Micelle-Mediated Chemiluminescence as an Indicator for Micellar Transitions.
The structural phase of micelles plays an important role in controlling the micellar performance. Despite the great developments of some advanced characterization techniques, it remains challenging to achieve fast and sensitive determination of micellar transitions in solution. Herein, a novel indicator system for micellar transitions was developed based on the micelle-mediated peroxyoxalate chemiluminescence that showed a sensitive response toward the changes of micellar morphologies. A peroxyoxalate derivative and a fluorophore were first coassembled into the hydrophobic cavities of micelles of the typical cationic surfactant cetyltrimethylammonium bromide (CTAB). A strong and rapidly falling chemiluminescence response was exhibited in spherical micelles as a result of the loose arrangement of CTAB molecules. By contrast, rodlike or wormlike micelles transformed from spherical micelles could induce a compact arrangement of CTAB molecules, leading to a weak chemiluminescence emission with a slow decay rate. The practicability and universality of the chemiluminescent indicator were demonstrated by determining the micellar transitions in a variety of surfactant solutions (ionic, nonionic, and polymeric). These findings open attractive perspectives for the practice of chemiluminescence technique in micelle characterization.


Effectiveness of hyperbaric oxygen therapy in patients with acute and chronic cochlear disorders.
Over the course of 18 months 359 patients with defined acute and chronic inner ear disorders who had not responded to treatment with medication were given hyperbaric oxygen (HBO) therapy. The inner ear diseases of the patients were divided, based on the duration of their conditions, into four symptomatic groups. Of the patients who had had hearing loss for less than 3 months, noticeable improvement or complete recovery was seen in 13% (20 dB in at least three test frequencies); 25.2% showed an improvement between 10 and 20 dB. Changes up to 10 dB or less were not considered to be positive. Patients with a pretreated hearing loss for more than 3 months had markedly less benefit from HBO therapy. Two percent regained normal hearing function. In 30% an improvement of more than 10 dB was achieved. For patients who had suffered from tinnitus for less than 3 months excellent improvement was seen in 6.7% and noticeable improvement in 44.3% expressed by means of a visual analog scale. In 44.3% the tinnitus was described as unchanged. Patients who had had tinnitus for more than 3 months before HBO therapy showed a less favorable response to HBO. In none of the patients did the tinnitus disappear; 34.4% of the patients described a noticeable improvement in their complaints.


Hypnotic relaxation results in elevated thresholds of sensory detection but not of pain detection.
Many studies show an effectiveness of hypnotic analgesia. It has been discussed whether the analgesic effect is mainly caused by the relaxation that is concomitant to hypnosis. This study was designed to evaluate the effects of hypnotic relaxation suggestion on different somatosensory detection and pain thresholds. Quantitative sensory testing (QST) measurements were performed before and during hypnosis in twenty-three healthy subjects on the dorsum of the right hand. Paired t-test was used to compare threshold changes. The influence of hypnotic susceptibility was evaluated by calculating correlation coefficients for threshold changes and hypnotic susceptibility (Harvard group scale). During hypnosis significantly changed somatosensory thresholds (reduced function) were observed for the following sensory detection thresholds: Cold Detection Threshold (CDT), Warm Detection Threshold (WDT), Thermal Sensory Limen (TSL) and Mechanical Detection Threshold (MDT). The only unchanged sensory detection threshold was Vibration Detection Threshold (VDT). No significant changes were observed for the determined pain detection thresholds (Cold Pain Thresholds, Heat Pain Thresholds, Mechanical Pain Sensitivity, Dynamic Mechanical Allodynia, Wind-up Ratio and Pressure Pain Threshold). No correlation of hypnotic susceptibility and threshold changes were detected. Hypnotic relaxation without a specific analgesic suggestion results in thermal and mechanical detection, but not pain threshold changes. We thus conclude that a relaxation suggestion has no genuine effect on sensory pain thresholds. ClinicalTrials.gov, Identifier: NCT02261155 (9th October 2014).


A simple spatial model to explain the distribution of human tick-borne encephalitis cases in hungary.
Tick-borne encephalitis (TBE) is a common medical problem in Hungary and throughout much of Europe and Asia. This paper develops a geographic model that helps to predict the distribution of human tick-borne encephalitis cases in Hungary. The model is tested on a dataset of serologically confirmed TBE cases mapped by patients' residences. Case densities (incidence rates) are compared to predicted distributions of TBE derived from digital land-cover data. Maps are analyzed at the county level and on a smaller spatial scale. The analyses identified three major factors that shape the geographic distribution of human TBE cases in Hungary. The most important component is the distribution of forest habitat. TBE incidence correlates positively with the amount of forested habitat in each county. On a finer scale, the amount of forests within a 2500-meter radius of each town and village correlated significantly with TBE incidence rate. Based on these data, about 30% of the variation in TBE incidence is accounted for by the specific distribution of forest habitats in Hungary. Besides the distribution of forests, differences in human land-use practices among regions also affect the distribution of TBE cases. Additionally, because of the low transmission rate of the virus to humans, the perceived distribution of TBE cases is affected by random stochastic events. As a consequence of stochastic variation, meaningful patterns in the distribution of TBE cases can be only recognized when data are analyzed over broader temporal and spatial scales.


Clinical comparison of the AutoMicrobic system gram-positive identification card, API Staph-Ident, and conventional methods in the identification of coagulase-negative Staphylococcus spp.
In an effort to rapidly identify coagulase-negative staphylococci (CNS), a clinical comparison was conducted with the AutoMicrobic system Gram-Positive Identification Card (GPI) (Vitek Systems, Inc.), the API Staph-Ident (Analytab Products), and the conventional methods of W. E. Kloos and K. H. Schleifer (W. E. Kloos and K. H. Schleifer, J. Clin. Microbiol. 1:82-88, 1975). CNS isolates tested included 157 from blood and 33 from urine in pure culture at greater than 10(5) CFU/ml. S. epidermidis accounted for 79.6 and 60.6% of the isolates from blood and urine, respectively. S. saprophyticus was the next most frequent urine isolate (27.4%). Other CNS species were isolated from blood and urine specimens with frequencies of less than 5%. Overall, the GPI correctly identified 158 (83.2%) of the 190 CNS, whereas the Staph-Ident identified 124 (65.3%) without further testing. This resulted in the GPI and Staph-Ident correctly identifying 95.9 and 74.5% of the S. epidermidis and 100 and 33% of the S. saprophyticus, respectively. The GPI misidentified 8 (47%) of the S. hominis and S. warneri isolates as S. saprophyticus, indicating the need for novobiocin testing. These data suggest that the GPI is a more definitive method for the rapid identification of S. epidermidis than the Staph-Ident and that both systems require additional testing to identify S. saprophyticus.


CD44 functions in Wnt signaling by regulating LRP6 localization and activation.
Wnt reception at the membrane is complex and not fully understood. CD44 is a major Wnt target gene in the intestine and is essential for Wnt-induced tumor progression in colorectal cancer. Here we show that CD44 acts as a positive regulator of the Wnt receptor complex. Downregulation of CD44 expression decreases, whereas CD44 overexpression increases Wnt activity in a concentration-dependent manner. Epistasis experiments place CD44 function at the level of the Wnt receptor LRP6. Mechanistically, CD44 physically associates with LRP6 upon Wnt treatment and modulates LRP6 membrane localization. Moreover, CD44 regulates Wnt signaling in the developing brain of Xenopus laevis embryos as shown by a decreased expression of Wnt targets tcf-4 and en-2 in CD44 morphants.


Identification of epithelial to mesenchymal transition as a novel source of fibroblasts in intestinal fibrosis.
Intestinal fibrosis is a major complication of Crohn disease (CD), but the precise mechanism by which it occurs is incompletely understood. As a result, specific therapies to halt or even reverse fibrosis have not been explored. Here, we evaluated the contribution of epithelial to mesenchymal transition (EMT) to intestinal fibrosis associated with a mouse model of CD and also human inflammatory bowel disease. Mice administered intrarectal 2,4,6-trinitrobenzene sulfonic acid (TNBS) develop inflammation and fibrosis that resembles CD both histologically and by immunologic profile. We utilized this model to molecularly probe the contribution of EMT to intestinal fibrosis. Additionally, we utilized double-transgenic VillinCre;R26Rosa-lox-STOP-lox-LacZ mice, in which removal of the STOP cassette by Cre recombinase in villin(+) intestinal epithelial cells activates permanent LacZ expression, to lineage trace epithelial cells that might undergo EMT upon TNBS administration. TNBS-induced fibrosis is associated with the presence of a significant number of cells that express both epithelial and mesenchymal markers. In the lineage tagged transgenic mice, the appearance of LacZ(+) cells that also express the fibroblast marker FSP1 unequivocally demonstrates EMT. Transforming growth factor (TGF)-beta1, a known inducer of EMT in epithelial cells, induces EMT in rat intestinal epithelial cells in vitro, and bone morphogenic protein-7, an antagonist of TGF-beta1, inhibits EMT and fibrosis both in vitro and in the TNBS-treated mice. Our study demonstrates that EMT contributes to intestinal fibrosis associated with the TNBS-induced model of Crohn colitis and that inhibition of TGF-beta1 with recombinant human bone morphogenic protein-7 prevents this process and prevents fibrosis.


Effect of water density on the absorption maximum of hydrated electrons in sub- and supercritical water up to 400 degrees C.
The optical absorption spectra of the hydrated electron (e(aq) (-)) in supercritical (heavy) water (SCW) are measured by electron pulse radiolysis techniques as a function of water density at three temperatures of 380, 390, and 400 degrees C, and over the density range of approximately 0.2-0.65 g/cm(3). In agreement with previous work, the position of the e(aq) (-) absorption maximum (E(A(max) )) is found to shift slightly to lower energies (spectral "redshift") with decreasing density. A comparison of the present E(A(max) )-density data with other measurements already reported in the literature in subcritical (350 degrees C) and supercritical (375 degrees C) water reveals that at a fixed pressure, E(A(max) ) decreases monotonically with increasing temperature in passing through the phase transition at t(c). By contrast, at constant density, E(A(max) ) exhibits a minimum as the water passes above the critical point into SCW. These behaviors are explained in terms of simple microscopic arguments based on the crucial role played by local density and configurational fluctuations (associated with criticality) in providing pre-existing polymeric clusters, which act as trapping sites for electrons.


Strain specific behavioural response to environmental enrichment in the mouse.
The influence of environmental enrichment on the behaviour of the mouse has been studied in two inbred strains (C57BL and BALB/c). Male mice of each of the two strains were subjected to behavioural tests after being housed for two months either under standard housing conditions or in an enriched environment. The results of the behavioural test indicated that the C57BL mice housed in the enriched environment were more reactive and alert compared to mice housed in the standard environment. In the BALB/c mice results may be interpreted as if enriched environments lead to an increased level of anxiety. It is concluded that environmental enrichment has a strain specific effect on the behaviour of mice.


Daptomycin plus fosfomycin, a synergistic combination in experimental implant-associated osteomyelitis due to methicillin-resistant Staphylococcus aureus in rats.
The aim of this study was to evaluate the combination of daptomycin and fosfomycin in experimental chronic implant-associated osteomyelitis due to methicillin-resistant Staphylococcus aureus (MRSA). Infection was induced in the tibiae of rats by the insertion of a bacterial inoculum (1 to 5×10(8) CFU/ml) of a clinical MRSA isolate and a titanium wire. Four weeks after infection, each animal was assigned to a treatment group: daptomycin monotherapy at 60 mg/kg of body weight once daily (n=10), fosfomycin monotherapy at 40 mg/kg once daily (n=10), or daptomycin and fosfomycin combined at 60 mg/kg and 40 mg/kg, respectively, once daily (n=9). Ten animals were left untreated. After a 3-week treatment period, the animals were euthanized, and the infected tibiae and implants were processed for quantitative bacterial cultures. The bacterial cultures from bones were positive for MRSA in all animals in the untreated group, the daptomycin group, and the fosfomycin group, with median bacterial counts of 2.34×10(6) CFU/g bone, 1.57×10(6) CFU/g bone, and 3.48×10(2) CFU/g bone, respectively. In the daptomycin-fosfomycin group, 6 out of 9 animals were positive for MRSA, with a median count of 7.92 CFU/g bone. Bacterial cultures derived from the titanium wires were negative in the fosfomycin- and daptomycin-fosfomycin-treated groups. Based on bacterial counts in bones, treatment with daptomycin-fosfomycin was statistically significantly superior to all that of the other groups (P≤0.003). Fosfomycin was superior to daptomycin and no treatment (P<0.0001). No development of resistance was observed in any treatment arm. The combination of daptomycin and fosfomycin demonstrated synergism against MRSA in experimental implant-associated osteomyelitis.


Effect of central urotensin II on heart rate, blood pressure and brain Fos immunoreactivity in conscious rats.
Central administration of urotensin II (UII) increases heart rate (HR), cardiac contractility, and plasma levels of epinephrine and glucose. To investigate the mechanisms causing these responses we examined the effects of i.c.v. administration of rat UII (10 microg) on the sympatho-adrenal and pituitary-adrenal axes in conscious rats, and we mapped the brain sites activated by UII by immunohistochemically detecting Fos expression. In six conscious rats i.c.v. UII, but not vehicle, increased HR significantly 60-90 min after treatment and increased plasma glucose at 60 and 90 min, both indicators of increased epinephrine release. Plasma corticosterone levels were significantly elevated 90 min after i.c.v. UII. Conscious rats, given i.c.v. UII (n=12) and killed after 100 or 160 min, showed increased Fos-immunoreactivity (Fos-IR) in the nucleus of the solitary tract and the central nucleus of the amygdala (CeA) at both time points, compared with vehicle (n=11). In UII-treated rats, Fos-IR in the paraventricular nucleus of the hypothalamus (PVN) was significantly elevated at 160 min, but not 100 min, compared with vehicle. There were no increases in Fos-IR in the rostral ventrolateral medulla or the A5 cell group, areas associated with sympathetic outflow to the adrenal gland. In summary, i.c.v. UII increased HR and plasma glucose and corticosterone in conscious rats. UII increased Fos-IR in the CeA and PVN, but over a longer time course in the latter. These findings indicate that UII acts on specific brain nuclei to stimulate the hypothalamo-pituitary-adrenal axis and to stimulate adrenal sympathetic nerve activity.


Quantification of the intragranular porosity formed in bioleaching of pyrite by Thiobacillus ferroxidans.
During the bacterial oxidation of a pure pyrite by Thiobacillus ferrooxidans, a great number of corrosion tunnels appear that are easily revealed by scanning electron microscopy observations. This involves an increase in the surface area without significant granulometric reduction of mineral grains. Thus, the evaluation of intragranular porosity, determined by elution front analysis, allows one to estimate accurately the fraction of oxidized sulphide, because of the development of deep holes (propagating pore mechanism). After 60 days of bioleaching, the intragranular porosity represents about 34% of the initial sulphide volume, which corresponds to 25 km of tunnels (2 microm i.d.) per gram of pyrite. On other hand, the granulometric reduction ( approximately 7%) is responsible for a 23% decrease of the initial sulphide volume. The elution front analysis appears as a nondestructive method for measuring the intragranular porosity of the bioleached pyrite.


Polyelectrolyte Multicomponent Colloidosomes Loaded with Nisin Z for Enhanced Antimicrobial Activity against Foodborne Resistant Pathogens.
Food grade micro- or nano-carrier systems (NCS) are being developed to improve the controlled release of antimicrobial agents. To augment the stability of liposomal NCS and to overcome the limitations associated with the use of free bacteriocin (nisin) in the food system, multi-component colloidosomes (MCCS) were developed by electrostatic interactions between anionic alginate and cationic chitosan (multilayer) around phospholipids based liposomes (core). Zeta-sizer results revealed the average diameter of 145 ± 2 nm, 596 ± 3 nm, and 643 ± 5 nm for nano-liposome (NL), chitosomes (chitosan coated NL) and MCCS, respectively. Zeta potential values of NCS varied from -4.37 ± 0.16 mV to 33.3 ± 6 mV, thus both chitosomes (CS) and MCCS were positively charged. Microstructure analysis by scanning electron microscope (SEM) revealed relatively higher size of MCCS with smooth and round morphology. TGA and DSC based experiments revealed that MCCS were thermally more stable than uncoated liposomes. Encapsulation efficiency of nisin in MCCS was observed to be 82.9 ± 4.1%, which was significantly higher than NL (56.5 ± 2.5%). FTIR analyses confirmed the cross-linking between sodium alginate and chitosan layer. Both qualitative (growth kinetics) and quantitative (colony forming unit) antimicrobial assays revealed that nisin loaded MCCS have superior potential to control resistant foodborne pathogens including Staphylococcus aureus, Listeria monocytogenes, and Enterococcus faecalis, (5.8, 5.4, and 6.1 Log CFUmL-1 reduction, respectively) as compared to free nisin, loaded NL or CS. Controlled release kinetics data fitted with Korsmeyer-Peppas model suggested that nisin release from MCCS followed Fickian diffusion. Cytotoxic studies on human blood cells and HepG2 cell lines revealed hemocompatibility and non-toxicity of MCCS. Thus, due to enhanced controlled release, stability and biocompatibility; these multi-component colloidosomes can be useful for incorporating antimicrobial agents into functional foods, beverages and pharmaceutical products to combat pathogenic and spoilage bacteria.


Divergent Perspectives of Filipino PLWH, Their Partners, and Care Providers on Sexuality After an HIV Diagnosis: A Q-Methodological Analysis.
This study explores the perspectives that Filipinos with professional and personal experience with people living with HIV hold about sexuality after an HIV diagnosis. Twenty people living with HIV (PLWH), 11 partners of PLWH, and 10 HIV care professionals in the Philippines were asked to rank-order 54 statements about sexuality post-HIV diagnosis. They shared the reasoning behind their rankings on an online survey platform. By-person factor analysis was done, with factors extracted based on principal component analysis followed by varimax rotation. The analysis yielded six factors with 22 males' and 3 females' Q-sorts exemplifying the views regarding sexuality post-HIV diagnosis: to be human, is to be sexual; information is power; fear of being othered; partnership for enhanced sexuality; disclosure and trust; and communication is foundational. This study revealed diverse viewpoints about sexuality after an HIV diagnosis. HIV care professionals play a decisive role in addressing concerns relating to the sexual health and well-being of newly diagnosed PLWH.


OsSUV3 functions in cadmium and zinc stress tolerance in rice (Oryza sativa L. cv IR64).
Protein of nuclear encoded SUV3 (suppressor of Var 3) gene is a DNA and RNA helicase, localized in mitochondria and is a subunit of the degradosome complex involved in regulation of RNA surveillance and turnover. To overcome the abiotic stress-induced loss of crop yield, a multi-stress tolerant trait is required. Beside salinity stress the heavy metals including cadmium and zinc also affect the yield and quality of food crops. Since rice is a one of the staple food therefore it is important to develop a multi-stress including salinity and metal tolerant variety. Recently we have reported the role of OsSUV3 in salinity stress tolerance in rice; however, its role in metal stress has not been studied so far. Here we report that in response to cadmium and zinc stress the OsSUV3 transcript level is induced in rice and its overexpression in transgenic IR64 rice plants confers the metal stress tolerance. In addition to its previously reported role in salinity stress tolerance, this study further shows the role of OsSUV3 helicase in cadmium and zinc stress tolerance suggesting its involvement in multi-stress tolerance.


Myogenesis in human denervated muscle biopsies.
Electron microscopic studies of long-term denervated rat muscles have identified very small, immature myofibers that are believed to arise from detached satellite cells that have fused to form new fibers within the interstitial space. At present, it is unknown whether and to what extent equivalent fibers exist in denervated human muscle. Serial sections of muscle biopsies from 66 patients diagnosed with polyneuropathy or amyotrophic lateral sclerosis were immunolabeled with anti-NCAM and anti-neonatal myosin heavy chain monoclonal antibodies that are both neurally and developmentally regulated. We evaluated 200 myofibers in each section. Of the biopsy specimens, 75% contained small myofibers that showed a thin perinuclear cytoplasmic rim. Small fibers expressing neonatal myosin heavy chain (MHCn+) were found in all of these biopsies (100%) and NCAM+ fibers in 98%. The percentage of MHCn+ small fibers averaged 82% and NCAM+ small myofibers averaged 40%. The percentage of NCAM+ small fibers was significantly lower than that of MHCn+ fibers. In contrast, the percentage of MHCn+ vs. NCAM+ angular atrophic fibers did not show a significant difference. A substantial subset of neurogenic biopsies showed small fibers that differ from angular atrophic fibers both in size and expression pattern of MHCn and NCAM. Myogenesis appears to be a frequent finding in neurogenic atrophy.


Coupling Underwater Superoleophobic Membranes with Magnetic Pickering Emulsions for Fouling-Free Separation of Crude Oil/Water Mixtures: An Experimental and Theoretical Study.
Oil/water separations have become an area of great interest, as growing oil extraction activities are increasing the generation of oily wastewaters as well as increasing the risk of oil spills. Here, we demonstrate a membrane-based and fouling-free oil/water separation method that couples carbon nanotube-poly(vinyl alcohol) underwater superoleophobic ultrafiltration membranes with magnetic Pickering emulsions. We demonstrate that this process is insensitive to low water temperatures, high ionic strength, or crude oil loading, while allowing operation at high permeate fluxes and producing high quality permeate. Furthermore, we develop a theoretical framework that analyzes the stability of Pickering emulsions under filtration mechanics, relating membrane surface properties and hydrodynamic conditions in the Pickering emulsion cake layer to membrane performance. Finally, we demonstrate the recovery and recyclability of the nanomagnetite used to form the Pickering emulsions through a magnetic separation step, resulting in an environmentally friendly, continuous process for oil/water separation.


Evaluation and Management of Cardiac Tumors.
Our purpose is to discuss the importance of multimodality imaging in the assessment of cardiac tumors and management. We have compiled a recent review of the scientific literature and embedded our clinical pathways and recommendations based on data and clinical experience. The use of contrast echocardiography in the assessment of cardiac masses has been shown to be helpful in distinguishing tumor from thrombus. Deformation imaging of cardiac tumors has been shown to differentiate better rhabdomyomas from fibromas in pediatric patients. Cardiac MRI (CMR) appears to be helpful in determining whether cardiac tumors are benign or malignant by identifying presence of infiltration, uptake of contrast in first pass perfusion and gadolinium enhancement. Patients with evidence of cardiac metastases by CMR show similar survival to stage IV cancer without cardiac metastases. In our institution, we use a standardized approach for the evaluation of cardiac masses, which includes multimodality imaging in the appropriate clinical context. The autotransplantation surgical technique has shown some promise in improving survival in patients with primary cardiac sarcomas. In our institution, we do not routinely recommend anticoagulation for "tumor-thrombus" in renal cell carcinoma due to risk of bleeding from primary tumor. Cardiac masses are often found incidentally, but sometimes can present with cardiovascular symptoms due to obstruction and valvular dysfunction, which may prompt imaging. It is important to determine whether the mass is a normal variant, imaging artifact, vegetation, thrombus, or tumor. Transthoracic echocardiography is ideally suited to be the initial imaging modality because of the portability, wide availability, lack of radiation, and relatively low cost. The gold standard cardiac imaging technique to distinguish tumor from thrombus is contrast enhanced CMR with prolonged inversion time. Advantages of CMR when compared to echocardiography regarding characterization of cardiac tumors are as follows: larger field of view, better spatial resolution, better tissue characterization, lack of attenuation, and ability to image at any prescribed plane. Primary and secondary cardiac tumors have particular characteristics in echocardiography and CMR. Imaging of cardiac tumors plays an important role in establishing a diagnosis and in planning management.


The confluence of Faraday's and Kirchoff's laws in bioelectrochemical systems.
When external measurements are made of electrochemical systems, including bioelectrochemical, there results an interaction. Such measurements cause electrochemical processes to take place that are significant. This work looks into the nature and significance of the interfacial processes on membrane and membrane phenomena. The conclusion reached is that interfacial processes are important and cannot be overlooked.


Structure-Energy Relationships of Halogen Bonds in Proteins.
The structures and stabilities of proteins are defined by a series of weak noncovalent electrostatic, van der Waals, and hydrogen bond (HB) interactions. In this study, we have designed and engineered halogen bonds (XBs) site-specifically to study their structure-energy relationship in a model protein, T4 lysozyme. The evidence for XBs is the displacement of the aromatic side chain toward an oxygen acceptor, at distances that are equal to or less than the sums of their respective van der Waals radii, when the hydroxyl substituent of the wild-type tyrosine is replaced by a halogen. In addition, thermal melting studies show that the iodine XB rescues the stabilization energy from an otherwise destabilizing substitution (at an equivalent noninteracting site), indicating that the interaction is also present in solution. Quantum chemical calculations show that the XB complements an HB at this site and that solvent structure must also be considered in trying to design molecular interactions such as XBs into biological systems. A bromine substitution also shows displacement of the side chain, but the distances and geometries do not indicate formation of an XB. Thus, we have dissected the contributions from various noncovalent interactions of halogens introduced into proteins, to drive the application of XBs, particularly in biomolecular design.


Use of Bariatric Ports in 4-Arm Robotic Partial Nephrectomy: A Comparative Study With the Standard 3-Arm Technique.
Objectives We aim to compare the outcomes of a 3-arm versus a 4-arm robotic assisted partial nephrectomy (RAPN) using the da Vinci Si model; as well as, illustrate the deployment of long ports to decrease arm collision during the 4-arm approach. Patients and Methods Results of RAPN in a Middle Eastern tertiary referral center from August 2013 to December 2017 are reported. Comparison between 3 versus 4-arm robotic approaches was done in regards to patient and tumor characteristics, operative parameters, and postoperative outcomes. Statistical analysis was performed with the Student's t-test and chi-squared test. Results Forty consecutive 3-arm RAPNs and 40 consecutive 4-arm RAPNs were retrospectively evaluated. Differences in tumor complexity between the two groups were statistically insignificant. Similarly, surgical margin positivity, mean ischemia time, estimated blood loss, length of hospital stay, and mean change in serum creatinine were statistically insignificant between the two groups. Mean operative time was significantly shorter by 42 minutes in the 4-arm vs 3-arm group (p=0.01). Conclusions The addition of a 4th arm in RAPN can be of benefit in centers that still rely on the da Vinci Si model. The ease of hilar dissection, retraction, and surgeon independence instigated a statistically significant decrease in operative time with 4-arm use.


[Clinical features of ventilator-associated pneumonia caused by acinetobacter].
To investigate the clinical features of ventilator-associated pneumonia (VAP) caused by acinetobacter. The clinical manifestations of 45 cases with ventilator-associated pneumonia caused by acinetobacter between 1995 and 2002 were analyzed. Bacterial susceptibility of acinetobacter strains was determined by Kerby-Bauer method. The mean age of the subjects was 58 +/- 13 years with 31 patients older than 60 years. All the patients had underlying diseases, most of which were respiratory diseases (37.8%), nervous system diseases (22.2%), and trauma (22.2%). Thirteen cases (28.9%) were mixed infections with other bacteria. The main manifestations were fever, purulent secretion, and solidification in the lung. X-ray revealed inflammatory infiltration in lower lobes of both sides. The mortality was 37.8%. The in vitro activity tests of 28 antibiotics against the acinetobacter strains showed that they were multiresistant. Polymysin B, imipenem, minocycline, ofloxacin, and amikacin were relatively active. The patients with VAP caused by acinetobacter usually had underlying diseases without unique features and high mortality, and the isolated strains were often mutiresistant. It is necessary to make early diagnosis, select the appropriate agents, and improve the disinfection of the breath loop in the ventilator.


Growth inhibition of Staphylococcus aureus after experimental infection of the udder by high and low concentration of lactoferrin and lysozyme in milk.
Ten Holstein-Friesian cows were distributed according to their lactoferrin and lysozyme concentrations in milk into groups with high and low concentrations. In each cow, a front and a rear mammary quarter was infected by inoculation of 10(8) colony forming units of Staphylococcus aureus while the other two quarters were infused with 2 ml of sterile milk. The reaction was observed during the following nine days. After 10 hours the cell count, the lactoferrin and lysozyme concentrations were increased in the infected and control quarters. In milk samples with a high initial lactoferrin concentration the colony forming units of S. aureus were higher than in those with a low concentration. In milk samples with a high lysozyme concentration with colony forming units of S. Aureus were significantly lower than in those with low concentrations. These results show, that the lysozyme concentration in milk of healthy udders could indicate the preparedness for defense against infectious diseases.


Roles of GILZ in protein metabolism of L6 muscle cells exposed to serum from septic rats.
Sepsis is a complex inflammatory response to infection, associating with dramatic metabolic disorders. Although the mechanisms of immune response during sepsis have been largely clarified, current studies rarely pay attention to the disordered protein metabolism in sepsis. In this study, L6 rat skeletal muscle cells treated with serum from septic rats were used as an in vitro model for sepsis-like condition in skeletal muscle. We found that the expression of glucocorticoid-induced leucine zipper (GILZ) positively correlates with glucocorticoid receptor and negatively correlates with myosin heavy chain expression in L6 muscle cells upon septic serum induction. Moreover, we propose that GILZ may associate with cytokines such as TNF-α, IL-1β as well as IL-10 to cooperatively modulate the glucocorticoid/glucocorticoid receptor-mediated regulation of protein metabolism during sepsis. So the present study provides a new approach and theoretical basis for further studies on the regulation of protein metabolism of skeletal muscle during sepsis.


Significant relationships and their impact on childbearing: a review.
This review has examined selected literature concerned with the influences of important relationships on the woman's childbearing experiences. THe effects of early childhood relationships with parents and subsequent relationships shared with others during pregnancy are found to be of major significance. Through both the early and adult relationships, the woman's feelings about the adequacy or inadequacy of herself as a mother take form. Within the literature, a dominant theme recurs: Experiences of others as supportive and helpful facilitate childbearing endeavors, while feeling relationships to be distressing or depleting hinders or makes impossible a successful childbearing outcome. Continuing research efforts focused on the woman's experiences of others in relation to her maternity experience is essential if we are to achieve a better understanding of the complexities of motherhood.


Effects of erythromycin base and erythromycin esters on protein synthesis in vivo in Escherichia coli.
The inhibitory effects on protein synthesis in vivo of erythromycin base and several erythromycin esters have been determined. An experimental method was used, especially suited for studies on short-lived antibiotics causing low levels of inhibition. Most of the tested derivatives were 2-3% as active as erythromycin base while a split product of erythromycin, anhydroerythromycin, was 4% as effective.


Associations between parental and postnatal metal mixture exposure and developmental delays in a Taiwanese longitudinal birth cohort of preschool children.
Studies have evaluated the impact of environmental exposure to neurotoxic metals on developmental delays (DDs). However, comprehensive understanding regarding the associations between parental and postnatal exposure to metal mixtures and the occurrence of DDs in offspring is limited. In this study, we assessed the relationships between parental and postnatal exposure to three metals (arsenic [As], cadmium [Cd], and lead [Pb], levels of which were measured in toenails) and suspected DDs (SDDs) in preschool children within a Taiwanese longitudinal birth cohort. In total between 2017 and 2021, 154 pairs of parents and their children under the age of 6 years were recruited, and 462 toenail samples and 154 completed questionnaires were collected. Metal concentrations in toenails were quantified using inductively coupled plasma-mass spectrometry after acid digestion of the toenails. We applied multivariable logistic regression and Bayesian kernel machine regression to evaluate the overall effect and to identify key components of the metal mixture that were associated with the SDD risk. Higher concentrations of As, Cd, and Pb were found in the toenails of the parents of children with SDDs compared with the toenails of the parents of children without SDDs. Our examination of the combined effects of exposure to the metal mixture revealed that As concentration in the father's toenail and Cd concentration in the mother's toenail were positively correlated with the risk of SDDs in their offspring. Notably, the effect of exposure to the metal mixture on the risk of SDDs was stronger in boys than in girls. Our findings suggest that parents taking measures to minimize their exposure to metals might enhance their children's developmental outcomes.


F-18 FDG PET/CT and Tc-99m sulfur colloid SPECT imaging in the diagnosis and treatment of a case of dual solitary fibrous tumors of the retroperitoneum and pancreas.
Although FDG PET is increasingly used for the staging of many types of sarcoma, little has been written regarding the FDG PET imaging characteristics of solitary fibrous tumor. We report a patient undergoing FDG PET/CT surveillance for squamous cell carcinoma of the tongue who was incidentally found to have two soft tissue masses in the retroperitoneum and pancreatic tail. Due to their low degree of FDG avidity, they were followed conservatively for approximately one year as they gradually increased in size. Technetium-99m sulfur colloid SPECT helped confirm that the pancreatic tail mass was not a splenule, after which both lesions were surgically resected and found to be extrathoracic solitary fibrous tumors without malignant features. These findings suggest that, as with other low-grade sarcomas, benign extrathoracic solitary fibrous tumors exhibit relatively little glycolytic metabolism in vivo.


The storage and re-infusion of autologous blood and BM as back-up following failed primary hematopoietic stem-cell transplantation: a survey of European practice.
Traditionally, autologous BM or PBSC have been stored as a secondary source ('back-up') of hematopoietic stem cells (HSC) prior to allogeneic and autologous HSC transplantation. We conducted an audit of a single transplant center practice for providing back-up HSC and compared this practice with other European centers. Laboratory records relating to the collection and re-infusion of consecutive HSC harvests were reviewed for 515 transplants (300 autologous and 215 allogeneic HSC transplants). In our experience, 2.3% (five of 215) of allogeneic HSC transplants required secondary HSC rescue for failure to engraft or graft failure (MUD, n = 2; un-manipulated sibling BMT, n = 1; T-cell depleted sibling BMT, n = 2). For autologous transplants, 4.7% (14 of 300) required rescue due to failure to engraft or late graft failure (ABMT for AML, n = 8; CD34+ cell selection/ex vivo expanded, n = 4; ABMT/PBSCT, n = 2). Among the European centers, 69.7% replied to a postal questionnaire, demonstrating that 81.4% and 45.6% of centers stored a secondary HSC source for manipulated and unmanipulated MUD BMT, respectively; 50% and 11.6% of centers stored a secondary source of HSC for manipulated and unmanipulated matched sibling BMT, respectively; 36.4% and 12.7% of centers stored HSC for manipulated and unmanipulated matched sibling PBSCT, respectively. In the autologous setting, 15.2% and 62.1% of centers stored back-up for unmanipulated and manipulated BMT, respectively and 19.5% and 68.5% stored back-up for unmanipulated and manipulated PBSCT, respectively, when myeloablative conditioning regimens were used. These data suggest that a small minority of patients require a secondary source of HSC rescue, most commonly in transplants with higher risk of graft failure. This is reflected in the practice across Europe of storing 'back-up' HSC. Guidelines should accommodate the need for storage of a secondary source of HSC only in those transplants associated with a higher risk of graft failure, especially in relation to graft engineering.


Dermoscopy in the Evaluation of Nail Disorders.
Nail dermoscopy was initially used only in the assessment of nail pigmentation, but now it is widely utilized for the evaluation of many nail disorders. In daily practice, dermoscopy may confirm clinical diagnoses and guides in the management of nail diseases and treatments, permitting a better visualization of symptoms. Dry dermoscopy is required for evaluation of the nail plate surface, while gel as an interface is necessary for assessment of nail pigmentation and onycholysis, as well as for the evaluation of the distal nail margin. In this review, we describe the dermoscopic features of the most important nail disorders, looking at the different areas of the nail. Dermatoscopic changes that usually accompany specific nail diseases are also reviewed.


Carlactone is converted to carlactonoic acid by MAX1 in Arabidopsis and its methyl ester can directly interact with AtD14 in vitro.
Strigolactones (SLs) stimulate seed germination of root parasitic plants and induce hyphal branching of arbuscular mycorrhizal fungi in the rhizosphere. In addition, they have been classified as a new group of plant hormones essential for shoot branching inhibition. It has been demonstrated thus far that SLs are derived from carotenoid via a biosynthetic precursor carlactone (CL), which is produced by sequential reactions of DWARF27 (D27) enzyme and two carotenoid cleavage dioxygenases CCD7 and CCD8. We previously found an extreme accumulation of CL in the more axillary growth1 (max1) mutant of Arabidopsis, which exhibits increased lateral inflorescences due to SL deficiency, indicating that CL is a probable substrate for MAX1 (CYP711A1), a cytochrome P450 monooxygenase. To elucidate the enzymatic function of MAX1 in SL biosynthesis, we incubated CL with a recombinant MAX1 protein expressed in yeast microsomes. MAX1 catalyzed consecutive oxidations at C-19 of CL to convert the C-19 methyl group into carboxylic acid, 9-desmethyl-9-carboxy-CL [designated as carlactonoic acid (CLA)]. We also identified endogenous CLA and its methyl ester [methyl carlactonoate (MeCLA)] in Arabidopsis plants using LC-MS/MS. Although an exogenous application of either CLA or MeCLA suppressed the growth of lateral inflorescences of the max1 mutant, MeCLA, but not CLA, interacted with Arabidopsis thaliana DWARF14 (AtD14) protein, a putative SL receptor, as shown by differential scanning fluorimetry and hydrolysis activity tests. These results indicate that not only known SLs but also MeCLA are biologically active in inhibiting shoot branching in Arabidopsis.


G-quadruplexes and G-quadruplex ligands: targets and tools in antiviral therapy.
G-quadruplexes (G4s) are non-canonical nucleic acids secondary structures that form within guanine-rich strands of regulatory genomic regions. G4s have been extensively described in the human genome, especially in telomeres and oncogene promoters; in recent years the presence of G4s in viruses has attracted increasing interest. Indeed, G4s have been reported in several viruses, including those involved in recent epidemics, such as the Zika and Ebola viruses. Viral G4s are usually located in regulatory regions of the genome and implicated in the control of key viral processes; in some cases, they have been involved also in viral latency. In this context, G4 ligands have been developed and tested both as tools to study the complexity of G4-mediated mechanisms in the viral life cycle, and as therapeutic agents. In general, G4 ligands showed promising antiviral activity, with G4-mediated mechanisms of action both at the genome and transcript level. This review aims to provide an updated close-up of the literature on G4s in viruses. The current state of the art of G4 ligands in antiviral research is also reported, with particular focus on the structural and physicochemical requirements for optimal biological activity. The achievements and the to-dos in the field are discussed.


Risk factors of musculoskeletal symptoms in university hospital nurses.
The purpose of this study was to investigate musculoskeletal symptom prevalence in university hospital nurses and explore the relation between musculoskeletal symptom prevalence and work related factors. A structured questionnaire was conducted with 620 nurses in a university hospital to look into the characters of responsibility and musculoskeletal symptom prevalence. The questionnaire respondents numbered 534, so the response rate was 86.1%. Among the respondents, three who gave insincere answers were excluded. The final study population was 531 respondents. ANSI Z-365 checklist was applied to look into ergonomic characteristics, and Korean Occupational Stress Scale Short Form was employed to measure job stress. In the case of the whole body, symptom prevalence amounted to 70.8%. Regarding each body region, shoulder symptom prevalence accounted for the highest, or 44.8%, waist 40.7%, and neck 33.3% in order. According to multiple logistic regression analysis, in the case of the whole body, the group with a high ANSI checklist grade had odds ratio of 3.59 (95% CI 1.48 ~ 8.76), and the group with high job stress had 3.19 (95% CI 2.01 ~ 5.07). Regarding the occupational factors related to musculoskeletal symptoms of university hospital nurses, it was found that ANSI Z-365 checklist high risk group, total job tenure, department, shiftworks, and job stress had high relation with musculoskeletal symptoms. It is necessary to find an ergonomic solution and a stress reduction plan to prevent musculoskeletal disease.


Busting myths and building resilience: Practices and approaches that go beyond mere plan development.
Dwight D. Eisenhower is often quoted as saying: 'In battle, plans are useless but planning is indispensable'. How many in the business continuity profession actually think about that statement and what it really means? Audit, compliance and regulatory requirements as well as the expectations of executives and business leaders result in an inordinate amount of time and effort devoted to plan development with scant attention paid to actual planning. Practitioners need to realise that the value of the plans they develop is not derived from the finished documents but from the work devoted to completing them. Experience and practice win out above detailed plans. One need look no further than Eisenhower's D-Day invasion of Normandy as evidence. Practitioners need to learn how to be better at instituting preparedness and not simply developing better plans.


Harmonic response of cellular membrane pumps to low frequency electric fields.
We report on harmonic generation by budding yeast cells in response to a sinusoidal electric field, which is seen to be minimal when the field amplitude is less than a threshold value. Surprisingly, sodium metavanadate, an inhibitor of P-type ATPases reportedly responsible for nonlinear response in yeast, reduces the threshold field amplitude, increasing harmonic generation at low amplitudes while reducing it at large amplitudes, whereas the addition of glucose dramatically increases the production of even harmonics. Finally, a simple model is proposed to interpret the observed behavior.


Structural and functional characterization of a ketosteroid transcriptional regulator of Mycobacterium tuberculosis.
Catabolism of host cholesterol is critical to the virulence of Mycobacterium tuberculosis and is a potential target for novel therapeutics. KstR2, a TetR family repressor (TFR), regulates the expression of 15 genes encoding enzymes that catabolize the last half of the cholesterol molecule, represented by 3aα-H-4α(3'-propanoate)-7aβ-methylhexahydro-1,5-indane-dione (HIP). Binding of KstR2 to its operator sequences is relieved upon binding of HIP-CoA. A 1.6-Å resolution crystal structure of the KstR2(Mtb)·HIP-CoA complex reveals that the KstR2(Mtb) dimer accommodates two molecules of HIP-CoA. Each ligand binds in an elongated cleft spanning the dimerization interface such that the HIP and CoA moieties interact with different KstR2(Mtb) protomers. In isothermal titration calorimetry studies, the dimer bound 2 eq of HIP-CoA with high affinity (K(d) = 80 ± 10 nm) but bound neither HIP nor CoASH. Substitution of Arg-162 or Trp-166, residues that interact, respectively, with the diphosphate and HIP moieties of HIP-CoA, dramatically decreased the affinity of KstR2(Mtb) for HIP-CoA but not for its operator sequence. The variant of R162M that decreased the affinity for HIP-CoA (ΔΔG = 13 kJ mol(-1)) is consistent with the loss of three hydrogen bonds as indicated in the structural data. A 24-bp operator sequence bound two dimers of KstR2. Structural comparisons with a ligand-free rhodococcal homologue and a DNA-bound homologue suggest that HIP-CoA induces conformational changes of the DNA-binding domains of the dimer that preclude their proper positioning in the major groove of DNA. The results provide insight into KstR2-mediated regulation of expression of steroid catabolic genes and the determinants of ligand binding in TFRs.


Land use diversification may mitigate on-site land use impacts on mammal populations and assemblages.
Land use is a major cause of biodiversity decline worldwide. Agricultural and forestry diversification measures, such as the inclusion of natural elements or diversified crop types, may reduce impacts on biodiversity. However, the extent to which such measures may compensate for the negative impacts of land use remains unknown. To fill that gap, we synthesised data from 99 studies that recorded mammal populations or assemblages in natural reference sites and in cropland and forest plantations, with or without diversification measures. We quantified the responses to diversification measures based on individual species abundance, species richness and assemblage intactness as quantified by the mean species abundance indicator. In cropland with natural elements, mammal species abundance and richness were, on average, similar to natural conditions, while in cropland without natural elements they were reduced by 28% and 34%, respectively. We found that mammal species richness was comparable between diversified forest plantations and natural reference sites, and 32% lower in plantations without natural elements. In both cropland and plantations, assemblage intactness was reduced compared with natural reference conditions, but the reduction was smaller if diversification measures were in place. In addition, we found that responses to land use were modified by species traits and environmental context. While habitat specialist populations were reduced in cropland without diversification and in forest plantations, habitat generalists benefited. Furthermore, assemblages were impacted more by land use in tropical regions and landscapes containing a larger share of (semi)natural habitat compared with temperate regions and more converted landscapes. Given that mammal assemblage intactness is reduced also when diversification measures are in place, special attention should be directed to species that suffer from land use impacts. That said, our results suggest potential for reconciling land use and mammal conservation, provided that the diversification measures do not compromise yield.


Synthesis of ZnO nanosheets by microwave thermal vapor method.
Two-dimensional single-crystalline ZnO nanosheets have been successfully synthesized in high yield from a mixture of ZnO and graphite powders via a microwave thermal vapor process. Morphological analysis indicates that the widths and thickness of the nanosheets are in the range of several to tens of microm and 20-80 nm, respectively. ZnO nanosheets grew along the [0001] and [2110] directions, and the width-to-thickness ratio of the nanosheets could reach up to 1,000. The room temperature photoluminescence revealed that the ZnO nanosheets exhibited a weak ultraviolet (UV) emission at approximately 378 nm and a strong green emission at approximately 505 nm.


[Modern anti-thrombotic drugs, accompanied by percutaneous coronary intervention in the treatment of acute coronary syndrome with ST segment elevation on the electrocardiogram in patients of older age groups].
In the review published data on what modern antithrombotic drugs are used to support percutaneous coronary intervention in the treatment of acute coronary syndrome with ST segment elevation on the electrocardiogram in patients of older age groups. It was shown the effectiveness and safety of new pharmacological combinations using both anticoagulants and antiplatelet agents as in patients with acute coronary syndrome in elderly. It was highlighted also the need to find new combinations of anticoagulants and antiplatelet agents, to improve the prognosis in elderly persons subjected to percutaneous coronary intervention in patients with ACS.


Gene transfer strategies in animal transgenesis.
Position effects in animal transgenesis have prevented the reproducible success and limited the initial expectations of this technique in many biotechnological projects. Historically, several strategies have been devised to overcome such position effects, including the progressive addition of regulatory elements belonging to the same or to a heterologous expression domain. An expression domain is thought to contain all regulatory elements that are needed to specifically control the expression of a given gene in time and space. The lack of profound knowledge on the chromatin structure of expression domains of biotechnological interest, such as mammary gland-specific genes, explains why most standard expression vectors have failed to drive high-level, position-independent, and copy-number-dependent expression of transgenes in a reproducible manner. In contrast, the application of artificial chromosome-type constructs to animal transgenesis usually ensures optimal expression levels. YACs, BACs, and PACs have become crucial tools in animal transgenesis, allowing the inclusion of distant key regulatory sequences, previously unknown, that are characteristic for each expression domain. These elements contribute to insulating the artificial chromosome-type constructs from chromosomal position effects and are fundamental in order to guarantee the correct expression of transgenes.


Short-term exposure to ambient air pollution and COVID-19 severity during SARS-CoV-2 Delta and Omicron waves: A multicenter study.
Air pollution may affect the clinical course of respiratory diseases, including COVID-19. This study aimed to evaluate the relationship between exposure of adult patients to mean 24 h levels of particulate matter sized <10 μm (PM10 ) and <2.5 μm (PM2.5 ) and benzo(a)pyrene (B(a)P) during a week before their hospitalization due to SARS-CoV-2 infection and symptomatology, hyperinflammation, coagulopathy, the clinical course of disease, and outcome. The analyses were conducted during two pandemic waves: (i) dominated by highly pathogenic Delta variant (n = 1440) and (ii) clinically less-severe Omicron (n = 785), while the analyzed associations were adjusted for patient's age, BMI, gender, and comorbidities. The exposure to mean 24 h B(a)P exceeding the limits was associated with increased odds of fever and fatigue as early COVID-19 symptoms, hyperinflammation due to serum C-reactive protein >200 mg/L and interleukin-6 >100 pg/mL, coagulopathy due to d-dimer >2 mg/L and fatal outcome. Elevated PM10 and PM2. 5 levels were associated with higher odds of respiratory symptoms, procalcitonin >0.25 ng/mL and interleukin >100 pg/mL, lower oxygen saturation, need for oxygen support, and death. The significant relationships between exposure to air pollutants and the course and outcomes of COVID-19 were observed during both pandemic waves. Short-term exposure to elevated PM and B(a)P levels can be associated with a worse clinical course of COVID-19 in patients requiring hospitalization and, ultimately, contribute to the health burden caused by SARS-CoV-2 variants of higher and lower clinical significance.


Brassinosteriod Insensitive 2 (BIN2) acts as a downstream effector of the Target of Rapamycin (TOR) signaling pathway to regulate photoautotrophic growth in Arabidopsis.
The components of the target of rapamycin (TOR) signaling pathway have been well characterized in heterotrophic organisms from yeast to humans. However, because of rapamycin insensitivity, embryonic lethality in tor null mutants and a lack of reliable ways of detecting TOR protein kinase in higher plants, the key players upstream and downstream of TOR remain largely unknown in plants. Using engineered rapamycin-sensitive Binding Protein 12-2 (BP12-2) plants, the present study showed that combined treatment with rapamycin and active-site TOR inhibitors (asTORis) results in synergistic inhibition of TOR activity and plant growth in Arabidopsis. Based on this system, we revealed that TOR signaling plays a crucial role in modulating the transition from heterotrophic to photoautotrophic growth in Arabidopsis. Ribosomal protein S6 kinase 2 (S6K2) was identified as a direct downstream target of TOR, and the growth of TOR-suppressed plants could be rescued by up-regulating S6K2. Systems, genetic, and biochemical analyses revealed that Brassinosteriod Insensitive 2 (BIN2) acts as a novel downstream effector of S6K2, and the phosphorylation of BIN2 depends on TOR-S6K2 signaling in Arabidopsis. By combining pharmacological with genetic and biochemical approaches, we determined that the TOR-S6K2-BIN2 signaling pathway plays important roles in regulating the photoautotrophic growth of Arabidopsis.


CodonPhyML: fast maximum likelihood phylogeny estimation under codon substitution models.
Markov models of codon substitution naturally incorporate the structure of the genetic code and the selection intensity at the protein level, providing a more realistic representation of protein-coding sequences compared with nucleotide or amino acid models. Thus, for protein-coding genes, phylogenetic inference is expected to be more accurate under codon models. So far, phylogeny reconstruction under codon models has been elusive due to computational difficulties of dealing with high dimension matrices. Here, we present a fast maximum likelihood (ML) package for phylogenetic inference, CodonPhyML offering hundreds of different codon models, the largest variety to date, for phylogeny inference by ML. CodonPhyML is tested on simulated and real data and is shown to offer excellent speed and convergence properties. In addition, CodonPhyML includes most recent fast methods for estimating phylogenetic branch supports and provides an integral framework for models selection, including amino acid and DNA models.


Infections after living donor liver transplantation in children.
The aim of this study was to evaluate the infectious complications after living donor liver transplantation (LDLT) in children. We enrolled 95 children (38 boys and 57 girls) who underwent LDLT from 1994 to 2004. The median age was 22 months (range, 6 months to 15 yr). We retrospectively investigated the proven episodes of bacterial, viral, and fungal infection. There occurred 150 infections in 67 (70%) of 95 patients (1.49 infections/patient); 74 in 43 patients were bacterial, 2 in 2 were fungal, and 74 in 42 were viral. The most common sites of bacterial infection were the bloodstream (33%) and abdomen (25%). Most of the bacterial infections occurred within the first month after LDLT. Bacterial and fungal infections did not result in any deaths. The most common causes of viral infection were Epstein-Barr virus in 37 patients and cytomegalovirus in 18. Seven of the 14 deaths after LDLT were associated with viral infection. Our study suggests that infection is one of the important causes of morbidity and mortality after LDLT. Especially careful monitoring and management of viral infections is crucial for improving the outcome of LDLT in children.


Body composition in asymptomatic HIV-infected men: cross-sectional and prospective assessment.
Data on body composition changes in HIV infected patients is sparse and controversial. The aim of this study was to assess body composition in asymptomatic HIV-infected men with normal body weight in comparison to healthy HIV-negative control men and to investigate possible body composition changes in HIV-positive patients over a 2-year observation period. One hundred eight asymptomatic seropositive men, aged 19-62 years, and 20 healthy sex, age and weight - matched controls were recruited for the cross-sectional part of the study. Fifty-eight of the HIV+ patients were followed up for 2 years. Body weight, BMI, Bone Mineral Content (BMC), body Fat mass (Fat), % Fat, body Lean mass (Lean) and % Lean was recorded for each subject at the beginning and at the end of the follow-up period. The same analysis was repeated separately for arms, trunk and legs. HIV+ men had increased fat mass and reduced lean mass compared to controls (%Fat in HIV+ 24.3, %Fat in controls 19.2, p=0.012; %Lean in HIV+ 72.1, %Lean in controls 77.0, p=0.014). Lean mass was lower in extremities while fat mass was higher in the trunk region in HIV+ in comparison to controls, irrespective of antiretroviral therapy. Longitudinally, patients with higher baseline %Fat (>24.2, median) presented 20% decrease in fat mass while patients with lower baseline %Fat (< or =24.2) showed a smaller, non-significant decrease in fat mass accompanied by a significant decrease (2.52%) in lean mass. Fat loss occurred in all subjects predominantly in the extremities (16.5-36.45% loss), with relative preservation of trunk fat. It is concluded that otherwise asymptomatic HIV+ men exhibit subtle body composition changes involving reduced lean mass and increased central fat mass. The pattern of weight loss over time depends on baseline fat store: patients with adequate fat stores lose predominantly fat while patients with lower baseline fat stores lose both fat and lean mass. In the entire cohort, there is a tendency towards central adiposity, with the majority of fat being lost from the extremities, a picture resembling metabolic x syndrome.


Extraction of SNOMED concepts from medical record texts.
Clinicians have traditionally documented patient data using natural language text. With the increasing prevalence of computer systems in health care, an increasing amount of medical record text will be stored electronically. However, for such textual documents to be indexed, shared, and processed adequately by computers, it will be important to be able to identify concepts in the documents using a common medical terminology. Automated methods for extracting concepts in a standard terminology would enhance retrieval and analysis of medical record data. This paper discusses a method for extracting concepts from medical record documents using the medical terminology SNOMED-III (Systematized Nomenclature of Human and Veterinary Medicine, Version III). The technique employs a linear least squares fit that maps training set phrases to SNOMED concepts. This mapping can be used for unknown text inputs in the same domain as the training set to predict SNOMED concepts that are contained in the document. We have implemented the method in the domain of congestive heart failure for history and physical exam texts. Our system has a reasonable response time. We tested the system over a range of thresholds. The system performed with 90% sensitivity and 83% specificity at the lowest threshold, and 42% sensitivity and 99.9% specificity at the highest threshold.


Photoinduced Multicomponent Reactions.
The combination of multicomponent approaches with light-driven processes opens up new scenarios in the area of synthetic organic chemistry, where the need for sustainable, atom- and energy-efficient reactions is increasingly urgent. Photoinduced multicomponent reactions are still in their infancy, but significant developments in this area are expected in the near future.


Trends in urinary tract cancer deaths.
Death from cancer of the urinary tract (bladder, kidney and renal pelvis) continues to be the fourth leading cause of cancer mortality among U.S. men. In 1988-89, 21,834 deaths from urinary tract cancer occurred among men aged 45-84 years, resulting in an age-adjusted mortality rate of 25.9 per 100,000. This rate was 7.2 lower than that reported for 1979-81 and all but 16 states had lower rates in 1988-89 than in 1979-81. The rates decreased or remained the same in all but the West South Central area of the country where there was a 2.5 percent increase in 1988-89. In states with 200 or more deaths from urinary tract cancer, the largest decrease in the age-adjusted mortality rate for men 45-84 was evident in New York and Virginia. The 16 rate increases ranged from 24 percent in Wyoming with 44 cases to 0.4 percent in Minnesota with 393 cases and 0.3 percent in Indian with 529 cases.


Reducing YAP expression in Pkd1 mutant mice does not improve the cystic phenotype.
The Hippo pathway is a highly conserved signalling route involved in organ size regulation. The final effectors of this pathway are two transcriptional coactivators, yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (WWTR1 or TAZ). Previously, we showed aberrant activation of the Hippo pathway in autosomal-dominant polycystic kidney disease (ADPKD), suggesting that YAP/TAZ might play a role in disease progression. Using antisense oligonucleotides (ASOs) in a mouse model for ADPKD, we efficiently down-regulated Yap levels in the kidneys. However, we did not see any effect on cyst formation or growth. Moreover, the expression of YAP/TAZ downstream targets was not changed, while WNT and TGF-β pathways' downstream targets Myc, Acta2 and Vim were more expressed after Yap knockdown. Overall, our data indicate that reducing YAP levels is not a viable strategy to modulate PKD progression.


Advances in pulmonary nuclear medicine.
Nuclear medicine plays a major role in the diagnosis of pulmonary embolism as well as in other lung diseases. Important innovations have concerned in recent years the equipment and radiopharmaceuticals. In ventilation studies the use of technegas, a monodisperse aerosol able to supply images of the same quality or even superior to gas images, is widespread in the clinical practice. Significant clinical results in the evaluation of acute thromboembolism have been achieved with antifibrin monoclonal antibodies and radioactive peptides specific for activated platelet receptors. Primary lung cancer and its metastases can now be visualized with tracers used for the study of myocardial perfusion (sestaMIBI, tetrofosmin) or labeled ocreotide, a molecule able to recognize lung tumors with somatostatin receptors. 99mTc-NR-LU-10 Fab immunoscintigraphy was shown to be very sensitive for tumors, while the major role of PET in the differential diagnosis of solitary pulmonary nodule, in the initial staging and in the response assessment to lung cancer therapy, is confirmed. SPECT is widespread in the clinical field with the use of 2-3 head gamma cameras and the possible combined imaging with CT or MRI. The use of PET with common gamma cameras with appropriate collimation systems or coincident recording without collimation is being studied. PET is used in the study of tumor metabolism as well as in the evaluation of intra-and extravascular lung water, regional blood flow and pulmonary vascular permeability. PET studies of vascular lung physiology as well as of receptor physiology, amine accumulation and clearance and drug transport to the areas of healthy or impaired lung, were also shown to be fundamental.


Dose-response mutation and spectrum analyses reveal similar responses at two microsatellite loci in benzo(a)pyrene-exposed mouse spermatogonia.
Identifying chemical exposures that can cause germline mutations is important as these mutations can be inherited, impacting both individual and population health. However, germline mutations are extremely rare and difficult to detect. Chemically induced germline mutations can be detected through analysis of highly unstable tandem repeat DNA. We recently developed a single-molecule PCR (SM-PCR) approach to quantify mutations at a mouse microsatellite locus (Mm2.2.1) in sperm for such purposes. In this study, we refine this approach through the combined analysis of mouse microsatellites Mm2.2.1 and Mm19.2.3. Mice were exposed to 0, 25, 50 or 100 mg/kg/day benzo(a)pyrene (BaP) by oral gavage for 28 days and sperm sampled 42 days after the end of exposure to measure effects on dividing spermatogonia. DNA was diluted to a single genome per PCR well for amplification of microsatellites in singleplex and multiplex reactions, and alleles were sized to identify mutations using capillary electrophoresis. Analysis of ~300-500 molecules per animal at both microsatellite loci, when tested individually, showed a ~2-fold increase in mutations relative to the controls at both the 50 and 100 mg/kg/day BaP doses. Multiplex SM-PCR revealed similar increases in mutation frequencies in both microsatellites. Comparison with results from a previous lacZ mutation assay conducted on the same mice revealed that although microsatellite mutations are a sensitive endpoint for detecting changes in mutation frequencies at lower doses, they appear to be saturable and thus have a reduced dynamic range. These results confirm that BaP is a male germ cell mutagen that broadly impacts tandem repeat DNA. Likewise, addition of a second hypervariable microsatellite increases the sensitivity of this assay.


Routine first-trimester pre-eclampsia screening and maternal left ventricular geometry.
Preeclampsia (PE) is a pregnancy complication associated with premature cardiovascular disease morbidity and mortality. PE is associated with adverse left ventricular (LV) remodeling in the peripartum and postpartum period - an independent risk factor for cardiovascular disease. However, it is unknown if adverse cardiac remodeling is evident in the first trimester in participants at high compared to low risk of PE. This was a prospective cohort study of singleton pregnancies that underwent screening for preterm PE as part of their routine first-trimester ultrasound assessment at a tertiary center in London, UK, between February 2019 and March 2020 at 11+0 weeks' gestation through 13+6 weeks' gestation. Screening for preterm PE was performed using the Fetal Medicine Foundation algorithm. Participants with a screening risk of ≥1 in 50 for preterm PE were classified as high-risk and those with a screening risk of ≤1 in 500 were classified as low-risk. All participants underwent two-dimensional and M-mode transthoracic echocardiography. A total of 128 participants in the first trimester of pregnancy were included in the analysis, with 57 (44.5%) participants screened as low-risk and 71 (55.5%) participants high-risk for PE. The risk groups did not vary in maternal age and gestational age at assessment. Maternal body surface area (BSA) and body mass index (BMI) were significantly higher in the high-risk group (all p<0.05). The high-risk participants were significantly more likely to be Afro-Caribbean, nulliparous, have a history of hypertensive disease in pregnancy and a family history of cardiovascular disease (all p<0.05). In addition, mean arterial blood pressure (p<0.001), heart rate (p<0.05), left ventricular mass (130.06 g, 113.62-150.5 vs. 97.44 g, 81.68-114.16, p<0.001) and left ventricular mass index (72.87 ± 12.2 g/m2 vs. 57.54 ± 12.72 g/m2 , p<0.001) were significantly higher in the high-risk group. Consequently, the high-risk group were more likely to have abnormal left ventricular geometry (37.1% vs. 7.1%, p<0.001). Early echocardiographic assessment in participants at high-risk of preterm PE may unmask clinically healthy individuals who are at increased risk for future cardiovascular disease. Adverse cardiac remodeling in the first trimester of pregnancy may be an indicator of decreased cardiovascular reserve and subsequent dysfunctional cardiovascular adaptation in pregnancy. This article is protected by copyright. All rights reserved.


Disorders of higher cerebral function in preschool children. 1.
In preschoolers, disorders of higher cerebral function are most likely to present as inadequate development of language, while in school-age children, learning disabilities and attention deficit predominate. The main considerations in the differential diagnosis in preschoolers with inadequate language are hearing loss, mental deficiency, dysphasia, and autistic spectrum disorders. Attention to the child's ability to engage in symbolic play and communicate meaningfully is the key to this often baffling differential diagnosis. With the exception of definitive assessment of hearing, classic medical investigations are seldom informative because structural brain lesions and metabolic errors are much rarer etiologies than prenatal and genetic influences on brain development. While many children improve with age, the underlying deficit(s) usually persists. The role of the physician is to detect the developmental problem, give the parents a correct diagnosis, refer the child for appropriate investigation and intervention, and provide follow-up and counseling. Early diagnosis is essential for effective remediation.


Laboratory evaluations to optimize outcomes of antioxidant nutrition therapy in diabetes management.
Medical nutrition therapy (MNT) guidelines acknowledge the need to identify deficiencies of antioxidant vitamins. However, the guidelines contain that such identification is difficult. Thus, there is evidence that available clinical laboratory tests for antioxidant vitamins C and E are not in perspective in clinical practice. Coenzyme-Q(10) and glutathione tests are also available in research laboratories. These indices are invaluable tools for discrete recommendation and monitoring of antioxidant nutrition therapies. This commentary addresses biomarker insight to what the MNT guidelines consider difficult. The importance and limits of the various dietary antioxidants is overviewed. It puts in perspective how clinical laboratory monitoring of vitamins C and E levels can be used to optimize the outcomes of dietary evaluations for diabetes management. Insight to how to interpret the laboratory results is presented. The importance of this commentary is hinged on the premise that the outcome of dietary therapy can be counter-productive when laboratory evaluation or limitations of the antioxidant nutrients are undermined.


A history of thalidomide in India.
In contrast to the well-known stories of the embryotoxic drug, thalidomide, in countries where it was responsible for large numbers of birth defects, there is limited information on its history in India. Its presence before 2002, when the country issued the first marketing licence for a thalidomide-containing preparation, is assumed to be negligible. This article challenges this view by showing that the drug entered the Indian subcontinent through the former Portuguese territory of Goa around 1960. We examine the subsequent development of its distribution, use and regulation in India from the mid-1960s up to the present situation. Colonial legacies are a crucial explanation for the early appearance of thalidomide on the Indian subcontinent. They also influenced its re-emergence as drug for treating leprosy reactions in India after 1965. We identify key actors in this process: the original German producer that delivered thalidomide free of charge, European doctors who worked for international non-governmental organizations, the World Health Organization (WHO), which supported clinical trials and later discouraged the use of the drug, and finally the Indian state institutions that limited its distribution and later quickly opened the way for the private sector to produce and market thalidomide and its analogues. Finally, we discuss the risk of thalidomide-induced birth defects by casting a critical look on the present state of regulatory provisions and the monitoring of birth defects in India.


Mapping the theories of preeclampsia and the role of angiogenic factors: a systematic review.
To evaluate claims that elevated soluble fms-like tyrosine kinase-1 receptor (sFlt-1) and decreased placental growth factor predict preeclampsia. MEDLINE (1966-March 2006), EMBASE (1980-June 2006), POPLINE (1980-June 2006), CINAHL (1982-June 2006), and LILACS (1982-June 2006) were searched, and experts contacted. Studies identified and included were those reporting blood and urine levels of sFlt-1 or placental growth factor obtained before gestational week 30 or overt preeclampsia. Ten of 184 available studies analyzing sFlt-1 and 14 of 319 studies analyzing placental growth factor were included in this review. There was considerable interreport heterogeneity in methodology and results for sFlt-1 measured before gestational week 25. After week 25 placental growth factor and sFlt-1 levels varied consistently between the normal pregnancy group and women destined to develop preeclampsia, achieving significance in women who developed severe preeclampsia. Third-trimester increases in sFlt-1 and decreases in placental growth factor levels are associated with preeclampsia, specifically severe disease, based on retrospective data. The evidence is insufficient to recommend these markers to be used for screening, and prospective studies employing rigorous laboratory and study design criteria are needed to determine the clinical usefulness of these tests.


Liraglutide Improves Estimated Glomerular Filtration Rate Slopes in Patients with Chronic Kidney Disease and Type 2 Diabetes: A 7-Year Retrospective Analysis.
Background: Liraglutide was administered to patients with type 2 diabetes, and its effects on estimated glomerular filtration rate (eGFR) slopes and albuminuria were retrospectively evaluated. Methods: This study included 568 patients with type 2 diabetes who received liraglutide therapy (up to 0.9 mg/day) >1 year and were followed-up for a maximum of 2 years before and 7 years after treatment. The decline in renal function was estimated as the slope of the individual linear regression line of eGFR over the follow-up time. Spot urine samples were collected to measure albuminuria, which were calculated using creatinine levels. In addition, HbA1c, body weight, blood pressure, and heart rate were monitored. Results: The mean liraglutide treatment period was 3.1 ± 2.0 years. The mean baseline eGFR slope [mL/(min ·1.73 m2·year)] was -2.75 ± 6.04. After liraglutide treatment, the mean eGFR slope significantly improved (-1.42 ± 4.30, P < 0.01). This effect appeared more pronounced for baseline eGFRs <45 mL/(min ·1.73 m2). Albuminuria, HbA1c, body weight, and systolic blood pressure levels were significantly reduced after treatment with liraglutide for 1 year, whereas diastolic blood pressure and heart rates were increased. Conclusions: Patients treated with liraglutide experienced a significantly slower annual decline in kidney function. The benefit appeared more pronounced in patients with the development and progression of diabetic kidney disease. These results suggest that the benefits of liraglutide on kidney function identified in clinical trials appear to be well generalizable to clinical practice.


[Teaching roentgenology to students at a medical institute].
The system of teaching roentgenology at the I.M. Sechenov First Moscow Medical Institute is described. The authors point to several reasons for which some rearrangement of teaching roentgenology in medical institutes is required. This type of rearrangement seems possible at the expense of intensive and skilled teaching without adding extra lessons in the curricula. The authors provide various forms of the presentation of lectures describe organizational stages in the optimization of practical studies and consider in detail the system of teaching roentgenology with the help of special programs based on the principle of programmed teaching. They also outline the prospects of further studies in the pedagogical process and possible ways of its improvement.


Organ distribution of the Ro (SS-A) antigen in the guinea pig.
Using an anti-Ro (SS-A)-specific "sandwich" enzyme-linked immunosorbent assay (ELISA) and Western immunoblotting, we determined the Ro (SS-A) content (both quantitative and qualitative) in saline-perfused organs of the guinea pig. All tissue extracts contained substantial concentrations of Ro (SS-A) antigen and could be grouped into 3 categories based on quantitative reactivity in the sandwich ELISA. The 60-kd and 52-kd molecular forms of Ro (SS-A) present in tissue extracts were similar to those described in Wi-L2 extracts, and the 54-kd molecular form of Ro (SS-A) in guinea pig erythrocytes was similar to that found in human erythrocytes. The tissue distribution of the isoforms of Ro (SS-A) was shown by Western immunoblotting to vary in different tissues, and the reactivity to the 60-kd Ro (SS-A) was correlated with the activity seen in the ELISA. Both the 60-kd and 52-kd Ro (SS-A) bands in guinea pig liver extracts were very weak on Western immunoblots, in contrast to the high concentration of Ro (SS-A) antigen in the ELISA. Other data suggest the possible existence of a unique form of Ro (SS-A) in the liver. Guinea pig tissues have 4 Y RNA that are equivalent to the 4 human RNA--hY1, hY3, hY4, and hY5--present in HeLa cells, while guinea pig red blood cells have only one Y RNA, which is equivalent in size to human hY4.(ABSTRACT TRUNCATED AT 250 WORDS)


[Childhood cutaneous leishmaniasis in Tunisia: retrospective study of 60 cases].
Cutaneous leishmaniasis (CL) is a widespread parasitic disease that represents a major public health problem in several countries including Tunisia. The aim of this study was to determine the characteristics of childhood CL in a university hospital center in Tunis. The files of all children treated for of CL in the Dermatology Department of Habib Thameur Hospital over a 23-year period were reviewed. A total of 60 children were included. The mean age was 9.2 years and the sex ratio was 0.93. All patients lived or had stayed in an endemic area. Infectious risk was highest in autumn (41.6%). The most frequent clinical finding consisted of crusty nodules (53.3%) that were most often the only manifestation (63.3%) and usually located on the face (65%). Clinical diagnosis was confirmed by either peripheral blood smear (56.6%) or histological examination (35%). The treatment of choice was Glucantime administered by the intralesional route in 70% of patients or by intramuscular route in 30%. The outcome was favorable in all cases within 2 weeks to 6 months. Sequels were noted in 9 cases (18%) in the form of pigmented (7 cases) or atrophic (2 cases) residual scars. The frequency of childhood CL is relatively high especially during the second decade of life. Childhood CL is characterized by a generally favorable outcome and lack of distinguishing clinical characteristics form adult CL. If possible, therapeutic abstention is more widely in the children due to the high risk of adverse reactions.


Bone Marrow-Derived Mesenchymal Stem Cells-Mediated Protection Against Organ Dysfunction in Disseminated Intravascular Coagulation Is Associated With Peripheral Immune Responses.
Disseminated intravascular coagulation (DIC) is a fatal thrombohemorrhagic disorder. Bone marrow-derived mesenchymal stem cells (BMSCs) are multipotent stem cells that have tremendous therapeutic effect. Our aim was to explore whether the immune mechanisms were associated with BMSCs-afforded protection against DIC. We generated a rat model of DIC by lipopolysaccharide (LPS, 3 mg/kg) injection via the tail vein. In the treatment group, rats were pre-treated with 1 × l03 , 1 × l04 , 1 × l05 , and 1 × l06 allogeneic BMSCs before LPS injection. Blood sample was withdrawn from the abdominal aorta at 0 (before), 4, and 8 h after LPS injection and used for biochemical analyses. After experiments, the mice were sacrificed and their organs were harvested and observed by H&E and PTAH staining. Continuous infusion of LPS into the rats gradually impaired the hemostatic parameters and damaged organ functions. However, pre-treatment with BMSCs dose-dependently improved the hemostatic parameters. Meanwhile, the treatment significantly suppressed the fibrin microthrombi formation and alleviated liver, heart, lung, and renal injuries. Flow cytometry analysis demonstrated that BMSCs pre-treatment inhibited LPS-induced upregulation of CD3+ CD8+ T cells and CD3+ /CD161a+ NKT cells in the peripheral blood. BMSCs pre-treatment reversed the upregualtion of the B-cell population and the percentage of CD43+ /CD172a+ monocytes in the DIC models. Finally, BMSCs pre-treatment decreased the levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), and interleukin-6 (IL-6) and increased the levels of interleukin-10 (IL-10) in LPS-induced DIC models. Pre-treatment with BMSCs can reduce coagulation and alleviate organ dysfunction via peripheral immune responses in LPS-induced DIC rat model. J. Cell. Biochem. 118: 3184-3192, 2017. © 2017 Wiley Periodicals, Inc.


Clinicopathological features of gallbladder papillary adenocarcinoma.
Although patients with gallbladder papillary adenocarcinoma (GBPA) appear to have better prognoses than patients with other pathological subtypes of gallbladder carcinoma (GBC), the clinicopathological features and outcomes of GBPA have not been fully explored. This study therefore analyzed the clinicopathological characteristics and outcomes of GBPA.This study included 16 patients with GBPA and 101 with gallbladder adenocarcinoma (GBA) not otherwise specified (NOS), all diagnosed pathologically after surgical resection. Clinicopathological and survival data were retrospectively collected and compared. Fever was significantly more common in GBPA (7/16 vs 10/101; P = 0.000). Serum carbohydrate antigen 19-9 level was increased in 1 of 9 patients with GBPA and 39 of 76 with GBA (P = 0.022). More patients with GBPA underwent curative resection (15/16 vs 54/101; P = 0.009). Pathologically, patients with GBPA were at much earlier tumor (T) (4 in situ, 8 T1; P = 0.000) and Tumor, Node, Metastases (TNM) stages (P = 0.000). The overall 1-, 3-, and 5-year survival rates were significantly higher in patients with GBPA (100%, 76.9%, and 76.9%, respectively), than in patients with GBA (72.2%, 38.8%, and 31.0%, respectively; P = 0.001). Preoperative jaundice (odds ratio 7.69; 95% confidence interval, 1.53-38.76; P = 0.013) was a significant prognostic factor in patients with GBA, but was no longer significant when the patients with GBA and GBPA were pooled together. The clinicopathological features of patients with GBPA differed from those in patients with GBA (not otherwise specified). Pooling of patients may mask prognostic factors in each group.


[Recent progress in photosynthetic microbial co-culture systems].
Co-culture systems consisted of photosynthetic microorganisms and others heterotrophic microbes have attracted great attention in recent years. These systems show many advantages when compared with single culture grown under autotrophic conditions, such as less vulnerable to pollution and more stability, thus have been applied to wastewater treatment, soil remediation, biodegradable harmful substances, and production of high value-added products. In order to explore basic theory and further applications, we summarize here recent progresses in artificial co-culture systems of using photosynthetic microorganisms, to provide a current scientific understanding for the rational design of the co-culture system based on photosynthetic microorganisms using synthetic biology.


Oral Aphthous: Pathophysiology, Clinical Aspects and Medical Treatment.
Oral aphthosis is a painful inflammatory process of the oral mucosa. Oral aphthous can appear alone or secondary to numerous distinct disease processes. If recurrence occurs frequently, it is called recurrent aphthous stomatitis. The pathophysiology of oral aphthous ulcers remains unclear but various bacteria are part of its microbiology. Three morphological types hold great importance in literature because these types help manage the illness properly. Google Scholar and PubMed databases were used to retrieve the relevant data and information. Different keywords including "Aphthous", "Aphthosis", "Canker sores", "Aphthous stomatitis", "Aphthous ulcer causes", "Aphthous ulcer AND Microbiota" and "Aphthous ulcer AND treatment". The causes for oral aphthous ulcerations are widespread and ranges from localized trauma to rare syndromes, underlying intestinal disease, or even malignant disease processes. A detailed history and thorough examination of systems can assist the physician or dermatologist in defining whether it is related to a systemic disease process or truly idiopathic. Management of oral aphthous ulcers is challenging. For oral aphthous or recurrent aphthous ulcers from an underlying disease, topical medications are preferred due to their minimum side effects. Systemic medications are necessary if the disease progresses. Within the limitation of research and literature provided, it is safe to say that topical corticosteroids are the first line of treatment. Herein, the author discusses the pathophysiology, types, causes, diagnosis, and appropriate treatment ladder of oral aphthous stomatitis as described in the literature.


Effects of growth factors and feeder cells on porcine primordial germ cells in vitro.
As embryonic stem (ES) cells are not available in swine, embryonic germ (EG) cells derived from primordial germ cells (PGCs) are an alternate source of pluripotent embryonic cells for genetic modification through homologous recombination. Although morphological and biochemical characteristics are similar between ES and EG cells, culture conditions are quite different. To optimize the culture condition for the establishment of porcine EG cells, porcine PGCs were cultured in vitro with various combinations of growth factors (leukemia inhibitory factor [LIF], stem cell factor [SCF], and basic fibroblast growth factor [bFGF]) and on different kinds of feeder cells (STO, TM(4), Sl/Sl(4) m220, porcine embryonic fibroblasts, and COS-7 cells). Optimal results were obtained when all three growth factors (LIF, SCF, and bFGF) were present in the media. Also, feeder cells expressing membrane-bound SCF are required for survival and establishment of porcine EG cells. Therefore, a combination of growth factors and proper feeder cells are critical for the establishment of undifferentiated porcine EG cells.


Accessory left gastric artery aneurysms in granulomatosis with polyangiitis: a case report and literature review.
Aneurysm formation is a potential complication of granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis. It is a very rare complication, but immediate diagnosis and therapy should be performed because an aneurysm can be life-threatening if it ruptures. An accessory left gastric artery (ALGA) is also a rare variant gastric artery that may obtain its blood supply from the left hepatic artery and left gastric artery. We herein describe a 57-year-old Japanese man who was diagnosed with GPA complicated by aneurysm rupture in an ALGA. Emergency surgery was performed after failure of arterial coil embolization to interrupt blood flow in the ALGA. The patient underwent partial resection of the lesser omentum, which contained all aneurysms. During partial resection of the lesser omentum, both the left gastric artery and ALGA were ligated because they were thought to be feeders of the aneurysms. Postoperative recovery was uneventful; no bleeding or recurrence of the aneurysms occurred. Immediate diagnosis and therapy should be performed for patients with GPA with symptoms of vascular ischemia or aortitis. Endovascular intervention is the first-choice therapy especially for hemodynamically stable patients with ruptured aneurysms or aneurysms located on variant arteries, which may have multiple blood supplies. In the present case, although endovascular treatment failed, the approach described herein was helpful during open surgery.


Endocardial center motion for quantification of left ventricular discoordination in heart failure using cine MRI.
To compare a novel cardiovascular magnetic resonance technique for the assessment of left ventricular (LV) mechanical discoordination by characterizing the endocardial center motion (ECM) in short-axis cine MRI in healthy volunteers and heart failure patients with left bundle branch block (HF-LBBB). To evaluate ECM analysis as mechanical discoordination measure, we retrospectively compared spatial and temporal features of the ECM between a group of healthy volunteers (n = 14) and conduction defect patients (HF-LBBB, n = 31). We tracked the center of the endocardial borders on short-axis view MRI cine loops during the cardiac cycle. From the ECM trajectory we calculated the overall traveled distance, the enclosed area, the eccentricity of the trajectory, and the maximum traveled distance. The ECM can be visualized in spatial coordinates as well as by its temporal behavior. We evaluated the classification performance of these measures for LBBB detection. We also quantified the coherence of the ECM on the longitudinal direction by considering the variability of the ECM measures between different short-axis slices. Patients with LBBB showed significantly higher traveled distance (p < 0.0001), enclosed area (p < 0.002), eccentricity (p < 0.02), and peak displacement (p < 0.02) of the endocardial center. Patients with positive late gadolinium enhancement showed a higher variability of ECM measures across different slices (p < 0.05). ECM analysis is feasible and it allows the assessment of left ventricular mechanical discoordination. Differences in ECM measures permit one to distinguish between LBBB and healthy volunteers.


Urinary testosterone glucuronide and sulphate in newborns and young infants.
Urinary testosterone glucuronide and sulphate was determined separately by gas chromatography in 39 newborns and young infants (34 males and 5 females). In all cases, testosterone sulphate was higher than glucuronide. Boys excreted more of both conjugates (sulphate 6.7, glucuronide 2.2 mug/24 h) than girls (1.1 and 0.7 mug/24 h, respectively). Boys older than 3 weeks had higher values than boys younger than 2 weeks. The levels correlated positively with chronological age, negatively with the gestational age and not at all with the bilirubin levels. It is concluded that testosterone is excreted preferentially as the sulphate in the newborn period and that the high sulphokinase activity in foetal and neonatal testes is more likely responsible for this phenomenon than an impaired glucuronizing capacity of the liver.


Karyotype analysis of three weevil species from the Genera Brachysomus (Boheman, 1845) and Strophosoma Billberg, 1820 (Coleoptera, Curculionidae).
Karyotypes of three weevil species, viz. Brachysomus dispar (2n=22, n males = 10 + X(y(p))), Brachysomus hirtus (3n=33, n females = 10 + X) and Strophosoma faber (2n=22, n males = 10 + X(y(p))) belonging to the tribes Sciaphilini and Brachyderini, were studied using the C-banding technique. The karyotype structures of the two bisexual and one parthenogenetic species are described for the first time. Most chromosomes are meta- or submetacentric. In the two species of the genus Brachysomus, the chromosomes resemble one another in having a rather small amount of heterochromatin restricted to the pericentromeric region, visible as dark stained blocks mainly during the early stages of nuclear division. Larger bands at mitotic metaphase and diakinesis occur only in Strophosomafaber. Geographic parthenogenesis in Brachysomus hirtus is briefly discussed.


Clozapine-related myocarditis and cardiomyopathy in an Australian metropolitan psychiatric service.
Myocarditis and cardiomyopathy are rarely reported complications of clozapine treatment. The incidence of clozapine-related myocarditis has been variably reported at between 0.03% and 0.19% of initiations and cardiomyopathy has been reported even less commonly. In our Brisbane-based service, nine of 94 patients initiated on clozapine over the previous 3 years appeared to have experienced myocarditis or cardiomyopathy. The unique co-location of our service with a major cardiothoracic hospital facilitated a review of identified cases to inform decisions regarding clozapine treatment and rechallenge in this service. Cases were identified by survey of psychiatric and cardiac medical staff at The Prince Charles Hospital and subjected to re-evaluation by a multidiscipline consensus panel. The panel compared cases to international reports and identified the clinical features that supported a diagnosis of clozapine-related myocarditis or cardiomyopathy. This process resulted in the stratification of the nine cases into the following categories of diagnostic likelihood: three highly probable, three probable, and two possible cases of clozapine-related myocarditis, and one possible case of clozapine-related cardiomyopathy. Successful clozapine rechallenge/continuation was undertaken in two patients and the panel agreed that this was a viable future option for several other patients. Findings of the panel review supported the initial clinical diagnoses. This confirmed that there was an apparent high incidence of clozapine-related myocarditis within this service, for which there was no clear reason. Mechanisms underlying clozapine-related myocarditis and cardiomyopathy, as well as successful clozapine continuation and rechallenge were considered, but definitive explanations remain unknown. This review highlighted the clinician's role in post-marketing drug surveillance to guide rational management of suspected adverse drug effects.