Treatment of heart failure associated with acute and chronic forms of ischaemic heart disease by captopril (Tensiomin, EGIS).
The effect of oral Tensiomin treatment, 53.4 mg daily in 29 patients suffering from congestive heart failure associated with acute of chronic forms of ischaemic heart disease, e.g., recent and/or advanced myocardial infarction, aneurysm etc. was studied. The acute and long-term beneficial haemodynamic effects were verified in 4 patients by thermodilution Swan-Ganz catheterization as well. The parameters of ejection function improved moderately, while left ventricular filling pressure (PCW) decreased significantly. The balanced vasodilator effect was not accompanied by an increased myocardial oxygen demand. The "double product" was lowered in response to Tensiomin. During the clinical follow-up (from 6 days to 2 years) there was an improvement in the NYHA functional class by an average of 1.2 however 4 patients died in spite of combined vasodilator and dobutamine treatment. Owing to the improvement of regional blood flow to the brain and the kidney Tensiomin seems to be well-tolerated in patients with low arterial blood pressure. In pts with acute myocardial infarction and angina the critical fall of blood pressure and that of the coronary blood flow should be avoided by giving the drug in approximately titrated. Side effects were observed only with higher doses of Tensiomin in a small number of patients, i.e., transient worsening of renal function in 3 patients and dysgeusia in 2. Our data indicate that Tensiomin treatment is effective and safe in patients suffering from all kinds of congestive heart failure complicating ischaemic heart disease.


Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol synthesis and esterification during the first cell cycle of liver regeneration.
The regenerating rat liver provides a unique in vivo synchronized system for study of the interrelationships between mevalonate and sterol metabolism during the cell cycle. The regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, cholesterol synthesis and acyl coenzyme A: cholesterol acyltransferase during the first cell cycle was investigated. At 8 h postoperative and prior to onset of DNA synthesis or S phase, cholesterol synthesis was depressed in the regenerating liver relative to that in sham-operated controls. This suppression was observed whether assayed in vitro with liver homogenates utilizing radiolabeled acetate, mevalonate or water or in vivo with tritium water. In contrast, at this time point, 3-hydroxy-3-methylglutaryl-CoA reductase activity was increased in microsomes prepared both in the presence and absence of NaF. By 24 h, well into S phase and approaching mitosis, reductase activity and cholesterol synthesis both approached levels observed in the sham-operated control animals. There were no detectable changes in acyl-CoA: cholesterol acyltransferase activity at any time point. Thus, at the 8 h time point, the regulation of the three processes appeared uncoupled. The increased levels of in vitro expressed 3-hydroxy-3-methylglutaryl-CoA reductase activity compared with the decrease in the rate of both cholesterol and squalene biosynthesis suggested diversion of mevalonate into products other than squalene or sterols. We propose that this may reflect the needs of the cell for a nonsterol metabolite of mevalonate necessary for entry of cells into S phase.


Detection of leprosy antigenuria through DOT-ELISA.
Fifty-five samples of urine from different grades of leprosy patients and normal persons were processed for detection of PGL-1 antigen through DOT-ELISA on nitrocellulose paper strips using anti-human IgG horse raddish peroxidaseconjugate. About 66.6% of the paucibacillary and 100% of the multibacillary leprosy cases were detectable through this technique on the basis of differential colour development on the strips. Possibility of its use in the field conditions has been discussed.


Non-paraxial investigation in the far field properties of controllable dark-hollow beams diffracted by a circular aperture.
Based on the angular spectrum representation and the method of stationary phase, an analytically asymptotic expression of the far field of a controllable dark-hollow beam (CDHB) diffracted by a circular aperture is derived. The normalized intensity distributions of an apertured CDHB in the far field are numerically demonstrated. The influence of the f-parameter on the non-paraxiality of the far field of an apertured CDHB is the largest, and the effect of the truncation parameter delta on the non-paraxiality of the far field is the smallest. The difference between the non-paraxial and the paraxial results is independent of the beam order N. The far field pattern of apertured CDHBs sometimes is only a central bright spot. Under certain conditions, a weakly brightly outer ring around the central bright spot is detected in the far field pattern.


Gravity-driven membrane filtration as pretreatment for seawater reverse osmosis: linking biofouling layer morphology with flux stabilization.
In this study gravity-driven membrane (GDM) ultrafiltration is investigated for the pretreatment of seawater before reverse osmosis (RO). The impacts of temperature (21 ± 1 and 29 ± 1 °C) and hydrostatic pressure (40 and 100 mbar) on dynamic flux development and biofouling layer structure were studied. The data suggested pore constriction fouling was predominant at the early stage of filtration, during which the hydrostatic pressure and temperature had negligible effects on permeate flux. With extended filtration time, cake layer fouling played a major role, during which higher hydrostatic pressure and temperature improved permeate flux. The permeate flux stabilized in a range of 3.6 L/m(2) h (21 ± 1 °C, 40 mbar) to 7.3 L/m(2) h (29 ± 1 °C, 100 mbar) after slight fluctuations and remained constant for the duration of the experiments (almost 3 months). An increase in biofouling layer thickness and a variable biofouling layer structure were observed over time by optical coherence tomography and confocal laser scanning microscopy. The presence of eukaryotic organisms in the biofouling layer was observed by light microscopy and the microbial community structure of the biofouling layer was analyzed by sequences of 16S rRNA genes. The magnitude of permeate flux was associated with the combined effect of the biofouling layer thickness and structure. Changes in the biofouling layer structure were attributed to (1) the movement and predation behaviour of the eukaryotic organisms which increased the heterogeneous nature of the biofouling layer; (2) the bacterial debris generated by eukaryotic predation activity which reduced porosity; (3) significant shifts of the dominant bacterial species over time that may have influenced the biofouling layer structure. As expected, most of the particles and colloids in the feed seawater were removed by the GDM process, which led to a lower RO fouling potential. However, the dissolved organic carbon in the permeate was not be reduced, possibly because some microbial species (e.g. algae) could convert CO2 into organic substances. To further improve the removal efficiency of the organic carbon, combining carrier biofilm processes with a submerged GDM filtration system is proposed.


Impact of CYP2C19 genotype on voriconazole exposure and effect of voriconazole on the activity of CYP3A in patients with haematological malignancies.
Voriconazole (VRC) is a first-line drug for the treatment of invasive fungal infections (IFIs) and an inhibitor of CYP3A activity. The aims of this study are to investigate the influence of related factors on the plasma concentration of voriconazole and the effect of voriconazole on the activity of CYP3A in patients with haematological malignancies.A total of 89 patients received an initial dose of 6 mg/kg followed by 4 mg/kg every 12 h were included in the study. Blood samples were collected before and 2 h after administration for subsequent testing and for the extraction of DNA samples. Voriconazole and voriconazole N-oxide in the plasma were detected by LC-MS/MS. The effect of voriconazole on CYP3A activity was evaluated by the ratio of the endogenous biomarkers 6β-hydroxycortisol and cortisol.During the study period, the overall incidence of adverse reactions was 33.6% (with no deaths). The metabolite type of CYP2C19 and combined use of CYP2C19 enzyme inhibitors both had a significant impact on voriconazole exposure. Voriconazole has a long-lasting and potent inhibitory effect on CYP3A activity. The exposure of CYP3A substrate in combination with metabolic enzyme inhibitors voriconazole could increase. Therefore, the combination uses with voriconazole need to be considered carefully and assessed adequately.


Protection of melatonin against acidosis-induced neuronal injuries.
Acidosis, a common feature of cerebral ischaemia and hypoxia, plays a key role in these pathological processes by aggravating the ischaemic and hypoxic injuries. To explore the mechanisms, in this research, we cultured primary neurons in an acidic environment (potential of hydrogen [pH]6.2, 24 hours) to mimic the acidosis. By proteomic analysis, 69 differentially expressed proteins in the acidic neurons were found, mainly related to stress and cell death, synaptic plasticity and gene transcription. And, the acidotic neurons developed obvious alterations including increased neuronal death, reduced dendritic length and complexity, reduced synaptic proteins, tau hyperphosphorylation, endoplasmic reticulum (ER) stress activation, abnormal lysosome-related signals, imbalanced oxidative stress/anti-oxidative stress and decreased Golgi matrix proteins. Then, melatonin (1 × 10-4 mol/L) was used to pre-treat the cultured primary neurons before acidic treatment (pH6.2). The results showed that melatonin partially reversed the acidosis-induced neuronal death, abnormal dendritic complexity, reductions of synaptic proteins, tau hyperphosphorylation and imbalance of kinase/phosphatase. In addition, acidosis related the activations of glycogen synthase kinase-3β and nuclear factor-κB signals, ER stress and Golgi stress, and the abnormal autophagy-lysosome signals were completely reversed by melatonin. These data indicate that melatonin is beneficial for neurons against acidosis-induced injuries.


Elimination of the geomagnetic field stimulates the proliferation of mouse neural progenitor and stem cells.
Living organisms are exposed to the geomagnetic field (GMF) throughout their lifespan. Elimination of the GMF, resulting in a hypogeomagnetic field (HMF), leads to central nervous system dysfunction and abnormal development in animals. However, the cellular mechanisms underlying these effects have not been identified so far. Here, we show that exposure to an HMF (<200 nT), produced by a magnetic field shielding chamber, promotes the proliferation of neural progenitor/stem cells (NPCs/NSCs) from C57BL/6 mice. Following seven-day HMF-exposure, the primary neurospheres (NSs) were significantly larger in size, and twice more NPCs/NSCs were harvested from neonatal NSs, when compared to the GMF controls. The self-renewal capacity and multipotency of the NSs were maintained, as HMF-exposed NSs were positive for NSC markers (Nestin and Sox2), and could differentiate into neurons and astrocyte/glial cells and be passaged continuously. In addition, adult mice exposed to the HMF for one month were observed to have a greater number of proliferative cells in the subventricular zone. These findings indicate that continuous HMF-exposure increases the proliferation of NPCs/NSCs, in vitro and in vivo. HMF-disturbed NPCs/NSCs production probably affects brain development and function, which provides a novel clue for elucidating the cellular mechanisms of the bio-HMF response.


Diclofenac oxidation by biogenic manganese oxides.
Diclofenac, a nonsteroidal anti-inflammatory drug, is one of the most commonly detected pharmaceuticals in sewage treatment plant (STP) effluents. In this work, biologically produced manganese oxides (BioMnOx) were investigated to remove diclofenac. At neutral pH, the diclofenac oxidation with BioMnOx was 10-fold faster than with chemically produced MnO(2). The main advantage of BioMnOx over chemical MnO(2) is the ability of the bacteria to reoxidize the formed Mn(2+), which inhibits the oxidation of diclofenac. Diclofenac-2,5-iminoquinone was identified as a major transformation product, accounting for 5-10% of the transformed diclofenac. Except for 5-hydroxydiclofenac, which was identified as an intermediate, no other oxidation products were detected. Diclofenac oxidation was proportional to the amount of BioMnOx dosed, and the pseudo first order rate constant k was 6-fold higher when pH was decreased from 6.8 to 6.2. The Mn(2+) levels remained below the drinking water limit (0.05 mg L(-1)), thus indicating the efficient in situ microbiological regeneration of the oxidant. These results combined with previous studies suggest the potential of BioMnOx for STP effluent polishing.


Accelerated Time-Resolved Contrast-Enhanced Magnetic Resonance Angiography of Dural Arteriovenous Fistulas Using Highly Constrained Reconstruction of Sparse Cerebrovascular Data Sets.
Time-resolved contrast-enhanced magnetic resonance angiography (MRA) is commonly used to noninvasively characterize vascular malformations. However, the spatial and temporal resolution of current methods often compromises the clinical value of the examinations. Constrained reconstruction is a temporal spatial correlation strategy that exploits the relative sparsity of vessels in space to dramatically reduce the amount of data required to generate fast high-resolution time-resolved contrast-enhanced MRA studies. In this report, we use a novel temporal spatial acceleration method termed HYPRFlow to diagnose and classify dural arteriovenous fistulas (DAVFs). Our hypothesis is that HYPRFlow images are of adequate diagnostic image quality to delineate the arterial and venous components of DAVFs and allow correct classification using the Cognard system. Eight patients with known DAVFs underwent HYPRFlow imaging with isotropic resolution of 0.68 mm and temporal resolution of 0.75 second and 3-dimensional time-of-flight (3DTOF) MRA. The 3DTOF images and HYPRFlow images were evaluated by 2 readers and scored for arterial anatomic image quality. Digital subtraction angiography (DSA) was available for comparison in 7 subjects, and for these patients, each DAVF was classified according to the Cognard system using HYPRFlow and DSA examinations. Digital subtraction angiography was considered the reference examination or criterion standard. HYPRFlow imaging classification was concordant with DSA in all but 1 case. There was no difference in the arterial image quality scores between HYPRFlow and 3DTOF MRA (95% confidence interval). Arterial-to-venous separation was rated excellent (n = 3), good (n = 4), or poor (n = 1), and arteriovenous shunting was easily appreciated. Undersampling artifacts were reduced by using a low pass filter and did not interfere with the diagnostic quality of the examinations. HYPRFlow is a novel acquisition and reconstruction technique that exploits the relative sparsity of intracranial vessels in space to increase temporal and spatial resolution and provides accurate delineation of DAVF vasculature.


The times and spaces of transplantation: queercrip histories as futurities.
With a focus on Larissa Lai's The Tiger Flu, this article explores how transplantation is part of the ongoing transformation of being in a body that is of the world. That is, it examines how we may require other ways of thinking bodies as constituted by histories, spaces and times that may be ignored in the biomedical arena. The Tiger Flu, I argue, calls for an intra- and inter-connected way of thinking how we treat bodies, and thereby ways of working with bodies affected by environmental disasters (both acute and ongoing capitalist and colonial projects), multiple selves and time as more than linear. I turn to queercrip as a way of defying a curative imaginary that dominates transplantation and in so doing examine the colonial, capitalist violence of present day living. I move through Eve Hayward's and Karen Barad's work to examine how the cut of transplantation is a transformation, as integral to the ongoing experience of having a body in the world and yet potentially unique in its force of bringing inter- and intra-relatedness to the fore of one's existence. Rather than sick or cured, I argue that transplantation is a transformation that captures our bodily changes, how the environment constitutes the self, how parts may feel integral to the self or easily disposed of, how viscera may tie us to others, and how the future may only be forged through a re-turn to the past (of the donor and a pre-transplant self). Transplantation is not about loss of self or gaining of an other, but rather about rendering apparent our multispecies, multiworld ties, and thus how we are bound by the histories we forge and the futures we re-member.


Endothelial cell hyperpolarization increases [Ca2+]i and venular microvessel permeability.
We tested the hypothesis that Ca2+ influx into endothelial cells forming the walls of intact venular microvessels was increased when the cell membranes were hyperpolarized. Cytoplasmic free Ca2+ concentration ([Ca2+]i) was measured after the endothelial cells forming the microvessel wall were loaded with fura 2, endothelial cell membrane potential was measured with the membrane potential dye bis-oxonol, and hydraulic conductivity (Lp) of the vessels was measured by the modified Landis technique to follow changes in microvessel permeability. When microvessels were exposed to low-K+ (0.1 mM) Ringer solution, the membrane of the endothelial cells was hyperpolarized approximately 27 mV and [Ca2+]i increased from 47 nM to a peak value of 151 +/- 28 nM. Under the same experimental conditions, Lp increased to a peak 6.3 times control. In the presence of ionomycin (5 microM), the initial peak [Ca2+]i measured with low-K+ Ringer solution was 347 +/- 58 nM compared with 252 +/- 58 nM with ionophore and normal Ringer solution. The corresponding initial increases in Lp were 28 times control and 10 times control, respectively. The results conform to the hypothesis that vasoactive substances that hyperpolarize the endothelial cell membrane may initiate and/or potentiate the inflammatory response in venular microvessels.


Design and Testing of Stimulation and Myoelectric Recording Modules in an Implanted Distributed Neuroprosthetic System.
Implantable motor neuroprostheses can restore functionality to individuals with neurological disabilities by electrically activating paralyzed muscles in coordinated patterns. The typical design of neuroprosthetic systems relies on a single multi-use device, but this limits the number of stimulus and sensor channels that can be practically implemented. To address this limitation, a modular neuroprosthesis, the "Networked Neuroprosthesis" (NNP), was developed. The NNP system is the first fully implanted modular neuroprosthesis that includes implantation of all power, signal processing, biopotential signal recording, and stimulating components. This paper describes the design of stimulation and recording modules, bench testing to verify stimulus outputs and appropriate filtering and recording, and validation that the components function properly while implemented in persons with spinal cord injury. The results of system testing demonstrated that the NNP was functional and capable of generating stimulus pulses and recording myoelectric, temperature, and accelerometer signals. Based on the successful design, manufacturing, and testing of the NNP System, multiple clinical applications are anticipated.


In silico analysis of peptide binding features of HLA-B*4006.
HLA-B*4006 is the most common allele amongst Indians. It belongs to the 'HLA-B44 supertype' family of alleles that constitute an important component of the peptide binding repertoire in populations world over. Its peptide binding characteristics remain poorly examined. The amino acid sequence and structural considerations suggest a small, poorly hydrophobic 'F' pocket for this allele that may adversely affect the interaction with the C terminal residue of the antigenic peptide. Contribution of auxiliary anchor residues (P3) of the peptide has also been indicated. To examine these aspects by in silico analysis, HLA-B*4001, 4002, and 4006 alleles were modeled using HLA-B*4402 as a template. Eleven peptides, known to bind alleles of this family, were used for docking and molecular dynamics studies. Interaction between the amino group (main-chain) of P3 residue and Tyr99 of the alleles was seen in majority of peptide-complexes. Hydrophobic interactions between Tyr7 and Tyr159 with N terminal residues of the peptide were also seen in all the complexes. Replacement of Trp95 by leucine in HLA-B*4006 resulted in reduction of binding free energy in 8 out of 9 complexes. In summary, the analysis of the modeled structures and HLA-peptide complexes strongly supports the adverse effect of Trp95 at pocket F and the possible role of the third residue of the antigenic peptide as an auxiliary anchor in HLA-B*4006 peptide complexes. In the light of suggested promiscuous peptide binding pattern and association with risk for tuberculosis/HIV for this allele, the ascertainment of the predicted effects of Trp95 and role of P3 residue as an auxiliary anchor by this preliminary in silico analysis thus helps define direction of the further studies.


Identification of a Nicotiana plumbaginifolia plasma membrane H(+)-ATPase gene expressed in the pollen tube.
In Nicotiana plumbaginifolia, plasma membrane H(+)-ATPases (PMAs) are encoded by a gene family of nine members. Here, we report on the characterization of a new isogene, NpPMA5 (belonging to subfamily IV), and the determination of its expression pattern using the beta-glucuronidase (gusA) reporter gene. pNpPMA5-gusA was expressed in cotyledons, in vascular tissues of the stem (mainly in nodal zones), and in the flower and fruit. In the flower, high expression was found in the pollen tube after in vitro or in vivo germination. Northern blotting analysis confirmed that NpPMA5 was expressed in the pollen tube contrary to NpPMA2 (subfamily I) or NpPMA4 (subfamily II), two genes highly expressed in other tissues. The subcellular localization of PM H(+)-ATPase in the pollen tube was analyzed by immunocytodecoration. As expected, this enzyme was localized to the plasma membrane. However, neither the tip nor the base of the pollen tube was labeled, showing an asymmetrical distribution of this enzyme. This observation supports the hypothesis that the PM H(+)-ATPase is involved in creating the pH gradient that is observed along the pollen tube and is implicated in cell elongation. Compared to other plant PM H(+)-ATPases, the C-terminal region of NpPMA5 is shorter by 26 amino acid residues and is modified in the last 6 residues, due to a sequence rearrangement, which was also found in the orthologous gene of Nicotiana glutinosa, a Nicotiana species distant from N. plumbaginifolia and Petunia hybrida and Lycopersicon esculentum, other Solanacae species. This modification alters part of the PM H(+)-ATPase regulatory domain and raises the question whether this isoform is still regulated.


Metabolic Resistance of Sogatella furcifera (Hemiptera: Delphacidae) toward Pymetrozine Involves the Overexpression of CYP6FJ3.
Sogatella furcifera (Horváth), which mainly threatens rice, shows various levels of pesticide resistance due to long-term overuse of pesticides. Our resistance monitoring of 20 field populations in Sichuan, China, revealed that they were susceptible to highly resistant toward pymetrozine (0.4-142.2 RR), and JL21 reached the highest level of resistance. The JL21 population exhibited cross-resistance to triflumezopyrim and dinotefuran but sensitivity to sulfoxaflor, acetamiprid, clothianidin, and nitenpyram. The increased P450 activity were support to involve in pymetrozine resistance by detoxification enzyme activities and synergist determination. Among 16 candidate P450 genes, CYP6FJ3 (5.25-fold) was the most up-regulated in JL21, while no significant change was found after LC25 pymetrozine treatment. Furthermore, the knockdown by RNAi and heterologous overexpression by the GAL4/UAS system confirmed that the CYP6FJ3 overexpression was involved in the pymetrozine resistance, and recombination in vitro confirmed that CYP6FJ3 could hydroxylate pymetrozine. Therefore, the overexpression of CYP6FJ3 promotes pymetrozine metabolic resistance in S. furcifera.


Effect of BG-Lures on the Male Aedes (Diptera: Culicidae) Sound Trap Capture Rates.
With global expansion of the two main vectors of dengue, Aedes aegypti (Linnaeus, Diptera: Culicidae) and Aedes albopictus (Skuse, Diptera: Culicidae), there is a need to further develop cost-effective and user-friendly surveillance tools to monitor the population dynamics of these species. The abundance of Ae. aegypti and Ae. Albopictus, and associated bycatch captured by Male Aedes Sound Traps (MASTs) and BG-Sentinel (BGS) traps that were unbaited or baited with BG-Lures were compared in Cairns, Australia and Madang, Papua New Guinea. Mean male Ae. aegypti and Ae. albopictus catch rates in MASTs did not significantly differ when deployed with BG-Lures. Similarly, males of both these species were not sampled at statistically different rates in BGS traps with or without BG-Lures. However, MASTs with BG-Lures caught significantly less male Ae. aegypti than BGS traps baited with BG-Lures in Cairns, and MASTs without BG-Lures caught significantly more male Ae. albopictus than BGS traps without BG-Lures in Madang. Additionally, BG-Lures significantly increased female Ae. aegypti catch rates in BGS traps in Cairns. Lastly, bycatch capture rates in BGS traps were not significantly influenced by the addition of the BG-Lures. While this study provides useful information regarding the surveillance of Ae. aegypti and Ae. albopictus in these locations, further development and investigation is required to successfully integrate an olfactory lure into the MAST system.


Preservation of retina ganglion cell function by morphine in a chronic ocular-hypertensive rat model.
The current study examined if opioid-receptor-activation by morphine can improve retinal function and retinal ganglion cell (RGC) integrity in a chronic glaucoma rat model. IOP was raised in Brown Norway rats by injecting hypertonic saline into the limbal venous system. Rats were treated daily with 1 mg/kg morphine for 28 days at 24-hour intervals; animals were examined for changes in IOP by a TonoLab tonometer. Pattern-ERG (PERG) was obtained in response to contrast-reversal of patterned visual stimuli. RGCs were visualized by fluorogold retrograde-labeling. Changes in the expression pattern of TNF-α and caspases were measured by Western blotting. A significant IOP elevation was seen as early as 7 days, and maintained for up to 8 weeks, after surgery. PERG amplitudes were significantly reduced in ocular-hypertensive eyes (15.84±0.74 μvolts) when compared with normal eyes (19±0.86 μvolts). PERG deficits in hypertensive eyes were reversed by morphine treatment (18.23±0.78 μvolts; P<0.05). In untreated rats, a 24% reduction in labeled RGCs was measured in the hypertensive eye compared with the normal eye. This reduction in RGC labeling was significantly ameliorated in the presence of morphine. In retinal samples, TNF-α, caspase-8, and caspase-3 expressions were significantly upregulated in ocular hypertensive eyes, but completely inhibited in the morphine-treated animals. These data provide evidence that activation of opioid receptors can provide significant improvement in PERG and RGC integrity against glaucomatous injury. Mechanistic data provide clues that activation of one or more opioid receptors can reduce glaucomatous-injury via suppression of TNF-α and caspase activation.


DNA unwinding by Escherichia coli DNA helicase I (TraI) provides evidence for a processive monomeric molecular motor.
The F plasmid TraI protein (DNA helicase I) plays an essential role in conjugative DNA transfer as both a transesterase and a helicase. Previous work has shown that the 192-kDa TraI protein is a highly processive helicase, catalytically separating >850 bp under steady-state conditions. In this report, we examine the kinetic mechanism describing DNA unwinding of TraI. The kinetic step size of TraI was measured under both single turnover and pre-steady-state conditions. The resulting kinetic step-size estimate was approximately 6-8 bp step(-1). TraI can separate double-stranded DNA at a rate of approximately 1100 bp s(-1), similar to the measured unwinding rate of the RecBCD helicase, and appears to dissociate very slowly from the 3' terminus following translocation and strand-separation events. Analyses of pre-steady-state burst amplitudes indicate that TraI can function as a monomer, similar to the bacteriophage T4 helicase, Dda. However, unlike Dda, TraI is a highly processive monomeric helicase, making it unique among the DNA helicases characterized thus far.


[Rehabilitative Intervention for Low Back Pain].
In the evolution process to a bipedalism animal, human's spinal structure has been formed by responding to the contradicting functions (firm and flexibility). Thus, low back pain easily occurs even by a break of extremely slight balance. As for the cause of the pain, a consistency theory is not established, and we need to depend on conservative treatment for the treatment And the leading role of the conservative therapy is rehabilitation. In this report, we introduce scientific evidence for the effect of the rehabilitative intervention for low back pain.


The "well-sibling" syndrome: hypnosis for the siblings of special needs children.
Often overlooked by caregivers because of their ability to adapt to a challenging home life by making few demands themselves, the siblings of special needs children have unacknowledged needs of their own. They often are reluctant to participate in therapy because of their self-concept of having to be the "normal" or "perfect" child. Therapy with these children requires non-pathologizing and attuned rapport building focused on creative self-exploration without requests for change. Two composite case vignettes illustrate the power and versatility of clinical hypnosis to facilitate new learning about becoming visible in the therapeutic relationship and beyond.


Albendazole resistance in Giardia is correlated with cytoskeletal changes but not with a mutation at amino acid 200 in beta-tubulin.
Albendazole resistance was induced in three different Giardia cultures following growth in successively increasing amounts of drug. One of the lines was previously resistant to high levels of metronidazole and was able to grow in 2 microM albendazole. The other two survived exposure to 0.8 microM, while normally lethal levels of albendazole against Giardia in vitro were around 0.1-0.2 microM. Albendazole-resistant Giardia were cross-resistant to parbendazole. Major chromosome rearrangements were evident in the line resistant to 2 microM albendazole and IFA with antitubulin antibody indicated differences in the cytoskeleton, particularly the median body, between sensitive and resistant lines. This implicates the cytoskeleton in the mechanism of resistance. Substitution of Tyr for Phe is a consistent beta-tubulin amino acid change in the benzimidazole-resistant helminths and fungi so far analyzed. PCR primers were designed from the published Giardia beta-tubulin gene sequence and spanned the region encoding Phe at position 200. Sequence data from albendazole-resistant Giardia demonstrated that the beta-tubulin gene did not carry a mutation in the codon for amino acid 200. These data suggest that Phe at position 200 in beta-tubulin is not necessary for benzimidazole resistance.


The Proportion of Complementary and Alternative Medicine Utilization Among Saudi Population for Eye Care: Cross-Sectional Study.
Purpose To estimate the prevalence, determinants and perceived benefit of complementary and alternative medicine (CAM) use for ophthalmic purposes among the Saudi population. Methods A cross-sectional study was carried out in 2019 targeting visitors of King Khaled Eye Specialist Hospital (KKESH), Riyadh, Saudi Arabia. The survey had 18 questions in Arabic regarding the use of CAM for eye ailments. The magnitude was associated to the demographic and eye-related factors. Results We interviewed 999 participants. The prevalence of CAM usage was 21.9% (95% confidence interval 19.3; 24.5). Castor oil (49.3%), antimony (khohl alethmed) (40.6%), chamomile (19.6%), and green tea leaves (11.4%) were the most common medications used. Other traditional eye treatments included eye vitamins, faith healing (prayer, reciting Quran, Zamzam water), cautery, cupping, and acupuncture. Conclusions One in five Saudi eye patients used CAM. The factors governing this health behavior should be studied to change this practice pattern.


Isolation, characterization, and identification of Geobacillus thermodenitrificans HRO10, an alpha-amylase and alpha-glucosidase producing thermophile.
Thermophilic and amylolytic aerobic bacteria were isolated from soil through a selective enrichment procedure at 60 degrees C with starch as the carbon source. One of the isolates designated as HRO10 produced glucose aside from limit dextrin as the only hydrolysis product from starch and was characterized in detail. The starch-degrading enzymes produced by strain HRO10 were determined to be alpha-amylase and alpha-glucosidase. Whereas the alpha-amylase activity was detected exclusively in the culture supernatant, alpha-glucosidase occurred intracellular, extracellular, or on the surface of the bacteria depending on the growth phase. The optimum temperature and pH required for the growth of strain HRO10 were about 50 degrees C and pH 6.5 to 7.5. The strain used different carbohydrates as the carbon source, but the maximum production of alpha-amylase occurred when 1.0% (w/v) starch or dextrin was used. The use of organic vs. inorganic nitrogen favored the production of alpha-amylase in strain HRO10. The metal ions Li+, Mg2+, and Mn2+ stimulated the production of both enzymes. Identification of strain HRO10 by physiological and molecular methods including sequencing of the 16S rDNA showed that this strain belongs to the species Geobacillus thermodenitrificans. Biochemically, strain HRO10 differs from the type strain DSM 465 only in its ability to hydrolyze starch.


Meta-analysis for diagnostic accuracy studies: a new statistical model using beta-binomial distributions and bivariate copulas.
There are still challenges when meta-analyzing data from studies on diagnostic accuracy. This is mainly due to the bivariate nature of the response where information on sensitivity and specificity must be summarized while accounting for their correlation within a single trial. In this paper, we propose a new statistical model for the meta-analysis for diagnostic accuracy studies. This model uses beta-binomial distributions for the marginal numbers of true positives and true negatives and links these margins by a bivariate copula distribution. The new model comes with all the features of the current standard model, a bivariate logistic regression model with random effects, but has the additional advantages of a closed likelihood function and a larger flexibility for the correlation structure of sensitivity and specificity. In a simulation study, which compares three copula models and two implementations of the standard model, the Plackett and the Gauss copula do rarely perform worse but frequently better than the standard model. We use an example from a meta-analysis to judge the diagnostic accuracy of telomerase (a urinary tumor marker) for the diagnosis of primary bladder cancer for illustration.


Acute, sub-acute and long-term subjective consequences of 'ecstasy' (MDMA) consumption in 430 regular users.
This study examined the reported psychological effects of different patterns of MDMA use in men and women, and how they are modified by use of other psychoactive substances. A semi-structured interview was conducted with 466 regular MDMA users, exploring the perceived acute, sub-acute and long-term subjective effects of this drug. Factor analysis established three main categories of acute effects of MDMA: (i) positive and (ii) negative effects on mental health, and (iii) physical effects. In terms of subacute effects, 83% of participants reported experiencing low mood and 80% reported impaired concentration between ecstasy-taking sessions. Factors affecting these effects included age, gender, extent of MDMA use and concomitant use of cocaine or amphetamine. The long-term effects most frequently reported included the development of tolerance to MDMA (59%), impaired ability to concentrate (38%), depression (37%) and 'feeling more open towards people' (31%). In terms of what might persuade users to stop using MDMA, their most prominent concern was the drug's long-term effects on mental health.


DNA microarrays: applicability to renal physiology and disease.
The utilization of DNA microarray is increasing in all areas of medical research as evidenced by the exponential increase in the number of publications on MedLine. Improvements in DNA microarray technology and the bioinformatic techniques for data analysis continue to take place and result in improved reliability, reproducibility, and volume of data. Replicate analysis remains important in order to allow statistical examination of significance. Expression of key genes should also be confirmed by alternative techniques. Single microarray experiments yield such vast amounts of data that shortage of manpower is the limiting factor to progression of full scientific discovery. Sharing of microarray data on the internet and its distribution to a broader scientific community will help overcome this manpower shortage. Currently, DNA microarray technology serves as a research tool. Ultimately, microarray technology may be used widely in the clinical setting as fingerprinting of cells, tissue, and disease states, though more targeted strategies using a limited repertoire of genes may be most valuable.


Harm reduction: a realistic approach toward injection drug users.
The injection use of illicit drugs is a major mode of HIV transmission in the heterosexual population. Indeed, because HIV is transmitted from injection drug users to their sexual partners and their children, there is widespread acknowledgement that controlling HIV infection in the general community may depend on controlling it in injection drug users. Unfortunately, a moralistic attitude toward illicit drugs and their users all too often deters health professionals from taking preventive action. This impractical attitude holds that stopping illicit drug use is the only answer. In today's age of AIDS, it's a dangerously simplistic stance.


The Length of Incision in Unicondylar Knee Arthroplasty Is More Affected by the Patient's Height Than Their Weight.
Objective Obesity leads to osteoarthritis due to increased loading forces on joint cartilage and inflammatory agents released from adipose tissue. In patients with a high body mass index (BMI), during hip and total knee arthroplasty, surgical technical challenges such as longer incisions and wider exposure are encountered, resulting in increased postoperative complications (wound healing problems and infection, venous thromboembolism (VTE)- pulmonary embolism (PE), dislocation, early implant failure) and ultimately decreased patient satisfaction and implant survival. This study investigates whether BMI, height, weight, and patient age are associated with longer incisions in patients undergoing unicondylar knee prosthesis (UKP) placement. Method Between January 2017 and December 2018, 30 patients (29 females and 1 male) who underwent UKP surgery due to medial gonarthrosis were included in the study. The UKP used in the procedures was the Oxford Knee Phase III by Biomet Ltd., UK. The study comprised 43 knees, 13 being bilateral cases, 8 on the right, and 9 on the left. Data regarding the patient's height, weight, BMI, age, and the operated side were collected and compiled. The relationships between these variables and the surgical incision length were statistically analyzed. Results The average age of the patients was 66.3 years, with an average weight and height of 77.6 kg (ranging from 62 to 98 kg) and 167 cm (ranging from 150 to 184 cm), respectively. The lengths of the surgical incisions ranged from 70 mm to 160 mm, with an average length of 124.5 mm. When comparing the incision lengths between the right and left sides, it was observed that the incisions on the left side were longer. The average incision length on the right side was 122.09 mm, while on the left, it was 126.86 mm. Moreover, in the 13 patients who underwent bilateral surgery, this difference in incision length was even more pronounced. The average incision length on the right side was 117.15 mm, whereas on the left, it was 124.23 mm. Bivariate correlation analyses were performed to examine the relationship between the length of the incision and BMI and age. However, no significant relationship was found between the incision length and BMI or age. On the other hand, there was a correlation between the patient's weight values and the incision length (p < 0.05, correlation 0.335). Furthermore, a higher correlation was observed between the patient's height and the incision length (p < 0.01, correlation 0.595). Conclusion The latest advances in surgical techniques and instrumentation have enabled surgeons to perform the procedure using a reliable mini-incision approach. Mid-term evaluation of UKP with mini-incision shows faster recovery and lower morbidity. The findings show that in UKP, the length of the surgical incision is more strongly related to the patient's height than their weight.


MdMYB6 regulates anthocyanin formation in apple both through direct inhibition of the biosynthesis pathway and through substrate removal.
Anthocyanin biosynthesis and sugar metabolism are important processes during plant growth, but the molecular interactions underlying these pathways are still unclear. In this work, we analyzed the anthocyanin and soluble sugar contents, as well as the transcript levels of transcription factors that are known to be related to the biosynthesis of anthocyanin in 'Hongcui 1' apple flesh during fruit development. Overexpression of MdMYB6 in red-fleshed calli was found to reduce anthocyanin content and result in downregulated expression of the MdANS and MdGSTF12 proteins. Yeast one-hybrid and electrophoretic mobility shift analyses showed that MdMYB6 could directly bind to the promoters of MdANS and MdGSTF12, indicating that MdMYB6 could inhibit anthocyanin biosynthesis by regulating MdANS and MdGSTF12. Overexpression of MdTMT1 in the Arabidopsis tmt1 mutant restored the glucose and fructose contents to the wild-type levels, while overexpression of MdTMT1 in red-fleshed calli increased the contents of glucose and fructose but reduced the contents of UDP-glucose, UDP-galactose, and anthocyanin. Using a GUS reporter system, yeast one-hybrid, chromatin immunoprecipitation-PCR and electrophoretic mobility shift analyses, we found that MdMYB6 could bind to the promoter of MdTMT1, resulting in increased promoter activity. Overexpression of MdMYB6 in calli overexpressing MdTMT1 increased the expression of MdTMT1, which led to reduced contents of UDP-glucose and UDP-galactose and decreased anthocyanin content compared to those of the calli that overexpressed MdTMT1. This finding suggested that MdMYB6 could also inhibit anthocyanin biosynthesis by regulating MdTMT1 to decrease the contents of UDP-glucose and UDP-galactose. Taken together, these results showed that MdMYB6 and MdTMT1 play key roles in both anthocyanin biosynthesis and sugar transport.


Development of image mappers for hyperspectral biomedical imaging applications.
A new design and fabrication method is presented for creating large-format (>100 mirror facets) image mappers for a snapshot hyperspectral biomedical imaging system called an image mapping spectrometer (IMS). To verify this approach a 250 facet image mapper with 25 multiple-tilt angles is designed for a compact IMS that groups the 25 subpupils in a 5 x 5 matrix residing within a single collecting objective's pupil. The image mapper is fabricated by precision diamond raster fly cutting using surface-shaped tools. The individual mirror facets have minimal edge eating, tilt errors of <1 mrad, and an average roughness of 5.4 nm.


Clinicopathologic characteristics of 29 invasive carcinomas arising in 178 pancreatic mucinous cystic neoplasms with ovarian-type stroma: implications for management and prognosis.
Information on the clinicopathologic characteristics of invasive carcinomas arising from mucinous cystic neoplasms (MCNs) is limited, because in many early studies they were lumped and analyzed together with noninvasive MCNs. Even more importantly, many of the largest prior studies did not require ovarian-type stroma (OTS) for diagnosis. We analyzed 178 MCNs, all strictly defined by the presence of OTS, 98% of which occurred in perimenopausal women (mean age, 47 y) and arose in the distal pancreas. Twenty-nine (16%) patients had associated invasive carcinoma, and all were female with a mean age of 53. Invasion was far more common in tumors with grossly visible intracystic papillary nodule formation ≥1.0 cm (79.3% vs. 8.7%, P=0.000) as well as in larger tumors (mean cyst size: 9.4 vs. 5.4 cm, P=0.006); only 4/29 (14%) invasive carcinomas occurred in tumors that were <5 cm; however, none were <3 cm. Increased serum CA19-9 level (>37 U/L) was also more common in the invasive tumors (64% vs. 23%, P=0.011). Most invasive carcinomas (79%) were of tubular type, and the remainder (5 cases) were mostly undifferentiated carcinoma (2, with osteoclast-like giant cells), except for 1 with papillary features. Interestingly, there were no colloid carcinomas; 2 patients had nodal metastasis at the time of diagnosis, and both died of disease at 10 and 35 months, respectively. While noninvasive MCNs had an excellent prognosis (100% at 5 y), tumors with invasion often had an aggressive clinical course with 3- and 5-year survival rates of 44% and 26%, respectively (P=0.000). The pT2 (>2 cm) invasive tumors had a worse prognosis than pT1 (≤2 cm) tumors (P=0.000), albeit 3 patients with T1a (<0.5 cm) disease also died of disease. In conclusion, invasive carcinomas are seen in 16% of MCNs and are mostly of tubular (pancreatobiliary) type; colloid carcinoma is not seen in MCNs. Serum CA19-9 is often higher in invasive carcinomas, and invasion is typically seen in OTS-depleted areas with lower progesterone receptor expression. Invasion is not seen in small tumors (<3 cm) and those lacking intracystic papillary (mural) nodules of ≥1 cm, thus making the current branch-duct intraductal papillary mucinous neoplasm management protocols also applicable to MCNs.


[Epidemiology of male infertility].
The responsibility of the male in the infertility of the couple has been ignored for long time; it is now universally recognized and obliges general practitioners to explore the possibility of male infertility. Clinical and laboratory examinations must be carried out simultaneously, with a systematic search for the major risk factors of male infertility, such as varicocele and history of genital infection or injury to the testis. The practitioner must also investigate the working conditions and the environment of the infertile male in search for occupational risk factors which are frequently overlooked but often have severe consequences.


Identification of a cDNA from the arbuscular mycorrhizal fungus Glomus intraradices that is expressed during mycorrhizal symbiosis and up-regulated by N fertilization.
A cDNA library was constructed with RNA from Glomus intraradices-colonized lettuce roots and used for differential screening. This allowed the identification of a cDNA (Gi-1) that was expressed only in mycorrhizal roots and was of fungal origin. The function of the gene product is unknown, because Gi-1 contained a complete open reading frame that was predicted to encode a protein of 157 amino acids which only showed little homology with glutamine synthetase from Helicobacter pylori. The time-course analysis of gene expression during the fungal life cycle showed that Gi-1 was expressed only during the mycorrhizal symbiosis and was not detected in dormant or germinating spores of G. intraradices. P fertilization did not significantly change the pattern of Gi-1 expression compared with that in the unfertilized treatment, whereas N fertilization (alone or in combination with P) considerably enhanced the Gi-1 transcript accumulation. This increase in gene expression correlated with plant N status and growth under such conditions. The possible role of the Gi-1 gene product in intermediary N metabolism of arbuscular mycorrhizal symbiosis is further discussed.


Quantum mechanics with a momentum-space artificial magnetic field.
The Berry curvature is a geometrical property of an energy band which acts as a momentum space magnetic field in the effective Hamiltonian describing single-particle quantum dynamics. We show how this perspective may be exploited to study systems directly relevant to ultracold gases and photonics. Given the exchanged roles of momentum and position, we demonstrate that the global topology of momentum space is crucially important. We propose an experiment to study the Harper-Hofstadter Hamiltonian with a harmonic trap that will illustrate the advantages of this approach and that will also constitute the first realization of magnetism on a torus.


Microcystic adnexal carcinoma: reconstruction of a large centrofacial defect.
We report a rare case of a large facial microcystic adnexal carcinoma in an elderly patient who underwent several rounds of excision. The patient was left with a large facial defect and remaining positive margins. The decision was made to stop further excision and proceed with reconstructive surgery. We show that the patient's function and quality of life were not impeded despite reconstruction in light of positive margins for tumor. We believe that this case will draw the surgeon's attention to the possibility of palliative reconstruction in the treatment of a patient with large debilitating facial defects after microcystic adnexal carcinoma excision.


Reproducibility of patient setup in the seated treatment position: A novel treatment chair design.
Radiotherapy in a seated position may be indicated for patients who are unable to lie on the treatment couch for the duration of treatment, in scenarios where a seated treatment position provides superior anatomical positioning and dose distributions, or for a low-cost system designed using a fixed treatment beam and rotating seated patient. In this study, we report a novel treatment chair that was constructed to allow for three-dimensional imaging and treatment delivery while ensuring robust immobilization, providing reproducibility equivalent to that in the traditional supine position. Five patients undergoing radiation treatment for head-and-neck cancers were enrolled and were setup in the chair, with immobilization devices created, and then imaged with orthogonal X-rays in a scenario that mimicked radiation treatments (without treatment delivery). Six subregions of the acquired images were rigidly registered to evaluate intra- and interfraction displacement and chair construction. Displacements under conditions of simulated image guidance were acquired by first registering one subregion; the residual displacement of other subregions was then measured. Additionally, we administered a patient questionnaire to gain patient feedback and assess comparison to the supine position. Average inter- and intrafraction displacements of all subregions in the seated position were less than 2 and 3 mm, respectively. When image guidance was simulated, L-R and A-P interfraction displacements were reduced by an average of 1 mm, providing setup of comparable quality to supine setups. The enrolled patients, who had no indication for a seated treatment position, reported no preference in the seated or the supine position. The novel chair design provides acceptable inter- and intrafraction displacement, with reproducibility equivalent to that reported for patients in the supine position. Patient feedback will be incorporated in the refinement of the chair, facilitating treatment of head-and-neck cancer in patients who are unable to lie for the duration of treatment or for use in an economical fixed-beam setup.


Influence of Age on Guideline-Concordant Cancer Care for Elderly Patients in the United States.
To examine the frequency of guideline-concordant cancer care in elderly patients, including "older" elderly (age ≥80 years). Using the Surveillance, Epidemiology and End Results-Medicare dataset in patients aged ≥66 years diagnosed with nonmetastatic breast cancer (n=55,094), non-small cell lung (NSCLC) (n=36,203), or prostate cancer (n=86,544) from 2006 to 2011, chemotherapy, surgery, and radiation (RT) treatments were identified using claims. Pearson χ2 tested associations between age and guideline concordance. Older patients were less likely to receive guideline-concordant curative treatment: in stage III breast cancer, receipt of postmastectomy RT (70%, 46%, and 21% in patients aged 66-79, 80-89, and ≥90 years, respectively; P<.0001); in stage I NSCLC, RT or surgery (89%, 80%, and 64% in age 66-79, 80-89, and ≥90 years; P<.0001); in stage III NSCLC, RT or surgery plus chemotherapy (79%, 58%, and 27% in age 66-79, 80-89, and ≥90 years; P<.0001); and in intermediate/high-risk prostate cancer, RT or prostatectomy (projected life expectancy >10 years: 85% and 82% in age 66-69 and 70-75 years; and ≤10 years: 70%, 42%, and 9% in age 76-79, 80-89, and ≥90 years; P<.0001). However, older patients were more likely to receive guideline-concordant de-intensified treatment: in stage I to II node-negative breast cancer, hypofractionated postlumpectomy RT (9%, 16%, and 23% in age 66-79, 80-89, and ≥90 years; P<.0001); in stage I estrogen receptor-positive breast cancer, observation after lumpectomy (12%, 42%, and 84% in age 66-79, 80-89, and ≥90 years; P<.0001); in stage I NSCLC, stereotactic body RT instead of surgery (7%, 16%, and 25% in age 66-79, 80-89, and ≥90 years; P<.0001); and in lower-risk prostate cancer, no active treatment (25%, 54%, and 68% in age 66-79, 80-89, and ≥90 years; P<.0001). Actual treatment of older elderly cancer patients frequently diverged from guidelines, especially in curative treatment of advanced disease. Results suggest a need for better metrics than existing guidelines alone to evaluate quality and appropriateness of care in this population.


Myricetin induces apoptosis and enhances chemosensitivity in ovarian cancer cells.
Ovarian cancer is the most lethal type of gynecological cancer and is the fifth leading cause of cancer-associated mortality in females globally. The majority of patients with ovarian cancer suffer from recurrent, progressive disease, due to the acquisition of a resistance phenotype towards various conventional chemotherapy drugs. Although paclitaxel has been demonstrated to be effective against ovarian tumors, there have been reports of the development of a resistant phenotype against Taxol® treatment. The multidrug resistance (MDR)-1/P-glycoprotein has previously been demonstrated to be associated with the acquisition of paclitaxel resistance in certain ovarian tumors. Therefore, the screening of novel drug candidates able to target MDR-1 in ovarian cancer cells and increase the sensitivity to Taxol® is required in order to improve the treatment of this disease. In the present study, the underlying mechanisms by which the dietary flavonoid myricetin enhances the cytotoxic potential of paclitaxel in ovarian cancer cells, was investigated. It was observed that myricetin induced significant cytotoxicity in A2780 and OVCAR3 ovarian cancer cells, with the IC50 value obtained at 25 µM. Myricetin treatment also resulted in the induction of apoptosis in the two cell lines, accompanied by the modulation of certain pro- and anti-apoptotic markers. It was also determined that the pre-incubation of ovarian cancer cells with a lower dose of myricetin was able to increase the cytotoxicity of paclitaxel, due to the significant downregulation of MDR-1 in these cells.


Racial Disparities in the Surgical Management of Benign Craniomaxillofacial Bone Lesions.
Racial disparities can influence surgical care in the United States. The purpose of this study was to determine if race and ethnicity were independent risk factors for adverse 30-day outcomes after surgical management of benign craniomaxillofacial bone tumors. This was a retrospective cohort study from 2012 to 2018 National Surgical Quality Improvement Program databases. Patients undergoing surgical removal of craniomaxillofacial benign lesions based on Current Procedural Terminology and International Classification of Diseases codes were included. Patients who had unrelated concurrent surgeries, or malignant, skull-based or soft tissue lesions were excluded. Primary outcomes were surgical complications and hospital length of stay (LOS). Univariate analyses were used with race as the independent variable to identify predictors of primary outcomes. Statistically significant factors were added to a multivariable logistic regression model. This study included 372 patients. Postoperative complications were highest among Black patients, who had a 4-fold increase in minor complications (P = 0.023) and over a 6-fold increase in major complications (P = 0.008) compared to White patients. Black patients also had a mean increase of 2.3 days in LOS compared to White patients (P < 0.001). The multivariate regression model showed higher rates of major complications and longer LOS for Black patients (P = 0.003, P = 0.006, respectively). Even when controlling for other variables, Black race was an independent risk factor for major complications and increased LOS. Further research should seek to identify the root cause of these findings in order to ensure safe and equitable surgery for all patients, regardless of race or ethnicity.


Influence of cerebral hemodynamics on stroke risk: one-year follow-up of 30 medically treated patients.
The importance of hemodynamic factors in the pathogenesis and treatment of ischemic cerebrovascular disease is not clear. We have investigated the relationship between cerebral hemodynamics and the subsequent risk of stroke in 30 medically treated patients with symptomatic occlusion or greater than 75% intracranial stenosis of the carotid arterial system. Positron emission tomography (PET) was used to evaluate the regional hemodynamic status of the cerebral circulation. Clinical follow-up to 1 year post-PET was available for all patients. The incidence at 1 year of all strokes was 1/9 for patients with normal hemodynamics and 1/21 for patients with abnormal hemodynamics. The 1-year incidence of ipsilateral ischemic stroke was 1/9 for hemodynamically normal patients and 0/21 in the abnormal group. The 21 patients in the abnormal group fulfilled entry criteria for the Extracranial-Intracranial Bypass Trial. The 0/21 incidence of ipsilateral ischemic stroke at 1 year was compared with the 1-year rate of 0.109 for the 714 medically treated patients from the Bypass Trial. We were able to reject with better than 90% certainty (p = 0.089) the hypothesis that our sample of patients came from a population with an ipsilateral ischemic stroke rate of 0.109 or greater. Thus, in this small sample, we found no evidence that PET evidence of abnormal cerebral hemodynamics identifies a subgroup of patients at higher risk for early stroke if treated medically with antithrombotic drugs.


Fine-Grained Parcellation of Brain Connectivity Improves Differentiation of States of Consciousness During Graded Propofol Sedation.
Conscious perception relies on interactions between spatially and functionally distinct modules of the brain at various spatiotemporal scales. These interactions are altered by anesthesia, an intervention that leads to fading consciousness. Relatively little is known about brain functional connectivity and its anesthetic modulation at a fine spatial scale. Here, we used functional imaging to examine propofol-induced changes in functional connectivity in brain networks defined at a fine-grained parcellation based on a combination of anatomical and functional features. Fifteen healthy volunteers underwent resting-state functional imaging in wakeful baseline, mild sedation, deep sedation, and recovery of consciousness. Compared with wakeful baseline, propofol produced widespread, dose-dependent functional connectivity changes that scaled with the extent to which consciousness was altered. The dominant changes in connectivity were associated with the frontal lobes. By examining node pairs that demonstrated a trend of functional connectivity change between wakefulness and deep sedation, quadratic discriminant analysis differentiated the states of consciousness in individual participants more accurately at a fine-grained parcellation (e.g., 2000 nodes) than at a coarse-grained parcellation (e.g., 116 anatomical nodes). Our study suggests that defining brain networks at a high granularity may provide a superior imaging-based distinction of the graded effect of anesthesia on consciousness.


Necrotizing myelopathy associated with malignancy. A clinicopathologic study of two cases and literature review.
Two cancer patients had extensive spinal cord necrosis at necropsy. One had carcinoma of the breast and the other, carcinoma of the lung. Case 1 was treated by mastectomy, systemic chemotherapy and cranial irradiation, where as Case 2 received local irradiation to the right upper chest and right supraclavicular zone. In both cases, the spinal cord necrosis affected grey and white matter along most of its extent. Neither local nor systemic causes to explain the spinal cord lesion were disclosed at necropsy. It is suggested that these are two new examples of paraneoplastic necrotizing myelopathy. There are 22 such cases in the English language medical literature since 1903.


Clinical significance of dynamic pulmonary vascular resistance in two populations at risk of pulmonary arterial hypertension.
Patients at risk of pulmonary arterial hypertension (PAH) may present with abnormal dynamic pulmonary vascular resistance (PVR) during exercise. However, its clinical significance remains unclear. The present study aimed at analysing the meaning of dynamic PVR in two populations at risk of PAH: secundum atrial septal defect (ASD) and systemic sclerosis (SSc). Adult patients with corrected ASD were consecutively selected from the database of Pediatric and Congenital Heart Disease of the University Hospitals Leuven. Patients with SSc were consecutively selected from the rheumatology database of the University Hospital Liège. At inclusion, all underwent a rest and bicycle stress echocardiography to obtain baseline right heart characteristics and dynamic PVR. Routine follow-up echocardiography was performed. Twenty-eight patients with corrected ASD (mean age 41 ± 17 years, 79% female) were followed for a median time of 3.7 [inter-quartile range (IQR) 2.9-4.1] years. No patient developed PAH. Dynamic PVR was significantly associated with right atrial dilatation at latest follow-up (Spearman's ρ 0.51, P = 0.013). Forty-five SSc patients (mean age 54 ± 13 years, 76% female) were followed for a median time of 2.4 (IQR 0.8-2.9) years. Thirteen patients (30%) developed PAH. Dynamic PVR was the only independent predictor of PAH (hazards ratio 1.22, 95% confidence interval 1.01-1.47). No significant right heart morphometric changes occurred. Dynamic PVR predicted PAH development in patients with SSc, whereas dynamic PVR was associated with right heart morphometric changes after ASD closure. The predictive role of dynamic PVR might depend on the underlying disease type. Larger studies are needed to confirm this hypothesis.


High sensitivity hydrogen sensing with Pt-decorated porous gallium nitride prepared by metal-assisted electroless etching.
A unique hydrogen sensor structure based on Pt-decorated porous gallium nitride (PGaN) was fabricated by a two-step process consisting of metal-assisted electroless etching to produce PGaN with highly anisotropic pores followed by electroless deposition of Pt in the pores from an ammoniacal PtCl(6)(2-) solution. The Pt-decorated PGaN structure contains 50-100 nm diameter nanopores which are 400 nm to 1 microm deep and filled with Pt islands. Both electroless etching and deposition steps are done in solution and allow for large-scale production. An AC four-point probe conductivity measurement was implemented at f = 1 kHz, a frequency where the impedance of Pt-PGaN is nearly entirely resistive, and the change in conductance upon H(2) exposure was measured for three sample types: PGaN with a surface sputtered layer of Pt only; unetched GaN (CGaN) with both sputtered and electrolessly deposited Pt; and PGaN with both sputtered and electrolessly deposited Pt. The hydrogen sensing performance of the Pt-filled PGaN sensor was more than an order of magnitude better than either of the other two sample types under all experimental conditions, an observation attributed to the significant increase in Pt-GaN interfacial area in the electrolessly decorated PGaN samples, exhibiting a response to H2 concentrations as low as 1 ppm. The conductance changes are ascribed to adsorption-induced changes in interfacial polarization that produce changes in band bending and thus to the width of the space charge region near the Pt-GaN interface.


Hepatic lipase gene -514C/T polymorphism in the Guangxi Hei Yi Zhuang and Han populations.
Hei Yi Zhuang is an isolated subgroup of the Zhuang minority in China. This study was designed to compare the difference in the hepatic lipase gene (LIPC) -514C/T polymorphism and its association with lipid profiles between the Guangxi Hei Yi Zhuang and Han populations. Genotyping of the LIPC -514C/T was performed in 873 subjects of Hei Yi Zhuang and 867 participants of Han Chinese. The frequency of -514T allele was 43.47% in Hei Yi Zhuang, and 36.10% in Han (P < 0.001). The frequencies of CC, CT and TT genotypes were 30.01, 53.04 and 16.95% in Hei Yi Zhuang, and 40.95, 45.91 and 13.14% in Han (P < 0.001); respectively. Serum high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B levels in both ethnic groups were higher in LIPC -514T carriers than in C carriers. In addition, serum triglyceride levels in Han were higher in TT genotype individuals than in CC genotype subjects (P < 0.05). Serum HDL-C levels were positively correlated with age, alcohol consumption and LIPC -514C/T genotypes, and negatively associated with hypertension and cigarette smoking in Hei Yi Zhuang (P < 0.05-0.01), whereas HDL-C levels were positively correlated with age, alcohol consumption and LIPC -514C/T genotypes, and negatively associated with body mass index and cigarette smoking in Han (P < 0.05-0.001). The differences in serum HDL-C levels between the two ethnic groups might partially attribute to the differences in the LIPC -514C/T polymorphism.


Relaxation-encoded NMR experiments for mixture analysis: REST and beer.
A new family of NMR experiments for mixture analysis (Relaxation-Encoded Selective TOCSY, REST) allows the extraction of component subspectra from mixtures. It uses isotropic mixing to label whole spin systems with the relaxation times (e.g. T1, T2) of individual spins.


Improvement of glucose tolerance in NIDDM by clofibrate. Randomized double-blind study.
A randomized double-blind study was performed to examine the effect of clofibrate on glucose tolerance in subjects with non-insulin-dependent diabetes mellitus (NIDDM). Clofibrate (1.5 g/day) or placebo was administered to 70 patients and an oral glucose tolerance test (OGTT) was performed before and 12 wk after treatment. Blood glucose levels were significantly improved in clofibrate-treated groups at all time points during OGTT, whereas there was no change in insulin levels. Improvement of fasting glucose levels required 8 wk of clofibrate treatment. Insulin binding to erythrocytes demonstrated no significant change in the clofibrate-treated subjects. These results suggest that clofibrate improves glucose tolerance in NIDDM subjects without a change in insulin receptors and that clofibrate increases insulin sensitivity through an unknown postreceptor mechanism.


Training non-native vowel perception: In quiet or noise.
Noise makes speech perception much more challenging for non-native listeners than for native listeners. Training for non-native speech perception is usually implemented in quiet. It remains unclear if background noise may benefit or hamper non-native speech perception learning. In this study, 51 Chinese-native listeners were randomly assigned into three groups, including vowel training in quiet (TIQ), vowel training in noise (TIN), and watching videos in English as an active control. Vowel identification was assessed before (T1), right after (T2), and three months after training (T3) in quiet and various noise conditions. Results indicated that compared with the video watching group, the TIN group improved vowel identification in both quiet and noise significantly more at T2 and at T3. In contrast, the TIQ group improved significantly more in quiet and also in non-speech noise conditions at T2, but the improvement did not hold at T3. Moreover, compared to the TIQ group, the TIN group showed significantly less informational masking at both T2 and T3 and less energetic masking at T3. These results suggest that L2 speech training in background noise may improve non-native vowel perception more effectively than TIQ background only. The implications for non-native speech perception learning are discussed.


Double-blind evaluation of suprofen and aspirin in the treatment of periodontal pain.
A double-blind, randomized, parallel group, placebo-controlled study was carried out to compare the safety and efficacy of single doses of suprofen (200 mg and 400 mg) with aspirin (650 mg) and placebo in relieving pain. In patients with pain resulting from periodontal surgery, a single dose of suprofen 200 or 400 mg was significantly better than placebo in reducing pain intensity and providing pain relief. The superiority of both doses of suprofen over placebo was demonstrated in every parameter in which pain intensity or pain relief was calculated. In addition, both doses of suprofen were better than, or at least equivalent to, aspirin 650 mg in every efficacy measure including the patients' overall acceptability of treatment.


Outbreak of hind limb paralysis in young CFW Swiss Webster mice.
An outbreak of paralysis among 16- to 20-week-old CFW Swiss Webster sentinel mice developed in one of our barrier facilities. Two months after arrival and over a period of four weeks, six of 400 mice purchased from an approved vendor, developed progressive hind limb paralysis without other clinical signs of disease. On the basis of the histopathologic changes and negative serologic test results, lymphoblastic lymphoma causing compression of the spinal cord was diagnosed. There were two leading features to this outbreak: its unusual epidemiologic presentation, and the localization of the lesions principally in the lumbar muscles. A presumptive diagnosis of retroviral infection with Abelson's murine leukemia virus (A-MuLV) was established on the basis of histopathologic and immunohistochemical findings. Little is known about retroviral status in many commercial colonies, and few users report presence of spontaneous lymphomas. This report points out complications derived from commercially available animals that carry endogenous retroviruses. It also emphasizes the need of diagnosing and reporting clusters of hind limb paralysis or lymphomas in mice to assess the prevalence and relevance of retroviral infections in commercial colonies.


[Panic disorder and angina pectoris].
Panic attacks are a frequently cited cause of noncardiac chest pain. A strict separation of the internist's job (i. e., ruling out an "organic" cause of the patient's complaints) from the psychiatrist's job (e. g., diagnosing and treating panic disorder if present) may not always be the most efficient way of diagnostic work-up. We present the case of a 56-year-old female referred to our institution for elective coronary arteriography. Significant cardiovascular risk factors and symptoms compatible with unstable angina illustrate the common problem of a high probability of cardiac pathology in a patient with possible psychiatric symptoms. A modified SCID-interview complementing the coronary angiography results finally led to the definite diagnosis in this patient after symptoms had been present for over 20 years.


Monolimb paralysis after laparoscopic appendectomy due to conversion disorder.
Limb paralysis can develop for various reasons. We found a 13-year-old patient who became paralyzed in her lower extremities after laparoscopic appendectomy. Some tests, including electrodiagnostic studies and magnetic resonance imaging, were performed to evaluate the cause of lower limb paralysis. None of the tests yielded definite abnormal findings. We subsequently decided to explore the possibility of psychological problems. The patient was treated with simultaneous rehabilitation and psychological counseling. Paralysis of the patient's lower extremity improved gradually and the patient returned to normal life. Our findings indicate that psychological problems can be related to limb paralysis without organ damage in patients who have undergone laparoscopic surgical procedures.


How do breath and skin emissions impact indoor air chemistry?
People are an important source of pollution indoors, through activities such as cleaning, and also from "natural" emissions from breath and skin. This paper investigates natural emissions in high-occupancy environments. Model simulations are performed for a school classroom during a typical summer in a polluted urban area. The results show that classroom occupants have a significant impact on indoor ozone, which increases from ~9 to ~20 ppb when the pupils leave for lunch and decreases to ~14 ppb when they return. The concentrations of 4-OPA, formic acid, and acetic acid formed as oxidation products following skin emissions attained maximum concentrations of 0.8, 0.5, and 0.1 ppb, respectively, when pupils were present, increasing from near-zero concentrations in their absence. For acetone, methanol, and ethanol from breath emissions, maximum concentrations were ~22.3, 6.6, and 21.5 ppb, respectively, compared to 7.4, 2.1, and 16.9 ppb in their absence. A rate of production analysis showed that occupancy reduced oxidant concentrations, while enhancing formation of nitrated organic compounds, owing to the chemistry that follows from increased aldehyde production. Occupancy also changes the peroxy radical composition, with those formed through isoprene oxidation becoming relatively more important, which also has consequences for subsequent oxidant concentrations.


Rat interferons. Homologous and heterologus rat serum activity.
Serum proteins from normal rat serum and induced with Sindbis virus were separated on Sephadex G-100. Interferon activity was studied in a system of homologous REC and heterologous LG cells. Proteins of normal serum as well as induced serum emerged in two peaks separated by a deep saddle. Four hours after induction, the serum gave two peaks with similar interferon activity in both cell systems. After 8-hour induction, two interferons were also obtained, but activity in the heterologous system was much lower than in the homologous system. Electrophoresis in polyacrylamide gel and on paper showed that interferon activity is connected mainly with the alpha1-globulin fraction.


Intratumoral application of standardized mistletoe extracts down regulates tumor weight via decreased cell proliferation, increased apoptosis and necrosis in a murine model.
The cytotoxic in vitro activity of standardized mistletoe extracts (ME) was examined by established assays towards the human ductal breast carcinoma cell line BT474. A dose-dependent (optimum 25 mg/mL medium) and significantly (p < 0.05) enhanced cytotoxic activity towards the BT474 cells was demonstrated. In vivo experiments on the antitumor activity of ME-A and ME-M were performed in a BALB/c-mouse / BT474 ductal breast carcinoma model. ME-A and ME-M were intratumorally administered according to an application schedule which was found to be optimal concerning dosage and time of administration. Standardized intratumoral application of ME-A and ME-M induced a significantly (p < 0.05) decreased tumor weight in experimental mice. Histological investigations were performed comprising analysis of mitosis and proliferation rates (Ki67 expression), as well as necrosis and apoptosis induction (ssDNA detection). As compared to tumors of control mice with intratumoral phosphate-buffered saline (PBS) injections, tumors of the ME-A and ME-M treated groups showed a decreased cell proliferation rate, as well as an increased cell necrosis and apoptosis rate. Standardized mistletoe extracts, interfering with defined tumor cell functions, e.g., proliferation, necrosis and apoptosis, may have an impact on local cancer treatment.


Supply chain finance and innovation efficiency: An empirical analysis based on manufacturing SMEs.
This paper firstly demonstrates the positive and negative effects of supply chain finance on the innovation efficiency of China's small and medium-sized enterprises (SMEs) in the manufacturing industry from the theoretical point of view. Based on the data of 267 manufacturing companies in China Growth Enterprise Market from 2015 to 2019, the DEA-SBM method was used to measure the comprehensive innovation efficiency of different companies, and it was further decomposed into technological innovation efficiency and organizational innovation efficiency. Afterwards, it conducts an empirical analysis through the double fixed effect model, and explores the difference in the impact of supply chain finance on innovation efficiency in enterprises with different industries and different property rights. The results show that supply chain financial services have a strong positive impact on the comprehensive innovation efficiency, technological innovation efficiency and organizational innovation efficiency of manufacturing SMEs. Further, supply chain finance has the most significant improvement on the technological innovation efficiency of the sample of private traditional enterprises, but it has a significant inhibitory effect on the organizational innovation efficiency of the sample of state-owned high-tech enterprises. Therefore, this paper suggests that the development of supply chain financial services should increase support for traditional manufacturing industries; appropriately tilt resources to private enterprises; improve relevant supply chain financial laws and regulations, establish and improve corresponding institutional arrangements, and encourage state-owned enterprises to participate in market competition.


SOCIAL ORGANIZATION WITHIN CLONES OF THE SEA ANEMONE ANTHOPLEURA ELEGANTISSIMA.
The aggregating form of the anemone Anthopleura elegantissima often lives in closely packed groups composed of genetically identical individuals. These clonal aggregations remain separated from each other because contact between non-clonemates elicits intraspecific aggression (Francis, 1973a & b). Since the anemones live in a dependable environment, are long-lived, have indeterminate growth, and reproduce sexually and asexually, and since predation does not appear to be severe, intraspecific competition for space is quite important. The ability to distinguish clonemates from non-clonemates allows the anemones to benefit from group living while interfering with all other conspecific competitors. A high proportion of the costs of this intraspecific aggression is paid by the anemones living at interclonal borders. The interclonal border warriors have more and larger acrorhagi (specialized structures used in intraspecific aggression) than clonemates elsewhere in the aggregation and were without gonads in June when many of their clonemates were ripe. They are smaller on an average than midclone anemones but not smaller than clonemates from an edge of the aggregation remote from other clones. In the field, the fission rates of warrior anemones is not higher, and may be lower than that of clonemates in other parts of the same aggregation. Lack of gonads, small size, and low fission rates probably indicate that the warriors have less energy available for growth and reproduction than do their clonemates away from the battle zone. Without physical connections among the individuals, the ability to coordinate and communicate is limited. Each anemone responds to its particular circumstances, and in so doing may fortuitously benefit its clonemates. Natural selection acts on the genotype (the clone). This is a very simple form of social organization both functionally and evolutionarily.


[Intraoperative radiation therapy with high-energy electron beams].
Over the last two decades, intraoperative radiation therapy (IORT) has been developed using high-energy electron beams in Japan, and more recently in the United States and other countries. IORT is a potentially innovative treatment modality for radioresistant cancers of the brain, abdomen, pelvis, soft tissues and bone where local control is difficult to achieve by the conventional use of external beam irradiation. IORT may improve the therapeutic ratio of tumor control vs. normal tissue injury through the direct visualization of tumors at the time of surgical exploration which leads to precise determination of the target volume, by the physical exclusion (operative mobilization) of dose-limiting normal tissues and by the selection of appropriate electron-beam energies. In this article, the historical background, the biological and physical rationale and the clinical aspects are reviewed.


Risk of Hand Syndromes in Patients With Diabetes Mellitus: A Population-Based Cohort Study in Taiwan.
The aim of this study was to assess the overall and cause-specific incidences of diabetic hand syndromes (DHS) in patients with diabetes mellitus (DM) by using age and sex stratifications.The DM and control cohorts comprised 606,152 patients with DM and 609,970 age- and sex-matched subjects, respectively, who were followed up from 2000 to 2008. We estimated the incidence densities (IDs) of overall and cause-specific DHS, namely carpal tunnel syndrome (CTS), stenosing flexor tenosynovitis (SFT), limited joint mobility (LJM), and Dupuytren disease (DD), and calculated the hazard ratios (HRs) of DHS in relation to DM by using a Cox proportional hazards model with adjustment for potential confounders.Over a 9-year period, 51,207 patients with DM (8.45%) and 39,153 matched controls (6.42%) sought ambulatory care visits for various DHS, with an ID of 117.7 and 80.7 per 10,000 person-years, respectively. The highest cause-specific ID was observed for CTS, followed by SFT, LJM, and DD, regardless of the diabetic status. After adjustment for potential confounders, patients with DM had a significantly high HR of overall DHS (1.51, 95% confidence interval [CI] = 1.48-1.53). Men and women aged <35 years had the highest HR (2.64, 95% CI = 2.15-3.24 and 2.99, 95% CI = 2.55-3.50, respectively). Cause-specific analyses revealed that DM was more strongly associated with SFT (HR = 1.90, 95% CI = 1.86-1.95) and DD (HR = 1.83, 95% CI = 1.39-2.39) than with CTS (HR = 1.31, 95% CI = 1.28-1.34) and LJM (HR = 1.24, 95% CI = 1.13-1.35).Men and younger patients with DM have the highest risk of DHS. Certain hand syndromes, such as SFT and DD, were more strongly associated with DM than with other syndromes and require the attention of clinicians.


Narcissistic transformations in adolescence.
This paper traces the transformation of narcissism, paralleling the transformations of object love, occurring between early and late adolescence. Narcissism is examined in terms of three lines of development: erotic self-love, omnipotence, and the regulations of self-esteem. The transition occurs relatively rapidly in most normal and psychoneurotic individuals and involves a massive reorganization of the psyche. The acquisition of a body image of an adult sort probably acts an organizer. A normal consequence is the first romantic love relationship. An understanding of these issues is of importance in psychoanalytic psychotherapy of both adolescents and adults.


Approaches for identifying heat-vulnerable populations and locations: A systematic review.
Heat related morbidity and mortality, especially during extreme heat events, are increasing due to climate change. More Americans die from heat than from all other natural disasters combined. Identifying the populations and locations that are under high risk of heat vulnerability is important for urban planning and design policy making as well as health interventions. An increasing number of heat vulnerability/risk models and indices (HV/R) have been developed based on indicators related to population heat susceptibility such as sociodemographic and environmental factors. The objectives of this study are to summarize and analyze current HV/R's construction, calculation, and validation, evaluate the limitation of these methods, and provide directions for future HV/R and related studies. This systematic review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework and used 5 datasets for the literature search. Journal articles that developed indices or models to assess population level heat-related vulnerability or risks in the past 50 years were included. A total of 52 papers were included for analysis on model construction, data sources, weighting schemes and model validation. By synthesizing the findings, we suggested: (1) include relevant and accurately measured indicators; (2) select rational weighting methods and; (3) conduct model validation. We also concluded that it is important for future heat vulnerability models and indices studies to: (1) be conducted in more tropical areas; (2) include a comprehensive understanding of energy exchanges between landscape elements and humans; and (3) be applied in urban planning and policy making practice.


Oxidation State Engineering in Octahedral Ni by Anchored Sulfate to Boost Intrinsic Oxygen Evolution Activity.
Promoting the electron occupancy of active sites to unity is an effective method to enhance the oxygen evolution reaction (OER) performance of spinel oxides, but it remains a great challenge. Here, an in situ approach is developed to modify the valence state of octahedral Ni cations in NiFe2O4 inverse spinel via surface sulfates (SO42-). Different from previous studies, SO42- is directly anchored on the spinel surface instead of forming from uncontrolled conversion or surface reconstruction. Experiment and theoretical calculations reveal the precise adsorption sites and spatial arrangement for SO42- species. As a main promoting factor, surface SO42- effectively converts the crystal field stable Ni state (t2g6eg2) to the near-unity eg electron state (t2g6eg1). Moreover, the inevitable oxygen vacancies (Vo) further optimize the energy barrier of the potential-determining step (from OH* to O*). This co-modification strategy enhances turnover frequency-based electrocatalytic activity about two orders higher than the control sample without surface sulfates. This work may provide insight into the OER activity enhancement mechanism by the oxyanion groups.


[Results in the use of blood components separated by cytophoresis in leukemia treated with cytostatics (our 1st experiences with flowing-effect centrifuge)].
Since the essence of the malign process is still unknown, together with the basic causal principle (or principles?) of the pathological, malign growth, we, are not in position to apply the adequate, the only correct causal therapy with leukosis. As a consequence, we have numberous therapeutical diagrams with leukosis. As a consequence, we have numerous therapeutical diagrams in which there is adomination of pharmacological substances having cytostatic effects of anti-microbal, substitutional and symptomatical therapies. Cytostatics represent an expressedly different therapy. Various, very powerful cytostatic combinations and procedures applied with a desire to bring the patient into remission often cause the therapeutist to have another, very important problem: how to prevent the haematological complications using the cytostatic therapy, primarily the leukopenia and thrombocytopenia which, in bodies damaged by malign processes, can cause difficult complications. In order to avoid these, a series of new methods have been developed within the cytophoresis and haemotherapy. With the advent of separators of blood components it seems that the problem of selective and precise haemotherapy has been solved completely. Namely, if the components are applied precisely, in the stage when the patient lacks them in the desired concentration, the possibility of manifold therapeutical applications offer a possibility for an adequate subtitutional therapy. This paper brings forward our initial results from this field. The CENTRIFUGE-- AMINCO was used for seperation. The seperation in it takes place in a closed system (infection impossible), and thanks to special construction which simulates the internal medium of blood vessels, the mechanical decay of tangible components in the extracorporal medium has been reduced to a minimum. By means of adjustment of peristaltic pumps, the desired seperation is possible to be achieved. Concentrated components obtained by means of separation (leukocytes and thrombocytes, separated or together), have been applied with patients having leukosis once or several times, in the stage when they, due to cytostatic treatment, had very low values of these components with the existing or threatening complications. The substitional therapy has been applied with 14 patients and very efficient effects have been observed.


Adherent-free generation of functional dendritic cells from purified blood monocytes in view of potential clinical use.
There is increasing interest in dendritic cells (DC) that are capable of initiating antitumor immune responses. An in vitro cell differentiation method has recently been developed that uses GM-CSF and IL-4 to generate human DC from adherent blood mononuclear cells cultured on tissue culture plastic. These cells are competent for antigen uptake but express relatively low levels of co-stimulatory molecules and thus correspond to immature resident tissue DC. We have adapted this method to consider some variables that are pertinent to clinical use, including a large scale differentiation of functional DC in a culture system suitable for clinical use. We report here that sizable numbers of monocytes purified by elutriation from blood leukocytes and cultured in Teflon bags develop with high efficiency into typical DC, as defined by morphology and membrane phenotype. When compared with usual adherent DC, cells generated under our adherent-free conditions exhibited lower CD1a expression and antigen capture capacity, but maintained the ability to present soluble antigens to T cells. They neoexpressed a high level of the co-stimulator molecule B7-2 (CD86) and was potent accessory cells for T cell proliferation, but they lacked the CD83 marker of DC full maturation. This study may constitute a prerequisite step for clinical investigations in tumor immunotherapy.


Bacterial lipid modification of proteins for novel protein engineering applications.
Functioning of proteins efficiently at the solid-liquid interface is critical to not only biological but also modern man-made systems such as ELISA, liposomes and biosensors. Anchoring hydrophilic proteins poses a major challenge in this regard. Lipid modification, N-acyl-S-diacylglyceryl-Cys, providing an N-terminal hydrophobic membrane anchor is a viable solution that bacteria have successfully evolved but remains unexploited. Based on the current understanding of this ubiquitous and unique bacterial lipid modification it is possible to use Escherichia coli, the popular recombinant protein expression host, for converting a non-lipoprotein to a lipoprotein with a hydrophobic anchor at the N-terminal end. We report two strategies applicable to non-lipoproteins (with or without signal sequences) employing minimal sequence change. Taking periplasmic Shigella apyrase as an example, its signal sequence was engineered to include a lipobox, an essential determinant for lipid modification, or its mature sequence was fused to the signal sequence of abundant outer membrane lipoprotein, Lpp. Lipid modification was proved by membrane localization, electrophoretic mobility shift and mass spectrometric analysis. Substrate specificity and specific activity measurements indicated functional integrity after modification. In conclusion, a convenient protein engineering strategy for converting non-lipoprotein to lipoprotein for commercial application has been devised and tested successfully.


Male and Female Sexual Dysfunction in Pediatric Cancer Survivors.
Pediatric cancer survivors suffer indirect long-term effects of their disease; however, there is a paucity of data regarding the effect of pediatric cancer survivorship on sexual function. To assess the prevalence and risk factors associated with sexual dysfunction among pediatric cancer survivors. Pediatric cancer survivors were recruited to complete an online survey using the Female Sexual Function Index (FSFI) or the International Index of Erectile Function (IIEF-5), both validated questionnaires to assess female sexual dysfunction (FSD) and erectile dysfunction (ED). Patient demographics, oncologic history, prior treatment, and sexual habits were also queried. Logistic regression was used to evaluate risk factors for sexual dysfunction, and Mann-Whitney U test was used to identify factors associated with individual domains of the FSFI. The main outcome measures were FSFI and IIEF-5 score, which are used to diagnose FSD (FSFI<26.55) and ED (IIEF-5<22). A total of 21 (72.4%) female respondents and 20 (71.4%) male respondents were sexually active and completed the survey and FSFI or IIEF-5 questionnaire, respectively. Mean (±SD) age was 23.7 (4.1) years, and average age at diagnosis was 9.1 (5.0), with no difference between genders. Overall, 25.0% (5/20) of male and 52.4% (11/21) of female pediatric cancer survivors reported sexual dysfunction (P = .11). Oncologic history and prior treatment were not associated with sexual function. Females who reported difficulty relaxing during intercourse in the last 6 months had higher odds of reporting sexual dysfunction (odds ratio: 13.6, 95% confidence interval: 1.2-151.2, P = .03). Subgroup analysis of FSFI domains found that previous radiation therapy was correlated with decreased lubrication and satisfaction during intercourse, whereas previous treatment to the pelvic region significantly reduced satisfaction and increased pain during intercourse. Female pediatric cancer survivors have higher odds of reporting sexual dysfunction after treatment and should be screened appropriately to provide early intervention and to mitigate risk. Our study includes validated questionnaires to assess FSD and ED and queries specific characteristics to assess their association with sexual dysfunction. However, the study is limited by sample size and its cross-sectional survey design. The prevalence of female sexual dysfunction in this cohort is higher than that in the general population of equivalent-aged individuals, and clinicians should be aware of these potential long-term sequelae. Greenberg DR, Khandwala YS, Bhambhvani HP, et-al. Male and Female Sexual Dysfunction in Pediatric Cancer Survivors. J Sex Med 2020;17:1715-1722.


Research governance and students: what are NHS trusts looking for?
Student research in the National Health Service (NHS) must now be conducted within the framework of research governance and research ethics. In this paper, Tony Soteriou and Gill Hek highlight the considerations that undergraduate, post-registration and postgraduate students, as well as their supervisors and course lecturers need to make at the outset of planning student research in the NHS.


High D-glucose does not affect binding of alpha-tocopherol to human erythrocytes.
The role of alpha-tocopherol uptake system in human erythrocyte in the uptake of plasma alpha-tocopherol has been suggested. However no information is available on alpha-tocopherol uptake activity of human erythrocytes in the presence of high levels of D-glucose which is known to lead to pathological alterations in different cells including human erythrocytes. Therefore, in order to examine the effect of D-glucose on the binding of alpha-tocopherol to human erythrocytes, the binding characteristics of alpha-tocopherol to these cells were established first. Binding of [3H]alpha-tocopherol to human erythrocytes was both saturable and specific. Scatchard analysis of alpha-tocopherol binding to these cells showed the presence of two independent classes of binding sites with widely different affinities. The high affinity binding sites had a dissociation constant (Kd1) of 90 nM with a binding capacity (n1) of 900 sites per cell, whereas the low affinity binding sites had a dissociation constant (Kd2) of 5.2 microM and a binding capacity (n2) of 105,400 sites per cell. Trypsin treatment abolished all the alpha-tocopherol binding activity. Competition for the binding of alpha-tocopherol to human erythrocytes was effective with other homologues of alpha-tocopherol (beta-tocopherol, gamma-tocopherol and delta-tocopherol) and their potency was almost equal to alpha-tocopherol itself. The order of preference was alpha-tocopherol > beta-tocopherol > or = gamma-tocopherol > or = delta-tocopherol. Incubation of human erythrocytes with various concentrations of D-glucose did not affect alpha-tocopherol uptake activity. Our data demonstrate the presence of an alpha-tocopherol uptake system in human erythrocytes and that the alpha-tocopherol uptake activity is not modulated by the presence of D-glucose.