Oyster shell for drinking water filtration compared with granular activated carbon: advantages and limitations.
Deliberate media selection can be conducted to achieve targeted objective in filters. In this study, three biofilters (BFs) packed with calcinated oyster shell (COS), granular activated carbon (GAC), and COS + GAC (Mix) were set up in parallel following a rough filter packed with natural oyster shell to compare the performance for treating micro-polluted source water. Different media showed selective removal effects for different pollutants. GAC outperformed COS in terms of TOC and UV254. COS achieved higher reduction in turbidity than GAC. Due to the removal of total bacteria, the absolute and relative abundance of antibiotic resistance genes (ARGs) both decreased much in rough filter treated water (1.16 × 1014 to 1.40 × 1013 copies L-1 and 81.6 to 36.9%, respectively). The highest diverse and rich bacterial community was found in the biofilms on the COS filler, so microbial leakage gave rise to high bacterial content, leading to the highest absolute abundance of ARGs in COS BF effluent (2.11 × 1013 copies L-1). The highest relative abundance of ARGs (41.2%) was found in GAC BF effluent. SourceTracker and biomarker analysis both suggested that treatment process played a more important role in shaping the bacterial community structure in Mix BF effluent than single media BFs, which contributed to the lowest absolute (8.69 × 1012 copies L-1) and relative abundance (25.2%) of ARGs in Mix BF effluent among the three BFs. Our results suggested that mix COS + GAC can not only give full play to their respective advantages for traditional pollutants, but also achieve highest reduction in ARGs.


Monoaminergic drugs and directly observable signs of LAAM withdrawal in rhesus monkeys.
Monoaminergic ligands modified a naltrexone discriminative stimulus in rhesus monkeys dependent on 2 mg/kg per day of the mu opioid L-alpha-acetylmethadol (LAAM). This study examined a role for monoamines in the directly observable and physiologic manifestations of LAAM withdrawal induced by naltrexone in the same monkeys. The effects of saline, clonidine (0.032 mg/kg), haloperidol (0.032 mg/kg), cocaine (1.0 mg/kg), amphetamine (1.0 mg/kg) and imipramine (10.0 mg/kg) were examined in LAAM-dependent monkeys that subsequently received saline or naltrexone (0.0001-1.0 mg/kg). Naltrexone dose-dependently increased respiration, abdominal rigidity and salivation. Clonidine attenuated each of these withdrawal signs, whereas haloperidol increased some (i.e. respiration) and decreased others (i.e. salivation). When administered alone, cocaine and amphetamine increased respiration and also increased the respiratory stimulant effects of naltrexone; cocaine and amphetamine did not attenuate any measure of withdrawal. With the exception of a decrease in naltrexone-induced salivation, imipramine was without effect. These results are strikingly different from results in these same LAAM-dependent monkeys showing that cocaine and amphetamine, but not clonidine, markedly attenuated a naltrexone discriminative stimulus. That monoaminergic ligands differentially alter the directly observable and discriminative stimulus effects of naltrexone in LAAM-dependent monkeys supports the view that monoamines differentially mediate the physical manifestations (norepinephrine) and subjective experience (dopamine) of opioid withdrawal.


Pentylenetetrazol: effect on carbaryl-induced changes of serotonin metabolism in pons-medulla of rat brain.
Oral administration of carbaryl to adult male albino rats produced a dose dependent increase in the steady state level of 5-hydroxytryptamine (5-HT) at 1.00 h in pons-medulla (PM). 5-Hydroxyindole acetic acid (5-HIAA) concentration was significantly elevated only in response to a higher dose of this pesticide under similar conditions. A time course study with carbaryl and pentylenetetrazol (PTZ) showed a characteristic elevation of the steady state level of 5-HT in PM, but the 5-HIAA level was significantly elevated at 0.5 h only after carbaryl treatment. No significant change of the 5-HIAA level was evident after administration of PTZ alone or in combination with carbaryl. Tryptophan concentration was significantly elevated in PM at 0.5 h after carbaryl treatment and at 1.0 h after carbaryl + PTZ treatment. No significant change of tryptophan concentration was evident after the administration of PTZ alone under similar conditions. Measurement of (1) pargyline induced (a) accumulation of 5-HT and (b) depletion of 5-HIAA levels, and (2) probenecid-induced accumulation of 5-HIAA level in presence and absence of carbaryl and revealed that carbaryl accelerated the synthesis as well as the breakdown of 5-HT, whereas PTZ alone or in combination with carbaryl accelerated the synthesis of 5-HT without affecting its catabolism. The potency of this pesticide in elevating the pargyline-induced accumulation of 5-HT is in the order of carbaryl + PTZ greater than PTZ congruent to carbaryl. These results suggest that the carbaryl-induced increase in the synthesis of 5-HT is potentiated, and the turnover is reduced, in PM when PTZ is administered to the carbaryl-intoxicated rats.


Temporal Stability and Prognostic Biomarker Potential of the Prostate Cancer Urine miRNA Transcriptome.
The development of noninvasive tests for the early detection of aggressive prostate tumors is a major unmet clinical need. miRNAs are promising noninvasive biomarkers: they play essential roles in tumorigenesis, are stable under diverse analytical conditions, and can be detected in body fluids. We measured the longitudinal stability of 673 miRNAs by collecting serial urine samples from 10 patients with localized prostate cancer. We then measured temporally stable miRNAs in an independent training cohort (n = 99) and created a biomarker predictive of Gleason grade using machine-learning techniques. Finally, we validated this biomarker in an independent validation cohort (n = 40). We found that each individual has a specific urine miRNA fingerprint. These fingerprints are temporally stable and associated with specific biological functions. We identified seven miRNAs that were stable over time within individual patients and integrated them with machine-learning techniques to create a novel biomarker for prostate cancer that overcomes interindividual variability. Our urine biomarker robustly identified high-risk patients and achieved similar accuracy as tissue-based prognostic markers (area under the receiver operating characteristic = 0.72, 95% confidence interval = 0.69 to 0.76 in the training cohort, and area under the receiver operating characteristic curve = 0.74, 95% confidence interval = 0.55 to 0.92 in the validation cohort). These data highlight the importance of quantifying intra- and intertumoral heterogeneity in biomarker development. This noninvasive biomarker may usefully supplement invasive or expensive radiologic- and tissue-based assays.


Direct access lifestyle training improves liver biochemistry and causes weight loss but uptake is suboptimal in patients with non-alcoholic fatty liver disease.
To evaluate the uptake and effectiveness of an existing open access lifestyle intervention forged in collaboration between a third sector organisation, funded by local government and a secondary care non-alcoholic fatty liver disease (NAFLD) service in the North West of England. A service outcome evaluation using precomparison design and postcomparison design was conducted to analyse changes between baseline clinical health records and 12-week follow-up for patients with NAFLD who completed the lifestyle intervention. Lifestyle factors, weight loss, changes in alanine aminotransferase (ALT) enzymes and lipid profiles were compared between patients who completed the programme vs 1:1 matched patients who did not. Only 16 of 167 patients with NAFLD offered the intervention completed the programme. Intervention patients achieved significant weight loss (-2.3% p≤0.05) over 12 weeks, where the non-intervention group had non-significant weight gain (+0.95%). ALT improved by 20.6 IU/L in the interventional group and 15.75 IU/L in the non-intervention group; however, this was not statistically different. This study presents first of its kind evaluation of a service collaboration in the UK. Only 1 in 10 patients offered the opportunity completed the programme, a limitation that could affect future strategies. Patient and public involvement research is needed to identify barriers to participation, address adherence issues and identify support mechanisms for lifestyle interventions in patients with NAFLD.


Potassium current and the effect of cesium on this current during anomalous rectification of the egg cell membrane of a starfish.
The kinetics of the membrane current during the anomalous or inward-going rectification of the K current in the egg cell membrane of the starfish Mediaster aequalis were analyzed by voltage clamp. The rectification has instantaneous and time-dependent components. The time-dependent increase in the K conductance for the negative voltage pulse as well as the decrease in the conductance for the positive pulse follows first-order kinetics. The steady-state conductance increases as the membrane potential becomes more negative and reaches the saturation value at about -40 mV more negative than the K equilibrium potential, V(K). The entire K conductance can be expressed by g(K).n; g g(K) represents the component for the time-independent conductance which depends on V-V(K) and [K+]o, and n is a dimensionless number (1 is greater than or equal to n is greater than or equal to 0) and determined by two rate constants which depend only on V-V(K). Cs+ does not carry any significant current through the K channel but blocks the channel at low concentration in the external medium. The blocking effect increases as the membrane potential is made more negative and the potential-dependent blocking by the external Cs+ also has instantaneous and time-dependent components.


Early short-term PXT3003 combinational therapy delays disease onset in a transgenic rat model of Charcot-Marie-Tooth disease 1A (CMT1A).
The most common type of Charcot-Marie-Tooth disease is caused by a duplication of PMP22 leading to dysmyelination, axonal loss and progressive muscle weakness (CMT1A). Currently, no approved therapy is available for CMT1A patients. A novel polytherapeutic proof-of-principle approach using PXT3003, a low-dose combination of baclofen, naltrexone and sorbitol, slowed disease progression after long-term dosing in adult Pmp22 transgenic rats, a known animal model of CMT1A. Here, we report an early postnatal, short-term treatment with PXT3003 in CMT1A rats that delays disease onset into adulthood. CMT1A rats were treated from postnatal day 6 to 18 with PXT3003. Behavioural, electrophysiological, histological and molecular analyses were performed until 12 weeks of age. Daily oral treatment for approximately 2 weeks ameliorated motor deficits of CMT1A rats reaching wildtype levels. Histologically, PXT3003 corrected the disturbed axon calibre distribution with a shift towards large motor axons. Despite dramatic clinical amelioration, only distal motor latencies were improved and correlated with phenotype performance. On the molecular level, PXT3003 reduced Pmp22 mRNA overexpression and improved the misbalanced downstream PI3K-AKT / MEK-ERK signalling pathway. The improved differentiation status of Schwann cells may have enabled better long-term axonal support function. We conclude that short-term treatment with PXT3003 during early development may partially prevent the clinical and molecular manifestations of CMT1A. Since PXT3003 has a strong safety profile and is currently undergoing a phase III trial in CMT1A patients, our results suggest that PXT3003 therapy may be a bona fide translatable therapy option for children and young adolescent patients suffering from CMT1A.


Quorum sensing between Gram-negative bacteria responsible for methane production in a complex waste sewage sludge consortium.
Quorum sensing (QS) plays a key role in activating bacterial functions through small molecules called autoinducers. In this study, the QS of Gram-negative bacteria in waste sewage sludge (WSS) was downregulated by adding the quorum quenching enzyme, AiiM lactonase, which cleaved the acyl-homoserine lactone (AHL) autoinducer signals from Gram-negative bacteria, and subsequently methane production was inhibited by over 400%. The pH was lowered after 2 days in the anaerobic fermentation whereas protease activity at the hydrolysis step was almost the same with or without AiiM. The production of acetic acid significantly increased during the fermentation in the presence of AiiM. The bacterial community at day 2 indicated that the population of Gram-positive bacteria increased in the presence of AiiM, and the percentage of Gram-negative bacteria decreased in the WSS containing AiiM. The change in the bacterial community in the presence of AiiM may be due to the different antimicrobial agents produced in the WSS because some of the Gram-positive bacteria were killed by adding the solid-phase extraction (SPE) fraction from the WSS without AiiM. In contrast, the SPE fraction with AiiM had reduced bactericidal activity against Gram-negative bacteria. Thus, bacterial signaling between Gram-negative bacteria is critical for methane production by the microbial consortia.


Affective disturbance in eating disorders.
Thirty-three bulimic and 14 restrictive anorexics were compared on DSM-III diagnoses of affective and anxiety disorders, observer-rated and self-rated measures of depression and anxiety, and family history. A subgroup of 18 eating disorder subjects was administered the dexamethasone suppression test. The same 18 subjects were compared to 13 subjects with affective disorder on the Schedule for Affective Disorders and Schizophrenia. It was found that a large group with bulimia and restrictive anorexia nervosa was subject to a depressive disorder. Thirty-eight percent of the sample fulfilled criteria for a major depressive episode. The dysphoric experience seemed as intense in the bulimic and restricter group. There was a high incidence of dexamethasone nonsuppression (55%), which was found to be related to various measures of depression. Bulimics and restricters differed in their family history of affective disorder. While 61% of bulimics had a positive history of depression, this was found in only 23% of restricters (p less than .03).


Identification of Corrosion Minerals Using Shortwave Infrared Hyperspectral Imaging.
In this study, we propose a new method to identify corrosion minerals in carbon steel using hyperspectral imaging (HSI) in the shortwave infrared range (900-1700 nm). Seven samples were artificially corroded using a neutral salt spray test and examined using a hyperspectral camera. A normalized cross-correlation algorithm is used to identify four different corrosion minerals (goethite, magnetite, lepidocrocite and hematite), using reference spectra. A Fourier Transform Infrared spectrometer (FTIR) analysis of the scraped corrosion powders was used as a ground truth to validate the results obtained by the hyperspectral camera. This comparison shows that the HSI technique effectively detects the dominant mineral present in the samples. In addition, HSI can also accurately predict the changes in mineral composition that occur over time.


Multi-dimensional sleep and mortality: The Multi-Ethnic Study of Atherosclerosis.
Multiple sleep characteristics are informative of health, sleep characteristics cluster, and sleep health can be described as a composite of positive sleep attributes. We assessed the association between a sleep score reflecting multiple sleep dimensions, and mortality. We tested the hypothesis that more favorable sleep (higher sleep scores) is associated with lower mortality. The Multi-Ethnic Study of Atherosclerosis (MESA) is a racially and ethnically-diverse multi-site, prospective cohort study of US adults. Sleep was measured using unattended polysomnography, 7-day wrist actigraphy, and validated questionnaires (2010-2013). 1726 participants were followed for a median of 6.9 years (Q1-Q3, 6.4-7.4 years) until death (171 deaths) or last contact. Survival models were used to estimate the association between the exposure of sleep scores and the outcome of all-cause mortality, adjusting for socio-demographics, lifestyle, and medical comorbidities; follow-up analyses examined associations between individual metrics and mortality. The exposure, a sleep score, was constructed by an empirically-based Principal Components Analysis on 13 sleep metrics, selected a priori. After adjusting for multiple confounders, a 1 standard deviation (sd) higher sleep score was associated with 25% lower hazard of mortality (Hazard Ratio [HR]: 0.75; 95% Confidence interval: [0.65, 0.87]). The largest drivers of this association were: night-to-night sleep regularity, total sleep time, and the Apnea-Hypopnea Index. More favorable sleep across multiple characteristics, operationalized by a sleep score, is associated with lower risk of death in a diverse US cohort of adults. Results suggest that interventions that address multiple dimensions may provide novel approaches for improving health.


A critique of the proposed prototype rating system for personality disorders in DSM-5.
The DSM-5 Personality and Personality Disorders (PDs) Work Group has recommended a reformulation of the PD section, one component of which is a replacement of specified operational criteria with a prototype matching dimensional rating system. The Work Group indicated that prototype ratings have been demonstrated to have good interrater reliability. No study was cited to support this statement, and a review of the reliability literature does not support this claim. The one study that directly compared the reliability of prototype and DSM-IV criteria counting approaches found the DSM-IV approach was much more reliably applied. The Work Group cited 2 studies supporting the validity of the prototype matching approach, one of which had significant methodological limitations and the other changed the a priori threshold on the PD prototype dimensional rating scale to categorize patients into PD positive and negative groups. The Work Group also cited 2 studies suggesting that prototype matching approaches are preferred by clinicians. Several studies have raised concerns about the adequacy of psychiatric diagnostic evaluations conducted in routine clinical practice thereby raising questions about the value of studies of clinicians' preferences in comparing different diagnostic practices. In conclusion, if the prototype matching dimensional approach described in the DSM-5 draft proposal is adopted, then it will have been adopted with essentially no empirical support demonstrating improved reliability or validity. In fact, there is evidence that reliability will be worse than the DSM-IV approach.


[Chidamide inhibits proliferation and promotes apoptosis of esophageal squamous cell carcinoma cells by inhibiting the PI3K/Akt and ERK1/2 pathways and increasing DNA damage].
To investigate the mechanism mediating the inhibitory effect of chidamide on esophageal squamous cell carcinoma (ESCC) cells. ESCC cell lines KYSE-150, KYSE-450 and KYSE-510 were treated with 5, 10, 20, or 40 μmol/L of chidamide, and the changes in cell proliferation, colony-forming capacity, cell apoptosis and cell cycle were assessed using MTT aasay, colony formation experiment and flow cytometry. Western blotting was performed to detect the expression levels of cleaved caspase-3, cleaved PARP, p21, cyclin D1, p-Akt, p-ERK1/2, γH2AX, H3K9ac, and Ki-67. In a nude mouse model bearing subcutaneous ESCC xenografts, the effects of intraperitoneal injection of 20 mg/kg chidamide for 3 days on tumor size and body weight were observed every 3 days, and Ki-67 and CD31 expressions in the tumor tissues were detected using immunohistochemistry. Tubular formation experiment was used to examine the effect of chidamide on tubular formation of human umbilical vein endothelial cells (HUVECs) in vitro. In cultured ESCC cell lines, chidamide significantly inhibited cell proliferation and colony formation (P < 0.05), promoted cell apoptosis, and increased the percentage of G0/G1 phase cells (all P < 0.01). Chidamide obviously up-regulated cleaved caspase-3, cleaved PARP, p21, γH2AX, and H3K9ac and down-regulated cyclin D1, p-Akt and p-ERK1/2, and Ki-67 in the cells (P < 0.01). In the tumor-bearing mouse models, treatment with chidamide significantly reduced the tumor volume (P < 0.05), tumor to body weight ratio (P < 0.01), and the expression levels of Ki-67 and CD31 in the tumors (P < 0.01). Chidamide also significantly inhibited tubule formation in cultured HUVECs (P < 0.05). Chidamide inhibits proliferation, induces apoptosis and blocks cell cycle of ESCC cells possibly by inhibiting the PI3K/Akt and ERK1/2 pathways and increasing DNA damage. Chidamide also inhibits subcutaneous tumorigenesis of ESCC cells in mice by inhibiting tumor cell proliferation and angiogenesis.


Cytokine profile in PFAPA syndrome suggests continuous inflammation and reduced anti-inflammatory response.
PFAPA syndrome is characterized by periodic episodes of high fever, aphthous stomatitis, pharyngitis, and/or cervical adenitis. It is of unknown etiology and manifests usually before 5 years of age. We determined serum and intracellular cytokine levels in six PFAPA patients (4 males, 2 females, mean age 8 years (+/- 1.2 SEM), range 4-13) during the symptom-free period as well as 6-12 hours and 18-24 hours after fever onset. Values were compared to age-matched, healthy controls. Febrile PFAPA attacks led to a significant increase in IL-6 and IFN-gamma serum concentrations compared to symptom-free periods and to controls, with IL-1beta, TNF-alpha and IL-12p70 levels being significantly higher than in controls. Lymphocytic IFN-gamma and CD8+ IL-2 production was consistently significantly elevated compared to healthy children. During the asymptomatic period, serum concentrations of IL-1beta, IL-6, TNF-alpha and IL-12p70 were significantly increased compared to controls. Intracellular TNF-alpha synthesis was not elevated at any time point. Soluble TNFRp55 levels were even lower in between febrile episodes, reaching values comparable to controls during attacks, whereas soluble TNFRp75 levels increased during attacks compared to healthy children. Anti-inflammatory IL-4 in serum was at all times lower in PFAPA patients compared to controls with no difference in levels of intracellular IL-4 and IL-10 or serum IL-10. The observed increase of pro-inflammatory mediators, even between febrile attacks, suggests a dysregulation of the immune response in PFAPA syndrome, with continuous pro-inflammatory cytokine activation and a reduced anti-inflammatory response.


Hemps, a novel EGF-like protein, plays a central role in ascidian metamorphosis.
All chordates share several characteristic features including a dorsal hollow neural tube, a notochord, a pharynx and an endostyle. Unlike other chordate taxa, ascidians have a biphasic life-history with two distinct body plans. During metamorphosis, the larval nerve cord and notochord degenerate and the pharyngeal gill slits and endostyle form. While ascidians, like other marine invertebrates, metamorphose in response to specific environmental cues, it remains unclear how these cues trigger metamorphosis. We have identified a novel gene (Hemps) which encodes a protein with a putative secretion signal sequence and four epidermal growth factor (EGF)-like repeats which is a key regulator of metamorphosis in the ascidian Herdmania curvata. Expression of Hemps increases markedly when the swimming tadpole larva becomes competent to undergo metamorphosis and then during the first 24 hours of metamorphosis. The Hemps protein is localised to the larval papillae and anterior epidermis of the larva in the region known to be required for metamorphosis. When the larva contacts an inductive cue the protein is released, spreading posteriorly and into the tunic as metamorphosis progresses. Metamorphosis is blocked by incubating larvae in anti-Hemps antibodies prior to the addition of the cue. Addition of recombinant Hemps protein to competent larvae induces metamorphosis in a concentration-dependent manner. A subgroup of genes are specifically induced during this process. These results demonstrate that the Hemps protein is a key regulator of ascidian metamorphosis and is distinct from previously described inducers of this process in terrestrial arthropods and aquatic vertebrates.


Hindlimb response to tactile stimulation of the pastern and coronet.
Lightweight tactile stimulators attached to the hind pasterns increase the height of the hind hoof flight arc but details of the induced changes in swing phase kinematics and kinetics have not been investigated. Stimulators on the hind pasterns are associated with increased hindlimb joint flexions and increased positive work performed by the hip and tarsal musculature. Nine nonlame horses trotted 4 times with and without 55 g tactile stimulators loosely attached around the hind pasterns. Height of the flight arc and peak flexion angles of the hindlimb joints were measured and net positive and negative work performed across each joint during the swing phase were calculated using inverse dynamics analysis and compared across paired conditions. Speed and stride duration did not change but stimulators were associated with a reduction in hind stance duration. The flight arc was higher with stimulators due to increased flexions of the stifle, tarsal, metatarsophalangeal and distal interphalangeal joints. Positive work increased in the tarsal musculature, but not in the hip musculature, and negative work increased across the stifle, metatarsophalangeal and distal interphalangeal joints. The effects of tactile stimulation of the hind pasterns on joint motion and muscle activation may be used in physiotherapy and rehabilitation to restore or increase flexion of the hindlimb joints with the exception of the hip joint. The ability to stimulate concentric activity of the tarsal musculature may have therapeutic applications in conditions such as toe dragging.


Alveolar Macrophage Chromatin Is Modified to Orchestrate Host Response to Mycobacterium bovis Infection.
Bovine tuberculosis is caused by infection with Mycobacterium bovis, which can also cause disease in a range of other mammals, including humans. Alveolar macrophages are the key immune effector cells that first encounter M. bovis and how the macrophage epigenome responds to mycobacterial pathogens is currently not well understood. Here, we have used chromatin immunoprecipitation sequencing (ChIP-seq), RNA-seq and miRNA-seq to examine the effect of M. bovis infection on the bovine alveolar macrophage (bAM) epigenome. We show that H3K4me3 is more prevalent, at a genome-wide level, in chromatin from M. bovis-infected bAM compared to control non-infected bAM; this was particularly evident at the transcriptional start sites of genes that determine programmed macrophage responses to mycobacterial infection (e.g. M1/M2 macrophage polarisation). This pattern was also supported by the distribution of RNA Polymerase II (Pol II) ChIP-seq results, which highlighted significantly increased transcriptional activity at genes demarcated by permissive chromatin. Identification of these genes enabled integration of high-density genome-wide association study (GWAS) data, which revealed genomic regions associated with resilience to infection with M. bovis in cattle. Through integration of these data, we show that bAM transcriptional reprogramming occurs through differential distribution of H3K4me3 and Pol II at key immune genes. Furthermore, this subset of genes can be used to prioritise genomic variants from a relevant GWAS data set.


Salivary melatonin rhythm as a marker of the circadian system in healthy children and those with attention-deficit/hyperactivity disorder.
Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood. Problems with sleep structure, efficiency, and timing have been reported in some, but not all, studies on ADHD children. As the sleep-wake cycle belongs to circadian rhythms, the timekeeping circadian system might be involved in ADHD. To assess whether the circadian system of ADHD children differs from that of controls, the rhythm of the pineal hormone melatonin was used as a reliable marker of the system. Saliva from 34 ADHD and 43 control 6- to 12-yr-old children was sampled at 2-h intervals throughout the entire 24-h cycle, and the melatonin profiles of the ADHD and control children were compared. The nocturnal melatonin peaks of the ADHD and control group did not differ significantly. The high nocturnal interindividual variability of the peaks seen in adulthood was present already in the studied children. The 24-h melatonin profiles of all the ADHD subjects did not differ significantly from those of the control subjects. Categorization of subjects according to age, into groups of 6- to 7-yr-old (9 ADHD, 5 control), 8- to 9-yr-old (16 ADHD, 26 control), and 10- to 12-yr-old (9 ADHD, 12 control) children, revealed significant differences between the ADHD and control group in the melatonin rhythm waveform, but not in nocturnal melatonin peaks; the peaks were about the same in both groups and did not change significantly with increasing age. In the oldest, but not in the younger, children, the melatonin signal duration in the ADHD group was shorter than in the control group. The difference might be due to the fact that whereas in the control group both the evening melatonin onset and the morning offset phase delayed in the oldest children relative to those in the youngest children, in the ADHD group only the onset, but not the offset, phase delayed with increasing age. The data may indicate subtle differences between the circadian system of ADHD and control children during development.


Biogeological mineralization in deep-sea hydrothermal deposits.
Oriented drill cores retrieved from active massive sulfide edifices at the Endeavour Segment of the Juan de Fuca Ridge contain an abundance of fossilized tube structures associated with vestimentiferan and annelid worms. The petrological evolution of these biogeological structures and their presence deep inside the edifice walls demonstrate that an initial, worm-mediated texture directly affects the subsequent steps of inorganic precipitation, wall infilling, and outward growth of these black smoker deposits. The presence of fossilized structures in hydrothermal discharge sites that are 2 kilometers apart and their similarity to structures observed in other modern and ancient deposits suggest that these biogeological processes are general phenomena.


Targeted massively parallel sequencing of autism spectrum disorder-associated genes in a case control cohort reveals rare loss-of-function risk variants.
Autism spectrum disorder (ASD) is highly heritable, yet genome-wide association studies (GWAS), copy number variation screens, and candidate gene association studies have found no single factor accounting for a large percentage of genetic risk. ASD trio exome sequencing studies have revealed genes with recurrent de novo loss-of-function variants as strong risk factors, but there are relatively few recurrently affected genes while as many as 1000 genes are predicted to play a role. As such, it is critical to identify the remaining rare and low-frequency variants contributing to ASD. We have utilized an approach of prioritization of genes by GWAS and follow-up with massively parallel sequencing in a case-control cohort. Using a previously reported ASD noise reduction GWAS analyses, we prioritized 837 RefSeq genes for custom targeting and sequencing. We sequenced the coding regions of those genes in 2071 ASD cases and 904 controls of European white ancestry. We applied comprehensive annotation to identify single variants which could confer ASD risk and also gene-based association analysis to identify sets of rare variants associated with ASD. We identified a significant over-representation of rare loss-of-function variants in genes previously associated with ASD, including a de novo premature stop variant in the well-established ASD candidate gene RBFOX1. Furthermore, ASD cases were more likely to have two damaging missense variants in candidate genes than controls. Finally, gene-based rare variant association implicates genes functioning in excitatory neurotransmission and neurite outgrowth and guidance pathways including CACNAD2, KCNH7, and NRXN1. We find suggestive evidence that rare variants in synaptic genes are associated with ASD and that loss-of-function mutations in ASD candidate genes are a major risk factor, and we implicate damaging mutations in glutamate signaling receptors and neuronal adhesion and guidance molecules. Furthermore, the role of de novo mutations in ASD remains to be fully investigated as we identified the first reported protein-truncating variant in RBFOX1 in ASD. Overall, this work, combined with others in the field, suggests a convergence of genes and molecular pathways underlying ASD etiology.


The role of meniscal tissue in joint protection in early osteoarthritis.
It is widely accepted that partial meniscectomy leads to early onset of osteoarthritis (OA). A strong correlation exists between the amount and location of the resected meniscus and the development of degenerative changes in the knee. On the other hand, osteoarthritic changes of the joint alter the structural and functional integrity of meniscal tissue. These alterations might additionally compromise the limited healing capacity of the meniscus. In young, active patients without cartilage damage, meniscus therapy including partial meniscectomy, meniscus suture, and meniscus replacement has proven beneficial effects in long-term studies. Even in an early osteoarthritic milieu, there is a relevant regenerative potential of the meniscus and the surrounding cartilage. This potential should be taken into account, and meniscal surgery can be performed with the correct timing and the proper indication even in the presence of early OA.


Adverse events associated with fluoroscopically guided zygapophyseal joint injections.
In spite of the widespread performance of intra-articular zygapophyseal joint (IAZJ) injections, we know of no systematic analysis to date that examines the risks and types of adverse events when IAZJ injections are performed. To describe the type, incidence, and factors contributing to adverse events associated with fluoroscopically guided IAZJ injections. A retrospective, cohort study of English-speaking adults aged 18 - 90 years who underwent fluoroscopically guided IAZJ injections between March 8, 2004, and April 19, 2007. Following IAZJ injections, 3 senior researchers recorded the presence and type of adverse events. The relationship of adverse events with age, gender, fluoroscopy time, vital signs, and trainee presence was analyzed with Fisher's exact or Wilcoxon rank sum 2-sided tests. Frequency of immediate (during or immediately after the procedure) or delayed (within 24 - 72 hours following the procedure) adverse events. Tertiary, academic, outpatient physical medicine and rehabilitation interventional spine clinic. One hundred ninety-one patients (111 men) underwent 239 procedures. The mean and standard deviation (SD) of subject age was 56.4 (16.6) years ranging from 20 to 89. The mean and SD of pre-procedure 11-point Visual Analog Pain Scale was 5.5 (2.2) ranging from 0 to 10, and for post-procedure was 2.6 (2.6) ranging from 0 to 10. Trainees were involved in 52.3% of procedures. Reported immediate adverse events were vasovagal reaction (3.8%, n = 9) and steroid clogged needle (0.4%, n = 1). Follow-up data were available for 185/239 procedures (77.4%). There were 35 adverse events reported at mean follow-up interval of 1.8 days, of which the most frequent were injection site soreness (6.0%, n = 11), pain exacerbation (4.3%, n = 8), sleeplessness (2.2%, n = 4), and transient headache (1.6%, n = 3). Patient gender, age, trainee involvement, pre-procedural pain score, systolic or diastolic blood pressure, pulse, hemoglobin saturation as measured by pulse oximetry, volume of corticosteroid injected, and duration of fluoroscopy were not found to have a significant effect on immediate or delayed adverse events. This study is limited by a 24- to 72-hour follow-up window, which may have also been too small to capture more delayed complications, and a sample size too small to accurately define the incidence of rare complications. Fluoroscopically guided IAZJ injections have minimal adverse effects. The most common immediate adverse event was vasovagal reaction and most common delayed adverse event was injection site soreness.


miR-30a attenuates cardiac fibrosis in rats with myocardial infarction by inhibiting CTGF.
The mechanism of miR-30a in myocardial fibrosis in rats with myocardial infarction (MI) was investigated. rAAV9-miR-30a was constructed and transfected to heart via injecting into the left ventricular cavity of MI rats. The sham operation group, control group, miR-30a group and miR-30a-NC group were established. Besides, the 3'-UTR of CTGF was inserted into luciferase expression plasmid (pMir-report), then transfected into COS1 cells. miR-30a and control miRNA were, respectively, cotransfected into COS1 cells. The expression of luciferase was detected before and after knockdown of the binding site of miR-30a and the 3'-UTR of CTGF. Four weeks after MI surgery, cardiac function was measured by color Doppler echocardiography, including short axis shortening (FS) and left ventricular ejection fraction (LVEF); the myocardial collagen volume fraction (CVF) was observed by Masson's staining; deposition of collagen I and collagen III were evaluated by immunohistochemical stain; using real-time PCR to detect expression levels of miR-30a and CTGF; the expression of CTGF was observed by western blotting. In MI group, cardiac function was significantly improved, while the expression levels of CVF, collagen I and III, the ratio of type I/III collagen, CTGF were significantly reduced. After knockdown the binding site of miR-30a and the 3'-UTR of CTGF, luciferase expression in COS1 cells decreased significantly. miR-30a might inhibit the expression of CTGF by directly combining with the 3'-UTR site of CTGF after MI, thereby reduce the production of collagen in myocardia, inhibit myocardial fibrosis, then improve cardiac function.


Mycoplankton Biome Structure and Assemblage Processes Differ Along a Transect From the Elbe River Down to the River Plume and the Adjacent Marine Waters.
Rivers are transport systems and supply adjacent ecosystems with nutrients. They also serve human well-being, for example as a source of food. Microorganism biodiversity is an important parameter for the ecological balance of river ecosystems. Despite the knowledge that fungi are key players in freshwater nutrient cycling and food webs, data on planktonic fungi of streams with higher stream order are scarce. This study aims to fill this knowledge gap by a fungi-specific 18S ribosomal RNA (rRNA) gene tag sequencing approach, investigating mycoplankton diversity in the Elbe River along a transect from shallow freshwater, to the estuary and river plume down to the adjacent marine waters (sections of seventh stream order number). Using multivariate analyses and the quantitative process estimates (QPEs) method, questions (i) of how mycoplankton communities as part of the river continuum change along the transect, (ii) what factors, spatial and environmental, play a role, and (iii) what assembly processes, such as selection or dispersion, operate along the transect, were addressed. The partitioning of mycoplankton communities into three significant distant biomes was mainly driven by local environmental conditions that were partly under spatial control. The assembly processes underlying the biomes also differed significantly. Thus, variable selection dominated the upstream sections, while undominated processes like ecological drift dominated the sections close to the river mouth and beyond. Dispersal played a minor role. The results suggest that the ecological versatility of the mycoplankton communities changes along the transect as response, for example, to a drastic change from an autotrophic to a heterotrophic system caused by an abrupt increase in the river depth. Furthermore, a significant salinity-dependent occurrence of diverse basal fungal groups was observed, with no clade found exclusively in marine waters. These results provide an important framework to help understand patterns of riverine mycoplankton communities and serve as basis for a further in-depth work so that fungi, as an important ecological organism group, can be integrated into models of, e.g., usage-balance considerations of rivers.


Computer-assisted fluoroscopic targeting system for pedicle screw insertion.
Biplanar fluoroscopic imaging linked to a computer-driven mechanical end-effector is under development as a targeting system for spinal surgery. This technology has the potential to enhance standard intraoperative fluoroscopic information for localization of the pedicle entry point and trajectory, and it may be an effective alternative to the computed tomography-based image-guided system (IGS) in pedicle screw placement. A preclinical study to assess the accuracy and time efficiency of this system versus a conventional IGS was conducted. Pedicle screw placement was performed in six cadavers from T1 to S1 levels using the ViewPoint IGS (Picker International, Inc., Cleveland, OH) on one side versus the Fluorotactic guidance system (Z-Kat, Inc., Miami, FL) on the other side. Of 216 possible pedicles, 208 were instrumented; 8 pedicle diameters were too small or were not adequately imaged. Postinsertion, each pedicle was assessed for the presence and location of cortical perforation using computed tomographic scanning and direct visualization. The number of successful screw placements was 89 (87.3%) of 102 for IGS and 87 (82.1 %) of 106 for the Fluorotactic guidance system, respectively. The mean time to register and operate on one level using the Fluorotactic guidance system was 14:34 minutes (minutes:seconds), compared with 6:50 minutes using the IGS. The average fluoroscope time was 4.6 seconds per pedicle. Our data indicate that this first-generation fluoroscopy-based targeting system can significantly assist the surgeon in pedicle screw placement. The overall accuracy is comparable to an IGS, especially in the region of T9-L5. A second-generation system with a faster end-effector and user-friendly interface should significantly reduce the operating and fluoroscope time.


In Vitro and In Vivo Evaluation of Pellotine: A Hypnotic Lophophora Alkaloid.
Quality of life is often reduced in patients with sleep-wake disorders. Insomnia is commonly treated with benzodiazepines, despite their well-known side effects. Pellotine (1), a Lophophora alkaloid, has been reported to have short-acting sleep-inducing properties in humans. In this study, we set out to evaluate various in vitro and in vivo properties of 1. We demonstrate that 1 undergoes slow metabolism; e.g. in mouse liver microsomes 65% remained, and in human liver microsomes virtually no metabolism was observed after 4 h. In mouse liver microsomes, two phase I metabolites were identified: 7-desmethylpellotine and pellotine-N-oxide. In mice, the two diastereomers of pellotine-O-glucuronide were additionally identified as phase II metabolites. Furthermore, we demonstrated by DESI-MSI that 1 readily enters the central nervous system of rodents. Furthermore, radioligand-displacement assays showed that 1 is selective for the serotonergic system and in particular the serotonin (5-HT)1D, 5-HT6, and 5-HT7 receptors, where it binds with affinities in the nanomolar range (117, 170, and 394 nM, respectively). Additionally, 1 was functionally characterized at 5-HT6 and 5-HT7, where it was found to be an agonist at the former (EC50 = 94 nM, Emax = 32%) and an inverse agonist at the latter (EC50 = 291 nM, Emax = -98.6). Finally, we demonstrated that 1 dose-dependently decreases locomotion in mice, inhibits REM sleep, and promotes sleep fragmentation. Thus, we suggest that pellotine itself, and not an active metabolite, is responsible for the hypnotic effects and that these effects are possibly mediated through modulation of serotonergic receptors.


NOD1 and NOD2 signalling links ER stress with inflammation.
Endoplasmic reticulum (ER) stress is a major contributor to inflammatory diseases, such as Crohn disease and type 2 diabetes. ER stress induces the unfolded protein response, which involves activation of three transmembrane receptors, ATF6, PERK and IRE1α. Once activated, IRE1α recruits TRAF2 to the ER membrane to initiate inflammatory responses via the NF-κB pathway. Inflammation is commonly triggered when pattern recognition receptors (PRRs), such as Toll-like receptors or nucleotide-binding oligomerization domain (NOD)-like receptors, detect tissue damage or microbial infection. However, it is not clear which PRRs have a major role in inducing inflammation during ER stress. Here we show that NOD1 and NOD2, two members of the NOD-like receptor family of PRRs, are important mediators of ER-stress-induced inflammation in mouse and human cells. The ER stress inducers thapsigargin and dithiothreitol trigger production of the pro-inflammatory cytokine IL-6 in a NOD1/2-dependent fashion. Inflammation and IL-6 production triggered by infection with Brucella abortus, which induces ER stress by injecting the type IV secretion system effector protein VceC into host cells, is TRAF2, NOD1/2 and RIP2-dependent and can be reduced by treatment with the ER stress inhibitor tauroursodeoxycholate or an IRE1α kinase inhibitor. The association of NOD1 and NOD2 with pro-inflammatory responses induced by the IRE1α/TRAF2 signalling pathway provides a novel link between innate immunity and ER-stress-induced inflammation.


Upper gastrointestinal bleeding. With special reference to blood transfusion.
Upper gastrointestinal haemorrhage in 978 unselected patients during a 9-year period was reviewed in regard to incidence, diagnosis, treatment and mortality rate. The annual incidence was 1/1,000 of the catchment population. The source of bleeding was established in 89% of cases. Peptic ulcer accounted for 53% of total admissions. Blood transfusion was given only when the haemoglobin was less than 8.0 g/dl or if the patient was in shock. Emergency surgery was performed on only 31 patients (3%). The perioperative mortality was 13% and the overall mortality 6%. It is concluded that current treatment policy resulted in low rates of operation and mortality in these unselected cases of upper gastrointestinal haemorrhage. The results support the theory that a hypercoagulable state in gastrointestinal bleeding is counteracted by citrated stored blood.


Physical Activity, Sedentary Behaviors, and Retinal Vascular Caliber in Children and Adolescents With Type 1 Diabetes.
The aim of this study was to investigate associations of physical activity and sedentary behaviors with retinal vascular caliber in children and adolescents with type 1 diabetes. This was a hospital-based cross-sectional study. A study of 122 children and adolescents with type 1 diabetes was conducted over an 8-month period. Self-reported physical activity time and time spent watching TV or playing computer or video games were obtained using interviewer-administered questionnaires. Retinal vascular caliber was measured by a trained grader using a standardized protocol and later summarized as central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) using a semiautomated computer program. After adjusting for confounders (age, sex, ethnicity, body mass index, systolic blood pressure, HbA1c, maternal smoking status, age at which cow's milk was introduced, and CRVE/CRAE, respectively), narrower CRAE was independently related to more time spent playing computer/video games [ExpB = -3.85; 95% confidence interval (CI), -6.41 to -1.29; P = 0.004], whereas wider CRVE was independently related to lower physical activity level (ExpB = -1.08; 95% CI, -2.01 to -0.15; P = 0.03) and more time spent playing computer/video games (ExpB = 4.72; 95% CI, 0.52-8.92; P = 0.02). Television viewing time was not associated with retinal vascular caliber after adjustment. The results of this study suggest that physical activity and sedentary behaviors in the form of "screen viewing time" are associated with retinal vessel caliber early in life. These results suggest that retinal vascular caliber may provide prognostic information beyond current traditional cardiovascular risk factors. Future longitudinal and interventional studies are warranted to evaluate the relevance of these observations.


Development of a fish cell culture model to investigate the impact of fish oil replacement on lipid peroxidation.
Fish oils are rich in omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA), predominantly 20:5n-3 and 22:6n-3, whereas vegetable oils contain abundant C(18)-PUFA, predominantly 18:3n-3 or 18:2n-6. We hypothesized that replacement of fish oils with vegetable oils would increase the oxidative stability of fish lipids. Here we have used the long established and easily cultivated FHM cell line derived from the freshwater fish species fathead minnow (Pimephales promelas) to test this hypothesis. The FHM cells were readily able to synthesize 20:5n-3 and 24:6n-3 from 18:3n-3 but 22:6n-3 synthesis was negligible. Also, they were readily able to synthesize 20:3n-6 from 18:2n-6 but 20:4n-6 synthesis was negligible. Mitochondrial β-oxidation was greatest for 18:3n-3 and 20:5n-3 and the rates for 16:0, 18:2n-6, 22:6n-3 and 18:1n-9 were significantly lower. Fatty acid incorporation was predominantly into phospholipids (79-97%) with very little incorporation into neutral lipids. Increasing the fatty acid concentration in the growth medium substantially increased the concentrations of 18:3n-3 and 18:2n-6 in the cell phospholipids but this was not the case for 20:5n-3 or 22:6n-3. When they were subjected to oxidative stress, the FHM cells supplemented with either 20:5n-3 or 22:6n-3 (as compared with 18:3n-3 or saturated fatty acids) exhibited significantly higher levels of thiobarbituric reactive substances (TBARS) indicating higher levels of lipid peroxidation. The results are discussed in relation to the effects of fatty acid unsaturation on the oxidative stability of cellular lipids and the implications for sustainable aquaculture.


Oral diseases in older adults.
In the case presented, a 65-year-old man with multiple dental, medical, and social problems benefited from interdisciplinary assessment and treatment. Despite his poor oral-health status and oral-health behaviors upon admission, patient education and dental therapy resulted in improved daily oral hygiene, elimination of oral diseases, and improved oral function. The overall quality of life of any individual, particularly an older one, can be enhanced through oral-disease prevention, health promotion, and, when indicated, dental therapy. This patient was treated in a hospital environment with a well-established team approach to geriatric care. However, regardless of the care setting, the physician can play a key role in improving the oral health status and quality of life of older adults by including an oral screening examination as part of the periodic comprehensive geriatric assessment, recognizing oral pathology, requesting dental consultations and encouraging appropriate dental service utilization.


The marginal sinus normal anatomy and involvement with arteriovenous fistulae.
The marginal sinus is an infrequently recognized dural venous sinus at the rim of the foramen magnum. Recognition of this sinus and knowledge of its anatomy will enable the neurointerventionalist to treat dural arteriovenous fistulae (AVF) involving the marginal sinus. We present a report of the signs, symptoms, angiographic appearance, and treatment results of two patients with marginal sinus dural AVF. In addition, we review the literature concerning the marginal sinus and describe the anatomy of this region. Angiograms depicting normal variants are presented to illustrate the various patterns that may be encountered when the marginal sinus participates in the venous drainage of the cranium. In two patients with dural arteriovenous fistulae (AVF) the marginal sinus was found to be the venous receptacle. The marginal sinuses are dural venous sinuses located at the lateral margins of the foramen magnum. Superiorly, the marginal sinus connects to the occipital sinus, a single or paired midline venous channel arising at the torcular Herophili or the medial transverse sinus. The marginal sinus typically drains into the sigmoid sinus, and may connect to the condylar veins, the superior aspect of the internal venous plexus, or the occipital plexus. Occasionally, the occipital-marginal sinus system represents the primary drainage pathway of the cranium, completely replacing the transverse sinus. In the two patients we treated with dural AVF in this location, simple transvenous packing of the sinus effectively cured the lesion. The marginal sinus is a dural venous sinus that can rarely be involved with a dural AVF. Recognition that a dural AVF involves the marginal sinus can facilitate safe, effective therapy.


Erythropoietin causes down regulation of colony-stimulating factor (CSF-1) receptors on peritoneal exudate macrophages of the mouse.
We have shown that erythropoietin (epo), the primary regulator of erythrocyte formation, diminished the binding to peritoneal exudate macrophages (PEM) of the principal macrophage growth regulator, colony-stimulating factor (CSF-1). The effect of epo on 125I-CSF-1 binding was dose-dependent; at a concentration of 1-2 U of epo/ml (10(-10) M), CSF-1 binding was almost completely suppressed. Erythropoietin did not compete with CSF-1 for occupancy of the latter's receptors. The effect of epo on CSF-1 binding occurred at 37 degrees C but not at 2 degrees C, and during the continuous exposure of PEM to epo at 37 degrees C we found that CSF-1 binding reached a nadir at 1 h and recovered to pre-exposure levels in 7 h. Our novel results are consistent with the notion that specific receptors for epo exist on the cell surface of PEM and that binding of epo sets in motion a series of cellular events resulting in the internalization of CSF-1 receptors. Thus epo causes down regulation of CSF-1 receptors on PEM. We have previously shown that epo causes suppression of CSF-induced granulocyte-macrophage colony formation by mouse bone marrow cells. The results we present here provide a possible mechanism for these results.


The relationship between sleep habits, anxiety, and depression in the elderly.
The objective of this study is to determine which sleep-related behaviors are most often used by the elderly according to the presence or absence of anxiety and mood disorders. In particular, we are attempting to determine whether these behaviors are associated with the probability of suffering from a mental disorder. The behaviors being examined in the present study are taking naps, television watching or reading at bedtime, physical exercise at bedtime, relaxing activities at bedtime, and caffeine consumption in the evening. The sample in this study consists of 2,759 participants aged 65 and over, with a mean age of 73.8. They were recruited through a method of random generation of telephone numbers according to a sampling strategy based on geographic location. After the goal of the study was explained to them, the participants agreed to have health professionals visit their home and to answer questions in an hour-and-a-half-long structured interview (after signing a consent form). Taking naps is the activity most often practiced by the elderly. Watching television and reading at bedtime are also frequent practices among them. The probabilities of suffering from anxiety are greater if the person never or rarely consumes caffeine after 6 pm, if the individual takes naps during the day, or if the person practices relaxation before bedtime. Television watching, reading, and physical exercise before bedtime are activities that are not associated with the probability of suffering from a mental disorder. It would be beneficial for research to be conducted to support the findings on behavioral differences between depressive and anxious seniors so that these behaviors can become further indicators of the presence of mental disorders.


Spectrophotometric Quantitation of Metformin in Bulk Drug and Pharmaceutical Formulations using Multivariate Technique.
A sensitive and accurate UV spectrophotometric method with multivariate calibration technique for the determination of metformin hydrochloride in bulk drug and different pharmaceutical formulations has been described. This technique is based on the use of the linear regression equations by using relationship between concentration and absorbance at five different wavelength. The results were treated statistically and were found highly accurate, precise and reproducible. The method is accurate, precise (% recovery 102.50+/-0.063, CV</=0.56, r =0.997) and linear within the range 1-10 mug/ml. There was no interference from the excipients i.e Povidone K 30, magnesium stearate, lactose and hydroxypropylmethylcellulose. This statistical approach gives optimum results for the eliminating fluctuations coming from instrumental or experimental conditions.


Increased vulnerability to demyelination in streptozotocin diabetic rats.
Demyelination is a prominent feature in nerve biopsies of patients with diabetic neuropathy. The mechanism is unknown because diabetic rodents, unlike humans, do not consistently develop segmental demyelination. We examined how diabetes influences toxicant-induced demyelination, remyelination, Schwann cell nerve growth factor receptor (p75) expression, and endoneurial macrophage apolipoprotein E (apo E) synthesis in diabetic rats. Postnatal day 17 (P17) rats were given 110 mg/kg streptozotocin intraperitoneally and then fed a diet containing metallic tellurium (Te) from P20 to P27 to induce demyelination. Transverse electron micrographs and immunostained longitudinal cryosections were prepared from sciatic nerve during demyelination and remyelination. Diabetic rats had a mean serum glucose concentration of 490 mg/dl and consumed equivalent doses of peroral Te. The number of demyelinated fibers in electron micrographs was increased significantly by 17% (P < .0011). Endoneurial density of p75-stained Schwann cells was increased in diabetic rats in proportion to the increased number of injured internodes. Density of apo E- and ED1-positive macrophages also was significantly increased in diabetes. There was no delay in macrophage myelin clearance. and remyelination was not compromised. Increased Schwann cell vulnerability to stress, by increasing the turnover rate of myelinated units, may explain why myelin defects accumulate after long-standing diabetes.


Autoimmune disease and chronic lymphocytic leukemia: autoimmune hemolytic anemia, pure red cell aplasia, and autoimmune thrombocytopenia.
Immune dysregulation, a hallmark of chronic lymphocytic leukemia (CLL), manifests itself in three autoimmune diseases: warm autoimmune hemolytic anemia (AIHA); idiopathic thrombocytopenia (ITP); and, pure red cell aplasia (PRCA). AIHA occurs in 11% of advanced stage CLL patients. Prednisone is the first treatment of choice, with 90% responses and 65% complete responses. More than 60% of patients relapse when treatment is stopped. Intravenous immunoglobulin, the next line of treatment, causes responses in 40% of patients. While the data are very limited, cyclosporine A is a reasonable choice for third-line therapy. Alkylating agents, danazol, plasma exchange, immunoabsorption, vincristine-loaded platelets, splenectomy, and splenic irradiation are also reported to cause responses. The data on mechanisms of AIHA are most consistent with immune dysregulation leading to loss of tolerance to a self antigen which in turn leads to the immune-based hemolytic anemia. PRCA is underrecognized in CLL with 6% of CLL patients having PRCA when tested for it. Unlike AIHA, PRCA often occurs in early stage disease. Anemia, reticulocytopenia, and a marrow virtually devoid of red blood cell precursors are hallmarks of PRCA. Corticosteroid therapy is the first line of treatment. If a response is not obtained in 4 weeks, cyclosporine A should be added. Although the data on pathophysiology are very limited, PRCA appears to be the result of an abnormal T cell that both fails in its normal function to support growth and inhibits the growth of erythroid progenitor cells. ITP occurs in 2-3% of CLL patients, occurs in early stage disease and may be a presenting manifestation. Initial therapy for ITP mirrors the guidelines for primary ITP. Initial therapy should consist of prednisone. Seventy percent of patients respond. Splenectomy is a reasonable second-line treatment. Autoimmune phenomena, largely related to blood cells, are based in the immune dysregulation of CLL. Longer survivals in CLL patients, more treatment regimens per patient, and more immunosuppression with modern treatments, allow us to predict an increasing incidence of autoimmune blood cell diseases in CLL.


Pseudohyponatremia revisited: a modern-day pitfall.
Factitiously low sodium estimations are a hazard in most modern clinical laboratories. Most modern high-throughput analyzers use indirect ion-selective electrodes to estimate electrolyte concentrations in serum samples. This analysis is preceded by a dilution step of the sample. If the water concentration is altered by the presence of increased lipid or protein, the dilution step and the subsequent calculation of concentration by the analyzer results in a falsely low sodium value. This places patients at risk, particularly if the factitious result is acted upon by the physician. In this short review, we highlight this problem and review the methodology and situations where this artifact can occur and discuss strategies to circumvent this problem. When factitious results are suspected, whole blood sodium can be assessed using a direct ion-selective electrode, by measurement of osmolality, or by calculation of the serum water fraction and applying a correction to the reported value.


Reduction of cerebral DWI lesion burden after carotid artery stenting using the CASPER stent system.
Despite various measures to protect against distal embolization during carotid artery stenting (CAS), periprocedural ischemic lesions are still encountered. To evaluate the periprocedural cerebral diffusion weighted imaging (DWI) lesion burden after CASPER stent placement. Patients who underwent CAS using the CASPER stent system were reviewed. Degrees of carotid stenosis and plaque configuration were determined. All patients were pretreated with dual antiplatelet agents and cerebral pre- and postprocedural MRI was obtained. All CAS procedures were performed by a single operator. A total of 110 patients with severe carotid artery stenosis (median degree of stenosis 80%, median length of stenosis 10 mm) were treated with CAS. Hypoechogenic or heterogeneous, mostly hypoechogenic, plaques were documented in 48.6% (52/107) of patients. Carotid ulceration was present in 15.9% (17/107). Postprocedurally, 7.3% (8/110) of patients were found to have ischemic DWI lesions. They were asymptomatic in all patients. Follow-up at 90 days was available in 88.2% (97/110) of patients with excellent functional outcome (modified Rankin Scale score 0-1) in 95.9% (93/97). Carotid artery stenting using the new CASPER stent in combination with a distal embolic protection device is safe and results in a lower rate of periprocedural DWI lesion burden compared with reported results for historic controls.


Cost analysis of neonatal tele-homecare for preterm infants compared to hospital-based care.
Neonatal homecare (NH) can be used to provide parents the opportunity of bringing cardiopulmonary-stable preterm infants home for tube feeding and the establishment of breastfeeding supported by neonatal nurses visiting the home. However, home visits can be challenging for hospitals covering large regions, and, therefore, regular neonatal hospital care has remained the first choice in Denmark. As an alternative to home visits, telehealth may be used to deliver NH. Thus, neonatal tele-homecare (NTH) was developed. Positive infant outcomes and the optimization of family-centred care have been described, but the costs of telehealth in the context of NH remain unknown. This study aims to assess the costs of NTH compared to regular neonatal hospital care, from the health service perspective. The cost analysis was based on an observational study of NTH in Denmark (run from November 2015 to December 2016) and followed the Consolidated Health Economic Evaluation Reporting Standards. The intervention group were the families of preterm infants receiving NTH (n = 96). The control group comprised a historic cohort of families with preterm infants, receiving standard care in the neonatal intensive care unit (NICU) (n = 278). NTH infants and the historical group were categorized according to gestational age at birth at/under and over 32 weeks. The outcomes were NTH resource utilization, in-NICU hospital bed days, re-admissions and total costs on average per infant. The time horizon was from birth to discharge. The costs of NTH resource utilization were, on average, €695 per infant, and the total costs per infant, on average, were €12,200 and €4200 for infants at/under and over 32 weeks, respectively. The corresponding costs of the control group were €14,300 and €4400. The difference in total costs showed statistical significance for the group of infants under 32 weeks (p < 0.001). The cost analysis showed that NTH was less costly compared to regular hospital care, especially for infants born with gestational age at/under 32 weeks. NTH is an appropriate model of care for preterm infants and their families, is clinically effective and less expensive than similar services delivered in the hospital.


Enhancement characteristics of liver metastases, hepatocellular carcinomas, and hemangiomas with Gd-EOB-DTPA: preliminary results with dynamic MR imaging.
Our objective was to study Gd-EOB-DTPA for the characterization of focal liver lesions by means of dynamic MR imaging. A double-blind and randomized dose-ranging phase-2 clinical trial was performed in 31 patients (liver metastases n = 23, hepatocellular carcinoma n = 4, and hemangioma n = 4) at a field strength of 1.0 Tesla. Gd-EOB-DTPA (Schering AG, Berlin, Germany) was administered as an IV bolus (12.5, 25, or 50 micromol/kg body weight) with dynamic T1-weighted MRI during the distribution and cellular uptake of the contrast agent at multiple time points up to 45 min post contrast. Dynamic changes in tumor signal intensity, tumor-liver contrast, enhancement patterns, side effects, and adverse events were evaluated. Monitoring of vital signs revealed no significant changes during bolus injection of Gd-EOB-DTPA. Liver metastases demonstrated an inhomogeneous uptake of Gd-EOB-DTPA during the distribution phase with a washout effect on delayed images > 3 min and highest tumor-liver contrast 20 and 45 min post contrast. Hepatocellular carcinomas showed prolonged enhancement as compared with metastases and hemangiomas. Hemangiomas exhibited an early peripheral-nodular enhancement with subsequent partial or complete filling, persisting enhancement < 10 min following injection of Gd-EOB-DTPA, and delayed washout as compared with liver metastases. Initial clinical experience suggests that Gd-EOB-DTPA as a bolus injectable hepatobiliary MR contrast agent may offer useful features for the characterization of focal liver lesions.


Activation of guinea pig macrophages by bacterial lipopolysaccharide requires bone marrow-derived lymphocytes.
The activation of guinea pig peritoneal macrophages by Salmonella typhimurium lipopolysaccharide (LPS) was studied by using 14C-glucosamine uptake. Peritoneal exudate cells incorporated significant amounts of 14C-glucosamine when stimulated with LPS but neither purified macrophages nor nonadherent lymphocytes by themselves incorporated glucosamine. The activation of macrophages could be restored by adding nonadherent peritoneal lymphocytes, spleen cells, and lymph node cells but not thymocytes. Removal of B lymphocytes abolished the restorative capacity from active lymphoid cell populations. In contrast, B lymphocytes would restore glucosamine incorporation by macrophages stimulated with LPS but T lymphocytes did not. In addition, cell-free supernatants from LPS stimulated B lymphocytes but not from T lymphocytes could restore glucosamine incorporation by macrophages. These experiments demonstrate that LPS does not directly activate macrophages as measured by glucosamine incorporation but stimulates B lymphocytes which in turn activate macrophages.


High performance 3-coil wireless power transfer system for the 512-electrode epiretinal prosthesis.
The next-generation retinal prostheses feature high image resolution and chronic implantation. These features demand the delivery of power as high as 100 mW to be wireless and efficient. A common solution is the 2-coil inductive power link, used by current retinal prostheses. This power link tends to include a larger-size extraocular receiver coil coupled to the external transmitter coil, and the receiver coil is connected to the intraocular electrodes through a trans-sclera trans-choroid cable. In the long-term implantation of the device, the cable may cause hypotony (low intraocular pressure) and infection. However, when a 2-coil system is constructed from a small-size intraocular receiver coil, the efficiency drops drastically which may induce over heat dissipation and electromagnetic field exposure. Our previous 2-coil system achieved only 7% power transfer. This paper presents a fully intraocular and highly efficient wireless power transfer system, by introducing another inductive coupling link to bypass the trans-sclera trans-choroid cable. With the specific equivalent load of our customized 512-electrode stimulator, the current 3-coil inductive link was measured to have the overall power transfer efficiency around 36%, with 1-inch separation in saline. The high efficiency will favorably reduce the heat dissipation and electromagnetic field exposure to surrounding human tissues. The effect of the eyeball rotation on the power transfer efficiency was investigated as well. The efficiency can still maintain 14.7% with left and right deflection of 30 degree during normal use. The surgical procedure for the coils' implantation into the porcine eye was also demonstrated.


The Association between Leisure Time Physical Activity and Pancreatic Cancer Risk in Adults: A Systematic Review and Meta-analysis.
We conducted a meta-analysis of the association between leisure time physical activity (LTPA) and risk of pancreatic cancer to update previous analyses in light of newly published studies, to examine subgroups of interest and potential sources of heterogeneity. We searched the PubMed and MEDLINE databases for studies until February 2015. Study information was collected using a standardized form to abstract relevant data on study design, number of cases, participant and study characteristics, assessment of LTPA, risk estimates, and adjustments for confounding by two independent abstractors. We used random-effects models to pool estimates from included studies of lowest versus highest comparison of LTPA. The search identified 26 studies eligible for inclusion into the meta-analysis. The combined summary risk estimate was [relative risk (RR), 0.89; 95% confidence interval (CI), 0.82-0.96]. There was evidence of heterogeneity across studies (I(2) = 22.1%, Pheterogeneity = 0.130). Some of the heterogeneity could be explained by study design, with stronger protective effects observed among case-control studies (RR, 0.69; 95% CI, 0.59-0.81) compared with cohort studies (RR, 0.96; 95% CI, 0.91-1.02). Across study designs, age of population was a source of heterogeneity, with stronger effects observed among younger (<50 years) populations. The present meta-analysis supports a protective association between LTPA and pancreatic cancer with an 11% risk reduction observed. LTPA appears to have the strongest effect among young populations. Additional investigations are needed to provide insights regarding the impact of LTPA in healthy adult populations, to reduce the risk of pancreatic cancer and encourage increases in LTPA.


Molecular basis of transmembrane beta-barrel formation of staphylococcal pore-forming toxins.
Pathogenic bacteria secrete pore-forming toxins (PFTs) to attack target cells. PFTs are expressed as water-soluble monomeric proteins, which oligomerize into nonlytic prepore intermediates on the target cell membrane before forming membrane-spanning pores. Despite a wealth of biochemical data, the lack of high-resolution prepore structural information has hampered understanding of the β-barrel formation process. Here, we report crystal structures of staphylococcal γ-haemolysin and leucocidin prepores. The structures reveal a disordered bottom half of the β-barrel corresponding to the transmembrane region, and a rigid upper extramembrane half. Spectroscopic analysis of fluorescently labelled mutants confirmed that the prepore is distinct from the pore within the transmembrane region. Mutational analysis also indicates a pivotal role for the glycine residue located at the lipid-solvent interface as a 'joint' between the two halves of the β-barrel. These observations suggest a two-step transmembrane β-barrel pore formation mechanism in which the upper extramembrane and bottom transmembrane regions are formed independently.


[Deceased organ donation in 2020].
The success of solid organ transplantation induced an increased need for grafts and the necessary registration of transplant candidates on long waiting lists. Many patients die while waiting for transplantation, even in Belgium where the donation rates have been high these last years. In order to fight this lack of donor organs, the transplant centers widened donation criteria for brain dead donors, including older age and potential transmissible diseases. In addition, programs of donation after circulation death have been developed, first for kidneys, then for livers and recently for the hearts. Organ donation after euthanasia is also regularly performed in Belgium. All these policies lead to the fact that organ donation rates stay high in Belgium, and particularly in the Liege region, but efforts are still ahead if we aim to reduce waiting list mortalities.


Awareness of Heightened Sexual and Behavioral Vulnerability as a Trigger for PrEP Resumption Among Adolescent Girls and Young Women in East and Southern Africa.
East and Southern Africa are the epicenter of the HIV epidemic. High HIV incidence rates among adolescent girls and young women (AGYW) remain stable over the last decade despite access to daily oral PrEP. Some settings have experienced high PrEP uptake among AGYW; however, discontinuation has been high. This review sought to understand drivers of PrEP discontinuation in this population in order to identify potential mechanisms to facilitate PrEP restart and optimize PrEP use. Drivers of PrEP discontinuation included low perceived HIV acquisition risk, PrEP-associated side effects, pill burden, family/sexual partner disapproval, lack of/intermittent sexual activity, PrEP use stigma, fear of intimate partner violence, misinformation about long-term PrEP use, and limited/inconsistent access to PrEP. The most frequently reported driver of PrEP discontinuation was low perceived HIV acquisition risk. This indicates that innovative interventions to help AGYW recognize their HIV risk and make informed decisions about PrEP use are urgently needed.


Effect of rhythm and level of distraction on muscle structure: an animal study.
To determine the optimal rhythm of distraction and level of osteotomy for maximal muscle preservation during limb lengthening, histologic and ultrastructural analysis of the peroneus tertius muscle was performed in 46 goats. Thirty-nine animals with 20% or 30% tibial lengthening at the rate of 0.75 mm per day at each osteotomy level were divided in two groups. The first group included 15 animals undergoing tibial middiaphyseal lengthening with automated distractor producing one (n = 5), four (n = 5), or 720 (n = 5) increments per day. The second group included 24 animals in which lengthening was performed at the proximal (n = 4), middle (n = 6), distal (n = 6), or double (n = 8) level of the tibia with distraction rhythm of three times per day. The remaining seven animals served as controls. Histomorphologic features of the lengthened muscles were characterized by a polymorphous appearance with foci of necrosis, atrophy, and sclerosis scattered among apparently normal muscle fibers. The intensity and dispersion of degenerative changes were in direct proportion to the amount of lengthening but in reverse proportion to the frequency of distraction. Tibial lengthening at the diaphysis caused intense fibroblast proliferation and remarkable muscle sclerosis, whereas metaphyseal distraction was associated with a predominance of muscle tissue regeneration over atrophy and sclerosis. Bifocal lengthening and a more fractionated rhythm of distraction were associated with enhanced preservation of existing muscle fibers and greater regenerative activity of the muscle.


Kernel-based data fusion for gene prioritization.
Hunting disease genes is a problem of primary importance in biomedical research. Biologists usually approach this problem in two steps: first a set of candidate genes is identified using traditional positional cloning or high-throughput genomics techniques; second, these genes are further investigated and validated in the wet lab, one by one. To speed up discovery and limit the number of costly wet lab experiments, biologists must test the candidate genes starting with the most probable candidates. So far, biologists have relied on literature studies, extensive queries to multiple databases and hunches about expected properties of the disease gene to determine such an ordering. Recently, we have introduced the data mining tool ENDEAVOUR (Aerts et al., 2006), which performs this task automatically by relying on different genome-wide data sources, such as Gene Ontology, literature, microarray, sequence and more. In this article, we present a novel kernel method that operates in the same setting: based on a number of different views on a set of training genes, a prioritization of test genes is obtained. We furthermore provide a thorough learning theoretical analysis of the method's guaranteed performance. Finally, we apply the method to the disease data sets on which ENDEAVOUR (Aerts et al., 2006) has been benchmarked, and report a considerable improvement in empirical performance. The MATLAB code used in the empirical results will be made publicly available.


Differences in ME and CFS Symptomology in Patients with Normal and Abnormal Exercise Test Results.
Post-exertional malaise (PEM) is a cardinal symptom of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS), which often distinguishes patients with this illness from healthy controls or individuals with exclusionary illnesses such as depression. However, occurrence rates for PEM fluctuate from subject to how the symptom is operationalized. One commonly utilized method is exercise testing, maximal or submaximal. Many patients with ME and CFS experience PEM after participating in these tests, and often show abnormal results. However, some patients still exhibit normal results after participating in the exercise testing. This study examined the differences between two patient groups with ME and CFS, those with normal results and those with abnormal results, on several PEM-related symptoms and illness characteristics. The results suggest those that displayed abnormal results following testing have more frequent and severe PEM, worse overall functioning, and are more likely to be bedbound than those that displayed normal results.


Reducing inhalant use in Latino adolescents through synchronized parent-adolescent interventions.
This article presents the effects of a synchronized Latino youth/parent intervention on adolescent inhalant use. The analytic sample included only Latino adolescents (n = 487) between the ages of 12 and 14. Randomized at the school-level, the design included three possible conditions: (1) child and parent received the prevention interventions, (2) only the parent received the prevention intervention, (3) neither child or parent received the prevention interventions. Drawing from the eco-developmental perspective, the overall hypothesis was that youth randomly assigned to the condition with both interventions will report the strongest inhalant use prevention outcomes. Descriptive statistics and regression tests of significant group differences by treatment condition confirmed the overall hypothesis. Children receiving the youth intervention and whose parents received the synchronized parenting intervention reported the strongest desired inhalant prevention effects. The findings are interpreted from an eco-developmental perspective and implications for practice, policy, and future research are discussed.


Landscape structure and boundary effects determine the fate of mutations occurring during range expansions.
The interplay between the spatial dynamics of range expansion and evolutionary processes is receiving considerable attention. Recent theory has demonstrated that mutations occurring towards the front of a spatially expanding population can sometimes 'surf' to high frequency and spatial extent. Here, we extend this work to consider how the fate of a novel mutation is influenced by where and when it occurs. Specifically, we are interested in establishing how the origin of a mutation relative to a habitat edge influences its dynamics, and in understanding how this is mediated by the behaviour of individuals at those boundaries. Using a coupled-map lattice model, we demonstrate that the survival probability, abundance and spatial extent of surviving mutants can depend on their origin. An edge effect is often observed and can be quite different both qualitatively and quantitatively depending on the behavioural rules assumed. Mutations, especially those that are deleterious, that arise at a habitat edge with reflective boundary conditions can be many more times likely to survive for substantial periods of time than those that arise away from the edge. Conversely, with absorbing boundary conditions, their survival is greater when they arise well away from the edge. Our results clearly illustrate that landscape structure, habitat edges and boundary conditions have a considerable influence on the likely fate of mutations that occur during a period of range expansion.


Pre-Emptive Antimicrobial Locks Decrease Long-Term Catheter-Related Bloodstream Infections in Hemodialysis Patients.
This study aimed to prove that pre-emptive antimicrobial locks in patients at risk of bacteremia decrease infection. We performed a non-randomized prospective pilot study of hemodialysis patients with tunneled central venous catheters. We drew quantitative blood cultures monthly to detect colonization. Patients with a critical catheter colonization by coagulase-negative staphylococci (defined as counts of 100−999 CFU/mL) were at high risk of developing a catheter-related bloodstream infection. We recommended antimicrobial lock for this set of patients. The nephrologist in charge of the patient decided whether to follow the recommendation or not (i.e., standard of care). We compared bloodstream infection rates between patients treated with antimicrobial lock therapy versus patients treated with the standard of care (i.e., heparin). We enrolled 149 patients and diagnosed 86 episodes of critical catheter colonization by coagulase-negative staphylococci. Patients treated with antimicrobial lock had a relative risk of bloodstream infection of 0.19 when compared with heparin lock (CI 95%, 0.11−0.33, p < 0.001) within three months of treatment. We avoided one catheter-related bloodstream infection for every ten catheter-critical colonizations treated with antimicrobial lock [number needed to treat 10, 95% CI, 5.26−100, p = 0.046]. In conclusion, pre-emptive antimicrobial locks decrease bloodstream infection rates in hemodialysis patients with critical catheter colonization.


Administrative integration of vertical HIV monitoring and evaluation into health systems: a case study from South Africa.
In light of an increasing global focus on health system strengthening and integration of vertical programmes within health systems, methods and tools are required to examine whether general health service managers exercise administrative authority over vertical programmes. To measure the extent to which general health service (horizontal) managers, exercise authority over the HIV programme's monitoring and evaluation (M&E) function, and to explore factors that may influence this exercise of authority. This cross-sectional survey involved interviews with 51 managers. We drew ideas from the concept of 'exercised decision-space' - traditionally used to measure local level managers' exercise of authority over health system functions following decentralisation. Our main outcome measure was the degree of exercised authority - classified as 'low', 'medium' or 'high' - over four M&E domains (HIV data collection, collation, analysis, and use). We applied ordinal logistic regression to assess whether actor type (horizontal or vertical) was predictive of a higher degree of exercised authority, independent of management capacity (training and experience), and M&E knowledge. Relative to vertical managers, horizontal managers had lower HIV M&E knowledge, were more likely to exercise a higher degree of authority over HIV data collation (OR 7.26; CI: 1.9, 27.4), and less likely to do so over HIV data use (OR 0.19; CI: 0.05, 0.84). A higher HIV M&E knowledge score was predictive of a higher exercised authority over HIV data use (OR 1.22; CI: 0.99, 1.49). There was no association between management capacity and degree of authority. This study demonstrates a HIV M&E model that is neither fully vertical nor integrated. The HIV M&E is characterised by horizontal managers producing HIV information while vertical managers use it. This may undermine policies to strengthen integrated health system planning and management under the leadership of horizontal managers.


Distance estimation using a single computational camera with dual off-axis color filtered apertures.
In this paper, we present a novel computational imaging system using a dual off-axis color filtered aperture (DCA) for distance estimation in a single-camera framework. The DCA consists of two off-axis apertures that are covered by red and cyan color filters. The two apertures generate misaligned color channels in which the amount of misalignment of points in the image plane are a function of the distance from the camera of the corresponding points in the object plane. The primary contribution of this paper is the derivation of a mathematical model of the relationship between the color shifting values and distance of an object from the camera when the camera parameters and the baseline distance between the two apertures in the DCA are given. The proposed computational imaging system can be implemented simply by inserting an appropriately sized DCA into any general optical system. Experimental results show that the DCA camera is able to estimate the distances of objects within a single-camera framework.


Time course of self-desensitization of oral irritation by nicotine and capsaicin.
Nicotine contacting mucous membranes elicits irritation that decreases with repeated exposures (self-desensitization). We investigated the time course of nicotine self-desensitization and compared it with that of capsaicin. Nicotine (300 mM, 10 microl) was applied to one-half of the dorsal tongue and vehicle to the other. Following a rest period ranging from 0.5 to 48 h, nicotine (5 microl) was reapplied to each side of the tongue and subjects indicated on which side they experienced stronger irritation and separately rated the intensity of the sensation on each side. After intervals of 0.5, 1, and 24 h, a significant majority of subjects chose the vehicle-treated side as having stronger irritation and assigned significantly higher intensity ratings to that side, indicating self-desensitization. The effect was not present after 48 h. By comparison, 10 parts per million (ppm) (33 microM) capsaicin induced significant self-desensitization at 1 but not 24 h, whereas a higher concentration of capsaicin (100 ppm, 330 microM) induced significant self-desensitization at intervals of 1, 24, and 48 h. These results indicate that initial exposure to nicotine or capsaicin can markedly attenuate irritant sensations elicited by subsequent exposure to these irritants hours to days later.


Application of P,N-sulfinyl imine ligands to iridium-catalyzed asymmetric hydrogenation of olefins.
The utility of a novel class of P,N-ligands incorporating a chiral sulfinyl imine moiety is demonstrated in the iridium-catalyzed hydrogenation of both functionalized and unfunctionalized olefins, in which enantioselectivities of up to 94% are achieved. The modularity of the P,N-sulfinyl ligand class is highlighted by the facile preparation of a variety of sterically and electronically different ligands. Interesting structure-activity data for both the phosphine and sulfinamide components is provided by this expanded ligand set.


Stability of electrolyzed oxidizing water and its efficacy against cell suspensions of Salmonella typhimurium and Listeria monocytogenes.
Electrolyzed oxidizing (EO) water has proved to be effective against foodborne pathogens attached to cutting boards and poultry surfaces and against spoilage organisms on vegetables; however, its levels of effectiveness against Listeria monocytogenes and Salmonella Typhimurium in cell suspensions have not been compared with those of other treatments. In this study, the oxidation reduction potentials (ORPs), chlorine concentrations, and pHs of acidic and basic EO water were monitored for 3 days at 4 and 25 degrees C after generation. There were no differences between the pHs or ORPs of acidic and basic EO waters stored at 4 or 25 degrees C. However, the free chlorine concentration in acidic EO water stored at 4 degrees C increased after 24 h. In contrast, the free chlorine concentration in acidic EO water stored at 25 degrees C decreased after one day. Cell suspensions of Salmonella Typhimurium and L. monocytogenes were treated with distilled water, chlorinated water (20 ppm), acidified chlorinated water (20 ppm, 4.5 pH), acidic EO water (EOA), basic EO water (EOB), or acidic EO water that was "aged" at 4 degrees C for 24 h (AEOA) for up to 15 min at either 4 or 25 degrees C. The largest reductions observed were those following treatments carried out at 25 degrees C. EOA and AEOA treatments at both temperatures significantly reduced Salmonella Typhimurium populations by > 8 log10 CFU/ml. EOA and AEOA treatments effectively reduced L. monocytogenes populations by > 8 log10 CFU/ml at 25degrees C. These results demonstrate the stability of EO water under different conditions and that EO water effectively reduced Salmonella Typhimurium and L. monocytogenes populations in cell suspensions.


Endoscopic management of esophageal leaks.
Traditionally, gold standard treatment for an acute esophageal perforation has been operative repair. Over the past two decades, there has been a paradigm shift towards the use of esophageal stents. Recent advances in biomaterial allowed a new generation of stents to be manufactured that combined (I) a non-permeable covering; (II) radial force sufficient to occlude a transmural esophageal injury and (III) improved ease of removability. The amalgamation of these developments set the stage for utilizing esophageal stents as part of the management algorithm of an acute esophageal perforation. This provides a safe and less invasive treatment route in lieu of direct primary repair and its well-documented significant failure rate. Esophageal stent placement for failed operative repair or esophageal leaks also had the potential to minimize the need for esophageal resection and diversion. When included in a multimodality hybrid treatment protocol, esophageal stents can optimize healing success rates and minimize the risks of adverse complications. This review summarizes the modern history of esophageal stent use in the treatment of esophageal perforation as well as the evidenced based recommendations for the use of esophageal stent placement in the treatment of acute esophageal perforation.


Predicting tissue distribution and partitioning in terminal sire sheep using x-ray computed tomography.
The utility of x-ray computed tomography (CT) scanning in predicting carcass tissue distribution and fat partitioning in vivo in terminal sire sheep was examined using data from 160 lambs representing combinations of 3 breeds (Charollais, Suffolk, and Texel), 3 genetic lines, and both sexes. One-fifth of the lambs were slaughtered at each of 14, 18, and 22 wk of age, and the remaining two-fifths at 26 wk of age. The left side of each carcass was dissected into 8 joints with each joint dissected into fat (intermuscular and subcutaneous), lean, and bone. Chemical fat content of the LM was measured. Tissue distribution was described by proportions of total carcass tissue and lean weight contained within the leg, loin, and shoulder regions of the carcass and within the higher-priced joints. Fat partitioning variables included proportion of total carcass fat contained in the subcutaneous depot and intramuscular fat content of the LM. Before slaughter, all lambs were CT scanned at 7 anatomical positions (ischium, midshaft of femur, hip, second and fifth lumbar vertebrae, sixth and eighth thoracic vertebrae). Areas of fat, lean, and bone (mm(2)) and average fat and lean density (Hounsfield units) were measured from each cross-sectional scan. Areas of intermuscular and subcutaneous fat were measured on 2 scans (ischium and eighth thoracic vertebra). Intramuscular fat content was predicted with moderate accuracy (R(2) = 56.6) using information from only 2 CT scans. Four measures of carcass tissue distribution were predicted with moderate to high accuracy: the proportion of total carcass (R(2) = 54.7) and lean (R(2) = 46.2) weight contained in the higher-priced joints and the proportion of total carcass (R(2) = 77.7) and lean (R(2) = 55.0) weight in the leg region. Including BW in the predictions did not improve their accuracy (P > 0.05). Although breed-line-sex combination significantly affected fit of the regression for some tissue distribution variables, the values predicted were changed only trivially. Within terminal sire type animals, using a common set of prediction equations is justified. Tissue distribution and fat partitioning affect eating satisfaction and efficiency of production and processing; therefore, including such carcass quality measures in selection programs is increasingly important, and CT scanning appears to provide opportunities to do so.


[A study of genetic character of cultivar Shiyuan 321 from G. barbadense x G. thurberi x G. hirsutum using isozyme and RAPD techniques].
To study the genetic character of trispecific hybrid cultivar Shiyuan 321, we analyzed this cultivar and its parents by isozyme and RAPD techniques. The main results are as follows: (1) Esterase isozyme analysis showed that there was one specific band among cultivar Suiyuan 321 and its parents, G. thurberi and G. barbadense; (2) Six specific DNA fragments amplified by 4 primers were found among cultivar Shiyuan 321 and its parents G. barbadense, G. thurberi; (3) By comparing RAPD differences among Shiyuan 321 and its parents, it is indicated that the genetic heterogeneity of cultivar Shiyuan 321 is very high at its genomic DNA level. The above results proved that Shiyuan 321 is a trispecific cultivar from G. barbadense x G. thurberi x G. hirsutum as well as a new germplasm.


The influence of reproductive hormones on brain function in the menopausal transition.
Reproductive hormones have long been thought to have a significant impact on brain function in humans. Estrogens, progestins and androgens have all been shown to have effects on nerve growth and function in vitro. The neurofunctional domains of cognition, mood and sleep are now receiving increased study to determine both the relationship of endogenous sex steroids through the menopausal transition and the effect of menopausal hormone therapy on these complex functions. All three domains are the source of frequent concern in midlife women, but the relative contribution of ovarian versus somatic aging is only now being untangled. Cognitive function has been most extensively studied, with mixed results in both observational studies and clinical trials, largely due to the remarkably complex aspects of human cognition requiring extensive and targeted testing of specific components. Both mood and sleep disorders have been associated with the menopausal transition, but observed effects appear modest. To date, clinical trial data are insufficient to support the use of hormone therapy specifically for the prevention or treatment of cognitive, mood or sleep disorders in midlife women.