Effects of salvinorin A on locomotor sensitization to D2/D3 dopamine agonist quinpirole.
Locomotor sensitization induced by the dopamine agonist quinpirole can be potentiated by co-treatment with the synthetic kappa opioid agonist U69593. The identification of salvinorin A, an active component of the psychotropic sage Salvia divinorum, as a structurally different agonist of kappa-opioid receptors raised the question of whether this compound would similarly potentiate sensitization to quinpirole. Rats were co-treated with 0.5 mg/kg quinpirole and either salvinorin A (0.04, 0.4 or 2.0 mg/kg) or U69593 (0.3 mg/kg). Control groups were co-treated with vehicle and saline, vehicle and quinpirole (0.5 mg/kg), or saline and salvinorin A (0.4 mg/kg). Rats were injected biweekly for a total of 10 injections and locomotor activity measured after each treatment. Results showed that the highest dose of salvinorin A potentiated sensitization to quinpirole as did U69593, the middle salvinorin A dose had no effect on quinpirole sensitization, and the lowest dose of salvinorin A attenuated sensitization to quinpirole. These findings indicate that structural differences between salvinorin A and U69593 do not affect the potentiation of quinpirole sensitization. Moreover, the opposite effects of high and low salvinorin A doses suggest that salvinorin A can produce bidirectional modulation of sensitization to dopamine agonists.


Developing evidence-based guidance for the treatment of dry eye disease with artificial tear supplements: A six-month multicentre, double-masked randomised controlled trial.
To assess the six-month therapeutic profiles of lipid and non-lipid-based artificial tear supplements in managing dry eye disease (DED). Ninety-nine participants fulfilling the TFOS DEWS II diagnostic criteria for DED (64% females; mean ± SD age, 44 ± 16 years) were enrolled in a prospective, multicentre, double-masked, parallel group, randomised controlled trial. Participants instilled lipid-based nanoemulsion drops or non-lipid-based aqueous drops for six months, at least four times daily. Symptomology, tear film and ocular surface characteristics were assessed at Days 0, 30, 60, 90, 120, 150 and 180. Sustained reductions in OSDI, DEQ-5, and SANDE symptom scores from baseline were observed from Day 30 onwards in both groups (all p < 0.05) and decreased superior lid wiper epitheliopathy grades from Day 60 onwards (all p ≤ 0.01). Improvements in non-invasive tear film breakup time, and sodium fluorescein and lissamine green staining scores followed from Day 120 onwards in both groups (all p < 0.05). Tear lipid layer grades increased from Day 90 onwards only with the lipid-based drops, and with significantly greater improvement in those with suboptimal lipid layer thickness at baseline (grade ≤3; p = 0.02). By Day 180, 19% of participants no longer fulfilled the diagnostic criteria for DED. Over a six-month treatment period, improvements in dry eye symptomology preceded tear film and ocular surface changes with regular use of both lipid and non-lipid-based artificial tear supplements. Both formulations addressed most mild-to-moderate forms of aqueous deficient and evaporative DED, while evaporative cases benefitted preferentially from lipid-based supplementation. This represents a first step towards mapping DED therapeutic strategies according to disease subtype and severity.


[The role of toxininduced autoimmune activity in formation of the endotoxemia during the lead exposure].
Here presented the features of formation of endotoxemia at microsaturnism. Here are the results of the retrospective study of toxininduced autoimmune activity and their role in toxemia depending on the degree of exposure of lead. Investigated the mechanisms of production of toxins and damaging potentials activity, molecular size toxins and parameters of their distribution and accumulation in the blood stream, due to the strength of toxinbearing fractions depending on the degree of microsaturnism.


Research on the Construction of Age-Friendly Community Based on Fuzzy Comprehensive Evaluation Model: Evidence from Community in Hefei of China.
The construction of an age-friendly community is beneficial to meeting the needs of the elderly and coping with ageing. It is significant to evaluate the quality of age-friendly communities through scientific methods. The study aims to evaluate the livability of communities among the elderly in China. The data used in this study were sourced from the community of Hefei in China, including 1426 participants aged 60 and above. Taking community in Hefei of China as an example, the analytic hierarchy process fuzzy comprehensive evaluation model was used to evaluate the community. Furthermore, this paper constructs an evaluation index system for the livable elderly community and evaluates the comprehensive community system with the fuzzy comprehensive evaluation method. This study constructs the evaluation index system of an age-friendly community that includes five first-level evaluation indexes and 33 second-level evaluation indexes. The first-level indexe satisfaction from high to low are community safety, community comfort, community health and convenience, and community service. Among them, flat roads (more than 74.3%), greening (more than 78%), quietness (more than 76.8%), health situation (more than 65%), and public transport facilities (more than 66%) were relatively satisfactory. However, in terms of community service, the overall satisfaction of the elderly is not high. This study revealed that the level of the age-friendly community in Hefei of China is relatively high. The community safety score is the highest, comfort is relatively high, followed by community health and convenience. The score of community service was low. Moreover, the results indicated that improving the quality of service has become the key to improving the satisfaction of the elderly in the community.


Effects of power training on muscle thickness of older men.
The present study aimed at comparing the effects of traditional resistance training (TRT) and power training (PT) in inducing muscle hypertrophy in older men. Twenty older men (aged between 69 and 76 years) were divided in two groups: TRT training (n=9) and PT training (n=11). The volunteers trained twice a week, during 10 weeks. Both groups performed an equal work output and the same exercises with loads between 40% and 60% of 1 RM. Three sets of eight repetitions of each exercise were performed with rest intervals of 90 s between sets. Muscle thickness was measured by ultrasound at the biceps brachii (BIC) and rectus femoris (RF), using a 12 MHz high resolution scanning probe. An ANCOVA was used to compare post training muscle thickness values between TRT and PT, using baseline values as covariates. According to the results, RF muscle thickness increased only in PT, while BIC muscle thickness increased in both groups, but with larger increases in PT. In conclusion, ten weeks of PT induced muscle hypertrophy of the upper and lower limb muscles in older men. PT training may yield better results in muscle hypertrophy when compared with TRT.


Impact of positive ZEB1 expression in patients with epithelial ovarian carcinoma as an oncologic outcome-predicting indicator.
Several previous studies have revealed that the expression of zinc finger E-box binding homeobox 1 (ZEB1) in solid malignancies has an important significance on the clinical outcome of patients. However, the association between ZEB1 expression and survival in patients with epithelial ovarian carcinoma (EOC) remains unclear. The objective of the present study was to examine the extent of ZEB1 expression in EOC using immunohistochemical staining and investigate its association with patient outcome. A total of 40 patients with EOC initially treated with cytoreductive surgery and systematic chemotherapy were enrolled. ZEB1 expression was immunohistochemically categorized as negative, weak, moderate and strong according to the size of the staining area, and intensity. Subsequently, the associations between ZEB1 expression and recurrence/progression-free survival (RFS) rate were examined. The median age of patients in the current study was 54 years old (range, 22-72 years old). Among these patients, 15 (37.5%) exhibited International Federation of Gynecology and Obstetrics stage I disease, and 10 (25.0%), 13 (32.5%), and 2 (5%) had stage II, III, and IV disease, respectively. No patients with negative expression of ZEB1 experienced recurrence. In addition, ZEB1 expression was identified to be a significant predictor of a poorer RFS rate compared with negative expression (negative vs. weak, moderate and strong, P=0.0126). Furthermore, multivariate analyses revealed that moderate and strong ZEB1 expression levels were significant prognostic indicators of a poorer RFS rate in patients with EOC (hazard ratio, 2.265; 95% confidence interval, 1.072-8.021; P=0.0349). Confining analysis to patients with the clear-cell/mucinous histological type, those with moderate/strong ZEB1 expression demonstrated a significantly poorer RFS rate (P=0.0025). Positive ZEB1 expression may be an indicator to predict unfavorable RFS in patients with EOC.


Management of diabetic gastroparesis.
Symptoms suggestive of gastroparesis occur in 5% to 12% of patients with diabetes. Such a complication can affect both prognosis and management of the diabetes; therefore, practicing clinicians are challenged by the complex management of such cases. Gastroparesis is a disorder characterized by a delay in gastric emptying after a meal in the absence of a mechanical gastric outlet obstruction. This article is an evidence-based overview of current management strategies for diabetic gastroparesis. The cardinal symptoms of diabetic gastroparesis are nausea and vomiting. Gastroesophageal scintiscanning at 15-minute intervals for 4 hours after food intake is considered the gold standard for measuring gastric emptying. Retention of more than 10% of the meal after 4 hours is considered an abnormal result, for which a multidisciplinary management approach is required. Treatment should be tailored according to the severity of gastroparesis, and 25% to 68% of symptoms are controlled by prokinetic agents. Commonly prescribed prokinetics include metoclopramide, domperidone, and erythromycin. In addition, gastric electrical stimulation has been shown to improve symptoms, reduce hospitalizations, reduce the need for nutritional support, and improve quality of life in several open-label studies.


Microfluidics-Based Sensing of Biospecies.
Over the past decades, microfluidic devices based on many advanced techniques have aroused widespread attention in the fields of chemical, biological, and analytical applications. Integration of microdevices with a variety of chip designs will facilitate promising functionality. Notably, the combination of microfluidics with functional nanomaterials may provide creative ideas to achieve rapid and sensitive detection of various biospecies. In this review, focused on the microfluids and microdevices in terms of their fabrication, integration, and functions, we summarize the up-to-date developments in microfluidics-based analysis of biospecies, where biomarkers, small molecules, cells, and pathogens as representative biospecies have been explored in-depth. The promising applications of microfluidic biosensors including clinical diagnosis, food safety control, and environmental monitoring are also discussed. This review aims to highlight the importance of microfluidics-based biosensors in achieving high throughput, highly sensitive, and low-cost analysis and to promote microfluidics toward a wider range of applications.


[Lipid droplets and their possible pathways of origin in rat pituicytes].
Callan's hypothesis of the constant movement of the chromomere DNA axis was checked with the method of 3H-uridine radioautography. The hypothesis was not corroborated as the RNA synthesis proceeded in chromomeres of lampbrush chromosomes on the stationary axis with formation of transcriptional units. Data on localization and count of transcriptional units are discussed with regard to structural and functional organization of chromomere in meiotic chromosomes of eukaryotes.


Tempering the tension between science and intuition.
Scientific ideas can be difficult to access if they contradict earlier-developed intuitive theories; counterintuitive scientific statements like "bubbles have weight" are verified more slowly and less accurately than closely-matched intuitive statements like "bricks have weight" (Shtulman & Valcarcel, 2012). Here, we investigate how context and instruction influences this conflict. In Study 1, college undergraduates (n = 100) verified scientific statements interspersed with images intended to prime either a scientific interpretation of the statements or an intuitive one. Participants primed with scientific images verified counterintuitive statements more accurately, but no more quickly, than those primed with intuitive images. In Study 2, college undergraduates (n = 138) received instruction that affirmed the scientific aspects of the target domain and refuted common misconceptions. Instruction increased the accuracy of participants' responses to counterintuitive statements but not the speed of their responses. Collectively, these findings indicate that scientific interpretations of a domain can be prioritized over intuitive ones but the conflict between science and intuition cannot be eliminated altogether.


Evaluation of novel AI-based extended field-of-view CT reconstructions.
Modern computed tomography (CT) scanners have an extended field-of-view (eFoV) for reconstructing images up to the bore size, which is relevant for patients with higher BMI or non-isocentric positioning due to fixation devices. However, the accuracy of the image reconstruction in eFoV is not well known since truncated data are used. This study introduces a new deep learning-based algorithm for extended field-of-view reconstruction and evaluates the accuracy of the eFoV reconstruction focusing on aspects relevant for radiotherapy. A life-size three-dimensional (3D) printed thorax phantom, based on a patient CT for which eFoV was necessary, was manufactured and used as reference. The phantom has holes allowing the placement of tissue mimicking inserts used to evaluate the Hounsfield unit (HU) accuracy. CT images of the phantom were acquired using different configurations aiming to evaluate geometric and HU accuracy in the eFoV. Image reconstruction was performed using a state-of-the-art reconstruction algorithm (HDFoV), commercially available, and the novel deep learning-based approach (HDeepFoV). Five patient cases were selected to evaluate the performance of both algorithms on patient data. There is no ground truth for patients so the reconstructions were qualitatively evaluated by five physicians and five medical physicists. The phantom geometry reconstructed with HDFoV showed boundary deviations from 1.0 to 2.5 cm depending on the volume of the phantom outside the regular scan field of view. HDeepFoV showed a superior performance regardless of the volume of the phantom within eFOV with a maximum boundary deviation below 1.0 cm. The maximum HU (absolute) difference for soft issue inserts is below 79 and 41 HU for HDFoV and HDeepFoV, respectively. HDeepFoV has a maximum deviation of -18 HU for an inhaled lung insert while HDFoV reached a 229 HU difference. The qualitative evaluation of patient cases shows that the novel deep learning approach produces images that look more realistic and have fewer artifacts. To be able to reconstruct images outside the sFoV of the CT scanner there is no alternative than to use some kind of extrapolated data. In our study, we proposed and investigated a new deep learning-based algorithm and compared it to a commercial solution for eFoV reconstruction. The deep learning-based algorithm showed superior performance in quantitative evaluations based on phantom data and in qualitative assessments of patient data.


Fast and Adaptive Construction of Gyral Morphological Networks Based on Morphometric Features of Cortical Surface.
The organization of cortical folding patterns are related to brain function, cognition and behaviors. Due to the enormous complexity and high inter-subject variability in cortical morphology, it has been a challenging task to effectively and efficiently quantify the gyrification patterns of cerebral cortex. To tackle these issues, the gyral net approach used a graph-based representation of cortical architecture by segmenting the gyral crests from the cortical meshes based on its morphological metrics. However, current morphology-based approaches are very time-consuming and not applicable for large-scale dataset. In this study, we develop a fast and adaptive method to automatically construct the gyral morphological graph within 10 seconds. Our method is robust to low contrast conditions and more computationally efficient, approximately 5 times faster than classical approaches. We evaluated the proposed method on 1081 young adults acquired from the HCP dataset and uncovered significant differences among functional brain networks from the perspective of morphological networks.


Real-time pixelwise phasor analysis for video-rate two-photon fluorescence lifetime imaging microscopy.
Two-photon fluorescence lifetime imaging microscopy (FLIM) is a widely used technique in biomedical optical imaging. Presently, many two-photon time-domain FLIM setups are limited by long acquisition and postprocessing times that decrease data throughput and inhibit the ability to image fast sub-second processes. Here, we present a versatile two-photon FLIM setup capable of video-rate (up to 25 fps) imaging with graphics processing unit (GPU)-accelerated pixelwise phasor analysis displayed and saved simultaneously with acquisition. The system uses an analog output photomultiplier tube in conjunction with 12-bit digitization at 3.2 GHz to overcome the limited maximum acceptable photon rate associated with the photon counting electronics in many FLIM systems. This allows for higher throughput FLIM acquisition and analysis, and additionally enables the user to assess sample fluorescence lifetime in real-time. We further explore the capabilities of the system to examine the kinetics of Rhodamine B uptake by human breast cancer cells and characterize the effect of pixel dwell time on the reduced nicotinamide adenine dinucleotide and reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) autofluorescence lifetime estimation accuracy.


Evaluation of Auditory Brainstem Response (ABR) in Vitamin B12 Deficiency.
Changes in the central nervous system are observed due to vitamin B12 deficiency. The purpose of this study is to assess the effects of vitamin B12 deficiency on the central auditory tracks utilizing ABR. 30 individuals (16 females, 14 males) with vitamin B12 deficiency and 30 individuals (17 females, 13 males) without any hearing problem and B12 deficiency have participated in the study. The ages of the individuals with vitamin B12 deficiency varied between 18 and 39, with a mean of 28±5.6, The ages of the individuals with normal hearing in the control group were between 18 and 42, with a mean of 30±6.2. The I, III and V. wave latencies and I-III, I-V and III-V inter-wave latencies and amplitudes of the participants with vitamin B12 deficiency and with normal hearing were evaluated using click stimulus. No statistically significant change was observed between the group with vitamin B12 deficiency and the normal group in the I, III and V. wave latencies and the I-III, I-V and III-V inter-latency values and amplitudes. Although vitamin B12 deficiency effects the central nervous system, normal latencies and amplitudes were obtained in the ABR test. It was especially observed that the brainstem region, where the I, III ve V. Waves originate, is not effected by vitamin B12 deficiency.


[Weight status and cardiorespiratory fitness in school students in the central region of Peru].
To determine the frequency of overweight and obesity in relation to cardiorespiratory fitness (CRF) levels in school students in 4 districts of the central region of Peru, and to analyze the relations among these variables. Weight, height and CRF were evaluated in 7841 school students who reside in four districts located on the coast, in the highlands and in the jungle of the central region of the country. Overweight and obesity were classified according to the criteria proposed by Cole. CRF was evaluated by a 12-minute run/walk test taken from the American Alliance for Health, Physical Education, Recreation and Dance's test battery. ANOVA and logistic regression were used to examine the differences of the averages and the associations among these variables. Both male and female school students have similar frequency of overweight and obesity (20.9% in women and 20.1% in men). Residents of the coast (Barranco) presen thigh frequency of overweight and obesity (37.8%). Age, sex, geographical area and CRF were significant predictors of overweight and obesity. School students who live in Barranco are five times more likely to be obese (OR=4.67; CI95%: 3.55-6.14), while those who reside in the highlands (Junin) are less likely to be obese (OR=0.03; CI95%: 0.01-0.20). Furthermore, in contrast with students with high CRF, those with low CRF are more likely to be obese (OR=11.82; CI95%: 7.25-19.27). There was a high frequency of overweight and obesity among school students who reside in Barranco. Low CRF is associated with overweight and obesity.


Cytokine Changes in Maternal Peripheral Blood Correlate With Time-to-Delivery in Pregnancies Complicated by Premature Prelabor Rupture of the Membranes.
Premature prelabor rupture of the membranes (PPROM) causes one-third of preterm births worldwide and is most likely caused by subclinical intrauterine infection and/or inflammation. We proposed that women with systemic inflammation at the time of PPROM would have shorter latency. Peripheral blood samples were collected from 20 singleton pregnant women with PPROM between 23 ± 1 and 33 ± 6 weeks. The first sample was drawn within 48 hours of admission, followed by weekly blood draws until delivery. Pregnancies complicated with acute chorioamnionitis, preeclampsia, intrauterine growth restriction, obesity, substance abuse, and chronic maternal disease were excluded. Twenty uncomplicated, gestational age-matched pregnancies served as controls. Plasma concentration of 39 cytokines was measured longitudinally using Luminex assays to investigate their value as predictive biomarkers of latency. Women with PPROM exhibited significantly lower plasma concentration of interferon-γ-inducible protein 10-Chemokine (c-x-c motif; IP10/CXCL10), Chemokine (c-x-c motif) Ligand 9 (MIG/CXCL9), Platelet-derived growth factor BB (PDGFbb), and cutaneous T cell-attracting chemokine, also known as CCL27/CCL27 than controls at admission but significantly elevated interleukin (IL)1RA, tumor necrosis factor α, monocyte chemotactic protein-1/CCL2 at delivery compared to admission. Women with PPROM who delivered within 7 days had significantly lower plasma concentration of anti-inflammatory cytokine IL1RA than those with latency periods >7 days. The IL1RA and endotoxin activity in conjunction with clinical parameters results in excellent prediction of latency to delivery (area under the receiver-operating characteristic curve = 0.91). We concluded that higher levels of anti-inflammatory cytokines in women with PPROM were associated with increased latency until delivery, likely due to counterbalancing of proinflammatory load. When used in conjunction with other predictive characteristics of time until delivery, cytokines may further assist clinical decision-making and optimize pregnancy outcomes in women with PPROM.


Tackling smoking among out of school youth in South Africa: An analysis of friendship ties.
Friendships during adolescence play a significant role in the initiation and maintenance of tobacco use. Smoking behaviour among adolescent friends has not been explored among out of school youth (OSY) in South Africa. Out of school youth (OSY), described as those between 13 and 20 years old, have not completed their schooling and are not currently enrolled in school, are at greater risk for tobacco use. The main aim of this study is to examine whether the smoking behaviour of OSY is associated with that of their OSY friends. Respondent driven sampling was used to recruit OSY and their OSY friends. A mixed effects logistic regression with a random intercept across school-province combinations was used to analyse survey data. Race and gender were also incorporated into the analyses as effect moderators (n = 391). Results of this study confirm that cigarette smoking was common among OSY and their OSY friends, with 53.5% of the respondents smoking in the past month (SD = 0.44). When OSY friends were either all non-smokers or half their friends were non-smokers, Coloured (mixed race) OSY were less likely to smoke compared to Black African and Other (mostly Asian descent) OSY. Cultural norms and values associated with the different race groups may play a role in the smoking behaviour of out of school youth friends. Understanding this relationship is useful for identifying those OSY that are vulnerable to the behaviours that place them at risk of tobacco related morbidity and mortality.


Establishment, present condition, and developmental direction of the new Korean healthcare accreditation system.
On July 23rd, 2010 a revised medical law (Article 58) was passed to change existing evaluation system of medical institutions to an accreditation system. The new healthcare accreditation system was introduced to encourage medical institutions to work voluntarily and continuously to improve patient safety and medical service quality. Changes regarding the healthcare accreditation system included the establishment of an accreditation agency, the voluntary participation of medical institutions, accreditation standards centering on the treatment process and patient safety, tracing methodology, and the announcement of comprehensive results concerning accreditation. Despite varying views on the healthcare accreditation system, including some that are critical, it is meaningful that the voluntary nature of the system acknowledges that the medical institutions must be active agents in improving medical service quality. Healthcare quality is not improved instantaneously, but instead gradually through continuous communication within the clinical field. For this accreditation system to be successful, followings are essential: the accreditation agency becomes financially independent and is managed efficiently, the autonomy and regulation surrounding the system are balanced, the professionalism of the system is ensured, and the medical field plays an active role in the operation of the system.


Synchronous resections of primary colorectal tumor and liver metastasis by laparoscopic approach.
Liver metastasis of colorectal cancer is common. Resection of solitary tumors of primary and metastatic colorectal cancer can have a favorable outcome. Open resection of primary colorectal tumor and liver metastasis in one operation or in separate operations is currently common practice. Reports have shown that synchronous resections do not jeopardize short or long-term surgical outcomes and that this is a safe and effective approach in open surgery. The development of laparoscopic colorectal surgery and laparoscopic hepatectomy has made a minimally invasive surgical approach to treating colorectal cancer with liver metastasis feasible. Synchronous resections of primary colorectal tumor and liver metastasis by laparoscopy have recently been reported. The efficacy and safety of laparoscopic colorectal resection and laparoscopic hepatectomy have been proven separately but synchronous resections by laparoscopy are in hot debate. As it has been shown that open resection of primary colorectal tumor and liver metastasis in one operation results in an equally good short-term outcome when compared with that done in separate operations, laparoscopic resection of the same in one single operation seems to be a good option. Recent evidence has shown that this new approach is a safe alternative with a shorter hospital stay. Large scale randomized controlled trials are needed to demonstrate the effectiveness of this minimally invasive approach.


Spatial transcriptional mapping of the human nephrogenic program.
Congenital abnormalities of the kidney and urinary tract are among the most common birth defects, affecting 3% of newborns. The human kidney forms around a million nephrons from a pool of nephron progenitors over a 30-week period of development. To establish a framework for human nephrogenesis, we spatially resolved a stereotypical process by which equipotent nephron progenitors generate a nephron anlage, then applied data-driven approaches to construct three-dimensional protein maps on anatomical models of the nephrogenic program. Single-cell RNA sequencing identified progenitor states, which were spatially mapped to the nephron anatomy, enabling the generation of functional gene networks predicting interactions within and between nephron cell types. Network mining identified known developmental disease genes and predicted targets of interest. The spatially resolved nephrogenic program made available through the Human Nephrogenesis Atlas (https://sckidney.flatironinstitute.org/) will facilitate an understanding of kidney development and disease and enhance efforts to generate new kidney structures.


Management and therapy of vasovagal syncope: A review.
Vasovagal syncope is a common cause of recurrent syncope. Clinically, these episodes may present as an isolated event with an identifiable trigger, or manifest as a cluster of recurrent episodes warranting intensive evaluation. The mechanism of vasovagal syncope is incompletely understood. Diagnostic tools such as implantable loop recorders may facilitate the identification of patients with arrhythmia mimicking benign vasovagal syncope. This review focuses on the management of vasovagal syncope and discusses the non-pharmacological and pharmacological treatment options, especially the use of midodrine and selective serotonin reuptake inhibitors. The role of cardiac pacing may be meaningful for a subgroup of patients who manifest severe bradycardia or asystole but this still remains controversial.


Subunit vaccines: distearoylphosphatidylcholine-based liposomes entrapping antigen offer a neutral alternative to dimethyldioctadecylammonium-based cationic liposomes as an adjuvant delivery system.
The adjuvanticity of liposomes can be directed through formulation to develop a safe yet potent vaccine candidate. With the addition of the cationic lipid dimethyldioctadecylammonium bromide (DDA) to stable neutral distearoylphosphatidylcholine (DSPC):cholesterol (Chol) liposomes, vesicle size reduces while protein entrapment increases. The addition of the immunomodulator, trehalose 6,6-dibehenate (TDB) to either the neutral or cationic liposomes did not affect the physiochemical characteristics of these liposome vesicles. However, the protective immune response, as indicated by the amount of IFN-γ production, increases considerably when TDB is present. High levels of IFN-γ were observed for cationic liposomes; however, there was a marked reduction in IFN-γ release over time. Conversely, for neutral liposomes containing TDB, although the initial amount of IFN-γ was slightly lower than the cationic equivalent, the overall protective immune responses of these neutral liposomes were effectively maintained over time, generating good levels of protection. To that end, although the addition of DSPC and Chol reduced the protective immunity of DDA:TDB liposomes, relatively high protection was observed for the neutral counterpart, DSPC:Chol:TDB, which may offer an effective neutral alternative to the DDA:TDB cationic system, especially for the delivery of either zwitterionic (neutral) or cationic molecules or antigens.


Cell-Laden and Cell-Free Matrix-Induced Chondrogenesis versus Microfracture for the Treatment of Articular Cartilage Defects: A Histological and Biomechanical Study in Sheep.
The aim of this study was to evaluate the regenerative potential of cell-laden and cell-free collagen matrices in comparison to microfracture treatment applied to full-thickness chondral defects in an ovine model. Animals (n = 30) were randomized into 5 treatment groups, and 7-mm full-cartilage-thickness defects were set at the trochlea and medial condyle of both knee joints and treated as follows: 2 scaffolds in comparison (collagen I/III, Chondro-Gide(®); collagen II, Chondrocell(®)) for covering microfractured defects (autologous matrix-induced chondrogenesis), both scaffolds colonized in vitro with autologous chondrocytes (matrix-associated chondrocyte transplantation), or scaffold-free microfracture technique. One year after surgery, cartilage lesions were biomechanically (indentation test), histologically (O'Driscoll score), and immunohistochemically (collagen type I and II staining) evaluated. All treatment groups of the animal model induced more repair tissue and showed better histological scores and biomechanical properties compared to controls. The average thickness of the repair tissue was significantly greater when a scaffold was used, especially the collagen I/III membrane. However, none of the index procedures surpassed the others from a biomechanical point of view or based on the histological scoring. Collagen type II expression was better in condylar defects compared to the trochlea, especially in those treated with collagen I/III membranes. Covering of defects with suitable matrices promotes repair tissue formation and is suggested to be a promising treatment option for cartilage defects. However, it failed to improve the biomechanical and histological properties of regenerated articular cartilage compared to microfracture alone in an ovine model under the given circumstances.


Molecular Docking and In Vivo Biological Studies of Sodium Salt of 3-(4-Methyl-2-oxo-2-H-quinoline-7-yloxy)-3-phenylacrylic Acid As Anticancer Agent.
Quinoline derivatives possess several therapeutic properties. Aim: studying the anticancer effect of 3-(4-methyl-2-oxo-2-H-quinoline-7-yloxy)-3-phenylacrylic acid's sodium solution on the Ehrlich ascites carcinoma (EAC). Median lethal dose (LD50) and dose response curve was determined for sodium salt solution of 3-(4-methyl-2-oxo-2-H-quinoline-7-yloxy)-3-phenylacrylic acid, then diving a group of one hundred Swiss albino mice, which are all females, into five groups: group 1: (negative control) where intraperitoneally injected with saline into mice for 10 successive days; group 2 (positive control), also namely (EAC-bearing group): where the EAC cells were intraperitoneally injected into mice (2.5 × 106 cells/mouse) only one time on the first day; group 3 which is defined as the (therapeutic group) where the Na+ salt of the synthetic compound was injected into the peritoneum of the mice (2.5 mg/kg) the very first day after the injection of the EAC, then the compound was injected every two days for a period of 10 days; group 4 which is the (preventive group) where the sodium salt of the synthetic compound (2.5 mg/kg) was injected in the peritoneum of the mice the day before the injection of the EAC, then the compound was successively injected every day for a period of ten days; and group 5 which is the (drug group) in which mice were repeatedly injected) in their peritoneum with the sodium salt of the synthetic compound (2.5 mg/kg on a daily basis over a period of ten days. On the eleventh day of the trial, EAC cells were harvested from each mouse in a heparinized saline, in addition to blood samples, liver and kidney tissues which are also collected. Molecular docking showed that compound's sodium salt was docked into (PDB: 2R7G) and (PDB: 2R3I), which are the retinoblastoma protein receptor and the cyclin D-1 receptor respectively. Compared to those in the positive control group, mice in both the therapeutic and preventive groups, has shown a significant decrease in MDA, cyclin D-1 levels in the tissues of both liver and kidney tissues, in addition to the serum ALT, AST, CK-MB, and LDH activities, and the serum urea and creatinine concentration. However, mice in the formerly mentioned groups, both therapeutic and preventive groups, have shown an increase in the serum albumin, total protein, retinoblastoma protein in both liver and kidney tissues as well as the total antioxidant capacity, when compared to mice in the positive control group. It is worth mentioning that histopathological findings have confirmed that. Sodium salt of 3-(4-methyl-2-oxo-2H-quinoline-7-yloxy)-3-phenylacrylic acid showed potential in vivo anticancer and antioxidant effects against Ehrlich ascites carcinoma cells; (EAC cells).


Effect of agitation speed and aeration rate on fructosyltransferase production of Aspergillus oryzae IPT-301 in stirred tank bioreactor.
Fructooligosaccharides (FOS) are prebiotic substances that have been extensively incorporated in different products of food industry mostly for their bifidogenic properties and economic value. The main commercial FOS production comes from the biotransformation of sucrose and intracellular and extracellular microbial enzymes-fructosyltransferases (FTase). Aspergillus oryzae IPT-301 produces FTase. In order to increase its production, this study focuses on evaluating the effects of different agitation speed and aeration rates which affect yields in a stirred tank bioreactor. Agitation had more influence on cell growth than aeration. The maximum intracellular FTase activity and the volumetric productivity of total intracellular FTase were obtained at 800 rpm and 0.75 vvm, and reached values of 2100 U g-1 and 667 U dm-3 h-1, respectively. The agitation speed had a strong influence on the activity of extracellular FTase produced which reached the maximum amount of 53 U cm-3. The higher value of total activity obtained was 22,831 U dm-3 at 0.75 vvm and 800 rpm. Aeration rates and agitation speed showed strong influence upon the growth and production of fructosyltransferase from Aspergillus oryzae IPT-301 in media containing sucrose as carbon source. The control of aeration rate and agitation speed can be a valuable fermentation strategy to improve enzyme production.


Relational factors and family treatment engagement among low-income, HIV-positive African American mothers.
Clinically derived hypotheses regarding treatment engagement of families of low-income, HIV-positive, African American mothers are tested using univariate and multivariate logistic regression models. Predictors are baseline family relational factors (family support, mother's desire for involvement with family, and family hassles) and mother's history of substance dependence. The study examines a subsample of 49 mothers enrolled in a clinical trial testing the efficacy of Structural Ecosystems Therapy (SET). SET is a family-based intervention intended to relieve and prevent psychosocial distress associated with HIV/AIDS. Participants in the subsample were randomly assigned to SET and attended at least two therapy sessions. Findings reveal that family relational factors predicted family treatment engagement (family support, p < .004; mother's desire for involvement with family, p < .008; family hassles, p < .027). Family support predicted family treatment engagement beyond the prediction provided by the other relational factors and the mother's own treatment engagement (p < .016). History of substance dependence was neither associated with family treatment engagement nor family support. Post hoc analyses revealed that family hassles (p < .003) and mother's desire for involvement with family (p < .018) were differentially related to family treatment engagement in low- versus high-support families. Implications for clinical practice and future research are discussed.


Three-year major clinical outcomes of phosphorylcholine polymer- vs biolinx polymer-zotarolimus-eluting stents: A propensity score matching study.
There are limited long-term outcome data comparing BioLinx polymer (B)-zotarolimus-eluting stents (ZES) with phosphorylcholine polymer (P)-ZES. The aim of this study was to compare the efficacy and safety of B-ZES with P-ZES in patients who underwent percutaneous coronary intervention (PCI) during a 3-year follow-up period.One thousand two hundred fifty four patients who underwent PCI with P-ZES (Endeavor [ZES-E] or Endeavor sprint [ZES-S], n = 356) or B-ZES (Endeavor resolute [ZES-R] or Resolute Integrity [ZES-I], n = 889) were enrolled. The primary endpoint was major adverse cardiac events (MACE); the composite of total death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), non-target vessel revascularization (Non-TVR), and the secondary endpoint was stent thrombosis (ST).After PSM, 2 propensity-matched (PSM) groups (275 pairs, n = 550, C-statistic = 0.730) were generated. During the 3-year follow-up period, the cumulative incidence of MACE (hazard ratio [HR], 1.525; 95% confidence interval [CI], 0.920-2.526; P = .101) and ST (HR, 1.248; 95% CI, 0.335-4.4649; P = .741) were similar between P-ZES and B-ZES after PSM. However, TLR rate was significantly higher in ZES-S than ZES-I (11.3% vs 3.8%, log rank P = .029) and TVR rate was higher in ZES-S than ZES-R (14.1% vs 4.8%, log rank P = .025).In this single-center, all-comer registry, despite different polymers, P-ZES, and B-ZES showed comparable safety and efficacy during a 3-year follow-up period after PCI.


Synthesis and characterization of thermosensitive and pH-sensitive poly (N-isopropylacrylamide-acrylamide-vinylpyrrolidone) for use in controlled release of naltrexone.
In this article N-isopropylacrylamide (NIPAAm)-acrylamide (AAm)-vinyl pyrrolidone (VP) terpolymers were prepared using free radical copolymerization method by varying feed ratios of monomers. The composition ratio and structure of polymer were determined by NMR and FTIR. The glass transition temperature was examined by DSC. The thermo-responsive behaviors of polymeric solutions were investigated by turbidimetry using UV-Visible spectroscopy. The sol-gel transition of the polymer solutions occurred reversibly within 1 min in response to the temperature. By alternating the monomer feed ratio, the synthesized terpolymers had their own distinctive lower critical solution temperature (LCST). In addition to the thermosensitivity, the terpolymers also showed a response to pH changes. The increase in ionic strength of the buffer solution with addition of salt lowered the LCST of the polymers. The ability to shift the phase transition temperature of the terpolymers provided excellent flexibility in tailoring transitions for specific uses. Swelling experiments were performed on the terpolymer disks in buffer solutions with different pH and ionic strength at varying temperature. We investigated naltrexone release as a model drug in phosphate buffer. Drug loading efficiency was varying from 8.75 to 55%. Gel composition, pH, and ionic concentration affected the drug loading. Finally in vitro drug release studies at 36-37 degrees C indicating 35-70% naltrexone release from terpolymers at the end of 30 days. In addition, these gels sustained naltrexone release for 30 days.


Analysis of multiple compound-protein interactions reveals novel bioactive molecules.
The discovery of novel bioactive molecules advances our systems-level understanding of biological processes and is crucial for innovation in drug development. For this purpose, the emerging field of chemical genomics is currently focused on accumulating large assay data sets describing compound-protein interactions (CPIs). Although new target proteins for known drugs have recently been identified through mining of CPI databases, using these resources to identify novel ligands remains unexplored. Herein, we demonstrate that machine learning of multiple CPIs can not only assess drug polypharmacology but can also efficiently identify novel bioactive scaffold-hopping compounds. Through a machine-learning technique that uses multiple CPIs, we have successfully identified novel lead compounds for two pharmaceutically important protein families, G-protein-coupled receptors and protein kinases. These novel compounds were not identified by existing computational ligand-screening methods in comparative studies. The results of this study indicate that data derived from chemical genomics can be highly useful for exploring chemical space, and this systems biology perspective could accelerate drug discovery processes.


X-ray dosimetry and contact microradiography with color film.
The effect of x-rays at various voltages and intensities, with monochromatic and polychromatic beams, on Ektachrome daylight and artificial-light film was investigated. The colors were rated according to the Munsell color system and ranged over all the spectrum except red. The color in terms of hue, value, saturation, and chroma was a function of wavelength as well as intensity, and thus the method may be useful in dosimetry as well as in radiography. Microradiographs of metals and wood were remarkable in showing detail not obtainable with conventional black-and-white photographic emulsions.


Provider management of menopause after the findings of the Women's Health Initiative.
A survey was conducted to determine current provider behaviors and concerns related to menopause management. All gynecology, internal medicine, and family medicine providers (both physicians and nurse practitioners) within a large Midwestern integrated health system were surveyed about current approaches to menopause management, frequency and reasons for hormone therapy (HT) use, approaches to HT discontinuation, treatments for symptom control, bone mineral density testing, and concerns related to menopause management. Descriptive statistics and chi-square tests were performed to examine frequencies and differences based on gender, specialty, and years in practice. Overall the response rate was 58% with providers from owned clinics, with female providers being the most likely to respond (P < 0.001). Changes in menopause management included using lower dose hormones (74%), encouraging use for shorter time periods (73%), and using different modes of delivery (21%). Most providers (89%) initiate HT use in symptomatic patients, and only 12% initiate use to prevent symptoms. Patients were most likely to discuss HT with gynecologists (78% gynecologists vs 64% family medicine providers and 48% internal medicine providers, P = 0.015). Nearly two thirds of providers (64%) claimed to order bone mineral density testing frequently. Providers' concerns related to information on symptom management, alternative and over-the-counter medications, the risk/benefits of medications, patients' sexual concerns, and maintaining bone health. We found that providers were responsive to current literature, shifting the agents and dosages they prescribe. Still they are faced with women reporting symptoms that interfere with their ability to function optimally and must continue to help women maintain healthy bones.


Environmental impact assessment of converting flexible packaging plastic waste to pyrolysis oil and multi-walled carbon nanotubes.
A solution to low recycling rates of plastic waste is the conversion into multi-walled carbon nanotubes (MWCNTs) that have high value and can create additional revenue for plant operators. The purpose of this study was to perform a life cycle assessment (LCA) of an integrated system that involves flexible packaging plastic waste (FPPW) pyrolysis, oil upgrading, and MWCNTs production. The objectives were to determine the environmental impact of MWCNTs synthesis from non-condensable pyrolysis gases, and to assess the environmental impact of MWCNTs synthesis from different plastic fractions. Integrating MWCNTs synthesis to the plastic pyrolysis process provides various environmental benefits including, reduction of contribution towards climate change, fossil depletion, human toxicity (cancer), and ionizing radiation potentials. Sensitivity analysis of MWCNTs yields provided the range of impacts on the environment and a critical yield of >2% for most impact categories was determined. Comparison of different plastic fractions indicated that using low PET content feedstock had lesser impact on the environment, and demonstrated comparable performance to mixed virgin plastics for most impact categories. The results highlighted the versatility of the integrated pyrolysis process for treating diverse plastic waste fractions with negligible effects from the impurities present in the actual FPPW during thermal processing.


The dynamic impact of CpG methylation in DNA.
Solid-state deuterium NMR is used to investigate perturbations of the local, internal dynamics in the EcoRI restriction binding site, -GAATTC- induced by cytidine methylation. Methylation of the cytidine base in this sequence is known to suppress hydrolysis by the EcoRI restriction enzyme. Previous solid-state deuterium NMR studies have detected large amplitude motions of the phosphate-sugar backbone at the AT-CG junction of the unmethylated DNA sequence. This study shows that methylation of the cytidine base in a CpG dinucleotide reduces the amplitudes of motions of the phosphate-sugar backbone. These observations suggest a direct link between suppression of the amplitudes of localized, internal motions of the sugar-phosphate backbone of the DNA and inhibition of restriction enzyme cleavage.


Conserved negative charges in the transmembrane segments of subunit K of the NADH:ubiquinone oxidoreductase determine its dependence on YidC for membrane insertion.
All members of the Oxa1/Alb3/YidC family have been implicated in the biogenesis of respiratory and energy transducing proteins. In Escherichia coli, YidC functions together with and independently of the Sec system. Although the range of proteins shown to be dependent on YidC continues to increase, the exact role of YidC in insertion remains enigmatic. Here we show that YidC is essential for the insertion of subunit K of the NADH:ubiquinone oxidoreductase and that the dependence is due to the presence of two conserved glutamate residues in the transmembrane segments of subunit K. The results suggest a model in which YidC serves as a membrane chaperone for the insertion of the less hydrophobic, negatively charged transmembrane segments of NuoK.


The better of two evils? Evidence that children exhibiting continuous conduct problems high or low on callous-unemotional traits score on opposite directions on physiological and behavioral measures of fear.
The present study examines whether heterogeneous groups of children identified based on their longitudinal scores on conduct problems (CP) and callous-unemotional (CU) traits differ on physiological and behavioral measures of fear. Specifically, it aims to test the hypothesis that children with high/stable CP differentiated on CU traits score on opposite directions on a fear-fearless continuum. Seventy-three participants (M age = 11.21; 45.2% female) were selected from a sample of 1,200 children. Children and their parents completed a battery of questionnaires assessing fearfulness, sensitivity to punishment, and behavioral inhibition. Children also participated in an experiment assessing their startle reactivity to fearful mental imagery, a well-established index of defensive motivation. The pattern of results verifies the hypothesis that fearlessness, assessed with physiological and behavioral measures, is a core characteristic of children high on both CP and CU traits (i.e., receiving the DSM-5 specifier of limited prosocial emotions). To the contrary, children with high/stable CP and low CU traits demonstrated high responsiveness to fear, high behavioral inhibition, and high sensitivity to punishment. The study is in accord with the principle of equifinality, in that different developmental mechanisms (i.e., extremes of high and low fear) may have the same behavioral outcome manifested as phenotypic antisocial behavior.


Transcriptomic analyses of rats exposed to chronic mild stress: Modulation by chronic treatment with the antipsychotic drug lurasidone.
Exposure to stressful experiences accounts for almost half of the risk for mental disorders. Hence, stress-induced alterations represent a key target for pharmacological interventions aimed at restoring brain function in affected individuals. We have previously demonstrated that lurasidone, a multi-receptor antipsychotic drug approved for the treatment of schizophrenia and bipolar depression, can normalize the functional and molecular impairments induced by stress exposure, representing a valuable tool for the treatment of stress-induced mental illnesses. However, the mechanisms that may contribute to the therapeutic effects of lurasidone are still poorly understood. Here, we performed a transcriptomic analysis on the prefrontal cortex (PFC) of adult male rats exposed to the chronic mild stress (CMS) paradigm and we investigated the impact of chronic lurasidone treatment on such changes. We found that CMS exposure leads to an anhedonic phenotype associated with a down-regulation of different pathways associated to neuronal guidance and synaptic plasticity within the PFC. Interestingly, a significant part of these alterations (around 25%) were counteracted by lurasidone treatment. In summary, we provided new insights on the transcriptional changes relevant for the therapeutic intervention with lurasidone, which may ultimately promote resilience.


Does dispositional optimism moderate the relationship between role conflict and risk of disability retirement?
This study determines whether dispositional optimism moderates the relationship between role conflict and the risk of disability retirement. The study was based on a combination of self-report survey questionnaire data on role conflict and dispositional optimism with official register data on disability benefits from the Norwegian Labour and Welfare Administration. The sample comprised 14,501 Norwegian employees from various occupations and industries. Role conflict was significantly related to higher risk (HR 1.35, 95% CI 1.19-1.53), whereas optimism was associated with decreased risk (HR 0.75, 95% CI 0.64-0.88), of disability retirement. Optimism did not modify the effect on role conflict on disability retirement. Having an optimistic life orientation decreases the risk of disability retirement in general, but does not protect against the detrimental effects of role conflict at the workplace. As optimism is a malleable personality characteristic, organizations may benefit from interventions that help employees experience daily events more positively.


Improvement in survival of breast cancer patients - trends over two time periods in a single institution in an Asia Pacific country, Malaysia.
There is improvement in breast cancer survival in the developed world, but information on breast cancer survival trends in the Asia Pacific region is limited. The aim of the study was to evaluate survival trends and factors that affect survival in Malaysia. Two prospective groups of 423 and 965 newly diagnosed breast cancer patients in University of Malaya Medical Centre, Kuala Lumpur, Malaysia diagnosed in two time periods ie. 1993 to 1997 and in 1998 to 2002 were studied. Vital status was obtained from the National Registry of Births and Deaths. The overall survival was calculated from the date of diagnosis to the date of death from any cause. The survival differences between the two groups were analysed using the log-rank or Peto-Wilcoxon method. Survival estimates and independent prognostic factors were estimated by the Kaplan-Meier method and multivariate analysis using Cox proportional hazard models. P values less than 0.05 were considered statistically significant. Analyses were performed using SPlus 2000 Professional Release 2. Median follow-up for the two groups were 55 months (SD 29.2 months) in the first group and 52 months (SD 24.43) in the second group. There was improvement in 5-year observed survival from 58.4% (CI 0.54-0.63) to 75.7% (CI 0.73-0.79). The improvement in survival was significantly seen in all co-variates (p< 0.05) except for those aged 40 years and below (p= 0.27), tumour size 2 to 5 cm (p=0.11), grade 3 (p=0.32) and patients with Stage IV disease (p= 0.80). Stage of disease, lymph node (LN) involvement, size and grade were identified as independent prognostic factors in cohort one. For the second cohort; stage and LN involvement remained independent factors with the addition of ER status and ethnicity. There was improvement in 5-year observed survival. Besides known prognostic factors, Malay ethnicity was an independent prognostic factor.


Childhood trauma is associated with early-onset but not late-onset suicidal behavior in late-life depression.
To examine the relationship between childhood traumatic experiences and early and late-onset suicidal behavior among depressed older adults. Cross-sectional study. Inpatient and outpatient psychiatric services in Pennsylvania. Our sample included 224 adults aged 50+ (M ± SD = 62.5 ± 7.4) recruited into three depressed groups: (1) 84 suicide attempters, (2) 44 suicide ideators, and (3) 58 non-suicidal comparisons, and a non-psychiatric healthy comparison group (N = 38). The Childhood Trauma Questionnaire measured experiences of childhood trauma such as emotional abuse, physical abuse, emotional neglect, physical neglect, and sexual abuse. Attempters were separated into early- and late-onset based on age of first attempt using a statistical algorithm that identified a cutoff age of 30 years old. Overall, we found group differences in emotional and physical abuse and neglect in both genders and sexual abuse in females, but not in males. Early-onset attempters experienced more childhood emotional abuse and neglect than late-onset attempters and were more likely to have experienced multiple forms of abuse. They also experienced more emotional abuse and neglect than all comparison groups. Consistently, early-onset attempters more often met criteria for current or lifetime PTSD relative to late-onset attempters and most comparison groups. Late-onset attempters had similar levels of childhood trauma as other depressed groups. Our study reaffirms that there are distinct pathways to suicidal behavior in older adults based on their age of first suicide attempt and that trauma experienced in childhood has long-lasting emotional and behavioral consequences, even into late life.


Aperture size effects on backscatter intensity measurements in Earth and space remote sensing.
Most materials show a peaked intensity versus phase (light-source-target-detector angle) curve. For nonnegligible angular apertures of the source and/or the detector, the measured intensity at and near zero phase (backscatter) is lower than the real one. We derive an averaging aperture integral that represents this effect, and with it we invert measured intensity values to obtain the actual intensity curve. We also give a practical formula for estimating the magnitude of the aperture effect in zero-phase intensity measurements and show that only two such measurements made at different apertures are sufficient for deriving the real intensity. These corrections are needed in the comparison of measured reflectances in an increasing number of validation efforts for remote sensing applications requiring ground truth measurements.


The concentrations of adipokines in goat milk: relation to plasma levels, inflammatory status, milk quality and composition.
The main objectives of our study were to measure the major adipokines adiponectin, leptin and resistin in goat milk, to assess their interrelationships and to assess their relationships with the plasma and serum concentrations of total protein, cholesterol, total lipids, plasma C-reactive protein (CRP), milk somatic cell count (SCC), milk total aerobic colony and lactobacillus count, and milk components in lactating Saanen goats. The study was performed on eighteen lactating Saanen goats. Milk and blood samples were collected on days 20, 35, 50, 65 and 80 of lactation postpartum. The milk and plasma adiponectin levels on days 50, 65 and 80 postpartum were significantly higher than those on day 20. The milk and plasma leptin levels were lower on day 20 than on days 35, 50, 65 and 80. The milk concentrations of these major adipokines were positively intercorrelated. The milk and plasma concentrations of these three adipokines were also positively correlated. The plasma CRP concentrations correlated positively with milk leptin and resistin concentrations and inversely with milk adiponectin concentration. Milk adiponectin concentration was inversely related with its SCC. These data confirm that adiponectin, leptin and resistin are present in goat milk. The milk concentrations of these three adipokines were interrelated and interacted with the general inflammatory marker, CRP. The inverse relationship between milk adiponectin concentrations and its SCC suggests that variations in milk adiponectin might be involved in the udder health of lactating goats, but clinical trials are needed to support this hypothesis.


Defects in Li4Ti5O12 induced by carbon deposition: an analysis of unidentified bands in Raman spectra.
Lithium titanate (Li4Ti5O12, LTO) has already occupied its niche as an anode material for high-power and long-lifespan lithium batteries, but some novel directions for basic and applied research are still open. One of the most promising approaches in improving its properties, e.g., electronic conductivity and rate capability, is based on controllable defect engineering. The "defects" may be intentionally introduced into LTO via doping, surface modifications, and the synergy between them. However, the defects, which have significant effects to the electrical and electrochemical properties, are usually extremely dilute. Reliable material characterizations are essential and challenging, but the instrumental tools for revealing dilute defects are still insufficient. Herein, detailed analyses on the surface or subsurface defects of carbon-coated LTO were performed using various material characterization methods. Raman spectroscopy has been identified as a unique tool for the probing of structural defects.


Acoustic multipole sources for the lattice Boltzmann method.
By including an oscillating particle source term, acoustic multipole sources can be implemented in the lattice Boltzmann method. The effect of this source term on the macroscopic conservation equations is found using a Chapman-Enskog expansion. In a lattice with q particle velocities, the source term can be decomposed into q orthogonal multipoles. More complex sources may be formed by superposing these basic multipoles. Analytical solutions found from the macroscopic equations and an analytical lattice Boltzmann wavenumber are compared with inviscid multipole simulations, finding very good agreement except close to singularities in the analytical solutions. Unlike the BGK operator, the regularized collision operator is proven capable of accurately simulating two-dimensional acoustic generation and propagation at zero viscosity.


Ligand structure and mechanical properties of single-nanoparticle-thick membranes.
The high mechanical stiffness of single-nanoparticle-thick membranes is believed to result from the local structure of ligand coatings that mediate interactions between nanoparticles. These ligand structures are not directly observable experimentally. We use molecular dynamics simulations to observe variations in ligand structure and simultaneously measure variations in membrane mechanical properties. We have shown previously that ligand end group has a large impact on ligand structure and membrane mechanical properties. Here we introduce and apply quantitative molecular structure measures to these membranes and extend analysis to multiple nanoparticle core sizes and ligand lengths. Simulations of nanoparticle membranes with a nanoparticle core diameter of 4 or 6 nm, a ligand length of 11 or 17 methylenes, and either carboxyl (COOH) or methyl (CH(3)) ligand end groups are presented. In carboxyl-terminated ligand systems, structure and interactions are dominated by an end-to-end orientation of ligands. In methyl-terminated ligand systems large ordered ligand structures form, but nanoparticle interactions are dominated by disordered, partially interdigitated ligands. Core size and ligand length also affect both ligand arrangement within the membrane and the membrane's macroscopic mechanical response, but are secondary to the role of the ligand end group. Moreover, the particular end group (COOH or CH(3)) alters the nature of how ligand length, in turn, affects the membrane properties. The effect of core size does not depend on the ligand end group, with larger cores always leading to stiffer membranes. Asymmetry in the stress and ligand density is observed in membranes during preparation at a water-vapor interface, with the stress asymmetry persisting in all membranes after drying.


Innate immune and chemically triggered oxidative stress modifies translational fidelity.
Translational fidelity, essential for protein and cell function, requires accurate transfer RNA (tRNA) aminoacylation. Purified aminoacyl-tRNA synthetases exhibit a fidelity of one error per 10,000 to 100,000 couplings. The accuracy of tRNA aminoacylation in vivo is uncertain, however, and might be considerably lower. Here we show that in mammalian cells, approximately 1% of methionine (Met) residues used in protein synthesis are aminoacylated to non-methionyl-tRNAs. Remarkably, Met-misacylation increases up to tenfold upon exposing cells to live or non-infectious viruses, toll-like receptor ligands or chemically induced oxidative stress. Met is misacylated to specific non-methionyl-tRNA families, and these Met-misacylated tRNAs are used in translation. Met-misacylation is blocked by an inhibitor of cellular oxidases, implicating reactive oxygen species (ROS) as the misacylation trigger. Among six amino acids tested, tRNA misacylation occurs exclusively with Met. As Met residues are known to protect proteins against ROS-mediated damage, we propose that Met-misacylation functions adaptively to increase Met incorporation into proteins to protect cells against oxidative stress. In demonstrating an unexpected conditional aspect of decoding mRNA, our findings illustrate the importance of considering alternative iterations of the genetic code.


Positive association between cognitive ability and cortical thickness in a representative US sample of healthy 6 to 18 year-olds.
Neuroimaging studies, using various modalities, have evidenced a link between the general intelligence factor (g) and regional brain function and structure in several multimodal association areas. While in the last few years, developments in computational neuroanatomy have made possible the in vivo quantification of cortical thickness, the relationship between cortical thickness and psychometric intelligence has been little studied. Recently, cortical thickness estimations have been improved by the use of an iterative hemisphere-specific template registration algorithm which provides a better between-subject alignment of brain surfaces. Using this improvement, we aimed to further characterize brain regions where cortical thickness was associated with cognitive ability differences and to test the hypothesis that these regions are mostly located in multimodal association areas. We report associations between a general cognitive ability factor (as an estimate of g) derived from the four subtests of the Wechsler Abbreviated Scale of Intelligence and cortical thickness adjusted for age, gender, and scanner in a large sample of healthy children and adolescents (ages 6-18, N=216) representative of the US population. Significant positive associations were evidenced between the cognitive ability factor and cortical thickness in most multimodal association areas. Results are consistent with a distributed model of intelligence.


The present is not the key to the past: a polar forest from the permian of antarctica.
An in situ Upper Permian fossil forest in the central Transantarctic Mountains near the Beardmore Glacier includes 15 permineralized trunks in growth position; the paleolatitude of the site was approximately 80 degrees to 85 degrees south. Numerous leaves of the seed fern Glossopteris are present in the shale in which the trunks are rooted. The trunks are permineralized and tree rings reveal that the forest was a rapidly growing and young forest, persisting in an equable, strongly seasonal climate-a scenario that does not fit with some climate reconstructions for this time period.


Mating preferences, sexual selection and patterns of cladogenesis in ray-finned fishes.
Evolutionary theory predicts that sexual selection may increase taxonomic diversity when emergent mating preferences result in reproductive isolation and therefore speciation. This theory has been invoked to explain patterns of diversity in ray-finned fishes (most notably in the cichlids), but the theory has not been tested comparatively in fish. Additionally, several other unrelated factors have been identified as promoters of cladogenesis, so it is unclear how important sexual selection might be in diversification. Using sister-clade analysis, I tested the relationship between the presence of sexually selected traits and taxonomic diversification in actinopterygiian fishes, a large clade that shows substantial diversity in mating preferences and related sexually selected traits. In all identified sister-families that differed with regard to the proportion of species manifesting sexually selected traits, sexual selection was correlated with increased diversification, and this association was significant across all sister clades (P=0.02). This suggests that sexual selection, when present, is a substantial driver of diversification in the ray-finned fishes, and lends further empirical support to the theoretical link between mating preferences and accelerated cladogenesis.


Does the type of judgement required modulate cue competition?
According to the comparator process hypothesis (Matute, Arcediano, & Miller, 1996), cue competition in the learning of between-events relationships arises if the judgement required involves a comparison between the probability of the outcome given the target cue and the probability of the outcome given the competing cue. Alternatively, other associative accounts (the Rescorla-Wagner model: Rescorla & Wagner, 1972) conceive cue competition as a learning deficit affecting the target cue-outcome association. Consequently, the comparator process hypothesis predicts that cue competition occurs in inference judgements but not in contiguity ones, for only the first type of judgement implicitly involves such a comparison. On the other hand, the Rescorla-Wagner model predicts cue competition in both inference and contiguity judgements, because it establishes no relevant role for the type of judgement in producing cue competition. In Experiments 1 and 2 we manipulated the relative validity of cues and the type of question (inference vs. contiguity) in a predictive learning task. In both experiments we found a cue competition effect, but no interaction between the relative validity of cues and the type of question, suggesting that the Rescorla-Wagner theory suffices to explain cue competition.


Lateral diffusion of PDGF beta-receptors in human fibroblasts.
When platelet-derived growth factor (PDGF) binds to its receptors a number of biochemical reactions are elicited in the cell. Several models have been presented for the effects of ligand-induced receptor conformation and aggregation on signal transduction but little is known about the direct effects on receptor diffusion. This study concerns the lateral mobility of PDGF receptors in fibroblasts. It was assessed with fluorescence recovery after photobleaching (FRAP), using rhodaminated receptor antibodies or Fab-fragments of the antibody as ligands. The aims of the investigation were: (a) to compare the lateral mobility of membrane receptors of human fibroblasts labelled with either antibodies against the PDGF receptor or Fab-fragments of the same antibodies, and (b) to study the effects of serum or PDGF on the mobility of the receptors. Human foreskin fibroblasts (AG 1523) were grown on coverslips either under standard or under serum-free conditions yielding "normal" and "starved" cells, respectively. Two parameters of the diffusion were evaluated; the diffusion coefficient (D) and the mobile fraction (R) of the receptors. We found that normal fibroblasts had a smaller diffusion coefficient and a lower mobile fraction compared to starved cells using antibodies for receptor labelling. The addition of PDGF, just before the measurement, increased the D and R for normal cells, while starved cells, showing higher initial values, displayed slightly reduced values of D and R. After the addition of serum, D increased and R remained low for normal cells, whereas for starved cells both D and R increased to upper limits of 11.0 x 10(-10) cm2s-1 and greater than 90% respectively. In general, the D and R values, both in normal and starved cells, were higher for cells labelled with Fab-fragments than for antibody-labelled cells. The results are discussed in relation to the natural complexity of the receptor, and how PDGF, serum, antibodies and Fab-fragments might interfere with receptor structure, aggregation state and membrane diffusion characteristics.


[Use of complementary and alternative therapies in children with cancer].
Objective To determine the frequency, characteristics and related factors for the use of complementary and alternative therapies in pediatric patients with cancer in a Colombian pediatric oncology department. Cross-sectional study consisting of a survey of 398 caregivers of pediatrics patients with cancer evaluated in the Instituto Nacional de Cancerología in Bogotá, Colombia. The survey collected sociodemographic and clinical information and evaluated the type of complementary and alternative therapies, mechanisms of action, and patterns of use of these treatments. Logistic regression was conducted to identify predictors of complementary and alternative therapies use. Results In this study complementary therapies were used not as a substitute but in addition to conventional treatments to cure or to control the disease or to treat symptoms. A total of 326 patients (81.9 %, CI95 %: 77.8 % to 85.6 %) had received some type of complementary therapy and 81 different types of therapies were used. The most common type of complementary therapy corresponded to the group of biologically based therapies (mainly berry juices). Female family caregivers with higher educational status were more likely to use complementary therapies. Time from diagnosis and having received surgical treatment were also associated with the use of therapies. Reinforcement of the immune system appears to be the most likely mechanism of action. Conclusion A high prevalence of use of complementary therapies was found in this sample. Pediatricians need to ask their patients about complementary and alternative therapy practices considering the potential for interactions with pharmacological treatments or adverse effects.


An attempt to influence attitudes towards textured soya protein as an alternative to meat.
The effect of person-to-person discussions, demonstrations and advertising on the attitude of mothers of young families towards textured soya-bean protein products as an alternative to meat has been studied. The results show that person-to-person interviews can influence the attitudes towards textured vegetable protein although some individuals remain resistant to this approach.


Replication of the association of GLT6D1 with aggressive periodontitis in a Sudanese population.
Susceptibility to aggressive periodontitis (AgP) is influenced by genetic as well as environmental factors. Studies linking gene variants to AgP have been mainly centred in developed countries with limited data from Africa. To investigate whether previously reported candidate gene associations with AgP could be replicated in a population from Sudan. The investigation was a case-control design. Cases with AgP (n = 132) and controls (n = 136) were identified from patients attending the Periodontal Department in Khartoum Dental Hospital. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Analysis focused on gene variants with a minor allele frequency (MAF) > 25% in the Sudanese subjects that had previously been reported to be associated with AgP. One candidate gene rs1537415 (GLT6D1) was significantly associated with AgP, OR = 1.50 (95% CI 1.04-2.17), p = 0.0295 (increasing to p = 0.09 after correction for multiple testing). The association strengthened to OR = 1.56 (95% CI 1.15-2.16), p = 0.0042 when the controls were supplemented with data from the Hap map for the Yoruba in Ibadan (n = 147) and remained significant (p = 0.013) after correction for multiple testing. The study independently replicated the finding that rs1537415, a variant in glycosyl transferase gene GLT6D1, is associated with AgP and provided the first report of genetic associations with AgP in a Sudanese population.


Synthetic homeostatic materials with chemo-mechano-chemical self-regulation.
Living organisms have unique homeostatic abilities, maintaining tight control of their local environment through interconversions of chemical and mechanical energy and self-regulating feedback loops organized hierarchically across many length scales. In contrast, most synthetic materials are incapable of continuous self-monitoring and self-regulating behaviour owing to their limited single-directional chemomechanical or mechanochemical modes. Applying the concept of homeostasis to the design of autonomous materials would have substantial impacts in areas ranging from medical implants that help stabilize bodily functions to 'smart' materials that regulate energy usage. Here we present a versatile strategy for creating self-regulating, self-powered, homeostatic materials capable of precisely tailored chemo-mechano-chemical feedback loops on the nano- or microscale. We design a bilayer system with hydrogel-supported, catalyst-bearing microstructures, which are separated from a reactant-containing 'nutrient' layer. Reconfiguration of the gel in response to a stimulus induces the reversible actuation of the microstructures into and out of the nutrient layer, and serves as a highly precise 'on/off' switch for chemical reactions. We apply this design to trigger organic, inorganic and biochemical reactions that undergo reversible, repeatable cycles synchronized with the motion of the microstructures and the driving external chemical stimulus. By exploiting a continuous feedback loop between various exothermic catalytic reactions in the nutrient layer and the mechanical action of the temperature-responsive gel, we then create exemplary autonomous, self-sustained homeostatic systems that maintain a user-defined parameter--temperature--in a narrow range. The experimental results are validated using computational modelling that qualitatively captures the essential features of the self-regulating behaviour and provides additional criteria for the optimization of the homeostatic function, subsequently confirmed experimentally. This design is highly customizable owing to the broad choice of chemistries, tunable mechanics and its physical simplicity, and may lead to a variety of applications in autonomous systems with chemo-mechano-chemical transduction at their core.


Linguistic camouflage in girls with autism spectrum disorder.
Autism spectrum disorder (ASD) is diagnosed more frequently in boys than girls, even when girls are equally symptomatic. Cutting-edge behavioral imaging has detected "camouflaging" in girls with ASD, wherein social behaviors appear superficially typical, complicating diagnosis. The present study explores a new kind of camouflage based on language differences. Pauses during conversation can be filled with words like UM or UH, but research suggests that these two words are pragmatically distinct (e.g., UM is used to signal longer pauses, and may correlate with greater social communicative sophistication than UH). Large-scale research suggests that women and younger people produce higher rates of UM during conversational pauses than do men and older people, who produce relatively more UH. Although it has been argued that children and adolescents with ASD use UM less often than typical peers, prior research has not included sufficient numbers of girls to examine whether sex explains this effect. Here, we explore UM vs. UH in school-aged boys and girls with ASD, and ask whether filled pauses relate to dimensional measures of autism symptom severity. Sixty-five verbal school-aged participants with ASD (49 boys, 16 girls, IQ estimates in the average range) participated, along with a small comparison group of typically developing children (8 boys, 9 girls). Speech samples from the Autism Diagnostic Observation Schedule were orthographically transcribed and time-aligned, with filled pauses marked. Parents completed the Social Communication Questionnaire and the Vineland Adaptive Behavior Scales. Girls used UH less often than boys across both diagnostic groups. UH suppression resulted in higher UM ratios for girls than boys, and overall filled pause rates were higher for typical children than for children with ASD. Higher UM ratios correlated with better socialization in boys with ASD, but this effect was driven by increased use of UH by boys with greater symptoms. Pragmatic language markers distinguish girls and boys with ASD, mirroring sex differences in the general population. One implication of this finding is that typical-sounding disfluency patterns (i.e., reduced relative UH production leading to higher UM ratios) may normalize the way girls with ASD sound relative to other children, serving as "linguistic camouflage" for a naïve listener and distinguishing them from boys with ASD. This first-of-its-kind study highlights the importance of continued commitment to understanding how sex and gender change the way that ASD manifests, and illustrates the potential of natural language to contribute to objective "behavioral imaging" diagnostics for ASD.


Assisted reproductive techniques in mares.
A wide variety of assisted reproductive techniques (ARTs) are available to aid in managing aspects of equine reproduction. Embryo recovery and transfer can be used to obtain more than one foal per mare per year, and to obtain foals from mares that cannot carry a foal to term. Oocyte recovery and either transfer to the oviduct of an inseminated recipient mare (oocyte transfer), or intracytoplasmic sperm injection (ICSI) and embryo culture can be used to obtain foals from mares with some types of subfertility, such as problems of the tubular tract. ICSI can be used to obtain foals when sperm number or quality is low. Because of its ease of use for the mare owner and efficiency, oocyte recovery and ICSI is being used in some cases for management of normally fertile mares and stallions. Oocytes can be recovered from live mares by the referring veterinarian, and shipped overnight to a laboratory for ICSI, without any decrease in oocyte or embryo viability. In case of unexpected death of a mare, ovaries or oocytes can be transported to the ICSI laboratory for production of embryos. Embryos produced both in vitro and in vivo can be biopsied to determine their genetic makeup before they are transferred. Equine embryos can be vitrified successfully; collapse of the blastocoele cavity allows efficient vitrification of expanded blastocysts. In contrast, cryopreservation of unfertilized equine oocytes still has low success. Genetics of valuable animals can be preserved via nuclear transfer (cloning) and several commercial companies offer this service clinically.


Lack of glucagon receptors in Morris hepatoma 7800.
When compared to normal liver membranes, purified plasma membranes of regenerating liver and Morris hepatomas contain low but variable capacities to bind glucagon. This property is inversely related to the capacity of the isolated hepatocytes to bind to heterologous biomatrix glycoproteins. Since these parameters are characteristic of the proliferative state of the cells, it was important to further study the glucagon receptor protein and stimulation of adenylate cyclase activity. Our results show that 125I-iodinated plasma membranes obtained from normal liver contain three molecular species (117000, 98000, 86000 molecular weight) that can be eluted specifically with glucagon from a sepharose-glucagon affinity column. These proteins contain the putative glucagon receptor since binding of 125I- iodoglucagon is increased 150-fold as compared to unfractionated membranes. Plasma membranes obtained from Morris hepatoma (7800) and liver of chemically hepatectomized rats do not bind glucagon and lack these proteins. After inactivation with N-ethylmaleimide of the adenylate cyclase activity of the normal plasma membranes, they were fused with membrane of the hepatoma. The hybrid membranes showed 60% recovery of glucagon-stimulated cyclase activity. These results suggest that the plasma membranes of the proliferating liver cells do not contain receptor protein but have intact regulatory and catalytic subunits of the adenylate cyclase system.


[Committee for Human Rights and Medical Ethics of the Croatian Medical Association].
The historical development of ethical standards and institutions of Croatian Medical Association is presented. The first standards were "Medical order and Community" in 1895 and the ethical codex under the name "Main principles of Medical dignity" in 1901 resp. 1921. According to the new Association's Statute in 1990 the first "Committee on Human Rights and Medical Ethics" was founded. Since 1995 the Committee operates as a common "Committee on Medical Ethics and Deontology" of Croatian Medical Association and of Croatian Medical Chamber. In short the activities of committees in both periods, 1991-1995 and 1995-1999 are presented, including the establishing of a new "Codex of Medical Ethics". Since 1999 the Croatian Medical Chamber divorced the cooperation with Croatian Medical Association and founded his own Committee. The Croatian Medical Association is now without ethical committee. The establishment of a new, common Committee of the Medical Association, Medical Chamber and Universities is suggested.


Clustering of health risk behaviors in pregnant individuals: Data from the Brazilian risk factor surveillance system for non-communicable chronic diseases.
To investigate the clustering of health risk behaviors (HRB) and its association with demographics, physical exercise, overweight, perception of health, and diseases in Brazilian pregnant people. This is a cross-sectional study using data from the Risk Factor Surveillance System for Non-communicable Chronic Diseases by Telephone Survey (VIGITEL), the main health survey in Brazil. We used data on fruit and vegetable consumption, TV time, tobacco, and alcohol abuse in individuals who reported being pregnant (n = 4553). We used latent class analysis to identify optimal HRB clustering among participants. Multinomial regression (odds ratio [OR] and 95% confidence intervals [95%CI]) was applied to identify factors associated with HRB cluster. Three clustering classes were identified: "without HRB cluster" (i.e., least unhealthy behaviors) (n = 2402, 52,8%), "moderate HRB cluster" (n = 1983, 43,5%), and "high HRB cluster" (i.e., most unhealthy behaviors) (n = 168, 3,7%). Pregnant people aged 35-50 years (OR = 1.89, 95%CI = 1.01; 3.52) who did not practice physical exercise (OR = 1.94, 95%CI 1.11; 3.39) were more likely to be classified as "high HRB cluster". Participants with 9-11 years (OR = 0.11, 95%CI = 0.07; 0.17) and ≥ 12 (OR = 0.05, 95%CI = 0.02; 0.11) years of education had a lower likelihood of being in the "high HRB cluster". Three HRB clustering patterns were found in this study. Greater maternal age, low education, and absence of physical exercises increased the chances of being in the high HRB cluster group. Participants with higher educational levels were less likely to be in the High HRB cluster.


Biophysical mechanisms complementing "classical" cell biology.
This overview addresses phenomena in cell- and molecular biology which are puzzling by their fast and highly coordinated way of organization. Generally, it appears that informative processes probably involved are more on the biophysical than on the classical biochemical side. The coordination problem is explained within the first part of the review by the topic of endogenous electrical phenomena. These are found e.g. in fast tissue organization and reorganization processes like development, wound healing and regeneration. Here, coupling into classical biochemical signaling and reactions can be shown by modern microscopy, electronics and bioinformatics. Further, one can follow the triggered reactions seamlessly via molecular biology till into genetics. Direct observation of intracellular electric processes is very difficult because of e.g. shielding through the cell membrane and damping by other structures. Therefore, we have to rely on photonic and photon - phonon coupling phenomena like molecular vibrations, which are addressed within the second part. Molecules normally possess different charge moieties and thus small electromagnetic (EMF) patterns arise during molecular vibration. These patterns can now be measured best within the optical part of the spectrum - much less in the lower terahertz till kHz and lower Hz part (third part of this review). Finally, EMFs facilitate quantum informative processes in coherent domains of molecular, charge and electron spin motion. This helps to coordinate such manifold and intertwined processes going on within cells, tissues and organs (part 4). Because the phenomena described in part 3 and 4 of the review still await really hard proofs we need concerted efforts and a combination of biophysics, molecular biology and informatics to unravel the described mysteries in "physics of life".


Mannitol-1-phosphate dehydrogenase of Escherichia coli. Chemical properties and binding of substrates.
Mannitol-1-phosphate dehydrogenase was purified to homogeneity, and some chemical and physical properties were examined. The isoelectric point is 4.19. Amino acid analysis and polyacrylamide-gel electrophoresis in presence of SDS indicate a subunit Mr of about 22,000, whereas gel filtration and electrophoresis of the native enzyme indicate an Mr of 45,000. Thus the enzyme is a dimer. Amino acid analysis showed cysteine, tyrosine, histidine and tryptophan to be present in low quantities, one, three, four and four residues per subunit respectively. The zinc content is not significant to activity. The enzyme is inactivated (greater than 99%) by reaction of 5,5'-dithiobis-(2-nitrobenzoate) with the single thiol group; the inactivation rate depends hyperbolically on reagent concentration, indicating non-covalent binding of the reagent before covalent modification. The pH-dependence indicated a pKa greater than 10.5 for the thiol group. Coenzymes (NAD+ and NADH) at saturating concentrations protect completely against reaction with 5,5'-dithiobis-(2-nitrobenzoate), and substrates (mannitol 1-phosphate, fructose 6-phosphate) protect strongly but not completely. These results suggest that the thiol group is near the catalytic site, and indicate that substrates as well as coenzymes bind to free enzyme. Dissociation constants were determined from these protective effects: 0.6 +/- 0.1 microM for NADH, 0.2 +/- 0.03 mM for NAD+, 9 +/- 3 microM for mannitol 1-phosphate, 0.06 +/- 0.03 mM for fructose 6-phosphate. The binding order for reaction thus may be random for mannitol 1-phosphate oxidation, though ordered for fructose 6-phosphate reduction. Coenzyme and substrate binding in the E X NADH-mannitol 1-phosphate complex is weaker than in the binary complexes, though in the E X NADH+-fructose 6-phosphate complex binding is stronger.


Prostatic urethral angle might be a predictor of treatment efficacy of α-blockers in men with lower urinary tract symptoms.
We investigated the association of the prostatic urethral angle (PUA) with peak urinary flow rate (Qmax) and the severity of lower urinary tract symptoms (LUTS) on the aging male. We also evaluated the effect of the PUA on the treatment efficacy of tamsulosin on men with LUTS. The records were obtained from a prospective database for first-visit male patients with LUTS in the outpatient department of our institution. These patients underwent a detailed physical examination and taking of medical history. A transrectal ultrasound was performed on these patients. The prostate size, length of intravesical prostatic protrusion (IPP), PUA, and International Prostate Symptom Score (IPSS) of the patients were evaluated. Uroflowmetry and a bladder scan for residual urine were also performed on every patient. Tamsulosin 0.2 mg per day was prescribed. The IPSS and uroflowmetry were reevaluated after they had received treatment for 3 months. A total of 178 patients were included, and 149 of them completed this cohort study. The mean PUA was 48.32°±13.74°. The mean prostate volume was 39.19±20.87 mL, and the mean IPP was 5.67±7.85 mm. On multivariate linear regression analysis, the PUA was independently associated with the IPSS (P<0.001), Qmax (P=0.004), post-treatment IPSS change (P=0.032), and post-treatment Qmax change (P<0.001). However, the prostate volume and IPP were not associated with these clinical items. The PUA is significantly associated with Qmax and IPSS in men with LUTS. The PUA is also inversely correlated with changes in Qmax and IPSS after tamsulosin treatment. Namely, the PUA might be a predictor for the treatment efficacy of α-blockers in aging men with LUTS.


Right Heart Structure, Geometry and Function Assessed by Echocardiography in 6-Year-Old Children Born Extremely Preterm-A Population-Based Cohort Study.
Preterm birth has been associated with altered cardiac phenotype in adults. Our aim was to test the hypothesis that children surviving extremely preterm birth have important structural or functional changes of the right heart or pulmonary circulation. We also examined relations between birth size, gestational age, neonatal diagnoses of bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA) with cardiac outcomes. We assessed a population-based cohort of children born in Sweden before 27 weeks of gestation with echocardiography at 6.5 years of age (n = 176). Each preterm child was matched to a healthy control child born at term. Children born preterm had significantly smaller right atria, right ventricles with smaller widths, higher relative wall thickness and higher estimated pulmonary vascular resistance (PVR) than controls. In preterm children, PVR and right ventricular myocardial performance index (RVmpi') were significantly higher in those with a PDA as neonates than in those without PDA, but no such associations were found with BPD. In conclusion, children born extremely preterm exhibit higher estimated PVR, altered right heart structure and function compared with children born at term.


Watchful waiting in the treatment of the small renal mass.
Objectives : To evaluate the role and feasibility of observation with regard to the small renal mass. Methods : We performed a literature search of MEDLINE, reviewing the world literature relevant to the natural history, role of percutaneous biopsy and surveillance of the small renal mass. Results : The average yearly growth rate of most small renal masses ranges from 0.1 to 0.70 cm/yr with obvious exceptions. Clinical predictors of growth such as radiographic size at presentation, age, gender and tumor characteristics are not reliable. Approximately 1% develops metastatic disease while under surveillance. Contemporary series of percutaneous biopsy of small renal masses report sensitivity for malignancy to be 90%-98%. However, false-negative results can occur. For the majority of patients, the gold standard remains surgical extirpation. Conclusions : Watchful waiting is an acceptable option for management of small renal masses in the surgically unfit and elderly population. More information regarding the natural history and metastatic potential of small renal masses is needed. Percutaneous needle biopsy can be successful in detecting malignancy in selected patients with small renal masses. The role of needle biopsy for the small renal mass continues to evolve.


Self-similarity and vanishing diffusion in fluvial landscapes.
Complex topographies exhibit universal properties when fluvial erosion dominates landscape evolution over other geomorphological processes. Similarly, we show that the solutions of a minimalist landscape evolution model display invariant behavior as the impact of soil diffusion diminishes compared to fluvial erosion at the landscape scale, yielding complete self-similarity with respect to a dimensionless channelization index. Approaching its zero limit, soil diffusion becomes confined to a region of vanishing area and large concavity or convexity, corresponding to the locus of the ridge and valley network. We demonstrate these results using one dimensional analytical solutions and two dimensional numerical simulations, supported by real-world topographic observations. Our findings on the landscape self-similarity and the localized diffusion resemble the self-similarity of turbulent flows and the role of viscous dissipation. Topographic singularities in the vanishing diffusion limit are suggestive of shock waves and singularities observed in nonlinear complex systems.