Cell surface-bound TIMP3 induces apoptosis in mesenchymal Cal78 cells through ligand-independent activation of death receptor signaling and blockade of survival pathways.
The matrix metalloproteinases (MMPs) and their endogenous regulators, the tissue inhibitor of metalloproteinases (TIMPs 1-4) are responsible for the physiological remodeling of the extracellular matrix (ECM). Among all TIMPs, TIMP3 appears to play a unique role since TIMP3 is a secreted protein and, unlike the other TIMP family members, is tightly bound to the ECM. Moreover TIMP3 has been shown to be able to induce apoptotic cell death. As little is known about the underlying mechanisms, we set out to investigate the pro-apoptotic effect of TIMP3 in human mesenchymal cells. Lentiviral overexpression of TIMP3 in mesenchymal cells led to a strong dose-dependent induction of ligand-independent apoptosis as reflected by a five-fold increase in caspase 3 and 7 activity compared to control (pLenti6/V5-GW/lacZ) or uninfected cells, whereas exogenous TIMP3 failed to induce apoptosis. Concordantly, increased cleavage of death substrate PARP and the caspases 3 and 7 was observed in TIMP3 overexpressing cultures. Notably, activation of caspase-8 but not caspase-9 was observed in TIMP3-overexpressing cells, indicating a death receptor-dependent mechanism. Moreover, overexpression of TIMP3 led to a further induction of apoptosis after stimulation with TNF-alpha, FasL and TRAIL. Most interestingly, TIMP3-overexpression was associated with a decrease in phosphorylation of cRaf, extracellular signal-regulated protein kinase (Erk1/2), ribosomal S6 kinase (RSK1) and Akt and serum deprivation of TIMP3-overexpressing cells resulted in a distinct enhancement of apoptosis, pointing to an impaired signaling of serum-derived survival factors. Finally, heparinase treatment of heparan sulfate proteoglycans led to the release of TIMP3 from the surface of overexpressing cells and to a significant decrease in apoptosis indicating that the binding of TIMP3 is necessary for apoptosis induction. The results demonstrate that exclusively cell surface-bound endogenous TIMP3 induces apoptosis in mesenchymal Cal78 cells through ligand-independent activation of death receptor signaling and blockade of survival signaling pathways.


Sex disparity in secondary prevention pharmacotherapy and clinical outcomes following acute coronary syndrome.
We sought to investigate if sex disparity exists for secondary prevention pharmacotherapy following acute coronary syndrome (ACS) and impact on long-term clinical outcomes. We analysed data on medical management 30-day post-percutaneous coronary intervention (PCI) for ACS in 20 976 patients within the multicentre Melbourne Interventional Group registry (2005-2017). Optimal medical therapy (OMT) was defined as five guideline-recommended medications, near-optimal medical therapy (NMT) as four medications, sub-optimal medical therapy (SMT) as ≤3 medications. Overall, 65% of patients received OMT, 27% NMT and 8% SMT. Mean age was 64 ± 12 years; 24% (4931) were female. Women were older (68 ± 12 vs. 62 ± 12 years) and had more comorbidities. Women were less likely to receive OMT (61% vs. 66%) and more likely to receive SMT (10% vs. 8%) compared to men, P < 0.001. On long-term follow-up (median 5 years, interquartile range 2-8 years), women had higher unadjusted mortality (20% vs. 13%, P < 0.001). However, after adjusting for medical therapy and baseline risk, women had lower long-term mortality [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.79-0.98; P = 0.02]. NMT (HR 1.17, 95% CI 1.05-1.31; P = 0.004) and SMT (HR 1.79, 95% CI 1.55-2.07; P < 0.001) were found to be independent predictors of long-term mortality. Women are less likely to be prescribed optimal secondary prevention medications following PCI for ACS. Lower adjusted long-term mortality amongst women suggests that as well as baseline differences between gender, optimization of secondary prevention medical therapy amongst women can lead to improved outcomes. This highlights the need to focus on minimizing the gap in secondary prevention pharmacotherapy between sexes following ACS.


Functionalization of Rhodamine Platforms with 3-Hydroxy-4-pyridinone Chelating Units and Its Fluorescence Behavior towards Fe(III).
Functionalization of xanthene fluorophores with specific receptor units is an important topic of research aiming for the development of new analytical tools for biological sciences, clinical diagnosis, food and environmental monitoring. Herein, we report a new dihydrorosamine containing two active amino groups, which was functionalized with 3-benzyloxy-1-(3'-carboxypropyl)-2-methyl-4-pyridinone through an amide coupling strategy. Benzylated mono- and di-functionalized dihydrorosamine derivatives (H in position 9 of the xanthene) were obtained, but with modest reaction yields, requiring long and laborious purification procedures. Looking for a more efficient approach, rhodamine 110 was selected to react with the carboxypropyl pyridinone, enabling the isolation of the corresponding mono- and di-functionalized derivatives in amounts that depend on the excess of pyridinone added to the reaction. The structure of all compounds was established by 1H and 13C NMR, MS (ESI) and their absorption and emission properties were evaluated in dichloromethane. The fluorescence behavior of the debenzylated mono-rhodamine 110 derivative in the presence of Fe(III) was studied, making it an interesting fluorogenic dye for future optical sensing applications.


Single Extracellular Vesicle Analysis Performed by Imaging Flow Cytometry and Nanoparticle Tracking Analysis Evaluate the Accuracy of Urinary Extracellular Vesicle Preparation Techniques Differently.
Small extracellular vesicles isolated from urine (uEVs) are increasingly recognized as potential biomarkers. Meanwhile, different uEV preparation strategies exist. Conventionally, the performance of EV preparation methods is evaluated by single particle quantification, Western blot, and electron microscopy. Recently, we introduced imaging flow cytometry (IFCM) as a next-generation single EV analysis technology. Here, we analyzed uEV samples obtained with different preparation procedures using nanoparticle tracking analysis (NTA), semiquantitative Western blot, and IFCM. IFCM analyses demonstrated that urine contains a predominant CD9+ sEV population, which exceeds CD63+ and CD81+ sEV populations. Furthermore, we demonstrated that the storage temperature of urine samples negatively affects the recovery of CD9+ sEVs. Although overall reduced, the highest CD9+ sEV recovery was obtained from urine samples stored at -80 °C and the lowest from those stored at -20 °C. Upon comparing the yield of the different uEV preparations, incongruencies between NTA and IFCM data became apparent. Results obtained by both NTA and IFCM were consistent with Western blot analyses for EV marker proteins; however, NTA results correlated with the amount of the impurity marker uromodulin. Despite demonstrating that the combination of ultrafiltration and size exclusion chromatography appears as a reliable uEV preparation technique, our data challenge the soundness of traditional NTA for the evaluation of different EV preparation methods.


Investigation on Mycobacterium tuberculosis diversity in China and the origin of the Beijing clade.
Investigation of the genetic diversity of Mycobacterium tuberculosis in China has shown that Beijing genotype strains play a dominant role in the tuberculosis (TB) epidemic. In order to examine the strain diversity in the whole country, and to study the evolutionary development of Beijing strains, we sought to genotype a large collection of isolates using different methods. We applied a 15-loci VNTR typing analysis on 1,586 isolates from the Beijing municipality and 12 Chinese provinces or autonomous regions. The data was compared to that of 900 isolates from various other worldwide geographic regions outside of China. A total of 1,162/1,586 (73.2%) of the isolates, distributed into 472 VNTR types, were found to belong to the Beijing genotype family and this represented 56 to 94% of the isolates in each of the localizations. VNTR typing revealed that the majority of the non-Beijing isolates fall into two genotype families, which represented 17% of the total number of isolates, and seem largely restricted to China. A small number of East African Indian genotype strains was also observed in this collection. Ancient Beijing strains with an intact region of difference (RD) 181, as well as strains presumably resembling ancestors of the whole Beijing genotype family, were mainly found in the Guangxi autonomous region. This is the largest M. tuberculosis VNTR-based genotyping study performed in China to date. The high percentage of Beijing isolates in the whole country and the presence in the South of strains representing early branching points may be an indication that the Beijing lineage originated from China, probably in the Guangxi region. Two modern lineages are shown here to represent the majority of non-Beijing Chinese isolates. The observed geographic distribution of the different lineages within China suggests that natural frontiers are major factors in their diffusion.


Model for Interpretation and Correlation of Contact Angle Measurements
An improved formulation relating the contact angle to the surface coverage is presented and verified. The Ohmi et al. data (Particle Sci. Technol. 7, 229, 1993) for ultracleaning of wafer surfaces are analyzed and correlated mathematically. It is shown that the new formulation represents the Ohmi et al. and Englander et al. (J. Colloid Interface Sci. 179, 635, 1996) data satisfactorily. In addition, the present study provides some insight into the mechanism of the variation of the surface coverage and the contact angle. Copyright 1997Academic Press


Two-Dimensional Infrared Spectroscopy Reveals Molecular Self-Assembly on the Surface of Silver Nanoparticles.
The conformation of molecules, peptides, and proteins, self-assembled into structured monolayers on the surface of metal nanoparticles (NPs), can strongly affect their properties and use in chemical or nanobiomedical applications. Elucidating molecular conformations on the NP surface is highly challenging, and the microscopic details mostly remain elusive. Using polarization-selective third-order two-dimensional ultrafast infrared spectroscopy, we revealed the highly ordered intermolecular structure of γ-tripeptide glutathione on the surface of silver NPs in aqueous solution. Glutathione is an antioxidant thiol abundant in living cells; it is extensively used in NP chemistry and related research. We identified conditions where the interaction of glutathione with the NP surface facilitates formation of a β-sheet-like structure enclosing the NPs. A spectroscopic signature associated with the assembly of β-sheets into an amyloid fibril-like structure was also observed. Remarkably, the interaction with the metal surface promotes formation of a fibril-like structure by a small peptide involving only two amino acids.


Beta adrenergic influence on esophageal and colonic motility in man.
Gastrointestinal (GI) motility is centrally controlled through the sympathetic and parasympathetic nerves, sympathetic effects being partly mediated by beta adrenoceptors. Although beta adrenoceptor agonists and antagonists are widely used for different disorders, little is known about the influence of these agents on GI motility. The present study was initiated to investigate whether there is a physiological, beta adrenergic influence on human GI motility and to describe the effects of selective beta adrenoceptor stimulation on motility in the proximal and distal parts of the GI tract. Esophageal peristalsis was measured in healthy subjects using electronic catheters. Distal colonic motility was measured with an open-tipped, water-perfused catheter in the sigmoid colon and from an air-filled balloon in the rectum in healthy subjects and in patients with the irritable bowel syndrome (IBS). In one study, colonic motility was stimulated with continuous infusion of the octapeptide of cholecystokinin (CCK-OP). Esophagus: Peristaltic amplitude was increased in the distal smooth muscle part of the esophageal body after infusion of both the nonselective beta blocker propranolol and the beta-1 selective blocker metoprolol. After infusion of the beta-1 agonist prenalterol and the beta-2 selective agonist terbutaline, a profound decrease in esophageal peristaltic amplitude was seen. Pretreatment with metoprolol selectively blocked the response to a moderate dose of prenalterol but did not block the response to terbutaline. The latter response was blocked by propranolol. Peristaltic velocity in the proximal part of the esophagus was decreased by beta-1 stimulation and in the distal part by beta-2 stimulation. Distal colon: In healthy subjects the sigmoid motility index showed a dose-dependent increase after metoprolol and propranolol, respectively. The increase was more marked after propranolol infusion. Terbutaline decreased the sigmoid motility index both in healthy subjects and in patients with the IBS. Furthermore, the rectal motility index was decreased in the group of healthy subjects. The effects of prenalterol on rectal and sigmoid motility did not differ from those of placebo. The IBS patient group showed larger intraindividual variations in sigmoid motility from day to day and also lower rectal motility indices than the healthy subjects. Infusion of CCK-OP increased the sigmoid motility index compared to non-stimulated conditions. No effects on CCK-OP stimulated motility were seen after either terbutaline, prenalterol or placebo.(ABSTRACT TRUNCATED AT 400 WORDS)


Uncoupling nicotine mediated motoneuron axonal pathfinding errors and muscle degeneration in zebrafish.
Zebrafish embryos offer a unique opportunity to investigate the mechanisms by which nicotine exposure impacts early vertebrate development. Embryos exposed to nicotine become functionally paralyzed by 42 hpf suggesting that the neuromuscular system is compromised in exposed embryos. We previously demonstrated that secondary spinal motoneurons in nicotine-exposed embryos were delayed in development and that their axons made pathfinding errors (Svoboda, K.R., Vijayaraghaven, S., Tanguay, R.L., 2002. Nicotinic receptors mediate changes in spinal motoneuron development and axonal pathfinding in embryonic zebrafish exposed to nicotine. J. Neurosci. 22, 10731-10741). In that study, we did not consider the potential role that altered skeletal muscle development caused by nicotine exposure could play in contributing to the errors in spinal motoneuron axon pathfinding. In this study, we show that an alteration in skeletal muscle development occurs in tandem with alterations in spinal motoneuron development upon exposure to nicotine. The alteration in the muscle involves the binding of nicotine to the muscle-specific AChRs. The nicotine-induced alteration in muscle development does not occur in the zebrafish mutant (sofa potato, [sop]), which lacks muscle-specific AChRs. Even though muscle development is unaffected by nicotine exposure in sop mutants, motoneuron axonal pathfinding errors still occur in these mutants, indicating a direct effect of nicotine exposure on nervous system development.


Voltage-activated K+ currents of hypoglossal motoneurons in a brain stem slice preparation from the neonatal rat.
Whole cell, patch-clamp recordings were performed on motoneurons of the hypoglossus nucleus in a brain stem slice preparation from the neonatal rat brain. The aim was to investigate transient outward currents activated by membrane depolarization under voltage clamp conditions. In a Ca2+-free medium containing tetrodotoxin and Cs+, depolarizing voltage commands from a holding potential of -50 mV induced slow outward currents (Islow) with 34 +/- 6 ms (SE) onset time constant at 0 mV and minimal decline during a 1 s pulse depolarization. When the depolarizing command was preceded by a prepulse to -110 mV, the outward current became biphasic as it comprised a faster component (Ifast), which could be investigated in isolation by subtracting the two sets of records. Ifast showed rapid kinetics (9 +/- 4 ms 10-90% rise time and 70 +/- 20 ms decay time constant at 0 mV) and strong voltage-dependent inactivation (half inactivation was at -92.9 +/- 0.2 mV) from which it readily recovered with a biexponential timecourse (4.4 +/- 0.6 and 17 +/- 2 ms time constants at -110 mV membrane potential). Islow was selectively blocked by TEA (10-30 mM) while Ifast was preferentially depressed by 2-3 mM 4-aminopyridine. Analysis of tail current reversal indicated that both Islow and Ifast were predominantly due to K+ with minor permeability to Na+ (92/1 and 50/1, respectively). These results suggest that membrane depolarization activated distinct K+ conductances that, in view of their largely dissimilar kinetics, are likely to play a differential role in regulating the firing behavior of hypoglossal motoneurons.


Hwa-Byung among middle-aged Korean women: family relationships, gender-role attitudes, and self-esteem.
We surveyed 395 Korean middle-aged women and examined how their perceptions of family relationships, gender-role attitudes, and self-esteem were associated with Hwa-Byung (HB; Korean anger syndrome). Our regression analyses revealed that participants who reported worse family relationship problems experienced more HB symptoms. Having profeminist, egalitarian attitudes toward women's gender roles was also associated with more HB symptoms. Self-esteem was not significantly associated with HB. Based on the results, we suggest that what is crucial to understanding HB is not how women evaluate themselves, but rather the level of stress caused by family relationship problems and their perception of women's roles.


Molecular targeted therapies in non-GIST soft tissue sarcomas: what the radiologist needs to know.
Non-gastrointestinal stromal soft tissue sarcomas are uncommon neoplasms that have a dismal prognosis due to a high incidence of metastases and a poor response to conventional chemotherapy. The identification of characteristic genetic alterations in several of these tumors has opened the window for molecular targeted therapies in patients who have failed conventional chemotherapy. Imaging plays a critical role in assessing the response to these novel therapeutic agents. Just like the response of gastrointestinal stromal tumors to imatinib, the response of non-gastrointestinal stromal soft tissue sarcomas to molecular targeted drugs is better evaluated on imaging by alternate tumor response criteria such as the Choi criteria. In addition, these drugs are associated with distinct class-specific drug toxicities that can come to attention for the first time on imaging. The purpose of this article is to provide a primer for the radiologist on the various molecular targeted therapies in advanced/metastatic non-gastrointestinal stromal soft tissue sarcomas with emphasis on the role of imaging in assessing treatment response and complications.


Maize grain concentrations and above-ground shoot acquisition of micronutrients as affected by intercropping with turnip, faba bean, chickpea, and soybean.
Most research on micronutrients in maize has focused on maize grown as a monocrop. The aim of this study was to determine the effects of intercropping on the concentrations of micronutrients in maize grain and their acquisition via the shoot. We conducted field experiments to investigate the effects of intercropping with turnip (Brassica campestris L.), faba bean (Vicia faba L.), chickpea (Cicer arietinum L.), and soybean (Glycine max L.) on the iron (Fe), manganese (Mn), copper (Cu) and zinc (Zn) concentrations in the grain and their acquisition via the above-ground shoots of maize (Zea mays L.). Compared with monocropped maize grain, the grain of maize intercropped with legumes showed lower concentrations of Fe, Mn, Cu, and Zn and lower values of their corresponding harvest indexes. The micronutrient concentrations and harvest indexes in grain of maize intercropped with turnip were the same as those in monocropped maize grain. Intercropping stimulated the above-ground maize shoot acquisition of Fe, Mn, Cu and Zn, when averaged over different phosphorus (P) application rates. To our knowledge, this is the first report on the effects of intercropping on micronutrient concentrations in maize grain and on micronutrients acquisition via maize shoots (straw+grain). The maize grain Fe and Cu concentrations, but not Mn and Zn concentrations, were negatively correlated with maize grain yields. The concentrations of Fe, Mn, Cu, and Zn in maize grain were positively correlated with their corresponding harvest indexes. The decreased Fe, Mn, Cu, and Zn concentrations in grain of maize intercropped with legumes were attributed to reduced translocation of Fe, Mn, Cu, and Zn from vegetative tissues to grains. This may also be related to the delayed senescence of maize plants intercropped with legumes. We conclude that turnip/maize intercropping is beneficial to obtain high maize grain yield without decreased concentrations of Fe, Mn, Cu, and Zn in the grain. Further research is required to clarify the mechanisms underlying the changes in micronutrient concentrations in grain of intercropped maize.


A Rasch Analysis of the Irrational Procrastination Scale (IPS).
The present study analyses the psychometric properties of the irrational procrastination scale (IPS; Steel, 2002, 2010) in a sample of United States college students using the Rasch modeling approach. Results showed that the IPS items had a high level of reliability, good content validity, structural validity, and substantive validity, and no differential item functioning (DIF) effects in terms of gender. The IPS was found to be unidimensional, supporting the originally proposed theoretical structure by Steel (2002, 2010). Finally, psychometric implications derived from the results and study limitations are discussed; recommendations for future investigations are also offered.


Neonatal head ultrasound: systematic approach to congenital Central Nervous System anomalies. A pictorial essay.
Brain ultrasound is widely used for the screening of prematurely born babies. Although the best imaging modality for the central nervous system anomaly is brain MRI, the first imaging study in the post-natal period is brain ultrasonography in most cases. Anomalies could be found incidentally on screening ultrasound, or in those cases already suspected on prenatal ultrasound. In order not to miss congenital structural abnormalities of the brain on screening ultrasound, systematic approaches would be very helpful. The ventricles and sylvian fissures are very important structures to suspect central nervous system anomalies: they are symmetric structures so we should look for any asymmetry or maldevelopment. And then, on sagittal images, the midline structures including the corpus callosum and cerebellar vermis should be observed carefully. Finally, we should look for any abnormality in gyration or cortical development. Skull defect with herniation of intracranial contents, a spectrum of encephalo-meningocele, could be also identified on ultrasound. Congenital infections such as cytomegalovirus infection may show ventriculomegaly and malformation of the cortical development on imaging studies.


Acute-on-Chronic Liver Failure.
Over the past 2 decades, the concept of acute-on-chronic liver failure (ACLF) has been proposed as an alternate path in the natural history of decompensated cirrhosis. ACLF thus is characterized by the presence of a precipitating event (identified or unidentified) in subjects with underlying chronic liver disease leading to rapid progression of liver injury and ending in multi-organ dysfunction characterized by high short-term mortality. Multiple organ failure and an increased risk for mortality are key to the diagnosis of ACLF. The prevalence of ACLF ranges from 24% to 40% in hospitalized patients. The pathophysiological basis of ACLF can be explained using the following 4-part model: predisposing event, injury caused by a precipitating event, response to injury, and organ failure. Although several mathematic scores have been proposed for identifying outcomes with ACLF, it is as yet unclear whether these organ failure scores are truly prognostic or only reflective of the dying process. Treatment paradigms continue to evolve but consist of early recognition, supportive intensive care, and consideration of liver transplantation before onset of irreversible multiple organ failure.


Dave Eggers's a heartbreaking work of staggering genius: memoir as a "pain-relief device".
Dave Eggers's memoir is an important addition to the tradition of autobiography in America, and offers significant contributions to our understanding of creativity, sublimation, and the psychology of the memoir-writing process. A Heartbreaking Work of Staggering Genius is really two books--an autobiographical narrative about unbearable suffering, and a book of psychoanalytic commentary on the challenges of writing a memoir about catastrophic loss and trauma. The main narrative suggests the psychological resilience it takes to contain unbearable suffering. The metanarrative renders transparent the mind of someone who is both remembering his losses and constantly reflecting upon the process of writing about them. Eggers's identification with authorship, rather than bereavement or traumatization, may have played an important role in containing his affect and his sense of self when the heartbreaking events were originally unfolding. But a price is paid when a son uses his art to construct a new identity as an author--unconscious conflicts, primitive affect, anxieties about failing, as well as guilt about succeeding--consequences often missed by readers. Heartbreaking is a palimpsest, a story about story-telling superimposed on tales of death and survival, but its messages will be missed unless all its parts are preserved when being read or studied.


Intraoperative improvement of somatosensory evoked potentials and local spinal cord blood flow in patients with syringomyelia.
This report is the first to correlate data concerning intraoperative somatosensory evoked potentials (SSEPs) and local spinal cord blood flow (ISCBF) in patients with syringomyelia. In a consecutive study, bilateral median nerve SSEPs were recorded intraoperatively in 13 patients undergoing a syrinx shunt to the posterior fossa cisterns (syringocisternostomy). ISCBF was measured in five of these patients using laser doppler flowmetry (LDF) calibrated in arbitrary units (AU). SSEP recordings obtained 30 min after syrinx decompression demonstrated a slight but consistent reduction of N20 latencies (mean change: 0.53 ms right, p < 0.003; 0.58 ms left, p < 0.001) concurrent with a similar but less consistent increase of N20 amplitudes (0.16 mV right, p = 0.256; 0.29 mV left, p = 0.03). Prior to shunting, LDF recordings from the spinal cord overlying syrinxes revealed very low ISCBF values in five of five patients (mean LDF, 13.2 AU +/- 15.3 SD). Immediately after shunting, there was a dramatic rise of ISCBF (mean LDF, 241.2 AU +/- 106.3 SD) associated with visualized hyperemia of the spinal cord and pial vessels. The ISCBF fell to intermediate levels after 2 min (157.2 AU +/- 33.0 SD) and remained at these levels during the interval of recording (5 min). Hyperventilation testing in two patients prior to shunting revealed no change in ISCBF consistent with a loss of CO2 vascular reactivity and a paradoxical increase of ISCBF in one patient 5 min after shunting. Each patient in this study experienced neurological improvement in the immediate postoperative period associated with collapse or disappearance of the syrinx on magnetic resonance imaging scans. Because syrinx shunting results in an acute decompression of the distended spinal cord, it is possible that the rapid improvement of SSEPs reflects a relief of mechanical factors such as stretching and compression of nervous tissue. However, the LDF findings in this study suggest that distended spinal cord cavities are also capable of producing regional ischemia. A significant reduction of ISCBF is a possible contributing cause of neurological injury and SSEP abnormalities. Intraoperative improvement of SSEPs and ISCBF were found to correlate well with neurological recovery following syringocisternostomy. Our results indicate that SSEP monitoring can provide useful information during surgical procedures for syringomyelia and that further experience with LDF monitoring may provide insights into the pathophysiology of this condition.


Gastroesophageal reflux and sequelae of chronic tubotympanal disorders in children.
To compare sequelae of chronic tubotympanal disorders in children with and without gastroesophageal reflux (GER). In 32 patients with chronic tubotympanal disorders GER was studied by means of 24-h continuous esophageal pH monitoring. After a period of 2-6 years (mean 4 years) sequelae of the tubotympanal disorders were examined, together with the clinical status of the ears and hearing status. The criteria for classification into mild, moderate and severe sequelae were based on the clinical status of the ear. Hearing was determined using tonal audiograms. Conductive hearing loss was classified as either slight (< or = 35 dB hearing loss in speech frequencies) or severe (>35 dB hearing loss in speech frequencies). In the group of 16 patients (mean age 6.1 years) with GER, sequelae were observed in 29 ears (mild, n=11; moderate, n=5; severe, n=13). Hearing impairment was determined in 20 ears (mild, n=8; severe, n=12). In the group of 16 patients (mean age 7.1 years) without GER, sequelae were observed in 17 ears (mild, n=11; moderate, n=1; severe, n=5). Hearing impairment was determined in 10 ears (mild, n=6; severe, n=4). The total number of ears with sequelae and the total number of ears with conductive hearing impairment were significantly higher in patients with GER.


Interocular generalization: a study of mirror-image reversal following monocular discrimination training in the pigeon.
Generalization gradients along a continuum of angular orientation were obtained from four pigeons, following monocular training on a discrimination between a 45 degrees oblique line (S+) and a 135 degrees oblique line (S-). All pigeons were trained on a chain DRO VI 1 schedule of reinforcement. Generalization gradients obtained with the trained and untrained eye were compared. All pigeons responded maximally to the 45 degrees line (S+) when tested with only the trained eye open. During generalization tests of interocular transfer with only the untrained eye open, three pigeons responded maximally to S- (135 degrees ), the mirror-image of the stimulus associated with reinforcement during training (45 degrees ). The other pigeon failed to show interocular transfer of the discrimination. Interocular reversal of left-right mirror-image stimuli has not been reported for any other species.


A desalting approach for MALDI-MS using on-probe hydrophobic self-assembled monolayers.
One of the problems encountered in preparing samples for matrix-assisted laser desorption/ionization (MALDI) analysis is the presence of nonvolatile salts in the sample. This difficulty is often exacerbated by the necessity to prepare the sample in the appropriate sample-to-matrix ratio. This paper reports a probe surface derivatization method that greatly simplifies this sample preparation process. By constructing self-assembled monolayers of octadecyl mercaptan (C18) on the MALDI probe surface, we were able to generate a surface capable of reversibly binding polypeptides via hydrophobic interactions, which in turn, permits the analyte to be easily concentrated and desalted directly on the probe tip.


Thermally reversible self-assembly of nanoparticles via polymer crystallization.
The directed self-assembly of gold nanoparticles through the crystallization of surface-grafted polyethylene oxide (PEO) in ethanol-water mixtures is described. This process is fully reversible and tunable through either the size of the core or the polymeric coating. Characterization by X-ray scattering and electron microscopy of the self-assembled structures reveals order at the nanoscale, typically not the case for thermoresponsive gold nanoparticles coated with lower or upper critical solution temperature polymers. A further novelty is the result of selective binding of calcium ions to the PEO in the fluid state: a reversible thermoresponsive transition become irreversible.


Solitary fibrous tumor of the upper respiratory tract. A report of six cases.
We report six cases of a neoplasm that arose in the upper respiratory tract and had a histological appearance indistinguishable from that of solitary fibrous tumor of the pleura (SFT, so-called fibrous mesothelioma). The patients were adults who presented with nasal obstruction. The lesions lacked the characteristic features of other recognized neoplasms that occur in this region. The tumor cells were immunoreactive for vimentin but not for keratin. The occurrence of SFT in this location further supports the argument that SFT is a tumor of mesenchymal and not mesothelial origin. None of the tumors in this series had the histologic features of malignancy described for SFT in other locations, and there was no aggressive behavior in limited follow-up. Until more cases of SFT in unusual locations have been studied, we recommend that the same criteria used for assessing aggressiveness in SFT of the pleura be applied to them.


Enhanced Cathodic Electrochemiluminescence of Luminol on Iron Electrodes.
Electrochemiluminescence (ECL) behavior of luminol derivative was investigated in reduction on different electrode materials. We found that luminol and its widely used L-012 derivative, emitting at physiological pH values, exhibit strong cathodic ECL emission on iron and stainless steel electrodes with hydrogen peroxide, whereas no ECL signal was observed with other classic electrode materials (Au, Pt, and C). On a Ni electrode, a low cathodic ECL signal was observed. This points out to the essential role of iron-containing materials to enhance the cathodic ECL emission. Under the reported conditions, the cathodic ECL signal of L-012 is comparable to the classically used anodic ECL emission. Thus, dual bright ECL emissions with L-012 were obtained simultaneously in oxidation and in reduction on iron materials as imaged in a wireless bipolar electrochemistry configuration. Such an ECL system generating light emission concomitantly in oxidation and in reduction is extremely rare and it opens appealing (bio)analytical and imaging applications, in biosensing, remote detection, bipolar ECL analysis, and ECL-based cell microscopy.


Large Scale Synthesis of Nanopyramidal-Like VO₂ Films by an Oxygen-Assisted Etching Growth Method with Significantly Enhanced Field Emission Properties.
The present investigation reported on a novel oxygen-assisted etching growth method that can directly transform wafer-scale plain VO₂ thin films into pyramidal-like VO₂ nanostructures with highly improved field-emission properties. The oxygen applied during annealing played a key role in the formation of the special pyramidal-like structures by introducing thin oxygen-rich transition layers on the top surfaces of the VO₂ crystals. An etching related growth and transformation mechanism for the synthesis of nanopyramidal films was proposed. Structural characterizations confirmed the formation of a composite VO₂ structure of monoclinic M1 (P21/c) and Mott insulating M2 (C2/m) phases for the films at room temperature. Moreover, by varying the oxygen concentration, the nanocrystal morphology of the VO₂ films could be tuned, ranging over pyramidal, dot, and/or twin structures. These nanopyramidal VO₂ films showed potential benefits for application such as temperature-regulated field emission devices. For one typical sample deposited on a 3-inch silicon substrate, its emission current (measured at 6 V/μm) increased by about 1000 times after the oxygen-etching treatment, and the field enhancement factor β reached as high as 3810 and 1620 for the M and R states, respectively. The simple method reported in the present study may provide a protocol for building a variety of large interesting surfaces for VO₂-based device applications.


Intracellular Ca2+ regulating proteins in vascular smooth muscle cells are altered with type 1 diabetes due to the direct effects of hyperglycemia.
Diminished calcium (Ca2+) transients in response to physiological agonists have been reported in vascular smooth muscle cells (VSMCs) from diabetic animals. However, the mechanism responsible was unclear. VSMCs from autoimmune type 1 Diabetes Resistant Bio-Breeding (DR-BB) rats and streptozotocin-induced rats were examined for levels and distribution of inositol trisphosphate receptors (IP3R) and the SR Ca2+ pumps (SERCA 2 and 3). Generally, a decrease in IP3R levels and dramatic increase in ryanodine receptor (RyR) levels were noted in the aortic samples from diabetic animals. Redistribution of the specific IP3R subtypes was dependent on the rat model. SERCA 2 was redistributed to a peri-nuclear pattern that was more prominent in the DR-BB diabetic rat aorta than the STZ diabetic rat. The free intracellular Ca2+ in freshly dispersed VSMCs from control and diabetic animals was monitored using ratiometric Ca2+ sensitive fluorophores viewed by confocal microscopy. In control VSMCs, basal fluorescence levels were significantly higher in the nucleus relative to the cytoplasm, while in diabetic VSMCs they were essentially the same. Vasopressin induced a predictable increase in free intracellular Ca2+ in the VSMCs from control rats with a prolonged and significantly blunted response in the diabetic VSMCs. A slow rise in free intracellular Ca2+ in response to thapsigargin, a specific blocker of SERCA was seen in the control VSMCs but was significantly delayed and prolonged in cells from diabetic rats. To determine whether the changes were due to the direct effects of hyperglycemica, experiments were repeated using cultured rat aortic smooth muscle cells (A7r5) grown in hyperglycemic and control conditions. In general, they demonstrated the same changes in protein levels and distribution as well as the blunted Ca2+ responses to vasopressin and thapsigargin as noted in the cells from diabetic animals. This work demonstrates that the previously-reported reduced Ca2+ signaling in VSMCs from diabetic animals is related to decreases and/or redistribution in the IP3R Ca2+ channels and SERCA proteins. These changes can be duplicated in culture with high glucose levels.


In the spotlight: biomedical signal processing--a well established discipline or a paradigm to promising integrated visions?
Biomedical signals carry fundamental information about the nature and the status of the living systems under study. A proper processing of these signals obtains useful physiological and clinical information. A closer integration between signal processing and modeling of the relevant biological systems is capable to directly attribute pathophysiological meaning to the parameters obtained from the processing and vice versa. Another issue of great interest in which BSP plays an important role is the Brain-Computer Interface (BCI) or Brain-Machine Interface (BMI) where fast and reliable signal processing approaches are fundamental for a practical implementation. The physiological mechanisms underlying these heart rate variability findings are supposed to be related to stochastic processes at the cellular level, to influence of respiration on the heart rate, and to the interactions of the multiple feedback loops regulating the cardiovascular system. Another important area in which BSP plays a pivotal role is the "computational genomics and proteomics." It is true that "traditional" biomedical engineering studies biomedical signals which are obtained at the level of the major physiological systems.


AMP-activated protein kinase contributes to cisplatin-induced renal epithelial cell apoptosis and acute kidney injury.
Cisplatin, a commonly used anticancer drug, has been shown to induce acute kidney injury, which limits its clinical use in cancer treatment. Emerging evidence has suggested that AMP-activated protein kinase (AMPK), which functions as a cellular energy sensor, is activated by various cellular stresses that deplete cellular ATP. However, the potential role of AMPK in cisplatin-induced apoptosis of renal tubular epithelial cells has not been studied. In this study, we demonstrated that cisplatin activates AMPK (Thr172 phosphorylation) in cultured renal tubular epithelial cells in a time-dependent manner, which was associated with p53 phosphorylation. Compound C, a selective AMPK inhibitor, suppressed cisplatin-induced AMPK activation, p53 phosphorylation, Bax induction, and caspase 3 activation. Furthermore, silencing AMPK expression by siRNA attenuated cisplatin-induced p53 phosphorylation, Bax induction, and caspase 3 activation. In a mouse model of cisplatin-induced kidney injury, compound C inhibited p53 phosphorylation, Bax expression, caspase 3 activation, and apoptosis, protecting the kidney from injury and dysfunction. Taken together, these results suggest that the AMPK-p53-Bax signaling pathway plays a crucial role in cisplatin-induced tubular epithelial cell apoptosis.


The utilization of competing unfolding pathways of monellin is dictated by enthalpic barriers.
Direct evidence of the presence of competing pathways for the folding or unfolding reactions of proteins is difficult to obtain. A direct signature for multiple pathways, seen so far only rarely in folding or unfolding studies, is an upward curvature in the dependence of the logarithm of the observed rate constant (λU) of folding on denaturant concentration. In this study, the unfolding mechanism of the wild-type (wt) and E24A variants of monellin has been investigated, and both variants are shown to display upward curvatures in plots of log λU versus denaturant concentration. Curvature is distinctly more pronounced for E24A than for the wt protein. Kinetic unfolding studies of E24A were conducted over a range of denaturant concentrations and across a range of temperatures, and the kinetic data were globally analyzed assuming two parallel pathways L and H, which proceed through transition states TS(L) and TS(H), respectively. The observation of the upward curvature in the unfolding kinetics permitted a thermodynamic analysis of how unfolding switches from one pathway to the other upon a change in unfolding conditions. The m −N and ΔCp values indicate that TSL is more compact than TS(H). The major contribution to the free energy of activation on either pathway is seen to be enthalpic and not entropic in origin.


The effect of injection speed on the pain of lidocaine infiltration.
To determine whether reducing the speed of injection is effective in reducing injection pain for buffered and unbuffered lidocaine solutions. A prospective, single-blind, randomized, crossover, laboratory study was performed. Adult volunteers were recruited from ED staff at an urban teaching hospital to serve as subjects. Twenty-nine subjects each received 4 1-mL injections into the dorsum of the hands. Each subject received fast and slow injections of buffered and unbuffered lidocaine. Subjects rated the pain of each injection on a 100-mm visual analog scale (VAS). Mean pain scores for each intervention were compared using analysis of variance. The mean pain VAS score for fast injection of buffered lidocaine was 14.1 mm. For slow buffered injection, the mean pain score was 11.4 mm (p = 0.98). For unbuffered lidocaine, the means were 28.7 mm for fast injection and 22.2 mm for slow injection (p = 0.40). Reducing injection speed did not produce a statistically significant change in injection pain for either buffered or unbuffered solutions.


Monitoring Wnt Signaling in Zebrafish Using Fluorescent Biosensors.
In this chapter, we are presenting methods to monitor and quantify in vivo canonical Wnt signaling activities at single-cell resolution in zebrafish. Our technology is based on artificial enhancers, obtained by polymerization of TCF binding elements, cloned upstream to ubiquitous or tissue-specific promoters. The different promoter/enhancer combinations are used to drive fluorescent protein reporter constructs integrated in the zebrafish germline by microinjection of fertilized zebrafish eggs. Fish with a single integration site are selected by Mendelian analysis of fluorescent carriers, and heterozygous offspring are used to monitor and quantify canonical Wnt activities. Open source public domain software such as ImageJ/Fiji is used to calculate the integrated densities in the region of interest and compare the effect of experimental conditions on control and treated animals.


[Regional chemotherapy in advanced pancreatic carcinoma].
Even after resection median survival times in advanced pancreatic carcinoma are seldom more than one year. The aim of our study was to evaluate the effectivity of regional chemotherapy in patients suffering from unresectable pancreatic cancer. From 2/92 until 11/94 32 patients with unresectable pancreatic cancer (17 patients stage III, 15 patients stage IV) were treated by celiac trunc infusion. One cycle consisted of mitoxantrone (d 1), 5-FU, folinic acid (d 2 to 4) and cisplatinum (d 5). Besides a few severe complications, therapy was well tolerated in 101 cycles. In unresected patients with stage III tumors the median survival is 12 months compared to 4.8 months in patients with biliodigestive bypasses (p < 0.006) and 4 months in regionally infused patients stage IV compared to 2.7 months in untreated patients (n.s.). Regional chemotherapy in advanced pancreatic carcinoma is well tolerated and increases median survival in patients with stage III tumors.


A Comparative Investigation: Group 9 Cp*M(III)-Catalyzed Formal [4 + 2] Cycloaddition as an Atom-Economic Approach to Quinazolines.
A comparative study on the catalytic activity of different group 9 [Cp*M(III)] complexes in the formal [4 + 2] cycloaddition of arenes with rarely explored free imines and dioxazolones for the construction of multisubstituted quinazolines is reported herein. This investigation revealed that the cobalt catalyst is uniquely suited to this transformation due to its strong Lewis acidity and high sensitivity to steric hindrance.


Knowledge, attitude, practice, and determinants emergency contraceptive use among women seeking abortion services in Dire Dawa, Ethiopia.
Unplanned pregnancy from casual sex, unplanned sexual activity, and sexual violence are increasing. Emergency Contraceptives (EC) are used to prevent unplanned pregnancies thereby preventing the occurrence and consequences of unplanned pregnancy. Emergency contraception is widely available in Ethiopia particularly in major cities. Yet the use of EC is very low and abortion rate in cities is high compared to the national average. To assess knowledge, attitude and practice and determinants on the use of emergency contraception among women obtaining abortion service at selected health institutions in Dire Dawa, Eastern Ethiopia. A facility based cross-sectional study was conducted on 390 women selected by multi-stage random sampling technique. The samples were generated from government and private for non profit health facilities. Participant's knowledge and attitude towards emergency contraception were measured using composite index based on 7 and 9 questions, respectively and analyzed using mean score to classify them as knowledgeable or not, and have positive attitude or not. Practice was assessed if the women reported ever use of emergency contraception. Determinants of use of emergency contraception were analyzed using logistic regression. Out of 390 women interviewed, 162 women (41.5%) heard about EC, only 133 (34.1%) had good knowledge, and 200 (51.3%) of the respondents had positive attitudes towards to EC. Ever use of EC was reported by 38 (9.7%). Age, living arrangement, education, marital status, religion were found to be significantly associated with the use of emergency contraceptives. Women with poor knowledge were less likely to use EC compared to the knowledgeable ones [AOR = 0.027, 95% CI (0.007, 0.105)]. The study identified that most respondents lack adequate knowledge on the method of EC. In addition ever use of EC is very low. Health professions should give attention in increasing knowledge and uptake of Emergency Contraception.


Can magnetoencephalography track the afferent information flow along white matter thalamo-cortical fibers?
White matter thalamo-cortical fibers allow the communication of distant brain regions by carrying neuronal signals. Mapping non-invasively the information flow within white matter fibers is regarded so far as impossible. We investigated here whether information flow propagating along thalamo-cortical fibers can be detected using magnetoencephalography (MEG). Somatosensory evoked fields (SEFs) were recorded from healthy subjects and a patient with a unilateral, prenatally acquired, white matter lesion, which had induced the development of an abnormal trajectory of thalamo-cortical fibers. Equivalent current dipole (ECD) was used to model sources of SEFs. ECD at ~15 ms after stimulus onset was located within or close to the contralateral thalamus at the proximity of a hemodynamic response detected during a similar fMRI experiment. At the M20 peak latency, ECD was localized within the hand area of the contralateral primary somatosensory cortex (Brodmann area 3b (BA3b)). In healthy subjects, ECD changed dynamically position from thalamus to BA3b following a curved path, which was partially overlapping the thalamo-cortical fibers reconstructed by tractography. In the patient, ECD followed a similar path only in the intact hemisphere. In the affected hemisphere, the dipole trajectory circumnavigated the extended lesion on its way to the preserved primary somatosensory cortex--similar to the trajectory findings. Evidence from different methodological approaches converges on the conclusion that MEG can track the afferent information flow along thalamo-cortical fibers and in contrast to the traditional view can localize under presuppositions deep thalamic sources.


Aluminum effects on calcium fluxes at the root apex of aluminum-tolerant and aluminum-sensitive wheat cultivars.
The role of Ca(2+) transport in the mechanism of Al toxicity was investigated, using a Ca(2+)-selective microelectrode system to study Al effects on root apical Ca(2+) fluxes in two wheat (Triticum aestivum L.) cultivars: Al-tolerant Atlas 66 and Al-sensitive Scout 66. Intact 3-day-old low-salt-grown (100 micromolar CaCl(2), pH 4.5) wheat seedlings were used, and it was found that both cultivars maintained similar rates of net Ca(2+) uptake in the absence of Al. Addition of Al concentrations that were toxic to Scout (5-20 micromolar AlCl(3)) immediately and dramatically inhibited Ca(2+) uptake in Scout, whereas Ca(2+) transport in Atlas was relatively unaffected. The Al-induced inhibition of Ca(2+) uptake in Scout 66 was rapidly reversed following removal of Al from the solution bathing the roots. Similar studies with morphologically intact root cell wall preparations indicated that the Al effects did not involve Al-Ca interactions in the cell wall. These results suggest that Al inhibits Ca(2+) influx across the root plasmalemma, possibly via blockage of calcium channels. The differential effect of Al on Ca(2+) transport in Al-sensitive Scout and Al-tolerant Atlas suggests that Al blockage of Ca(2+) channels could play a role in the cellular mechanism of Al toxicity in higher plants.


Alterations in morphology and hepatorenal indices in rats subacutely exposed to bitumen extract.
Bitumen is a complex mixture of dense and extremely viscous organic liquids produced by distillation of crude oil during petroleum refining. Nigeria has a large deposit of natural bitumen, yet to be fully exploited. Discharges of petroleum hydrocarbons and other petroleum-derived products have caused environmental pollution and adverse human health effects in several oil-rich communities. In this study, bitumen obtained from a seepage source in Agbabu, the town of first discovery, was used in sub-acute toxicity studies in a rat experimental model, in order to assess potential health risks posed to local populace sequel to full exploitation of bitumen. Dosages were chosen to accommodate low to high cases of environmental exposures. Male Wistar rats were administered, per os, dosages of bitumen extract at 5, 3, 2, and 1 mg/kg body weight. Following euthanasia 28 days later, histological findings revealed severe portal congestion and cellular infiltration in the liver, while in the kidney there were protein casts in the tubular lumen. The relative liver and kidney weights in the 5 mg/kg groups were 34% and 40% higher than in the controls, with a concomitant decrease in food and water consumption. Furthermore, plasma clinical analyses revealed marked elevation in aspartate aminotransferase and triglycerides levels in bitumen extract-intoxicated rats. The results indicate the potential hepatorenal toxicity in adult rats following repeated exposure to bitumen extract.


Respiratory variation in aortic blood flow velocity as a predictor of fluid responsiveness in children after repair of ventricular septal defect.
This study aimed to compare respiratory variation in transthoracic echo-derived aortic blood flow velocity (∆Vpeak) and inferior vena cava diameter (∆IVCD) with central venous pressure (CVP) as predictors of fluid responsiveness in children after repair of ventricular septal defect (VSD). A prospective study conducted in pediatric intensive care unit investigated 21 mechanically ventilated children who had undergone repair of VSD. Standardized volume replacement (VR) was the intervention used. Hemodynamic measurements including CVP, heart rate, mean arterial pressure, transthoracic echo-derived stroke volume (SV), cardiac output, ∆Vpeak, and ∆IVCD were performed 1 h after patient arrival in the intensive care unit. Hemodynamic measurements were repeated 10 min after VR by an infusion of 6% hydroxyethyl starch 130/0.4 (10 ml/kg) over 20 min. The volume-induced increase in the SV was 15% or more in 11 patients (responders) and less than 15% in 10 patients (nonresponders). Before volume replacement, the ∆Vpeak (23.1 ± 5.7% vs. 14.0 ± 7.7%; p = 0.006) and ∆IVCD (26.5 ± 16.2% vs. 9.2 ± 9.1%; p = 0.008) was higher in the responders than in the nonresponders, whereas CVP did not significantly differ between the two groups. The prediction of fluid responsiveness was higher with the ΔVpeak, as shown by a receiver operating characteristic curve area of 0.83 (95% confidence interval [CI], 0.61-1.00; p = 0.01), a ΔIVCD of 0.85 (95% CI, 0.69-1.00; p = 0.01), and a CVP of 0.48 (95% CI, 0.22-0.73; nonsignificant difference). The ∆Vpeak and ∆IVCD measured by transthoracic echocardiography can predict the response of SV after volume expansion in mechanically ventilated children at completion of VSD repair.


[Retinoic acid nuclear receptor beta (RAR beta) inhibits breast carcinoma growth].
Retinoids are capable of modulating cellular differentiation and proliferation. Retinoids mediate gene function through a series of nuclear receptors. The retinoic acid receptor beta (RAR beta) has been shown to play an important role in the differentiation of a number of cell types. RAR beta is either absent or expressed at extremely low levels in a number of tumor types including breast carcinoma. It was demonstrated that transfection of RAR beta gene in breast carcinoma cell with its subsequent expression resulted in inhibition of cell growth. Retinoic acid significantly inhibited monolayer growth of the breast carcinoma cells expressing RAR beta, while it had no effect on the growth of the control cells. The RAR beta expressing cells formed much smaller and fewer colonies in soft agar and were significantly less tumorigenic in nude mice than the controls. These results suggest that RAR beta may function as a tumor suppressor in breast carcinoma cells.


Interaction of Long Time Pulses of an Nd3+:YAG Laser Beam with the Heusler AlloyNi45Co5Mn35.5In14.5.
In this paper, the laser processing of the surface of bulk and layered samples (of thickness 75 nm) of Ni45Co5Mn35.5In14.5 alloy (NC5MI) was investigated using microsecond laser pulses. A Q-switched pulsed Nd3+:YAG laser, operating in the 1st harmonic (which had a wavelength of 1064 nm) with a pulse duration of 250 µs, was used. NC5MI is a metal resistant to thermal laser processing because its reflection coefficient is close to unity for long wavelengths. The aim of this paper was to learn the forms of laser processing (heating, microprocessing, ablation) for which the above-specified type of laser is useful. The samples were irradiated with various fluences in the interval of 5-32 J·cm-2. The effect of the laser interaction with the surface was explored by SEM microscopy. The threshold fluences for the bulk sample were determined as: the visible damage threshold (Fthd = 2 ± 0.2 J·cm-2), the melting threshold (Fthm = 10 ± 0.5 J·cm-2), and the deep melting threshold (Fthdm = 32 J·cm-2). Unexpectedly, these values wereincreased for the layer sample due to its silicon substrate. We have concluded that this type of laser radiation is advantageous for the annealing and melting of, or drilling holes in, the alloy, but disadvantageousto the ablation of the alloy.


Integrating Social Determinants of Health With Tobacco Treatment for Individuals With Opioid Use Disorder: Feasibility and Acceptability Study of Delivery Through Text Messaging.
Individuals with opioid use disorder (OUD) have a high prevalence of smoking and frequently experience unmet social determinants of health (SDOH), which may be barriers to smoking cessation. Hospitalization is an opportunity to encourage smoking cessation. Unfortunately, many clinicians do not provide tobacco treatment to support the maintenance of cessation achieved during hospitalization. Interventions are required to support these high-risk individuals after hospital discharge. This study aimed to test the feasibility and acceptability of a 28-day SMS text messaging program tailored to individuals with OUD, which provides smoking cessation support and addresses unmet SDOH needs. From July to December 2019, we enrolled 25 individuals who were hospitalized with tobacco dependence and OUD at our large safety net hospital. The SMS text messaging program was initiated during hospitalization and continued for 28 days. Participants were enrolled in either the ready to quit within 30 days or the not ready to quit within 30 days program based on their readiness to quit. Automated SMS text messages were sent twice daily for 4 weeks. The topics included health and cost benefits of quitting, both general and opioid specific (16 messages); managing mood and stress (8 messages); motivation, coping strategies, and encouragement (18 messages); addressing medication misconceptions (5 messages); links to resources to address substance use (2 messages providing links to the Massachusetts Substance Use Helpline and Boston Medical Center resources), tobacco dependence (1 message providing a link to the Massachusetts Quitline), and unmet SDOH needs (6 messages assessing SDOH needs with links to resources if unmet SDOH needs were identified). Questionnaires and interviews were conducted at baseline and at 2 and 4 weeks after enrollment. The participants were 56% (14/25) female, 36% (9/25) African American, 92% (23/25) unemployed, and 96% (24/25) Medicaid insured. Approximately 84% (21/25) activated the program, and none of the participants unsubscribed. Approximately 57% (12/21) completed either the 2- or 4-week questionnaires. Program satisfaction was high (overall mean 6.7, SD 0.8, range 1-7). Many perceived that the SMS text messaging program provided social support, companionship, and motivation to stop smoking. Messages about the health benefits of quitting were well received, whereas messages on how quitting cigarettes may prevent relapse from other substances had mixed views, highlighting the importance of tailoring interventions to patient preferences. SMS text messaging to promote smoking cessation and address SDOH needs may be an effective tool for improving quit rates and health outcomes in individuals with tobacco dependence and OUD. Our study adds to the growing body of evidence that SMS text messaging approaches are feasible and acceptable for providing tobacco treatment to all individuals who smoke, even among low-income populations who have OUD and are not ready to quit.


Magnetic resonance tractography of the brachial plexus: step-by-step.
Magnetic resonance (MR) tractography of the brachial plexus (BP) is challenging due to different factors such as motion artifacts, pulsation artifacts, signal-to-noise ratio, spatial resolution; eddy currents induced geometric distortions, sequence parameters and choice of used coils. Notably challenging is the separation of the peripheral nerve bundles and skeletal muscles as both structures have similar fractional anisotropy values. We proposed an algorithm for robust visualization and assessment of BP root bundles using the segmentation of the spinal cord (SSC, C4-T1) as seed points for the initial starting area for the fibre tracking algorithm. Twenty-seven healthy volunteers and four patients with root avulsions underwent magnetic resonance imaging (MRI) examinations on a 3T MR scanner with optimized measurement protocols for diffusion-weighted images and coronal T2 weighted 3D short-term inversion recovery sampling perfection with application optimized contrast using varying flip angle evaluation sequences used for BP fibre reconstruction and MR neurography (MRN). The fibre bundles reconstruction was optimized in terms of eliminating the skeletal muscle fibres contamination using the SSC and the tracking threshold of the normalized quantitative anisotropy (NQA) on reconstruction of the BP. In our study, the NQA parameter has been used for fiber tracking instead of fractional anisotropy (FA). The diffusion data were processed in individual C4-T1 root bundles using the generalized q-sampling imaging (GQI) algorithm. Calculated diffusion parameters were statistically analysed using the two-sample t-test. The MRN was performed in MedINRIA and post-processed using the maximum intensity projection (MIP) method to demonstrate BP root bundles in multiple planes. In control subjects, no significant effect of laterality in diffusion parameters was found (P>0.05) in the BP. In the central part of the BP, a significant difference between control subjects and patients at P=0.02 was found in the NQA values. Other diffusion parameters were not significantly different. Using NQA instead of FA in the proposed algorithm allowed for a better separation of muscle and root nerve bundles. The presented algorithm yields a high quality reconstruction of the BP bundles that may be helpful both in research and clinical practice.


Design, synthesis and evaluation of human telomerase inhibitors based upon a tetracyclic structural motif.
There is currently significant interest in the development of inhibitors of human telomerase for the treatment of cancer. We describe here the design and synthesis of a new class of mono-substituted small-molecule inhibitors of human telomerase based upon a tetracyclic structural motif. In contrast to the structurally related molecule 9-hydroxyellipticine, recently shown to inhibit telomerase activity in cell cultures but found to be inactive in a cell-free system, we demonstrate direct inhibition of the telomerase enzyme by the tetracyclic compounds in a modified cell-free TRAP assay. The most potent compounds exhibit activity in the low micromolar range and are thus comparable with some of the more active small-molecule telomerase inhibitors based on planar aromatic chromophores, previously described by ourselves and others. These compounds may represent useful leads for the development of more potent inhibitors of human telomerase.


[Ecological demonstration activity and eco-civilization construction mode: review and prospects].
Ecological civilization is to normalize human development behaviors to harmonize the relationships between social and ecological development and eco-environment protection. In this paper, a comparative analysis was made on the ecological demonstration activities of ecological demonstration areas led by the Ministry of Environmental Protection, exemplar cities of national environmental protection, and ecological provinces, cities, and counties. It was considered that all the ecological demonstration activities had the problems of lacking pertinence of construction goals, disordered construction subjects, inefficient construction processes, and lacking continuous incentive mechanisms of assessment. In the meantime, through the analysis of the connotations of eco-civilization, the relationships between eco-civilization and eco-demonstration constructions were approached, and the eco-civilization construction mode was put forward in terms of construction goal, construction subject, and construction processes and assessment. The construction mode included the construction goal based on regional characteristics; the synergistic cooperation of construction subjects, the expanding ways of public participation, and the establishment of evaluation system for comprehensively measuring the 'actions and results'.


[A 85-year-old woman with one year history of convulsion, dementia, and consciousness disturbance].
We report a 85-year-old woman who died after one year history of convulsion, dementia, and consciousness disturbance. She was apparently well until January 6, 1995 when she was 85 year old; on that evening, she suddenly stated that some one was in her room and she became confused. A local MD gave her diazepam and she fell into sleep. At 3 o'clock in the following morning, she developed tonic-clonic convulsion in her right lower extremity which showed a march to her right upper extremity and the left lower extremity. She was admitted to our hospital. On admission, she was comatose with respiratory acidosis. She was intubated and placed on a ventilator. She was treated with intravenous phenytoin. She gradually gained consciousness and became alert. Respiration became normal. Her MRI revealed ventricular dilatation, fronto-parietal cortical atrophy, and a T1-low and T2-high signal intensity lesion in the left occipital lobe. She was discharged for out patient follow-up on February 4, 1995. Since then, she noted loss of memory and small step gait. A follow-up CT scan revealed a mass lesion which showed a ring-shaped enhancement in the left occipital lobe and was admitted again. On admission, she was alert but markedly demented. The optic fundi was unremarkable, but she appeared to have right homonymous hemianopsia. No motor weakness was noted. In Gd-DTPA enhanced MRI, the above tumor showed a ring enhancement. The diagnosis of glioblastoma was entertained, however, considering her age, she was treated with intravenous glycerol and intramuscular steroid. She was discharged for out-patient follow-up on July 15, 1995. Her gait disturbance had progressively become worse and she developed nausea and vomiting and was admitted again on October 2, 1995. On admission, she was somnolent and markedly demented. Brain stem responses were retained normally. She was unable to stand or walk. Deep tendon reflexes were slightly increased in the right upper extremity and the plantar response was extensor on the right. Her hospital course was complicated by respiratory tract infection and respiratory acidosis. She expired on November 2, 1995. The patient was discussed in a neurological CPC and the chief discussant arrived at the conclusion that she had a glioblastoma involving the left occipital lobe and the adjacent areas. Post-mortem examination revealed an infiltrating tumor in the left occipital lobe. On microscopic examination, the tumor was very cellular; nuclear atypism was marked and tumor cells undergoing mitosis were seen. In some areas, capillary proliferation was seen. Histologic characteristics were consistent with glioblastoma.


Lipidic carriers of siRNA: differences in the formulation, cellular uptake, and delivery with plasmid DNA.
RNA interference (RNAi) has become a popular tool for downregulating specific gene expression in many species, including mammalian cells [Novina, C. D., and Sharp, P. A. (2004) The RNAi revolution, Nature 430, 161-164]. Synthetic double-stranded RNA sequences (siRNA) of 21-23 nucleotides have been shown in particular to have the potential to silence specifically gene function in cultured mammalian cells. As a result, there has been a significant surge of interest in the application of siRNA in functional genomics programs as a means of deciphering specific gene function. However, for siRNA functional genomics studies to be valuable and effective, specific silencing of any given target gene is essential, devoid of nonspecific knockdown and toxic side effects. For this reason, we became interested in investigating cationic liposome/lipid-mediated siRNA delivery (siFection) as a meaningful and potentially potent way to facilitate effective functional genomics studies. Accordingly, a number of cationic liposome/lipid-based systems were selected, and their formulation with siRNA was studied, with particular emphasis on formulation parameters most beneficial for siRNA use in functional genomics studies. Cationic liposome/lipid-based systems were selected from a number of commercially available products, including lipofectAMINE2000 and a range of CDAN/DOPE systems formulated from different molar ratios of the cationic cholesterol-based polyamine lipid N(1)-cholesteryloxycarbonyl-3,7-diazanonane-1,9-diamine (CDAN) and the neutral helper lipid dioleoyl-L-alpha-phosphatidylethanolamine (DOPE). Parameters that were been investigated included the lipid:nucleic acid ratio of mixing, the extent of cationic liposome/lipid-nucleic acid complex (lipoplex) formation plus medium used, the lipoplex particle size, the mode of delivery, and dose-response effects. Results suggest that concentrations during siRNA lipoplex (LsiR) formation are crucial for maximum knockdown, but the efficacy of gene silencing is not influenced by the size of LsiR particles. Most significantly, results show that most commercially available cationic liposome/lipid-based systems investigated here mediate a significant nonspecific downregulation of the total cellular protein content at optimal doses for maximal specific gene silencing and knockdown. Furthermore, one pivotal aspect of using siRNA for functional genomics studies is the need for at least minimal cellular toxicity. Results demonstrate that CDAN and DOPE with and without siRNA confer low toxicity to mammalian cells, whereas lipofectAMINE2000 is clearly toxic both as a reagent and after formulation into LsiR particles. Interestingly, LsiR particles formulated from CDAN and DOPE (45:55, m/m; siFECTamine) seem to exhibit a slower cellular uptake than LsiR particles formulated from lipofectAMINE2000. Intracellularly, LsiR particles formulated from CDAN and DOPE systems also appear to behave differently, amassing in distinct but diffuse small nonlysosomal compartments for at least 5 h after siFection. By contrast, LsiR particles formulated from lipofectAMINE2000 accumulate in fewer larger intracellular vesicles.


Method of concentration of power in materials for x-ray amplification.
Recent experimental and theoretical results indicate that a new technique for the controlled concentration of power in materials may be feasible. The power levels that are potentially achievable are sufficient for the generation of amplification of x-ray wavelengths in the kilovolt range. The method of power concentration involves the combination of (1) a new ultrahigh brightness subpicosecond laser technology, (2) multiphoton coupling to atoms and molecules, and (3) a new channeled mode of electromagnetic propagation. The energy scaling of this approach is the most important consideration, and it is shown that the control of the propagation is the key factor that enables high levels of amplification in the kilovolt regime to be achieved with a total excitation energy of ~1 J.


Unconjugated bisphenol A cord blood levels in boys with descended or undescended testes.
Human toxicity of bisphenol A (BPA), a weak estrogenic environmental endocrine disrupting compound, widely used in plastics, baby bottles, cans and dental sealants, is under investigation. Fetal or perinatal exposure in rodents is associated with programmed adult reproductive diseases. Human epidemiological studies remain scarce, especially concerning testicular development. We have investigated the relationship between fetal exposure to BPA and cryptorchidism. Using a radioimmunoassay performed after extraction, validated by high-performance liquid chromatography and mass spectrometry, active levels of unconjugated BPA (uBPA) in cord blood (CB) were measured in 152 boys born after 34 weeks gestation, with cryptorchid or descended testes. Active uBPA was detectable in all CB samples, with values in the control group (n = 106) of 0.14-4.76 ng/ml, median: 0.9 ng/ml; mean ± SD: 1.12 ng/ml ± 0.86 ng/ml, which did not differ from cryptorchid boys (n = 46, 1.26 ± 1.13 ng/ml, P = 0.38). uBPA in controls correlated with CB inhibin B (P < 0.01) and total testosterone (P < 0.05), and with maternal milk polychlorinated bisphenyl 138 (P < 0.03). uBPA did not correlate with clinical maternal or fetal parameters or with other steroid or polypeptide CB hormones assessed. The presence of uBPA in all CB samples suggests placental transfer and fetal exposure. Similar uBPA levels in the control and cryptorchid groups make the participation of fetal exposure to uBPA in the physiopathology of undescended testes unlikely. However, the observed nanomolar uBPA concentrations support assessment of epidemiological relationships between CB uBPA and other human diseases.


Factors Affecting Ulcerative Colitis Flare-Ups: Associations With Smoking Habits and Other Patient Characteristics.
Background and study aims Currently, there are no studies conducted in the Kingdom of Saudi Arabia (KSA) that have assessed the relationship between ulcerative colitis (UC) flare-ups and smoking. The present study aims to assess the risk of UC flare-ups and evaluate the relationship between UC flare-ups and smoking in adult patients following up at King Abdulaziz University Hospital in Jeddah, KSA. Patients and methods This was a retrospective study involving patients with confirmed UC between January 2015 and December 2020. Various information was examined, including demographic, clinical, endoscopic, radiologic, and laboratory data. Descriptive statistics were used for summarizing findings and a logistic regression analysis was applied to test for possible associations. Results Eighty-nine patients with UC were included in the study. Almost half (48.3%) had recurrent UC flare-ups during follow-up. A non-significant relationship was found between recurrent UC flares and all types of smoking habits (cigarette smoking, P = 0.15; shisha smoking, P = 0.88; and vape smoking, P = 0.09). Participants who were underweight (P = 0.041), had family history of UC (P = 0.013), depression (P = 0.033), fecal incontinence (P = 0.003), iron deficiency anemia (P = 0.009), or a malignancy (P = 0.039) had a significantly higher probability of experiencing recurrent flares. Binary logistic regressions revealed that family history of UC (OR = 5.3, P = 0.007) and fecal incontinence (OR = 4.7, P = 0.006) were associated significantly with recurrent flares. Conclusion There was no clear association between smoking and recurrent UC flares identified in this cohort. Of the variables considered, UC patients with fecal incontinence or family history of UC were at the highest risk of developing recurrent flares.


When do the "dollars" make sense? Toward a conceptual framework for contingent valuation studies in health care.
There is growing interest in the application of cost-benefit analysis (CBA) as a technique for the economic evaluation of health care programs. A distinguishing feature of CBA is that costs and benefits are expressed in the same units of value--typically money. A popular method for estimating money values for health care programs is the use of willingness-to-pay (or accept) survey techniques known as contingent valuation. This paper presents a conceptual framework to help in the interpretation or design of contingent valuation studies in health care. To be consistent with the theory upon which CBA is built, the authors consider what types of questions should be asked of what populations. They conclude that studies undertaking contingent valuation should distinguish between compensating variation and equivalent variation, and recognize that respondents can be gainers or losers in utility and therefore should be asked willingness-to-pay (or accept) questions as appropriate. Current critical-appraisal guidance in the health care literature for CBA is poor and unlikely to offer useful demarcation between good and bad CBA studies. More work is needed exploring whether recently issued guidelines for contingent valuation in environment damage assessment are applicable to health care studies.


Patients with RET D631Y mutations most commonly present with pheochromocytoma and not medullary thyroid carcinoma.
Multiple endocrine neoplasia type 2a results from an activating germline mutation in the RET proto-oncogene. Carriers of a RET mutation are at risk of medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism. Most individuals with multiple endocrine neoplasia type 2a eventually develop medullary thyroid carcinoma and as there is a strong genotype-phenotype correlation, guidelines have been established as to the age recommended for prophylactic thyroidectomy. However for rare mutations in the RET proto-oncogene there is insufficient evidence to provide guidance as to the risk of medullary thyroid carcinoma. We present a family with the rare RET mutation, D631Y in which the proband initially presented with a pheochromocytoma, and review the available literature pertaining to this mutation. In 83% of index cases, pheochromocytoma was the presenting feature and only 37% of adult germline mutation carriers have developed medullary thyroid carcinoma, none of whom have been reported to have nodal or metastatic disease. Patients with a D631Y RET mutation typically present with pheochromocytoma and medullary thyroid carcinoma appears to occur with a later onset than reported with other RET mutations. Based on the current literature we recommend performing prophylactic total thyroidectomy by age 12 years for D631Y carriers although this recommendation may need to be reviewed as additional data becomes available.


[Vesicoureteral reflux in children with prenatal suspicion of urinary tract abnormalities].
The aim of the study was to assess indications to voiding cystourethrography (VCUG) in children with suspicion of urinary tract (UT) abnormalities in prenatal ultrasonography (US). We studied 93 children aged 1 day to 7 months (mean 1.4 +/- 1.3 months). Prenatal USG was done between 18-41 week of gestational age (mean 32.6 +/- 5.6). Congenital anomalies of UT were suspected in 88% fetuses with dilatation of UT and in 12% fetuses with other changes in UT. Postnatal US was done in all children between 1-122 day of life (mean 18.2 +/- 21.5); VCUG between 1 day to 13 months (mean 2.1 +/- 2.3 months), in this in 75 (81%) infants in the first months of life. Abnormal result of postnatal US had 84 (90%) children (dilatation of pyelocalyceal system and/or ureter, duplex kidney, multicystic dysplastic kidney, ureterocele). We found normal VCUG in 67 (72%) children, abnormal in 26 (28%). Vesicoureteral reflux (VUR) to 28 kidneys was detected in 20 (21.5%) children (1st--1 kidney, 2nd--14, 3rd--3, 4th--6 and 5th--4 kidneys); another anomalies in 6 (in 2 posterior urethral valves). VUR was observed in 17.3% VCUG performed before 3 months of age and in 38.9% performed later (p<0.05). VUR was recognized: in 17.2% kidneys with normal prenatal US and in 16.4% kidneys with dilatation of UT (NS); in 6 (8%) kidneys with normal postnatal US and 22 (29.8%) with abnormal (p=0.05). There was not statistically significant difference in frequency of VUR in kidney with normal (0-5 mm) and abnormal postnatal renal pelvic diameter (RPD) (11.3% vs 19%, NS). The sensivity and specifity of normal postnatal USG in detection VUR were 79% and 56% respectively, and of normal postnatal RPD were 61% and 46% respectively. 1. Indication to performing VCUG in children with prenatally detected hydronephrosis should be persistent dilatation of pyelocalyceal system and/or ureter in postnatal US or another abnormalities in UT. 2. Normal prenatal and postnatal USG does not exclude presence of VUR. 3. VCUG in children with prenatally detected hydronephrosis should be performed about 3 months of life, in specially situation earlier.


Dysosmobacter welbionis effects on glucose, lipid, and energy metabolism are associated with specific bioactive lipids.
The newly identified bacterium Dysosmobacter welbionis J115T improves host metabolism in high-fat diet (HFD)-fed mice. To investigate mechanisms, we used targeted lipidomics to identify and quantify bioactive lipids produced by the bacterium in the culture medium, the colon, the brown adipose tissue (BAT), and the blood of mice. In vitro, we compared the bioactive lipids produced by D. welbionis J115T versus the probiotic strain Escherichia coli Nissle 1917. D. welbionis J115T administration reduced body weight, fat mass gain, and improved glucose tolerance and insulin resistance in HFD-fed mice. In vitro, 19 bioactive lipids were highly produced by D. welbionis J115T as compared to Escherichia coli Nissle 1917. In the plasma, 13 lipids were significantly changed by the bacteria. C18-3OH was highly present at the level of the bacteria, but decreased by HFD treatment in the plasma and normalized in D. welbionis J115T-treated mice. The metabolic effects were associated with a lower whitening of the BAT. In the BAT, HFD decreased the 15-deoxy-Δ12,14-prostaglandin J2, a peroxisome proliferator-activated receptor (PPAR-γ) agonist increased by 700% in treated mice as compared to HFD-fed mice. Several genes controlled by PPAR-γ were upregulated in the BAT. In the colon, HFD-fed mice had a 60% decrease of resolvin D5, whereas D. welbionis J115T-treated mice exhibited a 660% increase as compared to HFD-fed mice. In a preliminary experiment, we found that D. welbionis J115T improves colitis. In conclusion, D. welbionis J115T influences host metabolism together with several bioactive lipids known as PPAR-γ agonists.


The promise of atypical antipsychotics: fewer side effects mean enhanced compliance and improved functioning.
Five new antipsychotic drugs introduced in the United States in the last decade offer physicians the ability to treat patients with schizophrenia and bipolar mania without the adverse effects of the first-generation antipsychotics. In this article, the authors discuss the advantages and side effects of these agents and present a guide to help physicians choose the optimal drug in the most favorable formulation for each patient.


Molecular Mechanism Underlying the Regulatory Effect of Vine Tea on Metabolic Syndrome by Targeting Redox Balance and Gut Microbiota.
Metabolic syndrome (MS) is a metabolic disorder that arises from the increasing prevalence of obesity. The pathophysiology seems to be largely attributable to the imbalance of lipid and glucose metabolism, redox signaling pathways, and gut microbiota. The increased syndromes, such as type 2 diabetes and cardiovascular disease demands natural therapeutic attention for those at high risk. Vine tea, as a traditional medicinal and edible resource rich in flavonoids, especially for dihydromyricetin (DHM), exhibits promising health benefits on the intervention of MS, but the specific molecular mechanism has not been systematically elucidated. The present article aims to summarize the regulatory effects and biological targets of vine tea or DHM on MS, and analyze the underlying potential molecular mechanisms in cells, animals, and humans, mainly by regulating the redox associated signaling pathways, such as Nrf2, NF-κB, PI3K/IRS2/AKT, AMPK-PGC1α-SIRT1, SIRT3 pathways, and the crosstalk among them, and by targeting several key biomarkers. Moreover, vine tea extract or DHM has a positive impact on the modulation of intestinal microecology by upregulating the ratio of Firmicutes/Bacteroidetes (F/B) and increasing the relative abundance of Akkermansia muciniphila. Therefore, this review updated the latest important theoretical basis and molecular evidence for the development and application of vine tea in dietary functional products or drugs against MS and also imputed the future perspectives to clarify the deep mechanism among vine tea or DHM, redox associated signaling pathways, and gut microbiota.


Association of XRCC1 gene polymorphisms with breast cancer susceptibility in Saudi patients.
X-ray repair cross-complementing group 1 (XRCC1) plays a key role in the base excision repair pathway, as a scaffold protein that brings together proteins of the DNA repair complex. XRCC1 is reported to be a candidate influence on cancer risk. The aim of our present study was to assess the association of rs1799782 (Arg194Trp) and rs25487 (Arg399Gln) XRCC1 gene polymorphisms with breast cancer in the Saudi population. The two SNP's were analyzed in breast cancer patients and healthy control subjects. Genotypes were determined by TaqMan SNP genotype analysis technique and data were analyzed using Chi- square or t test and logistic regression analysis by SPSS16.0 software. Results showed that rs1799782 significantly increased susceptibility to breast cancer with Arg/Trp, Arg/Trp+Trp/Trp genotypes and at Trp allele overall study. It also increased risk of breast cancer in older age patients (above 48) and with the ER positive category. XRCC1rs25487 (Arg399Gln) did not showed any significant association. In conclusion the XRCC1rs1799782 polymorphism may be involved in the etiology of breast cancer in the Saudi population. Confirmation of our findings in larger populations of different ethnicities is warranted.


The effect of muscle fatigue on instep kicking kinetics and kinematics in association football.
The aim of this study was to examine the effect of leg muscle fatigue on the kinetics and kinematics of the instep football kick. Fatigue was induced by repeated, loaded knee extension (40% body weight) and flexion (50% body weight) motions on a weight-training machine until exhaustion. The kicking motions of seven male players were captured three-dimensionally at 500 Hz before and immediately after the fatigue protocol. The significantly slower ball velocity observed in the fatigue condition was due to both reduced lower leg swing speed and poorer ball contact. The reduced leg swing speed, represented by a slower toe linear velocity immediately before ball impact and slower peak lower leg angular velocity, was most likely due to a significantly reduced resultant joint moment and motion-dependent interactive moment during kicking. These results suggest that the specific muscle fatigue induced in the present study not only diminished the ability to generate force, but also disturbed the effective action of the interactive moment leading to poorer inter-segmental coordination during kicking. Moreover, fatigue obscured the eccentric action of the knee flexors immediately before ball impact. This might increase the susceptibility to injury.


Postural behavior of howler monkeys (Alouatta palliata, A. macconnelli, and A. caraya) during sleep: an assessment across the genus range.
Sleep is the longest and most continuous behavioral phase in the 24 h cycle of mammals. However, selection of postures, substrates, and tree parts during sleep has not been adequately explored, as well as their evolutionary consequences. The present study investigates postural behavior, substrate, and tree part use during sleep in three howler species (A. palliata, A. macconnelli, and A. caraya) in Nicaragua, French Guiana, and Argentina. All three species were consistent in the use of a crouched ball-like sit-in posture on large, horizontal, unramified, or bifurcated substrates, and in avoiding the periphery of tree crowns. The regularities of these sleeping patterns are very likely functionally associated with protection from potential predators and extreme weather conditions, biomechanical stability, thermoregulation, and enhancement of the digestive process of hard-to-decompose plant material.


Comparing light sensitivity, linearity and step response of electronic cameras for ophthalmology.
To develop and test a procedure to measure and compare light sensitivity, linearity and step response of electronic cameras. The pixel value (PV) of digitized images as a function of light intensity (I) was measured. The sensitivity was calculated from the slope of the P(I) function, the linearity was estimated from the correlation coefficient of this function. To measure the step response, a short sequence of images was acquired. During acquisition, a light source was switched on and off using a fast shutter. The resulting PV was calculated for each video field of the sequence. A CCD camera optimized for the near-infrared (IR) spectrum showed the highest sensitivity for both, visible and IR light. There are little differences in linearity. The step response depends on the procedure of integration and read out.


Efficacy and safety of triple combination therapy for treating chronic obstructive pulmonary disease: an expert review.
Introduction: The current recommendations of chronic obstructive pulmonary disease (COPD) suggest to escalate from inhaled corticosteroid/long-acting β2-adrenoceptor agonist (ICS/LABA) treatment to triple therapy in patients experiencing persistent breathlessness, exercise limitation, or exacerbation. The addition of an ICS to LABA/long-acting muscarinic antagonist (LAMA) combination is recommended for frequently exacerbating patients with high levels of blood eosinophils. Nowadays, three triple therapies have been approved as fixed-dose combinations (FDCs) for the treatment of COPD: beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FOR/GLY), fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), and budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR).Areas covered: This narrative review evaluates the efficacy and safety profile of triple FDC therapy for the treatment of COPD, by evaluating the data originating from pivotal randomized-controlled trials (RCTs).Expert opinion: The currently approved triple FDCs exert a protective effect against the risk of COPD exacerbation compared to ICS/LABA and LABA/LAMA, with some concerns regarding the risk of pneumonia for some specific FDCs. Since the assessed RCTs were characterized by important confounders, the obtained results should be interpreted with caution. Indeed, FDCs provide advantages in terms of improved adherence to treatment and lower errors in COPD management; however, direct head-to-head comparisons are needed to establish real differences between the currently approved triple FDCs.


Management of meconium stained amniotic fluid: a team approach.
Passage of meconium in utero is a serious neonatal disorder carrying high morbidity and mortality. Role of planned team approach with aggressive intrapartum suctioning and intensive neonatal management was studied to evaluate its impact on neonatal morbidity and mortality. Meconium Stained Amniotic Fluid (MSAF) was found amongst 7.4% of all deliveries and among these 238 (10.5%) babies developed meconium aspiration syndrome (MAS). Ninety five per cent babies with MSAF were born at > 36 weeks of gestation and 76% were more than 2.5 kg. Passage of thick and thin meconium was seen in 44 and 56% respectively. Passage of thick meconium was significantly associated with severe asphyxia and carried a bad prognosis with increased risk of development of meconium aspiration syndrome, hypoxic schemic encephalopathy, seizures and pulmonary air leak syndrome. Aggressive team approach was responsible for lowering the mortality to 7.7%.


Isolation and characterization of the Tn3 resolvase synaptic intermediate.
We have isolated in quantitative yield the synaptic intermediate formed during site-specific recombination by Tn3 resolvase and characterized it by restriction endonuclease mapping, electron microscopy and topological methods. The intermediate accumulates at low reaction temperatures and is stabilized by crosslinking of the resolvase protomers with glutaraldehyde. The DNA-resolvase complex that maintains the structure of the intermediate (the synaptosome) is approximately 100 A in diameter, forms specifically at resolution (res) sites, and requires two res sites in a supercoiled DNA molecule. Resolvase bound to individual res sites protects approximately -0.5 supercoil per site from relaxation by a topoisomerase, whereas the formation of the synaptosome protects -3 supercoils and condenses the associated DNA to a supercoil density 2.5 times that of the non-complexed substrate. Although recombination requires two directly repeated res sites, both direct and inverted sites form synaptosomes. We conclude that the specificity of recombination is achieved by a three-stage recognition system: binding of resolvase to separate sites, formation of the synaptosome and determination of site orientation from within the complex.


Inhibition of Rho-kinase protects cerebral barrier from ischaemia-evoked injury through modulations of endothelial cell oxidative stress and tight junctions.
Ischaemic strokes evoke blood-brain barrier (BBB) disruption and oedema formation through a series of mechanisms involving Rho-kinase activation. Using an animal model of human focal cerebral ischaemia, this study assessed and confirmed the therapeutic potential of Rho-kinase inhibition during the acute phase of stroke by displaying significantly improved functional outcome and reduced cerebral lesion and oedema volumes in fasudil- versus vehicle-treated animals. Analyses of ipsilateral and contralateral brain samples obtained from mice treated with vehicle or fasudil at the onset of reperfusion plus 4 h post-ischaemia or 4 h post-ischaemia alone revealed these benefits to be independent of changes in the activity and expressions of oxidative stress- and tight junction-related parameters. However, closer scrutiny of the same parameters in brain microvascular endothelial cells subjected to oxygen-glucose deprivation ± reperfusion revealed marked increases in prooxidant NADPH oxidase enzyme activity, superoxide anion release and in expressions of antioxidant enzyme catalase and tight junction protein claudin-5. Cotreatment of cells with Y-27632 prevented all of these changes and protected in vitro barrier integrity and function. These findings suggest that inhibition of Rho-kinase after acute ischaemic attacks improves cerebral integrity and function through regulation of endothelial cell oxidative stress and reorganization of intercellular junctions. Inhibition of Rho-kinase (ROCK) activity in a mouse model of human ischaemic stroke significantly improved functional outcome while reducing cerebral lesion and oedema volumes compared to vehicle-treated counterparts. Studies conducted with brain microvascular endothelial cells exposed to OGD ± R in the presence of Y-27632 revealed restoration of intercellular junctions and suppression of prooxidant NADPH oxidase activity as important factors in ROCK inhibition-mediated BBB protection.


Diagnosis and physiopathology of laryngeal deposits in autoimmune disease.
We report the clinical features and pathology of a previously unreported form of vocal fold disease seen in 4 patients, 3 of whom were diagnosed as autoimmune disease. The characteristic features of these lesions were found as bilateral transverse lesions in the mid portion of the vocal folds. The patients had dysphonia and diplophonia. Stroboscopic examinations showed 180-degree phase shifts between the anterior and posterior portion of the vocal folds. Case 1 had systemic lupus erythematosus, case 2 had Hashimoto's thyroiditis, and case 3 had progressive systemic sclerosis. Prior to the onset of hoarseness, autoimmune antibody titers were increased. These cases need differential diagnosis from vocal fold nodules and cysts. Two cases were recurrent after endoscopic surgery, 1 recurring 3 times. Glucocorticoid was effective in preventing the recurrence in the early phase. Recurrence may have occurred because the surgical strategy was the same as that used for vocal fold nodules or cysts.


[Human papillomaviruses infections among village women in Henan province].
To investigate the prevalence of Human papillomaviruses (HPVs) among village women in Henan and to determine its relevant risk factors. A population based cross-sectional study on cervical cancer was conducted among village women in Xinmi, Henan. Women aged 20 - 54 who had sexual intercourse experiences were enrolled in this study. Self-sampling and direct-sampling were used in collecting women's vaginal discharge. 13 high-risk HPVs were tested with HC2 for all of the specimens. Then women with abnormal results did colposcopy and biopsy. The biopsy results were regarded as the golden standard. There were 881 women enrolled in this paper and 881 self-sampling and 880 direct-sampling specimens were collected. The HPVs prevalence rates for the self-sampling and direct-sampling were 13.05% and 12.27%, respectively. Age-specific prevalence rates were 10.57% (20-), 9.60% (25-), 12.00% (30-), 9.52% (35-), 17.60% (40-), 13.74% (45-) and 12.80% (50 - 54). HPV prevalence rates were increased with progression of cervical disease (chi(2) = 200.69, P = 0.00). And HPV prevalence rates were higher in women with more advanced education background (chi(2) = 11.05, P = 0.01). HPV infection rate in women whose husbands have more than one sexual partner was 18.02% and whose husbands have only one sexual partner was 10.88% (chi(2) = 6.37, P = 0.01). The infection rate of high-risk HPVs in this area is high. The relationship of HPV infection with age has not been observed in this study, but the the sexual activity is the major risk factor for cervical cancer.