Friction and wear behavior of ultrahigh molecular weight polyethylene as a function of crystallinity in the presence of the phospholipid dipalmitoyl phosphatidylcholine.
In this study, the friction and wear behavior of ultrahigh molecular weight polyethylene (UHMWPE) were evaluated as a function of polymer crystallinity in the presence of the phospholipid dipalmitoyl phosphatidylcholine (DPPC) dissolved in ethanol. Samples of UHMWPE were separately heat treated to get high and low crystallinity samples. Degree of crystallinity was evaluated using differential scanning calorimetry. Quantitative friction and wear experiments were conducted using a custom-made microtribometer with commercially available spherical Si(3)N(4) probes in controlled and phospholipid-dissolved lubricants. The higher crystallinity sample exhibited slightly lower friction than the lower crystallinity in the control and decreased significantly when phospholipids were present. The higher crystallinity sample showed a higher wear resistance than the lower crystallinity sample during all reciprocating wear tests. DPPC acting as a lubricant had a marginal effect on the wear resistance of high crystallinity UHMWPE, whereas the low crystallinity sample became more prone to wear. Atomic force microscopy topography images and contact angle measurements of both samples before and after phospholipid exposure indicate that the higher crystallinity sample absorbed a greater density of DPPC. Increasing crystallinity is a way of escalating adsorption of surface active phospholipids onto UHMWPE to make it a more wear-resistant load-bearing material for total joint replacements.


Propolis Consumption Reduces Nosema ceranae Infection of European Honey Bees (Apis mellifera).
Nosema ceranae is a widespread obligate intracellular parasite of the ventriculus of many species of honey bee (Apis), including the Western honey bee Apis mellifera, in which it may lead to colony death. It can be controlled in A. mellifera by feeding the antibiotic fumagillin to a colony, though this product is toxic to humans and its use has now been banned in many countries, so in beekeeping, there exists a need for alternative and safe products effective against N. ceranae. Honeybees produce propolis from resinous substances collected from plants and use it to protect their nest from parasites and pathogens; propolis is thought to decrease the microbial load of the hive. We hypothesized that propolis might also reduce N. ceranae infection of individual bees and that they might consume propolis as a form of self-medication. To test these hypotheses, we evaluated the effects of an ethanolic extract of propolis administered orally on the longevity and spore load of experimentally N. ceranae-infected worker bees and also tested whether infected bees were more attracted to, and consumed a greater proportion of, a diet containing propolis in comparison to uninfected bees. Propolis extracts and ethanol (solvent control) increased the lifespan of N. ceranae-infected bees, but only propolis extract significantly reduced spore load. Our propolis extract primarily contained derivatives of caffeic acid, ferulic acid, ellagic acid and quercetin. Choice, scan sampling and food consumption tests did not reveal any preference of N. ceranae-infected bees for commercial candy containing propolis. Our research supports the hypothesis that propolis represents an effective and safe product to control N. ceranae but worker bees seem not to use it to self-medicate when infected with this pathogen.


Hybrid transgastric appendectomy is feasible but does not offer advantages compared with laparoscopic appendectomy: Results from the transgastric appendectomy study.
Very few transgastric procedures, the original objective of natural orifice translumenal surgery, have been reported in the international Natural Orifice Translumenal Surgery registers. In addition, most cases were controlled mainly by laparoscopy. To show the feasibility of hybrid transgastric appendectomy and to compare results with laparoscopic a prospective, nonrandomized study was conducted. From October 2010 to May 2013, patients with acute appendicitis were screened. If the patients met the inclusion criteria, transgastric appendectomy was offered. If the patient decided on laparoscopy, the consenting patients took part in the observational part of the study. The transgastric appendectomy procedure was controlled completely by the gastroscope, although a 3 mm grasper was used to tauten the appendix. Demographic and clinical parameters were collected. Quality of life and pain were measured with a Short Form-8 questionnaire and the Visual Analogue Scale. Of the 273 patients who underwent an appendectomy, 65 agreed to take part in this study. Out of these, 30 (46.15%) underwent transgastric appendectomy and 35 (53.85%) underwent laparoscopy. No intraoperative complications were recorded. The operation duration rate was greater in the transgastric appendectomy group (94.5 minutes vs 69 minutes; P < .001). Conversions to open appendectomy and complications were the same. There were no differences in pain preoperatively or postoperatively. In both the transgastric appendectomy and laparoscopic groups, the quality of life of all the subscales increased markedly after successful resection of the pathology. These preliminary results demonstrate the feasibility of transgastric appendectomy. The postoperative course and quality of life are comparable with laparoscopic appendectomy, but no improvement due to transgastric appendectomy could be demonstrated.


Base excision repair gene polymorphisms are associated with inflammation in patients undergoing chronic hemodialysis.
Chronic inflammation may increase the risk of mortality for patients undergoing hemodialysis, while enhanced oxidative stress and DNA oxidative damage are involved in the inflammatory response. The purpose of this study was to examine the associations between inflammation and polymorphisms in the base excision repair (BER) system, which protects against oxidative DNA damage, among hemodialysis patients. Data were analyzed from 167 hemodialysis patients and 66 healthy controls. All subjects were evaluated for the expression of inflammatory cytokines (IL-1β and IL-6) and genotyped for two BER genes, including hOGG1 c.977C>G, MUTYH c.972G>C and AluYb8MUTYH. The results showed that the hemodialysis patients had significantly higher levels of IL-1β and IL-6 than the healthy controls. In the healthy controls, no patterns of association were observed between the hOGG1 c.977C>G or MUTYH c.972G>C genotypes and IL-1β or IL-6 levels; however, patients with the MUTYH c.972G/G genotype presented higher levels of IL-1β than those with the C/C genotype. The AluYb8MUTYH genotype was strongly associated with increased IL-1β levels among controls and increased IL-1β and IL-6 levels among hemodialysis patients. Additionally, the synergetic effect of these variations of the BER genes on the levels of IL-1β and IL-6 was investigated. The combinations of the AluYb8MUTYH genotype with the hOGG1 c.977 C>G or MUTYH c.972 G>C genotypes were associated with the IL-1β and IL-6 levels in hemodialysis patients. This is the first report showing an association between BER genetic polymorphisms and the inflammatory state during hemodialysis; this association might be mediated by impaired anti-oxidant defense mechanisms.


The Association of Perceived Memory Loss with Osteoarthritis and Related Joint Pain in a Large Appalachian Population.
Previous studies have documented memory impairment in several chronic pain syndromes. However, the potential link between memory loss and osteoarthritis (OA), the second most common cause of chronic pain, remains little explored. In this cross-sectional study, we examine the association of perceived memory loss to OA and assess the potential mediating influence of sleep and mood disturbance in a large Appalachian population. Cross-sectional. US Ohio Valley. A total of 21,982 Appalachian adults age 40 years or older drawn from the C8 Health Project (N = 19,004 adults without and 2,478 adults with OA). All participants completed a comprehensive health survey between 2005 and 2006. Medical history, including physician diagnosis of OA, lifestyle factors, short- and long-term memory loss, sleep quality, and mood were assessed via self-report. After adjustment for demographic, lifestyle, health-related, and other factors, participants with OA were almost three times as likely to report frequent memory loss (adjusted odds ratios [ORs] for short- and long-term memory loss, respectively = 2.7, 95% confidence interval [CI] = 2.2-3.3, and 2.6, 95% CI = 2.0-3.3). The magnitude of these associations increased significantly with rising frequency of reported joint pain (adjusted OR for OA with frequent joint pain vs no OA = 3.3, 95% CI = 2.6-4.1, Ptrend < 0.00001). Including measures of mood and sleep impairment attenuated but did not eliminate these associations (ORs for any memory loss = 2.0, 95% CI = 1.6-2.4, and 2.1, 95% CI = 1.7-2.8, adjusted for sleep and mood impairment, respectively; OR = 1.8, 95% CI = 1.4-2.2, adjusted for both factors). In this large cross-sectional study, OA and related joint pain were strongly associated with perceived memory loss; these associations may be partially mediated by sleep and mood disturbance.


Predation risks of signalling and searching: bats prefer moving katydids.
Males signalling their attractiveness to females are at risk from predators that exploit mating signals to detect and locate prey. Signalling, however, is not the only risky activity in sexual interactions: mate searching can incur risk as well. Male Neotropical pseudophylline katydids produce both acoustic and vibrational signals (tremulations). Females reply to male signals with tremulations of their own, and both sexes walk to find one another. We asked if movement increases predation risk, and whether tremulation or walking was more attractive to predators. We offered the Neotropical gleaning bat Micronycteris microtis a series of two-choice tests, presenting the bats with katydid models that were motionless or moved in a way to mimic either tremulating or walking. We found that prey movements do put prey at risk. Although M. microtis can detect motionless prey on leaves, they preferred moving prey. Our study shows that movement can put searching or signalling prey in danger, potentially explaining why silent female katydids are frequently consumed by gleaning bats.


Supportive care for children with cancer.
In developed countries the survival rate of children with cancer exceeds 75%. Optimal supportive care is necessary to deliver the burdensome treatment protocols. As the intensity of primary treatment has escalated, so have the side effects like myelosuppression and infection. Children who receive aggressive chemotherapy have an approximately 40% chance of experiencing a febrile episode during neutropenia. Patients should be treated with intravenous broad-spectrum antibiotics even if they have been assessed as low risk. There is no proof of the usefulness of special measures concerning food products during neutropenia. In contrast to adults, most children who receive chemotherapy will have a central venous catheter inserted (≥ 80-90%). The two most important complications are infections and thrombosis. The Multinational Association of Supportive Care in Cancer (MASCC) guideline in adult oncology is available to prevent and treat nausea and vomiting. In highly emetogenic chemotherapy, the combination of a serotonin receptor antagonist plus a corticosteroid should be used. Pain in children with cancer is mainly therapy- or procedure-related. As in adults, the stepladder of the World Health Organization (WHO) is used as a guideline for adequate treatment of pain. It is of utmost importance that children receive optimal pain management during the initial procedures. Sedation is performed in many different ways. Palliative care starts with information about the incurability of the disease for parents, the patient, and the professionals involved. Children in palliative care for progressive cancer should be at home as much as possible, even in the terminal phase. The organization of health care and the facilities differ at a national level, so the requirements and choices for optimal care vary by country. Palliative care has to be incorporated into the structural base in the training of pediatricians and pediatric nurses. The first goal of palliative care is to reduce distressing symptoms. During the whole period of palliative care stepwise withdrawal and withholding of treatment options are important issues. The multidisciplinary approach should also span the broad field of psychosocial issues covering both the child's and the caregiver's specific psychosocial needs. Continuity of care is also depicted by contacts afterwards during family bereavement.


[Dental and gingival pain and associated factors among Brazilian adolescents: an analysis of the Brazilian Oral Health Survey 2002-2003].
The aim of this study was to estimate the prevalence of dental and gingival pain and associated factors among Brazilian adolescents (15-19 years of age). Data from 16,126 adolescents who participated in the Brazilian Oral Health Survey SB-Brazil 2002-2003 were used. The outcome measured was dental and gingival pain in the last six months. Independent variables were per capita income, schooling, school enrollment, gender, skin color, age, area of residence, time since last dental appointment, type of dental service, DMFT index and its components, dental calculus, and Dental Aesthetic Index. Simple and multiple Poisson regression analyses were performed. Prevalence of dental and gingival pain was 35.6% (95%CI: 34.8-36.4). Increased prevalence of pain was associated with: female gender, low income, non-students, students enrolled in public schools, and grade-for-age lag. In addition, adolescents with high levels of dental caries and dental calculus also reported higher prevalence of dental pain. Dental and gingival pain can be considered a relevant public health problem, suggesting the need for preventive measures.


Frequency-domain motion estimation using a complex lapped transform.
A frequency-domain algorithm for motion estimation based on overlapped transforms of the image data is developed as an alternative to block matching methods. The complex lapped transform (CLT) is first defined by extending the lapped orthogonal transform (LOT) to have complex basis functions. The CLT basis functions decay smoothly to zero at their end points, and overlap by 2:1 when a data sequence is transformed. A method for estimating cross-correlation functions in the CLT domain is developed. This forms the basis of a motion estimation algorithm that calculates vectors for overlapping, windowed regions of data. The overlapping data window used has no block edge discontinuities and results in smoother motion fields. Furthermore, when motion compensation is performed using similar overlapping regions, the algorithm gives comparable or smaller prediction errors than standard models using exhaustive search block matching, and computational load is lower for larger displacement ranges and block sizes.


Importance of pediatric rheumatologists and transitional care for juvenile idiopathic arthritis-associated uveitis: a retrospective series of 9 cases.
Juvenile idiopathic arthritis-associated uveitis (JIA-U) is a serious condition associated with the risk of blindness. However, pediatric rheumatologists rarely encounter cases of blindness, because most patients reach adulthood during the course of follow-up before blindness occurs. Here, we report the progress of 9 patients with JIA-U, including 2 patients who became blind after the transition period. We aimed to highlight the importance of the role of pediatric rheumatologists and transitional care in preventing blindness associated with JIA-U. We conducted a retrospective analysis of the case records of 9 JIA-U patients (1 male, 8 female; median age 16.8 years, range 5.5-19.8 years). All patients presented with oligo-juvenile idiopathic arthritis (oligo-JIA) (one presented with extended oligo-JIA); the median age of uveitis onset was 5.0 years (range 3.0-13.0 years), and the onset of uveitis preceded the onset of arthritis in 2 patients. The median disease duration was 12.5 years (range 3.5-24.7 years); 4 patients had anti-nuclear antibody (ANA) positivity (≧1:160) (all with a homogeneous and speckled-pattern subtype). All patients were negative for rheumatoid factor. Eight patients received methotrexate, 7 patients received one or more biologic drugs (etanercept, infliximab, adalimumab, and golimumab), and 6 patients required ophthalmic surgery at an early age (≦ 18 years). Two patients developed blindness after the transition period. Medical examination by pediatric rheumatologists and use of biologics had been delayed in both patients. One patient developed depression after transition and interrupted her own treatment. The reason for blindness in the 2 patients was thought to be the delay in the commencement of treatment and failure to provide transitional care. Inflammation is difficult to control in JIA-U even with appropriate treatment. Pediatric rheumatologists must be informed about the risk of JIA-U blindness, especially after transition. To ensure a good prognosis, the specialized treatment with the involvement of pediatric rheumatologists is necessary early on, and consideration for transitional medicine is essential. Therefore, this report reaffirms the importance of planned transitional care that has been advocated for globally.


Imaging of the renal arteries: value of MR angiography.
We compared the efficacy of MR angiography with that of conventional angiography for visualizing the renal arteries and detecting renovascular disease. Thirty-three MR angiographic studies, consisting of axial two-dimensional (2-D) phase-contrast, coronal 2-D phase-contrast, and coronal 2-D time-of-flight acquisitions, were performed within 48 hr of conventional arteriography. The studies were done to evaluate possible renovascular hypertension (n = 25) or potential donor nephrectomy (n = 8). The three MR image sets were interpreted independently, in random order by three observers, with regard to the number of renal arteries, degree of vessel visualization, arteriovenous overlap, and presence of renovascular disease. A fourth interpretation was based on the combined axial and coronal phase-contrast image sets. Evaluation was limited to the proximal 35 mm of each renal artery. Renal artery visualization and detection of renovascular disease were more complete with coronal phase-contrast (80% sensitivity, 91% specificity) than with time-of-flight (53% sensitivity, 97% specificity) images. Combined axial and coronal phase-contrast images permitted visualization of the proximal 35 mm of all dominant renal arteries and detection of 13 of 15 stenoses (87% sensitivity, 97% specificity). Our data suggest that biplanar MR angiography has considerable potential as a noninvasive screening technique for the evaluation of renovascular disease.


The effect of smoking on prostate cancer survival: a cohort analysis in Barcelona.
The aim of this study was to analyse the effect of smoking on prostate cancer-specific mortality and all-cause mortality. A retrospective cohort study was conducted with 1109 patients with prostate cancer diagnosed from 1992 to 2008, identified through the Hospital del Mar Cancer Registry (Barcelona, Spain). Information on smoking habits was retrieved from clinical records and patients were classified into three categories: never smoker, exsmoker and current smoker. Patients were followed up until December 2011. Survival curves were plotted using Kaplan-Meier methods. Cox models were used to estimate hazard ratios and 95% confidence intervals. Median age at diagnosis was 70.6 years and 16.7% of patients had stage IV tumours. During the follow-up period, 466 deaths occurred, 36.1% of them being specifically due to prostate cancer. The median follow-up time of the censored patients was 5.8 years. There was a significant difference in disease-specific survival between never smokers, exsmokers and current smokers (P=0.0001). Current smokers presented a worse 5-year survival rate (82.9%) compared with exsmokers (88.9%) and never smokers (89.6%). In the multivariate analysis, after adjusting for age, disease stage, Gleason score and prostate-specific antigen, the hazard ratio for smokers was 1.80 (95% confidence interval: 1.04-3.13) compared with never smokers. In the exsmokers group the risk for prostate cancer-specific mortality was very similar to that of never smokers. However, the statistical difference disappeared when we stratified by stage (I-III and IV). In conclusion, smoking was identified as an independent and negative prognostic factor for prostate cancer-specific and all-cause mortality. These findings suggest that smoking-cessation programmes could be beneficial for prostate cancer patients.


Gastric secretion: mechanism for production of hydrogen ions.
The passage of a direct electric current across a fixed-charge membrane interposed between neutral electrolyte solutions can give rise to the production of hydrogen and hydroxide ions at the solution-membrane boundary in equivalent amounts, each of which can approach and equal the number of faradays passed. At this unique boundary, the electric field can inhibit the rate of recombination of hydrogen and hydroxide ions strongly enough to increase the dissociation constant of water and other weak electrolytes by several orders of magnitude. These observations lead to a model of the gastric secretory process wherein the gastric potential, primarily due to the activity of a chloride-ion pump, is applied across an adjacent ionselective membrane also present in the mucosa. The dissociating weak electrolyte can be water, to produce hydrogen ions in the stomach and hydroxide ions which combine with carbon dioxide in the blood, or it can be carbonic acid to produce bicarbonate directly.


Historical recollections of freeze-drying.
The history of freeze-drying is surprisingly recent. Although Altmann used freeze-drying for the preparation of histological sections as early as 1890, his technique went unnoticed for over 40 years. Shackell independently rediscovered the technique in 1909 for the preservation of biologicals. The industrial applications of freeze-drying do not appear to have been appreciated prior to the patients of Tival in 1927 and Elser in 1934, rapidly followed by the important contributions of Flosdorf in the United States and Greaves in England who were largely responsible for making large scale applications of freeze-drying possible. Stimulated particularly by a series of symposia in England and the United States and the renowned courses on freeze-drying organized by Rey in France, the atmosphere in the 1950s and early 60s was one of optimism for the future of freeze-drying, particularly in its application to food stuffs. Many of the dreams of that time remain unfulfilled, largely because of the higher costs of quality processing. Nevertheless, although the optimism may have somewhat dimmed, the promise remains, and economic changes in the future may well stimulate another surge in development.


Impaired CD4+ T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis.
Immunosuppression following severe sepsis remains a significant human health concern, as long-term morbidity and mortality rates of patients who have recovered from life-threatening septic shock remain poor. Mouse models of severe sepsis indicate this immunosuppression may be partly due to alterations in myeloid cell function; however, the effect of severe sepsis on subsequent CD4(+) T-cell responses remains unclear. In the present study, CD4(+) T cells from mice subjected to an experimental model of severe sepsis (cecal ligation and puncture (CLP)) were analyzed in vitro. CD4(+)CD62L(+) T cells from CLP mice exhibited reduced proliferative capacity and altered gene expression. Additionally, CD4(+)CD62L(+) T cells from CLP mice exhibit dysregulated cytokine production after in vitro skewing with exogenous cytokines, indicating a decreased capability of these cells to commit to either the T(H)1 or T(H)2 lineage. Repressive histone methylation marks were also evident at promoter regions for the T(H)1 cytokine IFN-gamma and the T(H)2 transcription factor GATA-3 in naïve CD4(+) T cells from CLP mice. These results provide evidence that CD4(+) T-cell subsets from post-septic mice exhibit defects in activation and effector function, possibly due to chromatin remodeling proximal to genes involved in cytokine production or gene transcription.


Statistical inference for a two-stage outcome-dependent sampling design with a continuous outcome.
The two-stage case-control design has been widely used in epidemiology studies for its cost-effectiveness and improvement of the study efficiency (White, 1982, American Journal of Epidemiology 115, 119-128; Breslow and Cain, 1988, Biometrika 75, 11-20). The evolution of modern biomedical studies has called for cost-effective designs with a continuous outcome and exposure variables. In this article, we propose a new two-stage outcome-dependent sampling (ODS) scheme with a continuous outcome variable, where both the first-stage data and the second-stage data are from ODS schemes. We develop a semiparametric empirical likelihood estimation for inference about the regression parameters in the proposed design. Simulation studies were conducted to investigate the small-sample behavior of the proposed estimator. We demonstrate that, for a given statistical power, the proposed design will require a substantially smaller sample size than the alternative designs. The proposed method is illustrated with an environmental health study conducted at National Institutes of Health.


Effects of experimental cardiac volume loading on left atrial phasic function in healthy dogs.
OBJECTIVE To elucidate the relationship between acute volume overload and left atrial phasic function in healthy dogs. ANIMALS 6 healthy Beagles. PROCEDURES Dogs were anesthetized. A Swan-Ganz catheter was placed to measure mean pulmonary capillary wedge pressure (PCWP). Cardiac preload was increased by IV infusion with lactated Ringer solution at 150 mL/kg/h for 90 minutes. Transthoracic echocardiography was performed before (baseline) and at 15, 30, 45, 60, 75, and 90 minutes after volume loading began. At each echocardiographic assessment point, apical 4-chamber images were recorded and analyzed to derive time-left atrial area curves. Left atrial total (for reservoir function), passive (for conduit function), and active (for booster-pump function) fractional area changes were calculated from the curves. RESULTS Volume overload resulted in a significant increase from baseline in PCWP from 15 to 90 minutes after volume loading began. All fractional area changes at 15 to 90 minutes were significantly increased from baseline. In multiple regression analysis, quadratic regression models were better fitted to the relationships between PCWP and each of the total and active fractional area changes than were linear regression models. A linear regression model was better fitted to the relationship between PCWP and passive fractional area change. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that left atrial phasic function assessed on the basis of left atrial phasic areas was enhanced during experimental cardiac volume loading in healthy dogs. The effect of volume load should be considered when evaluating left atrial phasic function by indices derived from left atrial phasic sizes.


Acute kidney injury in sickle patients with painful crisis or acute chest syndrome and its relation to pulmonary hypertension.
The association between chronic kidney involvement and sickle cell disease (SCD) has been well characterized, but our knowledge on acute kidney injury (AKI) in relation to SCD remains limited. We retrospectively assessed 254 episodes of vaso-occlusive complication in 161 SCD patients who were admitted to our hospital: these included 174 episodes of painful crisis (PC), 58 episodes of moderate acute chest syndrome (ACS) and 22 episodes of severe ACS. The overall incidence of AKI [defined according to Acute Kidney Injury Network (AKIN) criteria] during vaso-occlusive complications was low (4.3%) but seemed to be related to its severity: 2.3% for PC vs 6.9% for moderate ACS and 13.6% for severe ACS (P = 0.03). This finding led us prospectively to look at specific risk factors for AKI occurrence in SCD patients admitted to our intensive care unit for severe ACS and, in particular, the possible link between AKI and haemodynamic status (transthoracic echocardiography). Among patients with severe ACS, those with AKI displayed significantly greater aminotransferases, bilirubin and lactate dehydrogenase levels than patients without AKI. Echocardiography identified higher systolic pulmonary artery pressure in patients with AKI than in those without, whereas the cardiac index was similar between groups. AKI incidence during vaso-occlusive complications of SCD is relatively low (<5%) and appears to be confined to patients with ACS and pulmonary hypertension. These findings suggest a pathophysiological process involving right ventricular dysfunction and venous congestion.


Prevalence and genetic diversity of coronaviruses in bats from China.
Coronaviruses can infect a variety of animals including poultry, livestock, and humans and are currently classified into three groups. The interspecies transmissions of coronaviruses between different hosts form a complex ecosystem of which little is known. The outbreak of severe acute respiratory syndrome (SARS) and the recent identification of new coronaviruses have highlighted the necessity for further investigation of coronavirus ecology, in particular the role of bats and other wild animals. In this study, we sampled bat populations in 15 provinces of China and reveal that approximately 6.5% of the bats, from diverse species distributed throughout the region, harbor coronaviruses. Full genomes of four coronavirues from bats were sequenced and analyzed. Phylogenetic analyses of the spike, envelope, membrane, and nucleoprotein structural proteins and the two conserved replicase domains, putative RNA-dependent RNA polymerase and RNA helicase, revealed that bat coronaviruses cluster in three different groups: group 1, another group that includes all SARS and SARS-like coronaviruses (putative group 4), and an independent bat coronavirus group (putative group 5). Further genetic analyses showed that different species of bats maintain coronaviruses from different groups and that a single bat species from different geographic locations supports similar coronaviruses. Thus, the findings of this study suggest that bats may play an integral role in the ecology and evolution of coronaviruses.


Primary Orbital Hydatid Cyst: A Case Report.
Hydatid cyst is a rare parasitic infection that involved all organs. It caused by the larval stage of Echinococcus tapeworms. Hydatid cyst of the head and neck is a very rare condition, even in areas where Echinococcus infestation is endemic. Orbital hydatid cyst is extremely rare and accounts for less than 1% of all hydatid cysts. Herein a 24-year-old man with primary orbital hydatid cyst is introduced. He complained from proptosis and diplopia. MRI images revealed a lesion with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, which displaced the optic nerve inferiorly and the globe inferolateral. The cyst was enucleated via frontotemporal craniotomy and superior orbitotomy approach. Histopathological examination of the fluid confirmed the diagnosis of hydatid cyst. Treatment of the orbital hydatid cyst is surgical excision followed by the systemic use of albendazole.


Perceived Clinical Practice Competency and Associated Factors Among Undergraduate Students of Medicine and Health Science Collage in Dilla University, SNNPR, Ethiopia.
The dynamic and uncertain nature of the healthcare environment requires competent health professionals to manage the changing environment. However, globally and regionally there is a shortage of competent health professionals. Understanding the causes of poor performance of healthcare is crucial to provide high-quality healthcare service. So this study aims to assess perceived clinical competence and associated factors among undergraduate medicine and health science students at Dilla University, medical and health Science College. Institutional-based cross-sectional study was conducted among 267 students. Initially, departments were stratified, then simple random sample was used to select students. A 2 days of training was given for data collectors and supervisors. Data were entered into Epi-info version 7 and analyzed using Stata version 12. Logistic regression analysis was used to assess associated factors of clinical competency. A total of 267 students participated in this study. The majority of students were males 197 (73.8%) and more than half of the participants 186 (69.7%) were in the age group of 20 to 24 years. The study found only 39.3%, 95% CI (33.3, 44.9) of the participants perceived themselves as clinically competent. This study also identified instructor provided constructive feedback (AOR= 2.12, 95% CI =1.164-3.861), instructor orientation about assessment method (AOR=1.855 95% CI =1.03-3.408) and staff encouragement during clinical practice (AOR= 2.608, 95% CI= 1.425-4.77) were statistically significant factors. In this study, perceived clinical competency was 39%. Teachers should give constructive feedback to their students to boost their confidence and ability. Furthermore, nationally there should be standard and clear assessment methods in which teachers, school administrators and responsible stakeholders should briefly explain assessment methods to their students and it also needs an action to improve the interaction between staff and students.


Dichotomy between opsonization and serum complement activation by encapsulated staphylococci.
Previous studies have demonstrated that encapsulated Staphylococcus aureus strains are not effectively opsonized by the serum complement system. Encapsulated staphylococci thereby "resist phagocytosis." To test whether this phenomenon might be explained by an inability of encapsulated strains to activate complement, the relationship between staphylococcal opsonization and serum complement activation was studied. Although encapsulation was found to interfere with opsonization by pooled human serum (human polymorphonuclear leukocytes phagocytized significantly fewer encapsulated bacteria than unencapsulated bacteria after incubation in this opsonic source), encapsulated (S. aureus M and Smith diffuse) and unencapsulated (S. aureus M variant and Smith compact) strains had similar capacities for complement activation as measured by C3-C9 consumption. When C2-deficient and immunoglobulin-deficient sera were studied, again C3-C9 consumption was not influenced by the presence or absence of a capsule. In addition, C3 was detected on the surface of both S. aureus M and M variant strains after incubation in pooled serum and staining with fluorescein-conjugated anti-C3 antibody. Thus, encapsulated staphylococci are not effectively opsonized even though complement is activated and C3 is present on the bacterial surface. The exact mechanism by which the capsule interferes with opsonization is still not known; however, inhibition of complement activation appears not to be the explanation of this phenomenon.


A rapid cycleave PCR method for distinguishing the vaccine strain Brucella abortus A19 in China.
Brucellosis is a widespread zoonotic disease caused by Brucella spp. Immunization with attenuated vaccines has proved to be an effective method of prevention; however, it may also interfere with diagnosis. Brucella abortus strain A19, which is homologous to B. abortus strain S19, is widely used for the prevention of bovine brucellosis in China. For effective monitoring of the control of brucellosis, it is essential to distinguish A19 from field strains. Single-nucleotide polymorphism-based assays offer a new approach to such discrimination studies. In the current study, we developed a cycleave PCR assay that successfully distinguished attenuated vaccine strains A19 and S19 from 22 strains of B. abortus and 57 strains of 5 other Brucella species. The assay gave a negative reaction with 4 non-Brucella species. The minimum sensitivity of the assay, evaluated using 10-fold dilutions of chromosomal DNA, was 7.6 fg for the A19 strain and 220 fg for the single non-A19/non-S19 Brucella strain tested (B. abortus 104M). The assay was also reproducible (intra- and interassay coefficients of variation: 0.003-0.01 and 0.004-0.025, respectively). The cycleave assay gave an A19/S19-specific reaction in 3 out of 125 field serum samples, with the same 3 samples being positive in an alternative A19/S19-specific molecular assay. The cycleave assay gave a total of 102 Brucella-specific reactions (3 being the A19/S19-specific reactions), whereas an alternative Brucella-specific assay gave 92 positive reactions (all also positive in the cycleave assay). Therefore, this assay represents a simple, rapid, sensitive, and specific tool for use in brucellosis control.


The multi-year effects of repeatedly growing cotton with moderate resistance to Meloidogyne incognita.
Meloidogyne incognita causes more damage to cotton in the US than any other pathogen. The objective of this study was to document the cumulative effect of moderate resistance on M. incognita population density, root galling, and yield suppression in the southern United States on a moderately resistant cotton genotype grown continuously for three years. Cotton genotypes were Phytogen PH98-3196 (77% suppression of M. incognita), Acala NemX (85% suppression of M. incognita), and Delta and Pine Land DP458 B/R (susceptible standard, 0% suppression). Cotton was grown in fumigated and non-fumigated plots to measure yield loss. Each genotype and nematicide combination was planted in the same place for three years at two sites to document cumulative effects. In 2006, following three years of the different genotypes, all plots at one site were planted with susceptible cotton to document residual effects of planting resistant genotypes. Root galling and nematode population densities in the soil were significantly lower, and percentage yield suppression was numerically lower, when moderately resistant cotton was grown compared to the susceptible standard in both fields in all three years. Differences between susceptible and moderately resistant genotypes are established quickly (after only one season) and then either maintained at similar levels or slightly increased in subsequent years depending on initial nematode levels. However, when susceptible cotton was grown following three years of the moderately resistant genotypes, the nematode suppression provided by moderate resistance was undetectable by the end of the first season. Moderately resistant cotton genotypes are more beneficial than previously reported and should be pursued for nematode management. Rotation of moderately resistant and susceptible cotton could be used along with nematicides to manage root-knot nematodes in a continuous cotton cropping system and reduce selection pressure on the nematodes.


Callisto: disk temperature at 3.71-centimeter wavelength.
We observed the radio emission of Callisto with a three-element interferometer at the time of the 1973 opposition of Jupiter. Special care was taken to remove the residual, unresolved contribution from Jupiter itself in the antenna side lobes. The resulting disk temperature at a wavelength of 3.71 centimeters, assuming a radius of 2500+/-75 kilometers for Callisto, was 101 degrees +/-25 degrees K. This temperature is much more consistent with emission from a simple dielectric sphere than the considerably higher temnperatures that have been reported for wavelengths of 3.5 and 8.2 millimeters.


Gaucher disease due to saposin C deficiency is an inherited lysosomal disease caused by rapidly degraded mutant proteins.
Saposin (Sap) C is an essential cofactor for the lysosomal degradation of glucosylceramide (GC) by glucosylceramidase (GCase) and its functional impairment underlies a rare variant form of Gaucher disease (GD). Sap C promotes rearrangement of lipid organization in lysosomal membranes favoring substrate accessibility to GCase. It is characterized by six invariantly conserved cysteine residues involved in three intramolecular disulfide bonds, which make the protein remarkably stable to acid environment and degradation. Five different mutations (i.e. p.C315S, p.342_348FDKMCSKdel, p.L349P, p.C382G and p.C382F) have been identified to underlie Sap C deficiency. The molecular mechanism by which these mutations affect Sap C function, however, has not been delineated in detail. Here, we characterized biochemically and functionally four of these gene lesions. We show that all Sap C mutants are efficiently produced, and exhibit lipid-binding properties, modulatory behavior on GCase activity and subcellular localization comparable with those of the wild-type protein. We then delineated the structural rearrangement of these mutants, documenting that most proteins assume diverse aberrant disulfide bridge arrangements, which result in a substantial diminished half-life, and rapid degradation via autophagy. These findings further document the paramount importance of disulfide bridges in the stability of Sap C and provide evidence that accelerated degradation of the Sap C mutants is the underlying pathogenetic mechanism of Sap C deficiency.


Rhabdomyolysis revisited: Detailed analysis of magnetic resonance imaging findings and their correlation with peripheral neuropathy.
The objective is to evaluate the magnetic resonance imaging (MRI) findings in rhabdomyolysis in detail and determine their correlation with the development of peripheral neuropathy.Magnetic resonance images for 23 patients with confirmed rhabdomyolysis with (n = 11) or without (n = 12) peripheral neuropathy were retrospectively reviewed for the signal intensity on T1- and T2-weighted images, intramuscular hemorrhage, enhancement pattern, shape and margin in the longitudinal plane, edema in the deep fascia and overlying subcutaneous layer, multiplicity, and bilateral limb involvement. The collected data were statistically analyzed and the relationship between the imaging findings and the development of peripheral neuropathy was determined.Abnormal signal intensities on T1- or T2-weighted images were observed for all patients except one. Fourteen patients (60.9%) showed intramuscular hemorrhage. Stippled enhancement (11/23; 47.8%) was the most common enhancement pattern. Nineteen patients (86.4%) showed a well-defined rectangular shape with a ragged margin in the longitudinal plane. The affected muscle volume usually increased (17/23; 73.9%), with edema in the deep fascia and the overlying subcutaneous layer (13/23; 56.5%). Multiplicity within a muscle, compartment, and limb was observed in 7 (31.8%), 18 (81.8%), and 16 (72.7%) patients, respectively. Bilateral involvement was observed in 7 patients (30.4%). Only multiplicity within a compartment showed a statistically significant correlation with peripheral neuropathy development.Common MRI findings in rhabdomyolysis include intramuscular hemorrhage, stippled enhancement, a well-defined rectangular shape with a ragged margin in the longitudinal plane, and multiplicity. Multiplicity within a compartment may be a predictor of the development of peripheral neuropathy.


[Hygienic significance of geohydrochemical features of the Moscow region].
The biochemical features of the Moscow artesian pool and the influence of water on the population's health are shown. The paper present information on the sources of the water-supply system in the town of Zelenograd whose population uses river and artesian waters. The drinking water in Zelenograd and in the populated areas of the Moscow Region contains toxic elements, such lithium, born, strontium, fluorine, barium in the quantities greater than the adopted specifications. It is stated that the presents of the above agents in the waters of the Moscow artesian pool suggests regional geochemical anomaly. Mixing artesian and river waters in Zelenograd has a positive effect, by causing a reduction in the incidence of fluorosis.


Heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus DNA antigens.
The persistent evolution of highly pathogenic avian influenza (HPAI) highlights the need for novel vaccination techniques that can quickly and effectively respond to emerging viral threats. We evaluated the use of optimized consensus influenza antigens to provide broad protection against divergent strains of H5N1 influenza in three animal models of mice, ferrets, and non-human primates. We also evaluated the use of in vivo electroporation to deliver these vaccines to overcome the immunogenicity barrier encountered in larger animal models of vaccination. Mice, ferrets and non-human primates were immunized with consensus plasmids expressing H5 hemagglutinin (pH5HA), N1 neuraminidase (pN1NA), and nucleoprotein antigen (pNP). Dramatic IFN-gamma-based cellular immune responses to both H5 and NP, largely dependent upon CD8+ T cells were seen in mice. Hemaggutination inhibition titers classically associated with protection (>1:40) were seen in all species. Responses in both ferrets and macaques demonstrate the ability of synthetic consensus antigens to induce antibodies capable of inhibiting divergent strains of the H5N1 subtype, and studies in the mouse and ferret demonstrate the ability of synthetic consensus vaccines to induce protection even in the absence of such neutralizing antibodies. After challenge, protection from morbidity and mortality was seen in mice and ferrets, with significant reductions in viral shedding and disease progression seen in vaccinated animals. By combining several consensus influenza antigens with in vivo electroporation, we demonstrate that these antigens induce both protective cellular and humoral immune responses in mice, ferrets and non-human primates. We also demonstrate the ability of these antigens to protect from both morbidity and mortality in a ferret model of HPAI, in both the presence and absence of neutralizing antibody, which will be critical in responding to the antigenic drift that will likely occur before these viruses cross the species barrier to humans.


[Autoimmunity induced by drugs. Immunological characteristics and etiopathogenic hypotheses].
Drug-induced autoimmune diseases have two immunological peculiarities. Firstly, some autoantibodies are present, which are virtually never seen in spontaneous human diseases and may be regarded as specific. This applies to antimitochondria antibody type 3 (anti M3) in the lupus-like syndrome caused by Venocuran, to antimitochondria antibody type 6 (anti M6) in iproniazide-induced hepatitis, to anti-insulin antibody found after treatment with methimazole, and to anti liver/kidney microsome antibody type 2 (anti LKM2) associated with hepatitis induced by tielinic acid. Secondly, a search for other autoantibodies shows that the immune disorder is much more limited than in spontaneous autoimmune diseases. Thus, contrary to myasthenia and idiopathic autoimmune haemolytic anaemia, we never found autoantibodies specifically directed against the thyroid, the stomach or the adrenal gland during treatment with D-penicillamine and alpha-methyldopa. Only some hypotheses may account for these peculiarities. Cross-reaction between drug and autoantigen may occur, but the fact that the antigen-antibody reaction is not inhibited by the drug or its metabolites does not support this explanation. Much more attractive is the "T-cell bypass" theory, according to which autoreacting suppressor T-cells are circumvented by helper T-cells stimulated by the drug-modified autoantigen. In this case, the autoimmune reaction would indicate to which body substance the drug is bound, thus making it immunostimulant, and not a structural similarity between the drug and the autoantigen.


Information underpinning anticipation of goal-directed throwing.
We identified the information used to anticipate throw direction in handball. In two experiments, we examined how anticipation performance is affected when the information from one of five body areas (right arm, shoulders, hips, trunk, or total throw side) was either neutralized or decoupled from the motion of other body segments. In the first experiment, performance was significantly reduced when information from the throwing arm was neutralized, irrespective of skill levels. Skilled participants were negatively affected when the shoulders, hips, and trunk were neutralized, whereas less-skilled participants showed trends toward improvement under identical conditions. In the second experiment, partially disrupting relative motion via decoupling was not enough to reduce the anticipation performance among skilled participants to chance levels, whereas less-skilled participants lost their ability to anticipate in three conditions. Our findings suggest that skilled and less-skilled participants employ different information extraction strategies, yet information from the throwing arm is critical to anticipation for both groups. The two experiments suggest that relative motion mediated by both the absolute displacement trajectories of individual marker locations and their relative timings are important in informing anticipation, irrespective of skill level.


Perioperative management of children with obstructive sleep apnea.
Obstructive sleep apnea syndrome (OSA) affects 1%-3% of children. Children with OSA can present for all types of surgical and diagnostic procedures requiring anesthesia, with adenotonsillectomy being the most common surgical treatment for OSA in the pediatric age group. Thus, it is imperative that the anesthesiologist be familiar with the potential anesthetic complications and immediate postoperative problems associated with OSA. The significant implications that the presence of OSA imposes on perioperative care have been recognized by national medical professional societies. The American Academy of Pediatrics published a clinical practice guideline for pediatric OSA in 2002, and cited an increased risk of anesthetic complications, though specific anesthetic issues were not addressed. In 2006, the American Society of Anesthesiologists published a practice guideline for perioperative management of patients with OSA that noted the pediatric-related risk factor of obesity, and the increased perioperative risk associated with adenotonsillectomy in children younger than 3 yr. However, management of OSA in children younger than 1 yr-of-age was excluded from the guideline, as were other issues related specifically to the pediatric patient. Hence, many questions remain regarding the perioperative care of the child with OSA. In this review, we examine the literature on pediatric OSA, discuss its pathophysiology, current treatment options, and recognized approaches to perioperative management of these young and potentially high-risk patients.


Baseline CXCL10 and CXCL13 levels are predictive biomarkers for tumor necrosis factor inhibitor therapy in patients with moderate to severe rheumatoid arthritis: a pilot, prospective study.
TNF inhibitors have been used as a treatment for moderate to severe RA patients. However, reliable biomarkers that predict therapeutic response to TNF inhibitors are lacking. In this study, we investigated whether chemokines may represent useful biomarkers to predict the response to TNF inhibitor therapy in RA. RA patients (n = 29) who were initiating adalimumab or etanercept were recruited from the rheumatology clinics at Cooper University Hospital. RA patients were evaluated at baseline and 14 weeks after TNF inhibitor therapy, and serum levels of CXCL10, CXCL13, and CCL20 were measured by ELISA. Responders (n = 16) were defined as patients who had good or moderate response at week 14 by EULAR response criteria, and nonresponders (n = 13) were defined as having no response. Responders had higher levels of baseline CXCL10 and CXCL13 compared to nonresponders (p = 0.03 and 0.002 respectively). There was no difference in CCL20 levels. CXCL10 and CXCL13 were highly correlated with each other, and were higher in seropositive RA patients. CXCL10 and CXCL13 levels were decreased after TNF inhibitor therapy in responders. Baseline additive levels of CXCL10 + 13 were correlated with changes in DAS score at 14 weeks after TNF inhibitor therapy (r = 0.42, p = 0.03), and ROC curve analyses for predictive ability of CXCL10 + 13 showed an AUC of 0.83. Elevated baseline levels of CXCL10 and CXCL13 were associated with favorable response to TNF inhibitor therapy in RA. Subjects with high CXCL10 and high CXCL13 may represent a subset of RA patients whose inflammatory reactions are primarily driven by TNF.


Roles of nucleus accumbens core and shell in incentive-cue responding and behavioral inhibition.
The nucleus accumbens (NAc) is involved in many reward-related behaviors. The NAc has two major components, the core and the shell. These two areas have different inputs and outputs, suggesting that they contribute differentially to goal-directed behaviors. Using a discriminative stimulus (DS) task in rats and inactivating the NAc by blocking excitatory inputs with glutamate antagonists, we dissociated core and shell contributions to task performance. NAc core but not shell inactivation decreased responding to a reward-predictive cue. In contrast, inactivation of either subregion induced a general behavioral disinhibition. This reveals that the NAc actively suppresses actions inappropriate to the DS task. Importantly, selective inactivation of the shell but not core significantly increased responding to the nonrewarded cue. To determine whether the different contributions of the NAc core and shell depend on the information encoded in their constituent neurons, we performed electrophysiological recording in rats performing the DS task. Although there was no firing pattern unique to either core or shell, the reward-predictive cue elicited more frequent and larger magnitude responses in the NAc core than in the shell. Conversely, more NAc shell neurons selectively responded to the nonrewarded stimulus. These quantitative differences might account for the different behavioral patterns that require either core or shell. Neurons with similar firing patterns could also have different effects on behavior due to their distinct projection targets.


Computationally Discovered Potentiating Role of Glycans on NMDA Receptors.
N-methyl-D-aspartate receptors (NMDARs) are glycoproteins in the brain central to learning and memory. The effects of glycosylation on the structure and dynamics of NMDARs are largely unknown. In this work, we use extensive molecular dynamics simulations of GluN1 and GluN2B ligand binding domains (LBDs) of NMDARs to investigate these effects. Our simulations predict that intra-domain interactions involving the glycan attached to residue GluN1-N440 stabilize closed-clamshell conformations of the GluN1 LBD. The glycan on GluN2B-N688 shows a similar, though weaker, effect. Based on these results, and assuming the transferability of the results of LBD simulations to the full receptor, we predict that glycans at GluN1-N440 might play a potentiator role in NMDARs. To validate this prediction, we perform electrophysiological analysis of full-length NMDARs with a glycosylation-preventing GluN1-N440Q mutation, and demonstrate an increase in the glycine EC50 value. Overall, our results suggest an intramolecular potentiating role of glycans on NMDA receptors.


Impact evaluation of different cash-based intervention modalities on child and maternal nutritional status in Sindh Province, Pakistan, at 6 mo and at 1 y: A cluster randomised controlled trial.
Cash-based interventions (CBIs), offer an interesting opportunity to prevent increases in wasting in humanitarian aid settings. However, questions remain as to the impact of CBIs on nutritional status and, therefore, how to incorporate them into emergency programmes to maximise their success in terms of improved nutritional outcomes. This study evaluated the effects of three different CBI modalities on nutritional outcomes in children under 5 y of age at 6 mo and at 1 y. We conducted a four-arm parallel longitudinal cluster randomised controlled trial in 114 villages in Dadu District, Pakistan. The study included poor and very poor households (n = 2,496) with one or more children aged 6-48 mo (n = 3,584) at baseline. All four arms had equal access to an Action Against Hunger-supported programme. The three intervention arms were as follows: standard cash (SC), a cash transfer of 1,500 Pakistani rupees (PKR) (approximately US$14; 1 PKR = US$0.009543); double cash (DC), a cash transfer of 3,000 PKR; or a fresh food voucher (FFV) of 1,500 PKR; the cash or voucher amount was given every month over six consecutive months. The control group (CG) received no specific cash-related interventions. The median total household income for the study sample was 8,075 PKR (approximately US$77) at baseline. We hypothesized that, compared to the CG in each case, FFVs would be more effective than SC, and that DC would be more effective than SC-both at 6 mo and at 1 y-for reducing the risk of child wasting. Primary outcomes of interest were prevalence of being wasted (weight-for-height z-score [WHZ] < -2) and mean WHZ at 6 mo and at 1 y. The odds of a child being wasted were significantly lower in the DC arm after 6 mo (odds ratio [OR] = 0.52; 95% CI 0.29, 0.92; p = 0.02) compared to the CG. Mean WHZ significantly improved in both the FFV and DC arms at 6 mo (FFV: z-score = 0.16; 95% CI 0.05, 0.26; p = 0.004; DC: z-score = 0.11; 95% CI 0.00, 0.21; p = 0.05) compared to the CG. Significant differences on the primary outcome were seen only at 6 mo. All three intervention groups showed similar significantly lower odds of being stunted (height-for-age z-score [HAZ] < -2) at 6 mo (DC: OR = 0.39; 95% CI 0.24, 0.64; p < 0.001; FFV: OR = 0.41; 95% CI 0.25, 0.67; p < 0.001; SC: OR = 0.36; 95% CI 0.22, 0.59; p < 0.001) and at 1 y (DC: OR = 0.53; 95% CI 0.35, 0.82; p = 0.004; FFV: OR = 0.48; 95% CI 0.31, 0.73; p = 0.001; SC: OR = 0.54; 95% CI 0.36, 0.81; p = 0.003) compared to the CG. Significant improvements in height-for-age outcomes were also seen for severe stunting (HAZ < -3) and mean HAZ. An unintended outcome was observed in the FFV arm: a negative intervention effect on mean haemoglobin (Hb) status (-2.6 g/l; 95% CI -4.5, -0.8; p = 0.005). Limitations of this study included the inability to mask participants or data collectors to the different interventions, the potentially restrictive nature of the FFVs, not being able to measure a threshold effect for the two different cash amounts or compare the different quantities of food consumed, and data collection challenges given the difficult environment in which this study was set. In this setting, the amount of cash given was important. The larger cash transfer had the greatest effect on wasting, but only at 6 mo. Impacts at both 6 mo and at 1 y were seen for height-based growth variables regardless of the intervention modality, indicating a trend toward nutrition resilience. Purchasing restrictions applied to food-based voucher transfers could have unintended effects, and their use needs to be carefully planned to avoid this. ISRCTN registry ISRCTN10761532.


EvolMarkers: a database for mining exon and intron markers for evolution, ecology and conservation studies.
Recent innovations in next-generation sequencing have lowered the cost of genome projects. Nevertheless, sequencing entire genomes for all representatives in a study remains expensive and unnecessary for most studies in ecology, evolution and conservation. It is still more cost-effective and efficient to target and sequence single-copy nuclear gene markers for such studies. Many tools have been developed for identifying nuclear markers, but most of these have focused on particular taxonomic groups. We have built a searchable database, EvolMarkers, for developing single-copy coding sequence (CDS) and exon-primed-intron-crossing (EPIC) markers that is designed to work across a broad range of phylogenetic divergences. The database is made up of single-copy CDS derived from BLAST searches of a variety of metazoan genomes. Users can search the database for different types of markers (CDS or EPIC) that are common to different sets of input species with different divergence characteristics. EvolMarkers can be applied to any taxonomic group for which genome data are available for two or more species. We included 82 genomes in the first version of EvolMarkers and have found the methods to be effective across Placozoa, Cnidaria, Arthropod, Nematoda, Annelida, Mollusca, Echinodermata, Hemichordata, Chordata and plants. We demonstrate the effectiveness of searching for CDS markers within annelids and show how to find potentially useful intronic markers within the lizard Anolis.


Why do we need new gene therapy viral vectors? Characteristics, limitations and future perspectives of viral vector transduction.
The use of viruses to transduce genes of interest into mammalian cells has been extremely revolutionary, both in terms of laboratory research and for clinical purposes. This approach has allowed expression and over-expression of proteins of interest as well as the understanding of both virus life cycles and eukaryotic cell mechanisms. Beginning in the late eighties gene transduction has been applied to clinical trials but mainly restricted to cancer treatment and genetic diseases. More recently it has been proposed for the cure of infectious diseases (AIDS), vascular diseases and others (Alzheimer's and Parkinson's disease). Viral vectors have been progressively modified in order to increase their transduction efficiency and to reduce their toxicity, immunogenicity and inflammatory potential. In this respect, much has been done in the last few years. By adding genes belonging to other viral species to the vectors' DNA, scientists were able to re-direct their tissue-specificity or to control protein expression. More recently, in the attempt of overcoming the limitations of each viral species, so-called chimeric viral vectors have been generated by combining favourable features of two or more different viruses into one. This review summarises the main characteristics of the most common viral vectors, including their advantages, limitations and possible future applications. It also briefly discusses development and evolution of chimeric vectors, treated in more details along this entire issue. Finally, we evaluate basic safety aspects, mandatory to consider for the clinical application of viral gene transduction.


Carcinoma of the pancreas: diagnosis and treatment.
We made a retrospective analysis of the hospital record of 65 cases of carcinoma of the pancreas occurring over a 16-year period at Bayley Seton Hospital, Staten Island, New York. The male sex predominated; the average age was 62.5 years. About 72% of the tumors were located at the head of the pancreas. The patients were divided into four groups: (1) those treated by pancreatoduodenectomy (Whipple resection) (14 cases), (2) those treated by bypass operations (21 cases), (3) those managed by exploration for biopsy only (12 cases), and (4) those in whom the carcinoma of the pancreas was found only at autopsy (18 cases). The operative mortality in the Whipple group was 7%; in the bypass group, 14%; and in the exploratory biopsy group, 36%. The mean survival in the Whipple group was 27.2 months with one survival more than ten years; in the bypass group, 6.5 months; and in the biopsy group, 2.6 months. Autopsy studies showed a high rate of regional and distant node metastasis, as well as nonnodal metastasis to other organs. Most of the patients died of carcinomatosis. The operative technics and the surgical literature are discussed.


MRI Risk Stratification for Tumor Relapse in Rectal Cancer Achieving Pathological Complete Remission after Neoadjuvant Chemoradiation Therapy and Curative Resection.
Rectal cancer patients achieving pCR are known to have an excellent prognosis, yet no widely accepted consensus on risk stratification and post-operative management (e.g., adjuvant therapy) has been established. This study aimed to identify magnetic resonance imaging (MRI) high-risk factors for tumor relapse in pathological complete remission (pCR) achieved by rectal cancer patients who have undergone neoadjuvant concurrent chemoradiation therapy (CRT) and curative resection. We analyzed 88 (male/female = 55/33, median age, 59.5 years [range 34-78]) pCR-proven rectal cancer patients who had undergone pre-CRT MRI, CRT, post-CRT MRI and curative surgery between July 2005 and December 2012. Patients were observed for post-operative tumor relapse. We analyzed the pre/post-CRT MRIs for parameters including mrT stage, mesorectal fascia (mrMRF) status, tumor volume, tumor regression grade (mrTRG), nodal status (mrN), and extramural vessel invasion (mrEMVI). We performed univariate analysis and Kaplan-Meier survival analysis. Post-operative tumor relapse occurred in seven patients (8.0%, n = 7/88) between 5.7 and 50.7 (median 16.8) months. No significant relevance was observed between tumor volume, volume reduction rate, mrTRG, mrT, or mrN status. Meanwhile, positive mrMRF (Ppre-CRT = 0.018, Ppre/post-CRT = 0.006) and mrEMVI (Ppre-CRT = 0.026, Ppre-/post-CRT = 0.008) were associated with higher incidence of post-operative tumor relapse. Kaplan-Meier survival analysis revealed a higher risk of tumor relapse in patients with positive mrMRF (Ppre-CRT = 0.029, Ppre-/post-CRT = 0.009) or mrEMVI (Ppre-CRT = 0.024, Ppre-/post-CRT = 0.003). Positive mrMRF and mrEMVI status was associated with a higher risk of post-operative tumor relapse of pCR achieved by rectal cancer patients, and therefore, can be applied for risk stratification and to individualize treatment plans.


Non-redundant functions of cyclooxygenases: oxygenation of endocannabinoids.
The two cyclooxygenase (COX) enzymes catalyze the oxygenation of arachidonic acid to prostaglandin endoperoxides, which are the common intermediates in the biosynthesis of the bioactive lipids prostaglandins and thromboxane. COX-1 and COX-2 are approximately 60% identical in amino acid sequence, exhibit highly homologous three-dimensional structures, and appear functionally similar at the biochemical level. Recent work has uncovered a subtle functional difference between the two enzymes, namely the ability of COX-2 to efficiently utilize neutral derivatives (esters and amides) of arachidonic acid as substrates. Foremost among these neutral substrates are the endocannabinoids 2-arachidonoylglycerol and arachidonoylethanolamide. This raises the possibility that COX-2 oxygenation plays a role in a novel signaling pathway dependent on agonist-induced release of endocannabinoids and their selective oxygenation by COX-2. Among the products of COX-2 oxygenation of endocannabinoids are glyceryl prostaglandins, some of which (e.g. glyceryl prostaglandin E(2) and glyceryl prostaglandin I(2)) exhibit interesting biological activities in inflammatory, neurological, and vascular systems. These compounds are produced in intact cells stimulated with physiological agonists and have been isolated from in vivo sources. Important concepts relevant to the hypothesis of a COX-2-selective signaling pathway are presented.


A robust and water-stable two-fold interpenetrated metal-organic framework containing both rigid tetrapodal carboxylate and rigid bifunctional nitrogen linkers exhibiting selective CO2 capture.
A microporous metal-organic framework, {[Co2(4,4'-bpy)(L)]·H2O·0.5(DMF)}n (1), was obtained from the self-assembly of cobalt(ii) nitrate hexahydrate, rigid tetrapodal carboxylic acid 4,4',4'',4'''-silanetetrayltetrabenzoic acid (H4L) and a rigid bifunctional linker 4'4'-bipyridine (4,4'-bpy) under solvothermal conditions. It was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, elemental analysis, and powder and single crystal X-ray diffraction. Its single crystal structure reveals the presence of a Co(ii)-paddle wheel core as the SBU, which is extended to form a doubly interpenetrated 3D framework with a (4,6)-connected sqc422-type uninodal net topology with the Schläfli point symbol {42·510·72·8}{42·54}. There are two types of open channels in this framework (rhombic and trigonal), which run along all three axes. Its thermal and chemical stabilities were established based on thermogravimetric analysis and in situ variable temperature powder X-ray diffraction. The activated framework (lattice solvent free) of 1 exhibits modest uptake of CO2 (53.8 and 36.4 cm3 g-1 at 273 and 298 K at 1 bar pressure, respectively), with moderately high selectivities for CO2/N2 and CO2/CH4 gas separation under ambient conditions (298 and 273 K under 1 bar pressure).


Prevalence and risk factors of upper extremity cumulative trauma disorder in dental hygienists.
Cumulative trauma disorder (CTD) refers to a number of conditions arising from overuse of joints or soft tissues. The common risk factors that contribute to the development of these disorders are related to personal and occupational variables. Job analysis of the tasks performed by the dental hygienist have shown that this occupation is particularly at risk. The objectives of this study were to determine the prevalence of CTD symptoms amongst dental hygienists in Israel and to identify which are the factors that are related to CTD. A questionnaire including items concerning demographic data, employment history, professional occupational information, use of instrumentation, and CTD symptomatology was mailed to all 530 registered dental hygienists. Two hundred forty-six hygienists (46%) returned the questionnaire; 63% of the respondents were classified as CTD 'sufferers', Age, year of graduation, hours worked per week, and frequency of changing instruments were found to be significantly related to CTD symptoms. Hygienists at high risk included those aged 50 years or more (Odds ratio, OR = 6), those who graduated before 1986 (OR = 3), those who work more than 34 h per week (OR = 2.5) and those who change two or fewer instruments per patient (OR = 2). The major recommendation resulting from this study is to make dental hygienists aware that they work in a high-risk profession. It is hoped that increased awareness of the risk will spur the hygienist to make appropriate work practice, administrative, and engineering modifications and to seek treatment at the first indication of CTD symptoms.


Osteogenic protein-1 prevents renal fibrogenesis associated with ureteral obstruction.
Unilateral ureteral obstruction (UUO) is a model of renal injury characterized by progressive tubulointerstitial fibrosis and renal damage, while relatively sparing the glomerulus and not producing hypertension or abnormalities in lipid metabolism. Tubulointerstitial fibrosis is a major component of several kidney diseases associated with the progression to end-stage renal failure. Here we report that when a critical renal developmental morphogen, osteogenic protein-1 (OP-1; 100 or 300 microg/kg body wt), is administered at the time of UUO and every other day thereafter, interstitial inflammation and fibrogenesis are prevented, leading to preservation of renal function during the first 5 days after obstruction. Compared with angiotensin-converting enzyme inhibition with enalapril treatment, OP-1 was more effective in preventing tubulointerstitial fibrosis and in preserving renal function. The mechanism of OP-1- induced renal protection was associated with prevention of tubular atrophy, an effect not shared with enalapril, and was related to preservation of tubular epithelial integrity. OP-1 blocked the stimulation of epithelial cell apoptosis produced by UUO, which promoted maintenance of tubular epithelial integrity. OP-1 preserved renal blood flow (RBF) during UUO, but enalapril also stimulated RBF. Thus OP-1 treatment inhibited tubular epithelial disruption stimulated by the renal injury of UUO, preventing tubular atrophy and diminishing the activation of tubulointerstitial inflammation and fibrosis and preserving renal function.


Adoption of Stroke Rehabilitation Technologies by the User Community: Qualitative Study.
Using technology in stroke rehabilitation is attractive. Devices such as robots or smartphones can help deliver evidence-based levels of practice intensity and automated feedback without additional labor costs. Currently, however, few technologies have been adopted into everyday rehabilitation. This project aimed to identify stakeholder (therapists, patients, and caregivers) priorities for stroke rehabilitation technologies and to generate user-centered solutions for enhancing everyday adoption. We invited stakeholders (n=60), comprising stroke survivors (20/60, 33%), therapists (20/60, 33%), caregivers, and technology developers (including researchers; 20/60, 33%), to attend 2 facilitated workshops. Workshop 1 was preceded by a national survey of stroke survivors and therapists (n=177) to generate an initial list of priorities. The subsequent workshop focused on identifying practical solutions to enhance adoption. A total of 25 priorities were generated from the survey; these were reduced to 10 nonranked priorities through discussion, consensus activities, and voting at Workshop 1: access to technologies, ease of use, awareness of available technologies, technologies focused on function, supports self-management, user training, evidence of effectiveness, value for money, knowledgeable staff, and performance feedback. The second workshop provided recommendations for improving the adoption of technologies in stroke rehabilitation: an annual exhibition of commercially available and developing technologies, an online consumer-rating website of available technologies, and a user network to inspire and test new technologies. The key outcomes from this series of stakeholder workshops provides a starting point for an integrated approach to promoting greater adoption of technologies in stroke rehabilitation. Bringing technology developers and users together to shape future and evaluate current technologies is critical to achieving evidence-based stroke rehabilitation.


A phylogenetic analysis of pygmy perches (Teleostei: Percichthyidae) with an assessment of the major historical influences on aquatic biogeography in southern Australia.
The biogeography of southern Australia is characterized by a repeated pattern of relatedness between the biota of southwestern and southeastern Australia. Both areas possess a temperate climate but are separated by a vast arid region, currently lacking permanent freshwater habitats, which has become increasingly drier since about 15 Ma. Aquatic organisms have thus potentially remained isolated for a considerable time. Pygmy perches (Nannatherina and Nannoperca, Percichthyidae) provide an excellent scenario for investigating biogeographic relationships between southwestern and southeastern regions as multiple species occur on either side of Australia. This allows us to potentially differentiate between "Multiple Invasion" and "Endemic Speciation," the two major hypotheses proposed to account for current distributions. The first suggests that multiple east-west movements have occurred, whereas the second suggests a single east-west split, with current biodiversity in each region being reciprocally monophyletic. Systematic relationships within this group were investigated with the mitochondrial cytochrome b gene; nuclear intron and exon sequences from S7, RAG1, and RAG2; and 53 allozyme loci. Our data supported the hypothesis of multiple movements across southern Australia based on a consistent lack of support for reciprocal monophyly of eastern and western species. This study appears to be the first example of an animal group displaying clear multiple east-west movement in southern Australia, as all other aquatic and terrestrial fauna previously examined displayed a single east-west split. Despite a high degree of sympatry within each region, the only evidence for hybridization was found between Nannoperca australis and N. obscura, with the latter having its mitochondrial genome completely replaced by that of N. australis, with no evidence for nuclear introgression. This is one of only a few confirmed examples of complete replacement of the mitochondrial genome in one species with that of another. Cryptic differentiation was also evident within the two most widespread species, N. australis and N. vittata, indicating that these likely consist of multiple species. We also highlight the need for multiple molecular markers with different strengths in order to obtain a more robust phylogeny, despite problems resulting from potential incongruences between data sets.


Improvement in the quality of abstracts in major clinical journals since CONSORT extension for abstracts: a systematic review.
We sought to determine if the publication of the Consolidated Standards of Reporting Trials (CONSORT)(1) extension for abstracts in 2008 had led to an improvement in reporting abstracts of randomized controlled trials (RCTs).(2) METHODS: We searched PubMed for RCTs published in 2007 and 2012 in top-tier general medicine journals. A random selection of 100 trial abstracts was obtained for each year. Data were extracted in duplicate on the adherence to the CONSORT extension for abstracts. The primary outcome was the mean number of items reported and the secondary outcome was the odds of reporting each item. We also estimated incidence rate ratios (IRRs).(3) RESULTS: Significantly more checklist items were reported in 2012 than in 2007: adjusted mean difference was 2.91 (95% confidence interval [CI](4) 2.35, 3.41; p<0.001). In 2012 there were significant improvements in reporting the study as randomized in the title, describing the trial design, the participants, and objectives and blinding. In the Results section, trial status and numbers analyzed were also reported better. The IRRs were significantly higher for 2012 (IRR 1.32; 95% CI 1.25, 1.39; p<0.001) and in multisite studies compared to single site studies (IRR 1.08; 95% CI 1.03, 1.15; p=0.006). There was a significant improvement in the reporting of abstracts of RCTs in 2012 compared to 2007. However, there is still room for improvement as some items remain under-reported.


Fibrinolytic variables in patients with recurrent venous thrombosis: a prospective cohort study.
To determine whether fibrinolytic testing predicts recurrent venous thrombosis, we have performed a prospective cohort study in which 303 patients with a first episode of venous thromboembolism underwent comprehensive fibrinolytic testing while receiving oral anticoagulants, and after anticoagulants had been discontinued. They were then followed for up to 3 years for recurrent venous thrombosis. No systematic differences in the levels or activity of type 1 plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (tPA) or euglobulin clot lysis times were detected between patients who did, or did not, suffer recurrent thrombosis. There were also no differences in these variables when patients whose initial thrombosis was idiopathic were compared to patients whose thrombosis occurred in the setting of a known thrombotic risk factor. Based on these results, neither measuring fibrinolytic parameters in patients with venous thromboembolism, nor modification of treatment based on the results of such testing, are justified. Our study also confirms that patients with idiopathic venous thromboembolism have a high risk of recurrence.


Smoothelin-like 1 protein regulates myosin phosphatase-targeting subunit 1 expression during sexual development and pregnancy.
Pregnancy coordinately alters the contractile properties of both vascular and uterine smooth muscles reducing systemic blood pressure and maintaining uterine relaxation. The precise molecular mechanisms underlying these pregnancy-induced adaptations have yet to be fully defined but are likely to involve changes in the expression of proteins regulating myosin phosphorylation. Here we show that smoothelin like protein 1 (SMTNL1) is a key factor governing sexual development and pregnancy induced adaptations in smooth and striated muscle. A primary target gene of SMTNL1 in these muscles is myosin phosphatase-targeting subunit 1 (MYPT1). Deletion of SMTNL1 increases expression of MYPT1 30-40-fold in neonates and during development expression of both SMTNL1 and MYPT1 increases over 20-fold. Pregnancy also regulates SMTNL1 and MYPT1 expression, and deletion SMTNL1 greatly exaggerates expression of MYPT1 in vascular smooth muscle, producing a profound reduction in force development in response to phenylephrine as well as sensitizing the muscle to acetylcholine. We also show that MYPT1 is expressed in Type2a muscle fibers in mice and humans and its expression is regulated during pregnancy, suggesting unrecognized roles in mediating skeletal muscle plasticity in both species. Our findings define a new conserved pathway in which sexual development and pregnancy mediate smooth and striated muscle adaptations through SMTNL1 and MYPT1.


Screening programs for common maternal mental health disorders among perinatal women: report of the systematic review of evidence.
Postpartum depression and anxiety are highly prevalent worldwide. Fisher et al., estimated the prevalence of depression and anxiety at 15.6% during the antenatal and 19.8% during the postpartum period. Their impact on maternal and child health is well-recognized among the public health community, accounting for high societal costs. The public health impact of these conditions has highlighted the need to focus on the development and provision of effective prevention and treatment strategies.In recent decades, some advances have been made in the development of effective universal and targeted screening programmes for perinatal depression and anxiety disorders. Recent research has shown potential benefits of universal and targeted screening for perinatal depression, to identify and treat undiagnosed cases, and help thwart its deleterious consequences. Ethical implications, however, for these screening programmes, without the provision of treatment have often been emphasized.The present mixed-methods systematic review and meta-analysis was conducted to collate evidence for screening programmes for perinatal depression and anxiety. It aims to answer the following questions, in a global context: For women in the perinatal period, do screening programmes for perinatal depression and anxiety compared with no screening improve maternal mental health and infant outcomes?A series of meta-analyses reveal a reduction in perinatal depression and anxiety among perinatal women undergoing screening programmes. For the outcome of depressive disorder, meta-analysis indicates a positive impact in favour of the intervention group (OR = 0.55, 95% CI: 0.45 to 0.66, n = 9009), with moderate quality of evidence. A significant improvement (high quality) was also observed in symptoms of anxiety among perinatal women (SMD = - 0.18, 95% CI: - 0.25 to - 0.12, n = 3654).


Risk of Suicide After Cancer Diagnosis in England.
A diagnosis of cancer carries a substantial risk of psychological distress. There has not yet been a national population-based study in England of the risk of suicide after cancer diagnosis. To quantify suicide risk in patients with cancers in England and identify risk factors that may assist in needs-based psychological assessment. Population-based study using data from the National Cancer Registration and Analysis Service in England linked to death certification data of 4 722 099 individuals (22 million person-years at risk). Patients (aged 18-99 years) with cancer diagnosed from January 1, 1995, to December 31, 2015, with follow-up until August 31, 2017, were included. Diagnosis of malignant tumors, excluding nonmelanoma skin cancer. All deaths in patients that received a verdict of suicide or an open verdict at the inquest. Standardized mortality ratios (SMRs) and absolute excess risks (AERs) were calculated. Of the 4 722 099 patients with cancer, 50.3% were men and 49.7% were women. A total of 3 509 392 patients in the cohort (74.3%) were aged 60 years or older when the diagnosis was made. A total of 2491 patients (1719 men and 772 women) with cancer died by suicide, representing 0.08% of all deaths during the follow-up period. The overall SMR for suicide was 1.20 (95% CI, 1.16-1.25) and the AER per 10 000 person-years was 0.19 (95% CI, 0.15-0.23). The risk was highest among patients with mesothelioma, with a 4.51-fold risk corresponding to 4.20 extra deaths per 10 000 person-years. This risk was followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach (2.20-fold) cancer. Suicide risk was highest in the first 6 months following cancer diagnosis (SMR, 2.74; 95% CI, 2.52-2.98). Despite low absolute numbers, the elevated risk of suicide in patients with certain cancers is a concern, representing potentially preventable deaths. The increased risk in the first 6 months after diagnosis may indicate an unmet need for psychological support. The findings of this study suggest a need for improved psychological support for all patients with cancer, and attention to modifiable risk factors, such as pain, particularly in specific cancer groups.


Long-Term Survival After High-Dose-Rate Brachytherapy for Locally Advanced or Recurrent Colorectal Adenocarcinoma.
We evaluated outcomes of intraoperative radiotherapy delivered with focal high-dose-rate (HDR) brachytherapy [intraoperative radiotherapy (IORT)] in the management of locally recurrent (LR) and locally advanced (LA) primary T4 colorectal carcinoma (CRC). LR CRC or LA primary disease is a clinical challenge due to the difficulty in obtaining negative margins after radical surgery and the high risk of subsequent recurrence. Few data exist on long-term outcomes of patients treated with surgery and HDR-IORT for LR or LA primary CRC. Three hundred CRC patients underwent HDR-IORT to the pelvis with gross surgical resection during November 1992-December 2007. Median follow-up for surviving patients was 53 (range 5-216) months. Eighty-eight patients (29 %) were treated for LA primary and 212 (71 %) LR disease. HDR-IORT was delivered using an iridium-192 remote afterloader and a Harrison-Anderson-Mick applicator. Median IORT dose was 1,500 (range 1,000-2,000) cGy. Five-year overall survival probability was 49 %. Positive margin status was associated with inferior overall survival and disease-free survival. Competing-risks analysis for time to local failure and distant metastases identified a 5-year cumulative incidence of local failure and distant metastases of 33 and 47 %, respectively. Five-year cumulative incidence of local failure was 22 % for the LA group and 38 % in the LR group. Five-year probability of disease-free survival was 48 and 31 % for LA and LR patients, respectively, and 5-year probability of overall survival was 56 and 45 % for LA and LR patients, respectively. HDR-IORT combined with resection results in encouraging local control rates with acceptable toxicity for patients with locally aggressive CRC.


Ecological and immunological determinants of influenza evolution.
In pandemic and epidemic forms, influenza causes substantial, sometimes catastrophic, morbidity and mortality. Intense selection from the host immune system drives antigenic change in influenza A and B, resulting in continuous replacement of circulating strains with new variants able to re-infect hosts immune to earlier types. This 'antigenic drift' often requires a new vaccine to be formulated before each annual epidemic. However, given the high transmissibility and mutation rate of influenza, the constancy of genetic diversity within lineages over time is paradoxical. Another enigma is the replacement of existing strains during a global pandemic caused by 'antigenic shift'--the introduction of a new avian influenza A subtype into the human population. Here we explore ecological and immunological factors underlying these patterns using a mathematical model capturing both realistic epidemiological dynamics and viral evolution at the sequence level. By matching model output to phylogenetic patterns seen in sequence data collected through global surveillance, we find that short-lived strain-transcending immunity is essential to restrict viral diversity in the host population and thus to explain key aspects of drift and shift dynamics.


Quantitative genetics of female mate preferences in an ancestral and a novel environment.
A female's mate preference is a potentially complex function relating variation in multiple male phenotypes with her probability of accepting individual males as a mate. Estimating the quantitative genetic basis preference functions within a population is empirically challenging yet key to understanding preference evolution. We employed a recently described approach that uses random-coefficient mixed models in the analysis of function-valued traits. Using a half-sibling breeding design in a laboratory-adapted Drosophila serrata population, we estimated the genetic (co)variance function of female preference for male sexual displays composed of nine contact pheromones. The breeding design was performed across two environments: the food to which the population was well adapted and a novel food that reduced average female productivity by 35%. Significant genetic variance in female preference was detected and the majority (64.2%) was attributable to a single genetic dimension (eigenfunction), suggesting that preferences for different pheromones are not genetically independent. The second eigenfunction, accounting for 24% of the total genetic variance, approached significance in a conservative test, suggesting the existence of a second, independent genetic dimension. There was no evidence that the genetic basis of female preference differed between the two environments, suggesting the absence of genotype-by-environment interactions and hence a lack of condition-dependent preference expression.


The biology of IQGAP proteins: beyond the cytoskeleton.
IQGAP scaffold proteins are evolutionarily conserved in eukaryotes and facilitate the formation of complexes that regulate cytoskeletal dynamics, intracellular signaling, and intercellular interactions. Fungal and mammalian IQGAPs are implicated in cytokinesis. IQGAP1, IQGAP2, and IQGAP3 have diverse roles in vertebrate physiology, operating in the kidney, nervous system, cardio-vascular system, pancreas, and lung. The functions of IQGAPs can be corrupted during oncogenesis and are usurped by microbial pathogens. Therefore, IQGAPs represent intriguing candidates for novel therapeutic agents. While modulation of the cytoskeletal architecture was initially thought to be the primary function of IQGAPs, it is now clear that they have roles beyond the cytoskeleton. This review describes contributions of IQGAPs to physiology at the organism level.


Radiographic outcome of surgical treatment of adolescent idiopathic scoliosis in males versus females.
Studies on adolescent idiopathic scoliosis have well documented the differences between natural history of male and female patients. There are also differences in responses to nonoperative treatment, but the results of operative treatment in male patients compared with females have not been widely reported. Only few studies had compared the outcomes of operative treatment between male and female patients with different results. We retrospectively reviewed the outcome of 150 (112 girls and 38 boys) consecutive patients with diagnosis of adolescent idiopathic scoliosis who were managed surgically between May 1996 and September 2005. Next, male radiographic parameters were compared with female ones pre- and postoperatively. Then, a subgroup of 38 matched girls was compared regarding the age, curve type, curve magnitude, and the instrumentation we used. In comparing male patients with unmatched girls, the boys had greater mean age (17.3 +/- 2.3 vs. 16.3 +/- 2.9; p = 0.049), greater primary curve (71.4 +/- 21.3 degrees vs. 62.7 +/- 17.5 degrees ; p = 0.013), less flexibility (30.1 +/- 13.5% vs. 40.3 +/- 17.8%; p = 0.01), and less correction percentage (51.3 +/- 12.9% vs. 58.8 +/- 16.5%; p = 0/013). The loss of correction was comparable between the two groups. In the matched comparison, the flexibility in boys was less than girls (30.1 +/- 13.5% vs. 38.1 +/- 17.5%; p = 0.027). Also, the boys had a smaller correction percentage compared to the girls, but this finding was not statistically significant. There was similar distribution curve pattern between male and female patients with AIS. Males had more rigid primary curves compared to females but a similar degree of postoperative scoliosis correction. Male AIS patients were older at the time of surgery. These preoperative gender differences, however; did not compromise the radiological outcomes of surgical treatment and the results were comparable between the genders.


Sirolimus-loaded exosomes as a promising vascular delivery system for the prevention of post-angioplasty restenosis.
Restenosis remains the main reason for treatment failure of arterial disease. Sirolimus (SIR) as a potent anti-proliferative agent is believed to prevent the phenomenon. The application of exosomes provides an extended-release delivery platform for SIR intramural administration. Herein, SIR was loaded into fibroblast-derived exosomes isolated by ultracentrifugation. Different parameters affecting drug loading were optimized, and exosome samples were characterized regarding physicochemical, pharmaceutical, and biological properties. Cytotoxicity, scratch wound assays, and quantitative real-time PCR for inflammation- and migration-associated genes were performed. Restenosis was induced by carotid injury in a rat carotid model and then exosomes were locally administered. After 14 days, animals were investigated by computed tomography (CT) angiography, morphometric, and immunohistochemical analyses. Western blotting confirmed the presence of specific protein markers in exosomes. Characterization of empty and SIR-loaded exosomes verified round and nanoscale structure of vesicles. Among prepared formulations, desired entrapment efficiency (EE) of 76% was achieved by protein:drug proportion of 2:1 and simple incubation for 30 min at 37 °C. Also, the optimal formulation released about 30% of the drug content during the first 24 h, followed by a prolonged release for several days. In vitro studies revealed the uptake and functional efficacy of the optimized formulation. In vivo studies revealed that %restenosis was in the following order: saline > empty exosomes > SIR-loaded exosomes. Furthermore, Ki67, alpha smooth muscle actin (α-SMA), and matrix metalloproteinase (MMP) markers were less expressed in the SIR-exosomes-treated arteries. These findings confirmed that exosomal SIR could be a hopeful strategy for the prevention of restenosis.


Combination immunotherapy which neutralises the effects of TNF alpha and IL-1 beta attenuates the circulatory failure and multiple organ dysfunction caused by endotoxin in the rat.
Pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF alpha) or interleukin-1 beta (IL-1 beta) are implicated in the pathogenesis of septic shock. Here we investigate the role of endogenous TNF alpha and IL-1 beta on (i) the circulatory failure, (ii) the multiple organ dysfunction syndrome (MODS) and (iii) the induction of the inducible isoform of nitric oxide (NO) synthase (iNOS) caused by endotoxin (LPS) in the anaesthetised rat. Here we demonstrate that (i) a polyclonal antibody against TNF alpha, (ii) a polyclonal antibody against IL-1, (iii) co-administration of polyclonal antibodies against TNF alpha and IL-1 and (iv) neutralisation of the effects of both TNF alpha and IL-1 with one polyclonal antibody directed against both cytokines reduces the circulatory failure, the liver injury/dysfunction, the pancreatic injury (but not the renal dysfunction) caused by endotoxin in the rat. The beneficial effects of these interventions on haemodynamics and organ injury/dysfunction are most likely due to prevention of the induction of iNOS. The two different interventions which neutralised the effects of both TNF alpha and IL-1 were superior in reducing the circulatory failure and the organ injury caused by endotoxin in the rat, than single interventions aimed at neutralising the effects of either cytokine. Thus, we propose that interventions which are able to neutralise the effects of both TNF alpha and IL-1 (combination immunotherapy) may be of benefit in the treatment of patients with septic shock.


A highly sensitive fluorescent sensor for ammonia detection based on aggregation-induced emission luminogen-doped liquid crystals.
As a toxic substance, ammonia can cause serious irritation to the human respiratory system and lungs. Although many detection techniques have been reported, most of them have drawbacks, such as expensive devices and complex and time-consuming fabrication processes. Thus, it is important to develop a simple method for ammonia detection. In this paper, we demonstrate a highly sensitive fluorescent sensor for ammonia detection based on aggregation-induced emission luminogen-doped liquid crystals without the use of polarizers. The homeotropic orientation of the liquid crystals on a modified substrate can be disturbed by ammonia, resulting in the fluorescence intensity change of an aggregation-induced emission luminogen. This aggregation-induced emission luminogen-doped liquid crystal-based fluorescent sensor for ammonia detection exhibited a low detection limit of 5.4 ppm, which is 3 times lower than previously reported liquid crystal-based optical sensors. The detection range is also broad from 0 ppm to 1600 ppm. Meanwhile, this sensor can be applied to detect aqueous ammonia with a low limit of detection of 1.8 ppm. The proposed fluorescent sensor for ammonia detection based on an aggregation-induced emission luminogen-doped liquid crystal is highly sensitive, highly selective, simple, and low cost with wide potential applications in chemical and biological fields. This strategy of designing a liquid crystal fluorescent sensor provides an inspiring stage for other toxic chemical substrates by changing specific decorated molecules.