Dynamic contact angles and hysteresis under electrowetting-on-dielectric.
By designing and implementing a new experimental method, we have measured the dynamic advancing and receding contact angles and the resulting hysteresis of droplets under electrowetting-on-dielectric (EWOD). Measurements were obtained over wide ranges of applied EWOD voltages, or electrowetting numbers (0 ≤ Ew ≤ 0.9), and droplet sliding speeds, or capillary numbers (1.4 × 10(-5) ≤ Ca ≤ 6.9 × 10(-3)). If Ew or Ca is low, dynamic contact angle hysteresis is not affected much by the EWOD voltage or the sliding speed; that is, the hysteresis increases by less than 50% with a 2 order-of-magnitude increase in sliding speed when Ca < 10(-3). If both Ew and Ca are high, however, the hysteresis increases with either the EWOD voltage or the sliding speed. Stick-slip oscillations were observed at Ew > 0.4. Data are interpreted with simplified hydrodynamic (Cox-Voinov) and molecular-kinetic theory (MKT) models; the Cox-Voinov model captures the trend of the data, but it yields unreasonable fitting parameters. MKT fitting parameters associated with the advancing contact line are reasonable, but a lack of symmetry indicates that a more intricate model is required.


Measurement of parenchymal extravascular R2* and tissue oxygen extraction fraction using multi-echo vascular space occupancy MRI at 7 T.
Parenchymal extravascular R2* is an important parameter for quantitative blood oxygenation level-dependent (BOLD) studies. Total and intravascular R2* values and changes in R2* values during functional stimulations have been reported in a number of studies. The purpose of this study was to measure absolute extravascular R2* values in human visual cortex and to estimate the intra- and extravascular contributions to the BOLD effect at 7 T. Vascular space occupancy (VASO) MRI was employed to separate out the extravascular tissue signal. Multi-echo VASO and BOLD functional MRI (fMRI) with visual stimulation were performed at 7 T for R2* measurement at a spatial resolution of 2.5 × 2.5 × 2.5 mm(3) in healthy volunteers (n = 6). The ratio of changes in extravascular and total R2* (ΔR2*) was used to estimate the extravascular fraction of the BOLD effect. Extravascular R2* values were found to be 44.66 ± 1.55 and 43.38 ± 1.51 s(-1) (mean ± standard error of the mean, n = 6) at rest and activation, respectively, in human visual cortex at 7 T. The extravascular BOLD fraction was estimated to be 91 ± 3%. The parenchymal oxygen extraction fraction (OEF) during activation was estimated to be 0.24 ± 0.01 based on the R2* measurements, indicating an approximately 37% decrease compared with OEF at rest.


Effect of upper body position on arterial stiffness: influence of hydrostatic pressure and autonomic function.
To evaluate changes in arterial stiffness with positional change and whether the stiffness changes are due to hydrostatic pressure alone or if physiological changes in vasoconstriction of the conduit arteries play a role in the modulation of arterial stiffness. Thirty participants' (male = 15, 24 ± 4 years) upper bodies were positioned at 0, 45, and 72° angles. Pulse wave velocity (PWV), cardio-ankle vascular index, carotid beta-stiffness index, carotid blood pressure (cBP), and carotid diameters were measured at each position. A gravitational height correction was determined using the vertical fluid column distance (mmHg) between the heart and carotid artery. Carotid beta-stiffness was calibrated using three methods: nonheight corrected cBP of each position, height corrected cBP of each position, and height corrected cBP of the supine position (theoretical model). Low frequency systolic blood pressure variability (LFSAP) was analyzed as a marker of sympathetic activity. PWV and cardio-ankle vascular index increased with position (P < 0.05). Carotid beta-stiffness did not increase if not corrected for hydrostatic pressure. Arterial stiffness indices based on Method 2 were not different from Method 3 (P = 0.65). LFSAP increased in more upright positions (P < 0.05) but diastolic diameter relative to diastolic pressure did not (P > 0.05). Arterial stiffness increases with a more upright body position. Carotid beta-stiffness needs to be calibrated accounting for hydrostatic effects of gravity if measured in a seated position. It is unclear why PWV increased as this increase was independent of blood pressure. No difference between Methods 2 and 3 presumably indicates that the beta-stiffness increases are only pressure dependent, despite the increase in vascular sympathetic modulation.


Long-term supplementation with an undenatured type-II collagen (UC-II®) formulation in dogs with degenerative joint disease: Exploratory study.
Undenatured type-II collagen (UC-II®) has demonstrated its benefits in degenerative joint disease (DJD) management. Exploratory clinical study to investigate the beneficial effects of FLEXADIN® Advanced in dogs. Multicentre clinical prospective study, 110 client-owned dogs with a clinical diagnosis of DJD. Dogs received FLEXADIN® Advanced during 6 months. Pain, general condition, appetite, mobility, and lameness were assessed monthly by veterinarians and owners for 6 months. Compliance was assessed at 3 and 6 months. Statistical analysis was performed with non-parametric tests (significance, p < 0.05). Parameters assessed were significantly lower comparing inclusion with all subsequent months (p < 0.0001). Compliance at 3 months showed a good score but was significantly lower (p < 0.0001) at 6 months. FLEXADIN® Advanced, containing UC-II®, can be considered as a good complementary feed to provide joint support in dogs with mild to moderate DJD.


Wavelength-Controlled Lasing in Znx Cd1- x S Single-Crystal Nanoribbons.
Znx Cd1 - x S single-crystal nanoribbons of controlled composition (where 0 ≤ x ≤ 1) can be synthesized by combining laser ablation with thermal evaporation. The nanoribbons exhibit lasing emission that can be continuously tuned within the ranges of 340-390 nm and 485-515 nm. These results suggest that Znx Cd1- x S nanoribbon lasers of pre-selected "tunable" wavelengths between 340 and 515 nm may be achievable by tailoring the value of x.


Exploration of the shared gene signatures and molecular mechanisms between periodontitis and inflammatory bowel disease: evidence from transcriptome data.
Periodontitis disease (PD) is associated with a systemic disorder of inflammatory bowel disease (IBD). The immune response is the common feature of the two conditions, but the more precise mechanisms remain unclear. Differential expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) were performed on PD and Crohn's disease (CD) data sets to identify crosstalk genes linking the two diseases. The proportions of infiltrating immune cells were calculated by using Single-sample Gene Set Enrichment Analysis. In addition, a data set of isolated neutrophils from the circulation was performed via WGCNA to obtain PD-related key modules. Then, single-cell gene set enrichment scores were computed for the key module and grouped neutrophils according to score order in the IBD scRNA-seq data set. Single-cell gene enrichment analysis was used to further explore the biological process of the neutrophils. A total of 13 crosstalk genes (IL1B, CSF3, CXCL1, CXCL6, FPR1, FCGR3B, SELE, MMP7, PROK2, SRGN, FCN1, TDO2 and CYP24A1) were identified via DEGs analysis and WGCNA by combining PD and CD data sets. The enrichment analysis showed that these genes were involved in interleukin-10 signaling and inflammatory response. The immune infiltration analysis showed a significant difference in the proportion of neutrophils in PD and CD compared with healthy patients. Neutrophils were scored based on the expression of a periodontitis-related gene set in the scRNA-seq data set of IBD. The enrichment analysis demonstrated that inflammatory response, TNFα signaling via NF-κB and interferon-gamma response were upregulated in the high-score group, which expressed more pro-inflammatory cytokines and chemokines compared with the low-score group. This study reveals a previously unrecognized mechanism linking periodontitis and IBD through crosstalk genes and neutrophils, which provides a theoretical framework for future research.


Pharmaceutical granulation and tablet formulation using neural networks.
Current-day pharmaceutical formulation may be trial and error in nature due to the absence of a clear relationship between the formulation characteristics (output variables) and the material and process variables (input variables). Neural networks are networks of adaptable nodes, which through a process of learning from task examples, store experiential knowledge and make it available for prediction. Prediction of a model granulation and tablet system characteristics from the knowledge of material and process variables utilizing neural networks is the basis of this presentation. The formulation design contained the following variables: granulation equipment, diluent, method of binder addition, and the binder concentration. The material, process, granulation evaluation, and tablet evaluation data of the formulations were used as the data set for training and testing of the neural network models. A comparison of the neural network prediction performance with that of regression models was also done. Both the granulation model and the tablet model converged fairly rapidly in the training step. In the testing step, the predictions for all granulation model variables (geometric mean particle size, flow value, bulk density, and tap density) were satisfactory. In the tablet model, the predictions for disintegration and thickness were also satisfactory. The predictions for hardness and friability were less than satisfactory. Two situations where the neural network may not perform adequately are discussed. The neural network prediction is better or comparable for all the predicted variables in this study compared to regression methods. The results clearly show the applicability of neural networks to formulation modeling.


[Reconstruction of neck vessels in endovascular repair of aortic arch aneurysms].
We report 6 cases of aortic arch aneurysms necessitating reconstruction of the neck vessel during stent-graft (SG) placement. All patients were male and their average age was 75 years. The proximal landing zone was zone 0 in 2, zone 1 in 2, and zone 2 in 2 patients. The left subclavian artery (LSCA) was revascularized in every case; using left common carotid artery (LCCA)-LSCA bypass in 3, axillo-axillary artery bypass in 2, and LSCA transposition in 1. Prophylactic LCCA revascularization was done in 2 in which obstruction of LCCA by SG was anticipated. The proximal portion of LSCA from the origin of the vertebral artery was ligated in 3, and divided in 1. Two types of SG were used; Z stent in 1 and Matsui-Kitamura stent in 5. There was no hospital death or perioperative stroke. In the patient with Z stent, SG could not be deployed because of kinking of the delivery system. This patient subsequently underwent surgical SG placement under hypothermic circulatory arrest. In the other 5, SG was deployed without any type of endoleak. Postoperative complication included incomplete phrenic nerve palsy in 1. Prophylactic bypass for LCCA was divided because SG did not obstruct the antegrade flow of LCCA. Revascularization of neck vessels can be performed with low morbidity in endovascular repair of aortic arch aneurysms.


Unprecedented isospecific 3,4-polymerization of isoprene by cationic rare earth metal alkyl species resulting from a binuclear precursor.
The isospecific 3,4-polymerization of isoprene has been achieved for the first time by use of a combination of a binuclear rare earth metal dialkyl complex, such as [Me2Si(C5Me4)(mu-PCy)YCH2SiMe3]2 (Cy = cyclohexyl), and an equimolar amount of [Ph3C][B(C6F5)4] as a catalyst system. A DFT calculation suggested that a binuclear monocationic monoalkyl species, such as [Me2Si(C5Me4)(mu-PCy)Y(mu-CH2SiMe3)Y(mu-PCy)(C5Me4)SiMe2]+, in which the alkyl group bridges the two metal centers, could be the true catalyst species.


Intelligence, inspection time and cognitive strategies.
The use of apparent motion cues to guide discriminations on the inspection time (IT) task has been taken to imply the vulnerability of IT to strategic processes by higher IQ subjects, and the questionable generality of the IT/IQ correlation. The current study examined verbal and non-verbal intelligence, personality and IT in 74 young adults, using light-emitting diodes to present IT, obtaining perceptual self-reports during IT itself. Forty-three (58 per cent) subjects in the sample reported using motion cues to guide IT discriminations; these subjects had faster ITs than individuals who did not use motion cues (t = 2.97, p < .005; effect size = .73). Cue users did not have higher verbal or non-verbal IQ than non-users. Although cue users were lower in neuroticism than non-cue users, this did not account for their faster ITs. Slower IT correlated with lower scores on a measure of non-verbal intelligence (r = -0.41, p < .001); the size of this correlation remained similar when the sample was divided into groups reporting the use of motion cues or not. Thus, despite motion cues enhancing performance on an IT task, the perception of these cues neither causes, nor reduces, the correlation between IT and IQ.


[Incidence and preventability of adverse events in patients hospitalised in three Colombian hospitals during 2006].
Determining adverse event (AE) incidence, preventability, classification and impact for establishing their importance as a public health problem within the Colombian Social Security System. This was a study of a prospective inpatient cohort from three Colombian general-practice institutions. at least 12 hours' length of hospital stay during 2006. suffering psychiatric disorders and AE which had occurred before hospitalisation indexing. The sample consisted of 6 557 patients. clinical charts. Being a three-phase design, the first phase consisted of translating and standardising screening and causation formats, phase II of actively monitoring screening criteria and phase III of evaluating causation regarding the care being provided, based on specialist committee concept on a 0-6 scale. The variables measured were age, gender, social security affiliation, cumulative AE incidence, temporality, preventability of AE and disability resulting from them. 6,688 patients were evaluated; 505 of them fulfilled positive screening criteria (95 % CI=7,9;7,3-8,6), 310 presented at least one AE during their hospitalisation (95 %CI for accumulated incidence=4,6; 4,1-5,1). AE were considered to have been preventable in 189 cases (95 % CI=61;55-66) and permanent disability occurred in 1,3 % of them. AE-associated mortality was 6,4 % (20/310). Hospitalisation became increased to 1 072 days as a direct consequence of AE. This study revealed an important incidence of AE in three Colombian hospitals, these being mainly preventable. Their ongoing monitoring as a part of risk management systems could reduce costs and AE-associated morbidity and mortality.


The immunogenicity of GSK's recombinant hepatitis B vaccine in children: a systematic review of 30 years of experience.
The World Health Organization recommends hepatitis B virus (HBV) vaccines to be included in national immunization schedules everywhere, and has adopted the strategic goal of halting viral hepatitis as a major public health threat by 2030, under which vaccination plays a major role. Engerix™ B (GSK HepB, GSK, Belgium) was the first recombinant HBV vaccine to be licensed, and marked its 30th anniversary in 2016. Areas covered: We conducted a systematic review of the literature summarizing 30 years of immunogenicity and safety data for GSK HepB in children and adolescents. Expert commentary: Primary 3-dose vaccination of healthy infants and children, including infants born to HBsAg-positive mothers, using the standard 0, 1, 6 month schedule was associated with seroprotection rates ≥96.0%. In high-risk infants, vaccine efficacy at year 5 was 96.0% after 3-dose priming in infancy and immunoglobulin at birth. Lower seroprotection rates were observed in children with severe underlying disease including human immunodeficiency virus infection and cancer. GSK HepB had a clinically acceptable safety profile in all of the populations studied. HBV vaccines have demonstrated long-term impacts on rates of fulminant hepatitis, chronic liver disease and hepatocellular carcinoma. GSK HepB will continue to contribute to global HBV control for the foreseeable future.


SDHB-Associated Paraganglioma in a Pediatric Patient and Literature Review on Hereditary Pheochromocytoma-Paraganglioma Syndromes.
Pheochromocytoma and paraganglioma are rare in the pediatric population occurring in approximately 1 in 50,000 children. While some cases are sporadic, they have commonly been associated with syndromes such as von Hippel-Lindau, multiple endocrine neoplasia types IIa and IIb, neurofibromatosis type 1, and hereditary pheochromocytoma-paraganglioma syndromes. In children less than 18 years of age approximately 60% of pheochromocytomas and paragangliomas are associated with a germline mutation. We present an 11-year-old child with an abdominal paraganglioma related to a succinate dehydrogenase subunit B gene mutation whose father had a previously resected abdominal paraganglioma and was found to carry the same mutation. In addition, we review the etiology, genetics, diagnostic approach, and challenges of preoperative management of secretory pheochromocytomas and paragangliomas in children.


Chest pain caused by multiple exostoses of the ribs: A case report and a review of literature.
The aim of this paper is to report an exceptional case of multiple internal exostoses of the ribs in a young patient affected by multiple hereditary exostoses (MHE) coming to our observation for chest pain as the only symptom of an intra-thoracic localization. A 16 years old patient with familiar history of MHE came to our observation complaining a left-sided chest pain. This pain had increased in the last months with no correlation to a traumatic event. The computed tomography (CT) scan revealed the presence of three exostoses located on the left third, fourth and sixth ribs, all protruding into the thoracic cavity, directly in contact with visceral pleura. Moreover, the apex of the one located on the sixth rib revealed to be only 12 mm away from pericardium. Patient underwent video-assisted thoracoscopy with an additional 4-cm mini toracotomy approach. At the last 1-year follow-up, patient was very satisfied and no signs of recurrence or major complication had occured. In conclusion, chest pain could be the only symptom of an intra-thoracic exostoses localization, possibly leading to serious complications. Thoracic localization in MHE must be suspected when patients complain chest pain. A chest CT scan is indicated to confirm exostoses and to clarify relationship with surrounding structures. Video-assisted thoracoscopic surgery can be considered a valuable option for exostoses removal, alone or in addiction to a mini-thoracotomy approach, in order to reduce thoracotomy morbidity.


Effect of spironolactone in resistant arterial hypertension: a randomized, double-blind, placebo-controlled trial (ASPIRANT-EXT).
This study was designed to assess the effect of the addition of low-dose spironolactone on blood pressure (BP) in patients with resistant arterial hypertension. Patients with office systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg despite treatment with at least 3 antihypertensive drugs, including a diuretic, were enrolled in this double-blind, placebo-controlled, multicentre trial. One hundred sixty-one patients in outpatient internal medicine departments of 6 hospitals in the Czech Republic were randomly assigned to receive 25 mg of spironolactone (N = 81) or a placebo (N = 80) once daily as an add-on to their antihypertensive medication, using simple randomization. This study was registered with ClinicalTrials.gov, number NCT00524615. A nalyses were done with 150 patients who finished the follow-up (74 in the spironolactone and 76 in the placebo group). At 8 weeks, BP values were decreased more by spironolactone, with differences in mean fall of SBP of -9.8, -13.0, -10.5, and -9.9 mm Hg (P < 0.001 for all) in daytime, nighttime, and 24-hour ambulatory BP monitoring and in the office. The respective DBP differences were -3.2, -6.4, -3.5, and -3.0 mm Hg (P = 0.013, P < 0.001, P = 0.005, and P = 0.003). Adverse events in both groups were comparable. The office SBP goal <14 mm Hg at 8 weeks was reached in 73% of patients using spironolactone and 41% using placebo (P = 0.001). Spironolactone in patients with resistant arterial hypertension leads to a significant decrease of both SBP and DBP and markedly improves BP control.


Validation of a Standard Protocol to Assess the Fermentative and Chemical Properties of Saccharomyces cerevisiae Wine Strains.
This paper reports on a common experiment performed by 17 Research Units of the Italian Group of Microbiology of Vine and Wine (GMVV), which belongs to the Scientific Society SIMTREA, with the aim to validate a protocol for the characterization of wine strains of Saccharomyces cerevisiae. For this purpose, two commercial S. cerevisiae strains (EC 1118 and AWRI796) were used to carry out inter-laboratory-scale comparative fermentations using both synthetic medium and grape musts and applying the same protocol to obtain reproducible, replicable, and statistically valid results. Ethanol yield, production of acetic acid, glycerol, higher alcohols, and other volatile compounds were assessed. Moreover, the Fourier transform infrared spectroscopy was also applied to define the metabolomic fingerprint of yeast cells from each experimental trial. Data were standardized as unit of compounds or yield per gram of sugar (glucose and fructose) consumed throughout fermentation, and analyzed through parametric and non-parametric tests, and multivariate approaches (cluster analysis, two-way joining, and principal component analysis). The results of experiments carried out by using synthetic must showed that it was possible to gain comparable results from three different laboratories by using the same strains. Then, the use of the standardized protocol on different grape musts allowed pointing out the goodness and the reproducibility of the method; it showed the main traits of the two yeast strains and allowed reducing variability amongst independent batches (biological replicates) to acceptable levels. In conclusion, the findings of this collaborative study contributed to the validation of a protocol in a specific synthetic medium and in grape must and showed how data should be treated to gain reproducible and robust results, which could allow direct comparison of the experimental data obtained during the characterization of wine yeasts carried out by different research laboratories.


Passive protection against lethal enterovirus 71 infection in newborn mice by neutralizing antibodies elicited by a synthetic peptide.
Enterovirus 71 (EV71) infections could lead to high mortalities and neither vaccine nor therapeutic treatment is available. We investigated vaccination with a synthetic peptide SP70 representing a neutralizing linear VP1 epitope of EV71 strain 41 (subgenogroup B4) and passive transfer of anti-SP70 antibodies to protect suckling Balb/c mice against EV71 infectivity. When the mouse anti-SP70 antisera with a neutralizing antibody titer of 1:32 were passively administered to one-day-old suckling mice which had been challenged with a lethal dose of 1000 TCID(50) per mouse, the neutralizing anti-SP70 antibodies were able to confer 80% in vivo protection. In contrast, suckling mice which did not receive any anti-SP70 antisera did not survive the viral challenge at day 21 postinfection. Histological examination and real-time RT-PCR assays revealed viral infiltration in small intestines of EV71-infected mice. Interestingly, anti-SP70 antibodies play a major role in the inhibition of EV71 replication in vivo and significantly reduced the viral titer. In conclusion, EV71-neutralizing antibodies elicited by the synthetic peptide SP70 were able to confer good in vivo passive protection against homologous and heterologous EV71 strains in suckling Balb/c mice.


Oral Health Screening for Risk Reduction for Early Periprosthetic Joint Infections of Hip and Knee Endoprostheses-Results of a Prospective Cohort Study.
This prospective observational study had two aims: (I) to assess whether a preoperative dental screening before endoprosthesis (EP) implantation with need-based dental intervention would decrease the prevalence of periprosthetic joint infection (PJI) and (II) to evaluate whether instructed orthopedic surgeons would achieve similar results in oral screening as dentists. The preoperative oral health statuses of the patients, prior to EP insertion, were either evaluated by the patients' general dentists (Ia) or, if the patient had not visited a general dentist, by an instructed orthopedic surgeon (Ib). Both the dentist and orthopedic surgeon used standardized risk estimation (low risk, moderate risk, and high risk) for an oral-health-related infectious complication after EP insertion, including a recommendation for further management of the patient. If required, a need-based dental rehabilitation was performed. In addition, retrospective data evaluation of a comparison group (II) was performed, which had not been screened orally preoperatively. A total of 777 patients (screening group (I): n = 402, of which 229 were screened by a dentist (Ia), 173 were screened by an orthopedic surgeon (Ib); comparison group (II): n = 375) were included. No general association between early infection rate and preoperative oral screening in general was found (1% PJI in screening group (I), 1.6% PJI in comparison group (II); p = 0.455). However, screening performance (dentist vs. orthopedic surgeon) had a significant impact on the prevalence of developed PJIs (p = 0.021). Thereby, 100% of observed infections in the screening group (I) occurred in the group with previous oral screening by an orthopedic surgeon (Ib). Furthermore, the C-reactive protein (CRP) value at discharge was significantly lower when general preoperative oral screening had been performed (group I vs. group II, p = 0.03). Only preoperative oral screening by a dentist had the potential to reduce oral-focus-associated EP infections; therefore, increased attention should be paid to the further promotion of interdisciplinary work between dentists and orthopedic surgeons. Dental screenings, using objectifiable criteria, as applied in this study, seem reasonable but require further validation in larger cohorts.


Automatic exposure control in multichannel CT with tube current modulation to achieve a constant level of image noise: experimental assessment on pediatric phantoms.
Automatic exposure control (AEC) systems have been developed by computed tomography (CT) manufacturers to improve the consistency of image quality among patients and to control the absorbed dose. Since a multichannel helical CT scan may easily increase individual radiation doses, this technical improvement is of special interest in children who are particularly sensitive to ionizing radiation, but little information is currently available regarding the precise performance of these systems on small patients. Our objective was to assess an AEC system on pediatric dose phantoms by studying the impact of phantom transmission and acquisition parameters on tube current modulation, on the resulting absorbed dose and on image quality. We used a four-channel CT scan working with a patient-size and z-axis-based AEC system designed to achieve a constant noise within the reconstructed images by automatically adjusting the tube current during acquisition. The study was performed with six cylindrical poly(methylmethacrylate) (PMMA) phantoms of variable diameters (10-32 cm) and one 5 years of age equivalent pediatric anthropomorphic phantom. After a single scan projection radiograph (SPR), helical acquisitions were performed and images were reconstructed with a standard convolution kernel. Tube current modulation was studied with variable SPR settings (tube angle, mA, kVp) and helical parameters (6-20 HU noise indices, 80-140 kVp tube potential, 0.8-4 s. tube rotation time, 5-20 mm x-ray beam thickness, 0.75-1.5 pitch, 1.25-10 mm image thickness, variable acquisition, and reconstruction fields of view). CT dose indices (CTDIvol) were measured, and the image quality criterion used was the standard deviation of the CT number measured in reconstructed images of PMMA material. Observed tube current levels were compared to the expected values from Brooks and Di Chiro's [R.A. Brooks and G.D. Chiro, Med. Phys. 3, 237-240 (1976)] model and calculated values (product of a reference value multiplied by a dose ratio measured with thermoluminescent dosimeters). Our study demonstrates that this AEC system accurately modulates the tube current according to phantom size and transmission to achieve a stable image noise. The system accurately controls the tube current when changing tube rotation time, tube potential, or image thickness, with minimal variations of the resulting noise. Nevertheless, CT users should be aware of possible changes of tube current and resulting dose and quality according to several parameters: the tube angle and tube potential used for SPR, the x-ray beam thickness (tube current decreases and image noise increases when doubling x-ray beam thickness), the pitch value (a pitch decrease leads to a higher dose but also to a higher noise), and the acquisition field of view (FOV) (tube current is lower when using the small acquisition FOV compared to the large one, but the use of small acquisition FOV at 120 kVp leads to a peculiar increase of tube current and CTDIvol).


Accelerating Photogenerated Hole Tunneling through Passivation Layers via Reducing Interplanar Spacing for Efficient and Stable Perovskite Solar Cells.
Interfacial passivation engineering plays a crucial role in the explosive development of perovskite solar cells (PSCs). However, previous studies on passivation layers mainly focused on the defect-passivation mechanism rather than the interfacial charge transport efficiency. Here, by precisely tuning the interplanar spacing of the ammonium iodide passivation layer, we elucidate the promoting effect of the reduced interplanar spacing of the passivation layer on the photogenerated hole tunneling efficiency at the interface of the hole transport layer and perovskite. Compared with the commonly used phenethylammonium iodide passivation layer with a wider interplanar spacing, 2-chlorobenzylammonium iodide with a narrower interplanar spacing can help break through the thickness limitation of the passivation layer, thus showing a better comprehensive passivation effect. Therefore, we demonstrate photovoltaic devices with an enhanced fill factor (FF) and open-circuit voltage (VOC), which yield a high power conversion efficiency (PCE) of up to 23.1%. We thus identify an efficient scheme to achieve optimal passivation conditions for high-performance PSCs.


Therapeutic efficacy of three hyaluronic acid formulations in young and middle-aged patients with early-stage meniscal injuries.
[Purpose] To investigate and compare the efficacy of three hyaluronic acid formulations in patients with early-stage meniscal injuries. [Subjects and Methods] Male and female patients who were admitted to our clinic between January 2013 and December 2013, diagnosed with early-stage meniscus lesions of the knee, and given a hyaluronic acid treatment were included in this retrospective study. Patients were categorized into 3 groups according to their treatments: MONOVISC, OSTENIL PLUS, or ORTHOVISC. Scores from a Visual Analog Scale and the Western Ontario and McMaster Universities Arthritis Index were evaluated at baseline and one, three, and six months after baseline. [Results] A total of 55 patients were included in this study. Most of the patients were female (55%), and the mean age of the patients was 42.4 (± 8.1) years. Based on the pre- and post-injection data, there was significant reductions both in the Visual Analog Scale score and the Western Ontario and McMaster Universities Arthritis Index score after the injections for all groups. According to intergroup comparisons, no significant difference was observed in terms of efficacy. [Conclusion] Three hyaluronic acid formulations produced a similar efficacy in patients with meniscal injuries, and further studies are needed to evaluate long-term results.


The effect of the full bladder on vasopressin secretion in healthy young adults.
Interactions between the central nervous system, bladder and kidneys have been investigated for many years in animal studies and have shown that bladder distension, in animals, leads to decreased urine production. The objectives of the current study were to determine the effect of a full bladder on urinary output, vasopressin secretion and urine osmolality in humans. The study involved healthy volunteers. They were studied for a period of 48 hours. This period included two 24-hour studies, one involving regular and frequent voidings (to produce a minimal bladder filling) and the other voiding postponement (to produce maximal bladder distension). In contrast to enuresis studies a circadian rhythm of vasopressin secretion was observed in the males involved in this study, whereas no significant rhythm of vasopressin secretion could be detected in the female subjects. However, this study was unable to confirm that, in humans, a full bladder causes a decrease in urine production, an increase in vasopressin secretion or an increase in urine osmolality.


Limitations of statistical measures of error in assessing the accuracy of continuous glucose sensors.
Various statistical methods are commonly used to assess the accuracy of near-continuous glucose sensors. The performance and reliability of these methods have not been well described. We used computer simulation to describe the behavior of several statistical measures including error grid analysis, receiver operating characteristics, correlation, and repeated measures under varying conditions. Actual data from an inpatient accuracy study conducted by the Diabetes Research in Children Network (DirecNet) were also used to demonstrate these limitations. Sensors that were made artificially inaccurate by randomly shuffling the pairings to reference values still fell in Zone A or B 78% of the time for the Clarke grid and 79% of the time for the modified grid. Area under the curve values for these shuffled pairs averaged 64% for hypoglycemia and 68% for hyperglycemia. Continuous error grid analysis resulted in 75% of shuffled pairs designated as "Accurate Readings" or "Benign Errors." Correlation analysis gave inconsistent results for sensors simulated to have identical accuracies with values ranging from 0.50 to 0.96. Simplistic repeated-measures analyses accounting for subject effects, but ignoring temporal correlation patterns substantially inflated the probability of falsely obtaining a statistically significant result. In simulations where the null hypothesis was correct, 23% of observed P values were <0.05 and 12% of observed P values were <0.01. Commonly used statistical methods can give overly optimistic and/or inconsistent notions of sensor accuracy if results are not placed in proper context. Novel techniques are needed to assess the accuracy of near-continuous glucose sensors.


Formation of somatosensory detour circuits mediates functional recovery following dorsal column injury.
Anatomically incomplete spinal cord injuries can be followed by functional recovery mediated, in part, by the formation of intraspinal detour circuits. Here, we show that adult mice recover tactile and proprioceptive function following a unilateral dorsal column lesion. We therefore investigated the basis of this recovery and focused on the plasticity of the dorsal column-medial lemniscus pathway. We show that ascending dorsal root ganglion (DRG) axons branch in the spinal grey matter and substantially increase the number of these collaterals following injury. These sensory fibers exhibit synapsin-positive varicosities, indicating their integration into spinal networks. Using a monosynaptic circuit tracing with rabies viruses injected into the cuneate nucleus, we show the presence of spinal cord neurons that provide a detour pathway to the original target area of DRG axons. Notably the number of contacts between DRG collaterals and those spinal neurons increases by more than 300% after injury. We then characterized these interneurons and showed that the lesion triggers a remodeling of the connectivity pattern. Finally, using re-lesion experiments after initial remodeling of connections, we show that these detour circuits are responsible for the recovery of tactile and proprioceptive function. Taken together our study reveals that detour circuits represent a common blueprint for axonal rewiring after injury.


Three distinct pneumotypes characterize the microbiome of the lung in BALB/cJ mice.
Bacteria can rarely be isolated from normal healthy lungs using conventional culture techniques, supporting the traditional belief that the lungs are sterile. Yet recent studies using next generation sequencing report that bacterial DNA commonly found in the upper respiratory tract (URT) is present at lower levels in the lungs. Interpretation of that finding is complicated by the technical limitations and potential for contamination introduced when dealing with low biomass samples. The current work sought to overcome those limitations to clarify the number, type and source of bacteria present in the lungs of normal mice. Results showed that the oral microbiome is diverse and highly conserved whereas murine lung samples fall into three distinct patterns. 33% of the samples were sterile, as they lacked culturable bacteria and their bacterial DNA content did not differ from background. 9% of samples contained comparatively higher amounts of bacterial DNA whose composition mimicked that detected in the URT. A final group (58%) contained smaller amounts of microbial DNA whose composition was correlating to that of rodent chow and cage bedding, likely acquired by inspiration of food and bedding fragments. By analyzing each sample independently rather than working with group averages, this work eliminated the bias introduced by aspiration-contaminated samples to establish that three distinct microbiome pneumotypes are present in normal murine lungs.


Molecular biomarkers for assessing the heat-adapted phenotype: a narrative scoping review.
Heat acclimation/acclimatisation (HA) mitigates heat-related decrements in physical capacity and heat-illness risk and is a widely advocated countermeasure for individuals operating in hot environments. The efficacy of HA is typically quantified by assessing the thermo-physiological responses to a standard heat acclimation state test (i.e. physiological biomarkers), but this can be logistically challenging, time consuming, and expensive. A valid molecular biomarker of HA would enable evaluation of the heat-adapted state through the sampling and assessment of a biological medium. This narrative review examines candidate molecular biomarkers of HA, highlighting the poor sensitivity and specificity of these candidates and identifying the current lack of a single 'standout' biomarker. It concludes by considering the potential of multivariable approaches that provide information about a range of physiological systems, identifying a number of challenges that must be overcome to develop a valid molecular biomarker of the heat-adapted state, and highlighting future research opportunities.


Rice OsYSL15 is an iron-regulated iron(III)-deoxymugineic acid transporter expressed in the roots and is essential for iron uptake in early growth of the seedlings.
Graminaceous plants take up iron through YS1 (yellow stripe 1) and YS1-like (YSL) transporters using iron-chelating compounds known as mugineic acid family phytosiderophores. We examined the expression of 18 rice (Oryza sativa L.) YSL genes (OsYSL1-18) in the epidermis/exodermis, cortex, and stele of rice roots. Expression of OsYSL15 in root epidermis and stele was induced by iron deficiency and showed daily fluctuation. OsYSL15 restored a yeast mutant defective in iron uptake when supplied with iron(III)-deoxymugineic acid and transported iron(III)-deoxymugineic acid in Xenopus laevis oocytes. An OsYSL15-green fluorescent protein fusion was localized to the plasma membrane when transiently expressed in onion epidermal cells. OsYSL15 promoter-beta-glucuronidase analysis revealed that OsYSL15 expression in roots was dominant in the epidermis/exodermis and phloem cells under conditions of iron deficiency and was detected only in phloem under iron sufficiency. These results strongly suggest that OsYSL15 is the dominant iron(III)-deoxymugineic acid transporter responsible for iron uptake from the rhizosphere and is also responsible for phloem transport of iron. OsYSL15 was also expressed in flowers, developing seeds, and in the embryonic scutellar epithelial cells during seed germination. OsYSL15 knockdown seedlings showed severe arrest in germination and early growth and were rescued by high iron supply. These results demonstrate that rice OsYSL15 plays a crucial role in iron homeostasis during the early stages of growth.


Misunderstanding in the classification of diabetes mellitus. What's in a name?
To assess whether physicians, residents, medical students, hospital diagnosis coders, and patients properly use the designations insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) that were established by criteria of the National Diabetes Data Group, we reviewed clinic and hospital records and administered questionnaires. Although essentially all cases of true IDDM were identified as such and most cases of NIDDM not requiring insulin therapy were correctly identified by all groups, patients with NIDDM on insulin therapy were misidentified as having IDDM by 38% of residents in internal medicine clinics and 68% of primary care and surgical subspecialty residents. On a survey, of 22 patients with NIDDM on insulin therapy, 17 (77%) considered themselves to have IDDM. Thus, patients who have NIDDM by the established criteria who are on insulin therapy are commonly mislabeled as having IDDM. We present an approach for dealing with this problem by adapting nomenclature focusing on insulin deficiency and resistance. It would probably also be helpful to separately identify the subset of patients with "insulin-deficient diabetes" who are ketosis-prone. It is important to use immunologic profiling (islet cell antibody testing) and insulin sensitivity or deficiency testing (C-peptide levels).


Dynamics and thermodynamics of systems with long-range dipole-type interactions.
A Hamiltonian mean field model, where the potential is inspired by dipole-dipole interactions, is proposed to characterize the behavior of systems with long-range interactions. The dynamics of the system remains in quasistationary states before arriving at equilibrium. The equilibrium is analytically derived from the canonical ensemble and coincides with that obtained from molecular dynamics simulations (microcanonical ensemble) at only long time scales. The dynamics of the system is characterized by the behavior of the mean value of the kinetic energy. The significance of the results, compared to others in the recent literature, is that two plateaus sequentially emerge in the evolution of the model under the special considerations of the initial conditions and systems of finite size. The first plateau decays to a different second one before the system reaches equilibrium, but the dynamics of the system is expected to have only one plateau when the thermodynamics limit is reached because the difference between them tends to disappear as N tends to infinity. Hence, the first plateau is a type of quasistationary state the lifetime of which depends on a power law of N and the second seems to be a true quasistationary state as reported in the literature. We characterize the general behavior of the model according to its dynamics and thermodynamics.


Severe headache trajectory following aneurysmal subarachnoid hemorrhage: the association with lower sodium levels.
A clinical hallmark of aneurysmal SAH (aSAH) is headache. Little is known about post-aSAH headache factors which may point to underlying mechanisms. In this study, we aimed to characterize the severity and trajectory of headaches in relation to clinical features of patients with aSAH. This is a retrospective longitudinal study of adult patients admitted to an academic tertiary care center between 2012 and 2019 with aSAH who could verbalize pain scores. Factors recorded included demographics, aneurysm characteristics, analgesia, daily morning serum sodium concentration, and occurrence of vasospasm. Group-based trajectory modeling was used to identify headache pain trajectories, and clinical factors were compared between trajectories. Of 91 patients included in the analysis, mean age was 57 years and 20 (22%) were male. Headache score trajectories clustered into two groups: patients with mild-moderate and moderate-severe pain. Patients in the moderate-severe pain group were younger (P<0.05), received more opioid analgesia (P<0.001), and had lower sodium concentrations (P<0.001) than patients in the mild-moderate pain group. We identified two distinct post-aSAH headache pain trajectory cohorts and identified an association with age, analgesia, and sodium levels. Future prospective studies considering sodium homeostasis and volume status under standardized analgesic regimens are warranted.


Evaluating the Effects of Flexible Learning about Aseptic Compounding on First-year Students in a Pharmacy Skills Laboratory.
To evaluate how flexible learning via online video review affects the ability and confidence of first-year (P1) pharmacy students to accurately compound aseptic preparations. Customary instructions and assignments for aseptic compounding were provided to students, who were given unlimited access to 5 short review videos in addition to customary instruction. Student self-confidence was assessed online, and faculty members evaluated students' aseptic technique at the conclusion of the semester. No significant difference on final assessment scores was observed between those who viewed videos and those who did not. Student self-confidence scores increased significantly from baseline, but were not significantly higher for those who viewed videos than for those who did not. First-year students performed well on final aseptic compounding assessments, and those who viewed videos had a slight advantage. Student self-confidence improved over the semester regardless of whether or not students accessed review videos.


Human cathepsin H.
Cathepsin H was purified from human liver by a method involving autolysis and acetone fractionation, and chromatography on DEAE-cellulose, Ultrogel AcA 54, hydroxyapatite and concanavalin A-Sepharose. The procedure allowed for the simultaneous isolation of cathepsin B and cathepsin D. Cathepsin H was shown to consist of a single polypeptide chain of 28 000 mol.wt., and affinity for concanavalin A-Sepharose indicated that it was a glycoprotein. The enzyme existed in multiple isoelectric forms, the two major forms having pI values of 6.0 and 6.4; it hydrolysed azocasein (pH optimum 5.5), benzoylarginine 2-naphthylamide (Ba-Arg-NNap), leucyl 2-naphthylamide (Arg-NNap), (pH optimum 6.8). Arg-NNap and Arg-NMec, unlike Bz-Arg-NNap-, were not hydrolysed by human cathepsin B. Cathepsin H was similar to cathepsin B in being irreversibly inactivated by exposure to alkaline pH. Sensitivity to chemical inhibitors by 1 microM-leupeptin, which gave essentially complete inhibition of the other lysosomal cysteine proteinases, cathepsins B and L.


Spatial and Temporal Epidemiological Assessment of Breast Cancer Incidence and Mortality in Kazakhstan, 1999-2013.
Breast cancer incidence and mortality in Kazakhstan are considered to be increasing but exact statistics have hitherto been lacking. The present study was therefore undertaken to retrospectively assess data for the whole country, accessed from the central registration office, for the period 1999-2013. Age standardized data for incidence and mortality were generated and compared across age groups. It was determined that during the studied period 45,891 new cases of breast cancer were registered and 20,122 women died of this pathology. Average breast cancer incidence and mortality were 37.9±1.10/105 and 16.7±0.20/105 respectively, and the overall ratio of mortality/incidence (M/I) was 0.44. Incidence tended to increase (T=+2.3%), and mortality to decrease (T of =-0.3%). Peaks of incidence and mortality were noted in those aged 60-74 years and 75-84, respectively. Particularly high incidences were established in large cities of Kazakhstan, Astana (46.8±1.80/105) and Almaty (49.7±1.30/105), and high mortality was observed in the Pavlodar region (17.9±0.60/105) and Almaty city (20.1±0.40/105). Considerable variation in the mortality/incidence ratio was noted, suggesting the need for more stress on access to screening and clinical care in some regions of the country.


Atmospheric pressure plasma jet-mouse skin interaction: Mitigation of damages by liquid interface and gas flow control.
The possible benefits of an atmospheric pressure plasma jet skin treatment have been tested in vivo on mouse skin. Many studies have been conducted in vitro on mouse skin cells, but only a few in vivo where, due to the complexity of the biological system, plasma can cause severe damages. For this reason, we investigated how kHz plasma generated in a jet that is known to inflict skin damage interacts with mouse skin and explored how we can reduce the skin damage. First, the focus was on exploring plasma effects on skin damage formation with different plasma gases and jet inclinations. The results pointed to the perpendicular orientation of a He plasma jet as the most promising condition with the least skin damage. Then, the skin damage caused by a He plasma jet was explored, focusing on damage mitigation with different liquid interfaces applied to the treatment site, adding N2 to the gas mixture, or alternating the gas flow dynamics by elongating the jet's glass orifice with a funnel. All these mitigations proved highly efficient, but the utmost benefits for skin damage reduction were connected to skin temperature reduction, the reduction in reactive oxygen species (ROS), and the increase in reactive nitrogen species (RNS).


Cooverexpression of EpCAM and c-myc genes in malignant breast tumours.
The overexpression of epithelial cell adhesion molecule (EpCAM), a proto-oncogene, affects progression, treatment, and diagnosis of many adenocarcinomas. C-myc has been shown to be a downstream target of EpCAM and is also one of the most important proto-oncogenes routinely overexpressed in breast cancer. However, cooverexpression of EpCAM and c-myc genes has not been investigated in breast cancer tissues, particularly in Iranian population. The aim of this study was to assess the expression of EpCAM and c-myc genes in malignant breast cancer tissues using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) followed by analyses of the association between the outcomes. In this study, 122 fresh tissues, including 104 malignant and 18 benign samples, were disrupted by mortar and pestle, and then the RNA was isolated from the samples and converted to cDNA. The relative expression levels of EpCAM and c-myc genes were measured by 2-ΔΔCt method using RT-qPCR. EpCAM protein level was also assessed in 66 cases using Western blot technique. Using RT-qPCR method, our results showed that EpCAM was overexpressed in 48% of malignant and 11.1% of benign samples. Evaluating EpCAM protein overexpression in a portion of samples depicted the fully concordance rate between Western blot and RT-qPCR techniques. C-myc expression was first evaluated by RT-qPCR method, showing the overexpression rate of 39% and 28% in malignant and benign samples, respectively. These data were also quite concordant with the clinically available immunohistochemistry reports of the same samples studied in this study. Importantly, overexpression of EpCAM and c-myc was significantly associated and showed an agreement of 57.3%. This study demonstrated the cooverexpression of EpCAM and c-myc in breast tumours collected from breast cancer patients of the Iranian population. EpCAM and c-myc positive cases were significantly associated with reduced and enhanced risk of ER/PR positivity respectively. However, both were associated with grade III of breast cancer.


Analysis of the Human Proteome in Subcutaneous and Visceral Fat Depots in Diabetic and Non-diabetic Patients with Morbid Obesity.
No longer regarded as simply a storage depot, fat is a dynamic organ acting locally and systemically to modulate energy homeostasis, glucose sensitivity, insulin resistance, and inflammatory pathways. Here, mass spectrometry was used to survey the proteome of patient matched subcutaneous fat and visceral fat in 20 diabetic vs 22 nondiabetic patients with morbid obesity. A similar number of proteins (~600) were identified in each tissue type. When stratified by diabetic status, 19 and 41 proteins were found to be differentially abundant in subcutaneous fat and omentum, respectively. These proteins represent pathways known to be involved in metabolism. Five of these proteins were differentially abundant in both fat depots: moesin, 78 kDa glucose-regulated protein, protein cordon-bleu, zinc finger protein 611, and cytochrome c oxidase subunit 6B1. Three proteins, decorin, cytochrome c oxidase subunit 6B1, and 78 kDa glucose-regulated protein, were further tested for validation by western blot analysis. Investigation of the proteins reported here is expected to expand on the current knowledge of adipose tissue driven biochemistry in diabetes and obesity, with the ultimate goal of identifying clinical targets for the development of novel therapeutic interventions in the treatment of type 2 diabetes mellitus. To our knowledge, this study is the first to survey the global proteome derived from each subcutaneous and visceral adipose tissue obtained from the same patient in the clinical setting of morbid obesity, with and without diabetes. It is also the largest study of diabetic vs nondiabetic patients with 42 patients surveyed.


The role of basal forebrain cholinergic neurons in fear and extinction memory.
Cholinergic input to the neocortex, dorsal hippocampus (dHipp), and basolateral amygdala (BLA) is critical for neural function and synaptic plasticity in these brain regions. Synaptic plasticity in the neocortex, dHipp, ventral Hipp (vHipp), and BLA has also been implicated in fear and extinction memory. This finding raises the possibility that basal forebrain (BF) cholinergic neurons, the predominant source of acetylcholine in these brain regions, have an important role in mediating fear and extinction memory. While empirical studies support this hypothesis, there are interesting inconsistencies among these studies that raise questions about how best to define the role of BF cholinergic neurons in fear and extinction memory. Nucleus basalis magnocellularis (NBM) cholinergic neurons that project to the BLA are critical for fear memory and contextual fear extinction memory. NBM cholinergic neurons that project to the neocortex are critical for cued and contextual fear conditioned suppression, but are not critical for fear memory in other behavioral paradigms and in the inhibitory avoidance paradigm may even inhibit contextual fear memory formation. Medial septum and diagonal band of Broca cholinergic neurons are critical for contextual fear memory and acquisition of cued fear extinction. Thus, even though the results of previous studies suggest BF cholinergic neurons modulate fear and extinction memory, inconsistent findings among these studies necessitates more research to better define the neural circuits and molecular processes through which BF cholinergic neurons modulate fear and extinction memory. Furthermore, studies determining if BF cholinergic neurons can be manipulated in such a manner so as to treat excessive fear in anxiety disorders are needed.


What are cultural attractors?
Concepts from cultural attractor theory are now used in domains far from their original home in anthropology and cultural evolution. Yet these concepts have not been consistently characterised. I here distinguish four ways in which the cultural attractor concept has been used and identify three kinds of factors of attraction typically appealed to. Clarifying these explanatory concepts identifies problems and ambiguities in the work of cultural epidemiologists and commentators alike.


Cannabis constituents reduce seizure behavior in chemically-induced and scn1a-mutant zebrafish.
Current antiepileptic drugs (AEDs) are undesirable for many reasons including the inability to reduce seizures in certain types of epilepsy, such as Dravet syndrome (DS) where in one-third of patients does not respond to current AEDs, and severe adverse effects that are frequently experienced by patients. Epidiolex, a cannabidiol (CBD)-based drug, was recently approved for treatment of DS. While Epidiolex shows great promise in reducing seizures in patients with DS, it is used in conjunction with other AEDs and can cause liver toxicity. To investigate whether other cannabis-derived compounds could also reduce seizures, the antiepileptic effects of CBD, Δ9-tetrahydrocannabinol (THC), cannabidivarin (CBDV), cannabinol (CBN), and linalool (LN) were compared in both a chemically-induced (pentylenetetrazole, PTZ) and a DS (scn1Lab-/-) seizure models. Zebrafish (Danio rerio) that were either wild-type (Tupfel longfin) or scn1Lab-/- (DS) were exposed to CBD, THC, CBDV, CBN, or LN for 24 h from 5 to 6 days postfertilization. Following exposure, total distance traveled was measured in a ViewPoint Zebrabox to determine if these compounds reduced seizure-like activity. Cannabidiol (0.6 and 1 μM) and THC (1 and 4 μM) significantly reduced PTZ-induced total distance moved. At the highest THC concentration, the significant reduction in PTZ-induced behavior was likely the result of sedation as opposed to antiseizure activity. In the DS model, CBD (0.6 μM), THC (1 μM), CBN (0.6 and 1 μM), and LN (4 μM) significantly reduced total distance traveled. Cannabinol was the most effective at reducing total distance relative to controls. In addition to CBD, other cannabis-derived compounds showed promise in reducing seizure-like activity in zebrafish. Specifically, four of the five compounds were effective in the DS model, whereas in the PTZ model, only CBD and THC were, suggesting a divergence in the mode of action among the cannabis constituents.


Spectrum of sleep disorders in a patient with spinocerebellar ataxia 13.
We report the case of a 52-year-old female with spinocerebellar ataxia (SCA) 13. She presented with complaints of insomnia and had a history of restless legs syndrome. Her polysomnogram revealed that she had a significantly elevated periodic limb movement index, mild obstructive sleep apnea, and the absence of REM sleep. Sleep disorders have previously been described in patients with SCA 1, SCA 2, SCA 3, and SCA 6. To our knowledge, this is the first description of sleep disorders in a patient with SCA 13.


Interhemispheric subdural haematomas: seven cases and review of the literature.
Interhemispheric subdural haematoma (ISH) is a rare complication of head injury with only 19 cases reported since 1940, but it may also occur spontaneously (three cases). In both circumstances, clotting disorders are frequent (six cases). We have recorded seven cases (five traumatic, two spontaneous). Classically ISH is due to tearing of bridging veins or cortical contusions. In one of our cases, it was due to arterial bleeding from a pericallosal branch. CT scan shows that ISH may extend above the tentorium and on the hemispheric convexity. Mortality is high (35%). The best operative procedure is parasagittal craniotomy. Chronic interhemispheric subdural haematomas also occur.


Biogeography of a Novel Ensifer meliloti Clade Associated with the Australian Legume Trigonella suavissima.
Here, we describe a novel clade within Ensifer meliloti and consider how geographic and ecological isolation contributed to the limited distribution of this group. Members of the genus Ensifer are best known for their ability to form nitrogen-fixing symbioses with forage legumes of three related genera, Medicago L., Melilotus Mill., and Trigonella L., which are members of the tribe Trifolieae. These legumes have a natural distribution extending from the Mediterranean Basin through western Asia, where there is an unsurpassed number of species belonging to these genera. Trigonella suavissima L. is unusual in that it is the only species in the tribe Trifolieae that is native to Australia. We compared the genetic diversity and taxonomic placement of rhizobia nodulating T. suavissima with those of members of an Ensifer reference collection. Our goal was to determine if the T. suavissima rhizobial strains, like their plant host, are naturally limited to the Australian continent. We used multilocus sequence analysis to estimate the genetic relatedness of 56 T. suavissima symbionts to 28 Ensifer reference strains. Sequence data were partitioned according to the replicons in which the loci are located. The results were used to construct replicon-specific phylogenetic trees. In both the chromosomal and chromid trees, the Australian strains formed a distinct clade within E. meliloti The strains also shared few alleles with Ensifer reference strains from other continents. Carbon source utilization assays revealed that the strains are also unusual in their ability to utilize 2-oxoglutarate as a sole carbon source. A strategy was outlined for locating similar strains elsewhere.IMPORTANCE In this study, we employed a biogeographical approach to investigate the origins of a symbiotic relationship between an Australian legume and its nitrogen-fixing rhizobia. The question of the ancestral origins of these symbionts is based on the observation that the legume host is not closely related to other native Australian legumes. Previous research has shown that the legume host Trigonella suavissima is instead closely related to legumes native to the Mediterranean Basin and western Asia, suggesting that it may have been introduced in Australia from those regions. This led to the question of whether its rhizobia may have been introduced as well. In this study, we were unable to find persuasive evidence supporting this hypothesis. Instead, our results suggest either that the T. suavissima rhizobia are native to Australia or that our methods for locating their close relatives elsewhere are inadequate. A strategy to investigate the latter alternative is proposed.


The Relationship Between Vertical Facial Type and Maxillary Anterior Alveolar Angle in Adults Using Cone-Beam Computed Tomography.
Background Cone-beam computed tomography (CBCT) imaging provides detailed and thorough information about the dentofacial complex. However, not all aspects have been yet explored among different types of malocclusion. The maxillary anterior alveolus is one of the components of the maxillary bone which affects the upper lip position and the esthetics of the smile. The inclination of this alveolus may vary between the different vertical growth patterns of patients who may seek orthodontic treatment. The objective of this study was to investigate possible differences in maxillary anterior alveolar angle (MAAA) among orthodontically untreated adults with different vertical facial types in a Syrian sample. Methods CBCT images of 84 orthodontically untreated adult patients were included. Three groups of vertical facial type (n=28 for each group; 14 males, 14 females) were created using disproportionate multi-stratified random sampling. CBCT-derived lateral cephalograms were used to categorize the patients into three groups. Measurements were made at three regions (region 1 (R1), region 2 (R2), and region 3 (R3)), located in the maxillary anterior alveolar bone using OnDemand3D™ software (Cypermed Inc., Seoul, South Korea). Results No significant differences in the mean MAAA were detected between females and males for the three measured regions in all groups. Analysis of variance showed significant inter-group differences in the MAAA (p<0.05) for all measured regions. The hyperdivergent facial type group had the greatest MAAA mean value of 68.72° (± 6.01), 67.30° (± 4.15), and 68.01° (± 5.12) at R1 in the female, male, and the entire sample of both sexes respectively. Whereas the hypodivergent facial type group had the least mean MAAA values of 58.47° (± 5.34) at R3, 59.83° (± 6.23) at R2, and 59.23° (± 5.75) at R3 in the female, male, and the entire sample of both sexes respectively. Conclusions The maxillary anterior alveolar bone was more buccally inclined in the hypodivergent facial type. The MAA bone inclination did not differ between females and males in the same vertical facial type group.


DeepBranch: Deep Neural Networks for Branch Point Detection in Biomedical Images.
Morphology reconstruction of tree-like structures in volumetric images, such as neurons, retinal blood vessels, and bronchi, is of fundamental interest for biomedical research. 3D branch points play an important role in many reconstruction applications, especially for graph-based or seed-based reconstruction methods and can help to visualize the morphology structures. There are a few hand-crafted models proposed to detect the branch points. However, they are highly dependent on the empirical setting of the parameters for different images. In this paper, we propose a DeepBranch model for branch point detection with two-level designed convolutional networks, a candidate region segmenter and a false positive reducer. On the first level, an improved 3D U-Net model with anisotropic convolution kernels is employed to detect initial candidates. Compared with the traditional sliding window strategy, the improved 3D U-Net can avoid massive redundant computations and dramatically speed up the detection process by employing dense-inference with fully convolutional neural networks (FCN). On the second level, a method based on multi-scale multi-view convolutional neural networks (MSMV-Net) is proposed for false positive reduction by feeding multi-scale views of 3D volumes into multiple streams of 2D convolution neural networks (CNNs), which can take full advantage of spatial contextual information as well as fit different sizes. Experiments on multiple 3D biomedical images of neurons, retinal blood vessels and bronchi confirm that the proposed 3D branch point detection method outperforms other state-of-the-art detection methods, and is helpful for graph-based or seed-based reconstruction methods.


Evaluation of the Denture Impact on the Palatal Rugae: An Original Research.
The palatal rugae may alter their shape based on the various physical pressures that they had to endure. This study's objective is to assess the various alterations in the palatal rugae parameters among the complete denture wearers. Forty subjects in all were chosen for the study. The control group interventional groups had an equal number of participants who were further equally distributed based on gender. For all of the participants, mucostatic maxillary alginate imprints were taken, and gypsum castings were created. They were called at the scheduled intervals of 2, 6, and 12 months following the treatment. The models used during those recalls and all of the palatal rugae were examined under a microscope for quantity, length, form, orientation, and unifications. The unpaired t-test was used to statistically examine palatal rugae alterations. Following the wear of the dentures, the experimental group's primary, secondary, and fragmented rugae all gradually shrank in length. In terms of statistics, the alteration solely affected primary rugae and was significant (P < 0.001). After a year of wearing dentures, a minimal change in rugae's form was noticed in the denture groups, but it was statistically not substantial (P > 0.05). Due to the prolonged mechanical stress the dentures placed on the palatal rugae, complete denture users saw a significant reduction in the length of their primary rugae. Rugae number, orientation, and unification were among the other criteria that did not change during the course of the study. Analysis of the palatal rugae may not be useful in identifying people wearing full dentures. However, in forensic investigations, rugae may act as an adjunct to other methods like fingerprints and DNA analysis.


A predictor index for hospitalization for patients with acute asthmatic attack.
Thirty-nine patients, aged 14 to 50 years (mean 33), were treated for an acute asthmatic attack in the hospital emergency room. A scored index was estimated on admission for each patient, based on pulse, respiratory and peak expiratory flow rates (PEFR), amplitude of paradoxical pulse and degree of dyspnea, wheezing and accessory muscle use. All patients were treated according to a standard protocol including oxygen, fluids, salbutamol inhalations and aminophylline infusions, with hydrocortisone infusion in selected patients. The decision to hospitalize of discharge was based on clinical grounds and was taken after 4 to 8 h of treatment without prior knowledge of the patient's index. The mean index of 13 hospitalized patients (Group 1) was 4.5 +/- 1.7 (mean +/- 2 SD), compared with 4.3 +/- 1.3 of 7 patients who were discharged but returned for additional treatment within 10 days (Group 2). Both indices were significantly higher than that of 19 patients who were discharged and remained well (2.5 +/- 1.5) (Group 3). The most important differentiating parameters were the degree of dyspnea, wheezing and PEFR. We conclude that patients with scored indices of greater than 4 should be hospitalized immediately, those with indices less than 4 could probably be discharged with relative safety, and patients with an index of 4 should be considered individually, with dyspnea, wheezing and PEFR being the major criteria for the decision.


Alterations in Faecal and Serum Metabolic Profiles in Patients with Neovascular Age-Related Macular Degeneration.
Neovascular age-related macular degeneration (nAMD) is a common and multifactorial disease in the elderly that may lead to irreversible vision loss; yet the pathogenesis of AMD remains unclear. In this study, nontargeted metabolomics profiling using ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry was applied to discover the metabolic feature differences in both faeces and serum samples between Chinese nonobese subjects with and without nAMD. In faecal samples, a total of 18 metabolites were significantly altered in nAMD patients, and metabolic dysregulations were prominently involved in glycerolipid metabolism and nicotinate and nicotinamide metabolism. In serum samples, a total of 29 differential metabolites were founded, involved in caffeine metabolism, biosynthesis of unsaturated fatty acids, and purine metabolism. Two faecal metabolites (palmitoyl ethanolamide and uridine) and three serum metabolites (4-hydroxybenzoic acid, adrenic acid, and palmitic acid) were selected as potential biomarkers for nAMD. Additionally, the significant correlations among dysregulated neuroprotective, antineuroinflammatory, or fatty acid metabolites in faecal and serum and IM dysbiosis were found. This comprehensive metabolomics study of faeces and serum samples showed that alterations in IM-mediated neuroprotective metabolites may be involved in the pathophysiology of AMD, offering IM-based nutritional therapeutic targets for nAMD.


A systematic review of the epidemiology of multiple sclerosis in South America.
Hundreds of publications dealing with the prevalence of multiple sclerosis (MS) throughout the world exist, but little data have been published from South America. Epidemiological studies of MS vary according to environmental, racial and genetic factors; a better understanding of MS in South America would help us to elucidate the disease pattern in this population. The aim of this study is to review the evidence relevant to MS epidemiology in South America. We performed a systematic review of articles of MS epidemiology in South America, with special emphasis on those providing information on the incidence and prevalence of MS (population-based studies). Six papers provided information on MS epidemiology. One paper used the capture-recapture methodology, while the remainder employed traditional methods to collect the data. Population-based studies showed an MS prevalence rate ranging from 1.48 to 17 per 100 000 inhabitants. Available data suggest that the prevalence of MS is lower in South America than in developed countries. The reason for this observation is unknown. Some investigators suggest that certain environmental factors like sun exposure and vitamin D supplementation or the called 'hygiene hypothesis' may protect this population. Future studies will contribute to elucidate the etiology of that difference.


Pre-surgical Provisional Prosthesis for Immediate Non-occlusal-loaded Flapless Implant.
A 49-year-old patient reported for immediate replacement of missing maxillary anterior teeth with implant-retained prosthesis. Elevation of flap alters the mucosal level, causes discomfort, and delays the restorative procedure. To maintain the esthetics, flapless surgery was planned. Since placement of an implant is pre-planned in a predetermined site, fabrication of the prostheses before commencement of the surgery, especially when replacing the teeth in the anterior region, could be a viable option. This case report explains the method of fabrication of the provisional restoration for flapless surgery in the presurgical phase. The technique would avoid any micromotion and implant instability caused due to abutment preparation and impression procedure postsurgically.


Isotachophoretic Fluorescence in Situ Hybridization of Intact Bacterial Cells.
A counter-pressure-assisted capillary isotachophoresis method in combination with a sieving matrix and ionic spacer was used to perform in-line fluorescence in situ hybridization (FISH) of bacterial cells. A high concentration of sieving matrix (1.8% w/v HEC) was introduced at one end of the capillary, and the bacterial cells were suspended in the spacer electrolyte for injection. Using a 2 min injection with 18 psi counter-pressure, 50% of the cells injected into the capillary were hybridized with the fluorescently labeled oligonucleotide, and the excess unhybridized probe was separated from the hybridized cell-probe complexes in a two-stage ITP method. With an LOD (6.0 × 104 cells/mL) comparable with the CE analysis of a sample processed using an off-line FISH protocol, the total analysis time was reduced from 2.5 h to 30 min. Provided the appropriate probe is selected, this approach can be used for specific detection of bacterial cells in aqueous samples.


Low endotoxin recovery and its impact on endotoxin detection.
Endotoxin exists on the outer membrane of Gram-negative bacteria and poses risks to human health by triggering a series of immune responses. Therefore, its accurate detection is essential. The Limulus amoebocyte lysate (LAL) test is the most pharmacopeia-recognized and popular technique for endotoxin detection. Despite its wide industry adoption, the low endotoxin recovery (LER) phenomenon can compromise the LAL test's reliability. This review summarizes the possible reasons attributing to the LER phenomenon from three different perspectives: the endotoxin standards used in hold time study, protein active pharmaceutical ingredients, and excipients. Potential mechanisms and strategies to mitigate the LER phenomenon are also discussed as presented by different research groups.


[Use of cloridarol in coronary insufficiency].
The therapeutical activity of a new oral drug with a coronaric and myocardiotrophic action of choice, 2-benzofuryl-p-chlorophenyl-carbinol (Menacor, Menarini) in 20 patients with chronic coronary insufficiency was studied by administering 750 mg/day for at least 20 days. General and gastroenteric tolerance was excellent, while good or fair therapeutic results were obtained in 16 cases (80%). It is felt that the drug can be usefully employed in the management of coronary insufficiency.


Resonance energies of vinylcarbenes.
The stabilization energy provided by resonance in singlet and triplet vinylcarbenes is evaluated using density functional and G3 theory, without symmetry restriction. Structural and charge change upon rotation are reviewed with singlet vinylcarbene exhibiting a larger barrier (1s-TS-1s-E), 5.49 (7.10) kcal/mol, than triplet (1t-TS-1t-E), 4.06 (4.54) kcal/mol. The changes in charge upon rotation for singlet vinylcarbene are consistent with a simple resonance picture for the ground state, whereas there is insignificant charge change for the triplet. Difficulties of the rotational analysis are avoided by evaluating the inductive stabilization difference between ethyl and vinyl in isodesmic equation 1. This inductive difference was determined by comparing the energy change for hydrogen loss for polyene series 2 (n double bonds) with polyene series 3 (n double bonds), which are combined in isodesmic equation 4. The effect of the ultimate vinyl group in equation 2 is restricted to inductive interaction by holding its pi-system so it is orthogonal to the remaining pi-system. Extrapolation of plots of the inductive difference (Delta inductive) revealed for equation 4 versus a through-bond inductive attenuation of 1.75(-2n) to n = 0 provides a Delta inductive for singlet vinylcarbene of -4.52 kcal/mol (R = 0.995) at B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d) + ZPE at B3LYP/6-31G(d) and -4.16 (R = 0.993) at the G3(MP2)//B3LYP level. Correcting for Delta inductive in eq 1, the resonance energy of singlet vinylcarbene is 9.2 (8.9) kcal/mol. An analogous analysis of triplet vinylcarbene suggests that inductive effects are 0-1 kcal/mol, which leads to a resonance energy of 11-14 kcal/mol.


Expressions of polypeptide: N-acetylgalactosaminyltransferase in leukemia cell lines during 1,25-dihydroxyvitamin D3 induced differentiation.
The effect of 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D3] on two leukemia cell lines, K562 and SHI-1, and its relation to the expression of different subtypes of polypeptide: N-acetylgalactosaminyltransferase (pp-GalNAc-T) was studied. With morphological and cell flow-cytometric method, it was found that 1,25(OH)(2)D3 induced the differentiation of both leukemia cell lines toward monocytic lineage, but not affected the cell growth and apoptosis. The expressions of different subtypes of pp-GalNAc-T, the initial glycosyltransferase in O-glycan synthesis, were studied with RT-PCR before and after the treatment of different concentrations of 1,25(OH)(2)D3. Among fourteen subtypes of pp-GalNAc-T (T1 approximately T14), K562 cells obviously expressed pp-GalNAc-T2, T4, T5, T7 (T2 was the highest) and SHI-1 cells apparently expressed pp-GalNAcT1, T2, T3 and T4 (T4 was the highest) only. After K562 cells were treated 1, 25(OH)(2)D3 for 72 h, pp-GalNAc-T2, T4, T5, T7 were increased in a dose dependent manner. In contrast, pp-GalNAc-T1 and T2, especially T1, were up-regulated in SHI-1 cells by 1,25(OH)(2)D3, but T3 was unchanged and T4 was down-regulated. The different alterations of pp-GalNAc-Ts in these two cell lines were probably related to the different structural changes of O-glycans during 1,25(OH)(2)D3 induced differentiation.


Genotype Distribution and Antibiotic Susceptibility Pattern of Clinical Isolates of Group B Streptococcus in a Tertiary Care Hospital in Puducherry, South India.
Streptococcus agalactiae apart from being a colonizer in the genital region is also associated with several other invasive infections in all age groups. With the varied distribution of serotypes across different regions of the world, universal vaccination is also unattainable. However, in India, the knowledge of group B Streptococcus (GBS) genotype distribution is deficient. Thus, this study was initiated to add data on this aspect. Methodology. A cross-sectional study was conducted using isolates of group B Streptococcus from all clinical specimens. Along with that, the clinical specimen type and the antibiotic resistance profile of the isolates were correlated with the genotypes recognized through a multiplex PCR assay. Among the 86 isolates subjected to multiplex PCR for genotype identification, five genotypes were identified with genotype Ib as the predominant one (34.9%), followed by III (20.9%), II (16.3%), Ia (12.7%), and V (11.6%). The results demonstrated a correlation of types Ib and III with vaginal colonization and type II with urine specimens in the current study. This preliminary study exhibited the distribution of common genotypes and their antibiotic resistance profiles in various GBS isolates. However, multiple studies across the country with larger sample sizes are needed to validate these findings.


[On the origin and diagnostic value of the CSF-beta-globulins (author's transl)].
208 cerebrospinal fluid samples were taken from patients having various patterns of neurological diseases. The following beta-globulins: transferrin, haemopexin, beta-1 A-globulin, beta-1 E-globulin, beta-2-glycoproteid and beta-lipoproteid were determined immunologically quantitatively in the CSF and partly quantitatively in the serum, and their behaviour was compared with that of the beta and tau fraction in CSF electrophoresis. It was found that changes in the fractions in CSF electrophoresis agreed only slightly with those of the quantitatively determined globulins, although these globulins represent 70--80% of the beta and tau fraction. Increases in the number of beta-1 A and beta-1 E-globulins are more significantly marked in intracranial haemorrhages than with other diseases. In all other respects, increases or decreases in the number of beta-globulins do not appear to be typical of any particular disease pattern determined by electrophoresis or quantitatively. Due to the linearity of the changes in case of disturbances of the CSF barrier, and also on account of the absolutely parallel behaviour of the beta-globulins, it was concluded that transferrin--contrary to the opinion held so far--is produced cerebrally in only small quantities or possibly not at all, and that the entirety of beta-globulins originate from the serum.


Could stress cause psychosis in individuals vulnerable to schizophrenia?
It has long been considered that psychosocial stress plays a role in the expression of symptoms in schizophrenia (SZ), as it interacts with latent neural vulnerability that stems from genetic liability and early environmental insult. Advances in the understanding of the neurobiology of the stress cascade in both animal and human studies lead to a plausible model by which this interaction may occur: through neurotoxic effects on the hippocampus that may involve synaptic remodeling. Of late, the neurodevelopmental model of SZ etiology has been favored. But an elaboration of this schema that credits the impact of postnatal events and considers a role for neurodegenerative changes may be more plausible, given the evidence for gene-environment interaction in SZ expression and progressive structural changes observed with magnetic resonance imaging. Furthermore, new insights into nongliotic neurotoxic effects such as apoptosis, failure of neurogenesis, and changes in circuitry lead to an expansion of the time frame in which environmental effects may mediate expression of SZ symptoms.


Extending the Construct Network of Trait Disinhibition to the Neuroimaging Domain: Validation of a Bridging Scale for Use in the European IMAGEN Project.
Trait disinhibition, a clinical-liability construct, has well-established correlates in the diagnostic, self-rating, task-behavioral, and brain potential response domains. Recently, studies have begun to test for neuroimaging correlates of this liability factor, but more work of this type using larger data sets is needed to clarify its brain bases. The current study details the development and validation of a scale measure of trait disinhibition composed of questionnaire items available in the IMAGEN project, a large-scale longitudinal study of factors contributing to substance abuse that includes clinical interview, self-report personality, task-behavioral, neuroimaging, and genomic measures. Using a construct-rating and psychometric refinement approach, a scale was developed that evidenced: (a) positive relations with interview-assessed psychopathology in the IMAGEN sample, both concurrently and prospectively and (b) positive associations with scale measures of disinhibition and reported psychopathology, and a robust negative correlation with P3 brain response, in a separate adult sample ( Mage = 19.5). These findings demonstrate that a common scale measure can index this construct from adolescence through to early adulthood, and set the stage for systematic work directed at identifying neural and genetic biomarkers of this key liability construct using existing and future data from the IMAGEN project.


Permanent education in the vaccination room: what is the reality?
To understand, from the perspective of the professional, the Permanent Education (PE) in the vaccination room in its real context. Multiple holistic-qualitative case studies, based on Maffesoli's Interpretive Sociology with 56 participants from four microregions of the Western Extended Region of Minas Gerais State. They present PE as infrequent and insufficient. They denote that the practical-theoretical experience with vaccine contributes to the work; the search for knowledge, starting from the professional itself; and the professional training fails to perform in the vaccination room. The notions of PE are linked to the daily needs of individuals and services, with indication of being interactive, periodic, in specific and non-global issues for better assimilation. Obstacles to the non-implementation of PEH are realized by the workload associated with insufficient human resources, the distance of the nurses from the vaccination room and the lack of support from the higher levels.


[Utilization of health care resources and cost associated to fasciectomy in Dupuytren's disease in Spain].
To estimate the healthcare resource utilization and their associated costs secondary to fasciectomy of Dupuytren s disease (DD) treated under usual medical practice in Spain. This multicenter, observational, retrospective cohort study, extracted data through the revision of medical records of three tertiary public hospitals. Each center should recruit 40 patients operated for DD, as principal diagnose of Minimum Data Set, in which the surgical procedure conducted was fasciectomy, during 2007-2009. To collect all the resources used during surgery, a specific chart form was designed. Demographic (age, gender, occupational status), clinical (stage of contracture and comorbilities) and healthcare utilization (hospitalizations, medical visits, tests, drugs) data were collected under medical routine. Comparisons between stage of contracture grouped (I: stage N, 1 & 2; II: stage 3 & 4) and centers were made. A total of 123 subjects (52% group I; 86.2% men; 35.8% active workers) were identified. 81.3% of patients presented at least one comorbidity, being hypertension the most frequent. 28.4% of patients were operated in ambulatory surgery and 71.6% hospitalized. All the patients had follow-up visits after surgery, 27% needed physical therapy, 88% performed preoperative tests and 8% visit the emergency room after surgery. Healthcare mean (SD) costs were as follows: fasciectomy €1,074 (0); hospitalizations €978 (743); ambulatory €186 (10); follow-up visits €260 (173); emergency rooms €13 (53); tests €78(43); drugs €7 (9); physical therapy €46 (134). Mean total costs were €2,250 (839). There were no significant differences between study groups grouped by stage of contracture. However, the center and the severity of the CD seem explanatory variables of cost, p<0.05. Healthcare resources utilization for surgical treatment of Dupuytren's disease may cost €2,250 (839) per fasciectomy treated under usual medical practice.


Transduction of Escherichia coli in soil.
Bacteriophage P1-mediated generalized transduction of Escherichia coli K-12 was assessed in nonsterile soil. Auxotrophic recipient cells (thr- leu- thi- rpsL) were incubated in a sandy and a silty clay loam soil, and the transducing phage lysates from prototrophic strains carrying transposon 10(Tn10) in either purE or aroL regions were added. At intervals, the bacterial populations derived from the soils were plated on selective-differential media to enumerate prototrophic (thr+, leu+, or Tcr) transductants. Of 100 bacterial isolates obtained on the selective-differential media, 58 (14 thr+; 11, leu+; 33 Tcr) were confirmed E. coli transductants. The frequency of transduction in soil was ca. 10(-6). These data demonstrate the potential use of bacteriophage P1 to genetically manipulate E. coli in situ.


The Ras inhibitor farnesylthiosalicylic acid as a potential therapy for neurofibromatosis type 1.
Farnesylthiosalicylic acid (FTS) is a Ras inhibitor that dislodges all active Ras isoforms from the membrane. We assessed the ability of FTS to reverse the transformed phenotype of neurofibromatosis type 1 (NF1)-associated tumor cell lines of malignant peripheral nerve sheath tumor (MPNST). nf1 mutations were genotyped, allelic losses were analyzed, and neurofibromin expression levels were determined in MPNST cell lines ST88-14, S265P21, and 90-8. The effects of FTS on GTP-bound Ras (Ras-GTP) and its prominent downstream targets, as well as on cell morphology, anchorage-dependent and anchorage-independent growth, and tumor growth in mice, were assessed. The MPNST cell lines were biallelic, NF1 inactive, and neurofibromin deficient. We show that FTS treatment shortened the relatively long duration of Ras activation and signaling to extracellular signal-regulated kinase, Akt, and RalA in all NF1-deficient MPNST cell lines (NF1 cells) to that observed in a non-NF1, normally expressing neurofibromin MPNST cell line. These effects of FTS led to lower steady-state levels of Ras-GTP and its activated targets. Both anchorage-dependent and anchorage-independent growth of NF1 cells were dose dependently inhibited by FTS, and the inhibition correlated positively with Ras-GTP levels. NF1 cells were found to possess strong actin stress fibers, and this phenotype was also corrected by FTS. NF1 tumor growth in a nude mouse model was inhibited by oral FTS. FTS treatment of NF1 cells normalized Ras-GTP levels, resulting in reversal of the transformed phenotype and inhibition of tumor growth. FTS may therefore be considered as a potential drug for the treatment of NF1.


Hydrolyzed milk-serum peptides reduce body weight and fat content of dietary obese rats ameliorating their antioxidant status and liver functions.
Recent studies suggested that weight reduction under energy restriction required protein supplementation. Moreover, a significant decrease in serum cholesterol and triglycerides was observed when milk-serum proteins and, in particular, their hydrolyzed peptides were compared to milk casein. Six Sprague-Dawley rats were fed with the standard diet for 8 weeks. Eighteen rats were fed with the obesity- producing diet for 4 weeks. After this period and for the remaining 4 weeks, these rats were divided into 3 groups, the 1st was fed with the obesity-diet, the 2nd and the 3rd were fed with the casein--and with the hydrolyzed milk-serum peptides--restricted diet, respectively. Treatment with the obesity-diet, compared to standard-diet, induced an increase in the body weight and fat content, with a decrease in protein mass and dehydration state. There was also an increase in blood levels of cholesterol, triglycerides and glucose. The lipoperoxides content in the plasma, heart, brain and liver had also increased, while the content of glutathione and ATP and the membrane fluidity in the liver had significantly decreased. The administration of the restricted caloric diet, in particular the one containing the hydrolyzed peptides were capable of an improvement of all these parameters. The metabolic modifications induced by the hydrolyzed peptides-restricted diet contribute to control better the over-weight thus reducing the risk of the onset of the dismetabolic pathologies correlated to it.


Fabrication of capacitive acoustic resonators combining 3D printing and 2D inkjet printing techniques.
A capacitive acoustic resonator developed by combining three-dimensional (3D) printing and two-dimensional (2D) printed electronics technique is described. During this work, a patterned bottom structure with rigid backplate and cavity is fabricated directly by a 3D printing method, and then a direct write inkjet printing technique has been employed to print a silver conductive layer. A novel approach has been used to fabricate a diaphragm for the acoustic sensor as well, where the conductive layer is inkjet-printed on a pre-stressed thin organic film. After assembly, the resulting structure contains an electrically conductive diaphragm positioned at a distance from a fixed bottom electrode separated by a spacer. Measurements confirm that the transducer acts as capacitor. The deflection of the diaphragm in response to the incident acoustic single was observed by a laser Doppler vibrometer and the corresponding change of capacitance has been calculated, which is then compared with the numerical result. Observation confirms that the device performs as a resonator and provides adequate sensitivity and selectivity at its resonance frequency.


Assessment of nutritional status of pre-schoolers in slum areas of Udaipur City.
The present study was conducted in pre-schoolers (2-6 years) from ten different slums of Udaipur City in Rajasthan with the aim to their nutritional status. From the data collected and observations recorded was observed that majority of the subjects were from nuclear family with monthly family income of less than Rs.1500/-. Developmental pattern of these subjects indicated that the height with age of bothe male and female subjects increased, however, their body weight did not increase. More than 50% of these pre-schoolers showed symptoms of protein energy malnutrition and anaemia, while 22% had pigeon chest deformity due to vitamin D and calcium deficiency. Classification for degree of malnutrition as per IAP showed that majority of these subjects (66%) were under weight (Grade I and II). Waterlow's classification revealed that majority of these pre-schoolers were wasted (30%) or wasted and Stunted (42%). This malnutrition was either of PCM (past chronic) or CLM (current long duration) type as per Seoane and Latham's classification.


Surface-Localized Sealing of Porous Ultralow-k Dielectric Films with Ultrathin (<2 nm) Polymer Coating.
Semiconductor integrated circuit chip industries have been striving to introduce porous ultralow-k (ULK) dielectrics into the multilevel interconnection process in order to improve their chip operation speed by reducing capacitance along the signal path. To date, however, highly porous ULK dielectrics (porosity >40%, dielectric constant (k) <2.4) have not been successfully adopted in real devices because the porous nature causes many serious problems, including noncontinuous barrier deposition, penetration of the barrier metal, and reliability issues. Here, a method that allows porous ULK dielectrics to be successfully used with a multilevel interconnection scheme is presented. The surface of the porous ULK dielectric film (k = 2.0, porosity ∼47%) could be completely sealed by a thin (<2 nm) polymer deposited by a multistep initiated chemical vapor deposition (iCVD) process. Using the iCVD process, a thin pore-sealing layer was localized only to the surface of the porous ULK dielectric film, which could minimize the increase of k; the final effective k was less than 2.2, and the penetration of metal barrier precursors into the dielectric film was completely blocked. The pore-sealed ULK dielectric film also exhibited excellent long-term reliability comparable to a dense low-k dielectric film.


Evolutionary minority game: the roles of response time and mutation threshold.
In the evolutionary minority game, agents are allowed to evolve their strategies ("mutate") based on past experience. We explore the dependence of the system's global behavior on the response time and the mutation threshold of the agents. We find that the precise values of these parameters determine if the strategy distribution of the population has a U shape, inverse U shape, or W shape. It is shown that in a free society (market), highly adaptive agents (with short response times) perform best. In addition, "patient" agents (with high mutation thresholds) outperform "nervous" ones.


Exploration of the Chiral Recognition of Sugar-Based Diindolylmethane Receptors: Anion and Receptor Structures.
In this study, we have conducted a systematic investigation of the chiral recognition of carboxylic anions by D-glucuronic acid/diindolylmethane receptors. We investigate the influence of the anion structure on chiral recognition in the diindolylmethane/glucuronic acid-based receptor 1 a. We found that presence of an additional hydrogen-bond donor at the α position to the carboxylic function is essential for effective chiral differentiation in these systems. Furthermore, we present a synthetic procedure that allows for the synthesis of sugar-decorated receptors that possess a modified substituent at the anomeric position. Four new receptors 1 b-e have been synthesized, and their chiral-discrimination ability toward model carboxylates is studied. The obtained results show that the chiral recognition of these receptors can be fine-tuned by incorporation of a proper substituent into the receptor structure.