Characterization of hepatitis C virus pseudoparticles by cryo-transmission electron microscopy using functionalized magnetic nanobeads.
Cell entry and membrane fusion of the hepatitis C virus (HCV) depend on its envelope glycoproteins E1 and E2. HCV pseudotyped particles (HCVpps) are relevant and popular models to study the early steps of the HCV life cycle. However, no structural characterization of HCVpp has been available so far. Using cryo-transmission electron microscopy (cryo-TEM), providing structural information at nanometric resolution, the molecular details of HCVpps and their fusion with liposomes were studied. Cryo-TEM revealed HCVpps as regular 100 nm spherical structures containing the dense retroviral nucleocapsid surrounded by a lipid bilayer. E1-E2 glycoproteins were not readily visible on the membrane surface. Pseudoparticles bearing the E1-E2 glycoproteins of Semliki forest virus looked similar, whereas avian influenza A virus (fowl plague virus) haemagglutinin/neuraminidase-pseudotyped particles exhibited surface spikes. To further characterize HCVpp structurally, a novel method was designed based on magnetic beads covered with anti-HCV antibodies to enrich the samples with particles containing E1-E2. This strategy efficiently sorted HCVpps, which were then directly observed by cryo-TEM in the presence or absence of liposomes at low or neutral pH. After acidification, HCVpps looked the same as at neutral pH and closely contacted the liposomes. These are the first visualizations of early HCV membrane fusion events at the nanometer scale. Furthermore, fluorimetry analysis revealed a relative resistance of HCVpps regarding their fusion capacity when exposed to low pH. This study therefore brings several new molecular details to HCVpp characterization and this efficient strategy of virion immunosorting with magnetic nanobeads is direct, efficient and adaptable to extensive characterization of any virus at a nanometric resolution.


Pain Sensitization as a Potential Mediator of the Relationship Between Sleep Disturbance and Subsequent Pain in Rheumatoid Arthritis.
Many patients with rheumatoid arthritis (RA) experience sleep disturbances, commonly attributed to joint pain. Sleep disturbances could also influence pain. One mechanism may be through dysregulated pain processing, manifested by enhanced pain sensitivity. The present study was undertaken to examine the role of pain sensitization, measured by quantitative sensory testing (QST), as a mediator in the pathway of sleep disturbance leading to subsequent pain. We used longitudinal data from 221 patients with active RA who were followed for 12 weeks after initiating a disease-modifying antirheumatic drug. Baseline QST included pressure pain thresholds at articular (wrists, knees) and nonarticular (trapezius, thumbnails) sites, temporal summation (TS) at the wrist and forearm, and conditioned pain modulation (CPM). Baseline sleep disturbance and subsequent pain intensity were assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS). We evaluated correlations between sleep disturbance, QSTs, and subsequent pain intensity. Mediation analyses separately assessed each QST as a mediator, adjusting for baseline confounding factors. Sleep disturbance was correlated with all QST measures except wrist TS and CPM. Sleep disturbance significantly predicted subsequent pain (coefficient for a meaningful increase of 5 units in sleep disturbance = 0.32 (95% confidence interval 0.11, 0.50) in multiple regression. QST mediated 10-19% of this effect. Pain sensitization may be one mechanism through which sleep disturbance contributes to pain. The small magnitude of association indicates that unmeasured pathways may contribute to this relationship. Intervention studies are needed to establish causality and determine whether improving sleep can improve pain in patients with RA.


Burnout and Coping Perceptions of Volleyball Players Throughout an Annual Sport Season.
Burnout is a psychological syndrome of reaction to chronic stress that occurs in athletes who feel exhausted by a sport activity that was previously pleasurable and enjoyable. One technique to prevent and control the syndrome is through coping, which is the ability to deal with stressful situations. In contrast to traditional cross-sectional approaches, this study aimed to investigate burnout and coping strategy characteristics over time and to analyze the relationship between burnout dimensions and coping strategies. Fifty-four high-level volleyball athletes (twenty-eight men and twenty-six women, age M = 25.57, SD = 4.72, range 18-35) completed paper-and-pencil measures of burnout and coping four times throughout a sport season. The Friedman test presented a significant increase in the reduced sense of athletic accomplishment (X2 = 20.58; p < 0.01) and sport devaluation (X2 = 19.83; p < 0.01) perceptions during the season. However, no coping differences were observed through the longitudinal analysis. Burnout dimensions showed a moderate inverse correlation to confidence/motivation at all measurement points during the season. Overall, the findings suggest that burnout perceptions increase as the season progresses, highlighting the relevance for the periodization of burnout prevention and control.


Editorial on "Comprehensive geriatric care for patients with hip fractures: a prospective, randomized, controlled trial" published in The Lancet on April 25(th), 2015.
A third of elderly adults fall every year, many leading to hip fractures with a 24% mortality rate just within the first year. As a growing number of the US population approaches old age, these hip fractures are expected to cost the US over 25 billion annually. In the near future, physicians will need to not only improve the treatment for a larger patient population but also reduce the medical costs associated. The authors in this paper sought to determine whether specialized geriatric care positively impacted patient outcome compared to standard orthopaedic care for hip fractures. The study found that geriatric care significantly increased patient mobility within 4 months after hip fracture and will likely reduce overall medical costs. Similar studies have shown promising results as well. Moving forward, geriatric fracture programs need more prospective randomized trials to determine the effectiveness of these programs to increase patient quality while also reducing overall medical costs. This study in correlation with others further demonstrates the importance and need of specialized geriatric programs in the US.


A Survey of the Prevalence and Anthropometric Correlates of the Risk for Obstructive Sleep Apnoea in Abuja, Nigeria.
Obstructive Sleep Apnoea (OSA) is asignificant public health challenge, with increasing prevalence and mortality. A significant proportion of the burden of this disorder occurs in middle- and low-income countries. Unfortunately, the rising number of individuals with a new OSA diagnosis and its consequences are frequently underestimated. This study aims to evaluate the prevalence and the correlates of OSA in the community setting. The study was a cross-sectional community-based survey. A standardized self-administered Berlin questionnaire was administered to all the study participants. The questionnaire has three categories that assess snoring, daytime sleepiness, and OSA. The international physical activity questionnaire and Sheldon Cohen perceived stress was applied to assess physical activity and psychosocial stress levels. The subject's anthropometric and other clinical parameters were measured using the appropriate instrument for measurements. The data obtained were analyzed with SPSS version 21 software. Four hundred thirty-six (436) participants returned the completed questionnaire, out of which, 234 (53.7%) of the study population were men. The overall prevalence of the risk for OSA was 30% (36% in men vs. 24% in women). The risk of developing OSA was 1.8 times more in men. Hypertension was the most frequently reported comorbidity among the population at risk for developing OSA. Obstructive sleep apnoea is a common but frequently neglected medical condition. The proportion of individuals affected may be more than is currently suggested. Routine screening for OSA and initiation of early treatment is necessary to mitigate the attendant consequences.


Indirect flight of an African bat to Israel: an example of the potential for zoonotic pathogens to move between continents.
The transmission of harmful pathogens during commercial air flights is an increasing health concern. A potential, yet relatively overlooked source of zoonotic infectious diseases involves collisions of birds and bats with aircraft and long distance transport of their carcasses. We report a case of aerial transportation of the remains of an African fruit bat over three continents, following a collision with an aircraft, and demonstrate the relative ease with which zoonotic pathogens, such as rabies virus or other viruses associated with bats, may cross national boundaries and continents even. Improper handling and disposal of animal remains by airport personnel, may lead to exposure of both humans and local fauna to exotic pathogens. This in turn may trigger an epidemic with potentially devastating results.


Accurate Ballistocardiogram Based Heart Rate Estimation Using an Array of Load Cells in a Hospital Bed.
The ballistocardiogram (BCG), a cardiac vibration signal, has been widely investigated for continuous monitoring of heart rate (HR). Among BCG sensing modalities, a hospital bed with multi-channel load-cells could provide robust HR estimation in hospital setups. In this work, we present a novel array processing technique to improve the existing HR estimation algorithm by optimizing the fusion of information from multiple channels. The array processing includes a Gaussian curve to weight the joint probability according to the reference value obtained from the previous inter-beat-interval (IBI) estimations. Additionally, the probability density functions were selected and combined according to their reliability measured by q-values. We demonstrate that this array processing significantly reduces the HR estimation error compared to state-of-the-art multi-channel heartbeat detection algorithms in the existing literature. In the best case, the average mean absolute error (MAE) of 1.76 bpm in the supine position was achieved compared to 2.68 bpm and 1.91 bpm for two state-of-the-art methods from the existing literature. Moreover, the lowest error was found in the supine posture (1.76 bpm) and the highest in the lateral posture (3.03 bpm), thus elucidating the postural effects on HR estimation. The IBI estimation capability was also evaluated, with a MAE of 16.66 ms and confidence interval (95%) of 38.98 ms. The results demonstrate that improved HR estimation can be obtained for a bed-based BCG system with the multi-channel data acquisition and processing approach described in this work.


Proteomics and disease network associations evaluation of environmentally relevant Bisphenol A concentrations in a human 3D neural stem cell model.
Bisphenol A (BPA) exposure is associated with a plethora of neurodevelopmental abnormalities and brain disorders. Previous studies have demonstrated BPA-induced perturbations to critical neural stem cell (NSC) characteristics, such as proliferation and differentiation, although the underlying molecular mechanisms remain under debate. The present study evaluated the effects of a repeated-dose exposure of environmentally relevant BPA concentrations during the in vitro 3D neural induction of human induced pluripotent stem cells (hiPSCs), emulating a chronic exposure scenario. Firstly, we demonstrated that our model is suitable for NSC differentiation during the early stages of embryonic brain development. Our morphological image analysis showed that BPA exposure at 0.01, 0.1 and 1 µM decreased the average spheroid size by day 21 (D21) of the neural induction, while no effect on cell viability was detected. No alteration to the rate of the neural induction was observed based on the expression of key neural lineage and neuroectodermal transcripts. Quantitative proteomics at D21 revealed several differentially abundant proteins across all BPA-treated groups with important functions in NSC proliferation and maintenance (e.g., FABP7, GPC4, GAP43, Wnt-8B, TPPP3). Additionally, a network analysis demonstrated alterations to the glycolytic pathway, potentially implicating BPA-induced changes to glycolytic signalling in NSC proliferation impairments, as well as the pathophysiology of brain disorders including intellectual disability, autism spectrum disorders, and amyotrophic lateral sclerosis (ALS). This study enhances the current understanding of BPA-related NSC aberrations based mostly on acute, often high dose exposures of rodent in vivo and in vitro models and human GWAS data in a novel human 3D cell-based model with real-life scenario relevant prolonged and low-level exposures, offering further mechanistic insights into the ramifications of BPA exposure on the developing human brain and consequently, later life neurological disorders.


Adsorption of ammonia by sulfuric acid treated zirconium hydroxide.
The adsorption of ammonia on Zr(OH)(4), as well as Zr(OH)(4) treated with sulfuric acid, were examined. The results show that treating Zr(OH)(4) with sulfuric acid leads to the formation of a sulfate on the surface of the material, and that the sulfate contributes to the ammonia adsorption capacity through the formation of an ammonium sulfates species. Calcination of Zr(OH)(4) decreases the ammonia adsorption capacity of the material and limits the formation of sulfate species. NMR and FTIR spectroscopy results are presented that show the presence of two distinct ammonium species on the surface of the material. The adsorption capacity of the materials is shown to be a complex phenomenon that is impacted by the surface area, the sulfur content, and the pH of the material. The results illustrate that Zr(OH)(4), which is known to adsorb acidic gases, can be modified and used to adsorb basic gases.


Immediate implant in single rooted teeth - Study on primary stability and bone formation.
Dental implants (DI) are emerging as an alternative to dentures. Immediate placement of DI for esthetic concern has been always in demand. This is a retrospective analysis of the success rate of immediately placed DI in freshly extracted single-rooted tooth socket, by clinical, radiographical, soft and hard tissue changes in a follow-up period of 1 year. Retrospective analysis of all cases of immediate DI placed in the single rooted socket was performed. Cases were selected based on previously established inclusion and exclusion criteria. Age, gender, tooth, jaw, cause of impending tooth loss, tooth diameter along the cervical margin, the width of keratinized gingiva (WKG), and radiographic measures were performed for up to a year. Descriptive statistics and comparison of means were presented. P < 0.05 was taken as significant. Of the 324 immediate DI placed in 207 patients during the study period, 61 fulfilled the criteria. There were 49.2% males 31.15% had dental caries, 61% involving maxilla. The mean age of patients was 34.82 ± 7.97 years. Mean extraction socket diameter was 4.6 ± 1.78 mm. From complete stability of DI, the WKG decreased from baseline to 3 months period and regained at 12-month follow-up. The difference was statistically significant (P = 0.01). The same trend was noticed in the distance of the mesial and distal papilla as measured in the probe (P = 0.075). Radiographical changes also reflected a similar trend. The success of DI, in terms of clinical and radiographical parameters, in an immediate DI placed in a single rooted fresh extracted socket, gives adequate clinical results.


Internal Lower Incisor Morphology revealed by Computerized Microtomography.
This study evaluated the internal morphology of lower incisors using computerized microtomography (micro-CT) images. Eighty-nine lower incisors were scanned by micro-CT and reconstructed with NRecon software. 2D parameters (perimeter, root length, circularity and canal diameter) and 3D parameters (volume, surface area and structure model index) were evaluated with CTAn and CTVol software. The results are presented descriptively. It was found that 89.9% of the canals had a single main root canal (type I), followed by type II (6.7%) and III (3.4%), while 5.6% of the specimens presented lateral canals and 1.1% had an apical delta. Mean volume and surface area were 31.80mm³ and 90.58mm², respectively. The most prevalent shape of the root canal at CEJ level was circular (41.6%) and 1mm from the apex, 73% of the samples were classified as oval. Lower incisors with internal anatomical variations may offer a high degree of technical complexity and may result in treatment failure.


An update on genetic variants of the NKX2-5.
NKX2-5 is a homeodomain transcription factor that plays a crucial role in heart development. It is the first gene where a single genetic variant (GV) was found to be associated with congenital heart diseases in humans. In this study, we carried out a comprehensive survey of NKX2-5 GVs to build a unified, curated, and updated compilation of all available GVs. We retrieved a total of 1,380 unique GVs. From these, 970 had information on their frequency in the general population and 143 have been linked to pathogenic phenotypes in humans. In vitro effect was ascertained for 38 GVs. The homeodomain had the biggest cluster of pathogenic variants in the protein: 49 GVs in 60 residues, 23 in its third α-helix, where 11 missense variants may affect protein-DNA interaction or the hydrophobic core. We also pinpointed the likely location of pathogenic GVs in four linear motifs. These analyses allowed us to assign a putative explanation for the effect of 90 GVs. This study pointed to reliable pathogenicity for GVs in helix 3 of the homeodomain and may broaden the scope of functional and structural studies that can be done to better understand the effect of GVs in NKX2-5 function.


[Sonography of pancreatic carcinoma. Sonomorphology, diagnostic accuracy and tumor staging].
Ultrasonography was performed in 125 consecutive patients with clinically suspected carcinoma of the pancreas. The most important diagnostic criteria were reflectivity and echo amplitude, which were locally decreased in 71% (50/70) and increased in 27% (19/70) of the cancers. The echogenicity and reflectivity did not differ in four endocrine active tumors and adenocarcinomas. The diagnostic accuracy was 83% (101/122); in 3 patients ultrasonography failed to provide adequate information. Dilation of the biliary tree was found in 68% (43/50) of the carcinomas and dilation of the Wirsungian duct in 52% (32/58). There was some difficulty in differentiating between pancreatic carcinoma and chronic pancreatitis because the echogenicity is similar for both and inflammatory and neoplastic pancreatic processes are also present in both diseases. Although only 2-3 cm in diameter, 87% (7/8) of the carcinomas were already in the T3 stage. Angiography to evaluate resectability is unnecessary only when vascular encasement, extensive infiltration of peripancreatic fat, or tumor thrombus has been demonstrated sonographically.


Coping, emotion regulation, and self-blame as mediators of sexual abuse and psychological symptoms in adult sexual assault.
This study examined whether coping, emotion regulation, and self-blame mediate relationships of trauma histories with post-traumatic stress disorder and depression in adult sexual assault victims (N = 1863). A path analysis showed that theorized mediators partially mediated associations between trauma history variables and psychological symptoms. Specifically, child sexual abuse severity was related to greater post-traumatic stress disorder and depression indirectly through maladaptive coping and decreased emotion regulation but not self-blame. Other traumas had direct relationships with symptoms and partially mediated effects through maladaptive coping and emotion regulation. Child sexual abuse was unrelated to self-blame, but other traumas were related to greater self-blame. Results differed according to whether women had counseling post-assault. Implications are drawn for future research and clinical treatment of adult sexual assault victims.


Potential role of type I interferons in the treatment of pituitary adenomas.
Cytokines, particularly those endowed with pro-inflammatory properties, are known to influence the release of anterior pituitary hormones by a direct and indirect action at the level of pituitary gland and hypothalamus. Type I interferons (IFNs) represent a group of cytokines that act through a common receptor composed by two chains (IFNAR-1 and IFNAR-2). Several in vitro and in vivo studies underline the fact that type I IFNs are involved in the regulation of the immune-endocrine circuitry. Treatment with type I IFNs of patients affected by chronic viral hepatitis, multiple sclerosis and tumors influences the secretion of pituitary hormones. This article reviews the current knowledge about the effects of IFN-alpha and IFN-beta on hypothalamic-pituitary function and describes the potential role of type I IFNs in the treatment of pituitary adenomas.


GM allotypes and IgG subclass concentrations in blacks.
IgG subclass concentrations were measured in 352 black Americans. Sera were also typed for nine GM allotypes. Serum concentrations of IgG1, IgG3, and IgG4 varied, to different degrees, according to GM phenotypes. The concentration of IgG1 was lower in subjects with GM 1,3,17 5,6,13 compared to those who lacked this phenotype. Elevated levels of IgG3 and IgG4 were associated with GM 1,17 5,6,13 and GM 1,3,17 23 5,13, respectively. Subjects with GM 1,17 5,13,21 had lower levels of IgG3 than individuals with other phenotypes. IgG2 levels were not associated with any of the GM phenotypes. To our knowledge, this represents the first report of an association between GM allotypes and IgG subclasses in blacks.


Relationship between functional disc position and mandibular displacement in adolescent females: posteroanterior cephalograms and magnetic resonance imaging retrospective study.
The purpose of this study was to investigate the relationship between the disc positions of temporomandibular joints (TMJ), the vertical and lateral mandibular displacement (VMD and LMD, respectively) and age in female adolescents with signs and symptoms of the temporomandibular disorders (TMD). The VMD and LMD were assessed, using posteroanterior (PA) cephalograms. The disc positions were assessed by magnetic resonance imaging (MRI) and categorized as follows: normal disc position, functional disc displacement and functional disc dislocation. Excluding patients with osteoarthritis, the total number of subjects was 54 female adolescents who were grouped into three: the bilateral normal disc position group, the unilateral or bilateral functional disc displacement group, and the unilateral or bilateral functional disc dislocation group. We compared the extent of VMD and LMD between the three groups, and investigated their correlation with age. Results indicate that functional disc displacement and dislocation are related to mandibular displacement, and VMD did not correlate with age but LMD did correlate with age. This study suggests that the onset of disc displacement is related to the mandibular displacement and disturbs normal growth of the mandible three-dimensionally.


Phosphorylated paxillin and phosphorylated FAK constitute subregions within focal adhesions.
Integrin-mediated adhesions are convergence points for multiple signaling pathways. Their inner structure and diverse functions can be studied with super-resolution microscopy. Here, we examined the spatial organization within focal adhesions by analyzing several adhesion proteins with structured illumination microscopy (SIM). Paxillin (Pax) serves as a scaffold protein and signaling hub in focal adhesions, and focal adhesion kinase (FAK, also known as PTK2) regulates the dynamics of adhesions. We found that their phosphorylated forms, pPax and pFAK, form spot-like, spatially defined clusters within adhesions in several cell lines and confirmed these findings with additional super-resolution techniques. These clusters showed a more regular separation from each other compared with more randomly distributed signals for FAK or paxillin. Mutational analysis indicated that the active (open) FAK conformation is a prerequisite for the pattern formation of pFAK. Live-cell super-resolution imaging revealed that organization in clusters is preserved over time for FAK constructs; however, distance between clusters is dynamic for FAK, while paxillin is more stable. Combined, these data introduce spatial clusters of pPax and pFAK as substructures in adhesions and highlight the relevance of paxillin-FAK binding for establishing a regular substructure in focal adhesions.


Successful Liver Transplantation for Adolescent Patient With Pyruvate Kinase Deficiency-induced Cirrhosis.
We present the case of a successful liver transplant in a young adult patient with cholestasis and cirrhosis secondary to severe pyruvate kinase (PK) deficiency. Liver transplant resulted in resolution of liver dysfunction, decreased need for blood transfusions and eligibility for bone marrow transplantation. This case represents the third reported patient in the literature with severe PK deficiency who successfully underwent liver transplant as a result of profound cholestasis and liver failure. Explant pathology demonstrated a lack of significant iron deposition indicating that PK deficiency predisposes the liver to injury independent of transfusion-related iron overload.


Surgery for recurrent stress urinary incontinence: the views of surgeons and women.
The objectives were to explore the views of women with recurrent stress incontinence (SUI) with regard to treatment preferences and the acceptability of randomisation to a future trial, and to survey the views of UK specialists on treatment preferences and equipoise regarding different treatment alternatives. An online survey of the British Society of Urogynaecology (BSUG) and British Society of Urological Surgeons (BAUS) was carried out. Qualitative semi-structured interviews with a purposive sample of surgeons and women suffering from recurrent SUI from three UK centres. Two hundred fifty-six survey replies were received (176 gynaecology; 80 urology). Comparing the treatments offered, urogynaecologists were more likely to offer pelvic floor exercises (p < 0.05), and repeat midurethral tape (MUT) (p < 0.001). From the Surgical Equipoise Scale (SES) responses, "no preference" was rarely the commonest response. Marked differences for several options existed; midurethral tape dominated responses whenever it appeared. Twenty-one clinicians were interviewed. Treatment preferences were complex, influenced by a range of factors (reason for failure, patient comorbidity, investigations, personal experience, training). A future trial was regarded as important. Eleven women were interviewed. Most had considered more than one option, but felt that decision-making was more a process of elimination rather than a positive process. Randomisation to a study was regarded as unacceptable by most. No consensus exists among surgeons about preferred treatment options for recurrent SUI, and personal experience and training dominate decision-making. For patients, choices were usually based on an elimination of options, including that of a repeat failed procedure. This contrasts with surgeons, who mostly preferred a repeat MUT above other options. Any future comparative study will be challenging.


Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy (STRATEGY): a multicenter, randomized, controlled, non-inferiority clinical trial.
Despite the current guideline's recommendation of a timely stepwise intensification therapy, the "clinical inertia", termed as the delayed treatment intensification, commonly exists in the real world, which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy. In this clinical trial performed in 237 centers in China, 5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks. The patients who did not reach the glycated hemoglobin A1c (HbA1c) goal were then further randomized into glimepiride, gliclazide, repaglinide, or acarbose group for an additional 24-week triple therapy. A mean HbA1c reduction of 0.85% was observed when sitagliptin was added to the patients inadequately controlled with metformin in 16 weeks. Further HbA1c reductions in the 24-week triple therapy stage were 0.65% in glimepiride group, 0.70% in gliclazide group, 0.61% in repaglinide group, and 0.45% in acarbose group. The non-inferiority criterion for primary hypotheses was met for gliclazide and repaglinide, but not for acarbose, compared with glimepiride, when added to metformin/sitagliptin dual therapy. The incidences of adverse events (AEs) were 29.2% in the dual therapy stage and 30.3% in the triple therapy stage. Metformin/sitagliptin as baseline therapy, with the addition of a third oral antihyperglycemic agent, including glimepiride, gliclazide, repaglinide, or acarbose, was effective, safe and well-tolerated for achieving an HbA1c <7.0% goal in type 2 diabetic patients inadequately controlled with previous therapies. The timely augmentation of up to three oral antihyperglycemic agents is valid and of important clinical benefit to prevent patients from exposure to unnecessarily prolonged hyperglycemia.


Production of dextransucrase by Leuconostoc mesenteroides immobilized in calcium-alginate beads: I. Batch and fed-batch fermentations.
In batch fermentation Leuconostoc mesenteroides immobilized in calcium alginate beads produced a total dextransucrase activity equal to about 93% of that by free, suspended bacterial cells under comparable conditions in a bubble column reactor. Continuous sucrose feeding (5 g/L h) to the immobilized-cell culture in the airlift bioreactor increased production of enzymatic activity by about 107% compared with ordinary batch operation of this reactor. About 14% of the enzymatic activity produced by the immobilized cells appears as soluble activity in the cell-free broth compared with about 40% in case of free cells. In an airlift bioreactor, both the soluble and the intact (sorbed and entrapped) enzymatic activity produced by the immobilized bacterial cells was about 34% greater under automatic pH control, compared to that produced in a bubble column reactor with only manual pH control. During formation of dextran by intact enzyme within cells and beads, declines are observed in apparent enzymatic activity.


Endoscopic, Diagnostic and Therapeutic Procedures of the Biliary and Pancreatic Tract.
Endoscopic cannulation of the biliary tree and the pancreatic duct (ERCP) was first described in 1968. Six years later the technique of endoscopic sphincterotomy (ES) opened the door to endoscopic treatment procedures of pancreatic and biliary diseases. Techniques have been developed to remove bile duct stones, to break large stones and to drain bile duct or pancreatic duct strictures.


[Liposarcoma of the head].
Cephalic localization of liposarcoma is exceptional. We report three cases, in an 87-year-old patient with liposarcoma of the tongue, a 78-year-old patient with multiple recurrent liposarcoma of the orbit and a 42-year-old patient with ethmoido-orbital liposarcoma of metastasis origin. These three cases and a review of the literature were the basis of a summary of the incidence, the anatomic classification and therapeutic options for this type of liposarcomas.


Downregulation of miR-139-5p contributes to the antiapoptotic effect of liraglutide on the diabetic rat pancreas and INS-1 cells by targeting IRS1.
Liraglutide is administered as glucagon-like peptide-1 (GLP-1) receptor agonist for diabetic patients and can protect pancreatic β-cells by inhibiting their apoptosis. MicroRNA-139-5p (miRNA-139-5p) participates in the regulation of cancer cell apoptosis. However, it is not clear whether miR-139-5p contributes to the anti-apoptotic effect of liraglutide in β-cells. The objective of the present study was to investigate the role of miR-139-5p on apoptosis of pancreatic β-cells. MicroRNA levels in pancreatic tissue from diabetic rats and INS-1 cells treated with liraglutide were measured by real-time quantitative RT-PCR. The role of miR-139-5p on apoptosis was studied by transfecting INS-1 cells with miR-139-5p mimics. The mRNA and protein expression of the target gene, insulin receptor substrate-1 (IRS1), were measured by qRT-PCR and Western blot, respectively. Apoptosis in rat pancreatic tissue and INS-1 cells was detected by TUNEL and annexin V/propidium iodide costaining. Apoptosis of pancreatic tissue from diabetic rats and INS-1 cells was decreased by administration of liraglutide. The expression of miR-139-5p increased in the pancreas of diabetic rats and decreased with liraglutide treatment. Incubation with liraglutide (100 nM) for 48 h attenuated the expression of miR-139-5p and increased the mRNA and protein levels of IRS1. Direct regulatory effects of miR-139-5p on IRS1 were found by a dual-luciferase reporter assay. Transfection of INS-1 cells with miR-139-5p mimics led to decreases in the mRNA and protein expression of IRS1. In conclusion, our observations suggest that decreased miR-139-5p expression contributes to the anti-apoptotic effect of liraglutide on the diabetic rat pancreas and INS-1 cells by targeting IRS1.


A symmetrical 1,4-dihydropyridine with opposite actions on K(+)-induced contractions in guinea-pig ileum.
The effects of 1,4-dihydro-2,6-dimethyl-4-phenyl-pyridine-3,5-dicarboxylic acid dimethyl ester (DHMP) on Ca2(+)-evoked contractions in potassium-depolarized guinea-pig ileum longitudinal muscle were evaluated. DHMP (1-10 nM) potentiated Ca2(+)-evoked contractions; maximum enhancement was seen at 1 nM. A concentration-dependent inhibition of Ca2(+)-induced contractility was observed at higher concentrations. Racemic BAY K 8644 (1 nM - 1 microM), on the other hand, enhanced ileum responses to Ca2+ with a maximum effect at 3 nM. BAY K 8644, but not DHMP, directly elicited concentration-dependent contractions. The results provide further support for the hypothesis that dihydropyridines can act as both Ca2+ agonists and antagonists.


An abnormality of immune complex kinetics in murine lupus.
In order to understand better the role of immune complex metabolism in the pathogenesis of autoimmune diseases, we have investigated the early stages of immune complex uptake by the liver, the major organ responsible for clearance of soluble complexes in the mouse. Livers were perfused in situ via the portal vein over 3 to 5 min with trace amounts of radiolabeled soluble model immune complexes. In 4 nonautoimmune strains (BALB/c, DBA/2, CAF1, NZW) 60 to 72% of the model complexes perfused were taken up and remained in the liver after 20 min of continuous perfusion with oxygenated Krebs-Henseleit buffer. In NZB and NZB/W F1 female mice at ages 0.5 to 11 mo, 66 to 78% of the model complexes remined in the liver. However, when a dose of heat-aggregated human gamma-globulin sufficient to saturate the reticuloendothelial system was perfused 7 min after radiolabeled complexes, 15.2 +/- 7.2% (mean +/- SD) of the complexes were displaced in the nonautoimmune strains. In contrast, 32.6 +/- 10.5% of the complexes were displaced from the liver in NZB and NZB/W F1 female mice (p < 0.001). Thus, although hepatic uptake of immune complexes in autoimmune mice appears to be normal or even enhanced, there may be impaired phagocytosis by the hepatic RES or weaker binding of complexes to the surface of the Kupffer cells. Such surface-bound immune complexes remaining accessible to the circulation may contribute to the autoimmune process.


Folic acid improves vascular reactivity in humans: a meta-analysis of randomized controlled trials.
The effect of folic acid on endothelial function, a prognostic factor for cardiovascular diseases, is not well established. We calculated this effect in a meta-analysis of randomized, double-blind, placebo-controlled trials in humans. The objective of the study was to quantify the effect of folic acid on endothelial function, as measured with the use of flow-mediated dilatation (FMD). We conducted a meta-analysis of randomized, double-blind, placebo-controlled folic acid trials evaluating endothelial function. Trials were identified through MEDLINE (1966-15 Sept 2005), by hand-searching of references, and by contact with investigators for unpublished results. Two of us (AdB and RD) independently extracted trial data. A pooled estimate was calculated by using random-effects meta-analysis. Previously defined stratified analyses were conducted to explore the influence of study characteristics. Of 163 identified studies, 14 met inclusion criteria and provided data on 732 persons. Evidence for publication bias was not obvious. In the overall pooled estimate, folic acid improved FMD by 1.08 (95% CI: 0.57,1.59; P = 0.0005) percentage points over placebo. Of the study characteristics, only folic acid dose significantly influenced the outcome. Post hoc analysis, which should be interpreted with caution, seemed to indicate a dose-response effect: the change in FMD was -0.07 (95% CI: -0.37, 0.22) percentage points at doses between 400 and 800 microg/d, 1.37 (95% CI: 1.12, 1.54) percentage points at doses of 5000 microg/d, and 2.04 (95% CI: 1.43, 2.65) percentage points at doses of 10,000 microg/d. This study indicates that high doses of folic acid improve endothelial function, which could potentially reduce the risk of cardiovascular disease.


Effects of object use on reaching and postural balance: a comparison of patients with unilateral stroke and healthy controls.
To evaluate whether the functional use of certain task objects while standing influences reaching performance and postural balance in persons with left or right cerebral vascular accidents, and also in healthy individuals. Thirty-five stroke patients (20 patients with left and 15 patients with right cerebral vascular accidents) and 31 healthy controls (15 using the left and 16 the right arm) performed two experimental reaching tasks (task object present vs. absent) using the less affected arm while standing. For the object-present task, subjects held a glass and moved it forward as far as possible. For the object-absent task, subjects simply reached forward as far as possible. We measured reaching performance using kinematic analysis and assessed postural control using derivatives of the center of pressure, including forward displacement, mediolateral shift, and average velocity. Object presence did not significantly improve overall reaching performance in any group. However, for patients with left cerebral vascular accidents and controls (using either the left or the right arm), there were significant effects of object presence on the average velocity of the center of pressure. For patients with right cerebral vascular accidents, there were significant effects of task object on the forward distance and average velocity of the center of pressure. The positive findings regarding center-of-pressure derivatives suggest that a functional use of objects during a standing reaching task can decrease postural sway, as represented by the average velocity of the center of pressure, in individuals with and without stroke. Patients with right cerebral vascular accidents may benefit considerably more from functional object use during a standing reaching task, apparently because such tasks can facilitate greater forward displacement of the center of pressure.


[Morbidity among ore-dressing and processing enterprise workers, according to thorough medical examination results].
The authors analyzed materials of thorough medical examinations among ore-dressing and processing enterprise workers. All studied workers appeared to have increased risk of locomotor diseases and connective tissue disorders, ailments of respiratory tract, nervous system, ENT organs, digestive system, blood.


Recent advances in the synthesis of pharmaceutically active 4-quinolone and its analogues: a review.
4-Quinolone and its analogs are heterocyclic classes of organic compounds displaying biologically active and a broad spectrum of pharmaceutical drug scaffolds. 4-Quinolone is the first-line chemotherapeutic treatment for a wide spectrum of bacterial infections. Recently, 4-quinolone and its derivatives have been shown to have the potential to cure and regulate various acute and chronic diseases, including pain, ischemia, immunomodulation, inflammation, malarial, bacterial infection, fungal infection, HIV, and cancer, based on several reports. This review highlights and provides brief information to better understand the development of experimental progress made to date in the synthetic protocol towards 4-quinolone and its analogs. Thus, classical synthesis protocol, metal-free reaction protocol, and transition metal-catalyzed reaction procedures are briefly discussed along with the pharmaceutical activities of selected 4-quinolone derivatives.


A case of amebic liver abscess complicated by hemobilia due to rupture of hepatic artery aneurysm.
We report the case of a 51-year-old man with hepatic amebic abscess complicated by hepatic artery aneurysm. The patient first presented with peritonitis caused by perforating appendicitis. Surgical treatment resolved peritonitis but Entamoeba histolytica was detected in the colonic mucosa. Subsequently, liver abscess developed and the size of the abscess increased gradually after surgery in spite of continued treatment with metronidazole. Brown pus was drained from the abscess but 13 days after the drainage process the patient complained of right upper abdominal pain and the drained fluid became blood-colored and stool became tarry in color. Enhanced computed tomography showed a hepatic artery aneurysm that had ruptured into the liver abscess and duodenoscopy revealed bleeding from the ampulla of Vater. Transcatheter arterial embolization with several steel coils was successfully performed which resulted in cessation of bleeding from the ampulla of Vater. The patient was discharged without any complications five weeks after rupture of the aneurysm. Our case demonstrates rupture of the hepatic artery aneurysm as a rare complication of amebic liver abscess and the effectiveness of interventional embolotherapy in this condition.


[Anti-diabetics and chronic kidney disease].
Diabetes mellitus (DM) is the most important non-communicable disease after hypertension. Prevalence of type 2 DM has progressively increased over the last decades. In Italy, 11.8% of the general adult population can be identified as diabetic. The major complication of DM is diabetic nephropathy (DM-CKD), which develops in approximately one-third of diabetics. Achieving optimal glycemic control is the first therapeutic goal in the management of DM-CKD. In recent years, new antidiabetic drugs have been marketed (GLP1 analogues, DPP-4 inhibitors, SGLT-2 inhibitors) to ameliorate glycemia in patients nave or treated by means of traditional agents, such as sulfonylureas, metformin, glinides, insulin. However, use of these drugs in DM-CKD should be evaluated carefully, mainly because of the higher risk of hypoglycemia that requires dosing adjustments. Metformin still represents an adequate choice if proper dose adjustments are made on the basis of renal function. Sulfonylureas with limited renal clearance, i.e., gliquidone, glipizide and gliclazide are an alternative to metformin and more effective than repaglinide on glycemic control. Other antidiabetic agents with potential nephroprotective effects, namely DPP-4 inhibitors, incretin analogues and SGLT-2 inhibitors, may allow nephroprotective effects independent of glycemic control. Insulin remains the cornerstone of therapy when oral therapy is no longer effective.


Management of smell and taste problems.
Lost or impaired smell or taste should be taken seriously, as it puts a person at higher risk for toxic exposures, such as gas leaks, smoke, and rotting food, and it also takes away the enjoyment of some of life's pleasures, such as the fragrance of flowers or the taste of good food or fine wine. In many patients, the loss follows a viral upper respiratory tract infection, and the only real treatment is to reassure patients that the problem may resolve if the damaged sensory cells regenerate. In other patients, the loss has more subtle causes and deserves a careful investigation and appropriate treatment. This article reviews the proper steps to take when investigating and treating chemosensory difficulties.


Low-dose dobutamine stress echocardiography predicts the improvement of left ventricular systolic function and long-term prognosis in patients with idiopathic dilated cardiomyopathy.
It is unclear whether left ventricular (LV) contractile reserve assessed by low-dose dobutamine stress echocardiography (DSE) can predict the long-term prognosis together with LV functional changes in patients with idiopathic dilated cardiomyopathy (DCM). Contractile reserve was determined in 28 patients with DCM, and was then compared with changes in LV fractional shortening (FS) and cardiac events during a follow-up period of 68 ± 43 months. Nine events (2 sudden deaths, 5 heart failure deaths, and 2 rehospitalizations for heart failure) were observed. FS at peak dose was lower in patients with events (events group) than in those without events (no-events group) (20 ± 6 vs. 27 ± 7%; P < 0.05), although there were no differences in FS at baseline between the two groups. FS at follow-up was lower in the events group than in the no-events group (14 ± 7 vs. 21 ± 8%; P < 0.05). The change in FS during DSE (FS at peak dose/baseline) correlated with the change in FS during the follow-up time (FS at follow-up/baseline), and it was a predictor of events by multiple regression analysis. LV contractile reserve assessed by low-dose DSE is a useful marker not only to predict LV functional improvement, but also to determine the long-term prognosis in patients with DCM.


Activities of the peptidyl transferase center of ribosomes lacking protein L27.
The ribosome is the molecular machine responsible for protein synthesis in all living organisms. Its catalytic core, the peptidyl transferase center (PTC), is built of rRNA, although several proteins reach close to the inner rRNA shell. In the Escherichia coli ribosome, the flexible N-terminal tail of the ribosomal protein L27 contacts the A- and P-site tRNA. Based on computer simulations of the PTC and on previous biochemical evidence, the N-terminal α-amino group of L27 was suggested to take part in the peptidyl-transfer reaction. However, the contribution of this group to catalysis has not been tested experimentally. Here we investigate the role of L27 in peptide-bond formation using fast kinetics approaches. We show that the rate of peptide-bond formation at physiological pH, both with aminoacyl-tRNA or with the substrate analog puromycin, is independent of the presence of L27; furthermore, translation of natural mRNAs is only marginally affected in the absence of L27. The pH dependence of the puromycin reaction is unaltered in the absence of L27, indicating that the N-terminal α-amine is not the ionizing group taking part in catalysis. Likewise, L27 is not required for the peptidyl-tRNA hydrolysis during termination. Thus, apart from the known effect on subunit association, which most likely explains the phenotype of the deletion strains, L27 does not appear to be a key player in the core mechanism of peptide-bond formation on the ribosome.


Absence in monocotyledonous plants of the diffusible plant factors inducing T-DNA circularization and vir gene expression in Agrobacterium.
T-DNA circularization is one of the molecular events specifically induced in agrobacterial cells upon their infection of dicotyledonous plant cells. We developed a seedling co-cultivation procedure to determine whether or not monocotyledonous plants have the ability to induce T-DNA circularization and vir gene expression. Co-cultivation of Agrobacterium tumefaciens with seedlings of dicotyledonous plants showed that the circularization event takes place efficiently. The exudates and extracts of the seedlings also effectively induced T-DNA circularization and vir gene expression, indicating that dicotyledonous seedlings contain diffusible factors capable of inducing these molecular events. In contrast, neither T-DNA circularization nor vir gene expression was detectable when Agrobacterium was incubated with seedlings of monocotyledonous plants. Supplementing with acetosyringone, a known inducer of vir gene expression and T-DNA circularization, resulted in the induction of circularization during co-cultivation with moncotyledonous seedlings. These results indicate that the seedlings of monocotyledonous plants have no detectable amounts of diffusible inducers, unlike dicotyledonous seedlings. Therefore, it is unlikely that the vir genes are expressed in Agrobacterium inoculated in monocotyledonous plants. This may be one of the blocks in tumorigenesis of monocotyledonous plant by Agrobacterium.


Interventions for treating oral leukoplakia.
Oral leukoplakia is a relatively common oral lesion that in a small but significant proportion of cases changes into cancer. Since most leukoplakias are asymptomatic, the primary objective of treatment should be to prevent such malignant transformation. To assess effectiveness, safety and acceptability of treatments for leukoplakia. The following databases were searched for relevant trials: Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE. Handsearching was performed for the main oral medicine journals. References of included studies and reviews were checked. Oral medicine experts were contacted through an European mailing list (EURORALMED). Randomised controlled trials (RCTs), enrolling patients with a diagnosis of oral leukoplakia, were included. Any surgical or medical (topical and systemic) treatment was included. The primary outcome considered was malignant transformation of leukoplakia. Other outcomes considered were clinical resolution, histological modification and frequency of adverse effects. Data were collected using a specific extraction form. Malignant transformation of leukoplakia, demonstrated by histopathological examination, was the main outcome considered. Secondary outcomes included clinical resolution of the lesion and variation in dysplasia severity. The validity of included studies was assessed by two reviewers, on the basis of the method of allocation concealment, blindness of the study and loss of participants. Data were analysed by calculating relative risk. When valid and relevant data were collected, a meta-analysis of the data was undertaken. The possible effectiveness of surgical interventions, including laser therapy and cryotherapy, has never been studied by means of a RCT. Nineteen potentially eligible RCTs of non-surgical interventions were identified: eight were excluded for different reasons, four were ongoing studies, leaving seven studies to be included in the review. Two studies resulted at low risk of bias, four at moderate risk of bias and one at high risk of bias. Vitamin A and retinoids were tested by five RCTs (245 patients), the other drugs tested were bleomycin (one study), mixed tea (one study) and beta carotene (one study). Malignant transformation was recorded in just two studies: none of the treatments tested showed a benefit when compared with the placebo. Treatment with beta carotene and vitamin A or retinoids, was associated with significant rates of clinical resolution, compared with placebo or absence of treatment. Whenever reported, a high rate of relapse was a common finding. Side effects of variable severity were often described; however, interventions were well accepted by patients, since drop-out rates were similar between treatment and control groups. To date there is no evidence of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesion, however relapses and adverse effects are common.


Prevalence of Multiple Sclerosis in the Middle Black Sea Region of Turkey and Demographic Characteristics of Patients.
Multiple sclerosis (MS), a demyelinating disease of the central nervous system, is increasing in prevalence worldwide. Other than small-scale studies, there is a scarcity of data on the prevalence of MS in Turkey. The present study aimed to elucidate the prevalence of MS in the Middle Black Sea Region and the demographic characteristics of patients. Patients living in the Middle Black Sea Region and who were diagnosed with MS were included. The study was designed based hospital of Turkey. A total of 1,787 patients were interviewed, and a diagnosis of MS was confirmed in 1,584. The prevalence of MS was found to be 43.2/100,000 in the Middle Black Sea Region; this was calculated based on the total population and number of patients in the provinces and districts in this region. The mean age at the disease onset was 29.39±7.6 years. Among the patients, 1,299 (81.9%) had relapsing-remitting MS, 74 had secondary progressive MS, 77 had relapsing-progressive MS, 47 had primary progressive MS, and 87 had clinically isolated syndrome. The Middle Black Sea Region was found to have a high risk for the prevalence of MS. This study is the most comprehensive epidemiologic study having the largest geographical distribution on the prevalence of MS in Turkey.


Simultaneous Quantification of Multiple Representative Components in the Xian-Ling-Gu-Bao Capsule by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry.
Xian-Ling-Gu-Bao capsule (XLGB), a famous traditional Chinese medicine prescription, is extensively used for the treatment of osteoporosis in China. However, few studies on the holistic quality control of XLGB have been reported. In this study, a reliable method using 18 representative components in XLGB was successfully established and applied to evaluate 34 batches of XLGB samples by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). The choice of quantitative markers mostly followed four principles, i.e., absorbed components in plasma, bioactive compounds with in vitro anti-osteoporosis activity, those derived from multiple individual medicinal herbs in XLGB with multiple representative structure types, and quantitative chemical markers in the Chinese Pharmacopoeia. The results showed chemical consistency was good except for individual batches. Multivariate statistical analysis indicated that asperosaponin VI from Radix Dipsaci, epimedin C, magnoflorine, and icariin from Herba Epimedii as well as timosaponin BII from Rhizoma Anemarrhenae varied significantly in multiple samples, which hinted an assay for these four components should be completed during all of the manufacturing processes. Taken together, this study provided a feasible method for holistic quality control of XLGB by multiple chemical markers, which could play a vital role in guaranteeing the safety, effectiveness, and controllability of administering the capsules as a medication in clinics.


Clinical diagnosis of neck lumps: a practical guide.
The clinical presentation of a neck mass in a child is obviously not always pathognomonic but a careful clinical appraisal can certainly limit the diagnostic options and reduce the need for complex and sometimes invasive investigations.


Oral rehydration in infantile diarrhoea in the developed world.
Acute diarrhoea is an important health problem in developed countries, particularly in young children. The attack rates for viral diarrhoea are similar in developed and developing countries. Rotavirus is the most common pathogen, followed by adenovirus. Bacterial diarrhoea is less common in developed than developing countries. The 2 most common bacterial pathogens are Campylobacter jejuni and Salmonella. The most serious consequence of diarrhoea is dehydration, and the treatment for this is the same whatever the pathogen. Recently, there have been major changes in the management of diarrhoea with emphasis on oral rehydration and early feeding. Two controversial areas are the sodium content of solutions designed for developed countries and the best route of administration of fluids to children with moderately severe dehydration. There have been 4 randomised controlled trials in developed countries comparing oral and intravenous rehydration. The findings have confirmed the experience in developing countries that most children without shock can be rehydrated orally, thus substantially reducing the need for intravenous fluids. It is important to give physiologically balanced solutions which contain 2% glucose and 50 to 90 mmol/L of sodium. Many of the commercially available oral solutions are appropriate for rehydration and maintenance of hydration in infants with diarrhoea of all types. They are recommended particularly for the prevention of dehydration in children of all ages with severe diarrhoea and for the treatment of dehydration. Children with mild diarrhoea and no dehydration can be given commercial clear fluids diluted with water, or homemade solutions made with table sugar and water. Salt must not be used. Babies should continue on breast milk or formula with extra water. Education is the key to successful oral rehydration, and the ultimate aim should be the prevention of dehydration.


Immunohistochemical study of actin binding protein (p55) in the human kidney.
In clinical transplantation, "passenger" dendritic cells (DCs) in the allograft have been thought to induce allograft rejection. However, the presence of DCs in the normal human kidney is controversial. Most reports have relied on the examination of MHC class I and II antigen expression in combination with DC morphology for identification of DCs. The distribution of the p55 antigen (fascin), which is selectively expressed by human blood and lymphoid DCs, was investigated by immunohistochemistry. Our study demonstrates that p55-positive DCs are absent from the normal human kidney and CD1a- and S100-positive cells are absent or very rare. Furthermore, HLA-DR and factor VIII-related antigen show almost complete colocalization in capillaries. In contrast, all 16 kidney biopsies from patients with inflammatory processes demonstrated p55-positive DCs in the cellular infiltrates. These results suggest that DCs are not present or are very rare in normal renal tissues but may migrate into the renal interstitium with inflammatory changes.


Distinct Leishmania species infecting wild caviomorph rodents (Rodentia: Hystricognathi) from Brazil.
Caviomorph rodents, some of the oldest Leishmania spp. hosts, are widely dispersed in Brazil. Despite both experimental and field studies having suggested that these rodents are potential reservoirs of Leishmania parasites, not more than 88 specimens were analyzed in the few studies of natural infection. Our hypothesis was that caviomorph rodents are inserted in the transmission cycles of Leishmania in different regions, more so than is currently recognized. We investigated the Leishmania infection in spleen fragments of 373 caviomorph rodents from 20 different species collected in five Brazilian biomes in a period of 13 years. PCR reactions targeting kDNA of Leishmania sp. were used to diagnose infection, while Leishmania species identification was performed by DNA sequencing of the amplified products obtained in the HSP70 (234) targeting. Serology by IFAT was performed on the available serum of these rodents. In 13 caviomorph rodents, DNA sequencing analyses allowed the identification of 4 species of the subgenus L. (Viannia): L. shawi, L. guyanensis, L. naiffi, and L. braziliensis; and 1 species of the subgenus L. (Leishmania): L. infantum. These include the description of parasite species in areas not previously included in their known distribution: L. shawi in Thrichomys inermis from Northeastern Brazil and L. naiffi in T. fosteri from Western Brazil. From the four other positive rodents, two were positive for HSP70 (234) targeting but did not generate sequences that enabled the species identification, and another two were positive only in kDNA targeting. The infection rate demonstrated by the serology (51.3%) points out that the natural Leishmania infection in caviomorph rodents is much higher than that observed in the molecular diagnosis (4.6%), highlighting that, in terms of the host species responsible for maintaining Leishmania species in the wild, our current knowledge represents only the "tip of the iceberg."


The value of admission interviews in selecting accelerated second-degree baccalaureate nursing students.
Accelerated undergraduate nursing programs have attracted more qualified applicants than can be accommodated, yet higher-than-desired attrition rates continue for a variety of reasons (e.g., pace of program, poor lifestyle choices, role concerns). The financial effects of the loss of students from these programs has gone largely undocumented and is intensified by the knowledge that a better admission decision could have resulted in another nurse in the workforce. In this article, the inclusion of structured personal interviews into the admission decision-making process is discussed. Specifically, do interviews provide relevant data in making admission decisions? Attempts to reduce subjectivity through the development of a structured interview guide, the training of paired interview teams, and the institution of a "post-mortem" technique to guide revisions are also described. Interviews do result in denial of applicants who seem appropriate based on paper portfolio criteria, allowing for inclusion of other potentially successful applicants.


Aggregation of POSS monomers in liquid hexane: a molecular-simulation study.
Polyhedral oligomeric silsesquioxanes (POSS) are multifunctional molecules that can be employed as building blocks to develop nanocomposite materials whose mechanical properties often improve upon those of traditional polymeric materials. We report here molecular simulation results for the effective potential of mean force between octamethyl POSS monomers and between POSS monomers in which one methyl group has been substituted by a linear alkane chain of nine carbon atoms in liquid normal hexane at 300 and 400 K. The results are discussed and compared to available data for the effective interactions between octamethyl POSS monomers in normal hexadecane. Our results show that the effective short-ranged POSS-POSS attraction is significantly weaker in hexane than it is in hexadecane, perhaps explaining why normal hexane is often the solvent of choice for the preparation of POSS-containing materials. Additionally, we provide results for the radial distribution functions between selected sites in the POSS monomers that can be used both to understand the association between POSS monomers in solution and to parametrize coarse-grained simulation models. Such models will be used to study the formation of POSS-containing supramolecular structures such as lamellae or micelles that are currently not accessible by atomistic simulation and can be compared to experimental observations.


Shape Displays: Spatial Interaction with Dynamic Physical Form.
Shape displays are an emerging class of devices that emphasize actuation to enable rich physical interaction, complementing concepts in virtual and augmented reality. The ability to render form introduces new opportunities to touch, grasp, and manipulate dynamic physical content and tangible objects, in both nearby and remote environments. This article presents novel hardware, interaction techniques, and applications, which point to the potential for extending the ways that we traditionally interact with the physical world, empowered by digital computation.


Bendamustine: something old, something new.
Bendamustine (Treanda, Ribomustin) is a water-soluble, bifunctional chemotherapeutic agent that also has potential antimetabolite properties and only partial cross-resistance with other alkylators. Designed in 1963 and re-discovered in 1990s, this drug's unique mechanism of action and favorable side-effect profile promise a major role in the management of lymphoproliferative disorders. Bendamustine has been designated as an orphan drug in the United States, conferring prolonged market exclusivity. This article provides a comprehensive review of the data on efficacy and toxicity from trials investigating the use of bendamustine for the treatment of lymphoproliferative neoplasms. The pharmacology, pharmacokinetics, and pre-clinical studies with bendamustine are also reviewed. MEDLINE and Pubmed databases (1970-2010) were searched using the terms bendamustine, bendamustin, Treanda, Ribomustin, SDX-105, IMET-3393, and Cytostasan. All relevant articles were reviewed and references screened for additional articles. The databases of the American Society of Hematology (2004-2009) and the American Society of Clinical Oncology (1995-2009) were also searched for relevant abstracts. Bendamustine induces a remission in more than three-fourths of patients with rituximab-refractory indolent B cell non-Hodgkin lymphoma (NHL). Combined with rituximab in vitro, bendamustine shows synergistic effects against various leukemia and lymphoma cell lines. Clinical trials supporting these results show that bendamustine plus rituximab is highly effective in patients with relapsed-refractory indolent lymphoma, inducing remissions in 90% or more and a median progression-free survival of 23-24 months. Bendamustine has been reasonably well tolerated in clinical trials with low propensity to induce alopecia. Combination of bendamustine and rituximab has the potential to become a new standard first-line treatment option for patients with FL, MCL, and indolent lymphomas. Results of ongoing trials will help to further elucidate the optimal role of bendamustine in indolent NHL.


Norethisterone-Induced Liver Injury and a Short Survey Among Gynecologists.
Norethisterone, a commonly used oral contraceptive, and treatment for various gynecological disorders such as menorrhagia, abnormal uterine bleeding, and breast cancer, has been associated with multiple liver injuries. These injuries can manifest as hepatitis or cholestatic types of injury, benign neoplasms, peliosis hepatis, sinusoidal obstruction syndrome, and enlargement of existing hemangiomas. This report presents three cases in which liver enzyme levels were elevated due to norethisterone intake. Two of the cases were individuals undergoing evaluation as potential kidney donors in the nephrology department for their spouses, while the third case involved a patient with chronic kidney disease (CKD) stage-5 on maintenance hemodialysis. Regular follow-up of these patients, particularly due to the significance of two being kidney donors and one having advanced CKD, allowed for early detection of asymptomatic liver enzyme elevation and prompt discontinuation of norethisterone. Prescribing norethisterone is common in gynecological settings, including ours. To assess gynecologists' knowledge regarding norethisterone-related side effects, we conducted an online survey, the results of which are discussed in this report.


PDGF Promotes the Warburg Effect in Pulmonary Arterial Smooth Muscle Cells via Activation of the PI3K/AKT/mTOR/HIF-1α Signaling Pathway.
The enhanced proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a central pathological component in pulmonary arterial hypertension (PAH). Both the Warburg effect and platelet-derived growth factor (PDGF) are involved in the proliferation of PASMCs. However, the mechanism underlying the crosstalk between the Warburg effect and PDGF during PASMC proliferation is still unknown. We hypothesized that PDGF promotes the Warburg effect via activating the phosphatidylinositol 3-kinase (PI3K) signaling pathway and hypoxia-inducible factor 1-α (HIF-1α) in proliferative PASMCs. PASMCs were derived from pulmonary arteries of SD rats; cell viability, the presence of metabolites, and metabolic enzyme activities assay were determined by MTT assays, kit assays and western blot analysis, respectively. PDGF promoted PASMC proliferation in a dose- and time-dependent manner, accompanied by an enhanced Warburg effect. Treatment with PDGFR antagonists, Warburg effect inhibitor and PDK1 inhibitor significantly inhibited PI3K signaling activation, HIF-1α expression and PASMC proliferation induced by PDGF, respectively. Furthermore, treatment with PI3K signaling pathway inhibitors remarkably suppressed PDGF-induced PASMC proliferation and the Warburg effect. microplate reader (Biotek, Winooski The Warburg effect plays a critical role in PDGF-induced PASMC proliferation and is mediated by activation of the PI3K signaling pathway and HIF-1α.


Phosphorylation of initiation factor eIF2 in response to stress conditions is mediated by acidic ribosomal P1/P2 proteins in Saccharomyces cerevisiae.
Eukaryotic cells contain an unusually large cytoplasmic pool of P1/P2 phosphoproteins, which form the highly flexible 60S subunit stalk that is required to interact with and activate soluble translation factors. In cells, cytoplasmic P1/P2 proteins are exchanged for ribosome-bound proteins in a process that can modulate ribosome function and translation. Here, we analysed different S. cerevisiae stalk mutants grown under stress conditions that result in eIF2α phosphorylation. These mutants either lack a cytoplasmic pool of stalk proteins or contain free but not ribosome-bound proteins. Only cells that contain free P1/P2 proteins induce eIF2 phosphorylation in vivo in response to glucose starvation or osmotic stress. Moreover, we show that free S. cerevisiae P1/P2 proteins can induce in vitro phosphorylation of the initiation factor eIF2 by stimulating the autophosphorylation and activation of GCN2 kinase. Indeed, these ribosomal proteins do not stimulate other eIF2α kinases, such as PKR and HRI. P1/P2 and the known GCN2 activator deacylated tRNA compete for stimulating the eIF2α kinase activity of GCN2, although the P1/P2 proteins are considerably more active. These findings reveal a capacity of free cytoplasmic ribosomal stalk components to stimulate eIF2α phosphorylation, which in turn would modulate translation in response to specific forms of stress that may be linked with the previously described regulatory function of the ribosomal stalk.


Anxiety disorders in African Americans: an update.
This article discusses issues involved in the diagnosis of anxiety disorders, particularly panic disorder, in African Americans. Although epidemiological studies have shown similar prevalence rates of anxiety disorders among African Americans and non-African Americans, African Americans are underrepresented among those in treatment at mental health settings or serving as clinical research subjects. In addition, few studies have researched the unique demographic, diagnostic, and treatment characteristics of African-American patients with anxiety disorders. Most clinicians therefore are not educated to consider these issues in adapting their treatment approach to affect a more successful treatment outcome for African-American patients with anxiety-disorder. This article identifies and addresses relevant cross-cultural issues.


Synthesis of unstable carbides Ag2C(2n) (n = 3, 4) and characterization via crystallographic analysis of their double salts with silver(I) trifluoroacetate.
Two new silver(I) carbides, Ag2C6 and Ag2C8, have been synthesized, and single-crystal X-ray analysis of their crystalline silver(I) trifluoroacetate complexes, Ag2C6·8AgCF3CO2·6H2O, 4(Ag2C6)·16AgCF3CO2·14.5DMSO, and 2.5(Ag2C8)·10AgCF3CO2·10DMSO, provides detailed information on the influence of ligand disposition and orientation of the all-carbon anionic ligands in the construction of multidimensional supramolecular structures, which are consolidated by argentophilic and weak inter-/intramolecular interactions.


A new method for correlation analysis of compositional (environmental) data - a worked example.
Most data in environmental sciences and geochemistry are compositional. Already the unit used to report the data (e.g., μg/l, mg/kg, wt%) implies that the analytical results for each element are not free to vary independently of the other measured variables. This is often neglected in statistical analysis, where a simple log-transformation of the single variables is insufficient to put the data into an acceptable geometry. This is also important for bivariate data analysis and for correlation analysis, for which the data need to be appropriately log-ratio transformed. A new approach based on the isometric log-ratio (ilr) transformation, leading to so-called symmetric coordinates, is presented here. Summarizing the correlations in a heat-map gives a powerful tool for bivariate data analysis. Here an application of the new method using a data set from a regional geochemical mapping project based on soil O and C horizon samples is demonstrated. Differences to 'classical' correlation analysis based on log-transformed data are highlighted. The fact that some expected strong positive correlations appear and remain unchanged even following a log-ratio transformation has probably led to the misconception that the special nature of compositional data can be ignored when working with trace elements. The example dataset is employed to demonstrate that using 'classical' correlation analysis and plotting XY diagrams, scatterplots, based on the original or simply log-transformed data can easily lead to severe misinterpretations of the relationships between elements.


Interplay between motility and cell-substratum adhesion in amoeboid cells.
The effective migration of amoeboid cells requires a fine regulation of cell-substratum adhesion. These entwined processes have been shown to be regulated by a host of biophysical and biochemical cues. Here, we reveal the pivotal role played by calcium-based mechanosensation in the active regulation of adhesion resulting in a high migratory adaptability. Using mechanotactically driven Dictyostelium discoideum amoebae, we uncover the existence of optimal mechanosensitive conditions-corresponding to specific levels of extracellular calcium-for persistent directional migration over physicochemically different substrates. When these optimal mechanosensitive conditions are met, noticeable enhancement in cell migration directionality and speed is achieved, yet with significant differences among the different substrates. In the same narrow range of calcium concentrations that yields optimal cellular mechanosensory activity, we uncovered an absolute minimum in cell-substratum adhesion activity, for all considered substrates, with differences in adhesion strength among them amplified. The blocking of the mechanosensitive ion channels with gadolinium-i.e., the inhibition of the primary mechanosensory apparatus-hampers the active reduction in substrate adhesion, thereby leading to the same undifferentiated and drastically reduced directed migratory response. The adaptive behavioral responses of Dictyostelium cells sensitive to substrates with varying physicochemical properties suggest the possibility of novel surface analyses based on the mechanobiological ability of mechanosensitive and guidable cells to probe substrates at the nanometer-to-micrometer level.


Antithrombin III in oral contraceptive users and during normotensive pregnancy.
Plasma antithrombin III (AT III) was determined in four groups of subjects, by employing an automated chromogenic technique. In 25 women, discontinuing oral contraceptives led to a 9% elevation of AT III, while in 13 women AT III levels fell by 9% after starting with the pill. In 77 normotensive pregnant patients AT III levels were normal during the third trimester and did not differ from control values 6-8 weeks after delivery. Women taking the pill at that time did not have lower AT III levels than those who did not. Furthermore, AT III levels in 414 oral contraceptive users were the same as in 572 controls, when random samples were taken during pill cycle and menstrual cycle. It is concluded that although synthetic estrogens do cause a decrease in AT III levels, this decrease is probably the result of estrogen-induced hemodilution, which may also occur during the normal menstrual cycle. If low dose pills are thrombogenic, mass screening for AT III deficiency will not identify those at risk, with the exception of the rare cases of hereditary AT III deficiency.


Inuit interpreters engaged in end-of-life care in Nunavik, Northern Quebec.
Inuit interpreters are key players in end-of-life (EOL) care for Nunavik patients and families. This emotionally intensive work requires expertise in French, English and Inuit dialects to negotiate linguistic and cultural challenges. Cultural differences among medical institutions and Inuit communities can lead to value conflicts and moral dilemmas as interpreters navigate how best to transmit messages of care at EOL. Our goal was to understand the experience of Inuit interpreters in the context of EOL care in Nunavik in order to identify training needs. In the context of a larger ethnographic project on EOL care in Nunavik, we met with 24 current and former interpreters from local health centres and Montreal tertiary care contexts. Data included informal and formal interviews focusing on linguistic resources, experiences concerning EOL care, and suggestions for the development of interpretation training. Inuit working as interpreters in Nunavik are hired to provide multiple services of which interpretation plays only a part. Many have no formal training and have few resources (e.g. visual aids, dictionaries) to draw upon during medical consultations. Given the small size of communities, many interpreters personally know their clients and often feel overwhelmed by moral dilemmas when translating EOL information for patients and families. The concept of moral distress is a helpful lens to make sense of their experience, including personal and professional repercussions. Inuit interpreters in Nunavik are working with little training yet in context with multiple linguistic and cultural challenges. Linguistic and cultural resources and focused training on moral dilemmas unique to circumpolar contexts could contribute to improved work conditions and ultimately to patient care..


CD38 as a PET Imaging Target in Lung Cancer.
Daratumumab (Darzalex, Janssen Biotech) is a clinically approved antibody targeting CD38 for the treatment of multiple myeloma. However, CD38 is also expressed by other cancer cell types, including lung cancer, where its expression or absence may offer prognostic value. We therefore developed a PET tracer based upon daratumumab for tracking CD38 expression, utilizing murine models of non-small cell lung cancer to verify its specificity. Daratumumab was prepared for radiolabeling with 89Zr (t1/2 = 78.4 h) through conjugation with desferrioxamine (Df). Western blot, flow cytometry, and saturation binding assays were utilized to characterize CD38 expression and binding of daratumumab to three non-small cell lung cancer cell lines: A549, H460, and H358. Murine xenograft models of the cell lines were also generated for further in vivo studies. Longitudinal PET imaging was performed following injection of 89Zr-Df-daratumumab out to 120 h postinjection, and nonspecific uptake was also evaluated through the injection of a radiolabeled control IgG antibody in A549 mice, 89Zr-Df-IgG. Ex vivo biodistribution and histological analyses were also performed after the terminal imaging time point at 120 h postinjection. Through cellular studies, A549 cells were found to express higher levels of CD38 than the H460 or H358 cell lines. PET imaging and ex vivo biodistribution studies verified in vitro trends, with A549 tumor uptake peaking at 8.1 ± 1.2%ID/g at 120 h postinjection according to PET analysis, and H460 and H358 at lower levels at the same time point (6.7 ± 0.7%ID/g and 5.1 ± 0.4%ID/g, respectively; n = 3 or 4). Injection of a nonspecific radiolabeled IgG into A549 tumor-bearing mice also demonstrated lower tracer uptake of 4.4 ± 1.3%ID/g at 120 h. Immunofluorescent staining of tumor tissues showed higher staining levels present in A549 tissues over H460 and H358. Thus, 89Zr-Df-daratumumab is able to image CD38-expressing tissues in vivo using PET, as verified through the exploration of non-small cell lung cancer models in this study. This agent therefore holds potential to image CD38 in other malignancies and aid in patient stratification and elucidation of the biodistribution of CD38.


Sugarcane Smut, Caused by Sporisorium scitamineum, a Major Disease of Sugarcane: A Contemporary Review.
Sugarcane smut caused by the fungus Sporisorium scitamineum is one of the major diseases of sugarcane worldwide, causing significant losses in productivity and profitability of this perennial crop. Teliospores of this fungus are airborne, can travel long distances, and remain viable in hot and dry conditions for >6 months. The disease is easily recognized by its long whiplike sorus produced on the apex or side shoots of sugarcane stalks. Each sorus can release ≤100 million teliospores in a day; the spores are small (≤7.5 µ) and light and can survive in harsh environmental conditions. The airborne teliospores are the primary mode of smut spread around the world and across cane-growing regions. The most effective method of managing this disease is via resistant varieties. Because of the complex genomic makeup of sugarcane, selection for resistant traits is difficult in sugarcane breeding programs. In recent times, the application of molecular markers as a rapid tool of discarding susceptible genotypes early in the selection program has been investigated. Large effect resistance loci have been identified and have the potential to be used for marker-assisted selection to increase the frequency of resistant breeding lines in breeding programs. Recent developments in omics technologies (genomics, transcriptomics, proteomics, and metabolomics) have contributed to our understanding and provided insights into the mechanism of resistance and susceptibility. This knowledge will further our understanding of smut and its interactions with sugarcane genotypes and aid in the development of durable resistant varieties.


Movable multi-probes for plasma boundary measurement in Sino-UNIted Spherical Tokamak.
A novel movable multi-probes is developed to get local magnetic and electrostatic profiles on Sino-UNIted Spherical Tokamak (SUNIST). This multi-probes combines a four-tips Langmuir probe, a magnetic coil, and a retarding field energy analyzer (RFEA). It can be used to simultaneously measure the poloidal magnetic field Bp, electric field Er, electron temperature Te, electron density ne, and ion temperature Ti. Its small overall size (20 × 20 × 38 mm(3)) enables the movable multi-probes to measure the magnetic and electrostatic profiles in high spatial resolution, with negligible impact to plasma in SUNIST. This paper presents the design of the movable multi-probes, in particular, details of RFEA for reliable ion energy measurements. Preliminary experimental results of the movable multi-probes are given as well.


Polyneuropathy in Sjögren's syndrome. A case of prevalently autonomic neuropathy with tonic pupil and hypohidrosis.
A 38-year-old woman suffering from primary Sjögren's syndrome displayed a neurologic picture consisting of left tonic pupil, generalized tendon areflexia and left-sided hypohidrosis. Electrophysiological and pathological studies suggested a mild degree of peripheral nerve involvement. Moderate loss of large myelinated fibres and obliteration of small endoneurial vessels were seen in the sural nerve biopsy. Sympathetic skin response was absent and alterations of unmyelinated nerve fibres were found. A prevalently autonomic neuropathy with tonic pupils may represent a characteristic picture in the spectrum of peripheral nerve involvement in Sjögren's syndrome. Other similar cases reported in the literature are reviewed.


Live imaging of root hairs.
Root hairs are single cells specialized in the absorption of water and nutrients. Growing root hairs requires intensive cell wall changes to accommodate cell expansion at the apical end by a process known as tip growth. The cell wall of plants is a very rigid structure comprised largely of polysaccharides and hydroxyproline-rich O-glycoproteins. The importance of root hairs stems from their capacity to expand the surface of interaction between the root and the environment, in search for the necessary nutrients and water to allow plant growth. Therefore, it becomes crucial to deepen our knowledge of them, particularly in the light of the applicability in agriculture by allowing the expansion of croplands. Root hair growth is an extremely fast process, reaching growth rates of up to 1 μm/min and it also is a dynamic process; there can be situations in which the final length might not be affected but the growth rate is. Consequently, in this chapter we focus on a method for studying growth dynamics and rates during a time course. This method is versatile allowing for it to be used in other plant organs such as lateral root, hypocotyl, etc., and also in various conditions.


Adolescent depression screening in primary care: feasibility and acceptability.
Despite available depression treatments, only one fourth to one third of depressed adolescents are receiving care. The problem of underdiagnosis and underreferral might be redressed if assessment of suicidality and depression became a more formal part of routine pediatric care. Our purpose for this study was to explore the feasibility and acceptability of implementing adolescent depression screening into clinical practice. In this study we implemented a 2-stage adolescent identification protocol, a first-stage pen-and-paper screen and a second-stage computerized assessment, into a busy primary care pediatric practice. Providers tracked the number of eligible patients screened at both health maintenance and urgent care visits and provided survey responses regarding the burden that screening placed on the practice and the effect on patient/parent-provider relationships. Seventy-nine percent of adolescent patients presenting for health maintenance visits were screened, as were the majority of patients presenting for any type of visit. The average completion time for the paper screen was 4.6 minutes. Providers perceived parents and patients as expressing more satisfaction than dissatisfaction with the screening procedures and that the increased time burden could be handled. All providers wished to continue using the paper screen at the conclusion of the protocol. Instituting universal systematic depression screening in a practice with a standardized screening instrument met with little resistance by patients and parents and was well perceived and accepted by providers.


Normative data for the lower extremity functional scale (LEFS).
Background and purpose - The lower extremity functional scale (LEFS) is a well-known and validated instrument for measurement of lower extremity function. The LEFS was developed in a group of patients with various musculoskeletal disorders, and no reference data for the healthy population are available. Here we provide normative data for the LEFS. Methods - Healthy visitors and staff at 4 hospitals were requested to participate. A minimum of 250 volunteers had to be included at each hospital. Participants were excluded if they had undergone lower extremity surgery within 1 year of filling out the questionnaire, or were scheduled for lower extremity surgery. Normative values for the LEFS for the population as a whole were calculated. Furthermore, the influence of sex, age, type of employment, socioeconomic status, and history of lower extremity surgery on the LEFS were investigated. Results - 1,014 individuals fulfilled the inclusion criteria and were included in the study. The median score for the LEFS for the whole population was 77 (out of a maximum of 80). Men and women had similar median scores (78 and 76, respectively), and younger individuals had better scores. Participants who were unfit for work had worse scores. There were no statistically significant correlations between socioeconomic status and type of employment on the one hand and LEFS score on the other. A history of lower extremity surgery was associated with a lower LEFS score. Interpretation - High scores were observed for the LEFS throughout the whole population, although they did decrease with age. Men had a slightly higher score than women. There was no statistically significant correlation between socioeconomic status and LEFS score, but people who were unfit for work had a significantly worse LEFS score.


A meta-analysis of home visiting programs: Moderators of improvements in maternal behavior.
A meta-analysis of home visiting programs for at-risk families (K = 35, N = 6,453) examined differences in the effects of programs on maternal behavior. On average, programs with more frequent visitation had higher success rates. The frequency of home visits explained significant variance of effect sizes among studies in the United States, with two visits per month predicting a small, substantive effect. Intensive programs or programs with at least three visits per month were more than twice as effective as were less intensive programs. Home visiting programs using nurses or mental health professionals as providers were not significantly more effective than were programs using paraprofessionals. In general, programs showed a positive effect on maternal behavior, but programs with frequent home visits were more successful.


Efficacy of contact lens systems against recent clinical and tap water Acanthamoeba isolates.
A recent increase in Acanthamoeba keratitis (AK) cases has been associated with Complete MoisturePlus, although many cases used other solutions. Complete MoisturePlus contains taurine and hydroxypropyl methylcellulose, unlike other multipurpose solutions (MPSs). The purpose of this study is to (1) determine contact lens solution efficacy against recent clinical and tap water Acanthamoeba isolates and (2) determine whether taurine inclusion increases Acanthamoeba survival against contact lens solutions. Acanthamoeba T4 trophozoites from recent AK clinical and tap water isolates were placed on multiple concentrations of taurine-saline agar for 72 hours with Enterobacter aerogenes as prey. Amoebae were exposed for 6 and 24 hours to hydrogen peroxide solutions and MPSs (ReNu Multiplus, Complete MoisturePlus, AMO Trade Name, Opti-free Express, Clear Care, and UltraCare) and tested for survival. Plates were examined over the following week for growth. Strain type and solution affected survival. MPSs were ineffective, with 100% survival of all strains at 6-hour exposure. Hydrogen peroxide systems were more effective, with survival of 3/5 strains (Clear Care) and 1/5 strains (UltraCare) at 6 hours. The Chicago-area tap water strain was most resistant. Among hydrogen peroxide systems, no statistically significant difference in Acanthamoeba survival existed with taurine inclusion. Recent clinical and tap water Acanthamoeba strains, representing proven human pathogens and/or household strains, were highly virulent against contact lens solutions. The Chicago-area tap water strain was most resilient, a concern if tap water is contributing to the AK increase. Results further differentiated resistance among T4 strains, highlighting the importance of multiple strain testing.


Clinical response and prolactin concentration in hyperprolactinemic women during and after treatment for 24 months with the new dopamine agonist, CV 205-502.
Twenty-four hyperprolactinemic women of whom 23 previously had been given bromocriptine, were treated between 6 and 24 months with a new non-ergot dopamine agonist, CV 205-502 (quinagolide; Norprolac, Sandoz Ltd, Basle Switzerland). Twenty-four weeks of treatment resulted in normalization of prolactin secretion in 16 of the 24 women. All of these women as well as 4 of those who remained hyperprolactinemic had regular menstrual bleedings. Fifteen of the 24 women were treated for 24 months and all had normalized prolactin levels in serum at the end of this period. Regular menstrual bleedings were observed in 13 women. Mild to moderate galactorrhea was recorded at baseline in 14 of the 15 women. After 24 months of treatment, mild galactorrhea was still present in 3 women. All 15 women had been treated with bromocriptine or other dopamine agonists before they entered the study. In 9 of the women the tolerability had been judged to be fair (N = 4) or poor (N = 5). Five of the 15 women had previously discontinued bromocriptine treatment because of adverse effects but had few problems tolerating CV 205-502. Prolactin in serum increased in all the patients after discontinuation of the medication. The results confirm that CV 205-502 seems to be a valuable compound in the management of patients with hyperprolactinemia.


Production of an interferon-gamma homologue by an intestinal nematode: functionally significant or interesting artefact?
Chronic infection is a prominent feature of many intestinal nematode infections in man and animals. It is also clear that in such situations host immunity is activated but is unable to induce a protective response. A great deal of work has shown that genetic control of host immunity contributes to the variation in worm burdens often observed in the field. There is increasing appreciation, however, of the capability of infectious agents themselves to modulate the host immune response and potentiate their own survival. Using an immunologically well defined model of intestinal nematode infection in mice (Trichuris muris) we have shown that parasite derived molecules share cross reactive epitopes with the host cytokine interferon-gamma using cytokine specific monoclonal antibodies in ELISA, Western blotting and immunoprecipitation assays. Furthermore, the parasite molecules can be shown to bind to the interferon-gamma receptor and induce change in lymphoid cells similar to those induced by murine interferon-gamma. The functional activity of the molecule in vivo remains to be determined. Previous studies have established that interferon-gamma is critical for progression to chronic T. muris infection in mice and, therefore, it raises the distinct possibility that the production of an interferon-gamma homologue by the worm may be one mechanism whereby the parasite is able to interfere with the regulation of the host immune response and potentiate its own survival.


Temple syndrome and Kagami-Ogata syndrome: clinical presentations, genotypes, models and mechanisms.
Temple syndrome (TS) and Kagami-Ogata syndrome (KOS) are imprinting disorders caused by absence or overexpression of genes within a single imprinted cluster on human chromosome 14q32. TS most frequently arises from maternal UPD14 or epimutations/deletions on the paternal chromosome, whereas KOS most frequently arises from paternal UPD14 or epimutations/deletions on the maternal chromosome. In this review, we describe the clinical symptoms and genetic/epigenetic features of this imprinted region. The locus encompasses paternally expressed protein-coding genes (DLK1, RTL1 and DIO3) and maternally expressed lncRNAs (MEG3/GTL2, RTL1as and MEG8), as well as numerous miRNAs and snoRNAs. Control of expression is complex, with three differentially methylated regions regulating germline, placental and tissue-specific transcription. The strong conserved synteny between mouse chromosome 12aF1 and human chromosome 14q32 has enabled the use of mouse models to elucidate imprinting mechanisms and decipher the contribution of genes to the symptoms of TS and KOS. In this review, we describe relevant mouse models and highlight their value to better inform treatment options for long-term management of TS and KOS patients.


Neuroprotective effects of a combination of Boswellia papyrifera and Syzygium aromaticum on AlCl3 induced Alzheimer's disease in male albino rat.
Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by hippocampal, and cortical neuron deterioration, oxidative stress, and severe cognitive dysfunction. Aluminum is a neurotoxin inducer for cognitive impairments associated with AD. The treatment approaches for AD are unsatisfactory. Boswellia papyrifera and Syzygium aromaticum are known for their pharmacological assets, including antioxidant activity. Therefore, the current study explored the possible mitigating effects of a combination of Boswellia papyrifera and Syzygium aromaticum against aluminum chloride (AlCl3) induced AD. The AD model was established using AlCl3 (100 mg/kg), and the rats were orally administrated with Boswellia papyrifera or Syzygium aromaticum or a combination of them daily for 8 weeks. The Y-maze test was used to test cognition in the rats, while acetylcholinesterase (AChE) and oxidative stress markers were estimated in homogenates of the cerebral cortex and hippocampus. Also, the histopathological examination of the cortex and hippocampus were investigated. The results revealed that administration of either B. papyrifera or S. aromaticum extracts significantly improved the cognitive functions of AD rats, enhanced AChE levels, increased oxidative enzymes levels, including SOD and GSH, and reduced MDA levels in homogenates of the cerebral cortex and hippocampus and confirmed by improvement in histological examination. However, using a combination therapy gave better results compared to a single treatment. In conclusion, the present study provided primary evidence for using a combination of B. papyrifera and S. aromaticum to treat cognitive dysfunction associated with AlCl3 Induced AD by improving the AChE levels and modulating oxidative stress in the brain.