Neuropilin-1 expression on regulatory T cells enhances their interactions with dendritic cells during antigen recognition.
The interaction of T cells with dendritic cells (DCs) determines whether an immune response is launched or not. Recognition of antigen leads to formation of immunological synapses at the interface between the cells. The length of interaction is likely to determine the functional outcome, because it limits the number of MHC class II-peptide complexes that can be recruited into the synapse. Here, we show that regulatory T (Treg) cells and naive helper T (Th) cells interact differently with DCs in the absence of proinflammatory stimuli. Although differences in T cell receptor repertoire might contribute, Foxp3-induced phenotypic differences play a major role. We found that Neuropilin-1 (Nrp-1), which is expressed by most Treg cells but not naive Th cells, promoted prolonged interactions with immature DCs (iDCs), resulting in higher sensitivity to limiting amounts of antigen. This is likely to give Treg cells an advantage over naive Th cells, with the same specificity leading to a "default" suppression of immune responses in the absence of "danger signals."


Muscarinic acetylcholine receptors potentiate the GABAergic transmission in the developing rat inferior colliculus.
Postsynaptic currents (PSCs) were recorded using the patch-clamp technique in neurons of the rat inferior colliculus (IC) to investigate the muscarinic modulation of the GABAergic transmission. In the presence of strychnine (0.5 microM) and kynurenic acid (1 mM), spontaneous GABAergic PSCs were observed in all IC neurons investigated. Muscarine (10 microM) greatly potentiated the frequency of these GABAergic PSCs (618% of the control). 4-DAMP (50 nM), a M3 receptor preferring antagonist, greatly blocked the muscarine-evoked PSC frequency increase. The muscarinic antagonists telenzepine (50 nM; M1 preferring), methoctramine (10 microM; M2 preferring), and himbazine (10 microM; M4 preferring), and the nicotinic antagonist mecamylamine (10 microM) did not significantly affect the muscarine effect. These findings indicate that the muscarinic modulation of the GABAergic transmission is primarily mediated by M3 receptors, while M1-, M2- and M4- and nicotinic receptors do not participate substantially. In the presence of tetrodotoxin (0.5 microM), muscarine failed to increase the PSC frequency indicating that its effect depended on the generation of spikes. We suggest that GABAergic interneurones express M3 receptors at some distance from the terminal. Their activation excites GABAergic interneurones, thereby enhancing GABA release in the IC. The muscarinic modulation of the GABAergic transmission may play an important role in the maturation of inhibitory synapses in the developing IC.


Evidence supporting the activity of 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentafuranosylcytosine as a terminator in enzymatic DNA-chain elongation.
To investigate the stability of 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentafuranosylcytosine 3'-phosphoric acid, its thymidine ester was prepared via the phosphoramidite method using allyl protection for the phosphate function. This ester is stable under acidic conditions but extremely labile under basic conditions, decomposing with a cleavage of the internucleotide bond even at pH 7.3.


[Visualization of brain function using MRI-MR functional brain imaging].
The effects of photic stimulation on the visual cortex of human brain were studied by means of gradient-echo magnetic resonance imaging (MRI). Fast low-angle shot (FLASH) MRI was used to monitor changes in brain oxygenation in the human visual cortex during photic stimulation (PS). Whole-body 1.5 T clinical MR system was used. Elevation of image intensity up to 2% was observed in primary and associative visual cortex, corresponding to an increase of blood oxygenation in regions of increased neural activity. After the PS was switched off, the MR signal fell below the pre-PS baseline level, which may be understood as an displacement of the oxygen-hemoglobin dissociation curve (the Bohre effect).


Posture-correlated responses to vestibular polarization in vermal versus intermediate posterior cerebellar cortex.
Cerebellar lesion experiments have led to the concept that the medial longitudinal zone controls postural tone while the intermediate zone controls discrete movement. This study is a test of the hypothesis that, of the two zones, the medial zone is more closely linked to the resting discharge of vestibular afferent fibers, a prime source of neural tonus underlying the tonus of posture. Unilateral polarizations of the vestibular apparatus via the round window in awake, unrestrained guinea pigs caused step changes of postural attitude, the direction of which was polarity dependent. In anesthetized animals, these currents caused nonadapting step changes, or posture-correlated responses in the level of resting discharge in vestibular primary afferent fibers. In the medial and the intermediate cerebellar cortices of the posterior lobe, the proportion of step-like responses was similar, in contradiction to the hypothesis. This suggests that the cerebellar computations for controlling both postural tonus and discrete movements require information about vestibular tonus in terms of simple spike activity.


Studies of age-related changes in the metabolism of eosin in the rat.
Male rats of different age groups maintained normally on laboratory chow were injected with eosin (2,4,5,7-tetrabromo-11-carboxyfluorescein) after which the biliary excretion of the dye was studied. In 3 age groups below 42 weeks, the dye was excreted as 2 compounds which were identified by thin-layer chromatography as unchanged eosin (Rf 0.90--0.91) contributing about 80--90% and one conjugated compound of Rf 0.43--0.47 (14--9%) which was shown to be a glucuronide. Eosin metabolites could not be traced in 30 and 42 week-old rats. This finding is discussed in relation to: (i) age and enzymic activity, and (ii) bio-activated metabolites of this dye which may induce biochemical or toxicological and carcinogenic lesions.


Effectiveness of Intensively Applied Mirror Therapy in Older Patients with Post-Stroke Hemiplegia: A Preliminary Trial.
The present work was carried out to determine the effectiveness of neuromuscular stimulation triggered by mirror therapy (MT) in older patients with post-stroke hemiplegia by two different intervention protocols, either intensively or spaced. A preliminary trial conducted on Spanish rehabilitation centres was conducted. Forty older patients (>70 years) with diagnosed post-stroke hemiplegia were randomly distributed to intensive intervention group (5 times/week for 6 weeks) or to spaced intervention group (3 times/week for 10 weeks), which underwent a similar number of MT sessions (n = 30). Muscle strength and activity were measured at baseline and at the end of treatment. Functional ability was also evaluated. Although both interventions improved muscle activity parameters, intensive MT showed a significantly and statistically higher intervention effect on electromyographic activity (p < 0.001) and muscle strength (p < 0.001) than the spaced over time protocol. Attending to the Barthel Index scores, the effect on functionality was also greater in the intensive therapy group (p < 0.001), although the functional improvement measured by the Fugl-Meyer test was similar (p = 0.235). The effect of the interventions was independent of age and clinical antecedents. Intensive MT appears to be more effective than a more spaced over time therapy; therefore, at least in the older adults, this treatment protocol should be recommended in the post-stroke recovery of these patients. Further studies will confirm with certainty whether this treatment is the most suitable guideline for to treat these patients.


Behavioral health care provider's beliefs, confidence, and knowledge in treating cigarette smoking in relation to their use of the 5A's intervention.
Evidence-based smoking cessation interventions are underused settings where behavioral health treatment is provided, contributing to smoking-related health disparities in this patient group. This study assessed the relationship of provider's beliefs about patients' smoking, perceptions of treatment capability, and knowledge of referral options and their use of the 5A's (Ask, Advise, Assess, Assist, and Arrange) intervention for smoking cessation. Surveys were collected from providers in healthcare settings in Texas where patients receive behavioral health care (N = 86; 9 federally qualified health centers, 16 Local Mental Health Authorities (LMHAs), 6 substance use treatment programs in LMHAs, and 55 stand-alone substance use treatment centers). Logistic regression analyses were used to assess the association between provider's beliefs about patients' concern and desire to quit smoking; perceptions of their confidence, skills, and effectiveness in treating smoking; their knowledge of referral options; and their use of the 5A's with patients who smoked. Providers who believed that patients were concerned about smoking and wanted to quit; who perceived themselves as confident in providing cessation care, having the required skills, and being effective in providing advice; and/or who had greater referral knowledge were more likely to use the 5A's with patients who smoked than their (respective) provider counterparts (ps < 0.05). Provider-level constructs affect their 5A's provision for patients with behavioral health needs. Future work should train providers to correct misconceptions about patients' interest in quitting, bolster their confidence, and provide referral options to support tobacco provision efforts.


Photocatalytic direct borylation of carboxylic acids.
The preparation of high value-added boronic acids from cheap and plentiful carboxylic acids is desirable. To date, the decarboxylative borylation of carboxylic acids is generally realized through the extra step synthesized redox-active ester intermediate or in situ generated carboxylic acid covalent derivatives above 150 °C reaction temperature. Here, we report a direct decarboxylative borylation method of carboxylic acids enabled by visible-light catalysis and that does not require any extra stoichiometric additives or synthesis steps. This operationally simple process produces CO2 and proceeds under mild reaction conditions, in terms of high step economy and good functional group compatibility. A guanidine-based biomimetic active decarboxylative mechanism is proposed and rationalized by mechanistic studies. The methodology reported herein should see broad application extending beyond borylation.


Secretion of active human lysozyme by Acremonium chrysogenum using a Fusarium alkaline protease promoter system.
We constructed expression vectors for Acremonium chrysogenum using a Fusarium alkaline protease promoter region and tested their potential as secretion systems for foreign proteins using the human (h)-lysozyme gene as an indicator. The gene encoding h-lysozyme was linked to the coding region of (1) the carboxy terminal of the alkaline protease pre peptide, (2) the carboxy terminal of the prepro peptide, (3) three amino acids of the mature protein preceded by the prepro peptide and (4) the carboxy terminal of chicken lysozyme signal peptide, inserted into the genomic DNAs of A. chrysogenum and expressed under the control of the alkaline protease promoter. The transformants of A. chrysogenum with each of these plasmids secreted enzymatically active h-lysozyme. A maximum yield in excess of 40 mg l-1 was obtained when h-lysozyme was linked to the carboxy terminal of alkaline protease prepro peptide. The majority of the amino terminal sequence of the purified h-lysozyme from the culture supernatant was identical with that of authentic h-lysozyme, but it showed some heterogeneity.


Partial Segregation of Bi and Microvoid Formation on a Pure Cu Substrate After Solid-Solid Reactions.
With the trend of technology development and carbon reduction, reducing the process temperature to prevent greenhouse effects is of great urgency. The back-end process of semiconductors is increasingly important because of the limitation of Moore's Law. High-temperature bonding is serious for semiconductor packages, which induces high cost and device damage. One of the critical ways to reduce the process temperature is to adopt low-temperature solders. In this study, we utilize the low-temperature solder Sn58Bi to achieve energy savings and device protection. The interfacial reactions between Sn58Bi and Cu after reflow and aging reactions were investigated. The solubility of Bi in Sn influences the Bi segregation at the interface. Partial Bi segregation, microvoids, and uneven Cu3Sn were observed at the interface after aging. There is no doubt that the aforementioned structures are unfavorable for solder joint strength.


Proton-coupled protein transport through the anthrax toxin channel.
Anthrax toxin consists of three proteins (approx. 90kDa each): lethal factor (LF); oedema factor (OF); and protective antigen (PA). The former two are enzymes that act when they reach the cytosol of a targeted cell. To enter the cytosol, however, which they do after being endocytosed into an acidic vesicle compartment, they require the third component, PA. PA (or rather its proteolytically generated fragment PA63) forms at low pH a heptameric beta-barrel channel, (PA63)7, through which LF and OF are transported--a phenomenon we have demonstrated in planar phospholipid bilayers. It might appear that (PA63)7 simply forms a large hole through which LF and OF diffuse. However, LF and OF are folded proteins, much too large to fit through the approximately 15A diameter (PA63)7 beta-barrel. This paper discusses how the (PA63)7 channel both participates in the unfolding of LF and OF and functions in their translocation as a proton-protein symporter.


Aberrant expression of cystatin C in prostate cancer is associated with neuroendocrine differentiation.
To investigate the expression of cystatin C and the relationship with neuroendocrine differentiation and proliferation in benign and malignant prostatic tissues, as cystatin C, the most important inhibitor of human lysosomal cysteine proteases, is considered to be a major regulator of pathological protein degradation in inflammatory and neoplastic diseases. Immunoreactivity for cystatin C, prostate-specific antigen, Ki-67 and the neuroendocrine marker chromogranin A was examined in whole-mount radical prostatectomy specimens and using tissue microarrays. Cystatin C in tissue homogenates was analysed by Western blotting and enzyme-linked immunosorbent assay (ELISA). The expression and relative levels of cystatin C mRNA were assessed by in situ hybridization and quantitative real-time polymerase chain reaction (QRT-PCR). The intensity of cystatin C immunostaining in Gleason grade 2 and 3 prostate cancer was significantly higher than in benign prostatic tissues, but decreased significantly with increasing Gleason grades. There was strong expression of cystatin C in neuroendocrine-like cells, which increased significantly with increasing Gleason grades. The Ki-67 immunoreactivity also increased significantly during de-differentiation. In situ hybridization showed staining patterns in concordance with the immunohistochemical results. ELISA showed high concentrations of cystatin C in benign and malignant tissue extracts and QRT-PCR further corroborated that the cystatin C gene is highly expressed in both benign and malignant prostatic tissues. There was a significant decrease in the immunohistochemical expression of cystatin C in non-neuroendocrine prostate cancer cells, concomitant with increasing Gleason grades. That there were more strongly cystatin C-positive neuroendocrine-like cells in prostate cancer than in benign prostatic tissue suggests a connection between cystatin C and neuroendocrine differentiation in prostate cancer progression.


Severe hemolytic disease of the fetus and newborn due to allo-anti-D in a patient with a partial DEL phenotype arising from the variant allele described as RHD*148+1T (RHD*01EL.31).
RhD DEL variants may show complete or partial expression of RhD epitopes. There have been only rare reports of anti-D causing hemolytic disease of the fetus and newborn (HDFN) in this context. We report a case of severe HDFN associated with a recently described DEL variant. A multiparous woman presented with an allo-anti-D and showed incongruent phenotyping and genotyping results on initial study. Further investigations identified the RHD mutation, defined as RHD*148+1T and named RHD*01EL.31, which had been previously associated with a DEL phenotype. Extended RhD phenotyping by adsorption-elution showed that there was reactivity with four of nine monoclonal anti-D antibodies, suggesting a partial DEL phenotype. The first child showed no clinical evidence of HDFN, although the cord direct antiglobulin test was positive. The second child developed fetal anemia treated with intrauterine transfusion, and neonatal hyperbilirubinemia requiring exchange transfusion. The RHD allele, RHD*148+1T, results in a partial Del phenotype, and the anti-D formed in pregnant women with this phenotype is capable of causing severe HDFN.


Self-Healable Conductive Nanocellulose Nanocomposites for Biocompatible Electronic Skin Sensor Systems.
Electronic skins are developed for applications such as biomedical sensors, robotic prosthetics, and human-machine interactions, which raise the interest in composite materials that possess both flexibility and sensing properties. Polypyrrole-coated cellulose nanocrystals and cellulose nanofibers were prepared using iron(III) chloride (FeCl3) oxidant, which were used to reinforce polyvinyl alcohol (PVA). The combination of weak H-bonds and iron coordination bonds and the synergistic effect of these components yielded self-healing nanocomposite films with robust mechanical strength (409% increase compared to pure PVA and high toughness up to 407.1%) and excellent adhesion (9670 times greater than its own weight) to various substrates in air and water. When damaged, the nanocomposite films displayed good mechanical (72.0-76.3%) and conductive (54.9-91.2%) recovery after a healing time of 30 min. More importantly, the flexible nanocomposites possessed high strain sensitivity under subtle strains (<48.5%) with a gauge factor (GF) of 2.52, which was relatively larger than the GF of ionic hydrogel-based skin sensors. These nanocomposite films possessed superior sensing performance for real-time monitoring of large and subtle human motions (finger bending motions, swallowing, and wrist pulse); thus, they have great potentials in health monitoring, smart flexible skin sensors. and wearable electronic devices.


Blalock-Taussig shunt versus patent ductus arteriosus stent as first palliation for ductal-dependent pulmonary circulation lesions: A review of the literature.
Infants with ductal-dependent pulmonary blood flow (PBF) often undergo a palliative procedure to provide a stable source of PBF prior to definitive palliation or repair. In the current era, a surgical shunt or ductal stent is used to provide PBF. We aimed to review the current literature comparing ductal stents to surgical shunts. Four small, single-center studies and two larger multicenter studies were identified comparing ductal stent to surgical shunt. Combined, these studies showed ductal stent resulted in similar or improved pulmonary artery growth, fewer complications, shorter length of stay, less diuretic use, and improved survival compared to surgical shunt. Despite inherent minor variability among the studies, ductal stent appears to be associated with more frequent reinterventions. Surgical shunts remain essential to the care of these patients, but ductal stent is a reasonable alternative, and may provide some advantages in select patients with ductal-dependent PBF.


Secondary bladder amyloidosis due to Crohn's disease: a case report and literature review.
The presence of amyloid deposits in bladder walls is a rare histological finding. It can be linked to primary (limited to bladder) or secondary (systemic, associated with chronic inflammatory disorders) amyloidosis. Secondary bladder involvement is very uncommon; it usually presents with gross hematuria, which is challenging to manage, due to frail bladder mucosa and/or necrosis. We present a case of 54-year old man with secondary bladder amyloidosis due to Crohn's disease, that caused gross hematuria and severe anemia, which was managed conservatively by endoscopic transurethral resection, diatermocoagulation, clot evacuation and urinary drainage by bilateral percutaneous nephrostomy, with spontaneous resolution. Secondary bladder amyloidosis is a rare condition that presents with severe hematuria, difficult to control with standard management. Owing to chronic nature of the disease, treatment should be aimed to a conservative approach whenever possible. In case of failure, invasive procedures should be considered as salvage therapies.


Rapid, accurate and precise quantitative drug analysis: comparing liquid chromatography tandem mass spectrometry and chip-based nanoelectrospray ionisation mass spectrometry.
We have developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) system capable of achieving better than 2% accuracy, routinely over a wide concentration range of 1800 ng mL-1. We demonstrate that the necessary high precision, high accuracy and rapid analysis can be achieved using LC-MS/MS technology. Automated nanoelectrospray ionisation tandem mass spectrometry (nanoESI-MS/MS) technology can be employed to eliminate the chromatographic step completely. In this paper, nanoESI-MS/MS is evaluated and compared directly with LC-MS/MS for the quantitative analysis of two-test analytes, amitriptyline (ATT) and 5-methoxytryptamine (5-MTT), in aqueous/organic mixture. Calibration curves were found to be linear over a wide concentration range of 1800 ng mL-1 for both analytes using LC-MS/MS. Using nanoESI-MS/MS ATT gave a linear response while 5-MTT gave a non-linear response using nanoESI-MS/MS over the same concentration range as in LC-MS/MS. Accuracy and precision values of quality control samples (QCs) at four concentration levels were analysed in replicates of six at each level using 5-MTT and ATT as test analytes for both techniques. The LC-MS/MS system was capable of achieving accuracy levels of 99.50101.96% for ATT and 100.17100.40% for 5-MTT. Accuracy levels using nanoESI-MS/MS were not comparable to LC-MS/MS, they ranged from 90.09100.18% for ATT and 95.95113.55% for 5-MTT. The precision values obtained for nanoESI-MS/MS were in good agreement with those obtained by LC-MS/MS.


Feeding Behaviour on Host Plants May Influence Potential Exposure to Bt Maize Pollen of Aglais Urticae Larvae (Lepidoptera, Nymphalidae).
Non-target butterfly larvae may be harmed by feeding on host plants dusted with Bt maize pollen. Feeding patterns of larvae and their utilization of host plants can affect the adverse Bt impact because the maize pollen is distributed unequally on the plant. In a field study, we investigated the feeding of larvae of the Small Tortoiseshell, Aglais urticae, on nettles, Urtica dioica. Young larvae used smaller host plants than older larvae. In general, the position of the larvae was in the top part of the host plant, but older larvae showed a broader vertical distribution on the nettles. Leaf blades and leaf tips were the plant parts most often consumed. Leaf veins were consumed but midribs were fed on to a lesser extent than other plant veins, particularly by young larvae. The feeding behavior of the larvae may increase possible exposure to Bt maize pollen because pollen densities are expected to be higher on the top parts and along leaf veins of nettles.


Expression of CCL5 (RANTES) and CCR5 in prostate cancer.
Expression of the inflammatory chemokine CCL5 (RANTES) by tumor cells is thought to correlate with the progression of several cancers. CCL5 was shown to induce breast cancer cell migration, mediated by the receptor CCR5. A CCR5 antagonist was demonstrated to inhibit experimental breast tumor growth. Recently, CCL5 and CCR5 mRNA expression was reported in prostate cancer (PCa) tissues. Herein, we characterized CCL5 and CCR5 expression in cultures of PCa cells and explored possible functions of CCL5 in PCa progression. Quantitative RT-PCR, ELISA, and immunohistochemical staining were performed to examine CCL5 expression in prostate cell lines. CCR5 expression was measured by flow cytometry. Proliferation and invasion assays were performed to determine potential functions of CCL5 and CCR5 in PCa. Expression of CCL5 mRNA and protein was found in human PCa cell lines (PC-3; DU-145; LNCaP) and primary prostate adenocarcinoma cells. CCL5 and CCR5 were also detected in human PCa tissues. CCR5 expression was demonstrated on the cell surface of PCa cells, as well as in intracellular pools. Incubation with CCL5 (10-100 ng/ml) induced PCa cell proliferation, and the CCR5 antagonist TAK-779 inhibited CCL5-induced proliferation. CCL5 was found to stimulate PCa cell invasion, and TAK-779 blocked the effects of CCL5. In light of evidence that inflammation influences the pathogenesis of PCa, these results suggest that inflammatory chemokines, such as CCL5, expressed by prostate cells may act directly on the growth and survival of PCa cells. Chemokine receptor antagonists may thus block autocrine mechanisms of PCa progression.


Hypoglycemia.
In the present review, we have tried to briefly define the types of hypoglycemia which may be seen most frequently in medicine. Wherever possible, mechanisms and appropriate diagnostic tests have been described. Treatment of hypoglycemia has been purposely avoided, since therapy should be obvious once diagnosis is made and mechanisms are understood. While it is recognized that this review is not exhaustive, it should cover over 95 per cent of the cases of hypoglycemia encountered by the practicing physician.


Robotic facelift thyroidectomy: Facilitating remote access surgery.
A novel remote access robotic thyroidectomy technique has been described that uses as its portal a postauricular and occipital hairline (facelift) incision. Experimental investigation and clinical validation have been completed. A detailed technical description is provided. A young woman with a thyroid nodule was referred for surgery. Because of her concerns about a visible neck scar, she opted for remote access thyroidectomy. A left robotic facelift thyroidectomy was performed in less than 2 hours as a drainless, outpatient procedure. Videographic demonstration of the robotic resection is included. A number of remote access thyroidectomy techniques have proliferated. We developed and described an intuitive approach that uses familiar dissection planes and avoids the need for breast incisions and crossing the clavicle.


High completion of isoniazid preventive therapy among HIV-infected children and adults in Kinshasa, Democratic Republic of Congo.
We assessed isoniazid preventive therapy (IPT) completion and predictors among HIV-infected children and adults in two HIV clinics in Kinshasa, Democratic Republic of Congo. Between 1 September 2012 and 15 June 2013, 546 children (1-15 years) and 1532 adults (>15 years) were initiated on IPT; 86.6% (408/470) of the children and 88.2% (1129/1280) of the adults with an IPT outcome completed their therapy. Patients on antiretroviral therapy at IPT initiation were more likely to complete IPT.


Randomized controlled trial of early endoscopy for upper gastrointestinal bleeding in acute coronary syndrome patients.
Acute upper gastrointestinal bleeding (UGIB) in acute coronary syndrome (ACS) patients are not uncommon, particularly under dual antiplatelet therapy (DAPT). The efficiency and safety of early endoscopy (EE) for UGIB in these patients needs to be elucidated. This multicenter randomized controlled trial randomized recent ACS patients presenting acute UGIB to non-EE and EE groups. All eligible patients received intravenous proton pump inhibitor therapy. Those in EE group underwent therapeutic endoscopy within 24 h after bleeding. The data regarding efficacy and safety of EE were analyzed. It was early terminated because the UGIB rate was lower than expected and interim analysis was done. In total, 43 patients were randomized to non-EE (21 patients) and EE (22 patients) groups. The failure rate of control hemorrhage (intention-to-treat [ITT] 4.55% vs. 23.81%, p < 0.001; per-protocol [PP] 0% vs. 4.55%, p = 0.058) and 3-day rebleeding rate (ITT 4.55% vs. 28.57%, p = 0.033; PP 0% vs. 21.05%, p = 0.027) were lower in EE than non-EE group. The mortality, minor and major complication rates were not different between two groups. Male patients were at higher risk of minor and major complications after EE with OR (95% CI) of 3.50 (1.15-10.63) and 4.25 (1.43-12.63), respectively. In multivariate analysis, EE was associated with lower needs for blood transfusion (HR 0.13, 95% CI 0.02-0.98). Among patients who discontinued DAPT during acute UGIB, a higher risk (OR 5.25, 95% CI 1.21-22.74) of coronary artery stent re-thrombosis within 6 months was noticed. EE for acute UGIB in recent ACS patients has higher rate of bleeding control, lower 3-day rebleeding rate and lower needs for blood transfusion, but more complications in male patients. Further enrollment is mandatory to avoid bias from small sample size (ClinicalTrial.gov Number NCT02618980, registration date 02/12/2015).


Use of serotonin reuptake inhibitor antidepressants and the risk of bleeding complications in patients on anticoagulant or antiplatelet agents: a systematic review and meta-analysis.
Serotonin reuptake inhibitor (SRI) antidepressants are implicated in increasing the risk of bleeding among users; however, the comparative increase in bleeding risk with concurrent antithrombotic therapy (anticoagulant or antiplatelet) remains unclear. As such, we performed a systematic review and meta-analysis of all available evidence to evaluate the effects of SRI and the risk of bleeding complications among patients receiving antithrombotic therapy. We searched Medline, Embase, PubMed, PsycINFO, Cochrane Library, Web of Science, Scopus, CINAHL, and grey literature (Google Scholar and preprint reports) up to 26 November, 2020, with no language restrictions (updated on 31 July 2021). The primary outcome of interest was major bleeding. Secondary outcomes included intracranial haemorrhage, gastrointestinal bleeding, and any bleeding events. We used a random-effects model meta-analysis to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). We did not identify any randomised studies but found 32 non-randomized studies (cohort or case-control) with 1,848,285 patients that fulfilled the study selection criteria and were included in the meta-analysis. Among individuals receiving anticoagulants (13 studies), SRI users experienced a statistically higher risk of major bleeding compared to non-SRI users: pooled OR was 1.39 (95% CI, 1.23-1.58; p < .001; moderate heterogeneity). Among individuals receiving antiplatelet therapy (2 studies), SRI users were associated with an increased risk of major bleeding: pooled OR was 1.45 (95% CI, 1.17-1.80; p = .001; low heterogeneity). For secondary outcomes, the use of SRI among individuals treated with antithrombotic therapy revealed a higher risk of gastrointestinal bleeding or any bleeding events, whereas only anticoagulant use was illustrated an increased risk of intracranial haemorrhage. The use of SRI antidepressants among patients treated with antithrombotic therapy (either anticoagulant or antiplatelet) is associated with a higher risk of bleeding complications, suggesting that caution is warranted in co-prescription. CRD42018083917KEY MESSAGESIn this meta-analysis of 32 non-randomized studies, SRI users were associated with the risk of bleeding complications compared to non-SRI users, with concurrent antithrombotic use (either anticoagulant or antiplatelet).The risk was consistently elevated across types of bleeding events (major bleeding, gastrointestinal bleeding, or any bleeding events), whereas only anticoagulant use was associated with intracranial haemorrhage.To promote the rational use of medicines, our findings suggest that the risk-benefit ratio must account for the clear efficacy of SRI against safety concerns in terms of bleeding risks.


Transseptal puncture guided by intracardiac echocardiography during percutaneous transvenous mitral commissurotomy in patients with distorted anatomy of the fossa ovalis.
Positioning of the transseptal needle during percutaneous transvenous mitral commissurotomy (PTMV) can become a difficult and risky procedure when distortion of the interatrial septum exists. We present two cases where intracardiac echocardiography (ICE) facilitated the transseptal puncture in the presence of bulging of the fossa ovalis into the right atrium.


Localization of a specific germ cell marker, DAZL1, in testicular germ cell neoplasias.
DAZ-like 1( DAZL1) is a germ cell-specific protein expressed in both male and female gonads. The DAZL1 gene, which maps to chromosome 3 in humans, is an autosomal homologue to the Deleted in AZoospermia ( DAZ) gene(s) located on the Y chromosome. We studied the expression of DAZL1 by means of immunohistochemistry in order to determine its distribution among testicular germ cell neoplasias and among the intratubular lesions in their vicinity. Our results demonstrated that expression of DAZL1 protein was consistently observed in scattered cells in all intratubular germ cell neoplasias (IGCN) of the unclassified type, as well as in some of the intratubular seminomas. Foci of DAZL1 immunopositive cells were detected in pure seminomas, while single immunopositive cells were dispersed in the seminomatous component of mixed germ cell neoplasias. All the nonseminomatous components were negative for DAZL1 expression. These findings demonstrate an antigenic heterogeneity of seminoma cells. The localization of a specific germ cell protein, DAZL1, in the putative ontogenic progenitor, IGCN, and in their putative derivative, seminoma, provides further support for the hypothesis that IGCN is the precursor of germ cell neoplasias.


Mutagenicity of naphthacene, a non-bay-region aromatic hydrocarbon, in Salmonella.
Naphthacene (2,3-benzanthracene, tetracene) was tested for mutagenicity towards Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98 and TA100. Mutagenicity was seen in all strains except in TA1535 when liver S9 fraction from rats or mice was present. The increases in the number of revertants induced by naphthacene equalled those by other naturally occurring polycyclic aromatic hydrocarbons, benzo[a]pyrene and dibenz[ac]anthracene, in the strains TA98 and TA100.


Eccentric exercise improves joint flexibility in adults: A systematic review update and meta-analysis.
Eccentric exercise is thought to improve joint flexibility, but the size of the effect is not known. We aimed to quantify the overall effect of eccentric exercise on joint flexibility in adults. Systematic review, meta-analysis. AMED, CINAHL, MEDLINE, EMBASE, SportDiscus. Adults. Eccentric exercise compared to no intervention or to a different intervention. Joint range of motion or muscle fascicle length. Descriptive data of included trials and estimates of effect sizes were extracted. Standardised mean differences (SMD) of range of motion or fascicle length outcomes were meta-analysed using random effects models. Overall quality of evidence was assessed using the GRADE scale. 32 trials (1122 participants, 108 lost to follow-up) were included in the systematic review. The mean (SD) PEDro score was 5.2 (1.3). Four trials reported insufficient data for meta-analysis. Data from 27 trials (911 participants, 82 lost to follow-up) were meta-analysed. Eccentric exercise improved joint flexibility in adults (pooled random effects Hedges' g SMD = 0.54, 95% CI 0.34 to 0.74). The true effect size is different across studies and 50% of the variance in observed effects is estimated to reflect variance in true effects rather than sampling error (I2 = 50%, Q = 67.6, d.f. = 34, p = 0.001). Overall quality of evidence ranged from 'low' to 'high'. Eccentric exercise improves joint flexibility in adults. The overall standardised mean effect of eccentric exercise was moderately large, and the narrow width of the 95% confidence interval indicates the effect was estimated with good precision. Open Science Foundation (https://osf.io/mkdqr); PROSPERO registration CRD42020151303.


The probiotic potential of Lactobacillus plantarum strain RW1 isolated from canine faeces.
To evaluation the probiotic potential of Lactobacillus plantarum strain RW1 isolated from healthy dogs for its further utilization as a dietary supplement for dogs. This study aimed to evaluate the probiotic potential of L. plantarum strain RW1 isolated from canine faeces. After confirming by conventional and then by 16S rRNA sequencing, the identified strain RW1 was in vitro screened for its survivability in simulated gastrointestinal conditions, low pH, bile salts and adhesion to gut epithelial tissues, growth inhibitory effects on common pathogens and anti-inflammatory potential by measuring the mRNA expression level of IL-6, IL-8, IL-1β in Salmonella-infected MODE-K cells. Furthermore, the effects on epithelial barrier function and host defensin peptide (beta-defensin 3) was studied by measuring the mRNA expression level of tight junction protein (occludin) and beta-defensin 3 in MODE-K cells. The strain RW1 showed a considerable potential to survive in simulated gastrointestinal environmental conditions, low pH and high bile salt concentrations along with good adhesion to MODE-K cell line. Pathogenic bacterial growth and their adhesion to MODE-K cell line were significantly inhibited by the strain RW1. Real-time PCR analyses demonstrated that the strain RW1 inhibited Salmonella-induced pro-inflammatory cytokines (IL-6, IL-8 and IL-1β) production and reinforced the expression of tight junction protein (occludin). The strain RW1 did not induce mRNA expression of beta-defensin 3. Based on in vitro results, the strain RW1 has the potential to be used as a probiotic supplement in dogs. However, further study involving in vivo health effects is needed. Antibiotics have many side effects and nowadays the probiotics are considered as a potential alternative to antibiotics. This study evaluates the probiotic potential of dog isolated L. plantarum strain RW1 to use it as a dietary supplement in dogs feeding to control infectious diseases.


Patient-Physician Communication and Knowledge Regarding Fertility Issues from German Oncologists' Perspective-a Quantitative Survey.
Many people diagnosed with haematologic malignancies are of child-bearing age. Typical treatment courses pose a high risk of infertility, and a lot of people affected by this are in the midst of starting or growing their families. Thus, it is crucial that they are well informed about fertility preservation options and can discuss these with an oncologist early on in the development of their treatment plans. Unfortunately, however, this does not always happen. One hundred twenty oncologists from 37 German adult clinical facilities were surveyed regarding their discussions with young patients about fertility, family planning, and fertility preservation. Almost all of them said that they consider fertility preservation to be an important issue. They also reported several factors as having an influence on the likelihood and practicability of discussing these subjects. Most knew about the existence of cryoconservation of germ cells and the use of GnRH analogues (95 %), but only half of them claimed to have a thorough understanding of these options. Many said they would like to learn more about this and that informational brochures could be helpful. Even though many oncologists do have good working knowledge of the subject, patients of reproductive age are not yet consistently given comprehensive information about the options available to them. To improve oncologists' knowledge of reproductive medicine, cooperation with fertility specialists should be facilitated, and informational leaflets should be made available both to patients and their medical care providers.


Aspartame consumption in rats selectively bred for high versus low saccharin intake.
Whereas humans use aspartame as a sugar substitute, evidence to date from rats suggests that aspartame does not taste sweet or, more generally, hedonically positive to them. The present study provided a strong test of the appetitive properties of aspartame in rats by examining consumption of aspartame and, for comparison, several sugars by two lines of rats selectively bred for high (HiS) versus low (LoS) saccharin consumption. The HiS and LoS lines differed in consumption of fructose, glucose, sucrose, maltose, and saccharin solutions. Overall, the rats showed a weak but significant preference for aspartame. However, no line differences in aspartame consumption were observed. Thus, even among rats specifically bred on the basis of their responsiveness to sweet tastes, aspartame tastes minimally sweet or good.


Findings on serial MRI in a childhood case of L2-hydroxyglutaric aciduria.
We report of a 15-year-old patient who initially presented to the specialist children's hospital with neurologic problems including developmental delay, behavioral difficulty and poor cognition. Upon organic acid testing, the patient received a diagnosis of L2-hydroxyglutaric aciduria (L2HGA). Serial MRI scans were performed throughout the patients childhood, demonstrating an evolution of imaging features as the disease progressed. A radiologist's recognition of the key findings associated with L2HGA can help prompt the diagnosis in cases of a nonspecific clinical presentation. This case report highlights the key radiological features associated with L2HGA, whilst illustrating how these changes may evolve and appear over the time course of a patient's journey.


Pre-stressor cognitive control is related to intrusive cognition of a stressful film.
It has been suggested that relatively weak cognitive control existing prior to a stressful event may be associated with intrusive memories of that stressor afterwards. We explored this in two analog studies employing unselected participants who saw an emotional film fragment and completed behavioral (i.e., color-naming interference [CNI]) and self-report indices of intrusions. Prior to film presentation, several cognitive control tests were administered. Study 1 showed that better updating/monitoring was linked to less CNI from negative film-related words. However, better updating/monitoring was associated with more diary reports of intrusive memories. Study 2 showed that a better resistance to pro-active interference (PI) predicted less self-reported film-related intrusive cognition after 24h. However, after this delay, both self-reported intrusions and CNI were not related to updating/monitoring. Taken together, the results suggest that a specific pre-existing cognitive control function (i.e., resistance to PI) may be involved in the regulation of post-stressor intrusive memory phenomena.


Leishmania (L.) amazonensis-induced inhibition of nitric oxide synthesis in host macrophages.
Inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production was demonstrated in J774-G8 macrophages infected with Leishmania (L.) amazonensis promastigotes. The downmodulation of NO production observed in infected and LPS-stimulated J774-G8 cells correlated with a reduction in inducible nitric oxide synthase (iNOS) activity. Reduction in iNOS activity was not paralleled by decreased iNOS mRNA expression, suggesting that the parasite affects post-transcriptional events of NO synthesis. Supplementation with L-arginine or tetrahydrobiopterin did not increase NO production, suggesting that inhibition is not due to an insufficiency of substrate or co-factor. Treatment with anti-IL-10, anti-IL-4 or anti-TGF-beta neutralizing antibodies also failed to increase NO production, indicating that these cytokines are not involved in the observed parasite-induced inhibition of NO synthesis. However, treatment of the cultures with IFN-gamma resulted in a marked increase in NO production by infected LPS-stimulated cells. These results show that although L.(L.) amazonensis infection inhibits iNOS activity and NO production by J774-G8 cells, activation by IFN-gamma is capable of overriding the suppression of NO synthesis.


The role of contrast-enhanced MR angiography in the assessment of recently ruptured intracranial aneurysms: a comparative study.
We evaluated contrast-enhanced MR angiography (MRA) for the identification of recently ruptured cerebral aneurysms. We studied 23 aneurysms in 18 patients (age range 34-72 years) with aneurysms of the anterior (n = 17) and posterior (n = 6) circulation by comparing 3D time-of-flight (TOF), contrast-enhanced MRA and digital subtraction angiography (DSA). In four of 23 aneurysms, 3D-TOF did not show the lesion. Contrast-enhanced MRA successfully depicted all aneurysms except one. T1 contamination artefacts from subarachnoid or intraparenchymal haemorrhages were evident on the 3D-TOF images in six cases. The artefacts were completely eliminated on the contrast-enhanced MRA images by subtraction of the pre-contrast images. The diagnostic information in patients with subarachnoid haemorrhages (SAHs) provided by contrast-enhanced MRA was comparable to that provided by DSA.


A comparison of health inequalities in urban and rural Scotland.
Previous research suggests that there are significant differences in health between urban and rural areas. Health inequalities between the deprived and affluent in Scotland have been rising over time. The aim of this study was to examine health inequalities between deprived and affluent areas of Scotland for differing ruralities and look at how these have changed over time. Postcode sectors in Scotland were ranked by deprivation and the 20% most affluent and 20% most deprived areas were found using the Carstairs indicator and male unemployment. Scotland was then split into 4 rurality types. Ratios of health status between the most deprived and most affluent areas were investigated using all cause mortality for the Scottish population, 1979-2001. These were calculated over time for 1979-1983, 1989-1993, 1998-2001. Multilevel Poisson modelling was carried out for all of Scotland excluding Grampian to assess inequalities in the population. There was an increase in inequalities between 1981 and 2001, which was greatest in remote rural Scotland for both males and females; however, male health inequalities remained higher in urban areas throughout this period. In 2001 female health inequalities were higher in remote rural areas than urban areas. Health inequalities amongst the elderly (age 65+) in 2001 were greater in remote rural Scotland than urban areas for both males and females.


Effect of nasal antifungal therapy on nasal cell activation markers in chronic rhinosinusitis.
To examine the effect of nasal antifungal treatment on eosinophil cationic protein (ECP) and tryptase levels in samples of nasal lavage fluid from patients with chronic rhinosinusitis and nasal polyps. Prospective double-blind placebo-controlled clinical trial. Tertiary surgical center. Subjects with severe chronic rhinosinusitis and nasal polyps. Of 120 screened patients, 76 were eligible. Six patients withdrew because of minor adverse events, and 10 dropped out for other reasons. In total, 60 patients completed the study according to the study protocol. Nasal treatment with amphotericin B or saline control for 8 weeks. Nasal lavages were performed before and after treatment. Fungal elements were assessed by culture and with different polymerase chain reaction assays. Levels of ECP and tryptase were determined by fluorescent enzyme immunoassay. No correlation between cell activation markers and fungus detection was observed before treatment (all P>.20). Nasal amphotericin B treatment had no effect on levels of ECP (P = .17) or tryptase (P = .09) in nasal lavage samples. Moreover, successful fungus eradication, defined as fungus detection before but not after treatment, did not influence nasal ECP or tryptase levels (all P>.40). Neither topical amphotericin B therapy nor fungal state before and after treatment had any significant influence on activation markers of nasal inflammatory cells in chronic rhinosinusitis.


Characterization and application of fusidane antibiotic biosynethsis enzyme 3-ketosteroid-∆1-dehydrogenase in steroid transformation.
Microbial ∆(1)-dehydrogenation is one of the most important transformations in the synthesis of steroid hormones. In this study, a 3-ketosteroid-∆(1)-dehydrogenase (kstD(F)) involved in fusidane antibiotic biosynthesis from Aspergillus fumigatus CICC 40167 was characterized for use in steroid transformation. KstD(F) encodes a polypeptide consisting of 637 amino acid residues. It shows 51% amino acid identity with a kstD from Thermomicrobium roseum DSM 5159. Expression of kstD(F) in Escherichia coli and Pichia pastoris showed that all kstD(F) activity is located in the cytoplasm. This indicates that it is a soluble intracytoplasmic enzyme, unlike most kstDs from bacteria, which are membrane-bound. The expression of kstD(F) was performed in P. pastoris, both intracellularly and extracelluarly. The intracellularly expressed protein displayed good activity in steroid transformation, while the extracellularly expressed protein showed nothing. Interestingly, the engineered P. pastoris KM71 (KM71(I)) and GS115 (GS115(I)) showed different transformation activities for 4-androstene-3,17-dione (AD) when kstD(F) was expressed intracellularly. Under the same conditions, KM71(I) was found capable of transforming 1.0 g/l AD to 1,4-androstadiene-3,17-dione (ADD), while GS115(I) could transform 1.5 g/l AD to both ADD and boldenone (BD). The production of BD is attributed to a 17β-hydroxysteroid dehydrogenase in P. pastoris GS115(I), which catalyzes the reversible reaction between C17-one and C17-alcohol of steroids. The conversion of AD by GS115(I) and KM71(I) may provide alternative means of preparing ADD or BD. In brief, we show here that kstD(F) is a promising enzyme in steroid ∆(1)-dehydrogenation that is propitious to construct genetically engineered steroid-transforming recombinants by heterologous overexpression.


Differences in Attitudes About HIV Pre-Exposure Prophylaxis Use Among Stimulant Versus Alcohol Using Men Who Have Sex with Men.
Alcohol and stimulant use are independently associated with increased HIV acquisition among men who have sex with men (MSM). We assessed differences in acceptability and perceived barriers to uptake of pre-exposure prophylaxis (PrEP) among stimulant and alcohol-using MSM in Boston. From September 2012-2013, a quantitative assessment was conducted with 254 MSM respondents who reported recent condomless sex in the context of concurrent stimulant (crack/cocaine and crystal methamphetamine; n = 132) or alcohol use (n = 122). Thirteen (5.1 %) reported previous PrEP use. In multivariable models, stimulant users were more likely to be concerned that substance use would affect PrEP adherence (aRR = 2.79, 95 % CI 1.63-4.77), and were less concerned about HIV stigma as a barrier to PrEP uptake (aRR = 0.52, 95 % CI 0.30-0.90) compared to alcohol users. Barriers to PrEP uptake and adherence differ by type of substance used. Different strategies may be required for PrEP implementation among MSM who use stimulants and alcohol.


Marijuana use among cancer survivors: Quantifying prevalence and identifying predictors.
More and more U.S. states are legalizing marijuana use for both recreational and medical purposes. This study estimated the prevalence of current marijuana use and identified its individual-level predictors among adult cancer survivors (CS) living in 15 U.S. states and territories. U.S. nationally representative, cross-sectional data from the 2018 Behavioral Risk Factor Surveillance System Survey (BRFSS) Marijuana Use module were used. A total of 9325 CS was included. Analyses were weighted to account for BRFSS's complex survey design with results generalizable to 4.02 million CS. The outcome was current (past 30-day) marijuana use. Weighted prevalence estimates were computed. Multivariable logistic regression examined individual-level demographic, socio-economic, clinical, and behavioral predictors associated with marijuana use. Weighted analysis indicated that 9.2% reported current marijuana use, 50.5% of which used it for medical reasons with smoking being the main method of administration, 71.3%. Among racial/ethnic groups, non-Hispanic blacks had the highest prevalence of marijuana use (18.6%). The prevalence of current marijuana use decreased with age (P < .001). CS were more likely to use marijuana if they were male, non-Hispanic black (versus non-Hispanic whites), not married, uninsured, current and former tobacco smoker, binge drinker, ever having depressive disorder, and those who had fair/poor health. Marijuana use is prevalent among CS and certain subgroups are at higher risk for marijuana use. With the proliferation of marijuana legalization, identifying high-risk CS for marijuana use and informing them about its risks and safety is critical.


Overdrive versus conventional or closed-loop rate modulation pacing in the prevention of atrial tachyarrhythmias in Brady-Tachy syndrome: on behalf of the Burden II Study Group.
Optimizing dual-chamber pacing to prevent recurrences of atrial tachyarrhythmias (AT) in sinus node dysfunction is still debated. Despite the large number of studies, efficacy of sophisticated preventive algorithms has never been proven. It is not clear whether this is due to imperfect study designs or to a substantial inefficacy of pacing therapies. To intraindividually compare AT burden between an atrial overdrive and two heart rate modulation approaches: a conventional accelerometric-sensor-based DDDR mode and a contractility-driven rate responsive closed loop (CLS) algorithm. Four hundred fifty-one patients with Brady-Tachy syndrome (BTS), severe bradycardia, and a documented episode of atrial fibrillation were enrolled. One month after implant, each pacing therapy was activated for 3 months in random order. A simple log transformation was used to handle large and skew AT burden distributions. Estimates were adjusted for false-positive AT episodes and reported as geometric means (95% confidence interval). A significantly higher AT burden was observed during overdrive, 0.14% (0.09%, 0.23%) (adjusted, 0.12%[0.07%, 0.20%]). Both DDDR and CLS performed better: respectively, 0.11% (0.07%, 0.17%) (adjusted, 0.08%[0.05%, 0.14%]), 0.06% (0.03%, 0.09%) (adjusted, 0.04%[0.03%, 0.07%]). All the comparisons were statistically significant. During overdrive significantly more patients had AT episodes of duration between 1 minute and 1 hour. No significant differences were observed for longer episodes. Atrial overdrive showed the worst performance in terms of AT burden reduction and should not be preferred to heart rate modulation approaches that still have to be considered as a first-choice pacing mode in BTS.


Survival of cells implanted in the embryonic chick limb bud: a difference between normal and malignant rat brain cells.
Cells from normal rat brain tissue did not survive and few cells could be found 1 d after grafting. In contrast, cells from a glioma and a carcinogen-treated rat brain survived well and many mitoses were observed. These malignant cells also invaded the limb. The behaviour of normal and malignant cells was followed at shorter times after grafting and some invasion by the normal cells was detected. The first signs of degeneration of normal cells were apparent around 7 h after grafting, and after this the grafts progressively deteriorated. These results support the ideal that the ability of cells to survive and grow in embryonic tissues is a characteristic of malignant cells. The findings are discussed in relation to mechanisms of tumour formation.


The Evaluation of Forgivingness, Patience, Positivity and Mental Well-Being in Fibromyalgia Patients.
A versatile and comprehensive approach is required for the treatment of Fibromyalgia syndrome (FMS), which is characterized by multiple physical and psychological symptoms. Highlighting the psychopathology of FMS, might enable us choosing more suitable treatments. From these perspective, we planned to search the cha-racter strength and somepersonality traitsas Forgivingness, Patience, Positivity and Mental Well-Being, which are not searched before in FMS patients. Female patients with widespread musculoskeletal pain meeting the ACR 2010 Fibromyalgia criteria and age- and sex-matched control group were included to the study. All participants were asked to complete a semistructured sociodemographic and clinical data form. The Revised Fibromyalgia Impact Questionnaire (FIQR) was filled. Trait Forgivingness Scale (TFS), 3-Factor Patience scale, Positivity scale and Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) were performed. A total of 50 female patients with FMS and 36 age- and sex-matched healthy controls were evaluated. The scores of WEMWBSand Positivity Scale were significantly low in FMSgroup (p<001, p<0.001). There were no statistically significant difference in TFSand 3-FPSscores (p=0.751,p=0.364, respectively) (Table 2). There were no statistically significant correlation between parameters in FMS group. The study provides useful insights into the domains of some personality traits of FMS patients. Altough positivity and mental well being were found significantly low, there were no difference in patience and forgivingness.


Survivorship of penstemon grandiflorus in an oak woodland: combined effects of fire and pocket gophers.
The effects of fire and pocket gophers, Geomys bursarius, on the survivorship of Penstemon grandiflorus growing in an oak woodland in Minnesota were studied from 1986 to 1990. Plants growing in sparse vegetation experienced mortality rates twice that of plants growing in dense vegetation. This difference was due partly to pocket gophers whose earth moving activities reduce the density of vegetation and bury and kill individual Penstemon plants. Laboratory feeding trials showed that gophers readily eat Penstemon, particularly the fleshy roots. An experiment involving the removal of 25-75% of the root tissue in 90 plants showed that root loss significantly reduced survivorship, suggesting that gopher herbivory might also kill plants. When gophers were experimentally excluded, plants growing in sparse vegetation exhibited significantly lower mortality rates than those growing in dense vegetation. Plants in the smallest size class exhibited reduced survivorship following a late spring burn; however, overall patterns of survivorship of plants in burned areas did not differ markedly from those in the unburned areas. A longitudenal analysis of plants with different reproductive histories revealed no survivorship cost to reproduction. Mortality rates decreased with increasing plant size. Small plants were more likely to be killed by fire and by being buried under gopher mounds. Differences in underground energy reserves of small and large plants can account for most of the survivorship patterns observed in this study. The study shows that within openings of the oak woodland, fire and gophers reduce the survival of individual Penstemon plants. Nevertheless, since both gophers and fire also serve to perpetuate suitable habitat in the woodland, Penstemon is ultimately dependent on both for its long term persistence in the landscape.


Gastric motility is an important factor in the pathogenesis of indomethacin-induced gastric mucosal lesions in rats.
Effects of atropine, cimetidine, and 16,16-dimethyl prostaglandin E2 (16,16-dmPGE2) on indomethacin-induced gastric lesions were investigated in rats by correlating their effects on gastric acid and HCO3- secretion and motility. Subcutaneously administered indomethacin (25 mg/kg) produced gastric mucosal lesions within 4 hr. In parallel studies, an equivalent dose of indomethacin inhibited gastric HCO3- secretion, and stimulated gastric motor activity measured as intraluminal pressure recordings, whereas acid secretion was unaffected. The lesions induced by indomethacin were significantly prevented by three agents: cimetidine (100 mg/kg), which reduced acid secretion; atropine (1 mg/kg), which reduced acid secretion and gastric motility; and 16,16-dmPGE2 (10 micrograms/kg), which reduced acid secretion and motility and increased gastric HCO3- secretion. If acid (150 mM HCl) was infused into the stomach (1.2 ml/hr) during indomethacin treatment, only the latter two agents significantly prevented the formation of gastric lesions in response to indomethacin. Since only the effect on gastric motility was common to these two agents (atropine and 16,16-dmPGE2), the increased gastric motility may be an important pathogenetic factor in indomethacin-induced gastric lesions. The presence of acid as well as a deficiency of endogenous PGs may be prerequisite for later extension of the lesions but cannot account for the induction of mucosal lesions in rats following administration of indomethacin.


Relationships between binding of benzodiazepines to alpha-1-acid glycoprotein and human serum albumin and their retention on the protein and octadecylsilane columns.
Correlation between binding parameters of 6 benzodiazepines to free human serum albumin (HSA) and chromatographic retention parameters on the HSA stationary phase (HSA-SP) was better than the similar correlation with alpha-1-acid glycoprotein (AGP). Still better correlation was obtained between binding to both proteins and retention on an octadecylsilane (ODS) column. For 12 benzodiazepines the correlations of the retention parameters on both protein columns with the retention on the ODS column were additionally investigated. In the case of HSA this correlation was good.


[On the interpretation of Békésy audiograms (author's transl)].
A group of 112 subjects with sensorineural hearing loss was checked by an audiological test battery consisting of: pure tone audiometry, SISI Test, tone decay test and fixed frequency Békésy audiometry. Classification of Békésy tracings by two audiologists showes good agreement when introducing a hybrid type I/II, which completes Jerger's classification system of types I--IV. The results of our investigation exhibit no significant differences of manual pure tone threshold and automatic tracing contrary to some other authors. Finally the correlation of diagnosis and type of Békésy audiogram is discussed.


Evaluation of the effect of governmental control of human exposure to two phthalates in Japan using a urinary biomarker approach.
In Japan, the use of certain phthalates has been regulated. We analyzed the effectiveness of these measures using an analytical biomarker approach. We measured two phthalate metabolites, mono-n-butyl phthalate (MBP) and mono-2-ethylhexyl phthalate (MEHP) in urine samples from 36 participants using enzymatic deconjugation, offline solid phase extraction, and HPLC-ESI-MS/MS. From the levels measured and individual values of creatinine excretion rate the daily intake was determined and compared to each corresponding tolerable daily intake (TDI). The levels of urinary MBP and MEHP were < 1.8-280 and 0.76-25 microg/l, respectively. The ranges of the estimated daily intake of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) from 35 adult urine samples were 0.22-4.5 and 0.37-7.3 microg/kg/ day, respectively. These values were lower than the corresponding TDIs. After comparing these values to previous exposure assessment data on DEHP in Japan, it could be seen that the DEHP intake dropped over the period from 1998 to 2001. Children were not covered in the present study, so the results may only be applicable to adults, not to the Japanese population at large. Even so, the small number of people in one specific geographic area cannot be considered representative of the adult Japanese population. In addition to MEHP, the secondary metabolites of DEHP, which are more suitable biomarkers should be measured in the future.


Codon usage changes and sequence dissimilarity between human and rat.
This paper reports on the relationship between the number of silent differences and the codon usage changes in the lineages leading to human and rat. Examination of 102 pairs of homologous genes gives rise to four main conclusions: (1) We have previously demonstrated the existence of a codon usage change (called the minor shift) between human and rat; this was confirmed here with a larger sample. For genes with extreme C & G frequencies, the C & G level in the third codon position is less extreme in rat than in human. (2) Protein similarity and percentage of positive differences are the two main factors that discriminate homologous genes when characterized by differences between rat and human. By definition, positive differences result from silent changes between A or T and C or G with a direction implying a C & G content variation in the same direction as the overall gene variation. (3) For genes showing both codon usage change and low protein similarity, a majority of amino acid replacements contributes to C & G level variation in positions I and II in the same direction as the variation in position III. This is thus a new example of protein evolution due to constraints acting at the DNA level. (4) In heavy isochores (high C & G content) no direct correlation exists between codon usage change (measured by the dissymmetry of differences) and silent dissimilarity. In light isochores the opposite situation is observed: modification of codon usage is associated with a high synonymous dissimilarity. This result shows that, in some cases, modification of constrains acting at the DNA level could accelerate divergence between genomes.


Helicobacter pylori Targets in AGS Human Gastric Adenocarcinoma: In Situ Proteomic Profiling and Systematic Analysis.
Helicobacter pylori, a gram-negative bacterium, causes chronic stomach diseases in humans. Heat shock proteins (HSPs) are involved in cell integrity, cell growth, and gastric mucosa colonization by H. pylori. This study aimed to investigate HSP expression levels in H. pylori-infected gastric adenocarcinoma AGS cells. We determined protein expression levels using iTRAQ proteomics analysis. We analyzed the possible network interactions for H. pylori targets in AGS cells using the Ingenuity Pathway Analysis (IPA) software. H. pylori-infected AGS cells potentially targeted EIF2 and BAG2 signaling pathways to regulate cell physiology. In addition, after 3, 6, and 12 h of infection, western blotting revealed significantly decreased HSP70 and HSP105 expression. H. pylori decreases HSPs in AGS gastric adenocarcinoma cells, and this is associated with the regulation of EIF2 and BAG2 signaling pathways.


Bladder perforation during transurethral resection of bladder tumour is not a result of a deficient structure of the bladder wall.
Transurethral resection of the bladder tumour (TUR) is associated with a risk of bladder perforation. The underlying mechanisms and risk factors are not fully understood. The aim of this study was to determine if the bladder wall structure affects the risk of bladder perforation during TUR. Fifteen patients who underwent TUR complicated by a bladder perforation (group 1) and fifteen matched controls who underwent uncomplicated TUR (group 2) were retrospectively enrolled in this morphological analysis. Surgical specimens were collected from all participating patients to describe the quality and architecture of urothelium and bladder submucosa. Immunohistochemical studies were performed with primary mouse anti-human E-cadherin, beta-catenin, type IV collagen, cytokeratin 20 and epithelial membrane antigen antibodies. The intensity of the immunohistochemical reaction was assessed using an immunoreactive score (IRS). Ultrastructural examinations were performed by transmission electron microscopy. The microscopic assessment was focused on the intensity of fibrosis in the bladder submucosa and the presence of degenerative changes in the urothelium. Patients' age, sex distribution, tumour diameters, surgeon experience or cancer stage did not differ between study groups. The immunohistochemical analysis did not reveal statistically significant differences between group 1 and group 2. From a clinical point of view, ultrastructural analysis by electron microscopy showed a higher rate of severe fibrosis in group 1 (63.6% vs. 38.5%), with no differences in the rate and degree of urothelial changes. However, these differences were not statistically significant (p = 0.32). Bladder perforation during TUR is not a result of a deficient structure of the bladder wall. Based on available evidence, the surgical technique seems to play the most important role in its prevention.


Clinical effects of human macrophage inflammatory protein-1 alpha MIP-1 alpha (LD78) administration to humans: a phase I study in cancer patients and normal healthy volunteers with the genetically engineered variant, BB-10010.
BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha (hMIP-1 alpha) with improved pharmaceutical formulation properties. Although initially described as a pro-inflammatory cytokine, it is now recognised that hMIP-1 alpha has additional effects on haemopoietic stem cell cycling and on human immunodeficiency virus uptake by macrophages. In view of the potential clinical utility of the molecule, we have embarked on a clinical trials programme to evaluate the safety, tolerability and haematological effects of BB-10010. We now report the results of two phase I clinical studies in which 49 subjects (9 patients with advanced breast carcinoma and 40 normal healthy volunteers) received escalating doses of BB-10010, from 0.1 to 300 micrograms/kg using the subcutaneous (s.c.) or intravenous route (i.v.) of administration. Treatment was associated with a dose-related increase in monocyte count which peaked at 200% of steady-state levels and was preceded by an acute, short-lived, monocytopenia, 50-100% of baseline. no measurable effects were noted on other leucocyte subsets or on circulating progenitor cell numbers. In all cases, BB-10010 was extremely well tolerated with no significant toxicity observed at any dose level and a maximum tolerated dose was not defined. Pharmacokinetic analysis revealed that serum concentrations of BB-10010 were detectable using doses of > or = 10 micrograms/kg i.v. or > or = 30 micrograms/kg s.c., and that a single s.c. injection resulted in sustained plasma levels over a 24 h period. These preliminary studies have confirmed the safety and tolerability of BB-10010 using a dose range up to 300 micrograms/kg. Further clinical studies are ongoing to determine the biological effects and to investigate the potential myeloprotective properties using a variable dose range and schedule of BB-10010 in combination with cytotoxic chemotherapy.


Tumour status prediction by means of carbon-ion beam irradiation: comparison of washout rates between in-beam PET and DCE-MRI in rats.
Objective.Tumour response to radiation therapy appears as changes in tumour vascular condition. There are several methods for analysing tumour blood circulatory changes one of which is dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), but there is no method that can observe the tumour vascular condition and physiological changes at the site of radiation therapy. Positron emission tomography (PET) has been applied for treatment verification in charged particle therapy, which is based on the detection of positron emitters produced through nuclear fragmentation reactions in a patient's body. However, the produced positron emitters are washed out biologically depending on the tumour vascular condition. This means that measuring the biological washout rate may allow evaluation of the tumour radiation response, in a similar manner to DCE-MRI. Therefore, this study compared the washout rates in rats between in-beam PET during12C ion beam irradiation and DCE-MRI.Approach.Different vascular conditions of the tumour model were prepared for six nude rats. The tumour of each nude rat was irradiated by a12C ion beam with simultaneous in-beam PET measurement. In 10-12 h, the DCE-MRI experiment was performed for the same six nude rats. The biological washout rate of the produced positron emitters (k2,1st) and the MRI contrast agent (k2a) were derived using the single tissue compartment model.Main results.A linear correlation was observed betweenk2,1standk2a, and they were inversely related to fractional necrotic volume.Significance.This is the first animal study which confirmed the biological washout rate of in-beam PET correlates closely with tumour vascular condition measured with the MRI contrast agent administrated intravenously.


Natural History of Functional Tricuspid Regurgitation Quantified by Cardiovascular Magnetic Resonance.
Quantitation of tricuspid regurgitant (TR) severity can be challenging with conventional echocardiographic imaging and may be better evaluated using cardiovascular magnetic resonance (CMR). In patients with functional TR, this study sought to examine the relationship between TR volume (TRVol) and TR fraction (TRF) with all-cause mortality. We examined 547 patients with functional TR using CMR to quantify TRVol and TRF. The primary outcome was all-cause mortality. Thresholds for mild, moderate, and severe TR were derived based on natural history outcome data. During a median follow-up of 2.6 years (interquartile range: 1.7 to 3.3 years), there were 93 deaths, with an estimated 5-year survival of 79% (95% confidence interval [CI]: 73% to 83%). After adjustment of clinical and imaging variables, including RV function, both TRF (adjusted hazard ratio [AHR] per 10% increment: 1.26; 95% CI: 1.10 to 1.45; p = 0.001) and TRVol (AHR per 10-ml increment: 1.15; 95% CI: 1.04 to 1.26; p = 0.004) were associated with mortality. Patients in the highest-risk strata of TRVol ≥45 ml or TRF ≥50% had the worst prognosis (AHR: 2.26; 95% CI: 1.36 to 3.76; p = 0.002 for TRVol and AHR: 2.60; 95% CI: 1.45 to 4.66; p = 0.001 for TRF). This is the first study to use CMR to assess independent prognostic implications of functional TR. Both TRF and TRVol were associated with increased mortality after adjustment for clinical and imaging covariates, including right ventricular ejection fraction. A TRVol of ≥45 ml or TRF of ≥50% identified patients in the highest-risk strata for mortality. These CMR thresholds should be used for patient selection in future trials to determine if tricuspid valve intervention improves outcomes in this high-risk group.


Zebrafish jam-b2 Gal4-enhancer trap line recapitulates endogenous jam-b2 expression in extraocular muscles.
Members of the junctional adhesion molecule (JAM) family function as cell adhesion molecules and cell surface receptors. The zebrafish genome contains six different jam genes, and jam-b and jam-c were shown to be essential for myoblast fusion during skeletal muscle development. However, little is known about jam-b2 expression and function. We isolated the cDNA of zebrafish jam-b2. jam-b2 is expressed specifically in extraocular muscles (EOMs), jaw muscles, and pectoral fins in zebrafish larvae, but not in trunk muscles. The identified jam-b2 expression pattern is supported by the analysis of a zebrafish Gal4-enhancer trap line, in which the coding sequence of the transcriptional activator KalTA4 together with a Gal4-dependent UAS-mCherry expression cassette was inserted into the jam-b2 locus. Intercrosses with an UAS:EGFP strain proves the possibility for targeting transgene expression to EOMs, jaw muscles and fins. Finally, we characterized the concerted contraction pattern of EOMs in larvae performing an optokinetic response. The expression pattern of jam-b2 suggests that it may contribute different properties to EOMs, jaw muscles, and pectoral fins. The jam-b2:KalTA4-UAS-mCherry transgenic strain serves a dual role as both a reporter for these muscles and as a valuable genetic tool for targeting transgene expression to EOMs.


Effects of gypenosides on mouse splenic lymphocyte transformation and DNA polymerase II activity in vitro.
To study the effects of gypenosides (Gyp) on lymphocyte transformation and DNA polymerase II activity. Lymphocyte transformation response was induced by concanavalin A and lipopolysaccharides respectively. The activity of DNA polymerase II and DNA synthesis were assayed with TTP and [3H]TdR incorporation respectively in mixed lymphocyte culture test. Gyp 2.5-20 mg L-1 enhanced splenic T- and B- cell transformation, increased the DNA synthesis and potentiated the activity of DNA polymerase II. However, Gyp > 40 mg L-1 showed contrary effects. Gyp regulated lymphocyte transformation and DNA synthesis by regulating DNA polymerase II activity.


Effects of sentence context on phonemic categorization of natural and synthetic consonant-vowel tokens.
The purpose was to assess if phonemic categorization in sentential context is best explained by autonomous feedforward processing or by top-down feedback processing that affects phonemic representation. 11 listeners with normal hearing, ages 20-50 years, were asked to label consonants in /pi/-/ti/ consonant-vowel (CV) stimuli in 9-step continua. One continuum was derived from natural tokens and the other was synthetically generated. The CV stimuli were presented in isolation and in three sentential contexts: a neutral context, a context favoring /p/, and a context favoring /t/. For both natural and synthetic stimuli, the isolated and neutral context sentences yielded significantly more /t/ responses than sentence contexts primed for either /p/ or /t/. No other conditions were significantly different. Results did not show easily explainable semantic context effects. Instead, data clustering was more readily explained by top-down feedback processing affecting phonemic representation.


Quaternary Alkylammonium Conjugates of Steroids: Synthesis, Molecular Structure, and Biological Studies.
The methods of synthesis as well as physical, spectroscopic (¹H-NMR, 13C-NMR, and FT-IR, ESI-MS), and biological properties of quaternary and dimeric quaternary alkylammonium conjugates of steroids are presented. The results were contrasted with theoretical calculations (PM5 methods) and potential pharmacological properties (PASS). Alkylammonium sterols exhibit a broad spectrum of antimicrobial activity comparable to squalamine.


Long-term results of ileocecal continent urinary diversion in patients treated with and without previous pelvic irradiation.
Patients who receive pelvic irradiation may require urinary diversion to manage complications resulting from progressive malignancy or radiotherapy. The choice of urinary diversion is an important issue and remains controversial. We characterized the long-term outcome of urinary diversion with a continent ileocecal reservoir in patients who received pelvic irradiation versus those who underwent urinary diversion without previous irradiation. Continent urinary diversion with an ileocecal reservoir (Mainz pouch 1) was performed in 36 irradiated patients in a 9-year period. Morbidity, mortality, the reoperative rate and parameters associated with the surgical procedure were determined at a median followup of 57 months. Results were compared with those in 385 nonirradiated patients who received the same type of continent diversion after cystectomy for bladder cancer. Irradiated patients had a significantly higher rate of serious complications after ileocecal urinary diversion than nonirradiated controls. Continence mechanism failure occurred in 25% of patients in the irradiated group and 5.7% in nonirradiated patients, stomal complications were noted in 38.8% and 10.6%, and ureteral complications developed in 22.2% and 6.5%, respectively. In patients who have received pelvic radiotherapy, ileocecal Mainz pouch 1 continent urinary diversion is associated with a high rate of serious complications and should be avoided.


The influence of nutritional and environmental conditions on the accumulation of poly-beta-hydroxybutyrate in Bacillus mycoides RLJ B-017.
To optimize the nutritional and environmental conditions for growth of and poly-beta-hydroxybutyrate (PHB) accumulation in Bacillus mycoides RLJ B-017. An isolate, identified as B. mycoides, was grown on different sources of carbon and nitrogen. Among these, sucrose, beef extract and di-ammonium sulphate were found to be the most suitable for growth and PHB accumulation. The overall maximum value of PHB (%) in cells, PHB yield (Yp/s) and productivities (Qp and qp) were 69.4 +/- 0.4% dry cell weight (DCW), 0.21 gp gS(-1), 0.104 +/- 0.012 gp l(-1) h(-1) and 0.03 gp gx(-1) h(-1), respectively when grown in a medium containing 20 gs l(-1) sucrose, supplemented with di-ammonium sulphate. The addition of beef extract increased the value of PHB (%) in cells, PHB yield and productivities by 17.58 +/- 0,3, 23.8, 19.23 +/- 0.3 and 13.8 +/- 0.2% , respectively. The overall maximum values of PHB (% DCW), PHB yield and productivities were obtained at pH 7.0 +/- 0 .1, temperature 30 +/- 0.5 degrees C, agitation 650 rev min(-1) and oxygen transfer rate 3.8 mmol O(2) l(-1) h(-1). Sucrose, glucose and fructose were found to be more suitable for cell growth and PHB accumulation, but sucrose was less expensive than glucose. Among the nitrogen sources, beef extract and di-ammonium sulphate promoted PHB synthesis. The accumulation of PHB was observed to be growth associated. Gram-positive bacteria have not been reported to accumulate large amounts of polyhydroxyalkanoate and hence have not been considered as potent candidates for industrial production. A number of Bacillus spp. have been reported to accumulate 9-44.5% DCW PHB. By comparison, Bacillus RLJ B-017 contained 69.4 +/- 0.4% DCW PHB. Therefore, this strain has been considered as a potent organism for industrial interest. A relatively high yield of PHB was obtained in this wild strain and PHB synthesis was independent of nutrient limitation. The conditions for the higher PHB yield and productivity will be optimized in the next phase using fed-batch culture.


Clinical significance of sacral and pudendal nerve anatomy.
The neuroanatomy and neurophysiology of the external urethral closure mechanisms still are under debate because the motor fibers that emanate from the sacral plexus and pudendal nerve to supply this segment have not been traced, nor has their functional interrelationship been established. Therefore, we dissected 3 male human cadavers (aged 31 to 69 years) by tracing the entire sacral plexus, particularly the pudendal nerve, from the cauda equina throughout the branching of the nerves to their final destination. The dissection demonstrated that the extrinsic urethral sphincter, formed by the rhabdosphincter around the membranous urethra as well as the levator ani muscle and pelvic floor (especially the transversus perinei muscle), is innervated by somatic nerve fibers that emanate primarily from sacral roots S2 and S3. In 5 patients with neurogenic lower urinary tract dysfunction electrostimulation of the sacral root and pudendal nerve markedly increased intraurethral closure pressures. Stimulation of the pudendal nerve or its transversus perinei branch alone resulted in an increase in intraurethral closure pressure to 60 to 70 cm. water--an increase similar to that produced by stimulation of the sacral root without neurotomy. By means of neurotomy and/or neural blockade with lidocaine we were able to differentiate between the contributions of each muscular element to the external sphincteric mechanism. Almost 70 per cent of the closure pressure of the external urethral sphincter is induced by stimulation of the S3 ventral root, while the other 30 per cent derives from S2 and S4 neuronal impulses.


Sustained release formulation of an anti-tuberculosis drug based on para-amino salicylic acid-zinc layered hydroxide nanocomposite.
Tuberculosis (TB), is caused by the bacteria, Mycobacterium tuberculosis and its a threat to humans since centuries. Depending on the type of TB, its treatment can last for 6-24 months which is a major cause for patients non-compliance and treatment failure. Many adverse effects are associated with the currently available TB medicines, and there has been no new anti-tuberculosis drug on the market for more than 50 year, as the drug development is very lengthy and budget consuming process.Development of the biocompatible nano drug delivery systems with the ability to minimize the side effects of the drugs, protection of the drug from enzymatic degradation. And most importantly the drug delivery systems which can deliver the drug at target site would increase the therapeutic efficacy. Nanovehicles with their tendency to release the drug in a sustained manner would result in the bioavalibilty of the drugs in the body for a longer period of time and this would reduce the dosing frequency in drug administration. The biocompatible nanovehicles with the properties like sustained release of drug of the target site, protection of the drug from physio-chemical degradation, reduction in dosing frequency, and prolong bioavailability of drug in the body would result in the shortening of the treatment duration. All of these factors would improve the patient compliance with chemotherapy of TB. An anti-tuberculosis drug, 4-amino salicylic acid (4-ASA) was successfully intercalated into the interlamellae of zinc layered hydroxide (ZLH) via direct reaction with zinc oxide suspension. The X-ray diffraction patterns and FTIR analyses indicate that the molecule was successfully intercalated into the ZLH interlayer space with an average basal spacing of 24 Å. Furthermore, TGA and DTG results show that the drug 4-ASA is stabilized in the interlayers by electrostatic interaction. The release of 4-ASA from the nanocomposite was found to be in a sustained manner. The nanocomposite treated with normal 3T3 cells shows it reduces cell viability in a dose- and time-dependent manner. Sustained release formulation of the nanocomposite, 4-ASA intercalated into zinc layered hydroxides, with its ease of preparation, sustained release of the active and less-toxic to the cell is a step forward for a more patient-friendly chemotherapy of Tuberculosis.


Photorefractive keratectomy to treat myopia and astigmatism after radial keratotomy and penetrating keratoplasty.
Fifteen eyes with an initial myopia between -5.00 diopters (D) and -12.00 D were treated with radial keratotomy (RK) followed by photorefractive keratectomy (PRK) at least 6 months later and observed for 6 months to 24 months. Five eyes that had penetrating keratoplasty (PKP) were treated for residual ametropia by PRK and followed for up to two years. For the RK-treated eyes, mean pre-PRK refraction was -4.00 D sphere and + 1.25 D cylinder, which improved to -0.52 D sphere and + 0.73 D cylinder. Incidence of complications, including corneal haze, was extremely low in both the RK and PKP groups. In summary, PRK is a valuable method for correcting ametropia following RK and PKP, with risks similar to that for eyes having PRK as the initial refractive procedure.


Glycosaminoglycan-based hydrogels with programmable host reactions.
Glycosaminoglycan (GAG)-based, biohybrid hydrogels offering far-reaching control over their physical and biomolecular signaling properties have been successfully used in various cell and tissue culture applications. To explore the suitability of the materials for in vivo use, we herein studied the host reaction to in situ-assembling star(PEG)-GAG hydrogel variants upon subcutaneous implantation in immunocompetent C57BL/6J mice for up to 28 days. Specifically, we investigated the immune reaction and the angiogenic response to hydrogels with systematically varied cytokine functionalizations, physical network (and mechanical) properties, cell adhesiveness, and enzymatic degradability. The GAG-based hydrogel elicited only minor foreign body reaction with low immune cell infiltration and collagen deposition compared to similarly implanted medical grade silicone. Adjusting of the physical properties, biofunctionalization, and degradability allowed to program the host response from nearly no degradation and infiltration to fast integration of the gel scaffolds into the tissue within days. The results demonstrate that foreign body reactions and starPEG-GAG hydrogel tissue integration can be effectively controlled by defined adjustments of the hydrogel system, suggesting the in situ-assembling materials as safe and effective for in vivo tissue engineering applications.


A short-type peptidoglycan recognition protein from tongue sole (Cynoglossus semilaevis) promotes phagocytosis and defense against bacterial infection.
Peptidoglycan recognition proteins (PGRPs) are members of the innate immune system that interact with bacteria by binding to bacterial peptidoglycan. In this study, we examined the expression and function of a short type of PGRP, CsPGRP-SC2, from tongue sole (Cynoglossus semilaevis). CsPGRP-SC2 contains 164 amino acid residues and shares 54.5%-65.3% overall sequence identities with other teleost PGRPs. CsPGRP-SC2 possesses an amidase domain with a conserved zinc binding site. CsPGRP-SC2 expression occurred in multiple tissues and was upregulated by bacterial and viral infection. Purified recombinant CsPGRP-SC2 (rCsPGRP-SC2) was able to bind and agglutinate Gram-positive bacteria in a Zn(2+)-dependent manner. rCsPGRP-SC2 enhanced the uptake of the bound bacteria by host phagocytes and reduced bacterial dissemination and colonization in host tissues. These results indicate that CsPGRP-SC2 is an innate immune factor that participates in host defense against bacterial infection.


Vacuolar myopathy in an adult Warmblood horse.
Histopathological interpretation of semimembranosus muscle samples from an adult Warmblood mare with clinical signs suggestive of exertional rhabdomyolysis and intermittent mild elevations in muscle enzyme activities revealed abundant sarcoplasmic vacuoles in all fibre-types containing fine, apparently proteinaceous debris. Vacuolar contents stained lightly with PAS, but did not appear to contain amylopectate, lipid or acid phosphatase and their periphery was unstained with dystrophin immunohistochemistry. Electron microscopy revealed that vacuoles were not membrane bound. No vacuoles were detected in muscle samples evaluated at post mortem following 4 months of rest. To our knowledge, this is the first report of a presumed primary vacuolar myopathy in a horse.


Behaviour of heart rate and electrical muscle activity in the simultaneous dynamic action of larger and smaller sets of muscles in the permanent performance threshold range.
This study was undertaken to assess more comprehensively and with greater differentiation the reduction in the absolute electrical muscle activity (aEA) determined by different investigations in the permanent performance threshold range of the cardiovascular system (HKS) by means of the behaviour of the aEA of the highly stressed leg muscles and little stressed forearm muscles. Six healthy, untrained male subjects operated a hand ergograph alone in one test, and, in four more tests, in combination with a constant bicycle ergometer load of 40, 60, 80, and 100 W, respectively. As a result of these tests, a relative reduction in aEA for the leg muscles and an absolute reduction in aEA for the forearm muscles could be identified in the permanent performance threshold range of the HKS. Therefore, aEA is also considered to be an indicator of general stress that can define the permanent performance threshold range of the HKS more completely. The reduction in aEA is probably an expression of a negative feedback from the cardiovascular system to the neuromuscular system induced by the central nervous system.


Absolute high spectral resolution measurements of surface solar radiation for detection of water vapour continuum absorption.
Solar-pointing Fourier transform infrared (FTIR) spectroscopy offers the capability to measure both the fine scale and broadband spectral structure of atmospheric transmission simultaneously across wide spectral regions. It is therefore suited to the study of both water vapour monomer and continuum absorption behaviours. However, in order to properly address this issue, it is necessary to radiatively calibrate the FTIR instrument response. A solar-pointing high-resolution FTIR spectrometer was deployed as part of the 'Continuum Absorption by Visible and Infrared radiation and its Atmospheric Relevance' (CAVIAR) consortium project. This paper describes the radiative calibration process using an ultra-high-temperature blackbody and the consideration of the related influence factors. The result is a radiatively calibrated measurement of the solar irradiation at the ground across the IR region from 2000 to 10 000 cm(-1) with an uncertainty of between 3.3 and 5.9 per cent. This measurement is shown to be in good general agreement with a radiative-transfer model. The results from the CAVIAR field measurements are being used in ongoing studies of atmospheric absorbers, in particular the water vapour continuum.


Diffusion weighted magnetic resonance imaging in the diagnosis of reversible ischaemic deficits of the brainstem.
To evaluate the sensitivity of diffusion weighted magnetic resonance imaging (MRI) for the diagnosis of clinically suspected reversible ischaemic deficits of the brainstem. A total of 158 consecutive patients presenting with acute signs of brainstem dysfunction were investigated using EPI diffusion weighted MRI within 24 hours of the onset of symptoms. High resolution T1 and T2 weighted imaging was performed as a follow up after a median of six days. Fourteen of the 158 patients had a complete clinical recovery within 24 hours (transitory ischaemic attack (TIA)), and 19 patients recovered in less than one week (prolonged reversible neurological deficit (RIND)). Diffusion weighted MRI showed acute ischaemic deficits in 39% of patients with transient neurological deficits. The detection rate seemed to be higher in patients with longer lasting symptoms, but the difference between patients with TIA (29%) and RIND (47%) was not significant. Diffusion weighted MRI is a sensitive indicator of acute ischaemic brainstem deficits even in patients with reversible neurological deficit. Early identification of patients with TIA and increased risk of stroke may influence acute management and improve patient outcome.


The phenotype of antigen-specific suppressor T cells generated in human mixed leucocyte culture depends on the nature of the major histocompatibility regions recognized.
Following secondary stimulation of mixed leucocyte culture (MLC) populations with a class I plus II HLA difference, antigen-specific suppressor-effector cells of the OKT8+4- phenotype are generated. On the other hand, stimulation with a class II HLA genetic difference only gave rise to OKT4+ suppressor T cells. These effector cell populations which were maintained as "lines" by the addition of exogenous T cell growth factor (TCGF) and feeder cells, mediated antigen-specific suppression over a 6-8 week period during which they were assayed. The data reported here demonstrate that the phenotype of suppressor cells, generated in allogenic MLC, depends on the nature of the class of HLA antigen recognized as disparities in the suppressor-generating MLC. Moreover, both OKT8+4- and OKT4+ suppressors, obtained following stimulation with class I plus II or class II genetic disparities, respectively, appear to be specific for DR (or related class II product) antigens.


Non-invasive imaging and characterisation of human foot by multi-probe laser reflectometry and Monte Carlo simulation.
Diffusely backscattered signals from the human foot sole tissues of normal subjects (n = 5) were obtained by multiprobe laser reflectometry. The colour-coded images were constructed from data on the variation of normalised backscattered intensity (NBI), after interpolation and median filtering. The maximum and minimum NBI values at the arch and heel regions of the foot sole, respectively, were observed. The mean NBI at the arch region was significantly higher compared with that at other regions (p < 0.0001). The images of optical parameters of normal tissues show point-to-point variation, attributed to their compositional changes. The pattern of variation of the NBI of a diabetic subject (glucose level 170 mg dl(-1)) was associated with highly significant variation at the lateral sides of the fore- and middle-foot compared with that of normal subjects.