ST segment response to acute coronary occlusion: coronary hemodynamic and angiographic determinants of direction of ST segment shift.
To assess the relationship between the direction of ST segment response to transient coronary occlusion and collateral function, we studied 25 patients with diagnostic ST segment changes during transient occlusion of the proximal left anterior descending artery (LAD). Electrocardiographic leads I, II, V2, and V5; left ventricular filling, aortic, and distal coronary pressures; and great cardiac vein flow were measured during percutaneous transluminal coronary angioplasty (PTCA) of the LAD. During a 1 min LAD balloon occlusion, 16 patients had reversible ST elevation (group I) and nine patients had ST depression (group II). The ST responses in individual patients were consistent during repeated occlusions, and ST depression never preceded ST elevation. Angiography before PTCA showed less severe LAD stenosis in group I (69 +/- 15%) than in group II (88 +/- 10%; p less than .01) and collateral filling of the LAD in no group I patient but in six of nine patients in group II (p less than .01). During LAD occlusion, determinants of myocardial oxygen demand (left ventricular filling pressure, aortic pressure, heart rate, and double product) were similar in both groups. Group I patients, however, had lower distal coronary pressure (25 +/- 8 vs 41 +/- 16 mm Hg) and residual great cardiac vein flow (33 +/- 14 vs 51 +/- 22 ml/min) and higher coronary collateral resistance (3.1 +/- 2.1 vs 1.5 +/- 0.8 mm Hg/ml/min) than group II patients (all p less than .05). In patients with ST elevation during LAD occlusion, stenosis before PTCA was less severe, visible collaterals were not present, and hemodynamic variables during LAD occlusion reflected poorer collateral function.(ABSTRACT TRUNCATED AT 250 WORDS)


Stoichiometry of site-specific lysine acetylation in an entire proteome.
Acetylation of lysine ϵ-amino groups influences many cellular processes and has been mapped to thousands of sites across many organisms. Stoichiometric information of acetylation is essential to accurately interpret biological significance. Here, we developed and employed a novel method for directly quantifying stoichiometry of site-specific acetylation in the entire proteome of Escherichia coli. By coupling isotopic labeling and a novel pairing algorithm, our approach performs an in silico enrichment of acetyl peptides, circumventing the need for immunoenrichment. We investigated the function of the sole NAD(+)-dependent protein deacetylase, CobB, on both site-specific and global acetylation. We quantified 2206 peptides from 899 proteins and observed a wide distribution of acetyl stoichiometry, ranging from less than 1% up to 98%. Bioinformatic analysis revealed that metabolic enzymes, which either utilize or generate acetyl-CoA, and proteins involved in transcriptional and translational processes displayed the highest degree of acetylation. Loss of CobB led to increased global acetylation at low stoichiometry sites and induced site-specific changes at high stoichiometry sites, and biochemical analysis revealed altered acetyl-CoA metabolism. Thus, this study demonstrates that sirtuin deacetylase deficiency leads to both site-specific and global changes in protein acetylation stoichiometry, affecting central metabolism.


The rs878081 polymorphism of AIRE gene increases the risk of rheumatoid arthritis in a Chinese Han population: a case-control study.
The autoimmune regulator (AIRE), a transcriptional regulator expressed in medullary thymic epithelial cells, plays an important role in thymocyte education and negative selection. Several citations studying the association between the rs878081 exon polymorphism of the AIRE gene and the risk of rheumatoid arthritis (RA) in different populations have yielded conflicting findings. Thus, this case-control study involving 300 RA cases and 300 controls was aimed to identify whether such association existed in a Chinese Han population from East China. The rs878081 polymorphism of the AIRE gene was genotyped. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, and stratification analysis. Genetic model analysis showed significant correlations between the TT genotype and the risk of RA (OR: 1.89, 95%CI: 1.03-3.47 in TT vs CC; OR: 1.84, 95%CI: 1.02-3.31 in TT vs CC+TC). Stratification analyses of sex, age, smoking, and alcoholism suggested that the rs878081 polymorphism of the AIRE gene increased RA risk among non-smokers. In conclusion, rs878081 polymorphism of AIRE gene increases the risk of RA in a Chinese Han population.


[The analysis of urinary steroids using capillary gas-liquid chromatography].
Impaired steroid hormone secretion and metabolism may become the cause of symptomatic hypertension. Currently gas chromatography technique is employed for analysis of urinary steroids, that permits detection of the majority of components. To detect the important components present in but trace amounts gas chromatographic mass spectrometry is necessary. Gas chromatographic technique holds good promise for clinical studies, its potentialities are not inferior to those of radioimmunoassay.


Human ehrlichioses: newly recognized infections transmitted by ticks.
Human ehrlichioses are tick-borne infections caused by bacteria in the genus Ehrlichia. Human monocytic ehrlichiosis is caused by Ehrlichia chaffeensis and human granulocytic ehrlichiosis is caused by an agent similar to Ehrlichia equi. E. chaffeensis infects mononuclear phagocytes and is transmitted by Lone Star ticks (Amblyomma americanum) found in the south central and eastern United States. The agent of human granulocytic ehrlichiosis infects mostly neutrophils, it transmitted by Ixodes species ticks, and occurs mostly in the upper midwest and northeast United States. Despite the undifferentiated presentation of both ehrlichioses with fever, headache, myalgias, leukopenia, thrombocytopenia, and elevated liver enzyme activities, the diagnostic methods are distinct. Occasional severe complications include meningoencephalitis, adult respiratory distress syndrome, shock, and opportunistic infections. Immunocompromised patients are at high risk for death. An adverse outcome is associated with delayed diagnosis and therapy; thus, empirical treatment is advocated. Treatment with doxycycline usually results in prompt defervescence and cure.


Cognitive status and physical function in older african americans.
To investigate the relationship between global cognition, three specific domains of cognition, and lower extremity function in community-dwelling elderly African Americans (AAs) from two community settings. Cross-sectional study. Community. Ninety-six AA men and women aged 60 and older from two community settings, enrolled in the Boosting Minority Involvement (BMI) study, a community-based cohort study designed to increase research participation of older low-income AAs. Physical performance was assessed using Short Physical Performance Battery score, which is composed of three timed tests: a 4-m walking task, static balance assessment, and a chair stand test. The Bushke Memory Impairment Screen (MIS) and Mini-Mental State Examination were used to assess global memory and global cognition, respectively. For domain-specific performance, three z-score composite scores (attention, verbal memory, and executive function) were developed using the Computer-based Assessment of Mild Cognitive Impairment. All domains of cognition were significant predictors of lower extremity function except for verbal memory. Executive function and MIS were the best predictors of lower extremity function in adjusted models. Participants with poor executive function were more than four times as likely to have poorer lower extremity function (odds ratio=4.96, 95% confidence interval=1.07-23.0). Global memory and executive function were the best predictors of lower extremity function in a sample of community-dwelling AA adults. Deficits in lower extremity function may depend on multifaceted higher executive function control processes.


Physician extenders increase healthcare access.
To ensure rural residents access to primary care services, Saint Vincent Hospital and Health Center, Billings, MT, operates five physician-operated clinics, located between 8 and 81 miles from Billings. Two of the clinics are in communities that are not large enough to sustain a physician practice, so they are staffed by certified physician assistants (PA-Cs). Licensed and practicing with supervision of a physician, PAs provide a variety of patient care services in virtually every medical specialty and environment. One-third of the nation's PAs work in primary care health professional shortage areas, providing services comparable to those of a family practitioner. National studies reveal a high degree of satisfaction among both consumers and supervising physicians regarding the level of care provided by PAs. Professional liability claims against PAs are fewer than those against physicians, probably because of the higher degree of communication and attention patients receive as a result of the team approach. PAs can increase patient contact hours, decrease waiting times, and improve access to care overall. In addition, PA utilization is a cost-effective approach to healthcare delivery.


Toward Occlusion Handling in Visual Tracking via Probabilistic Finite State Machines.
Visual tracking has been an active research area in computer vision for decades. However, the performance of existing techniques is still challenged by various factors, such as occlusion and change in appearance of the target. In this paper, we propose a novel framework based on correlation filtering and probabilistic finite state machines (FSMs) to handle occlusion. In our tracking framework, the target is partitioned into several parts whose occlusion states are automatically detected. A set of states for the target is defined in terms of the combination of the parts' occlusion states. The probabilistic FSMs are then used to model the target's state transitions so as to reduce the effect of noise in the output response maps of correlation filters. Our target model's update strategy is adaptable online depending on the estimated state of the target. Extensive experiments have been performed on several public benchmarks and the proposed algorithm achieves competitive results against state-of-the-art techniques.


Rapid Ocular Responses Are Modulated by Bottom-up-Driven Auditory Salience.
Despite the prevalent use of alerting sounds in alarms and human-machine interface systems and the long-hypothesized role of the auditory system as the brain's "early warning system," we have only a rudimentary understanding of what determines auditory salience-the automatic attraction of attention by sound-and which brain mechanisms underlie this process. A major roadblock has been the lack of a robust, objective means of quantifying sound-driven attentional capture. Here we demonstrate that: (1) a reliable salience scale can be obtained from crowd-sourcing (N = 911), (2) acoustic roughness appears to be a driving feature behind this scaling, consistent with previous reports implicating roughness in the perceptual distinctiveness of sounds, and (3) crowd-sourced auditory salience correlates with objective autonomic measures. Specifically, we show that a salience ranking obtained from online raters correlated robustly with the superior colliculus-mediated ocular freezing response, microsaccadic inhibition (MSI), measured in naive, passively listening human participants (of either sex). More salient sounds evoked earlier and larger MSI, consistent with a faster orienting response. These results are consistent with the hypothesis that MSI reflects a general reorienting response that is evoked by potentially behaviorally important events regardless of their modality.SIGNIFICANCE STATEMENT Microsaccades are small, rapid, fixational eye movements that are measurable with sensitive eye-tracking equipment. We reveal a novel, robust link between microsaccade dynamics and the subjective salience of brief sounds (salience rankings obtained from a large number of participants in an online experiment): Within 300 ms of sound onset, the eyes of naive, passively listening participants demonstrate different microsaccade patterns as a function of the sound's crowd-sourced salience. These results position the superior colliculus (hypothesized to underlie microsaccade generation) as an important brain area to investigate in the context of a putative multimodal salience hub. They also demonstrate an objective means for quantifying auditory salience.


Central serous chorioretinopathy imaging biomarkers.
To identify the factors predicting the visual and anatomical outcomes in eyes with central serous chorioretinopathy (CSCR) through 12 months. Patients with diagnosis of CSCR, either acute or chronic, were included in this multicentric, retrospective study. Demographic factors; systemic risk factors; central macular thickness (CMT), subfoveal choroidal thickness (SFCT), linear extent of ellipsoid zone (EZ) and interdigitation zone damage on optical coherence tomography; details of leak on fluorescein angiography and indocyanine green angiography were included as predictors of anatomical and visual outcomes. Regression analysis was performed to correlate the changes in best corrected visual acuity (BCVA) and resolution of disease activity. A total of 231 eyes of 201 patients with a mean age (49.7±11.8 years) were analysed. A total of 97 and 134 eyes were classified as acute and chronic CSCR. BCVA (0.35±0.31 to 0.24±0.34; p<0.001), baseline optical coherence tomography (OCT) parameters including CMT (p<0.001), subretinal fluid (SRF) height (p<0.001) and SFCT (p=0.05) showed a significant change through 12 months. Multivariate regression analysis showed change in CMT (p≤0.01) and SRF height at baseline (p=0.05) as factors predictive of good visual outcome. Logistic regression analysis revealed changes in both CMT (p=0.009) and SFCT (p=0.01) through 12 months to correlate with the resolution of disease. OCT parameters such as changes in both CMT and SFCT along with subfoveal EZ damage can be predictive of disease resolution whereas changes in CMT and baseline SRF height correlate well with changes in BCVA through 12 months.


Effect of particle concentration on the microstructural and macromechanical properties of biocompatible magnetic hydrogels.
We analyze the effect of nanoparticle concentration on the physical properties of magnetic hydrogels consisting of polymer networks of the human fibrin biopolymer with embedded magnetic particles, swollen by a water-based solution. We prepared these magnetic hydrogels by polymerization of mixtures consisting mainly of human plasma and magnetic nanoparticles with OH- functionalization. Microscopic observations revealed that magnetic hydrogels presented some cluster-like knots that were connected by several fibrin threads. By contrast, nonmagnetic hydrogels presented a homogeneous net-like structure with only individual connections between pairs of fibers. The rheological analysis demonstrated that the rigidity modulus, as well as the viscoelastic moduli, increased quadratically with nanoparticle content following a square-like function. Furthermore, we found that time for gel point was shorter in the presence of magnetic nanoparticles. Thus, we can conclude that nanoparticles favor the cross-linking process, serving as nucleation sites for the attachment of the fibrin polymer. Attraction between the positive groups of the fibrinogen, from which the fibrin is polymerized, and the negative OH- groups of the magnetic particle surface qualitatively justifies the positive role of the nanoparticles in the enhancement of the mechanical properties of the magnetic hydrogels. Indeed, we developed a theoretical model that semiquantitatively explains the experimental results by assuming the indirect attraction of the fibrinogen through the attached nanoparticles. Due to this attraction the monomers condense into nuclei of the dense phase and by the end of the polymerization process the nuclei (knots) of the dense phase cross-link the fibrin threads, which enhances their mechanical properties.


Human urotensin II promotes hypertension and atherosclerotic cardiovascular diseases.
Human urotensin II (U-II), the most potent vasoconstrictor undecapeptide identified to date, and its receptor (UT) are involved in the pathogenesis of systemic and pulmonary hypertension. Here, we review recent advances in our understanding of the pathophysiology of U-II with particular reference to its role in atherosclerotic cardiovascular diseases. Single-nucleotide polymorphisms of U-II gene (S89N) are associated with onset of essential hypertension, type II diabetes mellitus, and insulin resistance in the Asian population. Plasma U-II levels are elevated in patients with vascular endothelial dysfunction-related diseases such as essential hypertension, diabetes mellitus, atherosclerosis, ischemic heart disease, and heart failure. Chronic infusion of U-II enhances atherosclerotic lesions in the aorta in apolipoprotein E-knockout mice. In human atherosclerotic plaques from the aorta and coronary and carotid arteries, U-II is expressed at high levels in endothelial cells (ECs) and lymphocytes, whereas UT is expressed at high levels in vascular smooth muscle cells (VSMCs), ECs, monocytes, and macrophages. U-II stimulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in human ECs as chemoattractant for monocytes, and accelerates foam cell formation by up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages. U-II produces reactive oxygen species (ROS) via nicotinamide adenine dinucleotide phosphate oxidase activation in human VSMCs, and stimulates VSMC proliferation with synergistic effects when combined with ROS, oxidized LDL, and serotonin. Clinical studies demonstrated increased plasma U-II levels in accordance with the severity of carotid atherosclerosis in patients with essential hypertension and that of coronary artery lesions in patients with ischemic heart disease. Here, we summarize the key roles of U-II in progression of hypertension and atherosclerotic cardiovascular diseases.


[Studies of the effects of long-term isolation on the quality of job performance among operators].
The work centers on the effects of long-term isolation on the quality of job performance of operators. The experiment was carried out with three operators who were to simulate manual redocking of transport vehicle Soyuz-TM to MIR. Data characterizing changes in the parameter at various phases of the experiment and during two 48-hour periods of continuous work were collected and analyzed. Degradation of the quality of job performance was observed at all stages, and particularly during continuous work. Weekly implementation of the task on manual piloting secured adequate maintenance of job skills throughout the experiment.


Stability of bipedal stance: the contribution of cocontraction and spindle feedback.
The aim of this study is to assess the contribution of cocontraction and spindle feedback to local stability during bipedal stance. To that aim, an existing nonlinear state space model of the human musculoskeletal system is linearized in a reference equilibrium state. The maximal real part of the eigenvalues of the linearized system matrix A and the low-frequency joint stiffness are used as a measure of local stability. Muscle properties, as represented in a Hill-type muscle model, are shown to improve the behavior, the improvement being larger at high cocontraction. However, even at maximal cocontraction the low-frequency joint stiffness generated by the muscle properties is insufficient to yield a locally stable system. It follows that feedback is necessary to ensure local stability. In this study, the potential contribution of spindle feedback is investigated by optimizing the feedback gains for contractile element length and velocity for each muscle. It is found that in the case of time-delayed negative feedback, it is impossible to stabilize the system on the basis of spindle feedback. When positive time-delayed feedback is allowed, a barely stable system is obtained. When the time delays are removed, the feedback gains can be chosen such that a locally stable system is obtained, indicating the limitations imposed by the presence of time delays. Finally, it is shown that for small perturbations the response of the linear system to an arbitrary perturbation is similar to that of the nonlinear system, indicating the validity of the approach used. It is concluded that the combination of muscle properties and time-delayed spindle feedback is insufficient to obtain a system with reasonable local stability.


Germline and somatic DNA methylation and epigenetic regulation of KILLIN in renal cell carcinoma.
We recently identified germline methylation of KILLIN, a novel p53-regulated tumor suppressor proximal to PTEN, in >1/3 Cowden or Cowden syndrome-like (CS/CSL) individuals who are PTEN mutation negative. Individuals with germline KILLIN methylation had increased risks of renal cell carcinoma (RCC) over those with PTEN mutations. Therefore, we tested the hypothesis that KILLIN may be a RCC susceptibility gene, silenced by germline methylation. We found germline hypermethylation by combined bisulfite restriction analysis in at least one of the four CpG-rich regions in 23/41 (56%) RCC patients compared to 0/50 controls (P < 0.0001). Of the 23, 11 (48%) demonstrated methylation in the -598 to -890 bp region in respect to the KILLIN transcription start site. Furthermore, 19 of 20 advanced RCC showed somatic hypermethylation upstream of KILLIN, with the majority hypermethylated at more than one CpG island (13/19 vs. 3/23 with germline methylation, P < 0.0001). qRT-PCR revealed that methylation significantly downregulates KILLIN expression (P = 0.05), and demethylation treatment by 5-aza-2'deoxycytidine significantly increased KILLIN expression in all RCC cell lines while only increasing PTEN expression in one line. Furthermore, targeted in vitro methylation revealed a significant decrease in KILLIN promoter activity only. These data reveal differential epigenetic regulation by DNA promoter methylation of this bidirectional promoter. In summary, we have identified KILLIN as a potential novel cancer predisposition gene for nonsyndromic clear-cell RCC, and the epigenetic mechanism of KILLIN inactivation in both the germline and somatic setting suggests the potential for treatment with demethylating agents.


Transcription factor engineering in CHO cells for recombinant protein production.
The continuous increase of approved biopharmaceutical products drives the development of more efficient recombinant protein expression systems. Chinese hamster ovary (CHO) cells are the mainstay for this purpose but have some drawbacks, such as low levels of expression. Several strategies have been applied to increase the productivity of CHO cells with different outcomes. Transcription factor (TF) engineering has emerged as an interesting and successful approach, as these proteins can act as master regulators; the expression and function of a TF can be controlled by small molecules, and it is possible to design tailored TFs and promoters with desired features. To date, the majority of studies have focused on the use of TFs with growth, metabolic, cell cycle or endoplasmic reticulum functions, although there is a trend to develop new, synthetic TFs. Moreover, new synthetic biological approaches are showing promising advances for the development of specific TFs, even with tailored ligand sensitivity. In this article, we summarize the strategies to increase recombinant protein expression by modulating and designing TFs and with advancements in synthetic biology. We also illustrate how this class of proteins can be used to develop more robust expression systems.


Lupus nephritis outcomes: health maintenance organizations compared to non-health maintenance organizations.
Patients with systemic lupus erythematosus (SLE) in USA increasingly have their care centered in health maintenance organizations (HMO). We examined whether HMO and non-HMO SLE patients with renal involvement, who had the same university rheumatologist, differed in their utilization of health care or renal outcomes. Consecutive patients with SLE with renal involvement (n = 24), 10 enrolled in an HMO, 14 not, were studied. Laboratory values were prospectively determined. At the first visit to the rheumatologist, there was no significant difference between HMO and non-HMO patients in laboratory values. There was no difference in the 2 groups in the final prednisone dose (HMO 12 mg vs non-HMO 15.9 mg) or use of azathioprine (20% vs. 57%; p = 0.07) or cyclophosphamide (60% vs. 57%). The serum creatinine was higher in the HMO patients (HMO 1.1 mg/dl vs. non-HMO 0.78 mg/dl; p = 0.05). No difference was found in the number of rheumatology visits. There was a significant difference in the number of communications from the rheumatologist to the HMO versus the HMO to the rheumatologist (p = 0.026). Other than the serum creatinine, there are no differences in the treatment or renal outcomes for HMO compared to non-HMO patients with SLE seeing the same rheumatologist. There is a potential barrier in physician communication, however, with the majority of communications going from the rheumatologist to the HMO provider.


Genetic basis of individual differences in the response to small-molecule drugs in yeast.
Individual response to small-molecule drugs is variable; a drug that provides a cure for some may confer no therapeutic benefit or trigger an adverse reaction in others. To begin to understand such differences systematically, we treated 104 genotyped segregants from a cross between two yeast strains with a collection of 100 diverse small molecules. We used linkage analysis to identify 124 distinct linkages between genetic markers and response to 83 compounds. The linked markers clustered at eight genomic locations, or quantitative-trait locus 'hotspots', that contain one or more polymorphisms that affect response to multiple small molecules. We also experimentally verified that a deficiency in leucine biosynthesis caused by a deletion of LEU2 underlies sensitivity to niguldipine, which is structurally related to therapeutic calcium channel blockers, and that a natural coding-region polymorphism in the inorganic phosphate transporter PHO84 underlies sensitivity to two polychlorinated phenols that uncouple oxidative phosphorylation. Our results provide a step toward a systematic understanding of small-molecule drug action in genetically distinct individuals.


Reduced 30-day gastrostomy placement mortality following the introduction of a multidisciplinary nutrition support team: a cohort study.
Percutaneous endoscopic gastrostomy feeding allows patients with dysphagia to receive adequate nutritional support, although gastrostomy insertion is associated with mortality. A nutrition support team (NST) may improve a gastrostomy service. The present study aimed to evaluate the introduction of a NST for assessment and follow-up of patients referred for gastrostomy. We included adult inpatients referred for gastrostomy insertion consecutively between 1 October 2010 and 31 March 2013. During the first 6 months, a multidisciplinary NST assessment service was implemented. Patient characteristics, clinical condition, referral appropriateness and follow-up were documented prospectively. We compared the frequencies of appropriate referrals, 30-day mortality and mental capacity/consent assessment time spent between the 6 months implementation phase and 2 years following establishment of the assessment service ('established phase'). In total, 309 patients were referred for gastrostomy insertion and 199 (64%) gastrostomies placed. The percentage of appropriate referrals rose from 72% (61/85) during the implementation phase to 87% (194/224) during the established phase (P = 0.002). Thirty-day mortality reduced from 10% (5/52) to 2% (3/147) (P = 0.01), whereas time allocated to assessment of mental capacity and attainment of informed consent rose from mean 3 days (limits of normal variation 0-7) to mean 6 (0-13) days. The introduction of a NST to assess and select patients referred for gastrostomy placement was associated with a rise in the frequency of appropriate referrals and a decrease in 30-day mortality following gastrostomy insertion. Concomitantly, time spent on patient assessment and attainment of informed consent increased.


Clinical applications of mesenchymal stem cells in laryngotracheal reconstruction.
During the past several years, mesenchymal stem cells (MSCs) derived from adult tissue have rapidly moved from in vitro and animal studies into clinical trials as a therapeutic modality for a diverse group of clinical applications, including head and neck reconstruction. For many diseases, cell therapy could affect the underlying pathophysiologic processes through multiple pathways providing an advantage over current treatment modalities. There is an emerging body of evidence that MSCs have unique immunomodulatory properties in addition to the ability to differentiate into multiple tissue lineages which make them even more attractive for regenerative medicine. A variety of pre-clinical and clinical studies have shown that MSCs may have a useful role in tissue repair as well as engineering strategies in head and neck reconstructive surgery. Clinically, this has ranged from injection laryngoplasty to the implantation of a tracheal construct seeded with MSC-derived chondrocytes. Recent advances in stem cell immunobiology can offer insight to the multiple mechanisms through which MSCs could affect underlying pathophysiologic processes ranging from vocal fold scarring to composite tissue defects. Thorough evaluation of the current literature is necessary in understanding how MSCs could potentially revolutionize our approach to head and neck defects. The purpose of this review is to highlight the advances in MSC-based therapies in head and neck surgery, specifically laryngotracheal reconstruction. The clinical role of tissue-derived MSCs, though not well understood, holds promise for many therapeutic applications in regenerative medicine and reconstruction.


Cardiopulmonary exercise testing following hay exposure challenge in farmer's lung.
In patients experiencing an acute episode of hypersensitivity pneumonitis (HP), the alveoli and interstitium show a marked inflammation. The effects of this infiltration with effector cells on gas exchange and the cardiopulmonary system are not well characterized, and there are no data regarding cardiopulmonary exercise testing during hypersensitivity pneumonitis. The aim of this study was to gain new insights into the pathophysiology of acute farmer's lung using cardiopulmonary exercise testing. Cardiopulmonary exercise testing was performed in patients who had farmer's lung (n=21) before and 4 h after a standardized exposure with mouldy hay. Farmers who were asymptomatic for this condition (n=15) served as controls. At baseline, patients who had farmer's lung had a decreased breathing reserve and a greater alveolar to arterial oxygen difference. Following exposure, all of these patients developed hypersensitivity pneumonitis. Compared to the asymptomatic farmers, they showed an increase of alveolar to arterial oxygen difference and functional dead space ventilation during exercise and a reduction of the breathing reserve. In addition, 40% of the asymptomatic farmers demonstrated a pathological increase of the alveolar to arterial oxygen difference during exercise following exposure. In conclusion, our data signify that acute hypersensitivity pneumonitis induces significant changes in pulmonary gas exchange during exercise. Cardiopulmonary exercise testing may help to identify individuals with possible subclinical farmer's lung disease.


Encapsulation of acetylshikonin by polyamidoamine dendrimers for preparing prominent nanoparticles.
Acetylshikonin (AS) has demonstrated antitumor potential. However, the development of therapeutic applications utilizing AS is inhibited by its poor solubility in water. In the present work, polyamidoamine (PAMAM) dendrimers and their PEGylated derivatives were employed to increase the solubility of AS. A distinct color transition was observed during the encapsulation of AS suggesting strong intermolecular forces between PAMAM and AS. Ultraviolet-visible, high-performance liquid chromatography, and (1)H NMR were used to verify the interaction between PAMAM and AS. The maximum amount of combined AS to each PAMAM molecule was determined. The cytotoxicity of AS nanoparticles was evaluated against leukemia (K562) and breast cancer (SK-BR-3) cell lines; the AS nanoparticles were shown to effectively inhibit tumor cells.


Early experience with a computerized robotically controlled catheter system.
Recently, the use of robotic assisted surgery has been utilized in cardiac surgical procedures. The use of robotics may offer benefits in precision, stability and control of instruments remotely. We report early experience with a novel remote robotic catheter control system (CCS). We used a computerized robotically controlled catheter system that enables the user to remotely manipulate the tip of a catheter precisely in three dimensions. We tested the robotic catheter control systems ability to navigate within the heart and to make precise, rapid and repeatable movements. We compared the CCS with the ability of a standard quadripolar steerable ablation catheter placed in a deflectable sheath to navigate and make precision movements. Twelve ex-vivo porcine hearts were utilized to permit accurate measurements of navigation and precision. Eight targets were selected for navigation and precision testing. Time was measured for the catheter to reach the predefined target from a specific starting point to test navigation. In addition, time was measured to contact a discrete 0.8 mm target in order to test precision. The use of the CCS reduced the time needed for both navigation (8.5 +/- 13.9 sec vs. 22.7 +/- 26.7 sec, p = 0.002) and significantly decreased the time for precision targeting (10.1 +/- 6.9 sec vs. 29.6 +/- 26.4 sec, p < 0.001) in the specific RA and LA sites in the ex-vivo hearts. The use of a computerized robotically assisted catheter control system is feasible and shows promise in rapid precision movement of the catheter. Further study is needed to elucidate the role of such a system in-vivo and in patient specific catheter ablation and mapping.


CLINT: a clinical informatics system for an internal medicine ward.
This paper describes a clinical informatics system that provides access to electronic information management tools for clinicians. The Clinical Informatics Network (CLINT) provides a variety of tools for accessing information on an internal medicine ward. Evaluations based on the use of the tools will provide insight to clinicians' information needs, and how these needs can be addressed using electronic information management tools. Better access to information could enhance the quality of patient care.


Global imprint of mycorrhizal fungi on whole-plant nutrient economics.
Mycorrhizal fungi are critical members of the plant microbiome, forming a symbiosis with the roots of most plants on Earth. Most plant species partner with either arbuscular or ectomycorrhizal fungi, and these symbioses are thought to represent plant adaptations to fast and slow soil nutrient cycling rates. This generates a second hypothesis, that arbuscular and ectomycorrhizal plant species traits complement and reinforce these fungal strategies, resulting in nutrient acquisitive vs. conservative plant trait profiles. Here we analyzed 17,764 species level trait observations from 2,940 woody plant species to show that mycorrhizal plants differ systematically in nitrogen and phosphorus economic traits. Differences were clearest in temperate latitudes, where ectomycorrhizal plant species are more nitrogen use- and phosphorus use-conservative than arbuscular mycorrhizal species. This difference is reflected in both aboveground and belowground plant traits and is robust to controlling for evolutionary history, nitrogen fixation ability, deciduousness, latitude, and species climate niche. Furthermore, mycorrhizal effects are large and frequently similar to or greater in magnitude than the influence of plant nitrogen fixation ability or deciduous vs. evergreen leaf habit. Ectomycorrhizal plants are also more nitrogen conservative than arbuscular plants in boreal and tropical ecosystems, although differences in phosphorus use are less apparent outside temperate latitudes. Our findings bolster current theories of ecosystems rooted in mycorrhizal ecology and support the hypothesis that plant mycorrhizal association is linked to the evolution of plant nutrient economic strategies.


Asymmetric distribution of the Listeria monocytogenes ActA protein is required and sufficient to direct actin-based motility.
Listeria monocytogenes is a Gram-positive facultative intracytoplasmic bacterial pathogen that exhibits rapid actin-based motility in eukaryotic cells and in cell-free cytoplasmic extracts. The protein product of the actA gene is required for bacterial movement and is normally expressed in a polarized fashion on the bacterial surface. Here we demonstrate that the ActA protein is sufficient to direct motility in the absence of other L. monocytogenes gene products, and that polarized localization of the protein is required for efficient unidirectional movement. We have engineered a fusion protein combining ActA with the C-terminal domain of the LytA protein of Streptococcus pneumoniae, which mediates high-affinity binding to DEAE-cellulose and to choline moieties present in the S. pneumoniae cell wall. DEAE-cellulose fragments or S. pneumoniae coated uniformly with the ActA/LytA fusion protein nucleate actin filament growth in cytoplasmic extracts, but do not move efficiently. However, when ActA/LytA-coated S. pneumoniae is grown to polarize the distribution of the fusion protein, the bacteria exhibit unidirectional actin-based movement similar to the normal movement of L. monocytogenes.


Rapid quantitation of methylation differences at specific sites using methylation-sensitive single nucleotide primer extension (Ms-SNuPE).
We have developed a rapid quantitative method (Ms-SNuPE) for assessing methylation differences at specific CpG sites based on bisulfite treatment of DNA followed by single nucleotide primer extension. Genomic DNA was first reacted with sodium bisulfite to convert unmethylated cytosine to uracil while leaving 5-methylcytosine unchanged. Amplification of the desired target sequence was then performed using PCR primers specific for bisulfite-converted DNA and the resulting product isolated and used as a template for methylation analysis at the CpG site(s) of interest. This methylation-sensitive technique has several advantages over existing methods used for detection of methylation changes because small amounts of DNA can be analyzed including microdissected pathology sections and it avoids utilization of restriction enzymes for determining the methylation status at CpG sites.


Effects of plyometric jump training on the physical fitness of young male soccer players: Modulation of response by inter-set recovery interval and maturation status.
The effects of plyometric jump training on the physical fitness of male youth (age = 10-17 years) soccer players was examined in relation to inter-set recovery intervals and the maturity of the players in a single-blind, randomized-and controlled crossover trial. Jumping tests and kicking velocities were measured before (T0), after a 6 week control period (T1), after 6 weeks of plyometrics (T2), after 6 weeks of wash-out (T3), and after a further 6 weeks of plyometrics (T4). Subjects were divided into pre- and post- peak-height-velocity (PHV) groups, and were randomly assigned to 30 s or 120 s inter-set intervals during periods T2 and T4. Any changes in jumping and maximum kicking velocities during T1 and T3, had trivial effect sizes (0.01-0.15), but small to moderate improvements (effect size = 0.20-0.99) were observed in both groups during T2 and T4. Gains in pre-PHV players were similar for the two inter-set intervals, but gains in post-PHV players were greater (p < 0.05) with an inter-set recovery of 120 s than with a 30 s recovery. We conclude that plyometric jump training improves the physical fitness of adolescents, irrespective of their maturity, but that in older individuals gains are greater with a longer inter-set recovery interval.


Coordinated genomic control of ciliogenesis and cell movement by RFX2.
The mechanisms linking systems-level programs of gene expression to discrete cell biological processes in vivo remain poorly understood. In this study, we have defined such a program for multi-ciliated epithelial cells (MCCs), a cell type critical for proper development and homeostasis of the airway, brain and reproductive tracts. Starting from genomic analysis of the cilia-associated transcription factor Rfx2, we used bioinformatics and in vivo cell biological approaches to gain insights into the molecular basis of cilia assembly and function. Moreover, we discovered a previously un-recognized role for an Rfx factor in cell movement, finding that Rfx2 cell-autonomously controls apical surface expansion in nascent MCCs. Thus, Rfx2 coordinates multiple, distinct gene expression programs in MCCs, regulating genes that control cell movement, ciliogenesis, and cilia function. As such, the work serves as a paradigm for understanding genomic control of cell biological processes that span from early cell morphogenetic events to terminally differentiated cellular functions. DOI: http://dx.doi.org/10.7554/eLife.01439.001.


PM10 and PM2.5 composition over the Central Black Sea: origin and seasonal variability.
Daily PM10 and PM2.5 samples were collected between April 2009 and July 2010 at a rural site (Sinop) situated on the coast of the Central Black Sea. The concentrations of PM10 and PM2.5 were 23.2 ± 16.7 and 9.8 ± 6.9 μg m(-3), respectively. Coarse and fine filters were analyzed for Cl(-), NO3(-), SO4(2-), C2O4(2-), PO4(3-), Na(+), NH4(+), K(+), Mg(2+), and Ca(2+) by using ion chromatography. Elemental and organic carbon content in bulk quartz filters were also analyzed. The highest PM2.5 contribution to PM10 was found in summer with a value of 0.54 due to enhanced secondary aerosols in relation to photochemistry. Cl(-), Na(+), and Mg(2+) illustrated their higher concentrations and variability during winter. Chlorine depletion was chiefly attributed to nitrate. Higher nssCa(2+) concentrations were ascribed to episodic mineral dust intrusions from North Africa into the region. Crustal material (31%) and sea salt (13%) were found to be accounted for the majority of the PM10. The ionic mass (IM), particulate organic matter (POM), and elemental carbon (EC) explained 13, 20, and 3% of the PM10 mass, correspondingly. The IM, POM, and EC dominated the PM2.5 (~74%) mass. Regarding EU legislation, the exceeded PM2.5 values were found to be associated with secondary aerosols, with a particular dominance of POM. For the exceeded PM10 values, six of the events were dominated by dust while two and four of these exceedances were caused by sea salt and mix events, respectively.


Diversity and distribution patterns of Pronophilina butterflies (Lepidoptera: Nymphalidae: Satyrinae) along an altitudinal transect in north-western Ecuador.
Samplings of Pronophilina, a species-rich group of neotropical montane butterflies, were carried out along an elevational transect in Ecuador to assess the effect of altitude on their distribution patterns, diversity and community structure. All diversity indices were significantly correlated with altitude. Maximum diversity expressed in species-richness, Shannon index and Fisher alpha was recorded at 2600 m. Two assemblages of species were identified in the lower (below 2100 m) and upper (above 2300 m) sections of the transect by means of correspondence (CA) and cluster analysis. A comparison of Sørensen similarity coefficients showed lower values, thus higher turnover in the intermediate elevational band. Several closely related morphologically and ecologically species were found to have mutually exclusive altitudinal distribution patterns. A comparison with similar studies in Venezuela, Colombia and Peru revealed far reaching congruency of the patterns of altitudinal diversity of Pronophilina in distant areas of the Andes. In particular, the Shannon index reaches its maximum values at 2600-2850 m, which invariably correspond to ca. 400-500 m below the upper limit of cloud forest. Increase of diversity of Pronophilina with altitude is marginally related to higher limited resource availability. The lower pressure of predators and parasites at higher elevation can contribute with higher abundance, but cannot be directly correlated with higher diversity. Higher diversity is related with intrisic characteristics of the group, such as aggregated diversity by overlapping of elevational faunal assemblages and higher speciation ratio towards high elevations, particularly near timberline.


Transfusion Safety: The Nature and Outcomes of Errors in Patient Registration.
The transfusion chain is susceptible to error at every step. Accurate patient registration is a key first step that links a patient with their historical medical profile, yet patient registration is marked by its own challenges. Registration errors are deviations from standard operating procedures that occur during the process of patient registration. A frequent consequence of registration errors is the obfuscation of historical information and patient misidentification. Through duplicate registrations, patient information can be spread across multiple records and through hybrid registrations information from multiple patients can be combined into a single record. Patients with the same core identifiers, and the misuse of health insurance information also pose a threat to accurate registration. In the context of transfusion, this can lead to ABO discrepancies, failing to match for previously identified alloantibodies, and redundant serological investigations. Other consequences include missed billing opportunities and the inadvertent sharing of medical information. Reducing the occurrence of registration errors can be achieved through a multifaceted approach combining targeted educational efforts with technological improvements to the registration system. A recent development being the use of biometric identifiers. Despite their frequency, published reports on the occurrence and underlying cause of registration errors are rare. Most reports are found within articles on general medical errors or misidentification events and consequently, the true rate of registration errors among health information systems is not known. Here we summarize literature pertaining to how and why registration errors occur and their implications in the context of blood transfusion.


Understanding factors that facilitate the inclusion of pain education in undergraduate curricula: Perspectives from a UK survey.
Studies in Europe, North America and Australasia suggest that one in five adults suffer from pain. There is increasing recognition that pain, particularly chronic pain, represents a global health burden. Many studies, including two national surveys exploring the content of undergraduate curricula for pain education, identify that documented pain education in curricula was limited and fragmentary. The study design used a questionnaire which included an open text comment box for respondents to add 'further comments' as part of larger study previously published. The sample consisted of 19 UK universities that offered 108 undergraduate programmes in the following: dentistry, medicine, midwifery, nursing (adult, child, learning disabilities and mental health branches), occupational therapy (OT), pharmacy, physiotherapy and veterinary science. An inductive content analysis was performed, and the data were managed using NVivo 10 software for data management. A total of 57 participants across seven disciplines (dentistry, medicine, midwifery, nursing, pharmacy, physiotherapy and OT) completed the open text comment box (none were received from veterinary science). Analysis revealed two major themes of successes and challenges. Successes included expansion (extending coverage and/or increased student access), multidimensional curriculum content and diversity of teaching methods. Challenges included difficulties in identifying where pain is taught in the curriculum, biomedical versus biopsychosocial definitions of pain, perceived importance, time, resources and staff knowledge, and finally a diffusion of responsibility for pain education. This study identifies new insights of the factors attributed to successful implementation of pain education in undergraduate education. Many of the challenges previously reported were also identified. This is one of the first studies to identify a broad range of approaches, for pain education, that could be deemed as 'successful' across a range of health disciplines.


Use of pyridazinediones for tuneable and reversible covalent cysteine modification applied to peptides, proteins and hydrogels.
Reversible cysteine modification has been found to be a useful tool for a plethora of applications such as selective enzymatic inhibition, activity-based protein profiling and/or cargo release from a protein or a material. However, only a limited number of reagents display reliable dynamic/reversible thiol modification and, in most cases, many of these reagents suffer from issues of stability, a lack of modularity and/or poor rate tunability. In this work, we demonstrate the potential of pyridazinediones as novel reversible and tuneable covalent cysteine modifiers. We show that the electrophilicity of pyridazinediones correlates to the rates of the Michael addition and retro-Michael deconjugation reactions, demonstrating that pyridazinediones provide an enticing platform for readily tuneable and reversible thiol addition/release. We explore the regioselectivity of the novel reaction and unveil the reason for the fundamental increased reactivity of aryl bearing pyridazinediones by using DFT calculations and corroborating findings with SCXRD. We also applied this fundamental discovery to making more rapid disulfide rebridging agents in related work. We finally provide the groundwork for potential applications in various areas with exemplification using readily functionalised "clickable" pyridazinediones on clinically relevant cysteine and disulfide conjugated proteins, as well as on a hydrogel material.


Oxygen Saturation Index in Neonates with a Congenital Diaphragmatic Hernia: A Retrospective Cohort Study.
The oxygenation index (OI) is a marker for respiratory disease severity and adverse neonatal outcomes. The oxygen saturation index (OSI) is an alternative that allows for continuous noninvasive monitoring, but evidence for clinical use in critically ill neonates is scarce. The aim of this study was to evaluate the OSI as compared to the OI in term neonates with a congenital diaphragmatic hernia (CDH). A single-center retrospective cohort study was conducted including all live-born infants with an isolated CDH between June 2017 and December 2020. Paired values of the OI and OSI in the first 24 h after birth were collected. The relation between OI and OSI measurements was assessed, taking into account arterial pH, body temperature, and preductal versus postductal location of oxygen saturation measurement or arterial blood sampling. The predictive values for pulmonary hypertension, need for extracorporeal membrane oxygenation therapy, and survival at discharge were evaluated. Of 33 subjects included, 398 paired values of the OI (median 5.8 [3.3-17.2]) and OSI (median 7.3 [3.6-14.4]) were collected. The OI and OSI correlated strongly (r = 0.77, p < 0.001). The OSI values corresponding to the clinically relevant OI values (10, 15, 20, and 40) were 8.9, 10.9, 12.9, and 20.9, respectively. The predictive values of the OI and OSI were comparable for all adverse neonatal outcomes. No difference was found in the area under the receiver operating characteristic curves for the OI and the OSI for adverse neonatal outcomes. The OSI could replace the OI in clinical practice in infants with a CDH.


Spatiotemporal modelling of CheY complexes in Escherichia coli chemotaxis.
The chemotaxis pathway of Escherichia coli is one of the best studied and modelled biological signalling pathways. Here we extend existing modelling approaches by explicitly including a description of the formation and subcellular localization of intermediary complexes in the phosphotransfer pathway. The inclusion of these complexes shows that only about 60% of the total output response regulator (CheY) is uncomplexed at any moment and hence free to interact with its target, the flagellar motor. A clear strength of this model is its ability to predict the experimentally observable subcellular localization of CheY throughout a chemotactic response. We have found good agreement between the model output and experimentally determined CheY localization patterns.


Relationship between 3-Methyl-2,4-nonanedione Concentration and Intensity of Light-induced Off-odor in Soy Bean Oil.
A beany and green off-odor is developed in soy bean oil (SBO) under light-induced oxidative conditions. 3-Methyl-2,4-nonanedione (3-MND) was inferred as the compound responsible for the off-odor. In this study, we designed a simple quantification method for 3-MND in SBO, and evaluated the relationship between the 3-MND concentration and the intensity of the off-odor. 3-MND was analyzed by GC/MS with a thermal desorption unit system. By our method, the 3-MND concentration was found to increase with storage days and the SBO content under light exposure, and there was a high correlation between the measured 3-MND concentration and the intensity of the light-induced off-odor in SBO (R = 0.9586).


Histological comparison of postoperative wound care regimens for laser resurfacing in a porcine model.
The use of short-pulsed CO2 lasers for skin resurfacing is routinely performed, but few studies have examined postsurgical care. To determine which postoperative treatments are most beneficial in promoting optimal healing after laser resurfacing. Four pigs received laser resurfacing. The laser sites were randomly left untreated or treated with petroleum-based ointment or dressed with 1 of the following occlusive dressings: hydrocolloid, hydrogel or foam. Biopsies were taken from each treatment group on Days 2, 3, 4, 5, 8, 12, and 19. All samples were stained with hematoxylin and eosin. Each histological slide was evaluated by a blinded investigator. Differences were observed between treatment groups in the amount of cellular infiltrate, presence of necrotic tissue, progression of the epidermal sheet, maturation of the epidermis, presence of rete ridges, and appearance of new collagen. Postoperative treatments after laser resurfacing vary in their ability to influence the quality of healing.


Intestinal Parasites and Anthelmintic Treatments in a Laboratory Colony of Wild-caught African Pouched Rats (Cricetomys ansorgei).
African giant pouched rats (Cricetomys spp.) are large rodents native to subSaharan Africa. Wild-caught pouched rats identified as Cricetomys ansorgei (n = 49) were imported from Tanzania. A survey of gastrointestinal parasitism by fecal flotation revealed the presence of multiple parasites, including Nippostrongylus spp., Heterakis spp., Trichuris spp., Hymenolepis spp., Raillietina spp., and Eimeria spp. Oral self-administered fenbendazole (150 ppm), topical moxidectin (2 mg/kg), pyrantel pamoate (15 mg/kg), piperazine (100 mg/kg daily), and injectable ivermectin (0.25 mg/kg) were used to determine effective treatment options for the gastrointestinal parasites present in the colony. Pyrantel pamoate in a treat vehicle and piperazine in water bottles were easily administered and significantly reduced the numbers of animals shedding Nippostrongylus spp. and Heterakis spp. during the study. Moxidectin and ivermectin were clinically ineffective at reducing fecal egg shedding. Fenbendazole was most effective at clearing infection with Trichuris spp. Although 10 mg/kg praziquantel was ineffective, a single dose of 30 mg/kg praziquantel significantly reduced the number of African pouched rats that shed cestode embryos. A combination treatment may be necessary to successfully treat all parasites present in any given animal.


Intrinsic properties and regulation of Pannexin 1 channel.
Pannexin 1 (Panx1) channels are generally represented as non-selective, large-pore channels that release ATP. Emerging roles have been described for Panx1 in mediating purinergic signaling in the normal nervous, cardiovascular, and immune systems, where they may be activated by mechanical stress, ionotropic and metabotropic receptor signaling, and via proteolytic cleavage of the Panx1 C-terminus. Panx1 channels are widely expressed in various cell types, and it is now thought that targeting these channels therapeutically may be beneficial in a number of pathophysiological contexts, such as asthma, atherosclerosis, hypertension, and ischemic-induced seizures. Even as interest in Panx1 channels is burgeoning, some of their basic properties, mechanisms of modulation, and proposed functions remain controversial, with recent reports challenging some long-held views regarding Panx1 channels. In this brief review, we summarize some well-established features of Panx1 channels; we then address some current confounding issues surrounding Panx1 channels, especially with respect to intrinsic channel properties, in order to raise awareness of these unsettled issues for future research.


[Bibliographic review. The role of hypoestrogenism in postmenopausal osteoporosis--new perspectives].
Estrogen deficiency following menopause results in a significative bone loss, which is thought to be the result of an imbalance in bone remodeling process between formation activity and resorption, where the later is functionally higher than normal and could develop osteopenia or osteoporosis type I. Although it has been made a lot of scientific investigations to explain the way by hypoestrogenism affect skeleton, the renal mechanism remains unclear and it seems to be multifactorial. Therefore, the purpose of this review is to analyze the new perspectives about the effects of serum estradiol levels on bone tissue; special emphasize is made concerning the role of: estrogen receptors, cytokines, RANKL/RANK/OPG system, PTH and PTHrP, bone turnover markers, osteocytes apoptosis, estrogens serum levels and its metabolic pathways.


Quality of life and disease-specific functional status following microvascular reconstruction for advanced (T3 and T4) oropharyngeal cancers.
In an effort to evaluate quality-of-life benefits of ablative head and neck cancer surgery and microvascular reconstruction, a longitudinal study was undertaken in which patients with T3 or T4 oropharyngeal cancers without systemic metastases at presentation were administered both general and disease-specific quality-of-life instruments preoperatively and postoperatively. In an initial prospective pilot study, 17 cancer patients were evaluated both preoperatively and postoperatively using the Medical Outcomes Short-Form Health Survey questionnaire (SF-36) and the Performance Status Scale for Head and Neck Cancer Patients. In the second part of the study, the need was recognized for a different disease-specific measure, for more frequent intervals of longitudinal follow-up (rather than be limited by a single data collection point), and for a noncancer control group. Since then, 17 more cancer patients were evaluated in the second part of the study and were compared with patients who had similar reconstructions after suffering head and neck trauma and also with age-matched controls. Instead of the performance status scale, the University of Washington Head and Neck Quality of Life questionnaire was substituted. Interval assessments were done at 1, 3, 6, and 12 months and preoperatively. Whereas many of the general and disease-specific quality of life subclasses initially worsened following extensive surgery and radiation therapy, most returned to the preoperative baseline by 6 months following conclusion of treatment and surpassed pretreatment values at 1 year. It can be concluded, based on this study, that large resections and reconstructions for head and neck cancer patients are justified in terms of outcome; the resection controls the local disease, and the microvascular reconstruction restores quality of life and functional status.


Activating interactions of sulfanilamides with T cell receptors.
Activation and expansion of drug reactive T cells are key features in drug hypersensitivity reactions. Drugs may interact directly with immune receptors such as the human leukocyte antigens (HLA) or the T-cell receptors (TCR) itself, the pharmacological interaction [p-i] concept. To analyze whether the drug sulfamethoxazole (SMX) interacts directly with the TCR and thereby contributing to signaling and T cell activation, we analyze two SMX specific T cell clones (TCC "1.3" and "H13"). Proliferation to SMX and 11 related sulfanilamides, Ca++ influx in drug stimulated T-cells and the inhibitory effect of non-reactive sulfanilamides on SMX stimulation were analyzed. In silico docking of SMX and related sulfanilamide to the TCR were used to identify possible drug binding sites, and correlated to in vitro data to find the correct docking. In Ca++ influx assays, reactions occurred as early as 14 sec after adding SMX to TCC and APC. The broadly reactive clone ("H13") was stimulated by 5 additional sulfanilamide, while one TCC ("1.3") was reactive exclusively with SMX but not other sulfanilamides. Competition experiments with sulfanilamide inhibited SMX induced Ca++ influx and proliferation of the TCC 1.3 in a dose dependent way. Docking experiments with SMX and related sulfanilamides confirmed and explained the in vitro data as docking localized binding sites for SMX and the 5 stimulating sulfanilamides on the CDR2ß domain of the clone H13, while the 6 non-stimulatory SA failed to bind. In TCC 1.3, SMX could be docked on the CDR3α of the TCR. The other, non-stimulatory but inhibitory SA could also be docked to the same site. The combined analysis of in vitro and in silico data show that sulfanilamide can bind directly to TCRs. It shows that TCR, like other receptors, appear to be reamenable to manipulations by small molecules.


[Effect of deafferentation of the lateral geniculate body on its background activity].
Elimination of reticular inputs to the lateral geniculate body (LGB) by sectioning of one half of the midbrain operculum, did not affect significantly the characteristics of the LGB evoked potential to light stimulus. At the same time LGB response to stimulation of the reticular formation by a single current impulse, though did not disappear completely, but changed greatly: its latency became twice as long, the negative component of the response was no more recorded. In conditions of LGB deafferentation, the characteristics of all rhythms of its electrical activity, besides the alpha-like one, considerably changed. At the same time, exactly this last rhythm underwent the greatest changes on the EEG of the visual cortex. On the basis of the obtained data it is suggested that the reticular formation takes a considerable and multiple part in generation of LGB rhythmic activity and that changes in its characteristics are clearly reflected in the ECoG rhythms formation. Retention of the LGB visual evoked potential and of the response to stimulation of the reticular formation after the section of one half of the midbrain operculum testifies to the presence of several reticular inputs to LGB.


Neural stem cells: an overview.
This review focuses on the nature and functional properties of stem cells of the adult mammalian central nervous system (CNS). It has recently been shown that cell turnover, including neurons, does occur in the mature CNS, thanks to the persistence of precursor cells that possess the functional characteristics of bona-fide neural stem cells (NSCs) within restricted brain areas. We discuss how the subventricular zone of the forebrain (SVZ) is the most active neurogenetic area and the richest source of NSCs. These NSCs ensure a life-long contribution of new neurons to the olfactory bulb and, when placed in culture, can be grown and extensively expanded for months, allowing the generation of stem cell lines, which maintain stable and constant functional properties. A survey of the differentiation potential of these NSCs, both in vitro and in vivo, outlines their extreme plasticity that seems to outstretch the brain boundaries, so that these neuroectodermal stem cells may give rise to cells that derive from developmentally distinct tissues. A critical discussion of the latest, controversial findings regarding this surprising phenomenon is provided.


Neighborhood effects on the self-rated health of older adults from four racial/ethnic groups.
Building upon the sizable literature on individual-level predictors of self-rated health, this study examined the impact of neighborhood characteristics, using older adult samples of four racial/ethnic groups. The considered neighborhood characteristics include (a) the proportion of individuals age 65 and older, (b) the proportion of individuals below poverty, and (c) the proportion of individuals from the same racial/ethnic background in the Census-block group. The samples were drawn from the 2004-2005 Survey of Older Floridians, which includes Whites (n = 488), Blacks (n = 345), Cubans (n = 319), and non-Cuban Latinos (n = 230). Using the reported residential address, each participant was linked to the 2000 Census at block-group level to retrieve the above-mentioned neighborhood characteristics. Multilevel analysis of self-rated health was estimated for each racial/ethnic group, considering individual-level variables (e.g., age, gender, marital status, education, financial strain, and chronic conditions) and each of the neighborhood characteristics. Regardless of racial/ethnic groups, those living in the neighborhood with a higher proportion of residents below poverty were likely to report poorer health. The proportion of older adults in the neighborhood was significant only in Cubans, and the proportion of residents with the same ethnic background was only in Whites. The findings show the overall importance of neighborhood context in the health of older adults and indicate different implications of neighborhood characteristics for diverse racial/ethnic groups.


The Thrombin Receptor Restricts Subventricular Zone Neural Stem Cell Expansion and Differentiation.
Thrombin is frequently increased in the CNS after injury yet little is known regarding its effects on neural stem cells. Here we show that the subventricular zone (SVZ) of adult mice lacking the high affinity receptor for thrombin, proteinase activated receptor 1 (PAR1), show increased numbers of Sox2+ and Ki-67+ self-renewing neural stem cells (NSCs) and Olig2+ oligodendrocyte progenitors. SVZ NSCs derived from PAR1-knockout mice, or treated with a PAR1 small molecule inhibitor (SCH79797), exhibited enhanced capacity for self-renewal in vitro, including increases in neurosphere formation and BrdU incorporation. PAR1-knockout SVZ monolayer cultures contained more Nestin, NG2+ and Olig2+ cells indicative of enhancements in expansion and differentiation towards the oligodendrocyte lineage. Cultures of NSCs lacking PAR1 also expressed higher levels of myelin basic protein, proteolipid protein and glial fibrillary acidic protein upon differentiation. Complementing these findings, the corpus callosum and anterior commissure of adult PAR1-knockout mice contained greater numbers of Olig2+ progenitors and CC1+ mature oligodendrocytes. Together these findings highlight PAR1 inhibition as a means to expand adult SVZ NSCs and to promote an increased number of mature myelinating oligodendrocytes in vivo that may be of particular benefit in the context of neural injury where PAR1 agonists such as thrombin are deregulated.


Regulators of gene expression as biomarkers for prostate cancer.
Recent technological advancements in gene expression analysis have led to the discovery of a promising new group of prostate cancer (PCa) biomarkers that have the potential to influence diagnosis and the prediction of disease severity. The accumulation of deleterious changes in gene expression is a fundamental mechanism of prostate carcinogenesis. Aberrant gene expression can arise from changes in epigenetic regulation or mutation in the genome affecting either key regulatory elements or gene sequences themselves. At the epigenetic level, a myriad of abnormal histone modifications and changes in DNA methylation are found in PCa patients. In addition, many mutations in the genome have been associated with higher PCa risk. Finally, over- or underexpression of key genes involved in cell cycle regulation, apoptosis, cell adhesion and regulation of transcription has been observed. An interesting group of biomarkers are emerging from these studies which may prove more predictive than the standard prostate specific antigen (PSA) serum test. In this review, we discuss recent results in the field of gene expression analysis in PCa including the most promising biomarkers in the areas of epigenetics, genomics and the transcriptome, some of which are currently under investigation as clinical tests for early detection and better prognostic prediction of PCa.


Ultrastable and Durable Silicone Coating on Polycarbonate Surface Realized by Nanoscale Interfacial Engineering.
Delamination of coating layer from polymer substrate limits the lifetime and functionality of the protective films. Silicone coating is especially vulnerable to photo irradiation, hydrothermal degradation, and mechanical deformation due to the low interfacial adhesion and mechanical robustness. Herein, an ingenious approach is developed to fabricate ultrastable and durable silicone coating on polycarbonate (PC) substrate through well-controlled nanoscale interfacial engineering. A nanopillar array is fabricated on the PC surface by vacuum-assisted hot embossing using anodic aluminum oxide (AAO) templates. Significant improvement in interfacial shear strength (ISS) is achieved for the silicone coating on the nanostructured PC surface. The delamination mechanism can be controlled by tuning the nanopillar size, and the maximum ISS of 9.9 MPa was reached on a surface with a nanopillar diameter of 320 nm. Attributed to the increased interfacial area and mechanical interlocking structure, the nanostructured interface can effectively dissipate interfacial stress and prevent cracking; therefore, maintaining excellent transparency and performance in the harsh environment. The coating exhibits extraordinary stability and durability when subjected to UV irradiation for 168 h, hydrothermal aging for 120 h, mechanical bending for 1000 cycles, and even surface damage. Thus, the tough silicone coating on polymer substrate realized by nanoscale interfacial engineering is a promising technique for highly stable and durable transparent surface protection.


Evolution of temporal isolation in the wild: genetic divergence in timing of migration and breeding by introduced chinook salmon populations.
The timing of migration and breeding are key life-history traits; they are not only adaptations of populations to their environments, but can serve to increase reproductive isolation, facilitating further divergence among populations. As part of a study of divergence of chinook salmon, Oncorhynchus tshawytscha, populations, established in New Zealand from a common source in the early 1900s, we tested the hypotheses that the timing of migration and breeding are under genetic control and that the populations genetically differ in these traits despite phenotypic overlap in timing in the wild. Representatives of families from two populations were collected within a day or two of each other, reared in a common environment, and then released to sea from each of two different rivers, while other family representatives were retained in fresh water to maturity. The date of maturation of fish held in fresh water and the dates of return from the ocean and maturation of fish released to sea all showed significant differences between the two populations and among families within populations. The very high heritabilities and genetic correlations estimated for migration and maturation date indicated that these traits would respond rapidly to selection. Combined with the results of related studies on these chinook salmon populations, it appears that spawning time may not only evolve during the initial phases of divergence, but it may play an important role in accelerating divergence in other traits.


Assessing animal individuality: links between personality and laterality in pigs.
Animal individuality is challenging to explain because individual differences are regulated by multiple selective forces that lead to unique combinations of characteristics. For instance, the study of personality, a core aspect of individuality, may benefit from integrating other factors underlying individual differences, such as lateralized cerebral processing. Indeed, the approach-withdrawal hypothesis (the left hemisphere controls approach behavior, the right hemisphere controls withdrawal behavior), may account for differences in boldness or exploration between left and right hemispheric dominant individuals. To analyze the relationships between personality and laterality we tested 80 male piglets with established laterality patterns for 2 motor functions (tail curling direction and the side of the snout used for manipulation) and a combined classification integrating both motor functions using cluster analysis. We analyzed basal salivary testosterone and cortisol along with their behavior in standardized tests as pre-established indicators of different personality traits (Boldness, Exploration, Activity, Sociability, and Coping). We found that the direction of the single motor biases showed significant associations with few personality traits. However, the combined laterality classification showed more, and more robust, significant associations with different personality traits compared with the single motor biases. These results supported the approach-withdrawal hypothesis because right-biased pigs were bolder and more explorative in a context of novelty. Additionally, right-biased pigs were more sociable than left-biased pigs. Therefore, the present study indicates that personality is indeed related to lateralized cerebral processing and provides insight into the multifactorial nature of individuality.


Evaluation of the mental function of the elderly in a general practice.
A mental function test was carried out on 378 individuals over 70 years of age registered with a group practice in the city of Newcastle upon Tyne. A high score (11 or over) was observed in 64.9% of women and 78.3% of men; a medium score (between three and 10) was observed in 34.0% of women and 20.8% of men; and only 0.8% of individuals of both sexes were found to have a low score (less than three). It was found that older age groups of both sexes had lower scores than younger groups (P < 0.001) and this was more pronounced in women than men (P < 0.05).These observations are significantly different (P < 0.001) from those obtained in hospital studies. The need for surveillance which influences mortality, morbidity and resource allocation is discussed.


[Vascular manifestation of von Recklinghausen neurofibromatosis: case report of venous dysplasia].
We present the case report of a patient with neurofibromatosis and regional dysmorphism in the superficial femoral vein. Colour coded duplex sonography revealed an incidental finding: thickening of a short portion of the vein wall with calcification. This unusual finding strongly suggests a causal relationship. Pathological processes in the arteries have often been described in patients with von Recklinghausen's disease (neurofibromatosis). Dysplastic and hyperplastic reactions of the intramural nerve tissues and the smooth muscle elements in the vascular wall have been observed. This leads to the formation of aneurysms and arteriovenous fistulas and to stenosing processes in the peripheral, visceral and cerebral arteries. However, involvement of the veins in type 1 von Recklinghausen's neurofibromatosis has only been reported in old histopathological studies of medium-sized and small vessels.


Acoustically active injection catheter guided by ultrasound: navigation tests in acutely ischemic porcine hearts.
Catheters are increasingly used therapeutically and investigatively. With complex usage comes a need for more accurate intracardiac localization than traditional guidance can provide. An injection catheter navigated by ultrasound was designed and then tested in an open-chest model of acute ischemia in eight pigs. The catheter is made "acoustically active" by a piezo-electric crystal near its tip, electronically controlled, vibrating in the audio frequency range and uniquely identifiable using pulsed-wave Doppler. Another "target" crystal was sutured to the epicardium within the ischemic region. Sonomicrometry was used to measure distances between the two crystals and then compared with measurements from 2-D echocardiographic images. Complete data were obtained from seven pigs, and the correlation between sonomicrometry and ultrasound measurements was excellent (p < 0.0001, ρ = 0.9820), as was the intraclass correlation coefficient (0.96) between two observers. These initial experimental results suggest high accuracy of ultrasound navigation of the acoustically active catheter prototype located inside the beating left ventricle.


Cell populations in experimental contact dermatitis.
Sequential biopsy specimens from contact dermatitis induced in the guinea pig by the application of dinitrochlorobenzene were studied by histologic, histochemical, and electron microscopical methods. At 12 hours, mononuclear cells and polymorphonuclear cells reached their peak numbers. Increasing numbers of basophils were observed, and at 24 and 48 hours, the basophils reached their maximal numbers. The basophils were observed not only in the dermis but also in the epidermis, and they may have had an active role in inflammation or repair. A close relationship was noted between the macrophage and all of the successive cell populations in the dermis.


[Simulation of land use and assessment of ecosystem service value in the eastern coastal cities of Zhejiang Province, China].
Simulating the change of ecosystem service values (ESV) caused by land use/cover change (LUCC) in the eastern coastal cities of Zhejiang Province is of great significance for regional sustainable development and ecological security. Based on remote sensing images of land use and Statistics Yearbook of 2000, 2010, and 2020, we analyzed the influence of LUCC on ESV in the study area during 2000-2020. We used the PLUS model to simulate land use change under three scenarios, including inertial development, ecological protection, and urban development in 2030, analyzed the spatial distribution and concentration degree of ESVs based on grid scale, and clarified the sensitivity characteristics of ESVs. The results showed that the construction land area showed an increasing trend during 2000-2020. The area of forest, cultivated land and water decreased significantly, resulting in a continuous downward trend of ESVs, which decreased by 160×108 yuan. Under the simulation of three scenarios of inertial development, ecological development, and urban development, the construction land area would increase by 93624, 54927, and 111966 hm2, respectively. The eastern plain would become the agglomeration area of construction land expansion. The ESVs of those three scenarios was 1693×108, 1729×108, and 1688×108 yuan, respectively, which were all lower than the ESVs of the study area in 2020. The decline rate of ESV in the ecological protection scenario slowed down. The spatial distribution of ESVs in the study area was high in the west and low in the east. Hot spots and cold spots of ESVs were distributed in a large range with strong agglomeration. Hot spots were mainly concentrated in the west, while cold spots were mainly distributed in the east and north.


Lymph nodes tuberculosis: a retrospective study on clinical and therapeutic features.
Lymph nodes tuberculosis represents 30 percent of extra pulmonary tuberculosis in Morocco. We report here the experience of the pulmonology unit of the Avicenne Military Hospital in Marrakech for a period of 4 years. Our study interested 30 patients (15 males and 15 females) with an average age of 29 years old (10 to 62 years old). Tuberculosis has interested a single site in 28 patients, the other two patients had multiple but unilateral involvement. For the single sites, locations were jugulo-carotidian (20 patients), supra-calvicular (2 patients), axillary (2 patients), sub-mandibular (2 patients), spinal (2 patients) and mediastinal (2 patients). For the multiple locations, the involvement was jugulo-carotidian, sub-mandibular, spinal and sub-clavicular for one patient; and jugulo-carotidian and sub-clavicular for the other. Diagnosis was made by surgical biopsy and histology for all the patients. A six-month anti-tuberculous treatment was given afterward, with relapses in two patients.


Immunomodulation and liver protection of Yinchenhao decoction against concanavalin A-induced chronic liver injury in mice.
This study investigated the immunoregulatory and protective roles of Yinchenhao decoction, a compound of Chinese herbal medicine, in a mouse model of concanavalin A (ConA)-induced chronic liver injury. Female BalB/c mice were randomly divided into 4 groups: normal control, ConA model, ConA model treated with Yinchenhao decoction (400 mg/kg, orally), and ConA model treated with dexamethasone (0.5 mg/kg, orally). All treatments were given once a day for 28 d. Except of the normal control, mice received tail vein injection of ConA (10 mg/kg) on days 7, 14, 21, and 28, at 1 h after treatment with Yinchenhao decoction or dexamethasone or saline to induce chronic liver injury. Repeated ConA injection induced chronic liver injury, which was evidenced by inflammatory cell infiltration and necrosis, increased serum alanine aminotranferease activities, decreased albumin levels, and an imbalanced expression of immunoregulatory genes in the liver tissues including significantly enhanced interferon-γ, interleukin-4, monocyte chemotactic protein-1, and cluster of differentiation 163 mRNA levels, and reduced tumor necrosis factor-α and interleukin-6 mRNA levels. Treatment with Yinchenhao decoction significantly reversed the ConA-induced changes in immunoregulatory gene expression in the liver tissues, reduced serum alanine aminotranferease activity, enhanced serum albumin level, and attenuated the extent of liver inflammation and necrosis. Furthermore, Yinchenhao decoction did not result in hepatocyte degeneration and spleen weight loss that were observed in mice received long-term treatment with dexamethasone. Yinchenhao decoction treatment protected liver against the ConA-induced chronic liver damage and improved liver function, which were associated with the modulation of gene expression related to immune/inflammatory response.


Influence of Defensiveness on Disability in a Chronic Musculoskeletal Pain Population.
This study aimed to identify the following: (1) the proportion of the defensive high-anxious personality type in a chronic pain population; (2) whether personality type affects the relationships between cognitive factors and disability. Sixty patients with chronic musculoskeletal pain, referred to a hospital for treatment, completed questionnaires assessing defensiveness, trait anxiety, pain intensity, disability, depression, catastrophizing, self-efficacy, and kinesiophobia. Personality type was assessed using the State-Trait Anxiety Inventory and the Marlowe-Crowne Social Desirability Scale. Within the defensive high-anxious group, lower levels of self-efficacy, and high levels of depression and catastrophizing most strongly predicted perceptions of disability. Interestingly, the cognitive variables failed to significantly predict disability for individuals lower in anxiety and defensiveness; however, pain intensity did have a greater effect, explaining 36% of the variance. The interaction between defensiveness and anxiety plays an important role in patients' perceptions of, and outcomes from, chronic pain. Differentiating the defensive high-anxious group revealed different patterns of relationship between a range of cognitive factors and disability. This highlights the necessity of assessing personality characteristics that include defensiveness in order to identify those individuals who may be more vulnerable to cognitive factors influencing their perceptions of disability. If personality type is identified as a predictor of poor adjustment, interventions could be customized to the unique needs of this group (eg. high defensive and anxious individuals).


Asymptotic Performance of Port-Based Teleportation.
Quantum teleportation is one of the fundamental building blocks of quantum Shannon theory. While ordinary teleportation is simple and efficient, port-based teleportation (PBT) enables applications such as universal programmable quantum processors, instantaneous non-local quantum computation and attacks on position-based quantum cryptography. In this work, we determine the fundamental limit on the performance of PBT: for arbitrary fixed input dimension and a large number N of ports, the error of the optimal protocol is proportional to the inverse square of N. We prove this by deriving an achievability bound, obtained by relating the corresponding optimization problem to the lowest Dirichlet eigenvalue of the Laplacian on the ordered simplex. We also give an improved converse bound of matching order in the number of ports. In addition, we determine the leading-order asymptotics of PBT variants defined in terms of maximally entangled resource states. The proofs of these results rely on connecting recently-derived representation-theoretic formulas to random matrix theory. Along the way, we refine a convergence result for the fluctuations of the Schur-Weyl distribution by Johansson, which might be of independent interest.


Computer-related skin diseases.
The use of computers has increased vastly, occupationally as well as for private use, and in the last decade, a number of reports have been published in which skin problems are ascribed to the (intensive) use of computers. Not only irritant or mechanically induced contact dermatitis has been reported but also allergic contact dermatitis. As this appears to be a new group of occupational dermatoses, we present a brief overview of these cases, and aetiologic factors are discussed.


Crystal structure of the CUB1-EGF-CUB2 domain of human MASP-1/3 and identification of its interaction sites with mannan-binding lectin and ficolins.
MASP-1 and MASP-3 are homologous proteases arising from alternative splicing of the MASP1/3 gene. They include an identical CUB(1)-EGF-CUB(2)-CCP(1)-CCP(2) module array prolonged by different serine protease domains at the C-terminal end. The x-ray structure of the CUB(1)-EGF-CUB(2) domain of human MASP-1/3, responsible for interaction of MASP-1 and -3 with their partner proteins mannan-binding lectin (MBL) and ficolins, was solved to a resolution of 2.3A(.) The structure shows a head-to-tail homodimer mainly stabilized by hydrophobic interactions between the CUB(1) module of one monomer and the epidermal growth factor (EGF) module of its counterpart. A Ca(2+) ion bound primarily to both EGF modules stabilizes the intra- and inter-monomer CUB(1)-EGF interfaces. Additional Ca(2+) ions are bound to each CUB(1) and CUB(2) module through six ligands contributed by Glu(49), Asp(57), Asp(102), and Ser(104) (CUB(1)) and their counterparts Glu(216), Asp(226), Asp(263), and Ser(265) (CUB(2)), plus one and two water molecules, respectively. To identify the residues involved in interaction of MASP-1 and -3 with MBL and L- and H-ficolins, 27 point mutants of human MASP-3 were generated, and their binding properties were analyzed using surface plasmon resonance spectroscopy. These mutations map two homologous binding sites contributed by modules CUB(1) and CUB(2), located in close vicinity of their Ca(2+)-binding sites and stabilized by the Ca(2+) ion. This information allows us to propose a model of the MBL-MASP-1/3 interaction, involving a major electrostatic interaction between two acidic Ca(2+) ligands of MASP-1/3 and a conserved lysine of MBL. Based on these and other data, a schematic model of a MBL.MASP complex is proposed.


Strategies for Measuring Advances in Pharmacy Student Learning.
Objective. To provide guidance to authors and reviewers on how to design and evaluate educational research studies to better capture evidence of pharmacy student learning.Findings. A wide variety of assessment tools are available to measure student learning associated with educational innovations. Each assessment tool is associated with different advantages and disadvantages that must be weighed to determine the appropriateness of the tool for each situation. Additionally, the educational research design must be aligned with the intent of the study to strengthen its impact.Summary. By selecting research methods aligned with Kirkpatrick's levels of training evaluation, researchers can create stronger evidence of student learning when evaluating the effectiveness of teaching innovations.


Cystic pancreatic lymphangioma.
Lymphangioma of the pancreas is a rare benign tumor of lymphatic origin. Retroperitoneal lymphangiomas account for 1% of all lymphangiomas. Herein, we report a case of cystic pancreatic lymphangioma diagnosed in 34 year-old female patient who was hospitalized for a slight pain in the epigastrium and vomiting. Radiological imaging revealed a large multiloculated cystic abdominal mass with enhancing septations involving the upper retroperitoneum. During the laparoscopic surgery, a well circumscribed polycystic tumor was completely excised preserving the pancreatic duct. The patient made a complete recovery and is disease-free 12 months postoperatively.


Cross-cultural Adaptation of the Self-care of Hypertension Inventory Into Brazilian Portuguese.
Lifestyle changes and treatment adherence still constitute a challenge to healthcare providers involved in the care of persons with hypertension. The lack of validated instruments measuring the ability of hypertensive patients to manage their disease has slowed research progress in this area. The Self-care of Hypertension Inventory, originally developed in the United States, consists of 23 items divided across 3 scales: Self-care Maintenance, Self-care Management, and Self-care Confidence. These scales measure how well patients with hypertension adhere to treatment and manage elevated blood pressure, as well as their confidence in their ability to perform self-care. A rigorous cross-cultural adaptation and validation process is required before this instrument can be used in other countries. The aims of this study were to translate the Self-care of Hypertension Inventory into Brazilian Portuguese with cross-cultural adaptation and to evaluate interobserver reliability and temporal stability. This methodological study involved forward translation, synthesis of forward translations, back-translation, synthesis of back-translations, expert committee review, and pretesting. Interobserver agreement and the temporal stability of the scales were assessed. The expert committee proposed semantic and cultural modifications to some items and the addition of guidance statements to facilitate administration of the scale. Interobserver analysis demonstrated substantial agreement. Analysis of temporal stability showed near-perfect agreement. Cross-cultural adaptation of the Self-care of Hypertension Inventory successfully produced a Portuguese-language version of the instrument for further evaluation of psychometric properties. Once that step is completed, the scale can be used in Brazil.


Real-time imaging of the dynamics of death receptors and therapeutics that overcome TRAIL resistance in tumors.
Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induces apoptosis specifically in tumor cells and its efficacy has been tested in pre-clinical models by delivering it systemically as a purified ligand or via engineered stem cells (SC). However, about 50% of tumor lines are resistant to TRAIL and overcoming TRAIL resistance in aggressive tumors, such as glioblastoma-multiforme (GBM), and understanding the molecular dynamics of TRAIL-based combination therapies are critical to broadly use TRAIL as a therapeutic agent. In this study, we developed death receptor (DR)4/5-reporters that offer an imaging-based platform to identify agents that act in concert with a potent, secretable variant of TRAIL (S-TRAIL) by monitoring changes in DR4/5 expression. Utilizing these reporters, we show a differential regulation of DR4/5 when exposed to a panel of clinically relevant agents. A histone deacetylase inhibitor, MS-275, resulted in upregulation of DR4/5 in all GBM cell lines, and these changes could be followed in real time both in vitro and in vivo in mice bearing tumors and they correlated with increased TRAIL sensitivity. To further assess the dynamics of combinatorial strategies that overcome resistance of tumors to SC released S-TRAIL, we also engineered tumor cells to express live-cell caspase-reporters and SCs to express S-TRAIL. Utilizing DR4/5 and caspase reporters in parallel, we show that MS-275 sensitizes TRAIL-resistant GBM cells to stem cell (SC) delivered S-TRAIL by changing the time-to-death in vitro and in vivo. This study demonstrates the effectiveness of a combination of real-time reporters of TRAIL-induced apoptosis pathway in evaluating the efficacy of SC-TRAIL-based therapeutics and may have implications in targeting a broad range of cancers.


Spurious signals in direct digital frequency synthesizers due to the phase truncation.
Direct digital frequency synthesizers (DDS or DDFS) are widely used in modern communications and measurement devices. Their advantages are small size and power consumption together with excellent frequency stability, high frequency resolution, and short switching times. The difficulties are rather low output frequencies (500 MHz at the present state of the art) and a large set of the spurious signals very often above the -80 dB level. One source of spurious signals in DDS is the use of smaller number, W, of the most significant bits (MSB) applied for the output sine wave reconstruction from all R bits stored in the accumulator. The result is a phase modulation of the output signal. The problem was first solved in a rather complicated way with the result that the level of the largest spurious signal is about -6 W dB below the carrier with an increase of 3.9 dB in some instances. A simpler solution of the problem of spurious signal level due to the phase truncation in DDS was found earlier. However, no attention was paid to the validity of the corrections suggested. In this paper we will be concerned with this problem and investigate the validity and correctness of these generally cited results and provide a simple way for finding positions, levels, and numbers of these spurious signals generated by truncation to W bits of the phase information stored in the DDS accumulator memory of R bits (W<R).


Cryptic bioluminescence in a midwater shrimp.
The mesopelagic shrimp Sergestes similis emits ventrally directed bioluminescence that closely matches the intensity of downward-directed illumination and is able to rapidly modify its light output to match changes in background intensity. Masking experiments show that the photoreceptors involved are the compound eyes or adjacent tissues. Light emission originates from modified portions of the hepatopancreas and is similar to oceanic light in angular distribution and spectral characteristics. Normally oriented animals respond minimally to upward-directed light.


Re-design of a uniplanar, monolateral external fixator.
This work deals with the structural analysis of screw clamps for external fixator devices. Screw clamps are widely used in external fixators as a means to connect the half-pins to the fixator body. The analysis is carried out by both numerical and experimental techniques, based on the case study of a clamp produced by Citieffe (Bologna, Italy). As a preliminary activity, the tribological parameters involved in the screw-clamp interaction have been characterized by means of a mixed finite element analysis and experimental procedure. Then, an assessment of the current design of the clamp has been carried out. A re-design has been proposed, which, based on some targeted geometrical modifications, allows achieving higher strength requirements with the same overall dimensions and type of materials. A higher load-bearing capability for a given size may allow the fixator to be used on a broader population. Finally, a list of good practices for the design of this kind of clamps has been proposed.