structure parameters. The CO2 emission was most significantly related to number of >500 μm pores and FD, indicating that poorly developed pore structure under BR hindered the production and diffusion of CO2 from soil. These results enhanced our understanding of the relationship between soil pore structure and CO2 emission following biochar application, and provided evidence for decision making process in choosing proper straw managements to promote SOC sequestration and reduce CO2 emission.


An Integrated Epigenomic and Transcriptomic Map of Mouse and Human αβ T Cell Development.
αβ lineage T cells, most of which are CD4+ or CD8+ and recognize MHC I- or MHC II-presented antigens, are essential for immune responses and develop from CD4+CD8+ thymocytes. The absence of in vitro models and the heterogeneity of αβ thymocytes have hampered analyses of their intrathymic differentiation. Here, combining single-cell RNA and ATAC (chromatin accessibility) sequencing, we identified mouse and human αβ thymocyte developmental trajectories. We demonstrated asymmetric emergence of CD4+ and CD8+ lineages, matched differentiation programs of agonist-signaled cells to their MHC specificity, and identified correspondences between mouse and human transcriptomic and epigenomic patterns. Through computational analysis of single-cell data and binding sites for the CD4+-lineage transcription factor Thpok, we inferred transcriptional networks associated with CD4+- or CD8+-lineage differentiation, and with expression of Thpok or of the CD8+-lineage factor Runx3. Our findings provide insight into the mechanisms of CD4+ and CD8+ T cell differentiation and a foundation for mechanistic investigations of αβ T cell development.


Non-conventional mechanical ventilation in severe ARDS, illustrated by a complicated case.
When conventional respiratory strategies fail to maintain adequate oxygenation treatment of severe ARDS is largely empirical. Modern techniques such as inverse ratio ventilation, permissive hypercapnia, NO inhalation and lowering tidal volumes/pressures are advocated. We report on a patient with severe ARDS who showed all the complications of the disease. The risks and benefits of (non)conventional ventilatory strategies are discussed and illustrated.


Evaluation of the guaiac fecal occult blood test for detection of gastrointestinal bleeding in the rhesus macaque (Macaca mulatta).
Gastrointestinal (GI) hemorrhage accompanies several common diseases of rhesus macaques (Macaca mulatta). Guaiac fecal occult blood testing (gFOBT) is a non-invasive means to detect such bleeding in several species; however, there are currently no data indicating reliability of this test to detect GI hemorrhage in macaques. We evaluated sensitivity and specificity of gFOBT to detect simulated and biopsy-associated bleeding in the stomach, duodenum, and colon of 15 rhesus macaques. Fecal samples were analyzed via gFOBT for 72 hours. Guaiac fecal occult blood testing was more sensitive to detect lower vs upper GI bleeding; sensitivity was volume-dependent in the upper GI tract. Single-test specificity was 95.2%. Repeated fecal collections increased gFOBT sensitivity without affecting specificity. Guaiac fecal occult blood testing is a useful screening test for both upper and lower GI bleeding in rhesus macaques. For highest sensitivity, gFOBT should be performed on three fecal samples collected 24 hours apart.


Mediator release from isolated rat ileum in response to field stimulation.
The effect of electrical field stimulation on mediator release from the isolated rat ileum was evaluated by recording the muscle responses and by measuring acetylcholine and histamine appearing in the perfusion fluid. In the presence of cholinesterase inhibitors, supramaximal field stimulation (10 Hz) resulted in twitch responses accompanied by an increased release of acetylcholine. The resting output of histamine was measurable also in the absence of inhibition of cholinesterases, and neatly increased during electrical stimulation. Atropine produced a dose-related decrease in the release of histamine from electrically stimulated muscle, while eserine extends the time-course of the contractile response and of the histamine release as well. The results are discussed in the context of the role ascribed to acetylcholine as a physiological modulator of histamine release.


Diagnosis and subtype analysis of Blastocystis sp. in 442 patients in a hospital setting in the Netherlands.
Blastocystis sp. are among the most commonly observed intestinal parasites in routine clinical parasitology. Blastocystis in humans consists of at least 9 genetic subtypes. Different subtypes of Blastocystis may be associated with differences in pathogenicity and symptomatology. Advanced microscopy on two samples and sequence-confirmed PCR on a third sample from the same individual were used for Blastocystis diagnosis and subtype analyses on routine clinical samples in a university hospital. With a combined gold standard of sequence-confirmed PCR and positive advanced microscopy, 107 out of 442 (24.2%) patients were diagnosed with Blastocystis. infection, which is a high frequency of detection in comparison to previous reports from industrialized countries. The sensitivity of microscopy and sequence-confirmed PCR was 99.1% (106/107) and 96.3% (103/107), respectively.Among 103 typable samples, subtype 3 was most abundant (n = 43, 42%), followed by subtypes 1 and 2 (both n = 23, 22%), subtype 4 (n = 12, 12%), and single samples with subtypes 6 (1%) and subtype 7 (1%). The prevalence of Blastocystis infection was 38% in patients from the Department of Tropical Medicine and 18% in patients from other departments. A high prevalence of Blastocystis infection was found with both advanced microscopy and sequence-confirmed PCR in our patient population. Most cases were caused by subtypes ST1, ST2, ST3 and ST4. A significantly higher prevalence was found among patients with a history of recent travel to tropical countries.


Cultured murine dermal fibroblast-like cells from senescence-accelerated mice as in vitro models for higher oxidative stress due to mitochondrial alterations.
The senescence-accelerated mouse is a model for senescence acceleration, a higher oxidative stress status, and age-associated disorders. We studied whether fibroblasts cultured from accelerated senescence-prone SAMP11 mice could be used as in vitro models for oxidative stress in senescence. Dichlorofluorescein and hydroethidine assays demonstrated that cells from SAMP11 mice produced more reactive oxygen species than did cells from accelerated senescence-resistant SAMR1 mice. These differences were not due to the defective induction of antioxidants. Double labeling with hydroethidine and MitoTracker Green revealed that most of the reactive oxygen species were generated within the mitochondria. Nonyl acridine orange and JC-1 assays showed an increase in the mass of the mitochondria, especially those with low membrane potential, in SAMP11 cells. Ultrastructurally, mitochondria with degenerative morphology were increased in SAMP11 cells with longer culture periods. These results suggest that cells from SAMP11 mice are useful models for spontaneous higher oxidative stress in vitro due to dysfunctional mitochondria.


[Initial X-ray manifestations of bronchial carcinoma. Possibilities and limitations of early diagnosis (author's transl)].
Problems of defining "early diagnosis" and difficulties, arising from multiform clinical and radiological manifestations in bronchial carcinoma are discussed. Different types of manifestations offer unequal chances for early detection. In demonstrating some typical cases, auxiliary diagnostic means and possibilities for more efficient radiological diagnosis are discussed.


Promoting Stair Use is Possible by Displaying Signs, Even for Stairs of 80 or 105 Steps.
Installing signs is known to be effective in encouraging people to use stairs instead of escalators. However, it has been reported that the effectiveness of such signs is diminished as the number of stairs increases, and no effect was reported at 44 steps. Thus, this study examined whether stair use could be promoted even with 80 or 105 steps by presenting specific numerical values for the health benefits of using stairs. At two universities with parallel escalators and stairs (105 and 80 steps, respectively), we installed signs stating, "Going up one flight of stairs increases your life span by 4 seconds." A one-week baseline period was followed by a one-week intervention using signs displayed to passersby. Follow-up data were also collected for one week immediately after removing the signs. Measurements were collected Monday through Friday from 7:30 to 9:15 a.m. The number of passersby was recorded by categorizing them into four attributes: male and female students, and male and female faculty/staff. A total of 25,065 observations (963 stair users vs. 24,102 escalator users) at University A and 25,677 observations (1020 stair users vs. 24,657 escalator users) at University B were recorded. Sign installation promoted stair use at University A (odds ratio [OR], 1.513; 95% confidence interval [CI], 1.307-1.752) and University B (OR, 1.221; 95% CI, 1.046-1.425). However, there was no effect of the sign installation on the population with attributes that had a high percentage of stair use prior to this study, implying that there is a ceiling effect on the effectiveness of such signs. The implication of the findings is that it is effective to provide detailed information to passersby on the health benefits of stair use for stairs with 80 or 105 steps.


Insight on the Etiologies of Chronically Elevated Troponin.
Elevated troponins signify myocardial damage and raise concern for acute coronary syndrome (ACS). However, there are medical conditions that may cause a patient to have chronically elevated troponin levels in the absence of ACS. In our extensive review, we look at the conditions and their mechanisms that cause chronically elevated troponin levels and discuss them comprehensively. We also aim for our review to serve as a guide for physicians evaluating this complex group of patients.


Volume under the ROC surface for high-dimensional independent screening with ordinal competing risk outcomes.
We propose a screening method for high-dimensional data with ordinal competing risk outcomes, which is time-dependent and model-free. Existing methods are designed for cause-specific variable screening and fail to evaluate how a biomarker is associated with multiple competing events simultaneously. The proposed method utilizes the Volume under the ROC surface (VUS), which measures the concordance between values of a biomarker and event status at certain time points and provides an overall evaluation of the discrimination capacity of a biomarker. We show that the VUS possesses the sure screening property, i.e., true important covariates can be retained with probability tending to one, and the size of the selected set can be bounded with high probability. The VUS appears to be a viable model-free screening metric as compared to some existing methods in simulation studies, and it is especially robust to data contamination. Through an analysis of breast-cancer gene-expression data, we illustrate the unique insights into the overall discriminatory capability provided by the VUS.


Uterine choriocarcinoma fourteen years following bilateral tubal ligation.
A patient who developed choriocarcinoma of the uterus 14 years after bilateral tubal ligation and resection is presented. Non-patency of the fallopian tubes was demonstrated radiologically. The various mechanisms of occurrence of the clinical picture are discussed. Activation of dormant chorionic cells present since the patient's last known pregnancy (1960) appears to be the most probable explanation for the origin of the choriocarcinoma.


Resistance to root fracture of dowel channels with various thicknesses of buccal dentin walls.
The significance of the amount of remaining buccal dentin plate of the dowel channel in resisting root fracture under horizontally directed load was investigated. Forty cast gold dowels and cores were made for four groups of dowel channels that had, respectively, 1 mm, 2 mm, 3 mm, and 1 mm with a 60-degree bevel (collar) of the remaining buccal dentin at the entrance of the canal. An Instron tester in compressive mode was used to produce the horizontal force. Although significant differences in the failure loads for the four groups were not found, dowel channels with 1 mm of remaining buccal dentin walls were apparently more prone to fracture under horizontal impact than those that had 2 or 3 mm of buccal dentin walls. Contrary to popular belief, the addition of a metal collar did not enhance the resistance to root fracture.


SnapShot: FABP Functions.
Fatty acid binding proteins (FABPs) serve as intracellular chaperones for fatty acids and other hydrophobic ligands inside cells. Recent studies have demonstrated new functions of individual members of the FABP family. This Snapshot describes the overall functions of FABPs in health and disease and highlights emerging roles of adipose FABP (A-FABP) and epidermal FABP (E-FABP) in the fields of obesity, chronic inflammation, and cancer development. To view this SnapShot, open or download the PDF.