Variation in genes encoding for interferon λ-3 and λ-4 in the prediction of HCV-1 treatment-induced viral clearance.
In patients with chronic HCV-1 infection, recent evidences indicate that determination of a dinucleotide polymorphism (ss469415590, ΔG/TT) of a new gene, designated IFN λ-4, might be more accurate than the 12979860CC type of the IL28B locus in predicting sustained virological response (SVR) following peg-interferon and ribavirin. In addition, combined genotyping of different SNPs of the IL28B locus was shown to help dissect patients most prone to SVR among those with rs12979860CT. We examined whether single or combined genotyping of two IL28B SNPs, rs12979860 and rs8099917, and ss469415590 variation might improve the prediction of SVR. In the study cohort of 539 patients, 38% had SVR. The SNPs 12979860CC, rs8099917TT, and rs469415590TT/TT correlated significantly with SVR (68%, 50%, and 67%). Carriers of either the triplotype rs12979860CC_ss469415590TT/TT_rs8099917TT or the diplotype rs12979860CC_ss469415590TT/TT had the highest SVR rate (72%). In carriers of the rs12979860 T allele, neither the rs8099917 nor the ss469415590 improved the response prediction. After pooling this finding with data from previous studies, in rs12979860 T heterozygous individuals the co-presence of the rs8099917TT SNP was associated with improved response prediction. In HCV-1 patients, the rs12979860 polymorphism appeared as the hit SNP better predicting response following peg-interferon and ribavirin treatment. Additional ss469415590 or rs8099917 genotyping had no added benefit for response prediction. In the subset of carriers of the rs12979860 T allele, genotyping of the rs8099917 SNP was unhelpful in the present investigation, but may inform clinical prediction of treatment response when our data were pooled with previous investigations.


Sustained release choline theophyllinate in nocturnal asthma.
Nocturnal wheeze is common in patients with asthma, and slow release theophyllines may reduce symptoms. As theophyllines are stimulants of the central nervous system the effect of 10 days' twice daily treatment with sustained release choline theophyllinate or placebo on symptoms, overnight bronchoconstriction, nocturnal oxygen saturation, and quality of sleep were studied in a double blind crossover study in nine stable patients with nocturnal asthma (five men, four women, age range 23-64 years; forced expiratory volume in one second (FEV1) 0.85-3.8 1; vital capacity 1.95-6.1 1). When treated with the active drug all patients had plasma theophylline concentrations of at least 28 mmol/l (5 micrograms/ml) (peak plasma theophylline concentrations 50-144 mmol/l (9-26 micrograms/ml]. Morning FEV1 was higher when treated with sustained release choline theophyllinate (2.7 (SEM 0.3) 1) than placebo (2.1 (0.3) 1) (p less than 0.01). Both daytime and nocturnal symptoms were reduced when the patients were treated with sustained release choline theophyllinate and subjective quality of sleep was improved (p less than 0.002). When treated with the active drug, however, quality of sleep determined by electroencephalography deteriorated with an increase in wakefulness and drowsiness (p less than 0.05) and a reduction in non-rapid eye movement sleep (p less than 0.005). Treatment with choline theophyllinate had no effect on either the occurrence or the severity of transient nocturnal hypoxaemic episodes or apnoeas or hypopnoeas. In conclusion, sustained release choline theophyllinate prevents overnight bronchoconstriction, but impairs quality of sleep defined by electroencephalography.


Severe acute pancreatitis as a part of multiple dysfunction syndrome.
Acute pancreatitis is a disease with various degrees of clinical manifestations. Mild and moderate severe acute pancreatitis is an illness characterized with chemical inflammation which, in general, passes without major complications. Clinical picture of severe acute pancreatitis other side is commonly complicated with functional deterioration of other organs, and frequently has characteristics of multiple organ dysfunction or failure syndrome with or without bacterial super infection. We studied 82 patients admitted to the intensive care unit with severe acute pancreatitis, 14 died. The mortality was in statistically significant correlation with the severity of clinical condition at admission assessed by APACHE II score, and higher Ranson's and Glasgow criteria by admission. Adequate volume supplementation, on time, as well as percutaneous drainage of infected pancreas collection reduces a risk of pure outcome.


Dynamic distribution of artificial tears on the ocular surface.
To study the effects of artificial tear viscosity on tear film thickness, upper and lower tear menisci, and tear volume using optical coherence tomography. The central tear film and tear menisci before and immediately after the instillation of different artificial tears were imaged in 40 eyes of 20 healthy individuals. Carboxymethylcellulose sodium, 1.0% (viscosity, 70 cP), propylene glycol, 0.3%, and polyethylene glycol, 0.4% (10 cP), carboxymethylcellulose, 0.5% (3 cP), and isotonic sodium chloride solution (1 cP) were tested on 2 consecutive days. All measurements, including tear film thickness, the height, radius, and area of the tear meniscus, and the estimated tear volume, were obtained at 0, 5, 20, 40, and 60 minutes after instillation. At instillation, all artificial tears and isotonic sodium chloride solution caused an increase in all tear variables (P < .001). Tear film thickness remained significantly elevated for all drops at 5 minutes (P < .001) and returned to baseline at 20 minutes. Other variables returned to baseline at 5 minutes. Comparing the different drops, tear film thickness and lower meniscus variables at instillation were increased with the more viscous drops (P < .05). Optical coherence tomography demonstrated that all tear preparations, including isotonic sodium chloride solution, increased tear film thickness for at least 5 minutes and other variables immediately after instillation.


Temperature-related emergency injury visits in Hanoi, Vietnam.
The short-term association between increasing temperatures and injury has been described in high-income countries, but less is known for low-income and-middle-income countries, including Vietnam. We used emergency injury visits (EIV) data for 2017-2019 from 733 hospitals and clinics in Hanoi, Vietnam to examine the effects of daily temperature on EIV. Time-series analysis with quasi-Poisson models was used to estimate a linear relative risk increase (RRI) for overall populations and ones stratified by age and sex. Exposure-response curves estimated non-linear associations as an RR between daily temperature and injury. Models were adjusted for the day of week, holidays, daily relative humidity, daily particulate matter, and long-term and seasonal trends. A total of 39 313 EIV were recorded averaging 36 injuries daily. Injuries more likely occurred in males and those aged 15-44, and aged 44-60. For linear effects, a 5°C increase in same day mean temperature was associated with an overall increased EIV (RRI 4.8; 95% CI 2.3 to 7.3) with males (RRI 5.9; 95% CI 3.0 to 8.9) experiencing a greater effect than females (RRI 3.0; 95% CI -0.5 to 6.5). Non-linear effects showed an increase in EIV at higher temperatures compared with the threshold temperature of 15°C, with the greatest effect at 33°C (RR 1.3; 95% CI 1.2 to 1.6). Further research to investigate temperature-injury among different populations and by the cause of injury is warranted.


Evaluation of outcome associated with subcutaneous and intramuscular hemangiosarcoma treated with adjuvant doxorubicin in dogs: 21 cases (2001-2006).
To evaluate outcome associated with subcutaneous and intramuscular hemangiosarcomas treated with adjuvant doxorubicin in dogs. Retrospective case series. 21 dogs. Records of dogs with histologically confirmed hemangiosarcoma, no detectable metastasis at initial evaluation, and adequate local tumor control were included. Age, sex, number of treatments, treatment interval, radiation therapy, and concurrent use of cyclophosphamide or deracoxib were evaluated for associations with disease-free interval (DFI) or survival time. Three to 6 cycles of doxorubicin were planned. Disease-free interval was defined as time of definitive surgery to time of local recurrence, metastasis, or both. Survival time was defined as the beginning of the DFI to time of death. 17 tumors were subcutaneous, and 4 were intramuscular. Median age was 9 years. Median weight was 31.1 kg (68.4 lb). Five dogs received adjuvant radiation therapy. Median DFI for subcutaneous tumors was 1,553 days (95% confidence interval [CI], 469 days to not estimable). Median DFI for intramuscular tumors was 265.5 days (95% CI, 123 to 301 days). Median survival time for subcutaneous tumors was 1,189 days (95% CI, 596 days to not estimable). Median survival time for intramuscular tumors was 272.5 days (95% CI, 123 to 355 days). For dogs with subcutaneous tumors, younger age (< 9 years) was associated with longer DFI and survival time. Dogs with subcutaneous tumors that did not receive radiation therapy had longer DFI. Dogs with subcutaneous hemangiosarcoma had a more favorable outcome, compared with dogs with intramuscular hemangiosarcoma, when treated with adequate local control and adjuvant doxorubicin.


Circulating growth hormone binding protein levels and mononuclear cell growth hormone receptor expression in uremia.
Resistance to growth hormone (GH) in end-stage renal disease (ESRD) causes growth retardation and muscle wasting. In humans, circulating GH binding protein (GHBP), the extracellular domain of the GH receptor that is shed into the circulation and is believed to reflect tissue GH receptor levels, is reduced in uremia and suggests that cellular GH receptor levels are correspondingly reduced. If true, this could be a cause of GH resistance. We set out to establish whether serum GHBP levels reflect cellular GH receptor levels and whether changes in serum GHBP levels are related to nutritional or inflammatory status. GH receptor protein expression in peripheral blood mononuclear cells (PBMC) from 21 ESRD and 14 normal subjects were analyzed by fluorochrome flow cytometry. The GH receptor density and percent total PBMCs expressing the GH receptor were similar in the 2 groups, and there was no difference in percent GH receptor positive T or B cells or monocytes. In contrast, serum GHBP levels were 80% lower in ESRD. GHBP levels did not correlate with serum albumin, body mass index, or muscle mass but seemed to be partly related to the log serum C-reactive protein levels. Serum GHBP levels are markedly reduced in ESRD; this seems to occur independent of nutritional status and may in part be caused by inflammation. Because GH receptor expression on PBMC of ESRD and control subjects was similar, our findings argue against a reduction in GH receptor as a cause of GH resistance and the use of serum GHBP levels as a reliable marker of specific tissue GH receptor levels.


Strong saturation absorption imaging of dense clouds of ultracold atoms.
We report on a far above saturation absorption imaging technique to investigate the characteristics of dense packets of ultracold atoms. The transparency of the cloud is controlled by the incident light intensity as a result of the nonlinear response of the atoms to the probe beam. We detail our experimental procedure to calibrate the imaging system for reliable quantitative measurements and demonstrate the use of this technique to extract the profile and its spatial extent of an optically thick atomic cloud.


On-site toluidine blue staining and screening improves efficiency of fine-needle aspiration cytology reporting.
We investigated the role of on-site toluidine blue staining and screening in fine-needle aspiration cytology (FNAC) reporting for patients with thyroid nodules, palpable breast lumps and palpable lymph nodes. A total of 200 consecutive patients with a palpable lymph node or a lump in the breast or thyroid referred to the outpatient department for FNAC were included in this study. We used toluidine blue to stain FNAC slides for the evaluation of smear adequacy. The toluidine blue-stained slides were compared with the same slides after being decolorised and Papanacolaou (PAP)-stained. Out of 200 cases, 28 (14%) were deemed unsatisfactory on the first attempt as assessed by rapid staining. These included 16 (38%) of 42 thyroid cases, 10 (10.4%) of 96 breast lump cases and 2 (3.2%) of 62 lymph node cases. A repeat FNAC in the same sitting on these 28 patients showed adequate material in 24 (12%) of them. Therefore, for 98%, a decision could be made at the very first visit to plan further management. We concluded that toluidine blue offers excellent cytological details for the preliminary identification of the lesion and to decide on the adequacy of the material for definitive diagnosis on FNAC slides.


Regular exercise alleviates renovascular hypertension-induced cardiac/endothelial dysfunction and oxidative injury in rats.
The importance of physical activity in the management of renovascular diseases is well-known, but lacks evidence of underlying mechanisms. The purpose of the study was to elucidate the protective/therapeutic effects of regular exercise on experimental renovascular hypertension (RVH)-induced oxidative stress and cardiac dysfunction. Wistar albino rats underwent a RVH surgery (2K1C, Goldblatt). Three weeks later half of the rats started swimming exercise for 9 weeks (n = 15), while the sedentary RVH group (n = 15) had no exercise during that period. Sham-operated control rats (n = 10), had the similar surgical procedures but the left renal artery was left unclipped. Body weights were monitored, and blood pressures were measured weekly using tail-cuff. Echocardiographic evaluation was performed on the 3(rd) week and on the 12(th) week of the experiment before the rats were decapitated. Heart and thoracic aorta were removed and serum was collected, while aortic samples were put in a 10% formaldehyde solution for immunochemistry. Cardiac tissue samples obtained from each animal were used for the determination of tissue myeloperoxidase (MPO) and catalase (CAT) activities, malondialdehyde (MDA), and glutathione (GSH) levels. In the sedentary RVH group, aortic contractile response (contraction/relaxation in isolated organ bath), left ventricular diastolic and systolic dimensions, and immunohistochemical staining of aortic inducible nitric oxide synthase (iNOS) were increased, while ejection fraction and aortic endothelial nitric oxide synthase (eNOS) staining were decreased. RVH in the sedentary rats resulted in increased pro-inflammatory cytokines (TNF-α, IL-2, IL-6), lipid peroxidation (malondialdehyde) and neutrophil infiltration (myeloperoxidase activity) along with reductions in antioxidant glutathione and catalase levels in the cardiac tissue. Exercise after RVH increased the immunohistochemical staining of aortic eNOS, decreased iNOS staining and reversed the alterations in echocardiographic and oxidative parameters. Regular exercise commenced after RVH surgery alleviated renovascular hypertension-induced oxidative injury, by modulating oxidant-antioxidant balance via the involvement of the endothelial NO system.


[Validation of a questionnaire for the diagnosis of urinary incontinence].
To validate a questionnaire applied in the Primary Care (PC) clinic which enables urinary incontinence (UI) and its different types to be diagnosed. A descriptive crossover study. A Urodynamics hospital out-patients clinic. Patients referred from PC to be tested for UI by Urodynamics. A self-filled questionnaire prior to the Urodynamics test to give a rough idea of the type of UI. Analysis of patients' characteristics and the internal validity of the questionnaire by comparing it with the Urodynamics test. The sample was 59 men and 432 women. For the rough diagnosis of UI caused by straining in women, a five-question survey had a positive predictive value (PPV) of 77.2% for four affirmative replies, which went up to 83% if maximum exterior flow was included. For the UI group arising from anticholinergic treatment, a four-question survey had low PPV (57.6%), but this figure went up to 85.7% with a flowmeter. A questionnaire to study the type of UI, along with further tests, approached the aetiological diagnosis of incontinence in women. A Urodynamics study, however, always needs to be performed on men.


Escaping from multiple visual threats: modulation of escape responses in Pacific staghorn sculpin (Leptocottus armatus).
Fish perform rapid escape responses to avoid sudden predatory attacks. During escape responses, fish bend their bodies into a C-shape and quickly turn away from the predator and accelerate. The escape trajectory is determined by the initial turn (stage 1) and a contralateral bend (stage 2). Previous studies have used a single threat or model predator as a stimulus. In nature, however, multiple predators may attack from different directions simultaneously or in close succession. It is unknown whether fish are able to change the course of their escape response when startled by multiple stimuli at various time intervals. Pacific staghorn sculpin (Leptocottus armatus) were startled with a left and right visual stimulus in close succession. By varying the timing of the second stimulus, we were able to determine when and how a second stimulus could affect the escape response direction. Four treatments were used: a single visual stimulus (control); or two stimuli coming from opposite sides separated by a 0 ms (simultaneous treatment), 33 ms or 83 ms time interval. The 33 ms and 83 ms time intervals were chosen to occur either side of a predicted 60 ms visual escape latency (i.e. during stage 1). The 0 ms and 33 ms treatments influenced both the escape trajectory and the stage 1 turning angle, compared with a single stimulation, whereas the 83 ms treatment had no effect on the escape trajectory. We conclude that Pacific staghorn sculpin can modulate their escape trajectory only between stimulation and the onset of the response, but the escape trajectory cannot be modulated after the body motion has started.


Fracture strengths of chair-side-generated veneers cemented with glass fibers.
CAD/CAM (computer-aided design and computer-aided manufacturing) systems have refreshed the idea of chair-side production of restorations, but the fracture of ceramic veneers remains a problem. Cementation with glass fibers may improve the fracture strengths and affect the failure modes of CAD/CAM-generated ceramic veneers. Therefore, this study compared the fracture strengths of ceramic veneers produced at chair side and cemented with or without glass fibers with those of composite veneers. Thirty intact mandibular incisors were randomly divided into three groups ( n = 10) and treated with CAD/CAM-fabricated veneers cemented with dual-cure composite resin luting cement (CRLC; Group 1), CAD/CAM-fabricated veneers cemented with a glass fiber network (GFN) and dual-cure CRLC (Group 2), and a direct particulate filler composite veneer constructed utilizing fiber and a restorative composite resin (Group 3). The specimens were tested with a universal testing machine after thermal cycling treatment. The loads at the start of fracture were the lowest for traditionally fabricated composite veneers and higher for CAD/CAM-generated. Veneers cemented either without or with the GFN. The failure initiation loads (N) for the veneers were 798.92 for Group 1, 836.27 for Group 2, and 585.93 for Group 3. The predominant failure mode is adhesive failure between the laminates and teeth for Group 1, cohesive failure in the luting layer for Group 2, and cohesive laminate failure for Group 3, which showed chipping and small fractures. Ceramic material is a reliable alternative for veneer construction at chair side. Fibers at the cementation interface may improve the clinical longevity and provide higher fracture strength values.


Drinking and Obesity: Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Interactions.
Alcohol and obesity are the main risk factors for alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD), respectively, and they frequently coexist. There are considerable synergistic interaction effects between hazardous alcohol use and obesity-associated metabolic abnormalities in the development and progression of fatty liver disease. Intermittent binge-drinking has been shown to promote steatohepatitis from obesity-related steatosis, and binge-drinking is associated with progression to cirrhosis even when average alcohol intake is within the currently used criteria for a NAFLD diagnosis. Recent longitudinal studies in NAFLD have shown that light-to-moderate alcohol use is associated with fibrosis progression and incident clinical liver disease, suggesting that there is no liver-safe limit of alcohol intake in the presence of NAFLD; a J: -shaped association between alcohol and all-cause mortality remains controversial. The interaction effects between alcohol and obesity make the present strict dichotomization of liver disease into alcoholic and NAFLD inappropriate, and require attention in future research, public health policy, individual counseling, and risk stratification.


Effect of vermicompost on growth, yield and nutrition status of tomato (Lycopersicum esculentum).
An experiment was conducted to determine the effects of vermicompost on growth, yield and fruit quality of tomato (Lycopersicum esculentum var. Super Beta) in a field condition. The experiment was a randomized complete block design with four replications. The different rates of vermicompost (0, 5, 10 and 15 t ha(-1)) was incorporated into the top 15 cm of soil. During experiment period, fruits were harvested twice in a week and total yield were recorded for two months. At the end of experiment, growth characteristics such as leaf number, leaf area and shoot dry weights were determined. The results revealed that addition of vermicompost at rate of 15 t ha(-1) significantly (at p < 0.05) increased growth and yield compared to control. Vermicompost with rate of 15 t ha(-1) increased EC of fruit juice and percentage of fruit dry matter up to 30 and 24%, respectively. The content of K, P, Fe and Zn in the plant tissue increased 55, 73, 32 and 36% compared to untreated plots respectively. The result of our experiment showed addition of vermicompost had significant (p < 0.05) positive effects on growth, yield and elemental content of plant as compared to control.


How Do Users Map Points Between Dissimilar Shapes?
Finding similar points in globally or locally similar shapes has been studied extensively through the use of various point descriptors or shape-matching methods. However, little work exists on finding similar points in dissimilar shapes. In this paper, we present the results of a study where users were given two dissimilar two-dimensional shapes and asked to map a given point in the first shape to the point in the second shape they consider most similar. We find that user mappings in this study correlate strongly with simple geometric relationships between points and shapes. To predict the probability distribution of user mappings between any pair of simple two-dimensional shapes, two distinct statistical models are defined using these relationships. We perform a thorough validation of the accuracy of these predictions and compare our models qualitatively and quantitatively to well-known shape-matching methods. Using our predictive models, we propose an approach to map objects or procedural content between different shapes in different design scenarios.


Differential effects of B7-1 blockade in the rat experimental autoimmune encephalomyelitis model.
Blocking the CD28-B7 T cell costimulatory activation pathway protects animals from developing experimental autoimmune encephalomyelitis (EAE). In the mouse EAE model, selective blockade of B7-1 by specific mAbs has been shown to protect animals from EAE. In the Lewis rat model, we have shown that CD28-B7 blockade by systemic administration of CTLA4Ig prevents actively induced EAE. Since CTLA4Ig binds to both B7-1 and B7-2, we used a mutant form of CTLA4Ig (CTLA4IgY100F) that binds only B7-1, to study the role of B7-1 blockade in this model. Such a reagent avoids the potential of signaling by mAbs. Systemic administration of CTLA4IgY100F in several dosing regimens did not protect from EAE, and in some protocols worsened disease, while CTLA4Ig was always protective. In contrast, systemic injection of APCs preincubated ex vivo with the encephalitogenic peptide of myelin basic protein and either CTLA4Ig or CTLA4IgY100F protected recipients from disease. In vitro studies confirmed the in vivo observations and showed that primed lymph node cells from protected animals had decreased proliferative responses to myelin basic protein as compared with controls, while lymphocytes from animals treated with systemic CTLA4gY100F did not. More importantly, systemic administration of CTLA4IgY100F abrogated the protective effect of ex vivo treated APCs. These data suggest an important regulatory role for B7-1, perhaps through binding to CTLA4, in this model of EAE. Understanding the role and mechanisms of selective blockade of costimulatory molecules has implications for therapy of autoimmune disease.


Peripheral vascular trauma from close-range shotgun injuries.
This report summarizes an eight-year experience (1976 to 1983) with 49 close-range shotgun blasts with associated major vascular injuries seen in a large urban hospital. Injuries to the upper extremity (40%), lower extremity (56%), and neck (4%) were seen. A high frequency of associated deep venous injury (82%), nerve injury (37%), fracture (33%), massive soft-tissue loss (43%), and compartmental hypertension (39%) was observed. There were no deaths in this series, and the limb salvage rate was 96%. Neither patient with multiple carotid artery injuries suffered a neurologic deficit. We attribute our success in the management of these complex injuries to rapid fracture immobilization, early and aggressive use of fasciotomy, adequate débridement of devitalized tissue, repair of deep venous injuries, arterial repair with autogenous tissue, and extra-anatomic bypass grafting in selected cases.


Homoeopathy for delayed onset muscle soreness: a randomised double blind placebo controlled trial.
To pilot a model for determining whether a homoeopathic medicine is superior to placebo for delayed onset muscle soreness (DOMS). Randomised double blind placebo controlled trial. Physiotherapy department of a homoeopathic hospital. Sixty eight healthy volunteers (average age 30; 41% men) undertook a 10 minute period of bench stepping carrying a small weight and were randomised to a homoeopathic medicine or placebo. Mean muscle soreness in the five day period after the exercise test, symptom free days, maximum soreness score, days to no soreness, days on medication. The difference between group means was 0.17 in favour of placebo with 95% confidence intervals +/- 0.50. Similar results were found for other outcome measures. The study did not find benefit of the homoeopathic remedy in DOMS. Bench stepping may not be an appropriate model to evaluate the effects of a treatment on DOMS because of wide variation between subject soreness scores.


[Routine clinical chemical analysis with prepared reagent carriers].
The determination of glucose, uric acid, urea, triglycerides, cholesterol, sodium, and potassium was investigated using an Ektachem DT 60 and the Ektachem DTE-module. The coefficients of variation ranged from 0.5 to 5.3% for within run and from 1.1 to 4.7% for within day precision. The deviations of the measured values from the assigned values (determined by gas chromatography and mass spectrometry, or by interlaboratory surveys were less than 5%. The determination of urea in control samples was influenced by matrix effects, but not the analysis of patients samples. The comparative analysis of patient samples with routine methods and multilayer reagent carriers showed good agreement. The linear coefficients of correlation ranged from 0.9318 (sodium) to 0.9945 (triglycerides). The analyser is easy to use and has been proved to be very reliable. The throughput of 65 substrate and 15 electrolyte determinations per hour is sufficient for the medical practitioner or small laboratories.


Molecular phylogeny of Besnoitia and the genetic relationships among Besnoitia of cattle, wildebeest and goats.
Knowledge on parasites of the genus Besnoitia is sparse, which are classified in the subfamily Toxoplasmatinae of the phylum Apicomplexa. This arrangement hypotheses that Besnoitia represents the sister group to species such as Toxoplasma gondii and Hammondia hammondi. In order to test this hypothesis, phylogenetic analyses of 18S ribosomal DNA (rDNA) from Besnoitia, Hammondia, Isospora, Frenkelia, Eimeria, Neospora, Sarcocystis and Toxoplasma were performed. The 18S rDNA of Besnoitia besnoiti, Besnoitia jellisoni and Eimeria alabamensis were amplified by PCR and sequenced. Phylogenetic analyses by parsimony and maximum-likelihood methods showed Besnoitia to be reproducibly the sister group to a clade containing Hammondia, Neospora and Toxoplasma. Furthermore, Besnoitia of cattle, wildebeest and goats had identical ITS1 rDNA sequences, which questions the use of the taxon Besnoitia caprae to describe the Besnoitia found in goats.


Proteomics approaches to uncover the repertoire of circulating biomarkers for breast cancer.
There is substantial interest in applying proteomics to cancer biomarker discovery. Proteomics is particularly suited for profiling biological fluids and uncovering circulating markers and is currently being applied to the identification of novel biomarkers for breast cancer. Novel proteomic approaches include direct profiling of serum using mass spectrometry, application of a variety of strategies to harness immunity for cancer diagnosis, protein tagging to capture subproteomes rich in diagnostic markers, the use of protein microarrays, and the use of multi-dimensional liquid protein separation technologies for comprehensive profiling of serum and other biological fluids. It is likely that the application of a wide range of proteomics tools to breast cancer will yield a panel of markers that have utility for breast cancer diagnosis.


One-Stage Treatment for Adult Patients With Crouzonoid Appearance by Orthognathic and Face Contouring Surgery.
Crouzon syndrome is a rare genetic disorder with autosomal-dominant inheritance that shows a triad of hallmark characteristics: craniosynostosis, exophthalmos, and midface retrusion. General treatment protocol for patients with Crouzon syndrome has already been established, but there is no standard treatment strategy for adult patients with Crouzonoid appearance. The authors present clinical patients of 1-stage orthognathic and face contouring surgery to achieve functional and aesthetic improvement.One-stage surgery was performed in adult patients with Crouzonoid appearance without a history of facial surgery. Orthognathic 2-jaw surgery was first performed to treat class III malocclusion. Face contouring surgery was conducted next to improve the aesthetic appearance using midface augmentation with onlay rib bone graft, advancement genioplasty, augmentation rhinoplasty, and ancillary procedures such as neck lift, fat graft, or fillers.Five patients (2 men, 3 women) were enrolled in this study. The mean age at the time of surgery was 19.0 years. No specific surgery-related complications such as infection, nerve injury, or recurred malocclusion were observed during the 3.5 years of follow-up. Normal class I occlusion was reached in all patients. The frontonasal angle, nasolabial angle, and labiomental angle improved from 125.1° to 135.1° (P > 0.05), 60.9° to 86.3° (P = 0.018), and 146.3° to 125.0° (P = 0.018), respectively. The Global Aesthetic Improvement Scale score was 4.75 and 5.00 in frontal and profile views, respectively.One-stage orthognathic and face contouring surgery may be an effective surgical option with good postoperative functional and aesthetic improvement in adult patients with Crouzonoid appearance.


[Not Available].
F. Lacaine Lymph node metastasis carries enormous prognostic weight in the evaluation of colon cancer and raises the question of how extensive a lymph node dissection should be. Lymph node dissection has several goals: 1) staging of the cancer at the time of intervention; 2) improving the chances for complete resection and cure; 3) evaluating the thoroughness and quality of a particular surgical procedure. The prognostic value of lymphadenectomy is evident from the direct practical decisions it entails: evidence-based recommendations (Level A) have proposed adjuvant chemotherapy for all patients with Stage III colon cancer since 1990. Studies have shown a statistically significant correlation between the number of nodes examined in an operative specimen and long-term survival in patients with Stage II disease. The more closely lymph nodes are examined, the more metastasis is found; one can then see the aberrations of stage migration described as the "Will Rogers Phenomenon." Without randomized studies, it is impossible to say whether resection of a larger number of lymph nodes actually improves the prognosis or whether that number is simply a marker of better surgical management including the quality of the surgical gesture, the careful pathologic examination of the specimen, and subsequent choices for adjuvant chemotherapy. The recovery of 12 lymph nodes correlates with a better global prognosis. At the very least, it is an effective marker for the quality of the surgical resection and can be used in the evaluation of professional practice.


Eyelid tumors anmd renal transplantation.
The high incidence of malignant neoplasms in renal transplant recipients and other immunosuppressed patients is well recognized. A large proportion of these neoplasms are skin cancers. The frequent occurrence of other ocular complications, such as cataract, elevated intraocular pressure, hypertensive retinopathy, cytomegalovirus retinitis, and herpetic keratitis in patients after kidney transplant, has also been described. This report presents the clinical and histopathologic features of eyelid involvement by keratoacanthoma and squamous cell carcinoma in two patients after renal transplantation and alerts ophthalmologists to the potential for this association.


Peptidergic agonists of activity-dependent neurotrophic factor protect against prenatal alcohol-induced neural tube defects and serotonin neuron loss.
Prenatal alcohol exposure via maternal liquid diet consumption by C57BL/6 (B6) mice causes conspicuous midline neural tube deficit (dysraphia) and disruption of genesis and development of serotonin (5-HT) neurons in the raphe nuclei, together with brain growth retardation. The current study tested the hypothesis that concurrent treatment with either an activity-dependent neurotrophic factor (ADNF) agonist peptide [SALLRSIPA, (SAL)] or an activity-dependent neurotrophic protein (ADNP) agonist peptide [NAPVSIPQ, (NAP)] would protect against these alcohol-induced deficits in brain development. Timed-pregnant B6 dams consumed alcohol from embryonic day 7 (E7, before the onset of neurulation) until E15. Fetuses were obtained on E15 and brain sections processed for 5-HT immunocytochemistry, for evaluation of morphologic development of the brainstem raphe and its 5-HT neurons. Additional groups were treated either with SAL or NAP daily from E7 to E15 to assess the potential protective effects of these peptides. Measures of incomplete occlusion of the ventral canal and the frequency and extent of the openings in the rhombencephalon were obtained to assess fetal dysraphia. Counts of 5-HT-immunostained neurons were also obtained in the rostral and caudal raphe. Prenatal alcohol exposure resulted in abnormal openings along the midline and delayed closure of ventral canal in the brainstem. This dysraphia was associated with reductions in the number of 5-HT neurons both in the rostral raphe nuclei (that gives rise to ascending 5-HT projections) and in the caudal raphe (that gives rise to the descending 5-HT projections). Concurrent treatment of the alcohol-consuming dams with SAL prevented dysraphia and protected against the alcohol-induced reductions in 5-HT neurons in both the rostral and caudal raphe. NAP was less effective in protecting against dysraphia and did not protect against 5-HT loss in the rostral raphe, but did protect against loss in the caudal raphe. These findings further support the potential usefulness of these peptides for therapeutic interventions in pregnancies at risk for alcohol-induced developmental deficits. Notably, the ascending 5-HT projections of the rostral raphe have profound effects in regulating forebrain development and function, and the descending 5-HT projections of the caudal raphe are critical for regulating respiration. Protection of the rostral 5-HT-system may help prevent structural and functional deficits linked to abnormal forebrain development, and protection of the caudal systems may also reduce the increased risk for sudden infant death syndrome associated with prenatal alcohol exposure.


Upregulation of H19 indicates a poor prognosis in gallbladder carcinoma and promotes epithelial-mesenchymal transition.
The imprinted oncofetal long non-coding RNA H19 has been reported to be involved in many kinds of human cancers. However, whether lncRNA H19 implicate in oncogenesis and cancer progression in gallbladder cancer remain largely unknown. In the present study, compared with adjacent normal tissues, the level of H19 was significantly upregulated in gallbladder cancer tissues and was positively associated with lymphatic metastasis and tumor size. The overall survival is shorter in those who had higher H19 expression among GBC patients. In vitro, both TGF-β1 and IL-6 treatment induced upregulation of H19, downregulated the protein level of E-cadherin while increased Vimentin, indicating an epithelial-mesenchymal transition (EMT) phenotype in GBC. The overexpression of H19 in GBC cells enhanced tumor invasion and promoted EMT by upregulated transcription factor Twist1. On the contrary, Loss of function studies indicated that H19 interference in GBC suppressed tumor cell invasion and promoted mesenchymal-epithelial transition (MET) via suppressing Twist expression. In vivo, the volume of the tumors in H19-inteference group was significantly decreased compared to those in the control group of nude mice. Both western-blot and immunohistochemistry confirmed that a MET phenotype existed in the H19 interference group when compared to control group. These results defined H19 as a novel prognostic factor for GBC, and indicated that it might play important regulatory roles in the EMT process.


Differential responses of endogenous adult mouse neural precursors to excess neuronal excitation.
Adult neurogenesis in the subgranular zone of the hippocampus (SGZ) is enhanced by excess as well as mild neuronal excitation, such as chemoconvulsant-induced brief seizures. Because most studies of neurogenesis after seizures have focused on the SGZ, the threshold of neuronal excitation required to enhance neurogenesis in the subventricular zone (SVZ) is not clear. Therefore, we examined the responses of SVZ precursors to brief generalized clonic seizures induced by a single administration of the chemoconvulsant pentylenetetrazole (PTZ). Cell cycle progression of precursors was analysed by systemic administration of thymidine analogues. We found that brief seizures immediately resulted in cell cycle retardation in the SVZ. However, the same effect was not seen in the SGZ. This initial cell cycle retardation in the SVZ was followed by enhanced cell cycle re-entry after the first round of mitosis, leading to precursor pool expansion, but the cell cycle retardation and expansion of the precursor pool were transient. Cell cycle progression in the PTZ-treated group returned to normal after one cell cycle. The numbers of precursors in the SVZ and new neurons in the olfactory bulb, which are descendants of SVZ precursors, were not significantly different from those in control mice more than 2 days after seizures. Because similar effects were observed following electroconvulsive seizures, these responses are likely to be general effects of brief seizures. These results suggest that neurogenesis in the SVZ is more tightly regulated and requires stronger stimuli to be modified than that in the SGZ.


End-stage renal disease after kidney donation: a single-center experience.
Although the risk of kidney donation has been determined in many studies to be low with respect to morbidity and mortality, it is important to keep in mind that patients are put at some risk when they donate an organ for transplantation. The reported incidence of end-stage renal disease (ESRD) among kidney donors ranges from 0.2% to 0.5% with varying follow-up times. Herein, we have reported four living kidney donors at our institution who progressed to ESRD. We reviewed registry data and medical records of patients who underwent donor nephrectomy at our institution between October 1, 1959, and June 30, 2005, particularly cases who developed ESRD. Between October, 1959, and the end of June, 2005, 3591 kidney transplants were performed at our center including 1195 of the organs (33%) from living donors, whose mean age was 41.9 years. Four kidney donors (0.33%) developed ESRD. Their mean age at donation was 31 years; the mean age at ESRD development was 46.5 years. All four patients donated to siblings with renal failure. Two of the four (50%) had another first-degree relative who subsequently developed renal failure. Two of the four (50%) smoked tobacco subsequent to donor surgery, and one (25%) was obese. Progression to ESRD is rare among living renal donors. Kidney donation is safe when strict eligibility criteria are met. There may be an increased risk for progression to ESRD among donors with a family history of renal disease.


Multi-time scale analysis of the spatial representativeness of in situ soil moisture data within satellite footprints.
We conduct a novel comprehensive investigation that seeks to prove the connection between spatial and time scales in surface soil moisture (SM) within the satellite footprint (~50 km). Modeled and measured point series at Yanco and Little Washita in situ networks are first decomposed into anomalies at time scales ranging from 0.5 to 128 days, using wavelet transforms. Then, their degree of spatial representativeness is evaluated on a per time-scale basis by comparison to large-spatial scale datasets (the in situ spatial average, SMOS, AMSR2 and ECMWF). Four methods are used for this: temporal stability analysis (TStab), triple collocation (TC), the percentage of correlated areas (CArea) and a new proposed approach that uses wavelet-based correlations (WCor). We found that the mean of the spatial representativeness values tends to increase with the time scale but so does their dispersion. Locations exhibit poor spatial representativeness at scales below 4 days, while either very good or poor representativeness at seasonal scales. Regarding the methods, TStab cannot be applied to the anomaly series due to their multiple zero-crossings and TC is suitable for week and month scales but not for other scales where datasets cross-correlations are found low. In contrast, WCor and CArea give consistent results at all time-scales. WCor is less sensitive to the spatial sampling density, so it is a robust method that can be applied to sparse networks (1 station per footprint). These results are promising to improve the validation and downscaling of satellite SM series and the optimization of SM networks.


Short-term effects of atorvastatin in normal dogs and dogs with congestive heart failure due to myxomatous mitral valve disease.
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may improve heart failure class and survival in people with congestive heart failure (CHF) of various etiologies. To evaluate the tolerability of atorvastatin in healthy dogs, and the short-term effects of atorvastatin on clinical markers of disease severity, lipid profiles, and markers of systemic inflammation and oxidative stress in dogs with CHF. Eleven normal dogs and 12 client-owned animals with CHF attributable to myxomatous mitral valve disease. Prospective nonblinded observational study. Normal dogs (n = 11) were first treated with atorvastatin and re-evaluated after 14 and 30 days for clinical tolerability and alterations in certain laboratory results. Subsequently, dogs with CHF (n = 12) were treated with atorvastatin at a dosage of 2 mg/kg q24 h for 8 weeks. Echocardiography, blood pressure (BP), quality of life questionnaire, and blood sampling were performed pre and post atorvastatin administration. Atorvastatin was well tolerated and did not result in apparent adverse effects or biochemical abnormalities in healthy dogs and in dogs with CHF. Healthy dogs experienced a decrease in total cholesterol (TC) concentration (P = .03) after atorvastatin administration. Decreases in TC concentration (P = .02), non-HDL cholesterol concentration (P = .02), total white blood cell count (P = .03), neutrophils (P = .01), and systolic BP (P = .01) were noted in the CHF group after 8 weeks of atorvastatin. Atorvastatin was well tolerated at clinically relevant doses in healthy dogs and dogs with CHF. Further investigation into the effects of statin treatment in dogs with CHF is warranted.


Coronary artery disease after radiation therapy for Hodgkin's lymphoma: coronary CT angiography findings and calcium scores in nine asymptomatic patients.
Long-term survivors of Hodgkin's lymphoma treated with radiation therapy have an increased incidence of coronary artery disease. The purpose of this study is to describe the coronary CT angiography findings and calcium scores of asymptomatic patients who had mediastinal irradiation for Hodgkin's lymphoma and to evaluate the impact of coronary CT angiography on patient management. We evaluated nine consecutive patients, age range 35-60 years, who had been treated for Hodgkin's lymphoma by radiation therapy between the ages of 11 and 27 years. The total mediastinal dose ranged from 34 to 45 Gy. All patients were evaluated with 64-MDCT with calcium scoring followed by CT angiography of the coronary arteries. Imaging findings and clinical follow-up were analyzed. Eight of nine patients had coronary artery disease. CT showed long segments of diffuse disease; areas of stenosis from soft plaque; and calcification in the proximal right coronary, left anterior descending, and left circumflex arteries. Calcium scores were significantly higher than in other patients of this age group. Additional tests, including selective coronary angiography, were necessary in patients with diffuse disease with calcifications. CT evaluation led to bypass surgery and angioplasty in two patients. Coronary CT angiography and calcium scores are useful tools for evaluation of irradiation-related coronary artery disease. Complementary tests might be necessary in selected patients. Prospective larger studies are needed to better define the role of coronary CT angiography and calcium scores and to establish an algorithm for evaluation and treatment of these patients.


Synthesis and Characterization of Zinc Oxide Nanoparticles with Small Particle Size Distribution.
Solvothermal synthesis has shown to have a great potential to synthesize Zinc Oxide nanoparticles (ZnO NPs) with less than 10 nm size. In this study, we present a rapid synthesis of ZnO NPs in which ZnO NPs with more uniform shape and highly dispersed were synthesized using zinc acetate dihydrate (Zn(CH3COO)2 2H2O) and potassium hydroxide (KOH) as a precursor and absolute ethanol as solvent via solvothermal method. Few techniques were exploited to characterize synthesized ZnO NPs including X-ray diffraction (XRD), transmission electron microscope (TEM), Brunauer-Emmett-Teller (BET), energy-dispersive X-ray spectroscopy (EDX), fourier transform infrared (FT-IR) spectroscopy, and ultraviolet visible (UV-Vis) spectroscopy. Synthesized ZnO NPs that were prepared via solvothermal synthesis method at 60 °C for 3 hours exhibited a wurtzite structure with a crystalline size of 10.08 nm and particle size of 7.4 ± 1.2 nm. The UV-vis absorption spectrum has shown peak at 357 nm indicate the presence of ZnO NPs. Hence, better quality with uniform size ZnO NPs can be easily synthesized with reduced amount of time via solvothermal synthesis method rather than using other complicated and lengthy synthesis methods.


Which factors make clean intermittent (self) catheterisation successful?
To explore which factors determine successful intermittent catheterisation. Intermittent catheterisation is a safe, effective treatment and is associated with improved quality of life, although negative issues are reported. Factors which determine adherence are largely unknown. An additional qualitative study was conducted to gain insight into patient's experience with intermittent catheterisation in everyday life. A prospective multicentre study was conducted between March 2012-March 2013 with one year follow-up. Patients with a variety of diagnoses referred to the outpatient clinic, ≥18 years, performed catheterisation at least once a day for ≥3 months were included. Data were obtained by patients' specific questionnaire Visual Analog Scale of quality of life regarding voiding problems, a questionnaire about catheterisation in daily practice, King's Health questionnaire, and a short questionnaire after one year. Of the 129 (72 male) patients, mean age 62 (22-86) years, seven died and 63 stopped, 32/63 (50%) due to recovered bladder function. Fifty-nine (47%) continued to perform catheterisation after one year. Forty-seven (86%) patients reported catheterisation had become part of their life or had a positive effect on their life. A weak correlation was found between increasing age and cessation of catheterisation. Visual Analogue Scale - score on quality of life improved for the total group. The King's Health questionnaire identified in the total group that the impact of the bladder problem in daily life, limitations in daily activities and negative emotions decreased over time. Adherence of successful intermittent catheterisation can be influenced negatively by increasing age. However, we think catheterisation should be considered as an option for older patients. We could not conform that if intermittent catheterisation was beneficial for the patient, it would positively influence adherence. Further prospective studies on adherence of intermittent catheterisation in larger groups need to be undertaken. After implementation of the national guideline in 2008, we were able to perform a multicentre study. This prospective study gives insight into patients who were undertaking intermittent catheterisation and which factors determine successful intermittent catheterisation adherence. After following the national guideline, we found no factors for additional interventions in assessment or coaching intermittent catheterisation. Post void residual volume turned out to be not a predictor for the necessity of intermittent catheterisation. A large group of patients could discontinue intermittent catheterisation during follow-up due to bladder function recovery. Although a weak correlation was found between increasing age and ceasing of catheterisation, we think the older can benefit from intermittent catheterisation. In the first period, additional support, for example given by a district nurse, may be necessary for this group to achieve better outcomes.


Learning spatial structures of proteins improves protein-protein interaction prediction.
Spatial structures of proteins are closely related to protein functions. Integrating protein structures improves the performance of protein-protein interaction (PPI) prediction. However, the limited quantity of known protein structures restricts the application of structure-based prediction methods. Utilizing the predicted protein structure information is a promising method to improve the performance of sequence-based prediction methods. We propose a novel end-to-end framework, TAGPPI, to predict PPIs using protein sequence alone. TAGPPI extracts multi-dimensional features by employing 1D convolution operation on protein sequences and graph learning method on contact maps constructed from AlphaFold. A contact map contains abundant spatial structure information, which is difficult to obtain from 1D sequence data directly. We further demonstrate that the spatial information learned from contact maps improves the ability of TAGPPI in PPI prediction tasks. We compare the performance of TAGPPI with those of nine state-of-the-art sequence-based methods, and TAGPPI outperforms such methods in all metrics. To the best of our knowledge, this is the first method to use the predicted protein topology structure graph for sequence-based PPI prediction. More importantly, our proposed architecture could be extended to other prediction tasks related to proteins.


[ESSENCE gathers the diagnoses into a whole].
Co-existence of attention-deficit/hyperactivity disorder, oppositional defiant disorder, tic disorders, developmental coordination disorder, language disorder, learning problems, and autism spectrum disorder and sharing of symptoms across disorders, contribute to the typical clinical presentation in child psychiatry as well as in developmental medicine. The acronym ESSENCE refers to Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations. Affected children are brought for clinical assessment because of impairing symptoms that raise concern before the age of about 5 years in general development, communication and language, social inter-relatedness, motor coordination, attention, activity, behaviour, mood, and/or sleep. Such children are usually in need of a range of expert assessments, but a holistic approach is rarely taken from the start. Major problems in at least one ESSENCE domain before 5 years of age predict poor mental health later in life. Expert ESSENCE centres for assessment, habilitation and treatment of these children are needed.


Biweekly triplet chemotherapy with gemcitabine, cisplatin and vinorelbine for advanced chemotherapy naïve non-small cell lung cancer.
To investigate the efficacy and tolerability of biweekly scheduled triplet chemotherapy consisting of gemcitabine, cisplatin and vinorelbine for chemotherapy-naïve advanced non-small cell lung cancer. Patients with stage IIIB/IV non-small cell lung cancer and performance status of 0-2 were eligible. Patients who had brain metastasis and of an older age were also enrolled in the study. The triplet combination chemotherapy consisted of gemcitabine, cisplatin and vinorelbine at the doses of 1000 mg/m(2), 25 mg/m(2) and 50 mg/m(2), respectively, were administered on day 1 and 14, every 28 days, up to 6 cycles. Thirty patients were enrolled in the study. Median age was 60 years (range, 42-74). Most of the patients (83%) had metastatic disease and 7 patients (23%) had brain metastasis. In assessing 24 patients for response evaluation, none had complete response. Partial responses were achieved in 18 (60%) patients. Four patients (13%) had stable disease and 2 (7%) progressed. Thirteen percent and 20% of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. Febrile neutropenia, severe thrombocytopenia, hepatic and renal toxicity were not seen. Overall and progression-free survival were 8.15 and 7.15 months, respectively. Patients who had no brain metastasis ( P = 0.069), who had more than 3 courses of chemotherapy (P <0.001), and who had chemotherapy applied without dose reduction (P = 0.018) had better survivals. The biweekly schedule of the triplet chemotherapy combination including gemcitabine, cisplatin and vinorelbine was effective in advanced, mostly metastatic non-small cell lung cancer with acceptable and manageable side effects.


A morphological and immunohistochemical study of healthy and atretic follicles in the ovary of the sexually immature ostrich (Struthio camelus).
The morphology of healthy and atretic follicles in the ovary of the sexually immature ostrich was described in the present study. In addition, the distribution of the intermediate filaments desmin, vimentin and smooth muscle actin, in these ovarian follicles, was demonstrated. Healthy and atretic primordial, pre-vitellogenic and vitellogenic follicles were present in the ovaries of the sexually immature ostrich. Atresia occurred during all stages of follicular development. Atretic primordial and pre-vitellogenic follicles were characterized by the presence of a shrunken oocyte surrounded by a multilayered granulosa cell layer. Two forms of atresia (types 1 and 2) were identified in vitellogenic follicles. In the advanced stages of type 1 atresia the follicle was dominated by a hyalinized mass. In contrast, in type 2 atresia the granulosa and theca interna cells differentiated into interstitial gland cells. Positive immunostaining for desmin was observed in the granulosa cells of only healthy primordial and pre-vitellogenic follicles. Atretic primordial and pre-vitellogenic follicles were immunonegative for desmin. Vimentin immunoreactivity was demonstrated in the granulosa cells of all follicles except the vitellogenic atretic follicles. The results of the present study indicate that ovarian follicles in the sexually immature ostrich undergo a cycle of growth and regression, which is similar to that reported in other avian species. Furthermore, based on the results of the immunohistochemical study, it would appear that the distribution and immunostaining of intermediate filaments changes during follicular development and atresia.


Administration of dendritic cells in cancer nodules in hepatocellular carcinoma.
Dendritic cells (DCs), the most potent antigen-presenting cells in vivo, are now used for cancer immunotherapy during which they are usually administered to the blood of patients with cancer. However, the route of administration of DCs affects the magnitude of immune responses. This study was conducted to assess the safety of the direct administration of DCs into cancer nodules. DCs were generated by culturing peripheral blood mononuclear cells with granulocyte-macrophage colony-stimulating factor and interleukin-4 for 7 days. After confirming the phenotype and function, one hundred thousand DCs were injected directly into the cancer nodules of 4 patients with hepatocellular carcinoma (HCC) under ultrasonography guidance 48 h after the administration of 100% ethanol. All patients were monitored for any alteration in generalized condition, signs of inflammation, and liver and kidney function for the next 14 days. In addition, the final assessment of the safety of the administration of DCs into cancer nodules was performed 6 months after therapy commencement. The injection of 100% ethanol disrupted the HCC nodules in all 4 patients. DCs were distributed uniformly in the cancer nodules as assessed by ultrasonography. The administration of DCs into cancer nodules was well tolerated by all patients and there were no immediate or delayed side effects. The tumor marker decreased in one patient after the direct administration of DCs. Direct administration of DCs into the cancer nodules of patients with HCC was safe.


A pilot study of the efficacy of wipes containing chlorhexidine 0.3%, climbazole 0.5% and Tris-EDTA to reduce Malassezia pachydermatis populations on canine skin.
Wipes containing chlorhexidine and azole derivates have been recommended for veterinary use. No study has been published about their activity against Malassezia pachydermatis. To evaluate the in vivo and in vitro activity of wipes soaked in a chlorhexidine, climbazole and Tris-EDTA solution against Malassezia pachydermatis. Five research colony shar-pei dogs. Wipes were applied once daily onto the left axilla, left groin and perianal area (protocol A), and twice daily on the right axilla, right groin and umbilical region (protocol B) for 3 days. In vivo activity was evaluated by quantifying Malassezia colonies through contact plates on the selected body areas before and after wipe application. The activity of the solution in which the wipes were soaked was assessed in vitro by contact tests following the European Standard UNI EN 1275 guidelines. Samples collected after wipe application showed a significant and rapid reduction of Malassezia yeast CFU. No significant difference in the Malassezia reduction was found between protocols A and B. In vitro assay showed 100% activity against Malassezia yeasts after a 15 min contact time with the wipe solution. Wipes containing chlorhexidine, climbazole and Tris-EDTA substantially reduced the M. pachydermatis population on the skin of dogs. The results, although this was an uncontrolled study performed on a small number of dogs, suggest that these wipes may be useful for topical therapy of Malassezia dermatitis involving the lips, paws, perianal area and skin folds.


Hemodynamic effects of the dipeptidyl peptidase-4 inhibitor linagliptin with renin-angiotensin system inhibitors in type 2 diabetic patients with albuminuria.
Concomitant treatment with angiotensin-converting enzyme (ACE) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors is increasingly common. Pharmacological studies have suggested a potential adverse drug interaction between ACE inhibitors and DPP-4 inhibitors resulting in unfavorable hemodynamic changes; very few studies have examined such an interaction between angiotensin II receptor blockers (ARBs) and DPP-4 inhibitors. We investigated blood pressure (BP) and heart rate (HR) during treatment with the DPP-4 inhibitor linagliptin in individuals receiving either ACE inhibitors or ARBs in the MARLINA-T2D trial. In this study, 360 individuals with type 2 diabetes and albuminuria receiving unchanged doses of ACE inhibitors or ARBs were randomized to linagliptin or placebo. Twenty-four-hour ambulatory BP monitoring, an exploratory endpoint, was conducted at baseline and after 24 weeks. Ambulatory BP monitoring data were available for 208 individuals (linagliptin: n = 111; placebo: n = 97). Baseline mean ± SD 24-h SBP and DBP were 132.5 ± 12.4 mmHg and 75.9 ± 9.4 mmHg, respectively; mean 24-h HR was 76.3 ± 10.1 bpm. At week 24, no overall effect of the DPP-4 inhibitor versus placebo was seen on mean 24-h SBP, DBP, or HR. Furthermore, in the subgroups receiving either an ACE inhibitor or an ARB, no effect on these hemodynamic parameters was seen as a result of concomitant DPP-4 inhibitor treatment. Adding linagliptin to treatment with ACE inhibitors or ARBs was not associated with any hemodynamic changes, supporting their concomitant use in individuals with type 2 diabetes and albuminuria.


Proteins with simplified hydrophobic cores compared to other packing mutants.
Efforts to design proteins with greatly reduced sequence diversity have often resulted in proteins with so-called molten globule properties. Substitutions were made at six neighboring sites in the major hydrophobic core of staphylococcal nuclease to create variants with all leucine, all isoleucine or all valine at these sites. The mutant proteins with simplified cores constructed here are quite unstable and have poorly packed cores, attested to by interaction energies. Eight related mutants with greater sequence diversity were also constructed. Comparison to these mutants and 159 other permutations of these 3 aliphatic side chains at these same 6 sites previously constructed shows that the simplified cores are not unusual in their stabilities or interaction energies. Further, crystal structures of the two mutants with the worst packing, as measured by interaction energies, showed no unusual disorder in the core. Therefore, reduction of sequence diversity is not necessarily incompatible with a single stable native structure. Other factors must also contribute to previous protein design failures.


A new mdr-1 encoded P-170 specific monoclonal antibody: (6/1C) on paraffin wax embedded tissue without pretreatment of sections.
The generation and characterisation of a monoclonal antibody that specifically recognises the mdr-1 encoded protein, P-glycoprotein (P-170), on routinely processed formalin fixed, paraffin wax embedded tissue sections. The monoclonal antibody, designated 6/1C, was produced following a combination of in vivo and in vitro immunisation regimens in Balb/c mice with a synthetic 12 amino acid peptide that corresponds to amino acids 21-32 (believed to be intracellularly located) of P-170 and has insignificant homology with the mdr-3 encoded P-170. Antibody 6/1C was characterised by western blotting and immunocytochemistry on cytospins of paired multidrug resistant or sensitive cell lines, including mdr-1 and mdr-3 transfected cells, and by immunohistochemistry on normal and malignant formalin fixed paraffin wax embedded tissue sections. Antibody 6/1C showed a single band at 170 kDa on western blots of multidrug resistant cell lysates and mdr-1 transfected cell lysates that was absent on similar preparations of drug sensitive cells and mdr-3 transfected cells. Immunocytochemical studies on cytospins of multidrug resistant cells and mdr-1 transfected cells revealed strong inner plasma membrane/cytoplasmic staining. Staining was negligible on drug sensitive cells and cells transfected with the mdr-3 gene. Immunohistochemical studies on formalin fixed, paraffin wax embedded normal adult kidney, liver, and breast tissue and a range of fetal tissues exhibited staining patterns of a variety of secretory surfaces consistent with documented mdr-1 specific staining. Specific staining of malignant cells in similarly treated sections of breast tumours was seen also with antibody 6/1C. Staining on paraffin wax embedded tissue with this antibody did not require any pretreatment of tissue sections. This new monoclonal antibody, chosen for its specificity with the mdr-1 encoded P-170 and its reactivity on routinely fixed paraffin wax embedded tissue samples without pretreatment, appears to be useful for the investigation of P-170 in archival material. It is especially useful for retrospective studies on pretreatment and post-treatment tissue sections, and could help establish when and how rapidly mdr-1 associated drug resistance develops during chemotherapeutic regimens. Immunohistochemical assessment of P-170 expression in many cancers has potential for diagnostic purposes and may influence the choice of chemotherapeutic drugs used in the treatment of refractory tumours.


Fucoidan from seaweed Fucus vesiculosus inhibits 2,4-dinitrochlorobenzene-induced atopic dermatitis.
Fucoidan, one activator of scavenger receptor class A (SR-A), plays important roles in a variety of biological activities, including anti-inflammatory, antioxidant, and antitumor actions. However, the effects of fucoidan on atopic dermatitis (AD) have not been elucidated. To assess this, 2,4-dinitrofluorobenzene (DNFB)-treated BALB/c mice were painted with fucoidan. Results showed that fucoidan significantly ameliorated ear swelling, improved abdomen skin lesions, and decreased inflammatory cell infiltration. In addition, fucoidan significantly suppressed the serum levels of IgE and IL-4 in DNFB-induced AD mice. The infiltration of CD4+ T cells in skin lesions and spleen was also reduced in fucoidan-treated AD mice. Furthermore, treatment with fucoidan promoted Treg cells but attenuated Th1/17 response in the spleens from DNFB-induced AD mice. Together, these results suggest that fucoidan, a natural seaweed-rich polysaccharide, has a potential therapeutic efficacy in the treatment of AD, correlates with the induction of higher anti-inflammatory response through inducing Treg cells.


Detection of regulatory receptors and distinctive surface markers.
Cell sorting has been used as an approach to describing surface markers and functional receptors of hemopoietic stem cells and progenitors. Significant enrichment of CFU-S was obtained with fluorescent cell sorting of human antihuman sperm-labelled bone marrow cells; significant enrichment of human CFU-C was obtained by cell sorting of hybridoma (KGP1)-labelled human bone marrow cells. Significant changes in human bone marrow CFU-C, but not CFU-E were observed by fluorescence polarization after exposure to a putative stimulator of CFU-C. A description of preliminary investigations of a hybrid clone from Dexter culture cells x Chinese hamster ovary and fluorescence polarization measurements after exposure to purified mouse-lung CSF are also presented.


Functional specificity of co-chaperone interactions with Hsp90 client proteins.
A wide array of proteins in signal transduction pathways depend on Hsp90 and other chaperone components for functional maturation, regulation, and stability. Among these Hsp90 client proteins are steroid receptors, members from other classes of transcription factors, and representatives of both serine/threonine and tyrosine kinase families. Typically, dynamic complexes form on the client protein, and these consist of Hsp90- plus bound co-chaperones that often have enzymatic activities. In addition to its direct influence on client folding, Hsp90 locally concentrates co-chaperone activity within the client complex, and dynamic exchange of co-chaperones on Hsp90 facilitates sampling of co-chaperone activities that may, or may not, act on the client protein. We are just beginning to understand the nature of biochemical and molecular interactions between co-chaperone and Hsp90-bound client. This review focuses on the differential effects of Hsp90 co-chaperones toward client protein function and on the specificity that allows co-chaperones to discriminate between even closely related clients.


Regulation of herpes simplex virus gamma(1)34.5 expression and oncolysis of diffuse liver metastases by Myb34.5.
Myb34.5 is a herpes simplex virus 1 (HSV-1) mutant deleted in the gene for ribonucleotide reductase (ICP6). It also carries a version of gamma(1)34.5 (a viral gene product that promotes the dephosphorylation of eIF-2alpha) that is under control of the E2F-responsive cellular B-myb promoter, rather than of its endogenous promoter. Myb34.5 replication in tumor cells results in their destruction (oncolysis). gamma(1)34.5 expression by HSV-1 subverts an important cell defense mechanism against viral replication by preventing shutoff of protein synthesis after viral infection. Infection of colon carcinoma cells with Myb34.5 results in greater eIF-2alpha dephosphorylation and viral replication compared with infection with HSV-1 mutants completely defective in gamma(1)34.5 expression. In contrast, infection of normal hepatocytes with Myb34.5 results in low levels of eIF-2alpha dephosphorylation and viral replication that are similar to those observed with HSV-1 mutants completely defective in gamma(1)34.5 and ICP6. When administered intravascularly into mice with diffuse liver metastases, Myb34.5 has greater antineoplastic activity than HSV-1 mutants with completely defective gamma(1)34.5 expression and more restricted biodistribution compared with HSV-1 mutants with wild-type gamma(1)34.5 expression. Myb34.5 displays reduced virulence and toxicity compared to HSV-1 mutants with wild-type gamma(1)34.5 expression. Portal venous administration of Myb34.5 significantly reduces liver tumor burden in and prolongs the life of mice with diffuse liver metastases. Preexisting Ab's to HSV-1 do not reduce the antitumor efficacy of Myb34.5 in vivo.


Anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of Rubiaceae, Fabaceae and Poaceae plants: A search for new sources of useful alternative antibacterials against MRSA infections.
In this study, we evaluated the effects of the extracts of the leaves of species from the Rubiaceae (Galium aparine L. and Asperula arvensis L.), Fabaceae (Lathyrus aphaca L. and Vicia narbonensis L.) and Poaceae (Digitaria sanguinalis (L.) Scop. and Hordeum murinum L.) plant families on a wide and extensive panel of isolated methicillin-resistant Staphylococcus aureus strains (MRSA). The effects of the methanolic leaf extracts of Rubiaceae, Fabaceae and Poaceae plants on MRSA were evaluated by the disc diffusion assay and the broth dilution method. Among a total of 177 S. aureus isolates, 92 (51.97%) were found to be methicillin-resistant in an antibiogram and this was confirmed by the presence of the mecA gene in polymerase chain reaction method. All MRSA isolates were sensitive to all extracts. There were dose-dependent inhibitions on tested microorganisms for all plant extracts which showed maximum inhibition zones at a concentration of 300 mg/L. L. aphaca, G. aparine and H. murinum exhibited the highest antibacterial activity on the MRSA strains compared to the positive control (P < 0.05), as well as higher total polyphenol and flavonoid contents than other plant extracts. Minimum inhibitory concentrations on MRSA isolates ranged from 388.4 ± 0.2 mg/L, in D. sanguinalis, to 5.5 ± 0.1 mg/L, in L. aphaca. The methanolic extracts of L. aphaca (Fabaceae), G. aparine (Rubiaceae), and H. murinum (Poaceae) proved to have high antibacterial activity on MRSA isolates, thus representing promising antimicrobial agents in clinical settings.


Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart.
Spaceflight causes cardiovascular changes due to microgravity-induced redistribution of body fluids and musculoskeletal unloading. Cardiac deconditioning and atrophy on Earth are associated with altered Trp53 and oxidative stress-related pathways, but the effects of spaceflight on cardiac changes at the molecular level are less understood. We tested the hypothesis that spaceflight alters the expression of key genes related to stress response pathways, which may contribute to cardiovascular deconditioning during extended spaceflight. Mice were exposed to spaceflight for 15 days or maintained on Earth (ground control). Ventricle tissue was harvested starting ~3 h post-landing. We measured expression of select genes implicated in oxidative stress pathways and Trp53 signaling by quantitative PCR. Cardiac expression levels of 37 of 168 genes tested were altered after spaceflight. Spaceflight downregulated transcription factor, Nfe2l2 (Nrf2), upregulated Nox1 and downregulated Ptgs2, suggesting a persistent increase in oxidative stress-related target genes. Spaceflight also substantially upregulated Cdkn1a (p21) and cell cycle/apoptosis-related gene Myc, and downregulated the inflammatory response gene Tnf. There were no changes in apoptosis-related genes such as Trp53. Spaceflight altered the expression of genes regulating redox balance, cell cycle and senescence in cardiac tissue of mice. Thus, spaceflight may contribute to cardiac dysfunction due to oxidative stress.


Angiopoietin-2 enhances retinal vessel sensitivity to vascular endothelial growth factor.
Increased expression of vascular endothelial growth factor (VEGF) in the retina starting after postnatal day (P)7 results in neovascularization originating from deep retinal capillaries, but not those in the superficial capillary bed. Doxycycline was administered starting P0 to double transgenic mice with inducible expression of VEGF in the retina. These mice showed proliferation and dilation of superficial retinal capillaries, indicating that at this stage of development, the superficial capillaries are sensitive to the effects of VEGF. Angiopoietin-2 (Ang2) is expressed along the surface of the retina for several days after birth, but by P7 and later, Ang2 is only expressed in the region of the deep capillary bed. In mice with ubiquitous doxycycline-inducible expression of Ang2, in the absence of doxycycline, intravitreous injection of a gutless adenoviral vector expressing VEGF (AGV.VEGF) resulted in neovascularization of the cornea and iris, but no retinal neovascularization. After treatment with doxycycline to induce Ang2 expression, intravitreous injection of AGV.VEGF caused retinal neovascularization in addition to corneal and iris neovascularization. The retinal neovascularization originated from both the superficial and deep capillary beds. These data suggest that Ang2 promotes sensitivity to the angiogenic effects of VEGF in retinal vessels.


Whooping cough dynamics in Chile (1932-2010): disease temporal fluctuations across a north-south gradient.
The spatial-temporal dynamics of Bordetella pertussis remains as a highly interesting case in infectious disease epidemiology. Despite large-scale vaccination programs in place for over 50 years around the world, frequent outbreaks are still reported in many countries. Here, we use annual time series of pertussis incidence from the thirteen different regions of Chile (1952-2010) to study the spatial-temporal dynamics of Pertussis. The period 1975-1995 was characterized by a strong 4 year cycle, while the last two decades of the study period (1990-2010) were characterized by disease resurgence without significant periodic patterns. During the first decades, differences in periodic patterns across regions can be explained by the differences in susceptible recruitment. The observed shift in periodicity from the period 1952-1974 to the period 1975-1995 across regions was relatively well predicted by the susceptible recruitment and population size. However, data on vaccination rates was not taken into account in this study. Our findings highlight how demography and population size have interacted with the immunization program in shaping periodicity along a unique latitudinal gradient. Widespread B. pertussis vaccination appears to lead to longer periodic dynamics, which is line with a reduction in B. pertussis transmission, but our findings indicate that regions characterized by both low birth rate and population size decreased in periodicity following immunization efforts.


Intravenous low-grade endometrial stromal sarcoma with intracardiac extension: A CASE OF inaccurate tumor location on contrast-enhanced computed tomography.
We herein report a case of low-grade endometrial stromal sarcoma with intracardiac extension in a 58-year-old woman with a uterine tumor with intravascular involvement. The tumor was suspected preoperatively to be an endometrial stromal sarcoma by magnetic resonance imaging. The extent of intravascular involvement was determined to be below the level of the renal veins on preoperative contrast-enhanced computed tomography (CT). However, perioperative echography revealed that the tumor extended to the right atrium. An emergency cardiotomy with extracorporeal circulation was required. The risk of tumor embolism was reduced through transection of the inferior vena cava, but the tumor was difficult to remove completely. Postoperative hormonal therapy reduced the size of the residual tumor and no recurrence was detected for 1 year. The preoperative contrast-enhanced CT was unable to detect the free-floating intravascular tumor. This case illustrates a limitation of CT and indicates that accurate determination of the tumor extent for planning a surgical strategy in similar cases should be performed using multiple imaging methods.


Mental Fatigue and Physical and Cognitive Performance During a 2-Bout Exercise Test.
The 2-bout exercise protocol has been developed to diagnose nonfunctional overreaching and the "overtraining syndrome." It consists of 2 maximal exercise bouts separated by 4 hours. Mental fatigue negatively influences performance, but the effects of its occurrence during the 2-bout exercise protocol have never been investigated. The aim of this study was to examine whether mental fatigue (induced during the rest period) influences physical and cognitive performance during/after the second exercise bout of the 2-bout exercise protocol. Nine healthy, well-trained male cyclists participated in a single-blind, randomized, placebo-controlled crossover study. The intervention consisted of either 1.5-hour rest (control) or performing a computer-based Stroop task to induce mental fatigue. Cognitive (Eriksen Flanker task), physiological (lactate, maximum heart rate, and maximum wattage), and subjective data (mental fatigue-visual analog scale, Profile of Mood States, and rating of perceived exertion) were gathered. Ratings of fatigue, tension, and mental fatigue were affected in the mental fatigue condition (P < .05). Neither physiological nor cognitive differences were found between conditions. Ratings of mental fatigue were already affected after the first maximum exercise test (P < .05). Neither physical nor cognitive performance was affected by mental fatigue, but subjective ratings did reveal significant differences. It is recommended to exclude mentally challenging tasks during the 2-bout exercise protocol rest period to ascertain unaffected subjective test results. This study should be repeated in athletes diagnosed with nonfunctional overreaching/overtraining syndrome.


Transcriptional organization and regulation of the dnaK and groE operons of Chlamydia trachomatis.
The transcriptional organization and regulation of the dnaK and groE heat shock operons of Chlamydia trachomatis were studied and found to resemble those of the cognate operons of Bacillus subtilis and Clostridium acetobutylicum. The gene order is conserved (hrcA-grpE-dnaK), but no dnaJ homolog could be identified in this region. The dnaK operon was transcribed as a low-abundance polycistronic mRNA whose levels did not increase upon exposure to heat shock. In contrast, a more abundant 2.3-kb mRNA encoding only the dnaK sequence was detectable, and its steady-state level increased upon heat shock. The transcription initiation sites of the dnaK and groE operons were found to be preceded by sequences that resemble an Escherichia coli sigma70 consensus promoter. Upstream of each putative promoter is an inverted repeat sequence which resembles a similar element (CIRCE [controlling inverted repeat of chaperone expression]) found upstream of the dnaK and groE operons in at least 27 eubacterial species. In vitro transcription studies utilizing partially purified C. trachomatis RNA polymerase demonstrated that the regions containing the putative promoter elements of the dnaK and groE operons are functional, although heat shock-regulated expression could not be demonstrated.


Association of Blood Groups with the Severity and Outcome of COVID-19 Infection in Children.
The objective of this study was to find out the association of ABO blood groups with the severity and outcome of corona virus disease 2019 (COVID-19) in children. It included all laboratory-confirmed cases of COVID-19 and post-COVID multisystem inflammatory syndrome in children (MIS-C)/ Kawasaki disease (KD) like illness, admitted from March to September, 2020 to The Children's Hospital, Lahore. Out of 66 children, 45 (68.2%) were COVID-19 and 21 (31.8%) MIS-C/KD temporally associated with SARS-C0V-2. The mean age was 7.9 ± 4.2 years. Majority of children had mild to moderate illness 38 (57.6%), while 23 (34.8%) had severe or critical disease. Among all patients, 24 (36.4%) had some underlying comorbidity. Blood group A was significantly associated with severe and critical disease (p=0.030). COVID-19 in children had generally a good outcome, but children with blood group A were more susceptible to severe/critical disease. Key Words: Coronavirus disease 2019, ABO blood groups, Children, Severity, Outcome.


Adjusted vs Total Body Weight-Based Dosing of Sedation and Analgesia Used in the Intensive Care Unit.
Background: The purpose of this study was to evaluate if dosing fentanyl, dexmedetomidine, and propofol based on ideal or adjusted vs actual weight in patients would decrease overall opioid and sedative use. Methods: This was a retrospective chart review comparing adjusted vs actual weight-based dosing protocol of mechanically ventilated (MV) intensive care unit (ICU) adult patients who required fentanyl and either propofol or dexmedetomidine. Results: A total of 261 patients were included in which 101 patients were in the actual weight group and 160 patients were in the adjusted weight group. Total doses per MV day of fentanyl was 1042 ± 1060 µg in the actual weight group vs 901 ± 1025 µg in the adjusted weight group (P = .13). Total doses per MV day of midazolam was 20 ± 19 mg in the actual group vs 15 ± 19 mg adjusted group (P = .02). Average MV days was 8.2 vs 7.1 days, ICU length of stay was 10.6 vs 9.4 days, and self-extubation rates were 17.8% vs 4.4% in the actual group and adjusted group, respectively. Conclusion: Total midazolam doses per MV day were lower in the adjusted group. No significant change was seen in MV days, ICU length of stay, or self-extubation rates.


Synthetic biology approaches to copper remediation: bioleaching, accumulation and recycling.
One of the current aims of synthetic biology is the development of novel microorganisms that can mine economically important elements from the environment or remediate toxic waste compounds. Copper, in particular, is a high-priority target for bioremediation owing to its extensive use in the food, metal and electronic industries and its resulting common presence as an environmental pollutant. Even though microbe-aided copper biomining is a mature technology, its application to waste treatment and remediation of contaminated sites still requires further research and development. Crucially, any engineered copper-remediating chassis must survive in copper-rich environments and adapt to copper toxicity; they also require bespoke adaptations to specifically extract copper and safely accumulate it as a human-recoverable deposit to enable biorecycling. Here, we review current strategies in copper bioremediation, biomining and biorecycling, as well as strategies that extant bacteria use to enhance copper tolerance, accumulation and mineralization in the native environment. By describing the existing toolbox of copper homeostasis proteins from naturally occurring bacteria, we show how these modular systems can be exploited through synthetic biology to enhance the properties of engineered microbes for biotechnological copper recovery applications.


Perceived psychosocial stress and gestational weight gain among women with gestational diabetes.
Growing evidence links perceived stress-a potentially modifiable psychosocial risk factor-with health behaviors and obesity. Yet little is known about the relationship between stress during pregnancy and gestational weight gain, particularly among women with pregnancy complications. We conducted a cross-sectional analysis to examine associations between psychosocial stress during pregnancy and gestational weight gain among women with gestational diabetes. We used baseline data from the Gestational Diabetes's Effects on Moms (GEM) study: 1,353 women with gestational diabetes who delivered a term singleton within Kaiser Permanente Northern California were included. Perceived stress near the time of gestational diabetes diagnosis was measured using the validated Perceived Stress Scale (PSS10). Gestational weight gain was categorized according to the 2009 Institute of Medicine recommendations. Binomial regression analyses adjusted for gestational age and maternal age at the time of gestational diabetes diagnosis, and race/ethnicity and estimated rate ratios (RR) and their 95% confidence interval (CI). Among women with a normal pregravid Body Mass Index (BMI 18.5-24.9 kg/m2), there was a significant association between high (Q4) PSS score and risk of both exceeding and gaining below the Institute of Medicine recommendations compared to those with lower stress (Q1) [adjusted RR = 2.16 95% CI 1.45-3.21; RR = 1.39 95% CI 1.01-1.91, respectively.] Among women with pregravid overweight/obesity (BMI≥25 kg/m2), there was no association. Although the temporal relationship could not be established from this study, there may be a complex interplay between psychosocial stress and gestational weight gain among women with gestational diabetes. Further studies examining stress earlier in pregnancy, risk of developing gestational diabetes and excess/inadequate gestational weight gain are warranted to clarify these complex relationships.


[Detection of phosphorylated pyrimidine precursors of riboflavin in yeasts].
The nature of products formed from GTP in the presence of NADPH under effects of dialyzed extracts of the prototrophic strain of Pichia guilliermondii ATCC 9058 and mutants rib2 and rib3 with blocked second and third steps of flavinogenesis, respectively, was studied. The unstable pyrimidine intermediates were identified on the basis of the nature of pteridines formed upon condensation of riboflavin precursors with diacetyl. It was shown that under the action of extracts of the mutants rib3 GTP was predominantly converted into 2,5-diamino-6-hydroxy-4-ribitylaminopyrimidine phosphate. In similar studies on the extracts of the prototrophic strain, 2,6-dihydroxy-5-amino-4-ribitylaminopyrimidine phosphate, 2,6-dihydroxy-5-amino-4-ribitylaminopyrimidine and trace amounts of 2,5-diamino-6-hydroxy-4-ribitylaminopyrimidine were detected. No ribitylated intermediates of riboflavin were formed in the extracts of rib2 mutants. The results obtained are indicative of the participation of phosphorylated pyrimidine precursors in the second and third steps of flavinogenesis in yeasts. 6,7-Dimethyl-8-ribityllumazine phosphate is not the substrate for P. guilliermondii riboflavin synthase.


18F-FDG PET detection of unknown primary malignancy in dermatomyositis.
Dermatomyositis is an inflammatory myopathy that has an association with malignancy in adults. We present a patient who initially presented with adenopathy and progressive muscular weakness and was diagnosed with dermatomyositis and lung carcinoma on further investigation. Whole-body PET/CT scan revealed diffuse proximal muscle hypermetabolism representing the inflammatory nature of dermatomyositis, and an intensely FDG-avid primary right lower lung small cell lung carcinoma and metastatic thoracic lymphadenopathy. PET/CT imaging may offer an "all-in-one" procedure as an alternative to other diagnostic procedures, reducing the number of unnecessary investigations in patients presenting with paraneoplastic syndromes searching for underlying malignancy.


Substance P and spinal neurones.
When applied by microiontophoresis, substance P (sP) had a strong, but slow and prolonged excitatory action on nearly half the neurones tested in the lumbar spinal cord of cats. Motoneuronal antidromic field potentials only occasionally showed a significant effect of sP. Cerebral cortical neurones in cats and rats were much less readily excited than spinal interneurones. Some unresponsive units showed evidence of a depressant effect of sP. Although sP may have a significant function in central afferent pathways, it is not likely to be a quickly-acting synaptic transmitter.


Validity of Accelerometer-Based Sensor System for Muscle Tightness Estimation through Vibration on the Upper Limb.
Spasticity is a condition that profoundly impacts the ability to perform everyday tasks. However, its diagnosis requires trained physicians and subjective evaluations that may vary depending on the evaluator. Focal vibration of spastic muscles has been proposed as a non-invasive, pain-free alternative for spasticity modulation. We propose a system to estimate muscular tightness based on the propagation of elastic waves in the skin generated by focal vibration of the upper limb. The developed system generates focalized displacements on the biceps muscle at frequencies from 50 to 200 Hz, measures the vibration acceleration on the vibration source (input) and the distant location (output), and extracts features of ratios between input and output. The system was tested on 5 healthy volunteers while lifting 1.25 - 11.25 kg weights to increase muscle tone resembling spastic conditions, where the vibration frequency and weight were selected as explanatory variables. An increase in the ratio of the root mean squares proportional to the weight was found, validating the feasibility of the current approach to estimating muscle tightness.Clinical Relevance- This work presents the feasibility of a vibration-based system as an alternative method to objectively diagnose the degree of spasticity.


The behavior of the X- and Y-chromosomes in the oocyte during meiotic prophase in the B6.Y(TIR)sex-reversed mouse ovary.
Sexual differentiation of the germ cells follows gonadal differentiation, which is determined by the presence or the absence of the Y-chromosome. Consequently, oogenesis and spermatogenesis take place in the germ cells with XX and XY sex chromosomal compositions respectively. It is unclear how sexual dimorphic regulation of meiosis is associated with the sex-chromosomal composition. In the present study, we examined the behavior of the sex chromosomes in the oocytes of the B6.Y(TIR) sex-reversed female mouse, in comparison with XO and XX females. As the sex chromosomes fail to pair in both XY and XO oocytes during meiotic prophase, we anticipated that the pairing failure may lead to excessive oocyte loss. However, the total number of germ cells, identified by immunolabeling of germ cell nuclear antigen 1 (GCNA1), did not differ between XY and XX ovaries or XO and XX ovaries up to the day of delivery. The progression of meiotic prophase, assessed by immunolabeling of synaptonemal complex components, was also similar between the two genotypes of ovaries. These observations suggest that the failure in sex-chromosome pairing is not sufficient to cause oocyte loss. On the other hand, labeling of phosphorylated histone gammaH2AX, known to be associated with asynapsis and transcriptional repression, was seen over the X-chromosome but not over the Y-chromosome in the majority of XY oocytes at the pachytene stage. For comparison, gammaH2AX labeling was seen only in the minority of XX oocytes at the same stage. We speculate that the transcriptional activity of sex chromosomes in the XY oocyte may be incompatible with ooplasmic maturation.


Cellular Classes in the Human Brain Revealed In Vivo by Heartbeat-Related Modulation of the Extracellular Action Potential Waveform.
Determining cell types is critical for understanding neural circuits but remains elusive in the living human brain. Current approaches discriminate units into putative cell classes using features of the extracellular action potential (EAP); in absence of ground truth data, this remains a problematic procedure. We find that EAPs in deep structures of the brain exhibit robust and systematic variability during the cardiac cycle. These cardiac-related features refine neural classification. We use these features to link bio-realistic models generated from in vitro human whole-cell recordings of morphologically classified neurons to in vivo recordings. We differentiate aspiny inhibitory and spiny excitatory human hippocampal neurons and, in a second stage, demonstrate that cardiac-motion features reveal two types of spiny neurons with distinct intrinsic electrophysiological properties and phase-locking characteristics to endogenous oscillations. This multi-modal approach markedly improves cell classification in humans, offers interpretable cell classes, and is applicable to other brain areas and species.


Protein catabolism in pregnant snakes (Epicrates cenchria maurus Boidae) compromises musculature and performance after reproduction.
In many species the high energetic demands of reproduction induce a negative energy balance, and thus females must rely on tissue catabolism to complete the reproductive process. Previous works have shown that both fat and protein are energy resources during prolonged fasting in vertebrates. While many ecological studies on energy costs of reproduction have focused on variations in fat stores, the impact of protein investment on the female has not been thoroughly investigated. Notably, as there is no specialized storage form for proteins, intense catabolism is likely to entail structural (musculature) loss that may compromise maternal physical performance after reproduction. Measurements on captive rainbow boas ( Epicrates cenchria maurus) confirm that reproducing females undergo significant protein catabolism (as indicated by elevated plasma uric acid levels) and show considerable musculature loss during gestation (as detected by reduced width of the epaxial muscles). Protein mobilization entailed a significant functional loss that was illustrated by decrements in tests of strength and constriction after parturition. In wild situations, such effects are likely to decrease the snakes' ability to forage and apprehend prey. Hence, the time period needed to recover from reproduction can be extended not only because the female must compensate losses of both fat stores and functional muscle, but also because the ability to do so may be compromised. Performance alteration is likely to be of equal or greater importance than reduced energy stores in the physiological mediation of elevated post-reproduction mortality rates and infrequent reproductive bouts (e.g. biannual or triannual), two common ecological traits of female snakes.