Complex valve operations: antegrade versus retrograde cardioplegia?
Increasingly complex cardiac procedures demand optimal myocardial protective techniques during the requisite interval of aortic cross-clamping. For complex procedures in which prolonged cross-clamp times are anticipated, we favor combined antegrade and retrograde cold blood cardioplegia. Advantages include rapid arrest, uniform distribution, and an uninterrupted operation. We retrospectively evaluated the cases of 194 consecutive patients who underwent complex cardiovascular procedures between January 1988 and October 1994. Procedures performed included valve repair and coronary artery bypass grafting (23.7%), valve replacement and coronary artery bypass grafting (19.1%), complex aortic arch and valve procedures (16.6%), valve repair only (16.5%), reoperative valve (9.8%), and multiple-valve replacements (9.3%). Cardioplegic arrest times averaged 113 +/- 38.5 minutes (range, 52 to 292 minutes). Postoperative left and right ventricular function was evaluated using transesophageal echocardiography. The echocardiograms revealed a 3.1% incidence of new left ventricular dysfunction and no case of right ventricular dysfunction. Of the patients evaluated, 75.7% required little (< 3 micrograms.kg-1.min-1 of dopamine hydrochloride) or no inotropic support postoperatively. The 30-day mortality rate was 3.1%, and no death was due to cardiac failure. We conclude that myocardial protection using a combined antegrade and retrograde cardioplegia technique permits excellent myocardial protection during complex cardiovascular procedures requiring long arrest times.


Structural role of the conserved cysteines in the dimerization of the viral transmembrane oncoprotein E5.
The E5 oncoprotein is the major transforming protein of bovine papillomavirus type 1. This 44-residue transmembrane protein can interact with the platelet-derived growth factor receptor β, leading to ligand-independent activation and cell transformation. For productive interaction, E5 needs to dimerize via a C-terminal pair of cysteines, though a recent study suggested that its truncated transmembrane segment can dimerize on its own. To analyze the structure of the full protein in a membrane environment and elucidate the role of the Cys-Ser-Cys motif, we produced recombinantly the wild-type protein and four cysteine mutants. Comparison by circular dichroism in detergent micelles and lipid vesicular dispersion and by NMR in trifluoroethanol demonstrates that the absence of one or both cysteines does not influence the highly α-helical secondary structure, nor does it impair the ability of E5 to dimerize, observations that are further supported by sodium dodecylsulfate polyacrylamide gel electrophoresis. We also observed assemblies of higher order. Oriented circular dichroism in lipid bilayers shows that E5 is aligned as a transmembrane helix with a slight tilt angle, and that this membrane alignment is also independent of any cysteines. We conclude that the Cys-containing motif represents a disordered region of the protein that serves as an extra covalent connection for stabilization.


Bridging medical simulation with computer science and engineering: A growing field of study.
Medical simulation has become an essential educational tool in the curricula of healthcare professionals. A literature review revealed a knowledge gap in healthcare simulation education with respect to the technological expertise required to operate highly sophisticated simulation equipment. With this motivation, a case study was designed to determine if implementing on-site technological expertise allows for the facile navigation of high fidelity manikins. Next, a research study was conducted to evaluate engineering students understanding of simulation, and their interest to attend a program in medical simulation. To determine if on-site technological expertise lifts barriers associated with manikin use and to assess levels of understanding and interest among engineering students following exposure to the technology used in healthcare simulation. A prospective, descriptive study with pre-post surveys. The Nursing Skills and Simulation Center at a New England University campus. Engineering students attending 6 different engineering programs (Computer Science, Computer Engineering, Mechanical Engineering, Biomedical Engineering, Electrical Engineering and Technology Management) and having different educational levels (undergraduate and graduate). Two assessments were applied to engineering students attending a class on technology used in healthcare simulation. A pre-test measured the understanding and interest of students in the engineering/computer science courses before attending a simulation class. A post-test assessment measured their improvement in understanding and interest to learn more about simulation technologies. Statistical analysis and comparisons of pre-and post-test assessments show a 23% gain in understanding of this field following exposure to the healthcare simulation class. Furthermore, post test results show greater than 67% of those surveyed have an interest in attending a program in healthcare simulation. The results indicate the collaboration of nursing and engineering has lifted known barriers to simulation education, and reveal engineering students have an interest in the field of medical simulation.


Alcohol use and fasting glucose in a developing southern Chinese population: the Guangzhou Biobank Cohort Study.
In observational studies, mainly from Western Caucasian populations, moderate alcohol use has been shown to be associated with a lower risk of diabetes. However, whether the protection is due to the attributes of alcohol or to those of moderate alcohol users is difficult to disentangle. A population with a different distribution of alcohol consumption and diabetes prevalence from Western populations was studied as a counterfactual comparison. Baseline data from the Guangzhou Biobank Cohort Study phases 1 and 2 (2003-6) were used to examine the adjusted associations, using multivariable censored linear regression, of alcohol use with fasting blood glucose in older (> or =50 years) men (n = 5740) and women (n = 14 274) from southern China. Moderate alcohol use was defined as weekly drinking of < or =210 g alcohol in men and < or =140 g in women. The expected associations of alcohol with high-density lipoprotein (HDL) cholesterol and blood pressure were also checked. Moderate alcohol users had very similar fasting glucose levels to never users, adjusted for age, sex, socioeconomic status, smoking and physical activity. In contrast, moderate alcohol users had higher HDL-cholesterol by 0.05 mmol/litre (95% CI 0.02 to 0.07). Excessive (more than moderate) alcohol users had higher fasting glucose. In an understudied population with a different pattern of alcohol use from the populations usually studied, the biologically expected effects of moderate alcohol use were seen, but there was little effect on fasting glucose. Although cross-sectional studies cannot be conclusive, this pattern of findings, if confirmed, suggests that moderate alcohol use may not affect fasting glucose, although excessive use may be a risk factor.


An International Continence Society (ICS) report on the terminology for single-use body worn absorbent incontinence products.
In 2016, the International Continence Society (ICS) Standardization Steering Committee appointed a working group to address the confusing plethora of synonyms currently used to describe single-use body worn absorbent incontinence products by recommending preferred terminology. An online questionnaire was posted in 2016/17 inviting input from stakeholders internationally. The data were analyzed and conclusions progressively refined through working group discussions, an open meeting at the 2017 annual ICS conference, and a review of further iterations-including from the parent ICS Standardization Committee-until consensus was reached. Partway in, the International Organization for Standardization started a project with similar scope and the two organizations liaised to harmonize their conclusions while respecting each other's processes. A hundred people from 18 countries responded to the questionnaire. About a third (32.2%) of those declaring their nationality were from the UK and a further third (34.5%) from other English-speaking countries. Two-thirds (67.8%) lived in Europe; around a quarter (23%) in North America; and 9.2% in Australasia. Seven main design categories of products were identified and, while clear consensus was readily achieved in naming some of them, others required more work to determine the best term among multiple contenders. The working group concluded that the seven product design categories should be called: (a) pads; (b) unbacked pads; (c) male pads; (d) male pouches; (e) pull-on pads (protective underwear); (f) all-in-ones (wrap-around pads, adult briefs); and (g) belted pads (belted products), in which the bracketed terms are judged acceptable (though not preferred) alternatives.


Inference of Ancestry in Forensic Analysis II: Analysis of Genetic Data.
Three approaches applicable to the analysis of forensic ancestry-informative marker data-STRUCTURE, principal component analysis, and the Snipper Bayesian classification system-are reviewed. Detailed step-by-step guidance is provided for adjusting parameter settings in STRUCTURE with particular regard to their effect when differentiating populations. Several enhancements to the Snipper online forensic classification portal are described, highlighting the added functionality they bring to particular aspects of ancestry-informative SNP analysis in a forensic context.


Optimal site for atrial lead implantation in myotonic dystrophy patients: the role of Bachmann's Bundle stimulation.
The aim of this study was to identify the optimal site for atrial lead implantation in myotonic dystrophy type 1 (MD1) patients. The atrial pacing lead was positioned in the high-lateral right atrial wall (site A), then in the right atrial appendage (site B), and finally on the interatrial septum (site C) in 22 patients. Pacing and sensing thresholds were obtained for all sites. The lead was repositioned and fixed at the optimal site, defined as the location with the lowest pacing and the highest sensing thresholds. Mean pacing thresholds were 1.46 +/- 0.32 V at site A, 1.45 +/- 0.33 V at site B, and 0.84 +/- 0.24 V at site C. P-wave amplitude was 1.52 +/- 0.45 mV at site A, 1.52 +/- 0.49 mV at site B, and 2.60 +/- 0.48 mV at site C. Atrial lead was implanted at site C in all patients without complications. Interatrial septum in the region of Bachmann's Bundle seems to be the optimal site for atrial lead implantation in MD1 patients.


M6A modification promotes blood-brain barrier breakdown during cerebral ischemia/reperfusion injury through increasing matrix metalloproteinase 3 expression.
Blood-brain barrier (BBB) breakdown is a critical event in cerebral ischemia-reperfusion (I/R) injury, and matrix metalloproteinases (MMPs), which are proteolytic enzymes, play essential roles in BBB breakdown through degrading the extracellular matrix. N6-Methyladenosine (m6A), the most common and reversible mRNA modification, has an important role in the progression of cerebral I/R injury. However, whether m6A is related to BBB breakdown and MMPs expression in cerebral I/R injury is still not clear. In this study, we explored the potential effects of m6A modification on BBB breakdown in cerebral I/R injury and its underlying mechanisms using mice subjected to transient middle cerebral artery occlusion and reperfusion (MCAO/R), and mouse brain endothelial cells treated with oxygen-glucose deprivation and reoxygenation (OGD/R). We find that MMP3 expression is highly expressed and positively associated with the m6A writer CBLL1 (Cbl proto-oncogene like 1) in cerebral I/R injury in vivo and in vitro. Furthermore, MMP3 mRNA occurs m6A modification in mouse brain endothelial cells, and the m6A modification level of MMP3 mRNA is significantly increased in cerebral I/R injury. Moreover, inhibition of m6A modification reduces MMP3 expression and ameliorates BBB breakdown in cerebral I/R in vivo and in vitro. In conclusion, m6A modification promotes BBB breakdown in cerebral I/R injury through increasing MMP3 expression, indicating that m6A may be a potential therapeutic target for cerebral I/R injury.


Ugandan Men Exposed to Intimate Partner Violence: A Cross-Sectional Survey of Nationally Representative Data.
Although women typically constitute the largest proportion of the population who experience the deleterious effects of intimate partner violence (IPV), understanding the bidirectional nature of IPV is important for developing nuanced prevention initiatives. This study examines data from the 2016 Ugandan Demographic and Health Survey. Participants were selected from households in all the 15 regions in Uganda using a two stage sampling design. A total of 2858 men who were in a heterosexual union or separated/divorced were included in the analysis. Univariate and multivariable logistic regression analyses were performed with the aim of identifying associations between selected demographic variables and male exposure to all forms of IPV combined, psychological violence, physical violence and sexual violence. The prevalence of lifetime IPV and during the 12 months preceeding the survey respectively was 43.6 and 30.5% in all forms, with 35.9 and 24.8% reporting psychological, 20.2 and 11.9% for physical and 8.2 and 5.7% sexual violence. The key factors associated with all forms of IPV were being afraid of their wife/partner most of the time (OR = 5.10, 95% CI 2.91, 8.96) controlling behaviour of the intimate partner (OR = 3.80, 95% CI 2.84, 5.07), bi-directional violence against the partner (OR = 3.20, 95% CI 2.49, 4.12), alcohol consumption by the intimate partner (OR = 1.85, 95% CI 1.40, 2.45). The factors associated with males who experience IPV appear to be modifiable and may warrant consideration for inclusion in programs supporting both males and females who experience IPV.


Certified reference materials for analytical mercury speciation in biological and environmental matrices: do they meet user needs?; a review.
The usefulness of a certified reference material (CRM) for analytical method validation and quality control purposes is attributed mainly to its key properties, namely homogeneity and stability. However, it is also advisable to select suitable CRMs in terms of representativeness. To assess the representativeness of a CRM for analytical mercury speciation, a number of aspects must be considered in regard to the routine samples analyzed: the origin of the matrix, the type of mercury species and the level of concentration. This review critically analyzes the availability of current CRMs for mercury speciation analysis in environmental and biological fields. The characteristics of the CRMs are compared with the matrices and samples covered in papers published in the last five years on mercury speciation, mainly in water, soils, sediments, sewage sludge, seafood, blood, urine and hair.


The additive effect of co-occurring anxiety and depression on health status, quality of life and coping strategies in help-seeking tinnitus sufferers.
Evaluating the effect of anxiety and depression on clinical measures of general health, tinnitus-specific quality of life, and coping abilities. Two hundred sixty-five chronic, subjective tinnitus sufferers were divided into four psychological symptom groups according to cut-off scores on anxiety and depression subscales of the Hospital Anxiety and Depression Scale: (1) no-symptoms, (2) anxiety-only, (3) depression-only, and (4) anxiety-plus-depression. General health-related quality of life (SF-36), tinnitus-specific quality of life (tinnitus reaction questionnaire and tinnitus handicap inventory), and coping abilities (tinnitus coping style questionnaire) were assessed and analyzed across these four psychological symptom groups, which did not differ on age, gender, marital, and working status. Statistically significant and clinically relevant differences on general health-related and tinnitus-specific quality of life and coping abilities were identified when comparing anxiety-plus-depression subgroup with the subgroups anxiety-only, depression-only, or no-symptoms. Highest associations were seen between the anxiety-plus-depression subgroup and impaired quality of life and maladaptive coping. Our results demonstrate the additive effect of both anxiety and depression in impairing general health-related and tinnitus-specific quality of life and application of coping strategies, and reiterate the need for investigating both symptoms in the clinical evaluation of tinnitus patients.


Intra-articular entrapment of the median nerve after elbow dislocation in children.
Two cases of intra-articular median nerve entrapment after reduction of elbow dislocations in children are described. The diagnosis of median nerve entrapment is often delayed. A proximal median nerve deficit, limited passive elbow motion, and an associated medial epicondyle avulsion after reduction of a child's posterior elbow dislocation should alert the surgeon to the possibility of nerve entrapment. Optimal management of this problem consists of early surgical exploration and nerve release.


The association between illness perception and quality of life among Chinese adults with epilepsy: The mediating role of coping style.
To evaluate the associations between illness perception, quality of life (QOL), and coping style among patients with epilepsy (PWE), and to establish the behavior of coping style as a mediator of the interplay between illness perception and QOL. A cross-sectional study of 135 adult Chinese PWE was performed. All patients completed clinical and demographic questionnaires, the Chinese version of the Revised Illness Perception Questionnaire (CIPQ-R), the quality of life in epilepsy-31 inventory (QOLIE-31), and the Simplified Coping Style Questionnaire (SCSQ). Collected data were assessed through correlation analyses, structural equation modeling (SEM), and multiple stepwise linear regression assessments. These patients exhibited a mean QOLIE-31 total score of 46.9 points, consistent with moderately low QOL. Under model III (F = 9.447, p < 0.01, R2 = 0.486), all included variables were found to explain 48.6% of the observed variation in QOL, with illness perception and coping style, respectively, explaining 27.3% and 7% of such variation. SEM findings illustrated that the total influence value of illness perception on QOL was 77.5% (β = -0.775, p < 0.001). Moreover, the illness perception was found to have a direct impact on QOL (β = -0.620, p = 0.001), negative coping (β = 0.309, p < 0.001), and positive coping (β = -0.265, p = 0.014), with negative coping (β = -0.256, p = 0.003), and positive coping (β = 0.288, p = 0.006) also having a direct impact on such QOL. Positive and negative coping styles also served as mediators of an indirect relationship between illness perception and QOL (β = -0.27*0.29 + 0.31* - 0.26 = -0.159, p = 0.001), with coping style thus serving as a significant mediator of the association between QOL and illness perception. The mediating impact of coping style on QOL accounted for 20.5% (-0.159/-0.775) of the total influence. Both coping style and illness perception were detected to be significantly correlated with the QOL of Chinese adult PWE, with coping style serving as a mediator of the association between QOL and illness perception in this patient population. As such, when seeking to control seizures, medical workers should assess illness perceptions and coping styles among PWE as quickly as possible in order to select the optimal interventions most likely to improve the QOL of these patients.


Halobacillus salicampi sp. nov., a moderately halophilic bacterium isolated from a solar saltern sediment.
A Gram-positive, moderately halophilic bacterium, designated strain TGS-15(T), was isolated from the sediment of a solar saltern pond located in Shinan, Korea. Strain TGS-15(T) was found to be a strictly aerobic, non-motile rod which can grow at pH 6.0-10.0 (optimum, pH 9.0), at 20-35 °C (optimum, 28 °C) and at salinities of 1-20 % (w/v) NaCl (optimum, 9 % NaCl). Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain TGS-15(T) belongs to the genus Halobacillus, with sequence similarity of 98.5-96.0 % to known type strains, showing high sequence similarity to Halobacillus locisalis MSS-155(T) (98.5 %), Halobacillus faecis IGA7-4(T) (98.2 %) and Halobacillus alkaliphilus FP5(T) (98.0 %), and less than 98.0 % sequence similarity to other currently recognised type strains of the genus. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, an unidentified glycolipid and an unidentified lipid. The cell wall peptidoglycan was found to be based on L-Orn-D-Asp, the predominant isoprenoid quinone was identified as menaquinone-7 (MK-7) and the major fatty acids were identified as anteiso-C15:0, iso-C15:0, anteiso-C17:0 and C16:1 ω7c alcohol. The DNA G+C content of this novel isolate was determined to be 45.3 mol %. Levels of DNA:DNA relatedness between strain TGS-15(T) and the type strains of 13 other species of the genus ranged from 52 to 9 %. On the basis of the polyphasic analysis conducted in this study, strain TGS-15(T) is concluded to represent a novel species of the genus Halobacillus, for which the name Halobacillus salicampi sp. nov. is proposed. The type strain is TGS-15(T) (=KACC 18264(T) = NBRC 110640(T)).


Experimental study of the action of COX-2 selective nonsteroidal anti-inflammatory drugs and traditional anti-inflammatory drugs in bone regeneration.
The aim of this study is to compare the effects of traditional nonsteroidal anti-inflammatory drugs with nonsteroidal anti-inflammatory drugs that are selective cyclooxygenase-2 (COX-2) inhibitors in the process of bone regeneration in a rat model. Forty-four Wistar strain rats were subjected to osteotomy of the right femur and randomly divided into 3 groups according to the drug to be given (diclofenac, rofecoxib, or placebo). Each group was divided into 2 subgroups according to the time to euthanasia after the surgery. The animals of Subgroup 1 were submitted to euthanasia 2 weeks after surgery, and those of Subgroup 2, underwent euthanasia 4 weeks after surgery. Radiographic examinations and bone callus histomorphometry were analyzed. No intergroup statistical difference was found in the bone callus area or in bone formation area 2 and 4 weeks after surgery. Intra-group analysis concerning the bone neoformation area inside the callus showed a significant difference within the diclofenac group, which presented less tissue. Fracture consolidation in Wistar rats occurs within less than 2 weeks, and the use of nonsteroidal anti-inflammatory drugs does not significantly influence this process.


Verapamil and collagenase differentially affect collagen metabolism in experimental model of Peyronie's disease.
Peyronie's disease (PD) is accompanied by remodelling of connective tissue into fibrotic plaque. Treatment of the inflammatory and fibrotic phases of the disease is not established. The aim of the study was to evaluate the effect of verapamil (VER) and bacterial collagenase (COLL) on collagen metabolism and cell migration in fibroblasts with experimental wound healing and inflammation as an in vitro model of PD. In vitro model of PD was designed using experimental model of inflammation induced by Interleukin-1 (IL-1) in cultured fibroblasts and mechanical damage of the cells. Cell viability, cell proliferation, collagen biosynthesis, prolidase activity and cell migration were studied in both models of the cells treated with VER and COLL. VER decreased cell viability, DNA and collagen biosynthesis and increased prolidase activity in control fibroblast, while in "wounded" fibroblasts it significantly decreased all the processes. COLL did not affect cell viability and DNA biosynthesis, while inhibited collagen biosynthesis and prolidase activity in both control and "wounded" fibroblasts. In IL-1-treated fibroblasts VER inhibited all studied processes except prolidase activity, while COLL inhibited only collagen biosynthesis and prolidase activity. COLL accelerated cell migration, while VER attenuated the process in fibroblast model of wound healing, compared to control cells. VER and COLL attenuate collagen biosynthesis in both fibroblast models. The VER-dependent inhibition of collagen biosynthesis was accompanied by inhibition of DNA biosynthesis at high prolidase activity, while COLL affected this process through inhibition of prolidase activity at high rate of DNA biosynthesis. It shows that anti-fibrotic activity of VER/COLL and anti-inflammatory activity of VER may represent approach to establish standard treatment of PD.


[Using administrative data to assess the impact of length of stay on readmissions: study of two procedures in surgery and obstetrics].
The prospective payment system for the French short-stay hospitals creates a financial incentive to reduce length of stay. The potential impact of the resulting decrease in length of stay on the quality of healthcare is unknown. Readmission rates are valid outcome indicators for some clinical procedures. Retrospective study of the association between length of stay and unplanned readmissions related to the initial stay, for two procedures: cholecystectomy and vaginal delivery. Administrative diagnosis-related groups database of "Assistance publique-Hôpitaux de Paris", a large teaching hospital, for years 2002 to 2005. The risk of readmission according to length of stay, taking age, sex, comorbidity, hospital and year of admission into account, followed a J-shaped curve for both procedures. The probability of readmission was higher for very short stays, with odds ratios and 95% confidence intervals of 6.03 [2.67-13.59] for cholecystectomies (1- versus 3-night stays), and of 1.74 [1.05-2.91] for vaginal deliveries (2- versus 3-night stays). For both procedures, the shortest lengths of stay are associated with a higher readmission probability. Suitable indicators derived from administrative databases would enable monitoring of the association between length of stay and readmissions.


Effects of tubocurarine on end-plate current rundown and quantal content during rapid nerve stimulation in the snake.
1. The effects of tubocurarine, pancuronium, vecuronium and trimethyl-tubocurarine were examined on the amplitudes of end-plate currents (EPC) produced by repetitive nerve stimulation in cut voltage-clamped fibres of the costocutaneous muscle of the garter snake. The effects of tubocurarine were further studied on the amplitudes of miniature end-plate currents (MEPC) recorded immediately before the trains of nerve stimulation, thus allowing estimates to be made of EPC quantal content. 2. All four compounds increased the decline of EPC amplitude with successive impulses (rundown), compared with that observed in control end-plates. There was little effect on the decay time constants of EPC and the effects on rundown were not dependent on membrane potential, indicating that end-plate ion channel blockade was not a major effect in producing rundown. 3. In the presence of tubocurarine the quantal content of the EPC in the plateau phase of the trains was reduced when compared with control, indicating a reduction of transmitter mobilization. However tubocurarine had no significant effect on the quantal content of the first EPC of the trains, indicating that the decreased mobilization is not due to an initial effect on transmitter release. 4. It is suggested that the prejunctional effect of tubocurarine which results in increased EPC train rundown is primarily on transmitter mobilization. It is also suggested that the actions of tubocurarine and the other neuromuscular blockers tested are mediated through a prejunctional nicotinic receptor which may act as a positive feedback mechanism modulating transmitter mobilization.


Roux-en-Y Gastrojejunostomy: is it an effective treatment for complex Hiatal hernias in the morbidly obese?
Primary repair failure rates for hiatal hernias (HH) can reach up to 40%, this is especially high in the morbidly obese patient. There is no clear data on how to manage this patient subset. This paper evaluates the efficacy of Roux-N-Y Gastrojejunostomy (RNY GJ) for treatment of symptomatic HH. A retrospective analysis of all patients who received a Roux-en-Y Gastrojejunostomy (RNY GJ) for HH at our institution between January 2016 and January 2021 was performed. Patient demographics, symptoms, and post-operative outcomes were recorded and univariate analysis was performed between preoperative and postoperative symptoms. Thirty-seven patients with a mean age of 56.9 years (SD 11.8) underwent RNY GJ. Patients were mostly female (81.1%) with a mean BMI of 36.8 (SD 8.4). An 78.4% reduction in symptoms of either heartburn, dysphagia, or regurgitation was noted at follow up (p < 0.001). RNY GJ represents a safe procedure for morbidly obese patients with hiatal hernias with no mortalities amongst our patient cohort along with a significant reduction in pre-operative symptoms and no symptomatic recurrences. RNY GJ should be considered as the operation of choice for repair for this patient population.


Melatonin potentiates cyclic AMP production stimulated by vasoactive intestinal peptide in human lymphocytes.
The present paper demonstrates the effect of melatonin on cyclic AMP production in human lymphocytes from peripheral blood. Melatonin by itself did not influence cyclic AMP accumulation in these cells at any dose studied; however, the drug potentiated the effect of vasoactive intestinal peptide (VIP) on the cyclic nucleotide production. In the presence of physiological concentrations of VIP (either 1, 10 or 100 pM), melatonin potentiated cyclic AMP production. However, at high doses of VIP (either 1, 10 or 100 nM), melatonin exhibited no such effect. The results suggest that human lymphocytes are a target for melatonin and that it may participate, jointly with VIP, in the regulation of immune function.


Influence of metal ions on the biosynthesis of N-acetylglucosaminyl polyprenols by the retina.
The following enzymatic process was investigated, catalyzed by an enzyme preparation from the retina of the embryonic chick: UDP-GlcNAc + dolichol phosphate GDPmannose leads to metal ions GlcNAc-P-P-polyprenol + (GlcNAc)2-P-P-polyprenol + Man-(GlcNAc)2-P-P-polyprenol. These reactions were carried out in the presence of a dolichol phosphate mannose-synthesizing system, shown previously to be an activator of GlcNAc-lipid synthesis. The process was also strongly influenced by the choice of the divalent cation used during the reactions. In the presence of Mg2+, not only was the extent of incorporation of radioactivity from UDP-[3H]GlcNAc increased 4-fold into the GlcNAc lipids, as compared to Mn2+, but the relative distribution of the products was affected as well. In the presence of Mg2+ the reaction was driven mainly in the direction of the formation of the first intermediate of the dolichol pathway, GlcNAc-P-P-polyprenol. Many of the other characteristics of the GlcNAc-transferases, such as pH optimum, requirement for dolichol phosphate and specificity for stimulation by sugar nucleotides, were similar for either the Mn2+ or Mg2+ systems. Retinol phosphate could not replace the requirement for dolichol phosphate. The influence of metal ions, in addition to the stimulation by dolichol phosphate mannose, on GlcNAc-lipid synthesis may be aspects of metabolic regulation of the dolichol pathway.


Anomaly of the left atrium in patients with atrial fibrillation detected by ECG-gated multi-slice computed tomography.
We illustrate pulmonary vein anatomy in 2 patients undergoing multi-slice computed tomography (MSCT) scanning prior to atrial fibrillation ablation, including anomaly of the pulmonary vein. The anomalous variations need to be investigated before catheter procedure, because of the anomalous variations. Non-invasive imaging using MSCT could have important clinical implications and provide the physicians useful information on morphological feature in patients with atrial fibrillation before catheter ablation.


Evolutionary conservation of EF-hand ΙΙ loop in aequorin: Priority of intensity to decay rate in bioluminescence emission.
As a Ca2+-regulated photoprotein, aequorin (Aeq) contains four EF-hand motifs, the second one lacks the standard sequence for Ca2+ coordination and doesn't bind to Ca2+. Here, we replaced this loop with a functional loop. According to structural studies, although the global stability of modified aequorin (4EFAeq) is higher than that of Aeq; increasing the local flexibility accompanied by internal structural rearrangements in 4EFAeq result in its penetrability to urea and acrylamide. A fast decay rate was observed for 4EFAeq. Assuming the presence of intermediate states in the luminescent reaction, this observation indicate that the loop replacement leads to the lowering of the half-life of intermediate states which results in increasing the rate of conformational switching of 4EFAeq to light emitting form. However, considerable reduction in initial luminescence intensity of 4EFAeq suggests that the number of functional complexes is reduced. Our findings demonstrate that the conformational effects of the second loop in Aeq elicit a delicate balance between local flexibility and global stability which may be considered as an important functional parameter in photoproteins. It was also concluded that evolutionary conservation of EF-hand ΙΙ in the current form is a consequence of priority of intensity to decay rate in bioluminescent organisms.


Altered growth characteristics of skin fibroblasts from wild-derived mice, and genetic loci regulating fibroblast clone size.
Mouse fibroblast senescence in vitro is an important model for the study of aging at cellular level. However, common laboratory mouse strains may have lost some important allele variations related to aging processes. In this study, growth in vitro of tail skin fibroblasts (TSFs) derived from a wild-derived stock, Pohnpei (Pohn) mice, differed from growth of control C57BL/6 J (B6) TSFs. Pohn TSFs exhibited higher proliferative ability, fewer apoptotic cells, decreased expression of Cip1, smaller surface areas, fewer cells positive for senescence associated-beta-galactosidase (SA-beta-gal) and greater resistance to H(2)O(2)-induced SA-beta-gal staining and Cip1 expression. These data suggest that TSFs from Pohn mice resist cellular senescence-like changes. Using large clone ratio (LCR) as the phenotype, a quantitative trait locus (QTL) analysis in a Pohn/B6 backcross population found four QTLs for LCR: Fcs1 on Chr 3 at 55 CM; Fcs2 on Chr X at 50 CM; Fcs3 on Chr 4 at 51 CM and Fcs4 on Chr 10 at 25 CM. Together, these four QTLs explain 26.1% of the variations in LCRs in the N2 population. These are the first QTLs reported that regulate fibroblast growth. Glutathione S transferase mu (GST-mu) genes are overrepresented in the 95% confidence interval of Fcs1, and Pohn TSFs have higher H(2)O(2)-induced GST-mu 4, 5 and 7 mRNA levels than B6 TSFs. These enzymes may protect Pohn TSFs from oxidation.


[Value of transabdominal ultrasonography in preoperative assessment of gastric carcinoma].
To investigate the value of transabdominal ultrasonography (TAUS) in preoperative assessment of TNM stage and tumor angiogenesis for patients with gastric carcinoma. Sixty- four patients with gastric carcinoma preoperatively underwent TAUS, in whom transabdominal color Doppler ultrasonography was used for measuring color Doppler vascularity index (CDVI) of each tumor in 37 cases and microvessel density (MVD) was evaluated by using immunohistochemical staining of surgical specimens with anti- CD34 antibody. The overall accuracy rate was 56.0% for T staging of gastric carcinoma (T (1) 2/3 cases, T (2) 28.6% , T (3) 73.1% , T (4) 50.0% , respectively) by TAUS. The diagnostic accuracy rate was 63.3% for lymph node status of gastric carcinoma. The diagnostic sensitivity and specificity for lymph node metastasis was 37.9% and 100% respectively. The overall accuracy for N staging of gastric carcinoma was 57.1% (N (0) 100% , N (1) 16.7% , N (2) 35.3% , respectively). The diagnostic sensitivity and specificity for determining distant metastases was 58.3% and 100% respectively. The CDVI of gastric carcinoma determined by color Doppler ultrasonography was significantly correlated to vascular invasion (P=0.0418), a linear correlation between CDVI and MVD was determined by logistic regression analysis (r=0.5628, P< 0.01). TAUS can be a routine diagnostic approach for preoperative gastric carcinoma patients.


Novel corticotropin-releasing hormone receptor genes (CRHR1 and CRHR2) linkage to and association with polycystic ovary syndrome.
Women with polycystic ovarian syndrome (PCOS) have increased hypothalamic-pituitary-adrenal (HPA) axis activation, pro-inflammatory mediators, and psychological distress in response to stressors. In women with PCOS, the corticotropin-releasing hormone (CRH) induces an exaggerated HPA response, possibly mediated by one of the CRH receptors (CRHR1 or CRHR2). Both CRHR1 and CRHR2 are implicated in insulin secretion, and variants in CRHR1 and CRHR2 genes may predispose to the mental-metabolic risk for PCOS. We phenotyped 212 Italian families with type 2 diabetes (T2D) for PCOS following the Rotterdam diagnostic criteria. We analyzed within CRHR1 and CRHR2 genes, respectively, 36 and 18 microarray-variants for parametric linkage to and/or linkage disequilibrium (LD) with PCOS under the recessive with complete penetrance (R1) and dominant with complete penetrance (D1) models. Subsequentially, we ran a secondary analysis under the models dominant with incomplete penetrance (D2) and recessive with incomplete penetrance (R2). We detected 22 variants in CRHR1 and 1 variant in CRHR2 significantly (p < 0.05) linked to or in LD with PCOS across different inheritance models. This is the first study to report CRHR1 and CRHR2 as novel risk genes in PCOS. In silico analysis predicted that the detected CRHR1 and CRHR2 risk variants promote negative chromatin activation of their related genes in the ovaries, potentially affecting the female cycle and ovulation. However, CRHR1- and CRHR2-risk variants might also lead to hypercortisolism and confer mental-metabolic pleiotropic effects. Functional studies are needed to confirm the pathogenicity of genes and related variants.


Preparation of Ni(OH)2/CuO heterostructures for improved photocatalytic degradation of organic pollutants and microorganism.
In this study, the Ni(OH)2/CuO heterostructured photocatalysts have been prepared via microwave (MW) hydrothermal method. The results indicate that the Ni(OH)2/CuO heterostructured composite exhibits a strong absorption in the UV and Vis regions. The construction of the heterojunction also improves the photogenerated carrier transport and inhibits the electron-hole separation due to the enhanced absorbance and the well alignment of the energy band at the Ni(OH)2/CuO interface. The photocatalytic capability of the heterostructured composites with different Ni(OH)2/CuO molar ratios is evaluated by the photodegradation of methylene blue under visible light illumination. The results reveal that the Ni(OH)2/CuO (1:1) heterostructures show the best photocatalytic efficiency, which is 2.18 and 6.13 times higher than that of pure Ni(OH)2 and CuO, respectively. Besides, the Ni(OH)2/CuO composites also reveal remarkable biocompatibility and strong photocatalytic activity in the degradation of antibiotics such as ciprofloxacin (CIP) and tetracycline (TC) and inactivation of Escherichia coli (E. coli).


Bis(formato-κO)bis-[1-(pyridin-2-yl)ethanone oxime-κN,N']nickel(II).
In the title compound, [Ni(HCOO)(2)(C(7)H(8)N(2)O)(2)], the Ni atom is six-coordinated by four N atoms from two oxime ligands and by two O atoms from two formate ions in a distorted octa-hedral geometry, with the oxime-N atoms mutually trans. The mol-ecular conformation is stabilized by intra-molecular O-H⋯O hydrogen bonds.


E-cadherin is critical for collective sheet migration and is regulated by the chemokine CXCL12 protein during restitution.
Chemokines and other immune mediators enhance epithelial barrier repair. The intestinal barrier is established by highly regulated cell-cell contacts between epithelial cells. The goal of these studies was to define the role for the chemokine CXCL12 in regulating E-cadherin during collective sheet migration during epithelial restitution. Mechanisms regulating E-cadherin were investigated using Caco2(BBE) and IEC-6 model epithelia. Genetic knockdown confirmed a critical role for E-cadherin in in vitro restitution and in vivo wound repair. During restitution, both CXCL12 and TGF-β1 tightened the monolayer by decreasing the paracellular space between migrating epithelial cells. However, CXCL12 differed from TGF-β1 by stimulating the significant increase in E-cadherin membrane localization during restitution. Chemokine-stimulated relocalization of E-cadherin was paralleled by an increase in barrier integrity of polarized epithelium during restitution. CXCL12 activation of its cognate receptor CXCR4 stimulated E-cadherin localization and monolayer tightening through Rho-associated protein kinase activation and F-actin reorganization. These data demonstrate a key role for E-cadherin in intestinal epithelial restitution.


Aging reduces somatosensory responsiveness of caudate neurons in the awake cat.
Neuronal activity was recorded in 7 awake cats (3 animals 11-15 years and 4 animals 1-3 years of age) to determine if the ability of caudate neurons to process facial somatosensory information was impaired in aged animals. Proportionately fewer neurons responded to somatosensory stimuli and facial receptive fields were larger in the aged cats. In addition, proportionately fewer caudate neurons responded to cortical activation, there were fewer excitatory responses and spontaneous firing decreasing in aged cats. These results provide additional evidence that excitability of caudate neurons is reduced in aged cats.


Management of acute aortic occlusion.
Acute aortic occlusion is most often seen in elderly patients with advanced cardiac disease. The management of these patients has been facilitated by the use of extraanatomic bypass. Over the past 2 years, six patients aged 55 to 87 years presented to our medical center with acute aortic occlusion, three after major operative procedures. One patient had a thrombosed abdominal aortic aneurysm; in the other five patients differentiation between saddle embolus and thrombosis of the distal aorta was impossible. There was one operative death. Four of the other five patients underwent axillobifemoral bypass and one underwent aortofemoral thrombectomy. All survived, and none required amputation. Two of the three patients who underwent preoperative aortography developed transient renal failure postoperatively. Aortography is of little value in diagnosis and is probably contraindicated in acute aortic occlusion. Our recommendation for operative management includes (1) preparation of the patient for possible axillobifemoral bypass, (2) angiography of distal runoff via both femoral arteries, (3) attempt at bilateral aortofemoral embolectomy with Fogarty catheters, and (4) axillobifemoral bypass if embolectomy fails to restore normal pulsatile flow.


Transition patterns of metabolic dysfunction-associated fatty liver disease status in relation to arterial stiffness progression: a health check-up cohort study.
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new diagnostic criterion based on hepatic steatosis and metabolic dysfunction. However, a comprehensive evaluation of the association of MAFLD dynamic transitions with arterial stiffness progression has yet to be conducted. This cohort study included 8807 Chinese health check-up participants (median follow-up = 50.2 months). Participants were categorized into four groups according to MAFLD status at baseline and follow-up (none, persistent, developed and regressed). Arterial stiffness progression was assessed by the annual brachial-ankle pulse wave velocity (ba-PWV) increase and arterial stiffness incidence. Compared with the non-MAFLD group, the annual increase in ba-PWV was highest in the persistent-MAFLD group [6.75 cm/s/year, (95% CI 4.03-9.33)], followed by the developed-[6.35 cm/s/year, (95% CI 3.80-8.91)] and the regressed-[1.27 cm/s/year, (95% CI - 2.18 to 4.72)] MAFLD groups. Similarly, compared with the non-MAFLD group, the persistent-MAFLD group had a 1.31-fold increased arterial stiffness risk [OR 1.31; 95% CI 1.03-1.66]. The associations of MAFLD transition patterns with arterial stiffness incidence did not differ across any clinically specific subgroups evaluated. Furthermore, the potential effect of dynamic changes in cardiometabolic risk factors on arterial stiffness incidence among persistent-MAFLD participants was mostly driven by annual fasting glucose and triglyceride increases. In conclusion, persistent MAFLD was associated with an increased risk of arterial stiffness development. Moreover, in persistent-MAFLD subjects, elevated blood glucose and triglyceride levels might facilitate the arterial stiffness incidence.


Uterine muscle relaxant drugs for threatened miscarriage.
Miscarriage is the spontaneous loss of a pregnancy before the fetus is viable. Uterine muscle relaxant drugs have been used for women at risk of miscarriage in the belief they relax uterine muscle, and hence reduce the risk of miscarriage. To assess the effects for the woman and her baby of uterine muscle relaxant drugs when used for threatened miscarriage. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (4 May 2004), and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2004). Randomised trials were included, and quasi-randomised trials were excluded. The participants were women with a pregnancy of less than 20 weeks' gestation having a threatened miscarriage. The interventions were any uterine muscle relaxing drugs (including tocolytic and antispasmodic agents) compared with either placebo or no drug. Primary outcomes for the review were miscarriage: defined as spontaneous pregnancy loss before fetal viability, baby death (stillbirth or neonatal death) and maternal death. Both review authors independently assessed studies for eligibility and trial quality, and extracted data. One poor quality trial (170 women) was included. This compared a beta-agonist with placebo. There was a lower risk of intrauterine death associated with the use of a beta-agonist (relative risk (RR) 0.25, 95% confidence interval (CI) 0.12 to 0.51). Preterm birth was the only other outcome reported (RR 1.67, 95% CI 0.63 to 4.38). There is insufficient evidence to support the use of uterine muscle relaxant drugs for women with threatened miscarriage. Any such use should be restricted to the context of randomised trials.


Spatially resolved detection of antibody-antigen reaction on solid/liquid interface using total internal reflection excited antigen fluorescence and charge-coupled device detection.
Spatially-resolved detection of antibody-antigen reactions at the solid/liquid interface was investigated by total internal reflection excited fluorescence from large area flat surfaces. Anti-HSA immunoglobulin G (IgG) antibody was immobilized at four spatially distinct spots. Binding of fluorescein-labeled human serum albumin (HSA) from the solution to immobilized antibody was detected by a cooled charge-coupled device (CCD) as a charge in the fluorescence intensity. A two-dimensional representation of the fluorescence was obtained during the binding reaction time of 25 mins. The contributions from bound and free antigen to the total signal were evaluated. The influence of the scattered excitation light and the normalization of fluorescence signal with respect to the two-dimensional incident light intensity distribution are discussed.


Alterations in Degree Centrality and Functional Connectivity in Parkinson's Disease Patients With Freezing of Gait: A Resting-State Functional Magnetic Resonance Imaging Study.
Freezing of gait (FOG) is a common disabling motor symptom in Parkinson's disease (PD), but the potential pathogenic mechanisms are still unclear. A total of 22 patients with PD with FOG (PD-FOG), 28 patients with PD without FOG (PD-nFOG), and 33 healthy controls (HCs) were recruited in this study. Degree centrality (DC)-a graph theory-based measurement of global connectivity at the voxel level by measuring the number of instantaneous functional connections between one region and the rest of the brain-can map brain hubs with high sensitivity, specificity, and reproducibility. DC was used to explore alterations in the centrality of PD-FOG correlated with brain node levels. PD-FOG cognitive network dysfunction was further revealed via a seed-based functional connectivity (FC) analysis. In addition, correlation analyses were carried out between clinical symptoms and acquired connectivity measurement. Compared to the PD-nFOG group, the PD-FOG group showed remarkably increased DC values in the right middle frontal gyrus (RMFG). There were no significant differences in other gray matter regions. Importantly, the clinical severity of FOG was related to the mean DC values in the RMFG. This brain region served as a seed in secondary seed-based FC analysis, and we further found FC changes in the right precuneus, right inferior frontal gyrus, right superior frontal gyrus (SFG), and cerebellum. Increased RMFG activity and FC network alterations in the middle frontal cortex with the precuneus, inferior, and SFG, and the cerebellum may have great potential in brain dysfunction in PD with FOG.


Effects of phenobarbital on hypothalamic-pituitary-thyroid axis in the rat.
It has been reported that phenobarbital (PB) increases the peripheral clearance of T4 and T3 and decreases serum T4 and T3 concentrations in the rat, but serum TSH remains unchanged. To explore a possible direct effect of PB on TSH secretion at the hypothalamic-pituitary level, adult male rats were given PB 100 mg/kg or vehicle IP for 10 days. No difference in their thyroid weights was observed. In the PB-treated group serum T4 was decreased (PB, 3 +/- 0.2 micrograms/dl vs. control, 3.8 +/- 0.1 micrograms/dl, mean +/- SE, p less than .002), as was serum T3 (PB, 51 +/- 6 ng/dl vs. control, 70 +/- 5 ng/dl, p less than .05), but serum TSH remained unchanged. Pituitary TSH and hypothalamic TRH contents also were unchanged. Further studies were carried out similarly in the thyroidectomized hypothyroid rat to eliminate the effect of PB on serum T4 and T3 levels. PB or vehicle were started two days after thyroidectomy. By postoperative day 12, TSH levels in the PB-treated rats were lower than in the controls (PB, 697 +/- 62 microU/ml vs. control, 891 +/- 53 microU/ml, p less than .05). Pituitary TSH and hypothalamic TRH contents again were similar in both groups. When TRH (500 ng/kg body weight, IV) was given, the increment in serum TSH at 10 minutes was significantly lower in the PB group (PB, 53 +/- 26 microU/ml vs. control, 131 +/- 18 microU/ml, p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)


Construction of new personal meanings by cancer patients: a qualitative analysis in an Italian patient population.
The goal of this study is to investigate the meaning that cancer patients in active therapy and/or rehabilitation give to their illness and resources they rely on to build new experiences of meaning and a future perspective. The present study consisted in a summative content analysis of answers to open questions of the Purpose In Life (PIL) Questionnaire administered to 158 consecutive patients with non-advanced cancer (no metastases). The PIL is an attitude scale that indicates the degree of attainment of meaning and purpose in life and is divided into three sections: a first 20-item quantitative section, with statements rated on a 7-point verbal scale with two anchoring phrases (part A); a qualitative section with 13 open-end items and paragraph composition section addressing the future goals (part B) and past meaningful experience (part C). For the present study, we analyzed the answers to open questions, most interesting in a therapeutic contest related to the meanings associated with life, illness, and suffering to understand the experienced of the cancer patients. The main recurring themes in PIL section B analyzed associated to the sense of life, disease, and death are as follows: meaning (positive/negative), personal dimension, religiousness; physical health, family, normal life; negative sense of death, the end, natural transition, religious belief, consolation, mystery, rejection; opportunity, negativity. Whereas main themes emerging from section C were associated to life goals of the interviewed patients: the desire of realization in the future perspective; the value of life; physical health and healing; guiding values; plus three more themes, distinguishable, but with a minor recurrence: legacy responsibility, religiousness, lack of purpose/resignation. The use of summative content analysis evidenced the recurrence of a strong sense of positivity, present in the majority of the interviews. In particular, this positivity is shown by the use of words associated frequently to self-consciousness and self-evaluation, desire of happiness, and desire of contributing to the good of significant others and of taking care of your own life in order to give a positive contribution.


Pharmacological actions of levallorphan allyl bromide (CM 32191), a new peripheral narcotic antagonist.
A dissociation of the effects of the newly synthesized quaternary ammonium narcotic antagonist, levallorphan allyl bromide (CM 32191) on morphine-induced analgesia and constipation in the mouse is reported. CM 32191 behaved as a pure morphine antagonist on the "in vitro" preparation of longitudinal muscle of guinea-pig ileum and antagonized dose-dependently the peripherally mediated morphine constipation (ID50:15.6 mg/kg) without significantly affecting morphine analgesia (ID50: greater than 80 mg/kg). Its peripheral selectivity was greater than that of another quaternary ammonium compound, N-methyl naloxone. It is proposed as a useful pharmacological tool to differentiate the peripherally mediated from the centrally mediated effects of opioids.


Evaluation of polymyxin susceptibility profile among KPC-producing Klebsiella pneumoniae using Etest and MicroScan WalkAway automated system.
Determination of polymyxin susceptibility profile is important to monitor resistance rates and for implementing control measures for polymyxin-resistant carbapenem-resistant Enterobacteriaceae. Some laboratorial methods have been used to determine the polymyxin susceptibility profile. However, the performance of MicroScan WalkAway has been poorly reported for KPC-producing Klebsiella pneumoniae, so far. To evaluate two different methods, Etest and the MicroScan automated system, in determining minimal inhibitory concentration (MIC) of polymyxin among KPC-producing K. pneumoniae isolated from patients in two care units (ICUs) of a tertiary hospital in Porto Alegre, Southern Brazil. A total of 101 KPC-Kb isolates were obtained from rectal swabs and clinical specimens (urine, blood, and endotracheal aspirate). Colistin and polymyxin B MICs were determined using MicroScan WalkAway automated system and Etest, respectively. Discrepant results were resolved by broth microdilution (BMD). MicroScan showed 88.1% of sensitivity for predicting polymyxin B resistance in KPC-producing K. pneumoniae compared to the results obtained by Etest. All discrepant results were tested by BMD and these were concordant with results obtained by Etest. The MicroScan automated system does not seem to be very efficient for the screening of polymyxin-resistant isolates once an inappropriate sensitivity is achieved. The results presented here show the need for confirmation of the susceptibility profile by use of a dilution method (Etest or BMD).


Chemical modification of chalcone isomerase by mercurials and tetrathionate. Evidence for a single cysteine residue in the active site.
Chalcone isomerase from soybean is inactivated by stoichiometric amounts of p-mercuribenzoate or HgCl2. Spectral titration of the enzyme with p-mercuribenzoate indicates that a single thiol group is modified. Treatment of modified enzyme with KCN or thiols results in a complete restoration of enzyme activity demonstrating that the inactivation is not due to irreversible protein denaturation. A product of the enzymatic reaction, naringenin, provides complete kinetic protection against inactivation by both mercurials. The binding constant (33 microM) for naringenin determined from the concentration dependence of the protection agrees with the inhibition constant (34 microM) for naringenin as a competitive inhibitor of the catalytic reaction. This agreement demonstrates that the observed kinetic protection results from the specific binding of naringenin to the active site. Incubation of native chalcone isomerase with sodium tetrathionate (0.1 M) results in a slow time-dependent loss of enzymatic activity. The inactivation of chalcone isomerase by tetrathionate and N-ethylmaleimide becomes very rapid in the presence of 6 M urea, indicating that the native tertiary structure is responsible for the low reactivity of the enzymatic thiol. The stoichiometric modification of reduced and denatured chalcone isomerase by [3H] N-ethylmaleimide indicates that the enzyme contains only a single cysteine residue and does not contain any disulfides. The evidence presented suggests that the only half-cystine residue in chalcone isomerase is located in the active site and thereby provides the first clue to the location of the active site in chalcone isomerase.


Quantitative determination of guanidinoacetate and creatine in dried blood spot by flow injection analysis-electrospray tandem mass spectrometry.
Guanidinoacetate (GAA) and creatine (Cr) are reliable biochemical markers of primary creatine disorders. The aim of this study was to develop and validate a method for the determination of GAA and Cr in dried blood spot through the use of stable isotope dilution and flow injection analysis (FIA)-ESI-MS/MS. Dried blood spots were extracted using methanol-water solution containing D3-Cr. After evaporation and formation of butyl esters, samples were analyzed using multiple reaction monitoring mode (m/z 174.2-->101.1 for GAA, 188.3-->90.1 for Cr and 191.3-->93.1 for D3-Cr). The analysis was very fast (1 min). The detection limits were 0.34 micromol/l of blood and 0.30 micromol/l of blood for Cr and GAA, respectively, and the response was linear over the range 0.25-12.5 micromol/l of blood for GAA and 3.57-624.7 micromol/l of blood for Cr. Recovery range was 93-101% for Cr and 94-105% for GAA and between-run CVs were 5.3% for GAA and 4.5% for Cr. Ion suppression effect was also studied. The method was applied to spots obtained from two patients affected by GAMT deficiency, four patients affected by AGAT deficiency (including a newborn) as well as 282 healthy subjects. The detection of GAA in dried blood spot by FIA-ESI-MS/MS is a highly reliable and high throughput method for the diagnosis of GAMT and AGAT deficiencies and a possible tool for newborn screening of both these tractable disorders.


Utility of 68 Ga-FAPI-04 PET/CT in Adenoid Cystic Carcinoma Compared With 18 F-FDG PET/CT : Two Case Reports.
68 Ga-fibroblast activation protein inhibitor (FAPI) PET/CT is an emerging imaging modality with high sensitivity and high tumor-to-background ratio in various cancers including in the head and neck regions. The authors present 2 cases of adenoid cystic carcinoma who underwent 68 Ga-FAPI-04 and 18 F-FDG PET/CT. Locoregional recurrence has been detected more precisely in the first case with 68 Ga-FAPI-04. In the second case, 68 Ga-FAPI-04 outperformed 18 F-FDG in the number of lesions and demonstrated intense FAP uptake on widespread metastases, which could provide a treatment option as a theranostic concept. These cases highlight that 68 Ga-FAPI-04 PET/CT may be useful for detecting local recurrence and metastases and help select patients for radionuclide treatments targeting cancer-associated fibroblasts.


Cancer in the population of Hanoi, Vietnam, 1988-1990.
The first results from the population-based cancer registry for the city of Hanoi, in northern Vietnam, are presented. In men, incidence rates are moderate-low with the most common cancers being lung, stomach and liver. Cancer of the penis, reportedly very common in early case series from Vietnam, is now rarely seen. In women, incidence rates are low with the most common cancer, breast cancer, having a recorded incidence similar to that in China. Cervix cancer incidence is very low, which contrasts strongly with hospital series from the south of Vietnam, and of 30 years earlier in Hanoi. The incidence of choriocarcinoma is high, and that of nasopharynx cancer (in both sexes) moderately so; both findings are typical of southeast Asian populations. The incidence rates are coherent with the results from recent studies of Vietnamese migrants in the USA and UK.


Three-dimensional flexible molybdenum oxynitride thin film as a high capacity anode for Li-ion batteries.
With the fast development of flexible wearable electronics, mobile electronic equipment, electric tool and electric vehicles, high specific capacity, superior cycle stability and excellent fast-charge performance are required for lithium-ion batteries (LIBs). Nevertheless, commercial graphite with the limited theoretical capacity (372 mAh g-1) and short lifespan is difficult to satisfy the requirements of the new generation of LIBs. In this work, the three-dimensional flexible molybdenum oxynitride (MNO) thin films with non-binder were prepared by magnetron sputtering approach. The charge transfer resistance and Li-ion diffusion coefficient were measured by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV), and the results show that molybdenum nitride is helpful to increase the diffusion and electron transfer of Li-ion. The MNO thin film annealed at 300 °C with irregular aggregate matrix structure shows a discharge capacity of 413 mAh g-1 after 180 cycles at 1 A g-1. The outstanding rate performance and cycle stability suggest that these binder-free thin film electrodes, especially nitrides, offer great opportunity for energy storage systems with fast-charge capabilities.


Giving the right tug for migration: cadherins in tissue movements.
Dynamically regulated cell-cell adhesion is crucial for morphogenesis during embryonic development and tumor progression. The cadherins as calcium-dependent cell-cell adhesion proteins represent key molecules in these tissue movements. How cadherins serve in maintaining tissue cohesion during migration, facilitate cell-cell communication and promote signaling will be summarized in this review.


The Parent-Baby Venture Program: prevention of child abuse.
The overwhelming obstacles adolescents face to successful achievement of the maternal role. To describe an innovative, community-based program to support high risk adolescents during the early postpartum period. A review of the literature related to programs designed to promote maternal-role attainment and prevent child abuse/neglect. Interviews with participants indicate a positive response to the intervention but regression to maladaptive behavior in some following termination.


Type-B trichothecene calibrants: Comparison of HPLC and GC-results within an intercomparison study.
Within the EC-financed project "Feasibility Study for the Production of Certified Calibrants for the Determination of Deoxynivalenol and other B-Trichothecenes", an intercomparison study was performed with 13 European participants.Main goals of the intercomparison study were to check the feasibility of a small batch of gravimetrically prepared calibrants, to directly compare common and individually prepared calibrants, to test the practicability of toxin mixtures as calibrant solutions and finally to give recommendations for the means of certification. Additionally, it focused on the comparison of gas chromatography (GC) and high performance liquid chromatography (HPLC) for the determination of pure type-B trichothecene solutions, which is described in this publication.The participating laboratories received calibrant solutions as well as toxin solutions of unknown concentration and employed mainly HPLC-UV; GC-ECD (electron capture detection) and GC-MS (mass spectrometry) methods were used less often.The intercomparison study generally suffered from a high rate of outliers (22% of all the data). Throughout the study, 48% of all GC results were classified as outliers and it soon became apparent, that GC results highly infuenced the outcome of the study and that the used GC methods were not robust enough for the certification of type-B trichothecene calibrants. The high discrepancy between HPLC and GC results in the intercomparison study presumably lies in the crucial step of derivatisation.


Charge movement in the membrane of striated muscle.
This account of charge movement in striated muscle membrane must be regarded as essentially tentative. I have tried to present, within a simplified descriptive scheme, one way in which the present confusion of results can be resolved into a self-consistent account. But I am sure that as more complete and more accurate measurements are made, the deficiencies of this account will become even clearer. Nevertheless I believe that any successful description of the dielectric properties of biological membranes will have to take account of slow and nonlinear polarization of numerous membrane constituents and of the improbability of finding within the experimentally available range any finite potential region where polarization is linear.


Mapping specific vulnerability of multiple confined and unconfined aquifers by using artificial intelligence to learn from multiple DRASTIC frameworks.
An investigation is presented to improve on the performances of the Basic DRASTIC Framework (BDF) and its variation by the Fuzzy-Catastrophe Framework (FCF), both of which provide an estimate of intrinsic aquifer vulnerabilities to anthropogenic contamination. BDF prescribes rates and weights for 7 data layers but FCF is an unsupervised learning framework based on a multicriteria decision theory by integrating fuzzy membership function and catastrophe theory. The challenges in the paper include: (i) the study area comprises confined and unconfined aquifers and (ii) Artificial Intelligence (AI) is used to run Multiple Framework (AIMF) in order to map specific vulnerability due to a specific contaminant. Predicted results by AIMF are referred to as Specific Vulnerability Indices, as the learned VIs are referenced to site-specific nitrate-N. The results show that correlation coefficient between BDF or FCF with nitrate-N is lower than 0.7 but the AIMF strategy improves it to greater than 0.95. The results are evidence for the proof-of-concept for transforming frameworks to models capable of further learning.


Fibronectin promotes VEGF-induced CD34 cell differentiation into endothelial cells.
Adult endothelial progenitor cells (EPC) may be a useful source for engineering the endothelialization of vascular grafts. However, the optimal factors that promote differentiation of EPCs into endothelium remain to be elucidated. The goal of this current report was to determine which extracellular matrix (ECM) protein might modulate or enhance the effects of EPCs on differentiation into mature endothelium. Human EPCs (CD34(+) cells) were cultured in ECM-coated six-well plates in MCDB-131 medium containing vascular endothelial growth factor (VEGF), insulin-like growth factor-1, and basic fibroblast growth factor. After 21 days, differentiated endothelial colonies were confirmed by immunofluorescence for von Willebrand factor (vWF) and vascular-endothelial (VE)-cadherin and mRNA expression of the endothelial markers Flk-1, vWF, and VE-cadherin. Cell migration toward the VEGF-matrix protein combinations was also measured. As judged by positive staining for endothelial markers vWF and VE-cadherin, the combination of VEGF with fibronectin (FN) produced significantly more endothelial colonies (P <.05) than did collagens I or IV or vitronectin. Defined fragments of FN did not enhance VEGF-mediated effects. Fibrinogen produced intermediate stimulation of differentiation. FN also enhanced VEGF-mediated CD34(+) cell migration. Blockade of alpha5beta1, but not alphavbeta3 or alphavbeta5, inhibited both VEGF-mediated CD34(+) cell differentiation and migration. VEGF and FN together significantly promote the migration and differentiation of CD34(+) cells. This synergism is specific to FN and the alpha5beta1 integrin. Combinations of VEGF and FN may be useful in promoting differentiation of circulating endothelial progenitors into endothelial cells for tissue engineering. Clinical relevance Treatment of injured or diseased tissues with adult stem cells is a promising approach. In particular, bone marrow derived circulating endothelial progenitors (CEP's) have been shown to differentiate into endothelial cells in vitro and promote tissue revascularization of ischemic limbs and myocardium in vivo. Because of the relative ease of obtaining CEP's and as well as its high proliferative rate, CEP's may have clinical potential for endothelialization of prosthetic vascular grafts and revascularization of injured myocardium. However, there is a need to better understand the molecular pathways involved in the proliferation and differentiation of CEP's to take full advantage of its clinical potential.


Deformity and functional outcome after treatment for supracondylar humerus fractures in children: a 5- to 10-year follow-up of 139 supracondylar humerus fractures treated by plaster cast, skeletal traction or crossed wire fixation.
At Haukeland University Hospital (HUH), we used overhead skeletal traction for displaced supracondylar humerus fractures (SCHF) in children until closed reduction and crossed wire fixation was introduced in the early 1990s. Though there are obvious and well-documented benefits of wire fixation, the aim of this study was to document and compare the results and complication rates for both methods. One hundred and thirty-nine patients treated for SCHF between 1988 and 1998 were available for follow-up. Of these, 40 children were treated with a plaster cast, 46 with overhead skeletal traction and 45 with crossed wire fixation. Eight children were treated with open reduction and crossed wires. The mean time to follow-up was 7.1 years [standard deviation (SD) 3.2]. The length of hospital stay was 2 days for those treated with crossed wire fixation compared to 11 days for traction (P < 0.001). The rate of nerve injury in Gartland type 3 fractures was 19%. There was no significant difference in the number of complications or in the functional outcome after skeletal traction or wire fixation, but there were more reoperations in the traction group (P = 0.04). Patients treated solely with a plaster cast had a mean of 4° increased extension of the affected elbow compared to 1° in the crossed pin fixation group (P = 0.02). Though this has little clinical relevance, it does indicate improved reduction in the operated patients, as one would expect. The introduction of crossed wire fixation has significantly reduced the number of days for which patients are hospitalised for SCHF. The rate of nerve injuries in Gartland type 3 fractures is high. Despite the fact that this study includes the first patients to be treated with crossed wire fixation at our institution, no significant increase in the risk of complications could be found compared to skeletal traction.


Effectiveness of growth hormone (GH) therapy in GH-deficient children and non-GH-deficient short children.
The growth response during short-term growth hormone (GH) treatment was evaluated in eight prepubertal non-GH-deficient (non-GHD) children and compared with six prepubertal GH-deficient (GHD) patients. Standard doses of GH can improve growth rate in GHD and in some non-GHD patients. In neither group the growth response can be predicted by the acute increase in Thymidine Activity or Somatomedin-C levels. A diagnostic trial of GH treatment may be the only certain method of selecting the short non-GHD patients who may benefit from long-term GH therapy.


Experimentally induced otitis and audiogenic seizure in the mouse.
Audiogenic seizures can be induced in genetically non-susceptible 17-day-old mice (Rb/3 strain) with various results. Priming only induces 9% of seizures, auditory insulation 3,8%, while experimental otitis leads to 79%. The hypothesis concerning disuse supersensitivity subsequent to acoustic deprivation was not confirmed by the experiment. However, modification of acoustic transmission at middle ear level induced by otitis or ear physical damage during the maturation period, exposes the upper nervous centers to intense stimulation to which the reaction is a recruiting response.


The non-random distribution of intronless human genes across molecular function categories.
It has been proposed that one function of introns is to coordinate expression across/within networks of related genes. This same hypothesis also predicts that intronless genes will not be uniformly distributed among the functional categories of human genes, but will be found most frequently in those categories that have less need to communicate changes in their expression. Statistical analysis demonstrates significant clustering of single exon genes among those with binding or signal transduction/receptor activities and fewer than expected among those with catalytic function.


Metabolomic approach to profile functional and metabolic changes in heart failure.
Heart failure (HF) is characterized by a series of adaptive changes in energy metabolism. The use of metabolomics enables the parallel assessment of a wide range of metabolites. In this study, we appraised whether metabolic changes correlate with HF severity, assessed as an impairment of functional contractility, and attempted to interpret the role of metabolic changes in determining systolic dysfunction. A 500 MHz proton nuclear magnetic resonance ((1)H-NMR)-based analysis was performed on blood samples from three groups of individuals: 9 control subjects (Group A), 9 HF patients with mild to moderate impairment of left ventricle ejection fraction (LVEF: 41.9 ± 4.0 %; Group B), and 15 HF patients with severe LVEF impairment (25.3 ± 10.3 %; Group C). In order to create a descriptive model of HF, a supervised orthogonal projection on latent structures discriminant analysis (OPLS-DA) was applied using speckle tracking-derived longitudinal strain rate as the Y-variable in the multivariate analysis. OPLS-DA identified three metabolic clusters related to the studied groups achieving good values for R(2) [R(2)(X) = 0.64; R(2)(Y) = 0.59] and Q(2) (0.39). The most important metabolites implicated in the clustering were 2-hydroxybutyrate, glycine, methylmalonate, and myo-inositol. The results demonstrate the suitability of metabolomics in combination with functional evaluation techniques in HF staging. This innovative tool should facilitate investigation of perturbed metabolic pathways in HF and their correlation with the impairment of myocardial function.


How to get (a)round: mechanisms controlling growth and division of coccoid bacteria.
Bacteria come in a range of shapes, including round, rod-shaped, curved and spiral cells. This morphological diversity implies that different mechanisms exist to guide proper cell growth, division and chromosome segregation. Although the majority of studies on cell division have focused on rod-shaped cells, the development of new genetic and cell biology tools has provided mechanistic insight into the cell cycles of bacteria with different shapes, allowing us to appreciate the underlying molecular basis for their morphological diversity. In this Review, we discuss recent progress that has advanced our knowledge of the complex mechanisms for chromosome segregation and cell division in bacteria which have, deceptively, the simplest possible shape: the cocci.


Anti-adrenal medullary antibodies in IDDM subjects and subjects at high risk of developing IDDM.
Previous reports have noted the presence of anti-adrenomedullary antibodies in subjects with insulin-dependent diabetes mellitus (IDDM). We initiated a study to evaluate the presence of complement-fixing anti-adrenomedullary antibodies (CF-ADM) in the following subjects: group 1 (age 4-60 yr), anti-islet cell antibody-positive (ICA+) subjects at high risk of developing diabetes, in which 9 (32%) of 28 were positive for CF-ADM; group 2 (age 6-41 yr), anti-ICA negative (ICA-) subjects at high risk of developing diabetes, in which 0 (0%) of 15 were positive for CF-ADM; group 3 (age 1-58 yr), ICA+ diabetic subjects, in which 7 (30%) of 23 were positive for CF-ADM; group 4 (age 5-68 yr), ICA- diabetic subjects, in which 1 (4%) of 24 was positive for CF-ADM; group 5 (age 20-56 yr), volunteer blood bank donor controls, in which 2 (6%) of 32 were positive for CF-ADM; and group 6, known healthy controls, in which 0 (0%) of 14 were positive for CF-ADM. CF-ADM were increased in group 1 compared with group 2 (P less than .02) and both control groups (P less than .02). CF-ADM were increased in group 3 compared with group 4 (P less than .03) and both control groups (P less than .03 vs. group 5, P less than .05 vs. group 6). Presence of CF-ADM was associated with presence of ICA in group 1 (P less than .02) and group 3 (P less than .03).(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical characteristics, treatment and long-term outcomes of patients with right-sided cardiac thrombus.
Right-sided cardiac thrombus is rare and may be caused by venous thromboembolism, in association with medical devices or stasis of blood in atrial fibrillation (AF) and cardiomyopathies. Complications include pulmonary embolism (PE) and paradoxical stroke. Current data are limited and mostly from case series and PE registries. We aimed to describe the clinical characteristics, echocardiographic features, treatments, and outcomes of right-sided cardiac thrombus patients. This was a retrospective observational study of 97 consecutive patients with right-sided cardiac thrombus detected on echocardiography. We studied co-morbidities, predisposing factors, thrombus characteristics, and therapeutic interventions and assessed their associations with the development of PE, paradoxical stroke, circulatory collapse, and all-cause mortality. The mean age was 58.7 years, and 55/97 (56.7%) of the participants were female. Ischemic heart disease (IHD), heart failure, chronic kidney disease, and malignancy were common co-morbidities. Right atrial (RA) thrombus was often associated with medical devices, while right ventricular (RV) thrombus was more commonly associated with cardiomyopathy. Thrombus mobility did not affect embolic events but was associated with greater short-term mortality. On multivariable analysis, anticoagulation (HR 0.25, 95% CI 0.09-0.68) and thrombus resolution (HR 0.28, 95% CI 0.13-0.62) were associated with greater survival. Right-sided cardiac thrombus is rare but may have potentially life-threatening complications such as PE and paradoxical stroke. Further research is needed to determine the optimal therapeutic strategies for this poorly studied population.


Carcinogenesis: alterations in reciprocal interactions of normal functional structure of biologic systems.
The evolution of biologic systems (BS) includes functional mechanisms that in some conditions may lead to the development of cancer. Using mathematical group theory and matrix analysis, previously, it was shown that normally functioning BS are steady functional structures regulated by three basis regulatory components: reciprocal links (RL), negative feedback (NFB) and positive feedback (PFB). Together, they form an integrative unit maintaining system's autonomy and functional stability. It is proposed that phylogenetic development of different species is implemented by the splitting of "rudimentary" characters into two relatively independent functional parts that become encoded in chromosomes. The functional correlate of splitting mechanisms is RL. Inversion of phylogenetic mechanisms during ontogenetic development leads cell differentiation until cells reach mature states. Deterioration of reciprocal structure in the genome during ontogenesis gives rise of pathological conditions characterized by unsteadiness of the system. Uncontrollable cell proliferation and invasive cell growth are the leading features of the functional outcomes of malfunctioning systems. The regulatory element responsible for these changes is RL. In matrix language, pathological regulation is represented by matrices having positive values of diagonal elements (TrA > 0) and also positive values of matrix determinant (detA > 0). Regulatory structures of that kind can be obtained if the negative entry of the matrix corresponding to RL is replaced with the positive one. To describe not only normal but also pathological states of BS, a unit matrix should be added to the basis matrices representing RL, NFB and PFB. A mathematical structure corresponding to the set of these four basis functional patterns (matrices) is a split quaternion (coquaternion). The structure and specific role of basis elements comprising four-dimensional linear space of split quaternions help to understand what changes in mechanism of cell differentiation may lead to cancer development.


Optimization of the extraction of anthocyanin from Bokbunja (Rubus coreanus Miq.) marc produced during traditional wine processing and characterization of the extracts.
The extraction of anthocyanin from Bokbunja (Rubus coreanus Miq.) marc generated during traditional wine processing was optimized using response surface methodology (RSM). A face-centered cube design (FCD) consisting of 17 experimental runs, including five replicates at the center point, was used to investigate the effects of the three variables (solid-liquid ratio, time, and temperature) on anthocyanin extraction, and the results showed that the relationship between the three variables and the total anthocyanin content followed a quadratic model (R2=0.8853). In addition, the RSM analysis predicted that the optimum conditions for extraction consisted of a solid-liquid ratio of 20, a time of 60min, and a temperature of 60 degrees C. Verification tests performed under these optimum conditions gave 34.7+/-1.4mg/100g of anthocyanin, which was close to predicted value of 37.2mg/100g. Additionally, analysis of water extracts prepared using the predicted optimum conditions revealed that the carbohydrates (sugar and pectin) in Bokbunja marc underwent significant variation toward the formation of by-products (glycerol and uronic acids) during yeast fermentation, and that the amount of anthocyanin produced was reduced 10-fold when compared to the original extraction. Further, the results of HPLC-PDA-MS/MS analysis of the anthocyanins extracted from Bokbunja marc revealed the presence of six anthocyanin components, which were tentatively identified as cyanidin 3-O-sambubioside, cyanidin 3-O-xylosylrutinoside, cyanidin 3-O-rutinoside, pelargonidin 3-O-rutinoside, delphinidin 3-O-rutinoside-?, and delphinidin 3-O-glucuronide.


The Emperor Has No Symptoms: The Risks of a Blanket Approach to Using Epinephrine Autoinjectors for All Allergic Reactions.
Fatal anaphylaxis in humans is rare and unpredictable. We note a trend to provide allergic individuals with care plans that recommend immediate use of epinephrine autoinjectors if allergen ingestion is suspected, even in the absence of any allergic symptoms, without any supporting evidence base. Instructions to use an autoinjector device, irrespective of reaction severity and especially when symptoms are actually absent, are likely to add to parental and patient anxiety. Of greater concern is the possibility of epinephrine being administered "too early" to treat initial, mild symptoms that then progress to severe anaphylaxis. It is not hard to visualize a scenario where one or both epinephrine autoinjectors have been deployed for mild symptoms, yet the reaction progresses to a severe reaction and no further epinephrine is available for administration. Epinephrine needs to be available as a rescue treatment for anaphylaxis, potentially buying valuable minutes while emergency medical services are activated to attend. Food-allergic individuals and their carers need to be provided with more constructive strategies and support than merely being told to "use your pen."


Infant oral health care: a survey of general dentists, pediatric dentists, and pediatricians in Virginia.
This study's purpose was to examine the current knowledge, attitudes, and experiences related to infant oral health for dental and medical providers in Virginia. A survey of infant oral health care was sent to: (a) 300 randomly selected general dentists; (b) 300 randomly selected pediatricians; and (c) all pediatric dentists in Virginia. Survey respondents were tabulated, and percent frequency distributions for responses to each item were computed. The surveys return rate was 48%. A total of 100% of pediatric dentists treated infants and were more likely to recommend that children be seen by age 1 (P < .001). All pediatricians treated infants as well, while only 5% referred for the first dental visit by 1 year of age. Forty-five percent of general dentists surveyed treated infants, and only 12% referred for the first dental visit by 1 year of age. The logistic regression results indicated that there were differences between practitioner type regarding the recommended age of the first dental visit and years in practice. The majority of pediatricians and general dentists are not advising patients to see the dentist by 1 year of age. There is a need for increased infant oral health care education in the medical and dental communities.


Populational dynamics of three annual species of alpine plants in the Rocky Mountains.
Survivorship, fecundity, and seed bank size were measured over two years in alpine populations of the annuals, Koenigia islandica, Polygonum confertiflorum, and P. douglasii. The major loss of individuals from all populations occurred between seed dispersal and germination. Survival of vegetative plants to maturity was high in all species, usually above 80%, and the average number of seeds produced per plant was less than 10 in all species in both years. Seed banks existed for all three species but were small since more than 80% of the viable seeds in the soil germinated in the spring. Both survival and fecundity were negatively correlated with density in P. confertiflorum. These patterns of population dynamics are similar to those found in many annuals of temperate environments.


Smartphone speech-to-text applications for communication with profoundly deaf patients.
Visual communication aids, such as handwriting or typing, are often used to communicate with deaf patients in the clinic. This study aimed to establish the feasibility of communicating through smartphone speech recognition software compared with writing or typing. Thirty doctors and medical students were timed writing, typing and dictating a standard set of six sentences appropriate for a post-operative consultation, and the results were assessed for accuracy and legibility. The mean time for smartphone dictation (17.8 seconds, 95 per cent confidence interval = 17.0-18.7) was significantly faster than writing (59.2 seconds, 95 per cent confidence interval = 56.6-61.7) or typing (44 seconds, 95 per cent confidence interval = 41.0-47.1) (p < 0.001). Speech recognition was slightly less accurate, but accuracy increased with time spent dictating. Smartphone dictation is a feasible alternative to typing and handwriting. Slow speech may improve accuracy. Early clinical experience has been promising.


Effects of transport infrastructures and climate change on ecosystem services in the integrated transport corridor region of the Qinghai-Tibet Plateau.
The ecosystem services of the Qinghai-Tibet Plateau have been hot topics in recent decades due to their unique value, and the region's sensitivity to climate change and human activities is considered to be of major importance. However, few studies have focused on the variations of ecosystem services in response to traffic activities and climate change. This study applied different ecosystem service models, along with the buffer analysis, local correlation and regression analysis to quantitatively analyze the spatiotemporal variations of carbon sequestration, habitat quality, and soil retention, further detected the climatic and traffic influences in the transport corridor region of the Qinghai-Tibet Plateau from 2000 to 2020. The obtained results showed the following: (1) The carbon sequestration and soil retention increased over time, while the habitat quality decreased during the railway construction period; in addition, the variations of ecosystem services between the two periods exhibited substantial spatial differences. (2) The distance trends of ecosystem service variations were similar for the railway and the highway corridors, and the positive ecosystem service trends were mainly observed within 2.5 km and 2 km of railway and highway corridors, respectively. (3) The impacts of climatic factors on ecosystem services were predominantly positive; however, temperature and precipitation displayed contrasting distance trends in their impacts on carbon sequestration. (4) The types of frozen ground and locations away from the railway or highway were the combined factors affecting the ecosystem services, among which carbon sequestration was negatively influenced by the distance from the highway in the continuous permafrost areas. It can be speculated that rising temperatures caused by climate change may intensify the decline of carbon sequestration in the continuous permafrost areas. This study provides guidance on ecological protection strategies for future expressway construction projects.


Counting contacts between neurons in 3D in confocal laser scanning images.
Study of neuronal networks requires an inventory of the neurons, knowledge of fiber in- and output, and qualitative and quantitative data on the intrinsic connectivity. For this purpose we combined in rat hippocampus fluorescence neuroanatomical tracing and intracellular fluorochrome injection of neurons. Multichannel confocal laser scanning microscopy was followed by computer assisted 3D object- and contact recognition. We describe the factors involved in scanning ('from biological object to voxel') and we compare operator-mediated manual recognition of small 3D objects and contacts with 'objective' processing through software. As in all digital object recognition, thresholding is pivotal. We obtained reproducible, 'objective' thresholds via 3D object-threshold analysis with ImageJ. Objective thresholds were subsequently used in SCIL_Image scripts to identify 3D objects, and to identify and count contacts between labeled fibers and intracellularly injected target neurons. At the extreme magnification necessary to distinguish contacts, Abbe diffraction causes voxels that belong to the pre-contact structure to overlap voxels belonging to the post-contact structure. We call this overlap the 'footprint' and we introduce such footprints and their size as criteria to recognize contacts. Automated contact recognition, applying footprints of 100 voxels (involved structures imaged in their specific channel) gave the highest correlation with findings using the manual approach. We conclude that computer identification and counting of contacts is the method of choice, since it combines reduced human bias with good reproducibility of results and saving of time. Of major importance is that threshold selection is not dependent on the human computer operator.


[Teaching, graduate education and training in psychotherapy].
Basic skills in the field of psychosocial-psychotherapeutic medicine are necessary for medical students and residents. Psychotherapy as a special discipline goes far beyond this knowledge. The most important guidelines for training in Austria, BRD and Switzerland are presented.


Longer-term follow-up and outcome by tumour cell proliferation rate (Ki-67) in patients with relapsed/refractory mantle cell lymphoma treated with lenalidomide on MCL-001(EMERGE) pivotal trial.
Patients with mantle cell lymphoma (MCL) generally respond to first-line immunochemotherapy, but often show chemoresistance upon subsequent relapses, with poor outcome. Several studies of the immunomodulator, lenalidomide, have demonstrated its activity in MCL including the MCL-001 study in relapsed/refractory patients who had failed defined prior therapies of anthracyclines or mitoxantrone, cyclophosphamide, rituximab and also bortezomib. We present here the long-term efficacy follow-up of the prospective phase II MCL-001 study (N = 134), including new exploratory analyses with baseline Ki-67 (MIB1), a biological marker of tumour proliferation. With longer follow-up, lenalidomide showed a 28% overall response rate [ORR; 8% complete response (CR)/CR unconfirmed (CRu)]. Median duration of response (DOR), progression-free survival and overall survival were 16·6, 4·0 and 20·9 months, respectively. Myelosuppression continued to be the most common grade 3/4 toxicity. Several studies of MCL patients treated with chemotherapy, rituximab and bortezomib have shown an inverse association between survival and Ki-67. Ki-67 data in 81/134 MCL-001 patients showed similar ORRs in both low (<30% or <50%) versus high (≥30% or ≥50%) Ki-67-expressing groups, yet lower Ki-67 levels demonstrated superior CR/CRu, DOR and survival outcomes. Overall, lenalidomide showed durable efficacy with a consistent safety profile in heavily pretreated, relapsed/refractory MCL post-bortezomib.


Tumour necrosis factor alpha potentiates ion secretion induced by histamine in a human intestinal epithelial cell line and in mouse colon: involvement of the phospholipase D pathway.
Patients suffering from inflammatory bowel disease show increased levels of the mast cell products histamine and tumour necrosis factor alpha (TNF-alpha). Treating these patients with antibodies against TNF-alpha diminishes the symptoms of diarrhoea. In this study, the effect of TNF-alpha on ion secretion induced by the mast cell mediator histamine in HT29cl.19A cells and mouse distal colon was investigated and the possible second messengers involved were studied. Electrophysiology of filter grown HT29cl.19A cells and isolated mouse distal colon was used to monitor the secretory response to histamine with and without prior exposure to TNF-alpha for 3-24 hours. Phospholipase D (PLD) activity and phosphatidic acid levels were analysed by 32P(i) labelling of HT29cl.19A cells. In both experimental systems TNF-alpha was found to potentiate ion secretion induced by histamine. Phospholipid analysis of HT29cl.19A cells revealed that histamine activates the PLD pathway. Furthermore, TNF-alpha pretreated cells were found to have decreased phosphatidic acid levels, the intermediate product of the PLD pathway, which indicates upregulation of the enzyme phosphatidic acid phosphatase. The mast cell products TNF-alpha and histamine synergistically stimulate ion secretion in intestinal epithelium via upregulation of the PLD pathway.


Mechanical, thermal, viscoelastic and hydrophobicity behavior of complex grape stalk lignin and bamboo fiber reinforced polyester composite.
This work aims to investigate the degradation stability of bamboo fiber-reinforced polyester composite toughened with complex lignin biopolymer derived from the waste grape stalks. The properties like mechanical, wear, thermal, DMA, and hydrophobic were studied after the addition of lignin and analyzed how the lignin addition influenced these properties. Prior to composite making the fiber and lignin was treated with silane. According to the results obtained incorporating 40 vol% of bamboo fiber into the polyester resin, the mechanical and wear properties enhanced. Further, the composite containing 2.0 vol% of lignin has maximum tensile strength, tensile modulus, flexural strength, flexural modulus, and ILSS. Similarly, the composite designation having 4 vol% lignin revealed the improved wear loss stability of 0.007 mm3/Nm (sp. wear rate). The highest degradation temperature reported for composite designation UBL4 it was 520 °C, with a relatively lesser weight loss of 19 %. Likewise, the highest storage modulus was about 4.5 GPa, and the lowest loss factor was up to 0.3 for the composite designation UBL4. The contact angle investigation revealed that all composite designations are not fall below 70°, indicating their hydrophobic stability. These composites with enhanced stability against load, heat and water could be utilized in the industrial, automotive and defense sectors where high performance outcomes are required.


Proteins in cerebrospinal fluid and plasma of postnatal Monodelphis domestica (grey short-tailed opossum).
1. The protein composition and concentrations of total protein in cerebrospinal fluid (CSF) and plasma of opossum (Monodelphis domestica) from birth until adulthood have been estimated. 2. Total protein in CSF increased from birth to a peak concentration between 5 and 10 days (500 mg/100 ml) after which it declined rapidly. 3. Total protein in plasma started at a low level at birth (below 400 mg/100 ml) and increased progressively to the adult value (8500 mg/100 ml). 4. Proteins identified in CSF and plasma were: albumin, alpha 1 antitrypsin, transferrin, alpha 2 macroglobulin, lipoproteins and immunoglobulin G. A fetal protein, probably alpha-fetoprotein, has been identified. 5. The only plasma proteins found within the brain, even in the very immature newborn of this species, appeared to have an intracellular rather than an extracellular distribution. This indicates that the blood-brain barrier is present very early in development and that there is also a CSF-brain barrier that appears to exclude CSF protein from brain extracellular space.