Sociodemographic differentials of selected noncommunicable diseases risk factors among adults in Matlab, Bangladesh: findings from a WHO STEPS survey.
The study examined noncommunicable diseases risk factors among adults 25 to 64 years old of the Matlab Health and Demographic Surveillance System using World Health Organization STEP-wise methodology. The prevalence of smoking was found to be very high for males (53.9%) and it increased initially with age, whereas smoking was almost nil for females (0.8%). About 30% each of males and females used smokeless tobacco and its consumption increased with age. Consumption of vegetable/fruit is very low in this population (90% below recommended level), whereas one third of males and two thirds of female have low levels of physical activities. The raised blood pressure was more prevalent among females than in males (21.0% vs 12.5%, respectively) and the same was true for being overweight (13.9% vs 10.3%, respectively). Raised blood pressure increased with age but overweight did not vary by age for males, whereas it increased initially for females. Smoking (males) and use of smokeless tobacco decreased with increase in education, but both blood pressure and overweight increased.


Interactive contour delineation and refinement in treatment planning of image-guided radiation therapy.
The accurate contour delineation of the target and/or organs at risk (OAR) is essential in treatment planning for image-guided radiation therapy (IGRT). Although many automatic contour delineation approaches have been proposed, few of them can fulfill the necessities of applications in terms of accuracy and efficiency. Moreover, clinicians would like to analyze the characteristics of regions of interests (ROI) and adjust contours manually during IGRT. Interactive tool for contour delineation is necessary in such cases. In this work, a novel approach of curve fitting for interactive contour delineation is proposed. It allows users to quickly improve contours by a simple mouse click. Initially, a region which contains interesting object is selected in the image, then the program can automatically select important control points from the region boundary, and the method of Hermite cubic curves is used to fit the control points. Hence, the optimized curve can be revised by moving its control points interactively. Meanwhile, several curve fitting methods are presented for the comparison. Finally, in order to improve the accuracy of contour delineation, the process of the curve refinement based on the maximum gradient magnitude is proposed. All the points on the curve are revised automatically towards the positions with maximum gradient magnitude. Experimental results show that Hermite cubic curves and the curve refinement based on the maximum gradient magnitude possess superior performance on the proposed platform in terms of accuracy, robustness, and time calculation. Experimental results of real medical images demonstrate the efficiency, accuracy, and robustness of the proposed process in clinical applications.


Gluten sensitivity masquerading as systemic lupus erythematosus.
Three patients are described whose original presentation and immunological profile led to the erroneous diagnosis of systemic lupus erythematosus. The correct diagnosis of gluten sensitivity was made after years of treatment with steroids and other immunosuppressive drugs. The immunological profile of IgA deficiency and/or raised double stranded DNA in the absence of antinuclear factor together with raised inflammatory markers and symptoms suggestive of an immune diathesis should alert the physician to the possibility of gluten sensitivity. The presence of an enteropathy is no longer a prerequisite for the diagnosis of gluten sensitivity, which can solely present with extraintestinal symptoms and signs. Knowledge of the diverse manifestations of gluten sensitivity is essential in avoiding such misdiagnosis.


Use of Non-Vitamin K Antagonist Oral Anticoagulants Among Patients with Nonvalvular Atrial Fibrillation and Multimorbidity.
Non-valvular atrial fibrillation (NVAF) is often accompanied by multiple comorbid conditions, which increase the associated risks and complexity of patient management. This study evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) among multimorbid patients with NVAF who were prescribed non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. A retrospective study of patients with NVAF and high multimorbidity who initiated apixaban, dabigatran, rivaroxaban, or warfarin from 1 January 2013 to 30 September 2015 was conducted using five insurance claims databases. Multimorbidity was defined as six or more comorbid conditions, and 1:1 propensity score matching (PSM) was conducted between the NOAC-warfarin and NOAC-NOAC cohorts. Cox proportional hazard models were used to evaluate the hazard ratios of stroke/SE and MB. Of the NVAF population (n = 466,991), 33.4% (n = 155,959) had multimorbidity, including 36,921 apixaban, 10,248 dabigatran, 45,509 rivaroxaban, and 63,281 warfarin patients. Compared to warfarin, apixaban and rivaroxaban were associated with a lower risk of stroke/SE (hazard ratio [HR] 0.63, 95% CI 0.54-0.74; HR 0.70, 95% CI 0.64-0.77, respectively). Apixaban and dabigatran were associated with a lower risk of MB (HR 0.61, 95% CI 0.56-0.67; HR 0.75, 95% CI 0.66-0.86, respectively) and rivaroxaban was associated with a higher risk of MB (HR 1.06, 95% CI 1.01-1.12) compared to warfarin. Among patients with NVAF and six or more comorbid conditions, NOACs were associated with varying risk of stroke/SE and MB compared to warfarin and to each other. Rather than a "one drug fits all" approach, our results may be useful for appropriate OAC treatment for multimorbid patients.


Association of digoxin therapy with case fatality rate in acute pulmonary embolism.
Despite wide usage of digoxin for various diseases in cardiology practice, its benefit is controversial and moreover it had been associated with unfavorable outcomes in some previous studies. The aim of this present study was to demonstrate whether digoxin usage was related with worse outcomes or not in patients with acute pulmonary embolisms. A total number of 1215 patients retrospectively enrolled for the study. Basic demographic features, pulmonary embolism severity index (PESI) scores, laboratory parameters and medications of patients who had been diagnosed with acute pulmonary embolism were recorded. Short (30 days) and long-term mortality were reported as the clinical outcomes. Total mortality was 15.4% in the study population and 78 of these subjects died within the first 30 days. The frequency of digoxin treatment was 8% and most of these patients were prior users. According to the binary logistic regression analyses the PESI score, right ventricle (RV) diastolic diameter, systolic pulmonary arterial pressure (sPAP), brain natriuretic peptide (BNP), troponin and digoxin therapy (odds ratio, OR: 2.82 95% confidence interval, CI: 1.39-8.31, P = 0.03) were found as independent predictors of short-term mortality. Beside these findings; sPAP, PESI score, RV diastolic diameter and digoxin therapy (hazard ratio, HR: 2.11 95%CI: 1.22-7.31, P = 0.03) were determined as independent predictors of long-term mortality in Cox regression analyses. In subgroup analysis, we determined significantly greater increase in short-term mortality with use of digoxin among patients who had chronic renal disease, among patients under thrombolytic therapy and under high dosage of digoxin therapy and among female patients. Digoxin has been used extensively for decades in the treatment of heart failure and arrhythmias despite some controversies over its benefit. For the first time in the literature, we have demonstrated independent association of digoxin therapy with short-term and long-term mortality in patients with acute pulmonary embolism.


The potential of L. scoparium, K. robusta and P. radiata to mitigate N-losses in silvopastural systems.
Silvopastoral systems aim to enhance economic, cultural and social principles by sustainably combining forest management with agriculture. In these typically high-nitrogen (N) environments, plant species selection can profoundly influence N fluxes. For grazed pastures, plants may be exposed to urine patches that have received the equivalent of up to 1000 kg N ha-1. We aimed to determine the growth and N fluxes in three potential trees that may be used in silvopastoral systems: L. scoparium, K. robusta and P. radiata. Plants were grown in a greenhouse lysimeter experiment, with controlled irrigation and temperature and exposed to N at rates of 200 kg ha-1 equiv. for 15 weeks, followed by the addition of 800 kg ha-1 N equiv, to simulate a urine patch. Urea produced a positive growth response of all plant species. Treatments containing L. scoparium and K. robusta leached lower amounts of nitrate (NO3-) (2 kg ha-1 NO3-) compared to P. radiata (53 kg ha-1). Measurements of N2O over 20 days after the application of 800 kg N ha-1 indicated an inhibitory effect of L. scoparium and K. robusta on denitrification, hence loss of N via N2O. Both L. scoparium and K. robusta demonstrated that they have potential to reduce N-losses in silvopastural systems, while producing valuable biomass.


A mutation in the catalytic subunit of yeast telomerase alters primer-template alignment while promoting processivity and protein-DNA binding.
Telomerase is a ribonucleoprotein complex that is required for maintenance of linear chromosome ends (telomeres). In yeast, the Est2 protein reverse transcribes a short template region of the TLC1 RNA using the chromosome terminus to prime replication. Yeast telomeres contain heterogeneous G(1-3)T sequences that arise from incomplete reverse transcription of the TLC1 template and alignment of the DNA primer at multiple sites within the template region. We have previously described mutations in the essential N-terminal TEN domain of Est2p that alter telomere sequences. Here, we demonstrate that one of these mutants, glutamic acid 76 to lysine (est2-LT(E76K)), restricts possible alignments between the DNA primer and the TLC1 template. In addition, this mutant exhibits increased processivity in vivo. Within the context of the telomerase enzyme, the Est2p TEN domain is thought to contribute to enzyme processivity by mediating an anchor-site interaction with the DNA primer. We show that binding of the purified TEN domain (residues 1-161) to telomeric DNA is enhanced by the E76K mutation. These results support the idea that the anchor-site interaction contributes to telomerase processivity and suggest a role for the anchor site of yeast telomerase in mediating primer-template alignment within the active site.


Pseudomonas exotoxin fusion proteins are potent immunogens for raising antibodies against P-glycoprotein.
Antibodies to specific regions of human P-glycoprotein have been difficult to obtain. We developed a method to express in E. coli fusions between Pseudomonas exotoxin and specific regions of human P-glycoprotein. We used the polymerase chain reaction to amplify the desired regions of MDR1 cDNA and to introduce appropriate restriction sites. These fragments were cloned into the 3' end of the Pseudomonas exotoxin gene. With this system we produced large amounts of fusion proteins for immunizations, and we obtained positive rabbit antiserum against P-glycoprotein with most of these antigens. We now have a comprehensive panel of polyclonal antibodies against P-glycoprotein. This system should be generally useful to raise antibodies against other eukaryotic proteins that are difficult to prepare in large quantities.


Comparing cross-situational word learning, retention, and generalisation in children with autism and typical development.
Word learning is complicated by referential ambiguity - there are often multiple potential targets for a newly-heard word. While typically developing (TD) children can accurately infer word meanings from cross-situational statistics, specific difficulties tracking word-object co-occurrences may contribute to language impairments in autism spectrum disorder (ASD). Here, we investigate cross-situational word learning as an integrated system including mapping, retention, and generalisation in both typical development and autism. In Study 1, children with ASD were as accurate at disambiguating the meanings of novel words from statistical correspondences as TD controls matched on receptive vocabulary. In Study 2, both populations spontaneously utilised social and non-social attentional cues to facilitate and accelerate their mapping of word-referent relationships. Across Studies 1 and 2, both groups retrieved and generalised word-referent representations with impressive and comparable accuracy. Although children with ASD performed very similarly to TD children on measures of learning accuracy, they were significantly slower to identify correct referents under both cued and non-cued learning conditions. These findings indicate that mechanisms supporting cross-situational word learning, and the relationships between them, are not qualitatively atypical in language-delayed children with ASD. However, the increased time required to generate correct responses suggests that these mechanisms may be less efficient, potentially impacting learning in natural environments where visual and auditory stimuli are presented rapidly. Our data support claims that word learning in the longer term is driven by the gradual accumulation of word-object associations over multiple learning instances and could potentially inform the development of interventions designed to scaffold word learning.


Infrequency of BRCA2 alterations in head and neck squamous cell carcinoma.
Alterations of BRCA2 result in increased susceptibility to breast cancer in both men and women (relative lifetime risks of 0.06 and 0.8 respectively). BRCA2 maps to 13q12-q13 and encodes a transcript of 10,157 bp. Other cancers that have been described in BRCA2 mutation carriers include those of the larynx. Human chromosome 13q has been shown previously by LOH studies to harbor several tumor suppressor genes for head and neck squamous cell carcinoma (HNSCCs). We therefore examined the role of BRCA2 in the development of these cancers. Only 6/22 (27%) of the laryngeal cancers we examined demonstrated LOH of the BRCA2-containing region. These and 10 other HNSCCs of different origins that were demonstrated by LOH studies to have lost the region of chromosome 13 containing BRCA2 were examined for alterations in this gene. SSCP analysis failed to reveal any alterations leading us to conclude that BRCA2 alterations are not frequently involved in the pathogenesis of HNSCCs and that the observed LOH of chromosome 13 loci is due to other, as yet, unidentified tumor suppressor gene(s). Interestingly tumors with LOH in this region (proximal to D13S118) were far more likely to be derived from women than men. This is unusual since HNSCCs are usually fourfold more common in men than in women.


Combination of Intravitreal Corticosteroid with Anti-vegf in Macular Edema Secondary to Retinal Vein Occlusion.
functional and anatomical results after combination of intravitreal dexamethasone implant with anti-VEGF bevacizumab in macular edema secondary to retinal vein occlusion. Retrospective analysis of 50 patients, average age 72 years, 15 men and 35 women. Inclusion criteria for treatment were retinal vein occlusion, best corrected visual acuity (BCVA) more than 20/200 and macular edema more than 250 μm. Algorithm of treatment was dexamethason, anti-VEGF (bevacizumab), dexamethason. Application of anti-VEGF bevacizumab was in interval between two applications of dexamethasone, for the first time in every patient. If there were nonperfusion areas on fluoresceine angiography (FA), or ischemia on slit lamp, repeatedly. Patients observed for 12 months at least. This cohort included patients with branch retinal vein occlusion together with central retinal vein occlusion. This is an evaluation of nonperfusion areas based on FA, BCVA, macular edema on optical coherence tomography (OCT) and number of reapplication of anti-VEGF bevacizumab. Observed adverse effects are elevation of intraocular pressure and number of patients who underwent cataract surgery. The gain of 8 letters in 1st month after 1st application of dexamethasone, central retinal thickness (CRT) reduced from 512 μm to 318 μm in average. 33 patients get 1, 3 patients get 2 and 14 patients 3 injections of bevacizumab. On the day of 2nd application of dexamethasone, in 7th month in average, the CRT increased on 465 μm, and 1th month after, the gain from the baseline was 10 letters and CRT reduced on 380 μm. All the patients were phackic at the baseline, 18 (36 %) patients underwent cataract surgery with intraocular lens implantation. Transient elevation of intraocular pressure in 15 (30 %) eyes, treated by local therapy. Combination of intravitreal dexamethasone implant with anti-VEGF bevacizumab is functionally and anatomically effective. Key words: retinal vein occlusion, macular edema, dexamethasone, bevacizumab.


Dynamic stem cell selection safeguards the genomic integrity of the epidermis.
Maintaining genomic integrity and stability is crucial for life; yet, no tissue-driven mechanism that robustly safeguards the epithelial genome has been discovered. Epidermal stem cells (EpiSCs) continuously replenish the stratified layers of keratinocytes that protect organisms against various environmental stresses. To study the dynamics of DNA-damaged cells in tissues, we devised an in vivo fate tracing system for EpiSCs with DNA double-strand breaks (DSBs) and demonstrated that those cells exit from their niches. The clearance of EpiSCs with DSBs is caused by selective differentiation and delamination through the DNA damage response (DDR)-p53-Notch/p21 axis, with the downregulation of ITGB1. Moreover, concomitant enhancement of symmetric cell divisions of surrounding stem cells indicates that the selective elimination of cells with DSBs is coupled with the augmented clonal expansion of intact stem cells. These data collectively demonstrate that tissue autonomy through the dynamic coupling of cell-autonomous and non-cell-autonomous mechanisms coordinately maintains the genomic quality of the epidermis.


The Place and the Role of Radiation Therapy in the Treatment of Thymic Carcinoma.
Thymic carcinomas arise from the epithelial cells of the thymus gland and are the most common tumors of the anterior mediastinum despite their overall rarity. Because of their rarity, their treatment remains a challenging topic. Although historically they have been treated surgically, radiation therapy (RT) has an important role either as a definitive or as a postoperative treatment. In this article, we present a review of the current therapies for the thymic carcinomas and try to identify the exact place of the RT in the optimal management of these patients.


Histidine-rich glycoprotein is present in human platelets and is released following thrombin stimulation.
Histidine-rich glycoprotein, and alpha 2-glycoprotein in human plasma, has been shown to interact with heparin, with the high-affinity lysine-binding site of plasminogen, with divalent cations, and is associated with the rosette formation between erythrocytes and lymphocytes. A specific enzyme-linked immunosorbent assay for histidine-rich glycoprotein has been developed and used to demonstrate that histidine-rich glycoprotein is present in human platelets. Histidine-rich glycoprotein was detected and quantified in detergent extracts of washed human platelets, with a mean level of 371 ng/10(9) platelets. Plasma histidine-rich glycoprotein, either in the platelet suspending medium or on the surface of the platelets, accounted for less than 3.4% of the detectable platelet histidine-rich glycoprotein. Histidine-rich glycoprotein was also demonstrated in human bone marrow megakaryocytes by immunofluorescence. The extent of histidine-rich glycoprotein release from platelets was dependent on the thrombin dose and correlated directly with the extent of serotonin release. The platelet and plasma histidine-rich glycoprotein were similar by immunochemical analysis. Anti-histidine-rich glycoprotein IgG did not inhibit platelet aggregation. Histidine-rich glycoprotein released by platelets following thrombin stimulation may play a significant role in modulating inflammatory events in the microenvironment of the platelet plug.


Inferior vena cava loop of the implantable cardioverter defibrillator endocardial lead: a possible solution of the growth problem in pediatric implantation.
The ICD is an important treatment option in adults and children with life-threatening tachyarrhythmias. The possibility of lead displacement caused by growth and the lack of dedicated leads and devices poses special problems in pediatric ICD implantation. We describe our experience in three children in whom we left a redundant lead loop within the inferior vena cava (IVC) is allow for further growth. Since February 1998, three children underwent ICD implantation at our institution. A lead (screw-in) was advanced into the right ventricular apex, and a loop was created in the IVC by progressively withdrawing the stylet and pushing in the lead. Satisfactory sensing and pacing threshold values were obtained and a successful single 16-J defibrillation test was performed. No complications were encountered. After a mean follow-up of 16 months, with a mean increase in body weight and height of 4.1 +/- 0.5 Kg and 6.3 +/- 0.4 cm, respectively, chest X ray showed some release of additional lead length, in the absence of dislodgments, while significant changes in pacing/sensing parameters were not found. In conclusion, the creation of a loop within the IVC allows the lead to adjust for growth in children receiving an ICD. This approach is feasible and safe.


Cannibalism of live lymphocytes by human metastatic but not primary melanoma cells.
The phenomenon of cell cannibalism, which generally refers to the engulfment of cells within other cells, was described in malignant tumors, but its biological significance is still largely unknown. In the present study, we investigated the occurrence, the in vivo relevance, and the underlying mechanisms of cannibalism in human melanoma. As first evidence, we observed that tumor cannibalism was clearly detectable in vivo in metastatic lesions of melanoma and often involved T cells, which could be found in a degraded state within tumor cells. Then, in vitro experiments confirmed that cannibalism of T cells was a property of metastatic melanoma cells but not of primary melanoma cells. In particular, morphologic analyses, including time-lapse cinematography and electron microscopy, revealed a sequence of events, in which metastatic melanoma cells were able to engulf and digest live autologous melanoma-specific CD8(+) T cells. Importantly, this cannibalistic activity significantly increased metastatic melanoma cell survival, particularly under starvation condition, supporting the evidence that tumor cells may use the eating of live lymphocytes as a way to "feed" in condition of low nutrient supply. The mechanism underlying cannibalism involved a complex framework, including lysosomal protease cathepsin B activity, caveolae formation, and ezrin cytoskeleton integrity and function. In conclusion, our study shows that human metastatic melanoma cells may eat live T cells, which are instead programmed to kill them, suggesting a novel mechanism of tumor immune escape. Moreover, our data suggest that cannibalism may represent a sort of "feeding" activity aimed at sustaining survival and progression of malignant tumor cells in an unfavorable microenvironment.


The cerebral cost of breathing: an FMRI case-study in congenital central hypoventilation syndrome.
Certain motor activities--like walking or breathing--present the interesting property of proceeding either automatically or under voluntary control. In the case of breathing, brainstem structures located in the medulla are in charge of the automatic mode, whereas cortico-subcortical brain networks--including various frontal lobe areas--subtend the voluntary mode. We speculated that the involvement of cortical activity during voluntary breathing could impact both on the "resting state" pattern of cortical-subcortical connectivity, and on the recruitment of executive functions mediated by the frontal lobe. In order to test this prediction we explored a patient suffering from central congenital hypoventilation syndrome (CCHS), a very rare developmental condition secondary to brainstem dysfunction. Typically, CCHS patients demonstrate efficient cortically-controlled breathing while awake, but require mechanically-assisted ventilation during sleep to overcome the inability of brainstem structures to mediate automatic breathing. We used simultaneous EEG-fMRI recordings to compare patterns of brain activity between these two types of ventilation during wakefulness. As compared with spontaneous breathing (SB), mechanical ventilation (MV) restored the default mode network (DMN) associated with self-consciousness, mind-wandering, creativity and introspection in healthy subjects. SB on the other hand resulted in a specific increase of functional connectivity between brainstem and frontal lobe. Behaviorally, the patient was more efficient in cognitive tasks requiring executive control during MV than during SB, in agreement with her subjective reports in everyday life. Taken together our results provide insight into the cognitive and neural costs of spontaneous breathing in one CCHS patient, and suggest that MV during waking periods may free up frontal lobe resources, and make them available for cognitive recruitment. More generally, this study reveals how the active maintenance of cortical control over a continuous motor activity impacts on brain functioning and cognition.


Effects of chronic ethanol consumption in experimental sepsis.
To evaluate the effects of chronic ethanol consumption on the development and the pathophysiology of sepsis, using an experimental model of polymicrobial peritonitis by feces i.p. injection. Forty-day-old male Wistar rats were divided into groups for two experiments: A and B. Experiment A was performed for determination of mortality rates, while experiment B was designed for biochemical analysis and measurement of cytokines before and after sepsis. In both the experiments, treated animals were exposed to a 10% ethanol solution as the single drinking source for 4 weeks, while untreated animals were exposed to tap water over the same period. Food was provided ad libitum. After this period, the animals underwent i.p. fecal injection for induction of sepsis. Experiment A showed that higher doses of ethanol resulted in early mortality from sepsis that was correlated with the alcohol consumption (high dose = 85.7%, low dose = 14.3%, P = 0.027). In experiment B, cytokine analysis demonstrated important changes resulting from sepsis, which were further affected by ethanol exposure. In addition, glucose and creatinine levels decreased and increased, respectively, after sepsis, but a significant change occurred only in the ethanol group (P < 0.003 glucose, P < 0.01 creatinine). The levels of pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-α, increased after sepsis, but were less evident after ethanol exposure. These differences may be the result of either early mortality or an increase in the severity of the septic process. Taking into account the high mortality rate and the extreme severity of sepsis after alcohol consumption, often encouraged by advertising, a caution should be given to patients with severe infections and a history of alcohol abuse.


Comparison of two skin temperature assessment methods after the application of topical revulsive products: Conductive iButton data logger system vs contact-free infrared thermometry.
Skin temperature assessments comprise conductive and contact-free techniques. Comparison between conductive data loggers and contact-free thermometry after the application of revulsive products is scarce. This study aimed to compare iButton data loggers with an infrared thermometer after the application of two revulsive products. Secondly, the relation between skin temperature kinetics with skin's perfusion of microcirculation was investigated. Healthy females (n = 25) were randomly allocated to two groups, representing the products A and B. Skin temperature was measured with "iButtons" and an infrared pistol at baseline and up to 1 hour after application. Skin's perfusion of microcirculation was monitored with a laser speckle contrast imager. Baseline "iButton" temperature values were significantly lower compared with infrared pistol values in both groups. After application of the products, skin temperature decreased as recorded with both devices followed by an increase to baseline values when measured with the pistol. The results obtained by the "iButtons" reached values above baseline in both products towards the end of the follow-up period. A moderate correlation was found between infrared pistol and "iButton" system in product A, with a weak negative correlation between skin's perfusion of microcirculation and temperature devices. For product B, the correlation between the devices was moderate and between skin's perfusion and temperature devices weak and positive. Both devices produced similar kinetics, except at baseline, where they may differ as metallic loggers have been insufficiently adapted to skin temperature. Skin's perfusion of microcirculation could not explain skin temperature changes.


Microbiological study of breast milk with special reference to its storage in milk bank.
Sixty five breast milk samples were subjected to bacteriological studies; each sample thrice (in fresh state, after heating at 1000C and freezing for 5 days at -20 degrees C). In fresh State, Staphylococci and diphtheroids were predominant organisms. After heating, none of the samples showed any micro-organisms while after freezing for 5 days, all the samples showing presence of micro-organisms earlier, showed decrease in colony counts. None of the milk samples showed inclusions of cytomegalovirus. Serum samples of mothers tested for Hepatitis B surface antigen and human immunodeficiency virus antibodies gave negative results. Such studies i.e. screening of breast milk samples are important if human milk is to be stored in banks and supplied to premature (high risk group) children.


Recurrence After Primary Pterygium Excision: Amniotic Membrane Transplantation with Fibrin Glue Versus Conjunctival Autograft with Fibrin Glue.
The aim of the present study was to compare the surgical results and recurrence rates of primary pterygium excision with conjunctival autografts versus amniotic membrane grafts fixated with fibrin glue. In this prospective study, 73 eyes of 65 patients who had undergone conjunctival autograft group (CAG) (n:37) or amniotic membrane group (AMG) (n:36) after pterygium excision were evaluated. Fibrin glue was used for the fixation of grafts in both groups. The patients were followed up for 12 months. Postoperative complications were recorded. The rate of recurrence was defined as the primary outcome measure. In the CAG, partial dehiscence of the graft was observed on the nasal edge on postoperative day 1 in two (5.4%) eyes that healed with secondary re-epithelialization at week 1. Twelve (32.4%) eyes showed a yellowish-orange or hemorrhagic edema of the graft on postoperative day 7 that spontaneously resolved in 1 to 3 weeks. In the AMG, partial dehiscence and folding of the amniotic membrane occurred in two (5.5%) eyes. Two eyes (5.4 %) in the CAG developed corneal recurrence and five eyes (13.8%) in the amniotic membrane graft group developed recurrence; one limbal (2.7%), four corneal recurrences (11.1%) (p = 0.25). Fibrin glue is a safe and effective method for attaching conjunctival or amniotic membrane grafts for wound closure following pterygium surgery. Although the results were not statistically significant, amniotic membrane grafting using fibrin glue seems to have a higher pterygium recurrence rate compared with conjunctival autografting.


Assessing the impact, genomics and evolution of type II secretion across a large, medically important genus: the Legionella type II secretion paradigm.
The type II secretion system (T2SS) plays a major role in promoting bacterial survival in the environment and in human hosts. One of the best characterized T2SS is that of Legionella pneumophila, the agent of Legionnaires' disease. Secreting at least 25 proteins, including degradative enzymes, eukaryotic-like proteins and novel effectors, this T2SS contributes to the ability of L. pneumophila to grow at low temperatures, infect amoebal and macrophage hosts, damage lung tissue, evade the immune system, and undergo sliding motility. The genes encoding the T2SS are conserved across the genus Legionella, which includes 62 species and >30 pathogens in addition to L. pneumophila. The vast majority of effectors associated with L. pneumophila are shared by a large number of Legionella species, hinting at a critical role for them in the ecology of Legionella as a whole. However, no other species has the same repertoire as L. pneumophila, with, as a general rule, phylogenetically more closely related species sharing similar sets of effectors. T2SS effectors that are involved in infection of a eukaryotic host(s) are more prevalent throughout Legionella, indicating that they are under stronger selective pressure. The Legionella T2SS apparatus is closest to that of Aquicella (another parasite of amoebae), and a significant number of L. pneumophila effectors have their closest homologues in Aquicella. Thus, the T2SS of L. pneumophila probably originated within the order Legionellales, with some of its effectors having arisen within that Aquicella-like progenitor, while other effectors derived from the amoebal host, mimiviruses, fungi and less closely related bacteria.


Experiences and benefits of volunteering in a community AIDS organization.
This qualitative study examines the AIDS service organization-volunteer relationship from the volunteer's point of view. Factors that led to a relationship with an AIDS service organization included personal values and individual characteristics and needs. Volunteers reported many rewards from the work itself and the responses of others. Volunteers also encountered challenges that included role demands, role-ability fit, and stress/burnout concerns as well as limited organizational resources and structural obstacles. These results suggest that care must be taken to ensure that the volunteer role meets the needs, skills, and abilities of the individual volunteering. The need to ameliorate challenges is clear for AIDS service organizations seeking to retain volunteers. Some of the preventive strategies include goal-setting and feedback, individual-sensitive role redesign, opportunity to participate in decisions, and increased communication.


Clinical staging and disease progression in frontotemporal dementia.
We aimed to develop a novel tool capable of staging disease severity in frontotemporal dementia (FTD) based upon functional dependence and behavioral changes, and to assess change over time in the 3 main FTD variants (behavioral variant FTD [bvFTD]; progressive nonfluent aphasia [PNFA]; and semantic dementia [SemD]). The Frontotemporal Dementia Rating Scale (FRS) was developed in a validation cohort of 77 consecutive clinic attendees (bvFTD = 29; PNFA = 20; SemD = 28) and applied to an independent sample of 75 patients (bvFTD = 28; PNFA = 21; SemD = 26) to establish intergroup differences. Assessments from 42 patients followed up after 12 months were used to determine annual progression. Finally, a combined sample (n = 152) was used to determine length of symptoms in each severity category. Six severity stages were identified and operationalized based upon a 30-item questionnaire (very mild to profound). The cross-sectional study revealed much greater levels of impairment in bvFTD than in the language variants, with limited correlation with general cognitive measures. Patients with SemD showed the closest association between length of symptoms and stage, taking, on average, 10 years to reach the severe stage. Patients with bvFTD appear to move most quickly between stages and patients with PNFA were intermediate. The FRS was capable of detecting functional deterioration in all 3 variants over 12 months. Disease progression differs across frontotemporal dementia (FTD) variants. Patients with behavioral variant FTD progress rapidly whereas those with semantic dementia progress more slowly. The Frontotemporal Dementia Rating Scale can aid in staging and determining disease progression. Length of symptoms and global cognitive assessments alone do not reflect disease severity and progression in FTD.


Evaluation and two-year follow-up of 455 infertile couples--pregnancy rate and outcome.
A total of 455 infertile couples were evaluated in our infertility clinic over a period of 2 years and were followed up for 2 years for occurrence of pregnancy. Couples were thoroughly investigated to determine the etiological factor in the male and female partners. One hundred and seventy-five women (38.5%) became pregnant, 47 (28%) before the complete evaluation, 66 (38%) after total work-up, and 62 (35%) after successful treatment. When both partners were normal, 40% of the woman became pregnant, but only 24% when a defect was detected in both. Half the women in the age group less than 25 years conceived compared to only one-fourth when age was more than 35 years. Sixty-five percent became pregnant when the duration of infertility was less than 2 years, and only 20% when duration was more than 4 years. One hundred and thirty (84.4%) had successful outcome of pregnancy, of which 58% had normal vaginal delivery. Spontaneous abortion occurred in 13% of cases; only one patient had an ectopic pregnancy. Cesarean section rate was 27%, and 11.8% were delivered by low midcavity forceps.


Corcoran Lecture. Cardiovascular genomics and oxidative stress.
The majority of modifiable cardiovascular risk factors are complex, polygenic, or at least oligogenic traits, with genetic and environmental determinants playing important roles in disease risk and its phenotypic expression. The Human Genome Project and subsequent mouse and rat genome data have provided powerful tools to commence the dissection of genetic determinants of hypertension and other cardiovascular risk factors. Despite several new methodologies such as genome-wide scans, genome-wide gene expression profiling, and proteomic screens, it is fair to say that the progress of genetic studies designed as nonhypothesis driven has been relatively slow. On the other hand, several interesting candidate pathways have been identified, where investigators allowed for hypothesis-driven functional studies. One example of such pathway is vascular oxidative stress with its extensive network of genes and proteins, many with proven contributions to cardiovascular disease. Therefore, in parallel to genome-wide or proteome-wide studies, it will be constructive to pursue "pathwayomics" defined here as functional studies of a candidate pathway for disease pathogenesis.


[Correlation between DNA repair synthesis and number of cells with micronuclei during gamma-irradiation of human peripheral blood lymphocytes stimulated and not stimulated with PHA].
The method of colony chromatography on BND-cellulose was used to study DNA repair synthesis (RS) after gamma-irradiation in PHA-stimulated and nonstimulated lymphocytes. The injury to lymphocytes at the cellular level was estimated by the micronuclear test. The comparison of the data on the rate of RS and the number of cells with micronuclei showed that RS inhibition, in the case of the postirradiation treatment of cells with arabinoside cytosine, leads to a decrease in viability of lymphocyte populations, the G0 cells being primarily damaged.


Metabolism of myricetin and related compounds in the rat. Metabolite formation in vivo and by the intestinal microflora in vitro.
1. The metabolism of a group of polyphenols related in structure to myricetin (3,5,7,3',4',5'-hexahydroxyflavone), including myricetin, myricitrin, 3,4,5-trihydroxyphenylacetic acid, delphinidin, robinetin, tricetin, tricin, malvin and 5,7-dihydroxy-3',4',5'-trimethoxyflavone, has been studied both in vivo after oral administration to the rat and in vitro in cultures of micro-organisms derived from the intestine of the rat. 2. It was shown that the rat intestinal microflora are able to degrade compounds of this group to the ring-fission products observed in urine after oral administration of the specific flavonoid. 3. All flavones and flavonols possessing free 5- and 7-hydroxyl groups in the A ring and a free 4'-hydroxyl group in the B ring gave rise to ring-fission products that included 3',5'-dihydroxyphenylacyl derivatives. 4. The metabolites 3,5-dihydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 3,5-dihydroxyphenylpropionic acid and 3-hydroxyphenylpropionic acid were isolated and identified by chromatographic and spectral methods. 5. On anaerobic incubation in a thioglycollate medium it was shown that intestinal micro-organisms can effect cleavage of glycosidic bonds, ring fission of certain flavonoid molecules showing 3',4',5'-trihydroxyphenyl substitution and dehydroxylation of certain flavonoid metabolites. 6. The urinary excretion of the metabolites 3,5-dihydroxyphenylacetic acid and 3-hydroxyphenylacetic acid was completely abolished when neomycin-treated rats were used.


Implantation of mouse embryonic stem cell-derived cardiac progenitor cells preserves function of infarcted murine hearts.
Stem cell transplantation holds great promise for the treatment of myocardial infarction injury. We recently described the embryonic stem cell-derived cardiac progenitor cells (CPCs) capable of differentiating into cardiomyocytes, vascular endothelium, and smooth muscle. In this study, we hypothesized that transplanted CPCs will preserve function of the infarcted heart by participating in both muscle replacement and neovascularization. Differentiated CPCs formed functional electromechanical junctions with cardiomyocytes in vitro and conducted action potentials over cm-scale distances. When transplanted into infarcted mouse hearts, CPCs engrafted long-term in the infarct zone and surrounding myocardium without causing teratomas or arrhythmias. The grafted cells differentiated into cross-striated cardiomyocytes forming gap junctions with the host cells, while also contributing to neovascularization. Serial echocardiography and pressure-volume catheterization demonstrated attenuated ventricular dilatation and preserved left ventricular fractional shortening, systolic and diastolic function. Our results demonstrate that CPCs can engraft, differentiate, and preserve the functional output of the infarcted heart.


The effect of epistasis on sexually antagonistic genetic variation.
There is increasing evidence of segregating sexually antagonistic (SA) genetic variation for fitness in laboratory and wild populations, yet the conditions for the maintenance of such variation can be restrictive. Epistatic interactions between genes can contribute to the maintenance of genetic variance in fitness and we suggest that epistasis between SA genes should be pervasive. Here, we explore its effect on SA genetic variation in fitness using a two locus model with negative epistasis. Our results demonstrate that epistasis often increases the parameter space showing polymorphism for SA loci. This is because selection in one locus is affected by allele frequencies at the other, which can act to balance net selection in males and females. Increased linkage between SA loci had more marginal effects. We also show that under some conditions, large portions of the parameter space evolve to a state where male benefit alleles are fixed at one locus and female benefit alleles at the other. This novel effect of epistasis on SA loci, which we term the 'equity effect', may have important effects on population differentiation and may contribute to speciation. More generally, these results support the suggestion that epistasis contributes to population divergence.


Sawdust--a green and economical sorbent for the removal of cadmium (II) ions.
The ability of sawdust (treated and untreated) waste, a waste material derived from the commercial processing of cedrus deodar wood for furniture production, to remove/preconcentrate Cd(II) ions from aqueous solution was determined. Sorption was found to be rapid (approximately 97% within 8 min). The binding of metal ions was found to be pH dependent, optimal sorption accruing at around pH 4-8. Potentiometric titrations of sawdust revealed two distinct pK(a) values, the first having the value similar to carboxylic groups (3.3-4.8) and second comparable with that of amines (8.53-10.2) with the densities 1.99 x 10(-4) and 7.94 x 10(-5), respectively. Retained Cd(II) ions were eluted with 5 ml of 0.1 mol l(-1) HCl. Detection limit of 0.016 microg ml(-1) was achieved with enrichment factors of 120. Recovery was quantitative using sample volume of 600 ml. The Langmuir and D-R isotherm equations were used to describe partitioning behavior for the system at different temperatures. Kinetic and thermodynamic behavior of sawdust for Cd(II) ions removal was also studied.


Selective and regulated trapping of nicotinic receptor weak base ligands and relevance to smoking cessation.
To better understand smoking cessation, we examined the actions of varenicline (Chantix) during long-term nicotine exposure. Varenicline reduced nicotine upregulation of α4β2-type nicotinic receptors (α4β2Rs) in live cells and neurons, but not for membrane preparations. Effects on upregulation depended on intracellular pH homeostasis and were not observed if acidic pH in intracellular compartments was neutralized. Varenicline was trapped as a weak base in acidic compartments and slowly released, blocking 125I-epibatidine binding and desensitizing α4β2Rs. Epibatidine itself was trapped; 125I-epibatidine slow release from acidic vesicles was directly measured and required the presence of α4β2Rs. Nicotine exposure increased epibatidine trapping by increasing the numbers of acidic vesicles containing α4β2Rs. We conclude that varenicline as a smoking cessation agent differs from nicotine through trapping in α4β2R-containing acidic vesicles that is selective and nicotine-regulated. Our results provide a new paradigm for how smoking cessation occurs and suggest how more effective smoking cessation reagents can be designed.


Control of standing balance at leaning postures with functional neuromuscular stimulation following spinal cord injury.
This study systematically explored the potential of applying feedback control of functional neuromuscular stimulation (FNS) for stabilizing various erect and leaning standing postures after spinal cord injury (SCI). Perturbations ranging from 2 to 6% body weight were applied to two subjects with motor complete thoracic level SCI who were proficient at standing with implanted multichannel neural stimulators to activate the ankle, knee, hip and trunk muscles. The subjects stood with four different postures: erect, forward, forward-right and forward-left. Repeatable and controlled perturbations were applied in the forward, backward, rightward and leftward directions by linear actuators pulling on ropes attached to the subjects via a belt worn just above the waist. Upper extremity (UE) forces exerted on a stationary walker were measured with load cells attached to the handles. A feedback controller based on center of pressure (CoP) varied the stimulation levels to the otherwise paralyzed muscles so as to resist the effects of the perturbations. The effect of the feedback controller was compared to the case where only open-loop baseline stimulation was applied. This was done in terms of: (a) maximum resultant UE force exerted by the subjects on the walker, (b) maximum resultant CoP overshoot and (c) CoP root-mean-square deviation (RMSD). Feedback control resulted in significant reductions in the mean values of the majority of outcome values compared to baseline open-loop stimulation. Maximum resultant UE force was reduced by as much as 50% in one of the postures for one of the subjects. RMSD and maximum CoPs were reduced by as much as 75 and 70%, respectively, with feedback control. These results indicate that feedback control can be used to reject destabilizing disturbances in individuals with SCI using FNS not only for erect postures but also for leaning postures typically adopted during reaching while attempting various activities of daily living.


Recruitment and delivery of the fission yeast Rst2 transcription factor via a local genome structure counteracts repression by Tup1-family corepressors.
Transcription factors (TFs) determine the transcription activity of target genes and play a central role in controlling the transcription in response to various environmental stresses. Three dimensional genome structures such as local loops play a fundamental role in the regulation of transcription, although the link between such structures and the regulation of TF binding to cis-regulatory elements remains to be elucidated. Here, we show that during transcriptional activation of the fission yeast fbp1 gene, binding of Rst2 (a critical C2H2 zinc-finger TF) is mediated by a local loop structure. During fbp1 activation, Rst2 is first recruited to upstream-activating sequence 1 (UAS1), then it subsequently binds to UAS2 (a critical cis-regulatory site located approximately 600 base pairs downstream of UAS1) through a loop structure that brings UAS1 and UAS2 into spatially close proximity. Tup11/12 (the Tup-family corepressors) suppress direct binding of Rst2 to UAS2, but this suppression is counteracted by the recruitment of Rst2 at UAS1 and following delivery to UAS2 through a loop structure. These data demonstrate a previously unappreciated mechanism for the recruitment and expansion of TF-DNA interactions within a promoter mediated by local three-dimensional genome structures and for timely TF-binding via counteractive regulation by the Tup-family corepressors.


SciQuest and the complete archive of the NZVJ launched online.
The complete archive of the New Zealand Veterinary Journal went online on 1 January 2003 on SciQuest (www.sciquest.org.nz), an innovative new e-publishing website developed by the New Zealand Veterinary Association (NZVA). This follows hot on the heels of the CD-Rom version released from the same platform in June last year. Subscribers in 2003 will be able to search and retrieve, online, the full text of any article published in the journal since its inception in 1952. To date, few veterinary science journals are able to offer such a complete and comprehensive resource. SciQuest's mission is to provide high-speed access to science and continuing education articles to scientists and veterinarians in a fully indexed and searchable format, both online (via the internet) and offline (via CD-Rom). Searching and browsing the archive online is free and abstracts are available for all articles published from 1972 onwards. Access to full text, which is presented in PDF format exactly as published, is restricted to journal subscribers. The site will be updated with each issue of the journal as it is published. The online format will largely suit institutional users and casual enquiries, whereas the offline version is designed to be loaded onto computer hard drives for immediate access, any-time, and is better suited to frequent users and veterinary practitioners. A major advantage of the offline resource is its speed and immediacy, returning search results and full text much faster than the online version, without the need for internet access. The search engine has been designed to suit specific problem-oriented enquiries, and great effort has been expended to ensure the archive is both complete and accurate. The same search engine and interface has been provided on both versions, which allows for fast and highly specific searching of titles and full text of all articles for the occurrence of any word or combinations of words, as well as indexes of author, volume, year, article type, animal type and subject. Search results can be instantly sorted by author and date of publication, and powerful secondary search features such as 'by the same author', 'in the same issue' and 'same subject' links add power and flexibility. The offline version will be updated with annual releases and is available for purchase to subscribers and members of the NZVA.


Technical note: Recording rules for behavioral studies in growing heifers fed high-concentrate diets.
Continuous recording over 24 h is an accurate method for behavioral measurements in ruminants but is very time-consuming. The aim of this study was to compare different recording rules, in particular continuous recording (CR) with different time samplings (TS) methods, when the behavior of growing heifers housed individually and fed a high-concentrate diet is recorded. Behavior of 8 growing heifers was recorded on 6 non-consecutive days. Continuous recording over 24 h, considered the control treatment, was used to evaluate TS methods by recording all the behaviors that occurred for 60 s at intervals of 2 (S2), 5 (S5), 10 (S10), 15 (S15), 20 (S20) and 30 (S30) min. Three additional TS methods were considered: a sampling of the first 10 min of every h (FS10), and a sampling during 4 h (4PF) and 8 h post-feeding (8PF). Two procedures to assess the accuracy of the relationship between CR and TS methods were used: a) data analysis using the GLIMMIX procedure of SAS together with the Pearson correlation coefficient, and b) linear regression analysis. In this last case, 1-time sampling was considered to accurately reflect true values obtained with CR if the following 3 criteria were met: the coefficient of determination () was greater than 0.76, the intercept did not differ from 0 ( > 0.05), and the slope did not differ from 1 ( > 0.05). The results of the present study suggest that the latter approach provides a much more focused and reliable way of ensuring the accuracy of each TS method. The S5 TS method produced an accurate estimate for all the behavioral activities, except for drinking, social behavior and rummaging in wood shavings, where it would be necessary to consider the S2 TS method, and S10 for self-grooming. Ruminating and resting can be accurately estimated using the S20 and S30 TS methods, respectively. However, FS10, 4PF and 8PF were inadequate TS methods to measure all the activities studied in the present experiment. In conclusion, not all the TS methods tested are adequate for measuring the behaviors recorded.


Quantification of Active Visual Attention using RGB camera.
Active visual attention (AVA) is the cognitive ability that helps to focus on important visual information while responding to a stimulus and is important for human-behavior and psychophysiological research. Existing eye-trackers/camera-based methods are either expensive or impose privacy issues as face videos are recorded for analysis. Proposed approach using blink-rate variability (BRV), is inexpensive, easy to implement, efficient and handles privacy issues, making it amenable to real-time applications. Our solution uses laptop camera/webcams and a single blink feature, namely BRV. First, we estimated participant's head pose to check camera alignment and detect if he is looking at the screen. Next, subject-specific threshold is computed using eye aspect ratio (EAR) to detect blinks from which BRV signal is constructed. Only EAR values are saved, and participant's face video is NOT saved or transmitted. Finally, a novel AVA score is computed. Results shows that the proposed score is robust across participants, ambient light conditions and occlusions like spectacles.


Hard to look on the bright side: neural correlates of impaired emotion regulation in depressed youth.
The cognitive regulation of emotion is impaired in major depressive disorder and has been linked to an imbalance of pre-frontal-subcortical brain activity. Despite suggestions that this relationship represents a neurodevelopmental marker of depression, few studies have examined the neural correlates of emotion regulation in depressed youth. We combined a 'cognitive reappraisal' paradigm with functional magnetic resonance imaging to study the neural correlates of emotional regulation in a large sample of non-medicated depressed adolescents and young adults (n = 53) and healthy controls (n = 64). As compared with healthy controls, young people with depression were less able to reduce negative affect during reappraisal, which corresponded to blunted modulation of amygdala activity. While in healthy individuals amygdala activation was modulated by age, no such relationship was observed in depressed individuals. Heightened activation of the ventromedial pre-frontal cortex (vmPFC) and reduced activation of the dorsal midline cortex was also found for the depressed group. Overall, these findings suggest that brain systems that support cognitive reappraisal are functionally altered in youth depression. We argue that excessive engagement of the vmPFC in particular, may be central to understanding how the process of putting a 'positive spin' on negative emotional material may be altered in depressed youth.


Fate of lyophilized xenogeneic corneal lenticules in intrastromal implantation and epikeratophakia.
The antigenicity of intrastromal and epikeratophakia xenografts of lyophilized corneal tissue was evaluated in nonimmune and immune recipients. Lyophilized feline lenticules were implanted into intrastromal pockets in unsensitized rabbits and rabbits sensitized to the donor cat. In both cases, the grafts remained clear. Sensitized rabbits with clear intrastromal grafts received fresh tissue penetrating keratoplasty grafts from the same donor cat, placed adjacent to the intrastromal grafts. The fresh tissue penetrating keratoplasty grafts were rapidly rejected, while the lyophilized intrastromal grafts remained clear. Cats sensitized to rabbits received lyophilized and rehydrated epikeratophakia grafts shaped from rabbit cornea; these lyophilized grafts also remained clear for the 3-month period of the study. The results indicate that lyophilized and rehydrated corneal stroma, which is devoid of living cells, is not antigenic and is not subjected to immunologic attack, even in cases where the donor and host are of different species and the host has been previously immunized to the donor.


Studies on the composition and properties of thermophilic Bacillus populations in subterranean thermal waters of Budapest (Hungary).
A collection of 148 thermophilic Bacillus isolates were obtained from two thermal wells (water temperature at about 70 degrees C) in the area of Budapest (Hungary). These isolates, furthermore seven authentic thermophilic reference strains of Bacillus spp. were submitted to detailed comparative biochemical-physiological studies. Overall similarities of these strains for 134 unit characters were determined by the SSM coefficient and clustering achieved using the UPGMA algorithm. According to the results of our computer aided numerical taxonomic analyses, numerous metabolic types, varieties and mutants of a single Bacillus sp. not identical with the known thermophilic Bacillus species constitute the major fraction of the indigenous thermophilic microbial communities in the thermal waters of the Pascal and Széchenyi wells. The data also revealed, (1) that the most adapted varieties of this Bacillus sp. can form the most dense local populations in these subterranean ecological systems. Furthermore, it seems to be probable (2) that the cells of the most commonly occurring varieties of this Bacillus sp. may be able to migrate in the underground thermal water systems between diverse subterranean regions located more or less far from one another.


Gender does not impact the short- or long-term outcomes of home-based pulmonary rehabilitation in patients with COPD.
Pulmonary rehabilitation, whether performed at home or in a specialised centre, is effective in the management of COPD. As gender-related differences in COPD were previously reported, we aimed to evaluate the impact of gender on pulmonary rehabilitation outcomes in the short, medium and long term. In this retrospective observational study of 170 women and 310 men with COPD, we compared the outcomes of an 8-week home-based pulmonary rehabilitation programme including an individualised plan of retraining exercises, physical activities, therapeutic education, and psychosocial and self-management support. Exercise tolerance, anxiety, depression, and quality of life (QOL) were assessed using the 6-min stepper test (6MST), Hospital Anxiety and Depression Scale (HADS) and Visual Simplified Respiratory Questionnaire (VSRQ), respectively. Assessments were carried out before, immediately after the pulmonary rehabilitation programme (T2) and at 8 (T8) and 14 months (T14). At baseline, women were younger (mean 62.1 versus 65.3 years), more often nonsmokers (24.7% versus 7.7%) and had a higher body mass index (28 versus 26.4 kg·m-2). They more often lived alone (50.6% versus 24.5%) and experienced social deprivation (66.7% versus 56.4%). They had significantly lower exercise tolerance (-34 strokes, 6MST) and higher anxiety and depression (+3.2 HADS total score), but there were no between gender differences in QOL (VSRQ). Both groups showed similar improvements in all outcome measures at T2, T8 and T14 with a tendency for men to lose QOL profits over time. Despite some differences in baseline characteristics, women and men with COPD had similar short-, medium- and long-term benefits of a home-based pulmonary rehabilitation programme.


Leg length and type 2 diabetes: what's the link?
Human leg length is determined by a complex interplay of genetics and environmental exposures during development, which may be associated with long-term metabolic disease risk. Here, we review recent literature on the link between relative leg length and type 2 diabetes in more and less economically developed societies, wherein the contextual influences on relative leg length are unique. We also hypothesize mechanisms underlying and mediating this association. Evidence from more economically prosperous Western populations and contemporary adult populations in China and Brazil indicates that lower relative leg length is associated with greater risk for impaired glucose homeostasis and type 2 diabetes. In Brazil, this association was stronger among women with early menarche. Although still poorly defined and in need of further research, the potential mechanisms likely involve suboptimal early-life net nutrition that simultaneously leads to retarded growth and impaired glucose regulation. An untested hypothesis is that the association is mediated by differences in skeletal muscle mass. Epidemiologic evidence from diverse settings points to humans with shorter legs relative to their stature having higher risk for type 2 diabetes. Although research is needed to test mechanistic hypotheses, the greatest potential for improving public health will come through identification of, and intervention upon, the upstream modifiable determinants of inadequate leg growth.


The pattern and habituation of the orienting response in man and rats.
Autonomic and central nervous indices of the orienting response (OR) were investigated in awake human subjects and sleeping rats. Ten acoustic stimuli of 60 dB and two stimuli of 80 dB were presented for 10 s each with a constant interstimulus interval of 50 s. Responses were averaged across subjects for each single trial. An exponential fit to scores of each physiological variable was used to compare OR, habituation and dishabituation between samples and variables. An OR to the first stimulus, habituation of response amplitude, and dishabituation in response to the change in stimulus intensity were observed for event-related EEG desynchronization, a negative-positive evoked potential complex in humans and rats, as well as for skin conductance in humans. While heart rate did not show systematic changes across the 60 dB tones in both samples, a deceleration was observed in response to the first 80 dB tone. Results suggest comparable patterns of orienting to acoustic stimuli and habituation of the OR in the awake human and the sleeping rat, suggesting the possibility of OR as a unitary response. Species differed with respect to speed of habituation but not with respect to sensitivity towards stimulus change.


A single-cell genome perspective on studying intracellular associations in unicellular eukaryotes.
Single-cell genomics (SCG) methods provide a unique opportunity to analyse whole genome information at the resolution of an individual cell. While SCG has been extensively used to investigate bacterial and archaeal genomes, the technique has been rarely used to access the genetic makeup of uncultivated microbial eukaryotes. In this regard, the use of SCG can provide a wealth of information; not only do the methods allow exploration of the genome, they can also help elucidate the relationship between the cell and intracellular entities extant in nearly all eukaryotes. SCG enables the study of total eukaryotic cellular DNA, which in turn allows us to better understand the evolutionary history and diversity of life, and the physiological interactions that define complex organisms. This article is part of a discussion meeting issue 'Single cell ecology'.


Secured Nanosynthesis-Deposition Aerosol Process for Composite Thin Films Incorporating Highly Dispersed Nanoparticles.
Application of nanocomposites in daily life requires not only small nanoparticles (NPs) well dispersed in a matrix, but also a manufacturing process that is mindful of the operator and the environment. Avoiding any exposure to NPs is one such way, and direct liquid reaction-injection (DLRI) aims to fulfill this need. DLRI is based on the controlled in situ synthesis of NPs from the decomposition of suitable organometallic precursors in conditions that are compatible with a pulsed injection mode of an aerosol into a downstream process. Coupled with low-pressure plasma, DLRI produces nanocomposite with homogeneously well-dispersed small nanoparticles that in the particular case of ZnO-DLC nanocomposite exhibit unique properties. DLRI favorably compares with the direct liquid injection of ex situ formed NPs. The exothermic hydrolysis reaction of the organometallic precursor at the droplet-gas interface leads to the injection of small and highly dispersed NPs and, consequently, the deposition of fine and controlled distribution in the nanocomposite. The scope of DLRI nanosynthesis has been extended to several metal oxides such as zinc, tin, tungsten, and copper to generalize the concept. Hence, DLRI is an attractive method to synthesize, inject, and deposit nanoparticles and meets the prevention and atom economy requirements of green chemistry.


Long-term efficacy following readministration of an adeno-associated virus vector in dogs with glycogen storage disease type Ia.
Glycogen storage disease type Ia (GSD-Ia) is the inherited deficiency of glucose-6-phosphatase (G6Pase), primarily found in liver and kidney, which causes life-threatening hypoglycemia. Dogs with GSD-Ia were treated with double-stranded adeno-associated virus (AAV) vectors encoding human G6Pase. Administration of an AAV9 pseudotyped (AAV2/9) vector to seven consecutive GSD-Ia neonates prevented hypoglycemia during fasting for up to 8 hr; however, efficacy eventually waned between 2 and 30 months of age, and readministration of a new pseudotype was eventually required to maintain control of hypoglycemia. Three of these dogs succumbed to acute hypoglycemia between 7 and 9 weeks of age; however, this demise could have been prevented by earlier readministration an AAV vector, as demonstrated by successful prevention of mortality of three dogs treated earlier in life. Over the course of this study, six out of nine dogs survived after readministration of an AAV vector. Of these, each dog required readministration on average every 9 months. However, two were not retreated until >34 months of age, while one with preexisting antibodies was re-treated three times in 10 months. Glycogen content was normalized in the liver following vector administration, and G6Pase activity was increased in the liver of vector-treated dogs in comparison with GSD-Ia dogs that received only with dietary treatment. G6Pase activity reached approximately 40% of normal in two female dogs following AAV2/9 vector administration. Elevated aspartate transaminase in absence of inflammation indicated that hepatocellular turnover in the liver might drive the loss of vector genomes. Survival was prolonged for up to 60 months in dogs treated by readministration, and all dogs treated by readministration continue to thrive despite the demonstrated risk for recurrent hypoglycemia and mortality from waning efficacy of the AAV2/9 vector. These preclinical data support the further translation of AAV vector-mediated gene therapy in GSD-Ia.


Linkage of pluripotent stem cell-associated transcripts to regulatory gene networks.
Knowledge of the transcriptional circuitry responsible for pluripotentiality and self-renewal in embryonic stem cells is tantamount to understanding early mammalian development and a prerequisite to determining their therapeutic potential. Various techniques have employed genomics to identify transcripts that were abundant in stem cells, in an attempt to define the molecular basis of 'stemness'. In this study, we have extended traditional genomic analyses to identify cis-elements that might be implicated in the control of embryonic stem cell-restricted gene promoters. The strategy relied on the generation of a problem-specific list from serial analysis of gene expression profiles and subsequent promoter analyses to identify frameworks of multiple cis-elements conserved in space and orientation among genes from the problem-specific list. Subsequent experimental data suggest that 2 novel transcription factors, B-Myb and Maz, predicted from these models, are implicated either in the maintenance of the undifferentiated stem cell state or in early steps of differentiation.


Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma.
The full potential of a graft-versus-myeloma effect after allogeneic hematopoietic cell transplantation (HCT) for patients with multiple myeloma (MM) has not been realized because of excessive early transplantation-related mortality (TRM) with conventional HCT. Autologous HCTs have been characterized by almost universal disease recurrences. The current trial combined autologous HCT with subsequent nonmyeloablative allogeneic HCT to maintain the benefits of both approaches with acceptable toxicity. Fifty-four patients, 52 years of age (median; range, 29-71 years), with previously treated stage II or III MM (52% refractory or relapsed disease) were given melphalan 200 mg/m2 and autologous HC transplants. Regimen-related toxicities after autologous HCT were moderate with a median of 6 days of neutropenia, 7 days of hospitalization, and 1 death from infection. Forty to 229 days later (median, 62 days), 52 patients received a single fraction dose of 2 Gy total body irradiation and HC transplants from HLA-identical siblings with postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). Patients experienced medians of 0 days of hospitalization, neutropenia, and thrombocytopenia. Sustained engraftment was uniform. With a median follow-up of 552 days after allografting, overall survival is 78%. One patient (2%) died before day 100 from disease progression. Thirty-eight percent of patients developed acute graft-versus-host disease (GVHD; grade II in all but 4 cases) and 46% chronic GVHD requiring therapy. Tumor responses occurred slowly. Thus far, 57% of patients have achieved complete remissions and 26% have achieved partial remissions for an overall response of 83%. Despite being evaluated in elderly patients with MM, this 2-step approach has reduced the acute toxicities of allogeneic HCT while achieving potent antitumor activities.


Pedometer step guidelines in relation to weight status among 5- to 16-year-old Australians.
The study aimed to establish pedometer step cut points in relation to weight status among 2,071 5-16 year old Australians. Height, weight and waist circumference were measured, and participants wore a pedometer for seven days. Pedometer values were taken as the average number of steps per day and weighted according to the ratio of weekdays to weekends. Receiver operating characteristic (ROC) curves were used to identify the optimal pedometer counts to predict overweight. Analysis of covariance (ANCOVA) was used to compare anthropometric variables across pedometer step quintiles. The ROC model for older females was nonsignificant. Optimal cut points were 12,000 for younger males, 11,000 for older males and 10,000 for younger females. These were largely confirmed by ANCOVA. The cut points were lower than previously reported for equivalent age groups. Cultural and environmental differences may necessitate population-specific guidelines to be established.


Acute renal failure and nephrotic syndrome due to membranoproliferative nephritis during the second trimester of pregnancy.
We report the case of a patient with acute renal failure and nephrotic syndrome during the second trimester of an otherwise uncomplicated pregnancy. Despite pregnancy, percutaneous renal biopsy was performed to evaluate the etiology, showing Type I membranoproliferative glomerulonephritis. Two therapeutic options were considered: pregnancy termination, suggested by the gynecologists, and our proposal of starting steroid therapy, in order to reduce proteinuria and improve renal function. The patient refused pregnancy termination. She received i.v. methylprednisolone boluses, followed by maintenance oral prednisone and aspirin, with prompt acute renal failure resolution and reduced proteinuria. At Week 34 + 5 days of gestation, cesarean section was performed, without intra- and postoperative complications both for mother and newborn. Clinical maternal and fetal outcomes were excellent. One-year follow-up showed normal renal function and absence of proteinuria. Lacking guidelines concerning treatment of acute renal failure due to primary nephropathy in pregnancy, we consider this case of interest for our decision-making process and for the favorable outcome.


Systematics of Halosarpheia based on morphological and molecular data.
The genus Halosarpheia (Halosphaeriales) was established for marine ascomycetes with obpyriform to sub-globose, coriaceous, brown to black ostiolate ascomata with long necks; hamathecia of catenophyses; thin-walled, unitunicate, persistent asci with thick-walled apices; and ellipsoid, one septate, hyaline ascospores equipped with coiled, threadlike apical appendages that unfurl in water. Emphasis on ascospore appendage morphology has led to the inclusion in the genus of morphologically disparate fungi from a variety of marine and freshwater habitats. To better understand the evolutionary relationships of Halosarpheia species, phylogenetic analyses were conducted on 16 Halosarpheia species, 13 other species of Halosphaeriales and representatives of the Microascales, Hypocreales, Sordariales and Xylariales using 18S and 28S rDNA sequence data. All of the Halosarpheia species occurred on the Halosphaeriales clade. The type species of the genus, H. fibrosa, occurred on a well-supported clade with two morphologically similar species, H. trullifera and H. unicellularis. This clade, which phylogenetically was distant from the clades of other Halosarpheia species, represents the genus Halosarpheia sensu stricto. The other Halosarpheia species were distributed among eight other well-supported clades clearly separated from one another based on molecular data. New generic names are established for six of these clades, one new species is described, and one species is transferred to Aniptodera. A table (Table I) comparing the morphology, habitat, substrate and distribution of the genera of aquatic ascomycetes with coiled, threadlike apical appendages treated in this study is provided, along with a key for their identification.


Dissemination of Linezolid Resistance Through Sex Pheromone Plasmid Transfer in Enterococcus faecalis.
Despite recent recognition of the ATP-binding cassette protein OptrA as an important mediator of linezolid resistance in Enterococcus faecalis worldwide, the mechanisms of optrA gene acquisition and transfer remain poorly understood. In this study, we performed comprehensive molecular and phenotypic profiling of 44 optrA-carrying E. faecalis clinical isolates with linezolid resistance. Pulse-field gel electrophoresis and DNA hybridization revealed the presence of optrA in the plasmid in 26 (59%) isolates and in the chromosome in 18 (41%) isolates. Conjugation experiments showed a successful transfer of optrA in 88.5% (23/26) of isolates carrying optrA in plasmids while no transfer occurred in any isolates carrying optrA in the chromosome (0/18). All 23 transconjugants exhibited in vitro resistance to linezolid and several other antibiotics and were confirmed to contain optrA and other resistance genes. Plasmid typing demonstrated a predominance (18/23,78%) of rep 9-type plasmids (pCF10 prototype) known to be the best studied sex pheromone responsive plasmids. Full plasmid genome sequencing of one isolate revealed the presence of drug resistance genes (optrA and fexA) and multiple sex pheromone response genes in the same plasmid, which represents the first sex pheromone responsive plasmid carrying optrA from a clinical isolate. PCR-based genotyping revealed the presence of three key sex pheromone response genes (prgA, prgB, and prgC) in 23 optrA-carrying isolates. Finally, functional studies of these isolates by clumping induction assay detected different degrees of clumping in 17 isolates. Our analysis suggests that optrA-mediated linezolid resistance can be widely disseminated through sex pheromone plasmid transfer.


Effects of High-Frequency Chest Wall Oscillation on Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
This study aimed to evaluate the efficacy of high-frequency chest wall oscillation for sputum expectoration and hospital length of stay in patients with acute exacerbations of chronic obstructive pulmonary disease. The improvements in pulmonary function and oxygenation were also investigated. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. Automated literature database searches were conducted from the earliest records to March 31, 2022. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias tool (RoB 2.0), and meta-analysis software (RevMan 5.4) was used to analyze the data. From 5439 identified articles, 13 studies (with 756 patients) were included in this meta-analysis. Compared to other airway clearance techniques, HFCWO significantly increased expectorated sputum volume by 6.18 mL (95% CI: 1.71 to 10.64; I2 = 87%), shortened hospital stay by 4.37 days (95% CI: -7.70 to -1.05; I2 = 84%). However, FEV1 (%), PaO2, and PaCO2 did not improve significantly. AECOPD patients may benefit from HFCWO therapy. HFCWO enables AECOPD patients to excrete more sputum and shorten their hospital stays. However, due to heterogeneity among the included research, these results should be interpreted with caution.


Evaluation and optimization of sample pretreatment for GC/MS-based metabolomics in embryonic zebrafish.
Metabolomics tactics have been applied in the research associated with embryonic zebrafish. However, the report regarding the evaluation of impacts of sample pretreatment on metabolomics results from zebrafish embryos is limited. In the present study, different data normalization approaches, extraction solvents, and extraction strategies for off-line derivatization gas chromatography coupled with mass spectrometry-based metabolomics analysis of zebrafish eleutheroembryos were evaluated and optimized. The results showed that, when 4-chlorophenylalanine normalization, sample homogenization and pure methanol combined with ultrasonic extraction were conducted, better repeatabilities, higher signals and broader coverages of detected metabolites can be achieved. The recovery and standard deviation of most standards were in the range of 82%-121% and 6.6%-12%, respectively, while the relative standard deviation of major detected metabolites ranged from 5.4% to 19%, indicating good extraction efficiencies and method precision. Under the developed method, 87 important endogenous metabolites such as citric acid and hypoxanthine were identified by universal databases or standards among 270 extracted metabolites, which consisted of sugars, amines, amino acids, nucleotides, fatty acids, and sterols. Therefore, the results could provide a proper pretreatment protocol for the analysis of wide-coverage metabolome in embryonic zebrafish. In addition, this study highlights the impact of normalization and extraction methods on the data quality of metabolomics analysis.


Correlation between Visible Length of the Iris and the Length of the Maxillary Central Incisor Using Digital Image Analysis- A Pilot Study.
Complete denture therapy is one such modality where science and art goes hand in hand. Selection of artificial teeth for completely edentulous patients is not easy in the absence of pre extraction records, because till date concrete guidelines do not exist. The purpose of this study was to determine if a correlation existed between the visible length of the iris and the length of the maxillary central incisor to potentially provide a guide for teeth selection. A total of 20 Indian dental students consented to participate in the pilot study. Standardized digital images of the face revealing the eyes and component of teeth on smiling was captured using a digital camera. The digital measurements of the visible iris length (medial aperture height, tangential to iris) and the length of the maxillary central incisor from the zenith to the incisal edge were analysed using Adobe Photoshop creative cloud software. The data was statistically evaluated and results were tabulated. Karl Pearson's Coefficient of Correlation was utilized to detect if any association existed between the two variables. The mean value of length of central incisor was 10.39 mm and the mean value of the visible length of iris was found to be 12.9 mm. A Pearson correlation analysis revealed an r-value <0.3 indicating minimal association between the two variables with a p-value >0.01 (.322). On inference, the correlation between the visible iris length and that of maxillary central incisor were unable to produce a strong positive statistical association. However, an association factor between the two has been obtained. Deduction of 2.5 mm from the dimension of visible iris length will help in attaining the length of artificial maxillary central incisor tooth.


[The progeny of male rats subjected to chronic exposure to a permanent magnetic field].
Offspring of male Wistar rats, exposed to continuous magnetic field of 0.5 T1 (3 hours daily during 60 days), did not have significant differences from the control according to such parameters as sex distribution, mortality rates, body mass dynamics, terms of ears coming off, eruption of teeth, onset of hearing and eyes opening. There was a tendency to the reduction of static physical efficiency in holding to the horizontal bar. Increased activity of test animals 30 days old in "the open field" and CNS excitability elevation according to reactions to a sound stress were revealed.


HCC, diet and metabolic factors: Diet and HCC.
Hepatocellular carcinoma is the most common primary liver malignancy and is an international public health concern, constituting one of the most deadly cancers worldwide. Infection with hepatitis B virus and hepatitis C virus is a major risk factor for HCC in developed countries. Emerging evidence indicates that there are other important lifestyle factors that contribute to the international burden of HCC, such as alcohol consumption, diabetes, obesity, and the intake of aflotoxin-contaminated food. Obesity and diabetes are also likely to be risk factors for HCC, the most frequent subtype of liver cancer. The chief pathway by which obesity increases risk involves the association between obesity and nonalcoholic fatty liver disease (NAFLD). Coffee consumption has been studied extensively and appears to have a favorable effect on the prevention of liver diseases, including HCC. One hypothesis suggests that coffee intake lowers serum levels of gamma-glutamyltransferase (GGT), which is associated with a lower incidence of HCC. It is estimated that more than 80% of HCC cases are attributable to four principal causes that are avoidable. It is difficult to make dietary recommendations, because it is unknown whether consuming higher amounts of specific antioxidants will decrease the risk of developing hepatocellular carcinoma. A diet rich that is in polyunsaturated fatty acids and, possibly, B-carotene could reduce the risk of HCC, and high dietary GL is associated with an increased risk independently of cirrhosis or diabetes.


Assigning and visualizing germline genes in antibody repertoires.
Identifying the germline genes involved in immunoglobulin rearrangements is an essential first step in the analysis of antibody repertoires. Based on our prior work in analysing diverse recombinant viruses, we present IgSCUEAL (Immunoglobulin Subtype Classification Using Evolutionary ALgorithms), a phylogenetic approach to assign V and J regions of immunoglobulin sequences to their corresponding germline alleles, with D regions assigned using a simple pairwise alignment algorithm. We also develop an interactive web application for viewing the results, allowing the user to explore the frequency distribution of sequence assignments and CDR3 region length statistics, which is useful for summarizing repertoires, as well as a detailed viewer of rearrangements and region alignments for individual query sequences. We demonstrate the accuracy and utility of our method compared with sequence similarity-based approaches and other non-phylogenetic model-based approaches, using both simulated data and a set of evaluation datasets of human immunoglobulin heavy chain sequences. IgSCUEAL demonstrates the highest accuracy of V and J assignment amongst existing approaches, even when the reassorted sequence is highly mutated, and can successfully cluster sequences on the basis of shared V/J germline alleles.


Home blood pressure monitoring among Canadian adults with hypertension: results from the 2009 Survey on Living with Chronic Diseases in Canada.
Canadians with hypertension are recommended to use home blood pressure monitoring (HBPM) on a regular basis. To characterize the use of HBPM among Canadian adults with hypertension. Respondents to the 2009 Survey on Living with Chronic Diseases in Canada who reported diagnosis of hypertension by a health professional (n=6142) were asked about blood pressure monitoring practices, sociodemographic characteristics, management of hypertension and blood pressure control. Among Canadian adults with hypertension, 45.9% (95% CI 43.5% to 48.3%) monitor their own blood pressure at home, 29.7% (95% CI 41.1% to 46.3%) receive health professional instruction and 35.9% (95% CI 33.5% to 38.4%) share the results with their health professional. However, fewer than one in six Canadian adults diagnosed with hypertension monitor their own blood pressure at home regularly, with health professional instruction, and communicate results to a health professional. Regular HBPM was more likely among older adults (45 years of age and older); individuals who believed they had a plan for how to control their blood pressure; and those who had been shown how to perform HBPM by a health professional - with the latter factor most strongly associated with regular HBPM (prevalence rate ratio 2.8; 95% CI 2.4 to 3.4). Although many Canadians with hypertension measure their blood pressure between health care professional visits, a minority do so according to current recommendations. More effective knowledge translation strategies are required to support self-management of hypertension through home measurement of blood pressure.


Umbilical cord mesenchymal stromal cells in serum-free defined medium display an improved safety profile.
Safety evaluations in preclinical studies are needed to confirm before translating a cell-based product into clinical application. We previously developed a serum-free, xeno-free, and chemically defined media (S&XFM-CD) for the derivation of clinical-grade umbilical cord-derived MSCs (UCMSCs), and demonstrated that intraperitoneal administration of UCMSCs in S&XFM-CD (UCMSCS&XFM-CD) exhibited better therapeutic effects than UCMSCs in serum-containing media (SCM, UCMSCSCM). However, a comprehensive investigation of the safety of intraperitoneal UCMSCS&XFM-CD treatment should be performed before clinical applications. In this study, the toxicity, immunogenicity and biodistribution of intraperitoneally transplanted UCMSCS&XFM-CD were compared with UCMSCSCM in rats via general vital signs, blood routine, blood biochemistry, subsets of T cells, serum cytokines, pathology of vital organs, antibody production and the expression of human-specific gene. The tumorigenicity and tumor-promoting effect of UCMSCS&XFM-CD were compared with UCMSCSCM in nude mice. We confirmed that intraperitoneally transplanted UCMSCS&XFM-CD or UCMSCSCM did not cause significant changes in body weight, temperature, systolic blood pressure, diastolic blood pressure, heart rate, blood routine, T lymphocyte subsets, and serum cytokines, and had no obvious histopathology change on experimental rats. UCMSCS&XFM-CD did not produce antibodies, while UCMSCSCM had very high chance of antibody production to bovine serum albumin (80%) and apolipoprotein B-100 (60%). Furthermore, intraperitoneally injected UCMSCS&XFM-CD were less likely to be blocked by the lungs and migrated more easily to the kidneys and colon tissue than UCMSCSCM. In addition, UCMSCS&XFM-CD or UCMSCSCM showed no obvious tumorigenic activity. Finally, UCMSCS&XFM-CD extended the time of tumor formation of KM12SM cells, and decreased tumor incidence than that of UCMSCSCM. Taken together, our data indicate that UCMSCS&XFM-CD display an improved safety performance and are encouraged to use in future clinical trials.


On correcting the overestimation of the permutation-based false discovery rate estimator.
Recent attempts to account for multiple testing in the analysis of microarray data have focused on controlling the false discovery rate (FDR), which is defined as the expected percentage of the number of false positive genes among the claimed significant genes. As a consequence, the accuracy of the FDR estimators will be important for correctly controlling FDR. Xie et al. found that the standard permutation method of estimating FDR is biased and proposed to delete the predicted differentially expressed (DE) genes in the estimation of FDR for one-sample comparison. However, we notice that the formula of the FDR used in their paper is incorrect. This makes the comparison results reported in their paper unconvincing. Other problems with their method include the biased estimation of FDR caused by over- or under-deletion of DE genes in the estimation of FDR and by the implicit use of an unreasonable estimator of the true proportion of equivalently expressed (EE) genes. Due to the great importance of accurate FDR estimation in microarray data analysis, it is necessary to point out such problems and propose improved methods. Our results confirm that the standard permutation method overestimates the FDR. With the correct FDR formula, we show the method of Xie et al. always gives biased estimation of FDR: it overestimates when the number of claimed significant genes is small, and underestimates when the number of claimed significant genes is large. To overcome these problems, we propose two modifications. The simulation results show that our estimator gives more accurate estimation.


End-digits preference for self-reported height depends on language.
When individuals report figures, they often prefer to round to specific end-digits (e.g. zero). Such preference has been found in reports of body weight, cigarette consumption or blood pressure measurements. Very little is known about self-reported body height. End-digit preference can distort estimates of prevalence and other statistical parameters. This study examines end-digit preference for self-reported height and how it relates with sex, age, educational level or cultural affiliation. We analysed reports of height of 47,192 individuals (aged 15 years or older) living in Switzerland and participating in one of the three population-based Swiss Health Surveys carried out in 1992/93, 1997 and 2002 respectively. Digit preferences were analysed by sex, age group, educational level, survey, smoking status, interview language (only for Swiss nationals) and nationality. Adjusted odds ratios (OR) with 95% confidence interval were calculated by using multivariate logistic regression. Italian and French nationals (44.1% and 40.6%) and Italian and French Swiss (39.6% and 35.3%) more strongly preferred zero and five than Germans and German Swiss (29.2% and 30.3%). Two, four, six and eight were more popular in Germans and German Swiss (both 44.4%). Compared to German Swiss (OR = 1), for the end-digits zero and five, the OR were 1.50 (1.38-1.63) for Italian Swiss and 1.24 (1.18-1.30) for French Swiss; 1.73 (1.58-1.89) for Italian nationals and 1.61 (1.33-1.95) for French nationals. The end-digits two, four, six and eight showed an opposite pattern. Different preferences for end-digits depending on language and nationality could be observed consistently in all three national health surveys. The patterns were strikingly similar in Swiss and foreign nationals speaking the same language, suggesting that preferences were specific to language rather than to nationality. Taking into account rounding preferences could allow more valid comparisons in analyses of self-reported data originating from different cultures.


Spectator-ion effect on the passage of ions through membranes.
In this paper, we investigate the interplay between geometric and dielectric factors in influencing the image force acting on an ion passing through a membrane, for a system having the approximate dimensions of Escherichia coli. We also study the effect of one ion in a membrane on the passage of a second ion through the membrane, by calculating the radial and angular forces experienced by the second ion due to the presence of the "spectator ion." Our conclusions follow from numerical studies on expressions obtained by solving (exactly) Laplace's equation for the model assumed in this paper. The conclusions are: (i) small changes in the dielectric constant of the membrane are far more significant in determining the image force acting on an ion in a membrane than dramatic changes in the dielectric character of the regions interior and/or exterior to the cell; (ii) a spectator ion in a membrane situated near a boundary may influence in a significant way the passage of a second ion through the middle third of the membrane. We suggest that this latter result should be taken into account in discussing the mechanism of ion migration across membranes.


Effect of intra-hippocampal injection of human recombinant growth hormone on synaptic plasticity in the nucleus basalis magnocellularis-lesioned aged rats.
In this study, we proposed that administration of hippocampal growth hormone in ageing animals with growth hormone deficiency can compensate long-term potentiation and synaptic plasticity in nucleus basalis magnocellularis (NBM)-lesioned rats. Aged male Wistar rats were randomly divided into six groups (seven in each) of sham-operated healthy rats (Cont); NBM-lesioned rats (L); NBM-lesioned rats and intrahippocampal injection of growth hormone vehicle (L + Veh); NBM-lesioned and intrahippocampal injection of growth hormone (10, 20 and 40 µg.2 µl-1) (L + GH). In vivo electrophysiological recording techniques were used to characterize maintenance of long-term potentiation at distinct times (1, 2, 3, 24 and 48 hours) after high-frequency stimulation. The population spike was enhanced significantly for about 48 hours following tetanic stimulation in rats treated with a dose-dependent growth hormone compared to the vehicle group (p < 0.05), possibly through neuronal plasticity and neurogenesis in affected areas.