Association between plasma alkaline phosphatase and C-reactive protein in Hong Kong Chinese.
Alkaline phosphatase (ALP) is a biomarker for hepatobiliary and skeletal diseases. It is also raised in sepsis. In atherosclerotic plaques, ALP is expressed. Similar to C-reactive protein (CRP), it may be another marker of systemic inflammation. Therefore, we investigated their association in a Hong Kong Chinese population. Plasma ALP and CRP were measured in 205 subjects (110 men, 95 women; age 55.2+/-11.6 years) in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 cohort. The blood levels of ALP and CRP were significantly correlated (r=0.30, p<0.001), which was due to a significant correlation in women (r=0.43, p<0.001). In a multivariate model, CRP level was related to ALP (beta=0.18, p=0.008). After adjusting for confounding factors and other liver enzymes, the relationship between ALP and CRP remained significant in women (beta=0.28, p=0.019), but in men, ALP was not an independent determinant of CRP levels. ALP may be another marker of systemic inflammation, especially in women. Whether it provides clinical information additional to CRP requires further study.


[Gastric ulcer in the infant: clinical contribution].
The authors, after a short review on the etiopathological classification and the clinical exordium of the gastric ulcer in infancy, report a relapsing case nevertheless the therapy with cimetidine and antacid drugs. Furthermore they note the importance of the careful anamnesis and early and repeated occult blood stool tests to value for eventual gastric fiberendoscopy.


Tumor necrosis factor-alpha genetic predisposing factors can influence clinical severity in nephropathia epidemica.
Severe human infection with Hantavirus is characterized by high fever, cold chills, thrombocytopenia, arterial hypotension, acute renal failure, and/or adult respiratory distress syndrome (ARDS)-like pulmonary involvement, but the clinical course varies greatly between individuals. We investigated whether genetically determined differences in tumor necrosis factor (TNF)-alpha production can influence the severity of Hantavirus disease. We studied a TNF-alpha single-nucleotide promoter polymorphism (SNP) at position -238 (a guanine [G]-to-adenine [A] transition) and ex vivo TNF-alpha production in a recall study of 36 Belgian patients who had a serologically proven form of Puumala virus-induced Hantavirus infection with the kidney as main target organ. In our study, the highest creatinine levels were found in patients with the lowest ex vivo TNF-alpha production. Creatinine levels correlated inversely with TNF-alpha production (R = -0.35, p < 0.05). The number of thrombocytes was significantly lower in patients with the GA-238 genotype (low TNF-alpha producers) compared with patients with the GG-238 genotype. In our study, genetically determined low production of TNF-alpha was associated with some parameters indicating a more severe clinical course of Puumala Hantavirus infection in humans, possibly by impaired activation of TNF-alpha-dependent antiviral mechanisms, which could in turn result in decreased clearance of Hantavirus.


Comparison between audio-only and audiovisual biofeedback for regulating patients' respiration during four-dimensional radiotherapy.
To compare audio-only biofeedback to conventional audiovisual biofeedback for regulating patients' respiration during four-dimensional radiotherapy, limiting damage to healthy surrounding tissues caused by organ movement. Six healthy volunteers were assisted by audiovisual or audio-only biofeedback systems to regulate their respirations. Volunteers breathed through a mask developed for this study by following computer-generated guiding curves displayed on a screen, combined with instructional sounds. They then performed breathing following instructional sounds only. The guiding signals and the volunteers' respiratory signals were logged at 20 samples per second. The standard deviations between the guiding and respiratory curves for the audiovisual and audio-only biofeedback systems were 21.55% and 23.19%, respectively; the average correlation coefficients were 0.9778 and 0.9756, respectively. The regularities between audiovisual and audio-only biofeedback for six volunteers' respirations were same statistically from the paired t-test. The difference between the audiovisual and audio-only biofeedback methods was not significant. Audio-only biofeedback has many advantages, as patients do not require a mask and can quickly adapt to this method in the clinic.


Stability, Activity, and Application of Topical Doxycycline Formulations in a Diabetic Wound Case Study.
Tetracycline molecules comprise a group of broad-spectrum antibiotics whose primary mechanism of action is the inhibition of protein synthesis through the binding of the bacterial ribosome. In addition, tetracyclines inhibit matrix metalloproteases (MMPs), a family of zinc-dependent proteases that contribute to tissue remodeling, inflammation, and angiogenesis and are overexpressed in certain pathophysiologies such as diabetic foot ulcers (DFUs). This study aims to develop a liquid chromatography and mass spectrometry (LC-MS/MS) doxycycline quantification methodology to facilitate the development of a stable topical doxycycline hyclate (DOXY) formulation as well as evaluate the topical DOXY formulation for the efficacy in MMP-9 inhibition in vitro and in a clinical application of diabetic lower extremity wounds. A simple quantification method utilizing LC-MS/MS was used to develop a topical DOXY formulation, a sample of which was analyzed in stability testing. The formulation was evaluated in vitro for MMP-9 activity using a commercial assay and compared with internal kit controls as well as in a clinical setting for wound healing. Two formulations of 2% (w/w) DOXY demonstrated acceptable stability (±10% target concentration) for 70 days when stored at 4°C. Using an in vitro assay of MMP-9 enzyme activity, the 2% DOXY formulation imparted a ~30% decrease in MMP-9 inhibitory potential as compared with the control drug alone (IC₅₀ values 62.92 µM and 48.27 µM, respectively). This topical product was evaluated for clinical utility in a patient with a DFU, and preliminary data suggest this intervention may promote wound healing. In summary, novel DOXY formulations may be stable and biologically active tools amenable to complex wound care.


Dose intense, dose dense and tailored dose adjuvant chemotherapy for early breast cancer: an evolution of concepts.
The introduction of adjuvant chemotherapy following surgery for early breast cancer (BC) and its integration into routine clinical practice has consistently improved clinical outcomes. Since the addition of other agents to the contemporary standard of care containing an anthracycline, cyclophosphamide and a taxane has not lead to further prolongation of survival, subsequent efforts concentrated on escalating the administered doses and reducing the time interval between chemotherapy cycles. These strategies have been extensively evaluated in randomized trials and dose dense chemotherapy is now recommended by clinical practice guidelines. Eligible trials were identified by searching the EMBASE, Pubmed, Scopus and Cochrane Library databases, as well as conference papers. The findings, shortcomings and impact of these studies are presented and critically discussed. Although a large number of randomized trials has established the value of adjuvant chemotherapy, important questions remain unanswered. Ongoing research focuses on omitting treatment in good risk patients, identifying patients most likely to benefit from a dose dense approach and on administering personalized doses such as in tailored dose chemotherapy. Adjuvant chemotherapy for early BC is an evolving art. Further optimizations could potentially improve outcomes for a patient subset and spare others from unnecessary treatment-related toxicity.


Role of the renal nerve in glucocorticoid hypertension.
The present study was designed to investigate the involvement of the renal nerve in glucocorticoid hypertension and to assess the role of the renin-angiotensin system in dexamethasone-induced hypertension. The elevated blood pressure in dexamethasone treated rats showing a significant increase in plasma renin concentration (PRC) and activity (PRA) was attenuated dose-dependently by the angiotensin I converting enzyme (ACE) inhibition. Bilateral renal denervation caused a partial decrease in the elevated blood pressure, abolished the increased PRC and PRA, and reduced the dose-dependent decrease in blood pressure with ACE inhibition in dexamethasone treated rats. Although the reduction in body weight and increases in urine volume, urinary sodium excretion and hematocrit were clearly seen following dexamethasone administration, dexamethasone-treated renal denervated rats showed the same degree of change in any of the variables as dexamethasone-treated sham-operated rats. Thus, our results indicate that the stimulation of the renin-angiotensin system through the activation of the renal nerve may be partially responsible for the dexamethasone-induced high blood pressure and, therefore, bilateral renal denervation reduces, partially but significantly, the elevated blood pressure, suggesting that the attenuation of oversecretion of renin contributes to the lowering of the blood pressure.


3D high resolution anorectal manometry in functional anorectal evaluation.
Anorectal manometry is a diagnostic tool designed for the evaluation of functional parameters and assessment of anorectal activity coordination. In the last decade, the development of 3D high-resolution (HR) manometry and its expansion in experimental and clinical settings has been evident. Literature search (in the MEDLINE and PubMed databases) focusing on studies about 3-dimensional HR manometry was performed. The aim of this paper is to offer an overview of the current state of the art of manometry while concentrating on indications, protocol of the procedure and applicability of this examination in clinical practice. Development of solid catheters with miniaturized semiconductor sensors has enabled very precise measurement (high resolution) and creation of anorectal 3D pressure models. In comparison with water-perfused manometry systems, this method offers more accurate and more detailed data that can be employed in functional disorders assessment. The indications for anorectal manomery are symptoms of faecal incontinence and functional constipation. This modality can also be used in biofeedback therapy, in functional anorectal pain and when assessing patients undergoing continent rectal resection. The HR manometry protocol should comprise the measurement of anorectal resting pressures, the squeeze manoeuvre, the bear down manoeuvre, the cough reflex test, the rectoanal inhibitory reflex examination, rectal sensitivity testing and rectal compliance measurement. Processed data are fundamental in determining an individually tailored treatment plan for patients suffering from anorectal functional disorders. Anorectal 3D HR manometry presents a valuable diagnostic modality offering a new dimension in anorectal function understanding and can reveal new pathophysiologic mechanisms of anorectal functional disorders.


Functional self-assembling bolaamphiphilic polydiacetylenes as colorimetric sensor scaffolds.
Conjugated polymers capable of responding to external stimuli by changes in optical, electrical, or electrochemical properties can be used for the construction of direct sensing devices. Polydiacetylene-based systems are attractive for sensing applications due to their colorimetric response to changes in the local environment. Here we present the design, preparation, and characterization of self-assembling functional bolaamphiphilic polydiacetylenes (BPDAs) inspired by nature's strategy for membrane stabilization. We show that by placing polar headgroups on both ends of the diacetylene lipids in a transmembranic fashion and by altering the chemical nature of the polar surface residues, the conjugated polymers can be engineered to display a range of radiation-, thermal-, and pH-induced colorimetric responses. We observed dramatic nanoscopic morphological transformations accompanying charge-induced chromatic transitions, suggesting that both side-chain disordering and main-chain rearrangement play important roles in altering the effective conjugation lengths of the poly(ene-yne). These results establish the foundation for further development of BPDA-based colorimetric sensors.


Histamine release induced by radiographic contrast media. Comparison between pulmonary and peritoneal mast cells derived from normotensive and spontaneously hypertensive rats.
Intravascular application of radiographic contrast media (RCM) can cause adverse allergic/pseudoallergic reactions in certain individuals. In view of the increased risk for the reactions associated with cardiovascular diseases, we have investigated histamine release from isolated mast cells derived from the peritoneal cavity and the lung of normotensive and spontaneously hypertensive rats. Six commonly used RCM were tested in their clinical formulations: Angiographin (amidotrizoate), Rayvist (ioglycate), Telebrix (ioxithalamate), Hexabrix (ioxaglate), Solutrast (iopamidol), and Ultravist (iopromide). The three RCM with low osmolality (Hexabrix, Solutrast and Ultravist) released little histamine from all cell populations tested. Mast cells derived from spontaneously hypertensive rats released significantly more histamine following challenge with high osmolar RCM than those derived from normotensive rats. Higher concentrations were required to elicit release from the peritoneal cells than from the pulmonary cells. These results indicate a role for underlying cardiovascular diseases in mediator release and should be followed up by investigations on basophils or mast cells obtained from control subjects and patients with cardiovascular disease.


STAT 5 and NF-Y are involved in expression and growth hormone-mediated sexually dimorphic regulation of cytochrome P450 3A10/lithocholic acid 6beta-hydroxylase.
The level of expression of a number of sexually differentiated liver proteins is primarily determined by plasma growth hormone (GH). Adult males have a pulsatile profile of GH release, while females have a relatively steady-state pattern of GH release. An important subset of these sexually differentiated hepatic proteins is certain cytochrome P450s (P450s). CYP3A10/6beta-hydroxylase is a male-specific P450 that catalyzes 6beta-hydroxylation of lithocholic acid, and the pattern of GH secretion is directly responsible for male-specific expression of this gene. The DNA element involved in GH-mediated regulation of CYP3A10/6beta-hydroxylase promoter activity binds a member of the STAT (signal transducers and activators of transcription) family of proteins. In this study we functionally demonstrate that two members of the STAT family, STAT 5a and STAT 5b, mediate GH-dependent regulation of CYP3A10/6beta-hydroxylase promoter activity. Furthermore, a neighboring DNA element binds NF-Y, a transcription factor involved in maintaining high levels of transcription of many genes and known to functionally interact with other factors. In the CYP3A10/6beta-hydroxylase gene, NF-Y also modulates binding of STAT 5, thereby modulating GH-mediated activation of its transcription.


Feeding live cultures of Enterococcus faecium and Saccharomyces cerevisiae induces an inflammatory response in feedlot steers.
Two experiments were conducted to investigate the effects of oral supplementation of the lactic-acid-producing bacterium Enterococcus faecium EF212 alone or in combination with Saccharomyces cerevisiae (yeast) on mediators of the acute phase response in feedlot steers. Eight fistulated steers were used to study the effects of E. faecium alone or with yeast in a crossover design with 2 Latin squares, 4 steers within each square, and 2 periods. The length of each period was 3 wk, with a 10-d adaptation and an 11-d measurement period. The experimental diet contained 87% steam-rolled barley, 8% whole-crop barley silage, and 5% supplement (DM basis). In Exp. 1, treatments were control vs. the lactic-acid-producing bacterium E. faecium (6 x 10(10) cfu/d). In Exp. 2, treatments were control vs. E. faecium (6 x 10(10) cfu/d) and S. cerevisiae (6 x 10(10) cfu/d). The bacteria and yeast supplements were blended with calcium carbonate to supply 6 x 10(10) cfu/d when top-dressed into the diet once daily at the time of feeding (10 g/d). Steers fed the control diet received only carrier (10 g/d). Blood samples were collected from the jugular vein on d 17 and 21 of each period, and serum amyloid A (SAA), lipopolysaccharide binding protein (LBP), haptoglobin, and alpha1-acid glycoprotein (alpha1-AGP) were measured. Supplementation of feed with E. faecium had no effect on concentrations of SAA, LBP, haptoglobin, or alpha1-AGP in plasma compared with those of controls. However, feeding E. faecium and yeast increased (P = 0.02) plasma concentrations of SAA, LBP, and haptoglobin but had no effect on plasma alpha1-AGP. In conclusion, oral supplementation of E. faecium alone had no effect on the mediators of the acute phase response that were measured, whereas feeding of E. faecium and yeast induced an inflammatory response in feedlot steers fed high-grain diets. Further research is warranted to determine the mechanism(s) by which E. faecium and yeast stimulated production of acute phase proteins in feedlot steers.


Transcriptional regulation of Zic3 by heterodimeric AP-1(c-Jun/c-Fos) during Xenopus development.
The heterodimeric c-Jun/c-Fos, an activator protein-1 (AP-1) has been implicated in mesoderm induction (Dong et al., 1996; Kim et al., 1998) whereas the homodimer of c-Jun was reported to be involved in neural inhibition during the early development of Xenopus embryos. During the early vertebrate development AP-1 involvement in the neural induction is still not clearly understood. We report here that AP-1 has a role in Zic3 expression, a critical proneural gene and a primary regulator of neural and neural crest development (Nakata et al., 1997; Nakata et al., 1998). AP-1 was able to induce the Zic3 gene in a dose dependent manner but other homo- or hetero-dimeric proteins, such as c-Jun/c-Jun, JunD/FosB or JunD/Fra-1 were not. The inhibition of AP-1 activity using morpholino antisenses of c-jun mRNAs blocked the Zic3 expression induced by activin. In addition, co-injection of c-jun mRNA rescued the down-regulated Zic3 expression. The promoter region of isolated Zic3 genomic DNA was found to possess several consensus-binding site of AP-1. Thus, in the functional assays, AP-1 could increase promoter activity of Zic3 gene. These findings suggest that proneural gene, Zic3 may be regulated by heterodimeric AP-1(c-Jun/c-Fos) and it may have a role in activin signaling for the regulation of neural specific gene, Zic3.


Mechanical load enhances the stimulatory effect of serum growth factors on cardiac fibroblast procollagen synthesis.
The mechanical environment is a key determinant of cellular activity in many tissues. In the cardiovascular system it plays a role in tissue remodelling during both development and disease. In the heart changes in mechanical tension stimulate myocyte hypertrophy and fibroblast collagen synthesis. To elucidate the mechanisms for the latter response, we determined the direct effect of mechanical load on cardiac fibroblast activity. Primary cultures of fetal rat cardiac fibroblasts were mechanically loaded in the presence or absence of fetal calf serum or growth factors, and the effects on fibroblast replication and procollagen metabolism and gene expression determined. Procollagen synthesis was increased by 99.7 +/- 4.3% in response to mechanical load and 10% fetal calf serum, compared to 10% fetal calf serum control (P<0.01) after 48 h. Procollagen alpha1(I) steady-state mRNA levels were increased two-fold. No effect was observed in the absence of serum. Transforming growth factor beta1 and insulin-like growth factor 1 have been demonstrated to stimulate procollagen metabolism by these cells. Mechanical load enhanced the response to these growth factors, stimulating alpha1(I) mRNA levels by 4.3 and three-fold, respectively, above growth factor alone controls. These results demonstrate a synergistic effect on procollagen gene expression and metabolism by mechanical load and profibrotic growth factors. Since these factors are released during the development of cardiac hypertrophy, interactions between the mechanical environment and these polypeptides may provide a mechanism for enhanced collagen deposition in the heart.


Indication of Formation Water Geochemistry for Hydrocarbon Preservation: New Applications of Machine Learning in Tight Sandstone Gas Reservoirs.
The migration of formation water plays a crucial role in hydrocarbon accumulation and preservation. The hydrodynamic field controls the content of various ions in formation water and is an important participant in hydrocarbon evolution. One potential high-yield gas field is the tight sandstone gas reservoirs in the northern Tianhuan Depression of the Ordos Basin, China. However, due to the complex gas-water relationship and limited water sample data, the development of gas reservoirs has encountered great difficulties; we thus analyzed the geochemical characteristics of a large scale of formation water acquired from the Permian in the Ordos Basin (60 water samples collected from 45 wells in the He8 Member). The results showed that formation water is the original sedimentary water in tight sandstone reservoirs, which represent a closed hydrological environment, which is conducive to gas accumulation. This is also related to the demonstrated strong water-rock reaction and diagenetic. We also developed a statistical model between these geochemical parameters and gas preservation based on machine learning algorithms (decision trees). Note that machine learning, as a data-driven artificial intelligence algorithm, generates massive correlation models that can learn from the structured training data sets to carry out predictions or evaluations in newly presented data. This algorithm can process large amounts of information data more quickly and can build more perfect correlation models through deep learning mechanisms than traditional statistical methods. The results suggest that the metamorphism coefficient has the best indication effect on the preservation of gas reservoirs. The hydrological environment with (Cl--Na+)/Mg2+ > 50.066, Na+/Cl- ≤ 0.476, and Ma2+/Ca2+ ≤ 0.102 is a good hydrocarbon accumulation area. This study can be applied, by analogy, to more comprehensively interpret the correlation between the geochemical characteristics of formation water and hydrocarbon storage and to improve the accuracy of predicting favorable hydrocarbon accumulation areas in tight sandstone gas reservoirs.


Cell adhesion and spreading behavior on vertically aligned silicon nanowire arrays.
In this report, we studied the interactions between biological cells and vertically aligned silicon nanowire (SiNW) arrays and focused on how SiNW arrays affected cellular behaviors such as cell adhesion and spreading. We observed that SiNW arrays could support cell adhesion and growth and guide cell adhesion and spreading behaviors. The results also showed that SiNW arrays could not only enhance the cell-substrate adhesion force but also restrict cell spreading. Combining the results from scanning electron microscopy images of cell morphology and the expression analysis of genes and proteins related to cell adhesion and spreading process, we proposed a mechanism on how cell adhesion and spreading was controlled by arrayed SiNWs. The effects of SiNW arrays in guiding cell adhesion and spreading behavior might be useful in the development of cell microarrays, tissue engineering scaffolds, and molecule delivery vehicles in which strong cell-substrate adhesion and reduced cell-cell communication were beneficial.


Effect of antigen-processing efficiency on in vivo T cell response magnitudes.
T lymphocytes eradicate and provide long-term immunity to infections caused by intracellular pathogens. The mechanisms that determine in vivo T cell response sizes are poorly understood. Although it is speculated that the relative processing efficiency of different epitopes determines the hierarchy of T cell responses following immunization, this hypothesis has not been rigorously tested. We therefore mutagenized the secreted p60 Ag of Listeria monocytogenes to alter the efficiency of T cell epitope generation. Ag-processing efficiencies in cells infected with the different L. monocytogenes mutants ranged from one H2-Kd-associated p60 217-225 epitope generated per 15 intracellularly degraded p60 molecules (1/15) to one epitope per 350 degraded p60 molecules (1/350), i.e., a spectrum encompassing a 20-fold range of efficiencies. Mice infected with L. monocytogenes secreting inefficiently processed p60 (1/350) did not mount p60 217-225-specific T cell responses. However, increasing the efficiency of Ag processing by a factor of 5 to 1/70 restored the T cell response size to normal, while further increases in the efficiency of p60 217-225 generation to 1/50, 1/35, and 1/17 did not further augment specific T cell responses. Our studies demonstrate an Ag-processing threshold for in vivo T cell activation. Surprisingly, once this threshold is achieved, further enhancement of Ag-processing efficiency does not enhance the size of T cell responses.


KLF11 Expression Predicts Poor Prognosis in Glioma Patients.
Glioma is a primary intracranial malignant tumor with high recurrence and mortality rates. It is very important to study the prognostic factors. KLF11 can function as an oncogene or a tumor suppressor, depending on the tumor and tissue types and the cancer stage. In this study, we aimed to determine whether KLF11 expression is related to the overall survival of glioma patients. We investigated KLF11 expression in 116 glioma patients with different grades using Western blot and immunohistochemistry assay. We analyzed the patients with different glioma grades and KLF11 expression levels by Kaplan-Meier survival curves. Independent prognostic factors for poor overall survival were identified by univariate and multivariate analyses. There were 37 patients in KLF11 low expression group and 79 patients in high expression group. There was no difference in gender, age, tumor diameter or tumor location between two groups. The patients in KLF11 high expression group had higher ECOG score (P =0.025) and higher WHO grades (P =0.029). Western blot and immunohistochemistry assay showed KLF11 expression was significantly upregulated in glioma groups compared with normal brain tissues group (P < 0.05), and the expression in grades III-IV was significantly higher than those in grades I-II (P < 0.05). Kaplan-Meier survival curve analysis showed high KLF11 expression tended to reduce the overall survival (P < 0.05). After univariate and multivariate analyses, KLF11 expression (P =0.003) and age (P =0.007) were independent prognostic factors for poor survival in glioma patients. KLF11 expression was increased in glioma tissues, and high KLF11 expression was associated with poor prognosis. KLF11 expression was an independent prognostic factor for poor survival in glioma patients. KLF11 may serve as a novel prognostic marker for gliomas and as a novel treatment target.


Cellular hypersensitivity in rheumatoid arthritis, ankylosing spondylitis, and anterior nongranulomatous uveitis.
The humoral and cellular responses to normal human ocular and joint tissue antigens were studied in rheumatoid arthritis, ankylosing spondylitis, and anterior non-granulomatous uveitis. No free-circulating autoantibodies could be detected by hemagglutination, immunodiffusion, and immunofluorescence. Uvea-retina, synovial membrane, and articular cartilage antigen preparations inhibited the migration of leukocytes from patients with rheumatoid arthritis. In ankylosing spondylitis inhibition could be induced only by synovial membrane antigens. Patients with anterior nongranulomatous uveitis were hypersensitive to uvea-retina antigens alone.


Resistance to fluoroquinolones in Pseudomonas aeruginosa and Klebsiella pneumoniae.
The fluoroquinolone sensitivity of Pseudomonas aeruginosa and Klebsiella pneumoniae was studied by determinations of Minimum Inhibitory Concentrations (MICs) of norfloxacin and ciprofloxacin in consecutive clinical isolates. In P. aeruginosa, resistance or reduced susceptibility (MIC > or = 8 mg/l for norfloxacin and > or = 2 mg/l for ciprofloxacin) was found in 17% (9/54) of the isolates. Reduced susceptibility (MIC > or = 2 mg/l for norfloxacin) was found in 12% (10/84) of K. pneumoniae isolates. P. aeruginosa strains isolated in 1991 had reduced susceptibility to both norfloxacin and ciprofloxacin significantly more often than isolates from 1984-85 (p = 0.02). 10/84 K. pneumoniae strains from 1991 had reduced susceptibility to norfloxacin, compared with 1/34 from 1984-85. This difference was not statistically significant (p = 0.11).


Total Synthesis of an Immunogenic Trehalose Phospholipid from Salmonella Typhi and Elucidation of Its sn-Regiochemistry by Mass Spectrometry.
Diphosphatidyltrehalose (diPT) is an immunogenic glycolipid, recently isolated from Salmonella Typhi. Despite rigorous structure elucidation, the sn-position of the acyl chains on the glycerol backbone had not been unequivocally established. A stereoselective synthesis of diPT and its regioisomer is reported herein. Using a hybrid MS3 approach combining collisional dissociation and ultraviolet photodissociation mass spectrometry for analysis of the regioisomers and natural diPT, the regiochemistry of the acyl chains of this abundant immunostimulatory glycolipid was established.


Choristoma: A rare congenital tumor of the tongue.
Most congenital masses of the mouth floor are cystic, irrespective of their origin. They may obstruct airway or digestive tract or may present other complications. Recognizing and treating these masses expeditiously is imperative. Choristoma is a mass of normal tissue in an abnormal location; they are classified according to the predominant epithelial lining. Few cases have been reported lined with gastric and respiratory epithelia within the same cyst. This case report presents a 5-month-old boy with an infected choristoma involving the floor of the mouth and its successful management.


Development and application of oncolytic viruses as the nemesis of tumor cells.
Viruses and tumors are two pathologies that negatively impact human health, but what occurs when a virus encounters a tumor? A global consensus among cancer patients suggests that surgical resection, chemotherapy, radiotherapy, and other methods are the primary means to combat cancer. However, with the innovation and development of biomedical technology, tumor biotherapy (immunotherapy, molecular targeted therapy, gene therapy, oncolytic virus therapy, etc.) has emerged as an alternative treatment for malignant tumors. Oncolytic viruses possess numerous anti-tumor properties, such as directly lysing tumor cells, activating anti-tumor immune responses, and improving the tumor microenvironment. Compared to traditional immunotherapy, oncolytic virus therapy offers advantages including high killing efficiency, precise targeting, and minimal side effects. Although oncolytic virus (OV) therapy was introduced as a novel approach to tumor treatment in the 19th century, its efficacy was suboptimal, limiting its widespread application. However, since the U.S. Food and Drug Administration (FDA) approved the first OV therapy drug, T-VEC, in 2015, interest in OV has grown significantly. In recent years, oncolytic virus therapy has shown increasingly promising application prospects and has become a major research focus in the field of cancer treatment. This article reviews the development, classification, and research progress of oncolytic viruses, as well as their mechanisms of action, therapeutic methods, and routes of administration.


Multi-year molecular quantification and 'omics analysis of Planktothrix-specific cyanophage sequences from Sandusky Bay, Lake Erie.
Planktothrix agardhii is a microcystin-producing cyanobacterium found in Sandusky Bay, a shallow and turbid embayment of Lake Erie. Previous work in other systems has indicated that cyanophages are an important natural control factor of harmful algal blooms. Currently, there are few cyanophages that are known to infect P. agardhii, with the best-known being PaV-LD, a tail-less cyanophage isolated from Lake Donghu, China. Presented here is a molecular characterization of Planktothrix specific cyanophages in Sandusky Bay. Putative Planktothrix-specific viral sequences from metagenomic data from the bay in 2013, 2018, and 2019 were identified by two approaches: homology to known phage PaV-LD, or through matching CRISPR spacer sequences with Planktothrix host genomes. Several contigs were identified as having viral signatures, either related to PaV-LD or potentially novel sequences. Transcriptomic data from 2015, 2018, and 2019 were also employed for the further identification of cyanophages, as well as gene expression of select viral sequences. Finally, viral quantification was tested using qPCR in 2015-2019 for PaV-LD like cyanophages to identify the relationship between presence and gene expression of these cyanophages. Notably, while PaV-LD like cyanophages were in high abundance over the course of multiple years (qPCR), transcriptomic analysis revealed only low levels of viral gene expression. This work aims to provide a broader understanding of Planktothrix cyanophage diversity with the goals of teasing apart the role of cyanophages in the control and regulation of harmful algal blooms and designing monitoring methodology for potential toxin-releasing lysis events.


Superficial bladder cancer: part 1. Update on etiology, classification and natural history.
Superficial 'nonmuscle-invasive' bladder tumors represent a heterogeneous group of cancers, which include those that are papillary in nature and limited to the mucosa (Ta), high grade, flat and confined to the epithelium (Tis) and those that invade the submucosa or lamina propria (T1). The natural history of these bladder cancers is that of disease recurrence and progression to higher grade and stage. Furthermore, recurrence and progression rates of superficial bladder cancer vary according to several tumor characteristics. The goal in the treatment of superficial bladder cancer is twofold: reducing tumor recurrence and the subsequent need for additional therapies, such as cystoscopy, transurethral resections, intravesical therapy and the morbidity associated with these treatments; and preventing tumor progression and the subsequent need for more aggressive therapy, such as radical cystectomy. The administration of intravesical chemotherapy and immunotherapy has become an important component in accomplishing these goals. This update is the first part of two articles reviewing important contemporary concepts in the etiology, classification and natural history of superficial bladder cancer, while part II of the series will review and highlight important aspects in management of superficial bladder cancer.


Oligosubstituted pyrroles directly from substituted methyl isocyanides and acetylenes.
The formal cycloaddition of alpha-metallated methyl isocyanides 1 onto the triple bond of electron-deficient acetylenes 2 represents a direct and convenient approach to oligosubstituted pyrroles 3. The scope and limitations of this reaction (24 examples, 25-97% yield) are reported along with an optimization of the reaction conditions and a rationalization of the mechanism. In addition, a related newly developed Cu(I)-mediated synthesis of 2,3-disubstituted pyrroles by the reaction of copper acetylides derived from unactivated terminal alkynes with substituted methyl isocyanides is described (11 examples, 5-88% yield).


Natural Products Containing a Nitrogen-Sulfur Bond.
Only about 100 natural products are known to contain a nitrogen-sulfur (N-S) bond. This review thoroughly categorizes N-S bond-containing compounds by structural class. Information on biological source, biological activity, and biosynthesis is included, if known. We also review the role of N-S bond functional groups as post-translational modifications of amino acids in proteins and peptides, emphasizing their role in the metabolism of the cell.


Role of endoscopy in the diagnosis of aneurysm-duodenal fistula.
Aneurysms complicated by enteric fistulae are uniformly fatal clinical conditions and therefore should be placed high on the list of possible diagnoses in any patient with aneurysmal disease and gastrointestinal bleeding. A number of different diagnostic techniques have been proposed, but most of them are usually of little help or even misleading. Between May 2000 and April 2002, endoscopy was performed in 290 consecutive patients with upper gastrointestinal bleeding. We retrospectively evaluated that endoscopy may provide an important diagnostic clue in aneurysm-enteric fistulae. Three patients with gastrointestinal bleeding presented with aneurysmal disease complicated by duodenal fistula formation. Two patients presented with aortoduodenal fistula, and the last one hepatic artery aneurysm with duodenal fistula formation. In all of our cases, endoscopic findings were suggestive and helpful for the preoperative diagnosis. Considering that prompt aggressive surgical intervention is mandatory for survival and more than 90% of aneurysmal disease with duodenal fistula formation should be within range of the endoscopists, aggressive and thorough endoscopy with a high index of clinical suspicion seems to be the most important diagnostic test in these difficult cases.


Cost-effectiveness of supported self-management for CFS/ME patients in primary care.
Nurse led self-help treatments for people with chronic fatigue syndrome/myalgic encephalitis (CFS/ME) have been shown to be effective in reducing fatigue but their cost-effectiveness is unknown. Cost-effectiveness analysis conducted alongside a single blind randomised controlled trial comparing pragmatic rehabilitation (PR) and supportive listening (SL) delivered by primary care nurses, and treatment as usual (TAU) delivered by the general practitioner (GP) in North West England. A within trial analysis was conducted comparing the costs and quality adjusted life years (QALYs) measured within the time frame of the trial. 296 patients aged 18 and over with CFS/ME diagnosed using the Oxford criteria were included in the cost-effectiveness analysis. Treatment as usual is less expensive and leads to better patient outcomes compared with Supportive Listening. Treatment as usual is also less expensive than Pragmatic Rehabilitation. PR was effective at reducing fatigue in the short term, but the impact of the intervention on QALYs was uncertain. However, based on the results of this trial, PR is unlikely to be cost-effective in this patient population. This analysis does not support the introduction of SL. Any benefits generated by PR are unlikely to be of sufficient magnitude to warrant recommending PR for this patient group on cost-effectiveness grounds alone. However, dissatisfaction with current treatment options means simply continuing with 'treatment as usual' in primary care is unlikely to be acceptable to patients and practitioners. The trial registration number is IRCTN74156610.


Promoting consumer participation through the implementation of a consumer academic position.
Consumer participation in mental health care is increasingly becoming an expectation. A review of the literature suggests that the negative attitudes of mental health professionals towards people diagnosed with mental illness constitutes a significant barrier to the realization of this goal. The education of health professionals has been identified as a major strategy for reducing the negatively of such attitudes, and to promoting a more participatory relationship between consumer and provider. This paper describes the process of the development and implementation of an academic role for a consumer of mental health services in teaching psychiatric nursing students. A personal case study by the consumer academic is provided to illustrate the process of this collaborative venture. This paper contributes to the development of framework to guide the implementation of similar positions.


Regeneration of aged vocal fold: first human case treated with fibroblast growth factor.
Aged vocal folds are characterized by atrophy of the mucosa, which causes dysphonia and is difficult to treat. We have revealed a therapeutic potential of basic fibroblast growth factor (bFGF) for tissue regeneration of the aged vocal fold. We report here the first human case that has been treated with bFGF. Institutional review board approved clinical human trial. A 63-year-old man with atrophied vocal folds was treated by local injection of 10 muicrog of bFGF into the left vocal fold under topical anesthesia. The effects of the injection were examined after 1 to 3 months by videostroboscopy, acoustic and aerodynamic measurements. The atrophy of the vocal fold was improved at 1 week after the injection and glottic gap disappeared. Aerodynamic and acoustic parameters also showed remarkable improvement. These positive effects were maintained up to 3 months. The first case with aged vocal folds treated with bFGF administration is presented. The results are encouraging, suggesting therapeutic effects of bFGF for atrophied vocal folds in human.


A novel modular approach to triazole-functionalized phthalocyanines using click chemistry.
A novel, elegant, and significantly improved protocol for the synthesis of a protected octaacetylene phthalocyanine is described. Inexpensive, mild, and environmentally benign iodination of 1,2-dibromobenzene and subsequent optimized chemoselective palladium-catalyzed cyanation are employed to effectively build up the key intermediate 4,5-dibromophthalonitrile in two steps. Introduction of the tert-butyldimethylsilyl-protected acetylene moieties via a Sonogashira cross-coupling provides the desired phthalonitrile precursor that, after cyclization, yielded the protected octaacetylene phthalocyanine. Subsequently, in situ deprotection and "clicking" are employed as a highly efficient and quantitative route to a novel class of octatriazole-functionalized phthalocyanines. The ability of such triazole-derived phthalocyanines to form well-defined supramolecular structures upon doping with zinc(II) triflate is demonstrated.


Porous Ion Gel: A Versatile Ionotronic Sensory Platform for High-Performance, Wearable Ionoskins with Electrical and Optical Dual Output.
The development of elastic ionic conductors offers opportunities to fabricate key wearable ionic components such as ionoskins that can perceive mechanical deformation. However, there is still plenty of room to overcome the trade-off between sensitivity and detectable range of previous systems and impart additional functionality. Here, we propose porous ion gels for high-performance, functional ionic sensory platforms. The porous ion gels can be effectively deformed by closing pores even with a small pressure, and a large change in the contact area of the gel and the electrode is induced, leading to a significant difference in electrical double-layer capacitance. The porous ion gels are applied to ionoskins after optimizing mechanical characteristics by adjusting gel parameters. The device indicates a high sensitivity of ∼152.8 kPa-1, a broad sensory pressure range (up to 400 kPa), and excellent durability (>6000 cycles). Successful monitoring of various human motions that induce different magnitudes of pressure is demonstrated with high precision. More interestingly, the functionality of the porous ion gel is extended to include electrochemiluminescence (ECL), resulting in the production of emissive ECL ionoskins. The ECL intensity from the emissive ionoskin is linearly correlated with the applied pressure, which can even be inferred even by the naked eye. The porous ion gel-based functional ionoskins are expected to be key components in future sensory ionotronics.


The retrourethral transobturator sling suspension in the treatment of male urinary stress incontinence: results of a single institution experience.
Objective. To evaluate functional outcome of the retrourethral transobturator sling suspension (RTS) in the treatment of stress urinary incontinence (SUI) caused by prior prostate surgery. Methods. The RTS (AdVance male sling) was implanted in 32 patients who suffered from mild to severe postsurgical-treatment incontinence at the University Hospital Ulm from September 2010 to September 2011 including 10 patients with prior radiation therapy. Functional data (uroflowmetry, daily pad use, and postvoid residual urine) as well as quality of life with impact of urinary problems (ICIQ-UI SF) were prospectively assessed at baseline and during followup. Results. After a median followup of 9 months (range, 3-14) the incontinence cure rate (no pad usage) was 56.2% and the improvement rate (1-2 pads/day or ≥50% reduction) was 21.9%. No improvement was observed in 21.9%. Daily pad use and ICIQ-UI SF score improved significantly. No major perioperative complications occurred. Postoperatively, 15.6% of the patients exhibited transient acute urinary retention which resolved without further treatment after a maximum of 3 weeks. One patient underwent sling explantation due to dislocation and persistent perineal pain. Conclusions. The implantation of the RTS is a safe and effective procedure in selected patients with SUI resulting from prostate surgery.


Contrast-enhanced magnetic resonance angiography in peripheral arterial disease: improving image quality by automated image registration.
In peripheral arterial disease, contrast-enhanced MR angiography (MRA) is a noninvasive imaging alternative for catheter-based digital subtraction angiography (DSA). In DSA, final images are generated by subtracting a native mask image from subsequent contrast-enhanced images. Image quality is routinely improved by digitally shifting the mask image prior to subtraction if the patient has moved during angiography. This study investigated whether such image registration may also help to improve the image quality of MRA. In all, 545 MRA examinations of pelvic and leg arteries in patients with symptoms of peripheral arterial disease were studied retrospectively. Standard nonregistered MRA was compared to automatically linear, affine, and warp registered MRA by visual analysis and by three image quality parameters, including vessel detection probability (VDP) of angiographic maximum intensity projections. Most MRA of pelvic and upper leg arteries showed good nonregistered image quality. However, the 15% of lower legs with a body shift of 1 mm or more had relatively low nonregistered image quality, which improved significantly with image registration (VDP gain more than 18%, P < 0.05). The visual analysis gave similar results. In conclusion, image registration can improve image quality of MRA in peripheral arterial disease, especially in the lower legs.


Sleep problems and temperament in young children with Down syndrome and typically developing controls.
Although group differences have been found between children with Down syndrome (DS) and typically developing (TD) children when considering sleep problems and temperament independently, none of the research conducted to date has examined sleep-temperament associations in children with DS. The present research was conducted to determine (1) whether the sleep problems experienced by children with DS are associated with temperament or (2) if the demonstrated relations between sleep and temperament differ from those that are observed in TD children. The present study included examination of relations between parent-reported sleep problems and temperament in 19 children with DS and 20 TD controls matched on developmental age. The results revealed group differences in temperament and sleep problems. Mediation models indicated that temperament (effortful control and inhibitory control) mediated the association between group and sleep problems; sleep problems also mediated the association between group and temperament (effortful and inhibitory control). Findings indicated that sleep problems may serve as both cause and consequence of variability in effortful and inhibitory control and provide insight as to future experimental studies that should be conducted to better elucidate these relations.


Hyponatremia and the brain.
Hyponatremia is a frequently encountered condition that requires careful management to avoid both complications of prolonged severe hyponatremia and life-threatening brain damage resulting from too-rapid correction of the problem. Treatment before the condition becomes severe is the aim. Correction should be carried out as slowly as the clinical condition will allow; serum sodium should not be increased more than 12 mEq per L (12 mmol/per L) per day. Too-rapid correction may lead to demyelination syndromes.


The case of botulinum toxin in milk: experimental data.
Botulinum neurotoxin (BoNT) is the most toxic substance known to man and the causative agent of botulism. Due to its high toxicity and the availability of the producing organism Clostridium botulinum, BoNT is regarded as a potential biological warfare agent. Because of the mild pasteurization process, as well as rapid product distribution and consumption, the milk supply chain has long been considered a potential target of a bioterrorist attack. Since, to our knowledge, no empirical data on the inactivation of BoNT in milk during pasteurization are available at this time, we investigated the activities of BoNT type A (BoNT/A) and BoNT/B, as well as their respective complexes, during a laboratory-scale pasteurization process. When we monitored milk alkaline phosphatase activity, which is an industry-accepted parameter of successfully completed pasteurization, our method proved comparable to the industrial process. After heating raw milk spiked with a set amount of BoNT/A or BoNT/B or one of their respective complexes, the structural integrity of the toxin was determined by enzyme-linked immunosorbent assay (ELISA) and its functional activity by mouse bioassay. We demonstrated that standard pasteurization at 72 degrees C for 15 s inactivates at least 99.99% of BoNT/A and BoNT/B and at least 99.5% of their respective complexes. Our results suggest that if BoNTs or their complexes were deliberately released into the milk supply chain, standard pasteurization conditions would reduce their activity much more dramatically than originally anticipated and thus lower the threat level of the widely discussed "BoNT in milk" scenario.


Scanning of own- versus other-race faces in infants from racially diverse or homogenous communities.
We examined the role of community face experience on 6- and 8-month-old Caucasian infants' scanning of own- and other-race face scanning. We measured infants' proportional fixation time and scan path amplitudes as indices of face processing. Proportional fixation time to informationally rich face regions varied as a function of age and face race for infants living in a racially homogeneous community, whereas scan path amplitudes varied as a function of age and face race for infants living in a racially diverse community. In both communities 6-month-old infants did not show different responding to own- and other-race faces, whereas 8-month-old infants responded differently to own- and other-race faces. However, 8-month-old infants from the two communities showed different patterns of cross-race face scanning. Therefore, experience in the community beyond the home appears to contribute to the development of differential scanning of own- versus other-race faces between 6 and 8 months of age.


Fatal winter dysentery with severe anemia in an adult cow.
An adult dairy cow fatally affected with winter dysentery was investigated pathologically and virologically. The cow had severe anemia and diarrhea with massive blood. Pathologically, the loss of surface epithelial cells and necrosis of crypt epithelial cells in the large intestine were observed. Bovine coronavirus (BCV) antigen was observed in necrotic crypt epithelial cells of the large intestine. Virus particles were found in the necrotic epithelial cells of the large intestine. Virologically, BCV was isolated from the feces of the dead cow. The dead cow had no serum antibody against BCV although the co-habitants did. These suggest that severe infection of BCV in the cow without the BCV antibody accompanied by severe hemorrhagic anemia resulted in the cow's death.


Studies of the behaviour of allogeneic cancellous bone grafts in inbred rats.
The degree of new bone formation in isografts and allografts has been assessed by a radiotracer technique. Allografts used have been either H-1-identical or H-1-disparate with the recipient. It was found that new bone formation is curtailed within the first 3 weeks after grafting. This curtailment was significantly greater in those donor-recipient combinations which were H-1-identical but disparate for many weak locus antigens than those in which H-1 disparity existed with only a few minor locus differences. There was no late phase (i.e., host-derived) osteogenesis in the combination with H-1 identity, but multiple minor antigen disparities. In isografts and H-1-disparate grafts significant late phase osteogenesis was found in about 30% of recipients. Resorption of the graft was found to be significantly impaired in both H-1-identical and disparate grafts in comparison with isografts. There was a significant negative correlation between weight of the graft and degree of osteogenesis in isografts during the first 2 weeks after grafting, and also during the later phase (6-8 weeks). A similar negative correlation was found during the late phase in H-1-disparate grafts with few minor antigen disparities, but no correlation was found at any time in H-1-identical grafts with multiple minor antigen disparities.


Mycotoxin production by Fusarium avenaceum strains isolated from Norwegian grain and the cytotoxicity of rice culture extracts to porcine kidney epithelial cells.
The secondary metabolites of 24 isolates of Fusarium avenaceum from Norwegian cereals and grown on rice have been characterized. Moniliformin (MON), enniatins (ENNs), and beauvericin (BEA) were analyzed by high-performance liquid chromatography. Porcine kidney epithelial cells (PK15, American Type Culture Collection) were used to study the cytotoxicity of MON in the extracts. The following metabolites were produced by all isolates, ranked by concentration in rice cultures: ENN-B, MON, ENN-B1, and ENN-A. BEA was produced by eight isolates. The productions of BEA and ENN-A were significantly correlated, as was the case with ENN-B and ENN-B1. MON production was correlated neither to any of the other toxins nor to toxicity.


Narratives of development, experiences of risk: adult women's perspectives on relationships and safer sex.
Mid-life women are increasingly at risk for HIV/AIDS, yet relatively few studies have targeted this age group. In this study, we explored views of relationships and safer sex practices among eight well-educated, single, heterosexual adult women through in-depth interviews and supplemental questionnaires. The women viewed themselves as competent, responsible, and mature in terms of their relationship and sexual choices. However, their actual sexual practices, and reasons given for these practices, were similar to those of adolescents and of inner-city women living in high-risk environments. Findings are significant in highlighting the power and importance of relationship factors, especially trust, as these relate to safer sex practices and prevention initiatives.


Is bruxism a disorder or a behaviour? Rethinking the international consensus on defining and grading of bruxism.
Inspired by the international consensus on defining and grading of bruxism (Lobbezoo F, Ahlberg J, Glaros AG, Kato T, Koyano K, Lavigne GJ et al. J Oral Rehabil. 2013;40:2), this commentary examines its contribution and underlying assumptions for defining sleep bruxism (SB). The consensus' parsimonious redefinition of bruxism as a behaviour is an advance, but we explore an implied question: might SB be more than behaviour? Behaviours do not inherently require clinical treatment, making the consensus-proposed 'diagnostic grading system' inappropriate. However, diagnostic grading might be useful, if SB were considered a disorder. Therefore, to fully appreciate the contribution of the consensus statement, we first consider standards and evidence for determining whether SB is a disorder characterised by harmful dysfunction or a risk factor increasing probability of a disorder. Second, the strengths and weaknesses of the consensus statement's proposed 'diagnostic grading system' are examined. The strongest evidence-to-date does not support SB as disorder as implied by 'diagnosis'. Behaviour alone is not diagnosed; disorders are. Considered even as a grading system of behaviour, the proposed system is weakened by poor sensitivity of self-report for direct polysomnographic (PSG)-classified SB and poor associations between clinical judgments of SB and portable PSG; reliance on dichotomised reports; and failure to consider SB behaviour on a continuum, measurable and definable through valid behavioural observation. To date, evidence for validity of self-report or clinician report in placing SB behaviour on a continuum is lacking, raising concerns about their potential utility in any bruxism behavioural grading system, and handicapping future study of whether SB may be a useful risk factor for, or itself a disorder requiring treatment.


Effect of environmental factors on the germination and emergence of Salvia verbenaca L. cultivars (verbenaca and vernalis): An invasive species in semi-arid and arid rangeland regions.
Salvia verbenaca (wild sage) is a commonly cultivated herbal medicine plant, which is native to the Mediterranean climate regions of Europe, Africa, Asia and the Middle East. However, it has become an invasive species in semi-arid and arid regions of southern Australia. Two varieties are present in this region, var. verbenaca and var. vernalis, each of which can be distinguished by differences in morphology and flowering period. Following trials to determine the optimum temperate regime for germination and response to light and dark, seeds of both varieties were tested for their response to variations in pH, moisture stress, salinity, and burial depth. The temperature and light trial was carried out using three different temperature regimes; 30/20°C, 25/15°C and 20/12°C, and two light regimes; 12 hours light/12 hours dark and 24 hours dark, with var. vernalis responding to relatively higher temperatures than var. verbenaca. The germination rate of neither species was significantly inhibited by complete darkness when compared to rates under periodic light exposure. Both varieties germinated at near optimum rates strongly to very strongly in all pH buffer solutions, from pH 5 to pH 10, but they responded most strongly at neutral pH. Var. vernalis showed slightly more tolerance to reduced moisture availability, moderate to strong salinity, and burial depth, compared to var. verbenaca. However, even a fairly shallow burial depth of 2 cm completely inhibited germination of both varieties. Thus, in circumstances where both varieties are present in a soil seedbank, var. vernalis could be expected to establish in more challenging conditions, where moisture is limited and salinity is 'moderate to high', implying that it is a more serious threat for invasive weed in conditions where crop plants are already challenged.


Proteomic analysis identified DJ-1 as a cisplatin resistant marker in non-small cell lung cancer.
The aim of study is to identify cisplatin-resistance associated biomarkers for non-small cell lung cancers (NSCLC). We use two-dimensional electrophoresis (2-DE) combined with MALDI-TOF mass spectrometry to compare the proteome between lung cancer cell line A549 and its cisplatin-resistant subline A549/DDP. Nine cisplatin resistance-related proteins were identified, and DJ-1, one of the differently expressed proteins, was selected for further validation and evaluation. Immunohistochemical results demonstrated that high expression level of DJ-1 was associated with cisplatin resistance and a predictor for poor prognosis in 67 locally advanced NSCLC patients. Furthermore, in vitro results showed that silencing DJ-1 increased the proliferation inhibitory effect of cisplatin to A549/DDP cells. In conclusion, DJ-1 might play an important role in the resistibility to cisplatin, and it could also act as a novel candidate biomarker for predicting the response of NSCLC patients to cisplatin-based chemotherapy.


Management of dengue with co-infections: an updated narrative review.
Dengue is a life-threatening mosquito borne viral disease. We are still in the era of supportive treatment where morbidity and mortality are a major concern. Dengue infection in presence of other co-infections makes this scenario rather worse. Timely recognition and raising alarm to be intensive is the need of the hour for primary care physicians practicing in the community and indoors. This review provides a comprehensive knowledge about the recent trends of coinfection in dengue as well as their management consideration which will be particularly helpful for physicians practicing in rural and remote areas of India.


Mitochondria-dependent apoptosis induced by nanoscale hydroxyapatite in human gastric cancer SGC-7901 cells.
Nanoscale hydroxyapatite (nano-HAP) has been reported to exhibit anti-cancer effect on several human cancers, but the molecular mechanism of which remains unclear. The aim of this study was to explore the mechanisms by investigating the effects of nano-HAP on human gastric cancer SGC-7901 cells. Our results showed that nano-HAP significantly reduced cell viability, and induced apoptosis in SGC-7901 cells characterized by hypodiploid DNA contents, morphological changes and DNA fragmentation. The increase in apoptosis was accompanied with the increased expression of Bax, a pro-apoptotic protein, and decreased expression of Bcl-2, an anti-apoptotic protein, the decrease of mitochondrial membrane potential and the release of cytochrome c from mitochondria into cytosol. Furthermore, the activation of caspases-3, and -9, but not activation of caspases-8 was induced by nano-HAP. Z-VAD-fmk, a universal caspase inhibitor, dose-dependently inhibited nano-HAP-induced apoptosis. This study demonstrates that nano-HAP inhibits the proliferation of SGC-7901 cells by inducing apoptosis, and the apoptotic pathway of nano-HAP-induced apoptosis is mediated through the mitochondrial-dependent and caspase-dependent pathway.


Involvement of the serotonin system in L-dopa-induced dyskinesias.
The ability of L-dopa to relieve the motor impairments in Parkinson's disease patients declines over time, and side-effects, such as dyskinesias, appear--limiting the use of the drug in the advanced stage of the disease. Serotonergic neurons are able to convert L-dopa to dopamine and to store this neurotransmitter in synaptic vesicles. This peculiarity might be very important in the advanced disease, when most of the dopaminergic neurons have degenerated. Indeed, an increasing body of evidence points to dopamine released as a false neurotransmitter from the serotonin terminals as the main pre-synaptic determinant of L-dopa-induced dyskinesias in animal models of Parkinson's disease. These findings make the serotonin system an intriguing target for anti-dyskinetic therapies.


Effects of various collagen crosslinking techniques on mechanical properties of collagen film.
We examined the relationship between collagen crosslinking techniques and dentinum reinforcement. In the present study, the tensile tests, imbibition test and antienzyme test were performed on collagen films mainly composed of type I collagen after ultraviolet irradiation and immersion in tannic acid and glutaraldehyde. The elastic modulus increased with the reaction time, but reduction of elongation at breaking point and increased stiffness were observed. This tendency was enhanced by ultraviolet irradiation. Tannic acid treatment resulted in slower crosslinking than the other two techniques. Antienzyme activity was markedly increased by treatment with tannic acid and glutaraldehyde.


Bifidobacterium breve prevents necrotising enterocolitis by suppressing inflammatory responses in a preterm rat model.
Necrotising enterocolitis (NEC) is associated with inflammatory responses and barrier dysfunction in the gut. In this study, we investigated the effect of Bifidobacterium breve M-16V on factors related to NEC development using an experimental rat model. Caesarean-sectioned rats were given formula milk with or without B. breve M-16V by oral gavage thrice daily, and experimental NEC was induced by exposing the rats to hypoxic conditions. Naturally delivered rats that were reared by their mother were used as healthy controls. The pathological score of NEC and the expression of molecules related to inflammatory responses and the barrier function were assessed in the ileum. B. breve M-16V reduced the pathological scores of NEC and resulted in some improvement in survivability. B. breve M-16V suppressed the increased expression of molecules related to inflammation and barrier function that resulted from NEC induction. B. breve M-16V normalised Toll-like receptor (TRL)4 expression and enhanced TLR2 expression. Our data suggest that B. breve M-16V prevents NEC development by modulating TLR expressions and suppressing inflammatory responses in a rat model.


Digital radiology using active matrix readout of amorphous selenium: detectors with high voltage protection.
A flat-panel x-ray imaging detector is being investigated for digital radiography and fluoroscopy. The detector uses a layer of amorphous selenium (a-Se) to convert x rays to a charge image, which is then electronically read out with a two-dimensional array of thin film transistors (TFTs). In order to sensitize the a-Se layer to x rays, a high voltage (of the order of several thousand volts) is applied to its top surface. The TFTs, which are at the bottom surface of the a-Se layer, are not subjected to any high voltage under normal radiological operational conditions since the pixel potential is < 10 V. However under a fault condition where these two events occur simultaneously: (1) suspended detector scan; and (2) an x-ray exposure more than ten times higher than normal, the voltage on the TFTs could rise to a damaging value. This paper describes a method for protecting the TFTs from high voltage damage under this fault condition. It employs a dual-gate TFT structure, one gate is for scanning control and the other is connected to the pixel electrode for high voltage protection. Before the pixel potential reaches a damaging value, the protection gate turns on the TFT automatically and drains excess charge away from the pixel thus providing a safe pixel saturation potential. In this paper, the characteristic curves of dual-gate TFTs are studied both theoretically and experimentally. The pixel x-ray response for imaging detectors with high voltage protection are predicted, and it is shown that with practical TFT designs the detector can provide a safe pixel saturation potential as well as satisfy the dynamic range required for diagnostic x-ray imaging applications.


BRCA1 185delAG truncation protein, BRAt, amplifies caspase-mediated apoptosis in ovarian cells.
Breast and ovarian cancer patients with germline mutations in BRCA1 respond more favorably to initial chemotherapy. We previously reported that cells from women carrying the BRCA1 185delAG founder mutation undergo an enhanced caspase-3-mediated apoptotic response. Here, we report on the transient and stable transfection of cDNA coding for the putative truncated protein product of the BRCA1 185delAG mutant gene into BRCA1 wild-type human ovarian surface epithelial cells and ovarian cancer cells, resulting in cells with a heterozygous background containing two BRCA1 wild-type alleles and the BRCA1 185delAG transcript. The BRCA1 185delAG truncation (BRAt) protein did not alter epithelial cell morphology or induce tumorigenesis. However, upon treatment with staurosporine, BRAt cells showed increased levels of active caspase-3 and increased cleavage of caspase-3 substrates, PARP and DFF45. Additionally, XIAP and cIAP-1 protein are at reduced levels in untreated BRAt cells as compared to control cells. BRAt also reduced levels of phosphorylated Akt and overexpression of activated Akt in BRAt cells restored caspase-3 activity to that seen in wild-type cells. Further, BRAt expression increased chemosensitivity in platinum-resistant ovarian cancer cells. Taken together, our data demonstrate that truncated proteins arising from BRCA1 185delAG mutation increase Akt-mediated apoptosis, suggesting a possible mechanism by which ovarian cancer patients with this germline BRCA1 mutation may respond better to initial chemotherapy.


A Synthetically Tunable System To Control MLCT Excited-State Lifetimes and Spin States in Iron(II) Polypyridines.
2,2':6',2″-Terpyridyl (tpy) ligands modified by fluorine (dftpy), chlorine (dctpy), or bromine (dbtpy) substitution at the 6- and 6″-positions are used to synthesize a series of bis-homoleptic Fe(II) complexes. Two of these species, [Fe(dctpy)2]2+ and [Fe(dbtpy)2]2+, which incorporate the larger dctpy and dbtpy ligands, assume a high-spin quintet ground state due to substituent-induced intramolecular strain. The smaller fluorine atoms in [Fe(dftpy)2]2+ enable spin crossover with a T1/2 of 220 K and a mixture of low-spin (singlet) and high-spin (quintet) populations at room temperature. Taking advantage of this equilibrium, dynamics originating from either the singlet or quintet manifold can be explored using variable wavelength laser excitation. Pumping at 530 nm leads to ultrafast nonradiative relaxation from the singlet metal-to-ligand charge transfer (1MLCT) excited state into a quintet metal centered state (5MC) as has been observed for prototypical low-spin Fe(II) polypyridine complexes such as [Fe(tpy)2]2+. On the other hand, pumping at 400 nm excites the molecule into the quintet manifold (5MLCT ← 5MC) and leads to the observation of a greatly increased MLCT lifetime of 14.0 ps. Importantly, this measurement enables an exploration of how the lifetime of the 5MLCT (or 7MLCT, in the event of intersystem crossing) responds to the structural modifications of the series as a whole. We find that increasing the amount of steric strain serves to extend the lifetime of the 5,7MLCT from 14.0 ps for [Fe(dftpy)2]2+ to the largest known value at 17.4 ps for [Fe(dbtpy)2]2+. These data support the design hypothesis wherein interligand steric interactions are employed to limit conformational dynamics and/or alter relative state energies, thereby slowing nonradiative loss of charge-transfer energy.


[Immunotoxicology].
The aim of the present paper is to inform Polish occupational physicians about a new medical discipline called immunotoxicology which developed during last decades. The importance of immunotoxicology resides in the fact that examinations performed on its basis make it possible to understand some toxic mechanisms which could not have been explained so far studying biochemical disorders. Immunotoxicology is regarded as an extension of toxicology. According to the principles of immunology, organism's reactions to xenobiotics action depends on the mechanisms regulating immunological system, i.e. on its activity or suppression. Considering the present scientific achievements, it can be said that both these states are related to disregulation of homeostatic mechanisms. Owing to the informative nature of this paper, many examples of immunological reactions were adopted from the relatively rich world literature. Readers who are interested in more comprehensive information may refer to source literature.


TI-I-174, a Synthetic Chalcone Derivative, Suppresses Nitric Oxide Production in Murine Macrophages via Heme Oxygenase-1 Induction and Inhibition of AP-1.
Chalcones (1,3-diaryl-2-propen-1-ones), a flavonoid subfamily, are widely known for their anti-inflammatory properties. Propenone moiety in chalcones is known to play an important role in generating biological responses by chalcones. In the present study, we synthesized chalcone derivatives structurally modified in propenone moiety and examined inhibitory effect on nitric oxide (NO) production and its potential mechanisms. Among the chalcone derivatives used for this study, TI-I-174 (3-(2-Hydroxyphenyl)-1-(thiophen-3-yl)prop-2-en-1-one) most potently inhibited lipopolysaccharide (LPS)-stimulated nitrite production in RAW 264.7 macrophages. TI-I-174 treatment also markedly inhibited inducible nitric oxide synthase (iNOS) expression. However, TI-I-174 did not significantly affect production of IL-6, cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α), implying that TI-I-174 inhibits production of inflammatory mediators in a selective manner. Treatment of macrophages with TI-I-174 significantly inhibited transcriptional activity of activator protein-1 (AP-1) as determined by luciferase reporter gene assay, whereas nuclear factor-κB (NF-κB) activity was not affected by TI-I-1744. In addition, TI-I-174 significantly inhibited activation of c-Jun-N-Terminal kinase (JNK) without affecting ERK1/2 and p38MAPK, indicating that down-regulation of iNOS gene expression by TI-I-174 is mainly attributed by blockade of JNK/AP-1 activation. We also demonstrated that TI-I-174 treatment led to an increase in heme oxygenase-1 (HO-1) expression both at mRNA and protein level. Transfection of siRNA targeting HO-1 reversed TI-I-174-mediated inhibition of nitrite production. Taken together, these results indicate that TI-I-174 suppresses NO production in LPS-stimulated RAW 264.7 macrophages via induction of HO-1 and blockade of AP-1 activation.


Relatedness among penicillin-binding protein 2b genes of Streptococcus mitis, Streptococcus oralis, and Streptococcus pneumoniae.
Penicillin-binding protein (PBP) 2b similarities among Streptococcus mitis, S. oralis, and S. pneumoniae using DNA fingerprinting and sequencing were investigated. The polymerase chain reaction (PCR) was performed on 41 penicillin-susceptible and -resistant clinical isolates of S. mitis and S. oralis using the susceptible S. pneumoniae R6 PBP 2b primers. PCR products were then analyzed using Hinf I and Sty I restriction enzymes. Of 41 S. mitis/S. oralis isolates studied 15 strains produced a PCR product of a similar size to that of S. pneumoniae R6. On fingerprinting these 15 strains, 11 different patterns were seen using Sty I restriction enzyme and 12 different patterns with Hinf I. The PBP 2b genes of the S. mitis and S. oralis isolates studied were found to be very heterogenous. The PBP 2b genes of two S. mitis isolates, MICs 0.5 and 2 micrograms/ml, were sequenced. These PBP 2b genes were found to possess a mosaic structure when compared to those of other S. pneumoniae and viridans streptococcal species. Analysis of these mosaic blocks indicates that both S. mitis strains contain areas that originated from S. pneumoniae as well as regions of unknown origin. PBP 2b sequence comparisons of a susceptible S. oralis with reported sequences of S. pneumoniae R6 and S. mitis NCTC 10712 revealed what appears at this stage to be nucleotide regions unique to S. oralis. A penicillin-resistant S. oralis strain contained a pneumococcal region of 272 bp that was flanked by S. oralis sequences. These specific S. oralis regions have been located in PBP 2b genes of penicillin-resistant S. oralis and S. pneumoniae isolates described from Europe and South Africa.


Measurement of tissue factor activity in extracellular vesicles from human plasma samples.
Tissue factor (TF) is the cellular receptor for plasma factor (F) VII/FVIIa and triggers blood coagulation. Extracellular vesicles (EVs) are small membrane vesicles that are released from activated cells and tumor cells. Different cell types, including activated monocytes and tumors cells release TF-positive EVs into the circulation. We developed an assay to measure levels of TF activity in EVs isolated from human plasma samples. We and others have used this assay to demonstrate increased levels of EV TF activity in a variety of diseases associated with thrombosis, including cancer. These studies suggest that EV TF can be used as a biomarker of thrombotic risk. The strength of this laboratory assay is that it is relatively sensitive and specific. However, the limitations of the assay are that it is labor intensive and the coefficient of variation is too high for it to be used as a clinical assay.


[Hemangiopericytoma at the transverse sinus presenting with intracerebral hemorrhage: case report].
The authors report on a patient with hemangiopericytoma(HPC). This 43-year-old female presented severe headache, vomiting and right homonymous hemianopsia. Magnetic resonance imaging and an angiogram showed a tumor above the left transverse sinus. The patient underwent a total resection of the tumor and reconstruction of the transverse sinus without additional neurological deficits. Based on the findings shown in this case report, hemangiopericytoma should be included in the differential diagnosis from benign meningioma. Because this tumor often undergoes recurrences and metastases, we recommend a combination of radical surgical extirpation of followed by postoperative radiotherapy.


An evaluation of the function of new special equipment for transrectal ultrasonotomography.
A new type of equipment for transrectal ultrasonotomography was described in a previous paper. This equipment was evaluated from the data obtained from 205 cases in which examinations were performed. Tomograms were successfully recorded in 94% of cases. Tomograms sufficiently useful for diagnosis and the measurement of organs were obtained in 89% of cases for the prostate, 78% for the urinary bladder, and 80% for the seminal vesicles. No basic problems in the procedure were found, although hypotension of unknown origin was observed during the examination in a few cases.


Impact of Social Frailty on Alzheimer's Disease Onset: A 53-Month Longitudinal Cohort Study.
We investigated the association between social frailty and Alzheimer's disease (AD) incidence among community-dwelling older adults in Japan. A 53-month follow-up cohort study was conducted in Obu City, Japan. Participants comprised 3,720 community-dwelling older adults (mean age, 71.7 years; 48.4% men). The operational definition of social frailty comprised five items: going out infrequently, rarely visiting friends, feeling unhelpful to friends or family, living alone, and not always talking with someone each day. During follow-up, the cumulative AD incidence risk between socially robust, pre-frail, and frail groups was 4.1%, 5.5%, and 10.7%, respectively. In both crude (HR 2.72, 95% CI 1.90-3.89, p < 0.001) and adjusted Cox proportional hazards models (HR 1.53, 95% CI 1.03-2.28, p = 0.035), social frailty was associated with a significantly higher AD incidence risk. The present study revealed that social frailty is strongly associated with AD incidence among Japanese older adults. Further research should elucidate whether social frailty prevention is effective for decreasing AD risk.


Dipping procedure for blood glucose determination with Dextrostix and the Eyetone reflectance meter. Assessment of a practical technique.
A dipping procedure for blood glucose determination with the Dextrastix-Eyetone system has been evaluated. The procedure involves the immersion of the Dextrostix reagent area for 1 min in a tube of whole blood followed by wash, blotting and reading as in the regular procedure. Sixty-five blood samples, covering a wide glucose concentration range, were estimated for their glucose content in random order both by the dipping procedure and a conventional Dextrostix-Eyetone procedure. An almost perfect agreement between the two methods was found, the coefficient of correlation being 0.99 and the regression line very close to the ideal line. The presence of a Dextrostix reagent area in the blood was found to bring about glycolysis. Except at high blood glucose levels, this glycolysis, however, was insignificant if the strip was correctly removed after 1 min. The dipping procedure overcomes the main technical problem of conventional procedures: the inconsistency of the drop application on the reagent area. As it is easy to perform and a reliable alternative to conventional procedures, it is recommendable in all cases where blood samples are available.


The Delta Neutrophil Index as a predictive marker of histological chorioamnionitis in patients with preterm premature rupture of membranes: A retrospective study.
Histological chorioamnionitis (HCA) is related to perinatal morbidity. However, there is no definite diagnostic method for detecting chorioamnionitis before delivery. We evaluated whether the delta neutrophil index (DNI) was an effective early marker of HCA in patients with preterm premature rupture of membranes (PPROM). We retrospectively evaluated 149 women diagnosed with PPROM (gestational age, 20+0 to 36+6 weeks) at Severance Hospital from January 2013 to December 2014. The women were categorized into the following two groups: (a) PPROM without HCA and (b) PPROM with HCA. The maternal white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP) level, and DNI were measured at admission. The DNI has been reported to reflect the fraction of circulating immature granulocytes associated with infection. Of the 149 patients, 87 were included in the PPROM without HCA group and 62 were included in the PPROM with HCA group. The interval between admission and delivery was significantly shorter in the PPROM with HCA group than in the PPROM without HCA group. There was no significant difference in the maternal WBC count. The serum CRP level, NLR, and DNI were significantly lower in the PPROM without HCA group than in the PPROM with HCA group, while the lymphocyte count was significantly lower in the PPROM with HCA group than in the PPROM without HCA group. A predictive equation was generated by combining the DNI, lymphocyte count, and CRP level, and the sensitivity and specificity for predicting a placental inflammatory response were 69.1% and 70.5%, respectively. The DNI could be a predictive marker for HCA in patients with PPROM. Our predictive equation involving the DNI, lymphocyte count, and CRP level may be helpful for predicting the placental inflammatory response in patients with PPROM.


Congenital stationary night blindness and a "Schubert-Bornschein" type electrophysiology in a family with dominant inheritance.
To present the clinical, psychophysical, and electrophysiological characteristics of a family with dominantly inherited congenital stationary night blindness (CSNB). Five affected family members from three generations were ascertained. Four affected individuals underwent ophthalmic examination and electrodiagnostic investigations. Three affected individuals also underwent scanning laser ophthalmoscopy and psychophysical testing. Affected individuals reported night blindness from an early age. Visual acuities were normal. Fundal appearances were normal apart from one older patient showing areas of peripheral chorioretinal atrophy. Autofluorescence images showed no gross abnormality. International Society for Clinical Electrophysiology of Vision (ISCEV) standard electroretinography (ERG) showed undetectable rod specific responses and electronegative maximal responses, but normal ISCEV cone responses. Additional S-cone specific ERG recordings were of reduced amplitude in all patients studied. There was no apparent rod component to the dark adaptation curve. Central 30 degrees thresholds were normal under photopic conditions but showed increased thresholds under scotopic conditions for both red and blue stimuli. Results from investigation of this family are consistent with an impairment of rod photoreceptor signalling. The ERG findings suggest an abnormality occurring after phototransduction with rod and S-cone pathway involvement. These findings differ from those rare families reported previously with dominant CSNB.


Effects of Periodontal Ligament Cells on Alveolar Bone Metabolism under the Action of Force and Inflammatory Factors and Its Molecular Mechanisms.
Periodontal ligament may have independent response to orthodontic stimulation and thus initiate alveolar bone osteogenesis and osteoclasts. Orthodontic-induced alveolar bone remodeling has no bone loss,while inflammation can lead to alveolar bone loss,suggesting that force signal and inflammatory factors may induce the differentiation of undifferentiated cells in the periodontal ligament via different pathways. The strength of the force and the nature of the force (basal tension and fluid shear force) may affect the differentiation of periodontal ligament cells,and may produce antagonistic or synergistic effect with the inflammatory factors through complex autocrine and paracrine regulation,resulting in local bone reconstruction,which is manifested as bone deposition and bone absorption. Studies have shown that Wnt signaling is an important regulatory pathway for osteoblast differentiation. Inflammatory factors can block the differentiation of stem cells into osteoblasts. The Wnt pathway is closely related to the effects of force and inflammatory factors on the differentiation of periodontal ligament cells.


Isolation, short-term culture, and transplantation of small hepatocyte-like progenitor cells from retrorsine-exposed rats.
Complete liver regeneration after partial hepatectomy (PH) in rats treated with the pyrrolizidine alkaloid retrorsine can be accomplished through the activation, expansion, and differentiation of a novel population of small hepatocyte-like progenitor cells (SHPCs). These cells have not been isolated in pure form, established in primary culture, or transplanted into syngeneic rats to examine their differentiation potential. Primary liver cells enriched for SHPCs were prepared by differential centrifugation of primary liver cell dispersions from retrorsine-exposed rats 6-8 days and 13-15 days after PH. Isolated SHPCs were characterized for cell size, morphology, and expression of cell type-specific markers (including hepatocyte and bile duct-oval cell markers), and established in short-term primary culture. Isolated SHPCs were transplanted into the livers of syngeneic rats to evaluate their ability to engraft and differentiate into mature hepatocytes. SHPCs obtained from retrorsine-exposed rats 6-8 days and 13-15 days after PH were small (10-12 microm in diameter), morphologically resembled hepatocytes, and were predominantly H.4 antigen-positive, alpha-fetoprotein-positive, and OV6-negative. SHPCs did not proliferate in culture and could not be passaged, but short-term cultures were established using protein substrates (collagen or laminin) and defined medium containing epidermal growth factor and nicotinamide. After transplantation into the livers of syngeneic hosts, SHPCs insert into hepatic plates and give rise to differentiated hepatocyte progeny. The SHPC-derived hepatocyte progeny express a differentiated phenotype (albumin-positive, transferrin-positive, alpha-fetoprotein-negative) and are able to proliferate in vivo in response to the growth stimulus provided by PH. The results demonstrate that enriched SHPC populations can be isolated from retrorsine-exposed rats and established in short-term culture, and they can engraft and differentiate after transplantation into the livers of syngeneic rats.


Expansion of mycobacterium-reactive gamma delta T cells by a subset of memory helper T cells.
Human gamma delta T cells expressing the V gamma 9/V delta 2 T-cell receptor have been previously found to proliferate in response to certain microorganisms and to expand throughout life, presumably because of extrathymic activation by foreign antigens. In vitro expansion of V gamma 9/V delta 2 cells by mycobacteria has been previously shown to be dependent on accessory cells. In order to gain an insight into the mechanisms involved in the expansion of these cells, we have undertaken to identify the peripheral blood subset of cells on which proliferation of V gamma 9/V delta 2 cells in response to mycobacteria is dependent. Contrary to their role in antigen presentation to alpha beta T cells, professional antigen-presenting cells, such as monocytes, B cells, and dendritic cells, were unable to provide the cellular support for the expansion of V gamma 9/V delta 2 cells. Selective depletion of T-cell subsets, as well as the use of highly purified T-cell populations, indicated that the only subset of peripheral blood cells that could expand V gamma 9/V delta 2 cells were CD4+ CD45RO+ CD7- alpha beta T cells. These cells underwent distinct intracellular signaling events after stimulation with the mycobacterial antigen. Expansion of V gamma 9/V delta 2 cells by alpha beta T cells was dependent on cell-cell contact. This is the first evidence that a small subset of the memory helper T-cell population is exclusively responsible for the peripheral expansion of V gamma 9/V delta 2 cells. These data illustrate a unique aspect of antigen recognition by gamma delta T cells and provide new means to study their immune defense role.


PET in oncology: will it replace the other modalities?
Medical imaging technology is rapidly expanding and the role of each modality is being redefined constantly. PET has been around since the early sixties and gained clinical acceptance in oncology only after an extreme number of scientific publications. Although PET has the unique ability to image biochemical processes in vivo, this ability is not fully used as a clinical imaging tool. In this overview, the role of PET in relation to other tumor imaging modalities will be discussed and the reported results in the literature will be reviewed. In predicting the future of PET, technical improvements of other imaging modalities need to be dealt with. The fundamental physical principles for image formation with computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), photon-emission tomography (PET), and single photon emission CT (SPECT) will not change. The potential variety of radiopharmaceuticals which may be developed is unlimited, however, and this provides nuclear imaging techniques with a significant advantage and adaptive features for future biologic imaging. The current applications of PET in oncology have been in characterizing tumor lesions, differentiating recurrent disease from treatment effects, staging tumors, evaluating the extent of disease, and monitoring therapy. The future developments in medicine may use the unique capabilities of PET not only in diagnostic imaging but also in molecular medicine and genetics. The articles discussed in this review were selected from a literature search covering the last 3 years, and in which comparisons of PET with conventional imaging were addressed specifically. PET studies with the glucose analogue fluorine-18-labeled deoxyglucose (FDG) have shown the ability of detecting tumor foci in a variety of histological neoplasms such as thyroid cancer, breast cancer, lymphoma, lung cancer, head and neck carcinoma, colorectal cancer, ovarian carcinoma, and musculoskeletal tumors. Also, the contribution of the whole body PET (WBPET) imaging technique in diagnosis will be discussed. In the current health care environment, a successful imaging technology must not only change medical management but also demonstrate that those changes improve patient outcome.


Drop edges and adapt: A fairness enforcing fine-tuning for graph neural networks.
The rise of graph representation learning as the primary solution for many different network science tasks led to a surge of interest in the fairness of this family of methods. Link prediction, in particular, has a substantial social impact. However, link prediction algorithms tend to increase the segregation in social networks by disfavouring the links between individuals in specific demographic groups. This paper proposes a novel way to enforce fairness on graph neural networks with a fine-tuning strategy. We Drop the unfair Edges and, simultaneously, we Adapt the model's parameters to those modifications, DEA in short. We introduce two covariance-based constraints designed explicitly for the link prediction task. We use these constraints to guide the optimization process responsible for learning the new 'fair' adjacency matrix. One novelty of DEA is that we can use a discrete yet learnable adjacency matrix in our fine-tuning. We demonstrate the effectiveness of our approach on five real-world datasets and show that we can improve both the accuracy and the fairness of the link prediction tasks. In addition, we present an in-depth ablation study demonstrating that our training algorithm for the adjacency matrix can be used to improve link prediction performances during training. Finally, we compute the relevance of each component of our framework to show that the combination of both the constraints and the training of the adjacency matrix leads to optimal performances.


Effect of head orientation on gaze processing in fusiform gyrus and superior temporal sulcus.
We used functional MRI with an event-related design to dissociate the brain activation in the fusiform gyrus (FG) and posterior superior temporal sulcus (STS) for multiple face and gaze orientations. The event-related design allowed for concurrent behavioral analysis, which revealed a significant effect of both head and gaze orientation on the speed of gaze processing, with the face and gaze forward condition showing the fastest reaction times. In conjunction with this behavioral finding, the FG responded with the greatest activation to face and gaze forward, perhaps reflecting the unambiguous social salience of congruent face and gaze directed toward the viewer. Random effects analysis showed greater activation in both the FG and posterior STS when the subjects viewed a direct face compared to an angled face, regardless of gaze direction. Additionally, the FG showed greater activation for forward gaze compared to angled gaze, but only when the face was forward. Together, these findings suggest that head orientation has a significant effect on gaze processing and these effects are manifest not only in the STS, but also the FG.


Human neutrophil adherence to thrombospondin occurs through a CD11/CD18-independent mechanism.
Thrombospondin (TSP), a 450-kDa trimeric glycoprotein secreted by platelets and endothelial cells at sites of tissue injury or inflammation, may play an important role in polymorphonuclear leukocyte (PMN) adherence to blood vessel walls before diapedesis. We have examined the adherence of PMN to TSP and compared it to adherence to other extracellular matrix proteins. PMN adherence to TSP-coated plastic was complete by 60 min with spreading completed by 2 h. The kinetics of adhesion and spreading on TSP were similar to that of vitronectin (VN), laminin (LN), and fibronectin (FN). Activation of PMN with the calcium ionophore A23187 or the chemotactic peptide FMLP increased PMN adherence to LN and FN, but not to TSP or VN, suggesting that PMN activation may differentially regulate expression of TSP and VN receptors as compared to LN and FN receptors. The specificity of PMN adherence to TSP was confirmed by competition with saturating amounts of TSP and inhibition with anti-TSP antibodies. mAb A6.1, which binds to the protease-resistant core of TSP, was the most effective in blocking PMN adherence to TSP. Using TSP proteolytic fragments, we demonstrated that the primary interaction of PMN with TSP was mediated through the 140-kDa COOH-terminal domain. Inasmuch as the 140-kDa fragment of TSP contains an Arg-Gly-Asp sequence similar to the cell recognition site of FN and VN, we determined whether RGDS peptides would inhibit PMN adhesion. RGDS did not significantly inhibit PMN adhesion to TSP, VN, or LN, but reduced PMN adhesion to FN by 50%. To determine if PMN adhesion to TSP was mediated by a beta 2 integrin receptor such as LFA-1, MO-1, or p150,95, we performed adhesion assays using PMN isolated from patients with leukocyte adhesion deficiency that lack beta 2 receptors. Leukocyte adhesion deficiency PMN exhibited normal adherence to TSP. In contrast, adherence to VN, LN, and FN was reduced by 95%. Therefore, adherence to TSP is probably not mediated by a beta 2 integrin receptor. These data contribute to the accumulating evidence that PMN can interact with extracellular matrix proteins through a CD11/CD18-independent process.


ATP-sensitive K(+) channels in the brain: sensors of hypoxic conditions.
Rapid minimization of energy consumption in excitable tissues is effective protection from lethal effects of extreme metabolic stress. The ATP-sensitive K(+) channels in the brain respond in ATP-depleted metabolic states such as hypoxia and may be involved in the protection mechanism against energy-consuming generalized seizure.


NAFLD evaluation: Which is more appropriate, multislice computed tomography or ultrasound real-time shear wave elastography?
This study aims to assess the value of ultrasound real-time shear wave elastography (US-SWE) for evaluation of nonalcoholic fatty liver disease (NAFLD) in a rabbit model compared with multislice computed tomography (MSCT). Twenty-six rabbits were fed with high-fat, high-cholesterol diet and six rabbits were fed with a standard diet. All rabbits were performed with MSCT and US-SWE at various time points to measure changes in liver parenchyma. The diagnostic efficiency of US-SWE was analyzed using receiver operating characteristics (ROC) curves compared with MSCT based on the liver pathology. The statistically significant differences in the areas under the ROC curves between using MSCT and US-SWE modalities were detected to discriminate between normal vs. NAFLD or higher severity pathology. Similarly, for normal or NAFLD vs. borderline or NASH livers, statistically significant differences between using US-SWE and MSCT modalities were also detected for nonalcoholic steatohepatitis (NASH) vs. lower severity pathology. MSCT, but not US-SWE, had a better ability to differentiate normal or NAFLD livers from higher severity NAFLD livers. However, the diagnostic efficiency of US-SWE was superior to that of MSCT for differentiating NASH from normal or lower severity NAFLD.