Novel oncogenic and chemoresistance-inducing functions of resistin in ovarian cancer cells require miRNAs-mediated induction of epithelial-to-mesenchymal transition.
Resistin plays a role in the growth, proliferation, angiogenesis, metastasis and therapeutic resistance in different cancers. However, such effects of resistin have never been evaluated in ovarian cancer, a deadly gynecological malignancy. We observed a significant induction of ovarian cancer cells' growth, invasion and cisplatin resistance, and established a mechanism of resistin action that included induction of EMT and stemness, as evidenced by down-regulated epithelial marker e-cadherin and up-regulated mesenchymal markers vimentin/ ZEB1 and stemness markers sox2, oct4 and nanog. The mechanism also included suppression of tumor suppressor miRNAs, let-7a, miR-200c and miR-186. Over-expression of these miRNAs significantly reversed the resistin-mediated effects on invasion and chemoresistance. We further validated our results in vivo where resistin administration significantly enhanced tumor growth in mice. Our results provide first evidence for such oncogenic effects of resistin in ovarian cancer models and a rationale for future studies to further understand the mechanistic role of resistin in ovarian cancer invasiveness, metastasis and therapy resistance.


Perforation of the heart by central venous catheters in infants: guidelines to diagnosis and management.
The frequent use of central venous catheters has resulted in improved monitoring and parenteral nutrition. However, these catheters have also been a source of numerous complications, some of them lethal. Two cases of perforation of the heart that resulted in cardiac tamponade and death are reported. Early detection of this complication depends on a high index of suspicion, both clinical and radiographic. Measures such as securing the catheter tip in the superior vena cava can prevent this complication; immediate evacuation of the pericardial fluid by gentle aspiration or pericardiocentesis can prove life-saving.


Immunoglobulin diversification in B cell malignancies: internal splicing of heavy chain variable region as a by-product of somatic hypermutation.
In this study we describe alternative splicing of somatically mutated immunoglobulin (Ig) variable heavy chain (V(H)) genes in three distinct primary B cell non-Hodgkin's lymphomas (B-NHL). In two V4-34 expressing lymphomas, ie a post-germinal center type B cell chronic lymphocytic leukemia (B-CLL) and a follicular lymphoma (FL), internally spliced V(H) gene transcripts were found in which a sequence stretch of 116 bp between the framework region 1 (FR1) and complementarity determining region 2 (CDR2) had been deleted. We provide evidence that for this alternative IgV(H) mRNA processing a known cryptic 5' splice donor site and a previously unidentified cryptic 3' splice acceptor site were used. Site-directed mutagenesis showed that the cryptic 3' splice acceptor site had been activated by specific somatic point mutations. The B-CLL further harbored a triplication of the rearranged JH3 gene segment including the putative N region and part of the JH3-JH4 intron sequence. This triplication probably took place via a repeated mechanism of DNA double strand break followed by homologous recombination, a mechanism which was recently proposed also involved in the somatic hypermutation process and is compatible with the post-germinal center derivation of this B-CLL. Finally, in a V4-34 expressing diffuse large B cell lymphoma, we observed alternative IgV(H) mRNA processing using the same cryptic 5' splice donor site and the normal splice acceptor site of the CH1-C(mu) exon. The significance of alternative IgV(H) processing in B cell malignancies and as a potential mechanism of somatic Ig diversification is discussed.


Quenching effect on gold nano-patterned cardiac troponin I chip by total internal reflection fluorescence microscopy.
Total internal reflection fluorescence microscopy (TIRFM) was investigated for enhanced detection sensitivity of cardiac troponin I (cTnI) on a gold nano-patterned protein chip. A 4×5 nanoarray patterning of a gold chip based on a single-molecule sandwich immunoassay was prepared with a spot diameter of 500 nm on glass substrates formed via electron-beam nanolithography. Quantitative trace analysis was possible as a function of increasing total internal reflection fluorescence intensity in the range of 84 aM-350 pM at prism-type and 35 aM-350 pM at objective-type TIRFM. Although using same gold nano-patterned cTnI chips, however, the objective-type TIRFM showed enhanced detection sensitivities 2.4 times better than the prism-type due to weaker gold quenching. This result is also about 7000 times lower in the detection limit compared with those obtained by conventional commercial sandwich enzyme-linked immunosorbent assay techniques.


Spectophotometric quantification of cell-cell adherence by an enzyme-linked immuno-cell adhesion assay.
In the present study a spectophotometric method was developed to determine the number of T cells binding to human epidermal keratinocytes (KC). In this cell adhesion assay the adherent T cells were detected with a cell-specific monoclonal antibody conjugated to horseradish peroxidase and the coloured substrate quantified in an ELISA reader at 492 nm. A correlation was demonstrated between the number of T cells and the extinction values measured. The enzyme-linked immuno-cell adhesion assay (ELICAA) was used to quantify KC/T lymphocyte adherence in a series of experiments designed to evaluate its reliability and reproducibility. Compared with the 51Cr-labelled adherence assay, the ELICAA was a safe, rapid and accurate method avoiding the use of radioactive material.


Effect of Dietary Organic and Inorganic Sulfur on the Performance of Coccidiosis Vaccine Challenged Broiler Chickens.
The objective of this study was to evaluate the effects of dietary sulfur from either organic (methyl sulfonyl methane, MSM) or inorganic (sodium sulfate, SS) sources on the growth performance of broiler chickens challenged against a high-dose coccidiosis vaccine. A total of 320 day-old Ross 308 broiler chicks were randomly placed into 32 pens of 10 birds each (keeping 16 pens/control group and 8 pens/treatment group until 21 days post-hatch) and reared for 28 days. The experimental diets were formulated by mixing a corn and soybean meal-based control diet with MSM or SS. At 21 days post-hatch, half (n = 8) of the control and all of the sulfur-added diet-fed (i.e., MSM and SS) groups were challenged with a 30-fold dose of a commercially available Eimeria vaccine (Livacox® T coccidiosis vaccine). Unchallenged control chicks (n = 8) were considered as the negative control group. At 21 days (before coccidiosis vaccine challenge), the production parameters and cecal short-chain fatty acids were not affected by dietary treatments. The concentrations of total antioxidant capacity in liver samples were elevated in both the MSM and SS groups compared with the control group (p = 0.001). During 21 to 28 days (i.e., one week post coccidiosis vaccine challenge), challenge tended to lower body weight and feed intake by an average of 5.3% (p = 0.262) and 2.8% (p = 0.504), respectively, but to increase the feed conversion ratio by an average of 2.7% (p = 0.087) compared with the non-challenged control groups. None of dietary sulfur groups affected the body weight gain, feed intake, or feed conversion ratio of vaccine-challenged chickens. Mild Eimeria-specific lesions were noted in duodenum (p = 0.006), jejunum (p = 0.017), and ceca (p = 0.047), but dietary sulfur treatments did not affect the Eimeria-induced gut lesion scores. At 28 days, Eimeria challenge significantly impaired (p = 0.001) the apparent ileal digestibility of crude protein and crude ash compared with the naïve control group. Dietary MSM increased the apparent ileal digestibility of crude ash by 15.5% on average compared with the coccidiosis vaccine control group. We conclude that dietary antioxidant sulfur of organic or inorganic origins at the inclusion level (i.e., 0.7 g sulfur/kg of diet) has a limited effect on the growth performance of chickens challenged with coccidiosis vaccine.


Clinical value of whole-blood interferon-gamma assay in patients with suspected pulmonary tuberculosis and AFB smear- and polymerase chain reaction-negative bronchial aspirates.
Combining a polymerase chain reaction (PCR) test with bronchoscopy is frequently performed to allow a rapid diagnosis of smear-negative pulmonary tuberculosis (PTB). However, limited data are available concerning clinical judgment in patients with suspected PTB and AFB smear- and PCR-negative bronchial aspirates (BA). The present study evaluated the usefulness of whole-blood QuantiFERON-TB Gold In-Tube (QFT) testing in these patients. Of 166 patients with suspected PTB who had undergone bronchoscopy because of smear-negative sputum or inadequate sputum production, 93 (56%) were diagnosed with culture-positive PTB. Seventy-four patients were either AFB smear- or PCR-positive. In the 75 patients whose BA AFB smear and PCR results were both negative, 19 were finally diagnosed with PTB by culture. The QFT test had a negative predictive value of 91% for PTB. The QFT test may be useful for excluding PTB in patients with suspected PTB whose BA AFB smear and PCR results are both negative.


Pain and Emergency Department Use in the Last Month of Life Among Older Adults With Dementia.
Pain may be a potentially modifiable risk factor for expensive and burdensome emergency department (ED) visits near the end of life for older adults with dementia. The objective of this study was to assess the effect of pain and unmet need for pain management on ED visits in the last month of life in older adults with dementia. This is a mortality follow-back study of older adults with dementia in the National Health and Aging Trends Study who died between 2012 and 2014, linked to Medicare claims. Two hundred eighty-one National Health and Aging Trends Study decedents with dementia met criteria (mean age 86 years, 61% female, 81% white). Fifty-seven percent had at least one ED visit in the last month of life, and 46.5% had an ED visit that resulted in a hospital admission. Almost three out of four (73%) of decedents experienced pain in the last month of life, and 10% had an unmet need for pain management. After adjustment for age, gender, race, educational attainment, income, comorbidities, and impairment in activities of daily living, pain was not associated with increased ED use in the last month of life (adjusted incident rate ratio 0.87, 95% CI 0.64-1.17). However, decedents with unmet need for pain management had an almost 50% higher rate of ED visits in the last month of life than those without unmet needs (adjusted incident rate ratio 1.46, 95% CI 1.07-1.99). Among older adults with dementia, unmet need for pain management was associated with more frequent ED visits in the last month of life.


Breath volatile organic compounds (VOCs) as biomarkers for the diagnosis of pathological conditions: A review.
Normal and abnormal/pathological status of physiological processes in the human organism can be characterized through Volatile Organic Compounds (VOCs) emitted in breath. Recently, a wide range of volatile analytes has risen as biomarkers. These compounds have been addressed in the scientific and medical communities as an extremely valuable metabolic window. Once collected and analysed, VOCs can represent a tool for a rapid, accurate, non-invasive, and painless diagnosis of several diseases and health conditions. These biomarkers are released by exhaled breath, urine, faeces, skin, and several other ways, at trace concentration levels, usually in the ppbv (μg/L) range. For this reason, the analytical techniques applied for detecting and clinically exploiting the VOCs are extremely important. The present work reviews the most promising results in the field of breath biomarkers and the most common methods of detection of VOCs. A total of 16 pathologies and the respective database of compounds are addressed. An updated version of the VOCs biomarkers database can be consulted at: https://neomeditec.com/VOCdatabase/.


[Ten years' experience of preimplantation genetic diagnosis in Paris: remaining obstacles and potential solutions].
Preimplantation genetic diagnosis (PGD) has been authorized in France since 1999. Encouraging results have been obtained during the past 10 years in our Paris center, where 832 patients have undergone 1056 IVF-PGD procedures. With the advent of new techniques for the identification of genetic disease markers, our center can now offer PGD procedures for aneuploidy and 75 single-gene diseases. New indications for PGD have also been developed, such as mitochondrial DNA diseases, amyloid neuropathy, pulmonary arterial hypertension, and HLA typing The implantation rate is currently 29,6% and, by 31 December 2009, 151 healthy babies had been born. Unfortunately, demand for PGD procedures far outstrips available technical capacity, and the waiting period is longer than 18 months. Increased funding is urgently needed


Prevalence of hyponatremia and associated factors in patients with chronic kidney disease: the Fukuoka Kidney Disease Registry (FKR) study.
Hyponatremia is a common and important electrolyte disorder. However, the prevalence and factors associated with hyponatremia in patients with chronic kidney disease (CKD) are unknown. We studied the factors associated with hyponatremia (< 135 mEq/L) in CKD patients registered in the Fukuoka Kidney Disease Registry (FKR) study using a logistic regression model variable selected using the variable reduction method. We analyzed the baseline characteristics of 4367 participants with CKD (age, 64 ± 16 years; male, 56.1%). Hyponatremia was detected in 2.0% of the patients at baseline, and multivariate logistic analysis showed that the independent factors for hyponatremia were body mass index (odds ratio [OR] 0.91; 95% confidence interval [CI] 0.85-0.97), prescription of benzodiazepine (OR 2.31; 95% CI 1.39-3.86), blood hemoglobin level (OR 0.76; 95% CI 0.65-0.88), and serum C-reactive protein level (OR 1.27; 95% CI 1.04-1.54). The cross-sectional analysis using baseline data from the FKR study revealed independent factors associated with hyponatremia in patients with decreased kidney function. Longitudinal analyses of the FKR cohort are needed to evaluate the effects of these factors on the prognosis of hyponatremia in patients with CKD.


A qualitative study of action plans for asthma.
To investigate the perspectives of patients with asthma on the use of an action plan and the implementation of this plan during an asthma attack that culminated in a visit to an emergency department. Qualitative study. Tertiary teaching hospital, suburban hospital, and rural hospital. 62 patients aged 18 to 69 years who presented to an emergency department with asthma over a two month period. 29 participants described having action plans given to them by their doctors. Most patients with action plans reinterpreted their plan from the perspective of their own experiences with asthma. 33 patients did not have an action plan, the most common reason being that they had not been given one by their doctor. Some occupational groups were significantly less likely to have been given an action plan by their doctor than others. Most patients with an action plan found them useful for management of their asthma. Action plans were viewed positively by patients. Participants modified their prescribed plan according to their experience of asthma. To facilitate the implementation of a prescribed action plan, doctors need to acknowledge and include the patient's personal experience of their disease.


Fathers' experiences of their child's life-limiting condition: An attachment narrative perspective.
When a child has a life-limiting illness, parental involvement is amplified, having to respond to the increased needs of the child. Both parents are affected by the illness, yet research has largely under-represented fathers' experiences of their child's illness. Seven fathers were interviewed about their experiences with their child's life-limiting illness. In addition, fathers' attachment strategies were assessed using the Adult Attachment Interview. Narrative analysis was implemented to explore the interviews, and indicators of attachment markers employed in the Adult Attachment Interview were also identified. The dominant themes were found to be 'experience of the diagnosis', 'living with the illness', 'struggling with emotions' and 'relationship with staff'. Within each theme, there were differences which related to the father's attachment strategies. This was particularly evident in parts of their narratives recounting critical moments of threat and anxiety in the course of discovering and adjusting to their child's illness. Importantly, the findings also suggested that the experience for the fathers stressed, and in some cases disrupted, their attachment coping strategies. All fathers told stories of trying to get it right for their children and family. Their experiences of, and adjustment to, the illness were related to their attachment strategies. The clinical implications for health professionals are discussed.


PHYSIOLOGICAL RESPONSES AND ENERGETICS OF COMPETITIVE GROUP EXERCISE IN FEMALE AEROBIC GYMNASTS WITH DIFFERENT LEVELs OF PERFORMANCE.
This study investigated the aerobic fitness and physiologic and energetic responses during competitive exercise in aerobic gymnasts. The gymnasts performed a graded treadmill test and competitive group exercises. Energetic response was calculated from oxygen uptake and blood lactate changes. Peak oxygen uptake was similar in International (M = 45.4 ml · kg(-1) · min.(-1), SD = 3.9) and National (M = 44.7 ml · kg(-1) · min.(-1), SD = 3.6) level groups. During their competitive routines, total energy and the fractions of aerobic, anaerobic alactic, and anaerobic lactic energy were 1,847.7 (SD = 293.9) and 1,747.3 (SD = 196.7) J · kg(-1), 53.5% (SD = 3.1) and 60.3% (SD = 6.1), 25.4% (SD = 5.9) and 21.4% (SD = 5.2), and 21.1% (SD = 5.8) and 18.3% (SD = 4.5) in international and national level athletes, respectively (p > .05). The contribution of anaerobic energy was higher in the international level group (p = .03). It is concluded that the aerobic fitness and absolute energetic and physiological responses of athletes during competitive activities were not different between the aerobic gymnasts groups with different levels of performance, but a higher relative contribution of anaerobic energy was observed in the group with a higher performance level.


Characterisation of renal antigens on distinct parts of the human nephron by monoclonal antibodies.
Ten monoclonal antibodies (TN 1-TN 10) directed against different renal antigens of distinct sites of the human nephron were derived from a fusion between P3-NS1/1-Ag4-1 mouse myeloma and spleen cells of a mouse hyperimmunized against isolated human kidney cells. Two of these reagents (TN 1, TN 10) were shown by immunoperoxidase labelling on frozen sections of five normal kidneys and of other selected human organs, as well as by immunofluorescence studies on normal peripheral blood cells and selected lymphohematopoietic cell lines, to detect antigens exclusively expressed on visceral glomerular or proximal tubular epithelial cells. The other eight antibodies were found to react with different determinants shared between renal structures, muscle cells, different epithelia, B-lymphocytes and granulocytes. In heterogeneous cultures of isolated kidney cells these monoclonal reagents could be used to identify distinct cell types of tubular origin. Thus such hybridoma-derived antibodies provide new tools to correlate structural characteristics of various renal epithelial cells with their functional properties and will contribute to the study of their influence on immunologically mediated kidney injuries in different forms of glomerulonephritis in man.


Resveratrol inhibits proliferation and induces apoptosis via the Hippo/YAP pathway in human colon cancer cells.
High malignancy and mortality in colon cancer require clarifying the underlying mechanisms of colon cancer carcinogenesis and exploring new targets or drugs for the clinical treatment of colon cancer. Resveratrol (Res), a natural compound, shows cytotoxicity against various tumors. However, the specific anti-cancer mechanism of Res remains unclear. In the present study, we aimed to explore the anti-cancer activity of Res against colon cancer cells and the possible mechanism. The results showed that Res could inhibit cell proliferation and induce cell cycle arrest and apoptosis in HCT116 cells. Western blotting and Polymerase chain reaction (PCR) showed that Res increased the phosphorylated YAP (pYAP) levels and decreased YAP total protein level and decreased the mRNA expression of the YAP signaling downstream genes CTGF and CYR61. The effects of Res on pYAP were enhanced by YAP inhibitor verteporfin (VP). VP also enhanced the effects of Res on decreasing viability and inducing apoptosis. Furthermore, the molecular docking analysis indicated Res could bind with YAP-TEAD through van der Waals, pi-alkyl, and pi-pi stacked interactions. Our findings suggested that the anti-cancer activity of Res may be mediated via activating Hippo/YAP signaling and partially disturbing the interaction between YAP and TEAD. All this evidence supports that Res may be an efficacious drug for colon cancer treatment.


Metabolic engineering strategies for naringenin production enhancement in Streptomyces albidoflavus J1074.
Naringenin is an industrially relevant compound due to its multiple pharmaceutical properties as well as its central role in flavonoid biosynthesis. On our way to develop Streptomyces albidoflavus J1074 as a microbial cell factory for naringenin production, we have significantly increased the yields of this flavanone by combining various metabolic engineering strategies, fermentation strategies and genome editing approaches in a stepwise manner. Specifically, we have screened different cultivation media to identify the optimal production conditions and have investigated how the additive feeding of naringenin precursors influences the production. Furthermore, we have employed genome editing strategies to remove biosynthetic gene clusters (BGCs) associated with pathways that might compete with naringenin biosynthesis for malonyl-CoA precursors. Moreover, we have expressed MatBC, coding for a malonate transporter and an enzyme responsible for the conversion of malonate into malonyl-CoA, respectively, and have duplicated the naringenin BGC, further contributing to the production improvement. By combining all of these strategies, we were able to achieve a remarkable 375-fold increase (from 0.06 mg/L to 22.47 mg/L) in naringenin titers. This work demonstrates the influence that fermentation conditions have over the final yield of a bioactive compound of interest and highlights various bottlenecks that affect production. Once such bottlenecks are identified, different strategies can be applied to overcome them, although the efficiencies of such strategies may vary and are difficult to predict.


Current issues and future directions in gymnastics research: biomechanics, motor control and coaching interface.
The sport of gymnastics is undergoing a global examination of its culture and the relationship between the gymnast, coach and environment is a central focus. The aim of this review is to explore biomechanics and motor control research in skill development and technique selection in artistic gymnastics with a focus on the underlying concepts and scientific principles that allow performance enhancement, skill development and injury risk reduction. The current review examines peer reviewed papers from 2000 onwards, with a focus on contemporary approaches in the field of gymnastics research, and highlights several key directions for future gymnastics research. Based on our review and the integration of the models of Newell (1986) and Irwin et al. (2005), we recommend that future gymnastics research should embrace at the very least a multidisciplinary approach and aim for an interdisciplinary paradigm.


Labeling of poly(A) associated RNA in synaptosomes and the other subcellular fractions of rat cerebral cortex in basal conditions and during training.
The labeling of total and poly(A) associated RNA from the subcellular fractions of cerebral cortex was studied after a 1-hour 3H-uridine pulse in control and trained rats. In the control animals, the fraction of newly synthesized brain cortex RNA which is found in synaptosomes is the minimal one. However, in synaptosomes the proportion of poly(A)+ RNA within newly synthesized RNA is maximal. Training of the rats does not influence total incorporation of label into RNA in the brain cortex and the distribution of newly synthesized RNA within the subcellular fractions. The proportions of poly(A)+ RNA within total labeled RNA in the various fractions are also unaffected.


A global pharmaceutical company initiative: an evidence-based approach to define the upper limit of body weight loss in short term toxicity studies.
Short term toxicity studies are conducted in animals to provide information on major adverse effects typically at the maximum tolerated dose (MTD). Such studies are important from a scientific and ethical perspective as they are used to make decisions on progression of potential candidate drugs, and to set dose levels for subsequent regulatory studies. The MTD is usually determined by parameters such as clinical signs, reductions in body weight and food consumption. However, these assessments are often subjective and there are no published criteria to guide the selection of an appropriate MTD. Even where an objective measurement exists, such as body weight loss (BWL), there is no agreement on what level constitutes an MTD. A global initiative including 15 companies, led by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), has shared data on BWL in toxicity studies to assess the impact on the animal and the study outcome. Information on 151 studies has been used to develop an alert/warning system for BWL in short term toxicity studies. The data analysis supports BWL limits for short term dosing (up to 7days) of 10% for rat and dog and 6% for non-human primates (NHPs).


Seminal plasma PSA in spinal cord injured men: a preliminary report.
The aim of the study was to evaluate the impact of spinal cord injury on seminal plasma PSA concentration. Semen obtained from normal controls (n = 20) and patients (n = 16) with spinal cord injury. The concentration of prostate specific antigen in seminal plasma depended on the level of spinal cord injury, with significantly lower concentrations in patients with spinal cord lesions below T7 compared to both normal age-matched controls (P = 0.007) and patients with spinal cord injuries at or above T7 (P = 0.017). The results add to the previously reported observations of the possible impact of neurogenic stimulation on prostate activity. More studies of neurogenic stimulation in prostate growth and development are warranted to further elucidate the possible impact of neurogenic factors in the development of prostatic diseases.


Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: Hierarchy and specificity of ligand-receptor interactions.
Receptor tyrosine kinases (RTKs) are a class of cell surface receptors that, upon ligand binding, stimulate a variety of critical cellular functions. The orphan receptor anaplastic lymphoma kinase (ALK) is one of very few RTKs that remain without a firmly established protein ligand. Here we present a novel cytokine, FAM150B, which we propose naming augmentor-α (AUG-α), as a ligand for ALK. AUG-α binds ALK with high affinity and activates ALK in cells with subnanomolar potency. Detailed binding experiments using cells expressing ALK or the related receptor leukocyte tyrosine kinase (LTK) demonstrate that AUG-α binds and robustly activates both ALK and LTK. We show that the previously established LTK ligand FAM150A (AUG-β) is specific for LTK and only weakly binds to ALK. Furthermore, expression of AUG-α stimulates transformation of NIH/3T3 cells expressing ALK, induces IL-3 independent growth of Ba/F3 cells expressing ALK, and is expressed in neuroblastoma, a cancer partly driven by ALK. These experiments reveal the hierarchy and specificity of two cytokines as ligands for ALK and LTK and set the stage for elucidating their roles in development and disease states.


Immobilization of amyloglucosidase using two forms of polyurethane polymer.
Amyloglucosidase was covalently immobilized using two hydrophilic prepolymers: Hypol FHP 2002 (creates foams) and Hypol FHP 8190H (creates gels). The foamable prepolymer was superior as a support for enzyme immobilization. The percent activity immobilized in the polyurethane foams was 25 +/- 1.5%. Large substrates (greater than 200,000 daltons in mol wt) were hydrolyzed as effectively as smaller ones by the immobilized enzyme. The Km value of the foam-immobilized enzyme increased from 0.76 mg/mL (free) to 0.86 mg/mL (immobilized), whereas the Vmax dropped from 90.9 (free) to 12.4 nmol glucose/min/mL (immobilized). The long-term (2 mo) storage stability of amyloglucosidase was enhanced by immobilization in foams (70% activity retained; free enzyme only retained 50%). Immobilization also improved the enzyme stability to various denaturing agents (sodium chloride, urea, and ethanol). The immobilized enzyme exhibited increased stability compared to the free enzyme at high temperatures (95 degrees C). Both glycogen and starch could be utilized by the immobilized enzyme, indicating that this technique could prove useful for starch hydrolysis.


Xanthosine-5'-phosphate amidotransferase from Escherichia coli.
The purified enzyme xanthosine-5'-monophosphate (XMP) aminase from Escherichia coli strain B-96 is shown to possess catalytic activity with either glutamine or ammonia as a substrate. This enzyme, which possesses identical subunits, has the following properties: (a) a pH optimum of 8.3 for both aminase and amidotransferase; (b) an apparent K-m for both glutamine and NH3 of 1 mM; (c) an amidotransferase that is approximately 2 times more active than the aminase; (d) a linear relationship between velocity and enzyme concentrationfor both activities; (e) inhibition of both activities by the glutamine analogue 6-diazo-5-oxo-L-norleucine, but the amidotransferase is more sensitive than the aminase; and (f) inhbiition of both activities by the adenosine analogue, psicofuranine, but again the amidotransferase activity is more sensitive than the aminase. The so-called XMP aminase from the E. coli mutant B-24-1 also has been examined in both crude extracts nad ammonium sulfate fractions and the following data have been obtained: (a) both preparations of enzyme contain aminase and amidotransferase activity; (b) both activities have the same substrate requirements; (c) the pH optima for both activities in the crude extract are identical with those found with the purified enzyme preparation; and (d) the amidotransferase activity in the crude extract and the ammonium sulfate fractions is 2- to 3-fold more active than the aminase. These data demonstrate that this enzyme from E. coli is not strictly a XMP aminase but is, in fact, an amidotransferase capable of utilizing either glutamine or NH3 as a substrate.


Assessment of coastal vulnerability to land-based sources of pollution and its application in Apulia, Italy.
The present paper deals with the assessment of the coastal vulnerability to pollution sources induced by land-based activities (LBAs). The coastal vulnerability is expressed and evaluated in relation to the land-based activities present in the coastal areas and a new index, namely Coastal Pollution Index from land-based activities (CPI_LBAs), is proposed. The index is calculated considering nine indicators using a transect-based approach. The nine indicators refer to point and non-point sources of pollution, and include: rivers quality status, seaports category, airports category, wastewater treatment facilities/submarine outfalls, aquaculture/mariculture areas, pollution load of urban runoff, type of artisanal/industrial facilities, farm/agriculture areas, type of suburban roads. Each indicator is quantified by means of quantitative scores, whereas the strength of cause-effects relationship is assessed by assigning weights using the Fuzzy Analytic Hierarchy Process approach (F-AHP). The indicators are then aggregated to obtain a synthetic index and classified in five categories of vulnerability. The main findings of this study include: i) the identification of key indicators of coastal vulnerability to LABs; ii) the development of a new index to identify the coastal transects where the effects of the LBAs may be the greatest. The paper explains the methodology for the index computation, and illustrates it with an application in Apulia, Italy. The results demonstrate the feasibility of the index and its usefulness to identify the most critical areas in terms of land pollution sources and to produce a vulnerability map. The application allowed to have a synthetic picture of the threat of pollution from LBAs, facilitating its analysis and the benchmarking between the transects. Regarding the case study area, results show that low vulnerability transects are characterized by small agricultural areas/artisanal activities and small urban areas, whereas in very high vulnerability transects all indicators assume high scores.


Carbon catabolite repression of invertase during batch cultivations of Saccharomyces cerevisiae: the role of glucose, fructose, and mannose.
When Saccharomyces cerevisiae are grown on a mixture of glucose and another fermentable sugar such as sucrose, maltose or galactose, the metabolism is diauxic, i.e. glucose is metabolized first, whereas the other sugars are metabolized when glucose is exhausted. This phenomenon is a consequence of glucose repression, or more generally, catabolite repression. Besides glucose, the hexoses fructose and mannose are generally also believed to trigger catabolite repression. In this study, batch fermentations of S. cerevisiae in mixtures of sucrose and either glucose, fructose or mannose were performed. It was found that the utilization of sucrose is inhibited by concentrations of either glucose or fructose higher than 5 g/l, and thus that glucose and fructose are equally capable of exerting catabolite repression. However, sucrose was found to be hydrolyzed to glucose and fructose, even when the mannose concentration was as high as 17 g/l, indicating, that mannose is not a repressing sugar. It is suggested that the capability to trigger catabolite repression is connected to hexokinase PII, which is involved in the in vivo phosphorylation of glucose and fructose.


Insulin-like growth factor-I stimulates diacylglycerol production via multiple pathways in Balb/c 3T3 cells.
We previously reported that insulin-like growth factor-I (IGF-I) induced sustained calcium cycling across the plasma membrane in primed competent Balb/c 3T3 cells (Kojima, I., Matsunaga, H., Kurokawa, K., Ogata, E., and Nishimoto, I. (1989) J. Biol. Chem. 263, 16561-16567). The present study was conducted to examine whether IGF-I affected cellular metabolism of 1,2-diacylglycerol (1,2-DAG). In primed competent cells prelabeled with [3H]myristate, 1 nM IGF-I caused a 50% increase in [3H]DAG within 10 min. This increase in [3H]DAG was accompanied by 1) a decrease in radioactivity in the glycosylphosphatidylinositol fraction in [3H]glucosamine-labeled cells and a concomitant increase in [3H]inositol-glycan, and 2) a decrease in [3H]phosphatidylcholine and a concomitant elevation of [3H]phosphorylcholine in [3H]choline-labeled cells. When [3H]choline-labeled cells were treated with 10 nM 12-O-tetradecanoylphorbol-4-acetate (TPA), [3H]phosphatidylcholine was reduced by 50%. The TPA-induced reduction of [3H]phosphatidylcholine was completely blocked by 50 microM sphingosine and 50 microM H-7, inhibitors of protein kinase C. Both sphingosine and H-7 attenuated IGF-I-mediated reduction of [3H]phosphatidylcholine. In addition, treatment with IGF-I for 3 h or more resulted in sustained increase in 1,2-DAG mass, which was attenuated by cycloheximide. The increase in DAG mass was accompanied by enhanced incorporation of [14C]glucose into 1,2-DAG. These results indicate that, in primed competent Balb/c 3T3 cells, IGF-I stimulates 1,2-DAG production via multiple pathways and that IGF-I may induce breakdown of phosphatidylcholine by a mechanism involving protein kinase C.


What if Astyanax had survived? War, children, and youth.
What, then, might have happened to Astyanax had he survived? He might have become a Greek slave and accepted his lot, or he might have felt loyalty and an obligation to his Trojan ancestry and organized acts of revenge. Depending on his personal characteristics and the people and the community that raised him, a number of outcomes are possible. The fact that after 3000 years we know little more than did the Homeric bards, however, gives us reason to be humble. There is evidence that each experience of loss or violence is additive and reduces coping ability. Although the psychologic disturbances of children and youth exposed to war do appear less intense than might have been expected, as Garmezy and Rutter noted in 1985, it is impossible to know the cost, the vulnerabilities that have been veiled, and what might have been. Perhaps the most remarkable thing is how some children seem able to transcend their misfortunes and even to be steeled by them. Coles has recorded how a 6-year-old, African-American girl, initiating school desegregation in New Orleans in the face of mob violence and daily threats to her life, told him that if she managed to get through with some success, she had an explanation: "It will be because there is more to me than I ever realized."


Residual interface tensile strength of ceramic bonded to dentin after cyclic loading and aging.
To guard against the potential risk of cusp fracture, esthetic onlay restorations have been advocated for teeth with large restorations. The influence of the adhesive resin cement is believed to play a role in strengthening these restorations. The durability of this tooth/adhesive/ceramic interface is critical to ensure clinical longevity. The purpose of this study was to assess the effects of cyclic loading and environmental aging on the residual interface strength of a ceramic bonded to dentin structure. Eighteen simple trilayer specimens were fabricated, consisting of a 1.5-mm-thick ceramic plate (ProCAD) bonded to a flattened human molar tooth with exposed coronal dentin. The ceramic plates were bonded using resin cement (Nexus 2) and manufacturer-recommended bonding techniques. The specimens were divided into 3 equal groups and were stored in water at 37 degrees C for 10 weeks as a control group (CT), 9 months as an aging group (AG), or placed in water at 37 degrees C while being subjected to 10 million vertical loading cycles between 20 N to 200 N, as a fatigue group (FG). After the specimens were subjected to the experimental conditions, they were sectioned perpendicular to the flat ceramic surface into 1 x 1-mm sticks. The mean residual interface microtensile bond (MTB) strength was determined for each specimen using only those sticks which contained ceramic bonded to dentin. The MTB strength data were analyzed using Weibull analysis methods to determine differences between groups. All subsequent failed specimen surfaces were evaluated under a stereomicroscope at x10 magnification to determine the apparent failure modes. Some specimens were selected from each failure mode category for surface evaluation under a scanning electron microscope (SEM). The characteristic Weibull means for the 3 groups were CT, 19.2, FG, 14.7, and AG, 11.7. The bond strength of group CT was significantly greater than both AG (P=.007) and FG (P=.014). Light microscopic categorization of the failure modes suggests that adhesive failure at the ceramic/cement interface was the most common (65%) for all 3 groups. SEM evaluation of failed surfaces of select specimens from each group could not distinguish any interface appearance differences. For indirect adhesive-retained ceramic restorations, both cyclic masticatory loading and hydrolytic degradation may contribute to a weakening of the interface bond. The ceramic/resin interface may be more susceptible to these changes over the time frame of this investigation than the dentin/resin interface.


Intra-Individual Comparison between 2-D Shear Wave Elastography (GE System) and Virtual Touch Tissue Quantification (Siemens System) in Grading Liver Fibrosis.
Ultrasound-based shear wave elastography (SWE) has recently gained substantial attention for non-invasive assessment of liver fibrosis. The purpose of this study was to perform an intra-individual comparison between 2-D shear wave elastography (2-D-SWE with a GE system) and Virtual Touch Tissue Quantification (VTTQ with a Siemens system) to assess whether these can be used interchangeably to grade fibrosis. Ninety-three patients (51 men, 42 women; mean age, 54 y) with liver disease of various etiologies (hepatitis B virus = 47, hepatitis C virus = 22; alcohol = 6, non-alcoholic steatohepatitis = 5, other = 13) were included. Using published system-specific shear wave speed cutoff values, liver fibrosis was classified into clinically non-significant (F0/F1) and significant (≥F2) fibrosis. Results indicated that intra-modality repeatability was excellent for both techniques (GE 2-D-SWE: intra-class correlation coefficient = 0.89 [0.84-0.93]; VTTQ: intra-class correlation coefficient = 0.90 [0.86-0.93]). Intra-modality classification agreement for fibrosis grading was good to excellent (GE 2-D-SWE: κ = 0.65, VTTQ: κ = 0.82). However, inter-modality agreement for fibrosis grading was only fair (κ = 0.31) using published system-specific shear wave speed cutoff values of fibrosis. In conclusion, although both GE 2-D-SWE and Siemens VTTQ exhibit good to excellent intra-modality repeatability, inter-modality agreement is only fair, suggesting that these should not be used interchangeably.


Analysis of the essential oil composition from the different parts of Eryngiumglaciale Boiss. from Spain.
The essential oil from the different parts (inflorescences, stems + leaves and roots) of Eryngium glaciale Boiss. gathered in Sierra Nevada (Spain) has been extracted by steam distillation and analysed by gas chromatography and gas chromatography coupled to mass spectrometry. Quantitative but not qualitative differences have been found between the analysed parts. The principal compounds from the inflorescences oil were found to be phyllocladene isomer (43.5%), (E)-caryophyllene (15.2%) and valencene (11.5%), while the oil from stems and leaves only showed phyllocladene isomer (41.3%) as main one. The oil from the roots presented phyllocladene isomer (49.4%) and linalool (19.1%) as major constituents. This is the first report on the chemical composition of this species.


Glomerulitis induced by cationized bovine serum albumin in the rat.
The effects of injected native and cationized bovine serum albumin (BSA- and BSA+ respectively) were evaluated in rats which subsequently received anti-BSA. Thrombocytopenia, low creatinine clearance (Ccr), increased proteinuria, capillary swelling, mild tuft necrosis and BSA+ deposits in glomeruli resulted within 24 h of BSA+ injection. Later BSA+ produced mesangial expansion glomerular capillary wall (GCW) thickening and deposits of BSA+ accompanied by rabbit anti-BSA and rat anti-BSA which correlated well with small mesangial, subendothelial and subepithelial electron-dense granular accumuli. These latter enlarged considerably after the injection of anti-BSA. BSA- controls showed minimal or no lesions. The disappearance from the blood (t1/2) of a single dose of immune complexes (IC) prepared with chromatography-purified, radioiodinated anti-BSA - BSA- and BSA+ was determined in another group of rats. The t1/2 of BSA- anti-BSA was 42.8 h (95% confidence: 39.8-46.2) while that of BSA+ anti-BSA was 52.5 h (48.1-57.8). These results suggested that serum sickness glomerulitis developed only in rats injected with BSA+, due to in situ IC which presumably grew by accretion of foreign anti-BSA. Circulating IC may have developed and colocated with the latter, with dissociation and recombination at these sites. It is postulated that the functional-immunomorphological changes and the slow removal of cationized IC reported herein could be explained by the highly positive net charge of the injected antigen.


Palladium-catalyzed direct coupling of 2-vinylanilines and isocyanides: an efficient synthesis of 2-aminoquinolines.
Palladium-catalyzed oxidative coupling of 2-vinylanilines and isocyanides constitutes a direct, facile, and efficient approach to 2-aminoquinolines. The procedure, employing palladium acetate and silver carbonate, is attractive in terms of assembly efficiency, functional group tolerance, and operational simplicity. A variety of 2-aminoquinolines were prepared in good to excellent yields.


Insights into thermal stability of thermophilic nitrile hydratases by molecular dynamics simulation.
Thermal stability is of great importance for industrial enzymes. Here we explored the thermal-stable mechanism of thermophilic nitrile hydratases (NHases) utilizing a molecular dynamic simulation. At a nanosecond timescale, profiles of root mean square fluctuation (RMSF) of two thermophilic NHases, 1UGQ and 1V29, under enhancing thermal stress were carried out at 300 K, 320 K, 350 K and 370 K, respectively. Results showed that the region A1 (211-231 aa) and A2 (305-316 aa) in 1UGQ, region B1 (186-192 aa) in 1V29, and most of terminal ends in both enzymes are hyper-sensitive. Salt-bridge analyses revealed that in one hand, salt-bridges contributed to maintaining the rigid structure and stable performance of the thermophilic 1UGQ and 1V29; in the other hand, salt-bridges involved in thermal sensitive regions are relatively weak and prone to be broken at elevated temperature, thereby cannot hold the stable conformation of the spatial neighborhood. In 1V29, region A1 was stabilized by a well-organized hook-hook like cluster with multiple salt-bridge interactions, region A2 was stabilized by two strong salt-bridge interactions of GLU52-ARG332 and GLU334-ARG332. In 1UGQ, the absence of a charged residue decreased its thermal sensitivity of region B1, and the formation of a small beta-sheet containing a stable salt-bridge in C-beta-terminal significantly enhanced its thermal stability. By radius of gyration calculation containing or eliminating the thermal sensitive regions, we quantified the contribution of thermal sensitive regions for thermal sensitivity of 1UGQ and 1V29. Consequently, we presented strategies to improve thermal stability of the industrialized mesophilic NHase by introducing stable salt-bridge interactions into its thermal sensitive regions.


The regional rate of serotonin synthesis estimated by the alpha-methyl-tryptophan method in rat brain from a single time point.
A simplified approach to the measurement of the rate of serotonin (5-HT) synthesis in laboratory animals is presented using autoradiography and labeled alpha-methyl-L-tryptophan. The method is based on the assumption that the volume of distribution of an apparent precursor pool is the same in all brain structures. The apparent distribution volume (Vapp) of the tracer was estimated from our previous data and found to be 0.45 +/- 0.1 ml g-1 (n = 147) as an average in all brain structures. When this value of Vapp was used, the rates of 5-HT synthesis in the rat brain structures, calculated from the single time point method, were not significantly different from those calculated by the dual time point method, where both Vapp and K* were estimated. The rates from the two approaches did not differ when compared by analysis of variance (p > 0.8), Mann-Whitney rank sum test (p > 0.11), Bonferroni-corrected two-tailed t test, or when the ratio between two groups was tested against the hypothesis of being 1. The agreement between rates of 5-HT synthesis estimated by the two methods was very good, suggesting that the simplified method proposed here is appropriate for these kind of measurements.


Antibody persistence after Pandemic H1N1 2009 influenza vaccination among healthcare workers in Pune, India.
The healthcare workers having seroprotection at 3 weeks (n = 127) following Pandemic H1N1 2009 influenza vaccination were followed up for antibody persistence. Seroprotection at 12 mo (60.2%) was significantly lower as compared with 3 weeks (74.7%), 3 mo (77.8%) and 6 mo (75.4%). The vaccine provided seroprotection up to one year.


Placental prolactin-like protein A. Identification and characterization of two major glycoprotein species with antipeptide antibodies.
The purpose of this investigation was to develop immunologic probes to prolactin-like protein A (PLP-A) that could be used to characterize the protein and its distribution in various tissues. Five oligopeptides corresponding to different regions of the predicted PLP-A amino acid sequence (peptides 1-13, 62-76, 101-114, 129-145, and 152-164) were chemically synthesized by solid phase methodology. The peptides were purified to homogeneity by reverse phase high pressure liquid chromatography and coupled to keyhole limpet hemocyanin. The peptide-keyhole limpet hemocyanin conjugates were used to immunize rabbits. Immune responses were monitored by enzyme-linked immunoassay. Reactivity of the antipeptide antisera with placental proteins was determined by immunoblotting and immunoprecipitation analyses. All of the peptides except peptide 1-13 yielded significant immune responses. Antisera to peptides 101-114, 129-145, and 152-164 each specifically recognized proteins of Mr 29,000 and 33,000 from cytosol preparations of rat placental tissue and showed limited or no cross-reactivity with other members of the prolactin-growth hormone family. Three experiments were performed to determine whether the Mr 29,000 and 33,000 species were glycosylated derivatives of an Mr 25,000 precursor. Treatment of placental cytosolic preparations with N-Glycanase prior to immunoblotting resulted in the identification of only an Mr 25,000 species. It was also determined that the Mr 29,000 and 33,000 species specifically bound to concanavalin A. Furthermore, tunicamycin shifted the synthesis of PLP-A by placental explants from the Mr 29,000 and 33,000 forms to the Mr 25,000 species. The Mr 29,000 and 33,000 species were identified in serum obtained from pregnant and fetal rats but not in serum from nonpregnant females or males. We conclude that PLP-A is expressed in rat placenta. An Mr 25,000 precursor (predicted from PLP-A cDNA and these results) is glycosylated to either the Mr 29,000 or 33,000 form, both of which predominate in placenta and in circulation.


Small vessel phenomena in the coronary microcirculation: phasic intramyocardial perfusion and coronary microvascular dynamics.
To place the characteristics of the coronary microcirculation in perspective to another muscular organ system, we have compared various parameters from exchange vessels in the heart and red skeletal muscle. The major differences between cardiac and skeletal muscle microcirculations relate to the larger density of capillaries in the heart. This increased density is responsible primarily for a greater capillary filtration coefficient-permeability-surface area product to various solutes, surface area, and decreased intercapillary distances. These features most likely represent an adaptation of the microcirculation of the heart to the very high, continual metabolic demands. Interestingly, capillary permeabilities and reflection coefficients of different solutes are in the same range (although the heart tends to have higher capillary permeabilities). Thus, the adaptation of the coronary circulation to facilitate exchange of nutrients and solutes is mediated via an increase in the numbers of exchange vessels, rather than modifications of the membrane characteristics of these exchange vessels. Within the last decade, there has been much information assimilated on the regulation of the coronary microcirculation. Most of the knowledge has been the result of many indirect approaches to studying the coronary microcirculation (indicator-dilution techniques, nuclide-labeled microspheres, plasma-lymph concentration of solutes). There are relatively few direct observations on regulation of the coronary microcirculation. This is primarily due to difficulties in techniques. Exploration of the phasic nature of intramyocardial perfusion is handicapped by the location of these intramuscular vessels. Visualization of the coronary microcirculation is hampered by movements of the heart, and such measurements are restricted to the superficial layers of the myocardium. It is worth emphasizing that direct observations of red cell velocities in epicardial capillaries, measurements of microvascular caliber, and the pressure profiles in the coronary microcirculation are restricted to the superficial, epicardial layer. It is not unreasonable to speculate that microvascular events and regulation occurring in the subepicardium may be quite different than that in the subendocardium. There are several salient points in this review that are worth emphasizing.(ABSTRACT TRUNCATED AT 400 WORDS)


Lattice cluster theory of associating polymers. II. Enthalpy and entropy of self-assembly and Flory-Huggins interaction parameter χ for solutions of telechelic molecules.
The lattice cluster theory for solutions of telechelic polymer chains, developed in paper I, is applied to determine the enthalpy Δh(p) and entropy Δs(p) of self-assembly of linear telechelics and to evaluate the Flory-Huggins (FH) interaction parameter χ governing the phase behavior of these systems. Particular focus is placed on examining how these interaction variables depend on the composition of the solution, temperature, van der Waals and local "sticky" interaction energies, and the length of the individual telechelic chains. The FH interaction parameter χ is found to exhibit an entropy-enthalpy compensation effect between the "entropic" and "enthalpic" portions as either the composition or mass of the telechelic species is varied, providing unique theoretical insights into this commonly reported, yet, enigmatic phenomenon.


[An indirect proof of stretch-induced Ca++ release from the sarcoplasmic reticulum in glycerinated skeletal and heart muscle preparations (author's transl)].
The existence of still functioning vesicles of the sarcoplasmic reticulum (SR) in glycerinated rabbit psoas muscle fibers and cat myocardium is demonstrated by the use of activation (force development and shortening) of the contractile system as an indicator for "sarcoplasmic", free Ca++ concentration and by electron microscopic studies. Furthermore, the conditions for Ca++ release and uptake by the SR vesicles were analyzed. (1) As indicated by electron microscopic studies, glycerinated skeletal and heart muscle preparations contain SR vesicles (diameter 0.1--0.2 mu). Detergent treatment as used by Julian (1971) causes neither morphological change in the contractile system nor in the SR vesicles. (2) The delay in tension development of glycerinated preparations after an increase in free Ca++ concentration of the bathing medium is demonstrated to be caused at least partly by Ca++ uptake in these SR vesicles. (3) The SR vesicles of glycerinated preparations are able to accumulate Ca++ just at concentrations which are subthreshold for tension development. The accumulated Ca++ can be detected by a transient force development resulting from abolishment of the Ca++ storage capacity of the SR vesicles caused by high concentrations of detergents. (4) Ca++-induced Ca++ release is also demonstrated in glycerinated preparations. After Ca++ loading this release mechanism occurs at Ca++ concentrations in the bathing medium starting at about 10(-7,48) Mol/l both in skeletal and heart muscle preparations. (5) Quick stretch of Ca++-loaded, relaxed preparations caused local contractions of the myofibrils in both single fibers and fiber bundles of glycerinated rabbit psoas muscle. Skeletal fiber bundles and cat myocardium show a transient tension development parallel to these local contractions. These effects are demonstrated to be due to a stretch-induced Ca++ release from the SR vesicles. (6) Length-controlled quick stretches or quick releases of partly activated preparations cause sinusoidal tension oscillations superimposed on the well-known, delayed active tension development. In contrast, fully activated preparations do not show superimposed oscillations in tension. Force-controlled quick stretches or quick releases induce equivalent oscillations in length which are more distinct than the tension oscillations, however. These oscillations are also demonstrated to be due to stretch or release-induced changes in the Ca++ fluxes between SR vesicles and the "sarcoplasm". (7) This stretch induced release of Ca++ from the SR could be one reason for the multiple-phase course of active and passive isometric tension development in vivo following quick changes in length, and could also partly explain the prestretch dependence of tension development which cannot be explained from the degree of overlapping of the contractile filaments alone...


Estimating the intrinsic rate of increase of a population from the average numbers of younger and older sisters.
Based on stable population theory, a mathematical relationship is developed between the intrinsic rate of increase (r) of a population and the ratio (Z) of the average number of younger sisters ever born to the average number of older sisters ever born, for a random sample of women in the population. This mathematical formula is then converted into a technique for estimating r from data on numbers of sisters. The extent to which the technique may be generalizable to actual populations is discussed.


Treatment of recalcitrant chronic urticaria with nonsedating antihistamines: is there evidence for updosing?
Nonsedating antihistamines are the first-choice treatment for all forms of urticaria. In patients with recalcitrant urticaria who do not respond to conventional doses of antihistamines, current guidelines recommend increasing doses by up to 4 times in order to obtain better control of the disease. Although few studies have been conducted, there are convincing data from controlled trials for cetirizine, levocetirizine, and desloratadine that support the use of increased doses of such drugs in unresponsive patients. The use of higher doses of antihistamines has not been associated with increased adverse effects or somnolence. More studies with other second-generation antihistamines are required in order to improve the treatment of patients with severe, recalcitrant urticaria.


Importance of the epiphyseal ring in OLIF stand-alone surgery: a biomechanical study on cadaveric spines.
To explore the function of endplate epiphyseal ring in OLIF stand-alone surgery using a biomechanical model to reduce the complications of endplate collapse and cage subsidence. In total, 24 human cadaveric lumbar function units (L1-2 and L3-4 segments) were randomly assigned to two groups. The first group was implanted with long fusion cages which engaged with both inner and outer regions of epiphyseal ring (Complete Span-Epiphyseal Ring, CSER). Those engaged with only the inner half of epiphyseal ring were the second group (Half Span-Epiphyseal Ring, HSER). Each group was divided into two subgroups [higher cage-height (HH) and normal cage-height (NH)]. Specimens were fixed in testing cups and compressed at approximately 2.5 mm/s, until the first sign of structural failure. Trabecular structural damage was analyzed by Micro-CT, as well as the difference of bone volume fraction (BV/TV), trabecular thickness (Tb.Th) et al. in different regions. Endplate collapse was mainly evident in the inner region of epiphyseal ring, where trabecular injury of sub-endplate bone was most concentrated. Endplate collapse incidence was significantly higher in HSER than CSER specimens (P = 0.017). A structural failure occurred at a lower force in HSER (1.41 ± 0.34 KN) compared with CSER (2.44 ± 0.59 KN). HH subgroups failed at a lower average force than NH subgroups. Micro-CT results showed a more extensive trabecular fracture in HSER specimens compared to CSER specimens, especially in HH subgroup. Endplate collapse is more likely to occur with short half span cages than complete span cages, and taller cages compared with normal height cages. During OLIF surgery, we should choose cages matching intervertebral disc space height and place the cages spanning over the whole epiphyseal ring to improve support strength.


Abnormalities of nerve fibers in the circular muscle of patients with slow transit constipation.
Abnormalities of the enteric nervous system are thought to explain the pathophysiology of motility disorders. Our aim was to determine if particular classes of enteric neurons are affected in slow transit constipation (STC). Specimens were taken from the terminal ileum and ascending, transverse and descending colon of patients undergoing subtotal colectomy for STC. Immunohistochemistry was performed using antisera to neuron-specific enolase, tachykinin, leu-enkephalin, choline acetyltransferase, vasoactive intestinal peptide, nitric oxide synthase, tyrosine hydroxylase and neuropeptide Y. The density of nerve fibres labelled with these antibodies in each layer was compared with age-matched controls. The density of nerve fibres with tachykinin and enkephalin immunoreactivity was reduced in the colonic circular muscle of the 15 patients with STC, whereas innervation of all other layers was normal. This reduction of tachykinin-immunoreactive nerve fibres also occurred in nine of the 12 specimens of terminal ileum examined. No difference was detected in the density or distribution of nerve fibres using the other antisera. Excitatory nerve fibres are present in the circular muscle in STC but they are deficient in tachykinins and enkephalin.


Clinicopathologic and immunologic characteristics of non-Hodgkin's lymphomas presenting in the orbit. A report of eight cases.
Of 325 consecutive cases of non-Hodgkin's malignant lymphomas, 8 patients (2.4%) showed orbital presentation. The clinicopathologic and immunologic analysis of the eight patients revealed characteristic biologic features. Despite the apparently isolated orbital presentation, all cases had subclinical systemic disease. Seven of the eight cases exhibited lymphoplasmacytic/cytoid features, with concurrent type II cryoglobulinemia in five of them. In addition, during their clinical course, five patients showed single or multiple subcutaneous nodules with the same histologic and immunologic pattern as the orbital tumor. This study demonstrates that most orbital lymphomas share particular clinicopathologic and immunologic features, suggesting an origin from a B-cell subset with preferential homing to orbital tissues and subcutis.


Natural killer T cells: innate lymphocytes positioned as a bridge between acute and chronic inflammation?
Natural killer T cells are an innate population of T lymphocytes that recognize antigens derived from host lipids and glycolipids. In this review, we focus on how these unique T cells are positioned to influence both acute and chronic inflammatory processes through their early recruitment to sites of inflammation, interactions with myeloid antigen presenting cells, and recognition of lipids associated with inflammation.


Small cell lung cancer. Complete remission and improved survival.
Thirty-two patients with limited-stage small cell lung cancer were treated with combined supervoltage radiotherapy and a combination of cyclophosphamide, doxorubicin and vincristine chemotherapy. The goal of obtaining a complete remission, the necessary step which precedes improved survival, was successful in 26 of 27 of completely re-evaluated patients. Fiberoptic bronchoscopy was useful in substantiating complete remission status. Seventeen of the 32 patients remain alive from 8+ to 28+ months (median 16+ months). Ten patients are alive and relapse-free from 12+ to 28+ months (median 19+ months). Transient granulocytopenia (mean nadir 650 cells/mm3) during induction therapy and the associated risk of infection were the most serious toxicities encountered. This therapy produces complete remission on roentgenography and bronchoscopy, symtomatic improvement and improved survival in the majority of patients with limited-stage small cell lung cancer. A portion of these patients may have their disease eradicated.


[Current role of total esopharyngo-laryngectomy in cervico-facial cancerology. Apropos of 11 cases].
Eleven patients underwent total esophagopharyngolaryngectomy for cancer, with colic or gastric digestive reconstructive surgery. Postoperative course is analyzed, contraindications and indications outlined and other methods of pharyngeal reconstruction discussed. An extension to the technique is proposed to include tumors requiring a circular pharyngolaryngectomy. Improvement in the very poor prognosis of these tumors can only be envisaged by the use of enlarged surgery combined with chemotherapy and radiotherapy.


Perfluorocarbon@Porphyrin Nanoparticles for Tumor Hypoxia Relief to Enhance Photodynamic Therapy against Liver Metastasis of Colon Cancer.
Photodynamic therapy (PDT) shows great promise for the treatment of colon cancer. However, practically, it is a great challenge to use a nanocarrier for the codelivery of both the photosensitizer and oxygen to improve PDT against PDT-induced hypoxia, which is closely related to tumor metastasis. Hence, an effective strategy was proposed to develop an oxygen self-supplemented PDT nanocarrier based on the ultrasonic dispersion of perfluorooctyl bromide (PFOB) liquid into the preformed porphyrin grafted lipid (PGL) nanoparticles (NPs) with high porphyrin loading content of 38.5%, followed by entrapping oxygen. Interestingly, the orderly arranging mode of porphyrins and alkyl chains in PGL NPs not only guarantees a high efficacy of singlet oxygen generation but also reduces fluorescence loss of porphyrins to enable PGL NPs to be highly fluorescent. More importantly, PFOB liquid was stabilized inside PGL NPs with an ultrahigh loading content of 98.15% due to the strong hydrophobic interaction between PGL and PFOB molecules, facilitating efficient oxygen delivery. Both in vitro and in vivo results demonstrated that the obtained O2@PFOB@PGL NPs could act as a prominent oxygen reservoir and effectively replenish oxygen into the hypoxic tumors with no need for external stimulation, conducive to augmented singlet oxygen generation, hypoxia relief, and subsequent downregulation of COX-2 expression. As a result, the use of O2@PFOB@PGL NPs for hypoxia relief dramatically inhibits tumor growth and liver metastasis in an HT-29 colon cancer mouse model. In addition, the O2@PFOB@PGL NPs could serve as a bimodal contrast agent to enhance fluorescence and CT imaging, visualizing nanoparticle accumulation to guide the subsequent laser irradiation for precise PDT.


Improvement in mechanical properties of plasma sprayed hydroxyapatite coatings by Al2O3 reinforcement.
Thermal sprayed hydroxyapatite coatings suffer from poor mechanical properties like tensile strength, wear resistance, hardness, toughness and fatigue. The mechanical properties of hydroxyapatite coatings can be enhanced via incorporation of secondary bioinert reinforcement material. In this study an attempt has been made to improve the mechanical properties of plasma sprayed hydroxyapatite by reinforcing it with 10, 20 and 30% Al2O3. The plasma sprayed coatings have been characterized using FE-SEM/EDAX, XRD, AFM and FTIR spectroscopy. Corrosion studies have been done in simulated body fluid and abrasive wear studies have been performed on flat specimens on a disk wear tester. Microhardness, tensile strength and wear resistance are found to be increased with increasing Al2O3 content. All types of coatings show superior resistance against corrosion in simulated body fluid.


A parallel permeability assay of peptides across artificial membranes and cell monolayers using a fluorogenic reaction.
Here, we report a facile permeability assay to quantitatively evaluate the membrane permeability of multiple peptides in parallel. With a fluorogenic click reaction between azidocoumarin and a terminal alkyne tag introduced on a peptide, the peptide that crossed an artificial membrane or a cell monolayer was quantitatively detected. The method allows a rapid measurement of the permeability of multiple compounds on a plate reader even in the presence of a complex mixture of biological molecules.


Activation of the ISR mediates the behavioral and neurophysiological abnormalities in Down syndrome.
Down syndrome (DS) is the most common genetic cause of intellectual disability. Protein homeostasis is essential for normal brain function, but little is known about its role in DS pathophysiology. In this study, we found that the integrated stress response (ISR)-a signaling network that maintains proteostasis-was activated in the brains of DS mice and individuals with DS, reprogramming translation. Genetic and pharmacological suppression of the ISR, by inhibiting the ISR-inducing double-stranded RNA-activated protein kinase or boosting the function of the eukaryotic translation initiation factor eIF2-eIF2B complex, reversed the changes in translation and inhibitory synaptic transmission and rescued the synaptic plasticity and long-term memory deficits in DS mice. Thus, the ISR plays a crucial role in DS, which suggests that tuning of the ISR may provide a promising therapeutic intervention.


Short-term impact of alcohol detoxification on facial emotions recognition.
Alcohol use disorder (AUD) is associated with impaired social cognition, including the disturbance of facial emotion recognition (FER). Previous studies have focused on the assessment of basic emotions decoding among patients with AUD, but the evolution of these performances in the early phase of alcohol withdrawal remains unknown. This study was based on evolution of social cognition over a period of 21 days in two groups of individuals: a group of 20 AUD patients and a control group of 25 healthy individuals. AUD patients were tested on admission in a detoxification ward and after a 3-week stay. We evaluated FER with the Reading the Mind in the Eyes Test (RMET). We assessed empathy with a multidimensional questionnaire, the Interpersonal Reactivity Index (IRI). We measured anxiety and depression through the self-rating scale Hospital Anxiety and Depression (HAD). We hypothesized that FER would be impaired in AUD patients on admission and improve after detoxification, while being stable in the control group. RMET scores on admission and at discharge were inferior in AUD patients to those observed in HC (P=2×10-6 and P=0.033, respectively). In the patient group, the RMET score improved over the stay (P=0.034). A time-by-group interaction for RMET score was observed (P=0.003). IRI scores on admission were superior in AUD patients (P=0.023) whichwas no longer observed at discharge (P=0.54). This suggests that RMET might be more accurate in measuring theory of mind evolution in AUD patients after withdrawal. HAD scores on admission and at discharge were inferior in AUD patients compared to controls (P=3×10-5 and P=0.007, respectively). After controlling for HAD initial score, a time-by-group interaction was still observed for RMET scores (P=0.026). FER is impaired in patients with Alcohol Use Disorder compared to controls. This alteration improves after alcohol detoxification. We suggest the RMET could be used to follow the improvement of FER during the first month of abstinence, especially as RMET performance has been associated with maintenance of alcohol withdrawal.


Genetic susceptibility to wild and vaccine polio virus: genotypes and their frequency.
The frequency of proposed genotypes which predispose to poliomyelitis, is tabled. Susceptibility is due to a gene or linkage group of genes with a frequency of 2% for the homozygote and 24% for the heterozygote. Two subgroups are identified where a second gene might make the persons susceptible to vaccine strains of virus. Cutter vaccinees might form a third group with increased susceptibility under special circumstances. The age at which genetic susceptibility changes to phenotypic susceptibility may be modified by physical factors such as those due to congenital syphilis and Salvarsan, and thalidomide.


A review of user needs to drive the development of lower limb prostheses.
The development of bionic legs has seen substantial improvements in the past years but people with lower-limb amputation still suffer from impairments in mobility (e.g., altered balance and gait control) due to significant limitations of the contemporary prostheses. Approaching the problem from a human-centered perspective by focusing on user-specific needs can allow identifying critical improvements that can increase the quality of life. While there are several reviews of user needs regarding upper limb prostheses, a comprehensive summary of such needs for those affected by lower limb loss does not exist. We have conducted a systematic review of the literature to extract important needs of the users of lower-limb prostheses. The review included 56 articles in which a need (desire, wish) was reported explicitly by the recruited people with lower limb amputation (N = 8149). An exhaustive list of user needs was collected and subdivided into functional, psychological, cognitive, ergonomics, and other domain. Where appropriate, we have also briefly discussed the developments in prosthetic devices that are related to or could have an impact on those needs. In summary, the users would like to lead an independent life and reintegrate into society by coming back to work and participating in social and leisure activities. Efficient, versatile, and stable gait, but also support to other activities (e.g., sit to stand), contribute to safety and confidence, while appearance and comfort are important for the body image. However, the relation between specific needs, objective measures of performance, and overall satisfaction and quality of life is still an open question. Identifying user needs is a critical step for the development of new generation lower limb prostheses that aim to improve the quality of life of their users. However, this is not a simple task, as the needs interact with each other and depend on multiple factors (e.g., mobility level, age, gender), while evolving in time with the use of the device. Hence, novel assessment methods are required that can evaluate the impact of the system from a holistic perspective, capturing objective outcomes but also overall user experience and satisfaction in the relevant environment (daily life).


Safety and immunogenicity of experimental stand-alone trivalent, inactivated Sabin-strain polio vaccine formulations in healthy infants: A randomized, observer-blind, controlled phase 1/2 trial.
To increase the global supply of affordable IPV vaccine, preferably using Sabin viruses to comply with GAPIII requirements, Takeda has assessed three dosages of a stand-alone sIPV. In this phase I/II study two cohorts of 40 adults and 60 toddlers, respectively, were initially assessed for safety after receiving high-dosage sIPV compared with placebo (adults) or Salk IPV (toddlers). A cohort of 240 infants was then enrolled and randomized (1:1:1:1) to receive low-, medium- or high-dosage sIPV, or a reference Salk IPV in a three-dose primary schedule at 6, 10 and 14 weeks of age. Parents completed safety diaries for 4 weeks after each dose, and immunogenicity was measured as neutralization antibody titers at baseline and four weeks after vaccination. All vaccinations were generally well-tolerated and sIPV had a comparable safety profile to the control arm in adults or the reference Salk IPV vaccine in toddlers and infants. Infants displayed dosage-dependent immune responses to sIPV when assayed using Sabin strains, which were equivalent to the reference IPV in the high-dosage sIPV group for serotypes 1 and 2, but not for Sabin and Salk serotype 3. Seroconversion rates (SCR) of the low- and medium-dosage groups were significantly lower than the Salk IPV group for both Sabin and Salk serotypes 1 and type 2 (p < 0.05), with no significant differences for Salk or Sabin serotypes 3. Responses to sIPV, particularly to Sabin types 1 and 2, were higher in initially seronegative infants, indicating possible interference by maternally-derived antibodies. A novel stand-alone Sabin-based IPV vaccine was well tolerated with an acceptable safety profile, but less immunogenic than reference Salk IPV at 6, 10 and 14 weeks of age for Salk serotypes 1 and 2, with apparent interference by maternal antibodies. Additional preclinical assessments will be made before any further clinical development.


Efficacy of a Brief Blended Cognitive Behavioral Therapy Program for the Treatment of Depression and Anxiety in University Students: Uncontrolled Intervention Study.
Blended cognitive behavioral therapy (bCBT)-the combination of cognitive behavioral therapy and digital mental health applications-has been increasingly used to treat depression and anxiety disorders. As a resource-efficient treatment approach, bCBT appears promising for addressing the growing need for mental health care services, for example, as an early intervention before the chronification of symptoms. However, further research on the efficacy and feasibility of integrated bCBT interventions is needed. This study aimed to evaluate the efficacy of a novel bCBT program comprising short (25 min), weekly face-to-face therapy sessions combined with a smartphone-based digital health app for treating mild to moderate symptoms of depression or anxiety. This prospective uncontrolled trial comprised 2 measurement points (before and after treatment) and 2 intervention groups. We recruited university students with mild to moderate symptoms of depression or anxiety. On the basis of the primary symptoms, participants were assigned to either a depression intervention group (n=67 completers) or an anxiety intervention group (n=33 completers). Participants in each group received 6 weekly individual psychotherapy sessions via videoconference and completed modules tailored to their respective symptoms in the smartphone-based digital health app. The depression group displayed medium to large improvements in the symptoms of depression (Cohen d=-0.70 to -0.90; P<.001). The anxiety group experienced significant improvements in the symptoms of generalized anxiety assessed with the Generalized Anxiety Disorder-7 scale with a large effect size (Cohen d=-0.80; P<.001) but not in symptoms of anxiety assessed with the Beck Anxiety Inventory (Cohen d=-0.35; P=.06). In addition, both groups experienced significant improvements in their perceived self-efficacy (Cohen d=0.50; P<.001 in the depression group and Cohen d=0.71; P<.001 in the anxiety group) and quality of life related to psychological health (Cohen d=0.87; P<.001 in the depression group and Cohen d=0.40; P=.03 in the anxiety group). Work and social adjustment of patients improved significantly in the depression group (Cohen d=-0.49; P<.001) but not in the anxiety group (Cohen d=-0.06; P=.72). Patients' mental health literacy improved in the anxiety group (Cohen d=0.45; P=.02) but not in the depression group (Cohen d=0.21; P=.10). Patient satisfaction with the bCBT program and ratings of the usability of the digital app were high in both treatment groups. This study provides preliminary evidence for the feasibility and efficacy of a novel brief bCBT intervention. The intervention effects were generalized across a broad spectrum of patient-reported outcomes. Hence, the newly developed bCBT intervention appears promising for treating mild to moderate depression and anxiety in young adults.


Peripheral parenteral nutrition: An evaluation of its use, safety and cost implications in a tertiary hospital setting.
Malnutrition is a common challenge among hospitalised patients and its associatiation with poor patient health-related outcomes places a significant financial burden on the healthcare system. Total parenteral nutrition (TPN) is the primary means for providing nutrition to individuals in whom enteral feeding is not possible but is costly and requires invasive central venous access. Peripheral parenteral nutrition (PPN) provides a suitable option for early nutrition provision in select patients; however, its routine use has been limited by safety and tolerability concerns, with high rates of phlebitis reported in previous studies. The objectives of this study were to review the use, safety, and costs of PPN in an Australian tertiary hospital. A single-site, prospective observational study was conducted over 15 months in a tertiary hospital. 139 participants (87 male and 52 female) were enrolled in the study. Data collected assessed the indication for PPN initiation, compliance with the hospital's protocols for PPN, total fasting days, the proportion of the patient's total energy and protein requirements provided by PPN, the incidence of phlebitis and potential cost implications associated with the use of PPN. 139 patients (62.6% male), median age 62 years (IQR (interquartile range) 48-74) were enrolled. Most patients had an emergency admission (80.6%) under a general surgical team (84.2%). Forty-eight patients (34.5%) were malnourished, as assessed by the Subjective Global Assessment tool (SGA). Patients fasted for a median of 3 days (IQR 2-5) before PPN commencement, with a median duration of PPN use of 3 days (IQR 2-4). PPN provided an average of 61.6% of the patients' required caloric intake and 46.4% of protein requirements. Progression to TPN was observed in 34.5% of patients. There were low rates of complications with phlebitis observed in 3.7%, extravasation in 1.1%, and no patients developed septicaemia, despite suboptimal compliance with the recommended cannula management guidelines for PPN (66.4% compliant). The cost of PPN was estimated to be AUD$187 per patient day. PPN is an effective short-term nutrient delivery solution to facilitate early feeding with small numbers of patients requiring transition to TPN. PPN was safe with low rates of cannula complications. Costs were favourable, with potentially significant cost savings as compared with TPN.


Human fibroblast-derived growth factor is a mitogen and chemoattractant for endothelial cells.
Human fibroblasts were found to produce a potent mitogen and chemoattractant for fetal bovine aortic endothelial cells. Homogenates from AG1523 and AG1518 foreskin, CCD18Lu lung, and CCD18Co colon fibroblasts produced half-maximal stimulation of endothelial cell growth at concentrations of 1-7 micrograms/ml. The factor was purified from large-scale cultures of the CCD18Co fibroblasts using cation exchange chromatography and heparin-Sepharose chromatography. Such preparations were mitogenic for endothelial cells in vitro at concentrations of about 5-10 ng/ml, and promoted chemotaxis at 0.1-1 ng/ml. Heparinase treatment of the cells prevented the chemotactic response. These properties suggest that the factor may be related to fibroblast growth factor.


Development and application of the TFA macrosimulation model: a case study of modelling the impact of trans fatty acid (TFA) elimination policies in Brazil.
The consumption of trans-fatty acids (TFA) is directly associated with cardiovascular disease risk and is responsible for a significant health burden globally. The policy strategies for reducing TFA include limiting their content in foods and eliminating partially hydrogenated oils (PHO) in the market. This study aims to describe a comparative risk assessment macrosimulation model and to apply this tool to estimate the potential reductions in CVD mortality gained from the compared scenarios of TFA reduction/elimination in Brazil. We developed and implemented a comparative risk assessment macrosimulation model estimates the potential CVD mortality reduction (coronary heart disease - CHD- and stroke) if TFA intake is reduced in diets. The TFA macrosimulation model estimates the change in the annual number of NCD deaths between baseline with current TFA consumption levels and alternate or counterfactual scenarios, such as considering different limits to TFA content in foods and the elimination of PHO in Brazil in 2018. The model incorporated additional outputs related to other impacts of TFA reduction on DPP, such as Years of Life Lost, Years of Productive Life Lost, and related economic impacts of premature deaths. In 2018, a 2% limit for TFA in the oils and fats and a 5% limit of TFAs for other foods could avert or postpone approximately 2,000 deaths (UI 95% 1,899-2,142) and save US$ 32.1 million savings in productivity losses to the economy associated to premature deaths. An intermediate scenario, applying a 2% limit of TFA in all food products In Brazil could prevent or postpone approximately 6,300 deaths (UI 95% 5,925-6,684) and the premature deaths prevented would represent US$ 100.2 million in economic saving. Finally, by banning PHO, approximately 10,500 deaths could be prevented or postponed (UI 95% 9,963 - 10,909), corresponding to US$ 166.7 million in savings to the economy because of premature deaths. The TFA macrosimulation model can efficiently compare different policy scenarios for trans fats reduction policies at the country level and proves that the elimination of PHOs from the food market in Brazil may significantly reduce the health burden of trans fatty acids in the country compared to other policy options. The model also represents a useful public health tool to support TFA reduction and elimination policies in other countries.


A Year in the College Life: Evidence for the Social Investment Hypothesis via Trait Self-Control and Alcohol Consumption.
The present study examined 12-month prospective relations among trait self-control, subjective role investment, and alcohol consumption in a sample of university students (N = 129). Using neo-socioanalytic theory and the social investment hypothesis as guiding frameworks, it was expected that greater initial role investment would predict greater self-control and less alcohol consumption at follow-up. Path analyses showed higher initial levels of subjective college student role investment predicted greater subsequent self-control and lower drinking amounts, controlling for initial standing on self-control and alcohol consumption. Greater initial trait self-control also predicted subsequent lower alcohol consumption. The discussion emphasizes the importance of incorporating subjective role investment, in addition to nominal role participation, in developmental accounts of personality traits, social identity, and behavior.


Platelet count, antiplatelet therapy and pulmonary embolism--a prospective study in patients with hip surgery.
Pulmonary embolism (PE) is a serious complication following hip surgery. Trials of antiplatelet thromboprophylaxis indicated a substantial reduction in PE rate, and we prospectively studied the effect of a combination of low-dose heparin and two different antiplatelets. Furthermore, our experience in previous studies suggested that platelet count (PC) levels could be useful to reliably suspect PE at a very early stage, and we prospectively tried to confirm our previous findings. Ours is a prospective study in 459 consecutive patients operated on because of hip fracture (265) or elective hip replacement (194), aimed to determine: 1) whether the benefits of antiplatelets plus heparin on PE outweigh the risks; 2) to assess the clinical usefulness of PC monitoring in these patients, so as to confirm whether PE could be recognized early. It was a prospective, randomized, double-blind study. All patients received unfractioned heparin (7500 IU sc twice daily, starting 2 h before operation). In addition, they received aspirin (200 mg thrice daily, with meals), Triflusal (300 mg thrice daily, with meals), or placebo. Real time B-mode ultrasonography (US) was performed on all patients on the 8-9th day after surgery. Venography was performed in patients with normal US, if clinical symptoms suggested venous thrombosis. Twelve out of the 459 patients (2.6%) had to discontinue prophylaxis, because of major bleeding (6 patients), or gastric intolerance (6 patients). There were no significant differences between groups in either deep vein thrombosis (26 patients (18%) with aspirin, 18 (12%) with Triflusal, 26 (17%) with placebo), or PE development (7 patients (5%) with aspirin, 3 (2%) with Triflusal, 8 (5%) taking placebo).(ABSTRACT TRUNCATED AT 250 WORDS)


Emphysematous cystitis presenting with subcutaneous emphysema.
A case is reported of subcutaneous emphysema of the neck in association with emphysematous cystitis and uncontrolled diabetes. Problems in its management are discussed. Anatomic pathway for the spread of the gas from the bladder to the subcutaneous tissues of the neck and the back is speculated.


Effect of Room Temperature Ionic Liquid on the Formation of the Complex Oxalate-Sodium Morin-5-Sulfonate-Aluminium(III): Application to the Fluorescence Determination of Oxalate Ion.
The effect of room temperature ionic liquid (RTIL) on the formation of the fluorescence ternary complex oxalate-sodium morin-5-sulfonate (NaMSA)-Aluminium(III) has been studied. In weakly acidic medium and in the presence of RTIL, 1-Butyl-3-methylimidazolium hexafluorophosphate (BMIM-PF6), total complex formation is achieved as compared with the formation of the binary complex of NaMSA-Aluminium(III). The fluorescence characteristics of the system allowed the establishment of a very sensitive method for the spectrofluorimetric determination of oxalate ion. The ternary complex formed its highest fluorescence signal at 513 nm and excitation at 420 nm. In these conditions, the method produces a detection limit of 0.57 ng mL(-1). The procedure has been satisfactorily applied to the determination of oxalate ion in a vegetal tissue (spinach leaves).


Stereotactic ablative body radiotherapy (SABR) for bone only oligometastatic breast cancer: A prospective clinical trial.
Stereotactic ablative body radiotherapy (SABR) is an emerging noninvasive approach for the treatment of oligometastases. Limited prospective evidence is available in breast cancer. To determine the safety and feasibility of single fraction SABR for patients with bone only oligometastatic breast cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity and response assessment. In this single institution prospective trial we screened patients with computed tomography, bone scan, and sodium fluoride positron emission tomography. Eligible patients had one to three bone only oligometastases. All patients were treated at a dose of 20Gy in 1 fraction to each metastasis. Kaplan-Meier methods were used to determine local and distant progression free survival (LPFS and DPFS). Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. 15 eligible patients were recruited to the study. Median follow-up time was 24 months. The treatment was feasible in 12 (80%) of patients with 3 (20%) of patients having treatment delayed by more than 3 days. 10 (67%) of patients experienced grade 1 treatment related toxicity, 4 (27%) experienced grade 2 toxicity and no patients experienced grade 3 or 4 treatment related toxicity. The two-year LPFS was 100%, DPFS was 67%. We observed that SABR is feasible, well tolerated and effective in this cohort with two thirds of patients disease-free at two years. In selected patients with bone-only oligometastatic disease, SABR could be considered a treatment option. Randomised trials are required to assess the impact of SABR on overall survival when compared to the standard of care.


The secreted oligomeric form of α-synuclein affects multiple steps of membrane trafficking.
α-Synuclein (α-syn) can be secreted from neurons into the extracellular space, affecting the homeostasis of neighboring cells, but the pathophysiology of secreted α-syn remains largely unknown. We found that when exogenously applied to COS-7 cells, α-syn secreted from differentiated SH-SY5Y cells was taken up by dynamin-dependent endocytosis. Upon internalization, α-syn significantly increased the rate of transferrin receptor (TfR) internalization and recycling, and subsequently the surface levels of TfR. The effects are attributable to the oligomeric form, but not monomeric or fibrillar form, of extracellular α-syn. Together, multiple alterations in membrane trafficking by secreted oligomeric α-syn may contribute to the early stages of pathogenesis in Parkinson's disease.


Caspase-1 cleaves PPARγ for potentiating the pro-tumor action of TAMs.
Tumor-associated macrophages are increasingly viewed as a target of great relevance in the tumor microenvironment, because of their important role in cancer progression and metastasis. However, the endogenous regulatory mechanisms underlying tumor-associated macrophage differentiation remain largely unknown. Here, we report that caspase-1 promotes tumor-associated macrophage differentiation by cleaving peroxisome proliferator-activated receptor gamma (PPARγ) at Asp64, thus generating a 41 kDa fragment. This truncated PPARγ translocates to mitochondria, where it directly interacts with medium-chain acyl-CoA dehydrogenase (MCAD). This binding event attenuates MCAD activity and inhibits fatty acid oxidation, thereby leading to the accumulation of lipid droplets and promoting tumor-associated macrophage differentiation. Furthermore, the administration of caspase-1 inhibitors or the infusion of bone marrow-derived macrophages genetically engineered to overexpress murine MCAD markedly suppresses tumor growth. Therefore, targeting the caspase-1/PPARγ/MCAD pathway might be a promising therapeutic approach to prevent tumor progression.Tumor associated macrophages (TAMs) promote cancer progression. Here, the author show that caspase-1 promotes TAMs differentiation by attenuating medium-chain acyl-CoA dehydrogenase activity and that inhibition of this axis results in suppression of tumour growth in a transgenic mouse model of breast cancer.


COL1A1-PDGFB fusion in a pediatric Bednar tumor with 2 copies of a der(22)t(17;22).
We present a 10-year-old girl with a pure Bednar tumor (pigmented dermatofibrosarcoma protuberans) of the right shoulder. Cytogenetic analysis demonstrated 47 chromosomes with 2 copies of a derivative chromosome 22, der(22)t(17;22)(q22;q13). Fluorescence in situ hybridization (FISH) analysis demonstrated the COL1A1-PDGFB fusion on both der(22) chromosomes. By RT-PCR and sequencing, we observed a fusion of the COL1A1 exon 41 with PDGFB exon 2. This pure pediatric Bednar tumor in a child, like childhood dermatofibrosarcoma protuberans, had a linear structural abnormality rather than a ring chromosome that is more commonly encountered in adult Bednar and dermatofibrosarcoma protuberans tumors. The underlying molecular abnormality in this pediatric Bednar tumor is the same as in dermatofibrosarcoma protuberans.


Vaccination with liposome-coupled glypican-3-derived epitope peptide stimulates cytotoxic T lymphocytes and inhibits GPC3-expressing tumor growth in mice.
Because therapeutic manipulation of immunity can induce tumor regression, anti-cancer immunotherapy is considered a promising treatment modality. We previously reported that glypican-3 (GPC3), an oncofetal antigen overexpressed in hepatocellular carcinoma (HCC), is a useful target for cytotoxic T lymphocyte (CTL)-mediated cancer immunotherapy, and we have performed clinical trials using the GPC3-derived peptide vaccine. Although vaccine-induced GPC3-peptide-specific CTLs were often tumor reactive in vitro and were correlated with overall survival, no complete response was observed. In the current study, we synthesized liposome-coupled GPC3-derived CTL epitope peptide (pGPC3-lipsome) and investigated its antitumor potential. Vaccination with pGPC3-liposome induced peptide-specific CTLs at a lower dose than conventional vaccine emulsified in incomplete Freund's adjuvant. Coupling of pGPC3 to liposomes was essential for effective priming of GPC3-specific CTLs. In addition, immunization with pGPC3-liposome inhibited GPC3-expressing tumor growth. Thus, vaccination with tumor-associated antigen-derived epitope peptides coupled to the surfaces of liposomes may be a novel therapeutic strategy for cancer.


Rate of fertilization in vitro and subsequent nuclear development as a function of the post-ovulatory age of the mouse egg.
Evidence is presented to indicate that older mouse eggs are fertilized more rapidly and also develop more rapidly to the pronuclear stage than younger ones. After a low (1.5 i.u.) or a high (7.5 i.u.) dose of PMSG, female mice were killed 13 or 17 h after hCG. The eggs were mixed in vitro with preincubated spermatozoa and fixed 1--1 1/4 h later. Although fertilization levels were high in all groups, the stages of egg activation and sperm head decondensation differed significantly. The observed ranking, from most to least rapid fertilization, of eggs obtained from females treated with 7.5 i.u. and killed 17 h after hCG, 1.5 i.u. and 13 h, and 7.5 i.u. and 13 h, was consistent with the approximate length of time the eggs had resided in the oviduct, i.e. the longer that time period, the more rapid the fertilization. When eggs were fixed 4 1/4 h after mixing with spermatozoa, the majority of older eggs were fully pronuclear while only a few of the younger eggs were as advanced, indicating accelerated nuclear development in the cytoplasm of the older eggs.