Fault diagnosis for train plug door using weighted fractional wavelet packet decomposition energy entropy.
As the passage for passengers to get on and off, train plug doors directly affect the operation efficiency of the train and the personal safety of passengers. This paper proposes a non-contact fault diagnosis method for train plug doors based on sound signals. First, empirical mode decomposition (EMD) is utilized to process the raw sound signals. A signal reconstruction method by selecting intrinsic mode functions (IMFs) using hybrid selection criteria is then proposed. Second, novel feature named weighted fractional wavelet packet decomposition energy entropy (WFWPDE) is developed by introducing the idea of fractional calculus and weight to wavelet packet decomposition energy entropy (WDPE). Third, a synchronous optimization strategy is proposed to optimize the weights and hyperparameters of support vector machine (SVM) synchronously. Finally, the superiority and feasibility of the proposed method are verified on field-collected data. By comparing with different fault diagnosis methods, the proposed method performs best on fault diagnosis of train plug doors, with accuracy of 97.87%.


Is the utility of prostate-specific antigen velocity for prostate cancer detection affected by age?
To determine whether prostate-specific antigen velocity (PSAV) is useful for prostate cancer detection in men from different age groups, and whether the same PSAV thresholds can reasonably be applied to all men aged >or=40 years. From a large prostate cancer screening study, 13,615 men had data on age and a calculable PSAV. We used statistical analysis to examine the ability of PSAV to predict prostate cancer risk in each age decade. For men of all ages, the median PSAV was 0.6-0.7 ng/mL/year in men with prostate cancer, and 0-0.1 ng/mL/year in men with no prostate cancer (P < 0.005 for all). On receiver operating characteristic (ROC) analysis, the area under the curve was 0.800, 0.697, 0.693, and 0.668 for predicting prostate cancer risk using PSAV for men aged 40-49, 50-59, 60-69 and >or=70 years, respectively. In the multivariate model controlling for race, family history, and the total PSA level, both PSA and PSAV were significant independent predictors of prostate cancer risk in men of all ages. The PSAV is significantly higher in men of all ages with prostate cancer compared with men with no prostate cancer; although on ROC analysis it performed the best in young men. Interestingly, the median PSAV in men with prostate cancer was <0.75 ng/mL/year regardless of age, suggesting that this threshold may be too high. Overall, this data confirms that PSAV is a useful tool for prostate cancer detection for men aged >or=40 years.


Very early thrombolytic therapy in suspected acute myocardial infarction. The Thrombolysis Early in Acute Heart Attack Trial Study Group.
Three hundred fifty-two patients with suspected acute myocardial infarction (AMI) were randomized to placebo (175) or tissue-type plasminogen activator (rt-PA) (177). Patients were eligible if evaluated within 165 minutes from onset of chest pain and if age was less than 75 years. Electrocardiographic criteria were not required. A mobile coronary care unit with a cardiologist present was used to initiate treatment at home in 29% of the patients. Primary endpoints were infarct size (serum lactate dehydrogenase isoenzyme activity), left ventricular function (radioangiography) and exercise capacity at 30 days. AMI was diagnosed in 59% of all randomized patients. The incidence was similar in the 2 groups (placebo, 108, rt-PA, 101). Among all randomized patients, rt-PA was associated with significantly decreased infarct size and an increased ejection fraction. Among rt-PA-treated patients there were significantly fewer Q-wave infarctions. No difference in exercise capacity could be detected. No benefit was found in subgroups of patients without ST-segment elevation on the initial electrocardiogram. There were 18 (10.3%) and 11 (6.2%) deaths (p = 0.23) within 30 days in the placebo and rt-PA groups, respectively. Adverse reactions were similar in both groups with no excess of complications in the home-treated group. Very early treatment with rt-PA in patients with a strong suspicion of AMI and ST-segment elevation limits infarct size and improves left ventricular function. The infarct pattern is shifted from Q-wave to non-Q-wave infarcts by rt-PA. The study suggests that thrombolysis can be given before hospital admission without additional risk. Furthermore, electrocardiographic records are useful for selection of patients.


LRRning the RIte of springs.
The determination of the crystal structure of the ribonuclease inhibitor-ribonuclease A complex provides exciting new insight on how the leucine-rich repeat allows a single molecule to get around the problem of inhibiting an entire family of enzymes.


Actin is associated with tissue injury in trauma patients and produces a hypercoagulable profile in vitro.
While tissue injury provokes fibrinolysis shutdown in trauma, the mechanism remains elusive. Cellular death causes release of structural proteins, including actin and myosin, which may interact with clot formation and structure. We hypothesized that tissue injury is associated with high circulating actin and that actin produces a hypercoagulable profile with decreased fibrinolysis in vitro. Blood was collected from trauma activation patients at a single Level I trauma center for thrombelastography and proteomics. Proteomic analyses were performed through targeted liquid chromatography coupled with mass spectrometry using isotope-labeled standards for quantification of actin and its endogenous inhibitor gelsolin. Based on the results, we added physiologic concentrations of cytoskeletal G-actin to whole blood from healthy volunteers and analyzed changes in thrombelastography, as well as to plasma and examined clot architecture using confocal microscopy of fluorescently labeled fibrinogen. Overall, 108 trauma patients were included: majority (71%) men, median age of 32.7 years, 66% blunt mechanism, median New Injury Severity Score (NISS) of 41. Compared with patients without severe tissue injury (NISS < 15, n = 10), patients with severe tissue injury (NISS > 15, n = 98) had higher levels of circulating actin (0.0428 vs. 0.0301, p = 0.02). Further, there was a trend toward lower gelsolin levels in patients with fibrinolysis shutdown (0.1844 vs. 0.2052, p = 0.17) and tissue plasminogen activator resistance (0.1676 vs. 0.2188, p = 0.06).Ten healthy volunteers were included in the in vitro experiments (50% male; median age, 31.3 years). Actin significantly increased angle (40.0° to 52.9°, p = 0.002) and decreased fibrinolysis (percent clot lysis 30 minutes after reaching maximum amplitude, 4.0% to 1.6%; p = 0.002), provoking fibrinolytic shutdown in three patients. The addition of actin to control plasma decreased fiber resolvability of fibrin clots, monitored by microscopy, and decreased plasmin-mediated fibrinolysis. Actin increases clot propagation and provokes fibrinolysis shutdown in vitro, through a mechanism of plasmin inhibition. High circulating levels of actin are present in trauma patients with severe tissue injury, suggesting actin contributes to fibrinolysis shutdown in the setting of tissue injury.


Pharmacologic response of endothelium to microvascular temporary clip application.
To assess the effects of microvascular temporary clip application on vessel relaxing capability and endothelial substance release, the carotid rings of rats clipped for various durations were studied via bioassay. Noradrenaline and phenylephrine produced an immediate contraction and subsequent relaxation that failed to be suppressed by lysine acetylsalicylate or nicotine in the controls and in the arteries clipped for 0.5, 1, and 5 minutes; however, this relaxation was greatly reduced when the duration was 10 minutes. The results suggest the possible role of inadequate endothelium-derived relaxing factor release following prolonged application of the clips.


The new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification for TA, T1 bladder tumors: is it an improvement?
The World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification of urothelial neoplasms of the urinary bladder was developed in an attempt to both improve upon prior classification systems as well as to adopt a classification system that would have widespread acceptance. Prior to this classification system, numerous diverse grading schemes for bladder cancer existed whereby the same lesion seen by different pathologists would result in very different diagnoses solely based on definitional differences of lesions. Another strength of the consensus classification system is that it provides detailed histological criteria for papillary urothelial lesions. In contrast, prior grading systems for bladder tumors were vague and subjective. The current classification system allows for designation of a lesion (papillary urothelial neoplasm of low malignant potential), which biologically has a very low risk of progression, yet is not entirely benign. In the past, these lesions were a source of controversy, as some experts in the field required very restrictive criteria for the diagnosis of papilloma and would label such lesions as malignant. Other experts in the field, not wanting to label a patient with such a low-grade papillary lesion as having carcinoma, would diagnose these lesions as papilloma. This intermediate category allows both schools of thought to diagnose a lesion as not fully malignant, yet still documents need for additional follow-up. Since its inception, several studies have been published documenting the relationship of tumors classified using the WHO/ISUP system to prognosis. These articles are summarized within this review.


Differences in knowledge of dementia among older adults with normal cognition, mild cognitive impairment, and dementia: A representative nationwide sample of Korean elders.
Lack of knowledge about a disease could impede early diagnosis and may lead to delays in seeking appropriate medical care. The aim of this study was to explore knowledge of dementia (KOD) and to find the determinants of KOD among three groups: older adults with normal cognition, mild cognitive impairment (MCI), and dementia. A representative nationwide sample of 6141 Korean elders aged 65 years or older participated in face-to-face interviews and answered 14 questions pertaining to general information, etiology, symptoms, and treatment of dementia. Stepwise multiple regressions and path analyses probed the relationships between various sociodemographic variables and KOD. The percentage of correct responses was only 62%. The item 'A person who remembers things that happened in the past does not have dementia' was answered correctly (false) by only 24.8-27% of the respondents in all groups. Older adults with normal cognition had higher KOD scores than those with MCI or dementia. In the normal-cognition group, KOD scores were higher among highly educated, younger, and literate women with no depression and a family history of dementia. In contrast with the determinants in the normal-cognition group, only the ability to read and write predicted KOD scores in the dementia group. Efforts to enhance KOD in elder adults are needed. Public education regarding the differences between dementia and healthy aging may increase KOD among normal elders and those with MCI. Among elders with dementia, educational materials that do not require literacy may be more helpful in increasing KOD with the aim of preventing treatment delay.


Control of protein kinase C activity, phorbol ester-induced cytoskeletal remodeling, and cell survival signals by the scaffolding protein SSeCKS/GRAVIN/AKAP12.
The product of the SSeCKS/GRAVIN/AKAP12 gene ("SSeCKS") is a major protein kinase (PK) C substrate that exhibits tumor- and metastasis-suppressing activity likely through its ability to scaffold multiple signaling mediators such as PKC, PKA, cyclins, calmodulin, and Src. Although SSeCKS and PKCα bind phosphatidylserine, we demonstrate that phosphatidylserine-independent binding of PKC by SSeCKS is facilitated by two homologous SSeCKS motifs, EG(I/V)(T/S)XWXSFK(K/R)(M/L)VTP(K/R)K(K/R)X(K/R)XXXEXXXE(E/D) (amino acids 592-620 and 741-769). SSeCKS binding to PKCα decreased kinase activity and was dependent on the two PKC-binding motifs. SSeCKS scaffolding of PKC was increased in confluent cell cultures, correlating with significantly increased SSeCKS protein levels and decreased PKCα activity, suggesting a role for SSeCKS in suppressing PKC activation during contact inhibition. SSeCKS-null mouse embryo fibroblasts displayed increased relative basal and phorbol ester (phorbol 12-myristate 13-acetate)-induced PKC activity but were defective in phorbol 12-myristate 13-acetate-induced actin cytoskeletal reorganization and cell shape change; these responses could be rescued by the forced expression of full-length SSeCKS but not by an SSeCKS variant deleted of its PKC-binding domains. Finally, the PKC binding sites in SSeCKS were required to restore cell rounding and/or decreased apoptosis in phorbol ester-treated LNCaP, LNCaP-C4-2, and MAT-LyLu prostate cancer cells. Thus, PKC-mediated remodeling of the actin cytoskeleton is likely regulated by the ability of SSeCKS to control PKC signaling and activity through a direct scaffolding function.


Effectiveness of the internet based parent education program on applied behavior analysis for parents of children with autism spectrum disorder.
Parent education (PE) in autism spectrum disorder (ASD) is recognized as an important component of support for families living with ASD. Specifically, the knowledge of how to interact with children based on applied behavior analysis (ABA) is useful for parents. In this study, a short-term, internet based on-demand PE program was conducted for parents of children with ASD to acquire knowledge of ABA and basic teaching techniques. Parents of children with ASD were recruited as study participants. They attended on-demand lectures from their homes, performed homework tasks based on lecture content and emailed them to our team. The General Health Questionnaire 30 (GHQ) and Knowledge of Behavioral Principle as Applied to Children (KBPAC) were assessed before and after the program. Of the 25 participants, 21 attended all programs and completed all homework tasks and pre- and post-assessments. However, communication among participants via the bulletin board was low. KBPAC scores increased significantly from pre- to post-program scores, and GHQ subscales regarding anxiety and mood modulation decreased significantly from pre- to post-program scores. Positive results were obtained in the post-questionnaires as well. These findings suggest the practical applicability of an online PE program for parents of children with ASD based on ABA.


[Angiography in the diagnosis of neurinomas of the acoustic nerve (author's transl)].
40 cases of neurinoma of the acoustic nerve, studied by vertebral arteriography and controlled at surgery are reviewed. The angiographic signs of the lesion are analysed and a number of examples presented.


Syndromes, disorders and maternal risk factors associated with neural tube defects (VII).
Neural tube defects (NTDs) may be associated with syndromes, disorders and maternal risk factors. This article provides a comprehensive review of the syndromes, disorders and maternal risk factors associated with NTDs, including DK phocomelia syndrome (von Voss-Cherstvoy syndrome), Siegel-Bartlet syndrome, fetal warfarin syndrome, craniotelencephalic dysplasia, Czeizel-Losonci syndrome, maternal cocaine abuse, Weissenbacher- Zweymller syndrome, parietal foramina (cranium bifidum), Apert syndrome, craniomicromelic syndrome, XXagonadism with multiple dysraphic lesions including omphalocele and NTDs, Fryns microphthalmia syndrome, Gershoni-Baruch syndrome, PHAVER syndrome, periconceptional vitamin B6 deficiency, and autosomal dominant Dandy-Walker malformation with occipital cephalocele. NTDs associated with these syndromes, disorders and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders and maternal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.


Explainable process trace classification: An application to stroke.
Medical process trace classification exploits the activity sequences logged by an healthcare organization to classify traces themselves on the basis of some performance properties; this information can be used for quality assessment. State-of-the-art process trace classification resorts to deep learning, a very powerful technique which however suffers from the lack of explainability. In this paper we aim at addressing this issue, motivated by a relevant application, i.e., the classification of process traces for quality assessment in stroke management. To this end we introduce the novel concept of trace saliency maps, an instrument able to highlight what trace activities are particularly significant for the classification task. Through trace saliency maps we justify the output of the deep learning architecture, and make it more easily interpretable to medical users. The good results in our use case have shown the feasibility of the approach, and let us make the hypothesis that it might be translated to other application settings and to other black box learners as well.


Ca2(+)-activated K+ current involvement in neuronal function revealed by in situ single-channel analysis in Helix neurones.
1. The properties of single calcium-activated potassium channels (or C-channels) were studied in cell-attached patches using the patch-clamp technique. Experiments were performed on identified Ca2(+)-dependent U cells in juvenile specimens (1-2 months old) of Helix aspersa. 2. The criteria used to identify C-channels were based on comparison between macroscopic C-currents and currents reconstructed from unitary recordings. Both currents had a slow activation rate at large positive potentials which turned into fast activation after large Ca2+ entries. Both currents were blocked by intracellularly injected EGTA. 3. The unitary conductance in normal (5 mM) or reduced (0.5 mM) [K+]o ranged from 24 to 65 pS (mean +/- S.D., 48 +/- 13; n = 64). With 85-110 mM [K+]o, which is approximately equal to the internal [K+], the conductance was 64 pS and the reversal potential was approximately 0 mV. 4. C-channels in U cells were distributed in clusters of three to ten channels (mean 5.05 channels in seventy-five patches). Calcium channels were present in patches containing clustered C-channels. C-channels within clusters behaved independently. 5. With patch electrode containing 8 mM-calcium, C-channels opened transiently upon patch depolarization. Reopenings in quiescent depolarized patches were induced by whole-cell spikes triggered by current pulses applied to an intracellular electrode. Apparent inactivation of C-channels in depolarized patches was in fact due to a decrease in [Ca2+]i resulting from inactivation of Ca2+ channels. 6. Calcium-free saline solutions in the patch electrodes prevented C-channels from opening upon patch depolarization. Entry of calcium through the surrounding membrane induced delayed openings in the patch. Peak opening probability Po occurred 330 +/- 30 ms after a brief Ca2+ entry with a lag period of 50-80 ms. With patch electrodes filled with Ca2(+)-containing saline solutions and under conditions which maximized C-channel opening, peak Po was reached in 20-50 ms. The same value was observed for the whole-cell C-current. 7. The peak Po at a given patch potential and in response to a whole-cell spike was not altered by a previous long-lasting patch depolarization, or by producing several successive Ca2+ entries. Thus, C-channels did not appear to be inactivated by depolarization or increase in [Ca2+]i. 8. C-channels were found to be relatively highly voltage dependent, with an e-fold increase in Po per 14.9 mV increase in potential.(ABSTRACT TRUNCATED AT 400 WORDS)


Effects of herbivore on seagrass, epiphyte and sediment carbon sequestration in tropical seagrass bed.
Herbivores strongly affect the ecological structure and functioning in seagrass bed ecosystems, but may exhibit density-dependent effects on primary producers and carbon sequestration. This study examined the effects of herbivorous snail (Cerithidea rhizophorarum) density on snail intraspecific competition and diet, dominant seagrass (Thalassia hemprichii) and epiphyte growth metrics, and sediment organic carbon (SOC). The growth rates of the herbivorous snail under low density (421 ind m-2) and mid density (842 ind m-2) were almost two times of those at extremely high density (1684 ind m-2), indicating strong intraspecific competition at high density. Herbivorous snails markedly reduced the epiphyte biomass on seagrass leaves. Additionally, the seagrass contribution to herbivorous snail as food source under high density was about 1.5 times of that under low density, while the epiphyte contribution under low density was 3 times of that under high density. A moderate density of herbivorous snails enhanced leaf length, carbon, nitrogen, total phenol and flavonoid contents of seagrasses, as well as surface SOC content and activities of polyphenol oxidase and β-glucosidase. However, high density of herbivorous snails decreased leaf glucose, fructose, detritus carbon, and total phenols contents of seagrasses, as well as surface SOC content and activities of polyphenol oxidase and β-glucosidase. Therefore, the effects of herbivorous snail on seagrass, epiphyte and SOC were density-dependent, and moderate density of herbivorous snail could be beneficial for seagrasses to increase productivity. This provided theoretical guidance for enhancing carbon sink in seagrass bed and its better conservation.


Catecholamine-induced cardiac hypertrophy uncouples beta-adrenoceptors from slow calcium channels.
Changes in the parameters of Ca(2+)-dependent slow action potentials (APs) and in their sensitivity to noradrenaline, forskolin, dibutyryl-cAMP and extracellular Ca2+ concentration were studied and compared in left ventricular trabeculae from normal control rats and rats with cardiac hypertrophy. Cytochemical studies were also carried out to determine changes in the activity of membrane-bound adenylate cyclase. Hypertrophy was induced by administration of 5 mg/kg isoproterenol once daily for 7 days. In hypertrophied cardiac muscle, the overshoot of the slow APs was increased by 75%, the maximum rate of rise (Vmax) increased by 76% and the AP duration at 50% repolarization (APD50) prolonged by 56%. The Vmax, an indicator of the slow inward Ca2+ current, increased, in a dose-dependent manner, in response to the beta-adrenoceptor agonist noradrenaline, the adenylate cyclase activator forskolin, the protein kinase activator cAMP and elevated Ca2+ concentration in normal control preparations, whereas in hypertrophied myocardium, the beta-agonist noradrenaline and the adenylate cyclase activator forskolin had no effect. In cytochemical studies with ATP as substrate, adenylate cyclase activity was localized in the sarcolemma, and significantly fewer reaction products appeared on the outer side of the cell membrane in hypertrophied myocytes than in control myocytes. The results suggest that catecholamine-induced cardiac hypertrophy damages the catalytic subunit of membrane-bound adenylate cyclase, thus uncoupling beta-adrenoceptors from slow Ca2+ channels in the transmembrane signalling process.


Choledochoduodenostomy with LAMS (Hot-Axios type) for malignant obstructive jaundice - An increasingly used technique.
An 82-year-old woman who presented with obstructive jaundice and constitutional syndrome was diagnosed with pancreatic adenocarcinoma. Palliative management was decided with endoscopic ultrasound drainage as it was impossible to perform ERCP due to anatomical alterations, a consequence of the neoplastic lesion.


A Comprehensive Study of the Impacts of Oat β-Glucan and Bacterial Curdlan on the Activity of Commercial Starter Culture in Yogurt.
This study provides important information about the impacts of various levels of oat (OBG) and bacterial (curdlan) β-glucan and fat contents in milk on survivability and metabolism of yogurt starter cultures. The results show that addition of β-glucans in the concentration higher than 0.25% reduced starter bacterial counts during storage and prolonged the milk acidification process. A significant increase in lactose consumption by starter cultures was noted in the yogurt samples with OBG addition up to 0.75%. The highest (by 567% on average) increase in lactic acid content was noted in the control yogurts. Whereas the lowest (by 351%) increase in lactic acid content was noted in yogurts with OBG. After 28-day storage, the acetic aldehyde content was significantly influenced by fat content, type and addition level of polysaccharide. A higher increase in acetoin content was noted in samples with 0.25% than in samples with 1% of polysaccharides. In turn, significantly lower increases in diacetyl and 2,3-pentanedione contents were observed in the yogurt samples with OBG than in these with curdlan, with diacetyl production increase along with the higher concentration of the polysaccharide. The addition of OBG and curdlan to milk contributed to differences in the starter culture metabolism, consequently, in the milk acidification dynamics.


HIF-1α inhibits mitochondria-mediated apoptosis and improves the survival of human adipose-derived stem cells in ischemic microenvironments.
Human adipose mesenchymal stem cells (hADSCs) show poor survival after transplantation, limiting their clinical application. Tissue regeneration resulting from stem cell treatment may be caused by attenuation of hypoxia-inducible factor-1α (HIF-1α). In this study, we constructed hADSCs stably expressing HIF-1α and investigated the potential effects of HIF-1α expression in the ischemic microenvironment on mitochondrial apoptosis and survival of hADSCs, and studied the mechanisms involved. Apoptosis was induced by an ischemic microenvironment in vitro. ADSCs with stable HIF-1α expression were established. Cell survival and apoptosis were observed by CCK-8 assay, western blotting, flow cytometry, and fluorescence staining. ADSCs were subcutaneously transplanted into nude mice in the location where a hypoxia ischemic microenvironment was simulated in vivo. After 1, 3, and 7 d, mitochondrial apoptotic proteins were evaluated by immunohistochemistry and immunofluorescence staining. Exogenous HIF-1α downregulated mitochondrial reactive oxygen species, cytochrome c, caspase-9, and caspase-3, but inhibited mitochondrial membrane potential depolarization and increased the Bcl-2/bax ratio. HIF-1α prevented apoptosis and promoted vascular endothelial growth factor (VEGF) secretion as demonstrated by enzyme-linked immunosorbent assay (ELISA), terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and flow cytometry analysis. HIF-1α enhanced the survival of transplanted ADSCs in nude mice. We have shown that through inhibition of the mitochondria-mediated apoptotic pathway and promotion of VEGF secretion in hADSCs in an ischemic microenvironment, HIF-1α may potentially be applied in clinical therapy and as an alternative strategy for improving hADSC therapy.


Lymphoma studies by the Australasian Leukaemia and Lymphoma Group.
The Australasian Leukaemia and Lymphoma Group (ALLG) can trace its origins to 1973. It now encompasses virtually all the major hospitals in Australia and New Zealand that treat leukaemias and lymphomas. Over the years the Group as a whole, and members individually, have participated in many clinical treatment trials for aggressive lymphomas. Initially trials were conceived and carried out locally, but in recent years, in addition to continuing its own studies, the Group has been a major contributor to international trials including two that have been particularly influential, known as MInT and CORAL. The MInT study confirmed the value of adding rituximab to standard chemotherapy for aggressive lymphomas; CORAL helped define optimum methods of autografting for relapse. The ALLG has contributed and continues to contribute to the improving outcome for patients with aggressive lymphomas.


Meta-analysis of vitamin D-binding protein and cancer risk.
Epidemiologic evidence supported a role for vitamin D and vitamin D receptor (VDR) polymorphisms in cancer risk. Beyond VDR, the biologic effects of vitamin D are mediated by the vitamin D-binding protein (DBP), a key protein in vitamin D metabolism. Furthermore, the gene encoding the DBP (GC, group-specific component) has an important role in the vitamin D pathway. Several studies investigated DBP serologic levels and GC polymorphisms in association with cancer risk with controversial results. Thus, we carried out a meta-analysis to investigate these associations. We included 28 independent studies concerning the following tumors: basal cell carcinoma, bladder, breast, colon-rectum, endometrium, liver, esophagus, stomach, melanoma, pancreas, prostate, and kidney. Through random-effect models, we calculated the summary odds ratios (SOR) for serum DBP and the GC polymorphisms rs2282679, rs12512631, rs7041, rs4588, rs17467825, rs1155563, and rs1352844. We found a borderline decrease in cancer risk for subjects with high compared with low levels of DBP [SOR, 0.75; 95% confidence interval (CI), 0.56-1.00]. Dose-response meta-analysis indicates a nonsignificant decrease risk for an increase of 1,000 nmol/L of DBP (SOR, 0.96; 95% CI, 0.91-1.01). We found no significant alterations in cancer risk for subjects carrying any of the studied GC polymorphisms compared with wild-type subjects both in the main analysis and in analyses stratified by cancer type and ethnicity. We found trends toward significance, suggesting a role of DBP in cancer etiology, which should be confirmed in further studies. To our knowledge, this is the first study to investigate GC polymorphisms and DBP serologic levels in association with any type of cancer.


Some effects of changing soil chemistry on decomposition of plant litters and cellulose on a Scottish moor.
Nitrogen (N), phosphorus (P), calcium (Ca) and soluble carbohydrates (CHO) were each added at three levels to a moorland podzol, and the decomposition of three constrasting untreated substrates (Calluna vulgaris stems,Molinia caerulea leaves, and cotton strips) compared between treated and untreated plots. All soil treatments increased decay rates of all three substrates, except for the highest levels of P and CHO, which appeared to inhibit decomposition of cotton andMolinia. The results generally indicated use by the decomposers of nutrients or energy sources from the soil to aid decomposition of untreated substrates. With all additives (N, P, Ca, CHO) maximum degree of change was inversely related to substrate quality. All responses were nonlinear. Optimal levels of N and Ca were in the same order as substrate quality, i.e. optimum forCalluna<cotton<Molinia, but this was not so with P and CHO. The patterns of change in decomposition rates with soil treatments could not be explained entirely by edaphic and substrate quality effects; it was also necessary to consider selection of decomposer organisms, both by substrate and by treatment. More generally, there were no simple 'limiting factors'. Rather, decay rates were controlled by the combined 'availability' of a number of resources (including availability of suitable decomposer organisms). The consequences of this, especially the importance of indirect and interactive effects, are discussed.


Identifying a long-term/chronic, non-cancer pain population using a one-dimensional verbal pain rating scale: an epidemiological study.
The usefulness of the verbal pain rating scale (VRS) included in the Short Form 36 (SF-36) in identifying characteristics of long-term pain conditions, was analyzed using data from the 1994 Danish Health and Morbidity Survey. Based on the rating of pain intensity during a 4-week recall period the respondents were categorized into three groups: a high pain group (HPG) consisting of persons reporting moderate to severe pain (VRS 4-6), a low pain group (LPG) who rated their pain as very mild or mild (VRS 2-3), and a control group (CG) with no pain (VRS 1). The investigated sample comprised 3992 persons (HPG=563 persons, LPG=1714, and CG=1715 persons). Older age, educational level (< 10 years of schooling), cohabitation status (divorce/separation), and moderate to severe physical job strain were found to be significant risk factors for reporting high pain intensity (HPG). Only minor differences were observed between the LPG and CG. The proportion of respondents with good perceived health was significantly lower in the HPG compared with LPG and CG. The dominant complaints in the HPG were related to the musculoskeletal system. During a 14-day period prior to the interview persons in the HPG had a mean of 1.19 working days lost due to illness compared with a mean of 0.2 for the LPG and CG. Analyzing the use of medical services during the year before the interview, persons belonging to the HPG had an average number of nine contacts to general practitioners and specialized doctors in the primary sector as compared to six for the LPG and four for the CG. Mean numbers of hospital admissions were 0.29 for the HPG, 0.15 for the LPG and 0.10 for the CG. Mean numbers of in-hospital days were 1.60, 0.80, and 0.43 for the HPG, LPG, and CG, respectively. Our study suggest that one-dimensional pain intensity scoring using a simple VRS-scoring is useful as a screening instrument for identifying persons suffering from pain of a more complex nature. High intensity scores on a pain intensity scale should indicate to the investigator that she/he might be facing a person whose pain complaints and behavior are not only based on a pure biological background, but in whom also severe psychological and social problems might be present.


A randomized, controlled clinical evaluation of two resin cement systems in the adhesion of CAD/CAM-fabricated resin nanoceramic restorations: 18-month preliminary results.
The purpose of this clinical study was to evaluate the performance of two different adhesive resin cement systems in the cementation of inlay/onlay restorations produced from resin nanoceramic blocks using the CAD/CAM system. A total of 70 inlay/onlay restorations made from Cerasmart (GC, Tokyo, Japan) resin nanoceramic blocks using CEREC Omnicam (Sirona Dental, Bensheim, Germany) were placed in 53 patients. The restorations were cemented with RelyX U200 Automix (3M ESPE, Seefeld, Germany) self-adhesive resin cement (RXU) after selective enamel etching or with G-CEM LinkForce (GC, Tokyo, Japan) adhesive resin cement (GCL) in combination with a universal adhesive (G-Premio Bond) in selective etch mode. At baseline and after 6, 12, and 18 months, restorations were examined by two calibrated clinicians according to modified USPHS criteria. The data were analyzed using Chi-square (χ2 ) test and Friedman test (p < 0.05). After 18 months, two teeth at RXU group were endodontically treated due to hypersensitivities. At GCL group, three restorations were lost due to debondings (2) and ceramic fracture (1). The survival rates of RXU (94.3%) and GCL group (91.4%) exhibited no statistically significant difference (p = 0.661). No significant differences were detected for surface texture, secondary caries, anatomic form, color match, marginal discoloration, marginal integrity, interproximal contacts, and patient satisfaction (p > 0.05). The two resin cement systems showed acceptable clinical performance for the cementation of resin nanoceramic CEREC Omnicam inlay/onlay restorations. Resin nanoceramic restorations fabricated using CEREC Omnicam and cemented with either a self-adhesive or a universal adhesive/resin cement system demonstrated clinically acceptable results for posterior teeth in a single visit.


The chloroacetate esterase reaction for mast cells in dermatopathology: a comparison with metachromatic staining methods.
This paper compares standard metachromatic methods with Leder's chloroacetate esterase reaction on mast cells in paraffin wax-embedded tissue of urticaria pigmentosa and a variety of inflammatory and benign neoplastic cutaneous conditions. Our conclusions are that Leder's method allows easier identification of mast cells and can be a useful adjunct to conventional metachromatic methods. The technique could be conveniently adopted in routine dermatopathology for mast cell identification.


A humanized IgG but not IgM antibody is effective in prophylaxis and therapy of yellow fever infection in an AG129/17D-204 peripheral challenge mouse model.
Yellow fever virus (YFV), a member of the genus Flavivirus, is a mosquito-borne virus found in tropical regions of Africa and South America that causes severe hepatic disease and death in humans. Despite the availability of effective vaccines, YFV is responsible for an estimated 200,000 cases and 30,000 deaths annually. There are currently no prophylactic or therapeutic strategies approved for use in human YFV infections. Furthermore, implementation of YFV 17D-204 vaccination campaigns has become problematic due to an increase in reported post-vaccinal adverse events. We have created human/murine chimeric MAbs of a YFV-reactive murine monoclonal antibody (mMAb), 2C9, that was previously shown to protect mice from lethal YFV infection and to have therapeutic activity. The new chimeric (cMAbs) were constructed by fusion of the m2C9 IgG gene variable regions with the constant regions of human IgG and IgM and expressed in Sp2 murine myelomas. The 2C9 cMAbs (2C9-cIgG and 2C9-cIgM) reacted with 17D-204 vaccine strain in an enzyme-linked immunosorbent assay and neutralized virus in vitro similarly to the parent m2C9. Both m2C9 and 2C9-cIgG when administered prophylactically 24h prior to infection protected AG129 mice from peripheral 17D-204 challenge at antibody concentrations ≥1.27 μg/mouse; however, the 2C9-cIgM did not protect even at a dose of 127 μg/mouse. The 17D-204 infection of AG129 mice is otherwise uniformly lethal. While the m2C9 was shown previously to be therapeutically effective in YFV-infected BALB/c mice at day 4 post-infection, the m2C9 and 2C9-cIgG demonstrated therapeutic activity only when administered 1 day post-infection in 17D-204-infected AG129 mice.


Exploration of Betalains and Determination of the Antioxidant and Cytotoxicity Profile of Orange and Purple Opuntia spp. Cultivars in Greece.
Replacing synthetic dyes with natural pigments has gained great attention over the past years in the food industry, due to the increased alertness of consumers for nontoxic and natural additives. Betalains are water-soluble nitrogenous natural pigments that are used as natural colorants in food industries, due to their applicability and their rich pharmacological profile including antioxidant, antimicrobial, and anticancer properties. Therefore, there is a need for a detailed exploration of betalains to fully exploit their properties. Opuntia spp. plants are one of the primary sources of betalains. The objective of this study was to identify betalain phytochemical content in prickly pear cactus of two different Opuntia species from Greece (an Opuntia ficus-indica (L.) Mill (OFI) orange prickly pear cultivar and an Opuntia spp. purple prickly pear cultivar) using modern analytical techniques as also to evaluate their antioxidant and cytotoxicity profile. To achieve this we used an array of analytical techniques, including ultra-violet-vis (UV-Vis) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and liquid chromatography-high resolution mass spectrometry (LC-HRMS) as also cell based in vitro assays. These enabled us to establish a rapid approach that can distinguish the different Opuntia spp. cultivars based on their phytochemical constituents through untargeted metabolomics analysis using ultra-high performance liquid chromatography-mass spectrometry - quadrupole time-of-flight (UPLC/MS Q-TOF). These findings could allow a further exploitation of Opuntia species and especially their enriched betalain phytochemical profile as viable source of natural food colorants.


Experimental tracheal revascularization with omentum.
We assessed omental revascularization of heterotopic tracheal implants in rats, and investigated the influence of factors that can enhance revascularization. The trachea of the donor animal was excised in two parts, and each tracheal allograft was implanted in the omentum of two recipients. The influence of mechanical factors was evaluated by applying traction at both ends of the graft with and without drainage of the tracheal lumen, and the influence of pharmacologic factors by giving cefonicid, hydrocortisone, cefonicid plus hydrocortisone, or cyclosporine and azathioprine during the postoperative period. Revascularization of the graft from the omentum with preservation of the tracheal structure was established. Graft viability showed significant differences between the tracheal implants to which no traction had been applied and those with traction at both ends. Tracheal allografts from animals receiving immunosuppressants were completely viable and no significant differences were found between the controls and animals in this group.


Acetaminophen hepatotoxicity in mice: Effect of age, frailty and exposure type.
Acetaminophen is a commonly used analgesic that can cause severe hepatotoxicity in overdose. Despite old age and frailty being associated with extensive and long-term utilization of acetaminophen and a high prevalence of adverse drug reactions, there is limited information on the risks of toxicity from acetaminophen in old age and frailty. This study aimed to assess changes in the risk and mechanisms of hepatotoxicity from acute, chronic and sub-acute acetaminophen exposure with old age and frailty in mice. Young and old male C57BL/6 mice were exposed to either acute (300 mg/kg via oral gavage), chronic (100 mg/kg/day in diet for six weeks) or sub-acute (250 mg/kg, t.i.d., for three days) acetaminophen, or saline control. Pre-dosing mice were scored for the mouse clinical frailty index, and after dosing serum and liver tissue were collected for assessment of toxicity and mechanisms. There were no differences with old age or frailty in the degree of hepatotoxicity induced by acute, chronic or subacute acetaminophen exposure as assessed by serum liver enzymes and histology. Age-related changes in the acetaminophen toxicity pathways included increased liver GSH concentrations, increased NQO1 activity and an increased pro- and anti-inflammatory response to acetaminophen in old age. Frailty-related changes included a negative correlation between frailty index and serum protein, albumin and ALP concentrations for some mouse groups. In conclusion, although there were changes in some pathways that would be expected to influence susceptibility to acetaminophen toxicity, there was no overall increase in acetaminophen hepatotoxicity with old age or frailty in mice.


The Cultural and Linguistic Adaptation to Brazilian Portuguese and Content Validity of the Patient Expectations and Satisfaction With Prenatal Care Instrument.
Patient satisfaction reflects how an individual's expectations, goals, and preferences are met by health care providers or services. Most research on patient expectations and satisfaction has been conducted in developed countries; there was no Portuguese language instrument to measure pregnant women's expectations and satisfaction with prenatal care. To adapt and test the Patient Expectations and Satisfaction with Prenatal Care (PESPC) instrument for use in Brazil. We conducted a systematic cultural and linguistic adaptation of the PESPC into Brazilian Portuguese and tested the validity of the adapted instrument. Implementation of this rigorous methodological process resulted in a valid, reliable, culturally, and linguistically appropriate instrument. We recommend further assessment of the Brazilian Portuguese PESPC with more diverse samples of Portuguese-speaking pregnant women in Brazil and other countries. Application of this structured approach to cultural and linguistic instrument adaptation is one way to further transcultural nursing research.


Structural systems biology: modelling protein interactions.
Much of systems biology aims to predict the behaviour of biological systems on the basis of the set of molecules involved. Understanding the interactions between these molecules is therefore crucial to such efforts. Although many thousands of interactions are known, precise molecular details are available for only a tiny fraction of them. The difficulties that are involved in experimentally determining atomic structures for interacting proteins make predictive methods essential for progress. Structural details can ultimately turn abstract system representations into models that more accurately reflect biological reality.


Spontaneous vs. naloxone-induced abstinence in dependent rats self-administering L-alpha-acetylmethadol (LAAM) or morphine.
Rats maintained dependence by the self-administration of LAAM or morphine. Following the substitution of saline for LAAM, REM sleep was not disrupted, and the frequency of lever pressing for saline self-injections peaked at about 24 hr. In contrast, following the substitution of saline for morphine, REM sleep was suppressed for 24 hr while the frequency of lever pressing for saline self-injections peaked within 8 hr. When abstinence was induced by hourly iv naloxone injections, REM sleep occurrences were suppressed to a similar degree and for similar durations during naloxone-induced abstinence from both morphine and LAAM. These results suggest that the level of physical dependence maintained during self-administration of LAAM and morphine was similar. The relatively mild abstinence syndrome that was seen during saline substitution in LAAM-dependent rats was most likely related to the long plasma half-lives of the pharmacologically active N-demethylated metabolites of LAAM.


Treatment of Chagas Disease in the United States.
Chagas disease (CD) is endemic to much of Latin America, but also present in the United States (U.S.). Following a lengthy asymptomatic period, CD produces serious cardiac or gastrointestinal complications in 30-40% of people. Less than 1% of the estimated six million cases in the Americas, including 326,000-347,000 in the U.S., are diagnosed. Infected persons are typically unaware and the bulk of clinicians are unfamiliar with current treatment guidelines. This review provides U.S. and other clinicians with the latest knowledge of CD treatment. Chagas cardiomyopathy (CCM) causes severe fibrosis and autonomic damage in the myocardium. Eliminating the parasite through antitrypanosomal therapy with benznidazole, a nitroimidazole derivative or nifurtimox, a nitrofuran compound, potentially prevents heart failure and other sequelae of advanced CCM. Benznidazole, recently approved by the U.S. Food and Drug Administration (FDA) for children 2-12 years old, is the first-line therapy; optimal dosages are currently being studied. Antitrypanosomal therapy prevents congenital transmission; produces high cure rates for acute, congenital, and early chronic cases; and improves clinical outcomes in adult chronic indeterminate cases. However, this benefit was not observed in a large clinical trial that included patients with advanced CCM. Treatment with antitrypanosomal drugs can cure CD in acute, congenital, and early chronic cases and provides improved clinical outcomes for chronic indeterminate cases. This treatment should be offered as early as possible, before advanced CCM develops.


Angiogenesis and prostate cancer: MicroRNAs comes into view.
Angiogenesis, the formation of new blood vessels, is an important stage in the growth of cancer. Extracellular matrix, endothelial cells, and soluble substances must be carefully coordinated during the multistep procedure of angiogenesis. Inducers and inhibitors have been found to control pretty much every phase. In addition to benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and angiogenesis have a critical role in the initiation and progression of prostate cancer. MicroRNA (miRNA) is endogenous, short, non-coding RNA molecules of almost 22 nucleotides play a role in regulating cellular processes and regulating several genes' expression. Through controlling endothelial migration, differentiation, death, and cell proliferation, miRNAs have a significant function in angiogenesis. A number of pathological and physiological processes, particularly prostate cancer's emergence, depend on the regulation of angiogenesis. Investigating the functions played with miRNAs in angiogenesis is crucial because it might result in the creation of novel prostate cancer therapies that entail regulating angiogenesis. The function of several miRNAs and its targeting genes engaged in cancer of the prostate angiogenesis will be reviewed in this review in light of the most recent developments. The potential clinical utility of miRNAs potentially a novel therapeutic targets will also be explored, as well as their capacity to control prostate cancer angiogenesis and the underlying mechanisms.


Immobilization of heavy metals in polluted soils by the addition of zeolitic material synthesized from coal fly ash.
The use of zeolitic material synthesized from coal fly ash for the immobilization of pollutants in contaminated soils was investigated in experimental plots in the Guadiamar Valley (SW Spain). This area was affected by a pyrite slurry spill in April 1998. Although reclamation activities were completed in a few months, residual pyrite slurry mixed with soil accounted for relatively high leachable levels of trace elements such as Zn, Pb, As, Cu, Sb, Co, Tl and Cd. Phytoremediation strategies were adopted for the final recovery of the polluted soils. The immobilization of metals had previously been undertaken to avoid leaching processes and the consequent groundwater pollution. To this end, 1100 kg of high NaP1 (Na6[(AlO2)6(SiO2)10] .15H2O) zeolitic material was synthesized using fly ash from the Teruel power plant (NE Spain), in a 10 m3 reactor. This zeolitic material was manually applied using different doses (10000-25000 kg per hectare), into the 25 cm topsoil. Another plot (control) was maintained without zeolite. Sampling was carried out 1 and 2 years after the zeolite addition. The results show that the zeolitic material considerably decreases the leaching of Cd, Co, Cu, Ni, and Zn. The sorption of metals in soil clay minerals (illite) proved to be the main cause contributing to the immobilization of these pollutants. This sorption could be a consequence of the rise in pH from 3.3 to 7.6 owing to the alkalinity of the zeolitic material added (caused by traces of free lime in the fly ash, or residual NaOH from synthesis).


Initiation and patterning of the snake dentition are dependent on Sonic hedgehog signaling.
Here we take the first look at cellular dynamics and molecular signaling in the developing snake dentition. We found that tooth formation differs from rodents in several respects. The majority of snake teeth bud off of a deep, ribbon-like dental lamina rather than as separate tooth germs. Prior to and after dental lamina ingrowth, we observe asymmetries in cell proliferation and extracellular matrix distribution suggesting that localized signaling by a secreted protein is involved. We cloned Sonic hedgehog from the African rock python Python sebae and traced its expression in the species as well as in two other snakes, the closely-related Python regius and the more derived corn snake Elaphe guttata (Colubridae). We found that expression of Shh is first confined to the odontogenic band and defines the position of the future dental lamina. Shh transcripts in pythons are progressively restricted to the oral epithelium on one side of the dental lamina and remain in this position throughout the prehatching period. Shh is expressed in the inner enamel epithelium and the stellate reticulum of the tooth anlagen, but is absent from the outer enamel epithelium and its derivative, the successional lamina. This suggests that signals other than Shh are responsible for replacement tooth formation. Functional studies using cyclopamine to block Hh signaling during odontogenesis prevented initiation and extension of the dental lamina into the mesenchyme, and also affected the directionality of this process. Further, blocking Hh signaling led to disruptions of the inner enamel epithelium. To explore the role of Shh in lamina extension, we looked at its expression in the premaxillary teeth, which form closer to the oral surface than elsewhere in the mouth. Oral ectodermal Shh expression in premaxillary teeth is lost soon after the teeth form reinforcing the idea that Shh is controlling the depth of the dental lamina. In summary, we have found diverse roles for Shh in patterning the snake dentition but, have excluded the participation of this signal in replacement tooth formation.


Effect of selenite on the morphology and respiratory activity of Phanerochaete chrysosporium biofilms.
The temporal and spatial effects of selenite (SeO3(2-)) on the physical properties and respiratory activity of Phanerochaete chrysosporium biofilms, grown in flow-cell reactors, were investigated using oxygen microsensors and confocal laser scanning microscopy (CLSM) imaging. Exposure of the biofilm to a SeO3(2-) load of 1.67mgSeL(-1)h(-1) (10mgSeL(-1) influent concentration), for 24h, resulted in a 20% reduction of the O2 flux, followed by a ∼10% decrease in the glucose consumption rate. Long-term exposure (4days) to SeO3(2-) influenced the architecture of the biofilm by creating a more compact and dense hyphal arrangement resulting in a decrease of biofilm thickness compared to fungal biofilms grown without SeO3(2-). To the best of our knowledge, this is the first time that the effect of SeO3(2-) on the aerobic respiratory activity on fungal biofilms is described.


Asymmetrical hydrocephalus following evacuation of a subdural haematoma.
A case of asymmetrical hydrocephalus complicating the surgical evacuation of a subdural haematoma is reported.


Swimming behavior and energy metabolism of the calanoid copepod invader Sinodiaptomus sarsi.
The appearance of invasive species threatens the integrity of aquatic ecosystems. Much is known about dispersal and introduction mechanisms while little is known on the biological properties of invasive species, such as behavior and energy efficiency, allowing them to successfully colonize new environments and compete with native species. This study examines the functional features of the Asian invasive copepod Sinodiaptomus sarsi (Rylov, 1923) that has invaded Europe since 2016. We focused on the energy metabolism and kinematic parameters of the main swimming types (i.e., gliding, hovering, small relocation jumps, and the escape reaction) of females and males of S. sarsi. Based on the above parameters, the mechanical energy for swimming and the respiration energy needed for movement were calculated. Females and males spend up to 95% of time hovering and slowly gliding at a speed of up to 0.5 cm s-1. During the remaining time, the average swimming speed was 8 cm s-1 by small jumps. In contrast, the average speed was 42 cm s-1 during escape swimming. Non-ovigerous females moved faster than ovigerous females during all relocation swimming types except for upward gliding. While performing small jumps with a frequency of 0.79 Hz, the respiration rate of active non-ovigerous females (0.32 ± 0.03 µg O2 ind-1 h-1) was 2.1 times higher than that of anesthetized individuals. The respiration energy associated with movement was 2.6 * 10-3 J h-1, while the total mechanical energy was only 4.2% of this value. The low energy cost of feeding along with the high speed of locomotion may explain the success of this Asian invader in European waters.


Serological and immunohistochemical detection of a 65-kDa oncofetal protein in breast cancer.
Sera from 132 breast cancer patients and 112 healthy female controls were tested with a double-antibody sandwich ELISA using two different monoclonal antibodies against the 65-kDa oncofetal protein, termed p65. Of cancer sera, 90.2% were positive for p65. The average level of p65 was 466.5 +/- 243.8 ng/ml (mean +/- S.D.) in carcinomas and 37.4 +/- 29.5 ng/ml (mean +/- S.D.) in controls (P < 0.0005). A selected group (n = 15) of these 132 patients were needle-biopsied and assessed immunohistochemically using monoclonal antibodies against p65. Nucleocytoplasmic expression was found in 12 patients (80%) using monoclonal antibodies. Expressions of p65 were concordant in 13 (86%) cases between serum and tumour tissues, but did not correlate with tumour DNA ploidy, histological grade or hormone receptors levels. Sera were also tested for CA 15-3 with the average value in cancer serum being 132.4 +/- 14.0 U/ml; there was no significant concordance between the two markers. Thus, p65 may be a potential serum and/or immunohistochemical marker for breast carcinoma.


Surgical therapy of perianal Crohn's disease.
The surgical management of perianal Crohn's disease is complex with a wide range of operations being described. The initial emergency treatment is to drain any source of underlying sepsis. A loose seton drainage or a defunctioning stoma can then be used as a 'bridge' to definitive treatment allowing both adequate assessment of the condition and preventing further sepsis. The likelihood of success of any surgical repair must be weighed against the risk of faecal incontinence. Improved results of a local surgical repair are seen with optimal surgical and medical management of perianal Crohn's disease.


Effect of package and storage conditions on viability and efficacy of the freeze-dried biocontrol agent Pantoea agglomerans strain CPA-2.
To reduce concentrations of protective and rehydrating media and to evaluate the effect of storage temperature, packaging and atmosphere conditions on the stability of freeze-dried Pantoea agglomerans cells. Efficacy against Penicillium digitatum of freeze-dried cells in orange fruits was also evaluated. Several concentrations of protective and rehydration media were tested to reduce processing costs. Freeze-dried cells were packed in glass vials or plastic bags under vacuum or nitrogen conditions at 4 and 25 degrees C. After 1 and 3 months, efficacy of freeze-dried P. agglomerans against P. digitatum was tested. The results indicate that it is possible to reduce the concentration of non-fat skimmed milk as a rehydration medium from 10% to 1%, maintaining viabilities of 100%. Moreover, freeze-dried cells could be stored in glass vials or in high barrier plastic bags at 4 degrees C for 3 months while maintaining high viabilities and efficacy against P. digitatum. The major obstacle in the commercialization of biocontrol products is the development of a shelf-stable formulated product that retains biocontrol activity at a level similar to that of fresh cells. This study suggests that it is possible to maintain viability and efficacy of freeze-dried P. agglomerans cells for at least 3 months.


Pupil size influences the eye-tracker signal during saccades.
While it is known that scleral search coils-measuring the rotation of the eye globe--and modern, video based eye trackers-tracking the center of the pupil and the corneal reflection (CR)--produce signals with different properties, the mechanisms behind the differences are less investigated. We measure how the size of the pupil affects the eye-tracker signal recorded during saccades with a common pupil-CR eye-tracker. Eye movements were collected from four healthy participants and one person with an aphakic eye while performing self-paced, horizontal saccades at different levels of screen luminance and hence pupil size. Results show that pupil-, and gaze-signals, but not the CR-signal, are affected by the size of the pupil; changes in saccade peak velocities in the gaze signal of more than 30% were found. It is important to be aware of this pupil size dependent change when comparing fine grained oculomotor behavior across participants and conditions.


Murine hybridoma antibodies against human transitional carcinoma-associated antigens.
Spleen cells from mice immunized with the human urinary bladder transitional cell carcinoma cell line 647V have been fused with a syngeneic myeloma cell line to produce hybridomas. Screening of supernatants from 40 hybridomas which reacted with the immunizing cell line identified antibodies recognizing a variety of common, shared and tumor-associated antigens as well as newborn calf serum dependent antigens. Three hybridoma antibodies, 9A7 , 2E1 and 2A6 , recognize antigens found on all the human transitional cell carcinoma cell lines and tissue preparations tested, but the antigens were not found on normal human tissue (including urothelium), thus demonstrating the capability of the antibodies to distinguish normal from malignant bladder transitional epithelium. These antibodies, however, otherwise differ in their patterns of reactivity, with 1 recognizing an antigen which is also expressed on highly anaplastic malignant non-transitional cell carcinoma cell lines and tumors, while the other 2 demonstrate reactivities which are far more restricted to transitional cell carcinoma.


Forced-Air Warmers and Surgical Site Infections in Patients Undergoing Knee or Hip Arthroplasty.
The majority of the evidence indicates preventing inadvertent perioperative hypothermia reduces the incidence of many perioperative complications. Among the results of inadvertent perioperative hypothermia are increased bleeding, myocardial events, impaired wound healing, and diminished renal function. Most researchers agree there is an increased incidence of surgical site infections in patients who experience inadvertent perioperative hypothermia. Forced-air warming is effective in preventing inadvertent perioperative hypothermia. Paradoxically, forced-air warmers have been implicated in causing surgical site infections in patients undergoing total knee or hip arthroplasty. The results of investigations suggest these devices harbor pathogens and cause unwanted airflow disturbances. However, no significant increases in bacterial counts were found when forced-air warmers were used according to the manufacturer's directions. The results of one study suggested the incidence of surgical site infections in patients undergoing total joint arthroplasty was increased when using a forced-air warmer. However these researchers did not control for other factors affecting the incidence of surgical site infections in these patients. Current evidence does not support forced-air warmers causing surgical site infections in patients undergoing total knee or hip arthroplasty. Clinicians must use and maintain these devices as per the manufacturer's directions. They may consider using alternative warming methods. Well-conducted studies are needed to help determine the role of forced-air warmers in causing infections in these patients.


Isolated granulomatous disease of the stomach. Report of three cases presenting as incidental findings in gastrectomy specimens.
Three cases of isolated granulomatous disease of the stomach are reported. Other granulomatous diseases were ruled out on the basis of clinical and histological studies. These cases differ from those previously described in having only mucosal granulomas which were discovered as incidental findings in stomachs removed for peptic ulcers. Perigastric lymph node involvement by granulomas was present in one of three cases.


The effects of combining norethindrone with a gonadotropin-releasing hormone agonist in the treatment of symptomatic endometriosis.
Treatment of endometriosis with gonadotropin-releasing hormone agonists (GnRH-a) is associated with side effects secondary to the induced hypoestrogenic state. In an effort to ameliorate these symptoms, 10 patients with symptomatic endometriosis self-administered the GnRH-a [D-His6(Imbzl)-Pro9-NET]-GnRH in combination with norethindrone daily for 24 weeks. Painful symptoms were significantly suppressed after therapy (P less than 0.005). Objective review of photographs taken at laparoscopy before and after therapy demonstrated significant reduction of visible implants (P less than 0.005). Vasomotor symptoms were minimized when compared with a group of 16 patients previously treated with GnRH-a alone. Bone mineral density of the distal radius assessed by single photon absorptiometry was not reduced during therapy, although lumbar spine bone density assessed by quantitative computerized tomography was minimally but reversibly reduced. No metabolic derangements were detected. The combination of norethindrone with GnRH-a is a well tolerated and effective means of treating symptomatic endometriosis.


Clinicopathologic and survival analyses of synchronous primary endometrial and epithelial ovarian cancers.
The aim of the study was to describe clinicopathologic characteristics, survival outcomes and the factors associated with recurrence in patients diagnosed with synchronous primary endometrial and epithelial ovarian cancers. In this retrospective study, 50 patients who were diagnosed with synchronous primary endometrial and epithelial ovarian cancers and underwent surgery between 1998 and 2010 were reviewed. In our study, the median age at the time of diagnosis was 53 years (range 28-79). The most common presenting symptom was abnormal uterine bleeding with a ratio of 36%. Fifty-four percent of the patients had endometrioid type endometrial cancer and endometrioid type ovarian cancer. All patients were surgically staged and the majority of the patients were in stage I for both endometrial cancer (58%) and ovarian cancer (60%). Nearly one-third (32%) of the patients had a recurrence during the follow-up period and by Cox regression analysis the level of cancer antigen 125 (P = 0.023) at diagnosis, serous or clear-cell histopathologic type ovarian cancer (P = 0.029) and stage of endometrial cancer above I (P = 0.048) were found to be independent risk factors associated with development of recurrence. Patients with endometrioid type endometrium histology and endometrioid type ovarian histology had favorable prognosis with 120.00 months mean disease-free survival and 92% disease-free survival rate at 36 months. In our cohort, we found that endometrioid/endometrioid type synchronous primary endometrial and ovarian cancer had different clinical histopathologic characteristics and favorable prognosis compared to the other histologic types of these cancers. Histopathologic type of the ovarian cancer component, stage of endometrial cancer and level of cancer antigen 125 at diagnosis were observed to have a great influence on the development of recurrence and survival of synchronous primary carcinomas of the endometrium and ovary.


A wolf in sheep's clothing: Dogs confer an unrecognized risk for their immunocompromised master.
Bordetella bronchiseptica is a pleomorphic gram-negative coccobacillus that commonly causes respiratory tract infections in canines, felines, and swine. Human infections are rare. We report a case of Bordetella bronchiseptica pneumonia in a 67-year-old immunocompromised host. His past medical history included multiple myeloma treated with autologous bone marrow transplant followed by a chimeric antigen receptor cell therapy for relapse. He was admitted with unrelenting diarrhea due to HHV-6 pancolitis. During the hospital course he developed high-grade fever (102.3°F), cough and respiratory failure requiring mechanical ventilation. Chest imaging demonstrated bilateral opacities most pronounced at lung bases and worsening mediastinal lymphadenopathy. Bronchoalveolar lavage cultures grew Bordetella bronchiseptica. He was treated with piperacillin/tazobactam, but developed progressive multiorgan failure, transitioned to comfort care, and expired in the hospital. Bordetella bronchiseptica is an organism that do not cause serious infection in immunocompetent persons but can sometimes cause serious illness in immunocompromised populations. It causes "kennel cough" in dogs and spready by respiratory droplets. Dogs and cats are not uniformly vaccinated against this pathogen. Therefore, transmission through animal contact is becoming increasingly common. Realize that unlike other Bordetella spp, this pathogen is not typically responsive to erythromycin and is often resistant to ampicillin and cephalosporins so the typical neutropenic fever coverage with an antipseudomonal cephalosporin and azithromycin might not be effective. Given the increasing recognition of this zoonosis as a threat to the immunocompromised, it is essential to educate immunocompromised patients to minimize zoonotic exposure, as immunization of pets might not confer protection to humans.


Helicobacter pylori eradication in patients on long-term H2 receptor antagonists. Economic and symptomatic benefits. A large prospective study in primary care.
A large proportion of patients in primary care are still being maintained on long-term acid suppression, without any attempts to identify Helicobacter pylori status and to treat those that test positive. To assess the prevalence and economic and symptomatic benefits of H. pylori eradication in patients maintained on long-term H2 receptor antagonists (H2RA) in primary care. Patients on long-term (i.e. 6 months or longer) H2RA were identified from the computerised records of six practices in north England. Helicobacter pylori status was identified using serology and H. pylori positive patients were then offered standard 7-day proton pump based triple therapy, followed by a urea breath test (UBT) to confirm H. pylori eradication. Those who had a positive UBT were offered a second line course of H. pylori eradication therapy. Follow up period was 1 year. The main outcome measures were improvement in dyspepsia symptom scores, amount of H2RA being consumed, and economic benefits after H. pylori eradication. One thousand and seven patients (1.5%) were identified on long-term H2RA, of whom 471 (46%) ultimately had their H. pylori serology assessed. Sixty-three (297) percent of the patients tested had a positive serology for H. pylori, the majority of whom (58%, 172) had prior evidence of peptic ulcer disease. The mean duration of therapy and mean time since endoscopy/barium studies was significantly longer in patients with peptic ulcer disease compared to their counterparts with nonulcer dyspepsia and gastro-oesophageal reflux disease, p =.0002 and.0001, respectively. After successful H. pylori eradication (which was possible in 84% of the patients), at the end of the 1-year study period, on an intention to treat basis 62% of the patients could either stop or significantly reduce dosage of their H2RA. There was also significant reduction in the mean dose of H2RA being consumed and severity of symptoms at the end of the study period (p <.00001). Almost two-thirds of patients on long-term H2RA in primary care will have a positive serology for H. pylori; the majority of these will have peptic ulcer disease. In over 60% of cases H. pylori eradication led to significant improvement in symptom scores and reduction in dosage of H2RA being consumed. Cessation or reduction in long-term H2RA prescribing is cost effective.


Lateral pelvic lymphadenectomy for low rectal cancer: a META-analysis of recurrence rates.
Locoregional recurrence (LR) remains a problem for patients with lower rectal cancer despite standardized surgery and improved neoadjuvant treatment regimens. Lateral pelvic lymph node dissection (LPLND) has been routine practice for some time in the Orient/East, but other regions have concerns about morbidity. As perioperative care and surgical approaches are refined, this has been revisited for selected patients. The question as to whether LPLND improves oncological outcomes was explored here. A systematic review of patients who underwent TME with or without LPLND from 2000 to 2020 was performed. The primary endpoint was the rate of LR between the two groups. Seven papers met the predefined search criteria in which 2000 patients underwent TME alone, while 1563 patients had TME and LPLND. The rate of LR was marginally higher with TME alone when compared with TME plus LPLND, but this result was not statistically significant (9.8 vs 9.4%, odds ratio 0.75, 95% CI 0.41-1.38, *p = 0.35). In addition, four studies reported on distant recurrence rates, with TME and LPLND showing a slight reduction in overall rates (27.3 vs 29.9%, respectively, OR 0.65, 95% CI 0.45-0.92, *p = 0.02). The addition of LPLND to TME is not associated with a significantly lower risk of LR in patients who undergo surgery for lower rectal cancer.


Evaluation of androgen assay results using a curated Hershberger database.
A set of 39 reference chemicals with reproducible androgen pathway effects in vivo, identified in the companion manuscript [1], were used to interrogate the performance of the ToxCast/Tox 21 androgen receptor (AR) model based on 11 high throughput assays. Cytotoxicity data and specificity confirmation assays were used to distinguish assay loss-of-function from true antagonistic signaling suppression. Overall agreement was 66% (19/29), with ten additional inconclusive chemicals. Most discrepancies were explained using in vitro to in vivo extrapolation to estimate equivalent administered doses. The AR model had 100% positive predictive value for the in vivo response, i.e. there were no false positives, and chemicals with conclusive AR model results (agonist or antagonist) were consistently positive in vivo. Considering the lack of reproducibility of the in vivo Hershberger assay, the in vitro AR model may better predict specific AR interaction and can rapidly and cost-effectively screen thousands of chemicals without using animals.


Conservative management of pediatric mandibular distal fractures-A retrospective study.
Pediatric mandibular distal fractures present unique treatment challenges which are usually managed with open reduction and internal fixation (ORIF) with the risk of developing tooth bud injuries. Conservative management through maxillomandibular fixation (MMF) with orthodontic bracket-elastic as an out-patient department (OPD) service has been used for these fractures presenting with derangement of occlusion. The aim of this study was to retrospectively analyze MMF with orthodontic bracket-elastic as a treatment method and its outcome for management of pediatric mandibular distal fractures. Data of seventeen pediatric cases diagnosed with displaced mandibular distal fractures managed with MMF with orthodontic bracket-elastic over a period of 5 years were analyzed. In this technique, two weeks of immobilization and one week for guiding elastics were used. The mean age of patients was 7.6 ± 1.6 years with a mean follow-up of 24 months. All fractures healed uneventfully with satisfactory occlusion. The cases included 23.5% minimally displaced, and 64.7% moderately displaced and 11.8% significantly displaced fractures with step deformity with successful remodeling of the lower border contours over a duration of 18 months ± 1 month. The developing tooth buds in the fracture line showed no complications except for root dilacerations/malformation (n = 3). MMF with orthodontic bracket-elastic is a viable and conservative technique for the management of pediatric mandibular distal fractures which need to be verified through randomized trials for generalization of the results.


Effects of triiodothyronine on the 5-hydroxytryptophan-induced head twitch and its potentiation by antidepressants in mice.
Daily injection of triiodothyronine (T3) for 3 consecutive days dose dependently enhanced 1-5-HTP (4 mg/kg)-induced head twitches in mice. This effect was blocked by 1-penbutolol. Pretreatment with a sub-effective dose of T3 (0.06 mg/kg) markedly enhanced the ability of clenbuterol but not indalpine to potentiate the response to 1-5-HTP. Likewise, the effects of T3 were more pronounced on the desipramine- or maprotiline-induced potentiation of head-twitches than on the action of citalopram or clomipramine. These data suggest that the increased responsiveness to 1-5-HTP caused by T3 involves an indirect (noradrenalin-mediated) rather than a direct effect on serotonergic processes.


The role of PET in the first-line treatment of the most common subtypes of non-Hodgkin lymphoma.
This Review focuses on the use of 18F-fluorodeoxyglucose (18F-FDG) PET in the assessment of diffuse large B-cell lymphoma, follicular lymphoma, and peripheral T-cell lymphoma. PET is important for staging and prognostication with stage migration compared with CT. Better outcomes for patients with early stage diffuse large B-cell lymphoma and follicular lymphoma suggests better delineation of disease has translated to improved outcomes in such patients beyond simple stage migration. The aim of treatment of diffuse large B-cell lymphoma and peripheral T-cell lymphoma is potential cure, during which PET is mainly used to assess remission. Interim PET can assess chemosensitivity in these lymphomas, but it does not predict treatment success sufficiently well to enable treatment modification, particularly in the absence of more effective therapies for patients who remain PET-positive on interim scanning. In follicular lymphoma, traditionally viewed as an incurable lymphoma, the aim of treatment is to control disease for several years, while maintaining quality of life. PET can predict prognosis for patients with follicular lymphoma with high tumour burden at the end of induction chemotherapy, and it is being evaluated as a platform for response-adapted treatment of follicular lymphoma.


Potentially migrating and residual components of biochar: Effects on phosphorus adsorption performance and storage capacity of black soil.
Biochar has great potential to increase the soil nutrient storage capacity. However, with aging, biochar gradually disintegrates and releases fractions with migration potential, resulting in unknown effects on soil nutrient regulation. Based on this problem, we used ultrasound to separate original biochar (TB) into potentially migrating biochar (DB) and residual biochar (RB). The elemental composition and pore characteristics of TB, DB and RB were analyzed. Different fractions of biochar were applied to black soil, and the kinetic model and isothermal adsorption models were used to explore the adsorption characteristics of different treatments. Then, the effects of initial pH and coexisting ions on adsorption were compared. The adsorption mechanism and potential leaching process of phosphorus in soil were investigated. The results showed that RB had higher O and H contents and was less stable than TB, while RB was more aromatic. The phosphorus adsorption capacity of different treatments was SRB (1.3318 mg g-1) > STB (1.2873 mg g-1) > SDB (1.3025 mg g-1) > SCK (1.1905 mg g-1). SRB had optimal phosphorus adsorption performance and storage capacity, with a maximum adsorption capacity of 1.6741 mg g-1 for the Langmuir isotherm, and it also showed excellent applicability in a pH gradient and with coexisting ions. The main adsorption mode of phosphorus by different treatments was monolayer chemisorption, related to electrostatic repulsion and oxygen-containing functional groups. DB was less effective in inhibiting soil phosphorus migration, with the cumulative leaching of SDB reaching 8.99 mg and the percentage of phosphorus in the 0-6 cm soil layer reaching only 15.42%. Overall, the results can help elucidate potential trends in the adsorption performance and migration process of soil phosphorus by biochar, and improve the comprehensive utilization efficiency of biochar.


Evaluation of the reproductive toxicity of gallium nitrate in mice.
Reproduction studies were performed with gallium nitrate, an antihypercalcaemic drug that is also used as a chemotherapeutic agent for the treatment of certain malignancies. Male mice were injected subcutaneously with gallium nitrate at doses of 0 (controls), 24, 48 and 96 mg/kg/day every other day for 14 days before mating with untreated females. Fertility and reproductive performance in the gallium nitrate-treated groups did not differ significantly from controls. No significant changes were observed in the relative testes and epididymis weights. Sperm counts in the gallium nitrate-dosed groups were comparable with those in the control group, whereas the percentage of motile cells was similar between treated and untreated animals. Histopathological examination of the testes and epididymis did not reveal any changes at any dose of gallium nitrate. The no-observed-adverse effect level was 96 mg/kg body weight. This dose is about 30 times higher than the current doses of gallium nitrate administered to humans.


Perceptual, motor and attentional deficits in seven-year-old children: neurological and neurodevelopmental aspects.
This study presents the results of neurological assessments of a representative sample of seven-year-old Swedish children with perceptual, motor and attentional deficits and their controls (N = 141). Among those children diagnosed as suffering from minimal brain dysfunction (MBD), the majority showed neurodevelopmental deviations indicative of the "clumsy child syndrome'. However, 20 per cent had slight signs of choreoathetosis, diparesis, hemiparesis or ataxia. Other associated neurodevelopmental deviations are considered. The correlation between neurological findings and background factors is discussed: the MBD group had higher scores for various "organic' background factors than the comparison children, and the children with neurological syndromes had somewhat higher scores than the remaining children with MBD. The difficulties in distinguishing MBD from mental retardation, cerebral palsy and childhood psychoses is clearly illustrated. Long-term follow-up will indicate the prognostic significance of these findings.


The interaction of conduct problems and depressed mood in relation to adolescent substance involvement and peer substance use.
Conduct problems are strong positive predictors of substance use and problem substance use among teens, whereas predictive associations of depressed mood with these outcomes are mixed. Conduct problems and depressed mood often co-occur, and such co-occurrence may heighten risk for negative outcomes. Thus, this study examined the interaction of conduct problems and depressed mood at age 11 in relation to substance use and problem use at age 18, and possible mediation through peer substance use at age 16. Analyses of multirater longitudinal data collected from 429 rural youths (222 girls) and their families were conducted using a methodology for testing latent variable interactions. The link between the conduct problems x depressed mood interaction and adolescent substance use was negative and statistically significant. Unexpectedly, positive associations of conduct problems with substance use were stronger at lower levels of depressed mood. A significant negative interaction in relation to peer substance use also was observed, and the estimated indirect effect of the interaction on adolescent use through peer use as a mediator was statistically significant. Findings illustrate the complexity of multiproblem youth.


Circular RNA circ_0008305 aggravates hepatocellular carcinoma growth through binding to miR-186 and inducing TMED2.
Dysregulation of circRNAs is reported to exert crucial roles in cancers, including hepatocellular carcinoma (HCC). So far, the function of circRNAs in HCC development remains poorly known. Currently, our data showed that circ_0008305 was highly elevated in HCC cell lines and 30 paired tissue samples of HCC. As evidenced, suppression of circ_0008305 repressed HCC cell growth significantly. Meanwhile, up-regulation of circ_0008305 significantly reduced HCC cell growth. Mechanistically, we displayed that circ_0008305 could bind with miR-186 by using bioinformatics analysis. miR-186 has been reported to be a crucial tumour oncogene in many cancers. In addition, we proved miR-186 was greatly decreased in HCC. The direct correlation between miR-186 and circ_0008305 was confirmed in our work. In addition, up-regulation of miR-186 obviously restrained HCC progression. Increased expression of transmembrane p24 trafficking protein 2 (TMED2) is significantly related to the unfavourable outcomes in cancer patients. At our present work, we proved that TMED2 could act as a direct target of miR-186. Mechanistically, we demonstrated that circ_0008305 up-regulated TMED2 expression by sponging miR-186, which resulted in significantly induced HCC progression in vitro and in vivo. These revealed the significant role of circ_0008305 in HCC progression, which might indicate a new perspective on circRNAs in HCC development.


The relation between Internet and social media use and the demographic and clinical parameters, quality of life, depression, cognitive function and sleep quality in hemodialysis patients: social media and hemodialysis.
There are very few studies in the literature investigating the Internet use in hemodialysis (HD) patients. However, no study examined the relationship between Internet and social media use and quality of life, depression, cognitive function and sleep problems in HD patients. The study is cross-sectional in design. All patients underwent history taking; physical examination; laboratory analysis and quality of life (by a short form of the Medical Outcomes Study), depression (by the Beck Depression Inventory), cognitive function (by the Standardized Mini Mental State Examination) and sleep problems (by the Pittsburgh Sleep Quality Index) evaluation. In total, 134 HD patients (male/female: 73/61, age: 53.0 ± 13.4 years) were included. Patients with mail, Facebook and Twitter accounts were younger, were less depressive, had better quality of life, had higher cognitive function and were more educated compared to patients who did not have these accounts. Patients with Internet-based research about their disease were less depressive, had better quality of life and sleep quality, had higher cognitive function and were more educated compared to patients who did not have Internet-based research. Internet and social media use was closely related with quality of life, depression, cognitive function and education in HD patients. Studies are needed on whether Internet use under the supervision of health care professionals will improve clinical outcomes, adherence, quality of life, depression and decision making in HD patients.


Acute myopericarditis complicating acute tonsillitis: beware the young male patient with tonsillitis complaining of chest pain.
We describe 11 cases of myopericarditis complicating bacterial tonsillitis. We performed a retrospective study of all cases of myopericarditis treated at one hospital during the years 2005 and 2006. The patients were all young men. The average latency from the onset of throat pain to the onset of chest pain was 4.6 days. All patients complained of chest pain. The most common electrocardiographic finding was transient ST segment elevations. The levels of cardiac enzymes and troponin were elevated in all cases. Otolaryngologists should be aware of this rare entity. Additional studies are indicated to evaluate the exact incidence of myopericarditis associated with acute streptococcal tonsillitis.


Palliation of endobronchial disease: flexible and rigid bronchoscopic options.
Many patients with lung cancer develop airway obstruction and hemoptysis. Endoscopic palliation can relieve symptoms and improve the quality of life for many patients. Patient factors, lesion characteristics and location, and regional expertise are important to consider when planning therapy. Cost, convenience, time to relief of symptoms, duration of palliation, and the need for serial procedures should also be considered. Further advances in technology will likely allow better palliation in the future. A wide armamentarium of modalities and careful communication with the patient's other providers are essential for optimal patient outcome.


Loss of bladder smooth muscle caveolae in the aging bladder.
Caveolae are specialized regions of the cell membrane that modulate signal transduction and alterations in these structures affect bladder smooth muscle (BSM) contraction. Since bladder dysfunctions are common in the elderly, we evaluated the effect of aging on the morphology of caveolae and caveolin protein expression in BSM. Caveolar morphology (number, size, and depth) in BSM was determined from electron microscopy images of young (10 weeks), adult (6-month old), and old (12-month old) rat urinary bladders. Changes in expression levels of caveolin proteins with age were investigated by Western blot and immunofluorescence microscopy. Caveolin-3 gene expression was determined by real-time RT-PCR in young and 19-month-old rat bladders. Twelve-month-old animals exhibited 50% fewer BSM caveolae compared to young (P < 0.01). The area of caveolae was significantly decreased at 6 and 12 months. Despite a decrease in the number of BSM caveolae at 12 months, the expression of caveolin-1 and cavin-1 were unaltered with age. In contrast, caveolin-2 and caveolin-3 protein expression and immunoreactivity were reduced in BSM at 6 and 12 months of age. Caveolin-3 gene expression was also downregulated at 19 months compared to young animals. Biological aging significantly decreases BSM caveolae number and morphology with associated selective alteration in caveolin protein expression. Since caveolae are protected membrane regions that regulate signal transduction, age-related alterations in caveolae and caveolin protein expression could alter BSM contractility resulting in bladder dysfunctions of the elderly.


Integrative proteomic and transcriptomic analyses reveal multiple post-transcriptional regulatory mechanisms of mouse spermatogenesis.
Mammalian spermatogenesis consists of many cell types and biological processes and serves as an excellent model for studying gene regulation at transcriptional and post-transcriptional levels. Many key proteins, miRNAs, and perhaps piRNAs have been shown to be involved in post-transcriptional regulation of spermatogenesis. However, a systematic method for assessing the relationship between protein and mRNA expression has not been available for studying mechanisms of post-transcriptional regulation. In the present study, we used the iTRAQ-based quantitative proteomic approach to identify 2008 proteins in mouse type A spermatogonia, pachytene spermatocytes, round spermatids, and elongative spermatids with high confidence. Of these proteins, 1194 made up four dynamically changing clusters, which reflect the mitotic amplification, meiosis, and post-meiotic development of germ cells. We identified five major regulatory mechanisms termed "transcript only," "transcript degradation," "translation repression," "translation de-repression," and "protein degradation" based on changes in protein level relative to changes in mRNA level at the mitosis/meiosis transition and the meiosis/post-meiotic development transition. We found that post-transcriptional regulatory mechanisms are related to the generation of piRNAs and antisense transcripts. Our results provide a valuable inventory of proteins produced during mouse spermatogenesis and contribute to elucidating the mechanisms of the post-transcriptional regulation of gene expression in mammalian spermatogenesis.


Preparation of novel chitosan polymeric nanocomposite as an efficient material for the removal of Acid Blue 25 from aqueous environment.
A novel, sustainable chitosan polymeric nanocomposite (CS-PVA@CuO) was synthesized and subjected to the removal of acid blue 25 (AB25) from the aqueous environment. The influence of different variables such as pH, contact time, initial dye concentration, temperature, and adsorption kinetics has been examined in the batch adsorption process. The CS-PVA@CuO composite was systematically characterized by XRD, FTIR, SEM, and EDX analysis. The pseudo-first order (PFO), pseudo-second order (PSO), and intra-particle diffusion kinetics equations were used to examine the kinetic data of the adsorption process. The adsorption kinetics confirms that the PSO model was a more exact fit. Thermodynamics study typically revealed that the uptake of AB25 by the adsorbent is spontaneous and endothermic in nature. Remarkably, the results reveal the highest adsorption capacity of the CS-PVA@CuO was 171.4 mg/g at 313 K. To be specific, CS-PVA@CuO polymer nanocomposite can be effectively used as a suitable adsorbent material for the potential elimination of anionic AB25 dye from the aqueous solutions.


Platelet-Rich Plasma: A Study of the Variables that May Influence Its Effect on Bone Regeneration.
Currently, the use of platelet-rich plasma in bone regeneration is a real option, although more than one opinion has alerted us to the absence of clinical benefits. Analysis of the factors able to modify the characteristics of the platelet preparation obtained by Curasan, Plasma Rich in Growth Factors (PRGF), Platelet Concentrate Collection System (PCCS) and SmartPrep systems, relating them to the type of clinical application and the final bone regeneration achieved. A search was conducted in PubMed using the keywords "platelet-rich plasma," "PRP," "platelet rich growth factors," and "oral bone regeneration." Four widely accepted protocols for the obtention of PRP (above) were analyzed. Any clinical studies with controls, using the four preparation protocols and with a 4 to 6 weeks follow-up period were compared. The protocols were also grouped according to the type of PRP application: PRP-alone, with bone, or with bone substitutes. Bone regeneration was not achieved in any of the cases using PRP obtained by Curasan and PCCS systems, whereas PRP obtained by SmartPrep achieved it only in one in three published cases and PRGF in one in six. Based on the poor results observed in current literature, the use of PRP in oral surgery cannot be recommended.


Murine Models for Viral Hemorrhagic Fever.
Hemorrhagic fever (HF) viruses, such as Lassa, Ebola, and dengue viruses, represent major human health risks due to their highly contagious nature, the severity of the clinical manifestations induced, the lack of vaccines, and the very limited therapeutic options currently available. Appropriate animal models are obviously critical to study disease pathogenesis and develop efficient therapies. We recently reported that the clone 13 (Cl13) variant of the lymphocytic choriomeningitis virus (LCMV-Cl13), a prototype arenavirus closely related to Lassa virus, causes in some mouse strains endothelial damage, vascular leakage, platelet loss, and death, mimicking pathological aspects typically observed in Lassa and other HF syndromes. This model has the advantage that the mice used are fully immunocompetent, allowing studies on the contribution of the immune response to disease progression. Moreover, LCMV is very well characterized and exhibits limited pathogenicity in humans, allowing handling in convenient BSL-2 facilities. In this chapter we outline protocols for the induction and analysis of arenavirus-mediated pathogenesis in the NZB/LCMV model, including mouse infection, virus titer determination, platelet counting, phenotypic analysis of virus-specific T cells, and assessment of vascular permeability.


The windows of opportunity.
Models to predict survival after kidney transplantation have been developed, which have assisted clinicians in the selection of patients suitable for kidney transplant wait-listing. However, these models have ignored the competing problem of delisting and wait-list mortality, which are equally important in the decision-making process for determining transplant suitability. This commentary focuses on a newly introduced concept that integrates and quantifies the probability of wait-list survival versus receiving a deceased donor kidney transplant.


Technetium-thallium scintiscanning for localization of parathyroid adenomas and hyperplasia. A reappraisal.
The dual tracer nuclear scintiscan using technetium and thallium to localize enlarged or ectopic parathyroid tissue has been reported to be highly accurate and efficacious. Fourteen previous series reporting results of the technique have been compiled from the literature and analyzed. This analysis has revealed a total of 317 surgically confirmed scan results with a low false-positive rate (17 of 317 scans), a sensitivity rate of 82 percent, and an overall accuracy rate of 78 percent. Forty-five patients from five Portland area hospitals have been retrospectively studied. They had a total of 49 preoperative scans. In our experience with the scan, a higher false-positive rate (4 of 45 scans), a sensitivity rate of 78 percent, and an overall accuracy rate of 73 percent were noted. The scan's effectiveness in acknowledged areas of difficulty in parathyroid surgery, such as patients with ectopic adenomas, hyperplastic glands, and those with previous neck explorations, has been analyzed. We conclude that the scan is a useful preoperative localization tool, especially in patients with ectopic adenomas or with persistent hypercalcemia after neck exploration. However, it is less accurate than initially reported in complex patients, and additional localization techniques are frequently required.