Parsing β-catenin's cell adhesion and Wnt signaling functions in malignant mammary tumor progression.
During malignant progression, epithelial cancer cells dissolve their cell-cell adhesion and gain invasive features. By virtue of its dual function, β-catenin contributes to cadherin-mediated cell-cell adhesion, and it determines the transcriptional output of Wnt signaling: via its N terminus, it recruits the signaling coactivators Bcl9 and Pygopus, and via the C terminus, it interacts with the general transcriptional machinery. This duality confounds the simple loss-of-function analysis of Wnt signaling in cancer progression. In many cancer types including breast cancer, the functional contribution of β-catenin's transcriptional activities, as compared to its adhesion functions, to tumor progression has remained elusive. Employing the mouse mammary tumor virus (MMTV)-PyMT mouse model of metastatic breast cancer, we compared the complete elimination of β-catenin with the specific ablation of its signaling outputs in mammary tumor cells. Notably, the complete lack of β-catenin resulted in massive apoptosis of mammary tumor cells. In contrast, the loss of β-catenin's transcriptional activity resulted in a reduction of primary tumor growth, tumor invasion, and metastasis formation in vivo. These phenotypic changes were reflected by stalled cell cycle progression and diminished epithelial-mesenchymal transition (EMT) and cell migration of breast cancer cells in vitro. Transcriptome analysis revealed subsets of genes which were specifically regulated by β-catenin's transcriptional activities upon stimulation with Wnt3a or during TGF-β-induced EMT. Our results uncouple the signaling from the adhesion function of β-catenin and underline the importance of Wnt/β-catenin-dependent transcription in malignant tumor progression of breast cancer.


The nature of semantic priming effects in the recognition of familiar people.
We report a series of experiments examining the nature of semantic priming effects in the recognition of familiar people. Experiment 1 showed that facilitation of the recognition of familiar target faces by related face primes occurs within the recognition system, since there is no equivalent priming when subjects are asked only to determine the sex of the target faces, rather than to recognize them as familiar. Experiments 2 and 3 examined the basis of the facilitatory effect of related primes, and showed that both for familiarity decision (Expt 2 and Expt 3) and face naming (Expt 3) tasks it is primarily based on close association of the prime and target people, rather than common membership of a semantic category. This associative component of semantic priming was further explored in Expt 4, which showed that cross-domain priming from face primes to target names was present for associated prime-target pairs, but was maximal when prime and target were the face (prime) and name (target) of the same person. The results of the experiments are consistent with the interactive activation simulation developed by Burton, Bruce & Johnston (1990), and set constraints which will have to be met by any other plausible account of semantic priming.


Reversible Photoswitching of a Spin-Crossover Molecular Complex in the Solid State at Room Temperature.
Spin-crossover metal complexes are highly promising magnetic molecular switches for prospective molecule-based devices. The spin-crossover molecular photoswitches developed so far operate either at very low temperatures or in the liquid phase, which hinders practical applications. Herein, we present a molecular spin-crossover iron(II) complex that can be switched between paramagnetic high-spin and diamagnetic low-spin states with light at room temperature in the solid state. The reversible photoswitching is induced by alternating irradiation with ultraviolet and visible light and proceeds at the molecular level.


A highly porous metal-organic framework for large organic molecule capture and chromatographic separation.
A highly porous metal-organic framework (MOF) with large pores was successfully obtained via solvothermal assembly of a "click"-extended tricarboxylate ligand and Zn(ii) ions. The inherent feature of large-molecule accessible pores endows the MOF with a unique property for utilization toward large guest molecules.


Safety evaluation of a stepwise tracheostomy decannulation program in pediatric patients.
In the event of failed tracheostomy decannulation, patients might have a tragic course of events. We retrospectively evaluated our stepwise tracheostomy decannulation program and examined its safety. A 12-year retrospective study of pediatric patients was conducted. The decannulation program was performed on patients who had airway patency by laryngobronchoscopy and whose cannula could be capped during the day. A stepwise decannulation program was performed: continuous 48-h capping trial during hospitalization (Phase 1), removal of the tracheostomy tube for 48 h during hospitalization (Phase 2), and outpatient observation (Phase 3). If a persistent tracheocutaneous fistula existed, the fistula was closed by surgery (Phase 4). The 77 patients in the study underwent 86 trials. The age at the first time of the decannulation program was 6.5 ± 3.6 years. Sixteen trials failed (18.6%): 8 trials in Phase 1, 2 trials in Phase 2, 4 trials in Phase 3, and 2 trials in Phase 4. Most decannulation failures were due to desaturation in Phase 1/2 and dyspnea in Phase 3/4. The time to reintubation after decannulation was 15-383 days in Phase 3/4. Patients could fail at every phase of the program, suggesting that a stepwise decannulation program contributes to safety.


[Non cardiac surgery in patient with coronary stenting: think sirolimus now!].
We describe a severe preoperative cardiogenic shock in a patient scheduled for a breast surgery. The cardiogenic shock was in relation with thrombosis of two sirolimus-eluting stents received 3 months ago. A percutaneous transluminal coronary angioplasty was successfully performed. The patient recovered well after a 1-day treatment including intraaortic balloon counter pulsation and dobutamine infusion. We discuss about the ideal timing to plan surgery and how to manage the shift of antiplatelet agents.


Serum levels of angiopoietin-1 in patients with pulmonary hypertension due to mitral stenosis.
The molecular basis and pathophysiology of pulmonary hypertension (PH) are rapidly evolving areas. Recently discovered angiopoietins (Ang) constitute a family of growth factors, and whether they play a causal or protective role in pulmonary hypertension has not been fully elucidated. Since left heart disease probably represents the most frequent cause of PH, we sought to determine whether there was a relationship between serum Ang-1 levels and pulmonary hypertension caused by mitral stenosis (MS). The study population was composed of 49 patients with isolated MS. These patients were then divided into group 1 [31 patients with severe MS: mitral valve area (MVA) ≤1.1 cm(2)] and group 2 (18 patients with mild-moderate MS: MVA 1.2-2.0 cm(2)). Twenty-one healthy volunteers comprised the control group (group 3). All of the subjects underwent complete transthoracic echocardiography with determination of systolic pulmonary artery pressure (PAPs). Ang-1 levels were determined in serum. Serum levels of Ang-1 were significantly higher in the control group compared to patients with severe (group 1) and mild-moderate (group 2) MS (p < 0.001). Ang-1 levels were found to have moderate inverse correlation with PAPs and left atrial (LA) diameter (r: -0.620, p < 0.001 and r: -0.489, p < 0.001, respectively). The AUC for the ROC curve for predicting PAPs <50 mmHg by serum Ang-1 level was 0.824 (95% CI 0.722-0.926, p < 0.001). A serum level of Ang-1 above 34,656 pg/ml has 74% sensitivity and 80% specificity for predicting that PH is not severe (PAPs <50 mmHg). In conclusion, the findings of this study are distinctive in the sense that they clearly demonstrate a negative correlation between serum Ang-1 levels and the degree of PH.


Dimensions of the operationalized psychodynamic diagnosis system that predict long-term outcome after inpatient psychotherapy.
To determine whether the Operationalized Psychodynamic Diagnosis (OPD) system can be useful in predicting patient outcome in the long term. OPD was assessed by the therapists prior to and after inpatient treatment. Patients completed psychometric scales at the start and completion of psychosomatic-psychotherapeutic inpatient treatment and at the follow-up. Outcome was defined by the general factor emerging from a principal component analysis of the Brief Symptom Inventory, Hospital Anxiety and Depression Scale and Inventory of Interpersonal Problems at katamnesis, representing individual differences in general distress. Several dimensions of the OPD system proved to be predictors of general distress at the follow-up in 253 former inpatients. Negative predictors of long-term outcome were the high internal impediments to change, namely high secondary gains from illness and also less integrated structural abilities. Positive OPD predictors of long-term outcome were the treatment success achieved at the end of inpatient psychotherapy in changing the illness concept towards a psychological understanding of symptoms, lower levels of complaints and a higher functional level. Also the achieved level of awareness for the individual maladaptive behavioral pattern is predictive of a favorable long-term outcome. The results provide evidence for the clinical relevance and the predictive value of OPD. © 2014 S. Karger AG, Basel.


Dextran sodium sulphate colitis mouse model: traps and tricks.
Inflammatory bowel disease (IBD) is a complex multifactorial disease of unknown etiology. Thus, dozens of different animal models of IBD have been developed in past decades. Animal models of IBD are valuable and indispensable tools that provide a wide range of options for investigating involvement of various factors into the pathogenesis of IBD and to evaluate different therapeutic options. However, the dextran sulphate sodium (DSS-) induced colitis model has some advantages when compared to other animal models of colitis. It is well appreciated and widely used model of inflammatory bowel disease because of its simplicity. It has many similarities to human IBD, which are mentioned in the paper. In spite of its simplicity and wide applicability, there are also traps that need to be taken into account when using DSS model. As demonstrated in the present paper, various factors may affect susceptibility to DSS-induced lesions and modify results.


A hydrothermal apparatus for x-ray absorption spectroscopy of hydrothermal fluids at DESY.
We present a new autoclave that enables in situ characterization of hydrothermal fluids at high pressures and high temperatures at synchrotron x-ray radiation sources. The autoclave has been specifically designed to enable x-ray absorption spectroscopy in fluids with applications to mineral solubility and element speciation analysis in hydrothermal fluids in complex compositions. However, other applications, such as Raman spectroscopy, in high-pressure fluids are also possible with the autoclave. First experiments were run at pressures between 100 and 600 bars and at temperatures between 25 °C and 550 °C, and preliminary results on scheelite dissolution in fluids of different compositions show that the autoclave is well suited to study the behavior of ore-forming metals at P-T conditions relevant to the Earth's crust.


Identifying subjects with insulin resistance by using the modified criteria of metabolic syndrome.
The objectives of this cohort analysis were to explore the relationship between insulin resistance (IR) and the criteria for metabolic syndrome (MetS) and to evaluate the ability to detect IR in subjects fulfilling those criteria. We enrolled 511 healthy subjects (218 men and 283 women) and measured their blood pressure (BP), body mass index, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and fasting plasma glucose levels. Insulin suppression testing was done to measure insulin sensitivity as the steady-state plasma glucose (SSPG) value. Subjects with an SSPG value within the top 25% were considered to have IR. The commonest abnormality was a low HDL-C level, followed by high BP. The sensitivity to detect IR in subjects with MetS was about 47%, with a positive predictive value of about 64.8%, which has higher in men than in women. In general, the addition of components to the criteria for MetS increased the predictive value for IR. The most common combination of components in subjects with MetS and IR were obesity, high BP, and low HDL-C levels. All of the components were positive except for HDL-C, which was negatively correlated with SSPG. The correlation was strongest for obesity, followed by high TG values. In subjects with MetS, sensitivity for IR was low. However, body mass index and TG values were associated with IR and may be important markers for IR in subjects with MetS.


Neodymium:YAG laser and brachytherapy in the management of inoperable bronchogenic carcinoma.
Neodymium:yttrium-aluminum garnet (Nd:YAG) laser therapy and endobronchial brachytherapy are useful modalities in the palliation of inoperable bronchogenic carcinoma. From 1983 to 1989, 218 patients underwent a total of 371 procedures involving endobronchial brachytherapy, Nd:YAG laser therapy, or both. Group 1 consisted of 130 patients who received Nd:YAG laser therapy. Group 2 consisted of 67 patients who had endobronchial brachytherapy only. Group 3 comprised 21 patients who underwent combined endobronchial brachytherapy and Nd:YAG laser therapy. All patients had received or were receiving concurrent radiotherapy. Three late deaths occurred in group 1, and 1 death occurred in group 2. More than 80% of patients achieved a good to excellent result. When applicable, we now use combined Nd:YAG laser therapy and endobronchial brachytherapy as part of the initial management of inoperable non-small cell bronchogenic carcinoma. A detailed analysis of these patients is given.


Antiproliferative action of vitamin D-related compounds and insulin-like growth factor-binding protein 5 accumulation.
Vitamin D-related compounds can inhibit cancer cell growth, but the biologic mechanism of this inhibition remains to be determined. We investigated the possibility that these compounds interfere with the activity of insulin-like growth factors. Such activity can be suppressed or otherwise modulated by specific insulin-like growth factor-binding proteins. The human breast cancer cell line MCF-7 was used in this study. The effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and two related compounds, EB1089 and KH1060, on cell proliferation were assessed by monitoring cell numbers and by measuring cellular incorporation of [3H]thymidine. Changes in the accumulation of insulin-like growth factor-binding proteins in cell-conditioned media (i.e., culture fluids) were assessed by means of standard protein blotting techniques; ligand blots were probed with [125I]insulin-like growth factor I, and immunoblots were probed with antibodies raised against specific binding proteins. Binding protein messenger RNA levels were determined by use of RNA blotting methods and complementary DNA probes. At concentrations of 10(-8) M and 10(-9) M, EB1089 and KH1060 exhibited stronger antiproliferative activity than 1,25(OH)2D3. When each of the vitamin D-related compounds was used separately at a concentration of 10(-9) M, a 20- to 25-fold increase in the concentration of insulin-like growth factor-binding proteins in MCF-7 cell-conditioned media was observed; this binding capacity was increased nine-fold, ninefold, and threefold, respectively, in the presence of 10(-10) M EB1089, KH1060, and 1,25(OH)2D3. Immunoblotting experiments demonstrated that all three vitamin D-related compounds induced the accumulation of insulin-like growth factor-binding protein 5 in cell-conditioned media. The accumulation of this binding protein was associated with an increase in cellular expression of its messenger RNA. EB1089 and 1,25(OH)2D3 attenuated the growth-promoting activity of insulin-like growth factor I on MCF-7 cells; however, these compounds did not inhibit the growth-promoting activity of long R3 IGF-I, an insulin-like growth factor I analogue with greatly reduced affinity for insulin-like growth factor-binding proteins. Our results indicate that vitamin D-related compounds stimulate production of insulin-like growth factor-binding protein 5, thereby indirectly suppressing cell proliferation.


Construction and analysis of random networks with explosive percolation.
The existence of explosive phase transitions in random (Erdös Rényi-type) networks has been recently documented by Achlioptas, D'Souza, and Spencer [Science 323, 1453 (2009)] via simulations. In this Letter we describe the underlying mechanism behind these first-order phase transitions and develop tools that allow us to identify (and predict) when a random network will exhibit an explosive transition. Several interesting new models displaying explosive transitions are also presented.


Nephrotoxicity of 4-aminophenol glutathione conjugate.
4-Aminophenol (p-aminophenol, PAP) causes selective necrosis to the pars recta of the proximal tubule in Fischer 344 rats. The basis for this selective toxicity is not known, but PAP can undergo oxidation in a variety of systems to form the 4-aminophenoxy free radical. Oxidation or disproportionation of this radical will form 1,4-benzoquinoneimine which can covalently bind to tissue macromolecules. Recent studies have shown that certain benzoquinol-glutathione conjugates can cause renal necrosis in rats. We have synthesized a putative glutathione conjugate of PAP. The effect on the kidney of this conjugate and the sulphate and N-acetyl conjugates, known metabolites of PAP, have been examined in Fischer 344 rats. 4-Amino-3-S-glutathionylphenol produced a dose-dependent (92-920 mumol kg-1) necrosis of the proximal tubular epithelium and altered renal excretory function. The lesion at the low dose was restricted to the pars recta of the proximal tubule in the medullary rays, while at the higher doses it affected the pars recta region of all nephrons. In contrast, PAP-O-sulphate and N-acetyl-4-aminophenol (paracetamol) caused no histological or functional alteration to the kidney at 920 mumol kg-1. The renal necrosis produced by 4-amino-3-S-glutathionylphenol was very similar to that produced by PAP (367-920 mumol kg-1), both functionally and histologically, except that smaller doses of the glutathione conjugate were required. These studies indicate that glutathione conjugation of PAP generates a metabolite that is more toxic to the kidney than the parent compound. A possible mechanism of toxicity (analogous to that reported for glutathione conjugates of certain quinones) involving oxidation to form a 1,4-benzoquinoneimine thioether that could redox cycle is discussed.


Gestational weight gain as a predictor of longitudinal body mass index transitions among socioeconomically disadvantaged women.
Socioeconomically disadvantaged women are at greater risk for gestational weight gain and postpartum weight retention compared to socioeconomically advantaged women. This study examines the effect of gestational weight gain on body mass index (BMI) transitions 5 years after pregnancy in socioeconomically disadvantaged women. Gestational weight gain was assessed in 2136 postpartum women participating in the Fragile Families and Child Well-being study who experienced full-term, singleton gestations. Longitudinal BMI transitions were defined as a change or stability in BMI category between two time points: BMI before the index pregnancy and BMI 5 years after the index pregnancy. Logistic regression models estimated the association between gestational weight gain and longitudinal BMI transitions, controlling for health before the index pregnancy, pregnancy history, and sociodemographic characteristics. Excessive gestational weight gain was related to transitioning to a higher BMI category 5 years after the index pregnancy. Compared to white women, black and Hispanic women were more likely to transition or maintain a higher BMI category. Pregnancy history (i.e., parity at index pregnancy, interim pregnancy) and public assistance participation were associated with transitioning to a higher BMI category. Among socioeconomically disadvantaged women, excessive gestational weight gain is related to transitioning to, but not maintaining, a higher weight category 5 years after the index pregnancy. Black and Hispanic women who are also socioeconomically disadvantaged and overweight or obese before conception may benefit from preconception or postpartum counseling about the long-term effect of gaining excessive weight during pregnancy and in the years immediately after childbirth.


Physical activity, VO2max, and jumping height in an urban population.
We studied the interrelations between, on the one hand, the physical activity (frequency, duration, intensity, and mode) measured by a questionnaire and, on the other, VO2max (submaximal bicycle ergometer test) and the explosive muscle strength (vertical jumping height). A random sample of 774 healthy subjects from the city of Turku participated in this study; the subjects were 25, 35, 45, or 55 yr of age. The VO2max of physically active 55-yr-old female subjects was on the same average level as of 25-yr-old females, who were physically inactive. Correspondingly, the average VO2max of physically active 55-yr-old male subjects was above the average level of 25-yr-old males, who were physically inactive. With the exception of the oldest female study group, the jumping test of physically active subjects gave similar results as those of their inactive counterparts who were 10 yr younger. On the basis of the sports events reported by the subjects, we classified the subjects into five activity mode categories. The mode of activity was significantly associated with VO2max in a three-way ANOVA (P = 0.0027) as well as with the jumping test result (P = 0.0001). Mixed training (includes varied types of exercise for the neuromuscular system) was the most beneficial mode of exercise for developing jumping height. The study suggests that the intensity, frequency, and duration of regular physical activity habits during leisure are associated with both VO2max and the jumping height, and that the jumping height results, in particular, are increased by mixed training.


Study of mitral valve in human cadaveric hearts.
The mitral valve is a complex structure that is altered by disease states. The classical image of the mitral valve is a bicuspid valve with two leaflets and two papillary muscles. The reason for the present study is to study the morphology and morphometry of the mitral valve. This study was carried out on 116 human cadaveric hearts. Hearts were opened along the left border through the atrioventricular valve. The diameter and circumference of the annulus was measured and the number of valve leaflets was observed. The mean annular diameter was 2.22 cm. The mean circumference of mitral valve annulus was 9.12 cm. The standard description of the mitral valve is bicuspid. In the present study, we found the number of cusps to be variable, from monocuspid to hexacuspid and classified them accordingly. The mitral valve is not always a bicuspid valve. The number of cusps varies greatly. An increase in the number of the cusp and their improper approximation most likely causes various valvular disorders.


Diagnosis of gastric polypoid lesions by magnifying endoscopy and dye endoscopy.
From July 1989 to June 1990, a total of 19 patients with gastric polyps were studied by magnifying endoscopy and dye endoscopy. After pretreatment with pronase, both close and magnified pictures were observed before and after sprays of 0.2% indigo carmine. Polypectomy or multiple biopsies were done after endoscopic examinations. Of the 19 patients; 13 were classified as hyperplastic polyps and 6 as neoplastic polyps by histologic examination. Twelve of the 13 hyperplastic polyps showed regular sulciolar or sulciolar-mesh mucosal patterns after magnification, only 1 showed an irregular sulciolar-mesh pattern. All 6 neoplastic polyps showed irregular or destructive mucosal patterns. Hyperplastic polyps have a significantly higher rate of regular, fine gastric mucosal patterns. Contrast staining with indigo carmine did not significantly improve the observations. We conclude that magnifying endoscopy is useful in the diagnosis of gastric polyps; polyps with fine, regular gastric pits indicate a diagnosis of hyperplastic polyps, while irregular or destructive mucosal patterns suggest a high possibility of neoplastic polyps.


Therapeutic lumbar facet joint nerve blocks in the treatment of chronic low back pain: cost utility analysis based on a randomized controlled trial.
Related to escalating health care costs and the questionable effectiveness of multiple interventions including lumbar facet joint interventions, cost effectiveness or cost utility analysis has become the cornerstone of evidence-based medicine influencing coverage decisions. Cost utility of therapeutic lumbar facet joint nerve blocks in managing chronic low back pain was performed utilizing data from a randomized, double-blind, controlled trial with a 2-year follow-up, with direct payment data from 2016. Based on the data from surgical interventions, utilizing the lowest proportion of direct procedural costs of 60%, total cost utility per quality adjusted life year (QALY) was determined by multiplying the derived direct cost at 1.67. Patients in this trial on average received 5.6 ± 2.6 procedures over a period of 2 years, with average relief over a period of 2 years of 82.8 ± 29.6 weeks with 19 ± 18.77 weeks of improvement per procedure. Procedural cost for one-year improvement in quality of life showed USD $2,654.08. Estimated total costs, including indirect costs and drugs with multiplication of direct costs at 1.67, showed a cost of USD $4,432 per QALY. The analysis of therapeutic lumbar facet joint nerve blocks in the treatment of chronic low back pain shows clinical effectiveness and cost utility at USD $2,654.08 for the direct costs of the procedures, and USD $4,432 for the estimated overall cost per one year of QALY, in chronic persistent low back pain non-responsive to conservative management.


NF-κBp50 and HDAC1 Interaction Is Implicated in the Host Tolerance to Infection Mediated by the Bacterial Quorum Sensing Signal 2-Aminoacetophenone.
Some bacterial quorum sensing (QS) small molecules are important mediators of inter-kingdom signaling and impact host immunity. The QS regulated small volatile molecule 2-aminoacetophenone (2-AA), which has been proposed as a biomarker of Pseudomonas aeruginosa colonization in chronically infected human tissues, is critically involved in "host tolerance training" that involves a distinct molecular mechanism of host chromatin regulation through histone deacetylase (HDAC)1. 2-AA's epigenetic reprogramming action enables host tolerance to high bacterial burden and permits long-term presence of P. aeruginosa without compromising host survival. Here, to further elucidate the molecular mechanisms of 2-AA-mediated host tolerance/resilience we investigated the connection between histone acetylation status and nuclear factor (NF)-κB signaling components that together coordinate 2-AA-mediated control of transcriptional activity. We found increased NF-κBp65 acetylation levels in 2-AA stimulated cells that are preceded by association of CBP/p300 and increased histone acetyltransferase activity. In contrast, in 2-AA-tolerized cells the protein-protein interaction between p65 and CBP/p300 is disrupted and conversely, the interaction between p50 and co-repressor HDAC1 is enhanced, leading to repression of the pro-inflammatory response. These results highlight how a bacterial QS signaling molecule can establish a link between intracellular signaling and epigenetic reprogramming of pro-inflammatory mediators that may contribute to host tolerance training. These new insights might contribute to the development of novel therapeutic interventions against bacterial infections.


Exploring the feasibility of a mental health application (JoyPopTM) for Indigenous youth.
The purpose of the current study was to explore the acceptability and feasibility of a resilience-focused mobile application, JoyPop™, for use with Indigenous youth. A Haudenosaunee community-based research advisory committee co-developed the research project, in accordance with OCAP™ principles. Adopting a mixed-method approach, five youths from an immersion school used the JoyPop™ app for four consecutive weeks, as well as completed pre-test questions and weekly usage surveys. Most participants also completed post-test questions and a semi-structured interview. Based on a semi-structured interview protocol, youth responded to questions, and the most common themes were categorized to capture the experience of using the app. All youth reported a positive impression, used the app daily, found it easy to navigate, and indicated that they would recommend it to a friend. All features were uniformly positively endorsed. There were features that youth used most often (Deep Breathing, "SquareMoves" game, and Art features) and moderately (Rate My Mood, Journaling, and SleepEase). The social connection feature, Circle of Trust, was least utilized, with youth reporting a preference for in-person problem-solving. The drop-down menu of crisis helplines was not used. Youth recommended more gaming options. In terms of cultural resonance, appreciation for the app's use of water sounds in the SleepEase feature was expressed, as was cultural consistency with the "Good Mind" perspective. Recommendations included additional nature sounds, Indigenous design elements, the inclusion of Native language words, and traditional stories. The JoyPop™ app was positively received by Six Nations youth, and ways to ensure its cultural appropriateness were identified. Moving forward, it is recommended that Indigenous designers create a new version with community design co-creation. Additional research with various groups of Indigenous youth is warranted as a pan-Indigenous approach is not recommended.


In Vitro Assessment of Selected Medicinal Plants Used by the Bapedi Community in South Africa for Treatment of Bacterial Infections.
There is very little scientific information on indigenous plants used for medicinal purposes. Therefore, the aim of the study was to evaluate the antibacterial and antioxidant activities of the leaves of Commelina africana, Elephantorrhiza elephantina, Dombeya rotundifolia, and the whole plant excluding the roots of Schkuhria pinnata indigenous medicinal plants from the Limpopo Province, which may be used for the treatment in humans infected with bacterial pathogens. The screening of different phytoconstituents using standard methods revealed the presence of terpenoids, flavonoids, tannins, and saponins. The total phenolic, tannin, and flavonoid content were estimated using spectrophotometric methods. D rotundifolia had the highest amounts of phenol (259.00 ± 2.65 mg of gallic acid equivalent [GAE]/g), tannin (330.33 ± 15.63 mg of GAE/g), and flavonoid (19.90 ± 0.75 mg of quercetin equivalent [QE]/g) content, while S pinnata had the least. All the plants had antibacterial activity against Escherichia coli and Pseudomonas aeruginosa with the bioautography method. The microbroth dilution assay revealed antibacterial activity with minimum inhibitory concentration values raining from 0.02 to 2.50 mg/mL. D rotundifolia had the highest antioxidant activity in both the free radical scavenging and ferric reducing power methods. S pinnata and C africana extracts had high antibacterial activity, while D rotundifolia had high antioxidant activity, which made them potential plants for isolation of bioactive compounds and possible application in the pharmaceutical industry.


Transcranial Doppler evaluation of middle cerebral artery stenosis.
Symptomatic stenoses of the middle cerebral artery (MCA) are not uncommon, although Corston observed the occurrence of stroke in 24% of patients with MCA stenoses during a 6-year follow-up study. We tried to use transcranial Doppler (TCD) sonography for the detection and evaluation of MCA stenoses. Intra-arterial angiography demonstrated 16 MCA stenoses of more than 30% diameter reduction in 15 patients (14 atheromatous stenoses, 2 dysplasias). Severe associated lesions were present in 2 cases (more than 75% internal carotid artery stenosis). These 15 patients with MCA stenosis were examined with TCD in a blind study. A Doppler signal from the MCA was obtained through the temporal bone and was recognized on the result of common carotid artery compression test. We ascertained MCA stenosis when TCD demonstrated 1) segmental flow acceleration with peak systolic frequency of more than 3 KHz with or without high energy low frequency direct or reverse components; or 2) segmental increase in systolic peak frequency of more than 20%. Using these criteria, we confirmed through TCD the presence of MCA stenosis in nine out of 12 cases with diameter reduction of at least 50%, and one among four cases with less than 50% diameter reduction. Although our results are consistent with Aaslid and von Reutern's figures, methodological problems and diagnostic criteria have to be improved. Nevertheless, TCD seems to be a useful tool for the detection of stenosis with at least 50% diameter reduction, where it proved to offer a 75% sensitivity. Further studies are necessary to improve sensitivity and specificity.


Identification and validation of inhibitor-responsive kinase substrates using a new paradigm to measure kinase-specific protein phosphorylation index.
Regulation of all cellular processes requires dynamic regulation of protein phosphorylation. We have developed an unbiased system to globally quantify the phosphorylation index for substrates of a specific kinase by independently quantifying phosphorylated and total substrate molecules in a reverse in-gel kinase assay. Non-phosphorylated substrate molecules are first quantified in the presence and absence of a specific stimulus. Total substrate molecules are then measured after complete chemical dephosphorylation, and a ratio of phosphorylated to total substrate is derived. To demonstrate the utility of this approach, we profiled and quantified changes in phosphorylation index for Protein Kinase CK2 substrates that respond to a small-molecule inhibitor. A broad range of inhibitor-induced changes in phosphorylation was observed in cultured cells. Differences among substrates in the kinetics of phosphorylation change were also revealed. Comparison of CK2 inhibitor-induced changes in phosphorylation in cultured cells and in mouse peripheral blood lymphocytes in vivo revealed distinct kinetic and depth-of-response profiles. This technology provides a new approach to facilitate functional analyses of kinase-specific phosphorylation events. This strategy can be used to dissect the role of phosphorylation in cellular events, to facilitate kinase inhibitor target validation studies, and to inform in vivo analyses of kinase inhibitor drug efficacy.


[Content and metabilism of nitric oxide in substrates of oral cavity and their role in pathogenesis of periodontite disease].
Content and metabolism of free NO in saliva, fluids of periodontal pockets and gingival tissue has been investigated by EPR (electron paramagnetic resonance) method with the use of nitric oxide spin-trap in patients suffering from periodontitis. It was found that increased generation of nitric oxide at early stages of periodontitis is of protective nature. However, at serious disorders of mitochondrial respiration and exaggerated formation of generators of reactive oxygen, nitric oxide converts into citotoxic peroxinitrite leading to destruction of parodontal tissue; part of free nitric oxide produces FeSNO, which in turn, supports and decreases content of free NO in gingival tissue. As a result, decreases local antimicrobial protection, hemocirculation, tissue nutrition, progresses inflammation. Periodontitis decreases local immunity due to NO deficiency in gingival tissue. Reduced content of NO in gingival tissue decreases regeneration ability of cells, which in turn, leads to deterioration on gingival tissue.


Percutaneous transhepatic embolization of an intrahepatic pseudoaneurysm following liver biopsy in a liver transplant patient.
A 41-year-old liver transplant patient had severe hemobilia from an intrahepatic pseudoaneurysm secondary to a liver biopsy. Selective intra-arterial embolization was not technically possible due to marked redundancy and tortuosity of the allograft hepatic artery. The pseudoaneurysm was localized by ultrasound and embolized using a direct percutaneous transhepatic approach. This is a novel way of approaching hemobilia in liver transplant patients after liver biopsy and may avoid the risks of arterial embolization.


Carbon Dots as Nontoxic and High-Performance Fluorescence Imaging Agents.
Fluorescent carbon dots (small carbon nanoparticles with the surface passivated by oligomeric PEG molecules) were evaluated for their cytotoxicity and in vivo toxicity and also for their optical imaging performance in reference to that of the commercially supplied CdSe/ZnS quantum dots. The results suggested that the carbon dots were biocompatible, and their performance as fluorescence imaging agents was competitive. The implication to the use of carbon dots for in vitro and in vivo applications is discussed.


Induction by UV light of the SOS function sfiA in Escherichia coli strains deficient or proficient in excision repair.
The influence of the nucleotide excision repair system on the induction by UV irradiation of the SOS function sfiA has been investigated. The level of sfiA expression was monitored by means of a sfiA::lacZ operon fusion in both the wild-type strain and a uvrA mutant. We found that the initial steady rate of sfiA expression was proportional to the UV dose and was identical in uvr+ and uvrA backgrounds. This suggests that the initial steady rate of sfiA expression is determined by the initial number of lesions and before any effect of excision repair. We confirmed that after 2 h of expression the net synthesis of sfiA product is, for the same UV dose, about five times lower in uvr+ than in uvrA strains. We show that this is due to earlier repression of the SOS system in uvr+ than in uvrA strains and not to different initial rates.


Effect of general anesthetics and pressure on aerobic metabolism of monkey kidney cells.
The authors examined the inhibition of aerobic metabolism in monkey kidney cell cultures exposed to halothane, enflurane, and isoflurane. The ability of hyperbaric pressure to reverse the halothane-induced metabolic inhibition also was examined. Incubation of two monkey kidney cell lines for 24 h with clinically equipotent concentrations (2.6 MAC) of halothane, enflurane, or isoflurane vapors increased the concentration of lactate in the media by 126 to 244% relative to nonexposed control cultures. The increased rate of lactate accumulation was proportional to the concentration of halothane and was accompanied by a decrease in media pH. Removal of halothane restored the normal rate of lactate production. Hyperbaric pressures of 25, 50, and 100 atmospheres did not alter the halothane-stimulated rate of lactate production relative to non-anesthetic-treated controls, although pressure alone did depress the rate of lactate accumulation in all cultures. The stimulation of lactate production likely reflects the known ability of halothane to inhibit mitochondrial respiration. The failure of pressure to reverse the stimulation of lactate production by halothane suggests that inhibition of mitochondrial metabolism cannot be reversed by pressure.


Development of a Novel Anti-HER2 Monoclonal Antibody H2Mab-181 for Gastric Cancer.
Human epidermal growth factor receptor 2 (HER2) is a type I transmembrane 185 kDa protein. HER2 is expressed in a variety of normal tissue types and cancer cells. HER2 is associated with cell proliferation, differentiation, and migration. The overexpression of HER2 has been observed in a number of cancers, including breast and gastric cancers. Gastric cancer is one of the most common cancers worldwide, with an annual case rate of ∼1 million people diagnosed with the disease. Trastuzumab is a humanized anti-HER2 monoclonal antibody (mAb) that has been utilized in gastric cancer therapy. In this study, we have developed a novel anti-HER2 mAb, H2Mab-181 (IgG1, kappa), through the immunization of mice with a purified recombinant extracellular domain of HER2. H2Mab-181 can specifically and sensitively detect HER2 in both flow cytometry and Western blot applications in gastric cancer cell lines and can also be utilized in immunohistochemical analyses of gastric cancer tissues. Together, H2Mab-181 could be useful for the diagnosis and therapy in gastric cancers.


MiR-3150b-3p inhibits the proliferation and invasion of cervical cancer cells by targeting TNFRSF11a.
The objective of this study was to determine the role of miR-3150b-3p in the cervical cancer (CC) progression. Real-time PCR and western blot analysis were conducted to test the expression of miR-3150b-3p, TNFRSF11a and p38 mitogen-activated protein kinase (MAPK) signaling pathway. The interaction between miR-3150b-3p and TNFRSF11a was verified by luciferase assay. Cell proliferation, migration and invasion were determined by CCK-8, wound healing and Transwell assays. In this study, we showed that miR-3150b-3p was significantly downregulated in CC cell lines. Additionally, miR-3150b-3p markedly attenuated the proliferation, migration and invasion of HeLa and SiHa cells. Moreover, we identified TNFRSF11a to be a novel target of miR-3150b-3p in CC cells. Enforced expression of TNFRSF11a abolished the antitumor effect of miR-3150b-3p. Besides, miR-3150b-3p was involved in the regulation of the p38 MAPK signaling pathway. In conclusion, our data suggested that miR-3150b-3p directly targets TNFRSF11a to inactivate the p38 MAPK signaling pathway, thus implicating miR-3150b-3p in the regulation of CC cell growth.


Genetic Susceptibility, Change in Physical Activity, and Long-term Weight Gain.
Whether change in physical activity over time modifies the genetic susceptibility to long-term weight gain is unknown. We calculated a BMI-genetic risk score (GRS) based on 77 BMI-associated single nucleotide polymorphisms (SNPs) and a body fat percentage (BF%)-GRS based on 12 BF%-associated SNPs in 9,390 women from the Nurses' Health Study (NHS) and 5,291 men from the Health Professionals Follow-Up Study (HPFS). We analyzed the interactions between each GRS and change in physical activity on BMI/body weight change within five 4-year intervals from 1986 to 2006 using multivariable generalized linear models with repeated-measures analyses. Both the BMI-GRS and the BF%-GRS were associated with long-term increases in BMI/weight, and change in physical activity consistently interacted with the BF%-GRS on BMI change in the NHS (P for interaction = 0.025) and HPFS (P for interaction = 0.001). In the combined cohorts, 4-year BMI change per 10-risk allele increment was -0.02 kg/m2 among participants with greatest increase in physical activity and 0.24 kg/m2 among those with greatest decrease in physical activity (P for interaction < 0.001), corresponding to 0.01 kg versus 0.63 kg weight changes every 4 years (P for interaction = 0.001). Similar but marginal interactions were observed for the BMI-GRS (P for interaction = 0.045). Our data indicate that the genetic susceptibility to weight gain may be diminished by increasing physical activity.


Evidence of parvovirus B19 infection in patients of pre-eclampsia and eclampsia with dyserythropoietic anaemia.
Parvovirus B19 (PVB19) infection can induce transient anaemia in patients with increased erythropoiesis. However, the dynamic change within the bone marrow after PVB19 infection is not well understood. Increased erythropoiesis is a physiological phenomenon in puerperital women. Nevertheless, anaemia as a result of PVB19 infection in puerperital women has never been reported. We report one patient with eclampsia and two patients with pre-eclampsia who had transient, severe anaemia during the puerperital period because of PVB19 infection. Viral genomes were detected in the peripheral blood during the anaemic period by polymerase chain reaction and became undetectable after the anaemia was resolved. Viral genomes and protein could also be detected in bone marrow by in situ hybridization and immunohistochemical staining, respectively. Serial aspiration cytology of bone marrow showed severe dysplastic change involving erythroid precursors with a few apoptotic cells at the initial onset of anaemia, markedly increased apoptotic cells that was confirmed by the increased expression of activated caspase 3, around the nadir of anaemia, and a normal marrow picture without features of apoptosis after recovery from anaemia. Our data indicates that PVB19 infection can induce transient, severe dyserythropoietic anaemia in puerperital women with pre-eclampsia/eclampsia and the pathogenetic mechanism may probably involve the induction of apoptosis following PVB19 infection.


Learning Curve for Laparoscopic Major Hepatectomy: Use of the Cumulative Sum Method.
Laparoscopic liver resection (LLR) has now become a worldwide practice. However, the adoption of laparoscopic major hepatectomy (LMH) was slow. We report our center's experience in laparoscopic major resections. A total of 156 LLRs from 2002 to 2014 were studied. The clinical parameters of LMHs were compared with those of minor resections. The learning curve of LMHs was investigated using the cumulative sum (CUSUM) analysis of operative time. Subgroup analysis of right posterior sectionectomies against anterolateral hepatectomies was conducted. Among the 156 LLRs, 49 (31%) were LMHs. CUSUM analysis showed that operative time improved after the 25th LMH. Beyond that proportion of pure laparoscopic LMHs increased (18/25 vs. 24/24, P=0.005); Pringle maneuver was not required (4/25 vs. 0/24, P=0.041). Blood loss (800 vs. 500 mL, P=0.034) and transfusion rate (13/25 to 3/24, P=0.003) improved in latter LMHs. Right posterior sectionectomies had significantly more blood loss than anterolateral LMHs (500 vs. 1500 mL, P=0.034). Laparoscopic major resection is safe and feasible; operative outcomes improved after overcoming the learning curve. Right posterior sectionectomy, however, should be further evaluated for its cost-effectiveness.


Effect of Different Media and Protein Source on Equine Gametes: Potential Impact During In Vitro Fertilization.
Equine in vitro fertilization (IVF) is still inconsistent. In the present work, we studied how modified Whitten's (MW) medium and Tissue Culture Medium 199 (TCM) added with Foetal Bovine Serum (FBS; 10% v/v) or Bovine Serum Albumin (BSA; 7 mg/ml) affected equine gametes to subsequently run IVF trials. Compact (Cp) and expanded (Ex) cumuli equine oocytes were matured and placed in TCM or MW supplemented with BSA or FBS for 18-20 h (no sperm added). In Ex oocytes, TCM-199 added with FBS or BSA resulted in higher metaphase II (MII) rates (75.7% and 62.7%, respectively) than MW added with BSA (54%) or FBS (52.2%; p < 0.05); this was not observed for Cp oocytes. Equine sperm were capacitated in the same media at 10 × 10(6) sperm/ml for 4 h at 37°C; total motility and protein tyrosine phosphorylation (PY) were evaluated. While motility remained unchanged, TCM or MW added with FBS enhanced the number of sperm showing PY-stained tails (25 ± 4.8% and 31 ± 6.6%; mean ± SEM, respectively) over BSA supplemented media (3 ± 1.2% and 11.7 ± 1.1%) for TCM and MW (p < 0.05). In view of the previous results, sperm were capacitated in TCM + FBS and MW + BSA (control); IVF trials were run in the same media supplemented with 200 ng/ml of progesterone, but no fertilization occurred. Our results show that TCM + FBS enhances Ex equine oocyte's meiotic competence over MW + BSA and TCM or MW added with FBS successfully induce equine PY over media supplemented with BSA.


[Mechanisms of immunoglobulins activity].
Intravenous immunoglobulin (IVIG) products are derived from plasma pools of thousands of healthy donors. These immunoglobulin concentrates contain large number of antibodies as well trace levels various other immunologically active molecules. Therapeutic Ig formulations contain intact IgG molecules, with variable amounts of monomeric and dimeric form existing in a dynamic equilibrium. Paradoxically, IgG can exert both pro-and anti-inflammatory activities, depending on its concentration. IVIG have been used for the treatment of primary immunodeficiency disorders for more than 25 years. IVIG products are also effective in the treatment of autoimmune and inflammatory disorders; however, the precise mechanism (s) of action is not known. Clinical and laboratory studies have documented various mechanisms of action of IVIG. The complex network of immunological reactions resulting from the infusion of IVIG includes changes in several cytokines, interactions with dendritic cells, T-and B-cell effects, macrophage effects, mediated by distinct Fc-gamma receptors. IVIG is also a recently recognized modifier of complement activation and injury. The complement--scavenging ability of Ig implies expansion of the use of IVIG to all disease in which generation of complement fragments plays a crucial role in pathogenesis. Recent studies showed that the anti-inflammatory activity of IVIG result from a minor population of the pooled IgG molecules that contains terminal a-2,6 sialic acid linkages on their Fc-linked glycans. This fully processed glycan is found in 1-3% of IgG in IVIG, which may explain the requirement for a high dose of IVIG. Recent data demonstrate, that the anti-inflammatory properties of IVIG can be recapitulated with fully recombinant preparation of appropriately sialylated IgG Fc fragments. This recombinant preparation had a 35 fold enhanced activity and potentially could be used at much lower doses than IVIG preparation in the treatment of autoimmune disorders.


Vasoactive intestinal peptide-induced expression of cytochrome P450 cholesterol side-chain cleavage and 17 alpha-hydroxylase enzyme activity in hen granulosa cells.
Experiments were conducted to determine whether vasoactive intestinal peptide (VIP) can regulate expression of cytochrome P450 side-chain cleavage (P450scc) and P450 17 alpha-hydroxylase (P450 17 alpha-OH) mRNA levels and enzyme activity in granulosa cells from nonhierarchal (6-8-mm) follicles. Initial studies demonstrated that immunoreactive VIP is localized within the theca (but not granulosa) layer of both resting (< 0.5-mm follicles) and 6-8-mm follicles, thus providing a potential paracrine mechanism of action for VIP. While short-term (3 h) incubation of granulosa cells with VIP (0.001-1.0 microM) failed to stimulate progesterone production from 6-8-mm follicle granulosa cells, a 4-h culture period in the presence of VIP resulted in increased cyclic AMP (cAMP) accumulation, and a 24-h culture period resulted in progesterone synthesis and increased P450scc mRNA levels; control levels of each endpoint measurement were not altered within the period observed. By contrast, culture with the growth factor transforming growth factor alpha (TGF alpha) in the presence of VIP (1 microM) prevented increases in P450scc mRNA levels and progesterone production. Similar effects of VIP and TGF alpha in the presence of VIP were demonstrated for P450 17 alpha-OH mRNA levels and enzyme activity. Finally, there was an additive effect of VIP (0.1 microM) plus recombinant human (rh) FSH (100 mIU) on the initiation of progesterone production in cultured 6-8-mm follicle granulosa cells compared to the addition of VIP or rhFSH alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Bayesian Optimization-Assisted Screening to Identify Improved Reaction Conditions for Spiro-Dithiolane Synthesis.
Bayesian optimization (BO)-assisted screening was applied to identify improved reaction conditions toward a hundred-gram scale-up synthesis of 2,3,7,8-tetrathiaspiro[4.4]nonane (1), a key synthetic intermediate of 2,2-bis(mercaptomethyl)propane-1,3-dithiol [tetramercaptan pentaerythritol]. Starting from the initial training set (ITS) consisting of six trials sampled by random screening for BO, suitable parameters were predicted (78% conversion yield of spiro-dithiolane 1) within seven experiments. Moreover, BO-assisted screening with the ITS selected by Latin hypercube sampling (LHS) further improved the yield of 1 to 89% within the eight trials. The established conditions were confirmed to be satisfactory for a hundred grams scale-up synthesis of 1.


Site-directed mutagenesis of Escherichia coli ornithine transcarbamoylase: role of arginine-57 in substrate binding and catalysis.
In the carbamoyl-transfer reaction catalyzed by ornithine transcarbamoylase, an arginine residue in the active site of the Escherichia coli enzyme has been suggested to bind the phosphate moiety of the substrate carbamoyl phosphate. With the application of site-specific mutagenesis, the most likely arginine residue among three candidates at the binding site of carbamoyl phosphate, Arg-57, has been replaced with a glycine. The resultant Gly-57 mutant enzyme is drastically inefficient in catalysis. In the synthesis of L-citrulline from carbamoyl phosphate and L-ornithine with the release of inorganic phosphate, the turnover rate of the mutant is 21,000-fold lower than that of the wild type. However, the mutation of Arg-57 affects only moderately the binding of carbamoyl phosphate; the dissociation constant of this substrate, measured under steady-state turnover condition, is increased from 0.046 to 3.2 mM by the mutation. On the other hand, ornithine binding is substantially affected as estimated by the change in the dissociation constant of its analogue L-norvaline. The dissociation constant of L-norvaline increases about 500-fold from 54 microM for the wild type to 25 mM for the mutant. Since Arg-57 is expected to be distal from the ornithine site and the amino acid (both ornithine and norvaline) binds only after carbamoyl phosphate in the wild-type reaction, the poor norvaline affinity to the mutant suggests that Arg-57 is involved in interactions essential for productive addition of the amino acid. This interpretation is supported by difference ultraviolet absorption spectra which show that the conformational changes induced in the wild type by carbamoyl phosphate upon binding are absent in the mutant. Furthermore, steady-state kinetic data reveal that the ordered binding mechanism of the wild-type enzyme is transformed into a random binding mechanism in the mutant. Thus, the presence of carbamoyl phosphate in the mutant active site is no longer a requisite for ornithine binding. In the 5-50 degrees C temperature range, transcarbamoylation catalyzed by either the wild type or the mutant observes the Arrhenius rate law with almost identical enthalpies of activation, 11 and 10 kcal/mol, respectively. The entropy of activation is -5.5 eu for the wild-type reaction and -29 eu for the mutant reaction, accounting for a loss of 6-7 kcal/mol in the rate-determining step of the enzymic reaction.(ABSTRACT TRUNCATED AT 400 WORDS)


IRB reformation: is unfettered access the answer?
The purpose of this column is to consider if research using only an interview should be evaluated by an institutional review board (IRB) or if it may be considered exempt. A review of atrocities committed by researchers both in the biomedical and psychosocial domains will be considered as a backdrop to the discussion. Issues that plague IRBs will be examined including lack of transparency, overreach of the process, and stipulations that change the nature of research. Finally, recommendations for reform will be entertained.


Psychometric assessment of families with X-linked mental retardation.
As part of an integrated approach to DNA-linkage analysis in X-linked mental retardation (XLMR), 29 members of five families suspected of having XLMR underwent psychometric assessment. Mental retardation was confirmed in all participants. The range of mental retardation varied from mild to profound within and between families. In addition, these preliminary results indicated family-specific cognitive profiles in MRX45 and MRX46. The fact that two non-overlapping loci were involved provides strong evidence that specific cognitive profiles are linked to specific loci (genes) in mental retardation. We therefore recommend the application of standardised psychometric tests for the assessment of XLMR.


Species climate range influences hydraulic and stomatal traits in Eucalyptus species.
Plant hydraulic traits influence the capacity of species to grow and survive in water-limited environments, but their comparative study at a common site has been limited. The primary aim of this study was to determine whether selective pressures on species originating in drought-prone environments constrain hydraulic traits among related species grown under common conditions. Leaf tissue water relations, xylem anatomy, stomatal behaviour and vulnerability to drought-induced embolism were measured on six Eucalyptus species growing in a common garden to determine whether these traits were related to current species climate range and to understand linkages between the traits. Hydraulically weighted xylem vessel diameter, leaf turgor loss point, the water potential at stomatal closure and vulnerability to drought-induced embolism were significantly ( P < 0·05) correlated with climate parameters from the species range. There was a co-ordination between stem and leaf parameters with the water potential at turgor loss, 12 % loss of conductivity and the point of stomatal closure significantly correlated. The correlation of hydraulic, stomatal and anatomical traits with climate variables from the species' original ranges suggests that these traits are genetically constrained. The conservative nature of xylem traits in Eucalyptus trees has important implications for the limits of species responses to changing environmental conditions and thus for species survival and distribution into the future, and yields new information for physiological models.


Adequacy of fluid/sodium balance and blood pressure control.
Hypotension and orthostatic hypotension are frequently observed in CAPD patients. In the present paper the possible causes of these complications were reviewed, and the roles of sodium and water were pointed out. In addition, we reported our experience using different sodium concentrations in CAPD dialysis fluid. In 38 CAPD patients sodium concentration in the dialysate was changed from 132 to 137 mEq/L. At first, arterial blood pressure increased in 4 patients (10%), and they were switched to 132 mEq/L sodium. Of the other 34 patients, 3 required larger doses of antihypertensive agents, while 9 reduced the number and/or dose of antihypertensive drugs. Thirst, body weight, residual renal function, 24-hour ultrafiltration, and biochemical examinations did not change using 137 mEq/L sodium concentrations for 6 months. In the 21 patients who did not change their antihypertensive treatment, upright blood pressure tended to increase, but the difference was not statistically significant. In 3 hypotensive patients sodium concentration was increased to 142 mEq/L. Thirst increased in 2 of the 3, one observed a transient increase in 24-hour ultrafiltration, and none showed changes in plasma sodium level. One patient developed reversible hypertension, one became normotensive, and the third had no changes in blood pressure.


Quantitation of albumin and alpha-1-acid glycoprotein in human cervical mucus.
1. Concentrations of albumin and alpha-1-acid glycoprotein (AGP) in human cervical mucus have been measured by a radial immunodiffusion technique. 2. The cervical mucus samples were obtained from women on combined oral contraceptives (Group A) and from women not taking this medication (Group B). In group A the mean level of albumin was 75.6 (range 22-198) mg l-1 and for AGP 6.5 (range 3-12) mg l-1. In group B the mean level of albumin was 72.9 (range 22-148) mg l-1 and for AGP 6.6 (range 3-14) mg l-1. 3. The levels of albumin and AGP in cervical mucus were less than 1% of the concentration in serum and were not affected by combined oral contraceptives. 4. The clinical and toxicological consequences of these observations, in terms of the disposition of drugs and other chemicals in the female genital tract, await elucidation.


Tea production characteristics of tea growers (plantations and smallholdings) and livelihood dimensions of tea workers in Assam, India.
This article provides summary data regarding tea production in Assam, India. Questionnaires were completed by tea producers and focus group discussions undertaken with tea workers. These data are presented for the four main tea growing regions of the state (Cachar, North Bank, South Bank and Upper Assam). Tables detail tea production characteristics of the tea plantations for both large- (> 10 ha) and small- (< 10 ha) holders. Figures provide supplementary information for research by Biggs et al. [1] regarding fertilizer application, landscape management strategies, healthcare provisioning and educational facilities within plantations, as well as detailing the livelihood dimensions of tea workers. The questions posed to producers are also included. For further context underpinning the research for which these data were collated, see 'The tea landscape of Assam: multi-stakeholder insights into sustainable livelihoods under a changing climate' by Biggs et al. [1].


Biologic effects of chronic ethanol consumption related to a deficient intake of carbohydrates.
Our present understanding of the many effects of chronic ethanol consumption originated mostly from the use of an experimental model in which animals were maintained on a liquid diet that provided 36% of the total calories as alcohol. Since this diet was considered to be nutritionally adequate, a concept developed that the observed effects were due to the toxicity of alcohol and its metabolites rather than malnutrition. However, several biologic effects can be attributed to a reduced carbohydrate ingestion that accompanies chronic alcohol consumption.


A fresh look at the photoelectron spectrum of bromobenzene: A third-order non-Dyson electron propagator study.
The valence-shell ionization spectrum of bromobenzene, as a representative halogen substituted aromatic, was studied using the non-Dyson third-order algebraic-diagrammatic construction [nD-ADC(3)] approximation for the electron propagator. This method, also referred to as IP-ADC(3), was implemented as a part of the Q-Chem program and enables large-scale calculations of the ionization spectra, where the computational effort scales as n(5) with respect to the number of molecular orbitals n. The IP-ADC(3) scheme is ideally suited for investigating low-lying ionization transitions, so fresh insight could be gained into the cationic state manifold of bromobenzene. In particular, the present IP-ADC(3) calculations with the cc-pVTZ basis reveal a whole class of low-lying low-intensity two-hole-one-particle (2h-1p) doublet and quartet states, which are relevant to various photoionization processes. The good qualitative agreement between the theoretical spectral profile for the valence-shell ionization transitions generated with the smaller cc-pVDZ basis set and the experimental photoelectron spectrum measured at a photon energy of 80 eV on the PLÉIADES beamline at the Soleil synchrotron radiation source allowed all the main features to be assigned. Some theoretical aspects of the ionization energy calculations concerning the use of various approximation schemes and basis sets are discussed.


Nasoseptal cyst after septorhinoplasty: late and unusual but preventable compliation.
Nasoseptal cyst after septorhinoplasty: late and unusual but preventable complication. Formation if a slowly growing cyst following septorhinoplasty is a rare but serious complication. Mucous cyst is more common than foreign body inclusion cyst. Typically, these cysts present as a solitary lesion that develops in the subcutaneous pace over the nasal bone along the line of nasal osteotomy several months or years after initial surgery. Rarely, the cyst onnects with the nasal septum. Surgery is the treatment of choice and consists of either complete excision of the cyst apsule or marsupialization of the cyst. ase report: A nasoseptal mucous cyst developed in a 46-year-old woman 10 years after septorhinoplasty. We successfully narsupialized the cyst with an endonasal endoscopic approach. onclusion:. Cysts can be removed by either complete resection of the cyst capsule or marsupialization via endonasal endoscopy. To prevent cyst formation, initial surgery must be conducted nontraumatically and tissue remnants cleared to prevent dispersion into subcutaneous spaces.


Differential localization of TGF-beta-precursor isotypes in normal human skin.
Transforming growth factor-beta (TGF-beta) can act as a multi-functional regulator of both cell growth and differentiation. Three isotypes of TGF-beta s namely TGF-beta 1, TGF-beta 2 and TGF-beta 3, have been found in human tissues. Up to now, little is known about the distribution patterns of the TGF-beta isotypes in human skin. Using the TGF-beta-precursor (latency-associated peptides) specific antibodies to confirm the specificity, we studied the immunohistochemical distribution of TGF-beta 1-3 in human skin. TGF-beta 2 was found mainly in the intercellular space of all the layers of the epidermis as well as in the cytoplasm with a weak staining. In contrast, TGF-beta 3 was present in the subepidermal area of the dermis. TGF-beta 1 was observed obviously in neither epidermis nor dermis. These results showed the differential localization of TGF-beta isotypes in human skin, suggesting that the TGF-beta 2 and TGF-beta 3 may regulate the human skin function in an epithelial autocrine or mesenchymal-epithelial interaction manner.


The ultrastructure of Candida albicans infections.
Scrapings of Candida albicans plaques from the tongue and buccal mucosa of patients with oral candidiasis were examined by electron microscopy. In addition, urine sediment from patients with infection of their catheterized urinary tracts was similarly examined. Three types of C. albicans-oral epithelial cell interactions were noted: a loose adherence apparently mediated by a ruthenium red positive matrix, a "tight" adherence where no space could be seen between the host and yeast cell. and invasion of host cells by yeast hyphal elements. Adhesion of Candida blastospores to hyphal elements and adhesion of bacteria to Candida cells was also frequently observed. Urine sediments from patients with mixed bacteria-yeast infections demonstrated adhesion of the bacteria to the yeast cells. This phenomenon was also demonstrated in in vitro experiments and fibrous ruthenium red material invariably occupied the zone of adhesion. Phagocytosis of yeast by polymorphonuclear leukocytes was found in urinary, but not in oral. candidiasis. Our in vivo and in vitro observations indicate that a ruthenium red positive matrix covers the surfaces involved in the yeast to yeast, yeast to host, and yeast to bacteria adhesion.


Influences on Patient Satisfaction Among Patients Who Use Emergency Departments Frequently for Pain-Related Complaints.
The primary purpose of this study was to assess relationships between opioid prescribing practices, patient and ED attributes, and patient satisfaction ratings of nursing and physician care among patients with high utilization of the emergency department for pain relief. A retrospective cohort study was conducted to examine 305 individual patient satisfaction surveys from users with high ED utilization for pain complaints. Responses were compared with an age-matched control group (n = 305) of nonfrequent ED users. Patient satisfaction survey responses and electronic medical records were used to model relationships between patient satisfaction and predictor variables. ED frequent users with pain complaints were 75% less likely to return a satisfaction survey compared with other patients (odds ratio = 0.2488; P < .0001). Patient satisfaction with physician behavior was largely accounted for by ED cleanliness, pain control, wait time for the physician, satisfaction with nursing, and feelings that ED staff cared about the patient personally. On the other hand, patient satisfaction with nursing care was largely accounted for by perceptions that nursing care was compassionate, feelings that the patient mattered personally, perceptions of safety precautions, and wait times. Receipt of prescriptions for scheduled drugs did not significantly influence patient satisfaction with physician or nursing behaviors. Emergency nurses can influence patient satisfaction scores by promoting clean, caring environments and prioritizing patient flow and pain management. ED providers can withhold opioids when appropriate without fear of a significant impact on patient satisfaction.


The Importance of Prostate-Specific Membrane Antigen Expression in Salivary Gland Tumors.
Prostate-specific membrane antigen (PSMA) is a cell membrane protein expressed by prostate tissues. It is not prostate specific and is also expressed by some non-prostatic solid neoplasms. Our study aimed to investigate the potential role of PSMA in salivary gland tumors. The present study was designed to retrospectively analyze our cases that presented with salivary gland tumors. The files of 105 patients were reviewed and their paraffin embedded blocks were retrieved from the pathology department. Immunohistochemical examination and staining were done using PSMA antibody. Tumor tissue PSMA immunohistochemical staining was scored semi-quantitatively with the modified quartile approach. Negative staining was scored 0, >0% and ≤25% tissue expression was considered weak (score 1), >25% and ≤50% tissue expression was considered mild (score 2), >50% and ≤75% tissue expression was considered moderate (score 3), and >75% tissue expression was considered strong (score 4). Eighty-eight patients (55 males, 33 females) were included in the study. Forty-eight patients had pleomorphic adenoma (PA), 35 had Warthin's tumor (WT), two had mucoepidermoid carcinoma, two had adenoid cystic carcinoma, and one had squamous cell carcinoma. There was statistically significant difference in terms of PSMA expression between PA and WT (p=0.003). PSMA expression was high in PA and absent in WT. PSMA is a potential source of inspiration for future studies on the development of novel diagnostic and theranostic investigations of salivary gland tumors. Prospective studies targeting intratumoral PSMA in salivary gland tumors should be planned.


Case Report: Analysis of Plasma Extracellular Vesicles in a Triple Negative Spindle-Cell Metaplastic Breast Cancer Patient.
Metaplastic breast cancer (MpBC) is a rare tumor representing 1% of all breast malignancies. The prognosis of this histologic subtype is actually poor and there are no current clear-cut therapeutic guidelines. Hence, despite its uniqueness, its aggressive prognostic profile strongly encourages further studies to identify new markers and therapeutic targets. Herein, we report a case of 32-years-old patient affected with of triple negative spindle-shaped MpBC. The research of molecular targets on the primary tumor did not allow performing an effective therapeutic choice. Extracellular Vesicles (EVs) are under intense study as new potential pathophysiological markers and targets for therapeutic applications, in different tumors for their role in tumor onset, progression and aggressiveness. Here, we examined the involvement of EVs in this case, to look into the MpBC microenvironment willing to identify new potential molecular targets, pathways of aggressiveness, and markers of prognosis and therapeutic efficacy. Firstly, we characterized MpBC patient EV dimensions and surface proteins. Moreover, we analyzed the EV RNA cargo supposed to be delivered to nearby and distant recipient cells. Interestingly, we observed a dysregulation EV-contained miRNAs, which could determine an increased expression of oncogenes in the tumor microenvironment, probably enabling cancer progression. These data suggest that the characterization of miRNA cargo of EVs could be important for the identification of new markers and for the application of future new target therapies.


Danhong Injection Alleviates Mechanical Allodynia via Inhibiting ERK1/2 Activation and Elevates BDNF Level in Sciatic Nerve in Diabetic Rat.
Danhong injection (DHI) has been widely used in China for cardiocerebrovascular diseases treatments. And in this study, we demonstrated the therapeutic effect of DHI on experimental diabetic neuropathy for the first time. Methods. Streptozotocin- (STZ-) induced SD rats were used. In experiment 1, 4-week treatment with DHI or saline started 4 weeks after STZ injection; mechanical allodynia was measured before and every 2 weeks after STZ injection. In experiment 2, chronic intrathecal infusion of U0126 was conducted during the 8th week of diabetes. Phosphorylated and total ERK1/2 in spinal cord were analyzed by western blot. BDNF level in sciatic nerve was evaluated by ELISA. Results. DHI treatment significantly alleviated mechanical allodynia at the end of the study and downregulated the expression of phosphorylated ERK1/2 in spinal cord. In addition, DHI treatment also elevated brain-derived neurotrophic factor (BDNF) level in sciatic nerve of DPN rat. In experiment 2, inhibition of ERK1/2 activation was confirmed to result in the alleviation of mechanical allodynia. Conclusions. We demonstrated that DHI was able to alleviate mechanical allodynia in diabetic neuropathy rat through inhibiting the activation of ERK1/2. The reduction of BDNF content in sciatic nerve was also partially reversed by DHI treatment.


High-resolution cell surface dynamics of germinating Aspergillus fumigatus conidia.
We used real-time atomic force microscopy with a temperature-controlled stage (37 degrees C) to probe the structural and physicochemical dynamics of single Aspergillus fumigatus conidia during germination. Nanoscale topographic images of dormant spores revealed the presence of a layer of rodlets made of hydrophobins, in agreement with earlier electron microscopy observations. Within the 3-h germination period, progressive disruption of the rodlet layer was observed, revealing hydrophilic inner cell wall structures. Using adhesion force mapping with hydrophobic tips, these ultrastructural changes were shown to correlate with major differences in cell surface hydrophobicity. That is, the rodlet surface was uniformly hydrophobic due to the presence of hydrophobins, whereas the cell wall material appearing upon germination was purely hydrophilic. This study illustrates the potential of real-time atomic force microscopy imaging and force spectroscopy for tracking cell-surface dynamics.


Analysis In Vivo of Bone Modulation in Hydrophilic and Hydrophobic Titanium Implant Surfaces.
To evaluate whether a hydrophilic surface treatment compared with a hydrophobic implant surface can enhance osseointegration by analysis of calcium deposition, bone-to-implant contact (BIC), bone volume (BV), and upregulation of genes involved in bone formation. Sixty implants (n = 60) with a hydrophobic (SAE) or hydrophilic (SAE-HD) surface treatment were placed bilaterally in each femur of 3-month-old male mice (n = 30). Scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDS) were utilized for quantifying the presence of calcium on the implant surface 7 days after implant placement. The specimens were analyzed after 14 and 21 days for BIC and BV by Nano CT scanning followed by histologic evaluation. Additionally, 1, 3, and 7 days postsurgery, femurs were harvested, implants were explanted, and gene expression (Sp7, Bsp, Sost, IL-1α, and IL-10) by quantitative real-time polymerase chain reaction was studied. Moreover, implants were characterized for surface roughness area. Data were statistically analyzed with two-way analysis of variance (ANOVA) followed by the Tukey test (P < .05). The amount of calcium on the surface was higher for SAE-HD after 7 days. Nano CT revealed significantly more BV in the SAE-HD than the SAE surface. The histologic assessment showed increased BIC in SAE-HD in comparison to SAE. SAEHD showed significantly increased levels of genes involved in bone formation. Both surfaces were able to modulate bone responses toward osteoblast differentiation. SAE-HD presented a better response compared with SAE.


Locally developed guidelines reduce immediate complications from percutaneous dilatational tracheostomy using the Ciaglia Blue Rhino technique: a report on 200 procedures.
Ciaglia Blue Rhino percutaneous dilatational tracheostomy is used as an aid to ventilatory weaning. It carries an immediate complication rate previously reported in 100 consecutive patients by Fikkers et al at 6% for "major" complications and 30% for "minor" complications. Mortality has been associated with the procedure. Our institution has performed dilatational percutaneous tracheostomy since 1998 and used the Blue Rhino technique since 2002. Consensus guidelines were developed following initial experiences. They focus on preoperative risk assessment including levels of ventilatory support and anatomical considerations, seniority of staff use of bronchoscopy and capnography and correction of coagulopathies. Following introduction of the guidelines we conducted an audit of the first 200 Ciaglia Blue Rhino tracheostomies performed. There was an immediate major complication rate of 3% and minor complication rate of 18%. No deaths occurred within 24 hours of the procedure. We conclude that applying our consensus guidelines produced an immediate complication rate for Ciaglia Blue Rhino percutaneous dilatational tracheostomy below published audits.


A study on the effects of diclofenac sodium and etoricoxib in the treatment of osteoarthritis.
Diclofenac sodium, a non-selective cyclo-oxygenase inhibitor and etoricoxib, a selective cyclo-oxygenase-2 inhibitor have been widely used in treatment of patients with osteo-arthritis. Five hundred and eighty-five patients with uncomplicated knee osteo-arthritis were randomly allocated into 3 equal groups and received either diclofenac sodium, etoricoxib or placebo in a double-blind manner. The response in both the drug groups was comparable and much more than placebo group. The study shows that etoricoxib provides better clinical efficacy and gastro-intestinal tolerability in osteo-arthritis in comparison to diclofenac sodium presumably due to the selective inhibition of cyclo-oxygenase-2 by etoricoxib.


Experimental visualization of the diffusion pathway of sodium ions in the Na3[Ti2P2O10F] anode for sodium-ion battery.
Sodium-ion batteries have attracted considerable interest as an alternative to lithium-ion batteries for electric storage applications because of the low cost and natural abundance of sodium resources. The materials with an open framework are highly desired for Na-ion insertion/extraction. Here we report on the first visualization of the sodium-ion diffusion path in Na3[Ti2P2O10F] through high-temperature neutron powder diffraction experiments. The evolution of the Na-ion displacements of Na3[Ti2P2O10F] was investigated with high-temperature neutron diffraction (HTND) from room temperature to 600°C; difference Fourier maps were utilized to estimate the Na nuclear-density distribution. Temperature-driven Na displacements indicates that sodium-ion diffusion paths are established within the ab plane. As an anode for sodium-ion batteries, Na3[Ti2P2O10F] exhibits a reversible capacity of ~100 mAh g(-1) with lower intercalation voltage. It also shows good cycling stability and rate capability, making it promising applications in sodium-ion batteries.


Testing for Hardy-Weinberg proportions: have we lost the plot?
Testing for Hardy-Weinberg proportions (HWP) is routine in almost all genetic studies of natural populations, but many researchers do not demonstrate a full understanding of the purposes of these tests or how to interpret the results. Common problems include a lack of understanding of statistical power and the difference between statistical significance and biological significance, how to interpret results of multiple tests, and how to distinguish between various factors that can cause statistically significant departures. In this perspective, which focuses on analysis of genetic data for nonmodel species, I 1) review factors that can cause departures from HWP at individual loci and linkage disequilibrium (LD) at pairs of loci; 2) discuss commonly used tests for HWP and LD, with an emphasis on multiple-testing issues; 3) show how to distinguish among possible causes of departures from HWP; and 4) outline some simple steps to follow when significant test results are found. Finally, I 5) identify some issues that merit particular attention as we move into an era in which analysis of genomics-scale datasets for nonmodel species is commonplace.


Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases.
The neuregulins (NRGs) are a family of multipotent epidermal-growth-factor-like (EGF-like) factors that arise from splice variants of a single gene. They influence the growth, differentiation, survival and fate of several cell types. We have now discovered a set of new neuregulin-like growth factors, which we call neuregulin-2 (NRG-2): these are encoded by their own gene and exhibit a distinct expression pattern in adult brain and developing heart. Like NRG-1, the EGF-like domain of the new ligands binds to both the ErbB3- and ErbB4-receptor tyrosine kinases. However, NRG-2 stimulates different ErbB-receptor tyrosine-phosphorylation profiles from NRG-1. Our results indicate that NRG-1 and NRG-2 mediate distinct biological processes by acting at different sites in tissues and eliciting different biochemical responses in cells.


Genomic epidemiology of a protracted hospital outbreak caused by multidrug-resistant Acinetobacter baumannii in Birmingham, England.
Multidrug-resistant Acinetobacter baumannii commonly causes hospital outbreaks. However, within an outbreak, it can be difficult to identify the routes of cross-infection rapidly and accurately enough to inform infection control. Here, we describe a protracted hospital outbreak of multidrug-resistant A. baumannii, in which whole-genome sequencing (WGS) was used to obtain a high-resolution view of the relationships between isolates. To delineate and investigate the outbreak, we attempted to genome-sequence 114 isolates that had been assigned to the A. baumannii complex by the Vitek2 system and obtained informative draft genome sequences from 102 of them. Genomes were mapped against an outbreak reference sequence to identify single nucleotide variants (SNVs). We found that the pulsotype 27 outbreak strain was distinct from all other genome-sequenced strains. Seventy-four isolates from 49 patients could be assigned to the pulsotype 27 outbreak on the basis of genomic similarity, while WGS allowed 18 isolates to be ruled out of the outbreak. Among the pulsotype 27 outbreak isolates, we identified 31 SNVs and seven major genotypic clusters. In two patients, we documented within-host diversity, including mixtures of unrelated strains and within-strain clouds of SNV diversity. By combining WGS and epidemiological data, we reconstructed potential transmission events that linked all but 10 of the patients and confirmed links between clinical and environmental isolates. Identification of a contaminated bed and a burns theatre as sources of transmission led to enhanced environmental decontamination procedures. WGS is now poised to make an impact on hospital infection prevention and control, delivering cost-effective identification of routes of infection within a clinically relevant timeframe and allowing infection control teams to track, and even prevent, the spread of drug-resistant hospital pathogens.


Gallbladder carcinoma: findings at MR imaging with MR cholangiopancreatography.
To describe magnetic resonance (MR) imaging and MR cholangiopancreatography (MRCP) findings in gallbladder carcinoma, and to correlate these findings with available surgical and biopsy information. Preoperative MR images (T1-weighted spin-echo, T2-weighted fast spin-echo, single shot fast spin-echo, and dynamic gadolinium-enhanced gradient echo) in 34 patients with gallbladder carcinoma were retrospectively reviewed for appearance of the primary neoplasm and for demonstration of hepatic, peritoneal, duodenal, and nodal involvement. Imaging findings were then compared with surgical findings (n = 19 patients) and histologic findings (n = 15 patients). Gallbladder carcinoma manifested at MR imaging as focal gallbladder wall thickening with an eccentric mass in 76% (26/34) of cases. The most common types of regional spread demonstrated were direct liver invasion in 91% (31/34), lymphadenopathy in 76% (26/34), and biliary tract invasion in 62% (21/34). Sensitivity for direct hepatic invasion was 100%, and was 92% for lymph node metastasis. MRI and MRCP can provide information relevant to preoperative staging of gallbladder carcinoma.


Endocannabinoid signaling in the gut mediates preference for dietary unsaturated fats.
Dietary fat exerts a potent stimulatory effect on feeding. This effect is mediated, at least in part, by a cephalic mechanism that involves recruitment of the vagus nerve and subsequent activation of endocannabinoid signaling in the gut. Here, we used a sham-feeding protocol in rats to identify fatty-acid constituents of dietary fat that might be responsible for triggering small-intestinal endocannabinoid signaling. Sham feeding rats with a corn oil emulsion increased endocannabinoid levels in jejunum, relative to animals that received either mineral oil (which contains no fatty acids) or no oil. Sham-feeding emulsions containing oleic acid (18:1) or linoleic acid (18:2) caused, on average, a nearly 2-fold accumulation of jejunal endocannabinoids, whereas emulsions containing stearic acid (18:0) or linolenic acid (18:3) had no such effect. In a 2-bottle-choice sham-feeding test, rats displayed strong preference for emulsions containing 18:2, which was blocked by pretreatment with the peripherally restricted CB1 cannabinoid receptor antagonists, AM6546 and URB447. Our results suggest that oral exposure to the monoenoic and dienoic fatty acid component of dietary fat selectively initiates endocannabinoid mobilization in the gut, and that this local signaling event is essential for fat preference.


[The expression of the correction of corneal astigmatism in the point spread function analysis system of human eyes].
To investigate the ocular optical imaging quality among corneal astigmatism subjects under different corrections by using the Point Spread Function analysis system (PSF). PSF 1000 analyzer was used to measure retinal image quality of eyes of 26 subjects with corneal astigmatism (sphere ranged from -3.00 to -6.00 DS, cylinder ranged from - 0.75 to - 3.00 DC), who were fully corrected with three different methods respectively: spectacles (SPE), rigid gas permeable contact lenses (RGPCL) and toric soft contact lenses (TSCL). The modulation transfer function (MTF) curve was recorded and evaluated. 12 points of the MTF curve (equivalent to the 12 points of Log Mar VA chart) were chosen for analysis. Equivalent moderate myopia 26 subjects without astigmatism were set up as control group. The MTF curve of each eye is enantiomorphous symmetrical. Compared with the control group ( < -0.75D), with 3.0 mm pupil, there's no statistical difference under low spatial frequency, the difference between middle and high frequency is significant (P < 0.05). With 6.0 mm pupil, there is statistical difference in all frequencies (P <0.01). With simulated 3.0 mm pupil and 6.0 mm pupil, MTF values of all these three methods are statistical different. With 3.0 mm pupil, the MTF value of eyes fitted with RGPCLs is higher than that fitted with TSCLs except in the following frequency 3.00, 3.78, 4.78, 30.00 and 37.80 c/deg (P <0.05). With 6.0 mm pupil, the three correction methods are statistical different in all frequencies (P <0.05). In all these three methods, MTF values with simulated 3.0 mm pupil are significantly higher than that with simulated 6.0 mm pupil (P <0.01). PSF analytical method is available for offering objective data of retina imaging quality. RGPCL and its induced tear film is improved not only correcting the corneal astigmatism, but also enhances the ocular optical quality by reducing diffraction, dispersion and other high order of aberration.


Design, Synthesis, and Conformational Analysis of Proposed β-Turn Mimics from Isoxazoline-Cyclopentane Aminols.
Constrained aminols from oxazanorbornene derivatives have the geometrical features to be used as β-turn inducers. Four different stereoisomers were prepared and spectroscopically characterized (MD calculations, NMR-titration and VT-NMR experiments). Temperature coefficients in DMSO are indicative for the existence of an intramolecular hydrogen bond. Chirooptical properties revealed a β-turn arrangement of all the synthesized compounds, where, depending on the absolute configuration of the cyclopentane spacer, they can be labeled as left- or right-handed turns.


Using ankle-brachial index to detect peripheral arterial disease: prevalence and associated risk factors in a random population sample.
The ankle-brachial index (ABI) is being used increasingly to diagnose peripheral arterial disease (PAD) that predicts cardiovascular morbidity and mortality. The aim of this study is to determine the prevalence of PAD and associated risk factors in a Spanish random population sample of age > or =40. PAD is defined as an ABI<0.9 in either leg. 784 participants of age > or =40 were randomly selected in a Spanish province. 55.4% of them were female. The prevalence of PAD in this sample was 10.5% (95% confidence interval (CI) 8.4-12.8); 9.7% in females and 11.4% in males. In logistic regression analyses, adjusted for age and gender, smoking per 10 pack-years (odds ratio (OR) 1.40, 95% CI 1.23-1.58), hypertension (OR 1.85, 95% CI 1.05-3.28), hypercholesterolemia (OR 1.76, 95% CI 1.04-2.98), and diabetes (OR 1.80, 95% CI 1.04-3.11) were positively associated with prevalent PAD. More than 91% of persons with PAD had one or more cardiovascular disease risk factors. We conclude that in our study hypertension, hypercholesterolemia, diabetes mellitus and smoking are associated with PAD. The majority of individuals with PAD had at least one important cardiovascular risk factor advanced enough to be considered eligible for an aggressive treatment.


Sudomotor function and sweat gland innervation in galanin knockout mice.
The presence of galanin and galanin binding sites in sweat gland has been demonstrated previously. In order to investigate whether galanin can influence sweat gland function, we compared sweating induced in footpads of wild type and galanin knockout mice by cholinergic and thermal stimulation using the silicone impression technique. Pilocarpine injections resulted in a similar number of reactive sweat glands and non-significant difference in the amount of sweat secretion in wild type and galanin knockout mice. However, thermal stimulation led to a significant increase in the number of secreting sweat glands in galanin knockout mice. To further evaluate possible differences in the innervation of sweat glands that could explain differences in their secretory activity, immunohistochemical labeling of cutaneous and sudomotor innervations against protein gene product 9.5, vasoactive intestinal polypeptide and choline acetyltransferase in plantar pads was performed. Immunohistochemical analysis revealed no significant differences in the distribution and intensity of the innervations between wild type mice and galanin knockout mice. Although our results indicate normal cholinergic responses and innervation of the sweat glands in galanin knockout mice, they also demonstrate that galanin plays a role in regulating the sudomotor activity in response to thermal stimulation.


Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid electrophysiological and neurotoxic effects in the guinea-pig cochlea.
We have recorded cochlear potentials after perilymphatic perfusion of cumulative doses of the excitatory amino acid alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) which selectively recognizes the non-N-methyl-D-aspartate ionotropic receptor formerly known as the quisqualate receptor. Our results show that AMPA (1-80 microM) caused a significant suppression of the amplitude of the compound action potential evoked by acoustic stimulation. A total elimination of this potential at the 100 microM concentration was observed in all animals. In no case was the cochlear microphonic potential, a hair cell receptor potential, affected by AMPA. Histological examinations were performed either at the end of the physiological studies or on cochleas perfused for 10 min with a single dose of AMPA (50 or 100 microM). In both experimental conditions, a selective dendritic swelling or radial afferent nerve endings under the sensory inner hair cells was observed. No damage was found in both types of hair cells supporting cells, lateral and medial efferent fibers and spiral afferent nerve ending on the outer hair cells. The occurrence of the radial dendrite swelling was prevented when 6,7-dinitroquinoxaline-2,3-dione (500 microM) was perfused in the cochlea 10 min prior, then concomitantly with AMPA. The present study strongly suggests that non-N-methyl-D-aspartate receptors, possibly of the AMPA subtype, are involved in the synaptic transmission between the inner hair cells and the primary auditory neurons. They provide further support for the hypothesis that L-glutamate, or another excitatory amino acid, acts as an inner hair cell neurotransmitter.


Relationship between visual hallucinations and REM sleep behavior disorder in patients with Parkinson's disease.
REM sleep behavior disorder (RBD) has been documented to precede or to co-occur with Parkinson's disease (PD). Parkinson's disease is one of the most common neurological conditions associated with visual hallucinations. Cognitive dysfunction is present in PD, even at the early stages of these diseases. In this study we aimed to investigate the relationship between visual hallucinations and RBD in patients with idiopathic Parkinson's disease (IPD). Additionally, we evaluated the association of the cognition and the pattern of cognitive impairment with VHs and RBD, effects of factors like duration and severity of the disease and duration of levodopa usage. Seventy-nine patients, diagnosed as PD, were included the study and then, patients were divided into four groups; with RBD and VHs (group 1), with RBD but no VHs (group 2), with VHs but no RBD (group 3), without RBD and VHs (group 4). We compared each group with the others according to demographic characteristics and neuropsychological test scores. Of all patients, in 46% (n=36) RBD and in 48% (n=38) VHs were observed. Our study established VHs in 58% of patients with RBD, and RBD in 55% of patients with VHs. However, due to a 40% incidence of VHs in patients without RBD, RBD and VHs were not found to be correlated. All of the neuropsychometric test scores did not reveal significant difference between groups. Although it seems like there is a small association between RBD and VHs in our patients, it was not significant. Group 1 presented with significantly worse scores in UPDRS total scores and I, II subscores.


Genome-Wide ChIP-seq and RNA-seq Analyses of STAT3 Target Genes in TLRs Activated Human Peripheral Blood B Cells.
Toll like receptors (TLRs) induced response plays a vital role in B-cell development and activation, in which TLR7-mediated and TLR9-mediated response interact together and play antagonistic or cooperative roles at different situations. Previous studies showed that the transcription factor signal transducer and activator of transcription (STAT) 3 was one of the key transcriptional factors (TFs) needed for both TLR7 and TLR9 signaling in B cell, and patients with autosomal dominant hyper IgE syndromes (AD-HIES) due to STAT3 mutations having defective TLRs response in B cells. However, how STAT3 affects its target genes and the downstream signaling pathways in B cell upon TLRs stimulation remains unclarified on a genome-wide level. ChIP-seq and RNA-seq was used in this study to identify the STAT3 targets in response to TLRs stimulation in human B cell. STAT3 ChIP-seq results showed a total of 611 and 2,289 differential STAT3-binding sites in human B cell after TLR7 and TLR9 agonists stimulation, respectively. RNA-seq results showed 1,186 and 1,775 differentially expressed genes after TLR7 and TLR9 activation, respectively. We identified 47 primary STAT3 target genes after TLR7 activation and 189 target genes after TLR9 activation in B cell by integration of STAT3 ChIP-seq and RNA-seq data. Among these STAT3 primary targets, we identified 7 TFs and 18 TFs for TLR7 and TLR9 response, respectively. Besides, we showed that STAT3 might regulate TLR9, but not TLR7 response in B cells through directly regulating integrin signaling pathway, which might further affect the antagonism between TLR7 and TLR9 signaling in B cell. Our study provides insights into the molecular mechanism of human TLRs response in B cell and how it can be regulated, which helps to better understand and modulate TLR-mediated pathogenic immune responses in B cell.


[Iron deficiency as a risk factor during the perinatal period].
Iron deficiency as a risk factor in the perinatal period--the review of the literature. The presence of iron is necessary for the metabolic processes, erythropoiesis, oxygen transport and respiration, thermoregulation and humoral and cellular immunity. Iron deficiency decreases the amplitude of adaptation of the pregnant women. It might be responsible for abortion or preterm labour as well as disarrangement of myometrial activity during labour and puerperium. Congenital fetal malformations and intrauterine growth retardation might be also stimulated by iron deficiency.