Brain death: confirmation by radionuclide cerebral angiography.
Dynamic radionuclide cerebral angiography was performed in 14 patients with suspected brain death. In 10 of 14 patients, no intracranial arterial perfusion was demonstrable, thus confirming brain death. In four patients, faint venous activity was seen in the sagittal sinus only. All these patients also eventually died. Radionuclide cerebral angiography provides a simple and noninvasive means to confirm brain death in critically ill patients maintained on life support systems particularly when an electroencephalogram and four vessel contrast angiography may be either impractical or equivocal.


[Dental care for foreigners in Hungary].
High quality elective dental care for foreign patients was not exceptional in Hungary before the collapse of the old regime in 1989. Nevertheless, it became business as usual only in the new era thanks to the open state borders and the international competitive market environment. Unfortunately, no scientific study concerning this phenomenon has been conducted so far, however its professional and economic significance has been indicated by day-to-day experience. Additionally, the term "dental tourism" also used in international scientific papers became a commonplace in Hungary with unfavourable connotations. The present survey was the first to study this phenomenon by scientific standards in the most involved areas, namely in the capital city Budapest and in three counties in the Western Hungarian Region. Data collecting was performed by a self-reported questionnaire sent via conventional mail to all members of the Dental Section of the Hungarian Medical Chamber practicing in those indicated regions. Respond rates were 20.65% in Budapest and 25.34% in Western Hungary. The sample obtained this way, clearly indicated dimensions of cross-border patient migration and its economic significance as well. In Western Hungary 80.81% of foreign patients came from the neighbouring Austria and two out of ten practices realized 40 to 100% of their income out of this business. In Budapest foreign patients' nationality was more diversified. The largest group arrived from the United Kingdom (9.93%). Nevertheless the economic impact of dental tourism in Budapest is not relevant and outbalanced by a considerable domestic demand on the local private market.


The role of thoracic consolidative radiotherapy in the setting of immunotherapy in extensive stage small cell lung cancer.
The improvement in treatment strategies and outcomes in small cell lung cancer (SCLC) has lagged behind other cancers. The addition of immune checkpoint inhibitors (ICIs), durvalumab and atezolizumab, to the platinum-based chemotherapy in frontline setting has improved the survival in extensive stage SCLC, (ES-SCLC), albeit modestly, and is now the new standard of care. Prior to advent of immunotherapy into the therapeutic armamentarium in ES-SCLC, consolidative thoracic radiotherapy (TRT) was associated with improved thoracic control and survival outcomes. In the era of ICIs, the role of TRT is not well defined, chiefly because TRT was not incorporated in any immunotherapy trials, secondly due to concerns regarding the increased risks of pneumonitis, and finally uncertain magnitude of benefit with this combined approach. In principle, radiation can increase in the immunogenicity of tumor and hence the activity of immune checkpoint blockade, thereby increasing efficacy both locally and distantly. Such an approach has been promising in non-small cell lung cancer with ICIs improving outcomes after concurrent chemoradiation, but remains unanswered in ES-SCLC. It is, thus, possible that the modest improvement in survival by addition of ICIs to chemotherapy in ES-SCLC can be further improved by the incorporation of consolidative TRT in selected patients. Several early phase trials and retrospective studies have suggested that such an approach may be feasible and safe. Prospective trials are ongoing to answer whether adding radiation therapy to chemoimmunotherapy will improve outcomes in ES-SCLC.


Mn(2+) in D-Glucosaminate Dehydratase from Pseudomonas fluorescens.
D-Glucosaminate (D-GlcNA) dehydratase from Pseudomonas fluorescens was inhibited stoichiometrically by metal-chelating agents (EDTA, 8-hydroxyquinoline-5-sulfonic acid, α,α'-dipyridyl and o-phenan-throline). The activity of EDTA-treated enzyme was restored by incubation with Mn(2+) (0.4mM) or Ca(2+) (2mM) in the presence of pyridoxal 5'-phosphate (PLP, 0.2mM) in veronal buffer (VB, 40 mM, pH 8) at 37°C for 30 min. The atomic absorption spectrum of the native enzyme showed that the enzyme contained 1 mol of Mn(2+) per mole of enzyme. Although the EDTA-treated enzyme was unstable at 4°C, addition of Mn(2+) and PLP to the solution of the EDTA-treated enzyme prevented the inactivation. The Km of the restored enzyme for D-GlcNA was somewhat lower than that of the original enzyme. However, the Km for PLP increased 14-fold. These results suggest that D-GlcNA dehydratase contains Mn(2+) near the PLP-binding site, and the metal ion appears to stabilize the structure of the active site.


Sum frequency generation vibrational spectroscopic and high-pressure scanning tunneling microscopic studies of benzene hydrogenation on Pt(111).
Sum frequency generation (SFG) vibrational spectroscopy and high-pressure scanning tunneling microscopy (HP-STM) have been used in combination for the first time to study a catalytic reaction. These techniques have been able to identify surface intermediates in situ during benzene hydrogenation on a Pt(111) single-crystal surface at Torr pressures. In a background of 10 Torr of benzene, STM is able to image small ordered regions corresponding to the c(2 radical3 x 3)rect structure in which each molecule is chemisorbed at a bridge site. In addition, individual benzene molecules are also observed between the ordered regions. These individual molecules are assumed to be physisorbed benzene on the basis of the SFG results showing both chemisorbed and physisorbed molecules. The surface becomes too mobile to image upon addition of hydrogen but is determined to have physisorbed and chemisorbed benzene present by SFG. It was spectroscopically determined that heating the platinum surface after poisoning with CO displaces benzene molecules. The high-coverage pure CO structure of (radical19 x radical19)R23.4 degrees imaged with STM is a verification of spectroscopic measurements.


Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon.
This study demonstrates a unique and crucial role of plasmacytoid dendritic cells (pDCs) and pDC-derived type I interferons (IFNs) in the pathogenesis of mouse coronavirus infection. pDCs controlled the fast replicating mouse hepatitis virus (MHV) through the immediate production of type I IFNs. Recognition of MHV by pDCs was mediated via TLR7 ensuring a swift IFN-alpha production following encounter with this cytopathic RNA virus. Furthermore, the particular type I IFN response pattern was not restricted to the murine coronavirus, but was also found in infection with the highly cytopathic human severe acute respiratory syndrome (SARS) coronavirus. Taken together, our results suggest that rapid production of type I IFNs by pDCs is essential for the control of potentially lethal coronavirus infections.


New insights on the genetic diversity of the honeybee parasite Nosema ceranae based on multilocus sequence analysis.
The microsporidian parasite Nosema ceranae is a common pathogen of the Western honeybee (Apis mellifera) whose variable virulence could be related to its genetic polymorphism and/or its polyphenism responding to environmental cues. Since the genotyping of N. ceranae based on unique marker sequences had been unsuccessful, we tested whether a multilocus approach, assessing the diversity of ten genetic markers – encoding nine proteins and the small ribosomal RNA subunit – allowed the discrimination between N. ceranae variants isolated from single A. mellifera individuals in four distant locations. High nucleotide diversity and allele content were observed for all genes. Most importantly, the diversity was mainly present within parasite populations isolated from single honeybee individuals. In contrast the absence of isolate differentiation precluded any taxa discrimination, even through a multilocus approach, but suggested that similar populations of parasites seem to infect honeybees in distant locations. As statistical evolutionary analyses showed that the allele frequency is under selective pressure, we discuss the origin and consequences of N. ceranae heterozygosity in a single host and lack of population divergence in the context of the parasite natural and evolutionary history.


When is dialysis indicated in acute kidney injury?
The indications for dialysis in patients with acute kidney injury (AKI), as well as the dose and timing of initiation, remain uncertain. Recent data have suggested that early initiation of renal replacement therapy (RRT) may be associated with decreased mortality but not with the recovery of kidney function. A blood urea nitrogen (BUN) level of 75 mg/dL is a useful indicator for dialysis in asymptomatic patients, but one that is based on studies with limitations. Different parameters, including absolute and relative indicators, are needed. Currently, nephrologists should consider the trajectory of disease, and the clinical condition and prognosis of the patient are more important than numerical values in the decision to initiate dialysis.


Biological consequences of oxidative stress-induced DNA damage in Saccharomyces cerevisiae.
Reactive oxygen species (ROS), generated by endogenous and exogenous sources, cause significant damage to macromolecules, including DNA. To determine the cellular effects of induced, oxidative DNA damage, we established a relationship between specific oxidative DNA damage levels and biological consequences produced by acute H2O2 exposures in yeast strains defective in one or two DNA damage-handling pathways. We observed that unrepaired, spontaneous DNA damage interferes with the normal cellular response to exogenous oxidative stress. In addition, when base excision repair (BER) is compromised, there is a preference for using recombination (REC) over translesion synthesis (TLS) for handling H2O2-induced DNA damage. The global genome transcriptional response of these strains to exogenous H2O2 exposure allowed for the identification of genes responding specifically to induced, oxidative DNA damage. We also found that the presence of DNA damage alone was sufficient to cause an increase in intracellular ROS levels. These results, linking DNA damage and intracellular ROS production, may provide insight into the role of DNA damage in tumor progression and aging. To our knowledge, this is the first report establishing a relationship between H2O2-induced biological endpoints and specific oxidative DNA damage levels present in the genome.


Prevalence of urinary incontinence in women powerlifters: a pilot study.
Increased intra-abdominal pressure is associated with urinary incontinence (UI) as is increasing age, obesity, and participating in sport at an elite level. We aimed to determine the prevalence of UI in competitive women powerlifters and establish if commonly cited risk factors affect the incidence of UI. The authors developed a 17-item questionnaire to investigate the prevalence of UI and the relationship of UI with age, body mass, resistance training experience, and competition grade in competitive women powerlifters. The questionnaire was distributed through three major powerlifting federations in Australia for 16 months. The data of 134 competitive women powerlifters were collected anonymously using Qualtrics, and were analysed using multivariate analysis. In combination, the age of lifters, resistance training experience, body weight categories, and competition grade accounted for a significant 28% of the variability in the Incontinence Severity Index (ISI) (p < 0.01). However, the ISI was not significantly different among age groups, body weight categories, or competition grade. Approximately, 41% of women powerlifters had experienced UI at some stage in life, and 37% of women powerlifters currently experienced UI during training, competition, or maximum effort lifts. However, the rate of UI experienced during daily life activities was approximately 11%. This study showed that competitive women powerlifters experience a higher rate of UI during lifting-related activities than in daily life and that the rate of UI correlates positively with age, body weight categories, resistance training experience, and competition grade.


Multiple-instrument polyphonic music transcription using a temporally constrained shift-invariant model.
A method for automatic transcription of polyphonic music is proposed in this work that models the temporal evolution of musical tones. The model extends the shift-invariant probabilistic latent component analysis method by supporting the use of spectral templates that correspond to sound states such as attack, sustain, and decay. The order of these templates is controlled using hidden Markov model-based temporal constraints. In addition, the model can exploit multiple templates per pitch and instrument source. The shift-invariant aspect of the model makes it suitable for music signals that exhibit frequency modulations or tuning changes. Pitch-wise hidden Markov models are also utilized in a postprocessing step for note tracking. For training, sound state templates were extracted for various orchestral instruments using isolated note samples. The proposed transcription system was tested on multiple-instrument recordings from various datasets. Experimental results show that the proposed model is superior to a non-temporally constrained model and also outperforms various state-of-the-art transcription systems for the same experiment.


[A rare clinical case of the patient with pulmonary hypertension associated with hereditary hemorrhagic telangiectasia. Case report].
The article describes a rare clinical case of the patient with pulmonary hypertension associated with hereditary hemorrhagic telangiectasia and discusses the issues of the treatment choice of these patients. The presented clinical case is of interest because pulmonary hypertension was initially revealed, then its hereditary nature was confirmed and OslerWeberRendu disease was diagnosed.


Vitamin C content in human milk (colostrum, transitional and mature) and serum of a sample of bangladeshi mothers.
The vitamin C content of human milk was determined among twenty-six newly delivered mothers. Milk samples (colostrum, transitional and mature) were obtained at different stages of lactation. Mean vitamin C concentration varied from 3.52 ± 0.56 mg/dl for colostrum to 3.03 ± 0.67 mg/dl for mature milk with the advancement of time, but was in agreement with the infant's daily requirement. Serum vitamin C of a sub-sample of mothers (n=7) was also estimated for a comparison of vitamin C concentration between maternal breastmilk and serum. Vitamin C level estimated in the serum was 0.44 ± 0.29 mg/dl, revealing an eight-fold lower concentration compared to the corresponding milk samples.


Multiple-Localization and Hub Proteins.
Protein-protein interactions are fundamental for all biological phenomena, and protein-protein interaction networks provide a global view of the interactions. The hub proteins, with many interaction partners, play vital roles in the networks. We investigated the subcellular localizations of proteins in the human network, and found that the ones localized in multiple subcellular compartments, especially the nucleus/cytoplasm proteins (NCP), the cytoplasm/cell membrane proteins (CMP), and the nucleus/cytoplasm/cell membrane proteins (NCMP), tend to be hubs. Examinations of keywords suggested that among NCP, those related to post-translational modifications and transcription functions are the major contributors to the large number of interactions. These types of proteins are characterized by a multi-domain architecture and intrinsic disorder. A survey of the typical hub proteins with prominent numbers of interaction partners in the type revealed that most are either transcription factors or co-regulators involved in signaling pathways. They translocate from the cytoplasm to the nucleus, triggered by the phosphorylation and/or ubiquitination of intrinsically disordered regions. Among CMP and NCMP, the contributors to the numerous interactions are related to either kinase or ubiquitin ligase activity. Many of them reside on the cytoplasmic side of the cell membrane, and act as the upstream regulators of signaling pathways. Overall, these hub proteins function to transfer external signals to the nucleus, through the cell membrane and the cytoplasm. Our analysis suggests that multiple-localization is a crucial concept to characterize groups of hub proteins and their biological functions in cellular information processing.


Systemic hypotension: a risk factor for glaucomatous damage?
Four glaucoma patients with rapid progression of visual field damage and excavation of the optic nerve head despite normal or well-controlled intraocular pressure had one factor in common: low systemic blood pressure. Furthermore, when monitored during 24 h, a sustained blood pressure drop during sleep was always observed. Systemic hypotension, therefore, might be a significant risk factor for glaucomatous damage. The authors recommend measuring the blood pressure frequently in such patients, especially at night.


Feasibility study on posterior laminar screw fixation techniques in the axis.
To get morphologic parameters of Chinese adults through observation and measurement on axial laminas, to evaluate the feasibility of placing axial laminar screws and to introduce the technique. Relative parameters of 28 sets of fresh Chinese adults'axial specimens, including distance from the superior and inferior entry points of axial laminar screws to the superior margins of axial laminas, superior, middle, inferior thickness and height of the axial laminas, length and angle of the axial laminar screw trajectories, distance from the entry points of axial laminar screws to the transverse foramen and central points of the inferior articular process, were measured with a digital caliper and a goniometer. Data were statistically analyzed. Averagely, distance from the superior and inferior entry points of axial laminar screws to the superior margins of axial laminas was 5 mm and 9 mm, superior, middle, inferior thickness and the height of the axial laminas were 3.2 mm, 6.7 mm, 5.5 mm and 12.8 mm respectively, and the length of the superior and inferior axial laminar screw trajectories was 26.2 mm and 25.5 mm, respectively. It is feasible and reliable to apply posterior laminar screw fixation techniques to the axes of Chinese adults. Also the C2 laminar screw fixation technique can be taken as a supplementary to conventional posterior screw fixations of C2.


A new imperialist competitive algorithm with spiral rising mechanism for solving path optimization problems.
Intelligent optimization algorithms have now become important means for solving global optimization problems. The imperialist competitive algorithm (ICA) is a nature-inspired meta-heuristic algorithm that imitates social behavior. ICA has been widely used in optimization problems, however, ICA tends to fall into a local optimal solution because of its fast convergence speed, which may lead to premature convergence when solving optimization problems. To solve these problems, a new improved ICA algorithm is proposed. Based on the original ICA algorithm, the theory of spiral rising is introduced to enlarge the search space and enhance the global search ability of the algorithm based on ensuring the necessary speed of convergence. In this paper, the improved optimization algorithm is applied to 19 classical benchmark functions, and the improved ICA is applied to the robot path optimization problems to solve the optimal path. The improved ICA algorithm improves the optimization ability and algorithm stability.


Optic Neuropathy in Thyroid Eye Disease: A Case Series.
In patients with thyroid disease, ocular involvement or thyroid ophthalmopathy is common, irrespective of their thyroid status. A common feature of thyroid eye disease is eyelid retraction, which leads to a classical starry gaze (Kocher sign). Treatment with radioactive iodine (RAI) is a known therapy for hyperthyroidism. However, this treatment may lead to or worsen thyroid ophthalmopathy. We report a case series of two patients with thyrotoxicosis, who presented with an atypical and subtle occurrence of thyroid eye disease (TED) soon after RAI therapy. One of the patients was initially diagnosed and treated for dry eyes; however, over a period of time, the patient's vision progressively deteriorated. Clinical and radiological investigations confirmed thyroid ophthalmopathy with low serum thyroid hormone levels. Both patients recovered well after immediate intensive intravenous steroid treatment. These cases highlight the importance of recognizing partial ptosis as one of the presenting signs of active TED among general practitioners and physicians.


The effect and mechanisms of implementation intention in improving prospective memory performance in schizophrenia patients.
People with schizophrenia (SCZ) have been shown to have prospective memory (PM) deficits. PM refers to the ability to remember to perform delayed intentions in the future and plays an important role in everyday independent functioning in SCZ. To date, few studies have investigated methods to improve PM in SCZ. This study aimed to examine whether implementation intention can improve PM performance and to explore its underlying mechanisms. Fifty people with SCZ and 50 demographically matched healthy controls (HC) participated in this study. Participants were randomly assigned to an implementation intention condition or a control instruction condition. Participants were required to make PM responses when PM cue words appeared while they were undertaking an ongoing task with two levels of cognitive load (1-back or 2-back). Results showed that people with SCZ were impaired in PM, and implementation intention improved PM performances for both SCZ and HC. Implementation intention improved PM performance in SCZ in both the low and the high cognitive load conditions without ongoing task cost, suggesting that implementation intention improved PM remembering in an automatic way. These results indicate that implementation intention may be a beneficial technique for improving PM performances in people with SCZ.


Renal ageing.
The function of the kidney, as well as its morphology, changes markedly with age. The glomerular filtration rate falls progressively, independent of overt pathology. Glomerular, vascular and accompanying parenchymal changes occur and other disorders associated with ageing, such as diabetes and hypertension, have a stochastic deleterious effect on both form and function. Declining renal function with age has important implications, not only for individual homeostasis but also for the use of drug therapy and for the receipt and donation of organs for transplantation. Molecular mechanisms and cellular changes underlying some of the functional and structural changes associated with ageing are becoming clearer, as are some of the ways in which genetic background, age and disease can combine to produce functional damage.


Solitary lytic lesion of the skull.
Thyroid carcinoma metastatic to the calvaria may result in a lytic, well-circumscribed lesion the appearance of which necessitates differential consideration of lytic lesions of the skull. The merits of angiography in the study of such lesions are noted. Even in young persons, the possibility of metastasis presenting as a solitary lytic defect in the skull must be kept in mind.


The genetic variants in 3' untranslated region of voltage-gated sodium channel alpha 1 subunit gene affect the mRNA-microRNA interactions and associate with epilepsy.
mRNA expression in a cell or subcellular organelle is precisely regulated for the purpose of gene function regulation. The 3' untranslated region (3'UTR) of mRNA is the binding target of microRNA and RNA binding proteins. Their interactions regulate mRNA level in specific subcellular regions and determine the intensity of gene repression. The mutations in the coding region of voltage-gated sodium channel alpha 1 subunit gene, SCN1A, were identified in epileptic patients and confirmed as causative factors of epilepsy. We investigated if there were genetic variants in 3'UTR of SCN1A, affecting the microRNA-mRNA 3'UTR interaction and SCN1A gene repression, potentially associated with epilepsy. In this case-control study, we identified twelve variants, NM_001202435.1:n.6277A > G, n.6568_6571del, n.6761C > T, n.6874A > T, n.6907 T > C, n.6978A > G, n.7065_7066insG, n.7282 T > C, n.7338_7344del, n.7385 T > A, n.7996C > T, and n.8212C > T in 3'UTR of SCN1A gene. We found that the variant of n.6978A > G in all our samples was completely mutated (G/G). In male group, T allele in n.7282 T > C was associated with epilepsy, while C allele was significantly less frequent in epileptic patients than in normal males (OR 0.424). Consequently, the haplotype "CTTACATGACGA" / "CTCTA" was significantly less frequent in male epileptic patients (0.173) than in normal males (0.305). The frequency of haplotype block found in females, "TTTAACA", "TTCAACA", and "CTTAACA" was 0.499, 0.254 and 0.234 respectively. Within STarMir model analysis, the "CTCTA" haplotype showed significantly higher site accessibility to microRNA targeting and higher downstream sequence accessibility for nonconserved binding than that of other haplotypes. Overall, the male genotypes have the higher accessibility of the downstream 30nt block of nonconserved site than the female genotypes. NM_001202435.1:n.7282 T > C is the genetic variant associated with epilepsy in males, and the related haplotype "CTTACATGACGA" / "CTCTA" in the region of chr2: 165991297-165989081, which has high site accessibility for microRNA binding, is the genetic protective factor against epilepsy in males. In female subset, the frequencies of haplotype block "TTTAACA", "TTCAACA", and "CTTAACA" were 0.499,0.254 and 0.234 respectively. Alleles and haplotypes distribution did not differ in female cases in comparison to female controls.


Continuous flow peptide synthesis on aminopolyoxyethylene-polystyrene graft copolymer using Fmoc-strategy.
An insoluble graft copolymer consisting of the covalently bound polyoxyethylene to cross-linked polystyrene (HO-POE-PS) was prepared by anionic polymerization of ethylene oxide on the resin. The copolymer was then converted to the corresponding amino-polymer (H2N-POE-PS) and the latter was employed as the solid carrier for peptide synthesis. Although HO-POE-PS has successfully been employed as a carrier for peptide synthesis by the standard shaking procedure using t-butoxycarbonyl-amino acids, now we deemed it of interest to test its suitability for the continuous flow synthesis. Thus, the C-terminal octapeptide of the porcine insulin B chain (B23-30) was prepared by this procedure using a photolabile anchoring group and fluoren-9-ylmethoxycarbonyl-amino acids. All the reactions were carried out in a continuous flow manner in a steel column under pressure using a high-performance liquid chromatography (HPLC) system. At the end of the synthesis, a sample of the protected peptide was cleaved from the support by photolysis. For the cleavage of another sample, an aqueous solution of sodium carbonate was employed. The protected peptide was purified on silica gel and Sephadex-LH 20. All the protecting groups of a sample of the octapeptide were removed with piperidine/dimethylformamide and trifluoroacetic acid and the deblocked peptide was purified by ion-exchange chromatography. The free peptide was shown to be homogeneous by thin-layer chromatography, HPLC, and electrophoresis. The identify of the free octapeptide was confirmed by amino-acid analysis, 13C-nuclear magnetic resonance measurement and field-desorption mass spectrometry. The peptide was also shown to be free of racemization.


Oligomerization process of the hemolytic lectin CEL-III purified from a sea cucumber, Cucumaria echinata.
CEL-III is a Ca(2+)-dependent lectin purified from a sea cucumber, Cucumaria echinata. This protein exhibits strong hemolytic activity as well as cytotoxicity toward some cultured cell lines. Hemolysis is caused by CEL-III oligomers formed in the cell membrane after binding to specific carbohydrate chains on the cell surface. We have found that the oligomerization of CEL-III is also induced by the binding of simple carbohydrates, such as lactose, in aqueous solution under high pH and high ionic strength conditions. From gel filtration analysis of the oligomerization of CEL-III, it was found that the formation of the CEL-III oligomer is effectively induced by the binding of lactose and lactulose, disaccharides containing a beta-galactoside structure. Electron micrographs of the resulting oligomers revealed them to exist as particles with a size of approximately 20-30 nm. The oligomerization process required more than 1 h, which is consistent with the increase in surface hydrophobicity as measured using a fluorescent probe, 8-anilinonaphthalene-1-sulfonate. However, a change in the far-UV CD spectra as well as small-angle X-ray scattering occurred within a few minutes, suggesting that a structural change in the protein takes place rapidly, but the following growth of the oligomer is a much slower process.


Cancer acidity: An ultimate frontier of tumor immune escape and a novel target of immunomodulation.
The link between cancer metabolism and immunosuppression, inflammation and immune escape has generated major interest in investigating the effects of low pH on tumor immunity. Indeed, microenvironmental acidity may differentially impact on diverse components of tumor immune surveillance, eventually contributing to immune escape and cancer progression. Although the molecular pathways underlying acidity-related immune dysfunctions are just emerging, initial evidence indicates that antitumor effectors such as T and NK cells tend to lose their function and undergo a state of mostly reversible anergy followed by apoptosis, when exposed to low pH environment. At opposite, immunosuppressive components such as myeloid cells and regulatory T cells are engaged by tumor acidity to sustain tumor growth while blocking antitumor immune responses. Local acidity could also profoundly influence bioactivity and distribution of antibodies, thus potentially interfering with the clinical efficacy of therapeutic antibodies including immune checkpoint inhibitors. Hence tumor acidity is a central regulator of cancer immunity that orchestrates both local and systemic immunosuppression and that may offer a broad panel of therapeutic targets. This review outlines the fundamental pathways of acidity-driven immune dysfunctions and sheds light on the potential strategies that could be envisaged to potentiate immune-mediated tumor control in cancer patients.


Enhanced efficiency of the executive attention network after training in preschool children: immediate changes and effects after two months.
Executive attention is involved in the regulation of thoughts, emotions and responses. This function experiences major development during preschool years and is associated to a neural network involving the anterior cingulate cortex and prefrontal structures. Recently, there have been some attempts to improve attention and other executive functions through training. In the current study, a group of 5 years old children (n=37) were assigned to either a training-group who performed ten sessions of computerized training of attention or a non-trained control group. Assessment of performance in a range of tasks, targeting attention, intelligence and regulation of affect was carried out in three occasions: (1) before, (2) after, and (3) two months after completion of training. Also, brain function was examined with a high-density electroencephalogram system. Results demonstrate that trained children activate the executive attention network faster and more efficiently than untrained children, an effect that was still observed two months after without further training. Also, evidence of transfer of attention training to fluid intelligence and, to a lesser degree, to regulation of affect was observed. Results show that efficiency of the brain system underlying self-regulation can be enhanced by experience during development, providing opportunities for curricular improvement.


Antibiotic resistance pattern of the allochthonous bacteria isolated from commercially available spices.
Spices are often used in dried form, sometimes with significant microbial contamination including pathogenic and food spoilage bacteria. The antibiotic resistance represents an additional risk for food industry, and it is worthy of special attention as spices are important food additives. During our work, we examined the microbiological quality of 50 different spices with cultivation methods on diverse selective media. The identification of the most representative bacteria was carried out using 16S rDNA gene sequence analysis. Antibiotic resistance profiling of twelve identified Bacillus species (B. subtilis subsp. stercoris BCFK, B. licheniformis BCLS, B. siamensis SZBC, B. zhangzhouensis BCTA, B. altitudinis SALKÖ, B. velezensis CVBC, B. cereus SALÖB isolate, B. tequilensis KOPS, B. filamentosus BMBC, B. subtilis subsp. subtilis PRBC2, B. safensis BMPS, and B. mojavensis BCFK2 isolate) was performed using the standard disk-diffusion method against 32 antibiotics. The study showed that the majority resistance was obtained against penicillin G (100%), oxacillin (91.67%), amoxyclav (91.67%), rifampicin (75%), and azithromycin (75%). Our findings suggest that spices harbor multidrug-resistant bacteria.


Dexamethasone increases the capacity of urea synthesis time dependently and reduces the body weight of rats.
Rats of 230 g were treated with 0.1 mg of dexamethasone twice daily for 2 days (n = 5) and 14 days (n = 9). Controls received isotonic saline. During the first week of dexamethasone treatment the rats lost weight rapidly (up to 9 g/day). The weight loss diminished during the second week of treatment. The fasting blood insulin concentration increased sevenfold in the dexamethasone-treated rats. Fasting blood glucagon and glucose concentrations were not different from controls. In the dexamethasone-treated rats the fasting alpha-amino-N concentrations were lower: 4.0 +/- 0.3 mmol/l (mean +/- SEM) versus 6.8 +/- 0.3 mmol/l in controls. The capacity of Urea-N Synthesis, determined during alanine loading was: after 2 days of treatment 14.7 +/- 1.7 mumol/(min 100 g), after 14 days of treatment 7.9 +/- 0.8 mumol/(min 100 g), and in controls 7.5 +/- 1.0 mumol/(min 100 g) (mean +/- SEM). In conclusion, glucocorticoid treatment leads to a transient change in the liver function as to hepatic amino-N conversion, implying that more amino-N than normal is eliminated as urea-N after 2 days of treatment. This may contribute to the early, but not the late body weight loss.


Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review.
Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo, following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms have been proposed for the anti-cancer effects of these omega-3 PUFAs; however, the exact mechanisms still remain unknown. While numerous studies have investigated the effects of DHA and EPA on solid tumors and the responsible mechanisms, there is no consensus regarding the effects and mechanisms of action of these two FAs in hematological malignancies. Here, we performed a systematic review of the beneficial effects of EPA and DHA on hematological cell lines as well as the findings of related in vivo studies and clinical trials. We summarize the key underlying mechanisms and the therapeutic potential of these PUFAs in the treatment of hematological cancers. Differential expression of apoptosis-regulating genes and Glutathione peroxidase 4 (Gp-x4), varying abilities of different cancerous and healthy cells to metabolize EPA into its more active metabolites and to uptake PUFAS are among the major factors that determine the sensitivity of cells to DHA and EPA. Considering the abundance of data on the safety of these FAs and their proven anti-cancer effects in hematological cell lines and the lack of related human studies, further research is warranted to find ways of exploiting the anticancer effects of DHA and EPA in clinical settings both in isolation and in combination with other therapeutic regimens.


Use of data mining to reveal body mass index (BMI): patterns among Pennsylvania schoolchildren, pre-k to grade 12.
Health eTools for Schools was developed to assist school nurses with routine entries, including height and weight, on student health records, thus providing a readily accessible data base. Data-mining techniques were applied to this database to determine if clinically significant results could be generated. Body mass index (BMI) data collected and entered in eTools by school nurses from 657,068 students attending 1156 schools in 49 of 67 Pennsylvania counties during 2005-2009 were analyzed. Students in each BMI category were sorted; regression was used to model mean and percentage trends. A chi-square test of individually matched BMI percentages was computed and migration across normal, overweight, and obese states determined. The highest percentage of obese students occured in middle school. The mean trends for obesity and overweight had increasing slopes of 0.189 and 0.227, respectively; with regression slope for overweight >59%. Within groups, substantial percentages of individually matched BMIs changed significantly (p < .0001) over 2 years, migrating between normal weight, overweight, and obese. A comparison of 2009 measured BMI for grades 9-12 from eTools with 2009 Pennsylvania Youth Risk Behavior Survey self-reported BMI yielded substantial diferences. A pattern of increasing BMI for elementary students with a corresponding decrease among middle and high school students emerged. The means trends for both overweight and obesity were greater in 2009 than in 2005, increasing steadily to 2008 and slightly declining to 2009. The dominant overall pattern flows from overweight to obese. If continued unabated, percentage of students who are obese will dominate over time.


Global warming contributions from alternative approaches to waste management in the Norwegian Armed Forces.
Greenhouse gas (GHG) emissions emanating from waste management practices in five Norwegian military camps were assessed. The GHG emission accounting practices examined included fuel provision upstream of a material recovery facility (MRF), operational activities at the MRF, and downstream processes. The latter means recycling of waste compared to primary production using virgin materials, or the incineration of waste with energy recovery compared to heating based on the average energy mix for both EU and Norway. The results show that the operational activities at the MRF cause more GHG emissions than the provision of fuel upstream of the MRF (116 vs. 16-21 tonnes CO2-eq., respectively). Furthermore, the downstream activities provided far greater avoidance of GHG emissions than the load caused by upstream activities and the activities at the MRF. Recycling proves to be beneficial over incineration of waste when compared to the EU energy mix (savings of--257 tonnes CO2-eq.), and the advantage is even larger when compared to the average energy mix for Norway (savings of--779 tonnes CO2-eq.). In conclusion, the results show that sorting of mixed waste at military camp collection sites followed by recycling of the separated fractions at MRF would result in significant avoidance of GHG emissions, compared to the current practice of incineration with energy recovery of the mixed waste.


[Meningococcal vulvovaginitis in a prepubertal girl].
Neisseria meningitidis is an uncommon cause of vulvovaginitis in the prepubertal girl. The microorganism must not be mistaken for Neisseria gonorrhoeae, as the consequences of such an error may be serious. Colonization or infection by Neisseria meningitis is not uncommon in adolescents and adults. Vulvitis, even when it is recurrent, is not per se a good indicator of sexual abuse, but some microorganisms found by vaginal swab can make it possible, likely or certain. Sexual transmission of N. meningitidis has not been described in the prepubertal child.


Skeletal metastasis: treatments, mouse models, and the Wnt signaling.
Skeletal metastases result in significant morbidity and mortality. This is particularly true of cancers with a strong predilection for the bone, such as breast, prostate, and lung cancers. There is currently no reliable cure for skeletal metastasis, and palliative therapy options are limited. The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target. Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments. In this review, we discuss pathologic process of bone metastasis, the roles of the Wnt signaling, and the available experimental models and treatments.


A visual portable microfluidic experimental device with multiple electric field regulation functions.
High portability and miniaturization are two of the most important objectives pursued by microfluidic methods. However, there remain many challenges for the design of portable and visual microfluidic devices (e.g., electrokinetic experiments) due to the use of a microscope and power supply. To this end, we report a visual portable microfluidic experimental device (PMED) with multiple electric field regulation functions, which can realize the electric field regulation functions of various basic microfluidic experiments through modular design. The internal reaction process of the microfluidic chip is displayed by a smartphone, and the experimental results are analyzed using a mobile phone application (APP). Taking the induced-charge electroosmosis (ICEO) particle focusing phenomenon as an example, we carried out detailed experiments on PMED and obtained conclusions consistent with numerical simulations. In addition to ICEO experiments, other functions such as alternating electroosmosis (ACEO), thermal buoyancy convection, and dielectrophoresis (DEP) can be realized by replacing module-specific covers. The device expands the application of microfluidic experiments and provides a certain reference for the further integration and portability of subsequent microfluidic experiment devices.


Levels and health risk assessments of particulate matters (PM2.5 and PM10) in indoor/outdoor air of waterpipe cafés in Tehran, Iran.
To determine the concentration of particulate matters (PM2.5 and PM10), 36 samples were collected from indoor/outdoor air of hookah cafés (HS), cigarette cafés (CS), both hookah and cigarette (HCS), and no-smoking building (NS) in Tehran City from December 2017 to March 2018. The mean ± SD of PM10 concentration in the indoor air of the cafés in terms of HS, CS, HCS, and NS sites has been 702.35, 220.20, 1156.60, and 60.12 μg/m3, while for PM2.5, the values have been 271.92, 111.80, 619.10, and 22.25 μg/m3, respectively. It was also found that the PM concentration inside the cafés was higher during weekend session (with a higher number of active smokers), than during the weekday sessions. Moreover, the PM levels in the indoor air of the cafés were considerably higher than those of the outdoors (p < 0.05). Based on path analysis, the number of "active smokers" had the highest influence on production of PM inside the cafés, followed by the tobacco type. Finally, the mean excess lifetime cancer risk (ELCR) for PM2.5 in the indoor air of cafés was observed in the range of 0.64 × 10-5-14.98 × 10-5. Also, the mean of hazard quotient (HQ) for PM2.5 and PM10 was calculated in range of 0.82-18.4 and 0.16-3.28, respectively, which corresponds to an unacceptably high risk for human health. The PM levels in the indoor air of smoking cafés in Tehran are significantly high, such that it can cause serious risks for the health of both the customers and personnel. Thus, it is necessary that suitable controlling strategies be adopted for this public health threat.


scGAMNN: Graph Antoencoder-Based Single-Cell RNA Sequencing Data Integration Algorithm Using Mutual Nearest Neighbors.
It is critical to correctly assemble high-dimensional single-cell RNA sequencing (scRNA-seq) datasets and downscale them for downstream analysis. However, given the complex relationships between cells, it remains a challenge to simultaneously eliminate batch effects between datasets and maintain the topology between cells within each dataset. Here, we propose scGAMNN, a deep learning model based on graph autoencoder, to simultaneously achieve batch correction and topology-preserving dimensionality reduction. The low-dimensional integrated data obtained by scGAMNN can be used for visualization, clustering and trajectory inference.By comparing it with the other five methods, multiple tasks show that scGAMNN consistently has comparable data integration performance in clustering and trajectory conservation.


Surgeon's Experience May Circumvent Operative Volume in Improving Early Outcomes After Pancreaticoduodenectomy.
Introduction Pancreaticoduodenectomy (PD) is a complex procedure with a significant proportion of postoperative complications and improving but notable mortality. PD was the prototype procedure that initiated the lingering debate about the relationship of better operative outcomes when performed at higher-volume centers. This has not translated into practice. Impediments include the absence of a universally accepted definition of a high-volume center among others. Contrary evidence suggests equivalent outcomes for PD at low-volume centers when performed by experienced hepatobiliary surgeons. We reviewed our perioperative outcomes for PD from an earlier period as a low-volume center with an experienced team. Methods A longitudinal study of all PDs completed in our department between 2012 and 2017 was performed. Results A total of 28 PD were performed during this period. Pylorus-preserving PD was performed in 23 patients and classical PD in the remaining. A separate Roux-en-Y loop was used for high-risk pancreatic anastomosis in six cases. The mean patient age was 49.3±12.4 years. The male-to-female ratio was 1.3:1. Preoperative drainage procedures were carried out in 19 patients. The mean serum total bilirubin level was 3.98(±4.5) mg/dL. There was no 90-day mortality. Postoperative complications included wound infection in 10 (36.7%) and respiratory complications in 10 (36.7%) patients. Postoperative bleeding requiring intervention occurred in one patient, and two patients had an anastomotic leak (one pancreatojejunostomy (PJ) and one gastrojejunostomy (GJ)). Delayed gastric emptying (DGE) was noted in three (10.7%) patients. The mean length of hospital stay was 14±7 days. The median overall survival (OS) was 84 months. Conclusion Comparable early outcomes can be achieved at low-volume centers for patients undergoing PD with an experienced team, optimal patient selection, and the ability to rescue for complications.


Effects of radiation on wound healing.
The pathological changes of radiation on wound healing in rats were observed by macroscopic, microscopic, and electronmicroscopic examination and detection of collagen types. We found that the wound healing process was obviously delayed by irradiation. First, the early phase inflammatory response was severely inhibited. In particular, the number of infiltrating macrophages and neutrophils was decreased, blood vessels were injured, and hemorrhage was evident. Second, the formation and maturation of granulation tissue were slowed down, fibroblasts were injured, and transcription of types and collagen mRNAs and synthesis and secretion of collagen were reduced. Finally, the reepithelialization process was delayed and the healing time was prolonged.


Protection of mice against fission neutron irradiation by WR-2721 or WR-151327.
Two phosphorothioate compounds, WR-2721 and WR-151327, were examined for their radioprotective efficacies against the effects of fission neutron irradiation in male and female mice. Within sex groups no significant difference in lethality at 30 or 100 days postirradiation was found between WR-2721 or WR-151327 pretreatment. The dose modification factors (DMFs) for male mice treated with either compound were 1.29 (LD50/30) and 1.24 (LD50/100), and those for drug-treated female mice were 1.21 (LD50/30) and 1.19 (LD50/100). Both WR-2721 and WR-151327 were found to be equally radioprotective when compared using DMFs as the end point. WR-151327 (500 mg/kg, ip) was found to be significantly more toxic to both male and female B6D2F1 mice than equimolar amounts of WR-2721. Small but significant sex differences in radioprotection were found: the DMFs for female mice pretreated with either compound were lower than those for similarly treated male mice; the incidence of mortality 31-100 days postexposure in male mice pretreated with WR-151327 was greater than for female mice. In addition, sex differences were noted in drug toxicity. Toxic death in female mice given WR-151327 (500 mg/kg, ip) is 2.6 times more probable than in males.


Enzymatic kinetics regarding reversible metabolism of CS-0777, a sphingosine 1-phosphate receptor modulator, via phosphorylation and dephosphorylation in humans.
1. CS-0777, a candidate compound for autoimmune diseases, becomes phosphorylated active metabolite, M1, by fructosamine 3-kinase (FN3K), FN3K-related protein (FN3K-RP); and M1 is reverted back to CS-0777 by alkaline phosphatase (ALP) in the body. We performed enzyme kinetic analysis of phosphorylation of CS-0777 by FN3K, FN3K-RP, human erythrocytes and human platelets; and dephosphorylation of M1 by various ALP isozymes and human liver, kidney, lung and small intestine microsomes. 2. The Michaelis constants of human FN3K, FN3K-RP and erythrocytes for CS-0777 phosphorylation were in the range from 498 μM to 1060 μM. FN3K inhibitor, 1-deoxy-1-morpholinofructose, suppressed only about 20% of CS-0777 phosphorylation activity in human erythrocyte lysate. Immunodepletion of FN3K and FN3K-RP decreased M1 formation activity by about 25% and 50%, respectively, in human erythrocyte lysate. 3. The Michaelis constants of four human ALPs and microsomes were in the range from 10.9 μM to 32.1 μM. The ALP inhibitor, levamisole, suppressed over 50% of M1 dephosphorylation activity in liver, kidney and lung microsomes. 4. FN3K-RP is expected to take a prominent role in the phosphorylation of CS-0777 in human erythrocytes; dephosphorylation of M1 was observed in all ALPs and human tissue microsomes examined, with a similar affinity towards M1 among them.


High-activity carbonic anhydrase isoenzyme (CA II) in human gallbladder epithelium.
Acidification of bile is one of the factors that prevents calcium precipitation and thereby gallstone formation. Carbonic anhydrase II (CA II) has previously been shown to be one of the key factors in the human alimentary tract that regulates the acid-base balance. We demonstrated CA II expression in the human gallbladder epithelium using immunohistochemical techniques, elucidated the CA II content of the epithelium by digital image analysis of the immunohistochemically stained enzyme in samples from 16 patients undergoing cholecystectomy, and correlated the results with the calcium content of the gallstones. Nine patients had symptomatic gallstone disease and seven an acalculous, histologically normal gallbladder. The patients were classified into two groups on the basis of the calcium content of their gallstones: no gallstones or gallstones containing no calcium (Group 1) and gallstones with 2-87% calcium by weight (Group 2). The immunohistochemical techniques showed distinct epithelial CA II-positive staining in most of the gallbladder samples, but digital image analysis revealed distinct variations in staining intensity among them. The median staining intensity index was significantly higher in Group 1 (0.4463) than in Group 2 (0.2376; p = 0.0262). The results suggest that CA II is abundantly expressed in the normal gallbladder epithelium and that decreased expression may be associated with the formation of calcified gallstones. These findings are relevant to the pathogenesis of gallstone disease.


Unmasking MASC: bringing to light the unique morphologic, immunohistochemical and genetic features of the newly recognized mammary analogue secretory carcinoma of salivary glands.
Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland neoplasm that is characterized by its striking morphologic and molecular similarities to secretory carcinoma of the breast. This review highlights the characteristic clinical, histologic, immunophenotypic, and molecular features of MASC, and draws attention to the differential diagnosis of this increasingly recognized tumor.


Pharyngeal peristaltic pressure variability, operational range, and functional reserve.
The present understanding of pharyngeal motor function remains incomplete. Among the remaining gaps of knowledge in this regard is the magnitude of variability of pharyngeal peristaltic pressure amplitude. Although variability can pose difficulty in interpretation of manometric findings, its magnitude can inform the operational range and reserve of the pharyngeal contractile function. We aimed to define the intra- and intersubject and intersession variability of select pharyngeal manometric parameters and, using this information, determine the number of swallow repetitions for acquiring reliable pharyngeal manometric data. We recorded pharyngeal peristalsis in 10 healthy subjects (age: 50 ± 25 yr, 5 women) by high-resolution manometry during two separate sessions of 20 sequences of 0.5-ml water swallows. Two-way ANOVA showed significant variation in the mean peak peristaltic pressure value across sites (P < 0.0001) as well as within the data at each site (P < 0.0001). Similarly, the pharyngeal contractile integral exhibited significant inter- (P = 0.003) and intrasubject (P < 0.001) variability. The Shapiro-Wilk normality test showed mixed results, in that some sites showed normally distributed data, whereas others did not. A robust Monte Carlo simulation showed that the nominal sample size was different for various tested metrics. For a power of 0.8, commonly accepted as an adequate threshold for acceptable statistical power, the optimal sample size for various peristaltic parameters ranged between 3 and 15. There is significant intra- and intersubject variability in site-specific and integrated parameters of pharyngeal peristalsis. The observed variance indicates a significant operational range and reserve in pharyngeal contractile function while necessitating parameter-specific sample size for reliable results.NEW & NOTEWORTHY Intra- and intersubject variability are significant and different at various sites within the contractile pharynx. In addition, significant swallow-to-swallow and subject-to-subject variability exists in pharyngeal contractile integral. The range of intrasubject variability indicates the existence of broad operational range and reserve. Lastly, our variability studies informed Monte Carlo and power analyses, yielding estimates of sample size that would ensure accurate representation of pressure metric variability.


[Identification of asthenozoospermia-associated proteins in human seminal plasma by shotgun proteomic strategy].
To identify asthenozoospermia-associated proteins in seminal plasma by the shotgun proteomic strategy. Six seminal plasma samples were collected by Percoll respectively from healthy fertile and asthenozoospermia volunteers, balanced, mixed, and then the mixture was separated by SDS-PAGE. The proteins in the gel were enzymolyzed, extracted and identified by the shotgun proteomic strategy. The identified proteins with the unique peptide count > or =2 or the unique peptide count=1 but the total count > or =4 were compared between the two groups. A total of 172 differential proteins were identified, of which, 89 were exclusively from the asthenozoospermia and 83 exclusively from the healthy fertile men. According to the molecular function, these differential proteins were mainly the types of signal transduction and catalytic activity. Functionally, 10 of the proteins are particularly important, which include annexin VI isoform 2, isoform 1 of interleukin-6 receptor subunit beta precursor, Mr 400,000 protein, cytosolic dynein heavy chain, alpha-actinin-4, receptor-type tyrosine-protein phosphatase eta precursor, vitamin D-binding protein precursor, protein S100-A11, protein S100-A9 and ANXA4.


Craniofacial serial dimensions related to age, sex, and cleft-type from six months of age to two years.
The first two postnatal years are a time of rapid craniofacial growth. We selected 30 cleft lip/palate children, each seen at 6, 12, 18, 24 months, at which time lateral X-ray headfilms were taken. There were five boys, five girls, in each of three cleft-types: cleft palate only (CP), unilateral cleft lip/palate (UCLP), and bilateral cleft lip/palate (BCLP). Three dimensions were selected: 1) anterior cranial base (S-N); 2) upper face height (N-Pt.A); 3) maxillary depth (Pt.A-Ptm). All were in the midsagittal plane. This is a repeated measures study on the factor patient age, so that for each combination of sex and cleft-type the same subject was measured at the four levels of patient age. The multiple comparison technique utilized was the Newman-Keuls Procedure. There is no significant joint effect in the 6-24 months period. The factors seem to operate singly. There is no main effect due to the factor sex. Dimensions N-Pt.A. and Pt.A-Ptm show a significant main effect due to the factor cleft-type. There is a highly significant main effect due to the patient age factor.


Preventive wrapping of the fragile tracheobronchial wall using a flap of latissimus dorsi muscle during esophagectomy after chemoradiotherapy.
Thanks to significant recent progress in the application of chemoradiotherapy (CRT) in the treatment of esophageal cancer, the numbers of operations on patients who have undergone preoperative CRT are increasing. In these patients, preoperative CRT often leads to formation of an unstable, scleroid layer comprised of what appears to be scar tissue around the tracheobronchial wall. This scleroid layer must be removed with the tumor, thereby weakening the wall. We performed preventive intrathoracic transposition of a pedicled latissimus dorsi muscle flap on 6 patients with clinically T4 esophageal cancer (6 males; age: 63-75 years). All 6 patients had undergone preoperative CRT (median, 43.0 Gy; range, 32.0-60.0 Gy; with cisplatin + 5-fluorouracil infusion) to relieve direct invasion of the airway. In 6 patients, preventive use of a pedicled latissimus dorsi muscle flap resulted in uneventful recovery from the tracheobronchial wall weakness. Anastomotic leakage, recurrent nerve paralysis and pneumonia occurred in 2 patients each (33.3%); there were no life-threatening complications or operation-related deaths, however. When performing an esophagectomy for thoracic esophageal squamous-cell cancer in patients who have received preoperative CRT, the weakened tracheobronchial wall can potentially be reinforced using a pedicled latissimus dorsi muscle flap.


Safety Profile of High-Dose Intravenous Push Lacosamide.
Lacosamide (LCM) is an antiseizure medication used to manage status epilepticus (SE). Previous retrospective analyses have demonstrated safety and efficiency in intravenous push (IVP) administration at 80 mg per minute. Quick administration can be achieved in a high-acuity setting without the additional time required for compounding. However, previous literature only partially represents high doses of IVP LCM, which limits the understanding of the safety profile of these doses. Our study was a single-center, retrospective, single-arm analysis of patients who received IVP LCM 300 mg or 400 mg during admission. The primary outcome was the incidence of infusion site reactions, hypotension, and bradycardia within 2 hours of IVP administration. Secondary outcomes included the incidence of PR prolongation. A total of 113 patients were evaluated for infusion site reactions. Of these, 108 patients had vital signs assessed within 2 hours of IVP LCM and could be evaluated for hypotension and bradycardia. The sample primarily consisted of LCM 400 mg IVP (85.8%). The primary outcome consisted of 7 (6.2%) infusion reactions, 12 (11.1%) hypotensive events, and no reports of bradycardia. Each adverse event was assessed using the Naranjo Adverse Drug Probability Scale. All events scored less than two, suggesting the possibility was likely related to factors other than the medication. In conclusion, LCM 300 mg and 400 mg IVP administration have the potential to facilitate more rapid treatment of seizures without additional risk of infusion site reactions, hypotension, and bradycardia.


Low plasma arginine:asymmetric dimethyl arginine ratios predict mortality after intracranial aneurysm rupture.
Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, predicts mortality in cardiovascular disease and has been linked to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In this prospective study, we assessed whether circulating ADMA, arginine:ADMA ratio, and nitrite/nitrate levels were associated with survival and cerebral vasospasm in SAH patients. One hundred and eleven patients were observed day 1 to 15 after SAH, with serial measurements of transcranial Doppler flow velocities (VMCA) and plasma biomarkers. Clinical status was assessed by the World Federation of Neurosurgical Societies grading scale. Overall 30-day mortality was 18%, but differed between patients grouped by low, midrange, and high arginine:ADMA ratio in the first week after SAH. Mortality rates were 14/37, 1/37, and 5/37 in the 3 groups, respectively (P-logrank=0.0003). Cox regression showed that low versus midrange or high arginine:ADMA was associated with a hazard ratio of 4.1 independent of World Federation of Neurosurgical Societies grade (95% confidence interval, 1.5-10.9; P=0.006). ADMA or arginine:ADMA had no association to VMCA, but there was an inverse relationship between VMCA and nitrite/nitrate levels (P<0.0001). The NOS3 894G/G genotype was associated with 15% lower VMCA (P=0.01). ATbG-NOS3 haplotype homozygosity was associated with up to 64% higher nitrite/nitrate levels (P=0.003). This study suggests that plasma arginine:ADMA ratios predict mortality after SAH. Both clinical and physiological measures of changes in cerebral hemodynamics are coupled to the nitric oxide system.


Global hypomethylation of genomic DNA in cancer-associated myofibroblasts.
Global hypomethylation has long been recognized as a feature of the malignant epithelial component in human carcinomas. Here we show evidence for this same type of epigenetic alteration in cancer-associated stromal myofibroblasts. We used methylation-sensitive SNP array analysis (MSNP) to profile DNA methylation in early-passage cultures of stromal myofibroblasts isolated from human gastric cancers. The MSNP data indicated widespread hypomethylation in these cells, with rare focal gains of methylation, conclusions that were independently validated by bisulfite sequencing and by a methylation-sensitive cytosine incorporation assay. Immunohistochemistry with anti-5-methylcytosine (anti-5-methyl-C) in a series of gastrectomy specimens showed frequent loss of methylation in nuclei of both the malignant epithelial cells and alpha-smooth muscle actin (ASMA)-positive stromal myofibroblasts of both intestinal-type and diffuse carcinomas. We confirmed this phenomenon and established its onset at the stage of noninvasive dysplastic lesions by immunohistochemistry for anti-5-methyl-C in a transgenic mouse model of multistage gastric carcinogenesis. These findings indicate similar general classes of epigenetic alterations in carcinoma cells and their accompanying reactive stromal cells and add to accumulating evidence for biological differences between normal and cancer-associated myofibroblasts.


[Diagnosis and management of vascular malformations : Interdisciplinary teamwork in demand].
Vascular anomalies are very rare, but can occur in children and adults in almost every region of the body. Due to the complexity of this disease, the path to a definitive diagnosis is often difficult. It requires interdisciplinary teamwork with close exchange of information between the individual treatment partners to reach the correct diagnosis and then to start the best therapy. This article provides an overview of the main types of vascular malformations from a clinical, imaging, and histological point of view, following the current classification of the International Society for the Study of Vascular Anomalies (ISSVA).


[Discovery of alpha-Klotho and FGF23 unveiled new insight into calcium and phosphate homeostasis].
Recent advances that have given rise to marked progress in clarifying actions of alpha-Klotho (alpha-Kl) and FGf23 can be summarized as follows ; (i) alpha-Kl binds to Na(+), K(+)-ATPase, and Na(+), K(+)-ATPase is recruited to the plasma membrane by a novelalpha-Kl dependent pathway in correlation with cleavage and secretion ofalpha-Kl in response to extracellular Ca(2+) fluctuation. (ii) The increased Na(+) gradient created by Na(+), K(+)-ATPase activity drives the transepithelial transport of Ca(2+) in the choroid plexus and the kidney, this is defective in alpha-kl(-/-) mice. (iii) The regulated PTH secretion in the parathyroid glands is triggered via recruitment of Na(+), K(+)-ATPase to the cell surface in response to extracellular Ca(2+) concentrations. (iv) alpha-Kl, in combination with FGF23, regulates the production of 1,25 (OH) (2)D in the kidney. In this pathway, alpha-Kl binds to FGF23, andalpha-Kl converts the canonical FGF receptor 1c to a specific receptor for FGF23, enabling the high affinity binding of FGF23 to the cell surface of the distal convoluted tubule where alpha-Kl is expressed. (v) FGF23 signal down-regulates serum phosphate levels, due to decreased NaPi-IIa abundance in the apical membrane of the kidney proximal tubule cells. (vi) alpha-Kl in urine increases TRPV5 channel abundance at the luminal cell surface by hydrolyzing the N-linked extracellular sugar residues of TRPV5, resulting in increased Ca(2+) influx from the lumen. These findings revealed a comprehensive regulatory scheme of mineral homeostasis that is illustrated by the mutually regulated positive/negative feedback actions of alpha-Kl, FGF23, PTH and 1,25 (OH) (2)D. In this regard, alpha-Kl and FGF23 might play pivotal roles in mineral metabolism as regulators that integrate calcium and phosphate homeostasis, although this concept requires further verification in the light of related findings. Here, the unveiling of the molecular functions of alpha-Klotho and FGF23 has recently given new insight into the field of calcium and phosphate homeostasis. Unveiled molecular functions of alpha-Kl and FGF23 provided answers for several important questions regarding the mechanisms of calcium and phosphate homeostasis that remained to be solved, such as : (i) what is the non-hormonal regulatory system that directly responds to the fluctuation of extracellular Ca(2+), (ii) how is Na(+), K(+)-ATPase activity enhanced in response to low calcium stimuli in the parathyroid glands, (iii) what is the exact role of FGF23 in calcium and phosphorus metabolism, (iv) how is Ca(2+) influx through TRPV5 controlled in the DCT nephron, and finally (v) how is calcium homeostasis regulated in cerebrospinal fluid. However, several critical questions still remain to be solved. So far reported,alpha-Kl binds to Na(+), K(+)-ATPase, FGF receptors and FGF23, and alpha-Kl hydrolyzes the sugar moieties of TRPV5. Does alpha-Kl recognize these proteins directly or indirectly?Is there any common mechanism?How can we reconcile such diverse functions of alpha-Kl?What is the Ca(2+) sensor machinery and how can we isolate it?How do hypervitaminosis D and the subsequently altered mineral-ion balance lead to the multiple phenotypes?What is the phosphate sensor machinery and how can we isolate it? How does the Fgf23/alpha-Kl system regulate phosphorus homeostasis?How are serum concentrations of Ca(2 + ) and phosphate mutually regulated?


Efficacy of prolonged intermittent therapy with combined 5-fluorouracil and methyl-CCNU following resection for carcinoma of the large bowel. A Veterans Administration Surgical Oncology Group report.
This prospective evaluation of 5-FU and methyl-CCNU administered in combination to patients with curative surgery for histologically proved colorectal adenocarcinoma is based upon 645 patients randomized between August 1973 and July 1979. Beyond the requirement that the resection be clinically and microscopically complete, patients were not stratified prior to random treatment assignment to surgery alone or surgery followed by adjuvant chemotherapy. Drug therapy consisted of discrete 5-day courses administered at 7-week intervals, start to start. Toxic reactions were reported in association with 40% of courses. In 10% of patients with hematologic toxicity, the reactions were sufficiently severe to require the suspension or discontinuation of treatment. Treated patients experienced a slightly more favorable survival than did controls. However, the advantage was seen only in the 216 patients (34% of total) with one to four positive lymph nodes in the resected specimen. Similar proportions of treated and control deaths were attributed to residual or recurrent disease.


Comparison of two school-based programmes for health behaviour change: the Belo Horizonte Heart Study randomized trial.
To assess the efficacy of two school-based programmes to promote students' willingness to engage in lifestyle changes related to eating habits and physical activity behaviours. Elementary school-based health promotion intervention, designed as a multicomponent experimental study, based on a behavioural epidemiological model. Nine intervention and eight comparative public and private elementary schools. The goal was to determine the impact on the longitudinally assessed outcomes of two programmes that addressed healthy nutrition and active living in a cohort of 2038 children. The evaluations used pre-intervention and follow-up student surveys that were based on the Transtheoretical Model of the stages of behaviour change. In the intervention group, there were significant (P < 0·001) differences between the pre- and post-intervention times in the stages of change, with a reduction in the percentage of children at the pre-contemplation and contemplation stages and increased percentages at the preparation, action and maintenance stages, leading to healthier behaviours in fatty food consumption, fruit and vegetable consumption, physical activity and time spent in sedentary activities. The determinants of the behaviour stage were the intervention programme, the type of school and the presence of motivated teachers. The comparison group did not show significant differences between the pre- and post-intervention times for any of the stages of behaviour. The intervention programme encouraged the students to make healthy lifestyle choices related to eating habits and physical activity behaviours.


Symmetry diagnosis and treatment in coordination dynamics therapy.
Forward-backward movement symmetry of the human CNS was investigated through pattern change during exercising on a special coordination dynamics therapy and recording device in the forward and backward direction. A mirror-image symmetry shift was found in a patient with cerebellar injury for the attractor patterns (movement patterns with the highest temporal stability) for exercising on the special coordination dynamics therapy device in forward and backward direction, with respect to pace and trot gait coordinations. Symmetry diagnosis and symmetry treatment are of importance in CNS repair because of the learning transfer to the movement symmetry counterpart: training of backward walking improves forward walking The theoretical and practical basis of Schalow Coordination Dynamics Therapy is given in the Method section including symmetry considerations with respect to CNS self-organization.


Ultrasmall Pb:Ag2 S Quantum Dots with Uniform Particle Size and Bright Tunable Fluorescence in the NIR-II Window.
Ag2 S quantum dots (QDs) are well-known near-infrared fluorophores and have attracted great interest in biomedical labeling and imaging in the past years. However, their photoluminescence efficiency is hard to compete with Cd-, Pb-based QDs. The high Ag+ mobility in Ag2 S crystal, which causes plenty of cation deficiency and crystal defects, may be responsible mainly for the low photoluminescence quantum yield (PLQY) of Ag2 S QDs. Herein, a cation-doping strategy is presented via introducing a certain dosage of transition metal Pb2+ ions into Ag2 S nanocrystals to mitigate this intrinsic shortcoming. The Pb-doped Ag2 S QDs (designated as Pb:Ag2 S QDs) present a renovated crystal structure and significantly enhanced optical performance. Moreover, by simply adjusting the levels of Pb doping in the doped nanocrystals, Pb:Ag2 S QDs with bright emission (PLQY up to 30.2%) from 975 to 1242 nm can be prepared without altering the ultrasmall particle size (≈2.7-2.8 nm). Evidently, this cation-doping strategy facilitates both the renovation of crystal structure of Ag2 S QDs and modulation of their optical properties.


Ab initio molecular orbitals study of the conformational preference in alpha-cyano-alpha-fluorophenylacetic acid ester.
The origin of conformational preference in alpha-cyano-alpha-fluorophenylacetic acid (CFPA) methyl ester that is a model system of alpha-cyano-alpha-fluoro-p-tolylacetic acid (CFTA) esters was theoretically investigated by means of DFT and MP2 calculations. Two stable conformations having the C-F bond syn and anti to the C=O bond, respectively, were obtained for CFPA methyl ester. A small energy difference (0.9 kcal mol-1 at the MP2(fc)/6-31++G(d,p)) was found between the two conformations. From the molecular orbital analysis based on the Natural Bond Orbital analysis and supported by calculations using the Orbital Deletion Procedure technique, we found that sigma-(sigma*+pi*)(C=O) and sigma-sigma*(Ph) and pi(Ph)-sigma* hyperconjugations are the main factors responsible for the conformational preference. The role of the fluorine atom on the stereogenic center was also clarified.


Nursing care management for children hospitalized with chronic conditions.
to understand the interactions of nurses managing nursing care for the hospitalized child with a chronic condition. Theoretical and methodological references were used, Complex Thought and grounded theory, respectively. In the study 18 subjects have participated arranged in three groups: nurses, nursing technicians and family members. A semi-structured interview was used as technique for data collection. The data analysis followed three stages of coding: open, axial and selective. the category "Needing to manage nursing care to the hospitalized child with chronic condition in Pediatric Inpatient Unit" and their subcategories show the complex inter subjective bindings established by nurses that support the practice of nursing care management. There are difficulties for nursing professionals to interact with the child's family and the dialogical order/disorder/interaction/organization in the implementation of the management process of care is.


Effect of silicon content on the sintering and biological behaviour of Ca10(PO4)(6-x)(SiO4)x(OH)(2-x) ceramics.
Silicated hydroxyapatite powders (Ca10(PO4)(6-x)(SiO4)x(OH)(2-x); Si(x)HA) were synthesized using a wet precipitation method. The sintering of Si(x)HA ceramics with 0 < or = x < or = 1 was investigated. For 0 < or = x < or = 0.5, the sintering rate and grain growth decreased slightly with the amount of silicate. For larger amounts, the sintering behaviour differed with the formation of secondary phases before total densification. Sintering parameters (temperature and time) were adjusted to each composition to produce dense materials having similar microstructure without formation of these secondary phases. Dense ceramics made of pure hydroxyapatite and Si(x)HA containing various amounts of silicate (up to x = 0.6) were biologically tested in vitro with human osteoblast-like cells. The proliferation of cells on the surface of the ceramics increased up to 5 days of culture, indicating that the materials were biocompatible. However, the silicon content did not influence the cell proliferation.


The roles of macrophages and nitric oxide in interleukin-3-enhanced HSV-Sr39tk-mediated prodrug therapy.
The herpes simplex virus thymidine kinase/ganciclovir (HSV-sr39tk/GCV) system is a well-established prodrug system used in cancer gene therapy. However, this system is currently not effective enough to eradicate malignant tumors completely. This study aimed to evaluate whether co-expression of interleukin-3 (IL-3) could enhance the anti-tumor activity of HSV-sr39tk/GCV prodrug gene therapy using a murine TRAMP-C1 prostate tumor model. In vitro results demonstrated that HSV-sr39tk-transfected cells exhibited enhanced sensitivity to the GCV prodrug, which was not affected by co-expression of the mIL-3 gene. However, in vivo studies showed that co-expression of the mIL-3 gene significantly increased the HSV-sr39tk/GCV-induced tumor growth delay and even cured the tumor. The TRAMP-C1-specific immune response of spleen lymphocytes from mice bearing HSV-sr39tk- and IL-3-expressing TRAMP-C1 tumors was measured by ELISA. Results showed that IL-3-activated IL-4-dominant lymphocytes became IFN-γ- dominant lymphocytes after combined HSV-sr39tk/GCV therapy. The efficacy of combined therapies on tumor regression was reduced when macrophages populations were depleted by carrageenan or NO production was inhibited by administration of the iNOS inhibitor, L-NAME. These results suggest that utilizing a bicistronic vector to express HSV-sr39tk and the IL-3 gene induced an enhanced macrophage- or NO-dependent anti-tumor effect.


Knotted double j ureteral stent: a case report and literature review.
Many complications due to double j (DJ) stent placement have been reported. DJ stent knotting is a rare complication, with only a few cases reported in the literature. We presented a case of DJ stent knotting and reviewed the literature regarding this complication. We reported a 20-year-old man with a history of cystinuria and ureteral stone managed with retrograde ureteroscopy and holmium laser three months ago. The patient comes for DJ stent removal. Firstly, we tried to remove the DJ stent via the cystoscopic procedure, which failed. A fluoroscopic image revealed a knotted DJ stent lodged at the ureteropelvic junction and was removed via holmium laser ureteroscopic procedure without complications. In conclusion, when cystoscopic procedure with simple traction fails to remove DJ stents, multimodality urological procedures such as holmium laser should be tried, especially in patients with urolithiasis predisposing factors.


Is restlessness best understood as a process? Reflecting on four boys' restlessness during music therapy in kindergarten.
ADHD can be considered an internationally recognized framework for understanding children's restlessness. In this context, children's restlessness is understood as a symptom of neurodevelopmental disorder. However, there are other possible understandings of children's restlessness. In this article, we explore four boys' collaborative and creative process as it is described and understood by three adults. The process is framed by a community music therapy project in a Norwegian kindergarten, and we describe four interrelated phases of this process: Exploring musical vitality and cooperation, Consolidating positions, Performing together, and Discovering ripple effects. We discuss these results in relation to seven qualities central to a community music therapy approach: participation, resource orientation, ecology, performance, activism, reflexivity and ethics. We argue that in contrast to a diagnostic approach that entails a focus on individual problems, a community music therapy approach can shed light on adult and systemic contributions to children's restlessness.


Separation and isolation methods for analysis of the active principles of Sho-saiko-to (SST) oriental medicine.
Sho-saiko-to (SST) was introduced into Japan as an oriental classical medicine from China approximately 1500 years ago, and it is currently the most representative Kampo medicine (traditional Japanese medicine). SST is manufactured in Japan as an ethical drug on a modern industrial scale in which the quality of ingredients is standardized with Good Manufacturing Practices (GMP) regulation. SST is widely used for the treatment of chronic hepatitis. Experimental and clinical studies including multi-center, placebo-controlled, double-blind studies have demonstrated the various pharmacological effects of SST. SST is prepared from the hot water extraction of seven raw materials, therefore many kinds of constituents are included. Three-dimensional (3D) HPLC analysis is useful for obtaining many kinds of constituents, especially low molecular ultraviolet (UV) quenching compounds, contained in SST as well as its fractions. Fingerprint pattern provided by 3D HPLC analysis makes possible to identify the overall-viewing of SST. Databases of UV spectra of the components of medicinal herbs obtained by reversed-phase (RP) HPLC using a photodiode array (PDA) and fingerprint patterns of crude drugs made by 3D HPLC analysis facilitate the identification, analysis and quality of herbal drugs. Studies using both PDA HPLC and an amino acid analysis with a fluorometric detector have found that SST contains fifteen major low molecular compounds (i.e. baicalin, wogonin-7-O-glucuronide, liquiritin, their three aglycons, liquiritin apioside, glycyrrhizin, saikosaponin b1, saikosaponin b2, ginsenoside Rg1, ginsenoside Rb1, (6)-gingerol, (6)-shogaol and arginine). These compounds have various pharmacological actions, and are assumed to be responsible, at least partly, for the pharmacological effects of SST. Although there have only been a few investigations on high molecular compounds with pharmacological actions contained in SST, several kinds of polysaccharides have been isolated from constituent herbs of SST. This review paper summarizes analytical methods of separation, isolation and identification of compounds with biological activities from SST, which is a mixture drug of medicinal herbs. Accordingly, this paper would not focus on methods of separation, isolation and analysis of particular compounds from each constituent herb of SST.


Intermediate wave function statistics.
We calculate statistical properties of the eigenfunctions of two quantum systems that exhibit intermediate spectral statistics: star graphs and Seba billiards. First, we show that these eigenfunctions are not quantum ergodic, and calculate the corresponding limit distribution. Second, we find that they can be strongly scarred, in the case of star graphs by short (unstable) periodic orbits and, in the case of Seba billiards, by certain families of orbits. We construct sequences of states which have such a limit. Our results are illustrated by numerical computations.


An in vitro stem cell model of human epiblast and yolk sac interaction.
Human embryogenesis entails complex signalling interactions between embryonic and extra-embryonic cells. However, how extra-embryonic cells direct morphogenesis within the human embryo remains largely unknown due to a lack of relevant stem cell models. Here, we have established conditions to differentiate human pluripotent stem cells (hPSCs) into yolk sac-like cells (YSLCs) that resemble the post-implantation human hypoblast molecularly and functionally. YSLCs induce the expression of pluripotency and anterior ectoderm markers in human embryonic stem cells (hESCs) at the expense of mesoderm and endoderm markers. This activity is mediated by the release of BMP and WNT signalling pathway inhibitors, and, therefore, resembles the functioning of the anterior visceral endoderm signalling centre of the mouse embryo, which establishes the anterior-posterior axis. Our results implicate the yolk sac in epiblast cell fate specification in the human embryo and propose YSLCs as a tool for studying post-implantation human embryo development in vitro.


Reconfigurable dual-channel dropping filters based on a self-coupled resonator Sagnac interferometer.
We report a reconfigurable dual-mode resonator-based dual-channel dropping filter. The dual dropping channels are generated within a free spectral range (FSR) via the interference between the electromagnetically induced transparency (EIT)-like and electromagnetically induced absorption (EIA)-like resonances despite only one resonator used. The reconfiguration of the dual channels enabling the truly on/off switching mechanism is realized, and the output modes resembling the add/drop/neutral states are provided. The compact, reliable, flexible, versatile, and extendable filter has profound implications for wavelength division multiplexing (WDM) applications in optical interconnection networks.


18F-FDG PET/CT in Oral Cuniculatum Carcinoma.
A 69-year-old woman was referred for initial staging of an oral cavity mass. F-FDG PET/CT displayed a homogeneous intense uptake of the 50-mm left hemipalatal mass with local extension to the dental arcade and maxillary sinus. Infracentimetric bilateral cervical nodes with faint uptake were also detected, contrasting with the usual presentation of other head and neck squamous cell carcinoma. Biopsy concluded to a rare head and neck squamous cell carcinoma subtype: oral cuniculatum carcinoma (OCC). After radiotherapy, 18F-FDG PET/CT showed metabolic complete response. Our case describing specifically the metabolic characteristics of OCC and radiotherapy evaluation for this rare tumor.


In vitro inhibition of endotoxin induced platelet aggregation with hydrocortisone sodium succinate (Solu-Cortef).
Citrated canine platelet rich plasma stimulated with ADP, thrombin, collagen and E. coli endotoxin demonstrated platelet aggregation when measured with Payton aggregometer. Following incubation with hydrocortisone sodium succinate (Solu-Cortef) the same platelet rich plasma did not undergo platelet aggregation when stimulated by these agents. Solu-Cortef added to platelet rich plasma during ATP, thrombin, collagen and endotoxin stimulated platelet aggregation resulted in a reversal of the optical density suggesting deaggregation. These in vitro observations support the beneficial effects observed when steroids are administered in vivo to experimental or clinical shock.


Changes in leaf trichomes and epicuticular flavonoids during leaf development in three birch taxa.
Changes in number of trichomes and in composition and concentrations of their exudates throughout leaf development may have important consequences for plant adaptation to abiotic and biotic factors. In the present study, seasonal changes in leaf trichomes and epicuticular flavonoid aglycones in three Finnish birch taxa (Betula pendula, B. pubescens ssp. pubescens, and B. pubescens ssp. czerepanovii) were followed. Trichome number and ultrastructure were studied by means of light, scanning and transmission electron microscopy, while flavonoid aglycones in ethanolic leaf surface extracts were analysed by high-pressure liquid chromatography. Density of both glandular and non-glandular trichomes decreased drastically with leaf expansion while the total number of trichomes per leaf remained constant, indicating that the final number of trichomes is established early in leaf development. Cells of glandular trichomes differentiate before those of the epidermis and produce secreted material only during the relatively short period (around 1-2 weeks) of leaf unfolding and expansion. In fully expanded leaves, glandular trichomes appeared to be at the post-secretory phase and function mainly as storage organs; they contained lipid droplets and osmiophilic material (probably phenolics). Concentrations (mg g(-1) d. wt) of surface flavonoids decreased with leaf age in all taxa. However, the changes in total amount ( microg per leaf) of flavonoids during leaf development were taxon-specific: no changes in B. pubescens ssp. czerepanovii, increase in B. pendula and in B. pubescens ssp. pubescens followed by the decline in the latter taxon. Concentrations of most of the individual leaf surface flavonoids correlated positively with the density of glandular trichomes within species, suggesting the participation of glandular trichomes in production of surface flavonoids. Rapid decline in the density of leaf trichomes and in the concentrations of flavonoid aglycones with leaf age suggests that the functional role of trichomes is likely to be most important at the early stages of birch leaf development.


Application and evaluation of NODDI in the cervical spinal cord of multiple sclerosis patients.
There is a need to develop imaging methods sensitive to axonal injury in multiple sclerosis (MS), given the prominent impact of axonal pathology on disability and outcome. Advanced multi-compartmental diffusion models offer novel indices sensitive to white matter microstructure. One such model, neurite orientation dispersion and density imaging (NODDI), is sensitive to neurite morphology, providing indices of apparent volume fractions of axons (vin), isotropic water (viso) and the dispersion of fibers about a central axis (orientation dispersion index, ODI). NODDI has yet to be studied for its sensitivity to spinal cord pathology. Here, we investigate the feasibility and utility of NODDI in the cervical spinal cord of MS patients. NODDI was applied in the cervical spinal cord in a cohort of 8 controls and 6 MS patients. Statistical analyses were performed to test the sensitivity of NODDI-derived indices to pathology in MS (both lesion and normal appearing white matter NAWM). Diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) analysis were also performed to compare with NODDI. A decrease in NODDI-derived vin was observed at the site of the lesion (p < 0.01), whereas a global increase in ODI was seen throughout white matter (p < 0.001). DKI-derived mean kurtosis (MK) and radial kurtosis (RK) and DTI-derived fractional anisotropy (FA) and radial diffusivity (RD) were all significantly different in MS patients (p < 0.02), however NODDI provided higher contrast between NAWM and lesion in all MS patients. NODDI provides unique contrast that is not available with DKI or DTI, enabling improved characterization of the spinal cord in MS.


Bactericidal activity of ethanol against glucose nonfermentative Gram-negative bacilli.
The bactericidal effect of ethanol on glucose nonfermentative Gram-negative bacilli (nonfermentative bacilli) and other species of micro-organisms was studied with emphasis on the former. At 20 degrees C, 10 to 20% v/v ethanol took 1 h or more to kill thirteen strains of nonfermentative bacilli while 40 to 99.5% concentrations produced a bactericidal effect within 1 min of exposure. Eleven strains of glucose fermentative organisms showed a similar tendency to that noted with nonfermentative bacilli, except that S. aureus was a little resistant to 99.5% ethanol. Using several strains of nonfermentative bacilli, the effects of temperature and equine serum on the bactericidal action of ethanol were determined. The bactericidal action of ethanol increased with rising of temperature (10-30 degrees C), and it was sufficient even at 10 degrees C provided that the concentration of ethanol was over 50%. The equine serum produced little effect on the bactericidal action of ethanol.


[Genotyping some Borrelia burgdorferi sensu lato isolates from Ixodes ricinus ticks in Russia and Ukraine].
The 4 Borrelia burgdorferi sensu lato isolates obtained from 1. Ricinus ticks collected in the natural foci in Russia and Ukraine, having an unusual RFLP Msel-pattern, were studied using sequencing rrfA-rrlB spacer and rrs gene. The Ir-5215 isolate from the tick collected in southern Ukraine represented recently described genospecies B. spielmanii pathogenic for humans. The three atypical isolates Ir-3519, Ir-4721, and Ir-4812 had 100% identity with the sequence of the atypical European B. burgdorferi sensu stricto strains. They constituted a subgroup of the B. burgdorferi sensu stricto on the grounds of Multilocus sequence analysis (MLSA). These data can be indicative of the genetic heterogeneity of the current group B. burgdorferi sensu stricto.


Sickle cell hepatopathy.
Sickle cell hepatopathy is a well-documented entity that ranges from the self-limiting hepatic right upper quadrant syndrome to the potentially lethal intrahepatic cholestasis and acute hepatic sequestration syndromes. We describe a 26-year-male with homozygous sickle cell disease who had this unique hepatic presentation and was documented to have characteristic findings of cholestasis, portal inflammation and sinusoidal dilatation on histopathology.


The Arg233Lys AQP0 mutation disturbs aquaporin0-calmodulin interaction causing polymorphic congenital cataract.
Calmodulin (CaM) directly interacts with the aquaporin 0 (AQP0) C-terminus in a calcium dependent manner to regulate the water permeability of AQP0. We previously identified a missense mutation (p.R233K) in the putative CaM binding domain of AQP0 C-terminus in a congenital cataract family. This study was aimed at exploring the potential pathogenesis of this mutation causative of cataract and mainly identifying how it influenced the binding of AQP0 to CaM. Wild type and R233K mutant AQP0 with EGFP-tag were transfected separately into Hela cells to determine the expression and subcellular localizations. The co-immunoprecipitation (CoIP) assay was used to detect the interaction between AQP0 and CaM. AQP0 C-terminus peptides were synthesized with and without R233K, and the binding abilities of these peptides to CaM were assessed using a fluorescence binding assay. Localizations of wild type and R233K mutant AQP0 were determined from EGFP fluorescence, and the chimeric proteins were both localized abundantly in the plasma membrane. Protein expression levels of the culture cells showed no significant difference between them. The results from CoIP assay implied that R233K mutant presented more weakly in association with CaM than wild type AQP0. The AQP0 C-terminal mutant peptide was found to have 2.5-fold lower binding affinity to CaM than wild type peptide. These results suggested that R233K mutation did not affect the expression, location and trafficking of the protein but did influence the interaction between AQP0 and CaM. The binding affinity of AQP0 C-terminus to CaM was significantly reduced. Due to lack of the modulation of the Ca2+-calmodulin complex, the water permeability of AQP0 was subsequently augmented, which might lead to the development of this cataract.


Factors affecting visibility of a target tissue in histologic sections.
The objective of histologic techniques is to stain the subject with high specificity and high visibility. Visibility depends on the microscope's resolution and contrast and on the microscopist's skill at optimizing the microscope's image. It also depends on histotechnological factors, which include specificity and differentiation of the stain, density of background staining (particularly in silver stains), innate color, and grayscale contrasts of the dyes in the stains and color and density of the counterstain. If contrast is not optimal, the image should be evaluated on the basis of 2 types of contrast-color and grayscale. Complementary colors have maximum color contrast, and the color triangle is useful in the selection of a suitable counterstain. Grayscale contrast is a function of the density of a stain. If dyes capable of staining the target and backgrounds tissue do not have optimal color contrast, the only method of increasing contrast is to change the grayscale value of one of the stains, usually the counterstain. Colors can have a subconscious effect on a viewer. Depending on whether they are aesthetically pleasing, they may influence the rigor of and time spent on the histopathologic examination. Maximizing the specificity of stains such as hematoxylin, eosin, trichrome, and Luxol fast blue (LFB) depends on optimal differentiation. In differentiation of counterstains such as methylene blue in the Ziehl-Neelsen stain, its recommended density is conveniently expressed as a grayscale value. Independent evaluation of color and grayscale contrasts is very helpful in determining the cause of low contrast in an image. This review discusses aspects of the histotechnique affecting the visibility of tissue components.