Effect of mitochondrial complex III inhibitors on the regulation of vascular tone in porcine coronary artery.
In order to gain insight into the regulation of vascular tone by mitochondria, the effects of mitochondrial complex III inhibitors on contractile responses in porcine isolated coronary arteries were investigated. Segments of porcine coronary arteries were set up for isometric tension recording and concentration response curves to contractile agents were carried out in the absence or presence of the complex III inhibitors antimycin A or myxothiazol. Activity of AMP kinase was determined by measuring changes in phosphorylation of AMP kinase at Thr172. Pre-incubation with 10 μM antimycin A (Qi site inhibitor), or myxothiazol (Qo site inhibitor) led to inhibition of the contraction to the thromboxane receptor agonist U46619. Similar effects were seen on contractile responses to extracellular calcium, and the L-type calcium channel opener BAY K 8644, suggesting that both antimycin A and myxothiazol inhibit calcium-dependent contractions. The inhibitory effect of antimycin A was still seen in the absence of extracellular calcium, indicating an additional effect on a calcium independent pathway. The AMP kinase inhibitor dorsomorphin (10 μM) prevented the inhibitory of antimycin A but not myxothiazol. Furthermore, antimycin A increased the phosphorylation of AMP kinase, indicating an increase in activity, suggesting that antimycin A also acts through this pathway. These data indicate that inhibition of complex III attenuates contractile responses through inhibition of calcium influx. However, inhibition of the Qi site can also inhibit the contractile response through activation of AMP kinase.


The effects of optically and digitally simulated aniseikonia on stereopsis.
To simulate both lens-induced and screen-induced aniseikonia, and to assess its influence on stereopsis. Additionally, to determine if screen-based size differences could neutralise the effects of lens-induced aniseikonia. A four-circle (4-C) paradigm was developed, where one circle appears in front or behind the others because of crossed or uncrossed disparity. This stereotest was used for three investigations: (1) Comparison with the McGill modified random dot stereogram (RDS), with anisometropia introduced with +2 D spheres and cylinders, and with aniseikonia introduced with 6% overall and 6% meridional (×180, ×90) magnifiers before the right eye; (2) Comparison of lens-induced and screen-induced 6% overall and meridional magnifications and (3) Determining if lens and screen effects neutralised, by opposing 6% lens-induced magnification to the right eye with screen-inducements of either 6% left eye magnification or 6% right eye minification. A pilot study of the effect of masking versus not masking the surround was also conducted. The 4-C test gave higher stereo-thresholds than the RDS test by 0.5 ± 0.2 log units across both anisometropic and aniseikonic conditions. However, variations in power, meridian and magnification affected the two tests similarly. The pilot study indicated that surround masking improved neutralisation of screen and lens effects. With masking, lens-induced and screen-induced magnifications increased stereo-thresholds similarly. With lens and screen effects opposed, for most participants stereo-thresholds returned to baseline for overall and ×180 magnifications, but not for ×90 magnification. Only three of seven participants showed good compensation for ×90 magnification. Effects of lens-induced aniseikonia on stereopsis cannot always be successfully simulated with a screen-based method. The ability to neutralise refractive aniseikonia using a computer-based method, which is the basis of digital clinical measurement, was reasonably successful for overall and ×180 meridional aniseikonia, but not very successful for ×90 aniseikonia.


[Recurrent periprosthetic capsular retraction under the pectoralis major muscle. Treatment, 2 unusual clinical cases].
Capsular contracture around breast prostheses still represents a challenge, in spite of the numerous papers published on this topic. The etiology and pathogenesis of this condition are perplexing resulting in considerable controversy concerning the rationale for surgical treatment. The authors report two cases of recurrent disease: one patient with recurrent contracture after breast augmentation, the other patient with recurrence after breast reconstruction. Both patients were operated according to an original technique which consists in a square-shaped incision of the pectoralis major muscle via an inframammary approach. This surgical technique allows the prosthesis to sink into deeper layers leading to a better shape of the breast and providing satisfactory skin cover of the prosthesis.


[Reconsideration of pancreatic reconstruction after pancreatoduodenectomy].
Pancreatic fistula is one of the most common and serious complications after digestive tract reconstruction.Grade A pancreatic fistula is defined as biochemical fistula only when the drainage fluid amylase level is elevated without affecting clinical decision-making.It is not a true pancreatic fistula, or a real surgical complication.Surgeons should pay more attention to the diagnosis and treatment of B and C pancreatic fistula, and it is more valuable to reduce the occurrence of B and C pancreatic fistula.Pancreatic fistula is not a purely surgical technical problem, but the quality of surgical reconstruction is very important.For pancreatic surgeons, the reconstruction of the pancreatic stump digestive tract after pancreaticoduodenectomy is accompanied by both opportunities and challenges.


Mean platelet volume and platelet distribution width in vascular dementia and Alzheimer's disease.
Activated platelets play a substantial role in Alzheimer's disease (AD) and atherothrombosis. Mean platelet volume (MPV) is an early marker of platelet activation, which is linked to a variety of pro-thrombotic and pro-inflammatory diseases. This study is to examine the association between platelet indices and vascular dementia (VaD) and AD. In this cross-sectional study, we investigated the levels of platelet count, MPV, and platelet distribution width (PDW) in 150 VaD patients, 110 AD patients, and 150 non-demented controls. MPV and PDW were significantly lower in patients with VaD and AD as compared with controls. The decrease in PDW for AD patients as compared with VaD patients was also significant (p < 0.001). In addition, there was a positive correlation between Mini-Mental State Examination (MMSE) and MPV and PDW, after adjusting confounding factors (r = 0.532 for MPV and r = 0.425 for PDW, p < 0.001 for both). Multivariate regression analysis showed that MPV and PDW were significantly associated with MMSE (β = 0.366 for MPV and β = 0.273 for PDW, p < 0.001 for both). In conclusion, MPV and PDW were both decreased in VaD and AD. PDW levels were significantly lower in AD as compared to those in VaD. Our findings suggest that PDW in combination with MMSE scores could be potential indicators for distinguishing VaD from AD.


Vaccination coverage among children in kindergarten - United States, 2013-14 school year.
State and local vaccination requirements for school entry are implemented to maintain high vaccination coverage and protect schoolchildren from vaccine-preventable diseases. Each year, to assess state and national vaccination coverage and exemption levels among kindergartners, CDC analyzes school vaccination data collected by federally funded state, local, and territorial immunization programs. This report describes vaccination coverage in 49 states and the District of Columbia (DC) and vaccination exemption rates in 46 states and DC for children enrolled in kindergarten during the 2013-14 school year. Median vaccination coverage was 94.7% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 95.0% for varying local requirements for diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccine; and 93.3% for 2 doses of varicella vaccine among those states with a 2-dose requirement. The median total exemption rate was 1.8%. High exemption levels and suboptimal vaccination coverage leave children vulnerable to vaccine-preventable diseases. Although vaccination coverage among kindergartners for the majority of reporting states was at or near the 95% national Healthy People 2020 targets for 4 doses of DTaP, 2 doses of MMR, and 2 doses of varicella vaccine, low vaccination coverage and high exemption levels can cluster within communities. Immunization programs might have access to school vaccination coverage and exemption rates at a local level for counties, school districts, or schools that can identify areas where children are more vulnerable to vaccine-preventable diseases. Health promotion efforts in these local areas can be used to help parents understand the risks for vaccine-preventable diseases and the protection that vaccinations provide to their children.


Effects of Xylopia aethiopica (Annonaceae) fruit methanol extract on gamma-radiation-induced oxidative stress in brain of adult male Wistar rats.
Xylopia aethiopica (XA) (Annonaceae) possesses great nutritional and medicinal values. This study was designed to investigate the effects of XA fruit methanol extract on oxidative stress in brain of rats exposed to whole body gamma-radiation (5 Gy). Vitamin C (VC) served as standard antioxidant. Forty-four rats were divided into 4 groups of 11 rats each. One group served as control, two different groups were treated with XA and VC (250 mg/kg), 6 weeks before and 8 weeks after irradiation, and fourth group was only irradiated. Rats were sacrificed 1 and 8 weeks after irradiation. The antioxidant status, viz. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and glutathione (GSH) were estimated. Results indicate a significant increase (p < 0.05) in levels of brain LPO after irradiation. LPO increased by 90% and 151%, after 1 and 8 weeks of irradiation, respectively. Irradiation caused significant (p < 0.05) decreases in levels of GSH and GST by 61% and 43% after 1 week and, 75% and 73%, respectively, after 8 weeks of exposure. CAT and SOD levels were decreased by 62% and 68%, respectively, after 8 weeks of irradiation. Treatment with XA and VC ameliorated the radiation-induced decreases in antioxidant status of the animals. These suggest that XA could have beneficial effect by inhibiting oxidative damage in brain of exposed rats.


Discrete and polymeric, mono- and dinuclear silver complexes of a macrocyclic tetraoxime ligand with AgI-AgI interactions.
Macrocyclic compounds that can bind cationic species efficiently and selectively with their cyclic cavities have great potential as excellent chemosensors for metal ions. Recently, we have developed a tetraoxime-type tetraazamacrocyclic ligand 1 formed through a facile one-pot cyclization reaction. Aiming to explore and bring out the potential of the tetraoxime macrocycle 1 as a chelating sensor, we report herein the preparation of several kinds of silver complexes of 1 and their unique coordination structures determined by single-crystal X-ray diffraction analyses. As a result, the formation of two kinds of discrete structures, monomeric complexes [Ag(1)X] (X = counter anions) and a dimeric complex [Ag2(1)2]X2, and two kinds of polymeric structures from a mononuclear complex, [Ag(1)]nXn, and from a dinuclear complex, [Ag2(1)X2]n, was demonstrated. In the resulting complexes, the structurally flexible macrocyclic ligand 1 was found to provide several different coordination modes. Notably, in some silver complexes of 1, AgI-AgI interactions were observed with different AgI-AgI distances which depend on the kind of counter anions and the chemical composition.


Multidisciplinary care in cancer: do the current research outputs help?
This review examined whether the increased attention on multidisciplinary care (MDC) in cancer over the last 10 years has been underpinned by an increase in methodologically vigorous intervention research in this field. Electronic search of Medline and CINAHL databases. This review examined whether the proportion of (1) data-based and (2) intervention research meeting Cochrane Effective Practice and Organisation of Care (EPOC) criteria increased between two time periods (1997-2001 and 2002-2006). Papers meeting the following inclusion criteria were identified: relevant to MDC for cancer patients; included the term 'multidisciplinary' in the abstract; published in English; published between 1997 and 2006. The proportion of data-based papers did not increase over time, nor did the proportion of intervention papers using EPOC-accepted designs. Only three intervention studies using EPOC-accepted designs were identified, all in the later time period. MDC is widely advocated in cancer care. This review indicates a pressing need to focus attention on the development of rigorous intervention research. Such research should answer important questions such as which models of MDC are most effective, for which outcomes and for which patients.


Waiting lists. Bone of contention.
The number of orthopaedic consultants has increased by 78 per cent since 1984, but average waiting time has hardly changed. Orthopaedics is one of the greatest problem areas for waiting lists although workloads have fallen by about a fifth in the past five years. An extra 85,000 orthopaedic patients will have to be admitted over the next five years if the government is to eliminate waits of more than six months. Consultants oppose the expansion of the staff grades. Specialist centres may have to be established to deal with the backlog.


RB·E2F1 complex mediates DNA damage responses through transcriptional regulation of ZBRK1.
RB plays an essential role in DNA damage-induced growth arrest and regulates the expression of several factors essential for DNA repair machinery. However, how RB coordinates DNA damage response through transcriptional regulation of genes involved in growth arrest remains largely unexplored. We examined whether RB can mediate the response to DNA damage through modulation of ZBRK1, a zinc finger-containing transcriptional repressor that can modulate the expression of GADD45A, a DNA damage response gene, to induce cell cycle arrest in response to DNA damage. We found that the ZBRK1 promoter contains an authentic E2F-recognition sequence that specifically binds E2F1, but not E2F4 or E2F6, together with chromatin remodeling proteins CtIP and CtBP to form a repression complex that suppresses ZBRK1 transcription. Furthermore, loss of RB-mediated transcriptional repression led to an increase in ZBRK1 transcript levels, correlating with increased sensitivity to ultraviolet (UV) and methyl methanesulfonate-induced DNA damage. Taken together, these results suggest that the RB·CtIP (CtBP interacting protein)/CtBP (C terminus-binding protein) /E2F1 complex plays a critical role in ZBRK1 transcriptional repression, and loss of this repression may contribute to cellular sensitivity of DNA damage, ultimately leading to carcinogenesis.


Tandem anion and cation exchange solid phase extraction for the enrichment of micropollutants and their transformation products from ozonation in a wastewater treatment plant.
The presence of organic micropollutants and their transformation products (TPs) from biotic and abiotic processes in aquatic environments is receiving intense public and scientific attention. Yet a suitable sample preparation method that would enable extraction and enrichment of a wide range of such compounds from water is missing. The focus of this paper was to develop an enhanced solid phase extraction (SPE) protocol which enabled isolation of parent compounds and low molecular weight transformation products (that are produced after treatment of water with ozone) from different water matrices. Ten SPE sorbents were evaluated with regard to their ability to extract acidic, neutral, and basic compounds from water at several pH values. Highest recoveries (91-99 %) for all analytes in pure water were obtained by combining strong anion and cation exchangers of two manufacturers in a tandem mode without pH adjustment. Tandem Oasis (MAX+MCX) was finally applied to extract the spiked analytes from tap water, surface water, and several wastewater samples. The efficiency of the used SPE procedure was examined using an optimized liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method using multiple reaction monitoring (MRM) mode. The occurrence of some of the investigated TPs in environmental water matrices was proven for the first time in this study. Method quantification limits (MQLs) for all compounds ranged from 3.7 to 15.3 ng/L in all matrices. Recoveries (%RE) were between 90 and 110 %. Intraday and interday precision, expressed as relative standard deviation, varied from 0.7 to 5.9 % and 1.8 to 10.3 %, respectively. Matrix effect (%ME) evaluation demonstrated that even complex sample matrices did not show significant ion suppression or enhancement. The applicability of the method was shown during two sampling campaigns at Ruhr river and a wastewater treatment plant (WWTP) equipped with an ozonation step after regular biological treatment. The parent compounds were found in all water matrices at concentrations ranging between low nanogram per liter and low microgram per liter. Concentration levels of the detected TPs were in the lower nanogram per liter range. Their concentrations increased after ozonation of treated wastewater but decreased substantially after a polishing biological treatment in the final effluent and in the receiving surface water; thus demonstrating that occurrence at critical concentrations in aquatic ecosystems is rather unlikely.


Thiosuccinyl peptides as Sirt5-specific inhibitors.
Sirtuins, a class of enzymes known as nicotinamide adenine dinucleotide-dependent deacetylases, have been shown to regulate a variety of biological processes, including aging, transcription, and metabolism. Sirtuins are considered promising targets for treating several human diseases. There are seven sirtuins in humans (Sirt1-7). Small molecules that can target a particular human sirtuin are important for drug development and fundamental studies of sirtuin biology. Here we demonstrate that thiosuccinyl peptides are potent and selective Sirt5 inhibitors. The design of these inhibitors is based on our recent discovery that Sirt5 prefers to catalyze the hydrolysis of malonyl and succinyl groups, rather than an acetyl group, from lysine residues. Furthermore, among the seven human sirtuins, Sirt5 is the only one that has this unique acyl group preference. This study demonstrates that the different acyl group preferences of different sirtuins can be conveniently utilized to develop small molecules that selectively target different sirtuins.


A Randomized Parallel Study to Compare the Effects of Powered and Manual Tooth Brushing on Gingival Health and Plaque.
To compare the effect of powered and manual tooth brushing on plaque and gingivitis following two and six weeks of home use. This was a randomized, three-arm, parallel-design clinical trial. Eligible participants were manual toothbrush users who were generally healthy non-smokers, aged 18-65 years, with a plaque score of = 1.8 per Lobene and Soparkar Modified Plaque Index (MPI), and mild to moderate gingivitis, defined as a Gingival Bleeding Index (GBI) = 1 on at least 20 sites. Subjects with advanced periodontal disease, excessive gingival recession, and heavy deposits of calculus or rampant decay were excluded. Enrolled participants were randomly dispensed one of three devices: a powered toothbrush (Philips Sonicare DiamondClean Smart with Premium Gum Care brush head) used in either Gum Heath mode (DC-GH) or Clean mode (DC-C), or an ADA reference manual toothbrush (MTB). Efficacy and safety variables were assessed at Baseline, and at two and six weeks following twice-daily product home use. For the primary endpoint, reduction in gingivitis per Modified Gingival Index (MGI) at Week 2, 188 subjects completed and were included in the analysis. Expressed as percent reduction from Baseline, the adjusted mean reduction and Standard Error (SE) estimates were 60.31% (1.95%) for DC-GH, 53.08% (1.95%) for DC-C, and 16.59% (1.96%) for MTB. The difference between each power toothbrush group and the manual toothbrush was statistically significant (p < 0.0001). Statistically significant differences were also observed between DC-GH, DC-C, and manual tooth brushing for MGI at Week 6, as well as for MPI and GBI at Weeks 2 and 6. The powered toothbrush, used in either Gum Health or Clean mode, was statistically significantly superior to a manual tooth brush in reducing gingival inflammation, gingival bleeding, and plaque following two and six weeks of home use.


In the article the data on the distribution of CYP21A2 gene mutations (gene deletion/conversion, c.290-13C>A/G, E110Vfs, I172N, cluster of mutations I236N, V237E, M239K, V281L, Q318X, R356W) among Ukrainian patients with congenital adrenal hyperplasia of different clinical phenotypes are presented. The most common mutation in the studied group (n = 27) is the CYP21A2 gene deletion/conversion. Possible patterns of the studied mutations distribution in different populations of the world and the patients' genotype – phenotype association are discussed.


Gastroesophageal reflux disease and head and neck cancers: A systematic review and meta-analysis.
Gastroesophageal reflux disease (GERD) has been associated with head and neck cancer (HNC), including laryngeal and pharyngeal anatomical sites. A systematic review and meta-analysis was performed to examine these associations. Articles were retrieved from the Medline, Web of Science, Scopus, and Embase databases using keywords "gastroesophageal reflux disease", "laryngopharyngeal reflux", "head and neck cancer", and associated variants. Inclusion criteria were English language publications, human subjects, and controlled studies with described development of head and neck cancer among individuals with GERD. 13 studies with a total of 39,824 patients were included. Overall, presence of GERD was associated with an increased risk of developing HNC (OR = 1.86, 95% Confidence Interval [CI] = 1.27-2.74). This association remained significant with laryngeal cancers (OR = 1.95, 95% CI = 1.33-2.86), but not pharyngeal cancers (OR = 1.56, 95% CI = 0.86-2.83). Subgroup analyses of hypopharyngeal (OR = 2.26, 95% CI = 0.67-7.68) and oropharyngeal subsites (OR = 1.39, 95% CI = 0.51-3.84) were not statistically significant. Meta-analysis of studies that objectively assessed reflux, such as pH monitor placement, showed statistical significance (OR = 2.81, 95% CI = 1.36-5.81), while studies that used subjective reporting or chart review of GERD were not significant (OR = 1.46, 95% CI = 0.89-2.40). Association between H. pylori infection and head and neck cancers was not statistically significant (OR = 2.66, 95% CI = 0.59-11.97). A diagnosis of GERD is associated with a later diagnosis of HNC, but this association is not significant for pharyngeal cancers. Associations of GERD with HNC may be specific to laryngeal cancers. Systematic review and meta-analysis of case control studies (3a).


Screening for dementia in the older Chinese with a single question test on progressive forgetfulness.
To assess the utility of asking for presence of progressive forgetfulness (PF) prior to administering the Abbreviated Mental Test (AMT) when screening for dementia in the community-dwelling elderly Chinese. This was a two-phased community-based survey of elderly subjects (>or=50 yrs). In phase one, subjects were asked for PF and administered the AMT. Those having PF or an impaired AMT performance were evaluated clinically for dementia in phase two, which also included a randomly selected sample of 35 subjects with no PF and who passed the AMT. 2,566 subjects completed phase one interview, of which 128 subjects completed phase two. Overall prevalence of PF, failed AMT and dementia were 2.4%, 2.2%, 0.9% respectively. The sensitivity of PF for dementia was 95.7% with specificity of 45.1%. PF was significantly associated with depression in the young-old (50-74 yrs) but not in the old-old (>or=75 yrs) age group, after adjusting for dementia. The probability of subjects (%) in the four possible diagnostic combinations of PF and AMT in the young-old and (old-old) age groups were 0 (0.06) in the no PF/ passed AMT, 0 (0.44) in the no PF/failed AMT, 0.23 (9.2) in the PF/passed AMT and 3.6 (43) in the PF/failed AMT groups. In screening for the most common dementias, AMT administration is not required if PF is absent. AMT is also of no added utility for diagnosing dementia in older subjects with PF. Younger subjects with PF should be closely evaluated for depression especially if they passed the AMT, and dementia, if they failed the AMT.


A network for scene processing in the macaque temporal lobe.
Spatial navigation is a complex process, but one that is essential for any mobile organism. We localized a region in the macaque occipitotemporal sulcus that responds preferentially to images of scenes. Single-unit recording revealed that this region, which we term the lateral place patch (LPP), contained a large concentration of scene-selective single units. These units were not modulated by spatial layout alone but were instead modulated by a combination of spatial and nonspatial factors, with individual units coding specific scene parts. We further demonstrate by microstimulation that LPP is connected with extrastriate visual areas V4V and DP and a scene-selective medial place patch in the parahippocampal gyrus, revealing a ventral network for visual scene processing in the macaque.


Performance and reliability comparison of French vertical flow treatment wetlands with other decentralized wastewater treatment technologies in tropical climates.
When implementing a sanitation system, the selection of treatment process can be difficult. Beyond removal efficiency and effluent concentrations, reliability should be taken into account. This study compares reliability of French vertical flow treatment wetlands (F-VFTW) with the four main decentralized wastewater treatment technologies in small communities in the French Overseas Territories (FOT). Analysis of 963 regulatory self-monitoring sampling campaigns performed on 213 wastewater treatment plants show that operational disruptions due to sludge loss and loss of nitrification are often reported for activated sludge technology; rotating biological contactors often suffer from weak settlement; facultative pond removal is limited by algae; and F-VFTW fulfills all the French regulatory objectives at a frequency of 90 to 95%. In addition, the data from this study are compared to a similar database from Brazil using a statistical approach (coefficient of reliability). Amongst the eight decentralized wastewater treatment technologies evaluated, F-VFTW appears to be the most appropriate for achieving the discharge standard with a reliability close to 95%. Its reliability to face both environmental (rainfall) and social (maintenance capacities) constraints is a key parameter.


Results of the promoting effective advance care planning for elders (PEACE) randomized pilot study.
The specific aim of the PEACE pilot study was to determine the feasibility of a fully powered study to test the effectiveness of an in-home geriatrics/palliative care interdisciplinary care management intervention for improving measures of utilization, quality of care, and quality of life in enrollees of Ohio's community-based long-term care Medicaid waiver program, PASSPORT. This was a randomized pilot study (n=40 intervention [IG], n=40 usual care) involving new enrollees into PASSPORT who were >60 years old. This was an in-home interdisciplinary chronic illness care management intervention by PASSPORT care managers collaborating with a hospital-based geriatrics/palliative care specialist team and the consumer's primary care physician. This pilot was not powered to test hypotheses; instead, it was hypothesis generating. Primary outcomes measured symptom control, mood, decision making, spirituality, and quality of life. Little difference was seen in primary outcomes; however, utilization favored the IG. At 12 months, the IG had fewer hospital visits (50% vs. 55%, P=0.65) and fewer nursing facility admissions (22.5% vs. 32.5%, P=0.32). Using hospital-based specialists interfacing with a community agency to provide a team-based approach to care of consumers with chronic illnesses was found to be feasible. Lack of change in symptom control or quality of life outcome measures may be related to the tools used, as these were validated in populations closer to the end of life. Data from this pilot study will be used to calculate the sample size needed for a fully powered trial.


The influence of tropical plant diversity and composition on soil microbial communities.
There is growing interest in understanding the linkages between above- and belowground communities, and very little is known about these linkages in tropical systems. Using an experimental site at La Selva Biological Station, Costa Rica, we examined whether plant diversity, plant community composition, and season influenced microbial communities. We also determined whether soil characteristics were related to differences in microbial communities. Phospholipid fatty acid (PLFA) composition revealed that microbial community composition differed across a plant diversity gradient (plots contained 1, 3, 5, or over 25 species). Plant species identity also was a factor influencing microbial community composition; PLFA composition significantly varied among monocultures, and among three-species combinations that differed in plant species composition. Differences among treatments within each of these comparisons were apparent in all four sampling dates of the study. There was no consistent shift in microbial community composition between wet and dry seasons, although we did see significant changes over time. Of all measured soil characteristics, soil C/N was most often associated with changes in microbial community composition across treatment groups. Our findings provide evidence for human alteration of soil microbial communities via the alteration of plant community composition and diversity and that such changes are mediated in part by changes in soil carbon quality.


Conspecific negative density dependence in rainy season enhanced seedling diversity across habitats in a tropical forest.
Conspecific negative density dependence (CNDD) could be one of the most important local-scale mechanisms shaping plant species coexistence. However, the spatial and temporal changes in the strength CNDD and the implications for the plant diversity remain unknown. We used 10 years of seedling data, in a seasonal tropical rainforest, to discover how CNDD influences tree seedling survival across habitats and seasons. We also evaluated the relation between CNDD and species diversity. We found the strength of CNDD in the valley habitat was significantly stronger than in ridge habitat in rainy season, but not significantly different in dry season. Corresponding to expectations of CNDD as mechanism of diversity maintenance, seedling species diversity was significantly higher in valley habitat than in ridge habitat and significantly correlated with CNDD. Additionally, conspecific and heterospecific seedling neighbour densities positively affected the survival of tree seedlings, but heterospecific adult neighbour density had a weak effect. Our study finds that CNDD varied significantly across habitats and was correlated with local seedling diversity. Our results highlight the importance of CNDD in driving species diversity at the local scale. Recognizing the spatial and temporal variation in the strength of CNDD will aid efforts to model and understand species coexistence.


Bradykinin Type 1 Receptor - Inducible Nitric Oxide Synthase: A New Axis Implicated in Diabetic Retinopathy.
Compelling evidence suggests a role for the inducible nitric oxide synthase, iNOS, and the bradykinin type 1 receptor (B1R) in diabetic retinopathy, including a possible control of the expression and activity of iNOS by B1R. In diabetic retina, both iNOS and B1R contribute to inflammation, oxidative stress, and vascular dysfunction. The present study investigated whether inhibition of iNOS has any impact on inflammatory/oxidative stress markers and on the B1R-iNOS expression, distribution, and action in a model of type I diabetes. Diabetes was induced in 6-week-old Wistar rats by streptozotocin (65 mg.kg-1, i.p.). The selective iNOS inhibitor 1400W (150 μg.10 μl-1) was administered twice a day by eye-drops during the second week of diabetes. The retinae were collected 2 weeks after diabetes induction to assess the protein and gene expression of markers by Western blot and qRT-PCR, the distribution of iNOS and B1R by fluorescence immunocytochemistry, and the vascular permeability by the Evans Blue dye technique. Diabetic retinae showed enhanced expression of iNOS, B1R, carboxypeptidase M (involved in the biosynthesis of B1R agonists), IL-1β, TNF-α, vascular endothelium growth factor A (VEGF-A) and its receptor, VEGF-R2, nitrosylated proteins and increased vascular permeability. All those changes were reversed by treatment with 1400W. Moreover, the additional increase in vascular permeability in diabetic retina induced by intravitreal injection of R-838, a B1R agonist, was also prevented by 1400W. Immunofluorescence staining highlighted strong colocalization of iNOS and B1R in several layers of the diabetic retina, which was prevented by 1400W. This study suggests a critical role for iNOS and B1R in the early stage of diabetic retinopathy. B1R and iNOS appear to partake in a mutual auto-induction and amplification loop to enhance nitrogen species formation and inflammation in diabetic retina. Hence, B1R-iNOS axis deserves closer scrutiny in targeting diabetic retinopathy.


The J-protein AtDjB1 is required for mitochondrial complex I activity and regulates growth and development through ROS-mediated auxin signalling.
AtDjB1 is a mitochondria-located J-protein in Arabidopsis thaliana It is involved in the regulation of plant growth and development; however, the exact mechanisms remain to be determined. We performed comparison analyses of phenotypes, auxin signalling, redox status, mitochondrial structure and function using wild-type plants, AtDjB1 mutants, rescued AtDjB1 mutants by AtDjB1 or YUCCA2 (an auxin synthesis gene), and AtDjB1 overexpression plants. AtDjB1 mutants (atj1-1 or atj1-4) exhibited inhibition of growth and development and reductions in the level of IAA and the expression of YUCCA genes compared to wild-type plants. The introduction of AtDjB1 or YUCCA2 into atj1-1 largely rescued phenotypic defects and the IAA level, indicating that AtDjB1 probably regulates growth and development via auxin. Furthermore, atj1-1 plants displayed a significant reduction in amount/activity of mitochondrial complex I compared to wild-type plants; this resulted in the accumulation of reactive oxygen species (ROS). Moreover, exogenous H2O2 markedly inhibited the expression of YUCCA genes in wild-type plants. In contrast, the reducing agent ascorbate increased the expression of YUCCA genes and IAA level in atj1-1 plants, indicating that the low auxin level observed in atj1-1 was probably due to the high oxidation status. Overall, the data presented here suggest that AtDjB1 is required for mitochondrial complex I activity and regulates growth and development through ROS-mediated auxin signalling in Arabidopsis.


Antifungal drugs affect adherence of Candida albicans to acrylic surfaces by changing the zeta-potential of fungal cells.
The effect of sub-inhibitory concentrations of antifungal drugs on the adherence of Candida albicans to acrylic surfaces was investigated. Among five antifungals tested, azalomycin F and aculeacin A significantly enhanced the adherence. The zeta-potential of fungal cells was affected by antifungal drugs, whereas no significant change in cell surface hydrophobicity was observed. The relationship obtained between the change in the adherence and that in zeta-potential suggests that the enhanced adherence was caused by decreased electric repulsive forces.


Lobster attack induces sensitization in the sea hare, Aplysia californica.
Studies of the neural mechanisms of learning, especially of sensitization, have benefitted from extensive research on the model species, Aplysia californica (hereafter Aplysia). Considering this volume of literature on mechanisms, it is surprising that our understanding of the ecological context of sensitization in Aplysia is completely lacking. Indeed, the widespread use of strong electric shock to induce sensitization (an enhancement of withdrawal reflexes following noxious stimulation) is completely unnatural and leaves unanswered the question of whether this simple form of learning has any ecological relevance. We hypothesized that sublethal attack by a co-occurring predator, the spiny lobster, Panulirus interruptus, might be a natural sensitizing stimulus. We tested reflex withdrawal of the tail-mantle and head of individual Aplysia before and after attack by lobsters. Lobster attack significantly increased the amplitude of both reflexes, with a temporal onset that closely matched that observed with electric shock. This result suggests that electric shock may indeed mimic at least one naturally occurring sensitizing stimulus, suggesting, for the first time, an ecological context for this well studied form of learning.


New double-quantum filtering schemes.
New double-quantum filtering (DQF) schemes are theoretically developed by reformulating the equations describing the double-quantum (DQ) signal. The equations describing the second- and third-rank DQ signals are simplified by restricting the RF phases as required for DQF. The equations are then factorized into two terms representing the separate contribution to the DQ signal from the RF pulses involved in the preparation and evolution times. This allows analysis of the DQ signal of a particular DQF scheme separately for each of these times in a concise manner. By use of the reformulated equations, the conventional DQF scheme is shown to be only one of four possible DQF schemes. The three new DQF schemes offer some desirable properties over the conventional DQF scheme. In the conventional DQF scheme, the third-rank DQ signal declines rapidly to null as the flip angles of the creation and readout RF pulses deviate from 90 degrees to 54.7 degrees or 125.3 degrees. In addition, the second- and third-rank DQ signals in the conventional DQF scheme are opposite in their polarities, resulting in attenuation of the total DQ signal due to destructive interference between them. In one of three new DQF schemes, the DQ signal does not vanish at 54.7 degrees and 125.3 degrees, but varies smoothly with the same functional dependence on the RF flip angles as the second-rank DQ and triple-quantum signals. Furthermore, in two of the three new DQF schemes, the second- and third-rank DQ signals have the same polarity so that the total DQ signal may be enhanced through constructive interference between them. These features of new DQF schemes have been confirmed experimentally.


Hollow metal target magnetron sputter type radio frequency ion source.
A 70 mm diameter 70 mm long compact ion source equipped with a hollow sputtering target has been designed and tested. The hollow sputtering target serves as the radio frequency (RF) plasma excitation electrode at 13.56 MHz. A stable beam of Cu(+) has been extracted when Ar was used as the discharge support gas. In the extracted beam, Cu(+) had occupied more than 85% of the total ion current. Further increase in Cu(+) ions in the beam is anticipated by increasing the RF power and Ar pressure.


A placebo-controlled trial of gabapentin for painful HIV-associated sensory neuropathies.
Painful HIV-associated sensory neuropathies (HIV-SN) are a common complication of HIV infection. The pathogenesis is unknown and the treatment very limited. Gabapentin (GBP) is effective in painful diabetic neuropathy and postherpetic neuralgia and its effectiveness on painful HIV-SN has been reported anecdotally. Multicenter, prospective, randomised, double-blind, placebo-controlled study. Patients were followed for a 1-week screening, a 4-week double-blind and a 2-week open treatment phase. GBP was initiated at 400 mg/d, titrated over 2 weeks to 1200 mg/d, and then either maintained at this level or-if not beneficial-titrated to 2400 mg/d. After 4 weeks the medication was unblinded and the patient had the choice to begin, to maintain or to increase GBP to 3600 mg/d. The primary outcome measure was an improvement in median pain on the Visual Analogue Scale (VAS) from the screening week compared to the 4(th) treatment week. A secondary efficacy measure was the median sleep score (VAS). 15 patients received GBP and 11 placebo. In each group one patient dropped out during the doubleblind phase. Median pain (GBP 5.1; placebo 4.7) and sleep score (GBP 4.5; placebo 5.6) did not differ between both groups at baseline. In the GBP-group there was a significant decrease of the pain to 2.85 (-44.1 %) as well as of the sleep VAS to 2.3 (-48.9 %). No significant decrease in the pain (median VAS=3.3, -29.8 %) as well as in the sleep score (median VAS=4.95, -11.6 %) was observed in the placebo-group. GBP was generally well tolerated. The most frequent side effect was somnolence reported in 80% of GBP-treated patients. GBP was more effective than placebo in reducing pain and sleep interference in patients with HIV-SN.


Stereotactic functional mapping of the cat motor cortex.
Epidural motor cortex stimulation is an increasingly used method to control refractory neuropathic pain although its mechanisms of action remain poorly understood. Animal models are currently developed that allow reproducing the conditions of this neurosurgical approach and clarifying its mechanisms. In this study we validate a new stereotactic functional map of the cat motor cortex carried out in epidural conditions, thus allowing future experimentations that closely mimic the technique used in humans.


Alterations of resting state functional connectivity in the default network in adolescents with autism spectrum disorders.
Autism spectrum disorders (ASD) are associated with disturbances of neural connectivity. Functional connectivity between neural structures is typically examined within the context of a cognitive task, but also exists in the absence of a task (i.e., "rest"). Connectivity during rest is particularly active in a set of structures called the default network, which includes the posterior cingulate cortex (PCC), retrosplenial cortex, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus. We previously reported that adults with ASD relative to controls show areas of stronger and weaker connectivity within the default network. The objective of the present study was to examine the default network in adolescents with ASD. Sixteen adolescents with ASD and 15 controls participated in a functional MRI study. Functional connectivity was examined between a PCC seed and other areas of the default network. Both groups showed connectivity in the default network. Relative to controls, adolescents with ASD showed widespread weaker connectivity in nine of the eleven areas of the default network. Moreover, an analysis of symptom severity indicated that poorer social skills and increases in restricted and repetitive behaviors and interests correlated with weaker connectivity, whereas poorer verbal and non-verbal communication correlated with stronger connectivity in multiple areas of the default network. These findings indicate that adolescents with ASD show weaker connectivity in the default network than previously reported in adults with ASD. The findings also show that weaker connectivity within the default network is associated with specific impairments in ASD.


Association between prenatal and neonatal factors and occurrence of asthma symptoms in six-year-old children.
The objective was to estimate association between prenatal and neonatal factors and asthma symptoms in children at six years of age. A cross-sectional study using secondary data from a cohort study with a sample of 578 children was carried out. Data were analyzed using three levels hierarchical Poisson Regression. Of the 578 children included in the study, 43.4% (95% CI 39.4; 47.4) had asthma symptoms. The variables with significantly higher prevalence of symptoms and asthma at six years of age were: male gender, with 5% higher prevalence (PR = 1.05 95% CI 1.01; 1.11) (p = 0.043); children of pregnant women presenting infectious diseases with 7% higher prevalence (PR = 1.07; 95% CI 1.02; 1.13) (p = 0.011); children who were not breastfed, with a 12% higher prevalence (PR = 1.12; 95% CI 1.02; 1.24) (p = 0.022) and children with respiratory problems in the first month of life, with a 14% higher prevalence (PR = 1.14; 95% CI 1.01; 1.29) (p = 0.033). It could be concluded that male gender, time-independent breastfeeding deprivation and respiratory problems in the first month of life were independently associated with asthma symptoms at six years of age. The occurrence of infectious diseases during pregnancy was the only factor with intrauterine physiology that was associated with the occurrence of asthma symptoms at six years of age.


How Should Medical Schools Foster Equity and Inclusion in Admissions?
This commentary in response to a case considers how merit and features of medical school applicants' dossiers should be drawn upon in admissions processes to promote equity and inclusion in medicine. It is argued that medical schools should incentivize inclusion by redefining merit in their admissions goals and processes, promote meaningful inclusion, and show institutional leadership in addressing social justice.


Insula volumes in first-episode and chronic psychosis: A longitudinal MRI study.
Alterations in insular grey matter (GM) volume has been consistently reported for affective and non-affective psychoses both in chronic and first-episode patients, ultimately suggesting that the insula might represent a good region to study in order to assess the longitudinal course of psychotic disorders. Therefore, in this longitudinal Magnetic Resonance Imaging (MRI) study, we aimed at further investigating the key role of insular volumes in psychosis. 68 First-Episode Psychosis (FEP) patients, 68 patients with Schizophrenia (SCZ), 47 Bipolar Disorder (BD) patients, and 94 Healthy Controls (HC) were enrolled and underwent a 1.5 T MRI evaluation. A subsample of 99 subjects (10 HC, 23 BD, 29 SCZ, 37 FEP) was rescanned after 2,53 ± 1,68 years. The insular cortex was manually traced and then divided into an anterior and posterior portion. Group and correlation analyses were then performed both at baseline and at follow-up. At baseline, greater anterior and lower posterior insular GM volumes were observed in chronic patients. At follow-up, we found that FEP patients had a significant GM volume increase from baseline to follow-up, especially in the posterior insula whereas chronic patients showed a relative stability. Finally, significant negative correlations between illness severity and pharmacological treatment and insular GM volumes were observed in the whole group of psychotic patients. The longitudinal assessment of both chronic and first-episode patients allowed us to detect a complex pattern of GM abnormalities in selective sub-portions of insular volumes, ultimately suggesting that this structure could represent a key biological marker of psychotic disorders.


Endovascular treatment for peripheral pulmonary artery aneurysm.
A 42-year-old male presented with recurrent hemoptysis owing to a leaking peripheral pulmonary artery aneurysm. He was treated with selective coil embolization of the right posterior basal segmental artery to achieve hemostasis. This case is reported for its unsuspected presentation and rarity and to highlight the use of catheter coil embolization to achieve endovascular exclusion of the aneurysm from pulmonary circulation.


Mitigating emotional responses to stressors: coping strategies, modifiers and support.
The stressful nature of the intensive care unit (ICU) environment is increasingly well characterised. The aim of this paper was to explore modifiers, coping strategies and support pathways identified by experienced Intensivists, in response to these stressors. Prospective qualitative study employing interviews with Intensivists in two countries. Participants were asked how they mitigated their emotional responses to the stressors of the ICU. Audio-recordings were transcribed and analysed by all researchers who agreed upon emerging themes and subthemes. A wide range of strategies were reported. Although several participants had sought professional help and all supported its utility, few disclosed accessing such help to others indicating stigma. Many felt a sense of responsibility for the well-being of other staff but identified barriers that suggest alternate support pathways are required. Further implications of these findings to training considerations are described. Several approaches were described as regularly employed by Intensivists to mitigate ICU environmental stressors. Intensivists perceive themselves to have limited training to provide support to others; they also perceive stigma in seeking professional help.


Physicians' psychosocial beliefs correlate with their patient communication skills.
To assess the relationship between physicians' beliefs about the psychosocial aspects of patient care and their routine communication with patients. Fifty community primary care physicians participating in a continuing medical education program and 473 of their patients in Portland, Oregon. Routine office visits were audiotaped and analyzed for communication behaviors and emotional tone using the Roter Interactional Analysis System (RIAS). Physician beliefs about psychosocial aspects of care were measured using a self-report questionnaire with a five-point Likert scale. Attitudes were correlated with communication behaviors using the Pearson correlation coefficient. Physicians' attitudes toward psychosocial aspects of care were associated with both physician and patient dialogue in visits. The physicians who had positive attitudes used more statements of emotion (i.e., empathy, reassurance) (p < 0.05) and fewer closed-ended questions (p < 0.01) than did their colleagues who had less positive attitudes. The patients of the physicians who had positive attitudes more actively participated in care (i.e., expressing opinions, asking questions), and these physicians provided relatively more psychosocial and less biomedical information (p < 0.05). Physician beliefs about psychosocial aspects of patient care are associated with their communication with patients in routine office visits. Patients of physicians with more positive attitudes have more psychosocial discussions in visits than do patients of physicians with less positive attitudes. They also appear more involved as partners in their care. These findings have implications for medical educators, teachers, and practicing physicians.


Targeted Analysis of Sphingolipids in Turkeys Fed Fusariotoxins: First Evidence of Key Changes That Could Help Explain Their Relative Resistance to Fumonisin Toxicity.
The effects of fumonisins on sphingolipids in turkeys are unknown, except for the increased sphinganine to sphingosine ratio (Sa:So) used as a biomarker. Fumonisins fed at 20.2 mg/kg for 14 days were responsible for a 4.4 fold increase in the Sa:So ratio and a decrease of 33% and 36% in C14-C16 ceramides and C14-C16 sphingomyelins, respectively, whereas C18-C26 ceramides and C18-C26 sphingomyelins remained unaffected or were increased. Glucosyl- and lactosyl-ceramides paralleled the concentrations of ceramides. Fumonisins also increased dihydroceramides but had no effect on deoxysphinganine. A partial least squfares discriminant analysis revealed that all changes in sphingolipids were important in explaining the effect of fumonisins. Because deoxynivalenol and zearalenone are often found in feed, their effects on sphingolipids alone and in combination with fumonisins were investigated. Feeding 5.12 mg deoxynivalenol/kg reduced dihydroceramides in the liver. Zearalenone fed at 0.47 mg/kg had no effect on sphingolipids. When fusariotoxins were fed simultaneously, the effects on sphingolipids were similar to those observed in turkeys fed fumonisins alone. The concentration of fumonisin B1 in the liver of turkeys fed fumonisins was 0.06 µmol/kg. Changes in sphingolipid concentrations differed but were consistent with the IC50 of fumonisin B1 measured in mammals; these changes could explain the relative resistance of turkeys to fumonisins.


Malignant mixed müllerian tumors of the ovary: experience with surgical cytoreduction and combination chemotherapy.
The role of surgical cytoreduction and combination chemotherapy for malignant mixed müllerian tumors (MMMT) of the ovary was evaluated. A retrospective review of 27 women with ovarian MMMT treated from 1980 to 1990 was performed. The International Federation of Gynecology and Obstetrics stages for the 27 women were 1 Stage I, 3 Stage II, 17 Stage III, and 6 Stage IV. Only 10 of the 23 patients with Stage III or IV disease were cytoreduced optimally. With respect to postoperative therapy, 3 women received no treatment, 6 were treated with whole abdomen radiotherapy, 1 received melphalan, and 17 received chemotherapy incorporating a platinum agent (3), doxorubicin (4), or both (10). The significant prognostic factors were stage (P < 0.001) and, for women with Stage III or IV disease, the feasibility of cytoreductive surgery (P = 0.03). The four patients in Stages I or II remained disease free after an interval of at least 5 years. The median and 5-year survival rates for patients with Stages III or IV disease was 18 months and 8%, respectively. Patients in Stage III or IV for whom optimal cytoreduction was not possible had a 2-year survival of 14%, whereas optimal cytoreduction was associated with a 52% 2-year survival. Median survival for the 14 women with Stage III or IV ovarian MMMT treated with combination chemotherapy was 25 months and nine women achieved progression free intervals of greater than 18 months. Aggressive surgical cytoreduction followed by combination chemotherapy may result in improved progression free intervals for women with advanced ovarian MMMT. However, a major improvement in prognosis for this rare malignancy has not yet been achieved.


Stem Cell Factor in Combination With Granulocyte Colony-Stimulating Factor Protects the Brain From Capillary Thrombosis-Induced Ischemic Neuron Loss in a Mouse Model of CADASIL.
Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) is a Notch3 mutation-induced cerebral small vessel disease, leading to recurrent ischemic stroke and vascular dementia. There is currently no treatment that can stop or delay CADASIL progression. We have demonstrated the efficacy of treatment with combined stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) (SCF+G-CSF) in reducing cerebral small vessel thrombosis in a TgNotch3R90C mouse model of CADASIL. However, it remains unknown whether SCF+G-CSF treatment protects neurons from microvascular thrombosis-induced ischemic damage. Using bone marrow transplantation to track thrombosis, we observed that capillary thrombosis was widely distributed in the cortex, striatum and hippocampus of 22-month-old TgNotch3R90C mice. However, the capillary thrombosis mainly occurred in the cortex. Neuron loss was seen in the area next to the thrombotic capillaries, and severe neuron loss was found in the areas adjacent to the thrombotic capillaries with bifurcations. SCF+G-CSF repeated treatment significantly attenuated neuron loss in the areas next to the thrombotic capillaries in the cortex of the 22-month-old TgNotch3R90C mice. Neuron loss caused by capillary thrombosis in the cerebral cortex may play a crucial role in the pathogenesis of CADASIL. SCF+G-CSF treatment ameliorates the capillary thrombosis-induced ischemic neuron loss in TgNotch3R90C mice. This study provides new insight into the understanding of CADASIL progression and therapeutic potential of SCF+G-CSF in neuroprotection under microvascular ischemia in CADASIL.


Generation of nonviral integration-free human iPS cell line KISCOi001-A from normal human fibroblasts, under defined xeno-free and feeder-free conditions.
KISCOi001-A is a healthy feeder-free and fully characterized human induced pluripotent stem (iPS) cell line cultured under xeno-free and defined conditions. The cell line is generated from normal human foreskin fibroblasts with non-integrating episomal plasmid vectors encoding OCT4, SOX2, KLF4, NANOG, LIN28, nontransforming L-MYC and dominant negative p53. The generated iPS cells are transgene-free and their pluripotency is confirmed by the expression of stem cell markers and capacity to differentiate into the cells of ectoderm, endoderm and mesoderm while their identity and karyotype stability is confirmed with Genomic assays.


Human acidic fibroblast growth factor has trophic effects on cultured neurons from multiple regions of brain and retina.
Neurotrophic activities of human recombinant acidic fibroblast growth factor (haFGF) were evaluated on primary cultured neurons from various brain regions and compared with those of CS23, modified human basic fibroblast growth factor. Survival of cultured neurons from embryonic day 16 (E16) rat cortex and substantia nigra was significantly increased by the addition of more than 10 ng/ml haFGF and that from the hippocampus was increased by 100 and 1000 ng/ml. However, enhancement of viability by haFGF was observed only in 1000 ng/ml-treated neurons from the striatum, thalamus, colliculus and cerebellum; and it was not observed in septal neurons. Survival of cultured neurons from postnatal day 15 rat on glial feeder layer was significantly increased by the addition of 1000 ng/ml haFGF, except for neurons from the septum. CS23 (10 ng/ml) increased the survival of cultured neurons from all regions mentioned above, and its effects were stronger than those of 1000 ng/ml haFGF. Addition of more than 10 ng/ml haFGF significantly increased the survival of cultured neurons from neonatal day 2 rat retina. Addition of 1000 ng/ml haFGF increased the choline acetyltransferase activity of E16 septal neurons slightly but significantly, but didn't increase the dopamine uptake activity of embryonic day E15 ventral midbrain. These results show that haFGF is effective on limited regions and ages of brain and retina, while CS23 is effective on all regions tested.


Excited-state properties of octahedral hexarhenium(III) complexes with redox-active N-heteroaromatic ligands.
New sulfide-capped octahedral hexarhenium(III) complexes containing 4-phenylpyridine (ppy) or 1,2-bis(4-pyridyl)ethane (bpe) ((n-C(4)H(9))(4)N)[mer-{Re(6)S(8)Cl(3)(ppy)(3)}] ((Bu(4)N)[1]), ((n-C(4)H(9))(4)N)(2)[trans-{Re(6)S(8)Cl(4)(ppy)(2)}] ((Bu(4)N)(2)[2a]), ((n-C(4)H(9))(4)N)(2)[cis-{Re(6)S(8)Cl(4)(ppy)(2)}] ((Bu(4)N)(2)[2b]), ((n-C(4)H(9))(4)N)(2)[trans-{Re(6)S(8)Cl(4)(bpe)(2)}] ((Bu(4)N)(2)[3a]), and ((n-C(4)H(9))(4)N)(2)[cis-{Re(6)S(8)Cl(4)(bpe)(2)}] ((Bu(4)N)(2)[3b]) were prepared, and X-ray single-crystal structure determination was carried out for (Bu(4)N)(2)[2a] and (Bu(4)N)(2)[3a]. The photophysical properties of these complexes were studied both in acetonitrile at 298 K and in the solid state at 298 and 80 K, along with those of the known 4,4'-bipyridine (bpy) analogues ((n-C(4)H(9))(4)N)[mer-{Re(6)S(8)Cl(3)(bpy)(3)}] ((Bu(4)N)[4]), ((n-C(4)H(9))(4)N)(2)[trans-{Re(6)S(8)Cl(4)(bpy)(2)}] ((Bu(4)N)(2)[5a]), and ((n-C(4)H(9))(4)N)(2)[cis-{Re(6)S(8)Cl(4)(bpy)(2)}] ((Bu(4)N)(2)[5b]). The photophysical data of [5a](2-) and [5b](2-) in solution and in the solid state were significantly different from those of other complexes. On the basis of experimental observations of [2a](2-) and [5a](2-) and density-functional theory (DFT) calculations, it was concluded that [5a](2-) and [5b](2-) exhibited metal (Re(6)S(8) core)-to-ligand (bpy) charge transfer (MLCT) type emission. This is the first unambiguous demonstration of MLCT type emissions for the hexarhenium complexes. The MLCT components, where present, are only minor in the case of the emissions of [1](-), [2a](2-), [2b](2-), and [4](-); these can be explained primarily as the contributions of the intracore electronic transitions. The emissions of [3a](2-) and [3b](2-) can be assigned almost completely to the electronic transitions within the Re(6)S(8) core. The different emission characteristics of the bis(bpy) complexes ([5a](2-) and [5b](2-)) from the tris(bpy) complex ([4](-)) are a result of the increase in the number of nitrogen donors on the Re(6)S(8) core, which stabilizes the Re(6)S(8) core energy to a lower level than the energy of the bpy ligand pi* orbital. On the other hand, it has been shown that the emissions of the bis(ppy) ([2a](2-) and [2b](2-)) and bis(bpe) complexes ([3a](2-) and [3b](2-)) are best characterized by the higher pi* energy level of each N-heteroaromatic ligand, which lead to a stronger metal character in the emissive excited state of the complex.


The study of polyplex formation and stability by time-resolved fluorescence spectroscopy of SYBR Green I-stained DNA.
Polyplexes are nanoparticles formed by the self-assembly of DNA/RNA and cationic polymers specifically designed to deliver exogenous genetic material to cells by a process called transfection. There is a general consensus that a subtle balance between sufficient extracellular protection and intracellular release of nucleic acids is a key factor for successful gene delivery. Therefore, there is a strong need to develop suitable tools and techniques for enabling the monitoring of the stability of polyplexes in the biological environment they face during transfection. In this work we propose time-resolved fluorescence spectroscopy in combination with SYBR Green I-DNA dye as a reliable tool for the in-depth characterization of the DNA/vector complexation state. As a proof of concept, we provide essential information on the assembly and disassembly of complexes formed between DNA and each of three cationic polymers, namely a novel promising chitosan-graft-branched polyethylenimine copolymer (Chi-g-bPEI), one of its building block 2 kDa bPEI and the gold standard transfectant 25 kDa bPEI. Our results highlight the higher information content provided by the time-resolved studies of SYBR Green I/DNA, as compared to conventional steady state measurements of ethidium bromide/DNA that enabled us to draw relationships among fluorescence lifetime, polyplex structural changes and transfection efficiency.


Transrectal Doppler sonography of uterine blood flow in cows during pregnancy.
Transrectal Doppler ultrasound was used for the noninvasive investigation of uterine blood flow in three cows during pregnancy. The uterine arteries ipsi and contralateral to the conceptus were scanned monthly. Blood flow was reflected by the following parameters: resistance index (RI), time-averaged maximum velocity (TAMV), diameter of the vessel (D) and the volume of blood flow (VOL). RI values were negatively correlated to all other blood flow parameters (P < 0.01). Positive correlations occurred between TAMV, D and VOL (P < 0.0001). While blood flow parameters did not differ between cows (P > 0.05), the month of gestation showed a positive effect on RI and negative effects on TAMV, D and VOL (P < 0.0001). The RI was lower and TAMV, D and VOL higher in the uterine artery ipsilateral to the conceptus (P < 0.05). RI values decreased continuously during the first 8 months of gestation and remained from then until birth at a relatively constant level. While TAMV increased especially in two-thirds of pregnancy, a relatively uniform rise of D was noticed. VOL increased exponentially with stage of gestation. The results show that transrectal Doppler sonography is a suitable, noninvasive method for the examination of uterine blood flow during pregnancy in cows. Using this technique it might be possible in the future to determine the role of uterine blood flow in cows at the risk of abortion.


A conserved flagellar pocket exposed high mannose moiety is used by African trypanosomes as a host cytokine binding molecule.
Trypanosomes use antigenic variation of their variant-specific surface glycoprotein (VSG) coat as defense against the host immune system. However, in order to sustain their growth, they need to expose conserved epitopes, allowing host macromolecule binding and receptor-mediated endocytosis. Here we show that Trypanosoma brucei uses the conserved chitobiose-oligomannose (GlcNAc(2)-Man(5-9)) moieties of its VSG as a binding ligand for tumor necrosis factor (TNF), a host cytokine with lectin-like properties. As endocytosis in trypanosomes is restricted to the flagellar pocket, we show that soluble flagellar pocket extracts, and in particular soluble VSG, inhibit the binding of (125)I-TNF to trypanosomes. The interaction between TNF and VSG is confirmed by affinity chromatography, biosensor, and dot-blot affinity measurements, and soluble VSG inhibition of TNF-mediated trypanolysis. In all approaches, removal of N-linked carbohydrates abrogates the TNF-VSG interaction. In addition, synthetic high mannose oligosaccharides can block TNF-VSG interactions, and a VSG glycopeptide carrying the GlcNAc(2)-Man(5-9) moiety is shown to inhibit TNF-mediated trypanosome killing in mixed parasite/macrophage cell cultures. Together, these results support the observation that TNF plays a role in growth control of trypanosomes and, moreover, suggest that, by the use of conserved VSG carbohydrates as lectin-binding epitopes, trypanosomes can limit the necessity to express large numbers of invariant surface exposed receptors.


Reemergence of the fetal pattern of L-type calcium channel gene expression in non infarcted myocardium during left ventricular remodeling.
The cardiac L-type voltage-dependent calcium channel (VDCC) is a critical component of cardiac action potential and excitation-contraction coupling. The objective of the present study was to examine the changes in expression in Motif IV, an alternatively spliced region of the alpha-1 subunit of the VDCC channel in postmyocardial infarction (MI) remodeled rat left ventricle. RNase protection assay was used to determine alteration in isoform expression in the noninfarcted hypertrophied ventricular myocardium 21 days post myocardial infarction. Our study demonstrates that cardiac hypertrophy is associated with significant increase in the mRNA level of the fetal isoform, with the reversion of fetal:adult isoform ratio to the fetal phenotype. Changes in isoform expression in the post-MI remodeled ventricle, not previously reported, is a pertinent genetic marker of cardiac hypertrophy.


Side-Chain Engineering of Diketopyrrolopyrrole-Based Hole-Transport Materials to Realize High-Efficiency Perovskite Solar Cells.
The design and synthesis of a stable and efficient hole-transport material (HTM) for perovskite solar cells (PSCs) are one of the most demanding research areas. At present, 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9'-spirobifluorene (spiro-MeOTAD) is a commonly used HTM in the fabrication of high-efficiency PSCs; however, its complicated synthesis, addition of a dopant in order to realize the best efficiency, and high cost are major challenges for the further development of PSCs. Herein, various diketopyrrolopyrrole-based small molecules were synthesized with the same backbone but distinct alkyl side-chain substituents (i.e., 2-ethylhexyl-, n-hexyl-, ((methoxyethoxy)ethoxy)ethyl-, and (2-((2-methoxyethoxy)ethoxy)ethyl)acetamide, designated as D-1, D-2, D-3, and D-4, respectively) as HTMs. The variation in the alkyl chain has shown obvious effects on the optical and electrochemical properties as well as on the molecular packing and film-forming ability. Consequently, the power conversion efficiency (PCE) of the PSC under one sun illumination (100 mW cm-2) is shown to increase in the order of D-1 (8.32%) < D-2 (11.12%) < D-3 (12.05%) < D-4 (17.64%). Various characterization techniques reveal that the superior performance of D-4 can be ascribed to the well-aligned highest occupied molecular orbital energy level with the counter electrode, the more compact π-π stacking with a higher coherence length, and the excellent hole mobility of 1.09 × 10-3 cm2 V-1 s-1, thus providing excellent energetics for effective charge transport with minimal charge-carrier recombination. Furthermore, the addition of the dopant Li-TFSI in D-4 is shown to deliver a remarkable PCE of 20.19%, along with a short-circuit current density (JSC), open-circuit voltage (VOC), and fill factor (FF) of 22.94 mA cm-2, 1.14 V, and 73.87%, respectively, and superior stability compared to that of other HTMs. These results demonstrate the effectiveness of side-chain engineering for tailoring the properties of HTMs, thus offering new design tactics to fabricate for the synthesis of highly efficient and stable HTMs for PSCs.


Unilateral Knee and Ankle Joint Fatigue Induce Similar Impairment to Bipedal Balance in Judo Athletes.
The purpose of this study was to compare the effects of unilateral ankle fatigue versus the knee muscles with and without vision on bipedal postural control. Elite judo athletes who competed at the national level with at least 10 years of training experience, were randomised into KNEE (n = 10; 20 ± 2 years) and ANKLE (n = 9; 20 ± 3 years) groups, who performed dynamic isokinetic fatiguing contractions (force decreased to 50% of initial peak torque for three consecutive movements) of the knee flexors and extensors or ankle dorsiflexors and plantar flexors, respectively. Static bipedal postural control (French Posturology Association normative standards) with eyes open and eyes closed was examined before and immediately after the fatiguing task. Postural variables examined were the centre of pressure (CoP) sway in the medio-lateral and antero-posterior directions, total CoP area sway and CoP sway velocity. Although unilateral ankle and knee fatigue adversely affected all bipedal postural measures, with greater disturbances with eyes closed, there were no significant main group or interaction effects between KNEE and ANKLE groups. Unilateral lower limb fatigue adversely affected bipedal balance, with knee extension/flexion fatigue affecting bipedal postural control to a similar extent as unilateral ankle dorsiflexion/plantar flexion fatigue. Hence unilateral fatigue can affect subsequent bilateral performance or also have implications for rehabilitation exercise techniques. Our findings may be limited to judo athletes as other populations were not tested.


S4646 polymorphism in CYP19A1 gene is associated with the efficacy of hormone therapy in early breast cancer.
The aim was to verify the potential association between CYP19A1 genetic polymorphisms and clinical outcome of hormone therapy in hormone receptor (HR)-positive early breast cancer. Genotyping for CYP19A1 rs4646 (C/A) polymorphism was performed on 287 women with HR-positive early breast cancer. Associations were evaluated between CYP19A1 rs4646 genotypes and disease-free survival (DFS). Totally, women with the minor allele (AA or AC) had an improved DFS when compared with those carrying the homozygous common allele (CC) (AA or AC vs. CC: 62.7 months versus 55.6 months; Hazard ratio (HR), 0.745; 95% CI, 0.562-0.988; P=0.04). The difference was further demonstrated by multivariate analyses (HR, 0.681; 95% CI, 0.506-0.917; P=0.011). In premenopausal women, AA genotype was associated with a prolonged DFS (AA versus CC or AC: 98.2 months versus 56.2 months; HR, 0.425; 95% CI, 0.198-0.914; P=0.024). In addition, women with the A allele had an improved DFS when compared with those carrying the homozygous C allele (AA or AC vs. CC: 62.7 months versus 55.6 months; HR, 0.709; 95% CI, 0.516-0.975; P=0.033). These findings were further confirmed by the Cox regression model (HR, 0.336, 0.670; 95% CI, 0.160-0.836, 0.479-0.938; P=0.017, 0.019). In postmenopausal women, rs4646 genotypes were significantly associated with DFS (AA versus AC versus CC: 32.7 months versus not reached versus 56.3 months; P=0.011). Women carrying AA variant had a poorer DFS than those with CC or AC genotypes (32.7 months versus 70.6 months; HR, 3.613; 95% CI, 1.380-9.457; P=0.005). Furthermore, being adjusted by the patients features in multivariate analyses, AA genotype remained an independent prognostic factor for DFS (HR, 3.614; 95% CI, 1.308-9.991; P=0.013). The homozygous minor allele (AA) of CYP19A1 rs4646 is significantly associated with improved clinical outcome of hormone therapy in premenopausal HR-positive early breast cancer patients, but with a worse impact on postmenopausal women. The findings are novel, if confirmed, genotyping for CYP19A1 rs4646 polymorphism may provide predictive information for better selection of endocrine treatment.


Intermediate-Term and Long-Term Outcomes With the Boston Type 1 Keratoprosthesis in Aniridia.
To report the intermediate- and long-term visual outcomes and complications with the Boston type 1 keratoprosthesis (KPro) for the management of aniridic keratopathy. A retrospective chart review of 46 eyes of 34 patients (20 females and 14 males) with aniridic keratopathy who underwent Boston type 1 KPro surgery by a single surgeon from 2004 to 2012 with minimum 2-year follow-up was conducted. Preoperative, intraoperative, and postoperative parameters were collected and analyzed. The primary outcome was the change in best-corrected visual acuity. Secondary outcomes included the rate of retroprosthetic membrane formation, glaucoma progression, glaucoma tube revisions, and KPro retention. Mean age of the patients was 43.5 ± 19.8 years with a mean follow-up period of 4.5 ± 1.6 years (range 2-7.4 years). Thirty-four eyes (74%) had previously failed keratoplasty. Thirty-five eyes (76%) previously underwent ocular surface stem cell transplantation, specifically a keratolimbal allograft. Within the first 6 months postoperatively, 74% (34/46) of patients experienced a gain of ≥2 lines of vision. Overall, there was a gain of ≥2 lines of vision in 43.5% (20/46) of patients at last follow-up. The rate of retroprosthetic membrane formation was 61%, the rate of glaucoma onset/progression was 26%, the rate of tube revision was 31%, and the KPro retention rate was 87%. This study confirms that initial visual improvement in aniridic keratopathy cases occurs at a high rate with the Boston type 1 KPro but also found progressive loss of these initial visual improvements.


Safety and efficacy of lacosamide in the intensive care unit.
Seizures are common in critically ill patients and can impact morbidity and mortality. Traditional anti-epileptic drugs (AEDs) in this setting are not always effective and are associated with adverse events and drug interactions. Lacosamide (LCM) is a new AED which is available in parental form although few studies have evaluated the safety and efficacy of LCM in critically ill patients. Critically ill patients at Emory University Hospital who received LCM from April 1, 2009 to February 1, 2010 were retrospectively reviewed. Primary outcome measure was incidence and time to seizure cessation. Adverse effects were also recorded. LCM was administered in 24 patients including 13 episodes of refractory status epilepticus (RSE) occurring in 10 patients and for treatment of isolated seizures or following resolution of RSE in an additional 14 patients. Seizure cessation was achieved in 5/13 (38%) episodes of RSE (mean 11.2 h) while there was at least a 50% decrease in seizure frequency in 7/13 (54%). 11/14 patients (76%) who received LCM for treatment of isolated seizures or prevention of seizure recurrence remained seizure free. Three patients experienced a decline in systolic blood pressure (> 20 mmHg) while one patient experienced unexplained fever and one patient had elevation of liver function tests. This preliminary data suggests that LCM may be a safe and effective alternative for treatment of seizures in critically ill patients. Further prospective, randomized controlled trials are needed to confirm these findings and further explore the incidence of adverse effects.


Assessment of the mutations of p53 suppressor gene and Ha- and Ki-ras oncogenes in malignant mesothelioma in relation to asbestos exposure: a study of 12 American patients.
In our previous study, we found no genetic alteration in exons 1 and 2 of Ha- and Ki-ras oncogenes nor in exons 5 to 9 of the p53 suppressor gene in seven Japanese malignant mesothelioma patients exposed to asbestos. To examine further whether malignant mesothelioma due to asbestos has genetic alterations in the p53 suppressor gene and in Ha- and Ki-ras oncogenes, we analyzed point mutations of these genes in paraffin embedded operative open biopsied samples of the primary tumor of malignant mesothelioma in twelve American patients. The genetic analysis was conducted by the PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) method in all patients and by sequencing analysis of DNA bases in the two patients with suspected gene mutation. The analysis of the p53 suppressor gene showed an amino acid converting mutation of exon 7 in one patient and a polymorphism of exon 6 in another patient; the former patient was a heavy smoker with a biphasic cell type. No genetic alteration was found in exons 1 and 2 of Ha- and Ki-ras oncogenes in any of the patients. The results suggest that the effects of asbestos on the p53 suppressor gene and Ha- and Ki-ras oncogenes in malignant mesothelioma are negligible. Further studies are needed to examine whether the observed mutation of the p53 suppressor gene is due to the combined effects of asbestos and smoking or to other unknown factors.


[Nerve baby-sitter in reverse end-to-side neurorrhaphy preserves the structure of denervated muscle in rats].
To explore the protected effect of sensory baby-sitter in reverse end-to-side fashion on denervated muscle. The tibial nerve of twelve female adult Sprague Dawley rats was transected. Six animals served as controls. In the other rats, the end of the sural nerve was connected to the side of the distal tibial nerve stump. After twelve weeks, the wet weight, cross-sectional area, motor endplate perimeter from gastrocnemius muscle were examined. The difference in wet weight between the experimental group and the control group was statistically significant (39.2% ± 6.8% vs. 19.5% ± 4.3%, P<0.05). Histological observation of the unprotected muscles displayed wide areas of atrophied fibers and considerable connective tissue hyperplasia, whereas the structure of the experimental rats was preserved and there was only a slight increase in connective tissue. The average cross-sectional area and motor endplate perimeter of muscle fibers were significantly larger in the experimental group than in the control group [(1 148.85 ± 547.18) μm² vs. (575.05 ± 140.51) μm², (102.84 ± 53.29) μm vs. (59.60 ± 26.71) μm, respectively]. Sensory baby-sitter in reverse end-to-side neurorrhaphy preserves the structure of denervated muscle in rats.


[Effective core formulae for lung cancer based on complex network and survival analysis].
The study on the effective core formulae (CEF) not only summarized traditional chinese medicine (TCM) treatment experience, but also helped reveal the underlying knowledge in the formulation of TCM prescriptions. The aim of the present paper was to investigate the method of data mining for the discovery of core effective formulae for lung cancer. In the present study, a prescription fingerprint approach was used to characterize the staged prescription information of patients. The D index was used to screen potential beneficial herbs. Then, based on a herbal compatibility network, the maximal clique searching algorithm (BK algorithm) and survival analysis were applied to discover CEF for lung cancer, and a mining analysis was made for the 322 cases from Longhua hospital. The correlation between prescriptions and survival time was analyzed by prescription fingerprints. Forty-three potentially beneficial herbs were obtained, and two CEFs were significant for the survival time by a parametric survival model based on lognormal distribution, the results were verified by a multivariate survival model. The rules of combination of the two CEFs basically conform to TCM onco-therapeutic theory of strengthening the body resistance and the actual conditions in clinic. All results showed that the established approach was feasible for discovering the core effective formulae for lung cancer and mining survival data for complex TCM onco-therapy.


Predictive human pursuit and "orbital goal" of microstimulated smooth eye movements.
1. Anticipatory saccades in smooth pursuit move the point of gaze from near the moving target to well ahead of it, interrupting accurate smooth pursuit. Their effects on the pursuit process were studied in 22 normal human subjects. We presented horizontal periodic target trajectories of 30 degrees amplitude and 30 degrees/s constant velocity or 0.4 Hz sinusoidal velocity in 40-s trials. Saccades and surrounding smooth eye movement (SEM) segments were marked and classified by computer. 2. Anticipatory saccades were often followed by slowed SEM that tended to intercept the target at the endpoint of its trajectory. This was seen in the distribution of projections of the initial 60 ms of postsaccadic SEM to the time of the trajectory endpoint. Magnitude of this SEM tended to follow a function of the time and location of the endpoint of the anticipatory saccade, decreasing as the anticipatory saccades landed closer to the trajectory endpoint. 3. The time and location of the target trajectory endpoint seemed to be the goal for this SEM. We believe this to demonstrate the predictive use of the period and amplitude of the trajectory in smooth pursuit, apart from the instantaneous velocity match of the target. 4. Gottlieb and coworkers in the frontal eye field and Ron and Robinson in the cerebellum produced SEMs in the monkey by microstimulation. At some sites in both structures, direction and velocity of the SEMs depended on the initial position of the eye in that the elicited SEMs appeared to be converging toward a common point, or "orbital goal", and the SEM velocity diminished as the gaze neared that goal.2+ Both our SEM after anticipatory saccades and microstimulated SEM in the monkey slowed as the initial position was brought closer to the inferred orbital goal. This similarity suggests that the goal-directed SEM sites in the monkey might be part of a mechanism for predictive pursuit.


Recent trends in Hispanic immigration to the United States.
Recent patterns of Hispanic immigration to the United States are examined using data from the U.S. Immigration and Naturalization Service. "From 1960 to 1978 Hispanic immigration increased significantly, reflecting the general acceleration in total immigration to the United States. Demographic trends reveal that Hispanic immigrants are increasingly working-age women. Their occupation composition is primarily blue collar, with operatives emerging as the predominant job category during the 1970s." The authors note that these immigrants settle primarily in a small number of urban centers of Hispanic population and culture in the United States, and thus the effects of immigration will be concentrated on the low-skill segment of particular urban labor markets that already contain large numbers of Hispanic workers.


Model calculations on the linearity behavior of combs used for optical attenuation in spectrophotometers.
Part I: For a multiwedge comb placed in the beam path of the radiation source of a spectrophotometer to achieve optical attenuation, formulas can be derived which express the linearity deviation as a function of comb position, number of wedges, and geometry of the wedges. These formulas are applicable provided the irradiance existing at the comb can be stated in a quadratic form expressing the attenuation of the irradiance toward the upper and lower edges of the aperture. The attenuation in the irradiance also functionally relates the position of the comb to wavelength and temperature. Part II: For a single-wedge comb, formulas for the linearity deviation can be derived provided (1) the radiation directed across the slit width of the monochromator is nonuniform, and (2) the size of the slit width is finite in relation to the length of the comb.


Nonspecific vaginitis among women attending a sexually transmitted diseases clinic.
We studied 33 women who presented to the sexually transmitted disease clinic at Boston City Hospital (Boston, Massachusetts); most of the women attended the clinic for management of uncomplicated anogenital gonococcal infection. A clinical diagnosis of nonspecific vaginitis was based on the finding of three or more of the following: homogeneous vaginal discharge, vaginal pH of greater than 4.5, abnormal odor on the addition of 10% KOH to vaginal secretions, and the presence of "clue cells." This diagnosis was assigned to 21 (64%) of the 33 women; it was confirmed by use of gas-liquid chromatographic analysis of vaginal secretions (succinate:lactate ratio of greater than 0.4 or detection of priopionate or butyrate) in 20 of the 21 women. About two-thirds of the women with nonspecific vaginitis were symptom-free. We conclude that nonspecific vaginitis is exceedingly common among women attending an inner-city clinic for sexually transmitted diseases and that most of the infected women are asymptomatic.


Swallowing function after transoral laser microsurgery (TLM) ± adjuvant therapy for advanced-stage oropharyngeal cancer.
To perform a longitudinal description of swallowing function following transoral laser microsurgery (TLM) ± adjuvant therapy for advanced-stage oropharyngeal cancer (OPC) and identify prognostic factors associated with swallowing performance. Retrospective analysis and longitudinal descriptive study of swallowing outcomes. Patients treated with TLM for AJCC stage III-IV OPC at Washington University from 1996 to 2008 were included. A search of medical records and direct patient contact were performed to obtain swallowing function at multiple time points. Persistently poor swallowing at 2 year after surgery was the primary outcome measure. Two year swallowing outcomes stratified by tumor site and T stage are presented. One hundred eighteen patients met criteria for the study (median follow-up 53.9 months). There were 44 T1's, 41 T2's, 23 T3's and 10 T4's. Forty seven percent received radiotherapy and 41% received chemoradiotherapy. Ninety-eight percent underwent neck dissection. Patients tolerated TLM well with 82% enjoying good swallowing at 1 month after surgery. During adjuvant therapy, at 3 months, good swallowing dropped to 55%. At 1 and 2 years after TLM, 89% and 88% of patients had good swallowing function, respectively. At 2 years, 9 patients had persistently poor swallowing function. 93% of patients with T1 through T3 enjoyed good swallowing at 2 years. T4 base of tongue disease was associated with persistently poor swallowing function in multivariate analyses (P = 0.0023), with 40% having good swallowing at 2 years. Preexisting comorbidities and conversion to an open procedure were associated with delayed return of swallowing function, but not with persistently poor swallowing. Seven patients developed late-onset swallowing dysfunction. Treatment of advanced stage OPC with TLM ± adjuvant therapy results in excellent swallowing outcomes for patients with either T1 to T3 tonsil or T1 to T3 base of tongue resections. A detailed, longitudinal swallowing profile is presented to assist in preoperative counseling.


Respiratory symptoms/diseases and environmental tobacco smoke (ETS) in never smoker Italian women.
To study the relationship between respiratory/allergic disorders and chronic environmental tobacco smoke (ETS) exposure to husband or at workplace among non-smoking women of a general population in Italy. Analyses regard 2195 married or employed women. Information was collected through a self-administered questionnaire. ETS exposure was validated by salivary cotinine. Exposure both to husband and at work resulted a significant risk factor for current dyspnoea (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.20-2.16), any shortness of breath at rest (OR 2.81, 95% CI 1.83-4.30), recent wheeze (OR 1.71, 95% CI 1.04-2.82), recent attacks of shortness of breath with wheeze (OR 1.85, 95% CI 1.05-3.26), asthma diagnosis/symptoms (OR 1.50, 95% CI 1.09-2.08), diagnosis of asthma or bronchitis/emphysema (obstructive lung diseases (OLD)) (OR 2.24, 95% CI 1.40-3.58), current cough/phlegm (OR 1.52, 95% CI 1.07-2.15), and rhino-conjunctivitis (OR 1.48, 95% CI 1.13-1.94). Exposure only at work yielded higher adjusted odds ratios for all health conditions, except for rhino-conjunctivitis. Overall, about 24% of shortness of breath at rest, 16% of dyspnoea, 17% of rhino-conjunctivitis, 12% of OLD, and 10% of asthma diagnosis/symptoms are attributable to the effect of exposures to both husband and at work. Twelve percent of shortness of breath at rest and 10% of rhino-conjunctivitis cases might be avoided by eliminating exposure only at work and only to husband, respectively. Lifetime ETS exposure, especially at work, is associated with respiratory symptoms/diseases, and it accounts for a sizeable proportion of such disorders. The combined effect of both exposures is higher than the separate effects.


Association between the HGF/c‑MET signaling pathway and tumorigenesis, progression and prognosis of hepatocellular carcinoma (Review).
Hepatocellular carcinoma (HCC) is one of the most aggressive and lethal malignancies with a rising incidence, and is characterized by rapid progression, frequent metastasis, late diagnosis, high postoperative recurrence and poor prognosis. Therefore, novel treatment strategies for HCC, particularly advanced HCC, are urgently required. The hepatocyte growth factor (HGF)/c‑mesenchymal‑epithelial transition receptor (c‑MET) axis is a key signaling pathway in HCC and is strongly associated with its highly malignant features. Available treatments based on HGF/c‑MET inhibition may prolong the lifespan of patients with HCC; however, they do not achieve the desired therapeutic effects. The aim of the present article was to review the basic knowledge regarding the role of the HGF/c‑MET signaling pathway in HCC, and examine the association between the HGF/c‑MET signaling pathway and the tumorigenesis, progression and prognosis of HCC.


Bone scintigraphy in pulmonary alveolar microlithiasis: a comparative study of radioactivity and density distribution.
A histologically proven case of pulmonary alveolar microlithiasis that demonstrated intense lung uptake of Tc-99m-MDP on a bone scan is presented. The spatial distribution within the lungs of the radioactivity and density was assessed either by single photon emission computed tomography (SPECT), or x-ray computed tomography (CT) respectively, and the regional magnitude of the two parameters were compared. The quantitative study of regional radioactivity and density revealed that both the parameters distributed symmetrically, showing gradual increase in magnitude from the upper to the lower lung regions. The radioactivity-density association observed in our patient may indicate on-going formation of microcalculi throughout the lungs, the degree of which is greater at the sites of more severe involvement.


Mutations in the S4 region isolate the final voltage-dependent cooperative step in potassium channel activation.
Charged residues in the S4 transmembrane segment play a key role in determining the sensitivity of voltage-gated ion channels to changes in voltage across the cell membrane. However, cooperative interactions between subunits also affect the voltage dependence of channel opening, and these interactions can be altered by making substitutions at uncharged residues in the S4 region. We have studied the activation of two mutant Shaker channels that have different S4 amino acid sequences, ILT (V369I, I372L, and S376T) and Shaw S4 (the S4 of Drosophila Shaw substituted into Shaker), and yet have very similar ionic current properties. Both mutations affect cooperativity, making a cooperative transition in the activation pathway rate limiting and shifting it to very positive voltages, but analysis of gating and ionic current recordings reveals that the ILT and Shaw S4 mutant channels have different activation pathways. Analysis of gating currents suggests that the dominant effect of the ILT mutation is to make the final cooperative transition to the open state of the channel rate limiting in an activation pathway that otherwise resembles that of Shaker. The charge movement associated with the final gating transition in ILT activation can be measured as an isolated component of charge movement in the voltage range of channel opening and accounts for 13% ( approximately 1.8 e0) of the total charge moved in the ILT activation pathway. The remainder of the ILT gating charge (87%) moves at negative voltages, where channels do not open, and confirms the presence of Shaker-like conformational changes between closed states in the activation pathway. In contrast to ILT, the activation pathway of Shaw S4 seems to involve a single cooperative charge-moving step between a closed and an open state. We cannot detect any voltage-dependent transitions between closed states for Shaw S4. Restoring basic residues that are missing in Shaw S4 (R1, R2, and K7) rescues charge movement between closed states in the activation pathway, but does not alter the voltage dependence of the rate-limiting transition in activation.


Dynamics of coupled light waves and electron-acoustic waves.
The nonlinear interaction between coherent light waves and electron-acoustic waves in a two-electron plasma is considered. The interaction is governed by a pair of equations comprising a Schrödinger-like equation for the light wave envelope and a driven (by the light pressure) electron-acoustic wave equation. The newly derived nonlinear equations are used to study the formation and dynamics of envelope light wave solitons and light wave collapse. The implications of our investigation to space and laser-produced plasmas are pointed out.


[Robotic-assisted and laparoscopic hepatic resections for nonparasitic cysts of posterior liver segments].
Results of 36 robotic-assisted and laparoscopic hepatic resections for nonparasitic cysts of posterior liver segments were demonstrated. Technical aspects of the procedure, advantages and drawbacks of each method were discussed. Important intra- and postoperative indexes were compared. The study allows to state, that the use of the da Vinci robotic surgical system has certain technical advantages over the standard laparoscopic technique in case of the posterior location of liver cysts.


Partially deglycosylated equine LH preferentially activates beta-arrestin-dependent signaling at the follicle-stimulating hormone receptor.
Deglycosylated FSH is known to trigger poor Galphas coupling while efficiently binding its receptor. In the present study, we tested the possibility that a deglycosylated equine LH (eLHdg) might be able to selectively activate beta-arrestin-dependent signaling. We compared native eLH to an eLH derivative [i.e. truncated eLHbeta (Delta121-149) combined with asparagine56-deglycosylated eLHalpha (eLHdg)] previously reported as an antagonist of cAMP accumulation at the FSH receptor (FSH-R). We confirmed that, when used in conjunction with FSH, eLHdg acted as an antagonist for cAMP accumulation in HEK-293 cells stably expressing the FSH-R. Furthermore, when used alone at concentrations up to 1 nM, eLHdg had no detectable agonistic activity on cAMP accumulation, protein kinase A activity or cAMP-responsive element-dependent transcriptional activity. At higher concentrations, however, a weak agonistic action was observed with eLHdg, whereas eLH led to robust responses whatever the concentration. Both eLH and eLHdg triggered receptor internalization and led to beta-arrestin recruitment. Both eLH and eLHdg triggered ERK and ribosomal protein (rp) S6 phosphorylation at 1 nM. The depletion of endogenous beta-arrestins had only a partial effect on eLH-induced ERK and rpS6 phosphorylation. In contrast, ERK and rpS6 phosphorylation was completely abolished at all time points in beta-arrestin-depleted cells. Together, these results show that eLHdg has the ability to preferentially activate beta-arrestin-dependent signaling at the FSH-R. This finding provides a new conceptual and experimental framework to revisit the physiological meaning of gonadotropin structural heterogeneity. Importantly, it also opens a field of possibilities for the development of selective modulators of gonadotropin receptors.