Intravenous tocolysis with Bryophyllum pinnatum is better tolerated than beta-agonist application.
To compare tolerability and tocolytic outcome between i.v. infused plant extract, Bryophyllum pinnatum, and beta-agonists. In a retrospective study, 67 pairs of pregnant women in preterm labor treated with intravenous B. pinnatum or beta-agonists were closely matched for maternal age, gestational age at tocolysis, CTG recorded contractions, cervical effacement, preterm premature rupture of the membranes, and history of preterm labor. Endpoints were prolongation of pregnancy, gestational age at delivery, pre- and postpartum duration of hospitalization, maternal tolerability, neonatal outcome and morbidity. Pregnant women with B. pinnatum and beta-agonists were equal in the prolongation of pregnancy (6.2 versus 5.4 days, NS), the gestaional age at delivery (38.0 versus 37.1 weeks, NS) and the duration of hospitalisations, but had less adverse effects (34.3 versus 55.2% with palpitation or dyspnea, P=0.02). The neonatal outcome and morbidity in the B. pinnatum group were equal or better (oxygen use 10.4 versus 44.8%, P<0.001; respiratory distress syndrome 4.5 versus 19.4%, P=0.01). In the management of preterm labor B. pinnatum is no less effective than beta-agonists, but is significantly better tolerated.


Challenges, recent development, and opportunities of smart waste collection: A review.
Population growth and changing consumption patterns make waste management a significant global challenge. Studies evaluated that by 2050 almost 67 % of the Earth's population will live in megacities, which guides the requirement of smart assistance to answer the citizens' demands. Waste collection is an efficient IoT service that takes advantage of cost and energy efficiency. The fundamental end of this study is a review of utilizing IoT for waste collection to introduce technologies for waste collection in an eco-friendly method. This study investigated information and communication technologies (ICTs), including spatial, identification, acquisition, and data communication technologies. It also reviews several energy harvesting technologies for more cost reduction. The results showed that applying these technologies reduces costs and energy usage and can change the future of waste management.


A fractal model of chromosomes and chromosomal DNA replication.
With the aim of clarifying topological problems involved in the process of chromosomal DNA replication, a fractal model of chromosomes was built based on the assumption that a part of a chromosome, e.g. a radial loop, is similar in shape to a whole chromosome and each radial loop represents structures in the lower-order organization (an assumption of self-similarity). Several other assumptions used include (i) one continuous DNA fiber makes a whole chromosome (a unineme hypothesis), (ii) in situ DNA exists in the form of a double duplex or a tetraplex which is made of two duplex DNAs, although a duplex DNA may appear transiently in S-phase (multi-strandedness hypothesis) and (iii) torsional stress on a DNA fiber causes the fiber to supercoil and thus stabilizes chromosome structure (torque-based stabilization). This model allowed to calculate of a fractal dimension of a representative metaphase chromosome (e.g. d = 2.34), to predict the mode of replication of double duplex and to furnish a topological basis for the decondensation unit hypothesis. It must also be admitted that all the arguments in this report except for the possible existence of split telomeres hold true without assuming a tetraplex organization of chromosomes. Implications of this model was discussed and the importance of the fractal dimension as a measure of chromatin condensation stressed.


Nodulation and nitrogen fixation (Acetylene reduction) in desert ironwood (Olneya tesota).
Acacia greggi, Cercidium floridium, and Olneya tesota seeds were inoculated with soil from beneath mature native desert trees and grown in the greenhouse on a nitrogen free media. Olneya tesota seedlings nodulated and reduced acetylene to ethylene. Nodulation or acetylene reduction was not observed in A. greggi or C. floridium. This is the first report of nodulation and nitrogen fixation in Olneya tesota.


Fas 670 promoter polymorphism is associated to susceptibility, clinical presentation, and survival in adult T cell leukemia.
Fas (TNFRSF6/Apo-1/CD95) is a type I transmembrane receptor, which mediates apoptosis. Fas gene mutations, aberrant transcripts, and abundant expression of Fas have been reported in adult T cell leukemia (ATL). To further elucidate the role of Fas in ATL pathogenesis, we investigated whether the -670 FAS promoter A/G polymorphism (STAT1-binding site) might contribute to susceptibility and clinical outcome in ATL. Thirty-one patients with ATL, 33 healthy, human T lymphotropic virus type 1-infected individuals, and 70 healthy, uninfected controls were genotyped for the FAS -670 polymorphism by PCR-restriction fragment-length polymorphism. The AA genotype was significantly over-represented in ATL patients in comparison with healthy controls (P=0.006), as well as asymptomatics (P=0.037), corresponding to an odds ratio (OR) of 3.79 [95% confidence intervals (CI; 1.28-11.41)] and 4.58 [95% CI (1.13-20.03)], respectively. The AA group also comprised significantly more aggressive (acute and lymphoma) clinical subtypes [P=0.012; OR=8.40; 95% CI (1.60-44.12)]. In addition, we observed a statistically significant association between GG genotype and survival (log rank test, P=0.032). Finally, IFN-gamma-induced but not basal FAS mRNA levels were increased significantly (P=0.049) in PBMCs from AA versus GG individuals, demonstrating the IFN-dependent functionality of the -670 polymorphism. In conclusion, our results demonstrate that a functional Fas promoter polymorphism is significantly associated to susceptibility, clinical manifestation, and survival in ATL.


Endoplasmic reticulum stress in bone marrow-derived cells prevents acute cardiac inflammation and injury in response to angiotensin II.
Inflammation plays an important role in hypertensive cardiac injury. The endoplasmic reticulum (ER) stress pathway is involved in the inflammatory response. However, the role of ER stress in elevated angiotensin II (Ang II)-induced cardiac injury remains unclear. In this study, we investigated the role of ER stress in Ang II-induced hypertensive cardiac injury. Transcriptome analysis and quantitative real-time PCR showed that Ang II infusion in mice increased ER stress-related genes expression in the heart. C/EBP homologous protein (CHOP) deficiency, a key mediator of ER stress, increased infiltration of inflammatory cells, especially neutrophils, the production of inflammatory cytokines, chemokines in Ang II-infused mouse hearts. CHOP deficiency increased Ang II-induced cardiac fibrotic injury: (1) Masson trichrome staining showed increased fibrotic areas, (2) immunohistochemistry staining showed increased expression of α-smooth muscle actin, transforming growth factor β1 and (3) quantitative real-time PCR showed increased expression of collagen in CHOP-deficient mouse heart. Bone marrow transplantation experiments indicated that CHOP deficiency in bone marrow cells was responsible for Ang II-induced cardiac fibrotic injury. Moreover, TUNEL staining and flow cytometry revealed that CHOP deficiency decreased neutrophil apoptosis in response to Ang II. Taken together, our study demonstrated that hypertension induced ER stress after Ang II infusion. ER stress in bone marrow-derived cells protected acute cardiac inflammation and injury in response to Ang II.


Studies on porcine high molecular weight kininogen. An improved method for the purification of porcine high molecular weight kininogen and cleavage of the kininogen by the action of porcine plasma kallikrein.
By introduction of stepwise DEAE Sephadex A-50 and copper-Chelating Sepharose 6B column chromatographies, about 18.5 mg of high molecular weight kininogen (HK) composed of a single polypeptide chain was obtained from 500 ml of porcine plasma. Molecular weights of reduced or non-reduced preparation were estimated to be 110 kDa and 116 kDa, respectively, by SDS-PAGE. Using the preparation, cleavage of HK by porcine plasma kallikrein (KK) was investigated. A single polypeptide HK was cleaved into two chains cross-linked by disulfide bond(s), accompanying the release of kinin. Further degradation was not observed. Molecular weights of heavy-chain (H-chain) and light-chain (L-chain) were estimated to be 61 kDa and 56 kDa, respectively, by SDS-PAGE. The amino- (N-) terminal sequences of intact HK, reduced and carboxymethylated- (RCM-) H-chain, RCM-L-chain and the peptide around the kinin moiety obtained by BrCN digestion were determined. Their sequences were highly homologous with those of bovine or human HK. These results indicate that plasma KK first cleaved the Arg-Ser bond of HK, and formed nicked HK. The second cleavage yielded bradykinin (BK) and kinin-free protein, which was apparently of equal size to the nicked HK. The structure of HK was from the N-terminus to the carboxy- (C-) terminus, H-chain-BK-L-chain.


Interaction between phage G13 and its oligosaccharide receptor studied by equilibrium dialysis.
The reversible binding of phage G13, a phi X174-like single-strand DNA phage, to a 3H-labelled nonasaccharide from the lipopolysaccharide of its natural host Escherichia coli C was studied with equilibrium dialysis. The binding constant (Ka) was determined to 1.3 x 10(7) M-1 in Scatchard and Lineweaver-Burk plots. Approximately one saccharide bound per G13 phage particle which suggests that only one of the 12 spikes in each G13 virion was engaged in the phage/receptor saccharide interaction. Equilibrium dialysis inhibition experiments with saccharides from lipopolysaccharides of an isogenic series of Salmonella typhimurium mutants showed that hepta- and pentasaccharides from two G13-sensitive bacteria, i.e., with efficiencies of plating of 0.1-1.0 compared to E. coli C, were efficient inhibitors with Ka-values greater than or equal to 1.2 x 10(7) M-1. The octa- and hexasaccharides from two G13 resistant strains, with efficiency of plating less than or equal to x 10(-4), were either greater than 1000-fold or greater than 15-fold less efficient as inhibitors with Ka-values less than or equal to 8.8 x 10(5) M-1. The results show that phage G13 binds in a specific and reversible way to penta-, hepta-, and nonasaccharides from G13 sensitive bacteria with the specificity residing in the hexose and heptose region of the core lipopolysaccharide.


Neocortex expansion in development and evolution - from cell biology to single genes.
Neocortex expansion in development and evolution reflects an increased and prolonged activity of neural progenitor cells. Insight into key aspects of the underlying cell biology has recently been obtained. First, the restriction of apical progenitors to undergo mitosis at the ventricular surface is overcome by generation of basal progenitors, which are free to undergo mitosis at abventricular location, typically the subventricular zone. This process involves basolateral ciliogenesis, delamination from the apical adherens junction belt, and loss of apical cell polarity. Second, proliferative capacity of basal progenitors is supported by self-produced extracellular matrix constituents, which in turn promote growth factor signalling. Humans amplify these processes by characteristic alterations in expression of key regulatory genes (PAX6), and via human-specific genes (ARHGAP11B).


Atypical GM1 ganglioside accumulation in a case of juvenile amaurotic idiocy.
The brain and liver from a 7-year-old Japanese girl with juvenile amaurotic idiocy were examined neuropathologically and biochemically. Visceromegaly and skeletal abnormalities were absent. Nerve cells in the central nervous system were swollen and contained fine fat granules. Electronmicroscopically, there were large numbers of irregular bodies in the perikarya and these corresponded to the curvilinear and membranous cytoplasmic bodies. Lipid analysis of the brain revealed that GM1 ganglioside was increased in the parietal and occipital areas, while the frontal lobe showed a normal ganglioside pattern. N-Acetyl neuraminic acid (NANA) content in all areas was not elevated. Determinations of beta-galactosidase activity were within normal ranges. The liver had no accumulation of GM1 ganglioside and showed a normal beta-galactosidase activity. These unusual findings in GM1 gangliosidosis were discussed.


Leeches and their microbiota: naturally simple symbiosis models.
Strictly blood-feeding leeches and their limited microbiota provide natural and powerful model systems to examine symbiosis. Blood is devoid of essential nutrients and it is thought that symbiotic bacteria synthesize these for the host. In this review, three distinct leech-microbe associations are described: (i) the mycetome, which is the large symbiont-containing organ associated with the esophagus; (ii) the nephridia and bladders that form the excretory system; and (iii) the digestive tract, where two bacterial species dominate the microbiota. The current knowledge and features of leech biology that promote the investigation of interspecific interactions (host-microbe and microbe-microbe) and their evolution are highlighted.


Speciation in the asexual realm: is the parthenogenetic weevil Naupactus cervinus a complex of species in statu nascendi?
Population genetic theory shows that asexual organisms may evolve into species, which behave as independent evolutionary units. As a result, they form genotypic clusters separated by deep gaps due to geographic isolation and/or divergent selection. Identification of several genetically divergent groups of weevils embodied in the nominal species Naupactus cervinus deserves further study, in order to test if these lineages are evolving independently. In the present paper we tested if the parthenogenetic weevil N. cervinus, native to South America and broadly distributed throughout the world, contains more than one evolutionary unit. For this purpose, we applied three different approaches, a multilocus phylogenetic analysis, the GMYC approach and the K/θ method. We accomplished these analyses through a survey of mitochondrial (COI and COII genes) and nuclear (ITS1 sequence) genetic variation and morphometric analysis in a sample which included individuals from different locations within the native geographic range of N. cervinus. In addition, we compared the divergence accumulated in this species with that in another weevil of the same tribe (Naupactini) showing identical reproductive mode to see if similar levels of morphological variation matches similar levels of genetic divergence. We report the presence of two independent evolutionary units living in sympatry in forest areas. The incongruence between mitochondrial and nuclear datasets analyzed herein reflects incomplete lineage sorting of the nuclear marker and different evolutionary rates between genomes. Ecological divergence driven by natural selection (sympatry) or secondary contact after geographic isolation (allopatry) might explain the deep gaps in mitochondrial phylogenies. Instead, Wolbachia infection was ruled out as a causal factor for such differentiation. We conclude that N. cervinus is probably a species complex with at least two well differentiated lineages that would represent a cluster of species in statu nascendi.


Stereotaxic biopsy and radioactive implantation for interstitial therapy of tumors of the pineal region.
Stereotaxic biopsy was performed in 10 patients with tumors of the pineal region. On the basis of intraoperative tissue diagnosis, low-energy radioactive sources (125I) were implanted in seven patients for interstitial irradiation during the same stereotaxic procedure. Results were good in five cases. This therapeutic modality appears to be indicated in cases of proven low-grade malignancy, inasmuch as the implantation of radioactive sources in a highly malignant lesion carries the risk of severe, often irreversible, damage to the surrounding brain, because of possible seed migration.


Graphene woven fabric-polydimethylsiloxane piezoresistive films for smart multi-stimuli responses.
The outstanding properties of graphene, including its electromechanical property, could be engineered for wearable electronic sensor platforms. The tubular graphene weaved into a mesh or graphene woven fabrics (GWF) has been reported as one of the most sensitive materials for deformation detection, as well as a promising temperature sensor. Herein, we present the performance of our developed flexible, stretchable, and multiple sensitive sensors fabricated from GWF embedded in polydimethylsiloxane (PDMS) film substrate. The GWF/PDMS sensor shows a pressure sensitivity of 0.0142 kPa-1 in a wide linearity range of 0-20 kPa, an outstanding Gauge factor (GF) of 582 at a strain of 6.2 %, and a very high positive sensitivity of 0.0238 °C-1 in the temperature range of 25-80 °C. A practical application as a high sensitivity air pressure sensor able to measure low pressures (in the range of Pa to kPa) was also demonstrated. This sensor platform having desirable performance characteristics is an excellent candidate for wearable devices in the healthcare sector.


Relict duck-billed dinosaurs survived into the last age of the dinosaurs in subantarctic Chile.
In the dusk of the Mesozoic, advanced duck-billed dinosaurs (Hadrosauridae) were so successful that they likely outcompeted other herbivores, contributing to declines in dinosaur diversity. From Laurasia, hadrosaurids dispersed widely, colonizing Africa, South America, and, allegedly, Antarctica. Here, we present the first species of a duck-billed dinosaur from a subantarctic region, Gonkoken nanoi, of early Maastrichtian age in Magallanes, Chile. Unlike duckbills further north in Patagonia, Gonkoken descends from North American forms diverging shortly before the origin of Hadrosauridae. However, at the time, non-hadrosaurids in North America had become replaced by hadrosaurids. We propose that the ancestors of Gonkoken arrived earlier in South America and reached further south, into regions where hadrosaurids never arrived: All alleged subantarctic and Antarctic remains of hadrosaurids could belong to non-hadrosaurid duckbills like Gonkoken. Dinosaur faunas of the world underwent qualitatively different changes before the Cretaceous-Paleogene asteroid impact, which should be considered when discussing their possible vulnerability.


Infection of rabbits with bovine immunodeficiency-like virus.
New Zealand white rabbits, which had been prepared for inoculation by intraperitoneal treatment with thioglycollate, were inoculated intraperitoneally with bovine immunodeficiency-like virus (BIV). Infected materials from various sources were used including cultured cells and culture fluids, peripheral blood leukocytes from infected cattle and spleen tissue from previously infected rabbits. Virus isolations and serological responses detected by western blotting provided clear evidence that infections had been established in inoculated rabbits and that the spleen was an important site of BIV infectivity. These results indicate that rabbits may be a useful species when testing for BIV infectivity in materials too toxic or highly contaminated to be inoculated directly into cell cultures. Furthermore, rabbits may also be useful in testing effects of coinfections with other bovine viruses on progression of BIV infection and for the initial evaluation of therapeutic regimens designed to suppress or eliminate BIV infections.


Novel mutations in the QRDR region gyrA gene in multidrug-resistance Corynebacterium spp. isolates from intravenous sites.
The resistance to fluoroquinolones in corynebacteria is due to mutations occurring in the quinolone-resistance-determining region (QRDR) of the gyrA gene encoding the enzyme gyrase A subunit. In recent years we can observe an increasing number of infections caused by multidrug-resistant Corynebacterium striatum, Corynebacterium jeikeium and Corynebacterium urealyticum, including wide range of disorders, such as invasive infections. In this study 14 Corynebacterium spp. isolated from intravenous sites were sequenced and new combinations of mutations in the QRDR of the gyrA gene were found in C. jeikeium and C. urealyticum. Nowadays, no study comparing mutations in this region and the susceptibility to fluoroquinolones in C. jeikeium and C. urealyticum has been described. All the isolates that showed double mutation (position 87 and 91) in the QRDR gyrA gene had high MIC to the fluoroquinolones tested.


[Subclavian-carotid artery transposition in the therapy of lesions of the proximal subclavian artery].
Employing an extrathoracic approach 10 patients were operated upon for 12 obstructive lesions of the subclavian arteries using carotid-subclavian anastomosis. The operation was indicated 3 times for the pathological entity of arterial stenosis embolizing into the vascular periphery, 3 times for claudication of the upper extremity and 4 times for cerebro-vascular insufficiency. Followed up to 31 months all anastomoses remained patent. All the complications were managed conservatively and were considered of minor importance.


Visuospatial problem solving, conceptual reasoning and sorting behaviour in multiple sclerosis out-patients.
Visuospatial problem solving, conceptual reasoning and shifting of set were studied in out-patients with definite and probable MS. The sample of MS patients was homogeneous with respect to 2 important dimensions. All were out-patients, leading a normal although handicap-restricted social life. Furthermore, in all patients relapse or obvious instability of the disease were absent for at least a month. On Raven's Progressive Matrices, the Category test and the Wisconsin Modified Card Sorting test, no significant differences were found between the group of MS patients and a control group of healthy volunteers. However, 18% of MS patients and 4% of controls were rated as performing slightly below the expected levels of cognition. Stepwise regression analysis failed to reveal effects of illness variables, and no difference between patients with definite and probable MS could be detected. Clearly, most socially integrated MS patients in stable disease stages are capable of normal visuospatial problem solving, abstract reasoning and shifting of set.


Design and synthesis of novel bis-pyridinium based-ionic liquids as potent antiparasitic agents.
Focused bis-pyridinium based-ionic liquids were successfully synthesized through the quaternization of the selected 1,2-di(pyridin-4-yl)ethane followed by metathetical anion exchange. The synthesized pyridinium derivatives were fully characterized using various NMR-spectroscopic techniques including 1H, 13C, 11B, 31P and 19F NMR. The synthesized compounds were tested for their potential effect against Toxoplasma gondii. It was revealed that compound 5 had higher antiparasitic activity compared to other compounds. Parasitic reduction percentage reached 38, 50, 77 and 79 for groups III, IV, V and VI respectively in the liver with noticed distortion and deformation in tachyzoites' shape. Surprisingly there was no statistically significant difference between the synthesized compound 5 and the known anti-toxoplasmosis drug pyrimethamine. Histopathological study proved the effectiveness of the synthesized compound 5 on liver, spleen and brain tissues with observed better histological features compared to pyrimethamine treated group. The present investigation may pave the way to the possible use of compound 5 to replace the known drug pyrimethamine with better antiparasitic profile and fewer side effects.


Carotid intima-media thickness is increased in patients with mucopolysaccharidoses.
The feasibility of carotid artery intima-media thickness (C-IMT), an established cardiovascular disease marker, as a cardiac risk marker in mucopolysaccharidosis (MPS) patients was explored. To determine if C-IMT is abnormal in MPS versus unaffected controls, and if C-IMT correlates with coronary artery diameter in MPS. Measurements of C-IMT via neck ultrasound and echocardiographic parameters, including coronary artery diameters, were obtained from MPS and control patients, and compared. Sixteen MPS subjects (6 MPS I, 6 MPS II, 2 MPS III, 1 MPS VI, 1 MPS VII) and sixteen age, ethnicity, and gender-matched controls were enrolled. Median MPS and control subject ages were 8.3±4.5 and 8.6±4.3 years, respectively (p=0.73). Mean MPS and control C-IMTs were 0.54±0.070 and 0.48±0.034 mm (p=0.0029). No differences in left main, left anterior descending, or right coronary artery diameters were seen between MPS and controls. A significant proportion of MPS subjects had mitral insufficiency (14/16; p=0.0002), aortic insufficiency (10/16; p=0.0021), and left ventricular dilatation (7/16, p=0.037) versus controls. C-IMT did not correlate significantly with age, height, weight, coronary measurements, or duration of treatment. C-IMT in MPS patients is increased compared to matched controls, likely reflective of arterial intima-medial glycosaminoglycan accumulation. MPS subjects demonstrated a high percentage of left-sided valvular insufficiency and ventricular dilatation. Additional studies should be performed in MPS patients to determine if C-IMT correlates with arterial elasticity, biomarkers of vascular dysfunction, and higher risk of cardiovascular events.


Acute pain management in patients with prior opioid consumption: a case-controlled retrospective review.
The patient with a history of current opioid consumption presenting in the acute postoperative setting presents a challenge for pain management. Standard treatment dosages and strategies are often ineffective in providing pain relief. This retrospective case-control study reviews 4 years' experience of the Acute Pain Service (APS) at our institution providing care for 202 chronic pain and opioid-consuming (CPOC) patients, 6.6% of 3058 patients undergoing urologic, gynecologic, orthopedic and general surgical procedures. Controls matched for age, gender, date and type of surgery, and postoperative pain relief modality were found for 180 (89%) of these patients. Patients were provided patient-controlled analgesia (PCA), or epidural opioid analgesia (EOA with boluses of preservative-free morphine or bupivacaine (1:16% + 2 micrograms/ml fentanyl (B/F)). Records were reviewed for patient demographics, diagnoses, surgical procedures, pre-operative opioid use, days-on-service, analgesic requirement, pain scores and incidence of moderate/severe side effects. Patient demographics were similar between CPOC and control groups. When considering PCA alone, mean 24-h usage in controls was 42.8 (32.0) mg morphine (MS) equivalents differing significantly from CPOC patients' use of 135.8 (68.5) mg MS equivalents (P = 0.0001). EOA and B/F case studies showed similar results. Moderate sedation was experienced by 50% of CPOC patients receiving PCA. Differences in opioid usage, side effects, pain scores, sedation and prescribed treatment with anxiolytics were shown between CPOC patients and matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)


A thiophen-thiooxorhodamine conjugate fluorescent probe for detecting mercury in aqueous media and living cells.
A rhodamine-based sensor RB-S2 was designed and synthesized by combination of the thiospirolacton chromophore and the thiophen ring block with high affinity to Hg(2+). Probe RB-S2 exhibits high selectivity and excellent sensitivity in both absorbance and fluorescence detection of Hg(2+) in aqueous solution. In addition, fluorescent imaging of Hg(2+) in MCF-7 cells is also successfully demonstrated.


Pitfalls in the use of carboxylic acid anhydrides for structural studies of nucleoprotein particles.
During modification of protein amino groups with carboxylic acid anhydrides, these reagents cause a fall in pH, which can be prevented by addition of base. Although unmodified nucleosomal particles are not affected by the local transient changes in pH induced by the base (NaOH) added to prevent a fall in pH during modification, the nucleosomal particles modified by acetic anhydride are dissociated, with release of single-stranded DNA.


Primary reconstruction of orbital fractures using patient-specific titanium milled implants: the Helsinki protocol.
Preoperative virtual planning and the use of patient-specific implants enable exact reconstruction of orbital fractures. We present our results and experience of reconstruction of isolated orbital fractures with patient-specific implants, according to the Helsinki protocol, in 15 patients who were followed up for at least three months postoperatively. The mean (range) difference between the positions of virtually planned, and postoperative, implants was 1.9 (0.5-5.6) mm. The postoperative volume of the fractured orbit was 1.34ml less than that of the non-fractured side, but this was not clinically relevant. None of the patients required reoperation and none had any implant-related complications during follow up. We conclude that patient-specific implants are an adaptable and reliable treatment for primary orbital trauma, and that the Helsinki protocol may have wider applications in the treatment of facial fractures.


Secure secondary utilization system of genomic data using quantum secure cloud.
Secure storage and secondary use of individual human genome data is increasingly important for genome research and personalized medicine. Currently, it is necessary to store the whole genome sequencing information (FASTQ data), which enables detections of de novo mutations and structural variations in the analysis of hereditary diseases and cancer. Furthermore, bioinformatics tools to analyze FASTQ data are frequently updated to improve the precision and recall of detected variants. However, existing secure secondary use of data, such as multi-party computation or homomorphic encryption, can handle only a limited algorithms and usually requires huge computational resources. Here, we developed a high-performance one-stop system for large-scale genome data analysis with secure secondary use of the data by the data owner and multiple users with different levels of data access control. Our quantum secure cloud system is a distributed secure genomic data analysis system (DSGD) with a "trusted server" built on a quantum secure cloud, the information-theoretically secure Tokyo QKD Network. The trusted server will be capable of deploying and running a variety of sequencing analysis hardware, such as GPUs and FPGAs, as well as CPU-based software. We demonstrated that DSGD achieved comparable throughput with and without encryption on the trusted server Therefore, our system is ready to be installed at research institutes and hospitals that make diagnoses based on whole genome sequencing on a daily basis.


Orthodontic treatment with fixed appliances and biofilm formation--a potential public health threat?
Orthodontic treatment is highly popular for restoring functional and facial esthetics in juveniles and adults. As a downside, prevalence of biofilm-related complications is high. Objectives of this review are to (1) identify special features of biofilm formation in orthodontic patients and (2) emphasize the need for strong concerted action to prevent biofilm-related complications during orthodontic treatment. Literature on biofilm formation in the oral cavity is reviewed to identify special features of biofilm formation in orthodontic patients. Estimates are made of juvenile and adult orthodontic patient population sizes, and biofilm-related complication rates are used to indicate the costs and clinical workload resulting from biofilm-related complications. Biofilm formation in orthodontic patients is governed by similar mechanisms as common in the oral cavity. However, orthodontic appliances hamper the maintenance of oral hygiene and provide numerous additional surfaces, with properties alien to the oral cavity, to which bacteria can adhere and form a biofilm. Biofilm formation may lead to gingivitis and white spot lesions, compromising facial esthetics. Whereas gingivitis after orthodontic treatment is often transient, white spot lesions may turn into cavities requiring professional restoration. Complications requiring professional care develop in 15 % of all orthodontic patients, implying an annual cost of over US$500,000,000 and a workload of 1,000 full-time dentists in the USA alone. Improved preventive measures and antimicrobial materials are urgently required to prevent biofilm-related complications of orthodontic treatment from overshadowing its functional and esthetic advantages. High treatment demand and occurrence of biofilm-related complications requiring professional care make orthodontic treatment a potential public health threat.


Association between serum ALT levels and incidence of new-onset diabetes in general population of Japanese: a longitudinal observational study (ISSA-CKD).
We aimed to clarify the relationship between serum alanine transaminase (ALT) levels and incidence of new-onset diabetes in a Japanese general population. Population-based retrospective cohort study using annual health check-up data for residents of Iki City, Nagasaki Prefecture, Japan. A total of 5330 Japanese individuals (≥30 years old) without diabetes at baseline were analysed. Serum ALT levels were determined using an enzymatic method and were classified into gender-specific quartile groups as follows: group 1 (3-16 U/L in men and 3-13 U/L in women), group 2 (17-21 U/L in men and 14-16 U/L in women), group 3 (22-29 U/L in men and 17-22 U/L in women) and group 4 (30-428 U/L in men and 23-268 U/L in women). The study outcome was the incidence of diabetes (fasting glucose ≥7.0 mmol/L, non-fasting glucose ≥11.1 mmol/L, glycated haemoglobin ≥6.5% or use of glucose-lowering therapies). After an average follow-up period of 5.0 years, 279 individuals developed diabetes. The incidence rate of diabetes increased with elevation of serum ALT levels (0.7% per 100 person-years in group 1, 0.9% in group 2, 0.9% in group 3 and 1.7% in group 4) (p<0.001 for trend). This association was significant after adjustment for other risk factors including age, sex, obesity, hypertension, dyslipidaemia, smoking, current daily alcohol intake and regular exercise (p<0.001 for trend). Comparable associations were observed between men and women (p=0.459 for interaction). Serum ALT levels were associated with future development of diabetes in the general Japanese population.


TNF alpha-induced Ras activation due to ethanol promotes hepatocyte proliferation independently of liver injury in the mouse.
Tumor necrosis factor alpha (TNFalpha) has been shown to be both proapoptotic and mitogenic for hepatocytes and necessary for alcohol-induced liver injury. Ras, a known proto-oncogene, is very important in the regulation of cellular responses to TNFalpha. Therefore, the purpose of this study was to investigate the role of Ras in alcohol-induced pathogenesis. Male C57Bl/6 mice were fed ethanol or high-fat control diet via intragastric cannulation for 4 weeks. Ras activity was increased significantly after 4 weeks of ethanol and correlated with an increase in pathologic features. However, in mice deficient in the receptor-type 1 for TNFalpha (TNFR1(-/-)), ethanol-induced liver injury and the increase in Ras activity were significantly blunted compared with wild-type mice. Furthermore, it was demonstrated that H-, K-, and R-Ras isoforms were increased after ethanol exposure in wild-type mice. In TNFR1(-/-) mice, R-Ras activity remained elevated by ethanol, whereas H-Ras and K-Ras activity was blunted significantly under these conditions. Interestingly, hepatocellular proliferation, which was elevated approximately fivefold after 4 weeks of chronic ethanol in wild-type mice, was also blunted in TNFR1(-/-) mice given ethanol. Inhibition of Ras with adenovirus containing a dominant-negative Ras had no effect on ethanol-induced liver injury, but significantly blunted ethanol-induced hepatocyte proliferation by more than 50%. Overexpression of mitochondrial superoxide dismutase using recombinant adenovirus blunted lipid peroxidation and attenuated hepatic injury resulting from ethanol, but had no effect on Ras activation and hepatocyte proliferation caused by ethanol. In conclusion, these data support the hypotheses that hepatocellular oxidative stress leads to cell death and that TNFalpha-induced Ras activation is important in hepatic proliferation in response to ethanol-induced liver injury.


Historical changes in motor vehicle death rates among the elderly.
Motor vehicle death rates among the elderly decreased substantially between 1940 and 1980, while the number of registered motor vehicles in the United States increased fourfold and death rates from motor vehicle injury changed little for the entire population. The annual death rate per 100,000 males aged 75-79 declined from 120 in 1940 to 41 in 1980. Much of the decrease can be attributed to reduced pedestrian deaths. Rates for other elderly age and sex groups showed similar patterns but the rates were lower and the changes smaller. Displaying age-specific motor vehicle death rates by birth cohort provides a graphic demonstration that these death rates have decreased markedly for all age groups 60 and older. Implications and possible causes of this decrease are discussed.


The development of an anti-cancer peptide M1-21 targeting transcription factor FOXM1.
Transcription factor FOXM1 is a potential target for anti-cancer drug development. An interfering peptide M1-21, targeting FOXM1 and FOXM1-interacting proteins, is developed and its anti-cancer efficacy is evaluated. FOXM1 C-terminus-binding peptides are screened by in silico protocols from the peptide library of FOXM1 (1-138aa) and confirmed by cellular experiments. The selected peptide is synthesized into its D-retro-inverso (DRI) form by fusing a TAT cell-penetrating sequence. Anti-cancer activities are evaluated in vitro and in vivo with tumor-grafted nude mice, spontaneous breast cancer mice, and wild-type metastasis-tracing mice. Anti-cancer mechanisms are analyzed. Distribution and safety profiles in mice are evaluated. With improved stability and cell inhibitory activity compared to the parent peptide, M1-21 binds to multiple regions of FOXM1 and interferes with protein-protein interactions between FOXM1 and its various known partner proteins, including PLK1, LIN9 and B-MYB of the MuvB complex, and β-catenin. Consequently, M1-21 inhibits FOXM1-related transcriptional activities and FOXM1-mediated nuclear importation of β-catenin and β-catenin transcriptional activities. M1-21 inhibits multiple types of cancer (20 µM in vitro or 30 mg/kg in vivo) by preventing proliferation, migration, and WNT signaling. Distribution and safety profiles of M1-21 are favorable (broad distribution and > 15 h stability in mice) and the tested non-severely toxic dose reaches 200 mg/kg in mice. M1-21 also has low hemolytic toxicity and immunogenicity in mice. M1-21 is a promising interfering peptide targeting FOXM1 for the development of anti-cancer drugs.


Anterior approach for tumor of the superior sulcus.
A new approach for the resection of tumors of the superior sulcus is described. The exposure is gained through a proximal median sternotomy extended into the anterior fourth intercostal space as well as to the base of the neck on the appropriate side. This approach guarantees excellent exposure of the tumor, subclavian artery, and brachial plexus as well as access to the ribs posteriorly and the border of the vertebral bodies. Hilar dissection is readily accomplished without change of the patient's position. Disadvantages relate to depth of exposure, especially in large individuals, and the complicated wound closure.


Hydroxyl radical and thermal annealing on amorphous InGaZnO4 films for DNA immobilizations.
The effect of hydroxyl radicals (OH) and thermal annealing on an amorphous InGaZnO4 (aIGZO) film surface was investigated for manipulation of DNA immobilization. X-ray photoemission and fluorescence measurements were conducted to reveal the status of surface OH coverage and DNA immobilization, respectively. Systematic examinations concerning OH termination on the film surface suggested that the surface coverage of OH leveling DNA immobilization was related to the local surface potential. Furthermore, OH affinity on the aIGZO film surface was sensitive to thermal annealing. A remarkable change in surface OH coverage was observed for the film surface annealed at high temperature. This behavior was framed by a structural change from amorphous to crystalline state, which regulated DNA immobilization. These results indicate that the OH affinity on aIGZO films is dependent on structural properties such as defects. This study suggests that an amorphous structure is critical for obtaining a high OH surface coverage governing DNA immobilization, and is hence more suitable for biosensing.


An experimental model for the endoscopic correction of subglottic stenosis with clinical applications.
The use of long-term endotracheal intubation in the treatment of respiratory distress syndrome in the newborn has seen an increase in the number of cases of acquired subglottic stenosis. Multiple methods of correction have been advocated in conjunction with the use of antibiotics, corticosteroids, and indwelling stents. An animal experiment utilizing 64 dogs was undertaken in an effort to devise an endoscopic procedure using the CO2 laser which might be successfully employed in the human patient. An attempt was also made to study the efficacy of antibiotics, corticosteroids, soft stents and rigid stents. Animals were divided into multiple groups, and their larynges were studied grossly and histologically some weeks after therapy was completed. Analysis of the results was undertaken, and the method with the best outcome was then employed in the human portion of the study. Twenty-four human patients, 12 with severe stenosis and 12 with partial stenosis were evaluated, and their outcome is reported.


Effects of nitric oxide synthase inhibitors on duodenal alkaline secretion in anesthetized rats.
We examined the effects of NG-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on duodenal HCO3- secretion in anesthetized rats. L-NAME (1-5 mg/kg i.v.), given as a single injection, increased HCO3- secretion in a dose-dependent manner. This effect of L-NAME was mimicked by NG-monomethyl-L-arginine (50 mg/kg i.v.) and was significantly antagonized by the simultaneous administration of L-arginine (200 mg/kg i.v.) but not D-arginine. The increased HCO3- response to L-NAME was also significantly reduced in vagotomized animals. These findings suggest that the inhibition of NO biosynthesis leads to an increase of duodenal HCO3- secretion, partly mediated by the vagus nerves.


APOE epsilon4 genotype is associated with an earlier onset of chronic temporal lobe epilepsy.
The authors analyzed the association between APOE epsilon4 genotype and clinical and MRI findings in 43 refractory temporal lobe epilepsy patients. The distribution of the alleles were normal. Ten patients (23%) had an APOE epsilon 4 allele and had an earlier onset of habitual seizures (with epsilon4 5 +/- 5 years; without epsilon4 15 +/- 10 years). Quantitative MRI findings were not influenced by the APOE epsilon4 genotype. APOE epsilon4 may shorten the latency between an initial injury and seizure onset.


Initial management decisions after a new consultation for low back pain: implications of the usage of physical therapy for subsequent health care costs and utilization.
To describe the utilization of physical therapy following a new primary care consultation for low back pain (LBP) and to examine the relations between physical therapy utilization and other variables with health care utilization and costs in the year after consultation. Retrospective cohort obtained from electronic medical records and insurance claims data. Single health care delivery system. Individuals (N=2184) older than 18 years with a new consultation for LBP from 2004 to 2008. Patients were categorized as receiving initial physical therapy management if care occurred within 14 days after consultation. Total health care costs for all LBP-related care received in the year after consultation were calculated from claims data. Predictors of utilization of emergency care, advanced imaging, epidural injections, specialist visits, and surgery were identified using multivariate logistic regression. The generalized linear model was used to compare LBP-related costs based on physical therapy utilization and identify other cost determinants. Initial physical therapy was received by 286 of the 2184 patients (13.1%), and was not a determinant of LBP-related health care costs or utilization of specific services in the year after consultation. Older age, mental health, or neck pain comorbidity and initial management with opioids were determinants of cost and several utilization outcomes. Initial physical therapy management was not associated with increased health care costs or utilization of specific services following a new primary care LBP consultation. Additional research is needed to examine the cost consequences of initial management decisions made following a new consultation for LBP.


Visual-motor contingency during symbol production contributes to short-term changes in the functional connectivity during symbol perception and long-term gains in symbol recognition.
Letter production relies on a tight coupling between motor movements and visual feedback-each stroke of the letter is visually experienced as it is produced. Experience with letter production leads to increases in functional connectivity, a measure of neural communication, among visual and motor brain systems and leads to gains in letter recognition in preliterate children. We hypothesized that the contingency between the motor and visual experiences of the written form during production would result in both effects. Twenty literate adults were trained on four sets of novel symbols over the course of one week. Each symbol set was trained through one of four training conditions: drawing with ink, drawing without ink, watching a handwritten symbol unfold as if being drawn, and watching a static handwritten symbol. Contingency of motor and visual experiences occurred in the drawing with ink condition. The motor and visual experiences were rendered non-contingent in each of the other three conditions by controlling for visual or motor experience. Participants were presented with the trained symbols during fMRI scanning at three time points: one pre-training, one post-training, and one after a week-long no-training delay. Recognition was tested after each training session and after the third scan. We found that the contingency between visual and motor experiences during production changed the pattern of functional connectivity among visual, motor, and auditory neural communities and resulted in better recognition performance at post-training than at pre-training. Recognition gains were maintained after the no-training delay, but the functional connections observed immediately after training returned to their pre-training baselines. Our results suggest that behaviors that couple sensory and motor systems result in temporary changes in neural communication during perception that may not directly support changes in recognition.


Disease Stage and Mode of Therapy Are Important Determinants of Treatment Outcomes for Medication-Related Osteonecrosis of the Jaw.
The treatment of patients with medication-related osteonecrosis of the jaw (MRONJ) is challenging. The purpose of the present study was to estimate the frequency and identify the factors associated with clinical improvement during treatment. We designed and implemented a retrospective cohort study and enrolled a sample of subjects diagnosed with MRONJ between 2004 and 2015. The primary predictor variables were a set of heterogeneous variables grouped into the following categories: demographic (age and gender) and clinical (location of necrosis, therapy duration, medication type, disease stage, and treatment type). The primary outcome variable was the treatment outcome, defined as stable or worse and improved or healed. The descriptive, bivariate, and multiple logistic statistics were computed, and statistical significance was defined as P < .05. The sample included 337 subjects with a mean age of 68.9 years. Of the 337 subjects, 256 were women (76%). A total of 143 patients (42.2%) experienced spontaneous necrosis. Twenty-four (7.1%) had had exposure to targeted antiangiogenic agents. Those with stage 1 or 2 disease were more likely to have better outcomes than those with stage 3 disease (stage 1, adjusted odds ratio [OR] 3.4, P = .005; stage 2, adjusted OR 2.2, P = .03). Treatment type was a significant variable. Subjects undergoing surgery were 28 times more likely to have a positive outcome than those receiving nonoperative therapy (adjusted OR 28.7, P < .0001). Subjects with MRONJ who presented with less severe disease or who underwent operative treatment were most likely to have improvement or complete healing of their MRONJ-related lesions.


An abundance of nodulation factors.
In this issue of Chemistry & Biology, Morón et al. [1] report that Rhizobium tropici CIAT899 produces different Nod factors in response to flavonoid induction under differing environmental conditions. This unanticipated environmental dependence has implications for altering or potentially improving the host-bacteria interaction in bean nodulation.


Experimental determination and prediction of bilitranslocase transport activity.
The transport activity of a membrane protein, bilitranslocase (T.C. # 2.A.65.1.1), which acts as a transporter of bilirubin from blood to liver cells, was experimentally determined for a large set of various endogenous compounds, drugs, purine and pyrimidine derivatives. On these grounds, the structure-activity models were developed following the OECD principles of QSAR models and their predictive ability for new chemicals was evaluated. The applicability domain of the models was estimated by Euclidean distances criteria according to the applied modeling method. The selection of the most influential structural variables was an important stage in the adopted modeling methodology. The interpretation of selected variables was performed in order to get an insight into the mechanism of transport through the cell membrane via bilitranslocase. Validation of the optimized models was performed by a previously determined validation set. The classification model was build to separate active from inactive compounds. The resulting accuracy, sensitivity, and specificity were 0.73, 0.89, and 0.64, respectively. Only active compounds were used to develop a predictive model for bilitranslocase inhibition constants. The model showed good predictive ability; Root Mean Squared error of the validation set, RMS(V)=0.29 log units.


Monoaminergic regulation of hemopoiesis under extreme conditions.
The role of the adrenergic, dopaminergic, and serotoninergic systems in the regulation of hemopoiesis was evaluated on various models of pathological processes (restraint stress, experimental neurosis, and cytostatic treatment). The proliferation, differentiation, and maturation of polypotent, multipotent, partially determined, and oligopotent hemopoietic precursors and functional activity of microenvironmental cells (stromal cells, macrophages, and Thy1,2(+) cells) were shown to be under the control of a complex system of monoaminergic regulation. Central monoamines have a direct or indirect (mediated by microenvironmental cells) regulatory effect on hemopoietic precursors of various classes, which is realized via specific receptors. The system of colony-stimulating factors is characterized by selective sensitivity to catecholamines. It should be emphasized that the effects of erythropoietin are mainly associated with serotonin. Irrespective of experimental conditions (hyperplasia of hemopoiesis, myelosuppression, and dysregulation of precursor cell proliferation and differentiation), the erythroid hemopoietic stem is more sensitive to serotoninergic influences. Granulocytopoiesis was revealed to be more sensitive to central catecholamines.


Perioperative management for people with kidney failure receiving dialysis: A scoping review.
People with kidney failure receiving dialysis (CKD-G5D) are more likely to undergo surgery and experience poorer postoperative outcomes than those without kidney failure. In this scoping review, we aimed to systematically identify and summarize perioperative strategies, protocols, pathways, and interventions that have been studied or implemented for people with CKD-G5D. We searched MEDLINE, EMBASE, CINAHL Plus, Cochrane Database of Systematic Reviews, and Cochrane Controlled Trials registry (inception to February 2020), in addition to an extensive grey literature search, for sources that reported on a perioperative strategy to guide management for people with CKD-G5D. We summarized the overall study characteristics and perioperative management strategies and identified evidence gaps based on surgery type and perioperative domain. Publication trends over time were assessed, stratified by surgery type and study design. We included 183 studies; the most common study design was a randomized controlled trial (27%), with 67% of publications focused on either kidney transplantation or dialysis vascular access. Transplant-related studies often focused on fluid and volume management strategies and risk stratification, whereas dialysis vascular access studies focused most often on imaging. The number of publications increased over time, across all surgery types, though driven by non-randomized study designs. Despite many current gaps in perioperative research for patients with CKD-G5D, evidence generation supporting perioperative management is increasing, with recent growth driven primarily by non-randomized studies. Our review may inform organization of evidence-based strategies into perioperative care pathways where evidence is available while also highlighting gaps that future perioperative research can address.


Kinetic studies of the phenol sulphate-phenol sulphotransferase of Aspergillus oryzae.
Arylsulphatase II of Aspergillus oryzae exhibits both hydrolytic and sulphotransferase activities. The kinetic data suggest the formation of an intermediate covalent enzyme-sulphate complex with transfer of sulphate from donor to acceptor proceeding via a Ping Pong mechanism. The unusual kinetic behaviour when 2-hydroxy-5-nitrophenyl sulphate is the substrate is also consistent with this mechanism.


Voice and Speech Changes in Transmasculine Individuals Following Circumlaryngeal Massage and Laryngeal Reposturing.
The purpose of this study was to measure the short-term effects of circumlaryngeal massage and laryngeal reposturing on acoustic and perceptual characteristics of voice in transmasculine individuals. Fifteen transmasculine individuals underwent one session of sequential circumlaryngeal massage and laryngeal reposturing with a speech-language pathologist. Voice recordings were collected at three time points-baseline, postmassage, and postreposturing. Fundamental frequency (f o), formant frequencies, and relative fundamental frequency (RFF; an acoustic correlate of laryngeal tension) were measured. Estimates of vocal tract length (VTL) were derived from formant frequencies. Twelve listeners rated the perceived masculinity of participants' voices at each time point. Repeated-measures analyses of variance measured the effect of time point on f o, estimated VTL, RFF, and perceived voice masculinity. Significant effects were evaluated with post hoc Tukey's tests. Between baseline and end of the session, f o decreased, VTL increased, and participant voices were perceived as more masculine, all with statistically significant differences. RFF did not differ significantly at any time point. Outcomes were highly variable at the individual level. Circumlaryngeal massage and laryngeal reposturing have short-term effects on select acoustic (f o, estimated VTL) and perceptual characteristics (listener-assigned voice masculinity) of voice in transmasculine individuals. https://doi.org/10.23641/asha.19529299.


Combining machine learning and data assimilation to forecast dynamical systems from noisy partial observations.
We present a supervised learning method to learn the propagator map of a dynamical system from partial and noisy observations. In our computationally cheap and easy-to-implement framework, a neural network consisting of random feature maps is trained sequentially by incoming observations within a data assimilation procedure. By employing Takens's embedding theorem, the network is trained on delay coordinates. We show that the combination of random feature maps and data assimilation, called RAFDA, outperforms standard random feature maps for which the dynamics is learned using batch data.


Brain Stem and Audio-Vestibular Regulation.
The central pathologies present with perverted auditory perception and compromised postural control. Considering the existing controversy this study involves assessments of 100 cases of post fossa tumefactions in which a detailed clinical and neuro-otological (pure tone audiometry, electronystagmography, brainstem evoked response audiometry) profile is compared with their imaging patterns. The CP angle schwannomas (N = 26) presented with abnormal speech tests (N = 18), abnormal auditory adaptation (N = 7) and ABR with pathologically increased latency of wave V (N = 32), poor formation of wave I (N = 31) along with abnormal inter-wave interval (N = 32). In lesions (N = 32) compressing deeper nuclei, vermis and axial parts of brain stem, a gross truncal ataxia, incoordination, nystagmus, speech defects, subtotal deafness and bilateral ABR abnormalities were observed. The abnormal optomotor activities were seen as saccadic (N = 44) and deformed slow pursuit eye movements (N = 20). Inability to sustain holding function resulted in gaze nystagmus (N = 71), and poor timing manifested as fixation overshoots (N = 42). The midline cerebellar and upper brain stem lesions revealed bilateral OKN abnormalities whereas paramedian pathology showed only ipsilateral distortion. Caloric tests revealed culmination frequency as the most sensitive parameter for assessment of the hypo-reflexia in diffuse cerebellopathies while slow phase velocity in cases of posterior fossa lesion. The caloric hypo-activity appears to be of a better localizing value than the directional preponderance. The slow pursuit tracking revealed Type III curve perhaps due to defective regulation of slow movements in partially intact cerebellum (N = 15), while gross cerebellar dysfunctioning resulted into Type IV curve (N = 5).


Relationship Among Body Fat Percentage, Body Mass Index, and All-Cause Mortality: A Cohort Study.
Prior mortality studies have concluded that elevated body mass index (BMI) may improve survival. These studies were limited because they did not measure adiposity directly. To examine associations of BMI and body fat percentage (separately and together) with mortality. Observational study. Manitoba, Canada. Adults aged 40 years or older referred for bone mineral density (BMD) testing. Participants had dual-energy x-ray absorptiometry (DXA), entered a clinical BMD registry, and were followed using linked administrative databases. Adjusted, sex-stratified Cox models were constructed. Body mass index and DXA-derived body fat percentage were divided into quintiles, with quintile 1 as the lowest, quintile 5 as the highest, and quintile 3 as the reference. The final cohort included 49 476 women (mean age, 63.5 years; mean BMI, 27.0 kg/m2; mean body fat, 32.1%) and 4944 men (mean age, 65.5 years; mean BMI, 27.4 kg/m2; mean body fat, 29.5%). Death occurred in 4965 women over a median of 6.7 years and 984 men over a median of 4.5 years. In fully adjusted mortality models containing both BMI and body fat percentage, low BMI (hazard ratio [HR], 1.44 [95% CI, 1.30 to 1.59] for quintile 1 and 1.12 [CI, 1.02 to 1.23] for quintile 2) and high body fat percentage (HR, 1.19 [CI, 1.08 to 1.32] for quintile 5) were associated with higher mortality in women. In men, low BMI (HR, 1.45 [CI, 1.17 to 1.79] for quintile 1) and high body fat percentage (HR, 1.59 [CI, 1.28 to 1.96] for quintile 5) were associated with increased mortality. All participants were referred for BMD testing, which may limit generalizability. Serial measures of BMD and weight were not used. Some measures, such as physical activity and smoking, were unavailable. Low BMI and high body fat percentage are independently associated with increased mortality. These findings may help explain the counterintuitive relationship between BMI and mortality. None.


Challenges for ATM management in times of market variability caused by the COVID-19 pandemic crisi.
One of the most important issues related to the management of an Automatic Teller Machine (ATM) network is the correct forecasting of the demand for cash. Typically, this demand, expressed as the value or number of ATM withdrawals, has some regularities that can be used to evaluate future values for these variables. However, forecasting becomes a challenge when a crisis occurs that could affect the behavior of ATM users. In this context, it is important to identify how the development of the crisis and the various information concerning it may affect people's attitudes to cash. This study aims to examine the impact of the COVID-19 pandemic on the behavior of ATM customers. On the basis of daily data from 81 ATMs, we analyze the changes in the value and number of withdrawals just before and during the COVID-19 pandemic in Poland. An event study analysis allows us to determine precisely the moments in which changes in user behavior took place. This means that it is also possible to examine the reaction of ATM users to the announcement and implementation of the pandemic restrictions, and to determine the factors that had an impact on the change in people's attitude to cash. Such a study is also important from a sociological point of view, as it enables one to understand people's reactions to the emerging crisis. Hence, its results may be useful not only for managers of ATM networks, but also for various authorities and policy makers.


The chemotactic peptide receptor. A model for future understanding of chemotactic disorders.
Chemotaxis by human phagocytes enables these cells to find sites of injury or inflammation in the host. This function is a complex orchestration of biochemical and morphologic events that begins with the occupancy of specific surface receptors for chemotactic agents. The response is propagated and amplified by a biochemical cascade of transduction reactions. This cascade is mediated by receptor interactions with guanyl nucleotide binding proteins, subsequent activation of phospholipase C, and a resulting increase in phospholipid turnover. These events are spatially and temporarily integrated as elevations in the concentrations of intracellular Ca++ and diacylglycerol combine to activate protein kinase C. At the macromolecular and subcellular level, integration of these functions with as yet undiscovered pathways results in stimulation of actin polymerization, shape change, degranulation, and membrane flow. Final integration of these events results in the morphologic process of directed migration of the cell along concentration gradients of chemotaxins. During this process, chemotactic receptors are continuously regulated and feed back information to the response system that adjusts the biochemistry and morphology accordingly. This article has briefly considered some of the relationships between these transduction events and the control of a specific chemotactic receptor system employing the N-formylated chemotactic peptides. It is hoped that knowledge of this regulation will aid the physician in understanding the origin of chemotactic disorders derived from defects in chemotactic receptor systems of the phagocytic cells.


A C-type lectin induces NLRP3 inflammasome activation via TLR4 interaction in human peripheral blood mononuclear cells.
Lectins are a large group of proteins found in many snake venoms. BjcuL is a C-type lectin from Bothrops jararacussu snake venom that does not present cytotoxicity action on human peripheral blood mononuclear cells (PBMCs) at concentrations of 5 and 10 μg/mL. BjcuL demonstrates an immunomodulatory role in PBMCs with the production of pro- and anti-inflammatory cytokines (IL-2, IL-10, IFN-γ, IL-6, TNF-α, and IL-17) in addition to stimulate T cells to produce reactive oxygen species (ROS) that could play a role in the acute inflammatory reaction observed in the victims. Inflammasomes are an essential arm in cells of innate immunity to detect and sense a range of endogenous or exogenous, sterile, or infectious stimuli to elicit cellular responses and effector mechanisms. NLRP3 inflammasome is a significant target for this study, because the lectin is responsible for leukocyte activation stimulating the release of inflammatory mediators, which results in dynamic cellular responses to remove the detrimental process to the body in snakebites. Thus, this study aimed to investigate how isolated BjcuL from B. jararacussu venom affects NLRP3 inflammasome activation on PBMCs. For this, the cells were isolated by density gradient and incubated with BjcuL at different periods and concentrations for the evaluation of the activation of the NLRP3 inflammasome through gene and protein expressions of ASC, CASPASE-1, and NLRP3 by RT-qPCR, Western blot, and immunofluorescence, as well as the participation of Toll-like receptor 4 (TLR4) and ROS in the IL-1β production, a product resultant of the NLRP3 inflammasome activation. Herein, BjcuL interacts with TLR4 as demonstrated by in vitro and in silico studies and induces cytokines release via NF-κB signaling. By genic and protein expression assays, BjcuL activates NLRP3 inflammasome, and the pharmacological modulation with LPS-RS, an antagonist of TLR4; LPS-SM, an agonist of TLR4; MCC950, a specific NLRP3 inhibitor, and rotenone, an inhibitor of mitochondrial ROS, confirmed the participation of TLR4 and ROS in the NLRP3 inflammasome activation and IL-1β liberation. The effects of BjcuL on the regulation and activation of the NLRP3 inflammasome complex via TLR4 activation with ROS participation may be determinant for the development of the inflammatory local effects seen in snakebite victims. In addition, in silico together with in vitro studies provide information that may be useful in the rational design of TLR agonists as well as new adjuvants for immunomodulatory therapy.


Methylation of estradiol-17 beta by a partially purified preparation of bovine pineal hydroxy-indole-O-methyltransferase.
A partially purified preparation of hydroxy-indole-O-methyltransferase (HIOMT) from bovine pineal was shown to O-methylate estradiol-17beta (E2). The HIOMT preparation was incubated with E2 and [3H]-S-adenosylmethionine (SAM). The [3H]-3 methyl-ether or estradiol [MeO-E2] produced was identified by thin layer chromatography (TLC) and crystallization to constant 3H/14C ratio in the presence of [14C]-MeO-E2 and unlabeled MeO-E2 standards. The kinetics of the enzyme reaction for melatonin formation from N-acetyl-serotonin (NAS) and for MeO-E2 were compared.


Survival and behavior patterns associated with hypoxia at different life stages of the pen shell Atrina cf. japonica.
Pen shell (Atrina cf. japonica) resources have been devastated in Ariake Bay, Japan, and to facilitate the recovery of this species, there is an urgent need to fully understand the factors contributing to its high levels of mortality. Pen shells living in natural waters grow through successive life stages, and environmental factors may affect these bivalves differently at different stages. Accordingly, to elucidate the causes of mortality in natural waters, it is necessary to gain an understanding of the quantitative effects of environmental factors on bivalves at each life stage. In this study, we sought to determine the differential effects of hypoxic conditions on 1-year-old (average shell length: 93.9 mm) and 2-year-old (146.5 mm) pen shells bred under artificial conditions. We exposed shells of each age group to six different dissolved oxygen (DO) concentrations for 96 h and monitored their behavior and survival rate. Based on the survival status, we estimated the lethal DO concentrations that induced 50%, 95%, and 5% mortality (LC50, LC95, and LC5, respectively) at each age. We found that for 1-year-old shells, the LC50 values at 48, 72, and 96 h were 0.51, 0.74, and 0.84 mg/L, respectively, whereas the corresponding values for 2-year-old shells were 0.74, 1.27, and 1.80 mg/L. Furthermore, we found that for 1- and 2-year-old shells, the estimated ranges from LC95 to LC5 at 48, 72, and 96 h were 0.39-0.68, 0.62-0.88, and 0.64-1.12 mg/L, and 0.31-1.75, 0.77-2.09, and 1.29-2.53 mg/L, respectively. Under low DO concentrations (0.47 to 1.93 mg/L and 0.49 to 3.30 mg/L for 1- and 2-year-old shells, respectively), we observed pen shells with more than half of their shell length protruding above the substrate. In addition to age and body size, the 1- and 2-year-old pen shells used in the present study also differed with respect to reproductive status, with 7.6% of 1-year-old and 96.7% of 2-year-old shells considered to be fully ripe. Collectively, our observations indicate that 2-year-old pen shells are less tolerant to hypoxic conditions than are 1-year-old pen shells, and we suspect that the differences in hypoxic tolerance could be attributable to differences in the physiological status of the pen shells during gonadal development. We believe the findings of this study will make an important contribution to enhancing our understanding of the effects of hypoxia on the viability of A. cf. japonica in natural waters.


Exacerbation of Atopic Dermatitis Associated with Ustekinumab Treatment in Crohn's Disease.
Ustekinumab inhibits interleukins 12 and 23 and modulates the T helper cell-mediated immune response of Crohn's disease. However, ustekinumab may also exacerbate atopic disease by increasing the T helper 2 cell-mediated pathway. We present the first known case of exacerbation of atopic dermatitis in a patient with Crohn's disease receiving ustekinumab. Additional associations in dose frequency, peripheral eosinophilia, and elevated serum IgE were observed. However, while novel in Crohn's disease, exacerbation of atopy after ustekinumab infusion has been observed in patients with psoriasis and psoriatic arthritis.


Decreased thrombomodulin mRNA expression on peripheral monocytes in disseminated intravascular coagulation patients relates to poor outcomes: the ex vivo effects of lipopolysaccharide and thrombin on monocyte thrombomodulin and CD14 mRNA.
Monocytes express substantial amounts of thrombomodulin, which is consumed throughout ongoing thrombin generation. The modulation of thrombomodulin may aggravate intravascular fibrin deposition and the clinical course of disseminated intravascular coagulation (DIC). Although thrombomodulin restoration has received considerable attention, no reports have been published on the in vivo expression status of thrombomodulin. CD14 expression on monocytes is important for regulation of the inflammatory response. We used an ex vivo stimulation study to evaluate the association of the levels of monocyte-expressed thrombomodulin and CD14 messenger RNA (mRNA) with the severity and prognosis of disseminated intravascular coagulation. A total of 78 patients with suspected DIC were enrolled. Thrombomodulin and CD14 mRNA levels were measured in peripheral blood by real-time quantitative reverse-transcription polymerase chain reaction. Thrombomodulin and CD14 mRNA were also assessed in ex vivo cultures of peripheral whole blood that were stimulated by lipopolysaccharide or thrombin. The levels of monocyte-expressed thrombomodulin mRNA were significantly lower in the non-survivors than in the survivors. A low level of monocyte-expressed thrombomodulin mRNA was a significant prognostic marker, but CD14 did not possess prognostic power. Monocyte-expressed CD14 mRNA correlated significantly with the severity of DIC in survivors. In addition, stimulation of ex vivo cultures of whole blood demonstrated that thrombin upregulates both thrombomodulin and CD14 mRNA, and lipopolysaccharide downregulates thrombomodulin mRNA. The downregulation of thrombomodulin on monocytes reflects the decompensated status of physiological defenses against hypercoagulopathy and represents the poor prognosis in DIC. The expression levels of thrombomodulin on monocytes may be a useful marker to screen for candidates eligible for recombinant thrombomodulin therapy in future.


Free transverse colon transplantation for functional reconstruction of intra-oral lining: a clinical and histologic study.
A variety of free-tissue transplantations are available for oropharyngeal (lining) reconstruction. The most commonly used flap, the radial forearm flap, is relatively thin, adaptable, and reliable but does not provide lubrication. In this study, the potential of the transverse colon to provide a lubricating tissue for replacement of oral lining was investigated. Eleven patients requiring replacement of oral lining received transverse colon flap transplantation between November of 1993 and December of 1995. There was one complete flap loss and one partial loss. Flap size used for reconstruction averaged 40.4 cm2, and average vessel length and diameter were 7 cm and 2.0 mm, respectively. In a follow-up period from 15 to 48 months, all colon flaps proved to be durable with continuous lubrication function. Histologic assessment of the transplanted colon flaps at various postoperative times showed an adequate amount of mucus-secreting goblet cells even after irradiation. There was no donor-site morbidity. The main disadvantage seemed a tendency to transplant too much tissue, which resulted in formation of redundant pockets affecting food handling. Thus, 8 out of 10 patients with flap survival required one to three debulking procedures. Given an accurate estimation of the area of mucosa defect and adequate trimming of the colon flaps, the transverse colon flap offers a good alternative for reconstruction of the oral lining, especially when lubrication is desirable in cases with large defects and preoperative or postoperative irradiation, or in case a radial forearm flap is not available.


Calculated Decisions: Pediatric National Institutes of Health Stroke Scale (PedNIHSS)
The PedNIHSS quantifies stroke severity using a child-specific version of the National Institutes of Health Stroke Score.


Synthesis of 5-(arylmethylideneamino)-4-(1H-benzo[d]imidazol-1-yl)pyrimidine hybrids: synthetic sequence and the molecular and supramolecular structures of two intermediates and three final products.
A concise and versatile synthesis of 5-(arylmethylideneamino)-4-(1H-benzo[d]imidazol-1-yl)pyrimidines has been developed, starting from 4-(1H-benzo[d]imidazol-1-yl)pyrimidines, and we report here the synthesis and spectroscopic and structural characterization of three such products, along with those of two intermediates in the reaction pathway. The intermediates 4-[2-(4-chlorophenyl)-1H-benzo[d]imidazol-1-yl]-6-methoxypyrimidine-2,5-diamine, (II), and 4-[2-(4-bromophenyl)-1H-benzo[d]imidazol-1-yl]-6-methoxypyrimidine-2,5-diamine, (III), crystallize as the isostructural monohydrates C18H15ClN5O·H2O and C18H15BrN5O·H2O, respectively, in which the components are linked into complex sheets by O-H...N and N-H...O hydrogen bonds. In the product (E)-4-methoxy-5-[(4-nitrobenzylidene)amino]-6-[2-(4-nitrophenyl)-1H-benzo[d]imidazol-1-yl]pyrimidin-2-amine, which crystallizes as a 1:1 solvate with dimethyl sulfoxide, C25H18N8O5·C2H6OS, (IV), inversion-related pairs of the pyrimidine component are linked by N-H...N hydrogen bonds to form cyclic centrosymmetric R22(8) dimers to which pairs of solvent molecules are linked by N-H...O hydrogen bonds. (E)-4-Methoxy-5-[(4-methylbenzylidene)amino]-6-[2-(4-methylphenyl)-1H-benzo[d]imidazol-1-yl]pyrimidin-2-amine, C27H24N6O, (V), crystallizes with Z' = 2 and the molecules are linked into a three-dimensional framework structure by a combination of N-H...N, C-H...N and C-H...π(arene) hydrogen bonds. The analogous product (E)-4-methoxy-5-[(4-chlorobenzylidene)amino]-6-[2-(4-methylphenyl)-1H-benzo[d]imidazol-1-yl]pyrimidin-2-amine, C26H21ClN6O, (VI), crystallizes from dimethyl sulfoxide in two forms: one, denoted (VIa), is isostructural with (V), and the other, denoted (VIb), crystallizes with Z' = 1, but as an unknown solvate in which the pyrimidine molecules are linked by N-H...N hydrogen bonds to form a ribbon containing two types of centrosymmetric ring.


Acute macular neuroretinopathy.
Acute macular neuroretinopathy is a rare, unilateral, or bilateral condition of abrupt onset causing parafoveal scotomata and occasionally reduced visual acuity. The features are described in five new cases, and the evolution of the lesions described over a period of 9 months to 9 years. One patient was studied by fine matrix perimetry, which indicated a generalized elevation of thresholds at the macula early in the disorder, together with parafoveal scotomata. The thresholds improved over several months, and the scotomata became less dense. In another case, the scotomata were still present at 9 years, although at this time they were less dense. The condition appears to mainly affect young women, and in this group there is a high incidence of a recent immunologic disturbance suggesting an immune-based etiology.


Advanced cardiac life support antiarrhythmic drugs.
As exemplified in this discussion of ACLS antiarrhythmic drugs, the evidence-based evaluation process has created a high standard for the acceptance and ranking of therapies for cardiac arrest. This process also has identified critical areas needing further investigation, fostered a healthy sense of discomfort with the adequacy of our present interventions for cardiac arrest, and hopefully will continue to spur the science while sifting the dogma out of CPR.


Increasing incidence of primary central nervous system lymphoma but no improvement in survival in Sweden 2000-2013.
This study aims to characterize the epidemiology of immunocompetent Primary central nervous system lymphoma (PCNSL) diagnosed 2000-2013 in Sweden. Cases were identified in the population-based Swedish Lymphoma Register. Incidence per 100 000 person-years and 95% confidence intervals (CI) were calculated, and PCNSL-specific survival was estimated using relative survival. Tests for temporal trends were performed using Poisson regression. Population incidence of all brain tumors was retrieved for comparison. With 359 identified PCNSL cases (median age 66 years), overall incidence was 0.26 (95% CI: 0.24-0.29) and the average annual increase 4% (P = .002). The increasing trend was primarily observed among elderly individuals (70+ years). Similarly, an increase in incidence of all brain tumors was noted only among the elderly. There was no significant improvement in relative survival across the study period although, among fit patients (with Eastern Cooperative Oncology Group, EGOC 0), survival plateaued 6 years after diagnosis. The increasing PCNSL incidence in the elderly was consistent with an increasing incidence of brain tumors of any type and may in part be attributable to improved diagnostics and reporting in this group. New treatment options have not yet translated into general survival improvements in a population-based setting, although the presence of long-term survivors among fit patients is encouraging.


Distribution of the Lewis blood-group system in 331 members of JNA.
The aim of this paper is to describe the phenotype distribution in Yugoslavians, members of JNA. The results are systematised into two groups: a. phenotype distribution of the blood-group system in tested persons; b. the relationship of phenotypes and ABO blood-group system.


Assessing the effectiveness and cost-effectiveness of prophylaxis against bleeding in patients with severe haemophilia and severe von Willebrand's disease.
To assess the effectiveness and cost-effectiveness of prophylaxis with clotting factor against bleeding in patients with severe haemophilia and von Willebrand's disease (vWD). Treatment details that related to 179 patients with severe (< 1 u dL-1) haemophilia A, B and vWD were retrospectively examined for the period 1980-95. A subgroup of these patients, 25 adults and 22 children, who had previously received treatment on demand and who had switched to treating with prophylaxis, were studied in order to examine the effects of the change. The cost-effectiveness of prophylaxis was also analysed using another subgroup of 38 patients and by adjusting their treatment details by age and method of treatment. Data were obtained on patients who were solely registered at the Royal Free Hospital Haemophilia Centre (RFHHC), London, UK. Bleeds. The median annual number of bleeds decreased from 23.5 (range 1-107) in 1980, to 14 (range 0-45) in 1995 (P < 0.0001). Switching from treating on demand to prophylaxis reduced bleeding frequency in 41 out of 47 patients within the period of 1 year. At the base scenario, switching to prophylaxis cost an additional pound547 per averted bleed; however, this figure was highly sensitive to certain variables. Prophylaxis can reduce bleeding frequency but requires more clotting factor than treatment on demand. More detailed proof of cost-effectiveness is likely to require the use of modelling techniques.


Targeted and controlled release delivery of daunorubicin to T-cell acute lymphoblastic leukemia by aptamer-modified gold nanoparticles.
Clinical administration of daunorubicin (Dau) in treatment of leukemia has been limited by its cardiotoxicity. Targeted delivery of chemotherapy drugs could reduce their side effects and increase the therapeutic efficacy of these drugs. Biocompatibility and large surface area of gold nanoparticles (AuNPs) make these nanoparticles great candidates for biomedical applications. In this study sgc8c aptamer (Apt)-Dau-AuNPs complex was designed and evaluated for treatment of Molt-4 cells (human acute lymphoblastic leukemia T-cell, target). Apt-Dau-AuNPs complex formation was analyzed by fluorometric analysis and gel retardation assay. Dau release profiles from the complex were evaluated in pHs 5.5 and 7.4. For cytotoxic studies (MTT assay) U266 (B lymphocyte human myeloma, nontarget) and Molt-4 cells (target) were treated with Dau Apt-Dau conjugate and Apt-Dau-AuNPs complex. Internalization was monitored by flow cytometry and confocal imaging. 12 μM Dau was efficiently loaded onto 1 mL of Apt-modified AuNPs. Dau was released from the complex in a pH-dependent manner (higher rate of release at pH 5.5). The results of flow cytometry analysis and confocal imaging showed that the complex was effectively internalized into Molt-4 cells, but not into U266 cells. The results of MTT assay also confirmed the internalization data. Apt-Dau-AuNPs complex was less cytotoxic in U266 cells compared to Dau alone and even Apt-Dau conjugate. The complex was more cytotoxic in target cells in comparison with Dau alone and even Apt-Dau conjugate. In conclusion, Apt-Dau-AuNPs complex was able to selectively target Molt-4 cells. Another advantage of this system was pH-dependent release of drug from the complex. Furthermore, this complex has characteristics which make it ideal for clinical use.


Moniliformin production by fusarium species.
A total of 132 Fusarium isolates belonging to 19 species sensu Nelson et al (1983) originating from Poland, Italy, and international cultures collections were examined for their ability to produce mycotoxin moniliformin.Moniliformin was produced by the following isolates:-F acuminatum Ell & Ev: 2 out of 2,130 - 2670mg/kg-F avenaceum (Fr) Sacc 18 out of 18,70 - 2670mg/kg-F anthophilum (A Braun) Wollenw. 1 out of 3, 200mg/kg-F dlamini Marasas et al: 2 out of 3,130 - 470mg/kg-F oxysporum Schlecht emend Snyd Hans: 4 out of 9,130 - 270 mg/kg-F proliferatum (Matsushima) Nirenberg: 3 out of 7,130 - 400 mg/kg-F solani (Mart) Appel & Wollenw: 1 out of 14,670 mg/kg-F subglutinans (Wollenw & Reinking) Nelson et al: 8 out of 20,70 - 1660 mg/kg-F tricinctum (Corda) Sacc: 2 out of 9,130 - 1330 mg/kgIn cultures ofF beomiforme Nelson, Toussoun & Burgess,F chlamydosporum Wollenw & Reinking,F compactum I Wollenw/ Gordon, F equiseti /Corda/Sacc,F poae I Peck / Wollenw,F moniliforme Sheldon,F napiforme Marasas, Nelson & Rabie,F nygamai Burgess & Timbold,F poly phialidicum Marasas et al,F sporotrichioides Sherb moniliformin was not detected.The highest amounts of moniliformin byF avenaceum using solid substrate were formed on rice and lower on oats kernels.


An Age and Activity Algorithm for Treatment of Type II SLAP Tears.
Type II SLAP tears predominantly occur in males between their third and fifth decades of life. The mechanism of injury is often repeated overheard activity but can also occur due to direct compression loads and traction injuries. The treatment options have changed over the years and include non-operative therapy, direct labral-biceps complex repair, and labral debridement with biceps tenodesis or tenotomy. To review the existing literature on the management of Type II SLAP tears and provide clinical recommendations based on patient age and activity level. A review of the existing literature through October 2017 investigating the management of Type II SLAP tears was performed. Emphasis was placed on distinguishing the outcomes based on age and activity level to provide an appropriate treatment algorithm. Patients with Type II SLAP tears should first be trialed with non-operative management and many patients will have a successful result with ability to return to their respective sports or activities. Surgical management should be considered if non-operative management does not provide symptomatic relief. Young, athletic, or high-demand patients should be treated with a SLAP repair while biceps tenodesis should be considered for older or worker's compensation patients. Patients undergoing revision surgery for a failed SLAP repair should be managed with biceps tenodesis. Type II SLAP tears remain a difficult pathology to manage clinically, but the treatment indications are narrowing. The age and activity algorithm described in this review provides an effective method of managing this complex clinical condition.


Ganglioside GM1/galectin-dependent growth regulation in human neuroblastoma cells: special properties of bivalent galectin-4 and significance of linker length for ligand selection.
Orchestrated upregulation of cell surface presentation of ganglioside GM1 and homodimeric galectin-1 is the molecular basis for growth regulation of human neuroblastoma (SK-N-MC) cells. Further study led to the discovery of competitive inhibition by galectin-3, prompting us to test tandem-repeat-type galectin-4 (two different lectin domains connected by a 42-amino-acid linker). This lectin bound to cells at comparably high affinity without involvement of the ganglioside, as disclosed by assays in the presence of cholera toxin B-subunit or galectin-1 and blocking glucosylceramide synthesis. Notably, when tested separately, binding of both lectin domains showed partial sensitivity to the bacterial agglutinin. Despite its ability for cross-linking surface association of galectin-4 did not affect proliferation, in contrast to homodimeric galectins. The truncation of linker length from 42 to 16 amino acids altered binding properties to let partial sensitivity to the bacterial lectin emerge. Cross-competition between parental and engineered proteins did not exceed 40%. No effect on cell growth was detected. This study reveals complete functional divergence between galectins differing in the spatial mode of lectin-site presentation and dependence of reactivity to distinct counter-receptor(s) on linker length. Due to the documented presence of galectin-4 in the nervous system and its affinity for sulfatide these in vitro results indicate the potential for a distinct functionality profile of this lectin in vivo, giving further research direction.


Occurrence and virulence properties of Vibrio and Salinivibrio isolates from tropical lagoons of the southern Caribbean Sea.
The Vibrionaceae are Gram-negative bacteria present in marine and estuarine environments worldwide, including several species known as important pathogens to humans and aquatic organisms. The aim of this research was to investigate the occurrence and virulence properties of Vibrio and Salinivibrio isolated from lagoons at Cuare Wildlife Refuge and Margarita Island in the southern Caribbean Sea. Water, plankton and oyster samples were collected during October 2011 and March 2012 and examined by specific PCR and culture methods. Vibrio genus DNA was detected in 95% of samples, while the intergenic spacer region (ISR) of Vibrio cholerae and the genes that code for the thermolabile direct haemolysin (tl) of Vibrio parahaemolyticus and the haemolysin/cytolysin (vvhA) of Vibrio vulnificus were absent or amplified in low proportions (23, 5, and 0%, respectively). Nine isolates from water and plankton were confirmed as Vibrio or Salinivibrio by phenotypic tests, 16S rRNA gene sequencing and phylogenetic analysis. All the isolates presented similar patterns of virulence factors, in which the genes ctxA (encoding for cholera toxin), tl and vvhA were lacking, whereas seven isolates displayed antibiotic resistance against ampicillin and cephalosporins. The 16S rRNA phylogenetic analysis showed the clustering of Vibrio isolates in three main clades: the plankton isolate from Cuare Wildlife Refuge formed a group with V. cholerae and Vibrio mimicus while the Margarita isolates clustered with sequences from the harveyi clade and Salinivibrio. This is the first time that Salinivibrio species are reported in tropical lagoons of the Caribbean Sea with antibiotic resistance.


[Osteosarcoma 1978 a turning point in prognosis through adjuvant chemotherapy following adequate surgery (author's transl)].
Results of surgery and chemotherapy in osteosarcoma are based on a retrospective investigation of 122 patients from 1930 till 1978 treated at the Orthopaedic Department of Vienna University and documented at the Viennese Bone Tumour Registry. Adequate surgery is considered to be the radical elimination of the tumour in an oncological sense, e.g. amputation or resection. Our own patients were examined in this light and different forms of chemotherapy are compared and their efficacy as adjuvant treatment is evaluated. The turning point in the prognosis of osteosarcoma came with the introduction of high-dose methotrexate therapy (HDMTX) in 1972 and which has been employed at the Orthopaedic Department of Vienna University since 1975. So far, HDMTX has been used in the management of 18 patients and the short-term results confirm the excellent results reported in the literature. The consequent change in policy with regard to the current surgical approach to osteosarcoma is discussed in detail.


Identification of ester glucuronide and sulfate conjugates of 5-hydroxy-6-methoxyindole-2-carboxylic acid and 6-hydroxy-5-methoxyindole-2-carboxylic acid in melanoma urine.
HPLC analysis of urine sample from a patient with wide-spread melanoma revealed the presence of unknown indolic compounds at extraordinarily high levels, detectable with electrochemical and/or fluorescent detectors. By enzymic and chemical hydrolyses, they were identified as ester glucuronide and sulfate conjugates of 5-hydroxy-6-methoxyindole-2-carboxylic acid and 6-hydroxy-5-methoxyindole-2-carboxylic acid. Urine samples from B16 melanoma-bearing mice contained the sulfate conjugates but not the ester glucuronide conjugates.


A Review of Recent Advances and Future Developments in Fetal Phonocardiography.
Fetal phonocardiography (fPCG) is receiving attention as it is a promising method for continuous fetal monitoring due to its non-invasive and passive nature. However, it suffers from the interference from various sources, overlapping the desired signal in the time and frequency domains. This paper introduces the state-of-the-art methods used for fPCG signal extraction and processing, as well as means of detection and classification of various features defining fetal health state. It also provides an extensive summary of remaining challenges, along with the practical insights and suggestions for the future research directions.


Global Gender Inequality, Older Women, and the Call for Change in the United States.
Gender inequality that persists through much of their lives, from birth through adulthood, impacts women and their quality of life in their later years. With some variation this holds true in every nation in the global community. In older adults, the most apparent indication of gender inequality-and a linchpin-is the disproportionate impoverishment of older women compared to older men. We take stock of global policy directions toward equality for girls and women, focusing specifically on derived avenues for furthering and protecting the economic well-being of older women in the United States, cognizant that these directions can rebound with implications for nations worldwide.


[Prone and supine position for percutaneous nephrolithotomy: is it necessary to change the operative technique?].
To assess the safety and effectiveness of percutaneous nephrolithotomy performed in the supine position. To investigate whether the change in operative technique, between prone and supine position, is easy. Thirty patients who underwent percutaneous nephrolithotomy, by one surgeon in one hospital, were studied retrospectively. The eight first cases were performed in prone position, and the following 22 patients were operated in supine position according to Valdivia's operative technique. Data were analyzed with t-test. We considered P<0.05 as significant. Surgical complication rate, transfusion rate and fever rate were the same for both groups. Success rate was 72% in supine position group and 63% in prone position group (P>0.05). These results were comparable with the data of the literature. Only operative time was shorter in supine position group with significant statistical difference (P=0.02). In our experience, percutaneous nephrolithotomy in the supine position was safe and efficient, and outcomes were similar to that in the prone position. Learning curve was easy and fast.


Attentional orienting induced by arrows and eye-gaze compared with an endogenous cue.
Exogenous orienting has been widely studied by using peripheral cues whereas endogenous orienting has been studied with directional central cues. However, recent evidence has shown that centrally presented eye-gaze and arrows may produce an automatic rather than voluntary orienting of attention. Therefore, the aim of the present study was to investigate the behavioural and electrophysiological (event-related potentials-ERP) correlates of the attentional shift induced by arrows and eye-gaze. In order to have a control condition, we compared arrows and eye-gaze with a purely endogenous cue, i.e., a texture arbitrarily coding one direction. We analyzed the ERP components (P1, N1, P2a, P2p, P3) elicited by the cue stimuli and the early lateralised attentional effect (early directing attention negativity-EDAN). In addition, in order to investigate the topography of the neural mechanisms underlying the cortical activity in each cueing condition, we applied a temporal segmentation procedure. The results showed that the three cueing conditions induced a different strength of activation within the same cortical network. Occipito-parietal regions were involved in the early processing of visual information, followed by an involvement of frontal areas, likely implicated in learning associations. These data confirm the assumption that, in contrast to purely endogenous cues, arrows and eye-gaze induce a very fast attentional shift. However, the similarity of the ERP components and of the topographical cortical maps among conditions suggest that this early orienting of attention is more likely related to an overlearned association mechanism rather than to a real exogenous attentional process.


The role of metal in liver alcohol dehydrogenase catalysis. Spectral and kinetic studies with cobalt-substituted enzyme.
The kinetic and spectral properties of native and totally cobalt-substituted liver alcohol dehydrogenase have been compared. Based on titrimetric determinations of enzyme active site concentration, the turnover number at pH 7.0 for cobalt enzyme was the same as for native enzyme. At pH 10, however, the turnover number was slower for cobalt-substituted enzyme, 3.14 s-1 as compared with 4.05 s-1 for native enzyme. A comparison between native and totally cobalt-substituted enzyme showed a blue-shifted enzyme-NADH double difference spectrum and a splitting and red-shifted enzyme-NAD+-pyrazole double difference spectrum in the near-ultraviolet. The 655-nm peak of the cobalt-substituted enzyme was perturbed by the formation of enzyme-NADH binary complex, enzyme-NAD+-trifloroethanol ternary complex, and enzyme-NAD+ binary complex formation. At pH 7.0, the only observable step in the reaction sequence with a significantly different rate constant for cobalt enzyme was the catalytic hydrogen-transferring step. The rate constant for this step is 92 s-1 for totally cobalt-substituted enzyme as compared with 138 s-1 for native liver alcohol dehydrogenase. The results of this study indicate that zinc is involved in catalysis alcohol and NADH.