Regulation of Hippocampal 5-HT Release by P2X7 Receptors in Response to Optogenetic Stimulation of Median Raphe Terminals of Mice.
Serotonergic and glutamatergic neurons of median raphe region (MRR) play a pivotal role in the modulation of affective and cognitive functions. These neurons synapse both onto themselves and remote cortical areas. P2X7 receptors (P2rx7) are ligand gated ion channels expressed by central presynaptic excitatory nerve terminals and involved in the regulation of neurotransmitter release. P2rx7s are implicated in various neuropsychiatric conditions such as schizophrenia and depression. Here we investigated whether 5-HT release released from the hippocampal terminals of MRR is subject to modulation by P2rx7s. To achieve this goal, an optogenetic approach was used to selectively activate subpopulation of serotonergic terminals derived from the MRR locally, and one of its target area, the hippocampus. Optogenetic activation of neurons in the MRR with 20 Hz was correlated with freezing and enhanced locomotor activity of freely moving mice and elevated extracellular levels of 5-HT, glutamate but not GABA in vivo. Similar optical stimulation (OS) significantly increased [3H]5-HT and [3H]glutamate release in acute MRR and hippocampal slices. We examined spatial and temporal patterns of [3H]5-HT release and the interaction between the serotonin and glutamate systems. Whilst [3H]5-HT release from MRR neurons was [Ca2+]o-dependent and sensitive to TTX, CNQX and DL-AP-5, release from hippocampal terminals was not affected by the latter drugs. Hippocampal [3H]5-HT released by electrical but not OS was subject to modulation by 5- HT1B/D receptors agonist sumatriptan (1 μM), whereas the selective 5-HT1A agonist buspirone (0.1 μM) was without effect. [3H]5-HT released by electrical and optical stimulation was decreased in mice genetically deficient in P2rx7s, and after perfusion with selective P2rx7 antagonists, JNJ-47965567 (0.1 μM), and AZ-10606120 (0.1 μM). Optical and electrical stimulation elevated the extracellular level of ATP. Our results demonstrate for the first time the modulation of 5-HT release from hippocampal MRR terminals by the endogenous activation of P2rx7s. P2rx7 mediated modulation of 5-HT release could contribute to various physiological and pathophysiological phenomena, related to hippocampal serotonergic transmission.


Disruption of downstream chromatin directed by a transcriptional activator.
Promoter-proximal pausing during transcriptional elongation is an important way of regulating many diverse loci, including the human hsp70 gene. Pausing of RNA polymerase can be enhanced by chromatin structure. We demonstrate that activation of hsp70 leads to disruption of transcribed chromatin in front of RNA polymerase. In vivo, disruption of chromatin in the first 400 bp of the transcribed region of hsp70 following heat shock is resistant to the transcriptional inhibitor alpha-amanitin. Disruption of chromatin farther downstream also occurs following activation but is sensitive to alpha-amanitin, suggesting that polymerase movement is needed to disrupt distal portions of the hsp70 gene. In vitro, disruption of transcribed chromatin is dependent on the presence of the human heat shock factor 1 (HSF1) activation domains. These experiments demonstrate that HSF1 can direct disruption of chromatin in transcribed regions. We suggest that this is one of the mechanisms used by HSF1 to facilitate transcriptional elongation.


[Professor He Pu-ren: the founder of Santong method of acupuncture and moxibustion].
Professor He Pu-ren, the founder of Santong method of acupuncture and moxibustion, is a well known acupuncturist at home and abroad. His main contributions include combined martial arts and Chinese medicine, showing obvious therapeutic effect; taking part in establishment of The Department of Acupuncture, Beijing Chinese Medicine Hospital; creating Santong method of acupuncture and moxibustion; advocating fire needle therapy; writing medical books and teaching students; advocating the culture of acupuncture; making the metal model of acupuncture and moxibustion, and others. His achievements have become an important part of acupuncture and moxibustion science.


A study on chronologic change of the relationship between cigarette smoking and lung cancer based on autopsy diagnosis.
Human cases autopsied at the Department of Pathology, University of Tokyo, were studied to investigate the chronologic changes in the relationship between cigarette smoking and lung cancer occurrence. The results obtained were as follows: (1) it was confirmed that the incidence of lung cancer was significantly higher among cigarette smokers than among nonsmokers, and that there was a definite dose-response relationship between the quantity of cigarettes smoked and the occurrence of lung cancer; and (2) over the time span studied, the incidence of lung cancer among autopsies showed a remarkable increase. However, this tendency was seen in both cigarette smokers and nonsmokers, and in fact, the increase was comparatively higher in the latter group. It should be stressed that the relative importance of cigarette smoking in human pulmonary carcinogenesis seems to have decreased in the past 40 years or so, and factors other than cigarette smoking seems to have become more important.


Cultural Practices Shaping Zoonotic Diseases Surveillance: The Case of Highly Pathogenic Avian Influenza and Thailand Native Chicken Farmers.
Effectiveness of current passive zoonotic disease surveillance systems is limited by the under-reporting of disease outbreaks in the domestic animal population. Evaluating the acceptability of passive surveillance and its economic, social and cultural determinants appears a critical step for improving it. A participatory rural appraisal was implemented in a rural subdistrict of Thailand. Focus group interviews were used to identify sanitary risks perceived by native chicken farmers and describe the structure of their value chain. Qualitative individual interviews with a large diversity of actors enabled to identify perceived costs and benefits associated with the reporting of HPAI suspicions to sanitary authorities. Besides, flows of information on HPAI suspected cases were assessed using network analysis, based on data collected through individual questionnaires. Results show that the presence of cockfighting activities in the area negatively affected the willingness of all chicken farmers and other actors to report suspected HPAI cases. The high financial and affective value of fighting cocks contradicted the HPAI control policy based on mass culling. However, the importance of product quality in the native chicken meat value chain and the free veterinary services and products delivered by veterinary officers had a positive impact on suspected case reporting. Besides, cockfighting practitioners had a significantly higher centrality than other actors in the information network and they facilitated the spatial diffusion of information. Social ties built in cockfighting activities and the shared purpose of protecting valuable cocks were at the basis of the diffusion of information and the informal collective management of diseases. Building bridges with this informal network would greatly improve the effectiveness of passive surveillance.


Overestimation of mentally retarded persons' IQs using the PPVT: a re-analysis and some implications for future research.
Numerous validity studies have shown that the PPVT consistently overestimates mentally retarded persons' IQs. One possible interpretation is that this phenomenon is an outcome of the dissociation between their cognitive level and their experience. Indeed, compared to intellectually average subjects of the same mental age, they have had more learning opportunities, simply because they have lived longer. In order to validate this hypothesis, the French version of the PPVT, Raven's Coloured Progressive Matrices (RCPM), and the 1966 version of the Binet-Simon were administered to 90 subjects of various chronological ages matched on mental age (30 nonretarded 5 year olds and two groups of 30 retarded subjects aged 10 and 16 years, respectively). The results indicate that CA exerts a strong effect on vocabulary, but not on RCPM performance. The research implications of this finding are discussed.


Running biomechanical alterations during a 40-km mountain race.
The purpose of this study was to analyze running biomechanical alterations according to different slopes (flat, uphill and downhill) and distance, during a 40-km mountain trail running race. Throughout the race, eight runners were equipped with Runscribe® inertial units placed on each running shoe. Measurements included spatiotemporal parameters (contact time, step frequency, stride length, running speed), kinetic (impact peak and braking force) and kinematic data (foot pronation velocity and foot pronation excursion). For data analysis, the race was divided in two halves, from which three types of matching segments were extracted: two uphill sections (U1, U2), two downhill sections (D1, D2) and two flat sections (F1, F2). Intra-section comparisons revealed that during the second part of the race, running speed decreased in all sections. In uphill sections, stride length increased, step frequency and contact time variability decreased. On flat and downhill sections, contact time increased whereas step frequency and stride length decreased. Step frequency and contact time variability increased for both uphill and downhill sections. With regards to downhill sections only, impact peak, horizontal braking force and foot pronation velocity decreased. Foot strike pattern switched from a rearfoot to a midfoot-strike pattern. Contact time, horizontal breaking force pronation velocity and foot strike pattern variability increased. Over a 40-km mountain trail running race, changes in running biomechanics are important data which should be taken into account by runners and coaches for training preparation, race strategy as well as for injury prevention.


Antioxidant Responses of Phenolic Compounds and Immobilization of Copper in Imperata Cylindrica, a Plant with Potential Use for Bioremediation of Cu Contaminated Environments.
This work examined the capability of Imperata cylindrica to respond, tolerate and accumulate Cu when growing at high Cu concentration (300 mg kg-1 of substrate) at different times of exposure (2, 14 and 21 days). The Cu accumulation in plants was examined by atomic absorption spectroscopy (AAS) and Cu localized by Scanning Electron Microscopy-Energy Dispersive X-Ray spectroscopy. Additionally, the phenolic compound identifications and concentrations were determined using liquid chromatography coupled to mass spectrometry. Our results showed that root biomass decreased significantly at high Cu levels, with a greater decrease at 21 days (39.8% less biomass in comparison to control). The root showed 328 mg Cu kg-1 dry weight at 21 days of exposure to Cu, being the tissue that accumulates most of the Cu. Lipid peroxidation was a clear indicator of Cu stress, principally in shoots. The exposure to Cu significantly increased the synthesis of phenolic compounds in shoots of plants exposed 21 days to Cu, where 5-caffeoylquinic acid reached the highest concentrations. Our results support that I. cylindrica is a Cu accumulator plant in root organs with a medium level of accumulation (between 200-600 mg Cu kg-1 biomass), which can tolerate the exposure to high Cu levels by means of increasing the synthesis of phenolic compound in shoots, suggesting a potential use as phytoremediation tool in Cu polluted environments.


Amplification of invasiveness in organotypic cultures after NBT-II rat bladder carcinoma stimulation with in vitro scattering factors.
Acidic fibroblast growth factor (aFGF) or transforming growth factor-alpha (TGF-alpha), in addition to being mitogenic, induce individual scattering of NBT-II rat bladder carcinoma cell clusters on tissue culture dishes, suggesting that they may contribute to tumor cell dissemination. To assay their scattering potential and their effect on cell invasiveness in a more complex and physiologically relevant model, we analyzed the behavior of NBT-II spheroids confronted with urinary bladder in organotypic cultures. NBT-II spheroids progressively replaced the urothelium at the site of contact with the bladder explant. In the absence of aFGF or TGF-alpha, inserted cells grew in a pattern suggestive of local hyperplasia, with occasional invasive cell protrusions. Exogenous scattering growth factors elicited a more rapid appearance of these protrusions, which were also more numerous. NBT-II cells transfected with cDNA constructs bearing the gene of aFGF, TGF-alpha or the oncogene hst/KFGF were also used. After exogenous or autocrine stimulation of NBT-II cells with the growth factors, a deeper penetration of the bladder wall in the form of nodular outgrowths and clusters of infiltrating cells was always observed. Altogether these observations suggest that the stimulation of NBT-II clusters by scattering/growth factors can promote cell shedding and amplify invasiveness in the complex extracellular environment of bladder tissues.


Influence of the upper joint surface and synovial lining in the outcome of chronic closed lock of the temporomandibular joint treated with arthroscopy.
Temporomandibular joint (TMJ) arthroscopy has been reported to be an effective and reliable technique for the treatment of chronic closed lock (CCL) of the TMJ. The purpose of the present study was to evaluate whether the status of the joint surface and the synovial lining directly visualized with arthroscopy could determine postoperative results in patients with CCL of the TMJ. In all, 257 of 500 patients (344 joints) fulfilled the inclusion criteria for CCL of the TMJ. Of these patients, 172 with unilateral TMJ involvement were finally selected for the study. Synovitis and chondromalacia were chosen as the main features for evaluation of the joint surface and synovial lining. Two groups of patients were established: 1) patients with scarce affectation (synovitis grades I-II and chondromalacia grades I-II); and 2) patients with severe affectation (synovitis grades III-IV and/or chondromalacia grades III-IV). Pain and maximal interincisal opening were chosen as dependent variables. All patients were assessed at 1, 3, 6, 12, and 24 months postoperatively. The paired-samples Student's t test was used to compare mean values for pain (using a visual analog scale) and maximal interincisal opening (MIO) both pre- and postoperatively. The Student's t test for unpaired data was applied for the statistical analysis. A P value less than .05 was considered statistically significant. Synovitis grades I-II were arthroscopically observed in 87 (50.58%) patients, whereas synovitis grades III-IV were present in 72 (41.86%) patients. Chondromalacia grades I-II were arthroscopically observed in 66 (38.37%) patients, whereas chondromalacia grades III-IV were present in 54 (31.39%) patients. A statistically significant decrease in pain (P < .001) with a parallel increase in mouth opening (P < .001) after arthroscopy was observed for patients with synovitis I-II, synovitis III-IV, chondromalacia I-II, and chondromalacia III-IV during the whole follow-up period. A significant difference (P = .01) in relation to VAS score was observed between patients with synovitis I-II and patients with synovitis III-IV at month 6 postoperatively. However, this difference did not persist during the rest of the follow-up period, as was the case in relation to mouth opening. No significant differences were observed in relation to decrease of pain and increase of MIO between patients with chondromalacia I-II and patients with chondromalacia III-IV at any time during the follow-up period. Although mean values for pain were lower in patients with synovitis I-II plus chondromalacia I-II in comparison to patients with synovitis III-IV plus chondromalacia III-IV for the whole follow-up period, no statistical significant differences were observed. In relation to the increase in mouth opening, slightly higher values were observed for patients with synovitis I-II plus chondromalacia I-II, although no statistical differences were observed with regard to patients presenting with synovitis III-IV plus chondromalacia III-IV. A significant decrease in pain with a parallel increase in MIO was achieved from month 1 postoperatively in patients with any grade of synovitis and/or chondromalacia. No statistical difference in pain or function was observed between patients with scarce involvement of the joint surface and the synovial lining and patients with severe involvement after arthroscopy.


Evaluating effects of episodic future thinking on valuation of delayed reward in cocaine use disorder: a pilot study.
Background: Episodic future thinking (EFT; i.e., envisioning oneself in future contexts) has been demonstrated to reduce discounting of future reward in healthy adults. While this approach has the potential to support future-oriented decision-making in substance use recovery, the impact of EFT on discounting behavior in illicit stimulant users has not yet been evaluated.Objectives: This pilot study aimed to (1) assess the feasibility of utilizing EFT methods in individuals with cocaine use disorder (CUD) and (2) conduct preliminary measurement of the EFT effect on discounting behavior in this population.Methods: Eighteen treatment-seeking individuals with CUD (17 males) were interviewed about positive and neutral events expected to occur at a range of future latencies. Future event information identified by participants was subsequently included on a subset of trials in an intertemporal choice task to promote EFT; within-subject differences in discounting between standard and EFT conditions were evaluated.Results: Participants identified relevant events and demonstrated decreased discounting of future reward when event descriptors were included (relative to discounting without event descriptors; p = .039). It was further noted that most events identified by participants were goals, rather than plans or significant dates.Conclusion: While methods previously used to study the effect of EFT on discounting behavior in healthy individuals are also effective in individuals with CUD, methodological factors - including types of events identified - should be carefully considered in future work. These preliminary findings suggest that EFT can reduce impulsive decision-making in cocaine use disorder and may therefore have therapeutic value.


Clinically relevant mutations in the PhoR sensor kinase of host-adapted Mycobacterium abscessus isolates impact response to acidic pH and virulence.
Difficult-to-treat pulmonary infections caused by nontuberculous mycobacteria of the Mycobacterium abscessus group have been steadily increasing in the USA and globally. Owing to the relatively recent recognition of M. abscessus as a human pathogen, basic and translational research to address critical gaps in diagnosis, treatment, and prevention of diseases caused by this microorganism has been lagging behind that of the better-known mycobacterial pathogen, Mycobacterium tuberculosis. To begin unraveling the molecular mechanisms of pathogenicity of M. abscessus, we here focus on the study of a two-component regulator known as PhoPR which we found to be under strong evolutionary pressure during human lung infection. We show that PhoPR is activated at acidic pH and serves to regulate a defined set of genes involved in host adaptation. Accordingly, clinical isolates from chronically infected human lungs tend to hyperactivate this regulator enabling M. abscessus to escape macrophage killing.


Differential effect of recombinant tissue plasminogen activator-induced thrombolysis in the central nervous system and systemic arteries.
Recombinant tissue plasminogen activator (rTPA) has been more effective in inducing thrombolysis in laboratory studies of intracranial thrombosis than clinical studies of systemic or coronary thrombosis would indicate. To evaluate this discrepancy, 21 rabbits were subjected to embolic occlusion of the right internal carotid artery (ICA) by retrograde injection of a tin-tagged, 2-hour-old autologous clot through the external carotid artery with angiographic monitoring in the same manner as in a previously reported model. The emboli lodged intracranially at the bifurcation of the ICA in 10 animals and in the cervical ICA in 11 animals. Digital subtraction angiography confirmed total occlusion of the ICA in all animals. Treatment started one-half hour after embolization and consisted of a bolus of 0.5 mg/kg of rTPA followed by an infusion of 1 mg/kg/h for 2 hours. All of the animals with intracranial emboli and 6 of the animals with cervical emboli were treated intravenously. The remaining 5 animals with cervical emboli were treated by intracarotid infusion of the same dose of rTPA. In the intravenously treated group, serial digital subtraction angiography documented thrombolysis in 9 of the 10 animals with intracranial emboli and only 1 of the 6 with cervical emboli. Thrombolysis occurred in 4 of the 5 rabbits with cervical emboli treated with intracarotid rTPA. Intravenous rTPA therapy produced a significantly (P less than 0.01) higher rate of thrombolysis in intracranial as compared to cervical thrombus.(ABSTRACT TRUNCATED AT 250 WORDS)


Prognostic Value of Optical Coherence Tomography Characteristics in Anterior Visual Pathway Meningiomas.
Anterior visual pathway meningiomas (AVPM) represent 2.5%-18% of all meningiomas. They may affect visual function, including visual acuity (VA) and visual field (VF). The principal modes of treatment are surgery and radiotherapy. The prognostic value of macular ganglion cell complex count (GCC) thickness has not been assessed in the literature thus far. The purpose of this study was to evaluate the prognostic value of pre-treatment optical coherence tomography (OCT) parameters (retinal nerve fiber layer and GCC) for visual outcomes in patients with AVPM. We retrospectively reviewed the medical records of all patients with AVPM who were treated in the Sheba Medical Center between 2011 and 2020. Included were patients with valid data containing preintervention OCT findings on the CIRRUS device and a minimum follow-up of 6 months. Preintervention and postintervention data on comprehensive ophthalmic examinations and OCT parameters of the affected eyes were retrieved. The correlation between preintervention OCT parameters and the visual outcome was assessed. The patients were also divided into 2 groups according to preintervention GCC (thin vs normal), and the visual outcome was compared between groups. In total, 186 patients' medical records were analyzed, and 38 patients who met the inclusion criteria were included in the study (mean age at diagnosis 52.8 ± 12.2 years, 28 women). Twenty-nine patients had 1 affected eye, and 9 had bilateral insult. A higher preinterventional average GCC was associated with better VA at 6 months, 1 year, and 2 years after intervention (r = -0.5, P ≤ 0.004, 0.005, and 0.03, respectively). There was a significant correlation between preinterventional GCC and VF mean deviation 2 years after intervention (r = 0.7, P ≤ 0.001). The thinner the GCC, the more prominent was the change in VA from before intervention to 2 years after intervention ( P ≤ 0.008). Correction for multiple comparisons with the Benjamini-Hochberg procedure did not change the significance of our findings. OCT parameters (GCC) have a predictive value in AVPM. There is strong correlation between preinterventional GCC and VA shortly after the intervention. Although a thin GCC is generally considered a negative prognostic factor, improvement in clinical parameters was also evident in patients with thin GCC. The potential of improvement despite preinterventional GCC thinning can add to the clinical discussion of the prognosis, and therefore, we recommend the patients with AVPM to undergo OCT and to be advised that GCC thinning alone should not be used as a major criterion in deciding whether treatment should be pursued.


Histamine release from cord blood basophils.
The histamine release (HR) after challenge with anti-IgE, concanavalin A, N-formyl-met-leu-phe and the calcium ionophore A23187 from 97 cord blood samples was determined by a microfiber-based assay. Maximum HR with anti-IgE showed great inter-individual variation (median: 20.5; range: 1-104 ng/ml blood), but was not significantly different from the results obtained in identically treated blood samples from 50 adults (median: 23; range: 1-93 ng/ml blood). Both the maximum HR and the sensitivity to anti-IgE were dependent on total plasma IgE content. Blood samples with plasma IgE greater than or equal to 0.5 IU/ml (n = 15) had significantly higher maximum HR than those with plasma IgE less than 0.5 IU/ml (n = 82; median: 32 vs. 18 ng/ml blood; p less than 0.01). Passive sensitization with IgE-rich atopic plasma increased the maximum HR with anti-IgE only in samples with a plasma IgE content of less than 0.5 IU/ml, although sensitivity to anti-IgE was universally increased. Preincubation with pharmacologic agents modulating the IgE-mediated HR produced effects generally similar to previous findings in adult blood. However, the effects of inhibiting the cyclooxygenase pathway in cord blood differed from our observations in adult blood, and may represent a maturational phenomenon. The family history of allergy was obtained by a questionnaire, and clinical observations were gathered from patient records. None of these parameters were found to influence HR with any secretagogue. However, HR stimulated by the calcium ionophore A 23187 was found to be highly dependent on the storage time of the EDTA-anticoagulated blood samples, which should be carefully controlled.


Aldehyde dehydrogenase 1 expression has prognostic significance in patients with glioma.
As a cancer stem cell marker associated with tumorigenesis, aldehyde dehydrogenase 1 (ALDH1) has recently been identified in gliomas. However, an insufficient number of clinical studies have been published to demonstrate its prognostic significance in glioma. In the present study, a systematic meta-analysis was performed to comprehensively evaluate the correlation of ALDH1 with age, sex, the World Health Organization (WHO) grade, and overall survival (OS) in patients with glioma. A search of relevant publications was conducted to select eligible studies on this subject, and the pooled hazard ratios (HRs) and related risks (RRs) with 95% confidence intervals (95% CIs) were assessed. Publication bias was also evaluated using Begg's funnel plots. A total of 6 articles were identified that included a total of 1,057 patients. OS analysis revealed that a high expression of ALDH1 was significantly associated with poor 5-year OS (n=6; HR, 2.10; 95% CI, 1.13-3.91; P<0.0001), and a high WHO grade (III+IV; n=4; RR, 2.28; 95% CI, 1.31-3.99; P=0.001). In conclusion, a high expression of ALDH1 is associated with a high WHO grade of gliomas and a worse prognosis in patients with glioma. Further, well-designed clinical studies are required to confirm its role in the process of selecting a suitable therapeutic approach in glioma.


η(4) -HBCC-σ,π-Borataallyl Complexes of Ruthenium Comprising an Agostic Interaction.
Thermolysis of [Cp*Ru(PPh2 (CH2 )PPh2 )BH2 (L2 )] 1 (Cp*=η(5) -C5 Me5 ; L=C7 H4 NS2 ), with terminal alkynes led to the formation of η(4) -σ,π-borataallyl complexes [Cp*Ru(μ-H)B{R-C=CH2 }(L)2 ] (2 a-c) and η(2) -vinylborane complexes [Cp*Ru(R-C=CH2 )BH(L)2 ] (3 a-c) (2 a, 3 a: R=Ph; 2 b, 3 b: R=COOCH3 ; 2 c, 3 c: R=p-CH3 -C6 H4 ; L=C7 H4 NS2 ) through hydroboration reaction. Ruthenium and the HBCC unit of the vinylborane moiety in 2 a-c are linked by a unique η(4) -interaction. Conversions of 1 into 3 a-c proceed through the formation of intermediates 2 a-c. Furthermore, in an attempt to expand the library of these novel complexes, chemistry of σ-borane complex [Cp*RuCO(μ-H)BH2 L] 4 (L=C7 H4 NS2 ) was investigated with both internal and terminal alkynes. Interestingly, under photolytic conditions, 4 reacts with methyl propiolate to generate the η(4) -σ,π-borataallyl complexes [Cp*Ru(μ-H)BH{R-C=CH2 }(L)] 5 and [Cp*Ru(μ-H)BH{HC=CH-R}(L)] 6 (R=COOCH3 ; L=C7 H4 NS2 ) by Markovnikov and anti-Markovnikov hydroboration. In an extension, photolysis of 4 in the presence of dimethyl acetylenedicarboxylate yielded η(4) -σ,π-borataallyl complex [Cp*Ru(μ-H)BH{R-C=CH-R}(L)] 7 (R=COOCH3 ; L=C7 H4 NS2 ). An agostic interaction was also found to be present in 2 a-c and 5-7, which is rare among the borataallyl complexes. All the new compounds have been characterized in solution by IR, (1) H, (11) B, (13) C NMR spectroscopy, mass spectrometry and the structural types were unequivocally established by crystallographic analysis of 2 b, 3 a-c and 5-7. DFT calculations were performed to evaluate possible bonding and electronic structures of the new compounds.


SMS 201-995, a very potent analogue of somatostatin. Assignment of the 1H 500 MHz n.m.r. spectra and conformational analysis in aqueous solution.
The conformations of a cyclic analogue of somatostatin, SMS 201-995, have been studied by n.m.r. spectroscopy at 500 MHz in aqueous solution. Assignments were made by use of 2D-correlated methods, especially by detecting long-range connectivities in order to identify the aromic amino-acid and long-range couplings between alpha protons of consecutive residues. Measurements of temperature coefficients of amide protons and of NH-C alpha H coupling constants enabled us to conclude that in water the molecule is rather flexible, with no evidence for a beta turn structure involving Thr6. An equilibrium involving two gamma turn conformations stabilized respectively by Cys2-D-Trp4 and Phe3-Lys5 hydrogen bonds, is responsible for the large upfield shift observed for the Lys5 gamma protons and is compatible with the measured JNH-C alpha H coupling constants.


Coumarin-Modified CQDs for Biomedical Applications-Two-Step Synthesis and Characterization.
Waste biomass such as lignin constitutes a great raw material for eco-friendly carbon quantum dots (CQDs) synthesis, which find numerous applications in various fields of industry and medicine. Carbon nanodots, due to their unique luminescent properties as well as water-solubility and biocompatibility, are superior to traditional organic dyes. Thus, obtainment of CQDs with advanced properties can contribute to modern diagnosis and cell visualization method development. In this article, a new type of coumarin-modified CQD was obtained via a hybrid, two-step pathway consisting of hydrothermal carbonization and microwave-assisted surface modification with coumarin-3-carboxylic acid and 7-(Diethylamino) coumarin-3-carboxylate. The ready products were characterized over their chemical structure and morphology. The nanomaterials were confirmed to have superior fluorescence characteristics and quantum yield up to 18.40%. They also possessed the ability of biomolecules and ion detection due to the fluorescence quenching phenomena. Their lack of cytotoxicity to L929 mouse fibroblasts was confirmed by XTT assay. Moreover, the CQDs were proven over their applicability in real-time bioimaging. Obtained results clearly demonstrated that proposed surface-modified carbon quantum dots may become a powerful tool applicable in nanomedicine and pharmacy.


Survey of advanced radiation technologies used at designated cancer care hospitals in Japan.
Our survey assessed the use of advanced radiotherapy technologies at the designated cancer care hospitals in Japan, and we identified several issues to be addressed. We collected the data of 397 designated cancer care hospitals, including information on staffing in the department of radiation oncology (e.g. radiation oncologists, medical physicists and radiation therapists), the number of linear accelerators and the implementation of advanced radiotherapy technologies from the Center for Cancer Control and Information Services of the National Cancer Center, Japan. Only 53% prefectural designated cancer care hospitals and 16% regional designated cancer care hospitals have implemented intensity-modulated radiotherapy for head and neck cancers, and 62% prefectural designated cancer care hospitals and 23% regional designated cancer care hospitals use intensity-modulated radiotherapy for prostate cancer. Seventy-four percent prefectural designated cancer care hospitals and 40% regional designated cancer care hospitals employ stereotactic body radiotherapy for lung cancer. Our multivariate analysis of prefectural designated cancer care hospitals which satisfy the institute's qualifications for advanced technologies revealed the number of radiation oncologists (P = 0.01) and that of radiation therapists (P = 0.003) were significantly correlated with the implementation of intensity-modulated radiotherapy for prostate cancer, and the number of radiation oncologists (P = 0.02) was correlated with the implementation of stereotactic body radiotherapy. There was a trend to correlate the number of medical physicists with the implementation of stereotactic body radiotherapy (P = 0.07). Only 175 (51%) regional designated cancer care hospitals satisfy the institute's qualification of stereotactic body radiotherapy and 76 (22%) satisfy that of intensity-modulated radiotherapy. Seventeen percent prefectural designated cancer care hospitals and 13% regional designated cancer care hospitals had a quality assurance committee. The numbers of radiation oncologists and other operating staff might be essential factors in the implementation of advanced radiotherapy technologies. Small proportions of regional designated cancer care hospitals satisfy the institute's qualifications of advanced technologies.


Long-term performance of bioreactors cleaning mercury-contaminated wastewater and their response to temperature and mercury stress and mechanical perturbation.
The long-term performance of bioreactors retaining mercury from contaminated industrial wastewater was analyzed at the laboratory scale, and its response to mechanical perturbations (gas bubbles and shaking) as well as to physical (increased temperature and hydraulic load) and chemical stresses (increased mercury concentration) likely to occur during on site operation was studied. Two packed-bed bioreactors with 80-cm(3) lava chips as biofilm carrier were inoculated with nine Hg(II)-resistant natural isolates of alpha- and gamma-proteobacteria. Chloralkali wastewater containing ionic mercury (3.0 to 9.7 mg/L Hg(2+)), amended with sucrose and yeast extract, flowed through the bioreactors at 160 mL/h. During the 16-month investigation the bioreactors showed no sign of depleted performance in terms of mercury-retaining capacity. After 16 months, both bioreactors still retained 96% of the mercury load. The performance of the bioreactors was sensitive to mechanical perturbations (e.g., sheer forces of gas bubbles). Shifts to higher Hg(2+) inflow concentrations initially decreased the mercury retention efficacy slightly. However, the bioreactors could adapt to Hg(2+) concentrations of up to 7.6 mg/L within several days. Old biofilms were less affected than the younger ones. The performance of the bioreactors was not affected by an increase in temperature up to 41 degrees C and an increased volumetric load (up to 240 mL/h). The bioreactors regained activity spontaneously after the stress had stopped. Recovery could be accelerated by increased nutrient concentration, although this may lead to blocking of the packed bed.


Identification of mRNA-miRNA-lncRNA regulatory network associated with the immune response to Aeromonas salmonicides infection in the black rockfish (Sebastes schlegelii).
In aquaculture, Aeromonas salmonicides (A. salmonicida) is a main fish pathogen because of its nearly worldwide distribution, and broad host range. Recently, an increasing number of evidences have uncovered the roles of mRNA-miRNA-lncRNA network in fish diseases. In current study, RNA-seq was conducted in the black rockfish spleen following A. salmonicida infection at 0 h (Sp0 or control) and three different post-infection time-points (2 h: Sp2, 12 h: Sp12 and 24 h: Sp24, respectively) to comprehensively identify differentially expressed (DE) mRNAs, miRNAs and lncRNAs. Enrichment analysis and protein-protein interaction (PPI) analysis of DE mRNAs were performed. Then, expression and correlation analysis for mRNAs and their upstream miRNAs and lncRNAs were conducted. Finally, a total of 1364 mRNAs, 17 miRNAs and 1584 lncRNAs exhibited significantly differential expressions during bacterial infection in the black rockfish spleen. Functional enrichment analysis suggested that they were significantly enriched in several immune-related pathways, including Amino sugar and nucleotide sugar metabolism, Cell adhesion molecules (CAMs), Neuroactive ligand-receptor interaction, Nicotinate and nicotinamide metabolism, Pentose and glucuronate interconversions, Phagosome, Proteasome, etc. Subsequently, 1091 lncRNA-miRNA-mRNA pathways (323 in Sp2, 609 in Sp12 and 207 in Sp24) were constructed including 400 lncRNAs, 69 miRNAs, and 70 mRNAs. Meanwhile, NLRC3/novel-264/LNC_00116154 pathway demonstrated important immune modulating function in the black rockfish against A. salmonicida infection. Finally, the novel mRNA-miRNA-lncRNA sub-networks were established, among which all mRNAs and ncRNAs possessed significant predictive values for further studies for immune responses in the black rockfish.


Accidental ingestion of a dental bur in an 84-year-old male.
This report describes the case of an 84-year-old male who was brought to the emergency room because a dental bur was swallowed accidentally during a dental procedure. The foreign body was successfully removed by gastroenterologists endoscopically 8 days after the ingestion and was identified as a 2-cm-long dental bur.


SUMO-1 modification of the Wilms' tumor suppressor WT1.
SUMO-1 conjugation modulates numerous cellular functions, including the subnuclear localization of its target proteins. The WT1 tumor suppressor encodes a four-zinc finger protein with distinct splicing isoforms. WT1(-KTS), encoding uninterrupted zinc fingers, functions as a transcription factor and has a diffusely nuclear distribution; WT1(+KTS), with an insertion of three amino acids (KTS) between zinc fingers three and four, localizes to discrete nuclear speckles, the function of which is unknown. Because the SUMO-1 E2-conjugating enzyme, Ubc9, interacts with WT1, we tested whether sumoylation modulates the cellular localization of WT1. We find here that both WT1 isoforms are directly sumoylated on lysine residues 73 and 177. Although RNA interference-mediated Ubc9 depletion effectively suppresses WT1 nuclear speckles, a SUMO-1-deficient WT1(+KTS)(K73, 177R) double mutant retains localization to speckles. Thus, direct sumoylation of WT1 is not responsible for its cellular localization, and other sumoylated proteins may target WT1 to these nuclear structures. Identification of other components of WT1-associated speckles is likely to provide clues to their function.


[A Case of Roux-en-Y Loop Reconstruction Using a Modified Aboral Pouch Technique for Y-Limb Obstruction Following Distal Gastrectomy].
A 53-year-old man underwentdistal gastrectomy with Roux-en-Y(R-Y)reconstruction for gastric cancer. An R-Y anastomosis was performed usinga 21mm circular stapler. Five years postoperatively, he visited our hospital with anorexia. An abdominal computed tomography scan showed dilatation of the afferent loop. He was diagnosed with afferent loop syndrome due to R-Y anastomotic stenosis that resulted in poor oral intake and malnutrition. A U-shaped bend created by an adhesion caused a bowel obstruction of the Y-anastomotic site for which the patient underwent R-Y loop reconstruction with an aboral pouch usinga 60mm linear stapler. He has been well without postoperative complaints. Here, we report a case of R-Y loop reconstruction with an aboral pouch for afferent loop obstruction complicated by stenosis of the Y-anastomotic site after distal gastrectomy.


The influence of wages and house prices on British interregional migration decisions.
The factors affecting choice of destination of U.K. internal migrants are analyzed using Labour Force Survey data. "A logit analysis of destination choice indicates that job movers are attracted to areas with high wages but are not affected by high house prices in such areas. In contrast, active non-job movers are deterred from areas of high house prices. Regional house price differences do not influence the destination choice of homemakers or the terminally sick but they do influence the destination choice of retirees. All groups prefer to travel the least distance when moving."


Impaired liver cytochrome P450 2C11 activity after dual antiplatelet therapy with aspirin and clopidogrel in rats.
1. Aspirin (ASA) and clopidogrel (CLP) are used in combination as dual antiplatelet therapy (DAPT) for acute coronary syndrome based on their complementary mechanisms for platelet aggregation inhibition. However, the pharmacokinetics of such drug combination usage has not been thoroughly investigated. 2. In the current study, an LC-MS/MS method was developed to simultaneously determine the plasma concentrations of ASA and its metabolite salicylic acid (SA) with CLP and its metabolites, clopidogrel carboxylic acid (CLPM) and clopidogrel active metabolite derivative (CAMD). The pharmacokinetics of ASA, SA, CLP, CLPM and CAMD in rats receiving two-week DAPT with ASA and CLP were then determined. 3. After two-week DAPT with ASA and CLP in rats, the activities of aspirin esterase and rCyp2c11, enzymes mediating rat metabolism of ASA and CLP, respectively, in prepared rat liver microsomes were measured followed by further determination of rCyp2c11 mRNA expressions. The results demonstrated that DAPT led to minimal impact on aspirin esterase activity but significant decrease in rCyp2c11 activity and mRNA expression. 4. In conclusion, our findings on impairment in rCyp2C11 activity and mRNA expression by DAPT in rats could provide guidance on its safe clinical use with other CYP 2C19 substrates.


MiR-4282 contributes to inhibit pancreatic cancer metastasis by negatively interacting with ABCB5.
To explore the regulatory mechanism of microRNA-4282 (miR-4282) on influencing pancreatic cancer progression by targeting ABCB5. MiR-4282 and ABCB5 levels in 58 cases of pancreatic cancer and paracancerous tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The influences of miR-4282 on pathological indicators and prognosis in pancreatic cancer patients were analyzed. MiR-4282 overexpression model was established in PANC-1 and BxPC-3 cells by transfection of miR-4282 mimic. Transwell and wound healing assay were conducted to illustrate the role of miR-4282 in influencing cell functions of pancreatic cancer. Bioinformatics analysis and Dual-Luciferase reporter assay were carried out to ascertain the interaction between miR-4282 and ABCB5. MiR-4282 was downregulated in pancreatic cancer samples. Low level of miR-4282 predicted high incidences of lymphatic metastasis and distant metastasis, as well as poor prognosis in pancreatic cancer patients. Overexpression of miR-4282 remarkably inhibited migratory ability in PANC-1 and BxPC-3 cells. MiR-4282 was targeted by ABCB5 through specific binding sites. In pancreatic cancer tissues, ABCB5 level was negatively correlated to that of miR-4282. Overexpression of ABCB5 could abolish the inhibitory effects of overexpressed miR-4282 on the malignant progression of pancreatic cancer. MiR-4282 is able to inhibit the migratory ability in pancreatic cancer cells by negatively targeting ABCB5, which may become a promising pancreatic cancer biomarker.


Efficacy and safety of cinitapride in functional dyspepsia.
To study the efficacy and safety of cinitapride in the treatment of functional dyspepsia, and to evaluate the improvement of patients' quality of life. The prospective cross-sectional multi-centre phase IV study was conducted at Jinnah Hospital, Lahore, Ziauddin Medical University, Karachi and Pakistan Railways General Hospital, Rawalpindi, from July 2009 to June 2010 and comprised 121 patients of functional dyspepsia who were given cinitapride 1mg thrice daily 15 minutes before meals and were followed up for four weeks. Primary clinical response was assessed by using the Global Index Score. Secondary response was seen by percentage change of the total score as well as of each dyspepsia symptom compared with baseline and the overall subjective assessment of patients by using the 7-point Likert's scale. Reduction in Nepean Dyspepsia Index-Short Farm was used to evaluate the improvement in quality of life of patients at week 2 and 4. SPSS 15 used for statistical analysis. After 4 weeks of treatment, the Global Index Score showed statistically significant reduction in 58 (48.92%) patients (p<0.01). Similar reduction (p<0.01) was seen in individual dyspepsia symptoms; early satiety, post-prandial fullness, and abdominal distension. The 7 point Likert's scale also showed similar improvement in subjective response (p<0.01).The quality of life also improved significantly at week 2 and 4 (p<0.01). No abnormal results were seen in vital signs, physical and laboratory examination except an unexplained rise in globulin level. Only one adverse event (sore throat) was reported during the study. The drug was effective in minimising dyspepsia symptoms, and improving the quality of life of patients. It was well tolerated and was almost free of side effects.


Crystal structure determination of FtsZ from Methanococcus jannaschii.
FtsZ is the polymer-forming protein of bacterial cell division. It is part of a ring in the middle of the dividing cell that is required for constriction of cell membrane and cell envelope to yield two daughter cells. FtsZ is a GTPase and is the only bacterial protein showing significant sequence homology to the eukaryotic tubulins. FtsZ can polymerize into tubes, sheets, and rings in vitro and is ubiquitous in eubacteria and archaea. Full-length FtsZ1 from Methanococcus jannaschii has been over expressed in Escherichia coli, employing the hyperthermophilic properties of the protein. Crystals grown from PEG400 and ethanol belong to spacegroup I213 with a = b = c = 159.1 A. Isomorphous replacement using one Hg derivative yielded a interpretable electron density map at 4 A resolution. The structure for residues 23-356 and one GDP has been refined to an Rfree of 0.28 (Rf = 0.20) at 2.8 A resolution. FtsZ consists of two domains with a connecting core helix. The N-terminal domain and the core helix contain all residues involved in nucleotide binding and resemble the fold of dinucleotide-binding proteins. The structures of tubulin and FtsZ show striking similarity; together with the functional similarities, this provides a strong indication that FtsZ is a true homolog of tubulin.


Langerhans cell histiocytosis arising after Hodgkin's disease.
We present the case of a 19-year-old male who suffered from Langerhans cell histiocytosis (LCH) 12 months after having been treated for recurrent Hodgkin's disease (HD). Immunophenotypic characterization and electron microscopic analysis were useful for the exclusion of a bone relapse of Hodgkin's disease or any other differential diagnosis. The association of LCH with HD or other malignancies is rare but more frequent than previously believed. The significance of such an association and the pathophysiology of LCH are still open questions.


A comparative study of topical 5% cysteamine versus 4% hydroquinone in the treatment of facial melasma in women.
To assess the efficacy and safety of topical 5% cysteamine versus 4% hydroquinone in the treatment of facial melasma in women. Topical 5% cysteamine is an antioxidant and tyrosinase inhibitor that has been shown to be effective in the treatment of melasma. However, to date, no study has compared the performance of topical cysteamine to hydroquinone for facial melasma. A quasi-randomized, multicenter, evaluator-blinded clinical trial was conducted on 40 women with facial melasma who were submitted to the nightly application of 5% cysteamine (CYS) or 4% hydroquinone (HQ) on hyperpigmented areas for 120 days. Both groups were required to use tinted sunscreen (SPF 50; PPD 19). Subjects were assessed at the inclusion and after 60 and 120 days of treatment for mMASI, MELASQoL, and the difference in colorimetric luminosity between melasma and the adjacent unaffected skin. The Global Aesthetic Improvement Scale was used to assess the difference in the appearance of the skin through standardized photographs. The mean reduction of the mMASI scores was 24% for CYS and 41% for HQ (P = 0.015) at 60 days, and 38% for CYS and 53% for HQ (P = 0.017) at 120 days. The photographic evaluation revealed up to 74% improvement for both groups, without statistically significant difference between them (P = 0.087). The MELASQoL score showed a progressive decrease for both groups over time, despite the greater reduction for HQ after 120 days (P = 0.018). Colorimetric assessment disclosed progressive depigmenting in both groups, without statistically significant difference between them (P > 0.160). No severe adverse effects were identified in either group. Erythema and burning were the most important local adverse effects with cysteamine, although their frequency did not differ between groups (P > 0.170). Cysteamine proved to be safe, well-tolerated, and effective, despite its inferior performance to hydroquinone in decreasing mMASI and MELASQoL in the treatment of melasma.


Enhanced diffiraction limited output powerof tapered gain semiconductor lasers.
The spatiotemporal dynamics of linearly and trumpet flared high brightness semiconductor lasers are compared and contrasted using a comprehensive model built up from the microscopic physics. While both devices display complex multi longitudinal mode dynamics, the trumpet flared device is less susceptible to transverse filamentation instabilities and, hence, displays superior time-averaged far-field imaging properties.


Corrective surgery of congenital heart defects in neonates: the Prague experience.
To assess the outcome and mortality trend in newborns undergoing corrective surgery for congenital heart defect. We reviewed the hospital records of 1,033 neonates under 30 days of life, who had congenital heart defects operated on at the Kardiocentrum, Motol University Hospital in Prague, Czech Republic, during 1977-2001. Early and late mortality and reoperation rates were analyzed. A total of 1,156 operations were performed in 1,033 neonates. Obstructive lesions were surgically treated in 56%, left-to-right shunts in 21%, and complex conotruncal lesions in 23% of the cases. Total correction has been achieved in 62% of the neonates. Most operations (75%) were performed in the first two weeks of neonate s life. Early 30-day hospital mortality was 13%. Late mortality, after the discharge from the hospital, was 10%. In the last three years, the hospital mortality rate decreased to about 2%. Out of 590 reinterventions in 379 neonates, with the mortality of 6%, 229 were secondary staged corrections and 190 further palliative procedures aimed mostly toward Fontan or Rastelli type of circulation. Residual or recurrent defects were solved in 62 neonates. There were 30 valve replacements, with 18 mechanical valves and 12 pulmonary valve autotransplantations (the Ross procedure). The homograft valved conduit was used in 38 children. Most newborns with critical congenital heart defects can undergo corrective operation under acceptable risk. Due to complex improvements in perioperative, anaesthetic, surgical, and postoperative care, contemporary hospital mortality can be reduced to 1-3%. Palliative procedures still play an important role in the staged treatment of severe complex heart defects in neonates.


Prostatic intraepithelial neoplasia and invasive carcinoma in total prostatectomy specimens: distribution, volumes and DNA ploidy.
Prostatic intraepithelial neoplasia (PIN) has been postulated to be the main precursor of invasive carcinoma of the prostate (IC). The occurrence, distribution and volumes of PIN and IC in addition to grade were studied in 54 patients who underwent total prostatectomy because of localised IC (T0d-T2 NO MO). PIN always occurred multifocally, localised generally in the peripheral zone (PZ) and was found in all cases. PIN 1 was the most common grade, PIN 3 the least. PIN 3 occurred exclusively in the PZ, in the vicinity of or intermingled with high grade IC. PIN and IC grades were usually concordant. The relative volumes of IC and PIN showed an inverse relationship, i.e. at small IC + PIN volumes PIN dominated, whereas at large IC + PIN volumes both relative and absolute PIN volumes were lower. Furthermore, with increasing PIN grade a tendency towards an increase in tumour volume, Gleason score and frequency of disruption of the basal cell layer was observed. These findings indicate progression from PIN to IC. DNA ploidy of PIN areas was determined by means of flow cytometry. Areas containing PIN 1, 2 or 3 were sampled (1 plug/ml of PIN). All foci displayed only diploid DNA profiles regardless of PIN volume and grade, even with coexistent IC displaying heterogeneous DNA patterns. Our results support the claim that low and medium grade prostatic carcinoma arises from near-diploid PIN stemlines and may progress into heterogeneous tumours containing non-diploid stemlines.


Life duration: a new systemic hypothesis.
A new hypothesis of ageing based on morphologic evidence is presented. The developmental process is determined by a kinetic curve of population growth which is typical for every association of cells. Every multicellular organism is considered as a system that consists of various cellular associations in symbiotic interaction. One of these associations is dominant and determines the developmental kinetics of the whole organism. The nervous system is the dominant cell association in mammals. The duration of its development is restricted by the lack of capability of neurons to regenerate in adult organisms. This may determine the duration of life and persistence of various pathologic processes.


Clinical evaluation of the rapid recovery of patients who underwent video-assisted thoracoscopic lung surgery under non-intubated anesthesia.
Non-intubated anesthesia thoracoscopic surgery is an evolving form of minimally invasive thoracic surgery. It has had encouraging results in the treatment of lung cancer, and the current concept of enhanced recovery after surgery has become indispensable to surgical treatment. Our center retrospectively evaluated the clinical effect of rapid postoperative rehabilitation in patients who underwent thoracoscopic lung surgery under non-intubated anesthesia. The clinical data of 192 patients undergoing video-assisted thoracoscopic surgery (VATS) at the Department of Thoracic Surgery of The First People's Hospital of Yunnan Province were retrospectively analyzed. Among them, 75 received double-lumen endotracheal intubation anesthesia, and 117 received a laryngeal mask instead of endotracheal intubated anesthesia. Comparing the intra-and post-operative indicators difference of these 2 groups. There were no significant differences in the postoperative complications, length of hospital stay, hemoglobin counts and platelet count 24 h after surgery between the non-intubated anesthesia and intubated anesthesia groups (P>0.05). In terms of the postoperative rehabilitation indicators of the VATS patients, the non-intubated anesthesia group had an earlier recovery in terms of water (food) intake, out-of-bed activity, and defecation (exhaust) times (P<0.001), less postoperative complications and adverse throat reactions (P<0.05), and higher levels of satisfaction (P<0.05) than the intubated anesthesia group. Compared to the intubated anesthesia group, the non-intubated anesthesia group had fewer changes of white blood cell counts, neutrophil percentages and lymphocytes percentages 24 h postoperatively (9.25×109 vs. 7.67×109, P=0.045; 7.06 vs. 5.53, P=0.039; 1.45 vs. 1.27, P=0.017), significant reduction pleural drainage after restoring oral intake in postoperative 24 and 48 h (198.43 vs. 131.07 and 114.04 vs. 57.47 mL, P<0.001), shorter postoperative thoracic tube drainage times (3.73 vs. 3.13 d, P<0.001). Notably, there was no difference between the smoking history and previous medical history of the patients in the 2 groups. Compared to intubation by general anesthesia, non-intubated thoracoscopic anesthesia is a safe and effective option. Patients who undergo non-intubated thoracoscopic lung surgery have a rapid recovery after surgery. Thus, it is worthy of promotion in clinical surgery settings.


Differential Proteome Analysis of Extracellular Vesicles from Breast Cancer Cell Lines by Chaperone Affinity Enrichment.
The complexity of human tissue fluid precludes timely identification of cancer biomarkers by immunoassay or mass spectrometry. An increasingly attractive strategy is to primarily enrich extracellular vesicles (EVs) released from cancer cells in an accelerated manner compared to normal cells. The Vn96 peptide was herein employed to recover a subset of EVs released into the media from cellular models of breast cancer. Vn96 has affinity for heat shock proteins (HSPs) decorating the surface of EVs. Reflecting their cells of origin, cancer EVs displayed discrete differences from those of normal phenotype. GELFrEE LC/MS identified an extensive proteome from all three sources of EVs, the vast majority having been previously reported in the ExoCarta database. Pathway analysis of the Vn96-affinity proteome unequivocally distinguished EVs from tumorigenic cell lines (SKBR3 and MCF-7) relative to a non-tumorigenic source (MCF-10a), particularly with regard to altered metabolic enzymes, signaling, and chaperone proteins. The protein data sets provide valuable information from material shed by cultured cells. It is probable that a vast amount of biomarker identities may be collected from established and primary cell cultures using the approaches described here.


The effects of sildenafil citrate on choroidal thickness as determined by enhanced depth imaging optical coherence tomography.
To investigate the effects of the phosphodiesterase-5 inhibitor, sildenafil citrate, on choroidal thickness using eye-tracked enhanced depth imaging spectral-domain optical coherence tomography. In a prospective interventional study, 8 healthy subjects (4 men and 4 women) with no ocular history underwent enhanced depth imaging spectral-domain optical coherence tomography at baseline, 1 hour, and 3 hours after the ingestion of 100 mg of sildenafil citrate. Choroidal thickness measurements for both eyes using enhanced depth imaging spectral-domain optical coherence tomography were taken by 2 masked readers at baseline, 1-hour, and 3-hour time points. Statistical analysis was performed to compare the measurements of choroidal thickness at each of the three intervals. The mean age of the subjects was 35.9 years (range 30-46 years). Mean choroidal thickness at baseline was 334 μm (± 57 μm). Mean choroidal thickness increased by 12.3% to 375 μm (± 68 μm) at 1 hour after ingestion (P < 0.001). At 3 hours after ingestion, the mean choroidal thickness remained elevated at 372 μm (± 61 μm), 11.6% thicker than baseline (P < 0.001). There was no significant difference in choroidal thickness between the 1-hour and the 3-hour intervals (P = 0.719). Sildenafil citrate appears to increase choroidal thickness as measured by eye-tracked enhanced depth imaging spectral-domain optical coherence tomography measurements in healthy subjects 1 hour and 3 hours after ingestion. These findings may be of relevance given that increased choroidal thickness appears to be a risk factor for central serous chorioretinopathy and that several reports have suggested an association between phosphodiesterase-5 inhibitors and this disorder.


Antifungal activity of 2-chloro-N-phenylacetamide: a new molecule with fungicidal and antibiofilm activity against fluconazole-resistant Candida spp.
In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter. This research aimed to evaluate the antifungal potential of 2-chloro-N-phenylacetamide against fluconazole-resistant clinical strains of C. albicans and C. parapsilosis. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), inhibition of biofilm formation and its rupture, sorbitol and ergosterol assays, and association between this molecule and common antifungal drugs, amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 µg.mL-1, and a MFC of 512-1,024 µg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. 2-chloro-N-phenylacetamide did not promote antifungal activity through binding to cellular membrane ergosterol nor it damages the fungal cell wall. Antagonism was observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal activity by inhibiting both planktonic cells and biofilm of fluconazole-resistant strains. Its combination with other antifungals should be avoided and its mechanism of action remains to be established.


Bursting and oscillating neurons of the cat basolateral amygdaloid complex in vivo: electrophysiological properties and morphological features.
1. To characterize the physiological properties of lateral and basolateral (BL) amygdaloid neurons, intracellular recordings were performed in barbiturate-anesthetized cats. Morphological identification of recorded cells was achieved by intracellular injection of neurobiotin. Two types of physiologically identified projection neurons were distinguished in the BL and lateral nuclei. 2. The first type of neurons prevailed in the BL nucleus (80% of BL cells). Their resting membrane potential (Vm) averaged -66 +/- 4.9 (SE) mV. They generated stereotyped spike doublets or bursts in response to threshold depolarizing pulses. In most cells, depolarizing pulses of higher amplitude elicited spike bursts or doublets at a shorter latency followed by a nonadapting train of single spikes whose frequency rose with the amplitude of the current pulses. However, 15% of BL bursting neurons generated repetitive spike bursts or doublets in response to prolonged depolarizing current pulses. The response of BL bursting neurons to hyperpolarizing current pulses revealed the presence of slow inward rectification in the form of a depolarizing sag, thus suggesting the presence of a hyperpolarization-activated current. 3. The second type of neurons prevailed in the lateral nucleus. Their resting Vm was quite polarized (-74 +/- 2.85 mV) and they generated slow Vm oscillations (2-10 Hz) upon steady depolarization beyond congruent to -62 mV. The frequency of the oscillation increased with the amount of depolarizing current. In the majority of cells, analysis of voltage responses to subthreshold current pulses revealed the presence of voltage- and time-dependent rectification in the depolarizing direction. Current pulses that brought the Vm to -65 mV and beyond elicited a voltage response that reached an early peak and then decayed. Increasing the amplitude of the pulse decreased the latency of the early peak until it triggered an action potential. Current-voltage plots demonstrated inward rectification in the depolarizing direction. At the break of hyperpolarizing current pulses applied at depolarized levels, the Vm overshot prepulse values and generated one or more oscillatory cycles. 4. An important proportion of bursting and oscillating neurons (45.8% and 29%, respectively) were physiologically identified as projection neurons by antidromic invasion from the basal forebrain, entorhinal cortex, or perirhinal cortex. The conduction velocity of bursting and oscillating neurons estimated from the latency of antidromic spikes was low (< or = 2.5 m/s). 5. Most bursting and oscillating neurons of the BL nucleus were spiny cells with a pyramidal morphology. Four to eight dendritic trunks emerged from the apex, base, and sides of their triangular soma.(ABSTRACT TRUNCATED AT 400 WORDS)


High hydrostatic pressure-induced inactivation of bacterial spores.
High hydrostatic pressure (HHP) is the most-widely adopted novel non-thermal technology for the commercial pasteurization of foods. However, HHP-induced inactivation of bacterial spores remains a challenge due to spore resistance to the treatment limits of currently available industrial HHP units (i.e. ~650 MPa and 50 °C). Several reports have demonstrated that high pressure can modulate the germination machinery of bacterial spores, rendering them susceptible to subsequent inactivation treatments. Unfortunately, high pressure-induced germination is a unique phenomenon for spores of the genus Bacillus but not of Clostridium. Alternative strategies to inactivate bacterial spores at commercially available pressure and temperature levels include promoting the germination step by inclusion of known germinants into the food formulation to increase the lethality of HHP treatments on bacterial spores. The aim of this review is to provide an overview of the molecular basis involved in pressure-triggered germination of bacterial spores and of novel strategies to inactivate bacterial spores with HHP treatments.


The use of discharge risk assessment tools in general psychiatric services in the UK.
Closure of asylums dismantled a system of risk control based on containment, resulting in a rise in homicides and suicides by discharged patients. Remedial action centred on a structured approach to managing multidisciplinary care (the Care Programme Approach) and a system of independent inquiries into homicides. A need for better discharge risk assessment was identified by government and health professions. The literature points to inherent limitations in the predictive power of actuarially based tools, restricting them to augmenting clinical judgement. This paper addresses the development and effective use of tools to predict risk to patients and public following discharge into the community. Methods used were: (i) a questionnaire to NHS Trusts in the UK; (ii) an analysis of documentation on tools in use; and (iii) interviews of hospital and community mental health teams at eight NHS Trusts. Findings point to: (i) a sporadic development of risk assessment tools at Trust level; (ii) that this has been stimulated by clinical governance but is unguided by any coherent national strategy; and (iii) that information technology for risk data collection is not well used in the UK, where there is reliance on use of paper records and informal communication. The implications for management and health professions are discussed.


Parotocinclus yaka, a new species of armored catfish (Loricariidae: Hypoptopomatinae), from the Amazon basin in Brazil.
Parotocinclus yaka is described as a new species of hypoptopomatine cascudinho from tributaries of the Rio Tiquié, tributary to the Rio Uaupés, upper Rio Negro drainage, Amazon basin, Amazonas State, Brazil. The new species is distinguished from its congeners in northeastern and southeastern Brazil by having the cheek canal plate elongated posteriorly on the ventral surface of the head and in contact with the cleithrum. Parotocinclus yaka is diagnosed from the Parotocinclus species of the Amazon, Orinoco and Guianas watersheds by having a conspicuous dark spots smaller than the pupil diameter distributed dorsally and laterally on the head; it is also differentiated from P. polyochrus (Casiquiare, Venezuela), P. longirostris (Rio Amazonas, Brazil), and P. eppleyi (Río Orinoco) by the absence of a Y-shaped light mark dorsally on the head. In addition, the absence of premaxillary and dentary accessory teeth and the presence of a Y-shaped spot on the snout distinguish the new species from P. collinsae (Essequibo River, Guyana), P. halbothi (Rio Trombetas, Brazil and Marowijne River, Suriname) and P. variola (Río Amazonas, Colombia). Parotocinclus yaka also differs from P. amazonensis (lower Amazon basin), P. aripuanensis (lower Amazon basin), P. britskii (Guyana, Suriname, eastern Venezuela, and Amapá State, Brazil), and P. dani (Rio Tapajós basin), by having more numerous oral teeth. The new species described herein is part of the group of small cascudinhos usually associated with marginal or submerged vegetation and submerged logs, of moderate current and clear transparency, found in conserved habitats in streams of the Amazon, Orinoco and Guianas rivers.


Regional differences in the pineal gland of the cotton rat, Sigmodon hispidus: light microscopic, electron microscopic, and immunohistochemical observations.
Light microscopic, electron microscopic and immunohistochemical observations of the various portions of the pineal gland of the cotton rat (Sigmodon hispidus) were made. The volume of the proximal half occupied about 30% of the whole organ, and pinealocytes were slightly smaller in size in the proximal portion than elsewhere. The distal and intermediate portions contained few interstitial cells and numerous astrocytes, but the proximal portion lacked interstitial cells and had more abundant astrocytes than elsewhere. Astrocytes, which were immunoreactive for glial fibrillary acidic protein, mainly lined the pericapillary spaces in the distal and intermediate portions, but in the proximal portion these cells often surrounded isolated or groups of pinealocytes. In the distal and intermediate portions, abundant sympathetic fibers and less numerous non-sympathetic, peptidergic fibers were mainly localized in the pericapillary spaces; these fibers were sparsely distributed in the parenchyma close to interstitial cells or astrocytes. In the proximal portion, non-sympathetic fibers were scarce and sympathetic fibers were distributed abundantly and almost exclusively in the parenchyma. Most of the sympathetic fibers were adjacent to astrocytes and, occasionally, made specialized contact with them. Fenestrae in the capillary endothelium were numerous in the distal portion but absent in the proximal portion. Thus, marked differences in structure existed between the distal and proximal portions of the pineal gland of the cotton rat suggesting that both portions are functionally dissimilar. In addition, the present study indicates that the proximal portion of the cotton rat was well developed and showed morphological features similar to the deeply situated pineal glands of other mammals.


Nucleobase recognition in ssDNA at the central constriction of the alpha-hemolysin pore.
Nanopores are under investigation for single-molecule DNA sequencing. The alpha-hemolysin (alphaHL) protein nanopore contains three recognition points capable of nucleobase discrimination in individual immobilized ssDNA molecules. We have modified the recognition point R(1) by extensive mutagenesis of residue 113. Amino acids that provide an energy barrier to ion flow (e.g., bulky or hydrophobic residues) strengthen base identification, while amino acids that lower the barrier weaken it. Amino acids with related side chains produce similar patterns of nucleobase recognition providing a rationale for the redesign of recognition points.


Tuning the activation threshold of a kinase network by nested feedback loops.
Determining proper responsiveness to incoming signals is fundamental to all biological systems. We demonstrate that intracellular signaling nodes can tune a signaling network's response threshold away from the basal median effective concentration established by ligand-receptor interactions. Focusing on the bistable kinase network that governs progesterone-induced meiotic entry in Xenopus oocytes, we characterized glycogen synthase kinase-3beta (GSK-3beta) as a dampener of progesterone responsiveness. GSK-3beta engages the meiotic kinase network through a double-negative feedback loop; this specific feedback architecture raises the progesterone threshold in correspondence with the strength of double-negative signaling. We also identified a marker of nutritional status, l-leucine, which lowers the progesterone threshold, indicating that oocytes integrate additional signals into their cell-fate decisions by modulating progesterone responsiveness.


Nurses' role in platelet transfusion clinical trials.
This article describes the crucial role of research nurses in studies coordinated by the NHS Blood and Transplant Clinical Trials Unit (CTU), using two recent trials studying platelet transfusions in adults and neonates as examples. CTU studies are coordinated by trial managers, most of whom are or were registered nurses, which supports relationships with research nurses in participating hospitals. During trials the CTU sustains research nurses with ongoing education and training, and establishes cooperative working between nurses and the unit, and between nurses in different locations. Regular feedback from research nurses guides the design and management of clinical trials.


Chemical Modulation of Alternative Splicing for Molecular-Target Identification by Potential Genetic Control in Agrochemical Research.
Alternative splicing (AS), the process of removing introns from pre-mRNA and the rearrangement of exons to produce several types of mature transcripts, is a remarkable step preceding protein synthesis. In particular, it has now been conclusively shown that up to ∼95% of genes are alternatively spliced to generate a complex and diverse proteome in eukaryotic organisms. Consequently, AS is one of the determinants of the functional repertoire of cells. Many studies have revealed that AS in plants can be regulated by cell type, developmental stage, environmental stress, and the circadian clock. Moreover, increasing amounts of evidence reveal that chemical compounds can affect various steps during splicing to induce major effects on plant physiology. Hence, the chemical modulation of AS can serve as a good strategy for molecular-target identification in attempts to potentially control plant genetics. However, the kind of mechanisms involved in the chemical modulation of AS that can be used in agrochemical research remain largely unknown. This review introduces recent studies describing the specific roles AS plays in plant adaptation to environmental stressors and in the regulation of development. We also discuss recent advances in small molecules that induce alterations of AS and the possibility of using this strategy in agrochemical-target identification, giving a new direction for potential genetic control in agrochemical research.


The Relationship Between Anxiety and Incident Agitation in Alzheimer's Disease.
Agitation in Alzheimer's disease (AD) has been hypothesized to be an expression of anxiety, but whether anxiety early in the course of dementia could be a risk factor for developing later agitation is unknown. We used the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to examine the longitudinal relationship between anxiety and incident agitation in individuals with a diagnosis of AD at baseline or during follow-up. Longitudinal neuropsychiatric symptom data from AD individuals who were agitation-free at study baseline (N = 272) were analyzed using mixed effects regression models to test the longitudinal relationship between baseline and incident anxiety with incident agitation. Anxiety at baseline was not associated with subsequent agitation, but there was a positive linear relationship between incident anxiety and agitation over the study duration. Baseline apathy and delusions were consistently associated with subsequent agitation and greater disease severity and illness duration also appeared to be risk factors for agitation. Our findings support the concept that anxiety and agitation are likely to be distinct rather than equivalent constructs in mild-moderate AD. Future longitudinal cohort studies are needed to replicate these findings and further characterize potential risk factors for agitation, such as apathy and delusions.


Value of ultrasound during the menstrual cycle and early pregnancy.
Ultrasound is a recently introduced technique that allows repeated noninvasive imaging of the uterus, ovaries and associated structures. It offers a relatively simple method for the repeated examination of the abdominal organs including growing fetuses, and is increasingly being used to measure blood flow in the identification of disease states. The clinical applications of real time pelvic ultrasonography are principally in the field of gynaecology to assess anatomical normality, and to monitor the progress of natural and stimulated cycles in assisted reproductive techniques. Once infertility treatment has been successful, ultrasound has proved to have a great value, when combined with established endocrinological parameters, to monitor the development of pregnancy, and the normality of fetal growth.


The Impact of teledermatology during the COVID-19 pandemic.
Teledermatology has been widely adopted during the COVID-19 pandemic as virtual patient care promotes social distancing and decreases viral exposure risk. As teledermatology has become more prominent during this period, it is essential to assess whether virtual visits allow for adequate patient care. To assess perceptions of advantages and disadvantages of teledermatology, a survey was sent to academic dermatologists through the Association of Professors of Dermatology (APD) listserv. Of the physicians surveyed, 94% reported their departments had implemented teledermatology during the COVID-19 pandemic. The majority (64%) described teledermatology as an effective tool for patient care because of improved access to care, decreased risk of COVID-19 exposure, and convenience. Frequently cited limitations of teledermatology were image quality, technical difficulties, and inability to perform a comprehensive skin examination. Thirty-seven percent of respondents reported teledermatology as a contributor to their professional burnout. Although teledermatology has become more prevalent as a result of the pandemic, its role moving forward is uncertain given its limitations.


A novel multi-relation regularization method for regression and classification in AD diagnosis.
In this paper, we consider the joint regression and classification in Alzheimer's disease diagnosis and propose a novel multi-relation regularization method that exploits the relational information inherent in the observations and then combines it with an L2,1-norm within a least square regression framework for feature selection. Specifically, we use three kinds of relationships: feature-feature relation, response-response relation, and sample-sample relation. By imposing these three relational characteristics along with the L2,1-norm on the weight coefficients, we formulate a new objective function. After feature selection based on the optimal weight coefficients, we train two support vector regression models to predict the clinical scores of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE), respectively, and a support vector classification model to identify the clinical label. We conducted clinical score prediction and disease status identification jointly on the Alzheimer's Disease Neuroimaging Initiative dataset. The experimental results showed that the proposed regularization method outperforms the state-of-the-art methods, in the metrics of correlation coefficient and root mean squared error in regression and classification accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve in classification.


Aims and methodological problems in multimodal treatment studies.
The paper outlines the growing acceptance and use of multimodal treatment approaches to treat a variety of psychiatric disorders in childhood and adolescence. It then explores some of the problems of multimodal treatment studies. Problems in assessing outcome of efficacy of the interventions, particularly as they pertain to specific interventions and particular areas of functioning are discussed as well as the issues of appropriate control and comparison groups. The problems with regard to appropriate control and comparison groups are explored with respect to diagnosis and interventions. Finally, an ongoing multimodal treatment study of children with attention deficit hyperactive disorder is used to illustrate how some of the problems described can be solved.


Mechanical in vitro fatigue testing of implant materials and components using advanced characterization techniques.
Implants of different material classes have been used for the reconstruction of damaged hard and soft tissue for decades. The aim is to increase and subsequently maintain the patient's quality of life through implantation. In service, most implants are subjected to cyclic loading, which must be taken particularly into consideration, since the fatigue strength is far below the yield and tensile strength. Inaccurate estimation of the structural strength of implants due to the consideration of yield or tensile strength leads to a miscalculation of the implant's fatigue strength and lifetime, and therefore, to its unexpected early fatigue failure. Thus, fatigue failure of an implant based on overestimated performance capability represents acute danger to human health. The determination of fatigue strength by corresponding tests investigating various stress amplitudes is time-consuming and cost-intensive. This study summarizes four investigation series on the fatigue behavior of different implant materials and components, following a standard and an in vitro short-time testing procedure, which evaluates the material reaction in one enhanced test set-up. The test set-up and the applied characterization methods were adapted to the respective application of the implant with the aim to simulate the surrounding of the human body with laboratory in vitro tests only. It could be shown that by using the short-time testing method the number of tests required to determine the fatigue strength can be drastically reduced. In future, therefore it will be possible to exclude unsuitable implant materials or components before further clinical investigations by using a time-efficient and application-oriented testing method.


Role of tip chemical reactivity on atom manipulation process in dynamic force microscopy.
The effect of tip chemical reactivity on the lateral manipulation of intrinsic Si adatoms toward a vacancy site on a Si(111)-(7 × 7) surface has been investigated by noncontact atomic force microscopy at room temperature. Here we measure the atom-hopping probabilities associated with different manipulation processes as a function of the tip-surface distance by means of constant height scans with chemically different types of tips. The interactions between different tips and Si atoms are evaluated by force spectroscopic measurements. Our results demonstrate that the ability to manipulate Si adatoms depends extremely on the chemical nature of the tip apex and is correlated with the maximal attractive force measured over Si adatoms. We rationalize the observed dependence of the atom manipulation process on tip-apex chemical reactivity by means of density functional theory calculations. The results of these calculations suggest that the ability to reduce the energy barrier associated with the Si adatom movement depends profoundly on tip chemical reactivity and that the level of energy barrier reduction is higher with tips that exhibit high chemical reactivity with Si adatoms. The results of this study provide a better way to control the efficiency of the atomic manipulation process for chemisorption systems.


Interplay between Charge-Density-Wave, Superconductivity, and Ferromagnetism in CuIr2-xCrxTe4 Chalcogenides.
We report the crystal structure, charge-density-wave (CDW), superconductivity (SC), and ferromagnetism (FM) in CuIr2-xCrxTe4 (0 ≤ x ≤ 2) chalcogenides. Powder x-ray diffraction (PXRD) results reveal that the CuIr2-xCrxTe4 series are distinguished between two structural types and three different regions: (i) layered trigonal structure region, (ii) mixed phase regions, and (iii) spinel structure region. Besides, Cr substitution for Ir site results in rich physical properties including the collapse of CDW, the formation of dome-shaped like SC, and the emergence of magnetism. Cr doping slightly elevates the superconducting critical temperature (Tsc) to its highest Tsc = 2.9 K around x = 0.06. As x increases from 0.3 to 0.4, the ferromagnetic Curie temperature (Tc) increases from 175 to 260 K. However, the Tc remains unchanged in the spinel range of 1.9 ≤ x ≤ 2. This finding provides a comprehensive material platform for investigating the interplay between CDW, SC, and FM multipartite quantum states.


Ultrastructural lesions in testes from hyperprolactinemic men.
Testicular tissue from eight men with prolactinomas and elevated serum prolactin were evaluated by light (LM) and transmission electron microscopy (TEM). A semiquantitative assessment of testicular morphology was employed to provide a morphology index for each tissue specimen. Although in each biopsy specimen germ cell exfoliation was evident, as was abnormal structural change in the seminiferous epithelium, there was no apparent correlation with the overall degree of tissue pathology (morphology index) and the serum level of prolactin. All of the tissue displayed variably thickened seminiferous tubule walls which, when viewed by TEM, were composed of thickened laminae propriae and redundant and involuted basal laminae. Likewise, all tubules contained Sertoli cells with overt cytoplasmic degeneration, principally in the apical (adluminal) region of the cell. This was visualized, in part, as a retraction of the apical cytoplasm from periluminal spermatids and degeneration or absence of Sertoli-germ cell junctional specializations. Sertoli-Sertoli cell junctional complexes appeared structurally intact. Leydig cell ultrastructure was typical of normal cells and contained a variable amount of lipid and smooth endoplasmic reticulum. This also was without positive correlation with the overall degree of tissue pathology or level of serum prolactin. Our results demonstrate the variable degree of testicular pathology associated with hyperprolactinemia in man, and suggest that abnormal tubule walls and altered Sertoli cell ultrastructure are consistent findings in this abnormal endocrine condition.


Determinants of clinical outcomes of surgery for isolated severe tricuspid regurgitation.
Although the incidence of patients with isolated tricuspid regurgitation (TR) is increasing, data regarding the clinical outcomes of isolated TR surgery are limited. This study sought to investigate the prognostic implications according to procedural types, and to identify preoperative predictors of clinical outcomes after isolated TR surgery. Among consecutive 2610 patients receiving tricuspid valve (TV) procedure, we analysed 238 patients (age, 59.6 years; 143 females) who underwent stand-alone TV surgery (repair, 132; replacement, 106) for severe TR. Primary outcome was the composite of all-cause mortality and heart transplantation. Clinical outcomes between the repair and the replacement groups were compared after adjusting with the inverse probability of treatment weighting (IPTW) method. During follow-up (median, 4.1 years), 53 patients died and 4 received heart transplantation. Multivariable analysis revealed that age (p=0.001), haemoglobin level (p=0.003), total bilirubin (p=0.040), TR jet area (p=0.005) and right atrial (RA) pressure (p=0.022) were independent predictors of the primary outcome. After IPTW adjustment, there were no significant intergroup differences in the risk of primary outcome (HR 1.01; 95% CI 0.55 to 1.87). In the subgroup analysis, tricuspid annular diameter was identified as a significant effect modifier (p=0.012) in the comparison between repair versus replacement, showing a trend favouring replacement in patients with annular diameter >44 mm. The outcomes of stand-alone severe TR surgery were independently associated with the severity of TR and RA pressure. In selected patients with severe annular dilation >44 mm, replacement may become a feasible option.


The subrenal capsule assay in mice. Prediction of rat tumor sensitivity to chemotherapy.
The predictive value of the subrenal capsule (SRC) assay for cancer chemotherapy was tested in five rat tumors. Tumor-bearing rats were used as controls. In order to simulate clinical chemotherapy, different dose regimens and drug combinations were used. All five tumors were evaluable in in the SRC assay. Taking into account cytotoxic drugs, 86% compatibility was obtained between the SRC assay and the rat model. Antitumor effect of three antiestrogenic compounds could not be predicted by the SRC assay. It is concluded that the SRC assay can be expected to have predictive value in the assessment of tumor sensitivity to single and combination chemotherapy based on experimental animal models.


Smectic membranes in motion: approaching the fast limits of x-ray photon correlation spectroscopy.
The dynamics of the layer-displacement fluctuations in smectic membranes have been studied by x-ray photon correlation spectroscopy (XPCS). We report transitions from an oscillatory damping regime to simple exponential decay of the fluctuations, both as a function of membrane thickness and upon changing from specular to off-specular scattering. This behavior is in agreement with recent theories. Employing avalanche photodiode detectors and the uniform filling mode of the synchrotron storage ring, the fast limits of XPCS have been explored down to 50 ns.


Bolus chasing: a new technique in peripheral arteriography.
Recent advances in digital angiographic equipment design have enabled a new technique of peripheral arteriography involving digital bolus chasing to be developed. This technique permits real-time visualization of the contrast bolus so that it can be followed peripherally with digital images being acquired at a suitable frame rate. We give the first description of this technique using the Philips Integris C2000 and compare it to conventional stepped arteriography. Sixty-one patients undergoing peripheral arteriography using the conventional stepped technique were compared with 55 patients using bolus chasing. The parameters assessed were the procedure time, the number of runs and screening time per investigation, the consumables used, the patient and radiologist radiation dose and the image quality. A reduction in the procedure time and the patient and radiologist radiation dose, and improvement in image quality are demonstrated with the bolus chasing technique. Bolus chasing represents an important advance in peripheral arteriography.


Behaviour of laying hens in two types of aviary systems on 25 commercial farms in Sweden.
1. Fifty-one flocks of laying hens in two high-density loose-housing systems were studied on 25 commercial farms in Sweden as part of a government test programme for evaluating new systems for laying hens. Six different hybrids were used in group sizes ranging from 250 to 5 000 birds. Stocking-densities varied from 10.2 to 19.1 birds per m2 floor area. No birds were beak trimmed. 2. The distribution of birds in the system, the frequency and location of aggressive pecks and feather pecks, the dust bathing activity and the birds' fear reaction to the keeper and to a novel object were measured. Direct behaviour observations were carried out twice per flock, at weeks 35 and 55. 3. The proportion of birds at the different locations was relatively constant across the 8-h observation period in the tiered system, but changed over time in the perch system, which may reflect a difference in access to resources between the systems. At night the top perches/tiers were preferred although when stocking-density increased, other sites were also used. 4. Aggression occurred mainly on the litter or in the nest areas. It did not differ between hybrids, but increased with age in the tiered system. Feather pecks occurred mainly on the litter. Brown hybrids feather pecked more than white ones, while white hybrids reacted more both to the keeper and to a novel object than did the brown hybrids. 5. It was concluded that access to nests was insufficient in both systems, as was litter space. Feed space was insufficient in the tiered system if food requirements increased. Design of the top perches, in the perch system, should be improved to allow birds to perch high up in the system without blocking access to feed etc. for others.


Uterus duplex bicollis, Vagina simplex in laboratory Guinea pigs (Cavia porcellus), rats (Rattus norvegicus forma domestica) and mice (Mus musculus forma domestica).
The female genital tract originates from the Müllerian ducts during embryological development. Fusion of the ducts occurs in different segments depending on the animal species, resulting in a variational number of the respective organ. Current literature on genital tract morphology of laboratory rodents is controversial. Therefore, the present study aimed at determining an anatomically correct definition of the uterus in laboratory guinea pigs, mice and rats. In all three rodent species, we found two separate cervical canals that communicate with an individual uterus via discrete ostia uteri interna. The correct anatomical definition should therefore be uterus duplex bicollis, vagina simplex.


Design of Novel PLA/OMMT Films with Improved Gas Barrier and Mechanical Properties by Intercalating OMMT Interlayer with High Gas Barrier Polymers.
Polymer/clay composites are an innovative class of materials. In this study, we present a facile method for the preparation of biodegradable and robust PLA/organomodified montmorillonite (OMMT) composite films with excellent gas barrier performance. When the design of PLA/OMMT composite films, in addition to making OMMT have good intercalation effect in the matrix, the compatibility of intercalating polymer and matrix should also be considered. In this work, two polymers with high gas barrier properties, namely poly(vinyl alcohol) (PVA) and ethylene vinyl alcohol copolymer (EVOH), were selected to intercalate OMMT. The morphology and microstructures of the prepared PLA/PVA/OMMT and PLA/EVOH/OMMT composites were characterized by the X-ray diffraction measurement, scanning electron microscopy, and differential scanning calorimetry. It was shown that the good dispersibility of PVA in the PLA matrix, rather than the intercalation effect, was responsible for the improved gas barrier and mechanical properties of PLA/PVA/OMMT composite. The elongation at break increases from 4.5% to 22.7% when 1 wt % PVA is added to PLA/OMMT. Moreover, gas barrier of PLA/PVA1/OMMT measured as O2 permeability is 52.8% higher than that of neat PLA. This work provides a route to intercalate OMMT interlayer with high gas barrier polymers and thus can be a useful reference to fabricate PLA/OMMT composites with improved gas barrier and mechanical properties. A comparison of oxygen permeabilities with existing commercial packaging films indicates that the biodegradable PLA/PVA/OMMT may serve as a viable substitute for packaging film applications.


Electrocardiographic detection of hypertensive left atrial enlargement in the presence of obesity: re-calibration against cardiac magnetic resonance.
Left atrial enlargement (LAE) has adverse prognostic implications in hypertension. We sought to determine the accuracy of five electrocardiogram (ECG) criteria for LAE in hypertension relative to cardiac magnetic resonance (CMR) gold standard and investigate the effect of concomitant obesity. One hundred and thirty consecutive patients (age: 51.4±15.1 years, 47% male, 51% obese, systolic blood pressure (BP): 171±29 mm Hg, diastolic BP: 97±15 mm Hg) referred for CMR (1.5 T) from a tertiary hypertension clinic were included. Patients with concomitant cardiac pathology were excluded. ECGs were assessed blindly for the following: (1) P-wave >110 ms, (2) P-mitrale, (3) P-wave axis <30°, (4) area of negative P-terminal force in V1 >40 ms.mm and (5) positive P-terminal force in augmented vector left (aVL) >0.5 mm. Left atrial volume ≥55 ml m-2, measured blindly by CMR, was defined as LAE. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under the receiver operator curve were calculated. The prevalence of LAE by CMR was 26%. All the individual ECG LAE criteria were more specific than sensitive, with specificities ranging from 70% (P-axis <30o) to 99% (P-mitrale). Obesity attenuated the specificity of most of the individual ECG LAE criteria. Obesity correlated with significant lower specificity (48% vs 65%, P<0.05) and a trend towards lower sensitivity (59 vs 43%, P=0.119) when ≥1 ECG LAE criteria were present. Individual ECG criteria of LAE in hypertension are specific, but not sensitive, at identifying LAE. The ECG should not be used to excluded LAE in hypertension, particularly in obese subjects.