The relevance of pharmacological dose--response curves to airway narrowing.
A defect in the smooth muscle of airways has been discarded as a possible cause of asthma in recent years because of the lack of correlation between airflow obstruction in patients and the contractile responsiveness of the isolated airway smooth muscle. Howard Mitchell and Malcolm Sparrow question the relevance of comparing parameters obtained from pharmacological dose-response curves (e.g. EC50) of strips of airways in vitro with those describing airways narrowing in vivo (e.g. resistance). They point out that in small airways the upper half of the dose-response curves seen in strips of airway wall is not represented in perfused tubular airway segments because they are fully constricted at or near the EC50 of the strip.


Prosthetic replacement of tricuspid valve: bioprosthetic or mechanical.
Tricuspid valve replacement is one of the most challenging operations in cardiac surgery. Selection of the suitable prosthesis is still debatable. In our institution, between January 1980 and December 2000, 129 tricuspid valve replacements were performed in 122 patients (14.7%). Bioprosthetic valves were used in 32 patients, whereas 97 patients had mechanical valve implantation. Twenty-two percent of replacements were done on men. Mean age was 35.27+/-11.56 years. In all patients, initially an annuloplasty technique was tried. Tricuspid valve replacement was performed when annuloplasty was not sufficient. In most of the cases, tricuspid valve interventions were done under cardiopulmonary bypass and on a beating heart. Early mortality was 24.5%. Patients were followed for 2 to 228 months. Seven patients underwent reoperation because of tricuspid valve dysfunction (7.6%). Nine patients died during the follow-up period. Late mortality was 9.7%. Actuarial estimates of survival in 20 years of follow-up for all tricuspid prosthetic valves, mechanical valves, and bioprosthetic valves were 65.1%+/-9.3%, 68.3%+/-10.6%, and 54.8%+/-12.1%, respectively. For the bioprosthetic valve group, freedom from structural valve degeneration was 90%+/-5.5%; for the mechanical valve group, freedom from deterioration, endocarditis, and leakage was 97.8%+/-4.2%, and freedom from thromboembolism was 92.6%+/-6.9%. We found that there was no statistically significant difference between the two groups in terms of early mortality, re-replacement, and midterm mortality (p > 0.05). Nevertheless, we recommend low profile modern bileaflet mechanical valves for prosthetic replacement of the tricuspid valve, due to their favorable hemodynamic characteristics and durability.


[Columella defects: yet a challenge!].
The repair of nasal defects is thought to be the most ancient of facial reconstructive procedures, dating back to at least 3000 BC in India. In spite of the development of nasal reconstruction concepts, leading to remarkable esthetic and functional improvements, columella reconstruction is yet a contemporary challenge. Columella defects may result from trauma, infections, carcinoma resection, syphilis, bilateral cleft lip, etc. Maintaining symmetry, contour and function are essential for a successful columella reconstruction. Multiple factors help to determine the optimal repair method, including the size of the defect, its depth and location, and the strength of the underlying nasal framework. This article presents a range of techniques and discusses the application of these methods to specific columella defects. A chronological review of columellar reconstruction procedures used for this partial rhinoplasty is exposed.


Gastrointestinal haemorrhage in a haemophiliac due to a jejunal haemangioma.
Spontaneous mucosal bleeding is not uncommon in hereditary coagulation factor deficiencies and is usually due to a local lesion. We report a case of repeated episodes of melaena in a known haemophiliac caused by a cavernous haemangioma in the jejunum.


The isolation and characterization of XC3H-3b: a CCCH zinc-finger protein required for pronephros development.
We describe the isolation and characterization of the RNA-binding protein XC3H-3b that is expressed during pronephros development. XC3H-3b is a member of the TTP/TIS family of CCCH tandem zinc-finger proteins, which are physiological stimulators of instability for the mRNA encoding tumor necrosis factor-alpha in certain cell types. XC3H-3b is localized primarily to the mesodermal tissues around the pronephros. Overexpression of XC3H-3b markedly and specifically inhibits kidney development. Morpholino-mediated knockdown of XC3H-3b also results in defects in nephrogenesis. In both cases, the expression of numerous pronephric marker genes, such as Xlim-1, Xpax-2, Xpax-8, Xwnt-4, and XWT1, is decreased and morphological development of the pronephric tubules is abrogated. We conclude that XC3H-3b plays an important role in the regulation of pronephros differentiation. This is the first report of a gene localized around the pronephros that regulates pronephros development.


Taxonomic review of the genus Lista Walker, 1859 from China (Lepidoptera, Pyralidae, Epipaschiinae), with descriptions of five new species.
The genus Lista Walker, 1859 from China is reviewed. Of the eighteen species treated, five species are described as new: L. furcellata Li Rong, sp. nov., L. serrata Li Rong, sp. nov., L. strumiformis Li Rong, sp. nov., L. yunnanensis Li Rong, sp. nov. and L. zhengi Li Rong, sp. nov. Photographs of adults and genitalia of the new speices are provided. A key based on male genitalia to all Chinese species is provided.


Choosing wisely - Preclinical test models in the era of precision medicine.
Through the introduction of a steadily growing variety of preclinical test models drug development and biomarker research has advanced. Next to classical used 2D cell line cultures, tissue-slice cultures, 3D organoid cell cultures, genetically engineered mouse models, cell line derived mouse models and patient derived xenografts may be selected for a specific question. All models harbor advantages and disadvantages. This review focuses on the available preclinical test models, novel developments such as humanized mice and discusses for which question a particular model should be employed.


Relationship between parathyroid hormone and renin-angiotensin-aldosterone system in hemodialysis patients with secondary hyperparathyroidism.
Hyperparathyroidism (HPT) is associated with mortality and cardiovascular disease (CVD) in dialysis patients. However, its mechanism is still unclear. It is suspected that parathyroid hormone (PTH) is associated with the renin-angiotensin-aldosterone system (RAAS) as a possible mechanism. Thus, we examined their hormonal interaction in hemodialysis patients with secondary HPT. Seventeen hemodialysis patients with HPT were included. All patients underwent total parathyroidectomy (PTx). Serum intact PTH (iPTH), calcium and phosphate levels, plasma renin activity (PRA), and plasma aldosterone levels (ALD) were measured pre- and post-PTx. Pre-serum iPTH tended to be correlated with pre-PRA and were significantly correlated with pre-ALD (pre-PRA: r = 0.44, p = 0.07, pre-ALD: r = 0.49, p < 0.05). With the reduction in serum iPTH after PTx, PRA and ALD significantly decreased after PTx. Additionally, the change in serum iPTH tended to be correlated with the changes in PRA and ALD (PRA; r = 0.46, p = 0.05, ALD; r = 0.45, p = 0.06). Our results suggest that PTH could be interrelated with RAAS in hemodialysis patients with secondary HPT.


Universal dissymmetry and the origin of biomolecular chirality.
Handed systems are distributed over four general domains. These span the fundamental particles, the molecular enantiomers, the crystal enantiomorphs, and the spiral galaxies. The characterisation of the molecular enantiomers followed from the identification of the crystal enantiomorphs and revealed a chiral homogeneity in the biomolecules of the organic world. The origin of the homogeneity has been variously ascribed to a universal dissymmetric force, from Pasteur, or to a chance choice of the initial enantiomer perpetuated by the stereoselection of diastereomer production with recycling, from Fischer's "key and lock" hypothesis. The classical chiral fields identified by Curie require a particular time or location on the Earth's surface for a determinate molecular enantioselection, as do the weak charged current agencies of the non-classical weak interaction. The weak neutral current of the electroweak interaction provides a constant and uniform chiral agency which favours both the L-series of amino acids and polypeptides and the parent aldotriose of the D-series of sugars. The enantiomeric bias of the electroweak interaction is small at the molecular level: it may become significant either as a trigger-perturbation guiding the transition from a metastable autocatalytic racemic process to one of the two constituent enantiomeric reaction channels, or by cumulative amplification in a large chirally-homogeneous aggregate of enantiomer units.


Isolation and characterization of fluorophore-binding RNA aptamers.
In vitro selection has been shown previously to be a powerful method for isolating nucleic acids with specific ligand-binding functions ('aptamers'). Given this capacity, we have sought to isolate RNA motifs that can confer fluorescent labeling to tagged RNA transcripts, potentially allowing in vivo detection and in vitro spectroscopic analysis of RNAs. Two aptamers that recognize the fluorophore sulforhodamine B were isolated by the in vitro selection process. An unusually large motif of approximately 60 nucleotides is responsible for binding in one RNA (SRB-2). This motif consists of a three-way helical junction with two large, highly conserved unpaired regions. Phosphorothioate mapping with an iodoacetamide-tagged form of the ligand shows that these two regions make close contacts with the fluorophore, suggesting that the two loops combine to form separate halves of a binding pocket. The aptamer binds the fluorophore with high affinity, recognizing both the planar aromatic ring system and a negatively charged sulfonate, a rare example of anion recognition by RNA. An aptamer (FB-1) that specifically binds fluorescein has also been isolated by mutagenesis of a sulforhodamine aptamer followed by re-selection. In a simple in vitro test, SRB-2 and FB-1 have been shown to discriminate between sulforhodamine and fluorescein, specifically localizing each fluorophore to beads tagged with the corresponding aptamer. In addition to serving as a model system for understanding the basis of RNA folding and function, these experiments demonstrate potential applications for the aptamers in transcript double labeling or fluorescence resonance energy transfer studies.


Pulmonary mucinous adenocarcinomas: architectural patterns in correlation with genetic changes, prognosis and survival.
Of pulmonary adenocarcinomas, about 25-30 % of cases is of a mucinous type. Mucinous adenocarcinomas are regarded as more aggressive compared to their non-mucinous counterparts. Invasive mucinous adenocarcinoma, colloid, and enteric adenocarcinomas are variants within adenocarcinomas. We investigated 76 invasive mucinous adenocarcinomas, including colloid variants, for predominant and secondary patterns, their different form of mucin storage and release, expression of cytokeratin 7 and 20, TTF1 and CDX2, MUC1, 2, and 5AC proteins, p14 and p16 proteins, possible rearrangements for EML4ALK and ROS1, as well as KRAS mutational status, and correlated this with survival. For comparison, 259 non-mucinous adenocarcinomas were selected. Overall survival for invasive mucinous adenocarcinomas corrected for T and N stage was not different from their non-mucinous counterpart. Most were of an acinar pattern. Neither pattern, nor type of mucin storage and release, such as luminal, extracellular, or goblet cell type had any influence on survival. Of adenocarcinomas expressing CK20, all but one expressed TTF1 either strongly or at least focally, and 8 co-expressed CDX2 focally. Most mucinous adenocarcinomas expressed either MUC1 or MUC5AC proteins, but rarely MUC2, while a few cases co-expressed both or all three. Loss of p16 expression correlated with worse outcome. KRAS mutation was found in 56 % of mucinous adenocarcinomas. Mutational status was neither correlated with architectural pattern nor survival. Codon 12 mutations were most frequent, and one case presented with KRAS mutations in codon 12 and 61. Goblet cell variants of mucinous adenocarcinomas presented predominantly with codon 12 mutations, while all colloid variants had KRAS mutation. Two cases had EML4 and ALK1 rearranged; ROS1 rearrangement was not found. Mucinous adenocarcinomas behave similar to non-mucinous variants. TNM stage is the most important factor followed by p16 loss predicting overall survival.


Nonresection triple arthrodesis: a retrospective analysis.
This case series examines triple arthrodesis using articular cartilage excision without bone resection. Due to the technically demanding nature of triple arthrodesis, the authors present a nonresection technique with its perceived advantages over joint resection triple arthrodesis in the presence of reducible deformity, such as minimal shortening of bone, ease of execution, and better bony apposition. Fourteen patients with nonresection triple arthrodesis from two medical centers are included in this report. Postoperative follow-up ranged from 6 to 36 months. Evaluation of results was performed subjectively and radiographically. There was a low incidence of nonunion (2% of joints) and minimal to no bone shortening (0.1 cm mean talonavicular shortening and 0.1 cm mean increase in talocalcaneal height). Mean time to fusion of joints fixed with screws was 9.91 weeks (SD = 3.61, n = 31), while fusion time for staple or pin fixation was 8.96 weeks (SD = 4.15, n = 10). There were no significant differences in time to fusion between screw and nonscrew fixation (p = .26) nor when comparing procedures within each patient (p = .30). At follow-up, five patients reported no pain at any time (36%); two patients reported mild occasional pain (14%). Moderate, daily pain was reported by seven patients (50%). While no direct comparison with resection triple arthrodesis was made, the positive subjective and objective results support this procedure.


Poly(-β-hydroxybutyrate) (PHB) depolymerase PHAZ Pen from Penicillium expansum: purification, characterization and kinetic studies.
Very few studies have been dedicated to R-hydroxyacids (R-HA) production using extracellular polyhydroxyalkanoate depolymerases (ePhaZs). Penicillium expansum produced maximum extracellular polyhydroxybutyrate depolymerase (~6 U/mL) by 72 h when grown in mineral salt medium containing 0.2 % w/v PHB, pH 5.0, at 30 °C and 200 rpm shaking conditions. Partial purification of the extracellular poly(-β-hydroxybutyrate) depolymerase PHAZ Pen from P. expansum by two steps using ammonium sulphate (80 % saturation) and affinity chromatography using concanavalin A yielded 22.76-fold purity and 43.15 % recovery of protein. The enzyme composed of a single polypeptide chain of apparent molecular mass of 20 kDa, as determined by SDS-PAGE, stained positive for glycoprotein by periodic-schiff base (PAS) staining. Optimum enzyme activity was detected between pH 4.0 and 6.0 at 45-50 °C with pH 5.0 and 50 °C supporting maximum activity. The enzyme was stable between pH 4.0 and 6.0 at 55 °C for 1 h with a residual activity of almost 70-80 %. The enzyme was completely inhibited by 1 mM DTT/1 mM HgCl2 and N-ethylmaleimide (10 mM) indicating the importance of essential disulphide bonds (cystine residues) and tyrosine for enzyme activity or probably for maintaining the native enzyme structure. Among the various divalent and trivalent metal ions, mercuric chloride, ferric citrate and ferrous sulphate inhibited enzyme activity. The enzyme showed substrate specificity towards only PHB and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and no other lipid or other p-nitrophenyl fatty acids or with polycaprolactone, showing that it was a true depolymerase and not any lipase or cutinase. Preliminary investigation revealed β-hydroxybutyrate as the end product of PHB hydrolysis by P. expansum, suggesting that the enzyme acted principally as an exo-type hydrolase. The above properties when compared with other fungal PHB depolymerases reported till date suggest the distinct nature of the PHB depolymerase of P. expansum.


Patterns of urban mercury contamination detected by bioindication with terrestrial isopods.
Mercury (Hg) is a trace element with high toxicological impact on potential receptors, including human beings. Global Hg emissions are predicted to increase significantly during the next 40 years. After emission, the metal is transported by air currents and precipitations, leading to increasing depositions even in areas far from emission sources. In the terrestrial environment, Hg is subjected to redistribution and transformation into different inorganic and metal-organic species that are taken up by vegetation and soil organisms. In the present study, the woodlouse (Porcellio scaber) was used as a biological indicator of total Hg pollution in the city of Dornbirn (province of Vorarlberg), Austria. Woodlice were collected from 30 sampling points scattered over the city area, 25 of them situated within a rectangular transect crossing the city area from west-northwest to east-southeast, starting near the Rheintal motorway and ending at the slopes of the Bregenzer Wald hills. In addition to woodlice, soil substrate samples were collected at nine of the selected sampling points. Total Hg concentrations were measured in isopod tissues and soil substrate samples by means of an Hg analyzer. Total Hg concentrations in isopod tissues were significantly correlated with Hg soil contents (P < 0.05). Moreover, a gradient of increasing Hg concentrations was observed in isopod samples along the transect across Dornbirn, with the lowest concentrations detected in woodlouse samples near the Rheintal motorway and the highest levels toward the ascending slopes of the Bregenzer Wald hills. This gradient of increasing Hg concentrations across the city matches a concomitant increase in wet precipitations along the same direction, indicating that deposition by wet precipitation may be an important source for Hg contamination in the city of Dornbirn. Overall, the degree of Hg contamination across the study area can be regarded as rather low, i.e., comparable with concentrations observed in other, unpolluted terrestrial habitats. It is concluded that bioindication by total Hg analysis in woodlice can be applied to distinguish between different levels and sources of contamination in urban areas.


Glycyl-tRNA synthetase from rat liver: The role of tRNA in formation of glycylhydroxamates.
One glycyl-tRNA synthetase from rat liver does not form glycylhydroxamates in the absence of tRNA. Glycyl-hydroxamate accumulated during the incubation of enzyme preparation with glycine, ATP, tRNA and NH(2)OH is formed by non-enzymatic hydroxylaminolysis of glycyl-tRNA.


Comparison of electrocardiographic data (P waves): test of a shape-based approach.
We tested a method for comparing ECG signals (P waves), in a sample of 10 normal males. In each subject, sets of 219 body surface ECGs were simultaneously recorded during tidal respiration. Only beats at end expiration and peak inspiration were considered. The beats of each group were subdivided into two subgroups of the same size (about 30 beats) and separately averaged. The two averaged beats at end expiration, assumed to be equal, were compared in order to estimate the noise variance (sigma2), i.e., the lowest value of variance at which the beats were statistically similar (P less than 0.05). At the same value of sigma2, the beat at end expiration significantly differed from that at peak inspiration. By considering the individual leads, significant differences were found in more than 50% of the 219 ECGs, in specific thoracic areas. The data indicated that the method can reveal differences between P waves occurring during tidal respiration and provide information on the topographical distribution of the differences.


Synthesis and Characterization of 40 wt % Ce0.9Pr0.1O2-δ-60 wt % NdxSr1-xFe0.9Cu0.1O3-δ Dual-Phase Membranes for Efficient Oxygen Separation.
Dense, H2- and CO2-resistant, oxygen-permeable 40 wt % Ce0.9Pr0.1O2-δ-60 wt % NdxSr1-xFe0.9Cu0.1O3-δdual-phase membranes were prepared in a one-pot process. These Nd-containing dual-phase membranes have up to 60% lower material costs than many classically used dual-phase materials. The Ce0.9Pr0.1O2-δ-Nd0.5Sr0.5Fe0.9Cu0.1O3-δ sample demonstrates outstanding activity and a regenerative ability in the presence of different atmospheres, especially in a reducing atmosphere and pure CO2 atmosphere in comparison with all investigated samples. The oxygen permeation fluxes across a Ce0.9Pr0.1O2-δ-Nd0.5Sr0.5Fe0.9Cu0.1O3-δ membrane reached up to 1.02 mL min-1 cm-2 and 0.63 mL min-1 cm-2 under an air/He and air/CO2 gradient at T = 1223 K, respectively. In addition, a Ce0.9Pr0.1O2-δ-Nd0.5Sr0.5Fe0.9Cu0.1O3-δ membrane (0.65 mm thickness) shows excellent long-term self-healing stability for 125 h. The repeated membrane fabrication delivered oxygen permeation fluxes had a deviation of less than 5%. These results indicate that this highly renewable dual-phase membrane is a potential candidate for long lifetime, high temperature gas separation applications and coupled reaction-separation processes.


Geoepidemiology of hepatocellular carcinoma in the island of Crete, Greece. A possible role of pesticides.
Geoepidemiological data of hepatocellular carcinoma (HCC) are lacking. Crete has a genetically homogeneous population and is suitable for studies to identify a possible contribution of environmental factors in HCC. Databases for HCC (316 cases), hepatitis B virus (HBV) (633) and hepatitis C virus (HCV) (392), constructed over the past 20 years in our Unit, were used. Data included place of birth and place of residence for the last 15 years. Hellenic Statistical Authority provided population statistics from 1980 to 2014. Time-spatial methods were applied in Gis-ArcMap 10 software. Spatial autocorrelation tests (Moran's index) detected differences between the spatial distribution to place of residence. Spatial density maps were created. Kriging Interpolation was applied, to produce prediction maps of HCC. Hepatitis C virus appears in areas of high prevalence while HBV is uniformly distributed. HCC is more prevalent in Eastern Crete. A spatial autocorrelation between HCC and either HCV (Moran's I = 0.88, P < 0.001) or HBV (I = 0.84, P < 0.02) was found as expected. However, there is a discrepancy in the South East of Crete, where a higher prevalence of HCC than expected was observed. This is an area where extensive use of pesticides in large green houses is practiced. Hepatocellular carcinoma is associated with the dispersion of HCV and HBVs. In an area with widespread use of pesticides, a higher than expected spatial distribution of HCC was detected.


Variation and specialisation of the forcipular apparatus of centipedes (Arthropoda: Chilopoda): a comparative morphometric and microscopic investigation of an evolutionary novelty.
The forcipules of centipedes are the only known example in the animal kingdom of an evolutionary transition from walking legs to venom-injecting appendages. They provide a classic case of an evolutionary novelty under most (but not all) definitions of that concept. Although there is a reasonable literature on forcipules, and on the forcipular segment more generally, it is fragmentary and scattered. Also, many previous studies have been based on a single species and hence have no comparative component. Here, we build on this earlier literature by providing detailed qualitative and quantitative information on the forcipular segments of representatives of the five extant orders of centipedes. Our results reveal notable differences between the orders - as well as considerable variation within some of them. The pattern of inter-group differences can be used to infer, albeit cautiously, a major evolutionary trend from a presumed scutigeromorph-like last common ancestor (LCA), in which the forcipules were probably leg-like (as in present-day scutigeromorphs) to a more specialized claw-like structure with movement restricted to the horizontal plane. This morphological trend may reflect an ecological trend from open-habitat ambush predation to leaf-litter and subterranean predatory opportunism.


Vacuolar nicotianamine has critical and distinct roles under iron deficiency and for zinc sequestration in Arabidopsis.
The essential micronutrients Fe and Zn often limit plant growth but are toxic in excess. Arabidopsis thaliana ZINC-INDUCED FACILITATOR1 (ZIF1) is a vacuolar membrane major facilitator superfamily protein required for basal Zn tolerance. Here, we show that overexpression of ZIF1 enhances the partitioning into vacuoles of the low molecular mass metal chelator nicotianamine and leads to pronounced nicotianamine accumulation in roots, accompanied by vacuolar buildup of Zn. Heterologous ZIF1 protein localizes to vacuolar membranes and enhances nicotianamine contents of yeast cells engineered to synthesize nicotianamine, without complementing a Zn-hypersensitive mutant that additionally lacks vacuolar membrane Zn(2+)/H(+) antiport activity. Retention in roots of Zn, but not of Fe, is enhanced in ZIF1 overexpressors at the expense of the shoots. Furthermore, these lines exhibit impaired intercellular Fe movement in leaves and constitutive Fe deficiency symptoms, thus phenocopying nicotianamine biosynthesis mutants. Hence, perturbing the subcellular distribution of the chelator nicotianamine has profound, yet distinct, effects on Zn and Fe with respect to their subcellular and interorgan partitioning. The zif1 mutant is also hypersensitive to Fe deficiency, even in media lacking added Zn. Therefore, accurate levels of ZIF1 expression are critical for both Zn and Fe homeostasis. This will help to advance the biofortification of crops.


Representations and uses of emergency contraception in West Africa. A social anthropological reading of a northern medicinal product.
Since the early 2000s a new form of progesterone based emergency contraception with no side effects has been on the African market, aimed at reducing contraceptive failure rates and the mortality associated with the practice of unsafe abortion. Studies of emergency contraception (EC) carried out in West Africa have only examined opinions and knowledge about EC. We hypothesized that representations and uses of this method takes place at the intersection of two dimensions: (i) a "Northern" pharmaceutical norm, and (ii) local understandings of the timing of conception. To test this hypothesis we used a discourse analysis of semi-structured interviews with 149 women and 77 with men aged between 18 and 40, of varying marital, social and professional status, resident in Dakar, Ouagadougou and Accra. The interviews were conducted in 2005-2007. EC is overwhelmingly perceived as a Northern medical treatment which encourages greater sexual freedom for women. Many respondents, both male and female, believe that EC is a "chemical" product that may cause sterility, and there is severe questioning of its supposed abortifacient character. EC is being used as recommended by the medical profession - in an occasional manner and in cases of urgent need; but it is also being used, like other post-coital methods which women have long employed, in a programmed and repeated manner. On the one hand the social issue raised by EC, namely the weakening of control by men of the sexuality and fertility of women, may be an obstacle to its diffusion. On the other hand, it may in the end be viewed as simply another post-coital method, whose use is framed by the prevailing systems of temporal representations in the three countries concerned in the study.


[Structure of nuclear pre-mRNA. IX. Hybridization of double-stranded portions of pre-mRNA with excess mRNA].
The hybridization of double-stranded regions of pre-mRNA from mouse Ehrlich ascites carcinoma cells, rabbit bone marrow cells and primary culture of rabbit kidney cells with an excess of total poly(A)+-mRNA of mouse or rabbit globin mRNA respectively was studied. The hybrids were detected as RNAase-stable acid precipitable material or by adsorbtion of the hybrid complexes of poly(U)-sepharose. The sizes of the hybrid complementary sequences and their thermal stability were estimated.


Aryl hydrocarbon hydroxylase induction in mitogen-stimulated lymphocytes by benzanthracene or cigarette tars adsorbed to asbestos fibers.
Human mitogen-stimulated lymphocytes, cultured in the presence of amosite asbestos (AS), demonstrated a slight increase in aryl hydrocarbon hydroxylase (AHH) activity compared with non-induced (control) cultures (P = 0.005). A much greater increase in enzyme activity occurred following addition of the inducers benzanthracene (BA) or cigarette tars (CT) to cell cultures (P less than 0.001 in both instances). Significant enzyme induction also occurred when AS fibers were first preincubated with CT or BA, washed with acetone, then added to lymphocyte cultures (P less than 0.003 in all instances). This increase in AHH activity was not as great, however, as the induction observed when BA or CT was added to cell cultures. No further increase in enzyme activity was noted when AS and CT or AS and BA were simultaneously added to culture lymphocytes (P greater than 0.070 in all instances). The results demonstrate that polycyclic aromatic hydrocarbons (PAH), such as BA and other components of CT, are adsorbed and transported by amosite AS particles. These AS-PAH complexes are capable of inducing AHH in cultured human lymphocytes.


Natural STING Agonist as an "Ideal" Adjuvant for Cutaneous Vaccination.
A potent adjuvant that induces strong protective immunity without incurring any significant skin reactogenicity is urgently needed for cutaneous vaccination. Here, we report that a natural agonist of stimulator of interferon genes (STING), 2'3'- cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), robustly augmented and prolonged the cellular and humoral immune responses provoked by H5N1 and 2009 H1N1 pandemic influenza vaccines after a single dose of intradermal, but not intramuscular, immunization. The potency of cGAMP for cutaneous vaccination was ascribed to a large number of antigen-presenting cells resident in the skin and ready for immediate activation when cGAMP was injected. However, its potency was severely compromised in the muscle, because antigen-presenting cells could not be promptly recruited to the injection site before the injected cGAMP was diffused out. The superior adjuvant effect and safety of cGAMP were also confirmed in a more clinically relevant swine model of skin. The vigorous immune responses elicited by cGAMP with no overt skin irritation was attributable to its stay in the skin, which was brief but sufficient to activate dermal dendritic cells. This small and well-characterized self-molecule holds great promise as an ideal adjuvant for cutaneous vaccination.


Anton syndrome after subarachnoid hemorrhage and delayed cerebral ischemia: A case report.
We report the case of a patient with ruptured middle cerebral artery aneurysm, subarachnoid hemorrhage and frontal intracerebral hemorrhage, who secondarily presented with delayed cerebral ischemia and bilateral occipital infarcts, with complete vision loss, visual anosognosia, and confabulations as the main symptoms. Additionally, the patient had defined features of Cotard syndrome, as revealed by persistent nihilistic delusions. The brain imaging studies showed a bilateral occipital ischemic lesion, as well as frontal and parietal hemorrhagic lesions in the right hemisphere. We address the general theories of anosognosia, confabulation and the problem of why a bilateral occipital lesion is not enough for these metacognitive defects to exist. The presence of right frontal and or parietal hemisphere lesions could be necessary features in most cases.


Glutathione-S-transferase polymorphism and clinical features of acute drug poisoning in children.
We studied the association of GSTM1 and GSTT1 and GSTP1 Ile105-Val105 polymorphism with the duration of intoxication, polyorgan failure, and severity of drug poisoning in children. The combination of GSTM1 and GSTT1 zero genotypes is a favorable sign for the duration of intoxication and severity of the disease.


[Phase I study of CPT-11 and continuous 5-FU / l-leucovorin combination therapy(modified AIO regimen)in patients with metastatic colorectal cancer].
A combination of CPT-11, continuous 5-fluorouracil(5-FU)and leucovorin(LV), the Arbeitsgemeinschaft für Internistische Onkologie(AIO)regimen, is widely used for the treatment of metastatic CRC. The efficacy and toxicity of this regimen, however, have not been determined in Japanese patients with metastatic CRC. Our objective was to evaluate the safety of the AIO regimen plus CPT-11 in Japanese colorectal carcinoma(CRC)patients. We investigated the maximum tolerated dose(MTD), dose-limiting toxicity(DLT), and recommended dose(RD)for CPT-11 and continuous 5-FU. CPT-11, 5-FU, and l-LV were administered on days 1, 8, and 15 of a 28-day cycle. The dose of CPT- 11 was escalated from 40 mg/m2 (level 1)to 80 mg/m2 (level 3). The 5-FU dose was then escalated from 1,000 mg/m2 (level 4)to 2,000 mg/m2 (level 5). If neither level met the criteria for the MTD, the recommended dose was defined as level 5, and the dose escalation was discontinued, because the maximum approved weekly dose of CPT-11 alone in Japan is 80 mg/m2 and the dose of 5-FU in the original AIO regimen was 2,000 mg/m2. A total of 18 patients were enrolled in this study. Hematological and non-hematological toxicity were infrequent and mild. There were no toxicities greater than grade 2 at each dose level. Level 5 did not meet the MTD criteria. Our results confirm that the modified AIO plus CPT-11 regimen is safe for Japanese patients. The recommended doses in the present study were CPT-11 80 mg/m2, 5-FU 2,000 mg/m2, and l-LV 250 mg/m2.


Anionic phospholipid-induced regulation of reactive oxygen species production by human cytochrome P450 2E1.
We suggest that the cytochrome P450 2E1 (CYP2E1)-induced formation of reactive oxygen species (ROS) can be regulated by anionic phospholipids and the presence of the N-terminal region of the enzyme. When the content of cardiolipin (CL) in membranes at the expense of phosphatidylcholine matrix was increased, the ROS produced by recombinant human CYP2E1 was decreased as a function of CL concentration. On the contrary, the N-terminally truncated CYP2E1 had a decreased effect on the lipid-induced reduction of ROS formation. These results suggest that specific phospholipids can regulate the function of CYP2E1 by interaction with the enzyme including the N-terminal region(s).


Performance degradation of the coherent averaging technique by a molding effect.
In coherent averaging, we show that when temporal alignment is performed by matched filtering, the SNR improvement may reach a stable limit after a certain number of averaged events. The source of this degradation lies in the noise that can be contained in the template of the matched filter. This effect depends on the SNR and the morphology of the signal and it can be reduced by a multipass averaging procedure or by a template updating technique.


Trauma induced increases in plasma vasopressin and angiotensin II.
Previous investigators have shown that hypotension will cause an increase in plasma levels of both vasopressin and angiotensin II. Significant increases in peripheral resistance after thermal trauma suggested that a similar increase in plasma vasopressin and angiotensin II levels might occur under this condition. This possibility has been studied in the pentobarbital anesthetized dog. Peripheral resistance was calculated from measured cardiac output and mean arterial blood pressure. Vasopressin and angiotensin II levels were measured by radio-immunoassay. The results of this study showed that vasopressin plasma levels increase 4 to 6 fold 15 minutes after thermal trauma and remained elevated (3 to 4 fold) for at least 6 hours. Angiotensin II increased in a linear manner from 15 minutes to 6 hours post trauma. At 6 hours post trauma angiotensin II plasma levels were 4 times pretrauma levels. For the first 4 hours post trauma there was a positive correlation between the sum of vasopressin and angiotensin II plasma levels and the increase in peripheral resistance. These results suggest that the trauma induced increase in peripheral resistance is due to increases in plasma vasopressin and angiotensin II.


Minimally invasive endoscope-assisted parotidectomy: a new approach.
To evaluate the benefits of a new approach, endoscopic parotidectomy through a postauricular skin incision by using an ultrasonically activated scalpel. An investigation of the outcome of endoscopic parotidectomy at a tertiary referral medical center. Fourteen operations for selected patients presenting with benign parotid tail disease were performed via minimally invasive endoscopic resection by a single surgeon (MK Chen). All 14 operations were successfully performed endoscopically, and no conversions to conventional open resection were necessary. The procedures lasted 60 to 160 minutes. Two patients had transient grade II facial paresis. The scars were almost invisible due to their concealed location behind the ear. Minimally invasive endoscope-assisted parotidectomy is a feasible method for treatment of benign lesions located in the parotid tail. The main advantage of this procedure is that the small operative scar is concealed in the postauricular area resulting in improved cosmetic results.


Linkage of angiotensin I-converting enzyme gene insertion/deletion polymorphism to the progression of human prostate cancer.
Angiotensin-converting enzyme (ACE) degrades vasodilator kinins and generates angiotensin II (Ang II). It has been reported that ACE is synthesized by the prostate and that the AT-1 receptor subtype is the predominant prostatic Ang II receptor. A polymorphism in the human ACE gene has been described and the highest levels of circulating and tissue ACE activity are found in carriers of the DD genotype. In the present study, ACE genotypes were determined in 170 patients with prostate cancer and their association with disease progression was analysed. It was found that the DD genotype was present in 31 of 78 (39.8%) patients with advanced disease and in 19 of 82 (23.2%) with localized disease: this difference was statistically significant (OR = 2.18, 95% CI = 1.11-4.03; p = 0.024). Step-wise logistic regression analysis was used to identify predictive parameters of advanced disease and it was observed that the DD genotype (p = 0.002, OR = 5.4, 95% CI = 1.84-16.06), high-grade tumour (p < 0.001, OR = 8.04, 95% CI = 3.03-21.33), and high serum PSA (p < 0.001, OR = 10.87, 95% CI = 4.06-29.13) were significantly associated with advanced disease. The results of this study support the hypothesis that genetic factors related to ACE may influence the behaviour of human prostate cancer.


The microtubule plus end-binding protein EB1 is involved in Sertoli cell plasticity in testicular seminiferous tubules.
Sertoli cells of testis belong to a unique type of polarized epithelial cells and are essential for spermatogenesis. They form the blood-testis barrier at the base of seminiferous tubule. Their numerous long, microtubule-rich processes extend inward and associate with developing germ cells to sustain germ cell growth and differentiation. How Sertoli cells develop and maintain their elaborate processes has been an intriguing question. Here we showed that, by microinjecting lentiviral preparations into mouse testes of 29 days postpartum, we were able to specifically label individual Sertoli cells with GFP, thus achieving a clear view of their natural configurations together with associated germ cells in situ. Moreover, compared to other microtubule plus end-tracking proteins such as CLIP-170 and p150(Glued), EB1 was highly expressed in Sertoli cells and located along microtubule bundles in Sertoli cell processes. Stable overexpression of a GFP-tagged dominant-negative EB1 mutant disrupted microtubule organizations in cultured Sertoli cells. Furthermore, its overexpression in testis Sertoli cells altered their shapes. Sertoli cells in situ became rod-like, with decreased basal and lateral cell processes. Seminiferous tubule circularity and germ cell number were also reduced. These data indicate a requirement of proper microtubule arrays for Sertoli cell plasticity and function in testis.


Ultrasonic Sound Speed Estimation for Liver Fat Quantification: A Review by the AIUM-RSNA QIBA Pulse-Echo Quantitative Ultrasound Initiative.
Non-alcoholic fatty liver disease (NAFLD) is a significant cause of diffuse liver disease, morbidity and mortality worldwide. Early and accurate diagnosis of NALFD is critical to identify patients at risk of disease progression. Liver biopsy is the current gold standard for diagnosis and prognosis. However, a non-invasive diagnostic tool is desired because of the high cost and risk of complications of tissue sampling. Medical ultrasound is a safe, inexpensive and widely available imaging tool for diagnosing NAFLD. Emerging sonographic tools to quantitatively estimate hepatic fat fraction, such as tissue sound speed estimation, are likely to improve diagnostic accuracy, precision and reproducibility compared with existing qualitative and semi-quantitative techniques. Various pulse-echo ultrasound speed of sound estimation methodologies have been investigated, and some have been recently commercialized. We review state-of-the-art in vivo speed of sound estimation techniques, including their advantages, limitations, technical sources of variability, biological confounders and existing commercial implementations. We report the expected range of hepatic speed of sound as a function of liver steatosis and fibrosis that may be encountered in clinical practice. Ongoing efforts seek to quantify sound speed measurement accuracy and precision to inform threshold development around meaningful differences in fat fraction and between sequential measurements.


Stereoselective nicotine-induced release of dopamine from striatal synaptosomes: concentration dependence and repetitive stimulation.
Using a sensitive perfusion system we have studied the nicotine-induced release of [3H]dopamine ([( 3H]DA) from striatal synaptosomes. Nicotine-evoked release was concentration dependent with an EC50 of 3.8 microM. The response to 1 microM nicotine was comparable to that to 16 mM K+; 10 microM veratridine evoked a larger response. All three stimuli were Ca2+ dependent but only the response to veratridine was blocked by tetrodotoxin. Repetitive stimulations by 1 microM (-)-nicotine (100 microliters) at 30-min intervals resulted in similar levels of [3H]DA release; higher concentrations of (-)-nicotine resulted in an attenuation of the response particularly following the third stimulation. This may reflect desensitisation or tachyphylaxis of the presynaptic nicotinic receptor. The action of nicotine was markedly stereoselective: a 100-fold higher concentration of (+)-nicotine was necessary to evoke the same level of response as 1 microM (-)-nicotine. It is proposed that these presynaptic nicotinic receptors on striatal terminals are equivalent to high-affinity nicotine binding sites described in mammalian brain.


Understanding the "Weekend Effect" for Emergency General Surgery.
Several studies have identified a "weekend effect" for surgical outcomes, but definitions vary and the cause is unclear. Our aim was to better characterize the weekend effect for emergency general surgery using mortality as a primary endpoint. Using data from the University HealthSystem Consortium from 2009 to 2013, we identified urgent/emergent hospital admissions for seven procedures representing 80% of the national burden of emergency general surgery. Patient characteristics and surgical outcomes were compared between cases that were performed on weekdays vs weekends. Hospitals varied widely in the proportion of procedures performed on the weekend. Of the procedures examined, four had higher mortality for weekend cases (laparotomy, lysis of adhesions, partial colectomy, and small bowel resection; p < 0.01), while three did not (appendectomy, cholecystectomy, and peptic ulcer disease repair). Among the four procedures with increased weekend mortality, patients undergoing weekend procedures also had increased severity of illness and shorter time from admission to surgery (p < 0.01). Multivariate analysis adjusting for patient characteristics demonstrated independently higher mortality on weekends for these same four procedures (p < 0.01). For the first time, we have identified specific emergency general surgery procedures that incur higher mortality when performed on weekends. This may be due to acute changes in patient status that require weekend surgery or indications for urgent procedures (ischemia, obstruction) compared to those without a weekend mortality difference (infection). Hospitals that perform weekend surgery must acknowledge and identify ways to manage this increased risk.


Comparative analysis of genomic- and EST-SSRs in European plum (Prunus domestica L.): implications for the diversity analysis of polyploids.
Simple sequence repeats (SSRs) are among the most useful DNA markers in plant science. The aim of this study was to compare the features and usefulness of genomic SSR (gSSR) and EST-SSRs in European plum (Prunus domestica L.), an economically important, hexaploid stone fruit crop globally cultivated to produce fleshy fruits and derived foodstuff. The analysis of an ample set of morphologically diverse varieties indicated that gSSRs and EST-SSRs provide different estimates of some of the locus-based indicators of diversity. Moreover, the two classes of SSRs gave different, weakly correlated, estimations of distance-based parameters with gSSRs being more powerful for discriminating purposes. The two SSR classes provide complementary information in European plum, making the contribution of EST-SSRs useful not only as non-neutral markers. The differences between SSR classes are discussed considering the neutral and non-neutral evolution, and the polyploidy and asexual propagation of the cultivated tree varieties.


None of polymorphism of ovine fecundity major genes FecB and FecX was tested in goat.
The polymorphism of mutation Q249R in BMPR-IB gene (FecB) and loci FecX(I), FecX(H), FecX(G), FecX(B) in BMP15 gene was analyzed by forced PCR-RFLP method in 550 individuals from 6 flocks or breeds of goats with litter size varied from 1.4 to 2.7 including Boer (209), Haimen (128), second generation of Boer goat crossed with Huanghuai goat (82), Huanghuai (71), Nubi (37) and Matou (23) goat. None of mutations was detected in these goat breeds and their crossbreed. These results suggest that fecundity of goat is not linked to the same loci in BMPR-IB and BMP15 as sheep. Therefore, it is necessary to seek for other genes or loci in order to develop marker assistance selection techniques and study the prolific mechanism of the goat.


The effects on human health and hydrogeochemical characteristics of the Kirkgeçit and Ozancik Hot Springs, Canakkale, Turkey.
This investigation was carried out to determine the hydrogeochemical characteristics of the Kirkgeçit and Ozancik hot springs. The study areas are located northeast and southwest of the town of Can, Canakkale. During the investigation, geological maps of the hot springs and its surroundings were prepared, and hot waters and rock samples were collected from the study sites. The Paleogene-Neogene aged andesite, trachyandesite, andesitic tuff, silicified tuff and tuffites form the basement rocks in the Ozancik hot spring area. In the Kirkgeçit hot spring area, there are Lower Triassic aged mica and quartz schists at the basement rocks. The unit is covered by limestones and marbles of the same age. They are overlain by Quaternary alluvial deposits. A chemical analysis of the Kirkgeçit hot water indicates that it is rich in SO(4)2- (1200.2 mgL-1), Cl- (121.7 mgL-1), HCO3- (32.5 mg L-1), Na+ (494 mg L-1), K+ (30.2 mg L-1), Ca2+ (102 mg L-1), Mg2+ (15.2 mg L-1), and SiO2 (65.22 mg L-1). Chemical analysis of the Ozancik hot water indicates that it is rich in SO(4)2- (575 mg L-1), Cl- (193.2 mg L-1), HCO3- (98.5 mg L-1), Na+ (315 mg L-1), K+ (7.248 mg L-1), Ca2+ (103 mg L-1), Mg2+ (0.274 mg L-1), and SiO2 (43.20 mg L-1). The distribution of ions in the hot waters on the Schoeller diagram has an arrangement of r(Na(+) + K+) > rCa2+ > rMg2+ and r(SO(4)2-) > rCl- > r(HCO3-). In addition, the inclusion of Fe2+, Cu2+, Cr3+, Mn2+, Ni2+ and Hg2+ in the hot water samples indicates potential natural inorganic contamination. The water analysis carried out following the ICPMS-200 technique was evaluated according to the World Health Organisation and Turkish Standards. The use and the effects of the hot water on human health are also discussed in the paper.


Short-term Outcomes of Laparoscopic and Open Distal Pancreatectomy Using Propensity Score Analysis: A Real-world Retrospective Cohort Study.
This study aimed to compare the short-term outcomes between laparoscopic and open distal pancreatectomy for lesions of the distal pancreas from a real-world database. Reports on the benefits of laparoscopic distal pancreatectomy include 2 randomized controlled trials; however, large-scale, real-world data are scarce. We analyzed the data of patients undergoing laparoscopic or open distal pancreatectomy for benign or malignant pancreatic tumors from April 2008 to May 2020 from a Japanese nationwide inpatient database. We performed propensity score analyses to compare the inhospital mortality, morbidity, readmission rate, reoperation rate, length of postoperative stay, and medical cost between the 2 groups. From 5502 eligible patients, we created a pseudopopulation of patients undergoing laparoscopic and open distal pancreatectomy using inverse probability of treatment weighting. Laparoscopic distal pancreatectomy was associated with lower inhospital mortality during the period of admission (0.0% vs 0.7%, P <0.001) and within 30 days (0.0% vs 0.2%, P =0.001), incidence of reoperation during the period of admission (0.7% vs 1.7%, P =0.018), postpancreatectomy hemorrhage (0.4% vs 2.0%, P <0.001), ileus (1.1% vs 2.8%, P =0.007), and shorter postoperative length of stay (17 vs 20 d, P <0.001). The propensity score analysis revealed that laparoscopic distal pancreatectomy was associated with better outcomes than open surgery in terms of inhospital mortality, reoperation rate, postoperative length of stay, and incidence of postoperative complications such as postpancreatectomy hemorrhage and ileus.


Some issues relating to the use of perfluorooctanesulfonate (PFOS) samples as reference standards.
Samples of potassium perfluorooctanesulfonate (PFOSK) from three suppliers were analyzed by LC-ESI-MS/MS for purity and by LC-ESI-MS for the percentage of linear isomer present. Our data indicated that the purity ranged from 80% to 98% and the percentages of linear isomer from 67% to 79%. The proportion of branched isomers present in the samples was also estimated using (19)F NMR. These results agreed quite closely with those found by LC-ESI-MS indicating that there is essentially no difference in overall SIM response factor for the branched isomers vs. that of the linear isomer. Several further observations relevant to the use of standards when analyzing for PFOS were encountered during this study. It appears unlikely that matrix effects attributable to the cation (sodium or potassium) present in PFOSNa or PFOSK internal standards is an issue. In seeking potential matrix effects, it was found that the chromatography was improved substantially when the standard was injected as a solution in 80:20 methanol/water rather than 100% methanol. Notably, in concert with the improvement in chromatography, an increase of about 10% in response was observed. In some closely related studies, when (18)O(2) mass-labeled perfluorohexanesulfonate was used as an internal standard, the actual and theoretical concentration ratios matched closely those for related native sulfonates as long as they did not co-elute. However, when they did co-elute, the peak intensities of the native species were enhanced by about 5%, while those of the labeled compound were suppressed by a similar amount. If this effect were not taken into account, the concentration of the native would be inflated by 10%.


Arterial compression of nerve is the primary cause of trigeminal neuralgia.
Whether arterial or venous compression or arachnoid adhesions are primarily responsible for compression of the trigeminal nerve in patients with trigeminal neuralgia is unclear. The aim of this study was to determine the causes of trigeminal nerve compression in patients with trigeminal neuralgia. The surgical findings in patients with trigeminal neuralgia who were treated by micro vascular decompression were compared to those in patients with hemifacial spasm without any signs or symptoms of trigeminal neuralgia who were treated with microvascular decompression. The study included 99 patients with trigeminal neuralgia (median age, 57 years) and 101 patients with hemifacial spasm (median age, 47 years). There were significant differences between the groups in the relationship of artery to nerve (p < 0.001) and the presence of arachnoid adhesions (p < 0.001) but no significant difference in relationship of vein to nerve. After adjustment for age, gender, and other factors, patients with vein compression of nerve or with artery compression of nerve were more likely to have trigeminal neuralgia (OR = 5.21 and 42.54, p = 0.026 and p < 0.001, respectively). Patients with arachnoid adhesions were less likely to have trigeminal neuralgia (OR = 0.15, p = 0.038). Arterial compression of the trigeminal nerve is the primary cause of trigeminal neuralgia and therefore, decompression of veins need not be a priority when performing microvascular dissection in patients with trigeminal neuralgia.


Clinical implementation and feasibility of long-course fractionated MR-guided chemoradiotherapy for patients with esophageal cancer: An R-IDEAL stage 1b/2a evaluation of technical innovation.
This R-Ideal stage 1b/2a study describes the workflow and feasibility of long-course fractionated online adaptive MR-guided chemoradiotherapy with reduced CTV-to-PTV margins on the 1.5T MR-Linac for patients with esophageal cancer. Patients with esophageal cancer scheduled to undergo chemoradiation were treated on a 1.5T MR-Linac. Daily MR-images were acquired for online contour adaptation and replanning. Contours were manually adapted to match the daily anatomy and an isotropic CTV-to-PTV margin of 6 mm was applied. Time was recorded for all individual steps in the workflow. Feasibility and patient tolerability were defined as on-table time of ≤60 min and completion of >95% of the fractions on the MR-Linac, respectively. Positioning verification and post-treatment MRIs were retrospectively analyzed and dosimetric parameters were compared to standard non-adaptive conventional treatment plans. Nine patients with esophageal cancer were treated with chemoradiation; eight patients received 41.4 Gy in 23 fractions and one received 50.4 Gy in 28 fractions. Four patients received all planned fractions on the MR-Linac, whereas for two patients >5% of fractions were rescheduled to a conventional linac for reasons of discomfort. A total of 183 (86%) of 212 scheduled fractions were successfully delivered on the MR-Linac. Three fractions ended prematurely due to technical issues and 26 fractions were rescheduled on a conventional linac due to MR-Linac downtime (n = 10), logistical reasons (n = 3) or discomfort (n = 13).The median time per fraction was 53 min (IQR = 3 min). Daily adapted MR-Linac plans had similar target coverage, whereas dose to the organs-at-risk was significantly reduced compared to conventional treatment (26% and 12% reduction in mean lung and heart dose, respectively). Daily online adaptive fractionated chemoradiotherapy with reduced PTV margins is moderately feasible for esophageal cancer and results in better sparing of heart and lungs. Future studies should focus on further optimization and acceleration of the current workflow.


Metastatic hepatocellular carcinoma: when surgery and successive palliative treatments lead to remission.
Hepatocellular carcinoma (HCC) is the third leading cause of death by cancer worldwide. The prognosis of patients with metastatic HCC remains limited, with an expected median survival lower than 50% at 1 year. Here, we report the case of a 63-year-old man who suffered from a small HCC in the liver and a large unique metastasis in the right adrenal gland. A surgical resection of both lesions was performed. Seven months later, HCC recurred with an isolated right renal metastatic lymphadenopathy and a high alpha-fetoprotein level. HCC was brought under control by sorafenib; the alpha-fetoprotein level was greatly reduced but remained moderately elevated and stable over 2 years after the onset of chemotherapy. Additional external radiotherapy on the metastatic lymphadenopathy led to a normalization of the alpha-fetoprotein level and discontinuation of sorafenib treatment. One year after the end of radiotherapy, a second isolated metastasis occurred in the right lung. This tumor was surgically removed. Twenty-one months after this second surgical procedure, i.e., more than 5.5 years after the initial diagnosis of metastatic HCC, the patient was asymptomatic and tumor free.


Evaluation of leucocyte adherence inhibition in hepatocellular carcinoma.
The value of the leucocyte adherence inhibition (LAI) test in the diagnosis of hepatocellular carcinoma (HCG) was investigated in 36 patients with this tumour. The sensitivity and specificity of the tube LAI test was assessed in 21 patients with HCC, 15 apparently healthy individuals, 9 patients with various forms of benign liver disease and 5 patients with non-hepatic neoplasms. In only 42% of the HCC patients tested was leucocyte adherence to glass reduced to a greater extent than in the healthy controls and in the patients with non-hepatic neoplasms, and the differences were not statistically significant. Moreover, positive results were obtained in 6/9 patients with benign hepatic disease. A further 15 patients were tested against extracts of HCC tissue using the haemacytometer LAI method. Of these, 53% gave positive results. In all, only 17/36 patients (47%) gave positive LAI responses. The test is thus of limited value in the diagnosis of HCC. The high false-negative result rate may be due either to abrogation of the immune response in HCC patients with large tumour burdens or to antigenic heterogeneity in HCC.


Thyroid function and risk of bloodstream infections: Results from the Norwegian prospective population-based HUNT Study.
Previous studies on thyroid function and risk of infection is conflicting and often stem from intensive care cohorts were nonthyroidal illness syndrome (NTIS) may be present. The objective of this study was to identify the risk of bloodstream infections (BSI) and BSI-related mortality with thyroid-stimulating hormone (TSH) levels within the reference range in a general population. Prospective follow-up. The HUNT2 (1995-97) included 34,619 participants with information on TSH levels. Hazard ratios (HRs) with 95% confidence interval (CI) confirmed BSIs and BSI-related mortality until 2011. During a median follow-up of 14.5 years, 1179 experienced at least one episode of BSI and 208 died within 30 days after a BSI. TSH levels within the reference range of 0.5-4.5 mU/L were not associated with the risk of first-time BSI, with an HR of 0.97 (95% CI: 0.90-1.04) per mU/L. Stratified by baseline age < or ≥65 years, TSH was inversely associated with the risk of BSI (HR: 0.88; 95% CI: 0.78-1.00 per mU/L) in the youngest age group only. Persons with any baseline thyroid disease had a 30% risk and the hyperthyroid subgroup a 57%, and hypothyroidism a 20% increased risk of BSI. TSH levels were not clearly associated with BSI mortality, but the HRs were imprecise due to few BSI-related deaths. There was some evidence of a weak inverse association between TSH levels and the risk of BSI in persons below 65 years of age. The increased risk seen in persons with thyroid illness is probably explained by confounding by concurrent ill health.


Association between High Blood Pressure and Intakes of Sodium and Potassium among Korean Adults: Korean National Health and Nutrition Examination Survey, 2007-2012.
The association between dietary sodium and potassium, the ratio of sodium to potassium, and blood pressure remains unclear. We evaluated the associations between blood pressure and dietary sodium and potassium intake in terms of the amount and ratio in Korean adults. This cross-sectional study was based on data from the fourth and fifth Korean National Health and Nutrition Examination Survey, 2007-2012. A total of 24,096 adults (aged ≥19 years) without history of antihypertensive medication use were selected. The 24-hour recall method was used for dietary assessment. We categorized the subjects into four groups using median intakes of sodium and potassium, and defined the low sodium/high potassium intake group as the reference group. High blood pressure (HBP) was defined as mean systolic or diastolic blood pressures of ≥140 or ≥90 mm Hg, respectively. Multivariate logistic regression was performed to estimate the odds ratio and 95% CI to investigate the association between the four groups of sodium and potassium intakes and HBP. Sodium intake was positively associated with diastolic blood pressure, with an increase of 0.21 mm Hg per 1 mg/kcal increase in sodium (P<0.001). In contrast, potassium intake was negatively associated with systolic blood pressure, with a decrease of 1.01 mm Hg per 1 mg/kcal increase in potassium (P<0.001). After adjusting for confounders, the high sodium/low potassium (odds ratio 1.21, 95% CI 1.02 to 1.44) and low sodium/low potassium intake groups (odds ratio 1.19, 95% CI 1.01 to 1.40) were at higher risk of HBP than the reference group. The risk of HBP in the high sodium/high potassium group did not differ from that in the reference group. Low potassium intake was associated with an increased risk of hypertension. These results suggest that increasing potassium intake might be beneficial for hypertension control among populations with low-potassium diets.


Effect of repeated intradermal injections of heat-inactivated Mycobacterium bovis bacillus Calmette-Guérin in adult asthma.
There are a number of reports in the Chinese medical literature from the last 30 years regarding the efficacy of repeated doses of heat-inactivated bacillus Calmette-Guérin (BCG) in established asthma. There is also epidemiological and experimental evidence that exposure to mycobacteria has the potential to suppress the development of asthma/atopy. Thirty-one Mantoux-negative adults with stable moderately severe asthma who were skin prick test positive to house dust mite were randomized to receive one injection (0.1 mL) a week for 4 weeks of heat-inactivated BCG or normal saline. Markers of asthma severity (including peak flow, forced expiratory volume in 1 s, major and minor exacerbations, symptom scores and beta-agonist use), blood eosinophil and IgE levels were monitored for 3 months. There were no statistically significant differences between the treatment group and placebo for any of the outcome variables. The recruitment to the trial was halted early and the number of injections reduced in a number of patients due to excessive local reactions to BCG. In addition to the lack of efficacy of repeated heat-inactivated BCG injections, the occurrence of severe local reactions will limit the therapeutic application of this approach in asthma.


When headaches are good.
Occasionally patients with headache present with the complaint of "a really good one." This paper examines three cases of patients with migraine who often referred to their headaches as "good." When the patients were asked what made the headaches good, they immediately tried to clarify their terminology as "just a figure of speech" that really meant bad. Further exploration usually revealed the headache symptoms had indeed been "good" in a relative sense, in that it had somehow served to help the patient avoid a more unpleasant emotional situation. The headache may have allowed a "time out" or a forced period of rest in a hectic schedule, resolved a conflict for the patient in an acceptable way by becoming sick, or represented a suppressed or repressed affect, usually anger. When headaches are described as good, there may very well be something in the patient's life that is worse.


Potential bioavailability of mercury in humus-coated clay minerals.
It is well-known that both clay and organic matter in soils play a key role in mercury biogeochemistry, while their combined effect is less studied. In this study, kaolinite, vermiculite, and montmorillonite were coated or not with humus, and spiked with inorganic mercury (IHg) or methylmercury (MeHg). The potential bioavailability of mercury to plants or deposit-feeders was assessed by CaCl2 or bovine serum albumin (BSA) extraction. For uncoated clay, IHg or MeHg extraction was generally lower in montmorillonite, due to its greater number of functional groups. Humus coating increased partitioning of IHg (0.5%-13.7%) and MeHg (0.8%-52.9%) in clay, because clay-sorbed humus provided more strong binding sites for mercury. Furthermore, humus coating led to a decrease in IHg (3.0%-59.8% for CaCl2 and 2.1%-5.0% for BSA) and MeHg (8.9%-74.6% for CaCl2 and 0.5%-8.2% for BSA) extraction, due to strong binding between mercury and clay-sorbed humus. Among various humus-coated clay particles, mercury extraction by CaCl2 (mainly through cation exchange) was lowest in humus-coated vermiculite, explained by the strong binding between humus and vermiculite. The inhibitory effect of humus on mercury bioavailability was also evidenced by the negative relationship between mercury extraction by CaCl2 and mercury in the organo-complexed fraction. In contrast, extraction of mercury by BSA (principally through complexation) was lowest in humus-coated montmorillonite. This was because BSA itself could be extensively sorbed onto montmorillonite. Results suggested that humus-coated clay could substantially decrease the potential bioavailability of mercury in soils, which should be considered when assessing risk in mercury-contaminated soils.


Driving impairments and duration of distractions: Assessing crash risk by harnessing microscopic naturalistic driving data.
Distracted and impaired driving is a key contributing factor in crashes, leading to about 35% of all transportation-related deaths in recent years. Along these lines, cognitive issues like inattentiveness can further increase the chances of crash involvement. Despite its prevalence and importance, little is known about how the duration of these distractions is associated with critical events, such as crashes or near-crashes. With new sensors and increasing computational resources, it is possible to monitor drivers, vehicle performance, and roadway features to extract useful information, e.g., eyes off the road, indicating distraction and inattention. Using high-resolution microscopic SHRP2 naturalistic driving data, this study conducts in-depth analysis of both impairments and distractions. The data has more than 2 million seconds of observations in 7394 baselines (no event), 1228 near-crashes, and 617 crashes. The event data was processed and linked with driver behavior and roadway factors. The intervals of distracted driving during the period of observation (15 seconds) were extracted; next, rigorous fixed and random parameter logistic regression models of crash/near-crash risk were estimated. The results reveal that alcohol and drug impairment is associated with a substantial increase in crash/near-crash event involvement of 34%, and the highest correlations with crash risk include duration of distraction through dialing on a cellphone, texting while driving, and reaching for an object. Using detailed pre-crash data from instrumented vehicles, the study contributes by quantifying crash risk vis-à-vis detailed driving impairment and information on secondary task involvement, and discusses the implications of the results.


Perceived and measurable performance of daily brushing and rinsing with an essential oil mouthrinse.
To determine whether the oral health benefits of recommending twice daily brushing and rinsing with an essential oil mouthrinse (EOM) are perceived and measurable by dentists and also perceived by their patients at a 3-month recall visit. This is a monadic, open label, uncontrolled study involving 766 generally healthy Italian subjects aged 19-66 years, with mild to moderate levels of gingivitis, no pockets of more than 4 mm, and at least 20 scorable teeth. Eight dentists scored subjects for plaque and gingivitis at baseline and at 90 days using simplified 4-point plaque and gingivitis indices. All subjects brushed twice daily, immediately followed by rinsing for 30 sec with 20 ml of an essential oil mouthrinse (Listerine(®)). 735 subjects completed the study (95.9%). Average score reductions were 51.9% and 45.7% for plaque and gingivitis, respectively. About 62% and 70% were judged by the dentists as improved for plaque control and gingival health. 85% of subjects judged the EOM as efficacious. The oral health benefits of brushing and rinsing twice daily with an essential oil mouthrinse are perceived by patients and professionals alike and measurable by dentists at a 3-month recall visit.


Clinical experience with autogenous ascitic fluid infusion for cirrhotic ascites.
Autogenous ascitic fluid infusion was found to be a safe and practical method in dealing with patients suffering advanced liver cirrhosis complicated by massive ascites.


Nitric oxide regulates Th1 cell development through the inhibition of IL-12 synthesis by macrophages.
We have previously reported that mice lacking inducible nitric oxide synthase (NOS2) developed enhanced Th1 cell responses. We now investigated the mechanism by which NO modulates Th1 cells differentiation. Peritoneal macrophages from NOS2-deficient mice infected with Leishmania major in vivo or stimulated with IFN-gamma or lipopolysaccharide (LPS) in vitro produced significantly higher levels of IL-12 than those from heterozygous or wild-type mice. A macrophage cell line, J774, produced significant amounts of IL-12 following activation with LPS, or LPS plus IFN-gamma. This could be markedly enhanced by the NOS inhibitor L-NG monomethyl arginine (L-NMMA), but profoundly inhibited by the NO-generating compound S-nitroso-N-acetyl-penicillamine (SNAP). The effect of NO in this system is selective, since SNAP enhanced and L-NMMA decreased TNF-alpha synthesis by LPS-activated J774 cells. The differential effect of NO on IL-12 and TNF-alpha is at the transcriptional level and is activation dependent. Since IL-12 is a major inducer of Th1 cells which produce IFN-gamma that can activate macrophages to produce IL-12, our data demonstrate that NO can be an inhibitor of this feedback loop, preventing the excessive amplification of Th1 cells which are implicated in a range of immunopathologies.


Determination of Trace, Micro and Macro Elemental Concentration of Eritrean Honeys.
In this study macro, micro and trace elemental concentrations were measured in Eritrean acacia honey samples by Inductively Coupled Plasma Optical Emission Spectrometry (Al, B, C, K, Mg, Na, P and S) and Inductively Coupled Plasma Mass Spectrometry (As, Ba, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Sr and Zn). The concentration of essential elements in the examined Eritrean acacia honeys decreased in the following order: K > P > Ca > Mg > Fe > Zn > Mn > Cu > Sr > Mo. Independent samples T test was used to determine the statistically verified differences between the two regions, but there was none; however there were remarkable differences among the measured element contents of specific honey samples. Elemental concentrations of Eritrean honeys are influenced by the characteristics of the collecting area (e.g. elevation, agricultural activities, water resources).Our samples showed low essential elemental concentration; therefore the consumption of these honeys does not contribute significantly to the nutrition reference value (NRV) (around 1% of NRV). Toxic elemental concentrations were also low; thus the calculated estimated daily intakes were much lower than the tolerable daily intakes. Consumption of these honeys presents no risk for the human body.


Motor cortex excitability in transient global amnesia.
To investigate the physiology of motor cortical areas in patients with transient global amnesia (TGA). We performed transcranial magnetic stimulation (TMS) and single photon emission computed tomography (SPECT) in 13 patients during and after the acute phase of a typical episode of TGA. Measures of cortical excitability included motor threshold (MT) to magnetic stimulation, cortical silent period (SP) duration and intracortical inhibition (ICI) using a paired-pulse TMS technique. We found thalamic hypoperfusion and an ipsilateral significantly decreased ICI during the acute phase of TGA. Reduced activity in inhibitory circuits may explain why PET studies of patients with TGA showed neocortical hypometabolism. Our findings are consistent with the hypothesis that frontal cortex dysfunction probably due to damage affecting the thalamocortical circuits may play an important role in the pathogenesis of the syndrome.


Central Nervous System Infections in the Immunocompromised Adult Presenting to the Emergency Department.
Over the past 2 decades, the population of immunocompromised patients has increased dramatically in the United States. These patients are at elevated risk for both community-acquired and opportunistic central nervous system infections. We review the most common and serious central nervous system pathogens affecting these patients and outline a diagnostic and therapeutic approach to their management in the emergency department. We recommend a broad diagnostic evaluation, including neuroimaging and cerebrospinal fluid studies where appropriate, empiric antimicrobial therapy, and early involvement of subspecialists to provide comprehensive care for these complex patients.


In-vitro anticancer evaluation of newly designed and characterized tri/tetra-substituted imidazole congeners- maternal embryonic leucine zipper kinase inhibitors: Molecular docking and MD simulation approaches.
Our cascading attempt to develop new potent molecules now involves designing a series of imidazole derivatives and synthesizing two sets of 2,4,5- tri-substituted (4a-4d) and 1,2,4,5-tetra-substituted (6a-6d) imidazole by the principle of Debus-Radziszewski multicomponent synthesis reaction. The structures of the obtained compounds were confirmed by 1H/13C NMR, FT-IR, elemental analysis, purity and the retention time was analyzed by HPLC. Based upon the binding affinity in the molecular docking studies, we have synthesized different imidazole derivatives from which compound 6c have been found to show more anti-proliferative activity by inducing apoptosis at a higher rate than the other compounds corroborating the in-silico prediction. The structure and crystallinity of compound 4d have been confirmed by single XRD analysis. The synthesized molecules were screened for their in vitro anti-cancer properties in triple negative breast cancer cell line (MDA-MB-231), pancreatic cancer cell lines (MIA PaCa-2) and oral squamous cell carcinoma cell line (H357) and results indicated that all the compounds inhibited the cell proliferation in a concentration-dependent manner at different time points. The compounds 4b and 6d were found to be effective against the S. aureus bacterial strain whereas only compound 4d fairly inhibited the fungal strain of T. rubrum with a MIC 12.5 μg/mL. Molecular docking study reveals good interaction of the synthesized compounds with known target MELK involved in oncogenesis having high binding profiles. The lead compound 6c was further analyzed by the detailed molecular dynamics study to establish the stability of the ligand-enzyme complex.


The use of conventional antisera in the production of specific monoclonal antibodies.
Monoclonal antibodies specific for human alpha-2-macroglobulin (alpha 2M), a plasma glycoprotein, have been produced using a novel immunization method. Commercially available antisera to human alpha 2M was used to precipitate the antigen from whole serum. Immunization of animals with this immunoprecipitate resulted in the production of hybridomas with a specificity for human alpha-2-macroglobulin as confirmed by immunoprecipitation.


Synthesis, excited state dynamics, and optical characteristics of oligophenyl-based swivel cruciforms in solution and solid state.
Oligophenyl-based swivel cruciforms are an amorphous class of materials for potential use in display applications. In this work, we describe the design, synthesis, and structural and optical properties of a group of chromophores with varying degrees of π-conjugation that produce blue emission and high photoluminescence quantum yields (PLQYs). The swivel cruciforms are branched complexes consisting of two arms, and the relative rotation of these arms is an important factor that determines the optical properties of these systems. The studies reveal that the physical size of the system, that is, the arms, and the presence and position of functional groups results in different degrees of sterical effects. This has a dramatic impact on the interplay between nonradiative and radiative decay of the excited state. For the least π-extended system, control of the excited state decay can be achieved by modifying the properties of the medium through an increase in the viscosity, which is demonstrated accordingly. The data shows that an intramolecular excited state is responsible for the swivel cruciform emission in solution. The character of this "aggregate" and its emission is not dissimilar to an excimer, and we therefore attribute it to an intramolecular excimer. In the solid state, a combination of intra- and intermolecular excimers are the most likely source of the emission. The data also shows that intra molecular excimers can produce a surprisingly high PLQY, when either properties of the medium facilitate this or when functional groups introduce steric hindrance, which subsequently prevents the nonraditive decay through conformational change.


Fractal correlation properties of R-R interval dynamics in asymptomatic relatives of patients with dilated cardiomyopathy.
asymptomatic relatives of patients with familial dilated cardiomyopathy who have left ventricular enlargement [LVE] are at risk for progression to dilated cardiomyopathy. A novel index of the fractal correlation properties of heart rate variability (HRV), the short-term scaling component (proportional, variant(1)) in detrended fluctuation analysis, is a promising prognostic tool in left ventricular dysfunction. The aim of this study was to compare values of proportional, variant(1) and conventional HRV indices in LVE relatives with dilated cardiomyopathy patients and normal controls. time-domain and spectral HRV measures, and the short-term scaling component ( proportional, variant(1)) were assessed from 24-h Holter recordings from 22 LVE relatives (left ventricular end-diastolic dimension >112% predicted, normal fractional shortening), 24 dilated cardiomyopathy patients and 14 controls. the time domain index SDNN was lower in dilated cardiomyopathy patients [101.8(+/-44.0)] than in LVE relatives [161.7(+/-53.9)] or controls [152.9(+/-51.4)], P=0.01. Similarly, triangular index and spectral measures were reduced in dilated cardiomyopathy patients but not in LVE relatives or controls. In contrast, the short term scaling component ( proportional, variant(1)) in detrended fluctuation analysis was reduced in both dilated cardiomyopathy patients [1.06(+/-0.33)] and in LVE relatives [1.15 (+/-0.20)], compared with controls [1.32(+/-0.16)], P=0.01. Among DCM patients the short-term scaling component ( proportional, variant(1)) was significantly associated with echocardiographic deterioration during follow-up (3.7+/-2.1 year) (P=0.004). the short-term scaling component ( proportional, variant(1)) is reduced in asymptomatic relatives of dilated cardiomyopathy patients who have LVE.


Toxicity of avermectin to Eriocheir sinensis and the isolation of a avermectin-degrading bacterium, Ochrobactrum sp. AVM-2.
Avermectin is widely used in the prevention and treatment of parasites diseases in aquaculture. However, the residual avermectin has a serious impact on the growth and quality of aquatic animals including Eriocheir sinensis. This study shows that the LC50 of avermectin to E. sinensis for 24, 48, 72 and 96 h was 21.88, 13.40, 9.11 and 7.10 mg/L, respectively. After avermectin stress, the activities of superoxide dismutase (SOD), catalase (CAT) and phenol oxidase (PO) in the hepatopancreas of E. sinensis increased and reached the peak on the 6th day. The content of malondialdehyde (MDA) accumulated with the increase of exposure time and concentration of avermectin. After 15 days of avermectin exposure, hepatopancreas was damaged seriously. These results indicated that avermectin had toxicity to E. sinensis. In order to solve the pollution problem caused by residual avermectin, a degrading bacterium AVM-2 was separated from the sediment of E. sinensis breeding pond. The strain was confirmed to be Ochrobactrum sp by morphology observation, physiological and biochemical identification and 16 S rDNA sequences analysis. When the pH value was 7, the temperature was 30 ℃, the concentration of substrate was low, the quantity of inoculation was high, Ochrobactrum sp. AVM-2 had better degradation effect on avermectin. When the addition of Ochrobactrum sp. AVM-2 was 2.34 × 108 CFU/L, the residual avermectin in muscle and hepatopancreatine significantly decreased, and the degradation rate was about 66%. In summary, Ochrobactrum sp. AVM-2 could be used to solve the residual problem of avermectin and ensure the food safety of E. sinensis.


Multicenter prospective study showing a high gastrointestinal symptom burden in cystic fibrosis.
People with cystic fibrosis (PwCF) suffer from gastrointestinal (GI) symptoms affecting their quality of life (QOL). Despite the relevance of GI symptoms to the overall health of PwCF, a paucity of studies only have comprehensively assessed the prevalence, severity and QOL of GI symptoms in both children and adults with Cystic Fibrosis (CF). Eligible participants ≥2 years of age across 26 US CF centers were followed for 4 weeks. Three validated GI electronic patient-reported outcome measures (ePROMs) with a recall period of 2 weeks and a stool-specific questionnaire were administered weekly over four weeks. Total and domain scores of ePROMs were evaluated overall and in subgroups using linear mixed-effect models. Of 402 enrolled, 58% were ≥ 18 years of age (52% male). The mean (SD) of the total score for PAC-SYM was 0.52 (0.55), for PAGI-SYM was 0.63 (0.67), and for PAC-QOL was 0.67 (0.55). For specific ePROM questions, prevalence of moderate to very severe symptoms were as follows: straining (20.3%), fullness (18.3%), incomplete bowel movements (17.1%), bloating (16.4%), distension (16.4%), abdominal pain (upper-5.1%, lower-7.5%). Comparing participants ≥18 versus <18, a higher prevalence of bloating (63.7% versus 27.3%), lower abdominal pain (39.8% vs 26.2%), stomach fullness (75.6% versus 56.2%), and abdominal distension (60.2% versus 34.9%) was found. Both age groups reported high treatment dissatisfaction as measured with PAC-QOL, mean 1.39 (95% CI: 1.30, 1.47). GI symptoms were reported in all age ranges irrespective of gender, with higher prevalence observed amongst older and female subgroups. Dissatisfaction with GI targeted treatments were reported in a large proportion of participants despite therapy, highlighting an unmet need for clinical interventions. GOV: NCT03801993.


An automaton computer program for a microcomputerized real-time (thesaurus based) abstract medical record.
A study of the key wordings used by the doctors in medical records in ICU preceded this implementation; they constitute a thesaurus (2700 strings) organized in 2 trees. These strings are proposed along the dialogue which occurs between the microcomputer and the user; on these bases, several graphs allows movement in the tree by minimization of the pathway. The use of the thesaurus with the corresponding graphs necessitates only one automaton program. This medical data microcomputerized system is transparent for the user, thanks to a multilayered software. In the external layer the microcomputer provides access to the system by one of the following function keys: creation of a medical record, additional information on a medical record already known, research of a medical record, listing of the open medical records, printing of a medical record. Each one of these function keys provides access to the following 5 chapters: identity, antecedents, reasons for admission, evolution, destiny; these chapters use parameterized procedures. This software is implemented on a low-cost microcomputer fitted with a dual drive disk (170 kilobytes each) and a printer (90 characters/s).


dsCellNet: A new computational tool to infer cell-cell communication networks in the developing and aging brain.
Cell-cell interactions mediated by ligand-receptor complexes are critical to coordinating organismal development and functions. Majority of studies focus on the key time point, the mediator cell types or the critical genes during organismal development or diseases. However, most existing methods are specifically designed for stationary paired samples, there hasn't been a repository to deal with inferring cell-cell communications in developmental series RNA-seq data, which usually contains multiple developmental stages. Here we present a cell-cell interaction networks inference method and its application for developmental series RNA-seq data (termed dsCellNet) from the developing and aging brain. dsCellNet is implemented as an open-access R package on GitHub. It identifies interactions according to protein localizations and reinforces them via dynamic time warping within each time point and between adjacent time points, respectively. Then, fuzzy clustering of those interactions helps us refine key time points and connections. Compared to other published methods, our methods display high accuracy and high tolerance based on both simulated data and real data. Moreover, our methods can help identify the most active cell type and genes, which may provide a powerful tool to uncover the mechanisms underlying the organismal development and disease.


The risk of paradoxical levetiracetam effect is increased in mentally retarded patients.
Incidental paradoxical antiepileptic effect of levetiracetam has been described. The aim of the present study was to identify the epilepsy patients at risk. We performed a retrospective analysis in 207 patients treated with levetiracetam. This entailed evaluation of patient notes and patient interviews. A paradoxical effect was defined as an increased seizure frequency or the experience of more severe seizures including generalized tonic-clonic seizures (GTCS) within 1 month after starting levetiracetam (LEV). Thirty patients (14%) experienced a paradoxical effect. Eight of them (4%) developed de novo GTCS. We could not demonstrate any association between the paradoxical effect of levetiracetam and type of epilepsy or the antiepileptic comedication used. However we found that the paradoxical effect developed preferentially (p < 0.001) in mentally retarded patients. Because there is an increased risk of worsening epilepsy when starting levetiracetam treatment of mentally retarded epileptic patients, there is a need for caution and close observation during the first weeks of therapy.


Anti-IL-5 in pediatric allergic diseases.
Interleukin (IL)-5 is a potent mediator of the inflammatory cascade in the allergic response. Its predominant role in atopic reactions makes this cytokine an ideal target for blocking the eosinophilic inflammatory hyper-responsiveness to allergens. The management of allergic diseases in childhood-such as severe asthma, atopic dermatitis, and eosinophilic esophagitis-is a challenge. In particular, there are concerns regarding the use of high-dose corticosteroids. Over the last few years, biologics targeting IL-5 or IL-5 receptor-that are mepolizumab, reslizumab, and benralizumab-represent a new, promising, and more personalized therapeutic option.


Elucidating degradation properties, microbial community, and mechanism of microplastics in sewage sludge under different terminal electron acceptors conditions.
This study is designed to investigate the roles of five key terminal electron acceptors (TEAs): O2, NO3-, Fe3+, SO42-, and CH2O, typically existing in the sludge on the degradation rates and pathways of three representative MPs: polylactic acid (PLA), polyvinyl chloride (PVC), and polyhydroxyalkanoate (PHA). The results revealed that approximately 51.46 ∼ 52.70% of PHA was degraded within 43 days, despite PLA and PVC being degraded insignificantly. Different TEAs significantly affected the end-products of PHA. The production rate of acetate gradually decreased from 90.48, 42.67, 38.30, and 17.56 to 3.30% when the TEAs were tested with CH2O, O2, SO42-, NO3- and Fe3+, respectively. The main functional bacteria involved in the PHA degradation were hydrolysis bacteria Burkholderiaceae and homo-acetogenic bacteria Clostridiacea, which accounted for 0.83% and 18.91% of the microbes. The current investigation could help improve understanding of MPs degradation pathways and mechanisms and minimize their risks in practice.


Listeners' impressions of normal-hearing and hearing-impaired children.
This study investigated the relationship between speech of hearing-impaired children and listeners' ratings of the speakers' intelligence, achievement, personality, and appearance as a function of whether or not speakers wore hearing aids. Stimuli consisted of (1) tape-recorded speech samples of 12 speakers (4 normal hearing, 4 hard of hearing, and 4 deaf) and (2) two photographic slides of each speaker--one depicting him wearing a hearing aid and another depicting him not wearing a hearing aid. Listeners used a semantic differential scale to rate the stimuli. Analysis shows that there is a systematic increase in "less desirable" ratings with severity of hearing loss and that responses are more negative when the speaker wore a hearing aid.


[3 Tesla MRI: successful results with higher field strengths].
The recent development of 3 Tesla MRI (3T MRI) has been fueled by promise of increased signal-to-noise ratio(SNR). Many are excited about the opportunity to not only use the increased SNR for clearer images, but also the chance to exchange it for better resolution or faster scans. These possibilities have caused a rapid increase in the market for 3T MRI, where the faster scanning tips an already advantageous economic outlook in favor of the user. As a result, the global market for 3T has grown from a research only market just a few years ago to an ever-increasing clinically oriented customer base. There are, however, significant obstacles to 3T MRI presented by the physics at higher field strengths. For example, the T1 relaxation times are prolonged with increasing magnet field strength. Further, the increased RF-energy deposition (SAR), the larger the chemical shift and the stronger susceptibility effect have to be considered as challenges. It is critical that one looks at both the advantages and disadvantages of using 3T. While there are many issues to address aand a number of different methods for doing so, to properly tackle each of these concerns will take time and effort on the part od researchers and clinicians. The optimization of 3T MRI scanning will have to be a combined effort, though much of the work to date has been in neuroimaging. Multiple applications have been explored in addition to clinical anatomical imaging, where resolution is improved showing structure in the brain never seen before in human MRI. Body and cardiac imaging provide a great challenge but are also achievable at 3T. As an example, the full range of clinical applications currently achieved on today's state-of-the-art 1.5T cardiac MR scanners has also been demonstrated at 3T. In the body, the full range of contrast is available over large fields of view allowing whole liver studies in the clinic or, as needed, one may choose a smaller field of view for high-resolution imaging of the pancreas. The ability to increase resolution for musculoskeletal imaging has provided previously unseen detail. Bone structure, cartilage, and tendons and ligaments can be clearly visualized and pathology more easily detected due to an increased image quality. As the increase in field strength continues, a push to look at 7T has begun. The design philosophy is to keep the system as similar as possible, while changing only the frequency-dependent components. To date, both animal and human imaging have been performed on a whole body 7T scanner. Results show promise for both detailed imaging and functional MRI, but the road ahead is too long to be able to predict where it will end. The move toward higher field strengths is an exciting adventure in which 3T plays the role of trailblazer.


Feasibility and preliminary efficacy of a community support intervention for people with opioid use disorder.
People receiving agonist treatment for opioid use disorder often have family or friends who do not use illicit substances and could be mobilized to support recovery efforts. The present study evaluates the feasibility and preliminary efficacy of a community support intervention (CSI) designed to increase drug-free social support and expand drug-free network support. Participants receiving methadone treatment and using illicit drugs (n = 33) were randomly assigned to a weekly CSI or education group for 12 weeks. CSI participants attended the group with a drug-free family member or friend, and were scheduled to engage together in two community activities per week designed to meet drug-free people. Education participants attended a weekly education group and were given two weekly written homework sessions. CSI groups were well attended. CSI participation was associated with reduced conflict with the family member or friend, and with increased engagement in self-help groups. No condition differences were observed in social network variables or urinalysis results, though four CSI participants (24%) compared to 0 education participants met criteria for substantial (>75%) reductions in drug use. Many eligible patients chose not to participate. These findings suggest good implementation feasibility and acceptability, and low demand feasibility. Broader clinical implementation requires strategies to improve patient willingness to enlist available social support. Mobilizing family and friends to provide social support for people engaged in active drug use is possible. More work is needed on how to leverage support to change existing networks.


Spontaneous rupture of the Achilles tendon - a sign of hyperlipoproteinaemia (HLP) type II.
In biopsies from spontaneously ruptured Achilles tendons a serum lipid and lipoprotein analysis was performed in fifty nine patients. In nine males considerable histological signs of lipid deposition were detectable. The tendon fibers were found to be partly desintegrated. Only in these cases LDL-cholesterol values were found to exceed the normal range indicative of type II hyperlipoproteinaemia (HLP). None of the fifty remaining patients presented biochemical or clinical signs of disorders of lipid metabolism. The observations demonstrate that a spontaneous rupture of Achilles tendom may indicate a primary type II HLP.


The effects of an acetate-sensitive anion binding site on NADPH binding in glutamate dehydrogenase.
The nature of a general anion binding site that regulates NADPH binding to L-glutamate dehydrogenase has been explored. Dissociation constants for the enzyme-NADPH complex were measured by difference spectroscopy in the presence of phosphate, pyrophosphate, ADP and acetate ions. Whereas two molecules of phosphate, binding in a cooperative fashion, raise the Kd of the enzyme-NADPH complex 50-fold from 2.3 microM, a single pyrophosphate raises the Kd only 23-fold, disproving the notion that the anion binding site is simply the pyrophosphate binding site of NADPH. ADP raises the Kd of the enzyme-NADPH complex 2-fold for a given phosphate concentration, and formation of the enzyme-ADP complex is itself interfered with by phosphate and pyrophosphate, indicating that these anions interact with the same anion binding site. Acetate ion acts in a manner opposite to that of phosphate, pyrophosphate and ADP and reverses the weakening effect that these ions exert on NADPH binding, returning the Kd of the enzyme-NADPH complex to 2.3 microM. In the absence of these anions, however, acetate exerts no measurable effect on the Kd, suggesting an allosteric mechanism.


The differentiative and regenerative properties of human hematopoietic stem/progenitor cells in NOD-SCID/IL2rgamma(null) mice.
Biomedical research including immunology and stem cell biology has developed greatly because of the evolving technology of gene modification and conventional transplantation methods using the most common experimental laboratory animal, the mouse. To translate promising research findings based on mouse research into clinical medicine, however, we need to clarify whether similar events take place in humans. In the study of hematology and immunology, humanized mice provide a unique and efficient experimental system to evaluate differentiation, function, and interaction of human blood cells or immune components. Here we review the latest experimental findings in the fields of immunology, stem cell biology, and regenerative medicine using humanized mice.