Comparison of results of KTP/532 laser versus monopolar electrosurgical dissection in laparoscopic cholecystectomy.
A total of 641 laparoscopic cholecystectomies performed between January 1, 1991 and December 31, 1991 were reviewed to compare the results of Potassium Titanyl Phosphate (KTP/532) laser versus monopolar electrosurgery in laparoscopic cholecystectomy. KTP laser dissection was used alone in 199 cases (31%), and monopolar cautery was used in 442 (69%). During this same time period, 41 additional procedures were excluded because of conversion to open cholecystectomy. Procedures in which both modalities (N = 24) were used were also excluded from the study. Modality choice was dependent upon operating surgeon's preference. Data were analyzed with student t-test, chi-square with Yates correction, stepwise linear regression analysis, and correlation matrices. Five (2.5%) patients had five major complications when KTP laser dissection was used and 34 (7.7%) patients had 42 major complications when monopolar electrosurgical dissection was used (p < 0.05). Postoperative hospital stay with the KTP/532 laser dissection group was 1.4 +/- 0.06 days and for the monopolar electrosurgical dissection group it was 1.7 +/- 0.08 days (p < 0.05). The duration of the procedures was identical with either modality. The use of the KTP laser for dissection of the gallbladder during laparoscopic cholecystectomy may be a safer procedure with significantly decreased complication rates and savings in length of hospital stay. Although initially a more expensive procedure, the savings in length of hospital stay and treatment of complications may offset the initial expenditure and be worthwhile.


Tests for qualitative treatment-by-centre interaction using a 'pushback' procedure.
In multicentre clinical trials using a common protocol, the centres are usually regarded as being a fixed factor, thus allowing any treatment-by-centre interaction to be omitted from the error term for the effect of treatment. However, we feel it necessary to use the treatment-by-centre interaction as the error term if there is substantial evidence that the interaction with centres is qualitative instead of quantitative. To make allowance for the estimated uncertainties of the centre means, we propose choosing a reference value (for example, the median of the ordered array of centre means) and converting the individual centre results into standardized deviations from the reference value. The deviations are then reordered, and the results 'pushed back' by amounts appropriate for the corresponding order statistics in a sample from the relevant distribution. The pushed-back standardized deviations are then restored to the original scale. The appearance of opposite signs among the destandardized values for the various centres is then taken as 'substantial evidence' of qualitative interaction. Procedures are presented using, in any combination: (i) Gaussian, or Student's t-distribution; (ii) order-statistic medians or outward 90 per cent points of the corresponding order statistic distributions; (iii) pooling or grouping and pooling the internally estimated standard deviations of the centre means. The use of the least conservative combination--Student's t, outward 90 per cent points, grouping and pooling--is recommended.


Conical Ionic Amphiphiles Endowed with Micellization Ability but Lacking Air-Water and Oil-Water Interfacial Activity.
Micellization in water and reduction of the surface tension at water interfaces with air and oil are two archetypical properties of surfactants, caused by self-aggregation and Gibbs monolayer formation at the interfaces, respectively. We present here a new type of amphiphiles that possess a conical shape consisting of a hydrophobic apex and five ionic termini at the base of the cone. The conical shape and the high charge density cooperatively impede monolayer formation at the interfaces, hence preventing foaming and emulsification. On the other hand, the conical shape strongly assists micelle formation in water and hemimicelle formation on a solid surface to promote dissolution of nanoparticles such as magnetic nanoparticles and nanocarbons in water. The well-defined shape and charge locations distinguish the new amphiphiles from known polymer amphiphiles that show similar surface activity.


History of allergic disease and risk of meningioma.
Epidemiologic studies have consistently shown inverse associations of allergic disease with risk of glioma, but it is unclear whether this association also applies to meningioma. The authors conducted a pooled analysis of meningioma risk in relation to a history of allergic disease based on data from two population-based, case-control studies with 475 cases and 1,716 controls in the United Kingdom (2001-2004). Meningioma risk was significantly reduced in relation to self-reported, physician-diagnosed allergic disease (odds ratio = 0.76, 95% confidence interval (CI): 0.61, 0.96) but was nonsignificantly reduced for individual conditions: asthma (odds ratio = 0.85, 95% CI: 0.61, 1.18), hay fever (odds ratio = 0.81, 95% CI: 0.62, 1.06), and eczema (odds ratio = 0.72, 95% CI: 0.51, 1.02). Risk reductions were greatest for asthma (odds ratio = 0.43, 95% CI: 0.21, 0.89) and hay fever (odds ratio = 0.50, 95% CI: 0.25, 1.00) with an early age at onset (<10 years) and for eczema (odds ratio = 0.46, 95% CI: 0.21, 1.07) with an onset at ages 10-19 years; they were near unity for onset in adulthood. This study suggests an inverse association between a history of allergies and meningioma risk, but with smaller risk reductions than for glioma. The reasons for this association need clarification, as well as an etiologic explanation. Consideration also needs to be given to confounding or bias.


Basidioboliasis in anurans in Florida.
Members of the genus Basidiobolus, a saprophytic fungus, have been associated with the digestive tracts of a wide variety of amphibians and reptiles. To elucidate the relationship of Basidiobolus sp. with amphibians in central Florida (USA), we document the occurrence of the fungus in the digestive tracts of Bufo terrestris, Buffo quercicus, Hyla femoralis, Hyla cinerea, Hyla gratiosa, Hyla squirella, Osteopilus septentrionalis, and Rana utricularia. Species that occupy terrestrial habitats (B. terrestris, B. quercicus, and R. utricularis) were found to harbor Basidiobolus spp. more frequently (83, 78, and 91%, respectively) than those that occupied a more arboreal habitat (H. cinerea, H. squirella, H. femoralis, H. gratiosa, and O. septentrionalis (50, 56, 55, 56, and 70%, respectively).


Placement of self-expandable metallic stents for tracheal stenosis secondary to thyroid cancer.
The indications and suitable approaches for treating upper airway obstruction secondary to thyroid cancer are controversial. Patients with thyroid cancer generally have a good prognosis, but airway stenosis and vocal cord paralysis are not uncommon. Subglottic airway stenting may be challenging, due to stent migration, granulation tissue formation and supraglottic stenosis. In this study, we evaluated the application of covered self-expandable metallic stents to relieve upper airway obstruction. This was a retrospective study of 5 patients with airway stenosis due to thyroid cancer treated in 2009 and 2010. Immediate airway enlargement was achieved in 3 patients with stenosis at the middle mediastinum. Gradual enlargement over 2 months was observed in the remaining 2 patients with stenosis at the cervical level. The performance status was improved in all 5 patients, including a case with anaplastic carcinoma. The follow-up averaged 13 months (range, 8-27 months). Granulation tissue developed at both ends of the stent in 3 patients, sputum was retained in 2 cases and bacterial colonization was detected in all 5 cases. No stent migration was reported. Additional tracheostomy was required in 2 patients, due to proximal tumor growth or progressive bilateral vocal cord paralysis after 10 and 6 months, respectively. In conclusion, stenting for central airway stenosis secondary to thyroid cancer may be beneficial, even in patients with anaplastic carcinoma. Long-term regular bronchoscopic follow-up is required to monitor complications, as patients with thyroid cancer are at high risk of granulation tissue formation, sputum retention and bacterial colonization.


Use of Monte Carlo simulations for improved facility fit planning in downstream biomanufacturing and technology transfer.
Biologics manufacturing is capital and consumable intensive with need for advanced inventory planning to account for supply chain constraints. Early-stage process design and technology transfer are often challenging due to limited information on process variability regarding bioreactor titer, process yield, and product quality. Monte Carlo (MC) methods offer a stochastic modeling approach for process optimization where probabilities of occurrence for process inputs are incorporated into a deterministic model to simulate more likely scenarios for process outputs. In this study, we explore MC simulation-based design of a monoclonal antibody downstream manufacturing process. We demonstrate that this probabilistic approach offers more representative outcomes over the conventional worst-case approach where the theoretical minimum and maximum values of each process parameter are used without consideration for their probability of occurrence. Our work demonstrates case studies on more practically sizing unit operations to improve consumable utilization, thereby reducing manufacturing costs. We also used MC simulations to minimize process cadence by constraining the number of cycles per unit operation to fit facility preferences. By factoring in process uncertainty, we have implemented MC simulation-based facility fit analyses to efficiently plan for inventory when accounting for process constraints during technology transfer from lab-scale to clinical or commercial manufacturing.


Clinical trial program for iopentol. A new nonionic ratio 3.0 contrast medium with emphasis on clinical phases I and II.
Iopentol is a new nonionic, water-soluble ratio 3.0 roentgen contrast medium (CM) for vascular use. The aim is to present the vascular clinical trial program for iopentol and to report the findings from the clinical phases I and II. The clinical program started with an intravenous (IV) safety and pharmacokinetic phase I trial (24 volunteers) and continued with six open, noncomparative phase II trials (61 patients) for studying cardiovascular and arterial tolerance (two trials in cardioangiography), venous tolerance (two trials in IV computed tomography [CT] enhancement), and cerebral and arterial tolerance (2 trials in cerebral arteriography). One volunteer in the phase I trial was excluded because of a vasovagal reaction following saline injection, and four patients were protocol deviators in cardioangiography. Mainly renal glomerular filtration of unmetabolized iopentol, close to 100% recovered after 24 hours in the urine, was found in the phase I study. No unexpected or severe contrast-induced reactions were encountered in phases I and II. Good diagnostic efficiency was obtained in phase II. As also expected, iopentol seemed to be well-tolerated. However, its relative efficiency and tolerance profile can only be documented from the ongoing comparative phase III trials.


Ovarian development and spawning of Serra Spanish mackerel in coastal waters of Northeastern Brazil.
The Serra Spanish mackerel, Scomberomorus brasiliensis is an important fishery resource of the Atlantic Ocean and is a major component of artisanal fisheries in northern and northeastern Brazil. Ovarian development and spawning period of S. brasiliensis were investigated using both macroscopic and histological techniques. Mean monthly values of GSI and ovarian maturation indicate that the main spawning period occurs during the rainy season.


The three leg imaginal discs of Drosophila: "Vive la différence".
The imaginal discs of Drosophila are the larval primordia for the adult cuticular structures of the adult fly. Fate maps of different discs have been generated that show the localization of prospective adult structures. Even though the three legs differ in their morphology, only the fate map for the T1 (prothoracic) leg disc has been generated. Here we present fate maps for the T2 (meso-) and T3 (metathoracic) leg discs. We show that there are many similarities to the map of the T1 leg disc. However, there are also significant differences in the contributions of each disc to the thorax, in the morphology of joints connecting the legs to the thorax, in bristle patterns, and in the positioning of some sensory organs. We also tested the developmental potential of disc fragments and observed that T2 and T3 leg discs have more limited plasticity and are unable to transdetermine. The differences in the cuticle patterns between legs are robust and conserved in many species of dipterans. While most previous analyses of imaginal disc development have not distinguished between the different leg discs, we believe that the underlying differences of the three leg discs demonstrated here cannot be ignored when studying leg disc development.


Comparison of methods for handling covariate missingness in propensity score estimation with a binary exposure.
Causal effect estimation with observational data is subject to bias due to confounding, which is often controlled for using propensity scores. One unresolved issue in propensity score estimation is how to handle missing values in covariates. Several approaches have been proposed for handling covariate missingness, including multiple imputation (MI), multiple imputation with missingness pattern (MIMP), and treatment mean imputation. However, there are other potentially useful approaches that have not been evaluated, including single imputation (SI) + prediction error (PE), SI + PE + parameter uncertainty (PU), and Generalized Boosted Modeling (GBM), which is a nonparametric approach for estimating propensity scores in which missing values are automatically handled in the estimation using a surrogate split method. To evaluate the performance of these approaches, a simulation study was conducted. Results suggested that SI + PE, SI + PE + PU, MI, and MIMP perform almost equally well and better than treatment mean imputation and GBM in terms of bias; however, MI and MIMP account for the additional uncertainty of imputing the missingness. Applying GBM to the incomplete data and relying on the surrogate split approach resulted in substantial bias. Imputation prior to implementing GBM is recommended.


Assessment of healthcare professionals' knowledge, attitudes, and perceived challenges of clinical pharmacogenetic testing in Egypt.
Aim: We evaluated healthcare practitioners' perspectives regarding clinical pharmacogenetics in Cairo, Egypt. Materials & methods: We administered a paper-based survey to pharmacists and physicians practicing at Children's Cancer Hospital Egypt. The survey assessed practitioners' knowledge, attitudes, and perspectives about pharmacogenetic testing. Results: The study included 184 respondents (67.9% pharmacists; 32.1% physicians. Overall, the pharmacogenetic knowledge was low (mean = 41.7%) but attitudes toward pharmacogenetic testing and its potential clinical application were generally positive. Pharmacists responded more favorably than physicians to statements attributing the responsibility of applying pharmacogenetics in the clinical setting to their profession. However, several challenges were identified; the most common being: lack of pharmacogenetic knowledge and skill, lack of pharmacogenetic testing devices, and limited funding. Conclusion: Future efforts to promote pharmacogenetic implementation should focus on foundational education, practical training, and exploration of potential funding sources.


Treatment of hidradenitis suppurativa with biologic medications.
Given the absence of significant improvement in the treatment of hidradenitis suppurativa (HS) with traditional medical and surgical therapies, biologics have piqued the interest of research investigators. The efficacy of biologics in the treatment of inflammatory conditions like psoriasis and rheumatoid arthritis is well-documented. More recently, success with biologics has been demonstrated in atopic dermatitis, another dermatological condition associated with inflammatory states. Researchers have begun to probe the utility of biologic agents in less prevalent conditions that feature inflammation as a key characteristic, namely, hidradenitis suppurativa. Five agents in particular adalimumab, anakinra, etanercept, infliximab, and ustekinumab, have been explored in the setting of HS. Results to date put forward adalimumab and infliximab as biologic treatments that can safely be initiated with some expectant efficacy. Other biologic agents require more rigorous examination before they are worthy of addition to the treatment armamentarium.


Equation of state of metallic hydrogen from coupled electron-ion Monte Carlo simulations.
We present a study of hydrogen at pressures higher than molecular dissociation using the coupled electron-ion Monte Carlo method. These calculations use the accurate reptation quantum Monte Carlo method to estimate the electronic energy and pressure while doing a Monte Carlo simulation of the protons. In addition to presenting simulation results for the equation of state over a large region of the phase diagram, we report the free energy obtained by thermodynamic integration. We find very good agreement with density-functional theory based molecular-dynamics calculations for pressures beyond 600 GPa and densities above rho=1.4 g/cm(3) , both for thermodynamic and structural properties. This agreement provides a strong support to the different approximations employed in the density-functional treatment of the system, specifically the approximate exchange-correlation potential and the use of pseudopotentials for the range of densities considered. We find disagreement with chemical models, which suggests that a reinvestigation of planetary models--previously constructed using the Saumon-Chabrier-Van Horn equations of state--might be needed.


Polypoid Cystitis in an Adult without History of Catheterization.
Polypoid cystitis is a benign exophytic mucosal lesion of the bladder. Differentiating it from papillary transitional cell carcinoma is difficult due to their similar characteristics. Although indwelling catheter is the main well-known cause of polypoid cystitis, some case reports unrelated to catheterization have been described. However, the radiological findings of polypoid cystitis have rarely been reported. We hereby describe polypoid cystitis in a 20-year-old man without a history of catheterization along with the computed tomographic findings.


Recovery and outcome after minor pediatric surgery.
Recovery and outcome parameters of children undergoing surgery as outpatient are reported. There are minor differences between different drugs in terms of outcome, speed of recovery and recovery adverse events. There is a trend in increasing adverse events (most of all emergence delirium) during recovery from sevoflurane and nitrous oxide. Most complications (pain, nausea, vomiting, croup) are transient and managed before discharge. The most frequent complications at home are undertreated pain, loss of appetite, and behavioral changes.


Electronic endoscopy in perspective.
Electronic endoscopy, developed in 1983, enables the endoscopic image to be transmitted through electric signals that can be easily processed by computer. An electronic endoscope is composed of three vital parts, i.e., a charge-coupled device (CCD) that converts the image to electric signals, a video processor that converts analog electric signals to the digital and processes them to become video signals, and a television monitor. The introduction of electronic endoscopy has enabled computer management of endoscopic images, on one hand, and provided an opportunity for image processing and analysis, on the other. A digital image management system will further develop into a database of endoscopic images. Combined with the technologies of remote control and remote sensing, the introduction of CCD to endoscopy has made it possible to transform the endoscope, so that it could become a capsule. Future advances in the research of image processing and analysis will lead to the development of a system of automated endoscopic diagnosis.


Impact of Removable Partial Denture on Quality-of-life of Sudanese Adults in Khartoum State.
Tooth loss can affect a patient's quality-of-life (QoL), impacting on aspects, such as nutritional intake, psychological status, self-image, and daily engaging in social interaction. The purpose of this study was to assess the oral health-related QoL (OHRQoL) among adult Sudanese patients wearing removable partial dentures (RPDs) by utilizing oral health impact profile-14 (OHIP-14) to assess patient satisfaction with their dentures. The study population included 370 adult patients wearing RPDs. Of these, 99 were males and 271 females with the age range of 35 to above 60 years. Self-reported questionnaires were distributed randomly to be completed by the participants from each health sector after having read a consent letter. Two measures interpreting the OHIP-14 scales (sum and prevalence) were utilized for data collection. The relationship of patients' demographic characteristics, general and oral health status, and denture characteristics with their OHRQoL was investigated. The data were processed and analyzed by means of Statistical Package for the Social Sciences (SPSS). The means of OHIP-14 sum and OHIP-14 prevalence of partial denture wearers were 10.9 + 7.8 and 18.9% respectively. The most problematic aspects of OHIP-14 were functional limitation and psychological disability. On the contrary, the participants had little problem as a handicap and social disability aspects. The self-reported oral health, regular follow-up, denture satisfaction, duration of denture wearing use of the denture while eating, and frequency of denture cleaning positively contribute to oral health-related quality. Loss of teeth and use of RPD significantly affect patients' oral health status and QoL. Patients who are satisfied with their dentures have a better QoL than their unsatisfied counterparts.


Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like domain-dependent manner.
Accumulation of aberrant proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response pathway that helps the cell to survive under these stress conditions. Herp is a mammalian ubiquitin domain protein, which is strongly induced by the unfolded protein response. It is involved in ER-associated protein degradation (ERAD) and interacts directly with the ubiquitin ligase Hrd1, which is found in high molecular mass complexes of the ER membrane. Here we present the first evidence that Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like (UBL) domain-dependent manner. We found that upon exposure of cells to ER stress, elevation of Herp steady state levels is accompanied by an enhanced association of Herp with pre-existing Hrd1. Hrd1-associated Herp is rapidly degraded and substituted by de novo synthesized Herp, suggesting a continuous turnover of the protein at Hrd1 complexes. Further analysis revealed the presence of multiple Hrd1 copies in a single complex enabling binding of a variable number of Herp molecules. Efficient ubiquitylation of the Hrd1-specific ERAD substrate α1-antitrypsin null Hong Kong (NHK) required the presence of the Herp UBL domain, which was also necessary for NHK degradation. In summary, we propose that binding of Herp to Hrd1-containing ERAD complexes positively regulates the ubiquitylation activity of these complexes, thus permitting survival of the cell during ER stress.


[Determination of three bufogenins in toad venom using reversed-phase high performance liquid chromatography].
A reversed-phase high performance liquid chromatographic method for the quantitative determination of three bufogenins in toad venom was established. An Alltech Alltima C18 column (250 mm x 4.6 mm, 5 microm) was used. The mobile phase was acetonitrile-0.1 mol/L acetate buffer (pH 3.2) (50:50, v/v), and the flow rate was 0.8 mL/min. The detection wavelength was set at 299 nm. The method has good linearity in the ranges of 0. 25 -0.875 microg for cinobufagin (r = 0.999 0), 0.25 -0.875 microg for resibufogenin (r = 0.999 1), and 0.15 - 0.525 microg for bufalin (r = 0. 999 0). The average recoveries were 100.3%, 100.0% and 98.0% for cinobufagin, resibufogenin, and bufalin, respectively. The results indicate that the method is simple, accurate, reproducible, and can be used for the quality control of bufogenins in toad venom.


[Quantification of levels of serum antirabies antibodies in vaccinated individuals].
The authors developed a kit for the purpose of assessment of anti-rabies antibodies by the ELISA immunoenzymatic method in human immunized sera. The results of the detection and quantification of anti-rabies antibodies acquired by the ELISA method were compared with those originating from classical procedures (virusneutralizing test on mice, indirect hemagglutination test), and a sufficient correlation and sensitivity of the immunoenzymatic method were detected. By means of the developed test it is possible to detect the particular level of anti-rabies virusneutralizing IgG antibodies. (Tab. 2, Fig. 1, Ref. 25).


Insight into Ion Transfer through the Sub-Nanometer Channels in Zeolitic Imidazolate Frameworks.
A crack-free sub-nanometer composite structure for the study of ion transfer was constructed by in situ growth of ZIF-90 [Zn(ICA)2 , ICA=Imidazole-2-carboxaldehyde] on the tip of a glass nanopipette. The potential-driven ion transfer through the sub-nanometer channels in ZIF-90 is strongly influenced by the pH of the solution. A rectification ratio over 500 is observed in 1 m KCl solution under alkaline conditions (pH 11.58), which is the highest value reported under such a high salt concentration. Fluorescence experiments show the super-high rectification ratio under alkaline conditions results from the strong electrostatic interaction between ions and the sub-nanometer channels of ZIF-90. In addition to providing a general pathway for further study of mass-transfer process through sub-nanometer channels, the approach enable all kinds of metal-organic frameworks (MOFs) to be used as ionic permselectivity materials in nanopore-based analysis.


Characterization of clinical and immunological parameters during Ebola virus infection of rhesus macaques.
The rhesus macaque serves as an animal model for Ebola virus (EBOV) infection. A thorough understanding of EBOV infection in this species would aid in further development of filovirus therapeutics and vaccines. In this study, pathological and immunological data from EBOV-infected rhesus macaques are presented. Changes in blood chemistries, hematology, coagulation, and immune parameters during infection, which were consistently observed in the animals, are presented. In an animal that survived challenge, a delay was observed in the detection of viral RNA and inflammatory cytokines and chemokines which may have contributed to survival. Collectively, these data add to the body of knowledge regarding EBOV pathogenesis in rhesus macaques and emphasize the reproducibility of the rhesus macaque challenge model.


Internalization of Chlamydia by dendritic cells and stimulation of Chlamydia-specific T cells.
Chlamydia species are the causative agents of trachoma, various forms of pneumonia, and the most common sexually transmitted diseases. Although the infection cycle has been extensively characterized in epithelial cells, where the Chlamydia entry-vacuoles avoid fusion with host-cell lysosomes, the cellular immune response has received less attention. Moreover, despite the abundant presence of dendritic cells (DC) in the sites of infection, the interaction between Chlamydia and DC has never been studied. We observe that DC kill Chlamydia trachomatis and Chlamydia psittaci. The chlamydiae are internalized by the DC in a nonspecific manner through macropinocytosis, and the macropinosomes fuse subsequently with DC lysosomes expressing MHC class II molecules. The interaction induces maturation of the DC, since presentation of an exogenous Ag is severely inhibited after a 1-day incubation, although chlamydial Ags are still presented and recognized by Chlamydia-specific CD4+ T cells. Thus, DC most likely play a role in initiating the T cell response in vivo and could potentially be used in adoptive transfer therapies to vaccinate against Chlamydia.


[Evaluation of anticoagulant activity for low molecular-weight heparin by chromogenic substrate. Measurement of factor Xa and thrombin activities].
We described an amidolytic method for determining the anticoagulant activity of commercially available low molecular-weight heparin (LMWH) with the use of factor Xa (FXa) and thrombin (FIIa), and a chromogenic peptidyl substrate, S-2222 or S-2238. The procedures were based on the photometric determination of the inactivation of FXa and FIIa after incubation with LMWH in the presence of antithrombin III (AT III). At first, the optimal conditions of FXa and FIIa activities with respect to pH, temperature, and the amounts of AT III and LMWH-International Standards (LMWH-IS) were determined. And then, the anticoagulant activities of various LMWHs were determined under the established conditions. In the comparative study with LMWHs, significant differences were found in anti FXa and anti FIIa activities, and their ratios. The anti FIIa activity was reconfirmed to decrease with decreasing molecular weight of LMWHs. On the other hand, the anti Xa activity was, however, less dependent on the molecular weight of LMWHs.


Myoid Angioendothelioma of the Spleen: A Rare Case Report and Literature Review.
Most common tumors of the spleen are hematologic and lymphoid malignancies. Non-lymphoid and non-hematologic tumors of the spleen are very rare, the most common of which are vascular tumors. This group of tumors in the spleen is composed of heterogeneous tumors such as hemangioma, angioendothelioma (AE), littoral cell angioma, and angiosarcoma. There are several histologic forms of AE such as epithelioid AE, Kaposiform AE, and myoid AE. Among these splenic vascular tumors, myoid angioendothelioma (MAE) seems to be the least common type. It is a distinct tumor; composed of endothelium-derived tumor cells and a special type of stromal tumor cells that seems to have borderline low-grade malignant potential. Herein, we report our experience with a young woman presented with chronic abdominal pain and splenic mass that turned out to be myoid AE of spleen with an uneventful surgery and excellent recovery period. To the best of our knowledge, such an occurrence is very rare in the spleen.


[Measurement of intraocular pressure using the Tono-Pen in comparison with Goldmann applanation tonometry - a clinical study in 100 eyes].
In clinical practice ophthalmologists often need a tonometer which is independent of a slit lamp. Such a hand-held device is the Tono-Pen. We compared the precision of two equal Tono-Pens with Goldmann applanation tonometry. Measurement of intraocular pressure (IOP) was done in 100 eyes of 51 patients (mean age 63 +/- 15 years) suffering from ocular hypertension or glaucoma. According to a random table either the right or left eye was measured using Goldmann tonometer first and the Tono-Pen second. For the other eye the measurement was reversed. One of the two equal Tono-Pens (Solan/USA) was used according to a second random table. Three measurements were obtained with each instrument on both eyes within 15 minutes subsequently. Patients were placed in an upright position for all measurements. Even for well-trained ophthalmologists a learning curve of approximately 10 measurements was observed using the Tono-Pen. The Tono-Pen measured an average IOP of 16.9 mm Hg in all 100 eyes. The Goldmann tonometer measured an average IOP of 17.7 mm Hg. The difference was not statistically significant. The standard deviation for all measurements was better for the Tono-Pen (4.7 mm Hg vs 5.8 mm Hg for Goldmann tonometer). No reduction of the IOP after Tono-Pen measurement was observed (in contrast to the Goldmann tonometer). The reproducibility of the Tono-Pen on the same eye was inferior to the Goldmann tonometer by a factor of 2. There was an almost significant difference in reproducibility between two equal Tono-Pens. Measurement of IOP with the Tono-Pen is comparable to Goldmann applanation tonometry if an average of 3 measurements is used. The difference between two equal Tono-Pens indicates the need for improvement of the quality check during production.


Renal and pancreatic transplantation in the treatment of diabetic renal failure.
Twenty-two diabetic patients with renal failure have entered an integrated dialysis and transplant programme in 30 months. Ten have subsequently undergone combined renal and segmental pancreatic transplantation, and have been followed for between one month and 25 months. Currently 80 per cent of the kidneys and 40 per cent of the pancreatic grafts are functioning. Four of the 22 patients have died from myocardial disease. Pancreatic transplantation at the time of renal grafting in diabetics does not significantly increase morbidity, and currently offers a 40 per cent chance of freedom from exogenous insulin. The successful treatment of diabetic renal failure is not compromised by the addition of this developmental procedure.


Preliminary study of certain serotypes, genetic and antimicrobial resistance profiles of verotoxigenic Escherichia coli (VTEC) isolated in Bosnia and Germany from cattle or pigs and their products.
The aim of this study was to gather more information on the spread of VTEC serotypes, genetic profiles and resistance patterns from pigs or pork and from cattle or beef in different areas, and to improve detection of the source of outbreaks with a wider data pool. Of 130 Escherichia coli samples isolated from a cattle slaughter house and beef retail products in Sarajevo, Bosnia and Herzegovina (BiH), seven were identified as verotoxigenic (VTEC). In comparison, 22 VTEC of 264 E. coli isolates were isolated from bovine faeces (14) and beef products (8) from Germany. Furthermore 23 VTEC of 76 isolates were identified from pig carcasses (10), faeces (9) and pork products (4) from Germany. Gene detection and serotyping were carried out in our laboratory and in the National Reference Laboratory. Antimicrobial resistance was tested with the dilution method in microtitre plates. All porcine isolates belonged to serotypes thus far not associated with human disease. Bovine VTEC were either serotypes commonly associated with human diseases (O157:H7, O103:H2, O157:H-) or rare serotypes. One serotype (O96:H19) was found only in isolates from Sarajevo. Most German VTEC, especially those of porcine origin, had only vtx2 genes, whereas all Bosnian isolates had vtx1 and vtx2 genes. The eae gene was found only in "classical" VTEC serotypes. All 52 VTEC (100%) investigated were resistant to the three sulfonamides tested; porcine isolates were mainly resistant to oxytetracycline (43%) and chlortetracycline (37%), bovine isolates mainly to trimethoprim/sulfamethoxazole and ampicillin (10% each). If sulfonamide resistances are disregarded, more than half (53.8%) of porcine VTEC were multiresistant and one-fourth (25%) of German bovine isolates, but none of the Bosnian bovine isolates. The results show the considerable spread of resistances in VTEC. These results also point out the necessity of gathering data from different geographical areas in order to be able to identify typical local variations in serotypes or gene expression and thus to trace human infections more quickly to their source.


Transcriptome Engineering with RNA-Targeting Type VI-D CRISPR Effectors.
Class 2 CRISPR-Cas systems endow microbes with diverse mechanisms for adaptive immunity. Here, we analyzed prokaryotic genome and metagenome sequences to identify an uncharacterized family of RNA-guided, RNA-targeting CRISPR systems that we classify as type VI-D. Biochemical characterization and protein engineering of seven distinct orthologs generated a ribonuclease effector derived from Ruminococcus flavefaciens XPD3002 (CasRx) with robust activity in human cells. CasRx-mediated knockdown exhibits high efficiency and specificity relative to RNA interference across diverse endogenous transcripts. As one of the most compact single-effector Cas enzymes, CasRx can also be flexibly packaged into adeno-associated virus. We target virally encoded, catalytically inactive CasRx to cis elements of pre-mRNA to manipulate alternative splicing, alleviating dysregulated tau isoform ratios in a neuronal model of frontotemporal dementia. Our results present CasRx as a programmable RNA-binding module for efficient targeting of cellular RNA, enabling a general platform for transcriptome engineering and future therapeutic development.


Metabolomic Analysis of Alfalfa (Medicago sativa L.) Root-Symbiotic Rhizobia Responses under Alkali Stress.
Alkaline salts (e.g., NaHCO3 and Na2CO3) causes more severe morphological and physiological damage to plants than neutral salts (e.g., NaCl and Na2SO4) due to differences in pH. The mechanism by which plants respond to alkali stress is not fully understood, especially in plants having symbotic relationships such as alfalfa (Medicago sativa L.). Therefore, a study was designed to evaluate the metabolic response of the root-nodule symbiosis in alfalfa under alkali stress using comparative metabolomics. Rhizobium-nodulized (RI group) and non-nodulized (NI group) alfalfa roots were treated with 200 mmol/L NaHCO3 and, roots samples were analyzed for malondialdehydyde (MDA), proline, glutathione (GSH), superoxide dismutase (SOD), and peroxidase (POD) content. Additionally, metabolite profiling was conducted using gas chromatography combined with time-of-flight mass spectrometry (GC/TOF-MS). Phenotypically, the RI alfalfa exhibited a greater resistance to alkali stress than the NI plants examined. Physiological analysis and metabolic profiling revealed that RI plants accumulated more antioxidants (SOD, POD, GSH), osmolytes (sugar, glycols, proline), organic acids (succinic acid, fumaric acid, and alpha-ketoglutaric acid), and metabolites that are involved in nitrogen fixation. Our pairwise metabolomics comparisons revealed that RI alfalfa plants exhibited a distinct metabolic profile associated with alkali putative tolerance relative to NI alfalfa plants. Data provide new information about the relationship between non-nodulized, rhizobium-nodulized alfalfa and alkali resistance.


Role of ribonucleic acid synthesis in conjugational transfer of chromosomal and plasmid deoxyribonucleic acids.
A strain of Escherichia coli K-12 containing mutations that allow for the experimental control of RNA and DNA syntheses was constructed to investigate the role that RNA synthesis plays in conjugational DNA transfer when DNA replication is inhibited. The mutations possessed by this strain and its donor derivatives include: (i) thyA, which blocks synthesis of dTMP, causing a requirement for thymine; (ii) deoC, which blocks breakdown of deoxyribose 5-phosphate, permitting growth with low levels of thymine; (iii) pyrF, which blocks synthesis of UMP from OMP, imposing a requirement for uridine; (iv) cdd and pyrG, which block the deamination of cytidine to uridine and the synthesis of CTP from UTP, respectively, causing a requirement for cytidine; (v) codA and codB, which block the deamination of cytosine to uracil and cytosine transport, respectively, preventing the substitution of cytosine for cytidine; and (vi) dnaB, which blocks vegetative but not conjugational DNA replication at 42 degrees C. DNA synthesis can be blocked in the donor strains by the addition of excess uridine when exogenous thymine is not present. We found that RNA synthesis can also be blocked by addition of excess uridine when exogenous cytidine is not present. Blocking RNA synthesis prior to mating, under conditions in which DNA synthesis either is or is not inhibited, depresses DNA transfer. However, under conditions in which DNA synthesis is inhibited, the blocking of RNA synthesis immediately after mating has commenced had no effect on continued conjugational transfer of DNA. Thus, RNA synthesis is needed to initiate but not to continue conjugational DNA transfer.


Diffusion-weighted magnetic resonance imaging for predicting and detecting the early response to chemoradiotherapy of advanced esophageal squamous cell carcinoma.
The aim of this study was to investigate the utility of the apparent diffusion coefficient (ADC) value in diffusion-weighted magnetic resonance imaging (DWMRI) for prediction and early detection of treatment response in advanced esophageal squamous cell carcinoma. DWMRI was performed in 27 patients with primary cT4 esophageal carcinoma that were undergoing chemoradiotherapy before treatment and after 20 and 40 Gy. We calculated tumor ADCs and association of the treatment effect between responders and nonresponders. The ADC at the time of 20 Gy was significantly higher in responders compared to nonresponders (1.13 vs. 0.93; p = 0.005). The ADC cut-off value was set at 1.00 × 10(-3) mm(2)/s and the ADC predicted the responders with a sensitivity, positive predictive value and accuracy of 79, 73 and 74%, respectively. The increased rate of the ADC at the time of 20 Gy (ΔADC20) was also significantly higher in responders compared to nonresponders (35.4 vs. 1.5%; p = 0.0007). An ADC cut-off value for ΔADC20 of 15% predicted the responders with a sensitivity, positive predictive value and accuracy of 71, 100 and 85%, respectively. The ADC values predicted the prognosis of patients with advanced esophageal squamous cell carcinoma as well as the treatment response.


Refusal of Emergency Medical Treatment: Case Studies and Ethical Foundations.
Informed consent is an important component of emergency medical treatment. Most emergency department patients can provide informed consent for treatment upon arrival. Informed consent should also be obtained for emergency medical interventions that may entail significant risk. A related concept to informed consent is informed refusal of treatment. Patients may refuse emergency medical treatment during their evaluation and treatment. This article addresses important considerations for patients who refuse treatment, including case studies and discussion of definitions, epidemiology, assessment of decisional capacity, information delivery, medicolegal considerations, and alternative care plans.


Critical exponents of the random-field O(N) model.
The critical behavior of the random-field Ising model has long been a puzzle. Different methods predict that its critical exponents in D dimensions are the same as in the pure (D-2)-dimensional ferromagnet with the same number of the magnetization components contrary to the experiments and simulations. We calculate the exponents of the random-field O(N) model with the (4+epsilon)-expansion and obtain values different from the exponents of the pure ferromagnet in 2+epsilon dimensions. An infinite set of relevant operators missed in previous studies leads to a breakdown of the (6-epsilon)-expansion.


Tumor-suppressive effects of CDK8 in endometrial cancer cells.
CDK8 is either amplified or mutated in a variety of human cancers, and CDK8 functions as an oncoprotein in melanoma and colorectal cancers. Previously, we reported that loss or reduction of CDK8 results in aberrant fat accumulation in Drosophila and mammals, suggesting that CDK8 plays an important role in inhibiting lipogenesis. Epidemiological studies have identified obesity and overweight as the major risk factors of endometrial cancer, thus we examined whether CDK8 regulates endometrial cancer cell growth by using several endometrial cancer cell lines, including KLE, which express low levels of CDK8, as well as AN3 CA and HEC-1A cells, which have high levels of endogenous CDK8. We observed that ectopic expression of CDK8 in KLE cells inhibited cell proliferation and potently blocked tumor growth in an in vivo mouse model. In addition, gain of CDK8 in KLE cells blocked cell migration and invasion in transwell, wound healing and persistence of migratory directionality assays. Conversely, we observed the opposite effects in all of the aforementioned assays when CDK8 was depleted in AN3 CA cells. Similar to AN3 CA cells, depletion of CDK8 in HEC-1A cells strongly enhanced cell migration in transwell assays, while overexpression of CDK8 in HEC-1A cells blocked cell migration. Furthermore, gene profiling of KLE cells overexpressing CDK8 revealed genes whose protein products are involved in lipid metabolism, cell cycle and cell movement pathways. Finally, depletion of CDK8 increased the expression of lipogenic genes in endometrial cancer cells. Taken together, these results show a reverse correlation between CDK8 levels and several key features of the endometrial cancer cells, including cell proliferation, migration and invasion as well as tumor formation in vivo. Therefore, in contrast to the oncogenic effects of CDK8 in melanoma and colorectal cancers, our results suggest that CDK8 plays a tumor-suppressive role in endometrial cancers.


Multiple alterations in metabolite uptake in a mutant of Neurospora crassa.
A temperature-conditional lethal mutant of Neurospora crassa, un-t (55701), was resistant to neutral amino acid analogues by virtue of a decreased ability to transport these analogues and their natural congeners across the cell membrane. The uptake of acidic, but not basic, amino acids was also impaired, as was the uptake of potassium ions. After preincubation above the tolerated temperature, the ability to take up a still wider variety of metabolites was greatly reduced. Protoplasts of the mutant were more osmotically fragile than those of wild type. The possibility that the mutant has a generalized membrane defect is discussed.


An analysis of 72% chromated glycerin used for sclerotherapy: sterility, potency, and cost after extended shelf life.
Sclerotherapy is the treatment of reticular veins and telangiectasias of the lower extremities. Sclerosants destroy endothelial tissue and expose subendothelial collagen fibers, which lead to subsequent fibrosis of vessels, thus preventing recanalization. There are several available sclerosants including sodium tetradecyl sulfate (STS), polidocanol (POL), and chromated glycerin (CG) with varying efficacy, potency, side effect profile, and cost. To identify the possible bacterial contamination and potency of CG beyond the current recommended shelf life of 3 months and to prove if CG is as cost effective as other available sclerosants. Samples of 72% CG underwent bacterial endotoxin, sterility, and potency analysis at Days 0, 24, and 183. In addition, cost comparison was performed with other commercially available sclerosants including STS and POL. No samples of CG showed any bacterial contamination. All aliquots of glycerin remained sterile at Day 14. Potency at Day 24 was 99.2%, which was the same at Day 183. Cost comparison with other sclerosants revealed that CG is lower cost per milliliter than STS and POL. Seventy-two percent CG has no contamination and maintains its reported potency up to 6 months while comparable with the cost of other commercially available sclerosants.


Genetic Determinants of Increased Body Mass Index Partially Mediate the Effect of Elevated Birth Weight on the Increased Risk of Atrial Fibrillation.
Background: Although several observational studies have shown an association between birth weight (BW) and atrial fibrillation (AF), controversy remains. In this study, we aimed to explore the role of elevated BW on the etiology of AF. Methods: A two-sample Mendelian randomization (MR) study was designed to infer the causality. The genetic data on the associations of single-nucleotide polymorphisms (SNPs) with BW and AF were separately obtained from two large-scale genome-wide association studies with up to 321,223 and 1,030,836 individuals, respectively. SNPs were identified at a genome-wide significant level (p <5 × 10-8). The inverse variance-weighted (IVW) method was employed to obtain causal estimates as our primary analysis. Sensitivity analyses with various statistical methods were applied to evaluate the robustness of the results, and multivariable MR analysis was conducted to determine whether this association was mediated by the body mass index (BMI). Results: In total, 144 SNPs were identified as the genetic instrumental variables. MR analysis revealed a causal effect of elevated BW on AF (OR = 1.27, 95% CI = 1.14-1.40, p = 5.70 × 10-6). All the results in sensitivity analyses were consistent with the primary result. The effect of BW on AF was attenuated when adjusted for BMI (OR = 1.16, 95% CI = 1.01-1.33, p = 0.04). Conclusions: This study indicated that elevated BW was significantly associated with increased lifelong risk of AF, which may be partially mediated by BMI.


The Effect of Hydrothermal, Microwave, and Mechanochemical Treatments of Tin Phosphate on Sorption of Some Cations.
The samples of precipitated tin (IV) phosphate, modified using hydrothermal, microwave, and mechanochemical procedures, were studied in the process of Cs(I), Sr(II), and U(VI) ion sorption. The initial and modified samples were investigated before and after sorption using XRD, XRF, FTIR, and nitrogen adsorption-desorption. It was found that the modification procedures transformed the micro-mesoporous structure of the initial sample into a meso-macroporous structure. As a result, the sorption capacity in relation to all ions increases several times. This indicates the determining role of the porous structure, primary content, and mesopore size on the sorption activity of tin phosphate. The samples, treated in the form of a wet gel, which is a novel procedure, showed the maximum sorption indicators. The sorption of all the tested ions is described by the Langmuir isotherm.


Asymmetric optical transmission through periodic arrays of cone air holes in a metal film.
The metal film perforated with a micro-nano cone air hole (CAH) can serve as an optical device having asymmetric transmission. In this paper, we numerically investigate the metal film perforated with periodic arrays of cone air holes (PACAH) and find that the metal PACAH can also implement asymmetric optical transmission. In the short wave band of visible light, Al PACAH shows the most obvious effect of asymmetric optical transmission. And in the middle-long wave band, Ag PACAH shows the effect best. When R(L) (the radius of large end of hole) = 600 nm, R(S) (the radius of small end of hole) = 150 nm, t (the film thickness) = 1500 nm, and the substrate with a dielectric constant of 2.4 is placed on the side adjacent to the large end of hole, for Al PACAH (the CAHs arranged in a triangular array), the average forward transmittance and the average transmission ratio (the ratio of forward transmittance to backward one) in the region of 400 nm-600 nm are 28.4% and 7.6, respectively. Particularly, the forward transmittance and the transmission ratio at 448 nm are 43.0% and 12.4 respectively. And for Ag PACAH (the CAHs arranged in a square array), the average forward transmittance and the average transmission ratio in the region of 550 nm-800 nm are 25.4% and 5.7, respectively. Particularly, the forward transmittance and the transmission ratio at 611 nm are 36.5% and 8.5, respectively. This metal PACAH shows potential of application in secrecy equipment, such as a unidirectional optical transmission wall.


Integration of cortical and pallidal inputs in the basal ganglia-recipient thalamus of singing birds.
The basal ganglia-recipient thalamus receives inhibitory inputs from the pallidum and excitatory inputs from cortex, but it is unclear how these inputs interact during behavior. We recorded simultaneously from thalamic neurons and their putative synaptically connected pallidal inputs in singing zebra finches. We find, first, that each pallidal spike produces an extremely brief (∼5 ms) pulse of inhibition that completely suppresses thalamic spiking. As a result, thalamic spikes are entrained to pallidal spikes with submillisecond precision. Second, we find that the number of thalamic spikes that discharge within a single pallidal interspike interval (ISI) depends linearly on the duration of that interval but does not depend on pallidal activity prior to the interval. In a detailed biophysical model, our results were not easily explained by the postinhibitory "rebound" mechanism previously observed in anesthetized birds and in brain slices, nor could most of our data be characterized as "gating" of excitatory transmission by inhibitory pallidal input. Instead, we propose a novel "entrainment" mechanism of pallidothalamic transmission that highlights the importance of an excitatory conductance that drives spiking, interacting with brief pulses of pallidal inhibition. Building on our recent finding that cortical inputs can drive syllable-locked rate modulations in thalamic neurons during singing, we report here that excitatory inputs affect thalamic spiking in two ways: by shortening the latency of a thalamic spike after a pallidal spike and by increasing thalamic firing rates within individual pallidal ISIs. We present a unifying biophysical model that can reproduce all known modes of pallidothalamic transmission--rebound, gating, and entrainment--depending on the amount of excitation the thalamic neuron receives.


Hierarchically structured titania films prepared by polymer/colloidal templating.
Hierarchically structured titania films for application in hybrid solar cells are prepared by combining microsphere templating and sol-gel chemistry with an amphiphilic diblock copolymer as a structure-directing agent. The films have a functional structure on three size scales: (1) on the micrometer scale a holelike structure for reduction of light reflection, (2) on an intermediate scale macropores for surface roughening and improved infiltration of a hole transport material, and (3) on a nanometer scale a mesoporous structure for charge generation. Poly(dimethyl siloxane)-block-methyl methacrylate poly(ethylene oxide) (PDMS-b-MA(PEO)) is used as a structure-directing agent for the preparation of the mesopore structure, and poly(methyl methacrylate) (PMMA) microspheres act as a template for the micrometer-scale structure. The structure on all levels is modified by the method of polymer extraction as well as by the addition of PMMA particles to the sol-gel solution. Calcination results in structures with increased size and a higher degree of order than extraction with acetic acid. With addition of PMMA a microstructure is created and the size of the mesopores is reduced. Already moderate microstructuring results in a strong decrease in film reflectivity; a minimum reflectivity value of less than 0.1 is obtained by acetic acid treatment and subsequent calcination.


SARS-CoV-2 evolution in the Omicron era.
Since SARS-CoV-2 BA.5 (Omicron) emerged and spread in 2022, Omicron lineages have markedly diversified. Here we review the evolutionary trajectories and processes that underpin the emergence of these lineages, and identify the most prevalent sublineages. We discuss the potential origins of second-generation BA.2 lineages. Simple and complex recombination, antigenic drift and convergent evolution have enabled SARS-CoV-2 to accumulate mutations that alter its antigenicity. We also discuss the potential evolutionary trajectories of SARS-CoV-2 in the future.


Construction of a novel shuttle vector based on an RCR-plasmid from a haloalkaliphilic archaeon and transformation into other haloarchaea.
The pNB101 is the first plasmid to be isolated from an haloalkaliphilic archaea. With insertion of the ColE1 replicon of Escherichia coli, as well as two antibiotic resistance genes at its unique Hin dIII site, a novel shuttle vector between haloarchaea and E. coli was developed. This vector, named pNB102, was successfully transformed into two non-alkaliphilic haloarchaea, Halobacterium salinarum SNOB and Haloarcula hispanica ATCC33960. The presence and stability of pNB102 in the transformants were confirmed by PCR identification, Southern blotting and restriction endonuclease digestion. Results also indicated that the presence of restriction-modification (R-M) systems in some Halobacterium species prevented this transformation. It is the first report that the replicon of pNB101 has such a wide host range, and has taken the first step for construction of the vector/host system in haloalkaliphilic archaea.


Treatment of localized prostatic carcinoma.
Radical or total prostatectomy and interstitial irradiation with concomitant pelvic lymphadenectomy are discussed. Indications, relative merits, and pitfalls of each technique are examined, and the treatments are compared for efficacy.


A Comorbid Rat Model of Neuroendocrine-Immune System Alterations Under the Impact of Risk Factors for Stroke.
Hypercholesterolemia and carotid atherosclerosis contribute to the etiology of stroke. However, there has been a lack of appropriate comorbid animal models incorporating some of the ubiquitous characteristics that precede strokes. Curcumin is a natural active polyphenolic compound extracted from the rhizoma of Curcuma longa L. which possesses comprehensive bioactivities. The present study aimed to evaluate whether neurobehavioral deficits, neuroendocrine-immune dysregulations and cerebral microcirculation dysfunction, are part of the initial stages of cerebral ischemia in individuals suffering from carotid atherosclerosis resulting from a high cholesterol diet (HCD) and if they could be tested using a comorbid animal model. Furthermore, the utility of this model will be examined following the administration of curcumin. Adult wild-type SD rats were fed a regular diet or HCD and supplemented with either vehicle or curcumin for 4 weeks. Carotid injury was induced by an air-drying endothelial denudation method at the end of the second week. Plasma cholesterol, carotid pathomorphology, neurobehavioral tests, and neuroendocrine-immune parameters were measured. We found higher plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), intima and media (I/M) ratio, but lower high-density lipoprotein-cholesterol (HDL-C), spatial learning and memory capacity impairment, elevated NPY expression in the hypothalamus, increased plasma concentration of leptin, upregulated TNF-α, IL-1β, and CRP in the circulation as well as TNF-α and IL-1β in the cerebral cortex, plus enhanced ICAM-1, VCAM-1, and E-selectin in cerebral microvessels in HCD-fed model rats. All these alterations were ameliorated by curcumin. These results suggest that a comorbid rat model was effectively developed by HCD and carotid injury.


Potential Use of Interleukin-10 Blockade as a Therapeutic Strategy in Human Cutaneous Leishmaniasis.
Interleukin-10 overproduction has been associated with worse prognosis in human cutaneous leishmaniasis, while IFN-γ-dependent responses are associated with parasite killing and host protection. Innovative strategies are needed to overcome therapeutic failure observed in endemic areas. The use of monoclonal antibody-based immunotherapy targeting IL-10 cytokine was evaluated here. Partial IL-10 blockade in Leishmania braziliensis whole soluble antigen-stimulated cells from endemic area CL patients with active or healed lesions and asymptomatic controls was evaluated. Overall decrease in IL-10, IL-4, and TNF-α production was observed in all groups of subjects. Only patients with active lesions still produced some levels of TNF-α after anti-IL-10 stimulation in association with Leishmania antigens. Moreover, this strategy showed limited modulatory effects on IFN-γ-dependent chemokine CXCL10 production. Results suggest the potential immunotherapeutic use of partial IL-10 blockade in localized cutaneous leishmaniasis.


Determination of neutral tibial rotational alignment in rotating platform TKA.
Use of a fixed anatomic landmark to set rotation of the tibial component may lead to rotational malalignment. Post wear in stabilized components, backside wear in any conforming modular system, and patellar maltracking may result from tibiofemoral rotational incongruence. We aimed to quantify tibial rotational alignment in 109 primary rotating platform TKAs. After trial components were inserted with the knee properly balanced, we recorded the neutral point of the rotating tibial insert, in extension, relative to the most medial aspect of the tibial tubercle. We hypothesized that all neutral points would lie within 10 degrees of the mean. Divergence of the neutral point was recorded as being internal or external to the medial border of the tibial tubercle to the nearest 5 degrees increment. Our results showed a mean divergence of 5 degrees +/- 5 degrees external to the medial border of the tubercle. Five percent of knees, however, had neutral points > or = 10 degrees from the mean. Surgeons who use fixed-bearing modular components with any rotational constraint must be cautious in choosing a fixed anatomic tibial landmark to determine the rotational alignment of the tibial component. Doing so may create tibiofemoral rotational malalignment in full extension that may lead to suboptimal outcomes. Diagnostic study, Level II-3. See the Guidelines for Authors for a complete description of levels of evidence.


The Effect of Er,Cr:YSGG and Diode Laser Applications on Dental Implant Surfaces Contaminated with Acinetobacter Baumannii and Pseudomonas Aeruginosa.
Treatment of peri-implantitis through several implant surface decontamination techniques have been reported, however, some of them can negatively alter the implant surface or enhance more bacterial resistance. The aim of this in vitro study was to evaluate implant surface decontamination by means of Er,Cr:YSGG and diode lasers. Fifty micro-textured (MTX) dental implants were contaminated with Acinetobacter baumannii (n = 25) and with Pseudomonas aeruginosa (n = 25). All implants were then divided into five groups for the decontamination procedure. In group I (GI), decontamination was done with an Er,Cr:YSGG laser (2780 nm), while in group II (GII) decontamination was performed using photodynamic therapy (a 650 nm diode laser). In Group III (GIII) decontamination was performed with photodynamic therapy (an 808 nm diode laser), and in group IV (GIV) decontamination was performed with 0.12% chlorhexidine. Group V (GV) was the control group with no decontamination. After decontamination, colony forming units (CFU) were counted and implants were prepared for SEM analysis. A significant difference (p < 0.001) was observed for GI compared to the other groups, and also for GIV compared to both GII and GIII. The Er,Cr:YSGG laser (GI) showed the best results in decontaminating the implant surface. Chlorhexidine (GIV), proved to be better in decontaminating the implant surface than photodynamic therapy GII and diode laser GIII. No significant difference was found between group GII and GIII. The SEM analysis showed no significant change in the implant surface topography. The results of this study suggest that the Er,Cr:YSGG laser can be considered as an effective technique for reducing bacteria contamination on implant surfaces.


Application of QSPR to mixtures.
In this paper we report an attempt to apply the QSPR approach for the analysis of data for mixtures. This is an extension of the conventional QSPR approach to the analysis of data for single molecules. The QSPR methodology was applied to a data set of experimental measured density of binary liquid mixtures compiled from the literature. The present study is aimed to develop models to predict the "delta" value of a mixture i.e., deviation of the experimental mixture density (MED) from the ideal, mole-weighted calculated mixture density (MCD). The QSPR was investigated in two perspectives (QMD-I and QMD-II) with respect to the creation of training and test sets. The study resulted in significant ensemble neural network and k-nearest neighbor models having statistical parameters r2, q2(10cv) greater than 0.9, and pred_r2 greater than 0.75. The developed models can be used to predict the delta and hence the density of a new mixture. The QSPR analysis shows the importance of hydrogen bond, polar, shape, and thermodynamic descriptors in determining mixture density, thus aiding in the understanding of molecular interactions important in molecular packing in the mixtures.


Towards the realization of dynamically adaptable manufacturing automation systems.
The transition from traditional to truly smart dynamically adaptable manufacturing demands the adoption of a high degree of autonomy within automation systems, with resultant changes in the role of the human, in both the manufacturing and logistics functions within the factory. In the context of smart manufacturing, this paper describes research towards the realization of adaptable autonomous automation systems from both the control and information perspectives. Key facets of the approach taken at WMG are described in relation to human-machine interaction, autonomous approaches to assembly and intra-logistics, integration and dynamic system-wide optimization. The progression from simple distributed behavioural components towards autonomous functional entities is described. Effective systems integration and the importance of interoperability in the realization of more distributed and autonomous automation systems are discussed, so that operational information can propagate seamlessly, eliminating the traditional boundary between operational technology and information technology systems, and as an enabler for global knowledge collection, analysis and optimization. This article is part of the theme issue 'Towards symbiotic autonomous systems'.


Atmospheric contamination during dental procedures.
The aim of this study was to evaluate the level of aerosol pollution following dental procedures performed in 15 sessions with an ultrasound scaler and a bicarbonate cleaner. The air contamination was measured by means of the Surface Air System method and the "plate" method (Air Microbial Index). Each colony-forming unit per cubic meter of air was allotted a unit value for statistical analysis. The data were then compared with the hygienic assessments made in previous studies. The results showed that the initial environmental conditions in a dental office initiated at the level of mediocre, then became very bad during dental procedures, and fell between mediocre and very bad at the end of the procedures.


[Induction of Th1 immune response against tumor by genetically engineered fusion of tumor cells and dendritic cells].
To study the antitumor activity of engineered fusion of tumor cell and dendritic cells (DC). J558 tumor cells were transfected with mouse IL-12 (mIL-12) gene and then fused with DCs to develop a hybrid-engineered tumor vaccine. BALB/c mice were challenged with wild-type J558 tumor cells 14 days after vaccinated with hybrid-engineered J558. mIL-12 was detected at (870 +/- 60) pg.(10(5) cells)(-1).ml(-1) in the culture supernatants and the cell-fusion rate was about 30% by co-focal microscopy. In addition, the lymphocytes from popliteal nodes and groin nodes of these mice vaccinated with hybrid-engineered J558 secreted higher levels of IFN-gamma than that of other control mice, and vaccination of mice with the fusion vaccine induced more efficient tumor-specific CTL cytotoxicity against wild-type tumor cells in vitro and with efficient antitumor immunity in vivo. It suggested that vaccination of mice with the fusion vaccine induced stronger Th1-dominant responses and this approach could perhaps be applied to clinical settings of DCs-based cancer vaccines.


Trait Cheerfulness Does Not Influence Switching Costs But Modulates Preparation and Repetition Effects in a Task-Switching Paradigm.
Many studies have shown the beneficial effect of positive emotions on various cognitive processes, such as creativity and cognitive flexibility. Cheerfulness, understood as an affective predisposition to sense of humor, has been associated with positive emotions. So far, however, no studies have shown the relevance of this dimension in cognitive flexibility processes. The aim of this research was to analyze the relationship between cheerfulness and these processes. To this end, we carried out two studies using a task-switching paradigm. Study 1 aimed at analyzing whether high trait cheerfulness was related to better cognitive flexibility (as measured by reduced task-switching costs), whereas Study 2 aimed at replicating the pattern of data observed in Study 1. The total sample was composed of 139 participants (of which 86 were women) selected according to their high versus low scores in trait cheerfulness. In a random way, participants had to judge whether the face presented to them in each trial was that of a man or a woman (gender recognition task) or whether it expressed anger or happiness (expressed emotion recognition task). We expected participants with high versus low trait cheerfulness to show a lower task-switching cost (i.e., higher cognitive flexibility). Results did not confirm this hypothesis. However, in both studies, participants with high versus low trait cheerfulness showed a higher facilitation effect when the stimuli attributes were repeated and also when a cue was presented anticipating the demand to perform. We discuss the relevance of these results for a better understanding of cheerfulness.


A repeated course of constraint-induced movement therapy results in further improvement.
A recent therapeutic intervention, constraint-induced movement therapy (CIMT), has been shown to improve movement efficiency and quality of movement in the involved hand of children with hemiplegic cerebral palsy (CP). In the present study, we investigate the long-term effects of CIMT and the effect of a second course on involved limb function using an ABABA design. Eight children with mild to moderate hemiplegic CP (six males, two females; mean age 8y 7mo [SD 2y 6mo]; range 5-11y), who had received a CI therapy intervention 12 months before this study, participated in a second intervention. In both interventions, the children wore a sling on their non-involved upper extremity for 6 hours per day during 10 out of 12 consecutive days and were engaged in play and functional activities that provided structured practice using the involved upper extremity. The results indicated initial improvements in movement efficiency, as measured by the Jebsen-Taylor Test of Hand Function, the Speed and Dexterity subtest (no. 8) of the Bruininks-Oseretsky Test of Motor Proficiency, and caregivers' perceptions of amount of use and quality of movement of the involved limb, were retained 12 months after the first intervention. The second intervention resulted in further improvement on these measures. Results indicate that intensive practice associated with CIMT may be retained long term, and that continued improvements may occur after a second intervention dose.


Cigarette sharing and gifting in China: Patterns, associated factors, and behavioral outcomes.
The purpose of this study was to investigate the patterns and factors associated with cigarette sharing and gifting, and to explore whether smoking can be predicted by these social practices. A cross-sectional survey using a multi-stage sampling design was conducted online from 30 April to 30 July 2020 in China. A sample of 982 household heads from Guangdong Province and 530 household heads from Shaanxi province were involved in the data analysis. Demographic characteristics, social participation, beliefs and behaviors related to cigarette sharing and gifting were assessed. Chi-squared analysis and multiple logistic regression analysis were used to explore the key factors associated with cigarette sharing and gifting, and to identify their relationship with smoking. The shared and gift cigarettes were both mainly offered to friends, and receiving gift cigarettes mostly occurred during the holidays. Gender and province were associated with cigarette sharing, and marital status and social participation were associated with cigarette gifting. Cigarette gifting beliefs and smoking status were prominent predictors for both sharing and gifting cigarettes. Cigarette gifting beliefs were significantly higher among smokers than non-smokers, and people with high cigarette gifting beliefs were 1.68 (adjusted odds ratio, AOR=19.17; 95% CI: 13.31-27.61) times more likely to be a smoker. Offering shared cigarettes has been found to significantly predict tobacco use (AOR=19.17; 95% CI: 13.31-27.61), while people who received shared and gift cigarettes were 1.50 (95% CI: 1.08-2.09) and 2.58 (95% CI: 1.66-4.00) times more likely to be a current smoker than those who did not receive cigarettes, respectively. Cigarette sharing and gifting were especially pervasive among male smokers and married people in Shaanxi Province. Offering shared cigarettes and receiving shared/gift cigarettes might facilitate cigarette use. This study provides evidence-based data to support the design and implementation of tobacco control programs for the denormalization of gifting and sharing cigarettes.


Acute fulminant neuropathy in a patient with Churg-Strauss syndrome.
We report a patient with an acute neuropathy initially mimicking Guillain-Barré syndrome, both clinically and electrophysiologically. Persistent eosinophilia, positive antineutrophil cytoplasmic antibody and eosinophilic vasculitis in sural nerve biopsy later confirmed Churg-Strauss syndrome. Since vasculitic neuropathy can present in an acute and fulminant form, the role of early antibody testing and sural nerve biopsy in atypical cases of acute neuropathy is emphasized.


Evaluation of a single-item screening tool for depression after stroke: a cohort study.
To determine the accuracy and utility of a single-item screening tool for depression (the Yale, taken from the Yale-Brown Obsessive Compulsive Scale) in patients who have recently had a stroke. Comparison of a clinical classification of depression with a screening tool in a defined cohort. A large teaching hospital in Liverpool, UK. One hundred and twenty-two consecutive people admitted with an acute stroke who did not have severe cognitive or communication problems, and who were still in hospital in the second week post stroke. Classification of depression using the Montgomery-Asberg Depression Rating Scale was compared with the Yale, a single-item screening tool. When comparing the classification of depression according to the Montgomery-Asberg Depression Rating Scale and the response to the Yale we found that at week 2 the Yale had a sensitivity of 86% (57/66), a specificity of 84% (46/55), a positive predictive value of 86% (57/66) and a negative predictive value of 84% (46/55), with an overall efficiency of 85% (103/121); prevalence of depression was 54% (according to the Montgomery-Asberg Depression Rating Scale). At month 3 the Yale had a sensitivity of 95% (52/55), a specificity of 89% (32/36), a positive predictive value of 93% (52/56) and a negative predictive value of 91% (32/35), with an overall efficiency of 92% (84/91); prevalence of depression was 60%. The Yale, which only requires a 'yes' or 'no' answer to a single question, may prove a useful screening tool in identifying possible depression in people with stroke both two weeks and three months post stroke.


CF3DODA-Me induces apoptosis, degrades Sp1, and blocks the transformation phase of the blebbishield emergency program.
Cancer stem cells are capable of undergoing cellular transformation after commencement of apoptosis through the blebbishield emergency program in a VEGF-VEGFR2-dependent manner. Development of therapeutics targeting the blebbishield emergency program would thus be important in cancer therapy. Specificity protein 1 (Sp1) orchestrates the transcription of both VEGF and VEGFR2; hence, Sp1 could act as a therapeutic target. Here, we demonstrate that CF3DODA-Me induced apoptosis, degraded Sp1, inhibited the expression of multiple drivers of the blebbishield emergency program such as VEGFR2, p70S6K, and N-Myc through activation of caspase-3, inhibited reactive oxygen species; and inhibited K-Ras activation to abolish transformation from blebbishields as well as transformation in soft agar. These findings confirm CF3DODA-Me as a potential therapeutic candidate that can induce apoptosis and block transformation from blebbishields.


A novel electrochemical aptasensor based on core-shell nanomaterial labeling for simultaneous detection of acetamiprid and malathion.
At present, due to the coexistence of multiple pesticides in vegetables and the enhanced toxicity, a simultaneous detection method for multiple pesticides is urgently needed. In this work, two types of core-shell nanomaterials, Ag-Au core-shell nanoparticles (Ag@Au NPs) and Cu2O-Au core-shell nanoparticles (Cu2O@Au NPs), were synthesized and labeled with acetamiprid aptamer and malathion aptamer to prepare two novel electroactive signal probes, respectively. The two probes were hybridized on the surface of the electrode by the principle of base complementary pairing between the aptamers and the thiolated DNA oligonucleotide sequences, and a dual-signal electrochemical aptasensor for the simultaneous detection of acetamiprid and malathion was established by modified glassy carbon electrode (GCE). The limits of detection (LOD) were calculated to be 43.7 pg mL-1 for acetamiprid and 63.4 pg mL-1 for malathion. The aptasensor determined acetamiprid and malathion in spinach and rape with the recovery rates of 88.9%-112.5% and 98.0%-114.1%, respectively.


The grapevine NIP2;1 aquaporin is a silicon channel.
Silicon (Si) supplementation has been shown to improve plant tolerance to different stresses, and its accumulation in the aerial organs is mediated by NIP2;1 aquaporins (Lsi channels) and Lsi2-type exporters in roots. In the present study, we tested the hypothesis that grapevine expresses a functional NIP2;1 that accounts for root Si uptake and, eventually, Si accumulation in leaves. Own-rooted grapevine cuttings of the cultivar Vinhão accumulated >0.2% Si (DW) in leaves when irrigated with 1.5 mM Si for 1 month, while Si was undetected in control leaves. Real-time PCR showed that VvNIP2;1 was highly expressed in roots and in green berries. The transient transformation of tobacco leaf epidermal cells mediated by Agrobacterium tumefaciens confirmed VvNIP2;1 localization at the plasma membrane. Transport experiments in oocytes showed that VvNIP2;1 mediates Si and arsenite uptake, whereas permeability studies revealed that VvNIP2;1 expressed in yeast is unable to transport water and glycerol. Si supplementation to pigmented grape cultured cells (cv. Gamay Freáux) had no impact on the total phenolic and anthocyanin content, or on the growth rate and VvNIP2;1 expression. Long-term experiments should help determine the extent of Si uptake over time and whether grapevine can benefit from Si fertilization.


Practical aspects of a cholera surveillance programme.
The recent invasion of southern Africa by cholera stimulated the establishment of a regional cholera reference laboratory and surveillance centre. This article describes its activities in general and details the methods employed in the isolation of Vibrio cholerae from sewage, water, seafoods, patients, and carriers. Importance is also attached to the isolation of NAG (non-agglutinable) V. cholerae and V. parahaemolyticus from certain categories of specimens. In recognition of the importance of regional co-operation in combating the problem of cholera, the collaboration of other countries on the subcontinent was invited, and the response is encouraging.


Topical Versus Intravenous Lidocaine in Children With Upper Respiratory Infection Undergoing Anesthesia: A Randomized, Double Blind, Clinical Trial.
The current randomized double-blind clinical trial aimed to compare the incidence of post-operative cough with intravenous vs. topical lidocaine in children with mild upper respiratory infection (URI) anesthetized with laryngeal mask airway (LMA) in the university-affiliated medical center. To assess the incidence of adverse respiratory event including cough, apnea, laryngospasm, bronchospasm following two different methods of lidocaine administration in anesthetized children with mild URI. One hundred and thirty pediatric patients with mild URI (within the previous two weeks) aged between one and six years were enrolled. They were candidates to undergo immediate full ophthalmic examination, and randomly divided into two groups of 65to receive intravenous (1.5 mg/kg) or topical lidocaine on LMA. Anesthesia was induced with sevoflurane, subsequently LMA was inserted when the patient was in deep anesthesia status and maintained on (50% N2O, 50% O2) and 3% sevoflurane. Spontaneous ventilation was maintained throughout the procedure and LMA was removed in deep anesthesia. Outcomes (cough, laryngospasm, bronchospasm and vomiting) were evaluated peri-operatively and one day post-operation. One hundred and twenty four patients fulfilled the trial. Cough (primary outcome) was significantly more frequent among those with topical compared with intravenous lidocaine (46% vs. 26%; P = 0.004). The incidence of laryngospasm (32% vs. 27%), bronchospasm (18% vs. 12%), desaturation (18% vs. 12%) and vomiting (5% vs. 2%) was not statistically different between the groups. The pediatric patients undergoing general anesthesia with LMA with intravenous lidocaine experienced fewer incidence of postoperative cough compared to the ones in the topical lidocaine group.


Competing interactions in arrested States of colloidal clays.
Using experiments, theory and simulations, we show that the arrested state observed in a colloidal clay at high concentrations is stabilized by screened Coulomb repulsion (Wigner glass). Dilution experiments allow us to distinguish this disconnected state, which melts upon addition of water, from a low-concentration gel state, which does not melt. Theoretical modeling and simulations at high concentrations reproduce the measured small angle x-ray scattering static structure factors and confirm the long-range electrostatic nature of the arrested structure. These findings are attributed to the different time scales controlling the competing attractive and repulsive interactions.


Identification of the major Ascaris allergen and its purification to homogeneity by high-performance liquid chromatography.
The major allergen from the body fluid of adult Ascaris suum (ABF) has been identified and purified to homogeneity using gel permeation high-performance liquid chromatography (HPLC). The purity of the Ascaris body fluid allergen (ABA-1) was confirmed by HPLC and SDS-PAGE. ABA-1 appears to be a 25-kDa dimer in its native form, which runs as a 10-kDa monomer on SDS-PAGE under reducing conditions. The allergenicity of the HPLC-purified protein was confirmed using isolated in vivo-sensitised mast cells from infected rats in an in vitro histamine release assay. ABA-1 is responsible for less than 80% of the allergenicity of ABF in this sensitive and specific system. Amino acid composition analysis and N-terminal amino acid sequencing were performed on ABA-1. Comparisons are made between ABA-1 and some of the heterogeneous Ascaris allergen preparations previously published. It is suggested that Asc-1 and allergen A both contain ABA-1 in large quantities and that discrepancies in the literature result from contaminating proteins in these preparations and technical differences in characterization of the predominant molecules present in the preparations. Compositional data suggests that the ABA-1 monomer is a molecule of 94 amino acids (based on a molecular weight estimate of 10 kDa) with a composition resembling that previously published for allergen A. The first 10 amino acids are identical to those of a protein affinity purified from the body fluid of Ascaris suum at the Wellcome Laboratories for Experimental Parasitology (WLEP-14K). The similarity between ABA-1 and WLEP-14k is also apparent on SDS-PAGE.(ABSTRACT TRUNCATED AT 250 WORDS)


In vivo effects of the IKr agonist NS3623 on cardiac electrophysiology of the guinea pig.
The long QT syndrome is characterized by a prolongation of the QT interval measured on the surface electrocardiogram. Prolonging the QT interval increases the risk of dangerous ventricular fibrillations, eventually leading to sudden cardiac death. Pharmacologically induced QT interval prolongations are most often caused by antagonizing effects on the repolarizing cardiac current called IKr. In humans IKr is mediated by the human ether-a-go-go related gene (hERG) potassium channel. We recently presented NS3623, a compound that selectively activates this channel. The present study was dedicated to examining the in vivo effects of NS3623. Injection of 30 mg/kg NS3623 shortened the corrected QT interval by 25 +/- 4% in anaesthetized guinea pigs. Accordingly, 50 mg/kg of NS3623 shortened the QT interval by 30 +/- 6% in conscious guinea pigs. Finally, pharmacologically induced QT prolongation by a hERG channel antagonist (0.15 mg/kg E-4031) could be reverted by injection of NS3623 (50 mg/kg) in conscious guinea pigs. In conclusion, the present in vivo study demonstrates that injection of the hERG channel agonist NS3623 results in shortening of the QTc interval as well as reversal of a pharmacologically induced QT prolongation in both anaesthetized and conscious guinea pigs.


An accurate NH2(X2A'') CHIPR potential energy surface via extrapolation to the complete basis set limit and dynamics of the N(2D) + H2(X1Σ+g) reaction.
The amidogen radical (NH2) and its associated N(2D) + H2(X1Σ+g) → H(2S) + NH(X3Σ-) reaction have great significance in interstellar chemistry and the accurate potential energy surface (PES) is the basis for studying them. We report a new and accurate PES for the ground state NH2(X2A'') using the combined-hyperbolic-inverse-power-representation methodology based on 7970 ab initio energy points computed at the Davidson-corrected internally contracted multireference configuration interaction level of theory. Both aug-cc-pVTZ and aug-cc-pVQZ basis sets have been employed to extrapolate the energies to the complete basis set limit. The analytical PES reproduces well with the ab initio energy points with a root mean square deviation of 55.7 cm-1. The topographical features of the analytical PES are examined in detail and agree well with the previous theoretical results. The integral cross sections and rate constants of the N(2D) + H2(X1Σ+g) → H(2S) + NH(X3Σ-) reaction are obtained using the quasi-classical trajectory method and the time-dependent wave packet method and then compared with the available theoretical and experimental values.


[Gene therapy in cardiology].
The modification of genetic material of living cells for therapeutic purposes have been regarded by many as an unrealized promise. However, recent successful achievements in the field have contributed to vanish this perception and have reopened the possibility to use gene therapy as a medical intervention in humans. In the case of cardiovascular diseases, and despite its high prevalence, the number of approved human gene therapy protocols has remained low. This may be due, at least in part, to the availability of effective alternative therapies for some of the most common vasculopathies. However, recent advances in the understanding of the genetic and molecular bases of the cardiovascular system have opened the possibility to introduce gene therapy in the management of a great variety of cardiovascular disorders. The purpose of this communication is to briefly summarize the progress in this area.


A Continuous Late-Onset Sepsis Prediction Algorithm for Preterm Infants Using Multi-Channel Physiological Signals From a Patient Monitor.
The aim of this study is to develop an explainable late-onset sepsis (LOS) prediction algorithm using continuous multi-channel physiological signals that can be applied to a patient monitor for preterm infants in a neonatal intensive care unit (NICU). The algorithm uses features on heart rate variability (HRV), respiration, and motion, based on electrocardiogram (ECG) and chest impedance (CI). In this study, 127 preterm infants were included, of whom 59 were bloodculture-proven LOS patients and 68 were control patients. Features in 24 hours before the onset of sepsis (LOS group), and an age-matched onset time point (control group) were extracted and fed into machine learning classifiers with gestational age and birth weight. We compared the prediction performance of several well-known classifiers using features from different signal channels (HRV, respiration, and motion) individually as well as their combinations. The prediction performance was evaluated using the area under the receiver-operating-characteristics curve (AUC). The best performance was achieved by an extreme gradient boosting classifier combining features from all signal channels, with an AUC of 0.88, a positive predictive value of 0.80, and a negative predictive value of 0.83 during the 6 hours preceding LOS onset. This feasibility study demonstrates the complementary predictive value of motion information in addition to cardiorespiratory information for LOS prediction. Furthermore, visualization of how each feature in the individual patient impacts the algorithm decision strengthen its interpretability. In clinical practice, it is important to motivate clinical interventions and this visualization method can help to support the clinical decision.


Socioeconomic factors differentiating maternal and child health-seeking behavior in rural Bangladesh: A cross-sectional analysis.
There has been an increasing availability and accessibility of modern health services in rural Bangladesh over the past decades. However, previous studies on the socioeconomic differentials in the utilization of these services were based on a limited number of factors, focusing either on preventive or on curative modern health services. These studies failed to collect data from remote rural areas of the different regions to examine the socioeconomic differentials in health-seeking behavior. Data from 3,498 randomly selected currently married women from three strata of households within 128 purposively chosen remote villages in three divisions of Bangladesh were collected in 2006. This study used bivariate and multivariate logistic analyses to examine both curative and preventive health-seeking behaviors in seven areas of maternal and child health care: antenatal care, postnatal care, child delivery care, mother's receipt of Vitamin A postpartum, newborn baby care, care during recent child fever/cough episodes, and maternal coverageby tetanus toxoid (TT). A principal finding was that a household's relative poverty status, as reflected by wealth quintiles, was a major determinant in health-seeking behavior. Mothers in the highest wealth quintile were significantly more likely to use modern trained providers for antenatal care, birth attendance, post natal care and child health care than those in the poorest quintile (chi2, p < 0.01). The differentials were less pronounced for other factors examined, such as education, age, and the relative decision-making power of a woman, in both bivariate and multivariate analyses. Within rural areas of Bangladesh, where overall poverty is greater and access to health care more difficult, wealth differentials in utilization remain pronounced. Those programs with high international visibility and dedicated funding (e.g., Immunization and Vitamin A delivery) have higher overall prevalence and a more equitable distribution of beneficiaries than the use of modern trained providers for basic essential health care services. Implications of these findings and recommendations are provided.


Subcellular distribution of alpha 1-adrenergic receptors in rat liver.
The distribution of alpha 1-adrenergic receptors in rat liver subcellular fractions was studied using the alpha 1-adrenergic receptor ligand [3H]prazosin. The highest number of [3H]prazosin binding sites was found in a plasma membrane fraction followed by 2 Golgi and a residual microsomal fraction, the numbers of binding sites were 1145, 845, 629 and 223 fmol/mg protein, respectively. When the binding in these fractions was compared with the activity of plasma membrane 'marker' enzymes in the same fractions a relative enrichment of [3H]prazosin binding sites was found in the residual microsomes and one of the Golgi fractions. Photoaffinity labelling with 125I-arylazidoprazosin in combination with SDS-polyacrylamide gel electrophoresis revealed the specific binding to 40 and 23 kDa entities in a Golgi fraction, while in plasma membranes the binders had an apparent molecular mass of 36 and 23 kDa. When [3H]prazosin was injected in vivo into rat portal blood followed by subcellular fractionation of liver, a pattern of an initial rapid decline and thereafter a slow decline of radioactivity was noted in all fractions. Additionally, in the two Golgi fractions a transient accumulation of radioactivity occurred between 5 and 10 min after the injection. The ED50 values for displacement of [3H]prazosin with adrenaline was lowest in the plasma membrane fraction, followed by the residual microsomes and Golgi fractions, the values were 10(-6), 10(-5) and 10(-4) mol/l, respectively. On the basis of lack of correlation between distribution of alpha 1-adrenergic antagonist binding and adenylate cyclase activity, differences in the molecular mass of alpha 1-adrenergic antagonist binders, differences in the kinetics of in vivo binding and accumulation of [3H]prazosin and also differences in agonist affinity between plasma membrane and Golgi fractions, it is concluded that alpha 1-adrenergic receptors are localized to low-density intracellular membranes involved in receptor biosynthesis and endocytosis.


The Drosophila neurogenic locus mastermind encodes a nuclear protein unusually rich in amino acid homopolymers.
The neurogenic loci of Drosophila are required for proper partitioning of ectodermal cells into epidermal versus neural lineages. The loci appear to encode components of a developmental pathway involving cellular communication. In an effort to understand the role of the neurogenic locus mastermind in these processes, we have characterized its expression and sequence. The locus produces a number of transcripts that accumulate ubiquitously during early embryogenesis but more specifically in the central nervous system during later stages. Sequence analysis of a major cDNA product predicts an unusual protein containing an abundance of amino acid homopolymers and charge clusters typical of regulatory molecules. Nearly half of the mass of the predicted protein derives from only three amino acids: glutamine, glycine, and asparagine. Immunohistochemical studies of the protein in cell culture and early embryos show that the protein accumulates predominantly in the nucleus.


Kinetic Glomerular Filtration Rate Estimation Compared With Other Formulas for Evaluating Acute Kidney Injury Stage Early After Kidney Donation.
Kinetic glomerular filtration rate estimation may have more power and versatility than the Modification of Diet in Renal Disease or Cockcroft-Gault formula for evaluating kidney function when plasma creatinine fluctuates rapidly. After kidney donation, glomerular filtration rate rapidly fluctuates in otherwise healthy patients. We compared 3 formulas for estimating glomerular filtration rate: kinetic, Modification of Diet in Renal Disease, and Cockcroft-Gault, for determining stages of acute kidney injury early after kidney donation. In 42 living kidney donors, we measured serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin, and glomerular filtration rates before uninephrectomy and 3 days afterward. To estimate glomerular filtration rate, we used Cockcroft-Gault, Modification of Diet in Renal Disease, and kinetic equations. We sought the most accurate formula for staging acute kidney injury according to the risk, injury, failure, loss, and end-stage criteria. The kinetic glomerular filtration rate model found more cases of stage 3 acute kidney injury than did the Modification of Diet in Renal Disease or Cockcroft-Gault formula. Receiver operating characteristic curves showed that the kinetic glomerular filtration rate model had more sensitivity and specificity than the Cockroft-Gault formula for discriminating among risk, injury, failure, loss, and end-stage criteria stages of acute kidney injury, based on serum creatinine changes. On day 2 after donation, a more sensitive marker with a shorter half-life (serum neutrophil gelatinase-associated lipocalin) was more significantly correlated with kinetic glomerular filtration rate estimation. The kinetic glomerular filtration rate model was able to discriminate stages of acute kidney injury early after kidney donation according to risk, injury, failure, loss, and end-stage criteria better than the Modification of Diet in Renal Disease or Cockcroft-Gault formulas. The kinetic model detected failure-stage acute kidney injury ≥ 1 to 2 days earlier than the MDRD formula, CG formula detected no failure.