Physics-Based Method for Modeling Passive Membrane Permeability and Translocation Pathways of Bioactive Molecules.
Assessment of permeability is a critical step in the drug development process for selection of drug candidates with favorable ADME properties. We have developed a novel physics-based method for fast computational modeling of passive permeation of diverse classes of molecules across lipid membranes. The method is based on heterogeneous solubility-diffusion theory and operates with all-atom 3D structures of solutes and the anisotropic solvent model of the lipid bilayer characterized by transbilayer profiles of dielectric and hydrogen bonding capacity parameters. The optimal translocation pathway of a solute is determined by moving an ensemble of representative conformations of the molecule through the dioleoyl-phosphatidylcholine (DOPC) bilayer and optimizing their rotational orientations in every point of the transmembrane trajectory. The method calculates (1) the membrane-bound state of the solute molecule; (2) free energy profile of the solute along the permeation pathway; and (3) the permeability coefficient obtained by integration over the transbilayer energy profile and assuming a constant size-dependent diffusivity along the membrane normal. The accuracy of the predictions was evaluated against experimental permeability coefficients measured in pure lipid membranes (for 78 compounds, R2 was 0.88 and rmse was 1.15 log units), PAMPA-DS (for 280 compounds, R2 was 0.75 and rmse was 1.59 log units), BBB (for 182 compounds, R2 was 0.69 and rmse was 0.87 log units), and Caco-2/MDCK assays (for 165 compounds, R2 was 0.52 and rmse was 0.89 log units).


S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.
Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.


Saudi Arabia: A future regional hub for advanced education, research, science and technology.
Saudi Arabia is the largest country of the Arabian Peninsula, blessed with significant natural resources, including oil, gas and minerals. Saudi Arabia has recognised the importance of education in social and economic transformation, and has established a large number of universities, research and advanced technical institutes which have broken the metropolitan boundaries and have been extended to the far-flung areas of the country. There are 68 universities and degree-awarding institutes. The educational budget reached its highest-ever level of $56.56 billion for the year 2014. About 124,000 Saudi students are pursuing higher education in about 500 universities around the world. Saudi Arabia produced 177826 research papers in Institute for Scientific Information (ISI) database and in the year 2014 alone, 26168 research papers were published in indexed science journals with a rising h-index of 144. The country is turning into a regional hub for advanced education, research, science and technology while swiftly shifting from an oil-based to a knowledge-based economy.


Utility of CT in differentiating liver metastases of well-differentiated gastroenteropancreatic neuroendocrine neoplasms from poorly-differentiated neuroendocrine neoplasms.
To determine the capability of dynamic enhanced computed tomography (CT) to differentiate liver metastases (LMs) of well-differentiated from poorly-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Patients with LMs of GEP-NENs who underwent dynamic enhanced CT examination in Peking University Cancer Hospital from January 2009 to October 2015 were included and data were retrospectively analyzed. We assessed the qualitative and quantitative CT features to identify the significant differentiating CT features of LMs of poorly-differentiated GEP-NENs from those of well-differentiated GEP-NENs using univariate analysis and a multivariate logistic regression model. The study included 22 patients with LMs of well-differentiated GEP-NENs and 32 patients with LMs of poorly-differentiated GEP-NENs. Univariate analysis revealed statistically significant differences between the LMs of well- and poorly-differentiated GEP-NENs in terms of feeding arteries (36.4% vs. 75.0%, χ2=8.061, P=0.005), intratumoral neovascularity (18.2% vs. 59.4%, χ2=9.047, P=0.003), lymphadenopathy (27.3% vs. 81.2%, χ2=15.733, P<0.001), tumor-to-aortic ratio in the hepatic arterial and portal venous phase (T-A/AP: 0.297±0.080vs. 0.251±0.059, t=2.437, P=0.018; T-A/PVP: 0.639±0.138 vs. 0.529±0.117, t=3.163, P=0.003) and tumor-to-liver ratio in the hepatic arterial phase (T-L/AP: 1.108±0.267 vs. 0.907±0.240, t=2.882, P=0.006). The LMs of poorly-differentiated GEP-NENs showed more feeding arteries, more intratumoral neovascularity, more lymphadenopathy and a lower tumor-to-aortic ratio. Multivariate analysis suggested that intratumoral neovascularity [P=0.015, OR=0.108, 95% confidence interval (95% CI), 0.018-0.646], lymphadenopathy (P=0.001, OR=0.055, 95% CI, 0.009-0.323) and T-A/PVP (P=0.004, OR=5.3E-5, 95% CI, 0.000-0.044) were independent factors for differentiating LMs of poorly-differentiated from well-differentiated GEP-NENs. Dynamic enhanced CT features (intratumoral neovascularity, lymphadenopathy and T-A/PVP) are useful in the pathological classification of LMs of GEP-NENs.


Effects of 30-day head-down bed rest on ocular structures and visual function in a healthy subject.
We report ocular changes occurring in a healthy human subject enrolled in a bed rest (BR) study designed to replicate the effects of a low-gravity environment. A 25-yr-old Caucasian man spent 30 consecutive days in a 6 degrees head-down tilt (HDT) position at the NASA Flight Analogs Research Unit. Comprehensive ophthalmologic exams, optic disc stereo-photography, standard automated perimetry (SAP), and optic disc Spectralis OCT scans were performed at baseline, immediately post-BR (BR+0), and 6 mo post-BR. changes in best-corrected visual acuity, intraocular pressure (IOP), cycloplegic refraction, SAP, and Spectralis OCT measures. At BR+0 KIOP was 11 and 10 mmHg in the right (OD) and left eye (OS), respectively (a bilateral 4-mmHg decrease compared to baseline); SAP documented a possible bilateral symmetrical inferior scotoma; Spectralis OCT showed an average 19.4 microm (+5.2%) increase in peripapillary retinal thickness, and an average 0.03 mm3 (+5.0%) increase in peripapillary retinal volume bilaterally. However, there were no clinically detectable signs of optic disc edema. At 6 mo post-BR, IOP was 13 and 14 mmHg in OD and OS, respectively, and the scotoma had resolved. Spectralis OCT measurements matched the ones recorded at baseline. In this subject, a reduction in IOP associated with subtle structural and functional changes compared to baseline were documented after prolonged head-down BR. These changes may be related to cephalad fluid shifts in response to tilt. Further studies should clarify whether decreased translaminar pressure (i.e., the difference between IOP and intracranial pressure) may be responsible for these findings.


Accessory hemiazygos continuation of left inferior vena cava: CT demonstration.
The first CT description of accessory hemiazygos continuation of a left-sided inferior vena cava is presented. This venous anomaly appears as a mediastinal mass on plain chest films and may simulate an aortic dissection on CT or angiography. Careful attention to the various abnormal vascular pathways will obviate the need for further invasive testing.


Renovascular hypertension: an update.
Renovascular hypertension, the most common remediable cause of elevated blood pressure, is a controversial topic, but most authorities agree on several principles. The absolute risk of renovascular hypertension for a specific patient can be estimated using only clinical information, thereby sparing many patients further expensive and potentially dangerous evaluations. Patients with a high absolute risk of renovascular hypertension should have angiography only if they are willing to undergo revascularization if warranted. A screening test (captopril renography, Doppler ultrasonography, magnetic resonance angiography, or computed tomography) is recommended for those with an intermediate absolute risk. Angioplasty should be offered to patients with fibromuscular dysplasia. Whether intensive medical therapy (including an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker) for atherosclerotic renovascular hypertension is improved by angioplasty plus stent placement may be answered by ongoing studies, the largest of which may be the National Institutes of Health-funded Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial.


Associations Between Brain-Gut Axis and Psychological Distress in Fibromyalgia: A Microbiota and Magnetic Resonance Imaging Study.
An altered brain-gut axis is suspected to be one of the pathomechanisms in fibromyalgia (FM). This cross-sectional study investigated the associations among altered microbiota, psychological distress, and brain functional connectivity (FC) in FM. We recruited 25 FM patients and 25 healthy people in the present study. Psychological distress was measured using standardized questionnaires. Microbiota analysis was performed on the participants' stools. Functional magnetic resonance imaging data were acquired, and seed-based resting-state FC (rs-FC) analysis was conducted with the salience network nodes as seeds. Linear regression and mediation analyses evaluated microbiota, symptoms, and rs-FCs associations. We found altered microbiota diversity in FM, of which Phascolarctobacterium and Lachnoclostridium taxa increased the most and Faecalibacterium taxon decreased the most compared to controls. The Phascolarctobacterium abundance significantly predicted Beck depression inventory (BDI-II) scores in FM (β = 6.83; P = .033). Rs-FCs from salience network nodes were reduced in FM, of which rs-FCs from the right lateral rostral prefrontal cortex (RPFC) to the lateral occipital cortex, superior division right (RPFC-sLOC) could be predicted by BDI-II scores in patients (β = -.0064; P = .0054). In addition, the BDI-II score was a mediator in the association between Phascolarctobacterium abundance and rs-FCs of RPFC-sLOC (ab = -.06; 95% CI: -.16 to -9.10-3). In conclusion, microbial dysbiosis might be associated with altered neural networks mediated by psychological distress in FM, emphasizing the critical role of the brain-gut axis in FM's non-pain symptoms and supporting further analysis of mechanism-targeted therapies to reduce FM symptoms. PERSPECTIVES: Our study suggests microbial dysbiosis might be associated with psychological distress and the altered salience network, supporting the role of brain-gut axis dysfunction in fibromyalgia pathomechanisms. Further targeting therapies for microbial dysbiosis should be investigated to manage fibromyalgia patients in the future.


Sleep disorders in children.
In general, childhood sleep disturbances can be accurately clinically diagnosed by the primary care physician, neurologist, or psychiatrist. Careful characterization of the "spells," either by history or home videotaping, may be sufficient. Often, no laboratory studies are needed if the physician can recognize the sleep disturbance and clinically differentiate it from epilepsy or migraine. Although behavioral approaches or "tincture of time" often alleviates a great many sleep disturbances in children, psychopharmacologic therapy has a role in many and can be judiciously prescribed with safety and efficacy.


Primary pulmonary synovial sarcoma presenting with a large lump mass in the left upper mediastinum: A case report.
Primary pulmonary synovial sarcoma is a rare lesion that occurs in 0.5% cases of lung malignancies. Chest computed tomography (CT) reveals a heterogeneously enhancing mass in the lobe or hilum of the lungs, frequently calcified and with pleural invasion. Involvement of the mediastinum in the course of primary pulmonary synovial sarcoma, in particular detection of a large mass in the mediastinum as the sole initial imaging manifestation, is extremely rare, which may contribute to a delayed diagnosis or misdiagnosis. The present case report describes an extremely rare case of a patient with primary pulmonary synovial sarcoma presenting with a large mass in the left upper mediastinum. A 59-year-old patient was admitted to the Department of Respiratory Medicine of Taizhou People's Hospital in May 2014, complaining of a persistent cough and blood sputum for 2 weeks. Following admission, a chest CT showed a large mass in the left upper mediastinum. Thoracoscopy was performed and revealed that the left pulmonary artery was engulfed by the mass, and thus surgical resection of the tumor was abandoned. The patient was definitively diagnosed with primary pulmonary synovial sarcoma following the histopathological and immunohistochemical analysis of biopsy specimens obtained via thoracoscopy. Following the final diagnosis, the patient was transferred to the Department of Oncology for chemotherapy treatments with ifosfamide and doxorubicin. Unfortunately, no partial regression was achieved after two rounds of chemotherapy, and the patient was lost to follow-up 3 months after the diagnosis was confirmed. The present case may promote the consideration of primary pulmonary synovial sarcoma in the differential diagnosis of patients who present with a large mass in the mediastinum.


PAR1 activation induces rapid changes in glutamate uptake and astrocyte morphology.
The G-protein coupled, protease-activated receptor 1 (PAR1) is a membrane protein expressed in astrocytes. Fine astrocytic processes are in tight contact with neurons and blood vessels and shape excitatory synaptic transmission due to their abundant expression of glutamate transporters. PAR1 is proteolytically-activated by bloodstream serine proteases also involved in the formation of blood clots. PAR1 activation has been suggested to play a key role in pathological states like thrombosis, hemostasis and inflammation. What remains unclear is whether PAR1 activation also regulates glutamate uptake in astrocytes and how this shapes excitatory synaptic transmission among neurons. Here we show that, in the mouse hippocampus, PAR1 activation induces a rapid structural re-organization of the neuropil surrounding glutamatergic synapses, which is associated with faster clearance of synaptically-released glutamate from the extracellular space. This effect can be recapitulated using realistic 3D Monte Carlo reaction-diffusion simulations, based on axial scanning transmission electron microscopy (STEM) tomography reconstructions of excitatory synapses. The faster glutamate clearance induced by PAR1 activation leads to short- and long-term changes in excitatory synaptic transmission. Together, these findings identify PAR1 as an important regulator of glutamatergic signaling in the hippocampus and a possible target molecule to limit brain damage during hemorrhagic stroke.


Categories and continua of destructive and constructive marital conflict tactics from the perspective of U.S. and Welsh children.
Categories and continua of parents' marital conflict tactics based on multiple, conceptually grounded criteria were tested. Participants were 175 U.S. children, ages 8-16 years (88 boys, 87 girls) and 327 Welsh children, ages 11-12 years (159 boys, 168 girls). Children's responses (affective, cognitive, behavioral) to analog presentations of 10 everyday marital conflict tactics enacted by fathers or mothers showed substantial variation as a function of tactic used. Orderings of conflict tactics on the various response criteria varied as a function of moderators, particularly the gender of the parent expressing the conflict tactic. Conflict tactics were classified as either constructive or destructive according to criteria derived from the emotional security hypothesis. Except for calm discussion, classifications did not change regardless of cultural group, parent gender, or child age or gender. Recommendations for negotiating everyday marital conflict for the children's sake are discussed.


Risk for symptomatic intracerebral hemorrhage after thrombolysis assessed by diffusion-weighted magnetic resonance imaging.
The risk for symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic treatment has not been evaluated in large studies using diffusion-weighted imaging (DWI). Here, we investigated the relation between pretreatment DWI lesion size and the risk for sICH after thrombolysis. In this retrospective multicenter study, prospectively collected data from 645 patients with anterior circulation stroke treated with intravenous or intraarterial thrombolysis within 6 hours (<3 hours: n = 320) after symptom onset were pooled. Patients were categorized according to the pretreatment DWI lesion size into three prespecified groups: small (< or =10 ml; n = 218), moderate (10-100 ml; n = 371), and large (>100 ml; n = 56) DWI lesions. In total, 44 (6.8%) patients experienced development of sICH. The sICH rate was significantly different between subgroups: 2.8, 7.8, and 16.1% in patients with small, moderate, and large DWI lesions, respectively (p < 0.05). This translates to a 5.8 (2.8)-fold greater sICH risk for patients with large DWI lesions as compared with patients with small (or moderate) DWI lesions. The results were similar in the large subgroup (n = 536) of patients treated with intravenous tissue plasminogen activator. DWI lesion size remained an independent risk factor when including National Institutes of Health Stroke Scale, age, time to thrombolysis, and leukoariosis in a logistic regression analysis. This multicenter study provides estimates of sICH risk in potential candidates for thrombolysis. The sICH risk increases gradually with increasing DWI lesion size, indicating that the potential benefit of therapy needs to be balanced carefully against the risk for sICH, especially in patients with large DWI lesions.


[Effect of magnesium-free on glucocorticoid receptor expression in primary cultured cortical neurons of fetal rats in vitro].
To study the changes of glucocorticoid receptor (GR) expression in embryonic rat cortical neurons exposed to transient Mg(2+)-free treatment. Six days after rat cortical neuronal cultures, two groups were created based on the medium to which were transiently exposed. The control group was exposed to a physiological solution (PS), and the Mg(2+)-free group was exposed to the same medium as the control group except for the removal of magnesium. The expression of GR mRNA and protein was determined by real-time PCR and immunocytochemistry staining 1, 7 and 12 days after transient Mg(2+)-free treatment. Compared to the control group, the Mg(2+)-free group displayed the significantly less accumulated optical density (AOD) of GR immunoreactivity 12 days after transient Mg(2+)-free treatment (p<0.05). On the contrary, GR mRNA expression increased significantly 1 and 7 days after transient Mg(2+)-free treatment in the Mg(2+)-free group (p<0.05). GR expression is modified following Mg-free-induced injury in cultured developing neurons in rats.


Force fluctuations and polymerization dynamics of intracellular microtubules.
Microtubules are highly dynamic biopolymer filaments involved in a wide variety of biological processes including cell division, migration, and intracellular transport. Microtubules are very rigid and form a stiff structural scaffold that resists deformation. However, despite their rigidity, inside of cells they typically exhibit significant bends on all length scales. Here, we investigate the origin of these bends using a Fourier analysis approach to quantify their length and time dependence. We show that, in cultured animal cells, bending is suppressed by the surrounding elastic cytoskeleton, and even large intracellular forces only cause significant bending fluctuations on short length scales. However, these lateral bending fluctuations also naturally cause fluctuations in the orientation of the microtubule tip. During growth, these tip fluctuations lead to microtubule bends that are frozen-in by the surrounding elastic network. This results in a persistent random walk of the microtubule, with a small apparent persistence length of approximately 30 microm, approximately 100 times smaller than that resulting from thermal fluctuations alone. Thus, large nonthermal forces govern the growth of microtubules and can explain the highly curved shapes observed in the microtubule cytoskeleton of living cells.


Covalent protein-oligonucleotide conjugates by copper-free click reaction.
Covalent protein-oligodeoxynucleotide (protein-ODN) conjugates are useful in a number of biological applications, but synthesizing discrete conjugates-where the connection between the two components is at a defined location in both the protein and the ODN-under mild conditions with significant yield can be a challenge. In this article, we demonstrate a strategy for synthesizing discrete protein-ODN conjugates using strain-promoted azide-alkyne [3+2] cycloaddition (SPAAC, a copper-free 'click' reaction). Azide-functionalized proteins, prepared by enzymatic prenylation of C-terminal CVIA tags with synthetic azidoprenyl diphosphates, were 'clicked' to ODNs that had been modified with a strained dibenzocyclooctyne (DIBO-ODN). The resulting protein-ODN conjugates were purified and characterized by size-exclusion chromatography and gel electrophoresis. We find that the yields and reaction times of the SPAAC bioconjugation reactions are comparable to those previously reported for copper-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC) bioconjugation, but require no catalyst. The same SPAAC chemistry was used to immobilize azide-modified proteins onto surfaces, using surface-bound DIBO-ODN as a heterobifunctional linker. Cu-free click bioconjugation of proteins to ODNs is a simple and versatile alternative to Cu-catalyzed click methods.


Highly sensitive frequency metrology for optical anisotropy measurements.
In this paper we present a novel apparatus aimed at measuring very small birefringences and anisotropies and based on frequency metrology and not on polarimetry as usual. In our experiment, a very high finesse resonant cavity is used to convert the phase difference into a resonance frequency difference, which can then be measured with very high accuracy. We describe the setup and present the results of experimental tests, which exhibited a sensitivity delta n approximately = 2x10(-18), allowing for the measurement of long-predicted magnetoelectro-optical effects in gases. Since the shot-noise limited sensitivity of our apparatus lies well below the state-of-the-art sensitivity, frequency metrology appears as a promising technique for small birefringence measurements.


Clinically relevant hypoglycemia prediction metrics for event mitigation.
The purpose of this study was to develop a method to compare hypoglycemia prediction algorithms and choose parameter settings for different applications, such as triggering insulin pump suspension or alerting for rescue carbohydrate treatment. Hypoglycemia prediction algorithms with different parameter settings were implemented on an ambulatory dataset containing 490 days from 30 subjects with type 1 diabetes mellitus using the Dexcom™ (San Diego, CA) SEVEN™ continuous glucose monitoring system. The performance was evaluated using a proposed set of metrics representing the true-positive ratio, false-positive rate, and distribution of warning times. A prospective, in silico study was performed to show the effect of using different parameter settings to prevent or rescue from hypoglycemia. The retrospective study results suggest the parameter settings for different methods of hypoglycemia mitigation. When rescue carbohydrates are used, a high true-positive ratio, a minimal false-positive rate, and alarms with short warning time are desired. These objectives were met with a 30-min prediction horizon and two successive flags required to alarm: 78% of events were detected with 3.0 false alarms/day and 66% probability of alarms occurring within 30 min of the event. This parameter setting selection was confirmed in silico: treating with rescue carbohydrates reduced the duration of hypoglycemia from 14.9% to 0.5%. However, for a different method, such as pump suspension, this parameter setting only reduced hypoglycemia to 8.7%, as can be expected by the low probability of alarming more than 30 min ahead. The proposed metrics allow direct comparison of hypoglycemia prediction algorithms and selection of parameter settings for different types of hypoglycemia mitigation, as shown in the prospective in silico study in which hypoglycemia was alerted or treated with rescue carbohydrates.


Computational modeling and validation studies of 3-D structure of neuraminidase protein of H1N1 influenza A virus and subsequent in silico elucidation of piceid analogues as its potent inhibitors.
Emergence of the drug resistant variants of the Influenza A virus in the recent years has aroused a great need for the development of novel neuraminidase inhibitors for controlling the pandemic. The neuraminidase (NA) protein of the influenza virus has been the most potential target for the anti-influenza. However, in the absence of any experimental structure of the drug targeting NA protein of H1N1 influenza A virus as zanamivir and oseltamivir, the comprehensive study of the interaction of the drug molecules with the target protein has been missing. Hence in this study a computational 3-D structure of neuraminidase of H1N1 influenza A virus has been developed using homology modeling technique, and the same was validated for its reliability by ProSA web server in term of energy profile & Z scores and PROCHECK program followed by Ramachandran plot. Further, the developed 3-D model had been employed for docking studies with the class of compounds as Piceid and its analogs. In this context, two novel compounds (ChemBank ID 2110359 and 3075417) were found to be more potent inhibitors of neuraminidase than control drugs as zanamivir and oseltamivir in terms of their robust binding energies, strong inhibition constant (Ki) and better hydrogen bond interactions between the protein-ligand complex. The interaction of these compounds with NA protein has been significantly studied at the molecular level.


Paraneoplastic Hypocalcemia Developed in Gastric Cancer Accompanied by Osteoblastic Metastasis.
Paraneoplastic syndromes are generally defined as clinical disorders associated with malignant diseases, and hypocalcemia associated with cancer is a rare condition. A woman in her 60s was referred to our hospital for the further examination of massive ascites due to carcinoma of unknown primary origin. She complained of numbness around her lips, and marked hypocalcemia of 5.0 mg/dL was noted. After two courses of chemotherapy, computed tomography showed a decrease in the ascites, and her serum calcium level increased. Although hypocalcemia is a very rare condition in patients with gastric cancer, serum calcium values should be evaluated when neurological symptoms are observed.


Two mixed breed dogs with sensory neuropathy are homozygous for an inversion disrupting FAM134B previously identified in Border Collies.
Two unrelated 8-month-old male mixed breed dogs were presented for evaluation of progressive ataxia, knuckling, and lack of pain perception in the distal limbs. Because of the similarity in age of onset, progression, and clinical findings with previously described sensory neuropathy in Border Collies, the affected dogs were screened for an FAM134B mutation and were determined to be homozygous for the mutation. Despite few phenotypic similarities with other breeds, genetic testing for specific diseases should be considered in mixed breed dogs with compatible clinical signs, especially if ancestry is unknown.


Aneurysmal bone cyst of the talus.
Aneurysmal bone cysts localized in the talus are extremely rare. Such a case is described and the histological findings are analysed in relation to those in aneurysmal cysts in general. The pathomechanism of the lesions is discussed.


The MCCB impairment profile in a Spanish sample of patients with schizophrenia: Effects of diagnosis, age, and gender on cognitive functioning.
The MATRICS Consensus Cognitive Battery (MCCB) was administered to 293 schizophrenia outpatients and 210 community residents in Spain. Our first objective was to identify the age- and gender-corrected MCCB cognitive profile of patients with schizophrenia. The profile of schizophrenia patients showed deficits when compared to controls across the seven MCCB domains. Reasoning and Problem Solving and Social Cognition were the least impaired, while Visual Learning and Verbal Learning showed the greatest deficits. Our second objective was to study the effects on cognitive functioning of age and gender, in addition to diagnosis. Diagnosis was found to have the greatest effect on cognition (Cohen's d>0.8 for all MCCB domains); age and gender also had effects on cognitive functioning, although to a lesser degree (with age usually having slightly larger effects than gender). The effects of age were apparent in all domains (with better performance in younger subjects), except for Social Cognition. Gender had effects on Attention/Vigilance, Working Memory, Reasoning and Problem Solving (better performance in males), and Social Cognition (better performance in females). No interaction effects were found between diagnosis and age, or between diagnosis and gender. This lack of interactions suggests that age and gender effects are not different in patients and controls.


Intrauterine Fluid Instillation and Transtubal Flow: A Randomized Controlled In vitro Trial Comparing Gel and Water.
Possible transtubal spillage of malignant cells is a major concern in fluid instillation sonography, as it is in hysteroscopy. This study aims to compare the transtubal flow of gel and saline and validate the clinical hypothesis that application of fluids with higher viscosity causes less spillage. Randomized controlled in vitro trial comparing gel and saline infusion on 15 tissue specimens after hysterectomy with bilateral salpingectomy. Instillations are performed with saline and gel dyed with a 1% ink solution. Qualitative assessment of tubal spill is investigated as primary outcome. Secondary outcomes are instillation-volume and -pressure, assessed by measuring endometrial cavity dilation at in vitro ultrasound examination and subjective numeric 10-point scoring of the instillation pressure by a dedicated examiner. Tubal flow was more often observed during saline instillation (odds ratio 4.88, P = 0.008). Median subjectively assessed instillation pressures were nine arbitrary units for gel and three for saline (P < 0.001). Tubal flow occurred from 2 cc onward in the saline group versus five cc in the gel instillation group. Cavitary dilation did not differ between both groups. Gel instillation sonography is in vitro associated with less tubal flow and therefore could be a safer diagnostic test compared to saline infusion sonography or hysteroscopy. In vivo studies are necessary to confirm these results.


Impaired blood rheology in critically ill patients in an intensive care unit.
Critically ill patients are at increased risk of thromboembolic complications. Japanese patients admitted to the intensive care unit of Gunma University Hospital were divided into critically ill (high score) and moderately ill (low score) groups according to mean Acute Physiology and Chronic Health Evaluation (APACHE) II score. White blood cell count, potassium, creatinine, immunoglobulin G and blood passage time, measured using the microchannel method, were significantly higher and the platelet aggregation score and platelet count were significantly lower in the high-score group than in the low-score group, but other haemorheological parameters did not differ significantly between the two groups. White blood cell count, potassium, creatinine, APACHE II score and levels of immunoglobulins G, A and M were positively correlated with blood passage time in all patients. Critically ill patients had impaired blood rheology, which could result from increased white blood cell count, potassium, creatinine and immunoglobulins and may be associated with the pathophysiology of the thromboembolic process.


GABAergic mechanisms constraining the activity of the hypothalamo-pituitary-adrenocortical axis.
There are two major inhibitory mechanisms that constrain the activity of the hypothalamo-pituitary-adrenocortical axis: the hormonal negative feedback and the neural inhibition including that posed by the GABAergic neurons. This chapter summarizes our recent morphologic and functional findings on the role of gamma-aminobutyric acid (GABA) in the transcriptional regulation of hypophyseotropic neuropeptide genes in the parvocellular neurosecretory cells of the hypothalamic paraventricular nucleus (PVH). We used organotypic hypothalamic slice cultures and in vivo microinjection protocols in combination with in situ histologic and ultrastructural procedures to address the role of local interneurons in the regulation of hypothalamic effector neurons. Under basal conditions, an intrinsic GABAergic mechanism in the PVH microenvironment was revealed that by itself, without limbic contribution, impinged a tonic inhibitory influence on the parvocellular corticotropin-releasing hormone (CRH) neurons in vitro. In vivo, remote inputs were superimposed on the local circuit, allowing differential transcriptional regulation of CRH and arginine vasopressin (AVP) genes in the hypophyseotropic neurons. During stress, GABAergic cells that are known to project to the PVH become activated and are involved in restraining the cellular, transcriptional, and hormonal responses to stress.


Protein-Mediated Biosynthesis of Semiconductor Nanocrystals for Photocatalytic NAD(P)H Regeneration and Chiral Amine Production.
The use of predesigned bioengineered proteins for self-grown nanomaterials is a promising strategy that opens new scientific directions for biotic-abiotic nano-bio hybrid configurations. The unique properties of nanomaterials can alter the original biological paradigm to allow novel metabolic routes or new activation triggers. In this work, we present a synthetic methodology for self-grown cadmium sulfide quantum dots in a 12-mer bioengineered stable protein 1 under ambient conditions. The sized controlled crystalline QDs are characterized and utilized for NADPH regeneration that is in turn used for the activation of the imine reductase enzyme. The presented nano-bio hybrid system enables the production of a single enantiomeric product that is required for the pharmaceutical industry. Our designed system presents superior activity and can continuously operate for at least 22 hrs with 82 % conversion efficiency. The obtained results may lay the foundations for future nano-bio hybrid systems that can operate both in vitro and in vivo.


Face Masks for Noninvasive Ventilation: Fit, Excess Skin Hydration, and Pressure Ulcers.
Pressure ulcers (stages III and IV) are serious safety events (ie, never events). Healthcare institutions are no longer reimbursed for costs to care for affected patients. Medical devices are the leading cause of pediatric pressure ulcers. Face masks for noninvasive ventilation were associated with a high percentage of pressure ulcers at our institution. A prospective cohort study investigated factors contributing to pressure ulcer development in 50 subjects using face masks for noninvasive ventilation. Color imaging, 3-dimensional surface imaging, and skin hydration measurements were used to identify early skin compromise and evaluate 3 interventions to reduce trauma: (1) a silicone foam dressing, (2) a water/polyethylene oxide hydrogel dressing, and (3) a flexible cloth mask. A novel mask fit technique was used to examine the impact of fit on the potential for skin compromise. Fifty subjects age 10.4 ± 9.1 y participated with color images for 22, hydration for 34, and mask fit analysis for 16. Of these, 69% had diagnoses associated with craniofacial anomalies. Stage I pressure ulcers were the most common injury. Skin hydration difference was 317 ± 29 for sites with erythema versus 75 ± 28 for sites without erythema (P < .05) and smallest for the cloth mask (P < .05). Fit distance metrics differed for the nasal, oronasal, and face shield interfaces, with threshold distances being higher for the oronasal mask than the others (P < .05). Areas of high contact were associated with skin erythema and pressure ulcers. This fit method is currently being utilized to select best-fit masks from available options, to identify the potential areas of increased tissue pressure, and to prevent skin injuries and their complications. Improvement of mask fit is an important priority for improving respiratory outcomes. Strategies to maintain normal skin hydration are important for protecting tissue integrity.


Capturing medical students' idealism.
Students' idealism and desire to work with underserved populations decline as they progress from preclinical training through clerkships and residency. With an increasingly diverse population and increasing health disparities, academic health centers need to incorporate changes in their curricula to train socially responsible and idealistic physicians. International electives can provide valuable learning experiences to help achieve these goals. Sixty-six preclinical medical students at the University of Texas Medical Branch participated in an international elective from 1997 to 2005. After 1 week of didactics, they spent 3 weeks as part of a multidisciplinary medical team in rural Nicaragua. Postelective questionnaires were administered. From students' responses, we identified common learning themes and grouped them under the categories of attitudes, awareness, and skills. Limitations included a self-selection bias, lack of a control group, and limited follow-up. After the elective, students had an increased interest in volunteerism, humanitarian efforts, and working with underserved populations both in the United States and abroad, as well as more compassion toward the underserved. Students also reported a heightened awareness of social determinants of health and public health, and a broadened global perspective, as well as increased self-awareness. Our findings illustrate that a well-structured, mentored experience in international health can have a positive impact on preclinical students' attitudes, including their compassion, volunteerism, and interest in serving under-served populations, all measures of idealism.


Living-Skin Classification via Remote-PPG.
Detecting living-skin tissue in a video on the basis of induced color changes due to blood pulsation is emerging for automatic region of interest localization in remote photoplethysmography (rPPG). However, the state-of-the-art method performing unsupervised living-skin detection in a video is rather time consuming, which is mainly due to the high complexity of its unsupervised online learning for pulse/noise separation. In this paper, we address this issue by proposing a fast living-skin classification method. Our basic idea is to transform the time-variant rPPG-signals into signal shape descriptors called "multiresolution iterative spectrum," where pulse and noise have different patterns enabling accurate binary classification. The proposed technique is a proof-of-concept that has only been validated in lab conditions but not in real clinical conditions. The benchmark, including synthetic and realistic (nonclinical) experiments, shows that it achieves a high detection accuracy better than the state-of-the-art method, and a high detection speed at hundreds of frames per second in MATLAB, enabling real-time living-skin detection.


Lost opportunity. Fairly assigning value to physician administrative services.
The Resource-Based Relative Value System sets values for physician services that can be used to estimate the value of time spent on administrative tasks. This methodology assigns an appropriate place-of-service qualifier and the appropriate percentage of Medicare rates to the time being spent on administrative tasks. A variation of this methodology allows for a rate to be determined for an entire physician group or specialty.


Retrospective analysis of canine monocytic ehrlichiosis in Thailand with emphasis on hematological and ultrasonographic changes.
Canine monocytic ehrlichiosis (CME) is a tropical endemic tick-borne disease that causes fatality or chronic infection involving many organs in dogs. This study aimed to examine the prevalence, risk factors, and hematological and ultrasonographic changes in the liver, gallbladder, kidneys, and spleen following CME infection. This retrospective study used 30,269 samples collected from dogs at the hematology section of the pathology unit of a university veterinary hospital and 35 samples collected from dogs at the diagnostic imaging unit. CME was determined using the buffy coat smear method. Data were analyzed using descriptive statistics and odds ratios. The data revealed that the average yearly prevalence of CME was 1.32%. Risk factors contributing to CME infection were a tick on the body during physical examination, lack of ectoparasite control, and outdoor living. All 148 dogs with CME infection had low platelet counts. The percentages of CME-infected dogs with elevated serum alanine aminotransferase, alkaline phosphatase, and both enzymes above the normal range were 33.6%, 65.9%, and 29.8%, respectively. The rates for elevated serum levels of blood urea nitrogen, creatinine, and both compounds were 33.1%, 19.1%, and 17.3%, respectively. The most common ultrasonographic changes were liver abnormalities (hyperechogenicity or hypoechogenicity, hepatomegaly, and hypoechoic nodules), hyperechogenicity of the kidneys, and an enlarged spleen. These ultrasonographic changes were consistent with the hematology results, which showed a greater elevation of serum liver enzyme levels than renal enzymes. Ultrasonographic changes during CME infection and after treatment with doxycycline can help to monitor and identify persistent pathological changes in the target organs resulting from immune response to CME.


Insulin formulations--a review.
Although the improvement on insulin therapy since it was first conceived, it is still far from mimicking physiological secretion of pancreatic b-cells and research to find new insulin formulations and new routes of administration continues. Human biosynthetic insulin (rapid-acting, intermediate-acting and long-acting), produced by recombinant DNA technique, is currently available. The pharmacokinetic profile of rapid-acting insulin (regular) does not adequately reproduce the physiological post-prandial insulin response. This has led to the development of molecular analogues with slight modifications that prevent the spontaneous polymerisation underlying delayed absorption. Fast-acting analogues such as Lyspro and Aspart can be injected immediately before the meal, inducing a very fast and substantial peak of insulin, similar to that produced by b-cells, but have the disadvantage of short duration of action. For this reason, and because of the difficulty of obtaining sufficient basal insulin concentrations to control preprandial blood glucose levels with current long-acting insulins, analogues known as Glargine and Detemir have been synthesized. They have virtually no plasma peak and acts for about 24 h. These characteristics make it ideal to cover basal insulin requirement. With insulin analogues, it also seems possible to overcome the problem of intra- and inter-individual variability in absorption after subcutaneous injection. This variability is directly proportional to the duration of insulin action. Research into new routes of administration has led to production of inhaled insulin powder, soon to become commercially available. Insulin is absorbed through the lung alveoli. Trials to evaluate efficacy and toleration have shown that inhaled insulin has a similar kinetic profile to the fast-acting injected analogue and can therefore be used for mealtime requirement, combined with a single daily injection of long-acting insulin. Oral insulin is currently being studied in type 1 diabetes prevention with promising results.


"It's hip to be square": Grounding moral traits in geometric shapes.
To examine the hypothesis that there is a metaphoric link between geometric shapes (square vs. circle) and moral traits (integrity vs. deviousness), we conducted three experiments in China. In Study 1, integrity-related words were classified faster when embedded in a square than in a circle. Conversely, deviousness-related words were classified faster in a circle than in a square. Study 2 found that a person who preferred squares was perceived as more righteous and that a person who preferred circles was perceived as more devious. Study 3 revealed that the participants were more likely to pair a square with integrity-related words and a circle with deviousness-related words in a memory task. Given the negation of square-integrity and circle-deviousness emotional congruence, the findings of this research show that shape-related information is a meaningful part of the mental representations of moral traits.


Which periodontal changes are associated with HIV infection?
To assess the validity of diagnostic criteria for HIV-associated periodontal diseases, existing sets of criteria were applied post-hoc to cross-sectional data of the periodontal health of men with and without HIV and their ability to predict HIV infection was compared. Criteria for gingival or periodontal ulceration predicted HIV infection to a similar level. Criteria sensitive to erythema of the attached gingiva and interdental craters had high positive predictive values. Distinct gingival red bands did not predict HIV. 3 HIV-associated periodontal changes were recognised: erythema of the attached gingiva; necrotising periodontal disease and interdental craters. Epidemiological research should also consider conventional gingivitis and lost periodontal attachment. The presence or absence of all 5 conditions should be recorded at each site. Hierarchies of diagnoses with only the most severe condition assigned to each individual swamp valuable information.


An unconventional human Ccr4-Caf1 deadenylase complex in nuclear cajal bodies.
mRNA deadenylation is a key process in the regulation of translation and mRNA turnover. In Saccharomyces cerevisiae, deadenylation is primarily carried out by the Ccr4p and Caf1p/Pop2p subunits of the Ccr4-Not complex, which is conserved in eukaryotes including humans. Here we have identified an unconventional human Ccr4-Caf1 complex containing hCcr4d and hCaf1z, distant human homologs of yeast Ccr4p and Caf1p/Pop2p, respectively. The hCcr4d-hCaf1z complex differs from conventional Ccr4-Not deadenylase complexes, because (i) hCaf1z and hCcr4d concentrate in nuclear Cajal bodies and shuttle between the nucleus and cytoplasm and (ii) the hCaf1z subunit, in addition to rapid deadenylation, subjects substrate RNAs to slow exonucleolytic degradation from the 3' end in vitro. Exogenously expressed hCaf1z shows both of those activities on reporter mRNAs in human HeLa cells and stimulates general mRNA decay when restricted to the cytoplasm by deletion of its nuclear localization signal. These observations suggest that the hCcr4d-hCaf1z complex may function either in the nucleus or in the cytoplasm after its nuclear export, to degrade polyadenylated RNAs, such as mRNAs, pre-mRNAs, or those RNAs that are polyadenylated prior to their degradation in the nucleus.


Histological assessment of regenerative endodontic treatment in animal studies with different scaffolds: A systematic review.
The concept of regenerative endodontic procedures remains controversial. The aim of this study was to evaluate the histology of the tissues formed in immature animal teeth with necrotic and infected pulps after attempted endodontic regeneration procedures using different scaffolds. A systematic electronic literature search was performed in PubMed, Web of Science, Scopus, EMBASE, DOSS, and Cochrane Library databases. The terms used were a combination of the following: "immature permanent necrotic tooth or teeth" or "open apex or apices" and "regeneration or revitalization or revascularization" and "histology." The inclusion criteria comprised animal studies with histological examination following regenerative endodontics in immature necrotic-infected permanent teeth. From 123 screened studies, 13 met the inclusion criteria. Formation of dentin-like tissue on the dentinal walls was reported in only 4% of teeth treated with blood clot scaffold and 2% treated with blood clot with additional materials. Cementum-like hard tissue was found in 64% of teeth with blood clot, 80% treated with blood clot with additional materials, 50% treated with alternative scaffolds, and 5% that were left empty. Bone-like tissue was reported in 10% of teeth treated with blood clot, 2% treated with blood clot with additional materials, and 4% treated with alternative scaffolds. The tissues in the canal space were found to be connective tissue with infiltration of fibroblast-like cells and blood vessels. Forty-six percent of the studies reported formation of periodontal ligament-like tissues. None of the regeneration protocols resulted in the predictable formation of a true pulp-dentin complex.


Reticulate hyperpigmentation of Iijima, Naito and Uyeno. A European case.
A 15-year-old girl is presented with symmetric, hyperpigmented streaks and whorls on trunk and extremities. The pigmentation is located in the basal layer of the epidermis. The clinical and histopathological picture seems to be identical to the reticulate hyperpigmentation of Iijima, Naito and Uyeno, hitherto only described from Japan.


[Clinical and therapeutic considerations in pseudomyxoma peritonei].
Pseudomyxoma peritonei (PMP) is an uncommon clinical entity, lacking a precisely defined etiopathogenesis. Its clinical features are not specific and diagnosis is difficult. We analysed 10 patients, all of them women, whom we had treated surgically in combination with intraperitoneal chemotherapy. Postoperative complications had been minimal and no death had occurred. 5 patients were followed up in time, 4 of them presenting a favourable evolution (2 required reintervention), and 1 patient decreased. We analysed up-to-date therapeutic approaches and the benefit of their combinations in order to identify the optimal therapeutic strategy. We consider that the combinations surgery + intraperitoneal chemotherapy or surgery + intracavitary radiotherapy are the most effective up to date.


Influence of progesterone, androstenedione and oestradiol-17 beta on the incorporation of [3H]proline in the human follicular wall.
The incorporation of proline, a precursor for collagen specific hydroxyproline, is regarded to reflect the metabolism of collagen. In vitro experiments were carried out to investigate the influence of sex steroids on the incorporation of [3H]proline into the human follicular wall. Tissue pieces from the apical wall of follicles at different stages of development were incubated in the presence of the steroids and [3H]proline, and the tissue bound radioactivity was determined. Progesterone induced a decrease of radiolabelling in both unripe and pre-ovulatory follicles. Androstenedione caused a similar effect but only in pre-ovulatory follicles. The influence of oestradiol-17 beta on the incorporation of [3H]proline was less pronounced with a tendency towards a decrease of radiolabelling in both types of follicles. It is suggested that the observed biochemical changes induced by sex steroids are of importance for connective tissue remodelling preceding human follicular rupture.


The active site His-460 of human acyl-coenzyme A:cholesterol acyltransferase 1 resides in a hitherto undisclosed transmembrane domain.
Human acyl-coenzyme A:cholesterol acyltransferase 1 (hACAT1) esterifies cholesterol at the endoplasmic reticulum (ER). We had previously reported that hACAT1 contains seven transmembrane domains (TMD) (Lin, S., Cheng, D., Liu, M. S., Chen, J., and Chang, T. Y. (1999) J. Biol. Chem. 274, 23276-23285) and nine cysteines. The Cys near the N-terminal is located at the cytoplasm; the two cysteines near the C-terminal form a disulfide bond and are located in the ER lumen. The other six free cysteines are located in buried region(s) of the enzyme (Guo, Z.-Y., Chang, C. C. Y., Lu, X., Chen, J., Li, B.-L., and Chang, T.-Y. (2005) Biochemistry 44, 6537-6548). In the current study, we show that the conserved His-460 is a key active site residue for hACAT1. We next performed Cys-scanning mutagenesis within the region of amino acids 354-493, expressed these mutants in Chinese hamster ovary cells lacking ACAT1, and prepared microsomes from transfected cells. The microsomes are either left intact or permeabilized with detergent. The accessibility of the engineered cysteines of microsomal hACAT1 to various maleimide derivatives, including mPEG(5000)-maleimide (large, hydrophilic, and membrane-impermeant), N-ethylmaleimide, 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonic acid (small, hydrophilic, and ER membrane-permeant), and N-phenylmaleimide (small, hydrophobic, and ER membrane-permeant), were monitored by Western blot analysis. The results led us to construct a revised, nine-TMD model, with the active site His-460 located within a hitherto undisclosed transmembrane domain, between Arg-443 and Tyr-462.


Colon cleansing: a popular, but misunderstood natural therapy.
Intestinal inflammation and leaky gut syndrome can be at the root of many health problems. Colon cleansing is a popular therapy among alternative practitioners, but many myths surround it. The scientifically inaccurate way many traditional healers try to explain therapeutic mechanisms is one of the obstacles that inhibits dialog between traditional healers and practitioners of modern medicine. The therapy actually has clinical value, but the explanations used to promote the therapies are the stuff of herbal legends, not scientific fact. The concept of cleansing is actually a metaphorical explanation for a therapy that improves detoxification via the liver and gastrointestinal tract and reduces inflammation or irritation to mucous membranes of the GI tract.


In vivo quantification of amygdala subnuclei using 4.7 T fast spin echo imaging.
The amygdala (AG) is an almond-shaped heterogeneous structure located in the medial temporal lobe. The majority of previous structural Magnetic Resonance Imaging (MRI) volumetric methods for AG measurement have so far only been able to examine this region as a whole. In order to understand the role of the AG in different neuropsychiatric disorders, it is necessary to understand the functional role of its subnuclei. The main goal of the present study was to develop a reliable volumetric method to delineate major AG subnuclei groups using ultra-high resolution high field MRI. 38 healthy volunteers (15 males and 23 females, 21-60 years of age) without any history of medical or neuropsychiatric disorders were recruited for this study. Structural MRI datasets were acquired at 4.7 T Varian Inova MRI system using a fast spin echo (FSE) sequence. The AG was manually segmented into its five major anatomical subdivisions: lateral (La), basal (B), accessory basal (AB) nuclei, and cortical (Co) and centromedial (CeM) groups. Inter-(intra-) rater reliability of our novel volumetric method was assessed using intra-class correlation coefficient (ICC) and Dice's Kappa. Our results suggest that reliable measurements of the AG subnuclei can be obtained by image analysts with experience in AG anatomy. We provided a step-by-step segmentation protocol and reported absolute and relative volumes for the AG subnuclei. Our results showed that the basolateral (BLA) complex occupies seventy-eight percent of the total AG volume, while CeM and Co groups occupy twenty-two percent of the total AG volume. Finally, we observed no hemispheric effects and no gender differences in the total AG volume and the volumes of its subnuclei. Future applications of this method will help to understand the selective vulnerability of the AG subnuclei in neurological and psychiatric disorders.


Mast cells and pulmonary fibrosis. Identification of a histamine releasing factor in bronchoalveolar lavage fluid.
As elevated bronchoalveolar lavage (BAL) fluid histamine levels are noted in patients with pulmonary fibrosis (PF), we assayed BAL fluid from 16 patients with PF for the presence of a histamine releasing factor (HRF). HRF activity was assayed by measuring release of the preformed mast cell-derived mediators, histamine, or beta-hexosaminidase (beta-hex) from a purified population of IL-3 dependent mouse bone marrow derived mast cells (MBMMC) or human blood basophils. Mean BAL cell free histamine levels in the patients with PF was 1226 +/- 1349 pg/ml, whereas BAL histamine levels in a comparison group of six non-PF patients was 118 +/- 60 pg/ml. HRF was significantly elevated in BAL fluid of patients with PF (mean beta-hex release 24.5 +/- 12.9%; range 6.8 to 52.4%) compared to the non-PF group of patients (mean beta-hex release 7.9 +/- 7.7%; range 1.8 to 20.7%). The PF HRF not only degranulated MBMMC, but also induced the generation of the arachidonic acid metabolite leukotriene C4 from MBMMC (24.6 +/- 4.2 ng leukotriene C4/10(6) MBMMC). The PF HRF did not appear to be a cytokine previously identified in BAL fluid of patients with PF (i.e., platelet derived growth factor or insulin growth factor-1) or a human cytokine able to degranulate human basophils (i.e., IL-1, or granulocyte-macrophage-CSF) as these recombinant human cytokines did not induce MBMMC beta-hex release. Physicochemical characterization of the HRF revealed that it was relatively heat stable, pronase sensitive and on Sephadex G-75 and G-200 column chromatography had an apparent molecular mass of 30 to 50 kDa. The ability of PF BAL to induce beta-hex release from MBMMC was not dependent on IgE as unsensitized or lactic acid treated MBMMC release similar amounts of beta-hex compared to MBMMC sensitized with IgE. Thus, BAL fluid of patients with PF contains an HRF that induces beta-hex release from MBMMC via an IgE-independent mechanism. The presence of the HRF could explain elevated BAL histamine levels in patients with PF.


Gene Delivery of Calreticulin Anti-Angiogenic Domain Attenuates the Development of Choroidal Neovascularization in Rats.
Choroidal neovascularization (CNV) is a common pathological feature in neovascular age-related macular degeneration, which is the leading cause of vision loss among elderly populations in developed countries. This study evaluated the effect of a novel endogenous inhibitor of angiogenesis, calreticulin anti-angiogenic domain (CAD), subconjunctivally delivered by an adenoviral vector (Ad-CAD) in a rat model of laser-induced CNV. CAD was expressed in Ad-CAD-infected cells and inhibited the angiogenic activity in human umbilical vein endothelial cells in vitro. CAD expression was also found in various ocular tissues after in vivo subconjunctival Ad-CAD injection. Via bioluminescence imaging it is shown that a single subconjunctival injection of Ad-luciferase induced the expression of the transgene in the injected eyes within 24 h, which lasted for at least 112 days. Forty-two days after subconjunctival injection of Ad-CAD, retinal structure and function were unaffected, as measured using optical coherence tomography and electroretinography, respectively. After laser injury, subconjunctival Ad-CAD gene delivery significantly inhibited CNV lesions as measured via choroid flat-mounts (51% reduction at 21 days; p < 0.001), as well as by fundus fluorescein angiography (19.3%, 28.2%, 31%, and 27.5% reductions at days 21, 28, 35, and 42, respectively; p < 0.05) in rats. The data suggest that subconjunctival Ad-CAD gene therapy could effectively inhibit laser-induced CNV and might be an attractive therapeutic approach for the management of choroidal neovascularization.


Biocompatibility and biostability of metallic endovascular implants: state of the art and perspectives.
More than a million metallic endovascular devices are implanted each year, but the quest for the perfect material continues. The importance of interfacial properties in the overall biocompatibility of metals and alloys has been recognized for a long time. In particular, these properties modulate the hemocompatibility of devices in contact with blood and, in turn, strongly influence implantation outcomes. In this article, the relative properties of metallic materials commonly used in endovascular applications are reviewed. Particular emphasis is given to the corrosion behavior of metallic endovascular materials and the specific surface treatments used in the production processes. Issues relative to corrosion assays will also be reviewed in terms of their relevance to in vivo applications. The potential adverse effects of degradation products with respect to endovascular applications will be described. Finally, this review addresses future perspectives of metallic devices in endovascular procedures in view of the recent promises of antiproliferative strategies that are likely to profoundly modify current procedures.


Pir-B inhibits the DC function and disturbs the Th17/Treg balance in lung cancer murine model.
Paired immunoglobulin-like receptor B (Pir-B) was an inhibitory receptor expressed on the surfaces of dendritic cells (DCs). Pir-B inhibit T helper (Th) 1 response and induce Th2 cell differentiation, leading to the imbalance of Th1/Th2 cells. However, the role and potential mechanism of Pir-B on the balance of Th17/regulatory T cells (Tregs) is still largely unknown in lung cancer murine model. In the present study, the DC function and Th17/Treg balance were destroyed during the progression of lung cancer and this was accompanied by an increased expression of Pir-B. After transfection with Pir-B siRNA or administration of IL-6 in vitro, the decreased response of Th17 cells were restored, whereas the augmented differentiation of Tregs was diminished. Further, the transfer of Pir-B silenced DCs or the injection of IL-6 in vivo increased Th17 response and decreased Treg differentiation. Our study has demonstrated that Pir-B inhibits the DC function and disturbs the Th17/Treg balance via IL-6 pathway during the progression of lung cancer, contributing to inhibited antitumor immunity.


Lifestyle and psychosocial factors in musicians.
Musicians face professional challenges that may lead them to adopt unhealthy lifestyles. They also may present performance-related anxiety. We investigated anxiety and lifestyle patterns in musicians, both professional and trainees. A prospective controlled protocol was developed. Musicians (employed or students) and matched controls (also employed and students) were surveyed with several questionnaires on lifestyle and some psychological factors: anxiety and music performance anxiety. General anxiety and music performance anxiety are higher in music students compared with trained musicians. Musicians have also higher anxiety scores than their matched controls. Soloists have higher scores of anxiety, also percussion and keyboard students. Musicians smoke less than controls, but sleep also less, a factor perceived as an index for stress. BMI was also higher in musicians. Performing music is associated with anxiety levels that are higher than in control population. Trainees have higher scores than the employed musicians.


Oxidative damage and nitric oxide synthase induction by surgical uteroplacental circulation restriction in the rabbit fetal heart.
This study investigated the role of oxidative damage and nitric oxide (NO) synthases in the fetal heart using a model of intrauterine growth restriction induced by uteroplacental circulation restriction (UCR). New Zealand white rabbits kept under 12-h light cycles, with food and water provided ad libitum, were subjected at day 25 of pregnancy to 40-50% uteroplacental artery ligation. We analyzed the gene expression of enzymes linked to nitric oxide synthesis (iNOS, eNOS, HO-1, and ARG-2), hypoxia inducible factor 1 alpha (HIF-1α), and the state of oxidative stress (protein carbonyl levels) in fetal heart homogenates. Additionally, we studied the histological morphology of the fetal heart. We found that fetal growth restriction was associated with a significant reduction in heart weight but a normal heart/body weight ratio in UCR animals. Hematoxylin and eosin staining showed normal left and right ventricular thickness but increased vessel dilatation with hyperemia in the hearts of the UCR group. We observed HIF-1α, eNOS, p-eNOS, and iNOS induction concomitant with intensified protein carbonyl levels but observed no changes in HO-1 or ARG-2 expression, suggesting increased NO and oxidative stress in the hearts of UCR animals. Uteroplacental circulation restriction increased NO-linked enzymes, oxidative damage, and dilated coronary vessels in fetal hearts. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.


Brain fingerprinting field studies comparing P300-MERMER and P300 brainwave responses in the detection of concealed information.
Brain fingerprinting detects concealed information stored in the brain by measuring brainwave responses. We compared P300 and P300-MERMER event-related brain potentials for error rate/accuracy and statistical confidence in four field/real-life studies. 76 tests detected presence or absence of information regarding (1) real-life events including felony crimes; (2) real crimes with substantial consequences (either a judicial outcome, i.e., evidence admitted in court, or a $100,000 reward for beating the test); (3) knowledge unique to FBI agents; and (4) knowledge unique to explosives (EOD/IED) experts. With both P300 and P300-MERMER, error rate was 0 %: determinations were 100 % accurate, no false negatives or false positives; also no indeterminates. Countermeasures had no effect. Median statistical confidence for determinations was 99.9 % with P300-MERMER and 99.6 % with P300. Brain fingerprinting methods and scientific standards for laboratory and field applications are discussed. Major differences in methods that produce different results are identified. Markedly different methods in other studies have produced over 10 times higher error rates and markedly lower statistical confidences than those of these, our previous studies, and independent replications. Data support the hypothesis that accuracy, reliability, and validity depend on following the brain fingerprinting scientific standards outlined herein.


Intramolecular valence and spin interaction in meso and rac diastereomers of a p-quinonoid-bridged diruthenium complex.
The complexes meso- and rac-[(acac)2Ru(mu-L)Ru(acac)2]n, 1 and 2, where L(2-) = 1,4-dioxido-2,3-bis(3,5-dimethylpyrazol-1'-yl)benzene and acac- = 2,4-pentanedionato, were characterized structurally, magnetically, electrochemically, and spectroscopically as well as spectroelectrochemically (UV-vis-NIR, EPR) in the accessible redox states (n = 0, +, -, 2-). Due to steric interference, the neutral compounds contain a severely twisted L(2-) bridging ligand with 43-48 degree dihedral angles between the planes of the hydroquinone dianion and those of the ortho positioned pyrazolyl substituents. The difference between meso and rac isomers is rather pronounced in terms of the redox potentials (easier oxidation and reduction of the rac form 2) and with respect to the absorption spectra of the oxidized states. Susceptibility and EPR measurements confirm the {Ru(III)(mu-L(2-))Ru(III)} configuration of the neutral species, showing J values of -37 and -21 cm(-1) for the spin-spin interaction between the ca. 7.75 A separated metal centers in 1 and 2, respectively. Two-step reduction involves the metals and produces Ru(III)Ru(II) mixed-valent monoanions with comproportionation constants of ca. 10(4), with Ru(III)-type EPR signals, and with broad intervalence charge transfer bands at about 1200-1500 nm absorption maximum, suggesting localized valence (class II). Oxidation produces intense near-infrared absorption at 892 (1+) or 1027 nm (2+) and narrow isotropic EPR spectra at g approximately 2.005, signifying unprecedented spin localization at the p-semiquinone bridge. These results are not compatible with an (L(2-))-bridged {Ru(IV)Ru(III)} situation nor with an {Ru(III)(mu-L(*-))Ru(III)} three-spin arrangement with up-down-up spin configuration in the ground state, which would result in metal-centered spin through antiferromagnetic coupling between the adjacent individual spins. Only the {Ru(III)(mu-L(*-))Ru(III)} situation, with up-up-down spin configuration, leads to ligand-centered resulting spin through the strong antiferromagnetic coupling between the remote metal spins, an unusual situation which is favored here because of weakened metal-radical coupling resulting from the pyrazolyl/p-semiquinone twist.


Aspirin and tension-type headache.
Acetylsalicylic acid (ASA, Aspirin) is among the most used drugs worldwide. At present, Aspirin represents a quite versatile drug employed in the control of pain symptomatologies and in situations such as prevention of both ischaemic stroke and cardiovascular events. Aspirin causes inhibition of prostaglandin (PG) synthesis by inactivation of the cyclooxygenase (COX) enzyme. ASA constitutes the focus of new researches explaining more widely Aspirin's control of inflammation. The induction of the endogenous epimers lipoxins (Aspirin-triggered 15-epi-lipoxins, ATLs) represents one of the most recent achievements. This particular feature of Aspirin is not shared by other NSAIDs. ASA is well known as a headache medication, figuring as a possible treatment choice in tension-type headache but also in acute migraine attacks. Furthermore, a new Aspirin formulation with a greater rapidity of action has been introduced. In conclusion, little information exists on the subject and more studies are required.


Amplification of pulsatile glucagon counterregulation by switch-off of alpha-cell-suppressing signals in streptozotocin-treated rats.
Glucagon counterregulation (GCR) is a key protection against hypoglycemia that is compromised in diabetes via an unknown mechanism. To test the hypothesis that alpha-cell-inhibiting signals that are switched off during hypoglycemia amplify GCR, we studied streptozotocin (STZ)-treated male Wistar rats and estimated the effect on GCR of intrapancreatic infusion and termination during hypoglycemia of saline, insulin, and somatostatin. Times 10 min before and 45 min after the switch-off were analyzed. Insulin and somatostatin, but not saline, switch-off significantly increased the glucagon levels (P = 0.03), and the fold increases relative to baseline were significantly higher (P < 0.05) in the insulin and somatostatin groups vs. the saline group. The peak concentrations were also higher in the insulin (368 pg/ml) and somatostatin (228 pg/ml) groups vs. the saline (114 pg/ml) group (P < 0.05). GCR was pulsatile in most animals, indicating a feedback regulation. After the switch-off, the number of secretory events and the total pulsatile production were lower in the saline group vs. the insulin and somatostatin groups (P < 0.05), indicating enhancement of glucagon pulsatile activity by insulin and somatostatin compared with saline. Network modeling analysis demonstrates that reciprocal interactions between alpha- and delta-cells can explain the amplification by interpreting the GCR as a rebound response to the switch-off. The model justifies experimental designs to further study the intrapancreatic network in relation to the switch-off phenomenon. The results of this proof-of-concept interdisciplinary study support the hypothesis that GCR develops as a rebound pulsatile response of the intrapancreatic endocrine feedback network to switch-off of alpha-cell-inhibiting islet signals.


Optomechanics of Single Aluminum Nanodisks.
Aluminum nanostructures support tunable surface plasmon resonances and have become an alternative to gold nanoparticles. Whereas gold is the most-studied plasmonic material, aluminum has the advantage of high earth abundance and hence low cost. In addition to understanding the size and shape tunability of the plasmon resonance, the fundamental relaxation processes in aluminum nanostructures after photoexcitation must be understood to take full advantage of applications such as photocatalysis and photodetection. In this work, we investigate the relaxation following ultrafast pulsed excitation and the launching of acoustic vibrations in individual aluminum nanodisks, using single-particle transient extinction spectroscopy. We find that the transient extinction signal can be assigned to a thermal relaxation of the photoexcited electrons and phonons. The ultrafast heating-induced launching of in-plane acoustic vibrations reveals moderate binding to the glass substrate and is affected by the native aluminum oxide layer. Finally, we compare the behavior of aluminum nanodisks to that of similarly prepared and sized gold nanodisks.


Water-Dispersible Porous Aromatic Frameworks with Quasi-Amino Acid Structures via N-H Insertion Reactions.
As a class of materials with large specific surface area and chemical stability, porous aromatic frameworks (PAFs) have attracted much attention in the fields of gas adsorption, separation, and catalysis. However, synthetic methods for PAFs have been limited to a few coupling reactions, and PAF powders were usually obtained with a diameter of micrometer size. Here, we demonstrate an efficient N-H insertion reaction of diazoesters in the synthesis of PAFs with a diameter <200 nm. The established polymerization can be performed at room temperature, and four PAFs with different skeletons and composition can be obtained in high yields. The prepared PAFs have appreciable thermal and chemical stabilities. Because of the presence of ester groups in the backbone, the prepared PAFs with α-phenylglycine fragments can be easily obtained through the successive hydrolysis of the ester groups. The synthesized PAFs bearing phenylglycine moieties exhibit good water dispersibility and low cytotoxicity. We further show the potential of these PAFs in drug loading and photodynamic therapy.


A retrospective data analysis of antimicrobial dressing usage in 3,084 patients.
Knowledge about practice patterns and optimal usage criteria for topical antimicrobial dressings is limited. A retrospective data analysis was conducted to evaluate: 1) the length of time these dressings are applied in a typical episode of wound care, 2) the number of episodes of antimicrobial dressing use, and 3) whether antimicrobial dressings are applied in consideration of signs and symptoms of infection. Wound care registry data from a level-4 electronic medical record were analyzed, providing information on 3,084 patients older than 17 years seen from July 2003 through December 2008 in 26 hospital-based, outpatient wound centers in 14 states. The 5,541 recorded wounds ranged in size from 0.3 to 225 cm2. One antimicrobial dressing use episode was recorded for 71% of wounds (4.7% had four or more). Mean treatment episode length was 32.5 days (median 21 days). Clinicians used these dressings for a longer period of time if patients had multiple comorbidities (P = .0001), a refractory wound (P <.00001), or were prescribed oral antibiotics (P <.0002); first dressing use was more common in wounds with signs and symptoms of infection (P <.00001). During an average of 16 (median 10) visits and a follow-up time of 269 days, 61.4% of wounds healed (range 42.2% for flaps or grafts to 67.9% for surgical wounds of all 5,541 wounds). Antimicrobial dressing use for 2 to 4 weeks was associated with a higher proportion of healed wounds, but in wounds that healed, longer dressing use was associated with a longer healing time. The practice pattern observed suggests that antimicrobial dressing usage generally is based on patient and wound assessment variables but prospective studies are needed to develop optimal guidelines of care.


Porous nanotube network: a novel 3-D nanostructured material with enhanced hydrogen storage capacity.
A multiscale theoretical approach (ab initio and Grand Canonical Monte Carlo calculations) was used to investigate hydrogen storage in a novel three-dimensional carbon nanostructure. Our results show that a large-pore PNN can overpass the gravimetric capacity of 20% at 77 K while a Li-doped PNN can reach the value of 8% at room temperature.


[Selective peripheral neurotomy of the hamstring branches of the sciatic nerve in the treatment of spastic flexion of the knee. Apropos of a series of 11 patients].
A series of 11 patients (9 adults and 2 children) were operated on by selective peripheral neurotomy for spastic knee in flexion. The objective of surgery was to restore bipodal stance and therefore walking for the adult patients and to improve walking for the diplegic children. Spasticity was secondary to stroke or cranial trauma for the adult patients. The two children presented with Little disease. The delay between onset and surgery was on the average of 2 years. All the patients had a passive flexum of the knee of 20 degrees, and an excessive spasticity of the hamstrings (average Held score of 4.55). Peripheral selective neurotomies consist of a partial section of the spastic muscle's motor fascicles. The partial section concerns the afferent fibers to the spinal cord whose interruption leads to the disappearance of spasticity. The section also involves the motoneurones' axons and thus leads to partial denervation. The spasticity of the treated muscles disappeared in the 11 patients. Average follow-up was 16 months. The neurotomies led to improvement of walking without splint for 3 walking patients, and restored walking with a splint for 5 patients. One patient failed to walk. The two children had a dramatic improvement of their walk. Our results incite us to increasingly indicate this type of neurotomy in the treatment of the spastic lower limb.


[The care of patients with cerebral circulatory disorders in the catchment area of one of Warsaw's neurological hospital departments. II. Indications for active ambulatory care of patients discharged from the hospital].
In a continuation of the analysis of patients hospitalized for cerebrovascular disease their status upon discharge from the hospital was estimated. It was thought that at least 18% of the admitted patients and about 31% of the discharged patients aged below 80 years were suitable for outpatient rehabilitation treatment after discharge because of motor or speech disturbances, and about 9% of the discharged patients required speech reeducation due to aphasia. Among patients after cerebrovascular episodes qualified after discharge for ambulatory active care because of persistent motor deficit or speech disturbances those with past ischaemic stroke prevailed, they were aged mostly 70-79 years. It may be estimated that at least 7% of patients discharged home after stroke (and about 4% of all admitted cases) require special care and nursing because of coexistence of other serious diseases or previously suffered disability. They are potential candidates for care in welfare homes, and when they remain in their homes they depend on the help and care, in different grades, on the assistance of a nurse or at least an unqualified welfare worker.


Loci of TCF7L2, HHEX and IDE on chromosome 10q and the susceptibility of their genetic polymorphisms to type 2 diabetes.
TCF7L2, HHEX and IDE on chromosome 10q23-25 reside within the linkage region for type 2 diabetes (T2D). Previous studies including ours have demonstrated that genetic polymorphisms in these three loci are associated with T2D, respectively. But, it is unclear whether TCF7L2, independently or interactively with HHEX and IDE, confer the susceptibility to T2D. In the present study, we first replicated genetic association study of the TCF7L2 gene in a Swedish cohort including 528 non-diabetic healthy controls and 243 T2D patients and then evaluated combining effect from common risk polymorphisms in TCF7L2-HHEX-IDE loci. T2D patients were diagnosed in the intermediate study time. To avoid influence from anti-diabetic treatment, baseline data in all T2D patients were used for analysis. We found that SNPs rs7901695, rs4506565, rs7903146 and rs12255372 in the TCF7L2 gene were strongly associated with T2D (p<0.004). In rs7903146, T2D patients carrying genotypes CT or TT had higher fasting plasma glucose (FPG) levels (p=0.042) and lower HOMA-beta index (p=0.015) and BMI (p=0.015) compared to the patients carrying CC genotype. Furthermore, the risk alleles from TCF7L2 rs7903146 polymorphism either with IDE rs2251101 polymorphism (p=0.0257, OR=1.398) or with HHEX rs1544210 polymorphism (p=0.0024, OR=1.514) were significantly associated with T2D. When risk alleles from three loci were combined, the association with T2D remained significant (p=0.0018, OR=1.506). The present study thus provides evidence that TCF7L2, as the main gene, together with HHEX and IDE loci have combining effects on genetic predisposition to T2D.


MOROKOSHI: transcriptome database in Sorghum bicolor.
In transcriptome analysis, accurate annotation of each transcriptional unit and its expression profile is essential. A full-length cDNA (FL-cDNA) collection facilitates the refinement of transcriptional annotation, and accurate transcription start sites help to unravel transcriptional regulation. We constructed a normalized FL-cDNA library from eight growth stages of aerial tissues in Sorghum bicolor and isolated 37,607 clones. These clones were Sanger sequenced from the 5' and/or 3' ends and in total 38,981 high-quality expressed sequence tags (ESTs) were obtained. About one-third of the transcripts of known genes were captured as FL-cDNA clone resources. In addition to these, we also annotated 272 novel genes, 323 antisense transcripts and 1,672 candidate isoforms. These clones are available from the RIKEN Bioresource Center. After obtaining accurate annotation of transcriptional units, we performed expression profile analysis. We carried out spikelet-, seed- and stem-specific RNA sequencing (RNA-Seq) analysis and confirmed the expression of 70.6% of the newly identified genes. We also downloaded 23 sorghum RNA-Seq samples that are publicly available and these are shown on a genome browser together with our original FL-cDNA and RNA-Seq data. Using our original and publicly available data, we made an expression profile of each gene and identified the top 20 genes with the most similar expression. In addition, we visualized their relationships in gene co-expression networks. Users can access and compare various transcriptome data from S, bicolor at http://sorghum.riken.jp.


Multi-input CRISPR/Cas genetic circuits that interface host regulatory networks.
Genetic circuits require many regulatory parts in order to implement signal processing or execute algorithms in cells. A potentially scalable approach is to use dCas9, which employs small guide RNAs (sgRNAs) to repress genetic loci via the programmability of RNA:DNA base pairing. To this end, we use dCas9 and designed sgRNAs to build transcriptional logic gates and connect them to perform computation in living cells. We constructed a set of NOT gates by designing five synthetic Escherichia coli σ70 promoters that are repressed by corresponding sgRNAs, and these interactions do not exhibit crosstalk between each other. These sgRNAs exhibit high on-target repression (56- to 440-fold) and negligible off-target interactions (< 1.3-fold). These gates were connected to build larger circuits, including the Boolean-complete NOR gate and a 3-gate circuit consisting of four layered sgRNAs. The synthetic circuits were connected to the native E. coli regulatory network by designing output sgRNAs to target an E. coli transcription factor (malT). This converts the output of a synthetic circuit to a switch in cellular phenotype (sugar utilization, chemotaxis, phage resistance).


Extended Stent Coverage Decreases Distal Aortic Segmental Enlargement After the Endovascular Repair of Acute Complicated Type B Aortic Dissection: A Multi-Center Retrospective Study of 814 Patients.
This study aimed to investigate the effect of distal aortic segmental enlargement (DASE) after thoracic endovascular aortic repair for complicated type B aortic dissection (cTBAD). From March 2003 to October 2018, 814 patients with acute cTBAD from 5 medical centers were retrospectively identified. DASE is indicated as the enlargement of distal aortic segmental volume ≥1.6 fold of the preoperative volume compared with the most recent postoperative computed tomography angiography (CTA) scan. Of these patients, 635 (78%) were identified as non-DASE, and 179 (22%) were identified as DASE. Competing risk analysis was performed to compare late death and distal aortic reintervention between the groups. The morphological variables and false lumen thrombosis at 7 aortic levels were measured based on the preoperative CTA and the most recent CTA. Univariate and multivariate Cox regression analyses were used to assess the independent predictors of DASE. The mean follow-up time of the entire cohort was 5.6 years (interquartile range: 2.4-8.3 years). There were total of 208 late deaths, including 94 (14.8%) deaths in non-DASE group versus 114 (63.7%) deaths in the DASE group. Distal aortic reintervention was observed in 89 patients, with 43(6.7%) in the non-DASE group versus 46 (25.7%) in the DASE group. The cumulative incidence of late death and distal aortic reintervention were significantly higher in the DASE than in the non-DASE group (p<0.001). In morphological analysis, significant incomplete false lumen thrombosis was observed in all distal aortic segments above the aortic level of celiac artery (p<0.01). According to multivariate analysis, the Marfan syndrome, stent coverage to the level of diaphragm and the level of celiac artery were independent predictors of the DASE (p<0.001). Patients with extended stent coverage to the level of celiac artery have shown a lower incidence of DASE (p<0.010). Compared with the non-DASE group, patients with DASE demonstrated a higher rate of late death and distal aortic reintervention. For the cTBAD population, extended stent-graft coverage to the aortic section between diaphragm and celiac artery might serve as a "cost-efficient" cutoff point aiming to reduce the risk of DASE.


Factors Associated with the e-Health Literacy Among Older Adults with Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.
Background: The telemanagement model in chronic diseases needs older patients to have a certain level of e-Health literacy. According to Electronic Health Literacy model, factors associated with the e-Health literacy among older patients could be comprehensively investigated from individual, situational, and environmental aspects. Objectives: To investigate the e-Health literacy levels among older patients with chronic obstructive pulmonary disease (COPD) and explore associated factors. Methods: A cross-sectional study was conducted among older patients with COPD. The e-Health Literacy Scale was used to measure individuals' e-Health literacy. The multiple linear regression was applied to identify factors associated with e-Health literacy. Results: A total of 230 responses were included in the final analysis. The average score of e-Health literacy for older COPD patients was 24.66 (6.86). After adjusting the model, the results of multiple linear regression demonstrated that aging attitudes (B = 0.067, p < 0.001), technophobia (B = -0.285, p < 0.001), and self-efficacy (B = 0.431, p < 0.001) accounted for 68.3% (p < 0.001) of the total variation in e-Health literacy. Conclusion: This study identifies significant correlations of technophobia, aging attitudes, and self-efficacy, respectively, with e-Health literacy, and self-efficacy and technophobia may be constant predictive factors of e-Health literacy. In the future, intervention research on e-Health literacy should be conducted from a social psychology perspective, with particular emphasis on addressing negative aging attitudes and technophobia. That will promote the tele-management model of chronic diseases. Trial Registration: Chinese Clinical Trial Registry (ChiCTR): ChiCTR1900028563; http://apps.who.int/trialsearch/default.aspx.


Thrombomodulin activity is found in tissue thromboplastin preparations from placenta and from lung but not from brain.
Substantial thrombomodulin activity could be detected in tissue thromboplastin preparations from placenta or from lung but not from brain. When the amount of these preparations was adjusted to contain 1 unit of tissue factor activity, up to 0.85 units of thrombomodulin activity could be measured, corresponding to the generation of 17 pmol/ml/min of activated protein C when 1.5 microM human protein C was activated by 20 nM human alpha-thrombin in the presence of 5 mM CaCl2. After treatment by phospholipase C, thrombomodulin activity was reduced in these samples. Addition of mixed brain procoagulant phospholipids partially restored thrombomodulin activity in the phospholipase C-treated samples. These results emphasize the role of phospholipids in the expression of optimal thrombomodulin activity in tissue thromboplastin preparations from placenta or from lung.


Clinical course and treatment of vertebrobasilar dolichoectasia: a systematic review of the literature.
Vertebrobasilar dolichoectasia is a rare condition with unsettled clinical course and treatment. We performed a systematic review of the literature on clinical course and treatment of vertebrobasilar dolichoectasia. We systematically searched PUBMED, EMBASE, and the Cochrane Library and hand searched citations for studies on vertebrobasilar dolichoectasia with an average follow-up duration of at least 1 year and fulfilling predefined inclusion criteria. We pooled data to calculate proportions with corresponding 95% confidence intervals (CIs) for 5 year incidences of: (1) transient ischemic attack; (2) ischemic stroke; (3) subarachnoid hemorrhage; (4) other intracranial hemorrhage; (5) (progressive) brainstem compression; (6) clinical deterioration from (progressive) hydrocephalus; and (7) case fatality. We used the Cochrane collaboration five-item tool to assess risk of bias in treatment studies. From 958 citations identified, we included 12 manuscripts describing nine cohorts with 375 patients. Follow-up ranged 1·5-11·7 years. Estimated 5 year complication risks were for ischemic stroke 17·6% (95%CI: 12·4-22·8), brainstem compression 10·3% (95%CI: 6·4-14·1), transient ischemic attack 10·1% (95%CI: 6·3-14·0), hemorrhagic stroke 4·7% (95%CI: 2·4-8·3), hydrocephalus 3·3% (95%CI: 1·4-6·4), and subarachnoid hemorrhage 2·6% (95%CI: 1·1-5·1). The estimated five year case fatality was 36·2% (95%CI: 30·6-41·8). The 5 year prognosis is more favorable in patients who are asymptomatic at time of diagnosis. No randomized intervention trials were identified. In the included studies, treatment specifications were often not available for individual patients. None of the studies fulfilled any of the criteria to reduce risk of bias. Patients with vertebrobasilar dolichoectasia are at high risk of ischemic stroke, brainstem compression, and death. Hemorrhagic complications are less common. Risk of bias in the included studies was too high to make any recommendation regarding treatment.


Prevalence of gallbladder disease in American Indian populations: findings from the Strong Heart Study.
American Indians are believed to be at high risk of gallbladder disease (GBD), but there has been no systematic evaluation of its prevalence among diverse groups of American Indians. Therefore, we determined the prevalence of GBD and associated risk factors among specified American Indian populations using ultrasonography of the gallbladder and standardized diagnostic criteria. Enrolled members, aged 47 years and older, of 13 American Indian tribes or communities in Arizona, Oklahoma, and South and North Dakota who participated in the Strong Heart Study were analyzed. GBD was the sum of gallstones (determined by ultrasound examination) and cholecystectomy (determined by ultrasound and self-report). The proportion of American Indian heritage was based on the heritage of the grandparents of participants. GBD prevalence was determined among 3,296 participants at the 3 sites. Among women, 17.8% had gallstones, and 46.3% had evidence of a cholecystectomy, for a total of 64.1% with GBD. Among men, 17.4% had gallstones, and 12.1% had evidence of a cholecystectomy, for a total of 29.5% with GBD. When figures were adjusted for age and Indian heritage, there was no significant difference in GBD prevalence across the 3 geographical areas. In multivariate logistic regression analysis, age, American Indian heritage, and waist circumference were associated with GBD among men, and age, American Indian heritage, diabetes, and parity were associated with GBD among women. Body mass index was not independently associated with GBD in either sex. In conclusion, GBD was found in epidemic proportions in diverse American Indian populations.


Comparison of early embryonic and differentiating cell surfaces. Interaction of lectins with plasma membrane components.
1. Cells of the unincubated as well as those of primitive streak chick blastoderm, which are preparing for or are involved in morphogenetic movements, are agglutinated by wheat germ agglutinin, Ricinus communis agglutinin and concanavalin A, but not by fucose-binding protein. 2. Agglutination of these cells with soybean agglutinin occurs only after neuraminidase treatment, while that induced by concanavalin A, wheat germ and Ricinus communis agglutinins is not affected. 3. Trypsin treatment of blastoderm cells had no effect on lectin-mediated agglutination. 4. In contrast, cells derived from 10-and 12-day differentiating chick liver were agglutinated by wheat germ agglutinin only after trypsinization. 5. Mechanically dissociated embryonic liver cells, which are not agglutinated, bind more 3H-labelled wheat germ agglutinin per cell than trypsinized cells, suggesting that during differentiation there may be a spatial reorganization of wheat germ agglutinin receptors within the plasma membrane. 6. Membranes isolated from the above cell types were examined by analytical polyacrylamide gel isoelectric focusing and, in combination with affinity chromatography using wheat germ agglutinin conjugated to agarose, membrane material in the differentiating liver membrane, which binds to this lectin, was identified.


Immunogenicity and safety of an AS03-adjuvanted H7N1 vaccine in adults 65years of age and older: A phase II, observer-blind, randomized, controlled trial.
H7 influenza strains can cause severe and often fatal human infections, especially in the elderly. This phase II, observer-blind, randomized trial (www.ClinicalTrials.gov: NCT01949090) assessed the immunogenicity and safety of a novel AS03-adjuvanted H7N1 vaccine that may serve as a model H7-subtype vaccine. 360 adults ≥65years of age in stable health received either 1 of 4 adjuvanted A/mallard/Netherlands/12/2000 split virion vaccine formulations (3.75μg or 7.5μg hemagglutinin adjuvanted with either AS03A or AS03B) or saline placebo, given as a 2-dose series. Immunogenicity was assessed using hemagglutination-inhibition (HI) and microneutralization (MN) assays for the per-protocol cohort, comprising 332 participants at 21days post-each dose, 332 at month 6, and 309 at month 12 (HI assay only). Safety was assessed up to month 12 for all participants who had received ≥1 dose (360 participants). For H7N1 HI antibody assessment at day 42 (21days post-dose 2), seroprotection rates (SPR) in the vaccinated groups were 69.6%-88.7%, seroconversion rates (SCR) 69.6%-88.5%, mean geometric increase (MGI) 11.0-18.9, and HI geometric mean titers (GMTs) 55.0-104.8. These parameters declined by month 6 and month 12. Microneutralization GMTs were 46.2-74.7 in the vaccinated groups at day 42, while vaccine response rate (VRR; proportion with ≥4-fold increase in MN titer) was 46.4%-81.5%. For the cross-reactive H7N9 strain, at day 42, HI GMT were 64.3-201.3, SPR 78.6%-96.3%, SCR 79.3%-96.3%, and MGI 14.1-37.7; MN GMTs were 44.0-85.6, and VRR 46.4-85.2%. The most frequent solicited symptom was injection site pain (41.7%-65.0% of vaccine recipients). In total, 40 participants reported 67 serious adverse events; none were considered causally related to vaccination. In adults aged ≥65years, the adjuvanted H7N1 vaccine was immunogenic after 2 doses, and had an acceptable safety profile. www.ClinicalTrials.gov: NCT01949090.