Present and future trends in research and clinical applications of inodilators.
The rationale of combining vasodilatation with positive inotropic intervention in the treatment of chronic heart failure has found a new implementation in the "inodilator" drugs. Inodilators are characterized by the properties of exerting positive inotropic effect and inducing systemic vasodilatation. The cellular mechanisms involved in the regulation of contractility of cardiac and vascular muscle and the pathophysiological events occurring in heart failure are briefly discussed, and the pharmacological profile as well as the therapeutic use of these drugs are reviewed. On the basis of the mechanism of action, two groups of inodilators are distinguished, the phosphodiesterase inhibitors and the dopaminergic agents. The increase of [cAMP]i induced by the phosphodiesterase inhibitors is responsible for their vasodilating effect and for the positive inotropic action, but many of them have in addition the ability to enhance the Ca2+ sensitivity of cardiac contractile proteins. The complex organization and the cardinal role of the catecholaminergic receptor system in the control of cardiovascular function and its contribution to the pathophysiological events occurring in heart failure are the rational basis of the therapeutic use of dopaminergic agents. These drugs, acting on DA, beta-, and alpha-receptors, exert not only positive inotropic and vasodilating effects, but also a diuretic action, and can reduce aldosterone and renin secretion, blunt an excessive sympathetic activity, and possibly promote the release of atrial natriuretic peptide. The multireceptor mechanism of dopamine-like drugs, which accounts for their favorable hemodynamic, neurohumoral, and diuretic effects, represents the most promising approach to inodilator therapy.


Chlorophyll fluorescence emission can screen cold tolerance of cold acclimated Arabidopsis thaliana accessions.
An easy and non-invasive method for measuring plant cold tolerance is highly valuable to instigate research targeting breeding of cold tolerant crops. Traditional methods are labor intensive, time-consuming and thereby of limited value for large scale screening. Here, we have tested the capacity of chlorophyll a fluorescence (ChlF) imaging based methods for the first time on intact whole plants and employed advanced statistical classifiers and feature selection rules for finding combinations of images able to discriminate cold tolerant and cold sensitive plants. ChlF emission from intact whole plant rosettes of nine Arabidopsis thaliana accessions was measured for (1) non-acclimated (NAC, six week old plants grown at room temperature), (2) cold acclimated (AC, NAC plants acclimated at 4°C for two weeks), and (3) sub-zero temperature (ST) treated (STT, AC plants treated at -4°C for 8 h in dark) states. Cold acclimation broadened the slow phase of ChlF transients in cold sensitive (Co, C24, Can and Cvi) A. thaliana accessions. Similar broadening in the slow phase of ChlF transients was observed in cold tolerant (Col, Rsch, and Te) plants following ST treatments. ChlF parameters: maximum quantum yield of PSII photochemistry (FV/FM) and fluorescence decrease ratio (RFD) well categorized the cold sensitive and tolerant plants when measured in STT state. We trained a range of statistical classifiers with the sequence of captured ChlF images and selected a high performing quadratic discriminant classifier (QDC) in combination with sequential forward floating selection (SFFS) feature selection methods and found that linear combination of three images showed a reasonable contrast between cold sensitive and tolerant A. thaliana accessions for AC as well as for STT states. ChlF transients measured for an intact whole plant is important for understanding the impact of cold acclimation on photosynthetic processes. Combinatorial imaging combined with statistical classifiers and feature selection methods worked well for the screening of cold tolerance without exposing plants to sub-zero temperatures. This opens up new possibilities for high-throughput monitoring of whole plants cold tolerance via easy and fully non-invasive means.


Extending the dynamic range of biomarker quantification through molecular equalization.
Precision medicine requires highly scalable methods of multiplexed biomarker quantification that can accurately describe patient physiology. Unfortunately, contemporary molecular detection methods are generally limited to a dynamic range of sensitivity spanning just 3-4 orders of magnitude, whereas the actual physiological dynamic range of the human plasma proteome spans more than 10 orders of magnitude. Current methods rely on sample splitting and differential dilution to compensate for this mismatch, but such measures greatly limit the reproducibility and scalability that can be achieved-in particular, the effects of non-linear dilution can greatly confound the analysis of multiplexed assays. We describe here a two-pronged strategy for equalizing the signal generated by each analyte in a multiplexed panel, thereby enabling simultaneous quantification of targets spanning a wide range of concentrations. We apply our 'EVROS' strategy to a proximity ligation assay and demonstrate simultaneous quantification of four analytes present at concentrations spanning from low femtomolar to mid-nanomolar levels. In this initial demonstration, we achieve a dynamic range spanning seven orders of magnitude in a single 5 µl sample of undiluted human serum, highlighting the opportunity to achieve sensitive, accurate detection of diverse analytes in a highly multiplexed fashion.


Assessment of a new disposable introducer for spinal needles.
The compatibility between spinal needles and their introducers varies between manufacturers and can significantly influence the usable length of the spinal needle available resulting in failure to locate CSF in larger patients. The usable length of 90-mm pencil point spinal needles from four manufacturers ranged from 68 to 79 mm when the needle was used in combination with its introducer. A new purpose-built introducer needle is described which, when used with a 25 g or finer spinal needle, maximises the usable length of the needle. Using this new introducer the usable needle length of a 90-mm Whitacre needle was increased by a further 7 to 86 mm resulting in only a 4 mm loss of total needle length. The new introducer was well received by users.


Stereospecific assignments of side-chain protons and characterization of torsion angles in Eglin c.
Stereospecific assignments were obtained in the protein Eglin c for beta-methylene protons of 9 out of the 24 residues with AMX symmetry, for three residues with long side chains and for the gamma-methyl groups of 8 out of the 11 valines. This was achieved by analyzing the cross-peak multiplet structures in two-dimensional correlated spectra with spectral simulations and peak fitting, and by quantitative measurements of intraresidue nuclear Overhauser enhancements. In addition to the stereospecific assignments, information on the torsion angles phi and chi 1 was obtained. To estimate inferences of internal motions on this analysis, the effect of uniform averaging within a certain range of the torsion angle chi 1 on cross-peak multiplet structures and on relative intraresidue nuclear Overhauser enhancement is discussed.


Comparative studies on the effects of bradykinin and vagal stimulation on motility in the stomach and colon.
The effect of bradykinin on gastric and colonic motility was studied in anaesthetized cats with volume recording devices and compared with the effects of vagal nerve stimulation. When administered intrarterially bradykinin caused a profound and prolonged gastric relaxation. Stimultaneously there was a marked and likewise prolonged colonic contraction. The gastric relaxation closely mimicked the atropine resistant relaxation elicited by vagal nerve stimulation. These effects could not be blocked by antiadrenergic drugs and it is suggested that bradykinin and the unknown transmittor substance(s) released on vagal stimulation act in a similar way on the gastric smooth muscles and that a kinin mechanism may be involved in the vagal response. As regards the colonic motor response it was shown that bradykinin does not reproduce the vagal motility effects on colon smooth muscle but mimicks closely the atropine resistant expulsive contraction elicited by activation of the pelvic nerves.


Clinical impact of human papillomavirus in laryngeal squamous cell carcinoma: a retrospective study.
The purpose of this study is to determine the prevalence and clinical impact of human papillomavirus (HPV) related laryngeal squamous cell carcinoma (LSCC). A total of 106 LSCC patients who underwent primary surgical resection with or without adjuvant radiotherapy/chemoradiotherapy were enrolled retrospectively. Tumors collected from paraffin-embedded samples were used for HPV detection by polymerase chain reaction and in situ hybridization technique. Clinicopathological parameters were recorded for analysis. The prevalence of HPV in patients with LSCC was 13.2% in our series and 12 out of 14 (85.7%) HPV-positive tumors were HPV-16. The patients with HPV-positive tumors were older (p = 0.042), less local/regional recurrence (p = 0.037) and non-smoker (p = 0.068). There was no significant difference in the 5-year overall survival (OS) (p = 0.8056) between HPV-positive and -negative tumors. The patients with HPV-positive tumors had a better 5-year disease-specific survival (DSS) (100% vs. 84.8%, p = 0.1485), although the difference did not reach statistical significance. However, the local/regional control rate was significantly better in HPV-positive tumors than in HPV-negative tumors (100% vs. 75%, p = 0.0494). A low prevalence of HPV infection in our series suggests that HPV is not a major cause of LSCC. However, a 100% local/regional control rate and DSS were observed in HPV-positive tumors. This finding suggests a different tumor behavior between HPV-positive and HPV-negative LSCC. Further research with a larger sample size is necessary to confirm our observations.


THE SENSORY BASIS OF SEXUAL SELECTION FOR COMPLEX CALLS IN THE TÚNGARA FROG, PHYSALAEMUS PUSTULOSUS (SEXUAL SELECTION FOR SENSORY EXPLOITATION).
Male túngara frogs (Physalaemus pustulosus) vocalize to attract females, and enhance the attractiveness of their simple, whine-only call by adding chucks to produce complex calls. Complex calls contain more total energy and are of longer duration. By virtue of the greater frequency range of the chuck, complex calls also simultaneously stimulate both the amphibian papilla and the basilar papilla of the frog's inner ear. Female phonotaxis experiments using synthetic stimuli demonstrate that an increase in the call's acoustic energy is not sufficient to account for the enhanced attractiveness of the complex call. However, the stimulation of either or both of the female's sound-sensitive inner-ear organs is sufficient to elicit her preference. We suggest that the female's sensory system generates selection that equally favors at least three evolutionary alternatives for enhancing call attractiveness and that historical constraints imposed by the male's morphology determined which of the alternatives was more likely to evolve. These data are consistent with our hypothesis of sensory exploitation, which states that selection favors those traits that elicit greater stimulation from the female's sensory system and which emphasizes the nonadaptive nature of female preference.


HYDRATION IN THE SAND SHRIMP CRANGON SEPTEMSPINOSA: RELATION TO DIET.
Tissue hydration in the estuarine sand shrimp Crangon septemspinosa is correlated with nutritional conditions. Hydration levels of shrimp who are ingesting food remain normal. In starved shrimp or in individuals who are not ingesting adequate amounts of food, hydration levels are high. Presumably, water replaces metabolized tissues.


[Hirsutism - etiopathogenesis, diagnostics and treatment].
Hirsutism is defined as excessive terminal hair growth in distribution typical for postpubertal men. It affects approximately 5-10 % of women and most frequently manifests in puberty. Significant cosmetic stigmatization is the usual complaint that brings patient to the doctor and it is crucial to always rule out any primary underlying disease causing hirsutism - benign or malignant. In this review etiopathogenesis, diagnostic procedures and treatment options are discussed.


Mesangial cells are responsible for orchestrating the renal podocytes injury in the context of malignant hypertension.
Two populations of renal cells fully possess functional contractile cell apparatus: mesangial cells and podocytes. Previous studies demonstrated that in the context of malignant hypertension overproduction of Angiotensin-II by the contracting mesangial cells aggravated hypercellularity and apoptosis of adjacent cell populations. The role of podocytes in pathogenesis of malignant hypertension is unclear. We investigated responsiveness of normal vs. hyperglycaemic podocytes to pressure in a model of malignant hypertension. Rat renal podocytes and mesangial cells were subjected to high hydrostatic pressure, using an in vitro model of malignant hypertension. Part of them was pre-exposed to hyperglycaemic medium. Alternatively, the cells were cultured in conditioned medium collected from mesangial cells pre-exposed to pressure. Angiotensin-II was significantly increased in normoglycaemic mesangial cells subjected to pressure, triggering enhanced proliferation and apoptosis. No augmented Angiotensin-II, proliferation or apoptosis were evident in pressure-exposed normoglycaemic podocytes. In hyperglycaemic mesangial cells, but not podocytes, basal Angiotensin-II and apoptosis were augmented, along with abrogated proliferation. Challenge with exogenous Angiotensin-II or Angiotensin-II-containing conditioned medium, induced apoptosis both in podocytes and mesangial cells. 1. Unlike mesangial cells, podocytes do not respond to high pressure or hyperglycaemia per se. Resultantly, neither high pressure nor hyperglycaemia, trigger apoptosis of podocytes in vitro. However, surplus of Angiotensin-II, amply produced in vivo by the adjacent mesangial cells, would seem to be sufficient for initiating apoptosis of both mesangial cells and podocytes. 2. Hyperglycaemia abrogates cell replication. Resultantly, in diabetic patients regeneration of renal tissue damaged by the incidence of malignant hypertension may become compromised or completely lost.


Metabolic profiling of two maize (Zea mays L.) inbred lines inoculated with the nitrogen fixing plant-interacting bacteria Herbaspirillum seropedicae and Azospirillum brasilense.
Maize roots can be colonized by free-living atmospheric nitrogen (N2)-fixing bacteria (diazotrophs). However, the agronomic potential of non-symbiotic N2-fixation in such an economically important species as maize, has still not been fully exploited. A preliminary approach to improve our understanding of the mechanisms controlling the establishment of such N2-fixing associations has been developed, using two maize inbred lines exhibiting different physiological characteristics. The bacterial-plant interaction has been characterized by means of a metabolomic approach. Two established model strains of Nif+ diazotrophic bacteria, Herbaspirillum seropedicae and Azospirillum brasilense and their Nif- couterparts defficient in nitrogenase activity, were used to evaluate the impact of the bacterial inoculation and of N2 fixation on the root and leaf metabolic profiles. The two N2-fixing bacteria have been used to inoculate two genetically distant maize lines (FV252 and FV2), already characterized for their contrasting physiological properties. Using a well-controlled gnotobiotic experimental system that allows inoculation of maize plants with the two diazotrophs in a N-free medium, we demonstrated that both maize lines were efficiently colonized by the two bacterial species. We also showed that in the early stages of plant development, both bacterial strains were able to reduce acetylene, suggesting that they contain functional nitrogenase activity and are able to efficiently fix atmospheric N2 (Fix+). The metabolomic approach allowed the identification of metabolites in the two maize lines that were representative of the N2 fixing plant-bacterial interaction, these included mannitol and to a lesser extend trehalose and isocitrate. Whilst other metabolites such as asparagine, although only exhibiting a small increase in maize roots following bacterial infection, were specific for the two Fix+ bacterial strains, in comparison to their Fix- counterparts. Moreover, a number of metabolites exhibited a maize-genotype specific pattern of accumulation, suggesting that the highly diverse maize genetic resources could be further exploited in terms of beneficial plant-bacterial interactions for optimizing maize growth, with reduced N fertilization inputs.


Niacin ameliorates ulcerative colitis via prostaglandin D2-mediated D prostanoid receptor 1 activation.
Niacin, as an antidyslipidemic drug, elicits a strong flushing response by release of prostaglandin (PG) D2 However, whether niacin is beneficial for inflammatory bowel disease (IBD) remains unclear. Here, we observed niacin administration-enhanced PGD2 production in colon tissues in dextran sulfate sodium (DSS)-challenged mice, and protected mice against DSS or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in D prostanoid receptor 1 (DP1)-dependent manner. Specific ablation of DP1 receptor in vascular endothelial cells, colonic epithelium, and myeloid cells augmented DSS/TNBS-induced colitis in mice through increasing vascular permeability, promoting apoptosis of epithelial cells, and stimulating pro-inflammatory cytokine secretion of macrophages, respectively. Niacin treatment improved vascular permeability, reduced apoptotic epithelial cells, promoted epithelial cell update, and suppressed pro-inflammatory gene expression of macrophages. Moreover, treatment with niacin-containing retention enema effectively promoted UC clinical remission and mucosal healing in patients with moderately active disease. Therefore, niacin displayed multiple beneficial effects on DSS/TNBS-induced colitis in mice by activation of PGD2/DP1 axis. The potential efficacy of niacin in management of IBD warrants further investigation.


Short-term functional outcomes of first metatarsophalangeal total joint replacement for hallux rigidus.
Although metatarsophalangeal (MTP) arthrodesis has been advocated by many authors, implant arthroplasty appears to be successful option in advanced hallux rigidus (HR). The aim of our study was to evaluate the early results of the ToeFit-Plus prosthesis for the treatment of HR. Between December 2007 and January 2011, a total of 26 toes of 24 patients with MTP arthritis of the great toe were treated with ToeFit-Plus implant. The average follow-up time was 29.9 (range: 25 to 62) months. All patients were evaluated clinically and radiographically. Postoperative satisfaction and function were scored according to the American Orthopaedic Foot and Ankle Society (AOFAS) score. Pain was assessed with the use of a visual analogue scale. Mean preoperative AOFAS score improved from 42.7 (range: 36 to 59) to 88.5 (range: 59 to 98) at the final follow-up (P < .01). Preoperative average visual analogue scale pain scores improved from 7.4 preoperatively to 1.9 at the final follow-up (P < .01). The average MTP joint range of motion improved from 25.9 degrees preoperatively to 53.8 degrees at the final follow-up. No radiologic loosening was found, but radiolucency was observed in 2 patients with this implant. No revision was required for any of the patients during the follow-up period. This total first MTP joint prosthesis yielded good functional outcome and high patient satisfaction level with low early complication rate. Preservation of joint movement and good pain relief with early mobilization were the advantages of this procedure. Salvage arthrodesis remains an option if future revisions are indicated. Level IV, retrospective case series.


Molecular targets in metastasis: lessons from genomic approaches.
Microarray studies have yielded valuable information that can be used to determine a cancer patient's prognosis and allow for optimum treatment choices. Tumor profiling has also changed our perception of metastatic propensity. Genomic analyses clearly showed that a metastasis signature is encoded within the genome so that when a cancer develops, the likelihood of metastasis is high, whereas other cancers which do not have this genotype metastasize as a result of random mutations. It is certain however, that cells other than tumor cells contribute to the development of metastasis through their production of various pro-metastatic proteins. Here, we review the published metastasis profiling studies and the role of the host in metastasis. Collagen type I, CXCR4, CSF-1, OPN and RhoC are metastasis-associated genes for which evidence exists for a causal contribution to elements of the metastatic process. These genes are discussed in detail and represent excellent drug targets for anti-metastasis therapies.


Protodioscin (NSC-698 796): its spectrum of cytotoxicity against sixty human cancer cell lines in an anticancer drug screen panel.
Protodioscin (NSC-698 796) is a furostanol saponin isolated from the rhizome of Dioscorea collettii var. hypoglauca (Dioscoreaceae), a Chinese herbal remedy for the treatment of cervical carcinoma, carcinoma of urinary bladder and renal tumor for centuries. To systematically evaluate its potential anticancer activity, protodioscin was tested for cytotoxicity in vitro against 60 human cancer cell lines in the NCI's (National Cancer Institute, USA) anticancer drug screen. As a result, protodioscin was cytotoxic against most cell lines from leukemia and solid tumors in the NCI's human cancer panel, especially selectively against one leukemia line (MOLT-4), one NSCLC line (A549/ATCC), two colon cancer lines (HCT-116 and SW-620), one CNS cancer line (SNB-75), one melanoma line (LOX IMVI), and one renal cancer line (786 - 0) with GI50 < or = 2.0 microM. In the general view of mean graphs, leukemia, colon cancer and prostate cancer are the most sensitive subpanels, while ovarian cancer is the least sensitive subpanel. Based on an analysis of COMPARE computer program with protodioscin as a seed compound, no compounds in the NCI's anticancer drug screen database have cytotoxicity patterns (mean graphs) similar to those of protodioscin, indicating that a potential novel mechanism of anticancer action is involved.


Obstructive sleep apnea and cognition: insights gleaned from bibliometric analysis.
Obstructive sleep apnea (OSA) is associated with cognitive impairment. However, the broad trends of the research publications on OSA and cognition are unclear. This study aimed to investigate patterns of research on the relationship between OSA and cognitive function using bibliometric analysis and to identify future research directions by analyzing research trends and emerging hotspots in the field. We searched Web of Science for relevant publications from 2003 to 2022 and conducted a bibliometric analysis of OSA and cognitive research using CiteSpace, R, and VOSviewer. A total of 1995 articles met the eligibility criteria for the analysis of OSA and cognition research. There was a notable increase in publications over time, with significant contributions from the United States, particularly Harvard University, leading to substantial academic impact. Gozal D emerged as the most prolific author (59 articles) and influential researcher (3,612 citations) in this field. Hotspot analysis revealed that investigating the pathological physiology and mechanisms of OSA-associated cognitive dysfunction is a recent area of focus, while burst detection analysis identified sleep quality and mild cognitive impairment as top investigation topics. The study by Canessa N published in the American Journal of Respiratory and Critical Care Medicine received the highest number of 77 citations. Researchers are increasingly focusing on OSA and cognition. Currently, the majority of studies on OSA-related cognitive dysfunction are focused on correctable aspects of the condition. Future investigations into the pathology of OSA-induced cognitive impairment will facilitate more precise therapeutic interventions.


Prostanoid response in the kidney of hypertensive subjects as part of renal counteraction to gallopamil-induced blood pressure decrease.
The purpose of the study was to characterize the renal TxA2, PGI2 and PGF2 alpha release in response to arterial blood pressure (BP) fall induced by systemic and intrarenal vasorelaxation in subjects with essential hypertension. Significantly enhanced TxB2- and PGF2 alpha excretion and no change in ratio TxB2/6-keto-PGF1 alpha were found in urine in hypertensive patients after administration of the Ca++ entry blocker gallopamil, used to induce BP fall. This response was associated with significant PRA elevation in peripheral venous samples. In in vitro experiments, direct and indirect effects of gallopamil on renal tissue could be distinguished. Gallopamil resulted in significant diminution of TxA2 production and a decrease in TxB2/6-keto PGF1 alpha ratio in incubated rat kidney slices. This model was also used to test biochemically the effect of reflex sympathetic activation on prostanoid generation in kidney. It was concluded that this mechanism was only one among the indirect mechanisms by which gallopamil could induce that renal prostanoid response in hypertensive subjects. The response in urinary TxB2- and PGF2 alpha excretion was found to be significantly related to the changes in sodium reabsorption. These results suggested, that the increase in renal TxA2 and PGF2 alpha production in response to systemic and intrarenal "vasodilation" induced by gallopamil in hypertensive subjects can be interpreted as part of counteraction of the kidneys to BP fall.


Colorectal cancer patients with low abundance of KRAS mutation may benefit from EGFR antibody therapy.
Epidermal growth factor receptor monoclonal antibody was approved for treatment of metastatic colorectal cancer patients carrying KRAS wild type DNA. However, recent studies showed that patients with KRAS G13D mutation may benefit from EGFR antibody therapy. In this study we tried to explore whether the abundance of KRAS mutation could affect the efficacy of EGFR antibody therapy. We firstly established a PNA-PCR method which could calculate the percentage of KRAS mutation in total DNA and proved its ability on 47 colorectal cancer samples bearing KRAS mutations. Then we analyzed the correlation between the abundance of KRAS mutations and efficacy of EGFR antibody therapy in another 35 metastatic colorectal cancer patients. We proved that PNA-PCR assay could calculate the abundance of KRAS mutation and the percentage of mutant DNA in tumor cells varied a lot (10.8%∼98.3%) on the 47 colorectal cancer patients. The efficacy of EGFR antibody correlated with the abundance of KRAS mutations: in the KRAS mutation less than 30% group, the disease control rate was 44.4% (4/9); the disease control rate of 30∼80% group was 5.6% (1/18) and the >80% group was 12.5% (1/8) (P = 0.038). In summary, our study showed that PNA-PCR method could easily detect the percentage of KRAS mutation in tumor cells and colorectal cancer patients with low abundance of KRAS mutation might benefit from EGFR antibody therapy.


Current standards of care for inpatient glycemic management and metabolic control: is it time for definite standards and targets?
To review the available literature on the presence of diabetes in the inpatient population and its effect on outcomes. Diabetes is a progressively worsening epidemic in the United States. Patients with diabetes have a disproportionate representation among the inpatient population in this country, and their share of total health-care costs is both disproportionate and growing rapidly. Patients with diabetes are often admitted to the hospital not primarily because of their diabetes but rather because of the need for treatment of the end-stage complications of diabetes, such as cardiovascular, cerebrovascular, and peripheral vascular disease as well as diabetic nephropathy and retinopathy, or because of unrelated illnesses for which diabetes is a complication. Diabetes is a frequent comorbid condition and increases the duration of hospitalization by 1 to 2 days. Numerous organizations have issued guidelines for outpatient diabetes management and metabolic control and have updated them periodically; however, no such guidelines or standards have been formulated for inpatient diabetes management. In view of a rapidly growing body of evidence suggesting that enhanced glycemic control decreases morbidity and mortality in patients with hyperglycemia, such as those with new-onset diabetes, as well as in patients with previously established diabetes, the creation of clearly defined standards and targets for inpatient management of hyperglycemia and metabolic control seems important for improvement of outcomes in hospitalized patients with diabetes.


Quantitative comparison of initial soil erosion processes and runoff generation in Spanish and German vineyards.
The aim of this study was to enable a quantitative comparison of initial soil erosion processes in European vineyards using the same methodology and equipment. The study was conducted in four viticultural areas with different characteristics (Valencia and Málaga in Spain, Ruwer-Mosel valley and Saar-Mosel valley in Germany). Old and young vineyards, with conventional and ecological planting and management systems were compared. The same portable rainfall simulator with identical rainfall intensity (40mmh(-1)) and sampling intervals (30min of test duration, collecting the samples at 5-min-intervals) was used over a circular test plot with 0.28m(2). The results of 83 simulations have been analysed and correlation coefficients were calculated for each study area to identify the relationship between environmental plot characteristics, soil texture, soil erosion, runoff and infiltration. The results allow for identification of the main factors related to soil properties, topography and management, which control soil erosion processes in vineyards. The most important factors influencing soil erosion and runoff were the vegetation cover for the ecological German vineyards (with 97.6±8% infiltration coefficients) and stone cover, soil moisture and slope steepness for the conventional land uses.


Serum proteins of gnotobiotic rats.
Cellulose-acetate and agar gel immunoelectrophoresis were used to study the serum protein patterns of germfree rats before and after monoassociation with a pure culture of Staphylococcus aureus (phage type 80/81), Streptococcus faecalis, Lactobacillus acidophilus, Bacteroides fragilis, Pseudomonas aeruginosa, or Proteus vulgaris. All six bacteria quickly established themselves in the gastrointestinal tract of the germfree rat, and all six increased the animals' total serum proteins. Only S. aureus and P. aeruginosa caused a noticeable rise in gamma globulins. L. acidophilus, S. faecalis, and B. fragilis multiplied readily in the gastrointestinal tract but caused only minimal alterations in the serum proteins. P. vulgaris caused a marked increase in the alpha and beta, but not the gamma globulins.


Active Brownian motion with directional reversals.
Active Brownian motion with intermittent direction reversals is common in bacteria like Myxococcus xanthus and Pseudomonas putida. We show that, for such a motion in two dimensions, the presence of the two timescales set by the rotational diffusion constant D_{R} and the reversal rate γ gives rise to four distinct dynamical regimes: (I) t≪min(γ^{-1},D_{R}^{-1}), (II) γ^{-1}≪t≪D_{R}^{-1}, (III) D_{R}^{-1}≪t≪γ^{-1}, and (IV) t≫max(γ^{-1}, D_{R}^{-1}), showing distinct behaviors. We characterize these behaviors by analytically computing the position distribution and persistence exponents. The position distribution shows a crossover from a strongly nondiffusive and anisotropic behavior at short times to a diffusive isotropic behavior via an intermediate regime, II or III. In regime II, we show that, the position distribution along the direction orthogonal to the initial orientation is a function of the scaled variable z∝x_{⊥}/t with a nontrivial scaling function, f(z)=(2π^{3})^{-1/2}Γ(1/4+iz)Γ(1/4-iz). Furthermore, by computing the exact first-passage time distribution, we show that a persistence exponent α=1 emerges due to the direction reversal in this regime.


Promoting the confluence of tropical cyclone research.
Contributions of biologists to tropical cyclone research may improve by integrating concepts from other disciplines. Employing accumulated cyclone energy into protocols may foster greater integration of ecology and meteorology research. Considering experienced ecosystems as antifragile instead of just resilient may improve cross-referencing among ecological and social scientists. Quantifying ecosystem capital as distinct from ecosystem services may improve integration of tropical cyclone ecology research into the expansive global climate change research community.


Abrupt decline in the rate of accumulation of total protein and yolk in postvitellogenic egg chambers ofDrosophila.
The accumulation of endogenously synthesized non-yolk proteins, and of exogenously derived yolk, was quantitated during oogenesis and embryogenesis ofDrosophila. Rates of non-yolk protein accumulation were calculated, and were correlated with polysome content at each developmental stage. Three distinct phases of non-yolk protein accumulation were observed: 1) relatively slow accumulation, lasting to stage 9 of oogenesis; 2) very rapid accumulation between stages 10 and 12 of oogenesis, when half of the protein of the mature egg is accumulated in less than 4 h; and 3) no further protein accumulation from stage 12 of oogenesis through at least the gastrula stage of embryogenesis. During phases 1 and 2, rates of non-yolk protein accumulation correlate well with the polysome content of egg chambers. Surprisingly, during the entire phase 3 the content of polysomes remains at high levels, even though no detectable protein accumulation occurs. This finding is in agreement with the low levels of protein synthesis that have been measured during early embryogenesis, and strongly suggests that late in oogenesis the efficiency of translation suddenly drops by about 20-fold. Moreover, our results imply that polysome content cannot always be directly correlated with protein synthetic activity.


Cyanide-bridged Mn(III)-Fe(III) bimetallic complexes based on the pentacyano(1-methylimidazole)ferrate(III) building block: structure and magnetic characterizations.
Seven cyanide-bridged bimetallic complexes have been synthesized by the reaction of [Fe(1-CH3im)(CN)5]2- with Mn(III) Schiff base complexes. Their crystal structure and magnetic properties have been characterized. Five complexes, [Mn2(5-Brsalen)2Fe(CN)5(1-CH3im)] x H2O (1), [Mn2(5-Clsalen)2(H2O)2Fe(CN)5(1-CH3im)] x H2O (2), [Mn2(5-Clsaltn)2(H2O)2Fe(CN)5(1-CH3im)] (3), [Mn2(5-Clsaltmen)2(H2O)2Fe(CN)5(1-CH3im)] x H2O (4), and [Mn2(5-Brsaltmen)2(H2O)2Fe(CN)5(1-CH3im)] x CH3OH (5), are neutral and trinuclear with two [Mn(SB)]+ (SB2- = Schiff base ligands) and one [Fe(1-CH3im)(CN)5]2-. Complex {[Et4N][Mn(acacen)Fe(CN)5(1-CH3im)]}n x 6nH2O (6) is one-dimensional with alternate [Mn(acacen)]+ and [Fe(CN)5(1-CH3im)]2- units. The two-dimensional complex {[Mn4(saltmen)4Fe(CN)5(1-CH3im)]}n[ClO4]2n x 9nH2O (7) consists of Mn4Fe units which are further connected by the phenoxo oxygen atoms. Magnetic studies show the presence of ferromagnetic Mn(III)-Fe(III) coupling in the trinuclear compounds with the magnetic coupling constant (J) ranging from 4.5 to 6.0 cm-1, based on the Hamiltonian H = -2JSFe(SMn(1) + SMn(2)). Antiferromagnetic interaction has been observed in complex 6, whereas ferromagnetic coupling occurs in complex 7. Complexes 6 and 7 exhibit long-range magnetic ordering with a TN value of 4.0 K for 6 and Tc of 4.8 K for 7. Complex 6 shows metamagnetic behavior at 2 K, and complex 7 possesses a hysteresis loop with a coercive field of 500 Oe, typical of a soft ferromagnet.


Trisomy of 1q in preleukaemia with progression to acute leukaemia.
Marrow cells from an untreated man with preleukaemia were found to have trisomy for the long arm of chromosome 1 which was translocated to the end of the long arm of number 11, i.e., 46,XY, -11,+t (1:11) (q11 or q12; q25). The same abnormality was found in metaphases from 8 individual granulocytic colonies. With development of acute myelomonocytic leukaemia, in addition to the basic chromosome abnormality, trisomy of chromosome 8 and an extra chromosome number 19 with partial deletion were found. Fibroblasts grown from marrow biopsy material showed a normal diploid complement, 46,XY.


Surface-confined energy transfer in mixed self-assembled monolayers.
We have fabricated a set of self-assembled monolayers consisting of naphthalene and dansyl derivatives in a range of surface loading ratios for the purpose of examining excitation transport in mixed self-assembled monolayer systems. Both tethered chromophores were immobilized on an epoxide-terminated adlayer on silica via an identical spacer, where the linking chemistry produced an amide linkage. X-ray photoelectron spectroscopy (XPS), ellipsometry, and contact angle measurements were used to characterize these chromophore-containing layers. The excitation transfer behavior of these monolayers has been examined using steady-state and time-resolved fluorescence spectroscopy. Steady-state fluorescence measurements show that excitation transfer from the naphthalene to dansyl chromophores occurs, with the efficiency of excitation transport scaling with chromophore surface loading densities, as expected. The donor lifetimes decrease with increasing acceptor loading density, and the functional form of the acceptor decay was independent of the donor/acceptor ratio. Our findings are not consistent with a homogeneous adlayer, but do provide information on the structural heterogeneity that is characteristic of these interfaces.


A tutorial on ultrasonic physics and imaging techniques.
Ultrasound is a widely used modality for both therapy and diagnosis in medicine and biology. Currently, in the field of medical diagnosis, ultrasound is responsible for about one in five of all diagnostic images. The physical characteristics of medical ultrasound, along with its behaviour as it interacts with biological tissues, are described in this tutorial. The role of ultrasound in therapeutic and diagnostic applications is briefly described. In view of the importance of ultrasound as a medical imaging modality, the basic technological building blocks utilized in diagnostic ultrasound scanners are also described. Many of these topics are the subjects of other papers in this special issue where they are dealt with in more detail.


Manifestation of the malignant progression of glioma following initial intracerebral hemorrhage: A case report.
Intracranial hemorrhage is extremely rare during the initial stages of glioma. Here, we report a case of glioma with unclassified pathology and intracranial bleeding. After the second surgery for intracerebral hemorrhage, the patient experienced weakness in the left arm and leg, but could walk unassisted. One month after discharge, the weakness in the left limbs had exacerbated and the patient also suffered from headaches and dizziness. A third surgery was ineffective against the rapidly growing tumor. Intracerebral hemorrhage may be the initial symptom of glioma in some rare cases, and atypical perihematomal edema can be used for diagnosis during an emergency. Certain histological and molecular features seen in our case were similar to that of glioblastoma with a primitive neuronal component, which is termed diffuse glioneuronal tumor with features similar to oligodendroglioma and nuclear clusters (DGONC). The patient underwent three surgeries to remove the tumor. The first tumor resection had been performed when the patient was 14-years-old. Resection of the hemorrhage and bone disc decompression were performed when the patient was 39-years-old. One month after the last discharge, the patient underwent neuronavigation-assisted resection of the right frontotemporal parietal lesion plus extended flap decompression. On the 50th d after the third operation, computed tomography imaging showed rapid tumor growth accompanied by brain hernia. The patient was discharged and died 3 d later. Glioma can present as bleeding in the initial stage and should be considered in such a setting. We have reported a case of DGONC, which is a rare molecular subtype of glioma with a unique methylation profile.


[Origin of bilateral-symmetrical animals (Bilateria)].
The paper is an attempt to attack the old problem of the origin of Bilateria by the methods of evolutionary tetrad (i.e. combination of comparative anatomy, comparative embryology, paleontology, and molecular biology). Three groups of theories of classical comparative anatomy (planulod-turbellarian, archicoelomate, and metameric) are discussed. Comparative embryology brings out clearly that the ventral side of embryo comes from the blastoporal region in all groups of Bilateria (except Chordata, where the blastoporal region corresponds to the dorsal side that is come out of the upside-down morphology of chordates) and mouth and anus comes from the anterior and posterior ends of elongated blastopore. From the point of view of paleontology, some of vendian metazoans demonstrate transitional conditions between the Radiata and Bilateria. Vendian bilaterians are metameric organisms with normal or asymmetric position of segments and could be pictured as "bilateral coelenterates" creeping on the oral surface. In Cnidaria, the expression of homologues of "Brachyury", "goosecoid", and "fork head" genes are revealed in the circular region around the mouth. In Bilateria, these genes are expressed along the elongated blastopore and around the mouth and anus. These results support the old conception on the amphistomic origin of mouth and anus as well as the homology between the oral disc of cnidarians and ventral side of Bilateria. The combination of four mentioned approaches enables us to propose the conception of the origin of Bilateria from vendian bilateral coelenterates with numerous metameric pouches of gastral cavity. Bilaterian ancestors crawled on the oral disc (= ventral side). These ancestors gave rise to both phanerosoic cnidarians and triploblastic bilaterians. Cnidarian ancestors attached to bottom by the aboral pole with the resulting degradation of aboral nerve ganglion. Bilateral symmetry of anthozoans is considered to be primitive feature for cnidarians. In case of triploblastic Bilateria, the elongated blastopore closed in the middle and subdivided into mouth and anus (amphistomy) and gastral pouches separated from the central part of gastral cavity and transformed to metameric coelomic chambers. The primary bilaterians are supposed to be complicated organisms having coelom and segmentation. The complexity of primary Bilateria provides an explanation for the abundance of highly organized organisms (arthropods, mollusks etc.) in Cambrian time. It is postulated that Ctenophora is the only group recent eumetazoans with primary axial symmetry.


Sterilization Resistance of Bacterial Spores Explained with Water Chemistry.
Bacterial spores can survive for long periods without nutrients and in harsh environmental conditions. This survival is influenced by the structure of the spore, the presence of protective compounds, and water retention. These compounds, and the physical state of water in particular, allow some species of bacterial spores to survive sterilization schemes with hydrogen peroxide and UV light. The chemical nature of the spore core and its water has been a subject of some contention and the chemical environment of the water impacts resistance paradigms. Either the spore has a glassy core, where water is immobilized along with other core components, or the core is gel-like with mobile water diffusion. These properties affect the movement of peroxide and radical species, and hence resistance. Deuterium solid-state NMR experiments are useful for examining the nature of the water inside the spore. Previous work in our lab with spores of Bacillus subtilis indicate that, for spores, the core water is in a more immobilized state than expected for the gel-like core theory, suggesting a glassy core environment. Here, we report deuterium solid-state NMR observations of the water within UV- and peroxide-resistant spores from Bacillus pumilus SAFR-032. Variable-temperature NMR experiments indicate no change in the line shape after heating to 50 °C, but an overall decrease in signal after heating to 100 °C. These results show glass-like core dynamics within B. pumilus SAFR-032 that may be the potential source of its known UV-resistance properties. The observed NMR traits can be attributed to the presence of an exosporium containing additional labile deuterons that can aid in the deactivation of sterilizing agents.


[Communication in oncology].
Patient-doctor communication is an essential aspect of coping with cancer. In our "age of communication", information and data transfer often is mistaken for communication. Contrary to analogous or digital information transmission, a message received by the patient may widely differ from the message intended by the doctor. For in human communication, nonverbal and emotional contexts may extensively modify the perception, interpretation and processing of information. Moreover, in modern oncology patient-doctor communication is complicated by a growing incongruence between a patient's disease and his illness experience. To achieve satisfying doctor-patient communication, the setting, content and structure have to be directed towards a specific goal. Empirical data show that key elements and skills of efficient patient-doctor communication can be taught and learned.


Molecular weight of DNA from actinophage MSP2.
Actinophage MSP2 is infectious for Streptomyces venezuelae S13. Based upon electron microscopy of coliphage T4 mixed with MSP2, MSP2 had a head about 48 +/- 2 nm wide and 87 +/- 5 nm long. DNA from polyoma virus and from coliphages T4 and T7 served as reference markers in estimating the molecular weight of MSP2 DNA from sedimentation in sucrose gradients. Denatured MSP2 DNA was estimated to be about 17 x 10(6) and double-stranded MSP2 DNA was about (36 +/- 1.6) x 10(6) in molecular weight.


[Standardization of the Kent Infant Development Scale: implications for primary care pediatricians].
The purpose of this study was the standardization of an infant assessment protocol based on behavioral observations of Spanish parents. The Kent Infant Development (KIDS) scale was translated into Spanish and named "Escala de Desarrollo Infantil de Kent" (EDIK). The EDIK normative data were collected from the parents of 662 healthy infants (ages 1 to 15 months) in pediatric clinics. Infants born more than 2 weeks premature or who had serious physical or neurological illness were not included. EDIK raw scores of Spanish infants were converted to developmental ages by comparing them with the number of behaviors for each age group in the normative sample. We obtained the mean score and standard deviation for the full scale and different domains (cognitive, motor, social, language, and self-help). This study shows that EDIK is sensitive to differences in ages and a good instrument that allows one to make a classification between normal infants or those at risk. It should prove useful in developmental pediatric practice.


Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody 134-mG2a-f Exerts Antitumor Activities in Mouse Xenograft Models of Dog Epidermal Growth Factor Receptor-Overexpressed Cells.
The epidermal growth factor receptor (EGFR) is a type I transmembrane protein, which is a member of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. EGFR is a crucial mediator of cell growth and differentiation and forms homodimers or heterodimers with other HER family members to activate downstream signaling cascades. We previously established an anti-human EGFR (hEGFR) monoclonal antibody (mAb), clone EMab-134 (mouse IgG1), by immunizing mice with the ectodomain of hEGFR. In this study, the subclass of EMab-134 was converted from IgG1 to IgG2a (134-mG2a) and further defucosylated (134-mG2a-f) to facilitate antibody-dependent cellular cytotoxicity (ADCC). Although 134-mG2a-f was developed against hEGFR, it was shown to cross-react with dog EGFR (dEGFR) using flow cytometry. The dissociation constant (KD) of 134-mG2a-f against dEGFR-overexpressed CHO-K1 (CHO/dEGFR) cells was determined by flow cytometry to be 3.3 × 10-9 M, indicating that 134-mG2a-f possesses a high binding affinity to dEGFR. Analysis in vitro revealed that 134-mG2a-f contributed to high levels of ADCC and complement-dependent cytotoxicity (CDC) in experiments targeting CHO/dEGFR cells. Furthermore, the in vivo administration of 134-mG2a-f significantly inhibited the development of CHO/dEGFR in comparison with the results observed in response to control mouse IgG. Taken together, the findings of this study demonstrate that 134-mG2a-f could be useful as part of a therapeutic regimen for dEGFR-expressing canine cancers.


Investigation of the effects of phase transformations in micro and nano aluminum powders on kinetics of oxidation using thermogravimetric analysis.
Aluminum micro and nanoparticles are key ingredients in the synthesis of nano energetic materials. Hence it is important to characterize the kinetics and the rate controlling process of their oxidation. The literature shows that the mass diffusion and phase transformation within the aluminum oxide shell are important. However, the description of physical processes regarding simultaneous oxidation and phase transformation is lacking. In this paper, the controlled thermogravimetric (TGA) oxidation of 40-60 nm and 1 µm Al powders is investigated at constant heating rates and under isothermal conditions, respectively, upon varying the partial pressure of oxygen. It is found that the core-shell model of homogenous oxidation is applicable to explain the TGA results when the shell does not undergo phase transformation, which predicts the apparent activation energy in good agreement with the literature data. On the other hand, the simultaneous oxidation and phase transformation is able to be addressed using the JMAK model which reveals key parameters of the rate controlling processes. Mass diffusion is indeed rate determining during the oxidation of Al micro and nanopowders while the kinetics of the reaction is fast. Unlike the micron powders, the particle size distribution has a significant effect on the shape of the oxidation curves of the nanopowders.


Balancing selection and low recombination affect diversity near the self-incompatibility loci of the plant Arabidopsis lyrata.
The self-incompatibility (S-) locus region of plants in the Brassica family is a small genome region. In Arabidopsis lyrata, the S-genes, SRK and SCR, encode the functional female and pollen recognition proteins, which must be coadapted to maintain correct associations between the two component genes, and thus self-incompatibility (SI). Recombinants would be self-compatible and thus probably disadvantageous in self-incompatible species. Therefore, tight linkage between the two genes in incompatibility systems is predicted to evolve to avoid producing such recombinant haplotypes. The evolution of low recombination in S-locus regions has not been rigorously tested. To test whether these regions' per-nucleotide recombination rates differ from those elsewhere in the genome, and to investigate whether the A. lyrata S-loci have the predicted effect on diversity in their immediate genome region, we studied diversity in genes that are linked to the S-loci but are not involved in incompatibility and are not under balancing selection. Compared with other A. lyrata loci, genes linked to the S-loci have extraordinarily high polymorphism. Our estimated recombination in this region, from fitting a model of the effects of S-allele polymorphism on linked neutral sites, supports the hypothesis of locally suppressed recombination around the S-locus.


Evaluating SGLT2 inhibitors for type 2 diabetes: pharmacokinetic and toxicological considerations.
Inhibitors of sodium-glucose cotransporters type 2 (SGLT2), which increase urinary glucose excretion independently of insulin, are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). An extensive literature search was performed to analyze the pharmacokinetic characteristics, toxicological issues and safety concerns of SGLT2 inhibitors in humans. This review focuses on three compounds (dapagliflozin, canagliflozin, empagliflozin) with results obtained in healthy volunteers (including drug-drug interactions), patients with T2DM (single dose and multiple doses) and special populations (those with renal or hepatic impairment). The three pharmacological agents share an excellent oral bioavailability, long half-life allowing once-daily administration, low accumulation index and renal clearance, the absence of active metabolites and a limited propensity to drug-drug interactions. No clinically relevant changes in pharmacokinetic parameters were observed in T2DM patients or in patients with mild/moderate renal or hepatic impairment. Adverse events are a slightly increased incidence of mycotic genital and rare benign urinary infections. SGLT2 inhibitors have the potential to reduce several cardiovascular risk factors, and cardiovascular outcome trials are currently ongoing. The best positioning of SGLT2 inhibitors in the armamentarium for treating T2DM is still a matter of debate.


Complex population genetic structure in the endemic Canary Island pine revealed using chloroplast microsatellite markers.
The Canary archipelago, located on the northwestern Atlantic coast of Africa, is comprised of seven islands aligned from east to west, plus seven minor islets. All the islands were formed by volcanic eruptions and their geological history is well documented providing a historical framework to study colonization events. The Canary Island pine ( Pinus canariensis C. Sm.), nowadays restricted to the westernmost Canary Islands (Gran Canaria, Tenerife, La Gomera, La Palma and El Hierro), is considered an old (Lower Cretaceous) relic from an ancient Mediterranean evolutionary centre. Twenty seven chloroplast haplotypes were found in Canary Island pine but only one of them was common to all populations. The distribution of haplotypic variation in P. canariensis suggested the colonization of western Canary Islands from a single continental source located close to the Mediterranean Basin. Present-day populations of Canary Island pine retain levels of genetic diversity equivalent to those found in Mediterranean continental pine species, Pinus pinaster and Pinus halepensis. A hierarchical analysis of variance (AMOVA) showed high differentiation among populations within islands (approximately 19%) but no differentiation among islands. Simple differentiation models such as isolation by distance or stepping-stone colonization from older to younger islands were rejected based on product-moment correlations between pairwise genetic distances and both geographic distances and population-age divergences. However, the distribution of cpSSR diversity within the islands of Tenerife and Gran Canaria pointed towards the importance of the role played by regional Pliocene and Quaternary volcanic activity and long-distance gene flow in shaping the population genetic structure of the Canary Island pine. Therefore, conservation strategies at the population level are strongly recommended for this species.


Immunohistochemical study of cytokeratin expression in normal and pathologic middle ear mucosa of the rat.
The expression of cytokeratins in the epithelium of the middle ear and external auditory meatus of the rat was studied on cryosections of ethylenediaminetetraacetic acid-decalcified specimens by use of a panel of monoclonal antibodies. The normal middle ear epithelium revealed a complex cytokeratin profile, including regional differences. The induction of sterile middle ear effusions resulted in increased cytokeratin expression. Infective effusions were accompanied by both quantitative and qualitative changes in the cytokeratin expression patterns. The differences observed between the cytokeratin profiles of external meatal skin and those of middle ear epithelium may form a useful tool for research into cholesteatoma development.


Dimensions and determinants of trust in health care in resource poor settings--a qualitative exploration.
Trust in health care has been intensely researched in resource rich settings. Some studies in resource poor settings suggest that the dimensions and determinants of trust are likely to be different. This study was done as a qualitative exploration of the dimensions and determinants of trust in health care in Tamil Nadu, a state in south India to assess the differences from dimensions and determinants in resource rich settings. The participants included people belonging to marginalized communities with poor access to health care services and living in conditions of resource deprivation. A total of thirty five in depth interviews were conducted. The interviews were summarized and transcribed and data were analyzed following thematic analysis and grounded theory approach. The key dimensions of trust in health care identified during the interviews were perceived competence, assurance of treatment irrespective of ability to pay or at any time of the day, patients' willingness to accept drawbacks in health care, loyalty to the physician and respect for the physician. Comfort with the physician and health facility, personal involvement of the doctor with the patient, behavior and approach of doctor, economic factors, and health awareness were identified as factors determining the levels of trust in health care. The dimensions and determinants of trust in health care in resource poor settings are different from that in resource rich settings. There is a need to develop scales to measure trust in health care in resource poor settings using these specific dimensions and determinants.


Cone beam volumetric tomography vs. medical CT scanners.
This article describes the benefits and dental applications of a three-dimensional imaging technique known as cone beam volumetric tomography (CBVT). When compared to conventional medical CT scanners, CBVT is more accurate, requires less radiation, captures the maxilla and mandible in a single rotation of the X-ray source, and is cost-effective for patients. Here we describe the dental applications of CBVT and its advantages when placing dental implants.


The mechanism of the elaboration of ring B in ergosterol biosynthesis.
Methods for the preparation of [3alpha-(3)H]ergosta-7,22-dien-3beta-ol (5,6-dihydro-ergosterol), [5,6-(3)H(2)]ergosta-7,22-dien-3beta-ol and [3alpha-(3)H]ergosta-7,22-diene-3beta,5alpha-diol are described. It is shown that 5,6-dihydro[3alpha-(3)H]ergosterol on incubation under aerobic conditions with whole cells of Saccharomyces cerevisiae LK(2)G(12) is efficiently converted into ergosterol. Studies carried out with dihydro[5alpha,6alpha-(3)H(2)]-ergosterol demonstrate that the introduction of the 5,6-double bond in ergosterol biosynthesis is attended by an overall cis-elimination of two hydrogen atoms. To differentiate between a hydroxylation-dehydration mechanism and a dehydrogenation mechanism, the metabolism of [3alpha-(3)H]ergosta-7,22-diene-3beta,5alpha-diol was studied. It was shown that this diol is converted into ergosterol only under aerobic conditions. It is therefore suggested that the introduction of the 5,6-double bond of ergosterol does not occur through a hydroxylation-dehydration mechanism.


Chronic orchialgia: epidemiology, diagnosis and evaluation.
Chronic orchialgia is a vexing condition defined as chronic or intermittent scrotal pain lasting at least three months that significantly interferes with daily activities. There are currently no guidelines regarding the diagnosis and management of this condition despite it being the cause of 2.5-4.8% of urologic clinic visits. Men often present with chronic orchialgia in their mid to late 30s, although the condition can present at any age. A broad differential diagnosis of chronic orchialgia includes epididymitis, testicular torsion, tumors, obstruction, varicocele, epididymal cysts, hydrocele, iatrogenic injury following vasectomy or hernia repair, and referred pain from a variety of sources including mid-ureteral stone, indirect inguinal hernia, aortic or common iliac artery aneurysms, lower back disorders, interstitial cystitis, and nerve entrapment due to perineural fibrosis; approximately 25-50% of chronic orchialgia is idiopathic in nature. In such cases, it is reasonable to consider psychological and psychosocial factors that may be contributing to chronic pain. Invasive testing is not recommended in the work-up of chronic orchialgia.


Isolation and characterization of a novel human monoclonal antibody that neutralizes tetanus toxin.
A human monoclonal antibody, designated 53-2-4, has been isolated and characterized in terms of its ability to interact with clostridial neurotoxins. In enzyme-linked immunosorbent assay assays the antibody reacted with native tetanus toxin, tetanus toxoid and the C fragment obtained from the carboxyterminus of the toxin (AA 864-1314). The antibody did not react with the B fragment of tetanus toxin (AA 1-863) or with six serotypes of botulinum neurotoxin (A to F). Both culture supernatant from the clonal line producing the antibody as well as homogeneous protein obtained by affinity purification of the antibody neutralized tetanus toxin. When tested in vivo, the antibody provided complete production against a supralethal injection of toxin; when tested in vitro, the antibody produced at least 99% inactivation of a 1 x 10(-9) M solution of toxin. The exceptional neutralizing activity of the antibody was attributed to its high affinity for the toxin (4.2 x 10(-10) mol/liter). Animal experiments revealed a novel phenomenon that has been labeled delayed intoxication. At the appropriate ratio of antibody to antigen, the toxin was retained in the host in a latent form. After several days the biological activity of the toxin became apparent and there was onset of nervous system poisoning. Isolated tissue experiments showed that each antibody molecule is capable of associating with two antigen molecules. The antibody has greater neutralizing activity when mixed with free toxin than when mixed with toxin already bound to plasma membrane receptors.


Phase II treatment of central nervous system gliomas with high-dose etoposide and autologous bone marrow transplantation.
A total of 16 patients with progressive CNS gliomas who had previously received maximal radiation therapy and chemotherapy were treated on a phase II study using high-dose etoposide with autologous bone marrow transplantation to assure hematopoietic recovery. Three patients (19%) responded with both improved neurological status and decreased mass on computerized tomographic scan. Median survival for all treated patients was 4 months with the three responders living 9, 10, and 54+ months.


Development of a microsatellite-based approach to co-segregation analysis of familial hypercholesterolaemic kindreds.
Co-segregation studies based on a selection of intragenic restriction fragment length polymorphisms of the low density lipoprotein receptor (LDLR) gene have been used extensively both for research and diagnostic studies of familial hypercholesterolaemia (FH) families, because direct mutation screening remains complex. Here we describe the development and application of a more efficient approach to co-segregation studies based on highly informative dinucleotide and tetranucleotide repeats flanking the LDLR gene. A series of microsatellites (D19S391, D19S394, D19S221 and D19S179) were selected for study on the basis of linkage analysis in the CEPH families using intragenic polymorphisms for a TA repeat (exon 18) in the LDLR gene, and earlier data for a Pvu II polymorphism (intron 15). A physical map of the region of chromosome 19 also contributed to this selection. One marker in particular, D19S394, sited 150 kilobases telomeric to the gene, was extremely useful, displaying 90% heterozygosity, robust PCR of tetranucleotide repeats without stutter bands, and no recombination with the LDLR gene (theta = 0, LOD 68). Use of this marker in the families of twenty-three FH probands from Hampshire demonstrated co-segregation of the hyperlipidaemia phenotype with the LDLR gene region, except in one family with defective apolipoprotein B-100, and a family turning out to display familial combined hyperlipidaemia. This approach should facilitate the search for any families where FH does not co-segregate with the LDLR gene, and will enhance the repertoire of molecular diagnostic tools available for FH.


LU-Net: combining LSTM and U-Net for sinogram synthesis in sparse-view SPECT reconstruction.
Lowering the dose in single-photon emission computed tomography (SPECT) imaging to reduce the radiation damage to patients has become very significant. In SPECT imaging, lower radiation dose can be achieved by reducing the activity of administered radiotracer, which will lead to projection data with either sparse projection views or reduced photon counts per view. Direct reconstruction of sparse-view projection data may lead to severe ray artifacts in the reconstructed image. Many existing works use neural networks to synthesize the projection data of sparse-view to address the issue of ray artifacts. However, these methods rarely consider the sequence feature of projection data along projection view. This work is dedicated to developing a neural network architecture that accounts for the sequence feature of projection data at adjacent view angles. In this study, we propose a network architecture combining Long Short-Term Memory network (LSTM) and U-Net, dubbed LU-Net, to learn the mapping from sparse-view projection data to full-view data. In particular, the LSTM module in the proposed network architecture can learn the sequence feature of projection data at adjacent angles to synthesize the missing views in the sinogram. All projection data used in the numerical experiment are generated by the Monte Carlo simulation software SIMIND. We evenly sample the full-view sinogram and obtain the 1/2-, 1/3- and 1/4-view projection data, respectively, representing three different levels of view sparsity. We explore the performance of the proposed network architecture at the three simulated view levels. Finally, we employ the preconditioned alternating projection algorithm (PAPA) to reconstruct the synthesized projection data. Compared with U-Net and traditional iterative reconstruction method with total variation regularization as well as PAPA solver (TV-PAPA), the proposed network achieves significant improvement in both global and local quality metrics.


Cochlear Implant Insertion Depth Prediction: A Temporal Bone Accuracy Study.
The aim of this study was to present and validate the accuracy of a method to predict the required cochlear implant (CI) electrode array length for a specific angular insertion depth (AID). The human cochlea exhibits remarkable interindividual morphological differences. The prediction of the required array length for a specific AID can help to improve the outcome of cochlear implant surgery. We estimated the linear insertion depth required for an angular insertion of 540 degrees using computed tomography images of 16 temporal bone specimens (eight Thiel fixed, eight formalin fixed). Free fitting electrode arrays were marked accordingly and inserted through a custom-made insertion guide tube. The achieved AIDs were assessed using postoperative micro-computed tomography scans. In the Thiel specimens, the difference between the aimed depth of 540 degrees and achieved insertion depth was small (average 529 degrees, p = 0.076), with a mean prediction error of -11 degrees (maximum 30 degrees), indicating a small underestimation. By contrast, we observed early resistance during the insertions in the formalin specimens (average 409 degrees, p < 0.0001), resulting in a mean error of -131 degrees and bending of the electrode array in the cochlear basal turn in four of eight specimens. The equation presented in this study for calculating linear insertion depths can be helpful for the selection of adequate electrode array lengths in a clinical setting. The Thiel conservation is a highly suitable model for cadaveric electrode insertion studies. A free online calculator is available at http://www.hno.insel.ch/de/forschung/ci_estimator/.


Single dose pharmacokinetics of oral artemether in healthy Malaysian volunteers.
To determine the pharmacokinetics of artemether (ARM) and its principal active metabolite, dihydroartemisinin (DHA) in healthy volunteers. Six healthy male Malaysian subjects were given a single oral dose of 200 mg artemether. Blood samples were collected to 72 h. Plasma concentrations of the two compounds were measured simultaneously by reversed-phase h.p.l.c. with electro-chemical detection in the reductive mode. Mean (+/- s.d.) maximum concentrations of ARM, 310 +/- 153 micrograms l-1, were reached 1.88 +/- 0.21 h after drug intake. The mean elimination half-life was 2.00 +/- 0.59 h, and the mean AUC 671 +/- 271 micrograms l-1 h. The mean Cmax of DHA, 273 +/- 64 micrograms l-1 was observed at 1.92 +/- 0.13 h. The mean AUC of DHA was 753 +/- 233 micrograms h l-1'. ARM and DHA were stable at < or = -20 degrees C for at least 4 months in plasma samples. The relatively short half-life of ARM may be one of the factors responsible for the poor radical cure rate of falciparum malaria with regimens employing daily dosing. In view of the rapid loss of DHA in plasma samples held at room temperature (26 degrees C) it is recommended to store them at a temperature of < or = -20 degrees C as early as possible after sample collection.


The Anticonvulsant Screening Program of the National Institute of Neurological Disorders and Stroke, NIH: History and Contributions to Clinical Care in the Twentieth Century and Beyond.
The anticonvulsant screening program (ASP) of the national institute of neurological disorders and stroke (NINDS), National Institutes of Health has made substantial contributions to the drug armamentarium of the clinical neurologist. This program, originally a part of the overall Drug Development Program of the Epilepsy Branch, has been fortunate to have talented leadership, both at NINDS in Maryland and at the major contract site, the University of Utah-over a remarkable period of more than 40 years. Future discoveries by the ASP (now renamed the Epilepsy Therapy Screening) can be expected to make additional contributions to improving the health of persons with epilepsy.


Response of extrapancreatic glucagon to glycemic changes under chronic insulin deficiency in dogs.
Since the secretion of pancreatic glucagon is largely influenced by the changes in the blood glucose level, the response of extrapancreatic glucagon was investigated in totally pancreatectomized dogs under chronic insulin deficiency. Insulin-induced hypoglycemia did not alter plasma glucagon in the portal vein in a group of 5 pancreatectomized dogs, but the decrease of the blood glucose was small, by 70 mg/100 ml, in spite of a large amount of insulin. The administration of 2-deoxyglucose did not cause any changes in plasma glucagon in the portal vein in a group of 6 pancreatectomized dogs. Glucose-induced hyperglycemia, both transient and continuous, did not cause any changes in plasma glucagon in the portal vein, although blood glucose was significantly elevated. It is concluded that regulation of extrapancreatic glucagon differs from that of pancreatic glucagon.


Rapidly Evolving and Fatal Miliary Tuberculosis and COVID-19 Infection in an Infant.
Tuberculosis (TB) and SARS-CoV-2 (COVID-19) are two important infectious diseases causing morbidity and mortality worldwide. Active TB infection can stimulate host immune responses and together with COVID-19, may lead to cytokine storm and immune dysregulation leading to multi-organ failure. We present a rare case of both miliary tuberculosis and SARS-CoV-2 co-infection in an infant who was a 6-month-old previously healthy term boy. He had persistent cough and congestion, became severely ill, and was brought to the emergency department. He was found to be COVID-19 positive by PCR test. Laboratory studies showed pancytopenia, elevated inflammatory markers, and an abnormal coagulation profile with coagulopathy. He developed strokes, severe sepsis, and electrolyte abnormalities, and declined rapidly within 6 days. Autopsy examination showed multifocal micro-abscesses in multiple organs, which on microscopic examination showed necrotic foci teeming with Mycobacteria and were culture positive for M. tuberculosis Neuropathological examination showed infarction in the right middle and posterior cerebral artery territories. This patient helps illuminate some immunological and pathological aspects of two co-occurring infectious diseases and the susceptibility for the development of fatal complications with SARS-CoV-2 infection in the pediatric population.


Epidemiological investigation and prevention and control strategies of rubella in Anhui province, China, from 2012 to 2021.
Rubella is a highly contagious viral infection with mild manifestations that occurs most often in children and young adults. Infection during pregnancy, especially during the first trimester, can result in an infant born with congenital rubella syndrome (CRS). The purpose of this paper is to analyze the characteristics of rubella epidemics in Anhui province from 2012 to 2021 and explore the prevention and control strategies of rubella. A descriptive epidemiological approach was used to examine the epidemiological characteristics of rubella in Anhui Province between 2012 and 2021. From 2012 to 2021, a total of 4,987 cases of rubella were reported in Anhui province, with an average annual incidence of 8.11 per million, demonstrating an overall downward trend (χ2 trend =3141.06, P < 0.01). The average yearly incidence of rubella in southern Anhui, central Anhui, and northern Anhui were 9.99 per million, 11.47 per million, and 4.50 per million, respectively, with statistically significant differences (χ2 =792.50, P < 0.01). The male to female incidence ratio was 1.67:1, and the male incidence rate was higher than the female incidence rate. Most cases occurred among students, accounting for 56.59% of all cases, and the 10-34 age group accounted for ~73.71% of all cases. Regarding immunization history, 3.57% of cases had two doses or more, 6.62% had one dose, 16.40% had none, and the remainder were uncertain. The incidence of rubella in Anhui province from 2012 to 2021 continued to decline, with regional variations observed. The 10-34-year-old population without a history of rubella vaccination is at high risk for the disease. It is suggested to carry out rubella vaccination and congenital rubella syndrome monitoring according to the actual situation.


Endothelin-1 gene expression in endothelial cells is potently inhibited by a vasodilator, dilazep.
Endothelin-1 (ET-1) is considered to be involved in various cardiovascular and renal disorders. The objective of this study was to investigate whether a vasodilator and antiplatelet agent, 1,4-bis[3-(3,4,5-trimethoxybenzoyloxy) propyl]perhydro-1,4-diazepine dihydrochloride monohydrate (dilazep, DZ), has an ET-1-inhibiting effect in vitro. Bovine aortic endothelial cells (BAEC) and human umbilical vein endothelial cells (HUVEC) pretreated with fetal calf serum were treated with DZ and preproET-1 (PpET-1) transcription was evaluated by Northern blot analysis. ET-1 peptide release in culture medium was evaluated by radioimmunoassay. The effect of DZ on the ET-1 promoter/enhancer apparatus was evaluated in transfection experiments using -5 kb ET-1 promoter/enhancer constructs. Modest inhibition of PpET-1 gene transcription was detected after 30 min of DZ treatment (0.56+/-0.19 vs. 1 , p<0.01) and more marked inhibition was seen at 24 h (0.04+/-0.04 vs. 1, p<0.0001). ET-1 peptide release was suppressed strongly after 3 h (382.5+/-2.9 vs. 673.5+/-74.5pg/ml, p< 0.001) and 24 h (38.8+/-9.8 vs. 5,075+/-52.0pg/ml, p<0.0001). DZ potently inhibited PpET-1 transcription in a concentration-dependent manner (0.42+/-0.18 vs. 1, p<0.001, at 100micromol/l). DZ suppressed PpET-1 transcription in confluent HUVEC at 3 h (0.41 +/-0.11 vs. 1, p<0.0001). DZ strongly inhibited PpET-1 transcription after 1 h of thrombin (TH) treatment (0.30+/-0.01 vs. 1.51+/-0.03, p<0.0001). Transfection experiments using the 5 kb ET-1 promoter-luciferase plasmid revealed that DZ strongly suppressed ET-1 promoter activity by 99% (p<0.01). DZ potently inhibited ET-1 gene expression at the transcription level in serum- or TH-treated endothelial cells.


Single photon emission computer tomography of dopamine transporters in monkeys and humans with 99mTc-TRODAT-1.
The diagnosis of Parkinson's disease is presently based on non-specific symptoms. However, radionuclide dopamine transporters imaging can provide specific diagnostic tool for Parkinson's disease. This study was designed to investigate the effects of imaging of dopamine transporters with 99mTc-TRODAT-1 in early diagnosis or differential diagnosis of Parkinson's disease. Nine normal monkeys were used to establish N-methyl-4-phenyl-1, 2, 3, 6-tetra-hydropyridine (MPTP) hemi-Parkinsonian animal models, and they were subjected to imaging. Twenty-nine patients with Parkinson's disease, 12 age-matched healthy volunteers, and 18 age-matched patients with Parkinson's syndrome were investigated. Single photon emission computer tomography (SPECT) was performed 3 hours after intravenous injection of 740 MBq 99mTc-TRODAT-1. Striatum specific uptake of 99mTc-TRODAT-1 was calculated according to the ratio of striatum (ST) to cerebellum (CB) in dopamine transporters uptake. In normal monkeys, bilateral ratio of ST/CB was 2.34 +/- 0.41. After the injection of MPTP, uptake rate of 99mTc-TRODAT-1 at damaged region was much lower than that at the contralateral region, resulting in a significant difference in the ratio of ST/CB (right: ST/CB = 1.73 +/- 0.35; left: ST/CB = 1.90 +/- 0.30), especially in hemi-Parkinsonian model monkeys (right: ST/CB = 1.29 +/- 0.17; left: ST/CB = 1.80 +/- 0.33). The ratios of ST/CB were 1.57 +/- 0.17 and 1.61 +/- 0.14 for the right and left respectively in the healthy volunteers, 1.04 +/- 0.29 and 1.06 +/- 0.30 in the age-matched patients with Parkinson's disease, and 1.56 +/- 0.17 and 1.59 +/- 0.18 in the age-matched patients with Parkinson's disease syndrome. A significant difference was noted between group of Parkinson's disease, normal controls and Parkinson's disease syndrome. The results suggest that 99mTc-TRODAT-1 dopamine transporters SPECT has clinical application value in early diagnosis or differential diagnosis of Parkinson's disease.


[Monrad-Krohn: a norwegian neurologist].
Monrad-Krohn was born in Bergen and is a representative of Scandinavian neurologists. From 1912 to 1917, he studied clinical neurology in Paris and London. During his stay there, he was intensely influenced by several eminent neurologists, such as Dejerine, Marie, Babinski, Souques, Horsley, Stewart, and Wilson. He fulfilled his duties as a professor of neurology at the University of Oslo (Rikshospitalet) for four decades. One of his students, Sigvald Bernhard Refsum, succeeded him in 1959. Monrad-Krohn was interested in reflexology, language, and facial innervation. A peculiar phenomenon, paradoxical emotional hypermimia, is known as the Monrad-Krohn sign. He also coined the word dysprosody as a definite neurological sign. His masterpiece "The Clinical Examination of the Nervous System" made him world famous. It had a great reputation as an outstanding textbook of neurological examination, was translated into many languages, and went through several editions.


Niobium pentoxide phosphate invert glass as a mineralizing agent in an experimental orthodontic adhesive.
The aim of this study was to develop an experimental orthodontic adhesive and evaluate how adding phosphate invert glass containing niobium pentoxide (PIG-Nb) affected the adhesive's properties. PIG-Nb was added at 1, 2.5, and 5 wt% to experimental adhesive (75 wt% bisphenol A methacrylate [BisGMA], 25 wt% triethylene glycol dimethacrylate [TEGDMA], 5 wt% colloidal silica and photoinitiator system). The adhesives were evaluated for mineral deposition, degree of conversion (DC), softening solvent by Knoop microhardness (KNH) variation, pH changes, and shear bond strength (SBS). One-way analysis of variance (ANOVA) (DC and ΔKHN%), two-way ANOVA (SBS), repeated measures ANOVA (pH), and paired test (KNH1 and KNH2) were used at a significance level of P < .05. Adding PIG-Nb to orthodontic adhesives induced deposition on its surface associated with a constant neutral pH. The SBS increased after immersion in artificial saliva, and the PIG-Nb5 exhibited less softening. The addition of PIG-Nb into orthodontic adhesives induced mineral deposition. Experimental orthodontic adhesive containing 5% wt of PIG-Nb exhibited increased mineral deposition and suitable properties for orthodontic applications.


Primary care physicians' willingness to offer a new genetic test to tailor smoking treatment, according to test characteristics.
Emerging pharmacogenetics research may improve clinical outcomes for common complex conditions typically treated in primary care settings. Physicians' willingness to offer genetically-tailored treatments to their patients will be critical to realizing this potential. According to recent research, it is likely that genotypes used to tailor smoking will have pleiotropic associations with other addictions and diseases, and may have different frequencies across populations. These additional features may pose an additional barrier to adoption. To assess physicians' willingness to offer a new test to individually tailor smoking treatment according to specific test characteristics, we conducted a national mailed survey of 2,000 U.S. primary care physicians (response rate: 62.3%). Physicians responded to a baseline scenario describing a new test to tailor smoking treatment, and three additional scenarios describing specific test characteristics based on published research; there was random assignment to one of two survey conditions in which the test was described as a genetic or non-genetic test. Our findings indicate physicians' self-reported likelihood (0-100 scale) that they would offer a new test to tailor smoking cessation treatment ranged from 69%-78% across all scenarios. Relative to baseline scenario responses, physicians were significantly less likely to offer the test when informed that the same genotypes assessed for treatment tailoring: (1) may also identify individuals predisposed to become addicted to nicotine (p<.001), (2) differ in frequency by race (p<.004), and (3) may have associations with other conditions (e.g., alcohol and cocaine addiction, attention deficit hyperactivity disorder ADHD and Tourette Syndrome) (p<.01). Describing a new test to individually tailor smoking treatment as a "genetic" versus non-genetic test significantly reduced physicians' likelihood of offering the test across all scenarios, regardless of specific test characteristics (p<.0007). Effective education of primary care physicians will be critical to successful integration of promising new pharmacogenetic treatment strategies for smoking.


Ratiometric Fluorescence Detection of Mg2+ Based on Regulating Crown-Ether Modified Annihilators for Triplet-Triplet Annihilation Upconversion.
Detection of magnesium ion has been of great significance considering its critical physiological activities. Herein, we report ratiometric fluorescence detection of Mg2+ with high sensitivity and selectivity based on triplet-triplet annihilation (TTA) upconversion for the first time. Crown-ether functionalized anthracene derivatives were synthesized, which bifunctionally acted as not only annihilators to construct TTA upconversion systems but also the recognition probes for Mg2+ based on the photoinduced electron transfer (PET) mechanism. Their photophysical properties with the absence and presence of Mg2+ were comprehensively studied. It was found that solvents strongly influenced the photophysical properties and Mg2+-responsiveness. TTA upconversion systems with PtOEP as the sensitizer were further established and investigated. It turned out PtOEP/9-AEC in DCM exhibited an excellent linear relationship (R2 = 0.9979) between the intensity ratio (the integrated upconverted luminescence intensity (IUC) over the integrated downshifted phosphorescence intensity (IPL), IUC/IPL) and the concentration of Mg2+ under the excitation of 532 nm with a limit of detection value of 2.52 μM and a high selectivity to Mg2+. This work opened a new perspective of designs and applications of TTA-upconversion-based ratiometric fluorescence for ion detection.


Progress in the Molecular Characterization of Hepatobiliary Transporters.
Over the last 25 years, our understanding of the driving forces for hepatobiliary elimination and knowledge of the molecular basis of uptake and efflux transport in hepatocytes have undergone fundamental changes. This refers to bile acids and many other endogenous substances as well as to drugs that are eliminated on the hepatobiliary route. In this development, not only molecular cloning, functional characterization, and localization of transporters were decisive, but also the discovery of hereditary mutations in genes encoding sinusoidal uptake transporters and canalicular export pumps in humans and rodents. Uptake by passive diffusion and elimination into bile driven by the electrochemical gradient are no longer considered relevant for hepatobiliary elimination in the intact organism. Furthermore, insights into the relative roles of uptake transporters and unidirectional ATP-driven efflux pumps were obtained when we established double-transfected polarized cell lines stably expressing, as an example, the hepatocellular uptake transporter OATP1B3 and the apical (canalicular) efflux pump multidrug resistance protein 2 (MRP2; ABCC2). ATP-dependent efflux transporters localized to the basolateral (sinusoidal) hepatocyte membrane, particularly MRP3 (ABCC3) and MRP4 (ABCC4), pump substances from hepatocytes into sinusoidal blood. Bile acids are substrates for human MRP4 in the presence of physiological concentrations of reduced glutathione, which undergoes co-transport. These efflux pumps have been recognized in recent years to play an important compensatory role in cholestasis and to contribute to the balance between uptake and efflux of bile acids and other organic anions during the vectorial transport from blood into bile. This sinusoidal efflux not only enables subsequent renal elimination but also facilitates the re-uptake of substances into neighboring hepatocytes located more centrally and downstream in the sinusoid.


Critical song features for auditory pattern recognition in crickets.
Many different invertebrate and vertebrate species use acoustic communication for pair formation. In the cricket Gryllus bimaculatus, females recognize their species-specific calling song and localize singing males by positive phonotaxis. The song pattern of males has a clear structure consisting of brief and regular pulses that are grouped into repetitive chirps. Information is thus present on a short and a long time scale. Here, we ask which structural features of the song critically determine the phonotactic performance. To this end we employed artificial neural networks to analyze a large body of behavioral data that measured females' phonotactic behavior under systematic variation of artificially generated song patterns. In a first step we used four non-redundant descriptive temporal features to predict the female response. The model prediction showed a high correlation with the experimental results. We used this behavioral model to explore the integration of the two different time scales. Our result suggested that only an attractive pulse structure in combination with an attractive chirp structure reliably induced phonotactic behavior to signals. In a further step we investigated all feature sets, each one consisting of a different combination of eight proposed temporal features. We identified feature sets of size two, three, and four that achieve highest prediction power by using the pulse period from the short time scale plus additional information from the long time scale.


Salvage surgery in head and neck cancer: External validation of predictors of disease-specific survival.
Salvage surgery in recurrent head and neck squamous cell carcinoma (HNSCC) is associated with poor outcomes. There is great interest to better identify suitable surgical patients. This study aimed to validate the proposal of Hamoir et al. to use three items to predict the outcomes of salvage surgery. Single-center analysis of 577 patients undergoing salvage surgery for recurrent HNSCC during the period 1985-2016, with a minimal follow-up of 2 years. Patients were classified according to the prediction modeling proposed by Hamoir et al. This prediction modeling is based on three predictors: the tumor site (larynx vs non-larynx), initial staging (stage I-II vs stage III-IV), and site of recurrence (local or regional vs locoregional). Five-year disease-specific survival after salvage surgery was 54.0% (95% CI: 49.6-58.4%). Applying the prediction modeling tested, a total of 212 patients (36.7%) patients had no predictors of poor prognosis, 185 (32.1%) had one predictor, 146 (25.3%) two predictors, and 34 (5.9%) three predictors. Five-year disease-specific survival for patients with none, one, two and three predictors were 82.2%, 47.2%, 29.5% and 20.2% respectively (P = 0.0001). We have validated the prediction modeling based on the location of the tumor, initial staging and locoregional recurrence proposed by Hamoir et al. This prediction model is easy to apply and provides good information about the possibilities of success of salvage surgery.


Combinatorial vascular targeting in translational medicine.
In the post-genomic era, the phage display technology surfaces as an alternative approach for large-scale study of tissue-specific protein interactions with direct clinical and therapeutic applications. The unbiased identification of molecular complexes expressed on the surface of cells and blood vessels of organs and tissues may eventually lead to a considerably improved understanding of cellular and vascular proteomics. The ultimate value of this technology consists in the conception of a new ligand-directed pharmacology, with broad implications for both treatment and molecular imaging of cancer patients. In this review, we describe the use and applications of phage display for efficient development of targeted drug discovery and design.


A Method for Extracting Building Information from Remote Sensing Images Based on Deep Learning.
Semantic segmentation of remote sensing images is an important issue in remote sensing tasks. Existing algorithms can extract information more accurately, but it is difficult to capture the contours of objects and further reveal the interaction information between different objects in the image. Therefore, a deep learning-based method for extracting building information from remote sensing images is proposed. First, the deep learning semantic segmentation model DeepLabv3+ and Mixconv2d are combined, and convolution kernels of different sizes are used for feature recognition. Then, the regularization method based on Rdrop Loss improves the accuracy and efficiency of contour capture for objects of different resolutions, and at the same time improves the consistency of dataset fitting. Finally, the proposed remote sensing image information extraction method is verified based on the self-built dataset. The experimental results show that the proposed algorithm can effectively improve the algorithm efficiency and result accuracy, and has good segmentation performance.


Activated Ha-ras can cooperate with defective simian virus 40 in the transformation of nonestablished rat embryo fibroblasts.
We studied the ability of activated Ha-ras to cooperate with simian virus 40 (SV40) in the transformation of nonestablished rat embryo fibroblasts. Cotransfection with Ha-ras greatly accelerated the rate of focus induction by wild-type SV40. Moreover, a series of transformation-defective SV40 mutants could be partially complemented by Ha-ras. This was true not only for mutants retaining an intact N-terminal immortalization-competent domain, but also for a nonkaryophilic SV40 mutant. In the latter case, all detectable T antigen was cytoplasmic, indicating that efficient transformation can be achieved through the interaction of two nonnuclear proteins. By employing cell lines derived with various SV40 mutants, it was determined that the ability to complex with p53 depends on the integrity of a relatively large region in the C-terminal half of large T. Finally, we report that nonkaryophilic SV40 large T forms a complex with the major heat shock protein HSP70, and we discuss its possible implications.


Buspirone vs. Haloperidol: A Double-Blind Trial for Agitation in a Nursing Home Population With Alzheimer's Disease.
The authors report on a pilot double-blind comparison of buspirone with haloperidol in the treatment of agitation manifested by physical tension and motor activity in Alzheimer's disease (AD). A group of 26 nursing home residents underwent a 10-week comparison of 15 mg buspirone (n = 12) vs. 1.5 mg haloperidol (n = 14) per day. Tension and anxiety decreased to a greater extent in those patients who were treated with buspirone. Although it is not possible to draw definitive conclusions from a treatment study that does not include a placebo group, these findings suggest the potential value of further clinical research on buspirone in managing agitation in AD.


Imaging the molecular dynamics of dissociative electron attachment to water.
Momentum imaging experiments on dissociative electron attachment (DEA) to a water molecule are combined with ab initio theoretical calculations of the angular dependence of the quantum mechanical amplitude for electron attachment to provide a detailed picture of the molecular dynamics of dissociation attachment via the two lowest energy Feshbach resonances. The combination of momentum imaging experiments and theory can reveal dissociation dynamics for which the axial recoil approximation breaks down and thus provides a powerful reaction microscope for DEA to polyatomics.


Remarkable amphibian biomass and abundance in an isolated wetland: implications for wetland conservation.
Despite the continuing loss of wetland habitats and associated declines in amphibian populations, attempts to translate wetland losses into measurable losses to ecosystems have been lacking. We estimated the potential productivity from the amphibian community that would be compromised by the loss of a single isolated wetland that has been protected from most industrial, agricultural, and urban impacts for the past 54 years. We used a continuous drift fence at Ellenton Bay, a 10-ha freshwater wetland on the Savannah River Site, near Aiken, South Carolina (U.S.A.), to sample all amphibians for 1 year following a prolonged drought. Despite intensive agricultural use of the land surrounding Ellenton Bay prior to 1951, we documented 24 species and remarkably high numbers and biomass of juvenile amphibians (>360,000 individuals; >1,400 kg) produced during one breeding season. Anurans (17 species) were more abundant than salamanders (7 species), comprising 96.4% of individual captures. Most (95.9%) of the amphibian biomass came from 232095 individuals of a single species of anuran (southern leopard frog[Rana sphenocephala]). Our results revealed the resilience of an amphibian community to natural stressors and historical habitat alteration and the potential magnitude of biomass and energy transfer from isolated wetlands to surrounding terrestrial habitat. We attributed the postdrought success of amphibians to a combination of adult longevity (often >5 years), a reduction in predator abundance, and an abundance of larval food resources. Likewise, the increase of forest cover around Ellenton Bay from <20% in 1951 to >60% in 2001 probably contributed to the long-term persistence of amphibians at this site. Our findings provide an optimistic counterpoint to the issue of the global decline of biological diversity by demonstrating that conservation efforts can mitigate historical habitat degradation.


Antibacterial and Antibiofilm Activities of Chloroindoles Against Vibrio parahaemolyticus.
Vibrio parahaemolyticus is a food-borne pathogen recognized as the prominent cause of seafood-borne gastroenteritis globally, necessitating novel therapeutic strategies. This study examined the antimicrobial and antivirulence properties of indole and 16 halogenated indoles on V. parahaemolyticus. Among them, 4-chloroindole, 7-chloroindole, 4-iodoindole, and 7-iodoindole effectively inhibited planktonic cell growth, biofilm formation, bacterial motility, fimbrial activity, hydrophobicity, protease activity, and indole production. Specifically, 4-chloroindole at 20 μg/mL inhibited more than 80% of biofilm formation with a minimum inhibitory concentration (MIC) of 50 μg/mL against V. parahaemolyticus and Vibrio harveyi. In contrast, 7-chloroindole inhibited biofilm formation without affecting planktonic cell growth with a MIC of 200 μg/mL. Both chlorinated indoles caused visible damage to the cell membrane, and 4-chloroindole at 100 μg/mL had a bactericidal effect on V. parahaemolyticus within 30 min treatment, which is superior to the effect of tetracycline at the same dose. The quantitative structure-activity relationship (QSAR) analyses revealed that chloro and bromo at positions 4 or 5 of the indole are essential for eradicating the growth of V. parahaemolyticus. These results suggest that halogenated indoles have potential use in antimicrobial and antivirulence strategies against Vibrio species.