The kinesin Eg5 drives poleward microtubule flux in Xenopus laevis egg extract spindles.
Although mitotic and meiotic spindles maintain a steady-state length during metaphase, their antiparallel microtubules slide toward spindle poles at a constant rate. This "poleward flux" of microtubules occurs in many organisms and may provide part of the force for chromosome segregation. We use quantitative image analysis to examine the role of the kinesin Eg5 in poleward flux in metaphase Xenopus laevis egg extract spindles. Pharmacological inhibition of Eg5 results in a dose-responsive slowing of flux, and biochemical depletion of Eg5 significantly decreases the flux rate. Our results suggest that ensembles of nonprocessive Eg5 motors drive flux in metaphase Xenopus extract spindles.


The quality of studies evaluating antimicrobial stewardship interventions: a systematic review.
Antimicrobial stewardship aims to optimize antibiotic use and minimize selection of antimicrobial resistance. The methodological quality of published studies in this field is unknown. Our objective was to perform a comprehensive systematic review of antimicrobial stewardship research design and identify features which limit validity and translation of research findings into clinical practice. The following online database was searched: PubMed. Studies published between January 1950 and January 2017, evaluating any antimicrobial stewardship intervention in the community or hospital setting, without restriction on study design or outcome. We extracted data on pre-specified design quality features and factors that may influence design choices including (1) clinical setting, (2) age group studied, (3) when the study was conducted, (4) geographical region, and (5) financial support received. The initial search yielded 17 382 articles; 1008 were selected for full-text screening, of which 825 were included. Most studies (675/825, 82%) were non-experimental; 104 (15%) used interrupted time series analysis, 41 (6%) used external controls, and 19 (3%) used both. Studies in the community setting fulfilled a median of five out of 10 quality features (IQR 3-7) and 3 (IQR 2-4) in the hospital setting. Community setting studies (25%, 205/825) were significantly more likely to use randomization (OR 5.9; 95% CI 3.8-9.2), external controls (OR 5.6; 95% CI 3.6-8.5), and multiple centres (OR 10.5; 95% CI 7.1-15.7). From all studies, only 48% (398/825) reported clinical and 23% (190/825) reported microbiological outcomes. Quality did not improve over time. Overall quality of antimicrobial stewardship studies is low and has not improved over time. Most studies do not report clinical and microbiological outcome data. Studies conducted in the community setting were associated with better quality. These limitations should inform the design of future stewardship evaluations so that a robust evidence base can be built to guide clinical practice.


Vision Transformer for Parkinson's Disease Classification using Multilingual Sustained Vowel Recordings.
Parkinson's disease (PD) is the 2nd most prevalent neurodegenerative disease in the world. Thus, the early detection of PD has recently been the subject of several scientific and commercial studies. In this paper, we propose a pipeline using Vision Transformer applied to mel-spectrograms for PD classification using multilingual sustained vowel recordings. Furthermore, our proposed transformed-based model shows a great potential to use voice as a single modality biomarker for automatic PD detection without language restrictions, a wide range of vowels, with an F1-score equal to 0.78. The results of our study fall within the range of the estimated prevalence of voice and speech disorders in Parkinson's disease, which ranges from 70-90%. Our study demonstrates a high potential for adaptation in clinical decision-making, allowing for increasingly systematic and fast diagnosis of PD with the potential for use in telemedicine.Clinical relevance- There is an urgent need to develop non invasive biomarker of Parkinson's disease effective enough to detect the onset of the disease to introduce neuroprotective treatment at the earliest stage possible and to follow the results of that intervention. Voice disorders in PD are very frequent and are expected to be utilized as an early diagnostic biomarker. The voice analysis using deep neural networks open new opportunities to assess neurodegenerative diseases' symptoms, for fast diagnosis-making, to guide treatment initiation, and risk prediction. The detection accuracy for voice biomarkers according to our method reached close to the maximum achievable value.


Flagellated actinomycetes.
Shadowed motile elements from actinomycetes were observed with an electron microscope. Included were three strains of Actinoplanes, two of Ampullariella, two of Dermatophilus, two of Spirillospora, and four of "Nocardia" turbata. In addition, three types of previously undescribed actionmycetes were represented: (i) the C(4) group (four strains) forming substrate mycelium breaking into motile rods; (ii) strain 9-41, forming Microellobosporia-like sporangia with motile spores; and (iii) strain P(2), forming aerial hyphae releasing motile cocci when put in water. All the known chemical cell wall types of actinomycetes except the Nocardia asteroides type and the Actinomyces israeli type were represented in this array of motile actinomycetes. Motile elements were, depending on the genus, cocci, rods (often curved), or pyriform. Flagella were always in tufts (or single), never peritrichous. A relationship seems to exist between the location of the tuft and the cell wall composition. The spores of one strain of Actinoplanes were herniated, thus resembling plasmoptysis forms of bacteria.


[Structure and expression of human hepatitis B virus surface antigen].
In view of the growing occurrence rate of the virus-induced hepatitis B and also of the special role played by this particular virus (HBV) in the application of recombinant genetic techniques to the study of complex biological systems, an attempt was made to survey the available evidence concerning the widely investigated and practically the most important part of the viral genome, viz. the gene coding for the surface antigen (HBsAg) and the protein itself. The possible antigenic structure of the protein was investigated using data on the primary structure of 11 cloned HBsAg gene variants and on the synthesis of peptides simulating its immunological properties. Special emphasis was placed on quantitative assessment of antigenicity and immunogenicity. Expression of the gene in homologous systems was studied using cultures of eukaryotic tissues: both as part of HBV nucleotide sequences incorporated into the chromosome and as part of extrachromosomal DNA. The latest findings on HBsAg gene expression in yeast and bacteria are reviewed.


Measuring impairment and functional limitations in children with cerebral palsy.
The disablement model provides a theoretical framework for the assessments of individuals with cerebral palsy (CP). The purpose of this study was to evaluate the relative validity of multiple measures for impairment and functional limitations and to estimate the relationship between the two global factors using confirmatory factor analysis. Over 50 measures of impairment and functional limitations were collected for 57 children with spastic CP. There were 12, 10, 5, 7 and 23 children who were classified in Gross Motor Function Classification System (GMFCS) Levels I to V, respectively. The measures of impairment with the highest factor loadings were several single-item ratings of spasticity; the Modified Ashworth hamstring and biceps ratings, and goniometric measures. All of the functional limitation measures had high factor loadings, including the gross motor function measure, GMFCS, the Paediatric Evaluation of Disability Inventory and WeeFIM self care and mobility scales. The correlation between the global factors of impairment and functional limitations was 0.96, indicating that the two factors are highly correlated in spastic CP. The disablement model is a valuable theoretical tool that can be used to organise assessments in CP and to explain how they are related.


Pet ownership in immunocompromised children--a review of the literature and survey of existing guidelines.
Pet ownership has been associated with both emotional and physical health benefits. However, owning pets may also pose health risks to immunocompromised patients through zoonotic transmission of disease. Our initial impression was that there is a lack of any evidence base in information given by health care professionals regarding these risks. We therefore aimed to produce evidence-based guidelines addressing this issue. A Pubmed search was undertaken and a variety of literature on zoonoses reviewed. Existing guidelines were evaluated and a survey of all Paediatric Oncology Centres in the UK performed. There is a paucity of level 1 and 2 data addressing this issue and clearly more studies, particularly Randomised Controlled Trials (RCTs), are required. Nevertheless, general themes emerged and certain specific guidance was produced based on that produced by the Centres for Disease Control and Prevention in the US. Animal-associated pathogens of concern include Toxoplasma gondii, Cryptosporidium spp., Salmonella spp., Campylobacter spp., Giardia lamblia, Rhodococcus equi, Bartonella spp., Bordetella bronchiseptica, Chlamydia psittaci and dermatophytes. Despite this, the literature would suggest that with the exception of Bartonella henselae and dermatophytes only a relatively small number of infections in people are likely to be associated with pet contact. The majority of pet species do not appear to pose a major risk to immunocompromised children. Some animals, particularly reptiles, should be avoided because of the high risk of salmonellosis. Guidelines include general advice on good hygiene practices, veterinary care, pet foods, purchasing of new pets and age restrictions. Health care professionals should actively enquire about household pets and provide accurate information and practical advice on how to minimise the risk of infection. However, the overall benefits of the human-animal bond must be considered and with proper handling and husbandry immunocompromised patients should be able to continue to enjoy the significant benefits of pet ownership.


The relationship of flavonoid intake during pregnancy with excess body weight and gestational diabetes mellitus.
To investigate the relationship of flavonoid intake during pregnancy with maternal excessive body weight and gestational diabetes mellitus (GDM). A cross-sectional study was conducted among 785 adult women in singleton pregnancies, and data were collected at the time of the oral glucose tolerance test. For the body mass index (BMI) classification according to the gestational age, the criteria of Atalah was used, and the diagnosis of GDM was based on the World Health Organization of 2014. Two 24-hour dietary recalls were obtained, and the usual intake was determined by the Multiple Source Method. Adjusted multinomial logistic regression was used to investigate the relationship of the flavonoids with overweight and obesity, and adjusted non-conditional logistic regression for the relationship of the flavonoids with GDM. The mean (SD) age of the women was 28 (5) years, 32.1% were overweight, 24.6% were obese and 17.7% were diagnosed with GDM. The median (P25, P75) of total flavonoid intake was 50 (31,75) mg/day. Considering the eutrophic women as the reference, the pregnant women with a higher total flavonoid intake [OR 0.62 (95% CI 0.38; 0.96)] and anthocyanidin intake [OR 0.62 (95% CI 0.40; 0.99)] were less likely to be obese when compared to the women with lower intakes. No association of the flavonoids intake with overweight or GDM was found. A very low intake of flavonoids was observed. The data suggest that the intake of foods naturally rich in total flavonoids and anthocyanidin has a beneficial role regarding obesity among pregnant women.


Expression of annexin A1 in esophageal and esophagogastric junction adenocarcinomas: association with poor outcome.
Annexin A1 (ANXA1) is a calcium-binding protein involved in arachidonic acid metabolism and epidermal growth factor receptor tyrosine kinase pathway. ANXA1 has been implicated in early squamous cell carcinogenesis of esophagus and correlates with degree of tumor differentiation. However, the role of ANXA1 in esophageal adenocarcinoma is unclear. Our goal was to evaluate ANXA1 expression and determine its prognostic significance in adenocarcinoma of the esophagus and esophagogastric junction. This study included 104 consecutive patients with primary resected esophageal and esophagogastric junction adenocarcinomas (11 stage I, 24 stage II, 53 stage III, and 16 stage IV). ANXA1 protein expression in each tumor was assessed by immunohistochemical staining of tissue microarrays. ANAX1 expression level was classified as high (>/=25% of tumor cells with cytoplasmic staining), low (<25% of tumor cells with cytoplasmic staining), or negative; and was correlated with clinicopathologic features and patients' outcomes. High ANXA1 expression was present in 39% (41 of 104) of tumors and was associated with higher pathologic T stage (P = 0.03) and distant metastasis (P = 0.04). High ANXA1 expression correlated with increased recurrence rate (P = 0.004) and decreased overall survival (P = 0.003) in univariate analysis. In multivariate analysis, ANXA1 expression and pN stage significantly correlated with recurrence rate (P = 0.008 and P < 0.001, respectively) and overall survival (P = 0.02 and P < 0.001, respectively) independent of T stage. Our results indicate that high ANXA1 expression is frequent in esophageal and esophagogastric junction adenocarcinomas, correlates with more advanced pathologic T stage and the presence of distant metastasis, and is an independent prognostic factor for patient survival.


Functionality of glioma-infiltrated precentral gyrus: experience from 14 patients.
In this study we reviewed our experience with surgical removal of gliomas that infiltrated the precentral gyrus. From a consecutive series of 100 patients that were operated with intraoperative monitoring, 14 patients were retrospectively selected and analyzed for results of (sub)cortical electrical stimulation, extent of resection and temporary or permanent neurological deficits. In 10 of 14 patients there were no neurological deficits prior to surgery despite tumor-infiltrated precentral gyrus. Resection of these tumors was (severely) limited in 6 patients due to cortical or subcortical responses from precentral gyrus or corticospinal tract. These responses reflected limb or speech/language functions. In 2 patients the tumor was not resected or only partially removed due to the confounding influence of seizures during the operation. Overall, 4 tumors were completely resected. In one patient this resulted in a new and permanent minor motor deficit of the foot. We conclude from our study that the chance that a glioma can be resected from the upper parts of the precentral gyrus is low, especially in those cases where tumor margins are diffuse. Possible exceptions are gliomas that are hypointense on T1-weighted images and have sharp margins; these patients should a priori not be excluded from surgery. We could confirm previous reports in the literature that gliomas in the face area of the non-dominant hemisphere can be resected without permanent morbidity.


Serologic analysis of anti-porcine endogenous retroviruses immune responses in humans after ex vivo transgenic pig liver perfusion.
Improvements in xenotransplantation may significantly increase the availability of organs for human transplantation. The use of porcine organs, however, has raised concern about possible transmission of porcine endogenous retroviruses (PERV) to the recipients. The authors developed monoclonal antibodies specific to the PERV Gag viral product and show that these antibodies can detect PERV antigen under a variety of assay conditions, including enzyme linked immunosorbent assay (ELISA), Western blot, and immunofluorescence staining methods. Two patients in fulminant hepatic failure were treated by extracorporeal perfusion using transgenic porcine livers before receiving orthotopic liver transplants. Despite the use of immune suppression that allowed survival of the allograft, these patients both showed a strong immune response to the xenograft suggesting a largely intact capability to mount a humoral immune response. However, analysis of patient serum samples over a 3 to 4 year period has showed no evidence of an immune response to PERV antigens, suggesting a lack of PERV infection.


Spheroscope: A custom-made miniaturized microscope for tracking tumour spheroids in microfluidic devices.
3D cell culture models consisting of self-assembled tumour cells in suspension, commonly known as tumour spheroids, are becoming mainstream for high-throughput anticancer drug screening. A usual measurable outcome of screening studies is the growth rate of the spheroids in response to treatment. This is commonly quantified on images obtained using complex, expensive, optical microscopy systems, equipped with high-quality optics and customized electronics. Here we present a novel, portable, miniaturized microscope made of low-cost, mass-producible parts, which produces both fluorescence and phase-gradient contrast images. Since phase-gradient contrast imaging is based on oblique illumination, epi-illumination is used for both modalities, thus simplifying the design of the system. We describe the system, characterize its performance on synthetic samples and show proof-of-principle applications of the system consisting in imaging and monitoring the formation and growth of lung and pancreas cancer tumour spheroids within custom made microfluidic devices.


Patients living farther from a tertiary care center are more likely to undergo peripheral arterial bypass for acute and chronic limb-threatening ischemia.
The aim of this study was to assess the association between the proximity to the tertiary care hospital and the severity of peripheral arterial disease (PAD) at the time of lower extremity bypass (LEB) in a rural-urban mix region. Patients undergoing LEB from 2010 to 2020 at Penn State Milton S. Hershey Medical Center were reviewed and stratified into two study groups based on a median distance from hospital (ie, Group I: ≥34 miles and Group II: <34 miles). Patients' demographic features, preoperative data including comorbidities, and medications were analyzed. A univariate analysis for the patient characteristics between the two study groups, along with evaluation of postoperative outcomes, and a multivariate predictive modeling to study the PAD stage as the indication of LEB was performed. A P-value of < .05 was set as a significant difference between the groups for all the analyses. There were 175 patients (49.9%) in Group I and 176 patients (50.1%) in Group II with a mean age of 65 ± 11.92 years (median, 64.61 years). No significant difference was observed in gender (P = .530), age (P = .906), and functional status (P = .830) between study groups. It was observed that patients in Group I were more likely to be overweight or obese (71.3% vs 57%; P = .007) and had a prior history of myocardial infarction (24.3% vs 15.3%; P = .036) in comparison to Group II. No postoperative outcomes were found to be statistically different between the study groups. The multivariate analyses based on various confounders displayed that patients in Group I had 56% higher likelihood of LEB for chronic limb-threatening ischemia (adjusted odds ratio, 1.56; 95% confidence interval, 0.92-2.62; P = .042). Group I patients also had five times higher odds of LEB for acute limb ischemia (adjusted odds ratio, 5.07; 95% confidence interval, 1.42-18.13; P = .012) as compared with those in the Group II. Patients' proximity to a major tertiary hospital may have implications on the disease progression for patients with PAD and could also be related to inadequate vascular services in primary and secondary hospitals. Lack of preventive care and disease management in regions afar from a tertiary hospital could be other implicating factors and highlights the need for outreach programs, along with distribution of vascular specialists, to reduce geographical disparities and ensure equity in access to care.


Control of the aeration volume in an activated sludge process for nitrogen removal.
Biological nitrogen removal in an activated sludge process is obtained by two biological processes; nitrification and denitrification. Nitrifying bacteria need dissolved oxygen and a sufficiently large aeration volume for converting ammonium to nitrate in the wastewater. The objective of this paper is to develop an automatic control strategy for adjusting the aerated volume so that the effluent ammonium level can be kept close to a desired value despite major changes in the influent load. The strategy is based on applying exact linearization of the IAWO Activated Sludge Process Model No 1. Simulation results show that the suggested controller effectively attenuates process disturbances.


Endothelin (ETA) receptor number and calcium signalling are up-regulated by protein kinase C-beta 1 overexpression.
To evaluate the role of protein kinase C (PKC) in regulation of cellular responsiveness to mitogens, we used rat 6 (R6) fibroblasts that stably overexpress the beta 1 isoenzyme of protein kinase C (PKC-beta 1). The potent vasoconstrictor and mitogen endothelin-1 (ET-1; 100 nM) was substantially more effective in stimulating InsP3 accumulation in PKC-beta 1-overexpressing fibroblasts (PKC3 cells) than in control fibroblasts lacking the PKC-beta 1 cDNA insert. PKC3 cells were found to express a 7-fold greater number of endothelin receptors than did control cells, whereas both cell lines showed equivalent Kd values. These receptors were of the ETA subtype, as defined by a 1000-fold greater affinity for ET-1 than for ET-3. Changes in intracellular free Ca2+ levels ([Ca2+]i) in response to ET-1 measured with the fluorescent Ca2+ indicator fura-2 showed that ET-1 was more potent and efficacious in stimulating [Ca2+]i in PKC3 cells than in control fibroblasts. The ET-1-induced Ca2+ rise was completely blocked by the selective ETA antagonist BQ123, but only slightly diminished by extracellular application of 2 mM EGTA. In contrast with the effects of PKC-beta 1 overexpression on responsiveness to ET-1, alpha-thrombin, which was previously found to have a weaker effect on InsP3 accumulation in PKC-beta 1-overexpressing cells, was also a less effective stimulator of [Ca2+]i in PKC3 cells than in control cells. These results demonstrate that, although the Ca2+ response to alpha-thrombin is diminished by PKC-beta 1 overexpression, ETA receptor number and cellular responsiveness to ET-1 are increased in PKC-beta 1-overexpressing cells.


Insights on the Neuromagnetic Representation of Temporal Asymmetry in Human Auditory Cortex.
Communication sounds are typically asymmetric in time and human listeners are highly sensitive to this short-term temporal asymmetry. Nevertheless, causal neurophysiological correlates of auditory perceptual asymmetry remain largely elusive to our current analyses and models. Auditory modelling and animal electrophysiological recordings suggest that perceptual asymmetry results from the presence of multiple time scales of temporal integration, central to the auditory periphery. To test this hypothesis we recorded auditory evoked fields (AEF) elicited by asymmetric sounds in humans. We found a strong correlation between perceived tonal salience of ramped and damped sinusoids and the AEFs, as quantified by the amplitude of the N100m dynamics. The N100m amplitude increased with stimulus half-life time, showing a maximum difference between the ramped and damped stimulus for a modulation half-life time of 4 ms which is greatly reduced at 0.5 ms and 32 ms. This behaviour of the N100m closely parallels psychophysical data in a manner that: i) longer half-life times are associated with a stronger tonal percept, and ii) perceptual differences between damped and ramped are maximal at 4 ms half-life time. Interestingly, differences in evoked fields were significantly stronger in the right hemisphere, indicating some degree of hemispheric specialisation. Furthermore, the N100m magnitude was successfully explained by a pitch perception model using multiple scales of temporal integration of auditory nerve activity patterns. This striking correlation between AEFs, perception, and model predictions suggests that the physiological mechanisms involved in the processing of pitch evoked by temporal asymmetric sounds are reflected in the N100m.


The role of dynamic palmitoylation in Ca2+ channel inactivation.
N- and P/Q-type Ca(2+) channels regulate a number of critical physiological processes including synaptic transmission and hormone secretion. These Ca(2+) channels are multisubunit proteins, consisting of a pore-forming alpha(1), and accessory beta and alpha(2)delta subunits each encoded by multiple genes and splice variants. beta subunits alter current amplitude and kinetics. The beta(2a) subunit is associated with slowed inactivation, an effect that requires the palmitoylation of two N-terminal cysteine residues in beta(2a). In the current manuscript, we studied steady state inactivation properties of native N- and P/Q-type Ca(2+) channels and recombinant N-type Ca(2+) channels. When bovine alpha(1B) and beta(2a) and human alpha(2)delta were coexpressed in tsA 201 cells, we observed significant variations in inactivation; some cells exhibited virtually no inactivation as the holding potential was altered whereas others exhibited significant inactivation. A similar variability in inactivation was observed in native channels from bovine chromaffin cells. In individual chromaffin cells, the amount of inactivation exhibited by N-type channels was correlated with the inactivation of P/Q-type channels, suggesting a shared mechanism. Our results with recombinant channels with known beta subunit composition indicated that inactivation could be dynamically regulated, possibly by alterations in beta subunit palmitoylation. Tunicamycin, which inhibits palmitoylation, increased steady-state inactivation of Ca(2+) channels in chromaffin cells. Cerulenin, another drug that inhibits palmitoylation, also increased inactivation. Tunicamycin produced a similar effect on recombinant N-type Ca(2+) channels containing beta(2a) but not beta(2b) or beta(2a) subunits mutated to be palmitoylation deficient. Our results suggest that Ca(2+) channels containing beta(2a) subunits may be regulated by dynamic palmitoylation.


Respiratory and skin effects of exposure to wood dust from the rubber tree Hevea brasiliensis.
Potential health effects related to wood dust from the rubber tree, which produces natural rubber latex, have not been previously investigated. The main aim of this study was to investigate the relations of rubber tree dust exposure to respiratory and skin symptoms, asthma and lung function. A cross-sectional study was conducted among 103 workers (response rate 89%) in a rubber tree furniture factory and 76 office workers (73%) in four factories in Thailand. All participants answered a questionnaire and performed spirometry. Inhalable dust levels were measured in different work areas. Factory workers showed increased risk of wheezing, nasal symptoms and asthma compared to office workers. There was a dose-dependent increase in wheeze and skin symptoms in relation to dust level. Significantly increased risks of nasal symptoms (adj OR 3.67, 95% CI 1.45 to 9.28) and asthma (8.41, 1.06 to 66.60) were detected in the low exposure category. Workers exposed to ethyl cyanoacrylate glue had significantly increased risk of cough, breathlessness and nasal symptoms. There was dose-dependent reduction in spirometric lung function with wood dust level. This study provides new evidence that workers exposed to wood dust from the rubber tree experience increased risk of nasal symptoms, wheeze, asthma and skin symptoms and have reduced spirometric lung function. Exposure to cyanoacrylate is related to significantly increased respiratory symptoms. Results suggest that the furniture industry using rubber tree wood should implement appropriate exposure control measures to reduce wood dust exposure and cyanoacrylate glue exposure to protect their employees.


Synthesis and structure of intermediates in copper-catalyzed alkylation of diphenylphosphine.
Cu(I) catalysts for alkylation of diphenylphosphine were developed. Treatment of [Cu(NCMe)(4)][PF(6)] (1) with chelating ligands gave [CuL(NCMe)][PF(6)] (2; L = MeC(CH(2)PPh(2))(3) (triphos), 3; L = 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (XantPhos)). These complexes catalyzed the alkylation of PHPh(2) with PhCH(2)Br in the presence of the base NaOSiMe(3) to yield PPh(2)CH(2)Ph (4). The precursors Cu(dtbp)(X) (dtbp =2,9-di-t-butylphenanthroline, X = Cl (5) or OTf (6)), CuCl, and 1 also catalyzed this reaction, but dtbp dissociated from 5 and 6 during catalysis. Both 2 and 3 also catalyzed alkylation of PHPh(2) with PhCH(2)Cl/NaOSiMe(3), but XantPhos dissociation was observed when 3 was used. When CH(2)Cl(2) was used as the solvent for alkylation of PhCH(2)Cl with precursors 2 or 3, or of PhCH(Me)Br with 2, it was competitively alkylated to yield PPh(2)CH(2)Cl (7), which was formed exclusively using 2 in the absence of a benzyl halide. Cu(triphos)-catalyzed alkylation of PhCH(Me)Br gave mostly PPh(2)CHMePh (8), along with some Ph(2)P-PPh(2) (9), which was also formed in attempted alkylation of dibromoethane with this catalyst. The phosphine complexes [Cu(triphos)(L')][PF(6)] (L' = PH(2)Ph (10), PH(2)CH(2)Fc (Fc = C(5)H(4)FeC(5)H(5), 11), PHPh(2) (12), PHEt(2) (13), PHCy(2) (Cy = cyclo-C(6)H(11), 14), PHMe(Is) (Is = 2,4,6-(i-Pr)(3)C(6)H(2), 15), PPh(2)CH(2)Ph (16), PPh(2)CH(2)Cl (17)), and [Cu(XantPhos)(L')][PF(6)] (L' = PHPh(2) (18), PPh(2)CH(2)Ph (19)) were prepared by treatment of 2 and 3 with appropriate ligands. Similarly, treatment of dtbp complexes 5 or 6 with PHPh(2) gave [Cu(dtbp)(PHPh(2))(X)] (X = OTf (20a) or Cl (20b)), and reaction of PPh(2)CH(2)Ph (4) with 1 formed [Cu(PPh(2)CH(2)Ph)(3)][PF(6)] (21). Complexes 2, 3, 11-14, 16, 17, 19, and 21 were structurally characterized by X-ray crystallography. Deprotonation of diphenylphosphine complex 12 in the presence of benzyl bromide gave diphenylbenzylphosphine complex 16, while deprotonation of 12 in CD(2)Cl(2) gave 17 containing a PPh(2)CD(2)Cl ligand. Low-temperature deprotonation of the soluble salt 12-[B(Ar(F))(4)] (Ar(F) = 3,5-(CF(3))(2)C(6)H(3)) in THF-d(8) gave the phosphido complex Cu(triphos)(PPh(2)) (22). Thermally unstable 22 was characterized by NMR spectroscopy and, in comparison to 12, by density functional theory (DFT) calculations, which showed it contained a polarized Cu-P bond. The ligand substitution step required for catalytic turnover was observed on treatment of 16 or 17 with PHPh(2) to yield equilibrium mixtures containing 12 and the tertiary phosphines 4 or 7; equilibrium constants for these reactions were 8(2) and 7(2), favoring complexation of the smaller secondary phosphine in both cases. These observations are consistent with a proposed mechanism for catalytic P-C bond formation involving deprotonation of the cationic diphenylphosphine complex [Cu(triphos)(PHPh(2))][PF(6)] (12) by NaOSiMe(3) to yield the phosphido complex Cu(triphos)(PPh(2)) (22). Nucleophilic attack on the substrate (benzyl halide or CH(2)Cl(2)) then yields the tertiary phosphine complex [Cu(triphos)(PPh(2)CH(2)X)][PF(6)] (X = Ph (16) or Cl (17)), and ligand substitution with PHPh(2) regenerates 12.


An evaluation of a time-limited programme of dynamic group psychotherapy.
The outcome for a group of outpatients treated daily for 12 weeks in a dynamic group psychotherapy programme, was evaluated on both objective and subjective parameters. In the post-therapy year, the majority (82%) reduced their dependence on psychiatric services and showed considerable change in self-satisfaction, as assessed by an attitude test. Those available for follow-up three years later had maintained the change. There was a sub-group of patients (17%) who demonstrated an increase in service use in the post-therapy year.


Shoulder dystocia: when to use suprapubic or fundal pressure.
"The delivery of the head with or without forceps may have been quite easy, but more commonly there has been a little difficulty in completing the extension of the head. The hairy scalp slides out with reluctance. When the forehead has appeared it is necessary to press back the perineum to deliver the face ... time passes. The child's head becomes suffused. It endeavors unsuccessfully to breathe. Abdominal efforts by the mother or by her attendants produce no advance; gentle head traction is equally unavailing. Usually equanimity forsakes the attendants. They push, they pull. Alarm increases. Eventually by greater strength of muscle or by some infernal juggle, the difficulty appears to be overcome, and the shoulders and trunk of a goodly child are delivered. The pallor of its body contrasts with the plum-colored cyanosis of the face, and the small quantity of freshly expelled meconium about the buttocks. It dawns upon the attendants that their anxiety was not ill-founded, the baby lies limp and voiceless, and too often remains so despite all efforts at resuscitation".


Whispering gallery mode bio-sensor for label-free detection of single molecules: thermo-optic vs. reactive mechanism.
Thermo-optic and reactive mechanisms for label-free sensing of bio-particles are compared theoretically for Whispering Gallery Mode (WGM) resonators (sphere, toroid) formed from silica and stimulated into a first order equatorial mode. Although it has been expected that a thermo-optic mechanism should "greatly enhance" wavelength shift signals [A.M. Armani et al, Science 317, 783-787 (2007)] accompanying protein binding on a silica WGM cavity having high Q (10(8)), for a combination of wavelength (680 nm), drive power (1 mW), and cavity size (43 microm radius), our calculations find no such enhancement. The possible reasons for this disparity are discussed.


The HIV epidemic in Yunnan Province, China, 1989-2007.
To investigate the characteristics and trends in the HIV epidemic in Yunnan province, China, between 1989 and 2007. Statistical analysis of serological data from voluntary testing and counseling sites, medical case reports, mass screenings, sentinel surveillance, and other sources. By 2007, a cumulative total of 57,325 cases of HIV infection were reported in Yunnan, and unsafe drug injection practices and unsafe sexual behaviors were identified as the dominant modes of transmission. HIV affects injecting drug users most, particularly in Jingpo, Dai, and Yi ethnicities, more than 40% in 7 counties. HIV prevalence rates among female sex workers (FSWs) increased from 0.5% in 1995 to 4.0% in 2007; among men who have sex with men, from 4.0% in 2005 to 13.2% in 2007; among male clients of FSWs, from 0% in 1995-1997 to 1.8% in 2007; among male sexually transmitted disease clinic attendees, from 0% in 1992 to 2.1% in 2007; among pregnant women from 0.16% in 1992 to 0.5% in 2007; and among blood donors, from 0.0075% in 1992 to 0.084% in 2007. The HIV epidemic in Yunnan has progressed to a concentrated epidemic. Future efforts must focus on not only groups at risk for primary infection (injecting drug users, men who have sex with men, and FSWs) but also on their low-risk sexual partners.


[Clinico-statistical study of Ca of the mouth].
The Authors would like to underline an original statistical research on the cancer of the mouth, collected over a period of ten years of clinical observation with the principle aim of obtaining results which can be used on a pratique and operative bases.


A general practitioner primer on groin hernias.
Patients, particularly adult males, commonly present to general practice with groin hernias. Although rarely life-threatening, groin hernias can be associated with considerable morbidity and limitation of earning capacity. General practitioners should be equipped with a sound knowledge of the relevant anatomy, clinical findings and management principles in order to facilitate all aspects of the patient journey. Drawing on evidence from the literature and personal clinical experience, this article seeks to enhance understanding of groin hernias and provide information on what is considered current best practice. A number of key points have been generated that will serve to inform the management of patients with groin hernias in the primary care setting.


The effect of sevoflurane on the spatial recall ability and expression of apolipoprotein E and β amyloid in the hippocampus in rats.
This study aimed to observe the recent spatial recall ability and the changes of expression of hippocampal apolipoprotein E (ApoE) and amyloid β protein (Aβ) in adult rats after inhaling sevoflurane anesthetic drugs, and to analyze the mechanism of action. For this purpose, a total of 54 adult SD clean-grade rats were selected in this study and were randomly divided into the sevoflurane anesthesia group, carrier gas group and control group, 18 rats in each group. The rats in the carrier gas group were inhaled with 1 L/min of oxygen O2+1 L/min air mixed carrier gas for 2 h, and the rats in the sevoflurane anesthesia group were given 3.2%sevoflurane for 2 hours based on the carrier gas group, the control rats were naturally reared. Before the model was copied, the Morris water maze experiment was performed before the material was taken. Some rat brain tissues were extracted on the first day (T1), the third day (T3), and the seventh day (T7) after model replication. The immunohistochemistry was used to measure the mean optical density (MOD) value of APOE and Aβ in hippocampal CA1, CA3 and DG regions. The indicators above at different time points of each group were compared and analyzed. Results showed that the number of crossing the original platform at each time point, the residence time of the original platform quadrant, the number of entering the original platform quadrant, and the percentage of the original platform quadrant residence time in the sevoflurane anesthesia group and the carrier gas group were compared, and there were no significant differences between two groups (P>0.05). Compared with the carrier gas group, the MOD values of APOE in the hippocampus at T1 and T3 time points in the sevoflurane anesthesia group were decreased (P<0.05), the MOD values of Aβ in the hippocampus at the T7 time point were increased (P<0.05). It concluded that Inhalation of 3.2%sevoflurane has no obvious damage to the recent spatial recall ability of adult rats. Within 7 days after inhalation of 3.2% sevoflurane, it can inhibit hippocampus Aβ deposition through down-regulating APOE expression level. The critical time point for hippocampal Aβ increasing was 7 days after anesthesia.


Dog10K: an international sequencing effort to advance studies of canine domestication, phenotypes and health.
Dogs are the most phenotypically diverse mammalian species, and they possess more known heritable disorders than any other non-human mammal. Efforts to catalog and characterize genetic variation across well-chosen populations of canines are necessary to advance our understanding of their evolutionary history and genetic architecture. To date, no organized effort has been undertaken to sequence the world's canid populations. The Dog10K Consortium (http://www.dog10kgenomes.org) is an international collaboration of researchers from across the globe who will generate 20× whole genomes from 10 000 canids in 5 years. This effort will capture the genetic diversity that underlies the phenotypic and geographical variability of modern canids worldwide. Breeds, village dogs, niche populations and extended pedigrees are currently being sequenced, and de novo assemblies of multiple canids are being constructed. This unprecedented dataset will address the genetic underpinnings of domestication, breed formation, aging, behavior and morphological variation. More generally, this effort will advance our understanding of human and canine health.


Fructose: Toxic effect on cardiorenal risk factors and redox state.
To investigate the effects of fructose consumption on the antioxidant capacity in heart and kidney, cardiovascular disease risk factors, and evaluation of these variables after its removal. Male Wistar rats (n = 36) were divided into control group (n = 12): standard chow + water or F group: standard chow + fructose in drinking water (30%) for 15 weeks. After, F group was divided to continue receiving standard chow + fructose in drinking water (30%) (n = 12) or standard chow + water (Ex group, n = 12) for 9 weeks. Water, chow and caloric diaries intake, final body weight, adiposity index, plasma glucose and triacylglycerol, systolic blood pressure, and cardiac and renal hydrophilic antioxidant capacity were analyzed. Control and Ex groups consumed less chow and water compared to F group. Caloric intake was higher in control group. There was no difference in final body weight and adiposity index. Systolic blood pressure and cardiac and renal hydrophilic antioxidant capacity were worst in F group. Prolonged exposure to fructose induces oxidative stress, systolic blood pressure, and increase in triacylglycerol. When stopped fructose consumption, Ex group presented improvement in these variables, suggesting the toxicity effect of fructose when consumed in high amounts and prolonged exposure.


Epigenetic contribution to covariance between relatives.
Recent research has pointed to the ubiquity and abundance of between-generation epigenetic inheritance. This research has implications for assessing disease risk and the responses to ecological stresses and also for understanding evolutionary dynamics. An important step toward a general evaluation of these implications is the identification and estimation of the amount of heritable, epigenetic variation in populations. While methods for modeling the phenotypic heritable variance contributed by culture have already been developed, there are no comparable methods for nonbehavioral epigenetic inheritance systems. By introducing a model that takes epigenetic transmissibility (the probability of transmission of ancestral phenotypes) and environmental induction into account, we provide novel expressions for covariances between relatives. We have combined a classical quantitative genetics approach with information about the number of opportunities for epigenetic reset between generations and assumptions about environmental induction to estimate the heritable epigenetic variance and epigenetic transmissibility for both asexual and sexual populations. This assists us in the identification of phenotypes and populations in which epigenetic transmission occurs and enables a preliminary quantification of their transmissibility, which could then be followed by genomewide association and QTL studies.


[Investigation of the cerebral projection of the vestibular system using positron emission tomography].
The authors investigated the cerebral projection of the vestibular system, using positron emission tomography, in right-handed subjects. Both sided cold caloric stimulation was used in every volunteer (n = 6). A detailed map of activated and deactivated brain regions is included. This portrays changes caused by vestibular stimulation. The contralaterally activated regions according to the stimulation side were: postcentral gyrus, transvers temporal gyrus, superior temporal gyrus, posterior part of the insula, claustrum, putamen, inferior parietal lobule, precentral gyrus, premotor cortex, cingulate gyrus. The ipsilaterally activated regions were: transvers temporal gyrus, superior temporal gyrus, inferior parietal lobule, posterior part of the insula. There was no hemispherial dominance. The activated regions partially correspond with previous results in the literature. It would like to be pointed out the Brodmann 6 region as the cortical manifestation of involuntary isometric tightening of muscles. The contralaterally deactivated regions were: inferior, superior and medius temporal gyrus, medial and medius frontal gyrus, inferior occipital gyrus, parahippocampal gyrus and hippocampus. Ipsilaterally deactivated regions were: superior and medial frontal gyrus, inferior temporal gyrus, angular gyrus, parahippocampal gyrus and hippocampus, fusiform and inferior occipital gyrus. There was prominent hemispherial dominance in the stimulated, ipsilateral side. The deactivation based functional connection between the hippocampus and the vestibular system was pointed out in such a relation for the first time in this report.


Maternal immune activation and dietary soy isoflavone supplementation influence pig immune function but not muscle fiber formation.
The goals of this study were to determine the impact of maternal PRRSV infection on offspring muscle and immune development and the potential of dietary soy isoflavones to mitigate those effects. Thirteen first-parity gilts ("gilts") were randomly allotted into one of three treatments: not infected and fed a diet devoid of isoflavones (CON), infected with porcine reproductive and respiratory syndrome virus (PRRSV) and fed the control diet (POS) or that supplemented with 1,500 mg/kg soy-derived isoflavones (ISF). Gilts were inoculated with PRRSV intranasally on gestational day (GD) 70. After farrowing (GD 114 ± 2), 1-2 offspring ("pigs") closest to the average litter weight were selected either at birth (3 ± 2 d of age) or weaning (21 ± 2 d of age) to determine body, muscle, and organ weights as well as muscle cell number and size. Four weaned pigs of average body weight within each litter were selected for postnatal immune challenge. At PND 52, pigs were injected with 5 µg/kg BW lipopolysaccharide (LPS) intraperitoneally. Serum was collected at 0, 4, and 8 h following LPS administration to analyze tumor necrosis factor alpha (TNF-α). At PND 59, pigs were administered a novel vaccine to elicit an adaptive immune response. At PND 59, 66, and 73, peripheral blood mononuclear cells were isolated and T-cell populations determined by flow cytometry. Both POS and ISF pigs exhibited persistent PRRSV infections throughout the study (PND 1-73). At PND 3, whole body, muscle, and organ weights were not different (P > 0.22) between groups, with the exception of relative liver weight, which was increased (P < 0.05) in POS compared with CON pigs. At PND 21, ISF pigs had reduced (P ≤ 0.05) whole body and muscle weights, but greater (P < 0.05) kidney weight compared with CON, and greater (P < 0.05) relative liver weight compared with CON and POS. Muscle fiber number and size were not different (P > 0.39) between groups at birth or weaning. After LPS administration, TNF-α was greatest in ISF pigs (P < 0.05) at both 0 and 8 h post-challenge. At the peak time-point of 4 h post-challenge, ISF pigs had the greatest concentration of TNF-α and CON pigs had the lowest, with POS pigs being intermediate (P = 0.01). After vaccination, ISF offspring had shifts in T-cell populations indicating an impaired immune response. These data indicate that maternal PRRSV infection may impact offspring organ growth and immune function, particularly when the dam is supplemented with isoflavones.


[Surgical treatment of complex congenital heart defect in children and infants].
From January 1982 to June 1990, 2730 patients with congenital heart defects (CHDs) were treated. 537 patients had complex lesions. Fifty of them died, a mortality rate of 9.31%. The operative age ranged from 2 days to 11 years (mean 3.16 +/- 1.68 years), and weight from 2.2 kg to 29 kg (mean 12.2 +/- 3.99 kg). Repair with deep hypothermia plus circulatory arrest was performed in 58 patients, moderate hypothermia plus cardio pulmonary bypass in 459, and normal thermic bypass in 8. The clinical experience concludes that an accurate diagnosis should be made promptly in neonates with complex CHDs. In the cyanotic neonates, surgical results can be improved by use of PGE1 and balloon atrial septostomy. For congestive CHDs, operation must be performed earlier to prevent pulmonary hypertension.


Passenger head kinematics in abrupt braking and lane change events.
A test track study was conducted to quantify patterns of adult front seat passenger head motion during abrupt vehicle maneuvers. Eighty-seven men and women with a wide range of body sizes and ages participated in data collection on a closed test track in a passenger sedan under manual control by a test driver. Because a primary goal of the study was to gather "unaware" data, the participants were instructed that the study was concerned with vehicle dynamics and they were required to read from a questionnaire taped to the top of their thighs as the drive began. The first event was a hard brake (approximately 1 g) to a stop from 35 mph (56 kph). Within the space of approximately 5 min the participants also experienced an aggressive lane change, a sharp right turn with simultaneous hard braking, and a second hard braking event. A Microsoft Kinect v2 sensor was positioned to view the area around the front passenger seat. Head location was tracked using the Kinect data with a novel methodology that fit 3D head scan data to the depth data acquired in the vehicle. The mean (standard deviation) forward excursion of the estimated head center of gravity (CG) location in the first braking event was 135 (62) mm. The forward head CG excursion in the second braking event of 115 (51) mm was significantly less than that in the first, but the difference was small relative to the within-condition variance. Head excursion on the second braking trial was less than that on the first trial for 69% of participants. The mean maximum inboard head excursion in lane-change maneuvers was 118 (40) mm. Forward head excursions in braking were significantly smaller for older passengers and those with higher body mass index, but the combined factors accounted for less than 25% of the variance. Inboard head excursion in the lane-change event was significantly related to stature, but only about 7% of variance was related to body size. Head excursions for men and women did not differ significantly after accounting for body size. This is the first quantitative occupant dynamics study to use a large, diverse sample of passengers, enabling the exploration of the effects of covariates such as age and body size. The data demonstrate that a relatively large range of head positions can be expected to result from abrupt vehicle maneuvers. The data do not support simple scaling of excursions based on body size.


Aflatoxin (B1 , B2 , G1 , and G2 ) contamination in rice of Mexico and Spain, from local sources or imported.
Rice is an important cereal but it is often contaminated with aflatoxins (AFs). The purpose of this study was to identify and quantify AF (B1 , B2 , G1 , and G2 ) in 67 rice samples cultivated in Mexico and Spain, and from imported crops collected in 2008 and 2009. The methodology was validated, the rice samples were concentrated and purified with immunoaffinity columns and were quantified by high-pressure liquid chromatography (HPLC). The average total AF (AFt) in the Spanish rice was 37.3 μg/kg, the range was from 1.6 to 1383 μg/kg, the most contaminated samples being from San Juan de Aznalfarache, Sevilla (AFt = 138.6 μg/kg), from Tortosa, Tarragona (AFt = 104.6 μg/kg), and Calasparra, Murcia (AFt = 103.9 μg/kg). The rice imported from France to Spain had AFt of 26.6 μg/kg and from Pakistan AFt of 18.4 μg/kg, showing less AF contamination than the local one. The rice which originated from Mexico contained (AFt = 16.9 μg/kg), and those imported from the United States (AFt = 14.4 μg/kg) and Uruguay (AFt = 15.6 μg/kg). The imported rice had better quality in terms of the presence of AFs.


[Health transition in Spain from 1900 to 1990].
The concept of health transition is intended to define, from a plural point of view, the changes in health conditions that have contributed to a decrease in mortality associated with the demographic transition. The purpose of the study is to analyse the health transition in Spain during this century (1900-1990). The study of the different components of the health transition (epidemiological transition, risk transition and health care transition) has been based on historical series relating to Natural Population Changes. Annual Statistics and Housing Census Reports. Overall Mortality and Child Mortality rates have tended to decrease over the entire period: overall mortality has decreased by 70%, while child mortality has dropped by 96%. Life expectancy has increased by 42 years from 1900 (35) to 1990 (77), which in relative terms represents an increase of 120%. There has been a 95% decrease in infectious disease-related deaths and a 134% increase in non-infectious disease-related deaths. It can therefore be said that the epidemiological transition in Spain concluded in the fifties with the end of the previous pattern, mainly characterised by a high mortality rate (especially with respect to children), when the main cause of death was due to infectious diseases, then giving way to a new situation in which mortality rates dropped considerably and non-infectious diseases became the main cause of death (the turning point was in 1945). The new epidemiological trend that took place over the period studied appears to be the result of improved sanitary infrastructure and increased spending as well as better medical services, however also includes new health problems related to working conditions, massive urban development (particularly as of the sixties) and changes in lifestyle.


Estimation of postmortem interval based on the spectrophotometric analysis of postmortem lividity.
The color of postmortem lividity and control skin in 21 adult cadavers whose postmortem interval was within 72h, was measured by spectrophotometry in order to estimate the postmortem interval, objectively. The L *a *b * system, which has been widely used for the digital expression of skin color, was used and linear regression analysis was performed to determine the relationship between the postmortem interval and 31 color factors including L * (Value), a * and b * (Chroma and Hue) and C * (Chroma). The difference in Chroma between postmortem lividity and control skin (DeltaC * and DeltaC( *)/C(c)( *)) was only weakly correlated with the postmortem interval. We propose a new equation for calculating the postmortem interval using several color factors obtained by measurement of postmortem lividity, together with some autopsy findings that are known to affect the formation of postmortem lividity. The new equation makes it possible to estimate the postmortem interval within +/-4.76h.


Evolution and development of the outer acrosomal membrane (OAM) and evidence that acrosin-inhibitors are proteins of the OAM.
An antiserum to the purified porcine outer acrosomal membrane (OAM) was raised in rabbits and the IgG fraction isolated by ammonium sulphate precipitation and ion exchange chromatography. The antibodies reacted exclusively with the acrosomal cap of the sperm head as revealed by indirect immunofluorescence. In addition they cross-reacted not only with the acrosomal part of the spermatozoa of all mammalian species tested (bull, horse, rabbit, rat, mouse, hamster, mole, antelope, monkey, man) but also with the spermatozoa of the cock (Class: birds) and the rainbow trout (Class: fish). All the species exhibited similar development of the acrosomal cap during spermatogenesis, with the appearance of the immunofluorescent stain in early round spermatids. In the mole the localization of the acrosome in elongated testicular spermatids differed from that in all other species: Instead of prominent fluorescence over the apical part of the sperm an equatorial belt was formed. The cross-reactivity of the anti-boar OAM antibody with the acrosomes of different vertebrate species at the morphological level was supported by the results of Western blotting experiments with purified boar OAM proteins and the SDS-extractable proteins of bull and human spermatozoa, respectively. Using anti-OAM antibodies and antibodies against the acrosin inhibitors I and II described recently by Tschesche et al. (1982), in absorption and Western blotting experiments, it was demonstrated that the acrosin inhibitor proteins are integrated in the outer acrosomal membrane.


Impact of COVID-19 Pandemic on Gastroenterology Fellowship Training in Turkey: A Prospective Nationwide Survey Study.
The Coronavirus-2019 disease (COVID-19) pandemic has markedly restricted endoscopic and clinical activities in gastroenterology (GI), with a negative impact on trainee education. We aimed to inve stigate how and to what extent has GI trainees in Turkey are affected by the current pandemic in terms of general, psychological, and educational status. We conducted a web-based survey sent electronically to 103 official GI trainees in Turkey from 37 centers. The 32-item survey included questions to capture demographic (5-questions), endoscopic (7-questions), personal protective equipment (PPE) (3-questions), psychological and general well-being (11-questions), and educational (6-questions) data. Ninety-six (93.2%) trainees completed the survey, of which 56.3% (n = 54) reported a decrease in independently performed endoscopic procedures. Due to pandemic, 91.7% of standard diagnostic endoscopic procedures, 57.2% of standard therapeutic procedures, and 67.7% of advanced endoscopic procedures were decreased. Out of 96 respondents, we detected signs of anxiety in 88.5%, exposure concern in 92.7%, concerns for prolongation of training period in 49%, loss of concentration and interest in 47.9%, and burnout syndrome in 63.5%. Female gender (odds-ratio: 3.856, 95% confidence interval: 1.221-12.174, P = .021) was the only independently associated factor with pandemic-related anxiety. COVID-19 pandemic has led to high amounts of anxiety and non-negligible rates of burnout syndrome among GI trainees, with a significant reduction in endoscopic activities. More effort and novel strategies are required to deliver sufficient competence and general-psychological well-being to GI trainees.


Methods for rapid transfer and localization of lyme disease pathogens within the tick gut.
Lyme disease is caused by infection with the spirochete pathogen Borrelia burgdorferi, which is maintained in nature by a tick-rodent infection cycle. A tick-borne murine model has been developed to study Lyme disease in the laboratory. While naíve ticks can be infected with B. burgdorferi by feeding them on infected mice, the molting process takes several weeks to months to complete. Therefore, development of more rapid and efficient tick infection techniques, such as a microinjection-based procedure, is an important tool for the study of Lyme disease. The procedure requires only hours to generate infected ticks and allows control over the delivery of equal quantities of spirochetes in a cohort of ticks. This is particularly important as the generation of B. burgdorferi infected ticks by the natural feeding process using mice fails to ensure 100% infection rate and potentially results in variation of pathogen burden amongst fed ticks. Furthermore, microinjection can be used to infect ticks with B. burgdorferi isolates in cases where an attenuated strain is unable to establish infection in mice and thus can not be naturally acquired by ticks. This technique can also be used to deliver a variety of other biological materials into ticks, for example, specific antibodies or double stranded RNA. In this article, we will demonstrate the microinjection of nymphal ticks with in vitro-grown B. burgdorferi. We will also describe a method for localization of Lyme disease pathogens in the tick gut using confocal immunofluorescence microscopy.


Endpoint quantitative PCR assays for Bacteroides forsythus, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans.
Conventional polymerase chain reaction (PCR) assays for periodontal pathogens are so sensitive that they detect infections of no clinical significance. Quantitative PCR (qPCR) may provide a solution to this problem. However, most qPCR systems require expensive real-time thermal cyclers. Our goal was to develop qPCR assays which would allow endpoint quantification. 16S rRNA primers for Bacteroides forsythus, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans were adapted to the Amplifluor qPCR system, which incorporates fluorescein into the PCR product so that endpoint fluorescence is proportional to the original amount of template. DNA dilutions representing known numbers of cells were used as standard curves. Pooled subgingival plaques from the four deepest pockets of 21 severe adult periodontitis patients were assayed. Buccal molar supragingival plaque from 35 dental students provided healthy controls. Endpoint fluorescence was measured with a microplate reader. Optimized standard curves were linear in log-log or semilog fits over a range of 100-10(6) cells. Countable B. forsythus was present in all patients, with counts (as logs) from 2.4 to 7.3 (mean = 5.0), and 11 controls with counts from 2.1 to 4.5 (mean = 3.0). P. gingivalis was present in 11 patients and no controls, with counts from 2.2 to 4.7 (mean = 3.2). A. actinomycetemcomitans was present in two patients, with counts of 1.5 and 3.5. Amplifluor qPCR assays discriminated between plaque samples differing by one log or more, allowing major infections to be distinguished from minor ones. This approach allows high-throughput qPCR of plaque samples, using equipment available to many laboratories.


Structure-activity relationships of seco-prezizaane terpenoids in gamma-aminobutyric acid receptors of houseflies and rats.
Thirteen seco-prezizaane terpenoids isolated from star anise species (Illcium floridanum, Illcium parviflorum, and Illcium verum) were investigated for their ability to inhibit the specific binding of [(3)H]4'-ethynyl-4-n-propylbicycloorthobenzoate (EBOB), a non-competitive antagonist of gamma-aminobutyric acid (GABA) receptors, to housefly-head and rat-brain membranes. Veranisatin A was found to be the most potent inhibitor in both membranes, with an IC(50)(fly) of 78.5 nM and an IC(50)(rat) of 271 nM, followed by anisatin (IC(50)(fly)=123 nM; IC(50)(rat)=282 nM). Six of the other 11 tested compounds were effective only in housefly-head membranes. Pseudoanisatin proved to display a high (>26-fold) selectivity for housefly versus rat GABA receptors (IC(50)(fly)=376 nM; IC(50)(rat) >10,000 nM). Although pseudoanisatin does not structurally resemble EBOB, Scatchard plots indicated that the two compounds bind to the same site in housefly receptors. Anisatin and pseudoanisatin exhibited moderate insecticidal activity against German cockroaches. Comparative molecular field analysis (CoMFA), a method of three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis, demonstrated that seco-prezizaane terpenoids can bind to the same site as do picrotoxane terpenoids such as picrotoxinin and picrodendrins, and the CoMFA maps allowed us to identify the parts of the molecules essential to high activity in housefly GABA receptors.


The effect of attentional re-training and threat expectancy in response to acute pain.
This study aimed to investigate the efficacy of implicit attention re-training (AR) on pain ratings, threshold and tolerance during the cold-pressor task and to determine whether the effectiveness of AR was affected by threat expectancy. One hundred and four undergraduate psychology students were randomly assigned to receive either threat-alleviating or threat-inducing information about the task. Participants were then re-randomized to receive an AR that either trained them to implicitly attend to neutral and ignore pain-related stimuli (neutral training) or to attend towards pain-related stimuli (pain training). Hence, the present study had a 2 (threat expectancy: high vs low) x 2 (AR: pain vs neutral) design. Manipulation checks confirmed that the threat manipulation was effective in increasing threat expectancy and the training paradigm shifted attentional biases in predicted directions. Results showed that, relative to neutral re-training, those in the pain re-training group reported higher levels of pain 30s into the cold pressor task and registered pain more quickly. There was no difference in tolerance between the groups, nor pain at tolerance. This was the same pattern of results found for the threat induction. For initial pain ratings, there was an interaction that closely approached significance (p=0.053). These results show that AR affects individual's perceptions of and their responses to pain during an experimental task in a similar way to increasing the threat expectancy of the task. Future research should trial AR in real-life settings to determine whether these results can be generalized.


Engaging the capacity of comadronas as HIV prevention providers in rural Guatemala.
In this study the author address rural Guatemala's poor maternal health and HIV status by integrating an effective evidence-based HIV intervention (SEPA), with local implementing health partners to extend the capacity of comadronas (traditional Mayan birth attendants) to encompass HIV prevention. I employed a multi-method design consisting of a focus group, an interview, and participant observation to identify important factors surrounding comadrona receptivity towards expanding their capacity to HIV prevention. I analyzed data using thematic analysis and identified four categories: Project logistics, HIV knowledge and risk assessment, condom perceptions, and HIV testing perceptions. I affirm comadrona receptivity toward HIV prevention, and that will guide future cultural adaptation and tailoring of SEPA for comadrona training. I will use my results to create a prototype intervention that could be applied to other similarly underserved indigenous communities.


Molecular cloning of cDNA sequences coding for the major alpha- and beta-globin polypeptides of adult Xenopus laevis.
This report describes the synthesis and cloning of almost complete DNA copies of the mRNAs encoding the major alpha-globin and major beta-globin of X. laevis. Double-stranded globin cDNA was inserted into the PstI site of the plasmid pBR322 and two cloned recombinants (designated pXG6C1 and pXG8D2) were selected. These were shown to contain almost complete copies of X. laevis globin mRNA. Restriction enzyme maps were determined for each cDNA sequence using the established method of partial digestion of end labelled DNA. However, this procedure was modified such that isolation of individual DNA fragments was no longer required. Each plasmid was shown, by both hybrid arrested translation and filter selection of complementary RNA, to contain a sequence coding for one or other of the two major globin polypeptides. Sufficient DNA sequence information has been determined from each cDNA clone to demonstrate that pXG8D2 contains a beta-globin sequence and pXG6C1 contains an alpha-globin sequence.


Further studies on the substrate specificity and inhibition of the stereospecific CS2 secondary alkylsulphohydrolase of Comamonas terrigena.
A series of d-alkan-2-yl sulphate esters (C(7)-C(14)) were prepared by sulphation of the resolved parent alcohols by a method that entails complete retention of configuration. These sulphate esters were tested as substrates for the stereospecific CS2 secondary alkylsulphohydrolase of Comamonas terrigena. V(max.) reached a maximum with the C(9) compound, whereas logK(m) decreased linearly as the alkyl-chain length was increased from C(7) to C(14). A parallel series of l-alkan-2-yl sulphates was also prepared, and these esters, together with homologous series of primary alkyl sulphates and primary alkanesulphonates, were shown to be competitive inhibitors of the CS2 enzyme. For each series of compounds, logK(i) values decreased linearly with increasing alkyl-chain length. Plots of chain length against the standard free energy of binding (DeltaG(0)) of substrate and inhibitors to the CS2 enzyme showed that the standard free energy of association of a -CH(2)- group with the enzyme was 2.0-2.4kJ/mol for all classes of compound studied, indicating an important contribution from hydrophobic interactions to the overall binding. Plots for d-alkan-2-yl sulphate substrates and primary alkyl sulphate inhibitors were nearly coincident, suggesting that the overall interaction between a primary ester and the enzyme is the same as that between the isomeric secondary substrate and the enzyme. Plots for l-alkan-2-yl sulphate and alkanesulphonate inhibitors were very similar to each other, but were displaced by 1.5-3.0kJ/mol from that for substrate binding. This indicates that the binding of any one of these particular inhibitors involves one carbon atom fewer than the number involved in binding a substrate of the same chain length. These observations are discussed in terms of a three-point attachment of substrate to the enzyme involving the alkyl chain, sulphate group and the C-1 methyl group.


Noradrenergic potentiation of cerebellar Purkinje cell responses to GABA: cyclic AMP as intracellular intermediary.
Norepinephrine and the beta-adrenergic receptor agonist, isoproterenol, have been shown to potentiate the amplitude of GABAA receptor-mediated whole-cell current responses in Purkinje cells acutely dissociated from the rat cerebellum. However, the steps leading from the activation of beta-adrenergic receptors to the modulation of GABAA receptor remain to be delineated. This study tested the hypothesis that a sequelae of intracellular intermediaries involving the cyclic AMP second messenger system serves as the subcellular link to promote this heteroreceptor interaction. Exposure to cholera toxin, but not to pertussis toxin, increased the amplitude of GABA-activated current responses in acutely dissociated Purkinje cells. Intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate) also resulted in a time- and dose-dependent augmentation of the response to GABA. while guanosine 5'-O-(2-thiodiphosphate) blocked the norepinephrine-mediated facilitation. A positive modulation of the current response to GABA was observed following intracellular delivery of cyclic AMP or the catalytic subunit of the cyclic AMP-dependent protein kinase. Furthermore, the norepinephrine-induced potentiation of the GABA-activated current response was prevented in the presence of the Rp isomer of cyclic AMP, the regulatory subunit of cyclic AMP-dependent protein kinase and an inhibitor of cyclic AMP-dependent protein kinase. These findings led to the formulation of a working model in which activation of the beta-adrenergic receptor triggers a Gs-protein-mediated transduction cascade in cerebellar Purkinje cells which activates adenylate cyclase, resulting in a rise in intracellular levels of cyclic AMP, increased phosphorylating activity by cyclic AMP-dependent protein kinase and, ultimately, a potentiation of GABAA receptor function.


Divergent receptor proteins confer responses to different karrikins in two ephemeral weeds.
Wildfires can encourage the establishment of invasive plants by releasing potent germination stimulants, such as karrikins. Seed germination of Brassica tournefortii, a noxious weed of Mediterranean climates, is strongly stimulated by KAR1, the archetypal karrikin produced from burning vegetation. In contrast, the closely-related yet non-fire-associated ephemeral Arabidopsis thaliana is unusual because it responds preferentially to KAR2. The α/β-hydrolase KARRIKIN INSENSITIVE 2 (KAI2) is the putative karrikin receptor identified in Arabidopsis. Here we show that B. tournefortii expresses three KAI2 homologues, and the most highly-expressed homologue is sufficient to confer enhanced responses to KAR1 relative to KAR2 when expressed in Arabidopsis. We identify two amino acid residues near the KAI2 active site that explain the ligand selectivity, and show that this combination has arisen independently multiple times within dicots. Our results suggest that duplication and diversification of KAI2 proteins could confer differential responses to chemical cues produced by environmental disturbance, including fire.


Size Matters: Individual Variation in Ectotherm Growth and Asymptotic Size.
Body size, and, by extension, growth has impacts on physiology, survival, attainment of sexual maturity, fecundity, generation time, and population dynamics, especially in ectotherm animals that often exhibit extensive growth following attainment of sexual maturity. Frequently, growth is analyzed at the population level, providing useful population mean growth parameters but ignoring individual variation that is also of ecological and evolutionary significance. Our long-term study of Lake Erie Watersnakes, Nerodia sipedon insularum, provides data sufficient for a detailed analysis of population and individual growth. We describe population mean growth separately for males and females based on size of known age individuals (847 captures of 769 males, 748 captures of 684 females) and annual growth increments of individuals of unknown age (1,152 males, 730 females). We characterize individual variation in asymptotic size based on repeated measurements of 69 males and 71 females that were each captured in five to nine different years. The most striking result of our analyses is that asymptotic size varies dramatically among individuals, ranging from 631-820 mm snout-vent length in males and from 835-1125 mm in females. Because female fecundity increases with increasing body size, we explore the impact of individual variation in asymptotic size on lifetime reproductive success using a range of realistic estimates of annual survival. When all females commence reproduction at the same age, lifetime reproductive success is greatest for females with greater asymptotic size regardless of annual survival. But when reproduction is delayed in females with greater asymptotic size, lifetime reproductive success is greatest for females with lower asymptotic size when annual survival is low. Possible causes of individual variation in asymptotic size, including individual- and cohort-specific variation in size at birth and early growth, warrant further investigation.


A prospective, observational cohort study to elicit adverse effects of antiretroviral agents in a remote resource-restricted tribal population of Chhattisgarh.
To assess the adverse effects of antiretroviral therapy (HAART) and its adherence in HIV-infected patients, in remote and tribal area with restricted resources. This was a prospective, observational study carried out at Department of Medicine, Government Medical College, Jagdalpur. A set of questions were asked and adverse drug reactions (ADRs) were recorded for every patient. 79 HIV positive patients were analyzed. Among them, 68 (86%) had at least one ADR. The mean ADR per patient was 1.64 (+/-1.09). The most common ADR in our study was peripheral neuropathy (20.83%), followed by skin rashes (15.83%). Twenty-one patients (26.58%) had severe (grade-3 and grade-4) ADRs. Female patients had more ADRs (45.71%) than males (11.36%); severe ADRs had a statistically significant positive correlation with sex and CD4 cell count of the patients. In spite of high ADRs, HAART is the only answer to HIV/AIDS; thus, management requires a highly precise balance between benefits of durable HIV suppression and the risks of drug toxicity to achieve the therapeutic goals, with conventional drugs or with newer less toxic agents.


Is non-cavitated proximal lesion sealing an effective method for caries control in primary and permanent teeth? A systematic review and meta-analysis.
The aim of this study was to perform a systematic review and meta-analysis on the effectiveness of sealing non-cavitated proximal caries lesions in primary and permanent teeth. Only controlled clinical trials and randomized controlled clinical trials that evaluated the effectiveness of sealing on non-cavitated proximal caries with a minimum follow-up of 12 months were included in the study. The primary outcome should be arrestment/progression of proximal caries evaluated by bitewing radiographs. A risk of bias evaluation based on the Cochrane Collaboration common scheme for bias was carried out for each study. The meta-analysis was performed on the studies considered low risk of bias and with pair-wise visual reading results through RevMan software. A comprehensive search was performed in the Systematic Electronic Databases: Pubmed, Cochrane Library, Scopus, IBI Web of Science, Lilacs, SIGLE, and on website Clinical trials.gov, through until June 2013. From 967 studies identified, 10 articles and 3 studies with partial results were assessed for eligibility. However three articles were excluded and our final sample included 10 studies. According to the risk of bias evaluation, six studies were considered "high" risk of bias, and four "low" risk of bias. The forest plot of the meta-analysis showed low heterogeneity (I(2)=29%) and a favourable outcome for the Infiltrant. The chance of caries progression when this technique was used was significantly lower (p=0.002) compared with Placebo. Our results suggest that the technique of sealing non-cavitated proximal caries seems to be effective in controlling proximal caries in the short and medium term. Further long-term randomized clinical trials are still necessary to increase this evidence. Contemporary dentistry is focused in minimally invasive approaches that prevent the destruction of sound dental tissues next to carious lesions. This paper searches for evidence of the efficacy of sealing/infiltrating non-cavitated proximal caries in arresting caries progression both in permanent and primary teeth.


[Emergency stenting for acute left main coronary artery closure during cardiac catheterization].
We report a case of acute closure of the left main coronary artery, a rare complication of diagnostic cardiac catheterization, treated by emergency stenting prior to aorto-coronary bypass surgery. We suggest encroachment of the Judkins catheter into a calcified left main ostium; with dissection and acute thrombosis of this segment, as the possible mechanism. Clinically, the patient's condition deteriorated to cardiogenic shock and loss of consciousness. Remarkably, there was no angiographic evidence of significant left main coronary artery disease, besides the presence of calcification in the proximal part of the left coronary system and ventricularization of coronary pressure at the time of engagement. We chose to slide quickly the angioplasty guidewire through the left main coronary artery, which allowed prompt mechanical recanalization and rapid restoration of coronary flow, with dramatic clinical and hemodynamic improvement. This relatively simple procedure allowed stenting the left main artery after brief predilation, and the patient came to by-pass surgery in excellent condition. The rationale for surgery in this case was the need for complete coronary revascularization because of significant 3-vessel coronary artery disease.


[Painless myocardial ischemia in patients with rheumatoid arthritis].
To ascertain prevalence and prognostic implication of painless myocardial ischemia (PMI) in patients with rheumatoid arthritis (RA) in respect to stage, severity of inflammation and characteristics of the lipid profile. A 24-h Holter ECG monitoring, tests for total cholesterol, triglycerides and lipid spectrum were made in 94 patients with a documented rheumatoid arthritis (RA) aged 36-68 years (mean age 54.8 +/- 8.0 years, 13 males and 81 females) admitted to Toliatti municipal hospital N 4. The control group consisted of 20 patients with a history of myocardial infarction. Forty RA patients were followed up for mean 1.1 year after basic therapy. Holter ECG monitoring detected ischemic depression of ST segment in 46 (48.9%) RA patients and 9 (45%) patients with coronary heart disease. RA patients with PMI had changes in the lipid profile in the direction of elevation of atherogenic components and C-reactive protein characterizing severity of inflammation. Basic treatment of RA eliminated PMI symptoms in some patients. This correlated with attenuation of inflammation. Some RA patients had first symptoms of PMI, on the average, on follow-up year 1.1 and higher plasmic atherogenicity. About 50% RA patients free of clinical symptoms of coronary heart disease had PMI caused by both coronarogenic (atherosclerotic) factors and non-coronarogenic (immunocomplex inflammation) mechanisms.


Alexithymia: an experimental study of cerebral commissurotomy patients and normal control subjects.
This study assessed alexithymia in six patients with complete cerebral commissurotomy, two patients with partial commissurotomy, and eight matched control subjects. Comparisons were based on content-analytic measures of the subjects' spoken and written responses to a film that symbolically represented death and loss. The commissurotomized patients were more alexithymic on all four lexical-level variables, all six sentential-level variables, and all six global-level variables. Discriminant function analysis found a linear combination of four variables that effectively discriminated groups of fully commissurotomized, partially commissurotomized, and normal control subjects and correctly classified 15 of the 16 subjects.


Tilted elemental image array generation method for moiré-reduced computer generated integral imaging display.
In this paper, we propose a tilted elemental image array generation method for computer generated integral imaging display with reduced moiré patterns. The pixels of the tilted elemental image array are divided into border pixels and effective pixels. According to the optimal tilted angle, the effective pixels are arranged with uniform arrangement. Also, a pixel mapping method is proposed. Appropriate experiments are carried out and the experimental results show that not only the color moiré patterns are reduced remarkably, but also the resolution of the reconstructed 3D images are improved through the proposed method.


Growth oscillation in larger foraminifera.
This work shows the potential for applying three-dimensional biometry to studying cell growth in larger benthic foraminifera. The volume of each test chamber was measured from the three-dimensional model obtained by means of computed tomography. Analyses of cell growth based on the sequence of chamber volumes revealed constant and significant oscillations for all investigated specimens, characterized by periods of approximately 15, 30, 90, and 360 days. Possible explanations for these periods are connected to tides, lunar cycles, and seasonality. The potential to record environmental oscillations or fluctuations during the lifetime of larger foraminifera is pivotal for reconstructing short-term paleoenvironmental variations or for gaining insight into the influence of tides or tidal current on the shallow-water benthic fauna in both recent and fossil environments.


Canadian-Jewish seniors: marriage/cohabitation after age 65.
This is an exploratory qualitative study of 10 seniors (5 men and 5 women), who remarried or lived together after the age of 65. They were all Jewish, lived in Toronto, Canada, and had been married previously. The subjects were interviewed in their own homes, using a questionnaire. The study attempts to explore the pathways to recoupling, how the partners met, the differences between the first and second partners, and the major issues faced by the subjects in moving into a new relationship. The results in this article are significantly presented through the words of the respondents. This gives the reader the flavor of what is involved in senior relationships. The conclusions summarize the major findings of the study, and make suggestions for further research. We focus on implications for health and wellbeing from our findings.


Head and neck cancer in elderly patients: is microsurgical free-tissue transfer a safe procedure?
The safety and success of microvascular transfer have been well documented in the general population, but the good results achieved with the use of free flaps in elderly patients have received little attention. This study sought to identify differences in complications, morbidity and functional outcomes between elderly (≥ 75 years) and younger (< 75 years) patients treated surgically for advanced head and neck cancer using the Head and Neck 35 module of the European Organisation for Research and Treatment of Cancer quality of life questionnaire. Patient treatment consisted of composite resection, including excision of the primary tumour with ipsilateral or bilateral neck dissection and microvascular reconstruction. Eighty-five microvascular tissue transfers were performed to reconstruct major surgical defects. Postoperative radiation therapy was performed when indicated. Total flap loss occurred in three cases in elderly patients and two cases in younger patients. The rates of major surgical complication were 9% in young patients and 11% in elderly patients. No significant difference was observed between the two groups in the rates of major and minor flap complications, morbidity or long-term functional outcome. The results of the present analysis indicate that free-flap microvascular reconstruction can be considered a safe procedure in elderly patients with head and neck cancer.


Simultaneous determination of the total number of aquatic bacteria and the number thereof involved in respiration.
The electron transport system of respiring organisms reduces 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyl tetrazolium chloride (INT) to INT-formazan. Respiring bacteria deposit accumulated INT-formazan intracellularly as dark red spots. Corresponding to electron transport system activity, these deposits attain a size and a degree of optical density which allows them to be examined by light microscopy. If polycarbonate filters and epifluorescence microscopy are applied to analyze an INT-treated water sample, it is possible to differentiate between respiring and apparently nonrespiring bacteria. This differentiation, which permits determinations of the total number of bacteria and the proportion thereof involved in respiration, is realized directly within one and the same microscopic image. Initial applications of the present method for hydrobiological purposes showed that the proportion of respiring aquatic bacteria ranged between 6 to 12% (samples taken from coastal areas of the Baltic Sea) and 5 to 36% (samples taken from freshwater lakes and ponds). Cells of 1.6 to 2.4 micrometer (freshwater) and 0.4 micrometer (Baltic Sea) account for the highest proportion of respiring bacteria.


The Drosophila melanogaster PeptideAtlas facilitates the use of peptide data for improved fly proteomics and genome annotation.
Crucial foundations of any quantitative systems biology experiment are correct genome and proteome annotations. Protein databases compiled from high quality empirical protein identifications that are in turn based on correct gene models increase the correctness, sensitivity, and quantitative accuracy of systems biology genome-scale experiments. In this manuscript, we present the Drosophila melanogaster PeptideAtlas, a fly proteomics and genomics resource of unsurpassed depth. Based on peptide mass spectrometry data collected in our laboratory the portal http://www.drosophila-peptideatlas.org allows querying fly protein data observed with respect to gene model confirmation and splice site verification as well as for the identification of proteotypic peptides suited for targeted proteomics studies. Additionally, the database provides consensus mass spectra for observed peptides along with qualitative and quantitative information about the number of observations of a particular peptide and the sample(s) in which it was observed. PeptideAtlas is an open access database for the Drosophila community that has several features and applications that support (1) reduction of the complexity inherently associated with performing targeted proteomic studies, (2) designing and accelerating shotgun proteomics experiments, (3) confirming or questioning gene models, and (4) adjusting gene models such that they are in line with observed Drosophila peptides. While the database consists of proteomic data it is not required that the user is a proteomics expert.


Number word structure in first and second language influences arithmetic skills.
Languages differ in how they represent numerical information, and specifically whether the verbal notation of numbers follows the same order as the symbolic notation (in non-inverted languages, e.g., Hebrew, "25, twenty-five") or whether the two notations diverge (in inverted languages, e.g., Arabic, "25, five-and-twenty"). We examined how the structure of number-words affects how arithmetic operations are processed by bilingual speakers of an inverted and a non-inverted language. We examined Arabic-Hebrew bilinguals' performance in the first language, L1 (inverted) and in the second language, L2 (non-inverted). Their performance was compared to that of Hebrew L1 speakers, who do not speak an inverted language. Participants judged the accuracy of addition problems presented aurally in L1, aurally in L2 or in visual symbolic notation. Problems were presented such that they matched or did not match the structure of number words in the language. Arabic-Hebrew bilinguals demonstrated both flexibility in processing and adaptation to the language of aural-verbal presentation - they were more accurate for the inverted order of presentation in Arabic, but more accurate for non-inverted order of presentation in Hebrew, thus exhibiting the same pattern found for native Hebrew speakers. In addition, whereas native Hebrew speakers preferred the non-inverted order in visual symbolic presentation as well, the Arabic-Hebrew bilinguals showed enhanced flexibility, without a significant preference for one order over the other, in either speed or accuracy. These findings suggest that arithmetic processing is sensitive to the linguistic representations of number words. Moreover, bilinguals exposed to inverted and non-inverted languages showed influence of both systems, and enhanced flexibility in processing. Thus, the L1 does not seem to have exclusive power in shaping numerical mental representations, but rather the system remains open to influences from a later learned L2.


LMP7/TAP2 gene polymorphisms and HPV infection in esophageal carcinoma patients from a high incidence area in China.
Esophageal carcinoma is characterized by a widely ranged incidence variation among the different geographic regions. Anyang is a county in Henan Province of North China with the highest prevalence of esophageal carcinoma. Human papillomavirus (HPV) infection has been linked to the etiology of esophageal cancer in this area. In this study, we investigated correlations of the polymorphisms at low molecular weight polypeptide (LMP) and transporters with antigen processing (TAP) genes, with the risk of esophageal carcinoma. DNA extracted from either tumor specimens or esophageal epithelial cells was used to test HPV infection. Peripheral blood lymphocyte DNA was used for LMP/TAP genotyping. Polymerase chain reaction was performed to analyze HPV infection and LMP/TAP gene polymorphisms. The combined effect of LMP/TAP gene polymorphisms and HPV infection on esophageal carcinoma was analyzed by using unconditional logistic regression models. The TAP2 codons 379 isoleucine carriers and LMP7 codons 145 lysine carriers were found to be more susceptible to esophageal carcinoma (OR = 2.74, 95% CI = 1.15-6.49, P = 0.023 for TAP2; OR = 2.19, 95% CI = 1.09-4.37, P = 0.027 for LMP7). Patients carrying homozygous LMP7/TAP2 haplotype C, which contained the glutamine at LMP7 codons 145 and the isoleucine at TAP2 codons 379, were more prone to develop esophageal carcinoma (OR = 2.96, 95% CI = 1.13-7.81, P = 0.027). An additive effect on the risk of esophageal carcinoma development was found among individuals carrying LMP7/TAP2 haplotype C and infected by HPV (OR = 4.33, 95% CI = 2.53-7.42, P < 0.0001). LMP7/TAP2 haplotype C may act as the risk factor in esophageal carcinoma development and it may influence the tumorigenesis in HPV infected individuals.


An epithelial gene signature of trans-IL-6 signaling defines a subgroup of type 2-low asthma.
Asthma is stratified into type 2-high and type 2-low inflammatory phenotypes. Limited success has been achieved in developing drugs that target type 2-low inflammation. Previous studies have linked IL-6 signaling to severe asthma. IL-6 cooperates with soluble-IL-6Rα to activate cell signaling in airway epithelium. We sought to study the role of sIL-6Rα amplified IL-6 signaling in airway epithelium and to develop an IL-6+ sIL-6Rα gene signature that may be used to select asthma patients who potentially respond to anti-IL-6 therapy. Human airway epithelial cells were stimulated with combinations of IL-6, sIL-6Rα, and inhibitors, sgp130 (Olamkicept), and anti-IL-6R (Tocilizumab), to assess effects on pathway activation, epithelial barrier integrity, and gene expression. A gene signature was generated to identify IL-6 high patients using bronchial biopsies and nasal brushes. Soluble-IL-6Rα amplified the activation of the IL-6 pathway, shown by the increase of STAT3 phosphorylation and stronger gene induction in airway epithelial cells compared to IL-6 alone. Olamkicept and Tocilizumab inhibited the effect of IL-6 + sIL-6Rα on gene expression. We developed an IL-6 + sIL-6Rα gene signature and observed enrichment of this signature in bronchial biopsies but not nasal brushes from asthma patients compared to healthy controls. An IL-6 + sIL-6Rα gene signature score was associated with lower levels of sputum eosinophils in asthma. sIL-6Rα amplifies IL-6 signaling in bronchial epithelial cells. Higher local airway IL-6 + sIL-6Rα signaling is observed in asthma patients with low sputum eosinophils.


The Frontotemporal Dementia versus Primary Psychiatric Disorder (FTD versus PPD) Checklist: A Bedside Clinical Tool to Identify Behavioral Variant FTD in Patients with Late-Onset Behavioral Changes.
Differentiating early behavioral variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD) is complex and biomarkers have limited accuracy, leading to inaccurate diagnoses. Develop a simple bedside clinical tool to differentiate bvFTD from PPD. A checklist of clinical features differentiating bvFTD from PPD was developed based on literature and clinical experience. The checklist was filled prospectively for 29 consecutive patients (Montreal Neurological Hospital) with late-onset (≥ age 40) behavioral changes suggestive of bvFTD. The checklist was subsequently retrospectively completed on the baseline visit (N = 137) of the Late-Onset Frontal Lobe study (Amsterdam). In both cohorts, patients were followed 2 years to establish a final best clinical diagnosis, categorizing patients into Probable FTD (N = 46), Possible FTD (N = 8), Other Cognitive Disorder (N = 36), Other Neurological Disorder (N = 10), or PPD (N = 66). All items distinguished the two groups except "duration more than 5 years", which was removed to create a final 17-item version. Mean checklist scores were significantly different across all groups (Oneway ANOVA F(4,161) = 27.462, p < 0.001). The PPD group had lower scores than all other dementia categories, with the largest difference between Probable FTD (X¯= 12.04) and PPD (X¯= 7.48). A score ≥11 was found to be strongly indicative of bvFTD (specificity 93.9%, sensitivity 71.1%, PPV 89.2%). Scores ≤8 were strongly indicative of a PPD (specificity 91.3%, sensitivity 77.3%, PPV 92.7%). Patient with scores of 9-10 are considered indeterminate. Although further prospective validation is required, the "FTD vs PPD Checklist" could provide a simple tool to improve diagnostic accuracy, particularly in non-specialized settings.


Biplane transesophageal pacing echocardiography compared with dipyridamole thallium-201 single-photon emission computed tomography in detecting coronary artery disease.
TPE is a new diagnostic technique that uses simultaneous graded transesophageal left atrial pacing and biplane transesophageal echocardiography for the detection of pacing-induced wall motion abnormalities. In a prospective study 30 patients underwent biplane TPE, dipyridamole thallium-201 single-photon emission computed tomography (SPECT), and coronary arteriography. The sensitivity (86% vs 95%, p = not significant [NS]), specificity (89% vs 56%, p = NS), positive predictive value (95% vs 73%, p = NS), and negative predictive value (83% vs 83%, p = NS) of biplane TPE and thallium-201 SPECT in identifying patients with significant coronary artery disease was similar. In the 90 vascular territories analyzed, the agreement between biplane TPE and thallium-201 SPECT for presence or absence of significant disease was 71%. Analysis of the three major vascular territories demonstrated that each imaging modality had a high sensitivity and specificity in the left anterior descending and right coronary artery segments. However, the two techniques demonstrated poorly sensitivity in the segmental distribution of the circumflex coronary artery. In conclusion, biplane TPE compared favorably with thallium-201 SPECT in terms of safety and accuracy for detecting significant coronary artery disease. Accordingly, biplane TPE may be a suitable alternative for those patients with nondiagnostic thallium-201 SPECT studies and in those with contraindications to adenosine or dipyridamole.