Transdermal scopolamine as a cause of transient psychosis in two elderly patients.
We have described two elderly patients who had psychosis after beginning transdermal scopolamine therapy. In both cases, changes in mental status resolved promptly when the medication was discontinued.


Transmission electron microscopic studies on the mitotic cycle of nucleolar proteins impregnated with silver.
Hela cells were impregnated with silver according to Paweletz et al. (1967). In cells in mitosis not only the nucleolar organizer regions (NORs) are strongly impregnated but also part of the nucleolar material, which accumulates in and around the chromosomes. The treatment with adenosine, which in interphase cells spreads the nucleolar material within the nucleus, also distributes the argentophilic material in and around the chromosomes. During the reconstruction phase this material reassembles around the NORs to form parts of the new nucleolus. The silver impregnation technique clearly demonstrates that two main components are responsible for the argentophily of the nucleolus. This is in agreement with the results obtained by Lischwe et al. (1979).


Visualizing carrier status: fragile X syndrome and genetic diagnosis since the 1940s.
What does it look like to be the carrier of a genetic disease? Carrier status may be determined through the visual analysis of both genotypic and phenotypic evidence. Over the past 70 years, clinical geneticists have depended upon multiple strategies for identifying disease carriers within a family. This has included pedigree analysis, which was based upon clinical observations of individual family members and, in recent decades, cytogenetic and molecular methods. Newer techniques have offered novel opportunities to actually see the suspected etiological markers of certain genetic diseases, such as Fragile X syndrome. The visualization of these markers has both clarified and confused previously observed inheritance patterns, in some cases leading to the development of newly distinct diagnostic categories. As a result, what it means to be affected by, or the carrier of, a genetic disease has continuously evolved.


GIP's involvement in the pathophysiology of type 2 diabetes.
During the past four decades derangements in glucose-dependent insulinotropic polypeptide (GIP) biology has been viewed upon as contributing factors to various parts of the pathophysiology type 2 diabetes. This overview outlines and discusses the impaired insulin responses to GIP as well as the effect of GIP on glucagon secretion and the potential involvement of GIP in the obesity and bone disease associated with type 2 diabetes. As outlined in this review, it is unlikely that the impaired insulinotropic effect of GIP occurs as a primary event in the development of type 2 diabetes, but rather develops once the diabetic state is present and beta cells are unable to maintain normoglycemia. In various models, GIP has effects on glucagon secretion, bone and lipid homeostasis, but whether these effects contribute substantially to the pathophysiology of type 2 diabetes is at present controversial. The review also discusses the substantial uncertainty surrounding the translation of preclinical data relating to the GIP system and outline future research directions.


MBL2 polymorphism may be a protective factor of autoimmune thyroid disease susceptibility.
Genetic susceptibility is an essential pathogenetic mechanism in autoimmune thyroid disease (AITD). MBL2 gene polymorphisms have been shown to play a vital role in the pathogenesis of multiple autoimmune disorders, but its contribution to AITD is unclear. The aim of this study was to assess the linkage between MBL2 gene polymorphisms and AITD susceptibility in a Chinese Han population. One thousand seven hundred sixty seven subjects consisting of 965 AITD patients and 802 controls from a Chinese Han population were enrolled in the case-control study. Four common single-nucleotide polymorphisms (SNPs) in the MBL2 gene were tested using high-throughput sequencing technology for sequence-based SNP genotyping. The allele and genotype distribution results showed that the minor alleles of rs198266, rs10824793, and rs4935046 were significantly lower in Hashimoto's thyroiditis (HT) patients than in healthy controls. In further genetic model analysis, the dominant models of rs1982266, rs10824793, and rs4935046 for MBL2 in the AITD group exhibited a lower risk of morbidity. Finally, we discovered that haplotype AAGC was associated with Graves' disease (GD), while AGC was associated with HT. Our study provides strong evidence for a genetic correlation between MBL2 and AITD, and the polymorphism of the MBL2 gene may be a protective factor for AITD, especially for HT. These findings can advance our understanding of the etiology of AITD, as well as provide guidance for prevention and intervention toward AITD.


Distribution of organophosphate ester fractions in sediment of the Eastern China Marginal Seas and the influencing factors.
Organic pollutant fractions should be closely investigated because of their different ecological risks. In this study, we examined the distribution of organophosphate ester (OPE) fractions (labile, stable-adsorbed, and tight-adsorbed fractions) in sediments from Eastern China Marginal Seas (ECMSs) and assessed the influencing factor of the fractions. The mean values of total OPEs in ECMSs are 13.70 ± 6.16 μg L-1 in seawater and 32.04 ± 14.31 μg kg-1 in sediment. The results showed that OPE concentration decreased from the northern to the southern ECMSs, and tris(1-chloro-2-propyl) phosphate and tris(1,3-dichloro-2-propyl) phosphate were the primary OPEs. The mean contents of labile, stable-adsorbed, and tight-adsorbed fractions in the ECMSs were 9.50, 11.29, and 11.71 μg kg-1, respectively. Labile OPEs were predominant in offshore waters; the percentage of stable- and tight-adsorbed fractions increased progressively with offshore distance in ECMSs. The specific surface area and surface functional groups of sediment were not consistent with the fraction concentrations from the correlation coefficient, but the gross domestic product per coastline agreed well with the fraction distribution. Based on this, we conclude that human activity, rather than physicochemical characteristics of sediments, may be the primary influencing factor of the relative distribution of different OPE concentration fractions in ECMSs.


Off-pump plication of left ventricular aneurysm.
With a small left ventricular aneurysm, the surgeon finds it difficult to decide whether to repair the aneurysm or leave it alone; there are risks and benefits to consider. Our choice is plication rather than resection. The procedure may be performed on-pump or off-pump, and the results are easy to demonstrate with the help of transesophageal echocardiogram.


Membrane bending energy and shape determination of phospholipid vesicles and red blood cells.
A procedure is developed to calculate red blood cell and phospholipid vesicle shapes within the bilayer couple model of the membrane. The membrane is assumed to consist of two laterally incompressible leaflets which are in close contact but unconnected. Shapes are determined by minimizing the membrane bending energy at a given volume of a cell (V), given average membrane area (A) and given difference of the areas of two leaflets (delta A). Different classes of shapes exist in parts of the v/delta a phase diagram, where v and delta a are the volume and the leaflet area difference relative to the sphere with area A. The limiting shapes are composed of sections of spheres with only two values allowed for their radii. Two low energy axisymmetrical classes, which include discocyte and stomatocyte shapes are studied and their phase diagrams are analyzed. For v= 0.6, the discocyte is the lowest energy shape, which transforms by decreasing delta a continuously into a stomatocyte. The spontaneous membrane curvature (C0) and compressibility of membrane leaflets can be incorporated into the model. A model, where delta A is free and C0 determines the shapes at given V and A, is also studied. In this case, by decreasing C0, a discocyte transforms discontinuously into an almost closed stomatocyte.


Spinal cord metastasis of a non-neurofibromatosis type-1 malignant peripheral nerve sheath tumor: an unusual manifestation of a rare tumor.
Malignant peripheral nerve sheath tumors are rare spindle-cell sarcomas derived from Schwann cells or pluripotent cells of the neural crest. They arise from the spinal roots, peripheral nerves, brachial and lumbosacral plexi, cranial nerves and terminal nerve fibers within soft tissue, intestine, lung and bone. These tumors recur either locally, or metastasize distally. Most of these tumors occur in association with neurofibromatosis type 1. Spinal cord metastasis from malignant nerve sheath tumors associated with neurofibromatosis type 1 is very rare. We describe a rare case of near-total spinal cord metastasis in a patient with malignant nerve sheath tumor in the absence of neurofibromatosis, and highlight the microscopic findings and natural history of this disease process.


Highly Efficient CYP167A1 (EpoK) dependent Epothilone B Formation and Production of 7-Ketone Epothilone D as a New Epothilone Derivative.
Since their discovery in the soil bacterium Sorangium cellulosum, epothilones have emerged as a valuable substance class with promising anti-tumor activity. Because of their benefits in the treatment of cancer and neurodegenerative diseases, epothilones are targets for drug design and pharmaceutical research. The final step of their biosynthesis - a cytochrome P450 mediated epoxidation of epothilone C/D to A/B by CYP167A1 (EpoK) - needs significant improvement, in particular regarding the efficiency of its redox partners. Therefore, we have investigated the ability of various hetero- and homologous redox partners to transfer electrons to EpoK. Hereby, a new hybrid system was established with conversion rates eleven times higher and Vmax of more than seven orders of magnitudes higher as compared with the previously described spinach redox chain. This hybrid system is the most efficient redox chain for EpoK described to date. Furthermore, P450s from So ce56 were identified which are able to convert epothilone D to 14-OH, 21-OH, 26-OH epothilone D and 7-ketone epothilone D. The latter one represents a novel epothilone derivative and is a suitable candidate for pharmacological tests. The results revealed myxobacterial P450s from S. cellulosum So ce56 as promising candidates for protein engineering for biotechnological production of epothilone derivatives.


Bladder carcinoma treated by preoperative radiotherapy followed by cystectomy.
In 1969 a clinical trial was started where patients with bladder carcinoma stage T2 and grade 3 were subjected to preoperative radiotherapy followed by cystectomy. The survival rate in this series was higher than in a previous series of comparable patients who were given full irradiation without cystectomy.


The health and economic benefits of sugar taxation and vegetables and fruit subsidy scenarios in Canada.
A tax on sugar-sweetened beverages (SSB) has been implemented in various jurisdictions. Though research confirmed this tax to reduce sugar consumption and to prevent chronic diseases, it also revealed concerns: one concern relates to the small proportion of sugar in the diet coming from SSBs; and another concern relates to the disproportional tax burden to low-income groups. To inform public health decision makers on alternatives, we examined three 'real world' taxation and subsidy scenarios in Canada: 1) a CAD$0.75/100 g tax on SSBs; 2) a CAD$0.75/100 g tax on free sugar in all foods; and 3) a 20% subsidy on vegetables and fruit (V&F). Using national survey data and a proportional multi-state life table-based Markov model, we simulated the changes in disability-adjusted life years, healthcare costs, tax revenue, intervention costs, and incremental cost-effectiveness ratio for five income quintiles after implementing the three scenarios, over a lifetime of the 2015 Canadian adult population. The first, second and third scenario would prevent 28,921, 262,348 and 551 cases of type 2 diabetes, respectively. They would avert 752,353, 12,167,113, and 29,447 disability-adjusted life years and save CAD$12,942 million, 149,927 million, and 442 million in health care costs, respectively, over a lifetime. Combining the second and third scenarios would lead to the largest health and economic benefits. Although the lowest income quintile would bear a higher sugar tax burden (0.81% of income, CAD$120/person/year), this would be compensated by a coinciding subsidy on V&F (1.30% of income, CAD$194/person/year). These findings support policies that include a tax on all free sugar in foods and a subsidy on V&F as an effective means to reduce chronic diseases and health care costs. Although the sugar tax was financially regressive, the V&F subsidy could compensate for the tax burden of the disadvantaged groups and improve health and economic equity.


Copper(II) complexes with 3,5-dihalogeno-salicylaldehydes: Synthesis, structure and interaction with DNA and albumins.
Eight copper(II) complexes of 3,5-dichloro-salicyladehyde or 3,5-dibromo-salicyladehyde (3,5-diX-saloH, X = Br or Cl) were synthesized in the absence or presence of a N,N'-donor co-ligand such as 2,2'-bipyridylamine, 1,10-phenanthroline, or 2,2'-bipyridine. The resultant compounds were formulated as [Cu(3,5-diX-salo)2(MeOH)2] (1-2) and [Cu(3,5-diX-salo)(N,N'-donor)Cl] (3-8) and were characterized by diverse techniques. The crystal structures of three complexes were determined by single-crystal X-ray crystallography. Diverse techniques were employed in order to investigate the interaction of the complexes with calf-thymus DNA which showed intercalation as the most possible mode of their interaction. The affinity of the complexes for bovine serum albumin and human serum albumin was evaluated by fluorescence emission spectroscopy in order to calculate the binding constants which suggested a tight and reversible binding. SYNOPSIS: A series of copper(II) complexes with 3,5-dihalogen-substituted salicylaldehydes as ligands were isolated and characterized. In vitro biological studies showed the intercalation of the compounds with calf-thymus DNA and their tight and reversible binding with serum albumins.


Omnidirectional leaky opto-electrical fiber for optogenetic control of neurons in cell replacement therapy.
The pathophysiological progress of Parkinson's disease leads through degeneration of dopaminergic neurons in the substantia nigra to complete cell death and lack of dopamine in the striatum where it modulates motor functions. Transplantation of dopaminergic stem cell-derived neurons is a possible therapy to restore dopamine levels. We have previously presented multifunctional pyrolytic carbon coated leaky optoelectrical fibers (LOEFs) with laser ablated micro-optical windows (µOWs) as carriers for channelrhodopsin-2 modified optogenetically active neurons for light-induced on-demand dopamine release and amperometric real-time detection. To increase the dopamine release by stimulating a larger neuronal population with light, we present here a novel approach to generate µOWs through laser ablation around the entire circumference of optical fibers to obtain Omni-LOEFs. Cyclic voltammetric characterization of the pyrolytic carbon showed that despite the increased number of µOWs, the electrochemical properties were not deteriorated. Finally, we demonstrate that the current recorded during real-time detection of dopamine upon light-induced stimulation of neurons differentiated on Omni-LOEFs is significantly higher compared to recordings from the same number of cells seeded on LOEFs with µOWs only on one side. Moreover, by varying the cell seeding density, we show that the recorded current is proportional to the dimension of the cell population.


The impact of low vision on social function: The potential importance of lost visual social cues.
Visual cues usually play a vital role in social interaction. As well as being the primary cue for identifying other people, visual cues also provide crucial non-verbal social information via both facial expressions and body language. One consequence of vision loss is the need to rely on non-visual cues during social interaction. Although verbal cues can carry a significant amount of information, this information is often not available to an untrained listener. Here, we review the current literature examining potential ways that the loss of social information due to vision loss might impact social functioning. A large number of studies suggest that low vision and blindness is a risk factor for anxiety and depression. This relationship has been attributed to multiple factors, including anxiety about disease progression, and impairments to quality of life that include difficulties reading, and a lack of access to work and social activities. However, our review suggests a potential additional contributing factor to reduced quality of life that has been hitherto overlooked: blindness may make it more difficult to effectively engage in social interactions, due to a loss of visual information. The current literature suggests it might be worth considering training in voice discrimination and/or recognition when carrying out rehabilitative training in late blind individuals.


Supplementation with imuno-2865® in gilthead sea bream (Sparus aurata Linnaeus, 1758): Effects on hematological and antioxidant parameters.
The aim of this study was to evaluate the effects of IMUNO-2865(®) on hematological and antioxidative parameters in sea bream. Total of 640 sea bream were fed with diets containing 0 (Group 1), 1 (Group 2), 10 (Group 3) and 25 (Group 4) g of IMUNO-2865(®) kg(-1) feed during 90 days. Samples were taken each month and three months after the supplementation. A significant heterophils increase was observed in group 4 compared to group 1 after two months, and an increase in monocytes number was observed in group 4 compared to the other groups after one month. Glutathione peroxidase (GSH-Px) and paraoxonase-1 (PON1) were significantly increased in groups 3 and 4 compared to the control group three months into the experiment. Superoxide dismutase (SOD) was increased in group 4 compared to the control group from day 60 until the end of the experiment, and in groups 2 and 3 compared to the control after three months. Based on the differences in the cellular immunity and oxidative stress parameters, with an overall absence of mortality, the results of this study suggest that the use of IMUNO-2865(®) in aquaculture is safe and possess a cumulative immunostimulatory effect on sea bream.


Toxic smoke inhalation: cyanide poisoning in fire victims.
The most common cause of death in fires is the inhalation of noxious gases rather than thermal injury. Hydrogen cyanide gas, the most toxic product of combustion, seldom is recognized as a significant hazard in smoke inhalation. During the first four months of 1986, toxic amounts of cyanide were found in four of the six fatalities from house fires in Akron, Ohio. These cases illustrate the increasing frequency of cyanide poisoning in household fires. Sources of cyanide toxicity include the increased use of synthetic polymers in building materials and furnishings. Prompt recognition of and therapy for cyanide intoxication may reduce the morbidity and number of delayed deaths in fire victims. The key point in the diagnosis of cyanide poisoning is a high index of suspicion. The clinical presentation of cyanide intoxication, its diagnosis, and subsequent treatment are discussed. Finally, a prehospital protocol for treating smoke-inhalation victims who may have been exposed to cyanide gas is suggested.


A prospective study of trephined bone grafts of the tibial shaft and iliac crest.
Autogenous cancellous bone grafting is a common procedure in maxillofacial surgery. Open harvesting usually results in a long scar and considerable morbidity, but harvesting using a trephine can be done through a smaller scar with minimal morbidity. The commonly used anatomical areas for trephine harvesting are the iliac crest and the tibial shaft. A prospective study was carried out in 30 patients to compare the technique and the morbidity as perceived by patients using a visual analogue scale (VAS) and by an independent observer. The surgical anatomy and techniques are described. The results show no significant difference between the two groups, but the tibial trephine procedure is easier, quicker, and causes less blood loss. The total scores for pain and difficulty in walking were much less for tibial than that for the iliac grafts.


Beware of spurious tracheo-bronchial stents.
To present a case of accidental sheath removal of tracheo-bronchial self-expandable metallic airway stent in a patient with endotracheal tumour. Design: Case Report; Setting: Tertiary care hospital; Patient: One. A 65 years male, follow up case of endotracheal tumor with tracheo-bronchial self-expandable metallic stenting done presented with dry cough and difficulty in breathing since 8-10 days and suddenly coughed out thin whitish paper-like material 2 days back (which later proved as sheath of metallic stent). Direct laryngoscopy with flexible videobronchoscopy was done which showed tracheal stent well placed and intact, coughed out sheath couldn't be replaced back. Procedure was uneventful and patient was discharged in satisfactory condition and is doing well on regular follow up. Self-expandable metallic airway stents (SEMAS) represents a standard method of airways stenting especially when employed for the management of malignant central airway obstruction. Despite the obvious stenting advantages, it may be complicated with stent migration and accidental removal or coughing out of stent especially in high tracheal stenosis. In our case, as a peculiar complication there was accidental removal of the tracheal stent sheath which couldn't be replaced back whereas stent was well in place and intact. We need to be beware of such spurious tracheo-bronchial stents.


The interactional teaching patterns of mothers and fathers with their popular, moderately popular, or unpopular children.
The interactional teaching strategies of mothers and fathers toward their sociometrically determined popular, moderately popular, or unpopular children, and children's responses to them were examined during a structured puzzle task in a laboratory setting. Parents of popular children used more explanations in aiding their children to complete the puzzle task than parents of moderately popular or unpopular children. Mothers were more likely to offer suggestions, use explanations, and ask questions during the puzzle task than fathers. Analysis of children's responses revealed that popular children were more likely to ignore imperatives by their parents compared with unpopular children, while unpopular children showed a tendency to be more cooperative following imperatives by parents than popular children. Finally, popular children were less likely to ignore but were more likely to go off task following suggestions by parents than either unpopular or moderately popular children. The data are discussed with respect to the possible link between parental socialization patterns and children's popularity in the peer group and the need to consider the interaction patterns in both the peer and parent-child systems for intervention purposes.


[Parenteral use of oruvel (ketoprofen) for analgesia in the postoperative period].
Antiinflammatory and analgesic effects of oruvel (ketoprofene), a nonsteroid antiinflammatory drug, are demonstrated by many scientists. Both intramuscular and oral oruvel is acknowledged as an effective means for therapy of inflammatory and dystrophic rheumatic diseases. Moreover, oruvel in 100-mg flasks for infusions is intended for the treatment of postoperative pain, specifically, in orthopaedic surgery.


Nitrous oxide in pediatric anesthesia: friend or foe?
Nitrous oxide has been used in clinical practice for over 150 years, often for pediatric procedures. Not only are there problems when used in patients with a variety of inborn errors of metabolism, but effects of nitrous oxide on the developing human brain are unknown. A recent adult human trial found that the use of nitrous oxide was associated with increased adverse outcome. Animal studies in several species have shown that nitrous oxide can be associated with apoptosis in the developing brain. Nitrous oxide can also inhibit major enzymatic pathways and repeated exposure may lead to neurologic damage. Single nucleotide polymorphisms in at least one of these enzymes are common in the population. There is a growing body of evidence that supports avoidance of nitrous oxide in both pediatric and adult patients, but the thousands of patients who have been exposed to nitrous oxide without apparent complications would suggest that further studies on long-term side effects and possible neurologic consequences need to be done.


In vitro differentiation of pluripotent stem cells into hepatocyte like cells - Basic principles and current progress.
Research in the field of hepatology is limited by the incomplete recapitulation of all major aspects of human hepatic metabolism in most established models. This restricts our ability to study the molecular mechanisms underlying hepatic diseases, and it leads to inadequate assessment of toxicology during drug development, resulting in tremendous unnecessary costs for the pharma industry. Animal models differ in their metabolism compared to the human system, while primary human cells dedifferentiate rapidly and are not suitable for long-term culture and studies. To overcome these obstacles, several protocols for in vitro differentiation of pluripotent stem cells into hepatocyte like cells (HLCs) have been established. These cells are currently used for modeling inherited and acquired diseases, and to test for drug efficacy and toxicity. Unfortunately, HLCs lack maturity and resemble rather fetal than adult hepatocytes. Novel 3D-based models may overcome these drawbacks in the future. In this review, we critically analyse the most common differentiation protocols and their evolution. In addition, we introduce recently developed techniques for 3D differentiation. Finally, we discuss drawbacks, challenges, and advantages of the distinct systems for routine toxicity tests, disease modeling and future cell replacement therapies.


Mutations in the Arabidopsis Lst8 and Raptor genes encoding partners of the TOR complex, or inhibition of TOR activity decrease abscisic acid (ABA) synthesis.
The Target of Rapamycin (TOR) kinase regulates essential processes in plant growth and development by modulation of metabolism and translation in response to environmental signals. In this study, we show that abscisic acid (ABA) metabolism is also regulated by the TOR kinase. Indeed ABA hormone level strongly decreases in Lst8-1 and Raptor3g mutant lines as well as in wild-type (WT) Arabidopsis plants treated with AZD-8055, a TOR inhibitor. However the growth and germination of these lines are more sensitive to exogenous ABA. The diminished ABA hormone accumulation is correlated with lower transcript levels of ZEP, NCED3 and AAO3 biosynthetic enzymes, and higher transcript amount of the CYP707A2 gene encoding a key-enzyme in abscisic acid catabolism. These results suggest that the TOR signaling pathway is implicated in the regulation of ABA accumulation in Arabidopsis.


Effect of atorvastatin and fenofibrate on autonomic tone in subjects with combined hyperlipidemia.
This randomized open-label trial investigated whether autonomic cardiovascular control is altered in middle-aged men with combined hyperlipidemia and whether such alterations are affected by short-term, lipid-lowering therapy with atorvastatin and/or fenofibrate. Compared with normolipidemic subjects, untreated subjects with combined hyperlipidemia had several abnormalities of autonomic tone, indicating increased sympathetic tone and decreased baroreflex sensitivity. The alterations in autonomic cardiovascular control were partially reversible by each of the lipid-lowering drugs.


ERP correlates of language-specific processing of auditory pitch feedback during self-vocalization.
The present study investigated whether the neural correlates for auditory feedback control of vocal pitch can be shaped by tone language experience. Event-related potentials (P2/N1) were recorded from adult native speakers of Mandarin and Cantonese who heard their voice auditory feedback shifted in pitch by -50, -100, -200, or -500 cents when they sustained the vowel sound /u/. Cantonese speakers produced larger P2 amplitudes to -200 or -500 cents stimuli than Mandarin speakers, but this language effect failed to reach significance in the case of -50 or -100 cents. Moreover, Mandarin speakers produced shorter N1 latencies over the left hemisphere than the right hemisphere, whereas Cantonese speakers did not. These findings demonstrate that neural processing of auditory pitch feedback in vocal motor control is subject to language-dependent neural plasticity, suggesting that cortical mechanisms of auditory-vocal integration can be shaped by tone language experience.


Novel naphthylstyryl-pyridium potentiometric dyes offer advantages for neural network analysis.
The submucous plexus of the guinea pig intestine is a quasi-two-dimensional mammalian neural network that is particularly amenable to study using multiple site optical recording of transmembrane voltage (MSORTV) [Biol. Bull. 183 (1992) 344; J. Neurosci. 19 (1999) 3073]. For several years the potentiometric dye of choice for monitoring the electrical activity of its individual neurons has been di-8-ANEPPS [Neuron 9 (1992) 393], a naphthylstyryl-pyridinium dye with a propylsulfonate headgroup that provides relatively large fluorescence changes during action potentials and synaptic potentials. Limitations to the use of this dye, however, have been its phototoxicity and its low water solubility which requires the presence of DMSO and Pluronic F-127 in the staining solution. In searching for less toxic and more soluble dyes exhibiting larger fluorescence signals, we first tried the dienylstyryl-pyridinium dye RH795 [J. Neurosci. 14 (1994) 2545] which is highly soluble in water. This dye yielded relatively large signals, but it was internalized quickly by the submucosal neurons resulting in rapid degradation of the signal-to-noise ratio. We decided to synthesize a series of naphthylstyryl-pyridinium dyes (di-n-ANEPPDHQ) having the same chromophore as di-8-ANEPPS and the quaternary ammonium headgroup (DHQ) of RH795 (resulting in two positive charges versus the neutral propylsulfonate-ring nitrogen combination), and we tested the di-methyl (JPW3039), di-ethyl (JPW2081), di-propyl (JPW3031), di-butyl (JPW5029), and di-octyl (JPW5037) analogues, all of them soluble in ethanol. We found that the di-propyl (di-3-ANEPPDHQ) and the di-butyl (di-4-ANEPPDHQ) forms yielded the best combination of signal-to-noise ratio, moderate phototoxicity and absence of dye internalization.


Transient chloramphenicol acetyltransferase expression of the G gamma globin gene 5'-flanking regions containing substitutions of C----T at position -158, G----A at position -161, and T----A at position -175 in K562 cells.
The expression of G gamma is affected by mutations that occur in promoter sequences located in the 5'-flanking region of the gene. We have assayed the promoter activity of G gamma genes that have mutations of C----T at position -158 or G----A at position -161. In addition, we determined the activity of a promoter fragment containing T----A at position -175 (in the octamer motif) in combination with a -158 C----T which was produced during the polymerase chain reaction amplification procedure. Constructs containing these fragments were transfected by electroporation into K562 cells and the promoter activity was measured as chloramphenicol acetyltransferase activity. The data show a 4-5-fold enhancement of activity for the -158 C----T and the -161 G----A promoters over the 'normal' G gamma promoter and an 8-fold increase in the activity of the promoter with the double mutation (-158 C----T and -175 T----A). These results are consistent with data involving the increase in G gamma production in patients heterozygous for these mutations.


Effect of duration of stress on pain threshold in rats.
Rats were subjected to immobilization stress of varying duration and their pain thresholds were recorded. It was seen that stress of lesser duration did not affect the endogenous opioid analgesic system while stressor of longer duration stimulated this system to its maximum irrespective of further increasing the duration of the stress condition even upto two fold.


The Surgical Treatment of Proximal Humeral Fractures in Elderly Patients.
The goal of this study is to compare mortality, major adverse events, and complication rates after the surgical treatment of proximal humeral fractures with locked plate fixation (LPF) versus reverse total shoulder arthroplasty (RTSA) in elderly patients. Health insurance data from patients aged 65 and above for the period January 2010 to September 2018 were retrospectively evaluated. The median follow-up duration after LPF (40 419 patients) or RTSA (13 552 patients) was 52 months. Hazard ratios adapted to the patients' risk profiles were determined with the aid of multivariable Cox regression models. The p-values were adjusted using the Bonferroni-Holm method. After adaptation to the patients' risk profiles, reverse shoulder replacement showed statistically significantly lower mortality (HR 0.92, 95% confidence interval [0.88; 0.95]; p <0.001) and fewer major adverse events (HR 0.92 [0.89; 0.95]; p<0.001). Eight years after surgery, the risk of surgical complications was twice as high for LPF (12.2% [11.9; 12.7]; HR for RTSA versus LPF 0.5 [0.46; 0.55]; p<0.001 for both), with 3.8% [3.6; 4.0] of the patients receiving a secondary RTSA. Surgical complications were more common (p<0.05) in patients with a diagnosis of osteo - porosis, obesity, alcohol abuse, chronic polyarthritis, or frozen shoulder. The long-term findings are in agreement with clinical short-term findings from other studies and support the current trend toward more liberal use of reverse shoulder replacements in elderly patients.


[Not Available].
Tests with various clean-up materials after optimisation of different parameters showed that the use of Oasis® material resulted in matrixless chromatograms in HPLC-FLD. The selectivity and detection limit of the method was improved by using LC-MS/MS as the detection system. Mean recovery was 100%, and no negative food matrix effects could be observed.


Sequence and characterization of a sperm-specific histone H1-like protein of Mytilus californianus.
The major protein fraction of the protamine-like PL-II* (phi 2B) from the sperm of Mytilus californianus has been sequenced and characterized. Immunological and sequence analyses unequivocally show that this protein is indeed a member of the histone H1 family. Along with proteins of the histone H1 class, the protein also shows cross-reactivity and sequence identity, in its NH2-terminal region, with the major protamine-like protein component of Mytilus sperm: PL-III (phi 1), of smaller molecular mass. Indeed it is the unusual repetitive sequence motif of the NH2-terminal domain of PL-II* that bestows to this protein its protamine-like nature. Fourier-transform infrared spectroscopy spectroscopy indicates that the protein contains considerable secondary structure: 18% alpha-helix, 21% beta-sheet, 39% turns and bends, 22% random coil. At the higher levels of structure, PL-II* exhibits ionic strength-dependent folding which is indistinguishable from that of histone H5, as monitored by fluorescence anisotropy.


[Prevention and treatment of horseshoe-shaped rectal fistulas].
The paper deals with a newly developed effective method of the treatment of horseshoe fistulae, which was successfully applied in 110 patients. This method is distinguished for its low traumatic effect. The closure of the internal opening is carried out by means of the plasty with a wide layer of the mucous membrane displaced laterally.


Determination of intracellular reduced glutathione and glutathione related enzyme activities in cisplatin-sensitive and resistant experimental ovarian carcinoma cell lines.
The level of GSH in ovarian carcinoma cells which were sensitive and resistant to cisplatin was serially determined following tumor removal from the animals, in addition, activities of GSH-reductase and GSH-S-transferase were assessed. The GSH level in the resistant line (O-342/DDP) was almost twice as high as that in its sensitive counterpart (O-342), when determined immediately following removal of the tumor (1.55 +/- 0.47 vs. 0.81 +/- 0.32 nmol/10(6) cells). Culturing the cells resulted in a decrease of GSH levels in both cell lines during the first 4 h. Thereafter, GSH levels in both cell lines increased up to 24 h. At this time the GSH level was higher in O-342 than in O-342/DDP. GSH-reductase activity in O-342/DDP cells was significantly higher than in O-342 cells when the enzyme was determined immediately after tumor removal; at the same time there was no difference in activity of GSH-S-transferase between two cell lines. After 24 h in culture, no significant difference between O-342 and O-342/DDP cells could be observed in the activity of the two enzymes.


Curcumin protects cardiac myocyte against hypoxia-induced apoptosis through upregulating miR-7a/b expression.
Curcumin has properties of anti-inflammation, anti-oxidation, anti-infection and anti-tumor, benefiting for the treatment of many diseases. The present study was aimed to investigate the role of curcumin in myocardial infarction (MI) and its potential mechanism involving transcription factor specific protein 1 (SP1). After receiving curcumin, C57BL/6 mice subjected to left anterior descending (LAD) coronary artery occlusion to induce MI model. Infarct size was measured by triphenyl tetrazolium chloride staining. In vitro experiments, mouse cardiac myocytes (MCM) subjected to hypoxia after the incubation of curcumin, miR-7a/b and SP1 expression levels were detected by real-time PCR and western blot. Caspase-3 activity and TUNEL assay were performed to assess the cell apoptosis. In animal experiments, curcumin significantly reduced the infarct size compared with the control. It also up-regulated miR-7a/b expression and down-regulated SP1 expression. In hypoxia-induced MCM, curcumin led to the decrease of cell apoptosis. Transfected MCM with miR-7a/b inhibitor, curcumin induced the decrease of cell apoptosis and SP1 expression was reversed. Transfected with pcDNA-SP1, the decrease of cardiac myocytes apoptosis after the treatment of curcumin was also reversed. Curcumin pre-treatment protected against hypoxia-induced cardiac myocytes apoptosis through the up-regulation of miR-7a/b and the down-regulation of SP1 expression.


Computational tools for geroscience.
The rapid progress of the past three decades has led the geroscience field near a point where human interventions in aging are plausible. Advances across scientific areas, such as high throughput "-omics" approaches, have led to an exponentially increasing quantity of data available for biogerontologists. To best translate the lifespan and healthspan extending interventions discovered by basic scientists into preventative medicine, it is imperative that the current data are comprehensively utilized to generate testable hypotheses about translational interventions. Building a translational pipeline for geroscience will require both systematic efforts to identify interventions that extend healthspan across taxa and diagnostics that can identify patients who may benefit from interventions prior to the onset of an age-related morbidity. Databases and computational tools that organize and analyze both the wealth of information available on basic biogerontology research and clinical data on aging populations will be critical in developing such a pipeline. Here, we review the current landscape of databases and computational resources available for translational aging research. We discuss key platforms and tools available for aging research, with a focus on how each tool can be used in concert with hypothesis driven experiments to move closer to human interventions in aging.


Functional magnetic resonance imaging study of regional brain activation during implicit sequence learning in obsessive-compulsive disorder.
Corticostriatal circuitry has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). The serial reaction time (SRT) task, a paradigm that tests implicit sequence learning, has been used with imaging to probe striatal function. Initial studies have indicated that OCD patients exhibit deficient striatal activation and aberrant hippocampal recruitment compared with healthy control (HC) subjects. Here, we used the SRT and functional magnetic resonance imaging (fMRI) to replicate prior results in a larger sample and to test for relationships between regional activation and OCD symptom dimensions. Using SPM99, fMRI-SRT data from 12 OCD and 12 matched HC subjects were analyzed. Symptom dimensions followed a four-factor model scored on a 0- to 10-point scale. For the implicit learning versus random contrast, group by condition interactions revealed aberrant recruitment within the hippocampus as well as orbitofrontal cortex (OCD > HC) but no striatal group differences. However, an inverse correlation was found between striatal activation and specific symptom factors. These results replicate previous smaller studies showing aberrant hippocampal recruitment in OCD during SRT performance. Although findings of deficient striatal activation in OCD were not replicated, correlation results suggest that this inconsistency may be attributable to differences among OCD symptom dimensions.


The endothelin ETB receptor mediates both vasodilation and vasoconstriction in vivo.
It has been suggested that the endothelin (ET) ETB receptor could mediate endothelium-dependent vasodilation to ET-1 or ET-3, but its in vivo role is still largely unknown. We used sarafotoxin S6C, a selective agonist of the ETB receptor, to study the in vivo effects of ETB stimulation. SRTX S6C induced a transient decrease in blood pressure, followed by a long-lasting pressor response accompanied by a marked renal and mesenteric vasoconstriction. No constriction was observed in isolated mesenteric arteries in vitro, indicating that the in vivo vasoconstrictor effect is most likely indirect. The pressor effect of SRTX S6C was not dependent on central stimulation of ETB receptors and was not mediated by catecholamines from the adrenal medulla, prostanoids or ET-1.


The efficacy of iodine-125 permanent brachytherapy versus intensity-modulated radiation for inoperable salivary gland malignancies: study protocol of a randomised controlled trial.
Radiation therapy is the method of choice for subjects with inoperable salivary gland malignancies. I-125 brachytherapy, delivering a high radiation dose to a tumor but sparing surrounding normal tissues, is supposed to be ideal modality for the treatment of salivary gland malignancies. We designed a randomised controlled clinical trial to compare the efficacy of I-125 permanent brachytherapy (PBT) versus intensity-modulated radiation therapy (IMRT) for inoperable salivary gland malignancies. In this study, inclusion criteria are subjects with inoperable salivary gland malignancies, aged 18-80 years, have provided informed consent, with at least one measurable tumor focus, be able to survive ≥3 months, Karnofsky performance status ≥60, have adequate hematopoietic function of bone marrow, have normal liver and kidney function, and are willing to prevent pregnancy. Exclusion criteria include a history of radiation or chemotherapy, a history of other malignant tumors in the past 5 years, receiving other effective treatments, participating in other clinical trials, with circulatory metastasis, cognitive impairment, severe cardiovascular and cerebrovascular diseases, acute infection, uncontrolled systemic disease, history of interstitial lungdisease, and being pregnant or breast feeding. The study will be conducted as a clinical, prospective, randomised controlled trial with balanced randomisation (1:1). The planned sample size is 90 subjects. Subjects with inoperable salivary gland malignancies are randomised to receive either I-125 PBT or IMRT, with stratification by tumor size and neck lymph node metastasis. Participants in both groups will be followed up at 2, 4, 6, 9, 12, 15, 18, 21 and 24 months after randomization. The primary outcome is local control rate of the primary site (based on imaging findings and clinical examination, RECIST criteria) in 1 year. Secondary outcomes are progression-free survival, overall survival, quality of life (QOL) measured with the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30 and QLQ-H&N35) of Chinese version, and safety of treatment. Chi-squared test is used to compare the local control rates in both groups. The survival curves are estimated by the Kaplan-Meier method, and log-rank test is used to test the significant difference. Only few observational studies have investigated the effect of I-125 PBT on inoperable salivary gland malignancies. To our knowledge, this is the first randomised controlled trial to investigate the efficacy of I-125 PBT for subjects with inoperable salivary gland malignancies, and will add to the knowledge base for the treatment of these subjects. The study is registered to Clinical Trials.gov ( NCT02048254 ) on Jan 29, 2014.


The Effectiveness of Group Cognitive Behavioral Therapy in Treating Obsessive-Compulsive Disorder in Women with Multiple Sclerosis (MS): A randomized double-blind controlled trial.
Obsessive-compulsive disorder (OCD) is one of the most prevalent psychiatric disorders and can cause problems for individuals in all aspects of life, including social and personal dimensions. To study the effect of group cognitive-behavioral therapy on the reduction of OCD symptoms in female participants with multiple sclerosis (MS). This double-blind randomized control trial was conducted from May 2012 to December 2014. The participants included 75 patients with MS who suffered from OCD and were referred to the Loghman Hakim and Imam Khomeini hospitals in Tehran, Iran. Thirty participants had been diagnosed through Yale-Brown Obsessive-Compulsive Symptoms (Y-BOCS). The participants were randomly divided into an experimental group (n=15) and a control group (n=15). Eleven sessions of cognitive-behavioral therapy were provided for the experimental group. Patients in the control group continued with their normal living. Hypotheses were tested using an analysis of covariance (ANCOVA). A significant reduction was found in the experimental group's obsessive-compulsive symptoms after cognitive-behavioral therapy (p<0.001). In addition, mean scores for participants in the experimental group were significantly lower than for those in the control group (p=0.000). It can be inferred that cognitive-behavioral therapy could considerably reduce OCD symptoms in women with MS. The application of this method by therapists, especially Iranian clinicians, is recommended.


BCL11B tumor suppressor inhibits HDM2 expression in a p53-dependent manner.
BCL11B is a C2H2 zinc finger transcription factor that acts as a haploinsufficient tumor suppressor. Mutations and deletion in the human orthologue BCL11B have been identified in human T-cell acute lymphoblastic leukemia (T-ALL) and a mouse model of thymic lymphomas. Bcl11b(KO/+)p53(KO/+) doubly heterozygous mice, but not Bcl11b(KO/+) heterozygous mice, spontaneously develop thymic lymphomas at a high frequency, suggesting cooperativity of BCL11B and p53 in cancer development. In this study, we have examined whether or not BCL11B directly affects the p53 signaling pathway including HDM2, a ubiquitin ligase for p53 degradation. The p53 pathway regulates cell proliferation and the response to DNA damages to maintain genome integrity. Here we show that BCL11B binds to human HDM2-P2 promoter by ChIP (chromatin immuno-precipitation) assay and inhibits HDM2 expression in a p53-dependent manner. Deletion of the distal p53 responsive element in HDM2 promoter region or the lack of p53 in HCT116 cells greatly reduced the repressive effect of BCL11B on HDM2-P2 promoter activity. The repressive activity was alleviated in γ-ray induced DNA damage conditions that activate p53, suggesting interaction between BCL11B and p53 for HDM2 expression. These date suggest that BCL11B affects the activity of the p53-HDM2 feedback loop in basal and irradiated conditions. This may be a mechanism underlying the leukemic transformation in T-ALL and in Bcl11b(KO/+)p53(KO/+) mouse thymocytes.


Isolation and Annotation of Azira, a CT Cluster Phage That Infects Gordonia rubripertincta.
Azira is a CT cluster actinobacteriophage that infects Gordonia rubripertincta NRRL B-16540. The genome contains 67 predicted protein coding genes, of which 31 have a putative function. Azira has a lysis cassette encoding two endolysins and three transmembrane proteins. Azira contains four genes predicted to encode enzymes involved in thymine synthesis.


Novel approach to ecotoxicological risk assessment of sediments cores around the shipwreck by the use of self-organizing maps.
Marine and coastal pollution plays an increasingly important role due to recent severe accidents which drew attention to the consequences of oil spills causing widespread devastation of marine ecosystems. All these problems cannot be solved without conducting environmental studies in the area of possible oil spill and performing chemometric evaluation of the data obtained looking for similar patterns among pollutants and optimize environmental monitoring during eventual spills and possible remediation actions - what is the aim of the work presented. Following the chemical and ecotoxicological studies self-organising maps technique has been applied as a competitive learning algorithm based on unsupervised learning process. Summarizing it can be stated that biotests enable assessing the impact of complex chemical mixtures on the organisms inhabiting particular ecosystems. Short and simple application of biotests cannot easily explain the observable toxicity without more complex chemometric evaluation of datasets obtained describing dependence between xenobiotics and toxicological results.


WITHDRAWN: Marfan syndrome: An eyesight of syndrome.
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Are Proton Pump Inhibitors More Effective Than Histamine-2-Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients? A Systematic Review and Meta-Analysis of Cohort Studies.
Histamine-2-receptor antagonists (H2RAs) have been largely replaced by proton pump inhibitors (PPIs) for stress ulcer prophylaxis (SUP) despite the inconclusive evidence concerning comparative effectiveness. To compare the effectiveness of PPIs and H2RAs on SUP in real-world setting. PubMed, Embase, and the Cochrane Library were searched from inception to September 19, 2021. We included cohort studies comparing PPIs with H2RAs in critically ill adult patients and explicitly reporting the outcome of gastrointestinal (GI) bleeding or mortality. Newcastle-Ottawa Scale was used to assess potential risk of bias. We conducted a random-effects meta-analysis and only the studies with adjusted effect estimates were pooled. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the overall quality of the evidence. Thirteen cohort studies (N = 145 149) were eligible and 11 of them available for full texts were of low to moderate risk of bias. Meta-analysis of adjusted effect estimates indicated that PPIs were associated with a significantly higher risk of GI bleeding, compared with H2RAs (8 studies, odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.30-3.01, low certainty). Post hoc pooling analysis also suggested that PPIs were associated with a slightly higher risk of mortality in comparison with H2RAs (7 studies, OR = 1.27, 95% CI = 1.13-1.42, low certainty). The systematic review of cohort studies showed that PPIs were associated with higher risks of GI bleeding and mortality, although the certainty of evidence was low. Overall, we suggest not excluding H2RAs for SUP, while further studies are essential for elucidating the risk stratification, optimal regimen, and specific duration.


Integrating Postradiotherapy MRI-Detected Lymph Node Necrosis and Pre- and Posttreatment Epstein-Barr Virus-DNA for Risk Stratification in Nasopharyngeal Carcinoma.
Residual lymphadenopathy and detectable Epstein-Barr virus (EBV) DNA after radiotherapy (RT) are known negative prognostic factors for nasopharyngeal carcinoma (NPC). However, there is a need to distinguish between patients with residual disease that will metastasize and those who will not. To develop a prognostic model to improve the risk stratification of NPC patients after RT. Retrospective. Three hundred eighty-seven NPC patients treated with RT between January 2010 and January 2013. T1-, T2-weighted and enhanced T1-weighted imaging at 1.5 or 3.0 T pretreatment and 3-4 months post-RT. Post-RT central nodal necrosis (CNN) and other nodal characteristics on MRI were assessed by three radiologists independently. EBV DNA was measured by quantitative polymerase chain reaction. The association between these variables and the primary endpoint (5-year distant metastasis-free survival [DMFS], time from the day of diagnosis to any distant metastasis) was analyzed. Nomograms A (pre-/posttreatment EBV-DNA + N stage + post-RT retropharyngeal lymph node [RLN] CNN), B (tumor-node-metastasis [TNM] stage + pretreatment EBV-DNA), and C (TNM stage + post-RT EBV-DNA) were developed. Univariate and multivariate analyses were performed with the Cox regression model. Nomograms were developed based on the Cox regression model and two prognostic models. The concordance index (C-index) and calibration curve were used to evaluate the discriminative ability of the nomograms and TNM stage. P-values < 0.05 were considered statistically significant. Post-RT RLN CNN was an independent prognostic factor for 5-year DMFS (hazard ratio, 2.88 [1.48-5.62]). Nomogram A (C-index 0.728 [0.660-0.797]) demonstrated better risk discrimination than nomogram B (0.638 [0.571-0.705]), nomogram C (0.707 [0.636-0.778]), and the TNM stage (0.587 [0.515-0.659]) for 5-year DMFS in NPC. Nomogram A combining pretreatment EBV-DNA and N stage with post-RT EBV-DNA and RLN CNN improved the prognostic risk stratification for DMFS in NPC. 4 TECHNICAL EFFICACY: Stage 2.


Classical haemophilia in a girl.
A three-year-old white girl from a haemophiliac A family was a symptomatic carrier. The clinical and laboratory data concur with the form of a heterozygous symptomatic carrier state.


Discovery of LB30057, a benzamidrazone-based selective oral thrombin inhibitor.
Systematic variation of the so-called P-pocket moiety of benzamidrazone-based selective thrombin inhibitors led to the discovery of LB30057. It is potent (Ki = 0.38 nM for human thrombin), selective (Ki = 3290 nM for bovine trypsin), and orally bioavailable (58% oral bioavailability in dogs). LB30057 was efficacious in thrombosis animal models.


[Intrafamilial hepatitis C virus infection].
The role of blood and other biological fluids in transmission of HCV is already proven. The infection is acquired mainly by uncontrolled transfusion of blood products, percutaneous inoculation by contaminated equipment, mother-to-infant as well as sexual exposures. Infection by common contact in the family is very rare, but data are present in the literature. The authors demonstrate a clinical case of possible intrafamilial spread of hepatitis C virus. Forty-seven-year-old woman with chronic hepatitis C has one anti-HCV positive daughter. Because of the long period of incubation, less specific symptoms of acute C-hepatitis and often development of symptom-free disease, the patients and their families can be long in living together without being unaware of potential infection. Intrafamilial spread of hepatitis C virus may occur. It is strongly suggested to inform the patients about the possible risk and the importance of personal hygiene.


Relation of stroke and cardiac indices to serum catecholamines following open heart surgery.
Serum catecholamines (epinephrine, dopamine and norepinephrine) were measured two, four and six hours after open heart surgery. The ratios of stroke index (SI) and cardiac index (CI) to catecholamines (CA) were determined. Patients studied consisted of 27 with congenital and 14 with acquired heart disease. Extracorporeal circulation (ECC) time was longer than 90 minutes in 17 and shorter in 24 patients. SI and CI diminished in elder patients with congenital disease (Group Cg-ad), patients with acquired disease (Group Ac) and patients with a longer ECC time (Group L). Therefore, elder age and/or longer ECC time seems to be responsible to the lower indices. However, the ratios of the indices to CA showed that the lower indices indicated the poor response of the myocardium to CA in Group Ac and Group L. The response was larger in Group Cg-ad and the lower indices were related to lower serum CA level. It was concluded, therefore, that the indices of stroke volume and cardiac output had inverse correlation to ECC time, but not to age, namely, prolonged ECC compromised more severely the myocardium and resulted in the poor response of the myocardium to CA. Subsequently, to compensate for the poor response, serum CA levels were elevated probably to maintain due SI and CI in patients with prolonged ECC.


Open Choldecho-Enterostomy for Common Bile Duct Stones: Is it Out of Date in Laparo-Endoscopic Era?
Nowadays, biliary-enteric drainage (BED) is regarded as a last resort or obsolete therapeutic method for common bile duct stone (CBDS) not only because of advances in minimally invasive therapeutic modalities but also due to fears of higher morbidity, cholangitis, and "sump" syndrome. The present study aimed at evaluating the outcome of this procedure for choledocholithiasis. It is a retrospective review of 51 patients who underwent open choledochoenterostomy for CBDS between January 2005 and December 2009. About 40 women (78%) and 11 men underwent open BED (mean age 72 years). Indications were elderly patients (90%), multiple stones (54.9%) and unextractable calculi (15.4%). We performed 49 (96%) side to side choledochoduodenostomies, one end to side choledochoduodenostomy (CDS) and one end to side hepaticojejunostomy. The mortality rate was 3.9%. Overall morbidity was 12% with no biliary leakage. With a decline of 1-6 years, neither sump syndrome nor cholangiocarcinoma occurred. Side-to-side CDS is a safe and highly effective therapeutic measure, even when performed on ducts less than 15 mm wide, provided a few technical requirements are respected. Patients experiencing relapsing cholangitis after BED should be closely monitored for the late development of biliary tract malignancies.


Mechanisms and effects of arsanilic acid on antibiotic resistance genes and microbial communities during pig manure digestion.
High concentrations of residual arsanilic acid occur in pig manure due to its use in feed to promote growth and control diseases. This study compared the effects of arsanilic acid at three concentrations (0, 325, and 650mg/kg dry pig manure) on the abundance of antibiotic resistance genes (ARGs) and the microbial community during anaerobic digestion. Addition of 650mg/kg arsanilic acid enhanced the absolute abundances of tetC, sul2, ermB, and gyrA more than twofold in the digestion product. Redundancy analysis indicated that the change in the microbial community structure was the main driver of variation in the ARGs profile. The As resistance gene arsC co-occurred with four ARGs and intI1, possibly causing the increase in ARGs under pressure by arsanilic acid. High arsanilic acid concentrations can increase the risk of ARGs occurring in anaerobic digestion products. The amount of arsanilic acid used as a feed additive should be controlled.


Hahnemann's legacy in a new light--a systematic approach to the Organon of Medicine.
The sixth edition of Samuel Hahnemann's Organon of Medicine is an obligatory work of reference for homeopathy. Nevertheless, its philosophy can be questioned with constructivistic and historistic objections. Three levels of content may be distinguished: (1) practical directions and maxims, (2) theoretical explanations and hypotheses, (3) conceptual foundations and premises. Ideally, these levels should be considered, studied, and taught separately and gradually. My new German edition of the Organon, published in 2003, tries to meet these demands. It contains: (A) a complete version of Hahnemann's original text, in the original order of paragraphs, but in modern German with section headings, summary boxes, etc added, (B) another full version of its content, organized in three levels, as indicated above, (C) a glossary of about 400 problematic terms.


Removal of Cr(VI) from low-temperature micro-polluted surface water by tannic acid immobilized powdered activated carbon.
In this study, food-grade tannic acid-immobilized powdered activated carbon (TA-PAC) was prepared, and adsorption of Cr(VI) (0.500 mg/L) onto TA-PAC as a function of pH, contact time, adsorption capacities and adsorption isotherms at 280 K was investigated. The results indicated that the immobilization process introduced abundant acid functional groups. The adsorption capacity of TA-PAC was found to be pH-dependent, and the optimal pH value was found to be 4.0. The equilibrium time was 240 min for TA-PAC. Adsorption data for total chromium were modeled using both two-parameter and three-parameter isotherm models. Freundlich and linear forms of three-parameter models yielded the best results for all of the data. Desorption studies of immobilized material suggested that the immobilization of food-grade tannic acid is steady. The adsorption mechanism of Cr(VI) on TA-PAC was assumed to be a comprehensive process consisting of surface reduction of Cr(VI), esterification between catechol and chromate, and ion exchange.


Successful sealing of perforation of saphenous vein graft by coronary stent.
Coronary artery perforation is a rare occurrence during angioplasty and could lead to major complications requiring emergency surgical intervention. We describe a case of perforation of a saphenous vein graft during stenting. The perforation was successfully sealed by a second coronary stent.


Fifteen years' experience of radiation therapy for resected advanced heterotopic ossification following motor vehicle accidents: outcome and side effects.
Surgical resection is the primary treatment for advanced-stage heterotopic ossification (HO), with a high incidence of local recurrence reaching up to 50%. Postoperative radiotherapy (PORT) and indomethacin are commonly used prophylactic strategies following surgery. The study aims to assess the safety and effectiveness of PORT in advanced-stage HO patients having motor vehicle accidents (MVA). Medical records of patients having HO following MVA between 2006 and 2021 were retrospectively reviewed. Thirty-nine patients with advanced disease (35 had hip HO and 4 had elbow HO) were included in the study. Excision of HO with joint preservation was performed for 82% of patients, while 18% had a joint replacement. Seven to 8 Gy radiation was given to all patients within 3 days postoperatively. A ninty seven percent of patients regained partially the movement range. The mean follow-up time was 74 months. Six patients had treatment failure, with only one having a recurrence of HO. The 8-year treatment failure-free rate (8-y TFFR) was 79.3±9%, and the 5-year HO failure-free rate (5y-HOFFR) was 97.2±3%. Acute side effects were experienced in 13% of patients but resolved without any consequences. Despite the relatively long follow-up time, we did not report any absolute infertility or secondary malignancies related to the radiation. The testicular mean calculated dose was 33±44 cGy, and the mean measured dose was 58±40 cGy. Of the 35 patients who received radiation to the pelvis, 26 were married, and all did not experience infertility post-treatment. PORT proved an effective and safe treatment for advanced-stage HO disease. The treatment failure is mainly related to surgical difficulties due to advanced disease. Treatment using a 3-dimensional or intensity-modulated radiation therapy is not associated with serious side effects like second malignancy or absolute infertility.


Synthesis and biological evaluation of thiophenylbenzofuran derivatives as potential P-glycoprotein inhibitors.
P-Glycoprotein (P-gp) overexpression is a major mechanism by which cancer cells acquire the multidrug resistance (MDR) phenotype, and is associated with poor clinical outcome in patients. In an effort to develop MDR-reversal agents, we synthesized and evaluated a series of thiophenylbenzofuran derivatives (4-31) as P-gp inhibitors, among which compounds 4, 10, and 14 represented the optimal agent in reversing the MDR phenotype. These P-gp inhibitors were dramatically effective than verapamil in sensitizing the human ABCB1-overexpressing ABCB1/Flp-In™-293 cells and MDR KBvin cells to a series of chemotherapeutic agents, including vincristine and paclitaxel, as manifested by multi-fold decreases in the respective IC50 values to therapeutically attainable levels.


Pyridinic Nanographenes by Novel Precursor Design.
In this work we present the solution-synthesis of pyridine analogues to hexa-peri-hexabenzocoronene (HBC)-which might be called superpyridines-via a novel precursor design. The key step in our strategy was the pre-formation of the C-C bonds between the 3/3' positions of the pyridine and the adjacent phenyl rings-bonds that are otherwise unreactive and difficult to close under Scholl-conditions. Apart from the synthesis of the parent compound we show that classical pyridine chemistry, namely oxidation, N-alkylation and metal-coordination is applicable to the π-extended analogue. Furthermore, we present basic physical chemical characterizations of the newly synthesized molecules. With this novel synthetic strategy, we hope to unlock the pyridine chemistry of nanographenes.


Traumatic left ventricular false aneurysm with significant regurgitation from left ventricular outflow tract to left atrium: delineation by two-dimensional and color flow Doppler echocardiography.
A 22-year-old man was asymptomatic 23 months after an automobile accident but had clinical evidence of progressive mitral insufficiency. Two-dimensional and color flow Doppler echocardiography demonstrated a false aneurysm adjacent to the left ventricular outflow tract and significant regurgitation of blood through a traumatic channel from the left ventricular outflow tract to the left atrium. The patient underwent successful surgical closure of the false aneurysm and repair of the traumatic left atrial regurgitation.


Multiparametric magnetic resonance imaging and active surveillance: How to better select insignificant prostate cancer?
To evaluate the role of multiparametric magnetic resonance imaging in improving the predictive accuracy of the Prostate Cancer Research International: Active Surveillance and Epstein criteria for active surveillance in prostate cancer. A retrospective study was carried out with 126 prostate cancer patients treated with robot-assisted radical prostatectomy, but eligible for active surveillance according to the Prostate Cancer Research International: Active Surveillance criteria; 63 patients were also eligible according to the Epstein criteria. All patients underwent preoperative multiparametric magnetic resonance imaging, after at least 6 weeks from biopsy. The images from the multiparametric magnetic resonance imaging were assessed, and diagrams showing prostate sextants were used to designate regions of abnormalities within the prostate. Findings in the prostate were assigned to one of five categories according the Prostate Imaging-Reporting and Data System guidelines (v1.0), and considered positive for prostate cancer if the final Prostate Imaging-Reporting and Data System guidelines were >3 and negative if ≤3. Multivariate logistic regression analysis was carried out to evaluate the gain in accuracy of the Prostate Cancer Research International: Active Surveillance and Epstein criteria when added to multiparametric magnetic resonance imaging. Decision curve analysis was carried out to identify the net benefit of each model. The inclusion of multiparametric magnetic resonance imaging to the Epstein criteria and the Prostate Cancer Research International: Active Surveillance multivariate model significantly increased their accuracy in predicting pathologically-confirmed insignificant prostate cancer by 7% and 5%, respectively. At the decision curve analysis evaluation, the model including the Prostate Cancer Research International: Active Surveillance criteria and multiparametric magnetic resonance imaging improved the clinical risk prediction over the other models. The present findings suggest that multiparametric magnetic resonance imaging is able to increase the predictive accuracy of Prostate Cancer Research International: Active Surveillance and Epstein criteria to identify prostate cancer patients eligible for active surveillance.


Clinical characteristics and outcome of aortic endocarditis with periannular abscess in the International Collaboration on Endocarditis Merged Database.
The aims of this study were to determine the clinical characteristics and outcome of patients who had definite infective endocarditis (IE) complicated by aortic ring abscess formation that was detected with transesophageal echocardiography (TEE) and to determine the prognostic significance of abscess formation in aortic valve IE. Patients who had aortic valve IE were selected from the International Collaboration on Endocarditis Merged Database (ICE-MD) if they underwent TEE. Among 311 patients who had definite aortic valve IE, 67 (22%) had periannular abscesses. They were more likely to have infection in the setting of a prosthetic valve (40% vs 19%, p <0.001) and coagulase-negative staphylococcal IE (18% vs 6%, p < 0.01) and less likely to have streptococcal IE than were patients who did not develop abscess (28% vs 46%, p = 0.01). Systemic embolization, central nervous system events, and heart failure did not differ between those who developed abscess and those who did not, but power was limited. Patients who had abscess were more likely to undergo surgery (84% vs 36%, p <0.001), and their in-hospital mortality rate was higher (19% vs 11%, p = 0.09). Multivariate analysis of prognostic factors of mortality in aortic IE identified age (odds ratio [OR] 1.6, 95% confidence interval [CI]1.2 to 2.1), Staphylococcus aureus (S. aureus) infection (OR 2.4, 95% CI 1.1 to 5.2), and heart failure (OR 2.9, 95% CI 1.4 to 6.1) as variables that were independently associated with increased risk of death. Periannular abscess formation showed a nonsignificant trend toward an increased risk of death (OR 1.9, 95% CI 0.9 to 3.8). Multivariate analysis of prognostic factors of mortality in complicated aortic IE with abscess formation identified S. aureus infection (OR 6.9, 95% CI 1.6 to 29.4) as independently associated with increased risk of death. In conclusion, in the current era of TEE and high use of surgical treatment, periannular abscess formation in aortic valve IE is not an independent risk factor for mortality. S. aureus infection is an independent prognostic factor for mortality in patients who have abscess formation.


The medical management of idiopathic chylothorax in a domestic long-haired cat.
A 3-year-old, spayed female domestic long-hair was evaluated for a 2-week history of progressive tachypnea. Chylothorax was diagnosed through radiographic and pleural fluid evaluation. No primary cause was identified and the cat was managed medically. Thoracocentesis, dietary management, and oral rutin therapy resulted in substantial improvement of this idiopathic condition.


Comparative proteomic analysis of the saliva of the Rhodnius prolixus, Triatoma lecticularia and Panstrongylus herreri triatomines reveals a high interespecific functional biodiversity.
Triatomines are hematophagous arthropods that transmit Trypanosoma cruzi and Trypanosoma rangeli. Feeding behavior and pathogen transmission is known to vary between the different species, and this characteristic is directly or indirectly dependent on the bioactive molecules of the saliva that facilitate the vector-host-parasite interaction. Here, we identify, characterize and compare the sialoproteomic (from the Greek sialo: saliva) repertoire of important species of the main triatomine genera in the Americas (Rhodnius prolixus, Triatoma lecticularia and Panstrongylus herreri) to better explain this interaction through two-dimensional electrophoresis and mass spectrometry. We identified 221 proteins, 69 from R. prolixus, 100 from T. lecticularia and 52 from P. herreri. We identified high abundance molecules with a great potential to modulate host defenses and homeostasis, highlighting Nitrophorin-4 (28.7%), Salivary lipocalin-5 (65.2%) and Putative triabin (20.5%) in R. prolixus, T. lecticularia and P. herreri, respectively. We also observed that only a single hypothetical protein is shared among three species, which was not functionally categorized. This study corroborates previous findings with R. prolixus, increasing the knowledge about this species with relevant proteomic information and comparisons with the other two targets of the study, T. lecticularia and P. herreri, for which no studies are available from a proteomics perspective.


Secondary or concomitant neoplasms among adults diagnosed with acute lymphoblastic leukemia and treated according to the LALA-87 and LALA-94 trials.
Second malignant neoplasms are a serious complication after successful treatment of childhood acute lymphoblastic leukemia (ALL). Although treatment intensity and outcome were not comparable, with improvements in survival it is important to evaluate the rate and the type of second neoplasms in adults with ALL. The data from the GET-LALA group were analyzed. A cohort of 1494 patients, aged 15 to 60 years and enrolled in 2 successive multicenter protocols between 1987 and 2002, was observed to determine the incidence of second neoplasms and associated risk factors. The median follow-up from diagnosis was 6 years. By February 2005 secondary or concomitant neoplasms were documented in 23 patients, including 9 acute myeloid leukemias (AML) or myelodysplasias (MDS), 4 non-Hodgkin lymphomas (NHL), 5 skin tumors, and 5 other solid tumors (1 lung cancer, 1 tongue carcinoma, 1 thymoma, 1 condrosarcoma, 1 histiocytosis). Neoplasms developed 0.5 to 13.8 years (median, 4.5 years) after the diagnosis of ALL. There were 22 patients in first remission and 1 was in second remission. The overall cumulative risk of secondary neoplasms was 2.1% at 5 years, 4.9% at 10 years, and 9.4% at 15 years. The cumulative risk of developing a second hematologic malignancy was 1.8% at 5 years, 2.2% at 10 years, 3.3% at 18 years; that of developing a solid tumor was 0.2% at 5 years, 2.8% at 10 years, 6.2% at 15 years. The development of secondary neoplasm was not associated with the use of any specific cytotoxic agent. However, the risk of skin tumor increased with radiation dose and transplantation (P = .01). Overall survival (OS) after the diagnosis of a second malignant neoplasm was 55% at 10 years. However, the median OS in patients developing AML/MDS was 5.7 months. The data document that adult ALL survivors are at an increased risk of later malignancy. The risk of secondary or concomitant neoplasm appeared higher than that of childhood ALL previously reported in the literature. Considering the low survival rate of this large unselected adult ALL cohort (32% at 10 years) as compared with that observed in childhood ALL, the risk of second malignancy remains underestimated. Larger series with long-term follow-up are necessary, as well as methods of screening and identification of patients at increased risk.


[Bilateral idiopathic orbital myositis].
Orbital myositis is an idiopathic inflammation of the extraoccular muscles. It is often included under the broad description of orbital pseudotumor. It is commonly a unilateral affection. We report one case of bilateral orbital myositis in a 45-year-old woman. The first symptoms were diplopia and acute bilateral orbital pain exacerbated by eye movements. Physical examination especially neurological was normal. Serum creatine kinase and biological thyroid function were normal. CT scan found a bilateral enlargement of rectus oculi medialis and lateralis. Clinical improvement was obtained a few days after oral corticosteroid treatment with remission of all signs. Orbital myositis is a rare entity. 90-95p.cent of cases are unilateral. Bilateral forms are exceptional and in this case require search for specific etiologies particularly thyroid ophthalmopathy. There is controversy concerning treatment options but corticosteroids are still the most common first choice therapy with good outcome.


Effect of Lentinula edodes on Morphological and Biochemical Blood Parameters of Horses.
Shiitake mushrooms have been highly regarded as possessing enormous nutritive and medicinal values. No clinical studies have yet investigated the effect of shitake supplementation on the health of horses. The aim of this study was to evaluate the effect of shiitake mushroom supplementation on the morphological and biochemical blood properties in horses. A total of 17 adult horses were divided into two groups: supplemented and control. The supplemented group was fed 60 g of shiitake mushrooms per day for 5 months. Blood samples were collected in five sessions. Blood morphological analysis showed higher levels of lymphocytes in session 3 and monocytes in session 4 in the supplemented group. In addition, basophils, hemoglobin, and hematocrit were elevated compared to the control group. Biochemical analysis showed that the shiitake mushrooms affected a large number of parameters. In particular, alkaline phosphatase was found to be the most sensitive to shitake mushroom supplementation, for which the statistical differences were significant for sessions 2, 4, and 5. Furthermore, calcium was found to be affected by supplementation only in session 4, and gamma-glutamyl transferase in session 2. In addition, the bilirubin and glucose levels were lower in the supplemented group, and the albumin/globulin ratio was higher compared to the control group. The differences between the supplement and the control group in various sessions suggest that shiitake mushrooms are a beneficial nutritional supplement for horses.


Rotavirus gastroenteritis in infants and young children.
The electronmicroscopic examination of stool samples from 18 infants and young children with gastroenteritis, hospitalized at the Clinic of Infectious Diseases in Prague, was carried out. In ten children rotavirus was found in the faeces and the bacteriological findings were negative. Rotavirus particles were aggregated by convalescent child sera and by normal human gamma globulin. The clinical picture was characterized by the sudden onset of vomiting and fever, in one case with febrile convulsions. Diarrhoea was watery and yellow-green, and usually persisted for four to five days. The condition of the children improved rapidly after rehydration and a special diet. Older siblings, and in one family also adult members, were frequently affected.


Mental health and labor supply: Evidence from Canada.
This study investigates the relationship between mental health and employment using an instrumental variable approach with the 2012 Canadian Community Health Survey-Mental Health. Using a family member's mental health problem(s) as an instrument for poor mental health, the estimates reveal that poor mental health significantly reduces employment outcomes. These findings are robust to various specifications, such as an alternative instrument and a relaxation of the exclusion restriction assumption. In addition, the relationship is driven mainly by men and younger workers. Moreover, the findings suggest that the relationship is mediated by a decline in cognitive abilities, such as difficulties in concentration and motivation, and social relations with acquaintances and friends. Finally, the estimates show that this phenomenon is contagious: poor mental health has a significant spillover effect on coworkers' mental health in workplaces. This study demonstrates the importance of mental health illness in Canada and other developed countries.


Beam parameters optimization and characterization for a TUrning LInac for Protontherapy.
TULIP (TUrning LInac for Protontherapy) is a novel compact accelerator system for protontherapy mounted on a rotating gantry (Amaldi et al., 2013, 2010, 2009). Its high-energy Linac has the unique property of being able to modulate the beam energy from one pulse to the next, in only a couple of milliseconds. The main purpose of this study is to optimize the properties of the beam exiting the Linac to make them compatible to medical therapy and to characterize their medical physics properties for later implementation in a Treatment Planning System. For this purpose, multi-particle tracking and Monte Carlo (MC) simulations are used to follow the particles through their path up to the treatment isocenter, following the so-called phase-space method. The data compiled includes particle fluences in air and depth-dose curves and provides the basis for a specific model of the TULIP beam.


Target of brain activity: its own critical point.
The brain regulates not only the body and its internal environment and motor activity, but it also regulates the activity of its own very self. What is the set-point or target of the brain's regulation of its own activity? A proposal is that the kind of state known to physics by the name "critical" may give a valuable model of the set-point of the brain's self-regulation. The idea of dynamical scaling then corresponds with John Hughlings Jackson's doctrine of levels. The idea of marginal phase junctions corresponds with the stable lability of the will.


Label-Free quantitation of milk oligosaccharides from different mammal species and heat treatment influence.
Milk oligosaccharides (MOs) exhibit significant variations in concentrations and patterns among different species. However, there is limited knowledge about milk oligosaccharides in domestic animals and the impact of heat treatment on them. Here, we developed an LC-ESI-MS/MS method to analyze 11 milk oligosaccharides in 7 distinct species simultaneously. The results showed that human milk presented a completely different composition pattern of milk oligosaccharides from animals. In detail, animal milk predominantly contained sialylated oligosaccharides, and human milk had high levels of fucosylated neutral oligosaccharides. Notably, sheep milk exhibited similarities to human milk in terms of oligosaccharides composition. Then, the milk samples from dairy cows were treated with two common industrial heat treatments. We found that 65 °C treatment had no significant effect on the concentration of milk oligosaccharides, whereas 135 °C heating was associated with their decline, suggesting that high temperatures should be avoided in the processing of oligosaccharides supplemented/enriched products.


Symptomatic cluster-like headache triggered by forehead lipoma: a case report and review of the literature.
We describe the case of a patient with symptomatic strictly unilateral paroxysmal headache mimicking cluster headache related to an ipsilateral forehead lipoma. Interestingly, immediately after the surgical excision of the lipoma pain attacks disappeared with no recurrence during a follow-up period of 18 months. Like other descriptions of cluster-like headaches secondary to extracranial lesions, this case report focuses on the hypothetical role of a peripheral trigger factor for trigeminal autonomic cephalgias (TACs). To our knowledge, this is the first well-described cluster-like headache case secondary to an extracerebral lipoma. This case offered the opportunity to discuss the possible pathophysiological mechanisms underlying probable TACs and the relationship with peripheral extracerebral activation of the trigeminal-autonomic reflex.


Adenine nucleotide-dependent and redox-independent control of mitochondrial malate dehydrogenase activity in Arabidopsis thaliana.
Mitochondrial metabolism is important for sustaining cellular growth and maintenance; however, the regulatory mechanisms underlying individual processes in plant mitochondria remain largely uncharacterized. Previous redox-proteomics studies have suggested that mitochondrial malate dehydrogenase (mMDH), a key enzyme in the tricarboxylic acid (TCA) cycle and redox shuttling, is under thiol-based redox regulation as a target candidate of thioredoxin (Trx). In addition, the adenine nucleotide status may be another factor controlling mitochondrial metabolism, as respiratory ATP production in mitochondria is believed to be influenced by several environmental stimuli. Using biochemical and reverse-genetic approaches, we addressed the redox- and adenine nucleotide-dependent regulation of mMDH in Arabidopsis thaliana. Recombinant mMDH protein formed intramolecular disulfide bonds under oxidative conditions, but these bonds did not have a considerable effect on mMDH activity. Mitochondria-localized o-type Trx (Trx-o) did not facilitate re-reduction of oxidized mMDH. Determination of the in vivo redox state revealed that mMDH was stably present in the reduced form even in Trx-o-deficient plants. Accordingly, we concluded that mMDH is not in the class of redox-regulated enzymes. By contrast, mMDH activity was lowered by adenine nucleotides (AMP, ADP, and ATP). Each adenine nucleotide suppressed mMDH activity with different potencies and ATP exerted the largest inhibitory effect with a significantly lower K(I). Correspondingly, mMDH activity was inhibited by the increase in ATP/ADP ratio within the physiological range. These results suggest that mMDH activity is finely controlled in response to variations in mitochondrial adenine nucleotide balance.


Fundus findings and longitudinal study of visual acuity loss in patients with X-linked retinoschisis.
To determine the presence of fundus findings and natural course of visual acuity change in patients with juvenile X-linked retinoschisis (XLRS). A retrospective longitudinal study of 38 patients with juvenile XLRS (age range, 9-65 years) was conducted. Best-corrected visual acuity, Goldmann visual fields, and results of slit-lamp biomicroscopy of the anterior segment and dilated fundus examination were obtained for all patients. Visual acuity findings at the most recent and initial visits were compared. Follow-up ranged from 1 year to 28 years (mean, 10.2 years). Twenty-five patients were observed for > 5 years, and 11, for > or = 15 years. Foveal lesions varied from predominantly radial striations (3%), microcystic lesions (34%), honeycomblike cysts (8%), or their combinations (31%) to non-cystic-appearing foveal changes, such as pigment mottling (8%), loss of the foveal reflex (8%), or an atrophic-appearing lesion (8%). Twelve patients (32%) had situs inversus of their retinal vessels. We observed a superior nasal restriction in the peripheral visual field even in the absence of clinically apparent peripheral retinoschisis. Of the 38 patients who were seen more than once, using logarithm of the minimum angle of resolution (logMAR) comparison, 4 had a decrease in visual acuity of > 0.1 logMAR, equivalent to > 1 line on an ETDRS chart, in their better seeing eye, and 3 had a reduction in visual acuity of > 0.2 logMAR in their better eye. A limited change in visual acuity was observed in our cohort of 38 patients with XLRS even over an extended period. However, those patients with non-cystic-appearing changes within the fovea, including pigment mottling or an atrophic-appearing lesion, tended to have a more appreciable degree of visual acuity impairment compared with those patients with a cystic-appearing foveal change.


Gas chromatography-mass spectrometry of the N(O)-heptafluorobutyryl isobutyl esters of the protein amino acids using electron impact ionisation.
The N(O)-heptafluorobutyryl isobutyl esters of the protein amino acids have been analysed by combined gas chromatography-mass spectrometry using electron impact ionisation. The spectral data have been used to confirm the structures of the amino acid derivatives.


Preparation and assessment of a new radiotracer technetium-99m-6-hydrazinonicotinic acid-tyrosine as a targeting agent in tumor detecting through single photon emission tomography.
The goal of investigation was to bring up an impressive way to synthesize technetium-99 m-6-hydrazinonicotinic acid-tyrosine (99mTc-HYNIC-Tyr), a newfound radiotracer, and to assess the capacity of being as a tumor scintigraphy agent. The conjugate was prepared by solid phase method using tritely chloride resin. The precursor HYNIC-Tyr was labeled with 99mTc which was accomplished at 100 °C through the coligands tricine and EDDA. Furthermore, the serum albumin binding, cellular attachment, organs uptake and tumor accumulation were measured. C6 glioma cells were used for cellular and tumor uptake studies. 99mTc-HYNIC-Tyr was prepared with labeling yield of >99% (n = 3). Radiotracer showed stability in serum proteins in incubates temperature. Specific cellular attachment of radiotracer was noticeable in C6 glioma cells with dissociation constant in nano molar range (21.03 ± 1.54 nM). The amount of uptake in C6 rat glioma xenograft was 2.61 ± 0.12 percent of injection dose per gram after 30 min. In whole-body scintigraphy, C6 glioma tumor was easy to be traced and interpreted at 1 h after administration of radiotracer. Our data suggest that 99mTc-HYNIC-Tyr, a new radiotracer based on amino acid, efficiently differentiates the tumor cells and goes into them. Our results indicate that this radiotracer has excellent capacity to detect tumor cells in rat and to be included as a radiopharmaceutical for detecting cancer tumors.


Carrier DNA affects the integration of HSV-1 TK gene in the genome of L929TK- cells.
L929TK- cells were cotransfected with DNA mixtures containing tk gene of HSV-1, plasmids carrying LTR of MoMLV or RSV and carrier DNA of salmon sperm or chromosomal DNA of recipient cells. Selection of TK+ transformants was conducted in DMEM supplemented with HAT. Plasmids carrying LTR sequences of MoMLV or RSV retroviruses showed enhancing effect on the frequency of TK+ transformation. Southern blot analysis of chromosomal DNA of TK+ transformants demonstrated in clones deriving from cotransfections of tk gene and carrier DNA of L929TK- cells multiple copies of tk gene integrated into several genomic sites of host. Single copies of tk gene integrated into different sites of host genome occurred in chromosomal DNA of TK+ clones deriving from cotransfections of tk gene and carrier DNA of salmon sperm. Cells cotransfected with tk gene and plasmids carrying LTR sequences of MoMLV or RSV formed three dimensional colonies in semisolid agar medium. No effect of carrier DNA on the morphology of TK+ transformant clones was noticed.


Identifying sensitive periods when changes in parenting and peer factors are associated with changes in adolescent alcohol and marijuana use.
There are well-established associations between parental/peer relationships and adolescent substance use, but few longitudinal studies have examined whether adolescents change their substance use in response to changes in their parents' behavior or peer networks. We employ a within-person change approach to address two key questions: Are changes in parenting and peer factors associated with changes in adolescent marijuana and alcohol use? Are there sensitive periods when changes in parenting and peer factors are more strongly associated with changes in adolescent marijuana and alcohol use? We analyzed longitudinal data collected annually on 503 boys, ages 13-19, recruited from Pittsburgh public schools. Questionnaires regarding parental supervision, negative parenting practices, parental stress, physical punishment, peer delinquency, and peer drug use were administered to adolescents and their caretakers. Alcohol and marijuana use were assessed by a substance use scale adapted from the National Youth Survey. Reductions in parental supervision and increases in peer drug use and peer delinquency were associated with increases in marijuana frequency, alcohol frequency, and alcohol quantity. Increases in parental stress were associated with increases in marijuana and alcohol frequency. The magnitudes of these relationships were strongest at ages 14-15 and systematically decreased across adolescence. These associations were not due to unmeasured stable confounders or measured time-varying confounders. Reducing or mitigating changes in parenting and peer risk factors in early adolescence may be particularly important for preventing substance use problems as adolescents transition into young adulthood.


[Correlations between OCT4 expression and clinicopathological factors and prognosis of patients with lung adenocarcinoma].
In recent years, cases of lung adenocarcinoma morbidity have consistently grown. OCT4 is the key gene that controls the automatic renewal of stem cells, and regulates the proliferation and differentiation of cancer stem cells. The aim of this study is to detect OCT4 expression in lung adenocarcinoma tissues, and to evaluate its relevance in the metastasis, chemotherapeutic effect, and prognosis in lung adenocarcinoma patients. Immunofluorescence method was employed to detect OCT4 expression in lung adenocarcinoma tissues. The relationship between OCT4 expression and clinical pathological indicators is examined through chi-square test. Moreover, the survival rate is calculated through the Kaplan-Meier survivorship curve. Finally, the relevance between the indicators and patient survival is estimated using Cox analysis. Among the 126 tissue samples of lung adenocarcinoma, 91 showed OCT4 positive cells. OCT4 expression is closely related to metastasis and chemoresistance in lung adenocarcinoma patients, and negatively corresponds to the patients' disease-free survival and survival periods. OCT4 expression is related to metastasis and chemoresistance in lung adenocarcinoma patients, and thus indicates poor prognosis.


In-vitro and in-vivo hemostat evaluation of decellularized liver extra cellular matrix loaded chitosan/gelatin spongy scaffolds for liver injury.
Individually, Chitosan (C) and Gelatin (G) are increasingly being used for the simulation and testing of surgical procedures. In the present study, at combination of chitosan/gelatin (CG) was optimized and later enriched by the loading decellularized liver extracellular matrix powder (dLECM) prepared from porcine liver, we hypothesized CG-dLECM combination would enhance wound healing and reduce postoperative complications after liver surgery. Varying concentration of dLECM (1, 4, and 8 mg/ml) were loaded into CG, and evaluation was done to get the optimized composition. Preliminary analysis on the microstructure, in-vitro degradation, and blood clot kinetics and in-vitro cytocompatibility showed that the CG with 4 mg/ml dLECM (CG-E4) was the most suitable composition for further consideration. The prepared CG-E4 spongy scaffold enhances fast post-operative recovery with a higher blood absorption and fast clotting time (~50 s). In addition, CG-E4 spongy scaffold implanted at rat liver wound showed desired biocompatibility as evidenced by reduced wound size, earlier bioabsorption and accelerated liver regeneration. In the present study, we demonstrated that, CG with dLECM spongy scaffold as a potential hemostatic material in the prevention of excessive hemorrhage during surgeries.


Endoscopic fenestration of cavum velum interpositum cysts: a case study of two symptomatic patients.
Cavum velum interpositum (CVI) is commonly an incidental asymptomatic finding on imaging studies. Encystment can occur and, in most situations, is also asymptomatic. Clinical symptoms occurring in patients with CVI cysts have been reported infrequently with the result that the relationship of these symptoms and the cyst are usually unclear. This report contributes to the knowledge base of symptoms that can occur in patients with CVI and the response of symptoms to effective treatment. We report the clinical outcomes of a 3-year-old male patient and a 13-year-old female patient with symptoms and CVI cysts on imaging who were treated successfully with endoscopic fenestration. The developmental delay and occasional headache present in the 3-year-old male patient resolved after endoscopic fenestration; however, the 13-year-old patient who had neuropsychiatric symptoms did not improve. Our cases add to the literature describing the response to cyst treatment in symptomatic patients harboring CVI cysts. Symptoms due to CSF pathway obstruction may respond to cyst fenestration, while the response of symptoms in patents who do not have clear CSF circulation disorders is less predictable.