High attrition rates in commercial weight reduction programs.
The management of obesity is increasingly dominated by nonprofessional self-helping groups. Little information about the efficacy of these groups is available from independent sources. In a study of 108 women enrolled in a commercial weight reduction program, we found very high attrition rates; 50% of the members dropped out in six weeks and 70% in 12 weeks. Similar attrition rates have been reported in five other programs in three different countries. Very high attrition rates diminish the effectiveness of commercial weight reduction programs, and they suggest caution in the interpretation of data based on weight losses of persons who remain in these programs.


[Genetic diversity and molecular evolution of the influenza A viruses in Russia during 2006-2012].
The results of molecular genetic analysis of more than 280 strains of influenza A virus subtypes H1N1 and H3N2 circulating in Russia in 2006-2012 are presented. The genetic changes underlying the evolution of the virus strains and sensitivity to antiviral drugs were analyzed. Significant changes in the genetic structure of influenza A viruses circulating in the Russian Federation and their phylogenetic affiliation are shown to occur within the studied period. The studies identifying codons under the positive selection in silico in the genes encoding surface proteins of the influenza virus were demonstrated to be efficient for the analysis of the antigenic drift and direction of evolutionary variability of the influenza viruses.


Microvascular Disease and Small-Vessel Disease: The Nexus of Multiple Diseases of Women.
Microvascular disease, or small-vessel disease, is a multisystem disorder with a common pathophysiological basis that differentially affects various organs in some patients. The prevalence of small-vessel disease in the heart has been found to be higher in women compared with men. Additionally, other diseases prominently affecting women, including heart failure with preserved ejection fraction, Takotsubo cardiomyopathy, cerebral small-vessel disease, preeclampsia, pulmonary arterial hypertension (PAH), endothelial dysfunction in diabetes, diabetic cardiomyopathy, rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, may have a common etiologic linkage related to microvascular disease. To the best of our knowledge this is the first article to investigate this potential linkage. We sought to identify various diseases with a shared pathophysiology involving microvascular/endothelial dysfunction that primarily affect women, and their potential implications for disease management. Advanced imaging technologies, such as magnetic resonance imaging and positron-emission tomography, enable the detection and increased understanding of microvascular dysfunction in various diseases. Therapies that improve endothelial function, such as those used in PAH, may also be associated with benefits across the full spectrum of microvascular dysfunction. A shared pathology across multiple organ systems highlights the need for a collaborative, multidisciplinary approach among medical subspecialty practitioners who care for women with small-vessel disease. Such an approach may lead to accelerated research in diseases that affect women and their quality of life.


An EEG-based brain-computer interface for real-time multi-task robotic control.
The Brain Computer Interface (BCI) is the communication between the human brain and the computer. Electroencephalogram (EEG) is one of the biomedical signals which can be obtained by attaching electrodes to the scalp. Some EEG related applications can be developed to help disabled people, such as EEG based wheelchair or robotic arm. A hybrid BCI real-time control system is proposed to control a multi-tasks BCI robot. In this system, a sliding window based online data segmentation strategy is proposed to segment training data, which enable the system to learn the dynamic features when the subject's brain state transfer from a rest state to a task execution state. The features help the system achieve real-time control and ensure the continuity of executing actions. In addition, Common Spatial Pattern (CSP) can better extract the spatial features of these continuous actions from the dynamic data to ensure that multiple control commands are accurately classified. In the experiment, three subjects' EEG data is collected, trained and tested the performance and reliability of the proposed control system. The system records the robot's spending time, moving distance, and the number of objects pushing down. Experimental results are given to show the feasibility of the real-time control system. Compared to real-time remote controller, the proposed system can achieve similar performance. Thus, the proposed hybrid BCI real-time control system is able to control the robot in the real-time environment and can be used to develop robot-aided arm training methods based on neurological rehabilitation principles for stroke and brain injury patients.


G12 signaling through c-Jun NH2-terminal kinase promotes breast cancer cell invasion.
Signaling through the heterotrimeric G protein, G12, via Rho induces a striking increase in breast cancer cell invasion. In this study, evidence is provided that the c-Jun NH(2)-terminal kinase (JNK) is a key downstream effector of G12 on this pathway. Expression of constitutively-active Gα12 or activation of G12 signaling by thrombin leads to increased JNK and c-Jun phosphorylation. Pharmacologic inhibition of JNK or knockdown of JNK expression by siRNA significantly decreases G12-induced JNK activation as well as the ability of breast cancer cells to invade a reconstituted basement membrane. Furthermore, expression of dominant-negative Rho or treatment of cells with an inhibitor of the Rho kinase, ROCK, reduces G12-induced JNK and c-Jun activation, and ROCK inhibitor treatment also inhibits G12-induced cellular invasion. JNK knockdown or ROCK inhibitor treatment has no effect on activation of Rho by G12. Taken together, our data indicate that JNK activation is required for G12-induced invasion of breast cancer cells and that JNK is downstream of Rho and ROCK on this pathway. This study implicates a G12-stimulated mitogen-activated protein kinase cascade in cancer cell invasion, and supports a role for JNK in cancer progression.


A pilot study of consolidative immunotherapy in patients with high-risk pediatric sarcomas.
Patients with metastatic or recurrent Ewing's sarcoma family of tumors and alveolar rhabdomyosarcoma have <25% 5-year survival in most studies. This study administered a novel immunotherapy regimen aimed at consolidating remission in these patients. Fifty-two patients with translocation positive, recurrent, or metastatic Ewing's sarcoma family of tumors or alveolar rhabdomyosarcoma underwent prechemotherapy cell harvest via apheresis for potential receipt of immunotherapy. Following completion of standard multimodal therapy, 30 patients ultimately initiated immunotherapy and were sequentially assigned to three cohorts. All cohorts received autologous T cells, influenza vaccinations, and dendritic cells pulsed with peptides derived from tumor-specific translocation breakpoints and E7, a peptide known to bind HLA-A2. Cohort 1 received moderate-dose recombinant human interleukin-2 (rhIL-2), cohort 2 received low-dose rhIL-2, and cohort 3 did not receive rhIL-2. All immunotherapy recipients generated influenza-specific immune responses, whereas immune responses to the translocation breakpoint peptides occurred in 39%, and only 25% of HLA-A2(+) patients developed E7-specific responses. Toxicity was minimal. Intention-to-treat analysis revealed a 31% 5-year overall survival for all patients apheresed (median potential follow-up 7.3 years) with a 43% 5-year overall survival for patients initiating immunotherapy. Consolidative immunotherapy is a scientifically based and clinically practical approach for integrating immunotherapy into a multimodal regimen for chemoresponsive cancer. Patients receiving immunotherapy experienced minimal toxicity and favorable survival. The robust influenza immune responses observed suggest that postchemotherapy immune incompetence will not fundamentally limit this approach. Future studies will seek to increase efficacy by using more immunogenic antigens and more potent dendritic cells.


Psychological distress among women with breast problems.
Visiting a physician for evaluation of a breast problem which could be cancer is often assumed to be a highly stressful experience. This study evaluates the degree of emotional distress in women about to undergo examination for signs or symptoms of breast disease. Three hundred twenty-two women who attended the Breast Problem Clinic of the Wisconsin Clinical Cancer Center were studied. Each patient completed standard self-administered psychologic tests to evaluate mood disturbance (Profile of Mood States [POMS]) and responsibility taken for overall health care (Health Locus of Control [HLCS]). Results of these tests were compared to control populations of normal college women and female psychiatric outpatients. The women seen in the Breast Problem Clinic were significantly less distressed on POMS subscales which measure depression, anger, fatigue, and confusion than both psychiatric outpatients and normal college women (P less than 0.001). A second group of 17 women who were seen in the hospital 24 to 48 hours before definitive breast cancer surgery were also studied. Women evaluated as inpatients before breast cancer surgery were more distressed than the women attending the outpatient clinic on most POMS subscales, but were not clearly different from normal college women. No differences between the groups were seen for the HLCS. These data indicate that emotional distress among women attending a breast problem clinic is not extraordinary, but that emotional distress heightens when the diagnosis of breast cancer is known.


Scanning darkfield high-resolution microendoscope for label-free microvascular imaging.
Characterization of microvascular changes during neoplastic progression has the potential to assist in discriminating precancer and early cancer from benign lesions. Here, we introduce a novel high-resolution microendoscope that leverages scanning darkfield reflectance imaging to characterize angiogenesis without exogenous contrast agents. Scanning darkfield imaging is achieved by coupling programmable illumination with a complementary metal-oxide semiconductor (CMOS) camera rolling shutter, eliminating the need for complex optomechanical components and making the system portable, low-cost (<$5,500) and simple to use. Imaging depth is extended by placing a gradient-index (GRIN) lens at the distal end of the imaging fiber to resolve subepithelial microvasculature. We validated the capability of the scanning darkfield microendoscope to visualize microvasculature at different anatomic sites in vivo by imaging the oral cavity of healthy volunteers. Images of cervical specimens resected for suspected neoplasia reveal distinct microvascular patterns in columnar and squamous epithelium with different grades of precancer, indicating the potential of scanning darkfield microendoscopy to aid in efforts to prevent cervical cancer through early diagnosis.


Effects of hyperbaric oxygen treatment on gastric cancer cell line SGC7901.
Hyperbaric oxygen (HBO) has been previously identified as an effective adjunct treatment option for the management of brain injury, diabetic ulcers and chronic wounds. However, the roles of HBO as an adjunctive therapy for tumors remain controversial. The present research project was performed to explore the effects of HBO treatment on proliferation, autophagy and endoplasmic reticulum stress response of the gastric cancer cell line, SGC7901. The present study demonstrated that, after subjecting SGC7901 cells to HBO treatment, the increase in cell proliferation was significant, compared with that of the control group. In addition, there was a significant increase in LC3-phosphatidylethanolamine conjugate (LC3-II) level, as well as binding immunoglobulin protein level, and a significant decrease in CCAAT-enhancer-binding protein homologous protein level. These suggested that hyperbaric oxygen treatment alone may promote proliferation and cell survival of gastric cancer cell SGC7901, and inhibit apoptosis through regulating cell autophagy and oxidative stress.


Development of a low-cost and user-friendly system to create personalized human digital twin.
Creating a digital twin has enormous potential in biomedical engineering. However, it is also technically challenging. No existing system can allow people who don't have the art-and-design background to create their own digital twin. To fill this gap, this study proposes a low-cost wearable system and a user-friendly framework for creating personalized digital twins with a fast speed and high fidelity. The personalized human digital twin can capture synchronized facial expressions, gaze direction, and whole-body movements for real-time rendering. The system simplifies the complex process of creating digital humans, and allows for the creation of data-driven characters without specialized skills.Clinical Relevance- This system can be used to help doctors keep track record of the patient's health status in a more visual and realistic way, supporting them in making more accurate clinical decisions, and facilitating a more detailed medical intervention.


Pharmacokinetics and adverse reactions of a new liposomal cisplatin (Lipoplatin): phase I study.
Lipoplatin, a new liposomal cisplatin formulation, is formed from cisplatin and liposomes composed of dipalmitoyl phosphatidyl glycerol (DPPG), soy phosphatidyl choline (SPC-3), cholesterol and methoxy-polyethylene glycol-distearoyl phosphatidylethanolamine (mPEG2000-DSPE). Following intravenous infusion, the nanoparticles (110 nm) are distributed into tissues and concentrate preferentially at tumor sites supposedly via extravasation through the leaky tumor vasculature. This study was designed to investigate the pharmacokinetics and the toxicity of this new liposomal cisplatin in patients with pretreated advanced malignant tumors. The drug was infused for 8 h every 14 days at escalating doses. Twenty-seven patients were included and 3-5 patients were selected for each dosage level; levels started at 25 mg/m2 and were increased by 25 to 125 mg/m2. Three patients were also treated at higher dose levels, one each at 200, 250 and 300 mg/m2. Blood was taken at certain time intervals in order to estimate total platinum plasma levels. At level 5 (125 mg/m2), grades 1 and 2 GI tract and hematological toxicities were detected. No nephrotoxicity was observed. Seven additional patients were added at the 4th level (100 mg/m2) for further pharmacokinetic evaluation. Measurement of platinum levels in the plasma of patients as a function of time showed that a maximum platinum level is attained at 6-8 h. The half-life of Lipoplatin was 60-117 h depending on the dose. Urine excretion reached about 40% of the infused dose in 3 days. The data demonstrate that Lipoplatin up to a dose of 125 mg/m2 every 14 days has no nephrotoxicity and it lacks the serious side effects of cisplatin.


[The amniotic fluid volume in uncomplicated singleton pregnancies: the ultrasonic study technics].
In 750 uncomplicated singleton pregnancies, 1765 examinations have performed to establish the normograms for 4 Ultrasound techniques of measurement of amniotic fluid volume (AFV). The 90% and 95% and 98% confidence intervals for each method across gestation (16-43 weeks) were calculated from polynomial regression equation for 50th percentile from logarithmic transformed data, and antilog values were plotted in graphical representation for modified amniotic fluid Index (MAFI). The variations of the mean values of data between weeks were statistically significant (p < 0.00001). Normograms show the progressive increase of AFV up to 27-29 weeks (27-32 weeks plateau), then declined to term. In postdate period the decrease of AFV was 7%-10% weekly for MAFI. In term gestation, the mean AFV of 5th and 95th percentile that defines the lower and upper limits were 6.7 & 21.3 cm for MAFI, 6.2 & 19.9 cm for AFI (amniotic fluid index), and for maximum vertical single pocket (MVP)--2.5 & 7.4 cm and for two-diameter pocket (TDP)--10.4 & 51.0 c2.


An automated method for adaptive radiation therapy for prostate cancer patients using continuous fiducial-based tracking.
Electromagnetic tracking technology is primarily used for continuous prostate localization during radiotherapy, but offers potential value for evaluation of dosimetric coverage and adequacy of treatment for dynamic targets. We developed a highly automated method for daily computation of cumulative dosimetric effects of intra- and inter-fraction target motion for prostate cancer patients using fiducial-based electromagnetic tracking. A computer program utilizing real-time tracking data was written to (1) prospectively determine appropriate rotational/translational motion limits for patients treated with continuous isocenter localization; (2) retrospectively analyze dosimetric target coverage after daily treatment, and (3) visualize three-dimensional rotations and translations of the prostate with respect to the planned target volume and dose matrix. We present phantom testing and a patient case to validate and demonstrate the utility of this application. Gamma analysis of planar dose computed by our application demonstrated accuracy within 1%/1 mm. Dose computation of a patient treatment revealed high variation in minimum dose to the prostate (D(min)) over 40 fractions and a drop in the D(min) of approximately 8% between a 5 mm and a 3 mm PTV margin plan. The infrastructure has been created for patient-specific treatment evaluation using continuous tracking data. This application can be used to increase confidence in treatment delivery to targets influenced by motion.


Comparison of ETDRS 7-Field to 4-Widefield Digital Imaging in the Evaluation of Diabetic Retinopathy Severity.
To compare Early Treatment Diabetic Retinopathy Study (ETDRS) severity levels between two digital fundus imaging protocols for research studies of diabetic retinopathy: the gold standard 7-field (7F) imaging and the more recent 4-widefield (4W) imaging. Two hundred twenty-two participants enrolled in the Diabetes Prevention Program Outcomes Study underwent concurrent 7F and 4W imaging. The ETDRS levels from 220 paired gradable images were determined by masked graders. Each image was graded by two independent graders with adjudication by a senior grader, if necessary. Percent agreement between graders and between imaging protocols was evaluated with kappa statistics and weighted kappa statistics. Of 220 gradable eyes, diabetic retinopathy was seen in 11.8%; this was mild in 10.4% and more than mild in 1.4% using 7F imaging. The ETDRS levels showed exact agreement of 95% between 7F and 4W imaging (weighted kappa 0.86). Intergrader agreement for each modality had exact agreement of 89% (weighted kappa of 0.73) for 7F and 91% (weighted kappa 0.77) for 4W. There is substantial agreement in the ETDRS severity level between the 7F and 4W digital imaging protocols, demonstrating that the two imaging protocols are interchangeable. Both 4W and 7F digital imaging protocols can be used for assessing ETDRS levels, even in populations with minimal diabetic retinopathy. The 4W protocol requires fewer images than the 7F, is more comfortable for the patients, is easier for photographic capture, and provides diabetic retinopathy data that is equivalent to the 7F imaging protocol.


Fractures of the neck of the talus: evaluation of reproducibility of Hawkins' classification.
To evaluate the intraobserver and interobserver reproducibility of Hawkins' classification for fractures of the neck of the talus. 20 random cases of fracture of the talus were selected, to be defined according to the classification of types by eight orthopedic surgeons, 13 orthopedic residents and 15 radiology residents. Using the statistical test of Landis and Koch, measurements of 0.627 and 0.668 were obtained in the first and second evaluations, respectively. These values define a satisfactory agreement for Hawkins' classification. We conclude that this classification is reproducible between observers, with better values for the more experienced observers. Level of Evidence I, Study Diagnostic - Investigating a diagnostic test.


Use of technology in phonological intervention.
Microcomputers can support phonological intervention in a variety of ways. Software and hardware can assist clinicians in identifying errors and establishing appropriate treatment targets. Technology can also help to determine the nature of errors so that optimal intervention methods are used. Specific technology tools for addressing phonological errors due to problems with articulation, phonemic identification, and phonetic mapping are discussed. The use of technology to document and analyze treatment performance is also addressed.


Fatigue and psychiatric disorder: different or the same?
Fatigue and psychiatric symptoms are common in the community, but their association and outcome are sparsely studied. A total of 1177 patients were recruited from UK primary care on attending their general practitioner. Fatigue and psychiatric disorder was measured at three time points with the 12-item General Health Questionnaire and the 11-item Fatigue Questionnaire. Total scores for fatigue and psychiatric disorder did not differ between the three time points and were closely correlated (r around 0.6). The association between non-co-morbid ('pure') fatigue and developing psychiatric disorder 6 months later was the same as that for being well and subsequent psychiatric disorder. Similarly, having non-co-morbid psychiatric disorder did not predict having fatigue any more than being well 6 months previously. Between 13 and 15% suffered from non-co-morbid fatigue at each time point and 2.5% suffered from fatigue at two time points 6 months apart. Less than 1% of patients suffered from non-co-morbid fatigue at all three time points. The data are consistent with the existence of 'pure' independent fatigue state. However, this state is unstable and the majority (about three-quarters) of patients become well or a case of psychiatric disorder over 6 months. A persistent, independent fatigue state lasting for 6 months can be identified in the primary-care setting, but it is uncommon of the order of 2.5%. Non-co-morbid (pure) fatigue did not predict subsequent psychiatric disorder.


Combining procalcitonin with the qSOFA and sepsis mortality prediction.
To investigate whether procalcitonin (PCT) can improve the performance of quick sequential organ failure assessment (SOFA) score in predicting sepsis mortality, we conducted a retrospective multicenter cohort study with independent validation in a prospectively collected cohort in 3 tertiary medical centers. Patients with presumed sepsis were included. Serum PCT levels were measured at admission. Quick SOFA score and systemic inflammatory response syndrome (SIRS) criteria were calculated for each patient. PCT levels were assigned into 0, 1, and 2 points for a serum level of <0.25, 0.25 to 2, and >2 ng/mL, and added to the quick sepsis-related organ failure assessment (qSOFA) score. The incremental value of PCT to qSOFA was then evaluated by logistic regression, receiver-operating characteristic (ROC) curve, and reclassification analysis.In all, 1318 patients with presumed severe infection were enrolled with a 30-day mortality of 13.5%. Serum level of PCT showed a high correlation with qSOFA score and 30-day inhospital mortality. The area under the ROC curve was 0.56 for SIRS criteria, 0.67 for qSOFA score, and 0.73 for qSOFA_PCT in predicting 30-day mortality. The risk prediction improvement was reflected by a net reclassification improvement of 35% (17%-52%). Incorporation of PCT into the qSOFA model could raise the sensitivity to 86.5% (95% confidence interval 80.6%-91.2%). In the validation cohort, qSOFA_PCT greatly improved the sensitivity to 90.9%.A simple modification of qSOFA score by adding the ordinal scale of PCT value to qSOFA could greatly improve the suboptimal sensitivity problem of qSOFA and may serve as a quick screening tool for early identification of sepsis.


Total Capture, Convection-Limited Nanofluidic Immunoassays Exhibiting Nanoconfinement Effects.
Understanding nanoconfinement phenomena is necessary to develop nanofluidic technology platforms. One example of nanoconfinement phenomena is shifts in reaction equilibria toward reaction products in nanoconfined systems, which have been predicted theoretically and observed experimentally in DNA hybridization. Here we demonstrate a convection-limited nanofluidic immunoassay that achieves total capture of a target analyte and an apparent shift in the antibody-antigen reaction equilibrium due to nanoconfinement. The system exhibits wavefronts of the target analyte that propagate along the length of the nanochannel at a velocity much slower than that of the carrier fluid. We apply an analytical model describing the propagation of these wavefronts to determine the density of capture antibody binding sites in the enclosed nanochannel for a known concentration of the target analyte. We then use this binding site density to estimate the concentration of solutions with 5× and 10× less analyte. Our analysis suggests that nanoconfinement results in a preference toward binding of the target analyte with the surface-grafted capture antibody, as evidenced by an apparent reduction in the equilibrium dissociation constant. Our findings motivate the advancement of new biomedical and chemical synthesis technologies by leveraging nanoconfinement effects, and demonstrate a useful platform for studying the effect of nanoconfinement on chemical systems.


Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient.
We found that supernatants of leukapheresis products (SLPs) of patients mobilized with granulocyte-colony-stimulating factor (G-CSF) or the various components of SLPs (fibrinogen, fibronectin, soluble vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], and urokinase plasminogen activator receptor [uPAR]) increase the chemotactic responses of hematopoietic stem/progenitor cells (HSPCs) to stromal-derived factor-1 (SDF-1). However, alone they do not chemoattract HSPCs, but they do increase or prime the cells' chemotactic responses to a low or threshold dose of SDF-1. We observed that SLPs increased calcium flux, phosphorylation of mitogen-activated protein kinase (MAPK) p42/44 and AKT, secretion of matrix metalloproteinases, and adhesion to endothelium in CD34+ cells. Furthermore, SLPs increased SDF-dependent actin polymerization and significantly enhanced the homing of human cord blood (CB)- and bone marrow (BM)-derived CD34+ cells in a NOD/SCID mouse transplantation model. Moreover, the sensitization or priming of cell chemotaxis to an SDF-1 gradient was dependent on cholesterol content in the cell membrane and on the incorporation of the SDF-1 binding receptor CXCR4 and the small GTPase Rac-1 into membrane lipid rafts. This colocalization of CXCR4 and Rac-1 in lipid rafts facilitated guanosine triphosphate (GTP) binding/activation of Rac-1. Hence, we postulate that CXCR4 could be primed by various factors related to leukapheresis and mobilization that increase its association with membrane lipid rafts, allowing the HSPCs to better sense the SDF-1 gradient. This may partially explain why HSPCs from mobilized peripheral blood leukapheresis products engraft more quickly in patients than do those from BM or CB. Based on our findings, we suggest that the homing of HSPCs is optimal when CXCR4 is incorporated in membrane lipid rafts and that ex vivo priming of HSPCs with some of the SLP-related molecules before transplantation could increase their engraftment.


A comparative trial of the diagnostic quality of and tolerance for two low concentration low osmolality contrast media for phlebography.
We report a prospective randomised double blind study comparing the diagnostic quality of and tolerance for ascending phlebography in 100 patients using two different low osmolality contrast media, ioxaglate and iohexol, at a concentration of 200 mg I/ml. The immediate and delayed side effects were minimal in both groups and the difference between the two media was not statistically significant. All the phlebograms were of diagnostic quality. We conclude that both ioxaglate and iohexol are suitable agents for leg phlebography in low concentrations.


Critical limb ischaemia in the time of COVID-19: establishing ambulatory service provision.
The coronavirus disease 2019 (COVID-19) pandemic enforced changes to healthcare services at a pace and extent not seen previously in the NHS. The Royal Devon and Exeter provides regional vascular surgery services. A consultant-led urgent 'hot clinic' was established, providing patients with ambulatory care. We aim to describe the service for critical limb ischaemia (CLI) before and during the COVID-19 pandemic, and evaluate this against recommended best practice. Retrospective review of electronic databases and records of patients with CLI during a non-COVID vs COVID-19 period. Primary outcome measures were those established by guidance from the Vascular Society of Great Britain and Ireland. Non-COVID vs COVID-19: total patients n=97 vs 96, of which CLI patients n=29 vs 21. Median length of stay 15 vs 0 days (p<0.001); median time from referral to specialist review 0 vs 3 days (p<0.001); multidisciplinary team meeting (MDT) recorded 3% vs 29%; median time to intervention 6 vs 8 days; conservative management 52% vs 67%; endovascular 28% vs 10%; open surgery 21% vs 24%; 30-day survival 79% vs 76%. COVID-19 imposed a major change to the service for patients with CLI with a focus on ambulatory care pathways for diagnosis and intervention. We observe a significant reduction in overall length of stay with no clinically significant change in time to consultant review, time to imaging, overall management strategy or outcomes. The results of this study show that patients with CLI can be managed safely and effectively on an ambulatory basis in accordance with established best practice.


Mechanisms of surfactant dysfunction in early acute lung injury.
Surfactant dysfunction that occurs during acute lung injury is associated with alterations in phospholipid, total protein, and surfactant apoprotein content. The functional importance of these changes was examined by characterizing the biophysical properties and biochemical composition of lung surfactant from endotoxin-treated guinea pigs (LPS) with acute lung injury. Static and dynamic lung compliance significantly decreased following endotoxin exposure. Lavage fluid demonstrated a neutrophil predominance, and tissue histopathology revealed inflammation consistent with acute lung injury. LPS surfactant isolated by ultracentrifugation had minimum surface tensions of 21 dynes/cm compared to 2 dynes/cm among control samples. Biochemical abnormalities in LPS surfactant included increased total protein, decreased phosphatidylcholine, and increased sphingomyelin, phosphatidylethanolamine, and lysophosphatidylcholine. The addition to normal guinea pig surfactant of butanol extracts precipitated from lavage fluid of LPS animals and containing known amounts of protein caused elevations in minimum surface tensions to > or = 20 dynes/cm at protein to phospholipid ratios equivalent to those observed in LPS surfactant pellets. Addition of equal amounts of precipitate isolated from control animals had no effect on interfacial properties. Furthermore, addition of lysophosphatidylcholine and sphingomyelin to normal surfactant to simulate composition changes observed in LPS surfactant had minimal effect on surface film behavior. The results support the hypothesis that aqueous soluble inhibitors of surfactant are generated within the alveolar compartment during acute inflammation, and that surfactant dysfunction cannot be accounted for on the basis of phospholipid composition changes.


Trends in research on the tutor in problem-based learning: conclusions and implications for educational practice and research.
The tutor role in problem-based learning (PBL) has attracted the interest of many researchers and has led to an abundance of studies. This article reports on major trends in studies investigating the tutor during the past 10 years. Three major trends were observed by the authors while analysing the studies conducted: studies on the differential influence of content expert and non-content expert tutors on student achievement, studies on process variables, and studies on the relationship between tutor characteristics and differential contextual circumstances. The aim of this article is to summarize the main findings of the studies conducted so far within the three trends observed, to provide directions for educational practitioners and policy makers, and to suggest directions for future research questions. The studies included were selected by conducting a literature search in medical journals, which was complemented with the personal archives of the authors. The results of the studies conducted within the three trends of research have led to advanced insights in tutoring. The outcomes revealed that content expert tutors tend to use their subject-matter expertise more to direct the discussion in the tutorial group, whereas non-content expert tutors tend to use their process-facilitation expertise more to direct the tutorial group. Furthermore, a tutor's performance is not a stable characteristic but is partly situation specific. It is concluded that a tutor should both know how to deal with the subject matter expertise and should know how to facilitate the learning process. Faculty and policy makers should put substantial efforts into designing curricula and cases and developing tutors' skills by faculty development strategies that stimulate reflection. The research agenda should be driven more by modern educational theories of learning in which tutoring is a process aimed at stimulating constructive, self-directed, situated and collaborative learning by students. Furthermore, more qualitative studies should be conducted to gain better insights in teachers' conceptions about the tutor role and student learning to better understand their behaviours.


An ecological perspective of Listeria monocytogenes biofilms in food processing facilities.
Listeria monocytogenes can enter the food chain at virtually any point. However, food processing environments seem to be of particular importance. From an ecological point of view, food processing facilities are microbial habitats that are constantly disturbed by cleaning and sanitizing procedures. Although L. monocytogenes is considered ubiquitous in nature, it is important to recognize that not all L. monocytogenes strains appear to be equally distributed; the distribution of the organism seems to be related to certain habitats. Currently, no direct evidence exists that L. monocytogenes-associated biofilms have played a role in food contamination or foodborne outbreaks, likely because biofilm isolation and identification are not part of an outbreak investigation, or the definition of biofilm is unclear. Because L. monocytogenes is known to colonize surfaces, we suggest that contamination patterns may be studied in the context of how biofilm formation is influenced by the environment within food processing facilities. In this review, direct and indirect epidemiological and phenotypic evidence of lineage-related biofilm formation capacity to specific ecological niches will be discussed. A critical view on the development of the biofilm concept, focused on the practical implications, strengths, and weaknesses of the current definitions also is discussed. The idea that biofilm formation may be an alternative surrogate for microbial fitness is proposed. Furthermore, current research on the influence of environmental factors on biofilm formation is discussed.


[The role of stress axes in cancer incidence and proliferation].
Psychosocial stressors can modulate the different stages of neoplastic events. It is established that there is activation of 2 well-known stress axes under stress, the hypothalamic-pituitary-adrenal axis and sympatho-adrenal-medullary axis, where especially the proliferating promoting effects on the malignant tumor events are known to depend on β-adrenergic receptors. A new model focuses on the positive activating stress, which leads through the activation of the sympathetic hypothalamic-adipocyte axis to inhibition of tumor growth and reduction of obesity. This leads in mice to increased gene expression of the neurotrophin BDNF, which activates the sympathetic fibers of the white adipose tissue. Over consecutive stimulation of the β-adrenergic receptors and thus the release of leptin, its promotional effect on the tumor growth is inhibited. In the clinical context, these results support the role of complex β-adrenergic signal transduction pathways.


The Role of the Angular Gyrus in Goal-directed Behavior-Two Transcranial Magnetic Stimulation Studies Examining Response Outcome Learning and Outcome Anticipation.
Learning the contingencies between a situational context (S), one's own responses (R), and their outcomes (O) and selecting responses according to their anticipated outcomes is the basis of a goal-directed behavior. Previous imaging studies found the angular gyrus (AG) to be correlated to both the representation of R-O associations and outcome-based response selection. Based on this correlational relationship, we investigated the causal link between AG function and goal-directed behavior in offline and online TMS experiments. To this end, we employed an experimental R-O compatibility paradigm testing outcome anticipation during response selection and S-R-O knowledge to probe S-R-O learning. In Experiment 1, we applied 1-Hz rTMS offline to the AG or the vertex before participants performed the experimental tasks. In Experiment 2, we applied online 10-Hz pulse trains to the AG or used sham stimulation during an early action selection stage in half of the trials. In both experiments, the R-O compatibility effect was unaltered when response selection was outcome-based, suggesting no causal role of the AG in outcome anticipation during response selection. However, in both experiments, groups with AG stimulation showed significantly modulated knowledge of S-R-O associations in a posttest. Additionally, in an explorative analysis, we found an induced R-O compatibility effect later in the experiment when response selection was guided by stimulus-response rules, suggesting reduced selectivity of outcome anticipation. We discuss possible compensatory behavioral and brain mechanism as well as specific TMS-related methodical considerations demonstrating important implications for further studies investigating cognitive function by means of TMS.


[Clinical evaluation of fibromyalgia].
Fibromyalgia is characterized by diffuse, persistent and unexplained muscle pain associated with tenderness (mechanical allodynia) and unspecific symptoms. Diagnosis criteria as well as pathophysiological mechanisms are still unclear, justifying appropriate questionnaires and clinical investigations. Several questionnaires including visual analogic scales with respect to pain, fatigue, sleep or mood disorders have been used in fibromyalgia such as Fibromyalgia Impact Questionnaire (30 items) and the European List for Fibromyalgia Evaluation (53 items). Similarly several methods have been proposed to evaluate tenderness in fibromyalgia patients: The study of tender points involves their number (normal value < 4/18), or their pain mean intensity score and the sum of their sensitivities defining the tender point index (normal value < 11/72); The average pain threshold (normal value > 4 kg/cm(2)) is more precise, requiring sophisticated devices (mechanical algometers) and physician training; Less complex than pain threshold measurement, more reliable than the tender points number or index, the tensiometer induced myalgia (normal value > 210 mmHg) is probably a promising new alternative way to screen for fibromyalgia. Even if further studies are needed, diagnosis approach of fibromyalgia could be improved by new tools such as the European List for Fibromyalgia Evaluation and algotensiometry.


[Costs attributable to obesity, hypertension, and diabetes in the Unified Health System, Brazil, 2018Costos atribuibles a la obesidad, la hipertensión y la diabetes en el Sistema Único de Salud de Brasil, 2018].
To estimate the cost attributable to arterial hypertension, diabetes and obesity in the Unified Health System of Brazil in 2018. The study estimated the cost attributable to non-communicable chronic diseases based on relative risk and population prevalence of hypertension, diabetes, and obesity, considering the cost of hospitalizations, outpatient procedures, and medications distributed by the SUS to treat these diseases. Cost data were obtained from SUS information systems. The analysis explored the cost of disease according to sex and age in the adult population. The total cost of hypertension, diabetes, and obesity in the SUS reached R$ 3.45 billion (95%CI: 3.15-3.75) in 2018, that is, more than US$ 890 million. Of this amount, 59% referred to the treatment of hypertension, 30% to diabetes, and 11% to obesity. The age group from 30 to 69 years accounted for 72% of the total costs, and women accounted for 56%. When obesity was considered separately as a risk factor for hypertension and diabetes, the cost attributable to this diseases reached R$ 1.42 billion (95%CI: 0.98-1.87), i.e., 41% of the total cost. The estimates of costs attributable to the main chronic diseases associated with inadequate diet revealed a heavy economic burden of these disorders for the SUS. The data show the need to prioritize integrated and intersectoral policies for the prevention and control of hypertension, diabetes, and obesity, and may support the advocacy for interventions such as fiscal and regulatory measures to ensure that the objectives of the United Nations Decade of Action on Nutrition are met.


[Unusual case of pseudotumoral hip injury due to gout: case report].
Gout is known as arthropathy due to the deposit of monosodium urate crystals; This pathology comprises a set of clinical and radiographic tests in the context of the intra-articular presence of said crystals. It is a chronic disease associated with other comorbidities such as arterial hypertension, osteoarthritis, diabetes mellitus, etc. The case of a patient with gouty arthritis with consequent hip lesion with a pseudotumoral appearance difficult to diagnose is presented, in order to highlight the importance of this, as well as the appropriate follow-up and treatment for this chronic pathology. A 51-year-old male patient, with a history of hip osteoarthritis and gout. The symptoms and signs were pain in the right hip with an 8/10 on an analogue pain scale, associated with functional limitation characterized by reduced range of motion and impossibility of standing. Imaging studies are carried out which are suggestive of a tumor lesion at the proximal femur with malignant characteristics, for which a biopsy and subsequent histopathological diagnosis of gouty tophi is performed. Gout is a prevalent disease in the adult population, however, its infrequent joint location can result in a difficult diagnosis, so it is necessary not to rule out this entity and to carry out specific studies for its identification.


Stem cells: a potential treatment option for kidney diseases.
The prevalence of kidney diseases is emerging as a public health problem. Stem cells (SCs), currently considered as a promising tool for therapeutic application, have aroused considerable interest and expectations. With self-renewal capabilities and great potential for proliferation and differentiation, stem cell therapy opens new avenues for the development of renal function and structural repair in kidney diseases. Mounting evidence suggests that stem cells exert a therapeutic effect mainly by replacing damaged tissues and paracrine pathways. The benefits of various types of SCs in acute kidney disease and chronic kidney disease have been demonstrated in preclinical studies, and preliminary results of clinical trials present its safety and tolerability. This review will focus on the stem cell-based therapy approaches for the treatment of kidney diseases, including various cell sources used, possible mechanisms involved, and outcomes that are generated so far, along with prospects and challenges in clinical application.


Hemocyte types and total and differential counts in unparasitized and parasitized Anastrepha obliqua (Diptera, Tephritidae) larvae.
The hemocyte types, in addition to total and differential hemocyte counts were studied in parasitized and unparasitized Anastrepha obliqua larvae at the beginning and at the end of the third instar. In both developmental phases, in parasitized and unparasitized larvae, prohemocytes, plasmatocytes, granulocytes, adipohemocytes, spherulocytes and oenocytoids cells were observed. Mitotic figures indicate prohemocytes as stem cells. Prohemocytes, plasmatocytes and granulocytes are the most numerous cells in the hemolymph of A. obliqua. Difference in the total number of hemocytes was observed between unparasitized and parasitized larvae at the end of the third instar, but not at the beginning.


[Stress levels in health care workers from primary care units].
To determine stress levels in health care workers (HCW) from Primary Care Units (PCU). A descriptive study in HCW from two PCU was done to investigate stress in relation with environment, activity/occupation, relationship and lifestyle. The "Individual Evaluation Stress Inventory" was applied to 167 HCW from different job areas and categories. The mean age was 41 +/- 8 years; 31 % were males, and the worker seniority mean age was 16.2 +/- 5.9 years. The population was constituted by 32 % physicians; 38 % nurser/medical assistants and 30 % from the support areas. A low stress was presented in 11 %; minimum in 25 %; normal level in 37 %; high in 25 %, and 2 % had critical stress level. There was no significant association between stress and other variables. HCW with higher stress were married (56 % versus 78 %, p = 0.06), had less seniority (13.6 +/- 6.0 versus 16.6 +/- 6.0, p = 0.09). Females had higher stress than males. Stress in HCW was inferior to international and national score. The principal associated factors were: being married, having less seniority and being female.


Interplay between Vitamin D and Sphingolipids in Cardiometabolic Diseases.
Sphingolipids (SLs) are structural, bioactive molecules with several key cellular roles, whereas 1,25-dihydroxyvitamin D (1,25(OH)D), the active form of vitamin D, is considered the major regulator of calcium homeostasis, although it also exerts other extraskeletal effects. Many studies reported the physiological connection between vitamin D and SLs, highlighting not only the effects of vitamin D on SL metabolism and signaling but also the influence of SLs on vitamin D levels and function, thus strongly suggesting a crosstalk between these molecules. After a brief description of 1,25(OH)D and SL metabolism, this review aims to discuss the preclinical and clinical evidence on the crosstalk between SLs and 1,25(OH)D, with a special focus on cardiometabolic diseases.


Placental growth factor (PlGF) enhances breast cancer cell motility by mobilising ERK1/2 phosphorylation and cytoskeletal rearrangement.
During metastasis, cancer cells migrate away from the primary tumour and invade the circulatory system and distal tissues. The stimulatory effect of growth factors has been implicated in the migration process. Placental growth factor (PlGF), expressed by 30-50% of primary breast cancers, stimulates measurable breast cancer cell motility in vitro within 3 h. This implies that PlGF activates intracellular signalling kinases and cytoskeletal remodelling necessary for cellular migration. The PlGF-mediated motility is prevented by an Flt-1-antagonising peptide, BP-1, and anti-PlGF antibody. The purpose of this study was to determine the intracellular effects of PlGF and the inhibiting peptide, BP-1. Anti-PlGF receptor (anti-Flt-1) antibody and inhibitors of intracellular kinases were used for analysis of PlGF-delivered intracellular signals that result in motility. The effects of PlGF and BP-1 on kinase activation, intermediate filament (IF) protein stability, and the actin cytoskeleton were determined by immunohistochemistry, cellular migration assays, and immunoblots. Placental growth factor stimulated phosphorylation of extracellular-regulated kinase (ERK)1/2 (pERK) in breast cancer cell lines that also increased motility. In the presence of PlGF, BP-1 decreased cellular motility, reversed ERK1/2 phosphorylation, and decreased nuclear and peripheral pERK1/2. ERK1/2 kinases are associated with rearrangements of the actin and IF components of the cellular cytoskeleton. The PlGF caused rearrangements of the actin cytoskeleton, which were blocked by BP-1. The PlGF also stabilised cytokeratin 19 and vimentin expression in MDA-MB-231 human breast cancer cells in the absence of de novo transcription and translation. The PlGF activates ERK1/2 kinases, which are associated with cellular motility, in breast cancer cells. Several of these activating events are blocked by BP-1, which may explain its anti-tumour activity.


Cellular apoptosis susceptibility (chromosome segregation 1-like, CSE1L) gene is a key regulator of apoptosis, migration and invasion in colorectal cancer.
Cellular apoptosis susceptibility (chromosome segregation 1-like, CSE1L) gene maps to chromosomal region 20q13.13, a region frequently amplified in solid tumours. In this study, we investigated the roles played by CSE1L in colorectal cancer by examining CSE1L expression and clinico-pathological parameters in colorectal cancer and investigating the effect of CSE1L on the viability, adhesion and migration of colorectal cancer cells. RT-PCR showed that CSE1L mRNA was over-expressed in colorectal cancer. CSE1L depletion by knock-down with CSE1L-specific siRNA significantly reduced viability in HCT116 cells (p = 0.004) and SW480 cells (p = 0.003) whilst significantly increasing the proportion of apoptotic HCT116 cells (p < 0.001) and SW480 cells (p < 0.001). Furthermore, CSE1L depletion significantly reduced the adhesive capacity of HCT116 (p = 0.003) and SW480 cells (p = 0.004). Analysis by qRT-PCR following CSE1L siRNA treatment of HCT116 and SW480 cells showed significant modulation of key apoptotic (p53, p73 and BAK) and adhesive (E-cadherin, Ep-CAM and ICAM-1) molecules. Immunohistochemistry of a colorectal cancer tissue microarray showed that CSE1L had a significantly increased level in colorectal cancer compared to normal colorectal epithelium (p < 0.001). There were significant decreases in both nuclear (p = 0.006) and cytoplasmic (p = 0.003) staining of CSE1L in tumours with lymph node metastasis (stage 3 tumours) compared with lymph node-negative tumours (stage 1 and 2 tumours). In lymph node-negative patients, poor survival was associated with increased CSE1L cytoplasmic expression (p = 0.042). These results indicate that CSE1L is associated with viability and apoptosis, cellular adhesion and invasion, thus implicating CSE1L in the progression of colorectal cancer.


Translational Significance of GMF-β Inhibition by Indazole-4-yl-methanol in Enteric Glial Cells for Treating Multiple Sclerosis.
In the emerging context of gut-brain control of multiple sclerosis (MS), developing therapeutics targeting proinflammatory proteins controlling the gut-brain immunomodulation is welcoming. One such immunomodulator is glia maturation factor-β (GMF-β). GMF-β activation following GMF-β-ser-83 phosphorylation upregulates proinflammatory responses and exacerbates experimental autoimmune encephalomyelitis (EAE). Notably, GMF-β-/- mice exhibited no EAE symptoms. Thus, we identified 1H-indazole-4-yl-methanol (GMFBI.1) inhibitor which blocked GMF-β-ser-83 phosphorylation critical in EAE suppression. To establish gut GMF-β's role in EAE in the context of gut-brain involvement in neurodegenerative diseases, we altered gut GMFBI.1 bioavailability as an index of EAE suppression. At first, we identified Miglyol 812N as a suitable biocompatible GMFBI.1 carrier compared to other FDA-approved carriers using in silico molecular docking analysis. GMFBI.1 administration in Miglyol 812N enhanced its retention/brain permeability. Subsequently, we administered GMFBI.1-Miglyol 812N by subcutaneous/oral routes at different doses with differential GMFBI.1 bioavailability in gut and brain to assess the role of local GMFBI.1 bioavailability in EAE reversal by a pharmacokinetic approach. Deprival of gut GMFBI.1 bioavailability led to partial EAE suppression despite having sufficient GMFBI.1 in circulation to inhibit brain GMF-β activity. Restoration of gut GMFBI.1 bioavailability led to complete EAE reversal. Molecular pathology behind partial/full EAE reversal was associated with differential GMF-β-Ser-83 phosphorylation/GM-CSF expression levels in enteric glial cells owing to GMFBI.1 bioavailability. In addition, we observed leaky gut reversal, tight junction protein ZO-1 restoration, beneficial gut microbiome repopulation, recovery from gut dysbiosis, and upregulation of Treg cells. GMFBI.1's dual gut/brain targeting of GMF-β has therapeutical/translational potential in controlling autoimmunity in MS.


The effect of inclined position on stone free rates in patients with lower caliceal stones during SWL session.
To compare the outcomes of shock wave lithotripsy (SWL) combined with inclined position and SWL alone in patients with lower pole calyx stones. Seven hundred forty patients who underwent SWL treatment for lower pole renal stones with a total diameter of 2 cm or less were prospectively randomized into two groups. They were comparable in terms of age, sex, and stone diameters. Patients with lower calyceal stones (4-20 mm) were randomized to SWL (368 patients) or SWL with simultaneous inclination (372 patients) with 30o head down Trendelenburg position). Shock wave and session numbers were standardized according to stone size. Additional standardized shock waves were given to patients with stone fragments determined by kidney urinary bladder film and ultrasound at weeks 1, 4, 10. The overall stone free rate (SFR) was 73% (268/368) in patients with SWL alone and 81% (300/372) in SWL with inclination at the end of 12th week (p = 0.015). No significant adverse events were noted in both treatment groups. Simultaneous inclination of patients during SWL session increase SFR in lower caliceal stones significantly compared to SWL treatment alone.


Tibia Shaft Fractures in Adolescents: How and When Can They be Managed Successfully With Cast Treatment?
Despite the increasing popularity of operative treatment in adolescent tibia fractures, casting remains a viable first-line treatment. Because the selection bias in published reports does not allow direct comparison between casting and flexible nail treatment of closed pediatric tibia fractures, it is unclear whether flexible nailing offers any advantages over casting. This overview discusses parameters of acceptable alignment, indications, techniques for successful reduction and casting, subsequent inpatient and outpatient management including wedging of casted tibia fractures, expected outcomes, and comparison of casting with flexible nailing. As with any orthopaedic procedure, careful attention to patient selection, indications, and detail facilitates successful cast treatment in this older pediatric population.


More than meets the eye: relationship between low health literacy and poor vision in hospitalized patients.
Patient-centered care includes involving patients and their families in self-management of chronic diseases. Identifying and addressing barriers to self-management, including those related to health literacy and vision limitations, may enhance one's ability to self-manage. A set of brief verbal screening questions (BVSQ) that does not rely on sufficient vision to assess health literacy was developed by Chew and colleagues in the outpatient setting. The authors aimed to evaluate the usefulness of this tool for hospitalized patients and to determine the prevalence of poor vision among inpatients. In a prospective study, the BVSQ and the Rapid Estimate of Adult Learning in Medicine-Revised (REALM-R; among participants with sufficient vision, ≥ 20/50 Snellen) were administered to general medicine inpatients. Of 893 participants, 79% were African American, and 57% were female; the mean age was 53 years. Among 668 participants who completed both tools, the proportion with low health literacy was 38% with the BVSQ versus 47% with the REALM-R (p = .0001). Almost one fourth of participants had insufficient vision; participants with insufficient vision were more likely to be identified as having low health literacy by the BVSQ, compared with those with sufficient vision (59% vs. 38%, p < .001).


Metabolic cycles in a circannual hibernator.
Hibernation as manifested in ground squirrels is arguably the most plastic and extreme of physiological phenotypes in mammals. Homeostasis is challenged by prolonged fasting accompanied by heterothermy, yet must be facilitated for survival. We performed LC and GC-MS metabolomic profiling of plasma samples taken reproducibly during seven natural stages of the hibernator's year, three in summer and four in winter (each n ≥ 5), employing a nontargeted approach to define the metabolite shifts associated with the phenotype. We quantified 231 named metabolites; 106 of these altered significantly, demarcating a cycle within a cycle where torpor-arousal cycles recur during the winter portion of the seasonal cycle. A number of robust hibernation biomarkers that alter with season and winter stage are identified, including specific free fatty acids, antioxidants, and previously unpublished modified amino acids that are likely to be associated with the fasting state. The major pattern in metabolite levels is one of either depletion or accrual during torpor, followed by reversal to an apparent homeostatic level by interbout arousal. This finding provides new data that strongly support the predictions of a long-standing hypothesis that periodic arousals are necessary to restore metabolic homeostasis.


A method for extraction and 2-D gel electrophoresis of plant proteins with selective isoelectric points.
A procedure for extracting and separating plant proteins by isoelectric point and 2-dimensional gel electrophoresis (2-DGE) is presented. Resolution of basic proteins using nonequilibrium pH gradient electrophoresis (NEPHGE) increased when run without the presence of acidic proteins. Isoelectric focusing without basic proteins favored the migration of the acidic and the more neutrally charged proteins into tube gels. Without the basic groups, negatively charged proteins could be focused for 20 h and longer without consideration of cathodic drift effects. The procedure facilitates gel analysis by simplifying the protein pattern on second dimension gels. Another advantage is that greater relative amounts of any class of proteins can be electrophoresed in the first dimension gels.


Hepatoprotective activity of Patrinia scabiosaefolia Fisch and quality evaluation based on UPLC fingerprint and multi-component analysis.
To establish a quality evaluation method for Patrinia scabiosaefolia Fisch (PS), as well as to study the anti-inflammatory and hepatoprotective effects of the aqueous extract of Patrinia scabiosaefolia Fisch (APS). We used ultra performance liquid chromatography (UPLC) to establish fingerprint and content determination method for PS. The alcoholic liver injury model was prepared by feeding Lieber-DeCarli alcohol liquid feed to mice. We determined the levels of ALT, AST, TC, TG in serum, as well as GSH, MDA in the liver. The mRNA relative expression levels of TNF-α, IL-6, IL-1β, INOS and COX-2 were detected by qRT-PCR, and liver tissues were taken for pathological examination. The fingerprints of 16 batches of PS were established, and 3 component peaks were identified, which were chlorogenic acid (CA), isochlorogenic acid A (ICAA) and isochlorogenic acid C (ICAC). The similarity of the 6 common peaks was between 0.924 and 1.000. A mice model of alcoholic liver injury was successfully made by mixing alcohol liquid feed. The levels of ALT, AST, TC and TG in serum and MDA, TNF-α, IL-1β, LL-6, COX-2 and INOS mRNA in liver were effectively reduced in the drug administration group. The levels of GSH in mouse liver tissue were increased in the drug administration group. The method has good repeatability, stability and feasibility, and it meets the requirements for Quality evaluation. APS exhibits a protective effect against alcoholic liver injury (ALI) in mice.


Survival prediction in patients with glioblastoma multiforme by human telomerase genetic variation.
Glioblastoma multiforme (GBM) is the most common and aggressive glioma with the poorest survival. Use of biomarkers for screening patients with GBM may be used to modify treatments and improve outcomes. The level of human telomerase (hTERT) expression is an independent predictor of outcome of many cancers, and a functional variant of hTERT MNS16A (shorter tandem repeats or short [S] allele) is associated with increased hTERT mRNA expression. We investigated whether hTERT MNS16A variant genotype predicted survival in GBM patients. We genotyped hTERT MNS16A in 299 GBM patients using polymerase chain reaction and determined hTERT genotype by classifying the DNA band of 243 or 272 base pairs (bp) as S allele and 302 or 333 bp as long (L) allele. We compared overall survival using Kaplan-Meier estimates and equality of survival distributions using the log-rank test, and we computed univariate and multivariate Cox proportional hazards models to estimate the effects of selected variables. Overall survival differed significantly by hTERT MNS16A genotype, with median survivals of 25.1, 14.7, and 14.6 months for the SS, SL, and LL genotypes, respectively. Compared with the SS genotype, the hazard ratios for the SL and LL genotypes were 1.69 and 1.87, respectively, after adjustment for other factors. Multivariate Cox regression analysis showed an independent statistically significant association between the hTERT MNS16A variant genotype and outcome. A functional hTERT MNS16A genotype is a potential biomarker for assessment of survival outcome of GBM. Larger studies are needed to verify these findings.


Severe childhood malaria syndromes defined by plasma proteome profiles.
Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore it is important to understand the pathology underlying the development of CM and SMA, as opposed to uncomplicated malaria (UM). Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis of these syndromes. Plasma and comprehensive clinical data for discovery and validation cohorts were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, an urban and densely populated holoendemic malaria area in Nigeria. A total of 946 children participated in this study. Plasma was subjected to high-throughput proteomic profiling. Statistical pattern-recognition methods were used to find proteome-patterns that defined disease groups. Plasma proteome-patterns accurately distinguished children with CM and with SMA from those with UM, and from healthy or severely ill malaria-negative children. We report that an accurate definition of the major childhood malaria syndromes can be achieved using plasma proteome-patterns. Our proteomic data can be exploited to understand the pathogenesis of the different childhood severe malaria syndromes.


Chemical composition and free radical-scavenging, anticancer and anti-inflammatory activities of the essential oil from Ocimum kilimandscharicum.
The essential oil from the leaves of Ocimum kilimandscharicum (EOOK), collected in Dourados-MS, was investigated for anticancer, anti-inflammatory and antioxidant activity and chemical composition. The essential oil was extracted by hydrodistillation, and the chemical composition was performed by gas chromatography-mass spectrometry. The essential oil was evaluated for free radical-scavenging activity using the DPPH assay and was tested in an anticancer assay against ten human cancer cell lines. The response parameter (GI50) was calculated for the cell lines tested. The anti-inflammatory activity was evaluated using carrageenan-induced pleurisy in mice. The chemical composition showed 45 components with a predominance of monoterpenes, such as camphor (51.81%), 1,8 cineole (20.13%) and limonene (11.23%). The EOOK exhibited potent free radical-scavenging activity by the DPPH assay with a GI50 of 8.31 μg/ml. The major constituents, pure camphor (IC50=12.56 μg/ml) and mixture of the limonene: 1, 8 cineole (IC50=23.25 μg/ml) displayed a potent activity. The oral administration of EOOK (at 30 and 100 mg kg(-1)), as well as the pure camphor or a mixture of 1,8 cineole with limonene, significantly inhibited the carrageenan (Cg) induced pleurisy, reducing the migration of total leukocytes in mice by 82 ± 4% (30 mg kg(-1) of EOOK), 95 ± 4% (100 mg kg(-1) of EOOK), 83 ± 9% (camphor) and 80 ± 5% (mixture of 1,8 cineole:limonene 1:1). In vitro cytotoxicity screening against a human ovarian cancer cell line displayed high selectivity and potent anticancer activity with GI50=31.90 mg ml(-1). This work describes the anti-inflammatory, anticancer and antioxidant effects of EOOK for the first time. The essential oil exhibited marked anti-inflammatory, antioxidant and anticancer effects, an effect that can be attributed the presence of majorital compounds, and the response profiles from chemical composition differed from other oils collected in different locales.


"In Utter Fearlessness of the Reigning Disease": Imagined Immunities and the Outbreak Narratives of Charles Brockden Brown.
With an increased focus on the intersection of literature and medicine, contagion has become something of a scholarly buzzword in early American studies: it serves metaphorically to demarcate the postcolonial other, demonstrates the transmissibility of revolutionary rhetoric, highlights the instability of republican government, and embodies fears of racial mixture. In this essay, I shift the emphasis from a discourse of contagion (often associated with a fear of the foreign) to a discourse of immunity (a fear associated with foreign immunities) in order to demonstrate a more affirmative biopolitics in Charles Brockden Brown's 1790s outbreak narratives. This affirmative biopolitics can emerge only after deconstructing the intersection of biology and politics in the so-called "age of democratic revolutions."


Application of Novel Anion-Exchange Blend Membranes (AEBMs) to Vanadium Redox Flow Batteries.
Both cation-exchange membranes and anion-exchange membranes are used as ion conducting membranes in vanadium redox flow batteries (VRFBs). Anion-exchange membranes (AEMs) are applied in vanadium redox flow batteries due to the high blocking property of vanadium ions via the Donnan exclusion effect. In this study, novel anion-exchange blend membranes (AEBMs) were prepared, characterized, and applied in VRFBs. Bromomethylated poly(2,6-dimethyl-1,4-phenylene oxide), poly[(1-(4,4′-diphenylether)-5-oxybenzimidazole)-benzimidazole] (PBI-OO) and sulfonated polyether sulfone polymer were combined to prepare 3-component AEBMs with 1,2,4,5-tetramethylimidazole (TMIm) for quaternization. 3-component AEBMs showed significantly enhanced chemical and mechanical properties compared with those of 2-component AEBMs, resulting in an improved performance in VRFBs. The compositions of the anion-exchange polymers in 3-component AEBMs were systematically varied to optimize the AEBMs for the redox-flow battery application. While the 3-component AEBMs showed comparable efficiencies with Nafion® 212 membranes, they displayed improved vanadium ions cross-over as was confirmed by open circuit voltage tests and capacity fade tests conducted in VRFBs. In addition, one of the synthesized 3-component AEBM had a superior coulombic efficiency and capacity retention in a charging⁻discharging test over 300 cycles at a current density of 40 mA/cm². It can thus be concluded that 3-component AEBMs are promising candidates for long-term operation in VRFBs.


Changes in sarcomere length during isometric tension development in frog skeletal muscle.
1. Changes in sarcomere length during isometric contraction of isolated semitendinosus muscle fibres from the frog were studied using laser diffraction techniques. Movements of the first-order diffraction line relative to the zero-order reference were recorded from a screen on continuously moving film. Sarcomere length changes of 50 A could be resolved in this way.2. Following a latent period of approximately 12 msec after the stimulus of a single skeletal muscle fibre at 1-2 degrees C, there appeared to be a simultaneous onset of tension development and sarcomere shortening. Provided that the fibre was uniformly excited along its length, different regions shortened together by approximately the same amount. The extent of the shortening was a function of the total compliance of the tendons and tension measuring device.3. During the plateau of a smooth tetanus no fluctuations of first-order line width or zero- to first-order line spacing were detectable at any point examined along the preparation. This finding provides evidence that, in a functionally intact fibre, no synchronous oscillations of the sarcomeres, at least no length changes exceeding 50 A, occur during a fused tetanus. Furthermore, the fact that the first-order line did not increase in width as the preparation went from rest to full activity indicates that contraction proceeds without appreciable change in distribution of sarcomere lengths.4. The sarcomere movements during relaxation differed along the length of the fibre. As the tension declined smoothly, sarcomeres in some parts of the fibre underwent further shortening, while the end sarcomeres near the tendons and in one or two regions in the middle segment of the fibre were further extended. These data indicate that the duration of the mechanical activity differs in different regions along the length of the fibre. The pattern of relaxation, i.e. the behaviour of the sarcomeres in different fibre segments, is unique to any particular fibre.


Military small arms fire in association with acute decrements in lung function.
After introduction of unleaded ammunition, Norwegian Armed Forces received reports of acute respiratory symptoms in soldiers after exposure to fumes from firing the standard weapon, HK416. The aim of the present study was to examine lung function before and after exposure to fumes from HK416 in a double-blinded standardised study design using three different types of ammunition. Fifty-four healthy, non-smoking male volunteers (19-62 years) fired the weapons for 60 min with either leaded, unleaded or 'modified' unleaded ammunition. Gaseous and particulate emissions were monitored. Spirometry and exhaled nitric oxide (eNO) were performed within 14 days before (T0), shortly after (T1) and 24 hours after (T2) shooting. Methacholine provocation and diffusing capacity of carbon monoxide (DLCO) were carried out at T0 and T2. The mean forced expiratory volume in 1 s on a group level was significantly reduced both at T1 and T2 compared with T0, with means and 95% CI of 226 mL (158 to 294 mL) and 285 mL (218 to 351 mL), respectively. The same significant pattern was seen for DLCO, forced vital capacity and eNO. The methacholine test indicated a slight increase in bronchial hyper-reactivity. However, there were no significant differences between types of ammunition used. Exposure to fumes from military weapons might be a respiratory hazard for soldiers who do live-fire training regularly or are in a closed combat environment.


An Integrated Germanium-Based THz Impulse Radiator with an Optical Waveguide Coupled Photoconductive Switch in Silicon.
This paper presents an integrated germanium (Ge)-based THz impulse radiator with an optical waveguide coupled photoconductive switch in a low-cost silicon-on-insulator (SOI) process. This process provides a Ge thin film, which is used as photoconductive material. To generate short THz impulses, N++ implant is added to the Ge thin film to reduce its photo-carrier lifetime to sub-picosecond for faster transient response. A bow-tie antenna is designed and connected to the photoconductive switch for radiation. To improve radiation efficiency, a silicon lens is attached to the substrate-side of the chip. This design features an optical-waveguide-enabled "horizontal" coupling mechanism between the optical excitation signal and the photoconductive switch. The THz emitter prototype works with 1550 nm femtosecond lasers. The radiated THz impulses achieve a full-width at half maximum (FWHM) of 1.14 ps and a bandwidth of 1.5 THz. The average radiated power is 0.337 μ W. Compared with conventional THz photoconductive antennas (PCAs), this design exhibits several advantages: First, it uses silicon-based technology, which reduces the fabrication cost; second, the excitation wavelength is 1550 nm, at which various low-cost laser sources operate; and third, in this design, the monolithic excitation mechanism between the excitation laser and the photoconductive switch enables on-chip programmable control of excitation signals for THz beam-steering.


Do antiepileptic drugs or generalized tonic-clonic seizure frequency increase SUDEP risk? A combined analysis.
In an analysis of four case-control studies of sudden unexpected death in epilepsy (SUDEP), we found that yearly frequency of generalized tonic-clonic seizures (GTCS) and antiepileptic drug (AED) polytherapy were associated with an increased risk for SUDEP. The prior analysis, however, did not evaluate AEDs and GTCS frequency concurrently. We combined data from the three case-control studies with information on the frequency of GTCS and AED therapy, that is, carbamazepine, phenytoin, valproic acid, and other AED therapy. Number of AEDs was also considered. Lamotrigine and GTCS frequency were considered separately in two of the case-control studies. Logistic regression analysis was used to evaluate GTCS frequency, each of the AEDs, and number of AEDs. Adjusted analysis of the different AEDs accounted for study, age at death, gender, and GTCS frequency. In crude analysis, GTCS frequency, AED polytherapy, and number of AEDs were associated with an increased risk for SUDEP. Analysis of individual AEDs and of number of AEDs, adjusting for GTCS frequency, revealed no increased risk associated with AEDs as monotherapy, polytherapy, or total number. GTCS frequency remained strongly associated with an increased risk for SUDEP. Our findings-that none of the AEDs considered were associated with increased SUDEP risk as monotherapy or as polytherapy when GTCS frequency was taken into account-provide a consistent message that number of GTCS increases SUDEP risk and not AEDs. These results suggest that prevention of SUDEP must involve increased efforts to decrease GTCS frequency in order to avert the occurrence of this devastating epilepsy outcome.


Nonmarital Fertility, Union History, and Women's Wealth.
We use more than 20 years of data from the National Longitudinal Survey of Youth 1979 to examine wealth trajectories among mothers following a nonmarital first birth. We compare wealth according to union type and union stability, and we distinguish partners by biological parentage of the firstborn child. Net of controls for education, race/ethnicity, and family background, single mothers who enter into stable marriages with either a biological father or stepfather experience significant wealth advantages over time (more than $2,500 per year) relative to those who marry and divorce, cohabit, or remain unpartnered. Sensitivity analyses adjusting for unequal selection into marriage support these findings and demonstrate that race (but not ethnicity) and age at first birth structure mothers' access to later marriage. We conclude that not all single mothers have equal access to marriage; however, marriage, union stability, and paternity have distinct roles for wealth accumulation following a nonmarital birth.


Substitution of an SSRI with bupropion sustained release following SSRI-induced sexual dysfunction.
We examine changes in sexual functioning and depressive symptoms in patients' transition from a selective serotonin reuptake inhibitor (SSRI), which induced both a therapeutic response and sexual dysfunction, to bupropion sustained release (SR) over the course of an 8-week trial. The study included 11 adults (8 women and 3 men) who had a DSM-IV diagnosis of major depressive disorder in remission (Hamilton Rating Scale for Depression [HAM-D] score < 11) and were receiving an SSRI. Depression (using the HAM-D) and sexual dysfunction (using the Changes in Sexual Functioning Questionnaire) were assessed at baseline, 2 weeks after bupropion SR was added to the current antidepressant (combined treatment), 2 weeks after taper of the SSRI was initiated and completed, and after 4 weeks of bupropion SR monotherapy. T tests were performed to assess changes in depression and sexual function. Patient participation dropped from the initial group of 11 at week 2 to 9 at week 4 and to 6 by week 8. Sexual functioning improved from week 0 (baseline) to week 2 and from week 2 to week 4. The patients showed no significant change in mean HAM-D scores in weekly comparisons during the study period; 55% of patients completed the substitution without significant adverse events or recurrence of depressive symptoms. Bupropion SR as a treatment for depression also alleviates sexual dysfunction due to SSRI treatment. Results show that sexual functioning improves after the addition of bupropion SR to SSRI treatment and continues to improve, after discontinuation of the SSRI, with bupropion SR treatment alone.


[Polymorphism of ABCB1 and ABCG2 genes encoding drug transporters and their investigation by pyrosequencing].
Published data on the effect of transporter propeins of the ABC family in the features of drug pharmacokinetics in the human organism are reviewed. Clinical significance of mononucleotide polymorphisms in ABCB1 and ABCG2 genes is analyzed. A set of genetic tests based on pyrosequencing for determing the allele state in rs1128503 (1236 T > C), rs2032582 (2677T > A/G), rs1045642 (3435 T > A/C), rs2231142 (421C > A), and rs72552713 (376 C > T) polymorphisms in ABCB1 and ABCG2 genes has been developed and verified. These tests can be used in both research work and clinical practice for calculating recommended doses of various drugs, predicting their therapeutic efficacy, and determining groups of risk with respect to the developent of undesired secondary reactions.


Obesity and chronic gastrointestinal tract symptoms in young adults: a birth cohort study.
An unexplained epidemic of obesity is occurring but the relationship between obesity and gastrointestinal (GI) tract function is unclear. We aimed to evaluate the association between body mass index (BMI) and specific GI symptoms. A birth cohort in Dunedin, New Zealand, aged 26 yr (n = 980, 94% of total original sample) was evaluated using a validated GI symptom questionnaire. Categories of GI symptom complexes were defined a priori. The association of reported GI symptoms with BMI (kg/m(2)) was assessed adjusting for gender. The prevalence of obesity (BMI > or = 30 kg/m(2)) was 12%; 30% were overweight. There was a significant univariate positive association between increased BMI and diarrhea (>3 stools/day, loose stools, or urgency); the sex adjusted odds ratio for obese versus normal weight was 1.8 (95% CI 1.1, 2.9; p= 0.02). Abdominal pain associated with nausea or vomiting was positively associated with increased BMI (OR 2.0, 95% CI 1.0, 2.9; p= 0.04). Being overweight was negatively associated with abdominal pain and constipation (OR 0.4, 95% CI 0.2, 0.9; p= 0.02). Irritable bowel syndrome and reflux symptoms were not significantly associated with increased BMI. Waist-to-hip ratios were not significantly associated with GI symptoms. No study members were taking antiobesity medications. Hemoglobin A1c levels were not associated with any of the GI symptoms. In a general population sample of young adults, increasing BMI was associated with diarrhea and abdominal pain with nausea/vomiting.


Evaluation of oligonucleotide probes for identification of shiga-like-toxin-producing Escherichia coli.
Four synthetic oligonucleotide probes representing different regions of the Shiga-like toxin I (SLT-I) structural genes and one oligonucleotide derived from the SLT-II gene of Escherichia coli serotype O157:H7 strain 933 were examined for the identification of E. coli strains that produce cytotoxins for Vero or HeLa cells. E. coli strains that synthesize SLT-I alone or O157:H7 isolates that coexpress SLT-I and SLT-II hybridized with all four probes that were complementary to the SLT-I genes, suggesting that they have toxin genes with great homology in all the regions examined. In colony hybridization tests, these oligonucleotide probes did not react with E. coli strains that were nontoxigenic for Vero cells or that produced cytotoxins belonging to the SLT-II family. The probe derived from the slt-IIA gene distinguished E. coli strains that produced SLT-II alone from SLT-I-producing strains and hybridized to all E. coli O157:H7 strains that produced both SLT-I and SLT-II. Using two of these oligonucleotide probes that were complementary to slt-IA or slt-IIA sequences, we identified 50 of 52 cytotoxin-producing strains, whereas none of 416 nontoxigenic E. coli strains was reactive. The colony blot hybridization with the oligonucleotide probes described here can serve as a specific and sensitive test with potential diagnostic value.


Sleep apnoea syndrome--a report of 14 cases.
Patients with sleep apnoea syndrome suffer considerable morbidity and an increased mortality. We reviewed the characteristics of 14 patients with sleep apnoea syndrome (11 males and 3 females) who were studied since 1986. All were less than or equal to 60 years of age with the majority in their 4th and 5th decade. Obesity was present in 8 patients (57%) and hypertension in 6 (43%). Overnight sleep studies showed that 11 patients had obstructive sleep apnoea, 2 had central and one had predominantly mixed sleep apnoea. Ten patients (71%) had some form of nose and/or throat pathology. Tonsillectomy seemed an effective therapeutic procedure in those with upper airway obstruction due to enlarged tonsils. Four out of 5 patients had significant symptomatic improvement post-tonsillectomy. Nasal continuous positive airway pressure was also effective in alleviating apnoeas and relieving symptoms in 4 other patients who had no obvious upper airway obstruction. A high proportion of our patients had obstructive sleep apnoea due to enlarged tonsils. Tonsillectomy offered a simple and effective therapy for such patients. Nasal continuous positive airway pressure was also effective in the treatment of obstructive sleep apnoea.


Impact of hyaluronic acid injection on the knee joint friction.
The purpose of this in vitro study was to investigate whether or not hyaluronic acid supplementation improves knee joint friction during osteoarthritis progression under gait-like loading conditions. Twelve human cadaveric knee joints were equally divided into mild and moderate osteoarthritic groups. After initial conservative preparation, a passive pendulum setup was used to test the whole joints under gait-like conditions before and after hyaluronic acid supplementation. The friction-related damping properties given by the coefficient of friction µ and the damping coefficient c (in kg m2/s) were calculated from the decaying flexion-extension motion of the knee. Subsequently, tibial and femoral cartilage and meniscus samples were extracted from the joints and tested in an established dynamic pin-on-plate tribometer using synthetic synovial fluid followed by synthetic synovial fluid supplemented with hyaluronic acid as lubricant. Friction was quantified by calculating the coefficient of friction. In the pendulum tests, the moderate OA group indicated significantly lower c0 values (p < 0.05) under stance phase conditions and significantly lower µ0 (p = 0.01) values under swing phase conditions. No degeneration-related statistical differences were found for µend or cend. Friction was not significantly different (p > 0.05) with regard to mild and moderate osteoarthritis in the pin-on-plate tests. Additionally, hyaluronic acid did not affect friction in both, the pendulum (p > 0.05) and pin-on-plate friction tests (p > 0.05). The results of this in vitro study suggested that the friction of cadaveric knee joint tissues does not increase with progressing degeneration. Moreover, hyaluronic acid viscosupplementation does not lead to an initial decrease in knee joint friction.


Hepatocyte growth factor induces an endothelin-mediated decline in glomerular filtration rate.
Hepatocyte growth factor (HGF) is a multifunctional cytokine that plays a crucial role in renal development, injury, and repair. HGF also serves a protective role in chronic renal disease by preventing tissue fibrosis. Endothelin-1 (ET-1), produced primarily by endothelial cells, is a potent vasoconstrictor that also acts as a proinflammatory peptide, promoting vascular injury and renal damage. In addition to mediating a variety of epithelial cell responses, HGF also induces hemodynamic changes that are poorly understood. The aim of the present study was to study the acute and chronic effects of HGF on ET-1 production in the kidney. We hypothesized that hemodynamic changes upon HGF treatment are likely mediated by immediate ET-1 release, whereas protection from renal fibrosis in rats chronically treated with HGF is likely due to suppression of ET-1 production. Acute HGF infusion into rats caused a decline in blood pressure that was enhanced by pretreatment with bosentan (an endothelin A and B receptor antagonist). HGF infusion also resulted in a decline in glomerular filtration rate (GFR) that could be entirely prevented by bosentan, suggesting that HGF acutely increases production and/or release of ET-1, which then mediates the observed decline in GFR. In cultured glomerular endothelial cells, HGF induced ET-1 production in a dose-dependent manner. Moreover, although there was an initial increase in ET-1 production upon HGF treatment, longer administration suppressed ET-1 production. This finding was consistent with the observation in vivo of a decrease in ET-1 production in renal parenchyma of rats chronically treated with HGF. Our data suggest both a hemodynamic and biological role for HGF-mediated ET-1 regulation.


Null model analysis of species associations using abundance data.
The influence of negative species interactions has dominated much of the literature on community assembly rules. Patterns of negative covariation among species are typically documented through null model analyses of binary presence/absence matrices in which rows designate species, columns designate sites, and the matrix entries indicate the presence (1) or absence (0) of a particular species in a particular site. However, the outcome of species interactions ultimately depends on population-level processes. Therefore, patterns of species segregation and aggregation might be more clearly expressed in abundance matrices, in which the matrix entries indicate the abundance or density of a species in a particular site. We conducted a series of benchmark tests to evaluate the performance of 14 candidate null model algorithms and six covariation metrics that can be used with abundance matrices. We first created a series of random test matrices by sampling a metacommunity from a lognormal species abundance distribution. We also created a series of structured matrices by altering the random matrices to incorporate patterns of pairwise species segregation and aggregation. We next screened each algorithm-index combination with the random and structured matrices to determine which tests had low Type I error rates and good power for detecting segregated and aggregated species distributions. In our benchmark tests, the best-performing null model does not constrain species richness, but assigns individuals to matrix cells proportional to the observed row and column marginal distributions until, for each row and column, total abundances are reached. Using this null model algorithm with a set of four covariance metrics, we tested for patterns of species segregation and aggregation in a collection of 149 empirical abundance matrices and 36 interaction matrices collated from published papers and posted data sets. More than 80% of the matrices were significantly segregated, which reinforces a previous meta-analysis of presence/absence matrices. However, using two of the metrics we detected a significant pattern of aggregation for plants and for the interaction matrices (which include plant-pollinator data sets). These results suggest that abundance matrices, analyzed with an appropriate null model, may be a powerful tool for quantifying patterns of species segregation and aggregation.


A DFT study of the electronic spectrum of the alpha-keggin anion [Co(II)W(12)O(40)](6-).
Multiplet splittings for several excited configurations of [Co(II)W(12)O(40)](6-) were calculated using DFT methods. In agreement with the experimental interpretation of the spectrum the calculations found that the first strong band corresponds to Co d-d transitions, but it is worth noting that superposed to these transitions there are charge transfer transitions from cobalt to tungsten. The calculations also showed the importance of Jahn-Teller distortions in the excited states. With the exception of the consequences derived from a smaller splitting of d cobalt orbitals the d-d spectrum of [CoCl(4)](2-) is similar to that of the more complex Keggin anion. Finally, the energy of the bielectronic transition (4)A(2) --> (4)T(1)(P) was estimated via an approximate procedure based on ligand field theory.


Parenting children with Down syndrome: Societal influences.
Most studies of parenting children with Down syndrome (DS) have been conducted in industrialized countries. They suggest that sensitive communication on the part of professionals, and social support, can lead to acceptance and positive adjustments in the family. This study examined the impact of a diagnosis of DS on Ecuadorian families, in particular at how the diagnosis had been communicated and received, as well as the feelings and experiences which followed. Despite considerable progress in recent years, Ecuador is still marked by discriminatory attitudes which affect children with disabilities and their families, and by the persistence of widespread poverty. This qualitative study, conducted in Cuenca, Ecuador's third largest city, is based on a focus group discussion and four in-depth interviews with Ecuadorian parents of DS children attending a specialist center in the city. The study shows that, reflecting the effects of status differences and lack of appropriate training, professionals rarely communicate a DS diagnosis in an appropriate manner. Further, it is shown that lack of social support, and the widespread stigmatization confronting children with DS and their families, hinder development of positive and empowering adjustments that would best serve the child's and the family's interest.


Environmental component of morphological differentiation in birds.
Geographic character variation in birds is usually attributed to natural selection for phenotypes that reflect locally adapted genetic differences. However, experimental transplants of red-winged blackbird eggs between nests in northern and southern Florida, and from Colorado to Minnesota, show that in this species a significant proportion of the regional differences in nestling development is nongenetic. If natural selection is maintaining the clines of character variation that are observed in adult phenotypes, the genetic and nongenetic components of phenotypic variation must covary.


Charting a DNA Repair Roadmap for Immunoglobulin Class Switch Recombination.
Immunoglobulin (Ig) class switch recombination (CSR) is the process occurring in mature B cells that diversifies the effector component of antibody responses. CSR is initiated by the activity of the B cell-specific enzyme activation-induced cytidine deaminase (AID), which leads to the formation of programmed DNA double-strand breaks (DSBs) at the Ig heavy chain (Igh) locus. Mature B cells use a multilayered and complex regulatory framework to ensure that AID-induced DNA breaks are channeled into productive repair reactions leading to CSR, and to avoid aberrant repair events causing lymphomagenic chromosomal translocations. Here, we review the DNA repair pathways acting on AID-induced DSBs and their functional interplay, with a particular focus on the latest developments in their molecular composition and mechanistic regulation.


Thiamin Status in Adults Receiving Chronic Diuretic Therapy Prior to Admission to a Medical Intensive Care Unit: A Pilot Study.
The aim of the study was to determine serum thiamin concentrations in critically ill medical patients who required chronic diuretic drug treatment before admission to a medical intensive care unit (ICU). This prospective study was performed in a medical ICU. Subjects who received diuretic drug therapy for at least 6 months prior to ICU admission constituted the diuretic group. The control group was clinically matched adults admitted to the same ICU but without a history of diuretic therapy. A total of 50 subjects were included (25 subjects in each of the diuretic and control groups). In the diuretic group, daily dose of furosemide prior to admission was 40 mg/d (range of 20-160 mg/d). In all subjects, the ICU admission baseline blood thiamin concentrations were 31.2 ± 27.1 ng/mL. In the diuretic group, the baseline whole blood thiamin level was significantly lower compared with levels in the control group (15.5 ± 10.7 vs 46.8 ± 29.5 ng/mL; P < 0.001). On day 2 after entry, thiamin levels remained low (23.2 ± 15.4 ng/mL in the diuretic group vs 49 ± 38 ng/mL in the control group; P = 0.003). Low thiamin levels were found in 96% of patients at baseline and in 72% of patients on the second day in the diuretic group. Adults receiving chronic diuretic therapy and then requiring medical ICU care commonly exhibit thiamin depletion on admission to the ICU and during the initial days of ICU care.


Review of the Michigan Upper Peninsula bovine viral diarrhea virus eradication project.
To evaluate the effects of a voluntary regional bovine viral diarrhea virus (BVDV) control project implemented in the Upper Peninsula of Michigan. Longitudinal study. Sample-294 cattle producers and 11,917 cattle from the Upper Peninsula. Producer participation was assessed to determine the effectiveness of the project's promotional and educational campaigns. Participating herds were screened for cattle persistently infected (PI) with BVDV by real-time reverse transcriptase PCR assay on ear notch specimens from all newborn calves and cattle that did not calve (bulls and young stock) during the year of enrollment. Responses to a survey administered to producers 4 years after project initiation were evaluated to assess the project's effect on BVDV management practices implemented by producers. 294 of 495 (59%) known cattle producers in the Upper Peninsula participated in the project, and 11,917 cattle from 232 herds were tested for BVDV, of which 22 (0.18%) cattle from 9 (3.9%) herds were identified as PI with BVDV and euthanized or slaughtered. Of 140 survey respondents, 85 (61%) indicated they would test all new herd additions for BVDV, 83 (59%) would quarantine new herd additions for 30 days before introducing them to the main herd, and 81 (58%) would use the fact that their herd was free of cattle PI with BVDV for marketing purposes. Results indicated that the project enhanced producer knowledge about BVDV and led to changes in producer behavior regarding BVDV management. Stakeholder engagement was as critical to project success as was increased BVDV knowledge.


Role of educational institutions in identifying and responding to emerging health human resources needs.
The healthcare system continues to evolve, requiring innovation to promote patient-centred, fiscally responsible healthcare delivery. This evolution includes changes to the skills and competencies required of the health human resources (HHR), both regulated and unregulated, who are central supports to healthcare delivery. This has become a priority agenda item at the international, national, provincial, regional and local levels. This paper describes the system factors that drive the emergence of HHR skill and competency needs, and explores the roles of various institutions in the identification of and response to HHR needs. Educational institutions play an important role in responding to emerging HHR needs. Their actual response to HHR skill and competency needs will ultimately depend on the risk posed to the organizations of either addressing, or not addressing, these needs. These decisions are complex and are balanced against strategic, operational and educational risks, benefits and realities within each given educational institution. Educational institutions - through their linkages with the workplace, industry, professional organizations and government - have a unique view and understanding of many facets of the complexity of HHR planning. This paper proposes that educational institutions play a pivotal role as levers in a more coordinated response to emerging HHR needs and, as such, should be intimately involved in comprehensive HHR planning.