Three-dimensional path planning for virtual bronchoscopy.
Multidetector computed-tomography (MDCT) scanners provide large high-resolution three-dimensional (3-D) images of the chest. MDCT scanning, when used in tandem with bronchoscopy, provides a state-of-the-art approach for lung-cancer assessment. We have been building and validating a lung-cancer assessment system, which enables virtual-bronchoscopic 3-D MDCT image analysis and follow-on image-guided bronchoscopy. A suitable path planning method is needed, however, for using this system. We describe a rapid, robust method for computing a set of 3-D airway-tree paths from MDCT images. The method first defines the skeleton of a given segmented 3-D chest image and then performs a multistage refinement of the skeleton to arrive at a final tree structure. The tree consists of a series of paths and branch structural data, suitable for quantitative airway analysis and smooth virtual navigation. A comparison of the method to a previously devised path-planning approach, using a set of human MDCT images, illustrates the efficacy of the method. Results are also presented for human lung-cancer assessment and the guidance of bronchoscopy.


[Antipsychotic drugs. Risk factors for diabetes].
ANTIPSYCHOTICS AND DIABETES: After 50 years' use of antipsychotics, it is pertinent to draw-up a circumspect review of the side effects of these psychotropic agents. Moreover, few articles have attempted to elucidate the relationship between the monitoring of carbohydrate metabolism and the prescription of this type of medication. SEVERAL MECHANISMS AT THE ORIGIN OF AN IMBALANCE IN GLYCAEMIA: Antipsychotics, notably the atypical forms, represent an additional factor of risk for developing diabetes. The weight gain secondary to this treatment plays an important part in this imbalance, but other mechanisms may also contribute. DEPENDING ON THE TYPE OF ANTIPSYCHOTIC: Our present knowledge is insufficient to be able to quantify the effect of each atypical antipsychotic on diabetes. The only tendency that has been reproduced in several studies concerns the increased risk associated with dibenzodiazepine antipsychotics (clozapine and olanzapine), compared with the other antipsychotics.


[Morphology of experimental malignant hemangioendothelioma].
Various histological stains, histoautoradiography and electron microscopy were used to study the morphologic features of 77 malignant hemangioendotheliomas induced in CBA mice with subcutaneously injected 1,2-dimethylhydrazine. The histologic and cytologic structure of those tumors proved similar to those of malignant hemangioendothelioma in man. The ability of tumor cells to form vascular structures and degree of their neoplastic atypia were used to identify three types of neoplasia: "cavernous hemangioma" with cytologic signs of malignity and well- and poorly--differentiated malignant hemangioendotheliomas. Due to high rate of tumor development and inevitable growth in the renal capsule which makes tumor easy to detect at early stage, the model offers promise for evaluating morphogenesis of malignant hemangioendothelioma.


Extramedullary hematopoiesis in ribs and severe pulmonary hypertension disease following intermediate beta-thalassemia: a case report.
Thalassemia is a type of congenital hemoglobinopathy that falls into the category of hemolytic anemias. Extramedullary hematopoiesis is a complication of this disease, which is a mechanism to compensate for chronic anemia in these patients, and imaging is the best diagnostic method. In this report, a 36-year-old Caucasian female patient with intermediate beta thalassemia is presented who, at the time of referral, complained of exacerbated shortness of breath. Imaging showed diffuse expansion masses with soft tissue components in the ribs of both hemithoraxes, leading to the diagnosis of extramedullary hematopoiesis. Extramedullary hematopoiesis in the ribs is an uncommon finding in patients with thalassemia and is a sign of the severity of the disease and a poor prognostic factor that might be preventable if blood transfusion begins at younger ages.


Receptor- and G-protein-regulated 150-kDa avian phospholipase C: inhibition of enzyme activity by isoenzyme-specific antisera and nonidentity with mammalian phospholipase C isoenzymes established by immunoreactivity and peptide sequence.
A 150-kDa phospholipase C previously was purified from turkey erythrocytes and shown to be a P2Y-purinergic receptor- and guanine nucleotide-binding protein-regulated enzyme [J. Biol. Chem. 265:13508-13514 (1990)]. The relationship of this enzyme to the 150-kDa mammalian phospholipase C isoenzymes, termed phospholipase C-beta and -gamma, has been examined. Four antisera to the turkey erythrocyte phospholipase C recognized the avian enzyme in immunoblots but failed to recognize phospholipase C-gamma; one of the these weakly recognized phospholipase C-beta. Antibodies to phospholipase C-beta and -gamma failed to recognize the turkey erythrocyte phospholipase C. However, two antibodies raised against peptide sequence in regions of conserved sequence common to mammalian phospholipase C isoenzymes recognized the 150-kDa turkey erythrocyte phospholipase C. Antisera against the native form of the turkey erythrocyte phospholipase C inhibited the activity of this enzyme against phosphatidylinositol 4,5-bisphosphate presented as a component of mixed phospholipid vesicles or of mixed phospholipid and sodium cholate micelles; inhibition occurred as a decrease in Vmax, with no apparent change in Km for substrate or in the Ca2+ dependence of phospholipase C activity. Catalytic activity of phospholipase C-beta or -gamma against exogenous substrate was unaffected by antisera to the turkey erythrocyte enzyme. Antisera against the native form of the turkey erythrocyte phospholipase C also partially inhibited (50-60% inhibition) the capacity of AIF4- or adenosine 5'-O-(beta-thio) diphosphate plus guanosine 5'-O-(gamma-thio) triphosphate to stimulate phosphoinositide hydrolysis in ghosts prepared from [3H]inositol-prelabeled turkey erythrocytes. Moreover, the capacity of the purified 150-kDa enzyme to reconstitute receptor and G-protein-regulated phospholipase C activity in purified turkey erythrocyte plasma membranes devoid of this activity was completely inhibited by antisera to the turkey erythrocyte enzyme. Five peptides that were purified by high performance liquid chromatography from a tryptic digest of the turkey erythrocyte 150-kDa phospholipase C had no recognizable sequence homology with any deduced sequence of the mammalian phospholipase C isoenzymes. One turkey erythrocyte phospholipase C-derived peptide had clear homology with sequence in the first (X-domain) conserved region common to at least three of the mammalian phospholipase C isoenzymes, and another 16-amino acid peptide had partial sequence homology with the second (Y-domain) conserved region common to the mammalian enzymes. An 8-amino acid peptide from the tryptic digest had 75% homology with a sequence near the carboxyl terminus of mammalian phospholipase C-beta.(ABSTRACT TRUNCATED AT 400 WORDS)


The NIH Open Citation Collection: A public access, broad coverage resource.
Citation data have remained hidden behind proprietary, restrictive licensing agreements, which raises barriers to entry for analysts wishing to use the data, increases the expense of performing large-scale analyses, and reduces the robustness and reproducibility of the conclusions. For the past several years, the National Institutes of Health (NIH) Office of Portfolio Analysis (OPA) has been aggregating and enhancing citation data that can be shared publicly. Here, we describe the NIH Open Citation Collection (NIH-OCC), a public access database for biomedical research that is made freely available to the community. This dataset, which has been carefully generated from unrestricted data sources such as MedLine, PubMed Central (PMC), and CrossRef, now underlies the citation statistics delivered in the NIH iCite analytic platform. We have also included data from a machine learning pipeline that identifies, extracts, resolves, and disambiguates references from full-text articles available on the internet. Open citation links are available to the public in a major update of iCite (https://icite.od.nih.gov).


Afzelin attenuates asthma phenotypes by downregulation of GATA3 in a murine model of asthma.
Asthma is a serious health problem causing significant mortality and morbidity globally. Persistent airway inflammation, airway hyperresponsiveness, increased immunoglobulin E (IgE) levels and mucus hypersecretion are key characteristics of the condition. Asthma is mediated via a dominant T-helper 2 (Th2) immune response, causing enhanced expression of Th2 cytokines. These cytokines are responsible for the various pathological changes associated with allergic asthma. To investigate the anti-asthmatic potential of afzelin, as well as the underlying mechanisms involved, its anti-asthmatic potential were investigated in a murine model of asthma. In the present study, BALB/c mice were systemically sensitized using ovalbumin (OVA) followed by aerosol allergen challenges. The effect of afzelin on airway hyperresponsiveness, eosinophilic infiltration, Th2 cytokine and OVA‑specific IgE production in a mouse model of asthma were investigated. It was found that afzelin‑treated groups suppressed eosinophil infiltration, allergic airway inflammation, airway hyperresponsiveness, OVA-specific IgE and Th2 cytokine secretion. The results of the present study suggested that the therapeutic mechanism by which afzelin effectively treats asthma is based on reduction of Th2 cytokine via inhibition of GATA-binding protein 3 transcription factor, which is the master regulator of Th2 cytokine differentiation and production.


Comparison of pericapsular nerve group block and femoral nerve block in spinal anesthesia position analgesia for proximal femoral fractures in geriatric patients: a randomized clinical trial.
This study aimed to compare the analgesic efficacy of the femoral nerve block (FNB) with that of the pericapsular nerve group (PENG) block in the lateral decubitus position for spinal anesthesia in geriatric hip fracture surgery. Patients aged ≥65 years scheduled to undergo hip fracture surgery for proximal femur fractures with an American Society of Anesthesiologists physical status of class I-IV and body mass index of 18-40 kg/m2 were included in the study. The PENG block or FNB was performed 20 min before positioning for spinal anesthesia. Lateral position, hip flexion, and lumbar spine flexion pain were evaluated during spinal anesthesia. Sixty patients completed the study. The median pain scores for lateral positioning were 2 (0-4) and 2.5 in the PENG and FNB groups, respectively (P=0.001). The median pain scores during hip flexion were 1 (0-4) and 2.5 in the PENG and FNB groups, respectively (P<0.001). The median pain score during lumbar flexion was 1 (0-4) and 2.0 in the PENG and FNB groups, respectively (P=0.001). The two groups did not show a significant difference in the quality of the spinal anesthesia position (P>0.05). Pre-operative PENG block is more effective in reducing the pain associated with spinal anesthesia position than FNB in geriatric hip fractures. Both blocks had a similar effect on posture quality and the number of spinal interventions.


Evaluation of a computer-tailored lifestyle modification support tool for employees in Japan.
To examine the effectiveness of a computer-tailored support tool for lifestyle modification developed for employees, we conducted an intervention study of pre-post test design. The program was based on principles of behavior science referring to goal setting processes, self monitoring, and feedback. The program of the support process was fully automated. A total of 650 participants of four workplaces in Japan completed the baseline assessment, 185 (28.5%) of those returned for the post-test assessment 4 months later. There were significant improvements in lifestyle behaviors between baseline and post-test: In men, low energy intake (p<0.01) and exercise frequency (p<0.05), and in women, low salt intake (p<0.05) and exercise frequency (p<0.05). Furthermore, significant improvements were shown in the stage of change between baseline and post-test: Low salt intake (p<0.01) and regular exercise in men (p<0.01). Our results suggest a possibility that the program, utilizing a computer-tailored lifestyle modification support tool developed for use by employees, had a positive effect on participants' lifestyle behaviors in Japanese workplaces. The degree to which our results generalize to effects of the program is unclear but examination to develop more efficient and effective programs is warranted.


The use of condoms with other contraceptive methods among young men and women.
In a nationally representative sample of sexually experienced youths aged 14-22, 37% of young women and 52% of young men said the condom was the primary method used to prevent pregnancy at last intercourse; an additional 8% and 7%, respectively, said they used a condom at last intercourse; much of this represents dual use [corrected]. Condom use at last intercourse was reported by 25% of young men whose partner was using the pill. Significant independent predictors of condom use with the pill among men included younger age, black race, engaging in fewer nonsexual risk behaviors and having received instruction about HIV in school. Among young women, 21% of those relying on the pill reported also using a condom at last intercourse. For women, independent predictors of dual use included younger age, black race, older age at first sex, fewer nonsexual risk behaviors, having no partners in the previous three months and having talked to parents or other adult relatives about HIV.


Diffuse colonies of human skin fibroblasts in relation to cellular senescence and proliferation.
Development of personalized skin treatment in medicine and skin care may benefit from simple and accurate evaluation of the fraction of senescent skin fibroblasts that lost their proliferative capacity. We examined whether enriched analysis of colonies formed by primary human skin fibroblasts, a simple and widely available cellular assay, could reveal correlations with the fraction of senescent cells in heterogenic cell population. We measured fractions of senescence associated β-galactosidase (SA-βgal) positive cells in either mass cultures or colonies of various morphological types (dense, mixed and diffuse) formed by skin fibroblasts from 10 human donors. Although the donors were chosen to be within the same age group (33-54 years), the colony forming efficiency of their fibroblasts (ECO-f) and the percentage of dense, mixed and diffuse colonies varied greatly among the donors. We showed, for the first time, that the SA-βgal positive fraction was the largest in diffuse colonies, confirming that they originated from cells with the least proliferative capacity. The percentage of diffuse colonies was also found to correlate with the SA-βgal positive cells in mass culture. Using Ki67 as a cell proliferation marker, we further demonstrated a strong inverse correlation (r=-0.85, p=0.02) between the percentage of diffuse colonies and the fraction of Ki67+ cells. Moreover, a significant inverse correlation (r=-0.94, p=0.0001) between the percentage of diffuse colonies and ECO-f was found. Our data indicate that quantification of a fraction of diffuse colonies may provide a simple and useful method to evaluate the extent of cellular senescence in human skin fibroblasts.


Comparative Assessment of Clinical and Predicted Treatment Outcomes of Clear Aligner Treatment: An in Vivo Study.
The objective of this clinical study was to assess the predicted software models and clinical models and to compare the stage models of both the groups so as to evaluate the efficacy of tooth movement with clear aligner. The sample size included 10 cases with mild anterior crowding treated with aligner therapy. The predicted software models were superimposed on the clinical stereolithography (STL) models at various stages by using the MeshLab software. The predicted software models showing orthodontic tooth movement were compared with the actual movement achieved clinically. The results of the present study have shown that when a comparison was made on the basis of irregularity scores in both the groups, it was seen that the irregularity score was higher at 2.55 at T4, 1.65 at T6, and 1.0 at T8 in the clinical STL group at each stage, whereas it was 2.0 at T4, 0.90 at T6, and 0.25 at T8 in the software model group. In addition, in comparing the mean accuracy of these three stages, the analysis of data showed that the mean accuracy is 62.5% at T4, 68.8% at T6, and 78.1% at T8. The predicted software models do not accurately reflect the patient's tooth position. There is an overestimation by predicted software as compared with actual clinically achieved tooth position. There is a need of overcorrection to be built in the treatment planning stage itself and execution of the anticipated end result.


Supramolecular self-assembly of π-conjugated hydrocarbons via 2D cooperative CH/π interaction.
Supramolecular self-assembly on well-defined surfaces provides access to a multitude of nanoscale architectures, including clusters of distinct symmetry and size. The driving forces underlying supramolecular structures generally involve both graphoepitaxy and weak directional nonconvalent interactions. Here we show that functionalizing a benzene molecule with an ethyne group introduces attractive interactions in a 2D geometry, which would otherwise be dominated by intermolecular repulsion. Furthermore, the attractive interactions enable supramolecular self-assembly, wherein a subtle balance between very weak CH/π bonding and molecule-surface interactions produces a well-defined "magic" dimension and chirality of supramolecular clusters. The nature of the process is corroborated by extensive scanning tunneling microscopy/spectroscopy (STM/S) measurements and ab initio calculations, which emphasize the cooperative, multicenter characters of the CH/π interaction. This work points out new possibilities for chemical functionalization of π-conjugated hydrocarbon molecules that may allow for the rational design of supramolecular clusters with a desired shape and size.


Modelling feeding behaviour, rate of feed passage and daily feeding cycles, as possible causes of fatigued pigs.
This study was initiated to understand whether feeding behaviour and physiology may contribute to the rate of fatigued pigs at processing plants. Specifically, this study sought to determine: (1) how often pigs eat during the day, (2) the times of the day they eat and (3) a first approximation of the time from feed consumption to excretion (rate of passage) when housed in a group in conventional finishing facilities. Finally, models were constructed to try to predict the percentage of pigs with empty/diminished gastrointestinal (GI) tracts depending on the time of day of truck loading and transport durations. Pigs were randomly selected, weighed and selected for behavioural observations. From video records and live observations, the number of meals (feeding bouts) per day and the time of the day meals took place were recorded. Feed containing chromic oxide was fed to determine when a given meal was excreted. With the feeding times of day determined, models were constructed of the percentage of pigs that would have empty stomachs depending on the time of day pigs were removed from the barn and the length of transport/lairage. Finishing pigs housed in groups ate 5.6 ± 0.6 meals per day with an average feeding bout (meal) length of 11.3 ± 1.1 min. Many pigs fed ad libitum ate most of their meals during the afternoon and evening. The rate of passage of feed was 20.5 h (range = 18 to 24 h). Because fewer pigs ate in the late evening through morning, if pigs were shipped at these times they would have an increased risk of arriving at the stun at a plant with an empty GI tract. Some of the variation in rates of fatigued pigs and pork quality may be explained by times of day taken off feed and transport duration. Shipping in the afternoon or early evening may result in fewer pigs with empty/diminished GI tracts at processing which may influence the rate of fatigued pigs and pork quality.


Questionnaire of core beliefs related to drug use and craving for assessment of relapse risk.
This study was aimed at designing a questionnaire for the assessment of addiction-related core beliefs and craving. The sample comprised 215 patients (85.8% males and 14.2% females) in treatment for dependence to alcohol (40%), cocaine (36.3%) and cannabis (23.7%). Descriptive statistics were used to characterize the sample. Variance, regression and factorial analyses were conducted to study the questionnaire structure and its relation with variables such as abstinence and craving. Items about drug-related beliefs yielded a four-factor structure: what patient think that they could not do without drug use, lack of withdrawal, conditions required to use drugs again, and use of drugs as the only way to feel good. Items related to craving yielded three factors: negative emotions as precipitants of drug use, positive emotions, and difficulties attributed to coping with craving. Furthermore, beliefs were more important to predict craving than abstinence time. The present questionnaire allows to assess a set of significant factors to design prevention relapse programs.


Preconditioning with lidocaine and xylazine in experimental equine jejunal ischaemia.
Pharmacological preconditioning of dexmedetomidine on small intestinal ischaemia/reperfusion injury has been reported in different animal models including horses. The objective was to assess if xylazine and lidocaine have a preconditioning effect in an experimental model of equine jejunal ischaemia. Terminal in vivo experiment. Ten horses under general anaesthesia were either preconditioned with xylazine (group X; n = 5) or lidocaine (group L; n = 5). A historical untreated control group (group C; n = 5) was used for comparison. An established experimental model of equine jejunal ischaemia was applied, and intestinal samples were taken pre-ischaemia, after ischaemia and following reperfusion. Histomorphological examination was performed based on a modified Chiu score. Immunohistochemical staining for cleaved caspase-3, TUNEL and calprotectin was performed, and positive cell counts were expressed in cells/mm2 . There was no progression of histomorphological mucosal injury from ischaemia to reperfusion, and there were no differences in histomorphology between the groups. After ischaemia, group X had significantly less caspase-positive cells compared to the control group with a median difference of 227% (P = .01). After reperfusion, group X exhibited significantly lower calprotectin-positive cell counts compared to the control group, with a median difference of 6.8 cells/mm2 in the mucosa and 44 cells in the serosa (P = .02 and .05 respectively). All groups showed an increase in caspase- and calprotectin-positive cells during reperfusion (P < .05). TUNEL-positive cells increased during ischaemia, followed by a decrease after reperfusion (P < .05). The small sample size and the use of a historical control group. Preconditioning effects of the tested drugs may be masked by the protective effects of isoflurane in the anaesthetic protocol. Preconditioning with lidocaine did not have any effect on the tested variables. The lower cell counts of caspase- and calprotectin-positive cells in group X may indicate a beneficial effect of xylazine on ischaemia/reperfusion injury. Due to the absence of a concurrent reduction of histomorphological injury, the clinical significance remains uncertain.


Pancreatic Cancer Following Incident Diabetes in African Americans and Latinos: The Multiethnic Cohort.
Diabetes has been proposed to be a risk factor for and a consequence of pancreatic cancer (PC). The relationship between recent-onset diabetes and PC is not well understood, and data in minorities are sparse. We examined the relationships between recent-onset diabetes and PC incidence in African Americans and Latinos in the Multiethnic Cohort. A total of 48 995 African Americans and Latinos without prior diabetes and cancer at baseline (1993-1996) were included in the study. Questionnaires, Medicare data, and California hospital discharge files were used to identify new diabetes diagnoses. Cox regressions were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer associated with diabetes and with diabetes duration. A total of 15 833 (32.3%) participants developed diabetes between baseline and 2013. A total of 408 incident PC cases were identified during follow-up. Diabetes was associated with PC (HRage75 = 2.39, 95% CI = 1.91 to 2.98). Individuals with recent-onset diabetes (within three or fewer years of PC diagnosis) had a greater risk compared with those with long-term diabetes across all ages. The HRage75 for recent-onset diabetes was 4.08 (95% CI = 2.76 to 6.03) in Latinos and 3.38 (95% CI = 2.30 to 4.98) in African Americans. Diabetes was associated with a more than twofold higher risk of PC in African Americans and Latinos, but recent-onset diabetes was associated with a 2.3-fold greater increase in risk of PC than long-standing diabetes. Our findings support the hypothesis that recent-onset diabetes is a manifestation of PC and that long-standing diabetes is a risk factor for this malignancy.


Assessing proprioceptive function: evaluating joint position matching methods against psychophysical thresholds.
The importance of assessing proprioceptive function for rehabilitation after neurological or orthopedic injury has long been recognized. Yet, neither the validity nor the accuracy of the available tests is firmly established. Testing typically involves repeated matching of a given joint position with the same or opposite limb where the difference between the 2 positions indicates proprioceptive acuity. The aim of this study was to compare position sense acuity between ipsilateral and contralateral matching methods against a psychophysical threshold method to establish the accuracy and relationships between these models. A repeated-measures design was used. Assessment of forearm position sense for a 10-degree reference position in 27 young adults who were healthy. Psychophysical thresholds were revealed to be the most precise and least variable acuity measure. The mean (±SD) threshold (1.05°±0.47°) was significantly lower than mean position errors obtained by both joint position matching tasks (ipsilateral: 1.51°±0.64°; contralateral: 1.84°±0.73°)-a 44% to 75% difference in measurement accuracy. Individual participant position errors correlated poorly with respective thresholds, indicating a lack of concurrent validity. Position errors for both matching methods correlated only mildly with each other. The data represent performance of a healthy, young adult cohort. Differences between methods will likely be more pronounced in aging and clinical populations. Threshold testing and joint position matching methods examine different physiological aspects of proprioceptive function. Because threshold testing is based on passive motion, it most closely reflects afferent sensory feedback processing (ie, proprioception). Matching methods require active motion and are consequently influenced by additional sensorimotor processes. Factors such as working memory and transmission between brain hemispheres also influence joint matching task outcomes.


[BULLYING IN JAPANESE CHILDREN AND ADOLESCENTS WITH FOOD ALLERGIES].
To elucidate the prevailing circumstances of victimization, including bullying, faced by children afflicted with food allergies in Japan. From July to August 2021, we executed a web-based questionnaire survey targeting children with food allergies enrolled in the fourth grade or higher, who sought medical attention at the Department of Pediatrics in Showa University Hospital or were affiliated with three allergy-focused patient associations. The survey aimed to ascertain whether these children had encountered instances of bullying, the nature of the bullying incidents, and whether such acts of bullying triggered allergic symptoms. A total of sixty-six children with food allergies participated in the survey. Among them, forty-five (68%) were male, thirty-three (50%) were attending elementary school, and thirty-five (53%) reported experiencing some form of victimization throughout their lives. Specifically, fourteen (21%) had been subjected to bullying due to their food allergy, with two children being coerced into consuming allergens and one child experiencing symptoms induced by allergen-based bullying. It is evident that a significant number of children with food allergies face bullying. Therefore, it is imperative for healthcare providers and parents to acknowledge the inherent risk of bullying as an integral aspect of caring for children with food allergies. Prompt measures should be taken, such as educating both teachers and non-allergic children about this risk.


Assessing intonation and prosody in children with atypical language development: the PEPS-C test and the revised version.
A procedure for assessing prosody and intonation in children (PEPS-C: Profiling Elements of Prosodic Systems--Children), suitable for use by clinicians with both children and adults, is described. The procedure includes testing of four communication areas in which intonation/prosody has a crucial role: interaction, affect, boundary (chunking) and focus. Each area has parallel tasks for assessing understanding and expression of the functions and ability to discriminate and articulate the prosodic forms involved. The original and revised forms of the test are compared, with some discussion of procedural considerations. Past and present uses of the test and future applications are considered.


Role of lysophosphatidic acid in endothelin-1- and hematoma-induced alteration of cerebral microcirculation.
Cerebral hematoma increases cerebrospinal fluid (CSF) endothelin-1 (ET-1). Inhibitors of ET-1 synthesis prevent this increment and hematoma-induced modification of cerebral arteriolar reactivity. We hypothesized that intrathecal ET-1 injection could 1) modify pial arteriolar reactivity similarly to hematoma; 2) increase CSF lysophosphatidic acid (LPA), a potential contributor to altered cerebrovascular reactivity; and 3) reduce the level of adenosine 3',5'-cyclic monophosphate (cAMP) in the CSF. Either ET-1 (10(-7) M) or artificial CSF was injected over the left parietal cortex of newborn pigs. Four days later, cranial windows were implanted. CSF ET was increased from a basal level of 11 fmol/ml to 18 fmol/ml 4 days after ET-1 injection, whereas CSF cAMP was reduced from 2,700 to 950 fmol/ml. The mean diameter of pial arterioles was reduced 31%. In control animals, 10(-12) M ET caused dilation, and higher concentrations induced vasoconstriction. Four days after ET-1 injection topical ET-1 caused constriction instead of dilation at 10(-12) M, and constrictions at higher doses were enhanced. Norepinephrine-induced constrictions were potentiated in the ET-1-injected group. Dilations to cAMP-dependent (but not independent) vasodilators were attenuated after ET-1. The concentration of the vasoconstrictor lipid mediator LPA increased approximately fourfold. Thus intrathecal injection of ET-1 mimics hematoma-induced modification of cerebral vascular reactivity and increase in LPA production. The mechanism(s) of ET-1- and hematoma-induced modifications may involve LPA, which is known to contribute to the loss of dilator responses by inhibition of cAMP product on. The present study further suggests that ET-1 together with LPA could be causing changes in cerebrovascular reactivity following cerebral hemorrhage. ET-1 stimulates the release of LPA from brain parenchyma independent of serum so that LPA could serve as a secondary mediator.


Quantitative detection of single molecules in fluorescence microscopy images.
Fluorescence imaging and counting of single molecules adsorbed or bound to surfaces are being employed in a number of quantitative analysis applications. Reliable molecular counts with knowledge of counting uncertainties, both false-positive and false-negative probabilities, are critical to these applications. By counting stationary single molecules on a surface, spatial criteria may be applied to the image analysis to improve confidence in detection, which is especially critical when detecting single fluorescent labels. In this work, we describe a simple approach to incorporating spatial criteria for counting single molecules by using an intensity threshold to locate regions with multiple, adjacent intense pixels, where the size of these regions is guided by the point-spread function of the microscope. By requiring multiple, spatially correlated bright pixels, false-positive events resulting from random samples of background noise are minimized. The reliability of detection is established by quantitative knowledge of the distributions of background and signals. By measuring and modeling both the background and single-molecule intensity distributions, false-positive and false-negative detection probabilities are estimated for arbitrary threshold parameters by using combinatorial statistics. From this theory, detection parameters can be optimized to minimize false-positive and false-negative probabilities, which can be calculated explicitly. For detection of single rhodamine 6G molecules at a threshold set at 2.5 times the standard deviation above background, the false-negative probability was only 1.5%, determined from distributions of single-molecule intensities on well-populated surfaces, and the false-positive probability from background noise was 2.8 spots per 50 x 50 microm image. The false-positive events compare favorably with theoretical probabilities calculated using combinatorial statistical analysis and simulated false-positive events counted in images of random noise.


Failure of ultrasound in the investigation of sciatica.
This paper reports a prospective study of the value of ultrasonography in detecting lesions of the lumbar spine in patients with compressive sciatica. The measurements of the diameter of the spinal canal obtained by using ultrasound were compared with the findings at operation in 17 patients in whom a total of 50 sites were examined. The ultrasound beam failed to penetrate the spinal canal at 15 sites and at only 10 of the remaining 35 sites did the ultrasound correctly detect narrowing. It is concluded that ultrasonography is unreliable in identifying the site of compression of the spinal cord and nerve roots. The technical limitations and the probable causes of failure of the technique are discussed.


A 13µW 87dB dynamic range implantable ΔΣ modulator for full-spectrum neural recording.
Experiment analysis on in-vivo data sequences suggests a wide system dynamic range (DR) is required to simultaneously record local field potentials (LFPs), extra-cellular spikes, and artifacts/interferences. In this paper, we present a 13 µW 87 dB DR ΔΣ modulator for full-spectrum neural recording. To achieve a wide DR and low power consumption, a fully-differential topology is used with multi-bit (MB) quantization scheme and switched-opamp (SO) technique. By adopting a novel fully-clocked scheme, a power-efficient current-mirror SO is developed with 50% power saving, which doubles the figure-of-merit (FOM) over its counterpart. A new static power-less multi-bit quantizer with 96% power and 69% area reduction is also introduced. Besides, instead of metal-insulator-metal (MIM) capacitor, three high-density MOS capacitor (MOSCAP) structures are employed to reduce circuit area. Measurement results show a peak signal-to-noise and distortion ratio (SNDR) of 85 dB with 10 kHz bandwidth at 1.0 V supply, corresponding to an FOM of 45 fJ/conv.-step. which is implemented in a 0.18 µm CMOS.


Early childhood adversities and trajectories of psychiatric problems in adoptees: evidence for long lasting effects.
The aim of the present study is to investigate whether early childhood adversities determine the longitudinal course of psychiatric problems from childhood to adulthood; in particular if the impact of early maltreatment on psychopathology decreases as time passes. A sample of 1,984 international adoptees was followed (955 males and 1029 females; adopted at the mean age of 29 months). Parents provided information about abuse, neglect and number of placements prior to adoption at baseline and completed the Child Behavior Checklist or the Young Adult Behavior Checklist three times when their children were between 10 and 30 years of age. Multilevel analyses were performed to determine trajectories of psychiatric problems. Experience of early childhood adversity prior to adoption substantially increased the level of psychiatric problems, especially when maltreatment was severe. Moreover, the impact of early adversities on psychiatric problems remained markedly stable. This suggests that vulnerability of early-maltreated children persists even if they are taken out of their problematic environments and are raised in enriched circumstances.


Qualitative Consumer Research on Acceptance of Long-Acting Pre-Exposure Prophylaxis Products Among Men Having Sex with Men and Medical Practitioners in the United States.
Pre-exposure prophylaxis (PrEP) with oral Truvada® prevents HIV infection. However, the adherence to pill taking required for efficacy has sparked interest in developing new antiretroviral delivery systems that decrease such demands. Long-acting formulations, such as injections and implants, represent promising options that require less frequent adherence. It is important, however, that development of these new modalities be driven by understanding of the value seen in them by target users to maximize their uptake. To identify the key product features that impact user acceptance, we used a three-phase marketing research approach. In this study, we describe the results of the first-phase, qualitative focus group research performed in Chicago and San Francisco that explored subjective perceptions of oral versus alternative PrEP modalities among men having sex with men (MSM) and medical practitioners caring for MSM. Data revealed that potential value in long-acting PrEP lies more in simplifying the lives of users rather than in making them more confident in their adherence. The results provide an important guidance for designing and promoting these future long-acting products to enhance their contribution to increasing the current limited uptake of PrEP that will better stem the HIV epidemic.


Supraventricular tachycardia--part I.
Supraventricular tachycardias (SVTs) affect all age groups and are a source of significant morbidity. They are frequently encountered in otherwise healthy individuals without structural heart disease. Advances in the understanding of their mechanisms and anatomical locations have led to highly effective pharmacologic and nonpharmacologic treatment strategies. Recognition, identification, and differentiation of the various SVTs are of great importance in formulating an effective treatment strategy. Developments over the past four decades have made possible the accurate diagnosis of SVTs. Today, advances in catheter design, energy delivery systems, mapping systems, and remote navigation systems have rendered the ablation of most SVTs safe and effective. This monograph provides an in-depth discussion of the history, presentation, mechanism, and treatment strategies of the most commonly encountered SVTs. The monograph is divided into two parts. The first part is presented here.


[Effects of castration on the gonadotropin level in prepubertal males--a study on pubertal development].
The effects of prepubertal castration on circulating levels of LH and FSH were examined longitudinally in 3 male pseudohermaphrodites (1 yr., 6 yrs., 9 yrs.) and one Lt. monorchid (7 yrs.), and gonadotropin levels of prepubertal anorchism (9 yrs.) were also studied longitudinally. After castration, plasma LH and FSH concentration in the patient 1 yr. of age elevated significantly and progressively, but in two other patients 6 and 7 yrs. of age, a significant elevation of plasma LH and FSH was not observed from 90 to 450 days after the castration. Plasma LH and FSH concentration of one patient 9 yrs. of age, castrated at 1 yr., showed prepubertal values from 9 to 11 yrs. of age, and the abrupt elevation of LH and FSH occurred at 11-2/12 yrs. of age. From these observations we concluded that although castration in early childhood resulted in an immediate elevation of gonadotropin levels, a significant elevation of gonadotropin did not occur in midchildhood castration. These findings have also confirmed the evidence that the hypothalamic-pituitary-gonadal negative feedback mechanism is operative in early childhood, and supported the action of a CNS inhibitory mechanism which restrains the gonadotropin synthesis and secretion and inhibits puberty during the interval of mid-childhood.


Radius of gyration of plasmid DNA isoforms from static light scattering.
Despite the extensive interest in applications of plasmid DNA, there have been few direct measurements of the root mean square radius of gyration, R(G), of different plasmid isoforms over a broad range of plasmid size. Static light scattering data were obtained using supercoiled, open-circular, and linear isoforms of 5.76, 9.80, and 16.8 kbp plasmids. The results from this study extend the range of R(G) values available in the literature to plasmid sizes typically used for gene therapy and DNA vaccines. The experimental data were compared with available theoretical expressions based on the worm-like chain model, with the best-fit value of the apparent persistence length for both the linear and open-circular isoforms being statistically identical at 46 nm. A new expression was developed for the radius of gyration of the supercoiled plasmid based on a model for linear DNA using an effective contour length that is equal to a fraction of the total contour length. These results should facilitate the development of micro/nano-fluidic devices for DNA manipulation and size-based separation processes for plasmid DNA purification.


The 44-kb linear plasmid molecule in the relapsing fever agent Borrelia duttonii strain Ly serve as a preservation of vmp genes.
Borrelia duttonii strain Ly, a causative agent of relapsing fever, contains a linear one megabase chromosome and 12 linear plasmid molecules. Here we report that the sequence of the 44-kb linear plasmid of strain Ly is found to contain variable major protein (vmp) genes for antigenic variation of relapsing fever borreliae. The determined sequence is of 44,010 bp except for both ends of the molecule. Of 39 open reading frames (ORFs) found in the sequence, 21 ORFs (named vmpA to U) showed moderate similarities with vmp genes for Borrelia hermsii. However, most of the vmp homologues are apparently nonfunctional because of their frameshifts within the sequence and/or absence of promoter and ribosome-binding signals upstream of their genes. RT-PCR experiments using the specific primer for each vmp gene revealed that vmpE, one of the vmp genes, was expressed at the location of the 44-kb plasmid molecule. The result suggests that the plasmid molecule may play a role in the preservation of the serotype switching of vmp genes in a mammalian host.


The role of dietary factors in chronic disease control in China.
Using the dietary intake and chronic disease condition data of 39,843 adults aged over 18 years old from the 2002 National Nutrition and Health Survey in China (2002 CNHS) logistic regression analysis was applied to calculate the odd ratios (ORs) of hypertension, diabetes and dyslipidaemia for the various dietary patterns of the subjects. The higher percentage of energy intake from cereals was significantly associated with lower body mass index (BMI), lower total serum cholesterol (TC) and lower low density lipoprotein cholesterol (LDL-C), while it was significantly associated with lower risk of overweight/obesity, hypertension, high TC, high serum triglycerides (TG) and high LDL-C, but the prevalence of underweight was significantly higher in the cluster of subjects with cereal energy share more than 75%. The higher percentage of energy intake of fat was related to higher BMI, higher TC and higher LDL-C which were associated with a high risk of overweight/obesity, hypertension, TC and TG. The study confirmed the important role of dietary pattern in chronic disease control. In particular, an optimum energy contributed from cereals ranged from 55% to 65% of total dietary energy intake and dietary fat energy share no more than 30% which should be the focus of preventive measures.


Aqueous cytokine levels are associated with reduced macular thickness after intravitreal ranibizumab for diabetic macular edema.
It is controversial whether the administration of anti-vascular endothelial growth factor drugs for diabetic macular edema (DME) affects intraocular inflammatory cytokines. In this study, we measured cytokine concentration in aqueous humor before and after intravitreal injection of ranibizumab (IVR). The aim was to determine changes in cytokine concentration and their effects on DME reduction. Twelve patients (13 eyes) with DME received two IVR (0.5 mg) with a 1 month interval, and a total of 26 aqueous humor samples were obtained. Macular thickness was measured with an optical coherence tomography (OCT) using thickness-map mode with an Early Treatment Diabetic Retinopathy Study (ETDRS) 9-zone grid that was divided into two zones: a central circle with a diameter of 1 mm (zone1); and an outer circle with a diameter of 6 mm (zone2). The concentration of eotaxin-1 in aqueous humor samples decreased significantly after IVR. Baseline cytokine concentration was associated with IVR-induced DME reduction. In zone1, higher baseline concentration of interferon-induced protein (IP)-10, and in zone 2, higher baseline concentration of granulocyte-macrophage colony-stimulating factor, IP-10, and tumor necrosis factor (TNF) α; and lower baseline concentration of eotaxin-1, interleukin (IL)-5, and IL-8 were associated with improved DME. Cytokine changes were associated with IVR-induced DME reduction. In zone1, lower concentration of IP-10 compared to baseline or higher concentration of macrophage inflammatory protein (MIP) -α, and in zone 2, lower concentration of IL-5 compared to baseline, IL-8, and IP-10 or higher concentration of eotaxin-1 and MIP-1β were associated with improved DME. These findings suggest that ranibizumab affects the concentration of cytokines in aqueous humor. Various cytokines contribute to a decrease in retinal thickness, both in the center of the macula and in a larger area of the retina.


Progression of non-alcoholic steatosis to steatohepatitis and fibrosis parallels cumulative accumulation of danger signals that promote inflammation and liver tumors in a high fat-cholesterol-sugar diet model in mice.
Non-alcoholic fatty liver disease (NAFLD) is becoming a pandemic. While multiple 'hits' have been reported to contribute to NAFLD progression to non-alcoholic steatohepatitis (NASH), fibrosis and liver cancer, understanding the natural history of the specific molecular signals leading to hepatocyte damage, inflammation and fibrosis, is hampered by the lack of suitable animal models that reproduce disease progression in humans. The purpose of this study was first, to develop a mouse model that closely mimics progressive NAFLD covering the spectrum of immune, metabolic and histopathologic abnormalities present in human disease; and second, to characterize the temporal relationship between sterile/exogenous danger signals, inflammation, inflammasome activation and NAFLD progression. Male C57Bl/6 mice were fed a high fat diet with high cholesterol and a high sugar supplement (HF-HC-HSD) for 8, 27, and 49 weeks and the extent of steatosis, liver inflammation, fibrosis and tumor development were evaluated at each time point. The HF-HC-HSD resulted in liver steatosis at 8 weeks, progressing to steatohepatitis and early fibrosis at 27 weeks, and steatohepatitis, fibrosis, and tumor development at 49 weeks compared to chow diet. Steatohepatitis was characterized by increased levels of MCP-1, TNFα, IL-1β and increased liver NASH histological score. We found increased serum levels of sterile danger signals, uric acid and HMGB1, as early as 8 weeks, while endotoxin and ATP levels increased only after 49 weeks. Increased levels of these sterile and microbial danger signals paralleled upregulation and activation of the multiprotein complex inflammasome. At 27, 49 weeks of HF-HC-HSD, activation of M1 macrophages and loss of M2 macrophages as well as liver fibrosis were present. Finally, similar to human NASH, liver tumors occurred in 41% of mice in the absence of cirrhosis and livers expressed increased p53 and detectable AFP. HF-HC-HSD over 49 weeks induces the full spectrum of liver pathophysiologic changes that characterizes the progression of NAFLD in humans. NAFLD progression to NASH, fibrosis and liver tumor follows progressive accumulation of sterile and microbial danger signals, inflammasome activation, altered M1/M2 cell ratios that likely contribute to NASH progression and hepatic tumor formation.


Origins and functional diversification of salinity-responsive Na(+) , K(+) ATPase α1 paralogs in salmonids.
The Salmoniform whole-genome duplication is hypothesized to have facilitated the evolution of anadromy, but little is known about the contribution of paralogs from this event to the physiological performance traits required for anadromy, such as salinity tolerance. Here, we determined when two candidate, salinity-responsive paralogs of the Na(+) , K(+) ATPase α subunit (α1a and α1b) evolved and studied their evolutionary trajectories and tissue-specific expression patterns. We found that these paralogs arose during a small-scale duplication event prior to the Salmoniform, but after the teleost, whole-genome duplication. The 'freshwater paralog' (α1a) is primarily expressed in the gills of Salmoniformes and an unduplicated freshwater sister species (Esox lucius) and experienced positive selection in the freshwater ancestor of Salmoniformes and Esociformes. Contrary to our predictions, the 'saltwater paralog' (α1b), which is more widely expressed than α1a, did not experience positive selection during the evolution of anadromy in the Coregoninae and Salmonine. To determine whether parallel mutations in Na(+) , K(+) ATPase α1 may contribute to salinity tolerance in other fishes, we studied independently evolved salinity-responsive Na(+) , K(+) ATPase α1 paralogs in Anabas testudineus and Oreochromis mossambicus. We found that a quarter of the mutations occurring between salmonid α1a and α1b in functionally important sites also evolved in parallel in at least one of these species. Together, these data argue that paralogs contributing to salinity tolerance evolved prior to the Salmoniform whole-genome duplication and that strong selection and/or functional constraints have led to parallel evolution in salinity-responsive Na(+) , K(+) ATPase α1 paralogs in fishes.


Anakinra for corticosteroid-dependent and colchicine-resistant pericarditis: The IRAP (International Registry of Anakinra for Pericarditis) study.
Novel therapies are needed for recurrent pericarditis, particularly when corticosteroid dependent and colchicine resistant. Based on limited data, interleukin-1 blockade with anakinra may be beneficial. The aim of this multicentre registry was to evaluate the broader effectiveness and safety of anakinra in a 'real world' population. This registry enrolled consecutive patients with recurrent pericarditis who were corticosteroid dependent and colchicine resistant and treated with anakinra. The primary outcome was the pericarditis recurrence rate after treatment. Secondary outcomes included emergency department visits, hospitalisations, corticosteroid use and adverse events. Among 224 patients (46 ± 14 years old, 63% women, 75% idiopathic), the median duration of disease was 17 months (interquartile range 9-33). Most patients had elevated C-reactive protein (91%) and pericardial effusion (88%). After a median treatment of 6 months (3-12), pericarditis recurrences were reduced six-fold (2.33-0.39 per patient per year), emergency department admissions were reduced 11-fold (1.08-0.10 per patient per year), hospitalisations were reduced seven-fold (0.99-0.13 per patient per year). Corticosteroid use was decreased by anakinra (respectively from 80% to 27%; P < 0.001). No serious adverse events occurred; adverse events consisted mostly of transient skin reactions (38%) at the injection site. Adverse events led to discontinuation in 3%. A full-dose treatment duration of over 3 months followed by a tapering period of over 3 months were the therapeutic schemes associated with a lower risk of recurrence. In patients with recurrent pericarditis, anakinra appears efficacious and safe in reducing recurrences, emergency department admissions and hospitalisations.


Exploring the Effective Components and Mechanism of Action of Japanese Ardisia in the Treatment of Autoimmune Hepatitis Based on Network Pharmacology and Experimental Verification.
Japanese Ardisia is widely used as a hepatoprotective and anti-inflammatory agent in China. However, the active ingredients in Japanese Ardisia and their potential mechanisms of action in the treatment of autoimmune hepatitis (AIH) are unknown. The pharmacodynamic substance and mechanism of action of Japanese Ardisia in the treatment of AIH were investigated using network pharmacology and molecular docking technology in this study. Following that, the effects of Japanese Ardisia were evaluated using the concanavalin A (Con A)-induced acute liver injury rat model. The active ingredients and targets of Japanese Ardisia were searched using the Traditional Chinese Medicine Systems Pharmacology database, and hepatitis-related therapeutic targets were identified through GeneCards and Online Mendelian Inheritance in Man databases. A compound-target network was then constructed using Cytoscape software, and enrichment analysis was performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Molecular docking technology was used to simulate the docking of key targets, and the AIH rat model was used to validate the expression of key targets. Nineteen active chemical components and 143 key target genes were identified. GO enrichment analysis revealed that the treatment of AIH with Japanese Ardisia mainly involved DNA-binding transcription factor binding, RNA polymerase II-specific DNA transcription factor binding, cytokine receptor binding, receptor-ligand activity, ubiquitin-like protein ligase binding, and cytokine activity. In the KEGG enrichment analysis, 165 pathways were identified, including the lipid and atherosclerotic pathway, IL-17 signaling pathway, TNF signaling pathway, hepatitis B pathway, and the AGE-RAGE signaling pathway in diabetic complications. These pathways may be the key to effective AIH treatment with Japanese Ardisia. Molecular docking showed that quercetin and kaempferol have good binding to AKT1, IL6, VEGFA, and CASP3. Animal experiments demonstrated that Japanese Ardisia could increase the expression of AKT1 and decrease the expression of CASP3 protein, as well as IL-6, in rat liver tissues. This study identified multiple molecular targets and pathways for Japanese Ardisia in the treatment of AIH. At the same time, the effectiveness of Japanese Ardisia in treating AIH was verified by animal experiments.


tICA-Metadynamics: Accelerating Metadynamics by Using Kinetically Selected Collective Variables.
Metadynamics is a powerful enhanced molecular dynamics sampling method that accelerates simulations by adding history-dependent multidimensional Gaussians along selective collective variables (CVs). In practice, choosing a small number of slow CVs remains challenging due to the inherent high dimensionality of biophysical systems. Here we show that time-structure based independent component analysis (tICA), a recent advance in Markov state model literature, can be used to identify a set of variationally optimal slow coordinates for use as CVs for Metadynamics. We show that linear and nonlinear tICA-Metadynamics can complement existing MD studies by explicitly sampling the system's slowest modes and can even drive transitions along the slowest modes even when no such transitions are observed in unbiased simulations.


Mechanism of alpha-tocopheryl succinate-induced apoptosis of promyelocytic leukemia cells.
Selective induction of apoptosis in tumor cells is important for treating patients with cancer. Because oxidative stress plays an important role in the process of apoptosis, we studied the effect of alpha-tocopheryl succinate (VES) on the fate of cultured human promyelocytic leukemia cells (HL-60). The presence of fairly low concentrations of VES inhibited the growth and DNA synthesis of HL-60 cells, and also induced their apoptosis via a mechanism that was inhibited by z-VAD-fluoromethylketone (z-VAD-fmk), an inhibitor of pan-caspases. VES activated various types of caspases, including caspase-3, 6, 8, and 9, but not caspase-1. VES triggered the reaction leading to the cleavage of Bid, a member of the death agonist Bcl-2 family, and released cytochrome c (Cyt.c) from the mitochondria into the cytosol by a z-VAD-fmk-inhibitable mechanism. VES transiently increased the intracellular calcium level [Ca2+]i and stimulated the release of Cyt.c in the presence of inorganic phosphate (Pi). However, high concentrations of VES (approximately 100 microM) hardly induced swelling of isolated mitochondria but depolarized the mitochondrial membrane potential by a cyclosporin A (CsA)-insensitive mechanism. These results indicate that VES-induced apoptosis of HL-60 cells might be caused by activation of the caspase cascade coupled with modulation of mitochondrial membrane function.


LeDantec virus: identification as a rhabdovirus associated with human infection and formation of a new serogroup.
LeDantec virus, originally recovered in 1965 from a patient with a febrile illness in Senegal, was observed by thin section electron microscopy to be bullet-shaped, representative of members of the rhabdovirus group, with mean dimensions of 164 X 78 nm. Particles were observed budding from the plasma membrane and moderate numbers accumulated in the intercellular spaces. In three mammalian cell lines, LeDantec virus was rapidly cytopathic and replicated to moderately high titres. In complement fixation tests with other known rhabdoviruses, LeDantec was found to be related to Keuraliba virus, a previously ungrouped agent isolated from rodents in Senegal in 1968. We propose the formation of a new LeDantec serogroup comprising these two viruses.


Microbial ecology and biogeochemistry of continental Antarctic soils.
The Antarctica Dry Valleys are regarded as the coldest hyperarid desert system on Earth. While a wide variety of environmental stressors including very low minimum temperatures, frequent freeze-thaw cycles and low water availability impose severe limitations to life, suitable niches for abundant microbial colonization exist. Antarctic desert soils contain much higher levels of microbial diversity than previously thought. Edaphic niches, including cryptic and refuge habitats, microbial mats and permafrost soils all harbor microbial communities which drive key biogeochemical cycling processes. For example, lithobionts (hypoliths and endoliths) possess a genetic capacity for nitrogen and carbon cycling, polymer degradation, and other system processes. Nitrogen fixation rates of hypoliths, as assessed through acetylene reduction assays, suggest that these communities are a significant input source for nitrogen into these oligotrophic soils. Here we review aspects of microbial diversity in Antarctic soils with an emphasis on functionality and capacity. We assess current knowledge regarding adaptations to Antarctic soil environments and highlight the current threats to Antarctic desert soil communities.


Comparing morphologic features and complications of main clear corneal incision between junior and senior residents observed using anterior segment optical coherence tomography.
Wound construction is a critical step in phacoemulsification. Using anterior segment optical coherence tomography (AS-OCT), we compared the morphological features and complications of main incisions made by junior or senior residents during phacoemulsification. This cross-sectional comparative study included eyes with senile cataracts that underwent uneventful phacoemulsification with a clear corneal incision made by seven senior and eight junior ophthalmology residents. All eyes underwent postoperative image acquisition using AS-OCT on day one and at three months, examining for morphological features and potential complications of the main incision. We included 50 eyes of 50 patients with a male-to-female ratio of 22 (44%) to 28 (56%); 26 (52%) were operated on by junior residents and 24 (48%) by seniors. The mean geometric features of the main incisions and the frequency of early and late wound complications were comparable between the two groups (all P > 0.05). A significant correlation was found between the incision length and angle with the superior (r = + 0.80; P < 0.001 and r = - 0.63; P < 0.001, respectively) and inferior (r = + 0.84; P < 0.001 and r = - 0.68; P < 0.001, respectively) areas of the incision, as well as between the length and angle of incision (r = - 0.74; P < 0.001). The number of planes in the wound architecture was not significantly different according to senior or junior resident status (P > 0.05). Although the number of eyes with stromal hydration was significantly greater for junior residents than for seniors (P < 0.001), the corneal thickness at the entrance to the cornea or the anterior chamber, presence of endothelial wound gaping, and Descemet's membrane detachment were comparable between eyes with and without stromal hydration (all P > 0.05). At three months, 29 (58%) patients returned for examination, in whom seven (24%) had late wound complications. This study found no significant differences in the performances of junior and senior residents in terms of wound construction or its associated complications. However, considering the overall rate of some observed wound-related complications, we recommended revision of the resident educational curriculum concerning the structure and complications of the main incision.


Growth of herpes simplex virus types 1 and 2 in tissues of fertile hens' eggs in ovo and in vitro.
The growth characteristics of herpes simplex virus Types 1 and 2 were examined on the chorioallantoic membrane of the fertile hen's egg and in cell cultures derived from egg and embryo tissues. After chorioallantoic membrane inoculation, the yield of infectious Type 1 virus was highest at 2 days and declined rapidly thereafter. With the Type 2 virus replication continued longer, titres were higher, and these declined more slowly over the 7-day incubation period. In cell cultures derived from embryo tissues, both virus types multiplied well, but Type 1 gave consistently higher titres of infectious virus. Type 2 virus produced higher titres in chorioallantoic membrane-derived cell cultures than did Type 1, reflecting the findings in ovo. Temperature-marker tests in eggs showed that fresh isolates of Type 1 virus grew less readily at elevated temperatures than those of Type 2 or laboratory-adapted Type 1 strains. There was no difference in the capacity of laboratory strains of either type to grow in eggs at these temperatures.


Malignant renal arteriovenous fistulae. A cause of reversible cardiac failure.
A patient was investigated for painless haematuria, and a highly vascular renal cell carcinoma was shown on angiography. When this neoplasm was surgically removed, there was a remarkable improvement in the signs and symptoms of heart failure, from which the patient had been suffering for some time.


The risk for venous thromboembolism and cardiometabolic disorders in offspring from thrombosis-prone pedigrees.
Most family studies for venous thromboembolism (VTE) have focused on first-degree relatives. We took a pedigree-based approach and examined the risk of VTE and cardiometabolic disorders of offspring from extended pedigrees according to the densities of VTE in pedigrees. From the Swedish population, we identified a total of 482,185 pedigrees containing a mean of 14.2 parents, aunts/uncles, grandparents, and cousins of a core full-sibship that we term the pedigree offspring (n=751,060). We then derived eight empirical classes of these pedigrees based on the density of cases of VTE. The risk was determined in offspring for VTE and cardiometabolic disorders as a function of VTE density in their pedigrees. Bonferroni correction for multiple comparisons was performed. VTE was unevenly distributed in the population: the Gini Coefficient was 0.59. Higher VTE density in pedigrees was associated in the offspring with a higher risk of different VTE manifestations (deep venous thrombosis, pulmonary embolism, pregnancy- related VTE, unusual thrombosis, and superficial thrombophlebitis), thrombophilia, and lower age of first VTE event. Moreover, VTE density in pedigrees was significantly associated in the offspring with obesity, diabetes, gout, varicose veins, and arterial embolism and thrombosis (excluding brain and heart). No significant associations were observed for retinal vein occlusion, hypercholesterolemia, hypertension, coronary heart disease, myocardial infarction, ischemic stroke, atrial fibrillation, heart failure, primary pulmonary hypertension, cerebral hemorrhage, aortic aneurysm, peripheral artery disease, and overall mortality. Offspring of pedigrees with a high density of VTE are disadvantaged regarding VTE manifestations and certain cardiometabolic disorders.


Early serum sodium changes in elderly patients with nocturia receiving desmopressin.
The purpose of the study is to identify early serum sodium changes that could happen in elderly patients with nocturia receiving desmopressin. This study was conducted on 28 patients complaining of nocturia and receiving desmopressin. Inclusion criteria were patients diagnosed as having nocturia (at least one or more voids per night) aging ≥55 years with normal baseline serum sodium (135-150 mEq/L). All patients received desmopressin in the form of 60 μg at bedtime. Close follow-up was done for any adverse effects that may have occurred related to hyponatremia and serum sodium was reevaluated for all patients at 3, 7, 14, and 30 days from the start of the treatment. Desmopressin resulted in a significant decrease in nocturnal urine volume, a decrease in nocturnal polyuria index, number of night voids and the time to first void was delayed. Furthermore, statistically insignificant sodium drop in males and statistically significant sodium drop in females were noted with infrequent side effects, for example, headache (10.7%) and hyponatremia (7.14%) that started after treatment by 1 week. Hyponatremia can be avoided using the minimal effective dose of desmopressin. To receive desmopressin in elderly patients sodium baseline level must be ≥135 mmol/L. Close sodium monitoring has to be done at 7, 14, and 30 days from start of treatment for high-risk patients (especially elderly) or patients receiving other medication causing hyponatremia.


Method for effectively utilizing tunable one-pump fiber parametric wavelength converters as an enabling device for WDM routers.
In this paper a method is proposed to maximize the bandwidth of the WDM router based on one-pump fiber parametric wavelength converters. It is proved that for such converters there exists an optimum signal (idler) frequency at which the output (input) tuning range can be maximized. Analytical expressions of the optimum frequency and the maximal tuning range are deduced. Then a two-stage bidirectional wavelength conversion method is proposed. With this method the bandwidth of the WDM router based on such a converter can be significantly improved compared to the one-stage ones by 252% if ordinary highly nonlinear fibers are used or 390% if fibers with optimal fourth order dispersion are used.


Metabolic Response of Human Osteoarthritic Cartilage to Biochemically Characterized Collagen Hydrolysates.
The most frequent disease of the locomotor system is osteoarthritis (OA), which, as a chronic joint disease, might benefit more from nutrition than acute illnesses. Collagen hydrolysates (CHs) are peptidic mixtures that are often used as nutraceuticals for OA. Three CHs were characterized biochemically and pharmacologically. Our biophysical (MALDI-TOF-MS, NMR, AFM) and fluorescence assays revealed marked differences between CHs of fish (Peptan® F 5000, Peptan® F 2000) and porcine (Mobiforte®) origin with respect to the total number of peptides and common peptides between them. Using a novel dual radiolabeling procedure, no CH modulated collagen biosynthesis in human knee cartilage explants. Peptan® F 2000 enhanced the activities of the aggrecanase ADMATS4 and ADMATS5 in vitro without loss of proteoglycan from cartilage explants; the opposite effect was observed with Mobiforte®. Interleukin (IL)-6, matrix metalloproteinase (MMP)-1, -3 and -13 levels were elevated in explants that were treated with Mobiforte® and Peptan® F 5000, but not with Peptan® F 2000. In conclusion, the heterogeneous peptide composition and disparate pharmacological effects between CHs suggest that the effect of a CH preparation cannot be extrapolated to other formulations. Thus, the declaration of a CH as a safe and effective nutraceutical requires a thorough examination of its pleiotropic effects.


Priorities for hydrocephalus research: report from a National Institutes of Health-sponsored workshop.
Treatment for hydrocephalus has not advanced appreciably since the advent of cerebrospinal fluid (CSF) shunts more than 50 years ago. Many questions remain that clinical and basic research could address, which in turn could improve therapeutic options. To clarify the main issues facing hydrocephalus research and to identify critical advances necessary to improve outcomes for patients with hydrocephalus, the National Institutes of Health (NIH) sponsored a workshop titled "Hydrocephalus: Myths, New Facts, and Clear Directions." The purpose of this paper is to report on the recommendations that resulted from that workshop. The workshop convened from September 29 to October 1, 2005, in Bethesda, Maryland. Among the 150 attendees was an international group of participants, including experts in pediatric and adult hydrocephalus as well as scientists working in related fields, neurosurgeons, laboratory-based neuroscientists, neurologists, patient advocates, individuals with hydrocephalus, parents, and NIH program and intramural staff. Plenary and breakout sessions covered injury and recovery mechanisms, modeling, biomechanics, diagnosis, current treatment and outcomes, complications, quality of life, future treatments, medical devices, development of research networks and information sharing, and education and career development. The conclusions were as follows: 1) current methods of diagnosis, treatment, and outcomes monitoring need improvement; 2) frequent complications, poor rate of shunt survival, and poor quality of life for patients lead to unsatisfactory outcomes; 3) investigators and caregivers need additional methods to monitor neurocognitive function and control of CSF variables such as pressure, flow, or pulsatility; 4) research warrants novel interdisciplinary approaches; 5) understanding of the pathophysiological and recovery mechanisms of neuronal function in hydrocephalus is poor, warranting further investigation; and 6) both basic and clinical aspects warrant expanded and innovative training programs. The research priorities of this workshop provide critical guidance for future research in hydrocephalus, which should result in advances in knowledge, and ultimately in the treatment for this important disorder and improved outcomes in patients of all ages.


Cognitive performance and psychosocial functioning in patients with bipolar disorder, unaffected siblings, and healthy controls.
To assess cognitive performance and psychosocial functioning in patients with bipolar disorder (BD), in unaffected siblings, and in healthy controls. Subjects were patients with BD (n=36), unaffected siblings (n=35), and healthy controls (n=44). Psychosocial functioning was accessed using the Functioning Assessment Short Test (FAST). A sub-group of patients with BD (n=21), unaffected siblings (n=14), and healthy controls (n=22) also underwent a battery of neuropsychological tests: California Verbal Learning Test (CVLT), Stroop Color and Word Test, and Wisconsin Card Sorting Test (WCST). Clinical and sociodemographic characteristics were analyzed using one-way analysis of variance or the chi-square test; multivariate analysis of covariance was used to examine differences in neuropsychological variables. Patients with BD showed higher FAST total scores (23.90±11.35) than healthy controls (5.86±5.47; p < 0.001) and siblings (12.60±11.83; p 0.001). Siblings and healthy controls also showed statistically significant differences in FAST total scores (p = 0.008). Patients performed worse than healthy controls on all CVLT sub-tests (p < 0.030) and in the number of correctly completed categories on WCST (p = 0.030). Siblings did not differ from healthy controls in cognitive tests. Unaffected siblings of patients with BD may show poorer functional performance compared to healthy controls. FAST scores may contribute to the development of markers of vulnerability and endophenotypic traits in at-risk populations.


A long-term maternal diet transition from high-fat diet to normal fat diet during pre-pregnancy avoids adipose tissue inflammation in next generation.
Recent studies have suggested that maternal high-fat (HF) diet caused inflammation changes in adipose tissue; however, it remains unclear if maternal diet intervention before pregnancy rescues such effects in offspring. To address this question, female mice were continued on a normal-fat (NF group), or a HF diet (HF group) or transitioned from a HF diet to a NF diet at 1 (H1N group), 5 (H5N group) or 9 weeks (H9N group) prior to pregnancy. Among the three intervention groups, the H9N offspring displayed less and steady body weight gain, and maintained glucose tolerance, whereas the H1N and H5N offspring showed exacerbate these phenotypes. The H1N and H5N, but not the H9N offspring, displayed adipocyte hypertrophy associated with increased expression of genes involved in fat deposition. The H1N and H5N, but not the H9N adipose tissue, displayed increased macrophage infiltration with enhanced expression of inflammatory cytokine genes. In addition, overactivation of the NF-κB and the JNK signaling were observed in the H1N adipose tissue. Overall, our study showed that a long-term but not a short- or medium-term diet intervention before pregnancy released offspring adipose tissue inflammation induced by maternal HF diet, which adds details in our understanding how the maternal environment either promotes or discourages onset of disease in offspring. Clinically, this study is of great value for providing evidence in the design of clinical trials to evaluate the urgently required intervention strategies to minimize the intergenerational cycle of obesity.


Health-related quality of life in surgical children and adolescents with congenital heart disease compared with their age-matched healthy sibling: a cross-sectional study from a lower middle-income country, Pakistan.
Inconsistencies have been reported in health-related quality of life (HRQOL) in postoperative congenital heart disease (CHD). Despite the need for lifelong care due for residual symptoms, only a few studies have explored cardiac-related HRQOL but none in lower middle-income countries (LMIC). This study therefore addresses the gap by exploring HRQOL and its associated predictors in postoperative CHD in Pakistan. General and cardiac-related HRQOL, associated predictors. This cross-sectional study recruited patients with CHD and age-matched healthy siblings as controls (n=129 each) at a single centre in Pakistan. Patients and their siblings completed HQROL surveys (PedsQL 4.0 Generic Core, PedsQL Cognitive Functioning). Patients only completed PedsQL 3.0 Cardiac module. Generalised linear models identified predictors. The sample mean age was 8.84±3.87 years and 70% were below the poverty line for an LMIC. The majority (68%) had their first surgery after 1 year of age and were interviewed at a mean 4.08±1.91 years postoperatively.Patients with CHD had lower HRQOL in all domains compared with their age-matched siblings, with the biggest differences for total HRQOL (effect size, d=-1.35). Patients with complex CHD had lower HRQOL compared with simple to moderate CHDs in cardiac-related HRQOL. The lowest scores were for treatment problems (effect size, d=-0.91). HRQOL was worse for patients who were on cardiac medications, had complex CHD, longer cardiopulmonary bypass time, re-operations and were female. HRQOL issues persist in postoperative patients with CHD in LMIC, Pakistan. Solutions are needed to address poor HRQOL and lifelong concerns of patients and their parents.


The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity.
The response to pathogens and damage in plants and animals involves a series of carefully orchestrated, highly evolved, molecular mechanisms resulting in pathogen resistance and wound healing. In metazoans, damage- or pathogen-associated molecular pattern molecules (DAMPs, PAMPs) execute precise intracellular tasks and are also able to exert disparate functions when released into the extracellular space. The emergent consequence for both inflammation and wound healing of the abnormal extracellular persistence of these factors may underlie many clinical disorders. DAMPs/PAMPs are recognized by hereditable receptors including the Toll-like receptors, the NOD1-like receptors and retinoic-acid-inducible gene I-like receptors, as well as the receptor for advanced glycation end products. These host molecules 'sense' not only pathogens but also misfolded/glycated proteins or exposed hydrophobic portions of molecules, activating intracellular cascades that lead to an inflammatory response. Equally important are means to not only respond to these molecules but also to eradicate them. We have speculated that their destruction through oxidative mechanisms normally exerted by myeloid cells, such as neutrophils and eosinophils, or their persistence in the setting of pathologic extracellular reducing environments, maintained by exuberant necrotic cell death and/or oxidoreductases, represent important molecular means enabling chronic inflammatory states.


High performance piezocomposites for flexible device application.
Flexible piezocomposites have emerged as promising materials for highly durable wearable devices. Here, we propose a new design strategy, namely particle alignment engineering, to develop high performance flexible piezocomposites by dielectrophoresis (DEP). An ultrahigh piezoelectric voltage coefficient (g33) of 600 × 10-3 V m N-1 is achieved by a composite of (Ba0.85Ca0.15)(Ti0.90Zr0.10)O3 (BCZT) particles aligned in a polydimethylsiloxane (PDMS) matrix. To the best of our knowledge, this g33 value is by far the highest ever achieved in piezocomposites. The significantly improved poling electric voltage applied to the BCZT particles and hugely enhanced stress-transfer capability of the aligned composite synergistically contribute to the record-high piezoelectric response in flexible piezocomposites. The fabricated flexible piezoelectric touch sensor and wearable keyboard possess an excellent sensitivity and cycling stability, which demonstrate a promising strategy for exploring high performance piezocomposites for flexible device application.


The Cardiovascular Effects of Marijuana: Are the Potential Adverse Effects Worth the High?
Marijuana is the most commonly abused illicit drug in the United States (US) and much of the Westernized World with a steadily increasing prevalence in usage and abuse over the past decade, especially among adolescents. Much of the available data on 9-tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, relates to its neurological effects and anti-emetic properties, with very little on the cardiovascular (CV) effects of THC. Available literature shows that THC has three major effects on the CV and the peripheral vasculature in the form of "cannabis arteritis," cannabis-induced vasospasms, and platelet aggregation, with an unknown verdict on the relationship between marijuana use and atherosclerosis progression. This manuscript reviews these effects and possible mechanisms of action. Moreover, limitations on current views of marijuana and indirect causes of CV toxicity will be investigated, such as concurrent drug use, lifestyle, and mental health. The effects of marijuana on the CV system are extremely worrisome and likely need more attention due to the growing legalization of cannabis for medicinal and recreational use across the US. As a result, awareness among health care professionals about potential side effects and toxicities associated with acute and chronic exposure of cannabis will increase in importance.


Long-term outcomes of patients with extensively drug-resistant tuberculosis in South Africa: a cohort study.
Long-term treatment-related outcomes in patients with extensively drug-resistant (XDR) tuberculosis are unknown. We followed up a cohort of patients to address knowledge gaps. Between March, 2008, and August, 2012, we prospectively followed up a cohort of 107 patients from three provinces in South Africa, who had been diagnosed with XDR tuberculosis between August 2002, and February, 2008. Available isolates from 56 patients were genotyped to establish strain type and used for extended susceptibility testing. All patients were treated empirically as inpatients with a median of eight drugs (IQR six to ten). 44 patients (41%) had HIV. 36 (64%) of 56 isolates were resistant to at least eight drugs, and resistance to an increasing number of drugs was associated with the Beijing genotype (p=0·01). After 24 months of follow-up, 17 patients (16%) had a favourable outcome (ie, treatment cure or completion), 49 (46%) had died, seven (7%) had defaulted (interruption of treatment for at least 2 consecutive months), and 25 (23%) had failed treatment. At 60 months, 12 patients (11%) had a favourable outcome, 78 (73%) had died, four (4%) had defaulted, and 11 (10%) had failed treatment. 45 patients were discharged from hospital, of whom 26 (58%) had achieved sputum culture conversion and 19 (42%) had failed treatment. Median survival of patients who had failed treatment from time of discharge was 19·84 months (IQR 4·16-26·04). Clustering of cases and transmission within families containing a patient who had failed treatment and been discharged were shown with genotypic methods. Net sputum culture conversion occurred in 22 patients (21%) and median time to net culture conversion was 8·7 months (IQR 5·6-26·4). Independent predictors of probability of net culture conversion were no history of multidrug-resistant tuberculosis (p=0·0007) and use of clofazamine (p=0·0069). Independent overall predictors of survival were net culture conversion (p<0·0001) and treatment with clofazamine (p=0·021). Antiretroviral therapy was also a predictor of survival in patients with HIV (p=0·003). In South Africa, long-term outcomes in patients with XDR tuberculosis are poor, irrespective of HIV status. Because appropriate long-stay or palliative care facilities are scarce, substantial numbers of patients with XDR tuberculosis who have failed treatment and have positive sputum cultures are being discharged from hospital and are likely to transmit disease into the wider community. Testing of new combined regimens is needed urgently and policy makers should implement interventions to minimise disease spread by patients who fail treatment. European and Developing Countries Clinical Trials Partnership, South African National Research Foundation (SARChI), and the South African Medical Research Council.


Cluster of hemolytic-uremic syndrome caused by Shiga toxin-producing Escherichia coli O26:H11.
The epidemiology and clinical characteristics of the hemolytic-uremic syndrome (HUS) caused by Escherichia coli O157:H7 are well-known, but HUS attributable to non-O157:H7 Shiga toxin (Stx)-producing E. coli (STEC) are less thoroughly described. Here we report a cluster of HUS cases caused by STEC O26:H11 the most common non-O157:H7 STEC isolated from sporadic cases of HUS in Europe. Three children between 13 and 17 months of age, living in the same small town, developed HUS within an interval of 5 days. We present clinical and microbiologic data on the patients and their infecting isolates. The clinical course ranged from mild uncomplicated HUS to severe HUS complicated by multiorgan involvement. Microbiologic investigation demonstrated STEC of serotype O26:H11 in stools of all the patients. The phenotypic and molecular characterization of the STEC O26:H11 isolates demonstrated that these strains were identical and, unusual for STEC O26, they harbored the stx2 but not the stx1 gene. None of the patients had evidence of STEC O157:H7 infection either by culture or by E. coli O157 serology. The source of the STEC O26:H11 infection was undetermined. Our results demonstrate that diagnostic procedures based on the detection of stx genes and/or Stx production and subsequent subtyping of the isolates using molecular methods are necessary to identify such outbreaks caused by non-O157:H7 STEC.


Carboxyflavins, novel inhibitors of Taq DNA polymerase.
Carboxyflavins were found to be potent selective inhibitors of Taq DNA polymerase in a polymerase chain reaction. The inhibitions were dose-dependent, and complete inhibitions were observed at the concentration of 3.0 microM. Carboxyflavins were much less, or not sensitive to the DNA polymerases tested such as calf thymus DNA polymerase alpha, rat DNA polymerase beta, human immunodeficiency virus type 1 reverse transcriptase, the Klenow Fragment of E. coli DNA polymerase I and T4 DNA polymerase. To our knowledge, there is no other report of an agent that selectively inhibits only a thermophilic polymerase. Interestingly, the carboxyflavins were able to prevent DNA synthesis in the murine lymphoid leukemia cell line L1210 in vitro; almost complete inhibitory levels were achieved in the range of less than 10 microM.


Molecular cloning of quail thyroid-stimulating hormone (TSH) beta subunit.
Thyroid-stimulating hormone (TSH) beta subunit cDNA was obtained from Japanese quail (Coturnix japonica) by PCR and its nucleotide sequence was determined. The cDNA encodes a putative signal peptide and a mature protein consisting of 20 and 114 amino acids, respectively. The amino acid sequence of quail TSHbeta subunit shows homologies of 67-69% in mammalian species, 58% in amphibian and 43-49% in teleost fish. Comparison of the amino acid sequence with TSHbeta subunits of other species reveals some differences in several regions responsible for its biological functions and characteristic features of the avian TSHbeta subunit, suggesting that the functional domains have diverged cooperatively between the hormone and its receptor during evolution.


Diabetes in the national TV news: 1971-1981.
Millions of Americans get virtually all their current events information from the national nightly television news programs. The purpose of this study was to learn what diabetes-related information had been broadcast over the last 11 years by the network news programs. Another objective was to learn how that coverage compared with that given other chronic diseases. The Vanderbilt Television News Archives (VTNA) has videotaped every ABC, NBC, and CBS nightly newscast since mid-1968. The contents of each telecast have been catalogued and indexed. Indexes were searched for every segment that had anything to do with diabetes from 1971 through 1981. In the last 11 years there have been 32 diabetes-related news segments. More than a third were about the controversial attempt to ban saccharin. Because each network may carry essentially the same story, the number of nonoverlapping reports was 20. The total time of the diabetes-related segments was 70 minutes. The topics covered by the news reports included oral agents (5 reports), artificial sweeteners (12), biosynthetic human insulin (BHI) (7), and an assortment of unique items. The 32 diabetes-related segments compare with 23 about arthritis, 215 about heart diseases, and 925 dealing with cancer. A compilation of the non-overlapping segments has been shown to health professionals, who felt the stories were generally accurate. Diabetes is not portrayed as a killer. Therefore, diabetes seems less serious, and therefore less newsworthy, than heart disease or cancer.


SS18 together with animal-specific factors defines human BAF-type SWI/SNF complexes.
Nucleosome translocation along DNA is catalyzed by eukaryotic SNF2-type ATPases. One class of SNF2-ATPases is distinguished by the presence of a C-terminal bromodomain and is conserved from yeast to man and plants. This class of SNF2 enzymes forms rather large protein complexes that are collectively called SWI/SNF complexes. They are involved in transcription and DNA repair. Two broad types of SWI/SNF complexes have been reported in the literature; PBAF and BAF. These are distinguished by the inclusion or not of polybromo and several ARID subunits. Here we investigated human SS18, a protein that is conserved in plants and animals. SS18 is a putative SWI/SNF subunit which has been implicated in the etiology of synovial sarcomas by virtue of being a target for oncogenic chromosomal translocations that underlie synovial sarcomas. We pursued a proteomic approach whereby the SS18 open reading frame was fused to a tandem affinity purification tag and expressed in amenable human cells. The fusion permitted efficient and exclusive purification of so-called BAF-type SWI/SNF complexes which bear ARID1A/BAF250a or ARID1B/BAF250b subunits. This demonstrates that SS18 is a BAF subtype-specific SWI/SNF complex subunit. The same result was obtained when using the SS18-SSX1 oncogenic translocation product. Furthermore, SS18L1, DPF1, DPF2, DPF3, BRD9, BCL7A, BCL7B and BCL7C were identified. 'Complex walking' showed that they all co-purify with each other, defining human BAF-type complexes. By contrast,we demonstrate that human PHF10 is part of the PBAF complex, which harbors both ARID2/BAF200 and polybromo/BAF180 subunits, but not SS18 and nor the above BAF-specific subunits. SWI/SNF complexes are found in most eukaryotes and in the course of evolution new SWI/SNF subunits appeared. SS18 is found in plants as well as animals. Our results suggest that in both protostome and deuterostome animals, a class of BAF-type SWI/SNF complexes will be found that harbor SS18 or its paralogs, along with ARID1, DPF and BCL7 paralogs. Those BAF complexes are proteomically distinct from the eukaryote-wide PBAF-type SWI/SNF complexes. Finally, our results suggests that the human bromodomain factors BRD7 and BRD9 associate with PBAF and BAF, respectively.


[CT findings in "fresh" cerebral paragonimiasis].
There are few reports on CT findings in "fresh" cerebral paragonimiasis. We have experienced four cases of "fresh" cerebral paragonimiasis examined by CT scan. Three patients were children aged 7, 9, and 14 years, and one was an adult aged 25 years. Three patients were examined by CT scan 2 to 6 months after the onset of high grade fever, convulsion and focal deficit signs, and a patient was examined one month after his progressive visual disturbance. The unique CT findings are multilocular cystic lesions in temporo-occipital or in temporo-parietal lobes with extensive brain edema. Two cases were also associated with "soap-bubble" calcifications. The cysts were more dense than CSF and enhanced by contrast media. The histopathological specimen showed that the eggs of paragonimus were in the abscess cavity, of which the wall was composed with highly vascular gliomesenchymal capsule and numerous cell infiltration. Three patients underwent craniotomy for removal of abscess and decompression. Bitionol were administered and all patients recovered well. We also discussed the differential diagnosis of cerebral parasitic granulomas.


Cardiovascular and respiratory agents during pregnancy: implications for fetal development.
The management of common medical problems in pregnancy often requires adjustments in drug therapy to assure a healthy fetus. The management of steroid-dependent bronchial asthma in pregnancy requires oxygen supplementation as well as vigorous treatment of airway obstruction to protect the fetus from maternal hypoxemia. The hypertensive pregnant patient should discontinue dietary sodium restriction and diuretic therapy and should be managed with alphmethyldopa or beta-blocker therapy. Hydralazine may be added if hypertension is severe. Mitral valve prolapse appears to produce no difficulties during pregnancy and the use of prophylactic antibiotics is probably not necessary for routine vaginal delivery, unless complications occur. Digoxin and quinidine are safe to use in pregnancy, provided careful monitoring is maintained. Oral anticoagulants are contraindicated in pregnancy and should be replaced with heparin if pregnancy is desired.


Nanomechanical detection of Escherichia coli infection by bacteriophage T7 using cantilever sensors.
Viruses that infect bacteria (bacteriophages) are a promising alternative treatment for bacterial diseases, especially in the case of antibiotic resistance. Due to a renewed interest in phage therapies, development of rapid and specific detection methods for bacteria/bacteriophage interaction are gaining attention for proper diagnosis and treatment. This paper describes a new method to detect the interaction between Escherichia coli and bacteriophage T7 in a sensitive and quantitative way, using the nanomechanical motion of bacteria adhered to a cantilever surface. Our approach combines both deflection and dynamic frequency-domain characterization. The device was able to determine the viability of a low amount of living bacteria attached to the cantilever, and was used to monitor T7 interaction with E. coli over a wide range of virus concentrations up to 109 PFU ml-1. The nanomechanical assay described here requires no protein labeling and can be performed in a single reaction without additional reagents. The system was able to detect the interaction between a few thousand particles through the fluctuation of mechanical energy over a broad range of frequencies. The presented data provides the basis for more detailed studies of the sequence of molecular events that contribute to the motion of the device.


Elucidation of Binding Site and Chiral Specificity of Oxidovanadium Drugs with Lysozyme through Theoretical Calculations.
This study presents an implementation of the protein-ligand docking program GOLD and a generalizable method to predict the binding site and orientation of potential vanadium drugs. Particularly, theoretical methods were applied to the study of the interaction of two VIVO complexes with antidiabetic activity, [VIVO(pic)2(H2O)] and [VIVO(ma)2(H2O)], where pic is picolinate and ma is maltolate, with lysozyme (Lyz) for which electron paramagnetic resonance spectroscopy suggests the binding of the moieties VO(pic)2 and VO(ma)2 through a carboxylate group of an amino acid residue (Asp or Glu). The work is divided in three parts: (1) the generation of a new series of parameters in GOLD program for vanadium compounds and the validation of the method on five X-ray structures of VIVO and VV species bound to proteins; (2) the prediction of the binding site and enantiomeric preference of [VO(pic)2(H2O)] to lysozyme, for which the X-ray diffraction analysis displays the interaction of a unique isomer (i.e., OC-6-23-Δ) through Asp52 residue, and the subsequent refinement of the results with quantum mechanics/molecular mechanics methods; (3) the application of the same approach to the interaction of [VO(ma)2(H2O)] with lysozyme. The results show that convenient implementation of protein-ligand docking programs allows for satisfactorily reproducing X-ray structures of metal complexes that interact with only one coordination site with proteins and predicting with blind procedures relevant low-energy binding modes. The results also demonstrate that the combination of docking methods with spectroscopic data could represent a new tool to predict (metal complex)-protein interactions and have a general applicability in this field, including for paramagnetic species.


Evaluation of an anti-carcinoembryonic monoclonal antibody suitable for immunoscintigraphy.
An anti-carcinoembryonic antigen (CEA) monoclonal antibody (mAb 6D1. 1) was evaluated in vitro and in vivo to determine its suitability as a tracer for immunoscintigraphy of colorectal carcinomas. Determination of mAb affinity for CEA showed a constant of association of 0.63 +/- 0.11 x 10(9) M-1. Binding of technetium-99m (99mTc)-6D1.1, labeled by a direct method, to human cultured lineages was highly specific. Binding to only CEA-positive LS-174T cells resulted in a saturable curve inhibited by pre-incubation with unlabeled mAb. No binding at all was observed for the human lineages MeWo (melanoma) or ZR75-30 (breast carcinoma), neither of them expressing CEA cells. Intravenous injection of 99mTc-6D1.1 into nude mice xenografted with human LS-174T tumors resulted in planar images of excellent quality. Localization of an irrelevant mAb labeled with either 99mTc or iodine-125 was never observed in tumor masses. Biodistribution studies on excised tumoral tissue showed retention of 28.48% of the injected dose per gram of LS-174T tumor. The tumor-to-blood ratio was 3.46. The same analysis performed on the other three human xenografted tumors studied demonstrated that only the CEA-producing HT-29 (colorectal adenocarcinoma) retained 99mTc-6D1.1 while the other two (ZR75-30 and MeWo) did not. These data demonstrate that this mAb is an adequate tool for targeting CEA-expressing tumors in experimental models.