Angiogenic Response following Radioembolization: Results from a Randomized Pilot Study of Yttrium-90 with or without Sorafenib.
To compare the regulation of serum angiogenic factors in patients with unresectable early hepatocellular carcinoma (HCC) treated with yttrium-90 ((90)Y) radioembolization alone vs with sorafenib. In a single-center pilot study, 23 patients with unresectable HCC awaiting orthotopic liver transplantation were prospectively randomized to receive radioembolization alone (n = 12) or radioembolization with sorafenib (n = 11). Serum angiogenic markers (angiopoietin-2 [Ang-2], hepatocyte growth factor, interleukin [IL]-6, IL-8, c-reactive protein, platelet-derived growth factor [PDGF], and vascular endothelial growth factor [VEGF]) were assayed at baseline and at 2 and 4 weeks after radioembolization ((90)Y alone, n = 6; (90)Y plus sorafenib, n = 7). In the (90)Y-alone group, all growth factors were elevated above baseline levels at 2 and 4 weeks: VEGF increased 36% vs baseline at 2 weeks and 22% at 4 weeks, and PDGF increased 24% at 2 weeks and 3% at 4 weeks. In the (90)Y/sorafenib arm, Ang-2 and PDGF decreased at 2 weeks and the remainder increased. By 4 weeks, only PDGF remained below baseline levels. VEGF increased 49% at 2 weeks and 28% at 4 weeks, and PDGF decreased 31% at 2 weeks and 39% at 4 weeks. Differences were statistically significant for hepatocyte growth factor (P = .03) and PDGF (P = .02) at 2 weeks and for IL-6 (P = .05) at 4 weeks. Radioembolization is associated with a mild increase in angiogenic markers. The addition of sorafenib blunts PDGF response; other factors such as VEGF remain unaffected. The predominant effect of sorafenib may be through downregulation of PDGF and not VEGF.


Rheological properties of white blood cells are changed in diabetic patients with microvascular complications.
Erythrocyte and white blood cell suspensions were prepared from 22 Type 1 (insulin-dependent) and 37 Type 2 (non-insulin-dependent) diabetic patients and from 57 control subjects. Cell filterability was studied with the new "St. George's Filtrometer", which can discriminate between cell deformability and filter occlusion. A pronounced increase of filter clogging was found in diabetic patients compared with control subjects. There was no significant difference between Type 1 and Type 2 diabetic patients, but a significantly increased clogging was found in patients with retinopathy compared with retinopathy-free patients. Considering that filter occlusion is mainly due to leucocytes, our results show a reduced filterability of white blood cells in diabetic patients. Altered white blood cell function may act as an additional factor in the impairment of microvascular circulation in diabetic patients.


Clinical efficacy of mogamulizumab for relapsed/refractory aggressive adult T-cell leukemia/lymphoma: A retrospective analysis.
Although phase 2 studies have confirmed the efficacy of mogamulizumab for adult T-cell leukemia/lymphoma (ATL), real-world data on its benefits are limited. We assessed the benefits of mogamulizumab for relapsed/refractory ATL in clinical practice. We retrospectively analyzed patients with acute- and lymphoma-type ATL. Among 57 patients diagnosed with ATL between January 2008 and August 2018, 42 who received salvage therapy were eligible, including 24 who received mogamulizumab. The overall response rate to mogamulizumab was 54.2%. Median survival time (MST) and 1-year overall survival (OS) rate from mogamulizumab initiation were 7.7 months and 42.0%, respectively. Patients with acute-type ATL showed longer MST (15.1 months) and higher 1-year OS (63.6%). MST without skin rash was 5.0 months, and 1-year OS was 34.3%; however, MST with skin rash was not reached and 1-year OS was 66.7%. Among patients who received the salvage therapy, longer MST and higher 1-year OS were observed with mogamulizumab than without mogamulizumab (P = .078; 9.2 vs. 3.9 months; 47.9% vs. 17.6%, respectively). Mogamulizumab administration improved prognosis in patients with acute-type ATL and skin rash. In clinical practice, mogamulizumab improved OS in patients with relapsed/refractory ATL, especially those with acute-type ATL and skin rash.


Vegetation as a key driver of the distribution of microbial generalists that in turn shapes the overall microbial community structure in the low Arctic tundra.
Understanding the variability of microbial niches and their interaction with abiotic and biotic factors in the Arctic can provide valuable insights into microbial adaptations to extreme environments. This study investigates the structure and diversity of soil bacterial communities obtained from sites with varying vegetation coverage and soil biogeochemical properties in the low Arctic tundra and explores how bacteria interact under different environmental parameters. Our findings reveal differences in bacterial composition and abundance among three bacterial niche breadths (specialists, common taxa, and generalists). Co-occurrence network analysis revealed Rhizobiales and Ktedonobacterales as keystone taxa that connect and support other microbes in the habitat. Low-elevation indicators, such as vascular plants and moisture content, were correlated with two out of three generalist modular hubs and were linked to a large proportion of generalists' distribution (18%). Structural equation modeling revealed that generalists' distribution, which influenced the remaining microbial communities, was mainly regulated by vegetation coverage as well as other abiotic and biotic factors. These results suggest that elevation-dependent environmental factors directly influence microbial community structure and module formation through the regulation of generalists' distribution. Furthermore, the distribution of generalists was mainly affected by macroenvironment filtering, whereas the distribution of specialists was mainly affected by microenvironment filtering (species-engineered microbial niche construction). In summary, our findings highlight the strong top-down control exerted by vegetation on generalists' distribution, which in turn shapes the overall microbial community structure in the low Arctic tundra.


The influence of body weight support on ankle mechanics during treadmill walking.
The use of body weight support (BWS) systems during locomotor retraining has become routine in clinical settings. BWS alters load receptor feedback, however, and may alter the biomechanical role of the ankle plantarflexors, influencing gait. The purpose of this study was to characterize the biomechanical adaptations that occur as a result of a change in limb load (controlled indirectly through BWS) and gait speed during treadmill locomotion. Fifteen unimpaired participants underwent gait analysis with surface electromyography while walking on an instrumented dual-belt treadmill at seven different speeds (ranging from 0.4 to 1.6m/s) and three BWS conditions (ranging from 0% to 40% BWS). While walking, spatiotemporal measures, anterior/posterior ground reaction forces, and ankle kinetics and muscle activity were measured and compared between conditions. At slower gait speeds, propulsive forces and ankle kinetics were unaffected by changing BWS; however, at gait speeds ≥ approximately 0.8m/s, an increase in BWS yielded reduced propulsive forces and diminished ankle plantarflexor moments and powers. Muscle activity remained unaltered by changing BWS across all gait speeds. The use of BWS could provide the advantage of faster walking speeds with the same push-off forces as required of a slower speed. While the use of BWS at slower speeds does not appear to detrimentally affect gait, it may be important to reduce BWS as participants progress with training, to encourage maximal push-off forces. The reduction in plantarflexor kinetics at higher speeds suggests that the use of BWS in higher functioning individuals may impair the ability to relearn walking.


Antibodies against p53 are associated with poor prognosis of colorectal cancer.
Mutation of the p53 gene is a common event in colorectal cancer. This alteration can result in cellular accumulation of p53 and may also induce p53 antibodies. Accumulation of p53 in tumour cells has been associated with poor prognosis of colorectal cancer. We tested preoperative sera from 255 patients with colorectal cancer by enzyme-linked immunosorbent assay (ELISA). A total of 70.2% had reactivity that was higher than the 'low' control serum. Employing a cut-off level of 10% of the 'high' control sample, 25.5% of the patients were positive for p53 antibodies. The presence of p53 antibodies correlated with the following prognostic factors: histological differentiation grade, shape of the tumour, and tumour invasion into blood vessels. Patients with p53 antibodies were shown to have decreased survival and decreased disease-free survival. Specifically for patients with cancer stage A and B1 the presence of p53 antibodies selected a subgroup with poor prognosis.


Finger skin temperatures in 8- to 11-year-old children: determinants including physical characteristics and seasonal variation. The Physical Activity and Nutrition in Children (PANIC) Study.
The fingertip skin temperature (FST) reflects skin blood flow, and FST measurement has been suggested for the investigation of vascular responses. As a limitation, the multifactorial nature and the seasonal variation in measured values have been earlier described in adults but not in children. In the present study, we identify the modifiers of FST in a population sample of Finnish children. FST was measured in children (age range 8-11 years, n = 432) with infrared thermometer, and its possible determinants including the subjects' physical characteristics and seasonal variables, such as daylight time and outdoor temperature, were identified. In univariate regression models, FST was dependent on the sex, age and anthropometric characteristics of the children with the higher body fat content-related variables and a lower surface area-to-mass ratio as strongest single modifiers of FST. There was interaction between sex and puberty with FST. In addition, FST was directly related to daylight time and outdoor temperature although the children had stayed inside for at least 2 h before the measurements. The FST values were lowest in the winter and highest in the summer. In multivariate regression model, main determinants of FST were a higher body fat percentage (standardized regression coefficient β = 0.472; p < 0.001), male sex (β = 0.291; p < 0.001) and longer daylight time (0.226; p < 0.001). Altogether, complex effects of body composition and sex with the confounding effect of seasonal variation may complicate the use of FST as a tool to study the vascular function in children.


Strong σ-Hole Activation on Icosahedral Carborane Derivatives for a Directional Halide Recognition.
Crystal engineering based on σ-hole interactions is an emerging approach for realization of new materials with higher complexity. Neutral inorganic clusters derived from 1,2-dicarba-closo-dodecaborane, substituted with -SeMe, -TeMe, and -I moieties on both skeletal carbon vertices are experimentally demonstrated herein as outstanding chalcogen- and halogen-bond donors. In particular, these new molecules strongly interact with halide anions in the solid-state. The halide ions are coordinated by one or two donor groups (μ1 - and μ2 -coordinations), to stabilize a discrete monomer or dimer motifs to 1D supramolecular zig-zag chains. Crucially, the observed chalcogen bond and halogen bond interactions feature remarkably short distances and high directionality. Electrostatic potential calculations further demonstrate the efficiency of the carborane derivatives, with Vs,max being similar or even superior to that of reference organic halogen-bond donors, such as iodopentafluorobenzene.


Enhanced immunogenicity of leukemia-derived exosomes via transfection with lentiviral vectors encoding costimulatory molecules.
Tumor cell-derived exosomes (TEXs) have been widely used to induce antitumor immune responses in animal models and clinical trials. Similarly, leukemia cell-derived exosomes (LEXs) can induce antileukemia immune responses in animal models. However, the antileukemia immunity induced by LEXs is less effective, which may be due to an inadequate costimulatory capacity. In this study, we transduced L1210 leukemia cells with a lentiviral vector encoding two B7 costimulatory molecules (CD80, CD86) and obtained LEXs that highly expressed CD80 and CD86. The antileukemia immune response derived from these LEXs was examined in vitro and in vivo in animal models. We found that B7 gene-modified LEXs, including LEX-CD80, LEX-CD86, and LEX-8086, could significantly boost the expression of CD80 and CD86 in dendritic cells (DCs) and promote the secretion of functional cytokines such as TNF-α and IL-12. Moreover, these B7 gene-modified LEXs, particularly LEX-CD8086, could effectively induce CD4+ T cell proliferation, Th1 cytokine secretion, and an antigen-specific anti-leukemia cytotoxic T lymphocyte (CTL) response. Additional animal studies indicated that immunization with B7 gene-modified LEXs, in particular LEX-CD8086, could significantly retard tumor growth compared to the control LEXnull group. This study sheds light on the feasibility of obtaining LEXs that overexpress costimulatory molecules via genetically modified leukemia cells, thereby enhancing their anti-leukemia immunity and providing a potential therapeutic strategy that contributes to leukemia immunotherapy.


Practical Review on Preclinical Human 3D Glioblastoma Models: Advances and Challenges for Clinical Translation.
Fifteen years after the establishment of the Stupp protocol as the standard of care to treat glioblastomas, no major clinical advances have been achieved and increasing patient's overall survival remains a challenge. Nevertheless, crucial molecular and cellular findings revealed the intra-tumoral and inter-tumoral complexities of these incurable brain tumors, and the essential role played by cells of the microenvironment in the lack of treatment efficacy. Taking this knowledge into account, fulfilling gaps between preclinical models and clinical samples is necessary to improve the successful rate of clinical trials. Since the beginning of the characterization of brain tumors initiated by Bailey and Cushing in the 1920s, several glioblastoma models have been developed and improved. In this review, we focused on the most widely used 3D human glioblastoma models, including spheroids, tumorospheres, organotypic slices, explants, tumoroids and glioblastoma-derived from cerebral organoids. We discuss their history, development and especially their usefulness.


Near-infrared (NIR) disrelation mapping analysis for poly(lactic) acid nanocomposite.
Near infrared (NIR) imaging data of poly(lactic) acid (PLA) nanocomposite were analysed by disrelation mapping to prove the possible interaction between PLA matrix and montmorillonite-based nanoclay. The basic concept of disrelation mapping can be viewed as a spatial filter based on two-dimensional (2D) correlation function to elucidate specific areas where disrelated variation between intensities occurs. Correlation intensity develops on disrelation map only if spectral intensities at v1 and v2 within the local spatial area vary in a dissimilar manner. This feature is especially suitable for identifying the area where interaction between components occurs, which is not fully detected by the conventional visualizations based on a single wavenumber. Disrelation maps constructed with NIR bands arising from the crystalline and amorphous components of the PLA. The pattern appearing on the disrelation map indicated different distributions of the crystalline and amorphous components of the nanocomposite sample. In addition, the development of disrelation intensity becomes acute especially at the area adjacent to the clay, revealing that the clay essentially works as nucleating agent to cause the additional development of crystalline structure of PLA by lowering the surface energy barrier.


Toxic shock syndrome due to an infected human bite.
We report a case of nonmenstrual toxic shock syndrome. A 21-year-old man presented with severe pain in the right hand after an altercation in which he sustained a bite from a person. Physical examination revealed a small abscess on the right proximal interphalangeal joint with edema in the fourth and fifth digits and tenderness of the flexor sheath. The patient was hypotensive with diffuse macular erythematous skin. He responded to surgical drainage and antibiotics.


Erdheim-Chester disease.
Erdheim-Chester disease (ECD) is a rare form of non-Langerhans' cell histiocytosis. Diagnosis of ECD is based on the identification in tissue biopsy of histiocytes, which are typically foamy and immunostain for CD68+ CD1a-. Central nervous system involvement is a major prognostic factor in ECD. Interferon alpha may be the best first-line therapy and significantly improves survival of ECD. The BRAFV600E mutation is found in more than 50% of cases. Vemurafenib has been used for a small number of patients harbouring this mutation; inhibition of BRAF activation by vemurafenib was highly beneficial in these cases of severe multisystemic and refractory ECD.


GHG emission factors for bioelectricity, biomethane, and bioethanol quantified for 24 biomass substrates with consequential life-cycle assessment.
Greenhouse gas (GHG) emission savings from biofuels dramatically depend upon the source of energy displaced and the effects induced outside the energy sector, for instance land-use changes (LUC). Using consequential life-cycle assessment and including LUC effects, this study provides GHG emission factors (EFs) for bioelectricity, biomethane, and bioethanol produced from twenty-four biomasses (from dedicated crops to residues of different origin) under a fossil and a non-fossil energy system. Accounting for numerous variations in the pathways, a total of 554 GHG EFs were quantified. The results showed that, important GHG savings were obtained with residues and seaweed, both under fossil and non-fossil energy systems. For high-yield perennial crops (e.g. willow and Miscanthus), GHG savings were achieved only under fossil energy systems. Biofuels from annual crops and residues that are today used in the feed sector should be discouraged, as LUC GHG emissions exceeded any GHG savings from displacing conventional energy sources.


The relationship of smoking to cg05575921 methylation in blood and saliva DNA samples from several studies.
Numerous studies have shown that cg05575921 methylation decreases in response to smoking. However, secondary to methodological issues, the magnitude and dose dependency of that response is as of yet unclear. This lack of certainty is a barrier to the use of DNA methylation clinically to assess and monitor smoking status. To better define this relationship, we conducted a joint analysis of methylation sensitive PCR digital (MSdPCR) assessments of cg05575921 methylation in whole blood and/or saliva DNA to smoking using samples from 421 smokers and 423 biochemically confirmed non-smokers from 4 previously published studies. We found that cg05575921 methylation manifested a curvilinear dose dependent decrease in response to increasing cigarette consumption. In whole blood DNA, the Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) of cg05575921 methylation for predicting daily smoking status was 0.98. In saliva DNA, the gross AUC was 0.91 with correction for cellular heterogeneity improving the AUC to 0.94. Methylation status was significantly associated with the Fagerstrom Test for Nicotine Dependence score, but with significant sampling heterogeneity. We conclude that MSdPCR assessments of cg05575921 methylation are a potentially powerful, clinically implementable tool for the assessment and management of smoking.


Allergic reaction to orthodontic wire: report of case.
This case illustrates the importance of a thorough clinical history and the benefit of histopathologic examination. The history of contact allergy to jewelry provided an early clue, and the microscopic features confirmed the clinical impression of allergic stomatitis.


Correction to: Real‑world experience with dalbavancin therapy in gram‑positive skin and soft tissue infection, bone and joint infection.
The original version of this article unfortunately contained a mistake. The presentation of Fig. 1 was incorrect. The corrected figure is given below.


Thioredoxin interacting protein genetic variation is associated with diabetes and hypertension in the Brazilian general population.
To investigate the relationship between TXNIP polymorphisms, diabetes and hypertension phenotypes in the Brazilian general population. Five hundred seventy-six individuals randomly selected from the general urban population according to the MONICA-WHO project guidelines were phenotyped for cardiovascular risk factors. A second, independent, sample composed of 487 family-trios from a different site was also selected. Nine TXNIP polymorphisms were studied. The potential association between TXNIP variability and glucose-phenotypes in children was also explored. TXNIP expression was quantified by real-time PCR in 53 samples from human smooth muscle cells primary culture. TXNIP rs7211 and rs7212 polymorphisms were significantly associated with glucose and blood pressure related phenotypes. In multivariate logistic regression models the studied markers remained associated with diabetes even after adjustment for covariates. TXNIP rs7211 T/rs7212 G haplotype (present in approximately 17% of individuals) was significantly associated to diabetes in both samples. In children, the TXNIP rs7211 T/rs7212 G haplotype was associated with fasting insulin concentrations. Finally, cells harboring TXNIP rs7212 G allele presented higher TXNIP expression levels compared with carriers of TXNIP rs7212 CC genotype (p=0.02). Carriers of TXNIP genetic variants presented higher TXNIP expression, early signs of glucose homeostasis derangement and increased susceptibility to chronic metabolic conditions such as diabetes and hypertension. Our data suggest that genetic variation in the TXNIP gene may act as a "common ground" modulator of both traits: diabetes and hypertension.


Fibrin sealant patch for repair of acute type a aortic dissection.
The use of glues to repair disrupted tissue during acute type-A aortic dissection (TAD) surgery may be discontinuous, and cause embolization and cell necrosis. We report a method of fibrin sealant patch (FSP) to reinforce dissected aortic tissue with a collagen double layer coated with fibrinogen/thrombin on either side (TachoSil®; Takeda, Konstanz, Germany). In 12 patients (seven male, 66.9 ± 11.7 years) with acute TAD we performed FSP of the intima-media disruption at the proximal and distal anastomosis of the aorta. We analyzed the perioperative course and echocardiographical, radiological, and clinical outcomes up to one year. Additionally, we investigated the adhesive potential of the FSP in vitro. In vitro, the adhesive strength of the FSP was 60 N/cm(2). In-hospital mortality was 8.3% (n = 1), recovery was satisfactory with no major neurologic events, mean ICU stay was 13.6 ± 6.0 days, mean hospital stay was 20.7 ± 4.4 days. A total of 7.0 ± 2.6 RBC, 3.4 ± 1.5 platelets, and 8.0 ± 4.3 FFP were transfused. One-year survival was 83.3%. In 6/6 DeBakey II dissections the intimal tear was completely resected, in 2/6 DeBakey I dissections the false lumen in the descending aorta completely collapsed. No redissections and no relevant aortic valve insufficiencies were seen during follow-up. This analysis shows that FSP using a collagen matrix double layer coated with fibrinogen/thrombin is feasible, safe, and effective in repairing the dissected aortic tissue. It results in continuous reinforcement of aortic tissue and completely avoids the need for conventional glues.


Pharmacokinetic profile of irinotecan in patients with chronic kidney disease: Two cases and literature review.
There are limited pharmacokinetic data on the use of irinotecan in patients with reduced glomerular filtration rate (GFR) and no haemodialysis. In this case report, we present 2 cases and review the current literature. The dose of irinotecan in both patients was reduced pre-emptively due to reduced GFR. The first patient had her irinotecan dose reduced to 50%, but was nevertheless admitted to hospital because of irinotecan-induced toxicity, including gastrointestinal toxicity and neutropenic fever. The dose was reduced further to 40% for the second cycle; however, the patient was again admitted to the hospital, and irinotecan was stopped indefinitely. The second patient also had his irinotecan dose reduced to 50% and was admitted to the emergency department for gastrointestinal toxicity after the first cycle. However, irinotecan could be administered in the same dose in later cycles. The area under the curve to infinity of irinotecan and SN-38 in the first patient were comparable to those of an individual receiving 100% dose intensity. The area under the curve to infinity of irinotecan and SN-38 in patient 2 in both cycles were slightly less than reference values. Furthermore, clearance values of irinotecan and SN-38 in our patients were comparable to those without renal impairment. Our case report suggests that reduced GFR may not significantly affect the clearance of irinotecan and SN-38, but can still result in clinical toxicity. Reduced initial dosing seems indicated in this patient population. Further research is needed to fully understand the relationship between reduced GFR, pharmacokinetics, and toxicity of irinotecan and SN-38.


Determination of antibiotics and detergent residues in decellularized tissue-engineered heart valves using LC-MS/MS.
Residual chemicals that are presented during tissue processing in human tissue banks can be a risk for the allograft recipient. Determine the residual concentrations of the antibiotics and detergent used in the process of human decellularized tissue-engineered heart valves stored in isotonic saline solution up to 18 months. A total of 24 human decellularized allografts were stored in sterile sodium chloride and analyzed immediately after the decellularization process (0 months) and after storage for 6, 12, and 18 months, which includes the use of sodium dodecyl sulfate (SDS) and antibiotics (cefoxitin, vancomycin hydrochloride, lincomycin hydrochloride, polymyxin B sulfate). These valves were used for suitability tests, the zone of inhibition evaluation, and direct contact cytotoxicity assay. The stock solution from 32 valves was used for LC-MS/MS analysis of antibiotics and SDS. Tissue samples from decellularized valves showed a zone of inhibition formation for S. aureus and B. subtilis, suggesting the presence of an inhibitory molecule in the tissue. Cytotoxicity tests were negative. Polymyxin B, vancomycin, and SDS were detected and quantified in human decellularized aortic and pulmonary allografts during all periods of the study. There were no traces of residual cefoxitin and lincomycin in the tissue stock solution. We found residual concentrations of the antibiotics and detergent used in the process of human decellularized tissue-engineered heart valves stored in isotonic saline solution up to 18 months.


Residual valve and stricture after posterior urethral valve ablation: how to evaluate?
To investigate the clinical and radiological parameters of posterior urethral valve (PUV) patients with residual valve or strictures after primary valve ablation. A total of 127 PUV patients were treated in our clinic between 1986 and 2009. We retrospectively reviewed the records of 101 patients, who had at least 1 year of follow-up data, regarding the presence of valve remnants or urethral strictures after PUV ablation. A total of 21 patients (20.8%) underwent repeat-urethroscopy and, of these, residual valve leaflets or stricture were detected in 10 patients (10/101, 9.9%). In 2 of these 10 (20%), the urethra had been found to be normal on the first voiding cystourethrogram following ablation. However, these two boys underwent re-urethroscopy due to persistent vesicoureteral reflux in one and persistent hydroureteronephrosis in the other, and valve remnants were detected. The remaining 8 cases had radiological signs consistent with persistent infravesical obstruction in the early period. Obstruction was due to urethral stricture and residual valve remnants in 2 and 6 cases, respectively. There was clinical suspicion of residual valve in about 20% of the cases and in half of these the urethra was found to be normal on urethroscopy. The possible presence of residual valve remnants after primary valve ablation should be confirmed by careful clinical, radiological and endoscopic evaluation.


A differential behavior of α-amylase, in terms of catalytic activity and thermal stability, in response to higher concentration CaCl2.
A differential relationship was observed between thermal stability and catalytic activity of α-amylase in the presence of different concentrations of CaCl(2). The enzyme displays optimum catalytic activity in the presence of 1.0-2.0 mM CaCl(2). Further addition of CaCl(2) leads to inhibition of the enzyme, however, at the same time the enzyme gains an additional resistance against thermal denaturation. It was evident that the enzyme is thermodynamically more stable (compared to the active enzyme) in the presence of inhibitory concentration of CaCl(2). For example, the thermal transition temperature (T(m)) of optimally active α-amylase was found to be 64±1°C, whereas, for the less active enzyme (in the presence 10 mM CaCl(2)) the value was determined to be 71±1°C. Similarly, the activation energy of thermal inactivation (Ea) was found to be 228±12 kJ/mol and 291±15 kJ/mol for the optimally active enzyme and the enzyme in the presence of 10 mM CaCl(2), respectively. Biophysical analysis of different states of the enzymes in response to variable calcium level indicates no significant change in the secondary structure in response to different concentration of CaCl(2), however the less active but thermodynamically stable enzyme (in the presence of higher concentration of CaCl(2)) was shown to have relatively more compact structure. The results suggest that the enzyme has separate catalytic and structure stabilizing domains and they significantly vary in their functional attributes in response to calcium level.


Influence of walking speed on gait spatiotemporal parameters and the functional rockers of the foot in healthy adults.
The gait cycle is generally divided into stance phase and swing phase. The stance phase can also be divided into three functional rockers, each with a distinct fulcrum. It has been shown that walking speed (WS) influences both stance and swing phase but its influence on the functional foot rockers duration is unknown. The aim of the study was to analyze the WS influence on functional foot rockers duration. a cross-sectional study is completed with 99 healthy volunteers to assess the effect of WS on kinematics and foot rockers duration in treadmill walking at 4, 5, and 6 km·h-1 RESULTS: Friedman test exhibited that all spatiotemporal variables and the length of the foot rockers changed significantly with WS (p < 0.05) except rocker 1 at 4 and 6 km·h-1. Every spatiotemporal parameter and the duration of the three functional rockers are affected by walking speed, although not all rockers are affected equally. The findings of this study reveal that Rocker 2 is the primary rocker whose duration is influenced by changes in gait speed.


Role of diffusing capacity in predicting complications after lung resection for cancer.
The purpose of our study was to determine whether the assessment of the diffusing capacity of the lung for carbon monoxide (DL (CO)), together with the forced expiratory volume in 1 second (FEV (1)), could improve the selection of surgical patients. The data of 76 patients undergoing major lung resection (pnemonectomy, bilobectomy or lobectomy) for non-small cell lung cancer were retrospectively studied. All patients were reviewed for age, sex, preexisting medical conditions, operative, and pathological findings and postoperative outcome. Univariate and multivariable logistic regression analysis showed that ppoFEV (1) and ppoDL (CO) were the only statistically significant predictors of pulmonary complications. In the group of patients with marginal ppoFEV (1) (between 30 - 40 %), ppoDL (CO) predicted pulmonary morbidity with a better accuracy ( P < 0.005) than ppoFEV (1) ( P > 0.05). Multiple regression analysis showed that pneumonectomy was the only statistical factor correlated with mortality ( P < 0.05). Our experience seems to suggest that ppoDL (CO) is a strong predictor of pulmonary complications after major lung resection, allowing a better surgical selection of the patients with compromised respiratory function.


Elevation of CSF adenosine deaminase in HIV patient with meningitis from retroviral rebound syndrome, a case report.
Adenosine deaminase (ADA) in cerebrospinal fluid (CSF) is considered to be a useful biomarker in differentiating tuberculous meningitis (TBM) from other meningitis in non-HIV patients. However, its specificity decreases in patients with HIV, and other diseases such as cytomegalovirus encephalitis, toxoplasmosis or meningeal lymphomatosis can also elevate ADA in CSF. We here report a rare case of retroviral rebound syndrome in a HIV patient, whose ADA in CSF was elevated.


Insights into the induced fit mechanism in antithrombin-heparin interaction using molecular dynamics simulations.
Heparin was isolated in the beginning of the 20th century and until today remains as one of the most important drugs able to interfere with the haemostatic process. Due to the side effects produced by heparin therapy, new promising drugs have been developed, as the synthetic pentasaccharide (synthetically derived from the sequence GlcN-GlcA-GlcN-IdoA-GlcN). The anticoagulant activity of this compound is based on potentiation of antithrombin (AT) inhibitory activity upon serine proteinases of clotting cascade, a mechanism based on the conformational modification of AT. In this context, we present here a molecular dynamics (MD) study of the interaction between the synthetic pentasaccharide and AT. The obtained data correctly predicted an induced fit mechanism in AT-pentasaccharide interaction, showing a solvent-exposed P1 residue instead of a hided conformation. Also, the specific contribution of important amino acid residues to the overall process was also characterized, both in (2)S(0) and (1)C(4) conformations of IdoA residue, suggesting that there is no conformational requirement to the interaction of this residue with AT. Altogether, the results show that MD simulations could be used to characterize and quantify the interaction of synthetic compounds with AT, predicting its specific capacity to induce conformational changes in AT structure. Thus, MD simulations of heparin (and heparin-derived)-AT interactions are proposed here as a powerful tool to assist and support drug design of new antithrombotic agents.


Conformational equilibria and free energy profiles for the allosteric transition of the ribose-binding protein.
The ribose-binding protein (RBP) is a sugar-binding bacterial periplasmic protein whose function is associated with a large allosteric conformational change from an open to a closed conformation upon binding to ribose. The crystal structures of RBP in open and closed conformations have been solved. It has been hypothesized that the open and closed conformations exist in a dynamic equilibrium in solution, and that sugar binding shifts the population from open conformations to closed conformations. Here, we study by computer simulations the thermodynamic changes that accompany this conformational change, and model the structural changes that accompany the allosteric transition, using umbrella sampling molecular dynamics and the weighted histogram analysis method. The open state is comprised of a diverse ensemble of conformations; the open ribose-free X-ray crystal conformations being representative of this ensemble. The unligated open form of RBP is stabilized by conformational entropy. The simulations predict detectable populations of closed ribose-free conformations in solution. Additional interdomain hydrogen bonds stabilize this state. The predicted shift in equilibrium from the open to the closed state on binding to ribose is in agreement with experiments. This is driven by the energetic stabilization of the closed conformation due to ribose-protein interactions. We also observe a significant population of a hitherto unobserved ribose-bound partially open state. We believe that this state is the one that has been suggested to play a role in the transfer of ribose to the membrane-bound permease complex.


Traumatic rupture of the stomach after Heimlich maneuver.
Fatal complications following the performance of the Heimlich maneuver have been reported. A 76-year-old woman presented to the emergency department with signs of respiratory distress, abdominal pain and distension one day after airway obstruction and subsequent resuscitation. Despite successful immediate laparotomy and repair of a ruptured stomach, she later succumbed to the sequelae of aspiration of gastric contents and dehiscence of the gastric tear. This is the 4th case of stomach rupture and the 7th reported fatal complication following the Heimlich maneuver. It is recommended that persons who undergo the Heimlich maneuver be examined and observed by a physician, as soon as possible, to rule out complications.


Dual effect of external calcium on the frequency of miniature synaptic potentials in frog sympathetic ganglion cells.
The effect of calcium on spontaneous transmitter release and on the release induced by tetanic stimulation and by raising the external potassium concentration ([K]0) was studied in sympathetic ganglion cells of Rana esculenta. 1. In standard Ringer's solution the frequency of miniature excitatory postsynaptic potentials (mepsp) ranged from 0.05--2.0 s-1 (0.05 +/- 0.09 s-1, n = 37) at room temperature. 2. At a [K]0 of 2.5 mM mepsp frequency was approximately linearly related to the logarithm of the external calcium concentration (log [Ca]0) (0.1 mM less than or equal to [Ca]0 less than or equal to 20 mM). 3. Duration and amplitude of the potentiation of transmitter release after tetanic preganglionic stimulation increased depending on [Ca]0. 4. Mepsp frequency was strongly dependent on [K]0 between 10 and 20 mM; the frequency being increased to about 40 times control level at a [K]0 of 20 mM. 5. Raising [Ca]0 up to 1.8 mM in high K solutions resulted in an increase in mepsp frequency followed by a decrease at higher [Ca]0. 6. These results are consistent with the idea that the effect of calcium on mepsp frequency depends on: (a) the driving force for calcium entry, (b) the effect of Ca ions on the potential gradient within the nerve membrane.


Age-related alterations in retinal function.
Age-related visual deficits that occur in the absence of recognized visual disease are frequently observed. Many of the optical factors contributing to these deficits have been delineated, but the contributing neurophysiological alterations have not been clearly defined. This investigation examined age-related variations in the retinal and cortical processing of visual information. Pattern-specific retinal potentials (pattern electroretinogram or PERG in this series) and cortical potentials (VECPs) were recorded from nine young visual normals (20-30 years) and nine healthy elderly individuals (70-80 years). All subjects had best corrected visual acuity of 20/30 or better. Checkerboard patterns (7.5-60 min. checks) were modulated in a counterphase mode (2.0 and 7.5 rps). PERGs and VECPs were simultaneously recorded. Significant age-related alterations in waveform amplitude and latency were observed for both biopotentials. The VECP alterations were largely the result of the reduction in retinal illumination associated with senile miosis, but this factor could not account for most of the observed PERG alterations. These results suggest that neurophysiological changes in the retina may underlie some of the visual deficits observed in healthy elderly adults.


Antibiotic resistance assessment of Acinetobacter baumannii isolates from Tehran hospitals due to the presence of efflux pumps encoding genes (adeA and adeS genes) by molecular method.
Acinetobacter baumannii (A. baumannii) has caused many problems in nosocomial infections. Efflux pumps are considered as one of the most important mechanisms of resistance in this bacterium and have the ability to excrete toxic substances such as antibiotics out of the cell. In this study, 60 isolates of A. baumannii were collected from patients in several hospitals in Tehran, Iran. After diagnosis using standard biochemical methods, the pattern of antibiotic susceptibility was determined using the disk diffusion method according to CLSI guidelines. The adeA and adeS genes were identified by PCR method. The highest resistance to Piperacillin and the lowest resistance to Gentamicin were observed (100% compared to 48.4%). 6.6% of the isolates had only adeA gene and adeS gene was observed in 8.4% of isolates and both genes were detected in 73.4% of the samples. Despite the high resistance of t A. baumannii o antibiotics and due to the high frequency of genes of adeA and adeS efflux pumps in A. baumannii isolates, it can be concluded that these efflux pumps may play an important role in resistance of this bacterium. By determining the pattern of antibiotic the resistance before treatment, the resistance of this pathogen can be prevented in societies.


Presentation, diagnosis and management of tuberculosis in HIV-infected children in the UK.
Management of HIV-infected children with tuberculosis (TB) is challenging. The objective of this study was to assess current treatment and outcomes in a resource-rich setting in the era of highly active antiretroviral therapy (HAART). A retrospective case-note review of coinfected children was carried out in a large UK-based HIV family clinic. Of 328 HIV-infected children, 18 were diagnosed and treated for active TB. TB presentation led to HIV diagnosis in eight of these 18 children. TB was confirmed microbiologically in 33% of children. Fifteen of the 18 children presented with pulmonary TB, and three with extrapulmonary TB (EPTB). Immunological status at TB diagnosis did not predict EPTB. The mean CD4 T-cell count at TB presentation was 402 cells/microL (mean CD4 percentage 16%), with a range of 0-790 cells/microL (0-34%). In seven children concurrently treated with HAART and anti-tuberculous therapy (ATT), therapeutic drug monitoring (TDM) guided management. No immune reconstitution disease occurred. There was one death, unrelated to TB, 2 years after completion of ATT. An HIV test should be considered in all children diagnosed with TB, especially if there are epidemiological risk factors. Our experience shows that, even with deferral of HAART in concurrently infected children, good therapeutic responses to ATT can be achieved. Where necessary, TDM guiding concurrent HAART and ATT can facilitate good clinical and virological responses.


Production paroxysmal nocturnal hemoglobinuria-like red blood cells by tea.
Normal human red cells incubated with saline extracts of tea develop paroxysmal nocturnal hemoglobinuria-like defects as demonstrated by positive acid and sucrose hemolysis tests. All of a variety of tea preparations tested provoked a sensitivity to complement-dependent hemolysis and, with one exception, a moderate decrease in red cell acetylcholinesterase activity. Complement-dependent hemolysis in teaincubated red cells was inhibited by antisera to C3 and C3 activator, but not by antisera to C4. This suggests that incubation with tea may alter the red cell membrane in a way that specifically potentiates the lytic effects of the alternate pathway of complement, but not the classic pathway. Leupeptin, a protease inhibitor, also prevented complement-dependent hemolysis of red cells incubated with tea. Although the clinical consequences of these observations are unknown, the study was initiated following a report of a young male who had developed an acute limited intravascular hemolytic episode following ingestion of large quantities of a herbal tea.


Angiogenic biomaterials to promote therapeutic regeneration and investigate disease progression.
The vasculature is a key component of the tissue microenvironment. Traditionally known for its role in providing nutrients and oxygen to surrounding cells, the vasculature is now also acknowledged to provide signaling cues that influence biological outcomes in regeneration and disease. These cues come from the cells that comprise vasculature, as well as the dynamic biophysical and biochemical properties of the surrounding extracellular matrix that accompany vascular development and remodeling. In this review, we illustrate the larger role of the vasculature in the context of regenerative biology and cancer progression. We describe cellular, biophysical, biochemical, and metabolic components of vascularized microenvironments. Moreover, we provide an overview of multidimensional angiogenic biomaterials that have been developed to promote therapeutic vascularization and regeneration, as well as to mimic elements of vascularized microenvironments as a means to uncover mechanisms by which vasculature influences cancer progression and therapy.


Reversing diet-induced metabolic dysregulation by diet switching leads to altered hepatic de novo lipogenesis and glycerolipid synthesis.
In humans, low-energy diets rapidly reduce hepatic fat and improve/normalise glycemic control. Due to difficulties in obtaining human liver, little is known about changes to the lipid species and pathway fluxes that occur under these conditions. Using a combination of stable isotope, and targeted metabolomic approaches we investigated the acute (7-9 days) hepatic effects of switching high-fat high-sucrose diet (HFD) fed obese mice back to a chow diet. Upon the switch, energy intake was reduced, resulting in reductions of fat mass and hepatic triacyl- and diacylglycerol. However, these parameters were still elevated compared to chow fed mice, thus representing an intermediate phenotype. Nonetheless, glucose intolerance and hyperinsulinemia were completely normalized. The diet reversal resulted in marked reductions in hepatic de novo lipogenesis when compared to the chow and HFD groups. Compared with HFD, glycerolipid synthesis was reduced in the reversal animals, however it remained elevated above that of chow controls, indicating that despite experiencing a net loss in lipid stores, the liver was still actively esterifying available fatty acids at rates higher than that in chow control mice. This effect likely promotes the re-esterification of excess free fatty acids released from the breakdown of adipose depots during the weight loss period.


A comparative study of three low-molecular weight heparins (LMWH) and unfractionated heparin (UH) in healthy volunteers.
The levels of anti-IIa and anti-Xa activity, as reported in laboratory and clinical studies on low molecular weight heparin (LMWH) preparations, show a high degree of variability. This variation has been proposed as correlated to the variation in incidence of postoperative deep vein thrombosis (DVT) (8-30%) in different LMWH studies on comparable populations undergoing elective hip surgery. The aim of this study was to compare the ex vivo potency of Clexane (enoxaparin), Fragmin (dalteparin) and Logiparin (tinzaparin), applying the concept of bioequivalence, although unknown which activity/activities are best correlated to efficacy. Unfractionated heparin (UH) was included in the study as a reference drug. The drugs were studied with a cross-over technique in 12 healthy subjects and given subcutaneously in the doses recommended for orthopedic surgery. Blood samples were drawn each hour up to 10 h and at 12 h after administration. Anti-Xa and anti-IIa activities were measured using chromogenic substrate methods. The anti-Xa peak activity (Cmax) and the area under the curve (AUC) were highest for Clexane and Fragmin and lower for Logiparin and UH. Clexane and Fragmin were considered bioequivalent in anti-Xa activity. Regarding anti-IIa activity, no bioequivalence was found between the products. Fragmin was clearly different, with Cmax and AUC approximately twice as high as the other drugs. Whether the demonstrated differences in anti-Xa and anti-II activities are of any clinical significance remains unclear and can only be established by comparative clinical studies.


Redox regulation of carbonic anhydrases via thioredoxin in chloroplast of the marine diatom Phaeodactylum tricornutum.
Thioredoxins (Trxs) are important regulators of photosynthetic fixation of CO(2) and nitrogen in plant chloroplasts. To date, they have been considered to play a minor role in controlling the Calvin cycle in marine diatoms, aquatic primary producers, although diatoms possess a set of plastidic Trxs. In this study we examined the influences of the redox state and the involvement of Trxs in the enzymatic activities of pyrenoidal carbonic anhydrases, PtCA1 and PtCA2, in the marine diatom Phaeodactylum tricornutum. The recombinant mature PtCA1 and -2 (mPtCA1 and -2) were completely inactivated following oxidation by 50 μm CuCl(2), whereas DTT activated CAs in a concentration-dependent manner. The maximum activity of mPtCAs in the presence of 6 mm reduced DTT increased significantly by addition of 10 μm Trxs from Arabidopsis thaliana (AtTrx-f2 and -m2) and 5 μm Trxs from P. tricornutum (PtTrxF and -M). Analyses of mPtCA activation by Trxs in the presence of DTT revealed that the maximum mPtCA1 activity was enhanced ∼3-fold in the presence of Trx, whereas mPtCA2 was only weakly activated by Trxs, and that PtTrxs activate PtCAs more efficiently compared with AtTrxs. Site-directed mutagenesis of potential disulfide-forming cysteines in mPtCA1 and mPtCA2 resulted in a lack of oxidative inactivation of both mPtCAs. These results reveal the first direct evidence of a target of plastidic Trxs in diatoms, indicating that Trxs may participate in the redox control of inorganic carbon flow in the pyrenoid, a focal point of the CO(2)-concentrating mechanism.


EMT-MET in renal disease: should we curb our enthusiasm?
Renal epithelial cells arise during embryogenesis by mesenchymal to epithelial transition (MET). In the context of renal diseases, these cells can switch back to a mesenchymal phenotype, in a process thus reminiscent of an epithelial-to-mesenchymal transition (EMT) in which we referred to as "Epithelial Phenotypic Changes" (EPC). The pathophysiological consequence of EPC is controversial: in particular, to what extent EPC contribute to the pool of disease-associated renal fibroblasts is very uncertain. However, there is strong evidence that EPC correlate with a poor renal outcome. EPC indeed reflect an exposure to a profibrotic environment, at an early and potentially reversible stage. Detecting EPC has potential therapeutic implications for patients prone to renal fibrosis, both as a marker of efficacy or more directly as a target. In opposition to the EMT occurring during embryogenesis, EMT in fibrosis as well as in cancer is an anarchic cellular process actually developing at the expense of the whole organ(ism).


Massive immune hemolysis caused by anti-D after dual kidney transplantation.
Massive immune hemolysis due to passenger lymphocyte-derived anti-D has not been reported in renal transplantation. A 50-year-old (B-positive) male received a dual deceased-donor kidney transplant (B-negative) for diabetic renal failure. Two weeks post-transplant, the patient developed severe hemolytic anemia. The donor anti-D titer was 1:8. The recipient anti-D titer (zero pre-transplant) increased from 1:4 to 1:16 over 4 days. Rapid hemolysis caused severe anemia, minimum Hb = 4.2 g/dL, while selectively lysing the patient's autologous red cells during this time. The hemolytic anemia did not impair the allografts and subsided without monoclonal B-cell pharmacotherapy or apheresis. The anti-D titer decreased to barely detectable levels at four months and had cleared when checked 2 years post-transplant. Transfusion support subsided after two months. If complications of anemia can be avoided, the deleterious effects of hemolysis may be well tolerated by renal allografts using antigen negative transfusion alone.


Proliferation-dependent vulnerability of glucose-deprived astrocytes to nitric oxide-induced cytotoxicity.
The present study investigated the vulnerability of glucose-deprived astrocytes to nitric oxide (NO)-induced cytotoxicity. Primary murine cortical astrocyte cultures of different ages were deprived of glucose in the presence of the NO-releasing reagent 3-morpholinosydnonimine. Glucose-deprived astrocytes displayed an age-dependent vulnerability to NO cytotoxicity. However, this difference in vulnerability with age was found to be dependent on initial plating density. The augmented deaths of astrocyte cultures were consistent with the [3H]thymidine incorporation pattern. Thus, rapidly dividing astrocytes were much more susceptible to NO cytotoxicity under glucose-deprived conditions. The data indicate that the vulnerability of glucose-deprived astrocytes to NO cytotoxicity depends on the proliferative state rather than age in vitro.


An evaluation of community antenatal care.
A study to ascertain how the community based antenatal services in the East End of Glasgow related to the guidelines set by a Working Party on Ante-Natal and Intrapartum Care (Royal College of Obstetricians and Gynaecologists, 1982) is reported. All community based clinics were visited and described. The socio-economic status of the sample population was defined and users' views and preferences sought. The women sampled were often socially and economically disadvantaged. Unemployment was high. They received their community antenatal care from midwives, general practitioners and consultants in both health centres and general practitioner surgeries. Women were generally satisfied with the care they received. Answers to more specific questions indicated, however, that more information and individualised care would be appreciated.


Unbiased stereological method to assess proliferation throughout the subependymal zone.
The subependymal zone (SEZ), frequently named as adult subventricular zone (SVZ), is a niche of adult neural stem and progenitor cells that lines a large extension of the lateral ventricles of the brain. The majority of the studies do not analyze the SEZ throughout its entire extension. Instead, studies of cell populations within the SEZ typically focus their analysis on a narrow space between specific bregma coordinates that provides a perspective of only a small portion of the SEZ. We have previously proposed a standard division for the SEZ at the anterior-posterior and dorsal-ventral axes based on external brain anatomical hallmarks (Falcao et al., PLoS One 7:e38647, 2012). Herein, we describe in detail the procedure and a stereological approach that can be used to obtain an unbiased estimation of the SEZ cell proliferation under physiological and pathological conditions. This approach takes into consideration clear SEZ anatomical divisions, both on the anterior-posterior and dorsal-ventral axes, which will standardize future studies on the SEZ.


OpenTox predictive toxicology framework: toxicological ontology and semantic media wiki-based OpenToxipedia.
The OpenTox Framework, developed by the partners in the OpenTox project (http://www.opentox.org), aims at providing a unified access to toxicity data, predictive models and validation procedures. Interoperability of resources is achieved using a common information model, based on the OpenTox ontologies, describing predictive algorithms, models and toxicity data. As toxicological data may come from different, heterogeneous sources, a deployed ontology, unifying the terminology and the resources, is critical for the rational and reliable organization of the data, and its automatic processing. The following related ontologies have been developed for OpenTox: a) Toxicological ontology - listing the toxicological endpoints; b) Organs system and Effects ontology - addressing organs, targets/examinations and effects observed in in vivo studies; c) ToxML ontology - representing semi-automatic conversion of the ToxML schema; d) OpenTox ontology- representation of OpenTox framework components: chemical compounds, datasets, types of algorithms, models and validation web services; e) ToxLink-ToxCast assays ontology and f) OpenToxipedia community knowledge resource on toxicology terminology.OpenTox components are made available through standardized REST web services, where every compound, data set, and predictive method has a unique resolvable address (URI), used to retrieve its Resource Description Framework (RDF) representation, or to initiate the associated calculations and generate new RDF-based resources.The services support the integration of toxicity and chemical data from various sources, the generation and validation of computer models for toxic effects, seamless integration of new algorithms and scientifically sound validation routines and provide a flexible framework, which allows building arbitrary number of applications, tailored to solving different problems by end users (e.g. toxicologists). The OpenTox toxicological ontology projects may be accessed via the OpenTox ontology development page http://www.opentox.org/dev/ontology; the OpenTox ontology is available as OWL at http://opentox.org/api/1 1/opentox.owl, the ToxML - OWL conversion utility is an open source resource available at http://ambit.svn.sourceforge.net/viewvc/ambit/branches/toxml-utils/


PDCD6 is an independent predictor of progression free survival in epithelial ovarian cancer.
Programmed cell death 6 (PDCD6) beside its known proapoptotic functions may be a player in survival pathways in cancer. The purpose of this study is to further explore the roles of PDCD6 in epithelial ovarian cancer. Lentiviral vector with shRNA for PDCD6 was used to investigate the effects of PDCD6 knockdown on cell growth, cell cycle, apoptosis and motility in ovarian cancer cells. Two hundred twelve epithelial ovarian cancer tissues were analyzed for mRNA expression of PDCD6 using RT-PCR. Associations of its expression with clinical pathological factors, progression free and overall survival were evaluated. PDCD6 is highly expressed in metastatic ovarian cancer cells and positively regulates cell migration and invasion. Significantly, the level of PDCD6 expression in epithelial ovarian cancer correlates with clinical progression. Patients with medium or high levels of PDCD6 mRNA were at higher risk for disease progression, compared to those with low levels (HR, 1.29; P = 0.024 for medium levels; and HR, 1.57; P = 0.045 for high levels) after adjusting for age, disease stage, tumor grade, histologic type and residual tumor size. Kaplan-Meier survival analysis demonstrated similar results. However, no association was found between PDCD6 expression and overall survival. PDCD6 seems to play an important role in ovarian cancer progression and it may be an independent predictor of progression free survival in epithelial ovarian cancer. Further studies are needed to more completely elucidate the molecular mechanisms of PDCD6 involve in ovarian cancer progression.


Exploring boundaries in the nurse-client relationship: professional roles and responsibilities.
The creation and maintenance of boundaries as they pertain to the nurse-client relationship. To challenge readers to reflect on their fiduciary responsibilities by identifying boundary crossings and violations. Review of the literature and the authors' clinical and teaching experiences. Although self-awareness and monitoring, debriefing, and availing oneself of supervision and education are important tools in creating and maintaining boundaries, in the final analysis, the nursing profession needs nurses who have the ability to make decisions about boundaries based on the best interests of the clients in their care.


Regulation of ryanodine receptors by dopamine D1 receptors during methamphetamine-induced place conditioning.
Little is known about ryanodine receptors (RyRs) related to the methamphetamine (METH)-induced place preference. The present study was designed to ascertain whether RyRs could play a role in the development of METH-induced place preference in the mouse. The METH-induced place preference was dose-dependently suppressed by dantrolene, a RyRs receptor antagonist. The levels of RyRs 1 and 2 in the frontal cortex and RyRs 1 in the limbic forebrain were significantly increased in METH-conditioned mice. This up-regulation of RyRs were not inhibited by nifedipine. Both the dopamine D(1) receptor antagonist SCH23390 and the dopamine D(2) receptor antagonist sulpiride inhibited the development of METH-induced place conditioning. In contrast, the increases of RyRs 1 and 2 in the frontal cortex and of RyRs 1 in the limbic forebrain were completely abolished by SCH23390, whereas sulpiride had no effect. These findings indicate that up-regulation of RyRs is regulated through the activation of dopamine D(1) receptors in the METH-conditioning.


Reversed-phase dispersive liquid-liquid microextraction based on decomposition of deep eutectic solvent for the determination of lead and cadmium in vegetable oil.
In this work, a reversed-phase dispersive liquid-liquid microextraction procedure based on the decomposition of deep eutectic solvent was suggested for the first time. The procedure was utilized for fast and simple separation of lead and cadmium from vegetable oil samples. The procedure assumed mixing of oil sample and DES based on menthol, formic acid and water. Water as component of DES promoted its decomposition in sample matrix resulting menthol dissolution in the sample phase and dispersion of aqueous formic acid solution. In this procedure menthol acted as a dispersive solvent during DES decomposition for dispersion of aqueous formic acid solution. The metals were determined by the square-wave anodic stripping voltammetry. The limits of detection, were 0.01 µg kg-1 for lead and 0.006 µg kg-1 for cadmium. The RSD was less then 6% for both analytes. The enrichment factor was 36 and 39 for lead and cadmium, respectively.


Implementation of molecular matching in transplantation requires further characterization of both immunogenicity and antigenicity of individual HLA epitopes.
Over the past decade, high HLA epitope mismatch scores have been associated with inferior transplant outcomes using several tools, of which HLAMatchmaker is most well-known. This software uses theoretically defined polymorphic amino acid configurations, called eplets, for HLA compatibility analysis. Although consideration of eplet mismatch loads has potential for immunological risk stratification of transplant patients, the use of eplet matching in organ allocation algorithms is hindered by lacking knowledge of the immunogenicity of individual eplets, and the possibility that single mismatched amino acids, rather than complete eplets, are responsible for HLA antibody induction. There are several approaches to define eplet immunogenicity, such as antibody verification of individual eplets, and data-driven approaches using large datasets that correlate specific eplet mismatches to donor specific antibody formation or inferior transplant outcomes. Data-driven approaches can also be used to define whether single amino acid mismatches may be more informative than eplet mismatches for predicting HLA antibody induction. When using epitope knowledge for the assignment of unacceptable antigens, it important to realize that alleles sharing an eplet to which antibodies have formed are not automatically all unacceptable since multiple contact sites determine the binding strength and thus biological function and pathogenicity of an antibody, which may differ between reactive alleles. While the future looks bright for using HLA epitopes in clinical decision making, major steps need to be taken to make this a clinical reality.


Psychological antecedents of excess gestational weight gain: a systematic review.
Excess gestational weight gain (GWG), which has reached epidemic proportions, is associated with adverse outcomes during pregnancy and postpartum obesity in women and children. Psychological variables represent potentially modifiable factors. Moreover, previous systematic reviews on GWG interventions have called for the need for a clearer understanding of psychological factors affecting GWG. Hence, a systematic review was conducted to summarize the relation between psychological factors and GWG. Eight databases were searched, and the guidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. Methodological quality of the included studies was assessed using a modified Newcastle-Ottawa scale. Two assessors independently reviewed titles, abstracts and full articles, extracted data and assessed quality. A total of 6198 titles and abstracts were reviewed of which 90 full text articles were retrieved. Thirty-five studies (25 cohort, eight cross-sectional and two case-control) met the inclusion criteria, assessing 26 different psychological constructs in affect, cognitions and personality. Negative affective states such as depression, anxiety and stress were not related to excess GWG. Among weight-related and dietary-related cognitions, risk factors for excess GWG included concern about weight gain, negative body image and attitude towards weight gain, inaccurate perceptions regarding weight, higher than recommended target weight gain, less knowledge about weight gain, higher levels of cognitive dietary restraint, and perceived barriers to healthy eating. Protective factors included an internal locus of control for weight gain, lower than recommended target weight gain and higher self-efficacy for healthy eating. Only one study examined the relation between personality and excess GWG. In this systematic review, a number of cognitive factors were identified that were associated with excess GWG. To address excess GWG, more high quality, adequately powered studies are required examining cognitions, motivation and personality factors.


A phase II evaluation of cisplatin and 5-fluorouracil in patients with advanced squamous cell carcinoma of the cervix: a Gynecologic Oncology Group Study.
Cisplatin is one of the most active single agents in advanced squamous cell carcinoma of the cervix and is synergistic with 5-fluorouracil in the laboratory. The Gynecologic Oncology Group has conducted a phase II trial in which cisplatin at 50 mg/ml2 given intravenously on Day 1 was combined with 5-fluorouracil 1000 mg/m2 daily given as a 24-hr infusion on Days 1-5. Treatment was repeated every 21 days. Fifty-five patients were treated with this regimen, resulting in seven complete remissions (12.7%) and five partial remissions (9.1%). The median survival was 6.4 months. Toxic effects of grade 2 or greater were leukopenia in 10 patients (18.2%), thrombocytopenia in 2 patients (3.6%), gastrointestinal effects in 25 patients (45.5%), and renal effects in 1 patient (1.8%). On the basis of these results, the cisplatin and 5-fluorouracil regimen does not appear to have any advantage over cisplatin alone in advanced cervical cancer.


Whole body lipid and energy metabolism in the cancer patient.
The relationship between whole-body energy and lipid kinetics in eight cancer patients was investigated after an overnight fast. Respiratory gas exchange and indirect calorimetry were used to obtain resting energy expenditure (REE) and net substrate oxidation rates. Free fatty acid (FFA) turnover, oxidation, and clearance rates were obtained after a primed-constant infusion of albumin bound 1-14C-Na palmitate. This was followed by a primed-constant, two-stage infusion of unlabeled glycerol to measure plasma glycerol turnover and clearance. The REE was 1.3 times the predicted (by the Harris-Benedict equation) basal energy expenditure. FFA and glycerol, plasma concentrations, and turnover rates were higher in these depleted but hypermetabolic cancer patients, compared to reported values for healthy normals. The ratio of FFA turnover to glycerol turnover was 3.14 +/- 0.38, which is close to the theoretical value of 3, suggesting complete hydrolysis of triglycerides and the absence of any extensive reesterification of FFA in adipose tissue. The net fat oxidation accounts for 53 +/- 5% of fat mobilized and 29 +/- 3% of the FFA turnover was converted to CO2 in the process of supplying energy in cancer patients. The results suggest that fat is efficiently mobilized and utilized as a fuel source in hypermetabolic cancer patients in the postabsorptive state.


A consensus orthogonal partial least squares discriminant analysis (OPLS-DA) strategy for multiblock Omics data fusion.
Omics approaches have proven their value to provide a broad monitoring of biological systems. However, as no single analytical technique is sufficient to reveal the full biochemical content of complex biological matrices or biofluids, the fusion of information from several data sources has become a decisive issue. Omics studies generate an increasing amount of massive data obtained from different analytical devices. These data are usually high dimensional and extracting knowledge from these multiple blocks is challenging. Appropriate tools are therefore needed to handle these datasets suitably. For that purpose, a generic methodology is proposed by combining the strengths of established data analysis strategies, i.e. multiple kernel learning and OPLS-DA to offer an efficient tool for the fusion of Omics data obtained from multiple sources. Three real case studies are proposed to assess the potential of the method. A first example illustrates the fusion of mass spectrometry-based metabolomic data acquired in both negative and positive electrospray ionisation modes, from leaf samples of the model plant Arabidopsis thaliana. A second dataset involves the classification of wine grape varieties based on polyphenolic extracts analysed by two-dimensional heteronuclear magnetic resonance spectroscopy. A third case study underlines the ability of the method to combine heterogeneous data from systems biology with the analysis of publicly available data related to NCI-60 cancer cell lines from different tissue origins, which include metabolomics, transcriptomics and proteomics. The fusion of Omics data from different sources is expected to provide a more complete view of biological systems. The proposed method was demonstrated as a relevant and widely applicable alternative to handle efficiently the inherent characteristics of multiple Omics data, such as very large numbers of noisy collinear variables.


A facile electrochemical biosensor for coronavirus RNA assay with silver deposition.
Coronaviruses are highly infectious and pose a serious threat to human and animal healths. In this work, a facile electrochemical method based on Exonuclease III (Exo III) catalyzed digestion and silver deposition is developed for coronavirus RNA analysis. A magnetic separation procedure is performed to specifically identify target sequence and release single-stranded DNA modified gold nanoparticles (AuNPs). The nanoparticles can thus be immobilized at a screen-printed electrode and catalyze silver deposition for signal readout. This method allows sensitive analysis of PEDV and SARS-CoV-2 RNAs in the concentration range from 1 to 1000 nM with the limits of detection as low as 0.47 nM and 0.17 nM, respectively. Good specificities are demonstrated. Thus, the proposed method may have great potential use in the applications of coronaviruses analysis.


Patterns of disease progression on 18F-fluorodeoxyglucose positron emission tomography-computed tomography in patients with malignant pleural mesothelioma undergoing multimodality therapy with pleurectomy/decortication.
The aim of this study was to evaluate the patterns of disease progression in patients treated with pleurectomy/decortication (P/D), hyperthermic pleural lavage with povidone-iodine, prophylactic radiotherapy and adjuvant chemotherapy, using F-fluorodeoxyglucose (18F-FDG) PET/computed tomography (PET/CT). This was a retrospective study of 65 patients treated with a multimodality therapy including P/D between October 2004 and March 2012. Thirty-two patients underwent 18F-FDG PET/CT within 6 weeks of completion of adjuvant chemotherapy and 6-monthly thereafter at our institution. The first site of relapse on 18F-FDG PET/CT was recorded, and all scans were reviewed by an independent observer. Thirty-two patients (27 male, median age 61 years, range 45-73) underwent their 18F-FDG PET/CT scans at our institution. Eighteen of the 32 patients were alive at last follow-up (median follow-up 42 months, range 16-76). Nine patients were alive with disease recurrence. Fourteen patients died of disease progression (median survival 24.7 months, range 15-38). The median maximum standardized uptake value (SUVmax) in relapsing mesothelioma was 10.9 (range 4.9-27.3). There was a statistically significant correlation between the SUVmax and tumour lesion glycolysis of recurrent mesothelioma and overall survival (P=0.05). The site of disease recurrence was the pleura in the majority of the alive patients and was extrapleural in the dead patients. There was a statistically significant correlation between disease-free survival and complete macroscopic resection (P=0.02). After P/D with hyperthermic pleural lavage with povidone-iodine, prophylactic radiotherapy and adjuvant chemotherapy, the most frequent site of recurrence is the pleural cavity. Peritoneal seeding is rare. The tumour SUVmax and tumour lesion glycolysis correlate significantly with overall survival.


Short-chain alkyl esters of L-dopa as prodrugs for rectal absorption.
The bioavailability of L-dopa following rectal administration of a series of short-chain alkyl esters of L-dopa was determined in rats and dogs. The esters were stable (greater than 360 min) to hydrolysis in physiological buffer. In vitro enzymatic hydrolysis of the esters in plasma was species dependent, with the hydrolytic rate being faster in rat plasma (t 1/2 less than 5 min) than dog plasma (t 1/2 = 68-181 min) or human plasma (t 1/2 = 96-238 min). In vivo hydrolysis in dogs, as indicated by the L-dopa plasma profile following intravenous administration of the esters, was very rapid (high extravascular esterase activity). Significant L-dopa bioavailability was observed in rats following rectal administration of the methyl (46%), ethyl (14%), isopropyl (48%), butyl (100%), and 4-hydroxybutyl (13%) esters of L-dopa (rectal L-dopa absorption, less than 5%). In dogs, significant L-dopa bioavailability was also observed for the methyl (28%), isopropyl (30%), butyl (32%), and 4-hydroxybutyl (34%) esters of L-dopa in the presence of carbidopa. The data indicate that these highly water-soluble (greater than 600 mg/ml) esters of L-dopa are potential candidates for controlled-release rectal delivery systems designed to provide more constant plasma L-dopa levels.


Intersections of race, gender and the drug economy: Placing drugs in HIV discussions in Brazil.
While much research now demonstrates how social inequalities can drive HIV transmission, relatively little attention is given to the spatialized 'intersections' of race, class, and gender. Using this approach, this article considers an understudied phenomenon in Brazilian HIV discussions, the importance of the drug economy in shaping intimacy in favelas. Drawing on interviews with young women in Rio de Janeiro, it documents the intimate relations between young women and male drug workers to situate HIV vulnerability at the juncture of three social-spatial changes: (1) the rise of a drug economy that provides some racialized men, marginalized from mainstream society, with opportunities for work; (2) the precarious economic position of racialized women; and (3) the gendered dynamics including violence that can shape intimate relations. The paper shows how these relationships are contested by women who can cast their partners as living a 'wrong life.'


CDK5 regulates cell-cell and cell-matrix adhesion in human keratinocytes.
CDK5 is a member of proline-directed serine/threonine kinases. Although its cDNA was originally cloned as a homologue to those for the other members of the cyclin-dependent kinase (CDK) family, CDK5 has been shown to function differently from other CDKs. CDK5 is activated by non-cyclin partners, p35 and p39, and important during brain development by influencing adhesion, migration and differentiation of neurones. We sought to investigate the expression and functions of CDK5 in human keratinocytes. Expression of CDK5/p35, interaction of CDK5/p35 with adhesion molecules, and its roles in cell-cell and cell-matrix adhesion were studied by reverse transcriptase-polymerase chain reaction, immunoblotting and aggregation/adhesion assays in primary cultured normal human keratinocytes from infant foreskins and a human keratinocyte HaCaT cell line. Localization of CDK5 and p35 in normal human epidermis and psoriatic epidermis was studied by immunohistochemistry. Both CDK5 and p35 were expressed in primary cultured keratinocytes, HaCaT cells and normal human epidermis. Roscovitine, an inhibitor of CDK5, enhanced Ca2+-dependent (cadherin-dependent) aggregation of HaCaT cells whereas it inhibited adhesion of HaCaT cells to fibronectin associated with reduced active states of beta1 integrin. Interestingly, psoriatic skin showed reduced CDK5 and p35 expression in the lower half of the epidermis, which might be associated with decreased amount of activated beta1 integrin in the epidermis of psoriatic skin. CDK5/p35 may be involved in cell-cell and cell-matrix adhesion in human keratinocytes by differently regulating cadherins and integrins. Furthermore, reduced expression of CDK5/p35 in the epidermis might be involved in the pathogenesis of psoriasis.


Doppler parameters of maternal renal blood flow in normal pregnancy.
The purpose of this investigation was to evaluate changes in maternal renal arterial blood flow during pregnancy. The study included 40 non-pregnant, 200 pregnant, and 30 women after delivery. The authors measured pulsatility index (Pi) and resistance index (Ri) in the right and left renal arteries in the hilus. The authors compared the values between non-pregnant and women during first, second, and third trimester and post-partum period and tested correlation with gestational age. The authors did not find a statistical difference in Pi and Ri between the right and left kidneys. There was no difference in Pi and Ri in pregnancy trimester compared to the non-pregnant state. There was no correlation between the values of Pi and Ri and gestational weeks. During pregnancy there are no changes in the values of maternal renal Pi and renal Ri. Unchanged total vascular resistance may result from physiological changes of the glomerular filtration rate.


Cyclooxygenase-2 induction requires activation of nuclear factor of activated T-cells in Beas-2B cells after vanadium exposure and plays an anti-apoptotic role.
Vanadium, a potent toxic agent and carcinogen, is widely used in industry. Evidences show that exposure to vanadium is associated with an increased risk of lung cancer. But the mechanisms involved are far from fully understood. In this present study, we investigated that exposure of human bronchial epithelial cells (Beas-2B) to vanadium pentoxide resulted in an obvious induction of cyclooxygenase-2 (COX-2) expression and this induction was both dose- and time-dependent. Exposure of Beas-2B cells to vanadium pentoxide also led to significant activation of nuclear factor of activated T-cells (NFAT) on a time- and dose-dependent manner. Furthermore, we found that inhibition of NFAT by dominant negative mutant of NFAT (DN-NFAT) resulted in a dramatic inhibition of COX-2 expression induced by vanadium pentoxide, showing that NFAT activation was required for COX-2 induction by vanadium pentoxide in Beas-2B cells. Moreover, knockdown of COX-2 expression by COX-2-specific small interference RNA and blockage of NFAT pathway by DN-NFAT and NFAT3 small interference RNA showed an increased cell apoptosis in Beas-2B on vanadium exposure. Together, our results demonstrated that COX-2 expression could be induced by vanadium pentoxide in NFAT-dependent way and played an anti-apoptotic role in Beas-2B cells. From the results, we anticipate that the carcinogenesis of vanadium to human bronchial cells may result from anti-apoptosis mediated by the NFAT-dependent induction of COX-2, and we also assume that either pro-apoptotic or anti-apoptotic effect in certain type of cells after vanadium exposure may depend on the level of COX-2 induction.


A vegetable oil-based biopesticide with ovicidal activity against the two-spotted spider mite, Tetranychus urticae Koch.
A recently developed biopesticide made of safflower and cottonseed oils has excellent ovicidal activity against the hard-to-control spider mite Tetranychus urticae Koch (Acari: Tetranychidae). It has attracted attention as a sustainable treatment for controlling T. urticae because it has low potential for promoting resistance and little effect on the predatory mite Neoseiulus californicus (McGregor) (Acari: Phytoseiidae), which is an important natural enemy of spider mites. Here, we investigated the mechanism of its ovicidal activity against T. urticae. The oil droplets in the oil-in-water emulsion of the biopesticide strongly adhered to T. urticae eggs, seeped through the chorion being cut during hatching, and inhibited the embryonic rotational movement necessary for cutting and hatching. No adverse effect was observed on N. californicus eggs even in undiluted biopesticide. We conclude that this biopesticide and N. californicus can be used simultaneously in the integrated management of T. urticae in oily biopesticide-tolerant plant species.


AMSC-derived exosomes alleviate lipopolysaccharide/d-galactosamine-induced acute liver failure by miR-17-mediated reduction of TXNIP/NLRP3 inflammasome activation in macrophages.
Mesenchymal stem cell (MSC)-derived exosome administration has been considered as a novel cell-free therapy for liver diseases through cell-cell communication. This study was aimed to determine the effects and mechanisms of AMSC-derived exosomes (AMSC-Exo) for acute liver failure (ALF) treatment. AMSC-Exo were intravenously administrated into the mice immediately after lipopolysaccharide and D-galactosamine (LPS/GalN)-exposure and their effects were evaluated by liver histological and serum biochemical analysis. To elucidate its mechanisms in ALF therapy, the expression levels of miRNAs and inflammasome-related genes in macrophages were evaluated by qPCR and Western blot analysis, respectively. The exosomes from miR-17-knockdowned AMSCs (AMSC-ExomiR-17-KD) were used for further determine the role of miR-17 in AMSC-Exo-based therapy. AMSC-Exo administration significantly ameliorated ALF as determined by reduced serum alanine aminotransferase and aspartate aminotransferase levels and hepatic inflammasome activation. Further experiments revealed that AMSC-Exo were colocalized with hepatic macrophages and could reduce inflammatory factor secretion by suppressing inflammasome activation in macrophages. Moreover, miR-17, which can suppress NLRP3 inflammasome activation by targeting TXNIP, was abundant in AMSC-Exo cargo. While, the therapeutic effects of AMSC-ExomiR-17-KD on ALF were significantly abolished as they could not effectively suppress TXNIP expression and consequent inflammasome activation in vitro and in vivo. Exosome-shuttled miR-17 plays an essential role in AMSC-Exo therapy for ALF by targeting TXNIP and suppressing inflammasome activation in hepatic macrophages. AMSC-Exo-based therapy may present as a promising approach for TXNIP/NLRP3 inflammasome-related inflammatory liver diseases. FUND: Key R&D projects of Zhejiang province (2018C03019) and National Natural Science Fund (81470851 and 81500616).


Two arch criteria of the ilium for sex determination of immature skeletal remains: a test of their accuracy and an assessment of intra- and inter-observer error.
Although the assignment of sex to immature skeletal remains is considered problematic, some traits have been considered useful for both forensic and bioarchaeological applications. One such trait is the arch criterion found in subadult ilia, which is defined relative to the greater sciatic notch-auricular surface area. In adults, the composite arch has also been described in relation to this area and has proven relatively successful in sex determination. This study offers an examination of the accuracy of the arch criterion and the composite arch in determining the sex of subadult skeletal remains, and an assessment of intra- and inter-observer scoring error. A sample of 97 skeletons of known sex and age (<15 years) from the Lisbon collection (Portugal) were selected and the traits were scored by three observers on orthogonal photos of each ilium. In general the agreement within (67.7-88.5%) and between (50.5-76.3%) examiners was poor and overall accuracy (26.7-52.6%) did not meet the expectations of that reported in previous studies. The authors suggest that this derives from great variation in morphology, difficulties in interpreting criteria and possibly a lack of association between the expression of the traits and sex. Careful examination of sex-related morphology in the immature skeleton and additional blind tests of so-called useful traits should continue to be carried out.


NMR techniques for determination of lipid content in microalgal biomass and their use in monitoring the cultivation with biodiesel potential.
In the present investigation, the application of NMR spectroscopic techniques was extensively used with an objective to explore the biodiesel potential of biomass cultivated on a lab scale using strains of Chlorella vulgaris and Scenedesmus ecornis. The effect of variation in the composition of culturing medium on the neutral and polar lipids productivity, and fatty acid profile of solvent extracts of microalgae biomass was studied. Determination of unsaturated fatty acid composition (C18:N = 1-3, ω3 C20:5, ω3 C22:6), polyunsaturated fatty esters (PUFEs), saturated fatty acids (SFAs), unsaturated fatty acids (UFAs), free fatty acids (FFAs), and iodine value were achieved from a single (1)H NMR spectral analysis. The results were validated by (13)C NMR and GC-MS analyses. It was demonstrated that newly developed methods based on (1)H and (13)C NMR techniques are direct, rapid, and convenient for monitoring the microalgae cultivation process for enhancement of lipid productivity and their quality aspects in the solvent extracts of microalgal biomasses without any sample treatment and prior separation compared to other methods. The fatty acid composition of algae extracts was found to be similar to vegetable and fish oils, mostly rich in C16:0, C18:N (N = 0 to 3), and n-3 omega polyunsaturated fatty acids (PUFAs). The lipid content, particularly neutral lipids, as well as most of the quality parameters were found to be medium specific by both the strains. The newly developed methods based on NMR and ultrasonic procedure developed for efficient extraction of neutral lipids are cost economic and can be an effective aid for rapid screening of algae strains for modulation of lipid productivity with desired biodiesel quality and value-added products including fatty acid profile.


Global protein expression dataset acquired during isoniazid-induced cytoprotection against H2O2 challenge in HL-60 cells.
Isoniazid (INH) is one of the first-line anti-tuberculosis drugs. Its effect on oxidative stress, however, is unknown. Here we used a model of oxidative stress by employing glucose/glucose oxidase (GOx), which (based on the availability of glucose and oxygen) is known to produce H2O2. This reaction induces oxidative stress culminating in necrotic cell death in HL-60 cells (a human promyelocytic leukemia cell line). The changes in protein levels have been quantified using global proteome expression changes through stable isotope labeling by amino acids in cell culture (SILAC) followed by LC-MS/MS analysis. A total of 1459 and 1712 proteins were identified in forward and reverse experiments, respectively. However, only 390 proteins were reproducibly identified in both samples. These 390 proteins were taken into account for further analysis which has been described in "Cytoprotective effect of isoniazid against H2O2 derived injury in HL-60 cells" [1].


Review of pharmacological treatment in mood disorders and future directions for drug development.
After a series of serendipitous discoveries of pharmacological treatments for mania and depression several decades ago, relatively little progress has been made for novel hypothesis-driven drug development in mood disorders. Multifactorial etiologies of, and lack of a full understanding of, the core neurobiology of these conditions clearly have contributed to these development challenges. There are, however, relatively novel targets that have raised opportunities for progress in the field, such as glutamate and cholinergic receptor modulators, circadian regulators, and enzyme inhibitors, for alternative treatment. This review will discuss these promising new treatments in mood disorders, the underlying mechanisms of action, and critical issues of their clinical application. For these new treatments to be successful in clinical practice, it is also important to design innovative clinical trials that identify the specific actions of new drugs, and, ideally, to develop biomarkers for monitoring individualized treatment response. It is predicted that future drug development will identify new agents targeting the molecular mechanisms involved in the pathophysiology of mood disorders.


Adaptation difficulty and religious coping styles for the elderly in Turkey.
Many physical and psychosocial changes occur in elderly people due to aging. These changes affect the adaptation, coping style, and quality of life of elderly people. This study was conducted to determine the adaptation difficulty to the process of aging and religious coping styles used by elderly people. The research was conducted as a cross-sectional type. The sample consisted of 505 elderly people from seven family health centres of a city in Turkey. Data were collected via a personal information form, the Assessment Scale of Adaptation Difficulty for the Elderly, and the Religious Coping Scale. The adaptation difficulty for the elderly total mean score was 0.52 (SD = 0.56). The positive religious coping mean score was 23.49 (SD = 5.30), and the negative religious coping mean score was 7.88 (SD = 3.20). While there was a negative weak relationship between the adaptation difficulty for the elderly and the positive religious coping (r = -0.147, P = 0.001), there was no significant relation between the adaptation difficulty for the elderly and the negative religious coping (r = -0.028, P > 0.05). The results revealed that adaptation difficulty to the process of aging is low, elderly people use positive coping strategies, and adaptation to old age increased as positive coping strategies were used. Factors that affect religious coping must be considered to improve the health of elderly people.


Development and Validation of a Prognostic Model for One-year Survival of Cirrhosis Patients with First-ever Spontaneous Bacterial Peritonitis.
Spontaneous bacterial peritonitis (SBP) is one of the leading causes of death in patients with liver cirrhosis. We aimed to establish a prognostic model to evaluate the 1-year survival of cirrhosis patients after the first episode of SBP. A prognostic model was developed based on a retrospective derivation cohort of 309 cirrhosis patients with first-ever SBP and was validated in a separate validation cohort of 141 patients. We used Uno's concordance, calibration curve, and decision curve (DCA) analysis to evaluate the discrimination, calibration, and clinical net benefit of the model. A total of 59 (19.1%) patients in the derivation cohort and 42 (29.8%) patients in the validation cohort died over the course of 1 year. A prognostic model in nomogram form was developed with predictors including age [hazard ratio (HR): 1.25; 95% confidence interval (CI): 0.92-1.71], total serum bilirubin (HR: 1.66; 95% CI: 1.28-2.14), serum sodium (HR: 0.94; 95% CI: 0.90-0.98), history of hypertension (HR: 2.52; 95% CI: 1.44-4.41) and hepatic encephalopathy (HR: 2.06; 95% CI: 1.13-3.73). The nomogram had a higher concordance (0.79) compared with the model end-stage liver disease (0.67) or Child-Turcotte-Pugh (0.71) score. The nomogram also showed acceptable calibration (calibration slope, 1.12; Bier score, 0.15±0.21) and optimal clinical net benefit in the validation cohort. This prediction model developed based on characteristics of first-ever SBP patients may benefit the prediction of patients' 1-year survival.


Ethane-1,2-diaminium (R)-2-[4-(1-carboxyl-atoeth-oxy)phen-oxy]acetate.
In the title compound, C(2)H(10)N(2) (2+)·C(11)H(10)O(6) (2-), the two acetate groups of the cation form dihedral angles of 74.2 (4) and 63.9 (5)° with the central benzene ring. In the crystal, N-H⋯O hydrogen bonds link the cations and anions into layers parallel to the ab plane.


Incarcerated patellar tendon in Hoffa fracture: an unusual cause of irreducible knee dislocation.
Irreducible knee dislocation due to incarcerated soft tissue structures in associated fractures is extremely uncommon. We report a case of irreducible, closed dislocation of the knee secondary to incarcerated patellar tendon in a Hoffa fracture (unicondylar fracture of femur in the coronal plane) with associated communited fracture of patella and disruption of both cruciates. We treated this case initially with open reduction and internal fixation of fracture and repair of the patellar tendon. During the total followup period of eighteen months, the patient had restricted joint range of motion with no joint instability despite aggressive physiotherapy and further surgical intervention. The prognosis of such complex knee injuries with combination of ligamentous injuries and associated fractures is much worse when compared to either injuries alone.


Efficient pseudo-five-component coupling-Fiesselmann synthesis of luminescent oligothiophenes and their modification.
(Hetero)aryl bis-acid chlorides and terminal alkynes, or likewise acid chlorides and terminal dialkynes, and ethyl 2-mercaptoacetate can be reacted to give highly luminescent symmetrical terthiophenes and quinquethiophenes in the sense of a consecutive pseudo-five-component reaction in good to excellent yields. Further functionalization of the obtained oligomers can be readily achieved by halogenation followed by a metal-catalyzed coupling reaction to give α,ω-diester substrates for subsequent transformations into highly functionalized materials.


The effect of cysteamine on immunoreactive somatostatin in the rabbit retina.
Cysteamine hydrochloride was administered to rabbits at doses ranging from 0.3 to 10 mg by two intravitreal injections 24 h apart. Retinal immunoreactive somatostatin concentrations were reduced by about 50% at 24 h following the second injection. At doses of 0.3-3 mg, there was no demonstrable effect on retinal concentrations of immunoreactive substance P or of dopamine. Ten milligrams of cysteamine produced non-specific retinal damage. Cysteamine injected locally into the retina is a relatively specific drug for depletion of somatostatin.


Randomized withdrawal of long-term prednisolone treatment in rheumatoid arthritis: effects on inflammation and bone mineral density.
Short-term, low-dose glucocorticoid (GC) treatment has anti-inflammatory and disease-modifying effects in rheumatoid arthritis (RA). However, scientific support for long-term, low-dose GC treatment, although widespread, is poor, and information on the effects on bone density is scarce. The aim of this study was to investigate how long-term GC treatment in RA affects inflammation as well as bone density, and also to investigate the feasibility of withdrawal of GC. Fifty-eight patients with RA treated with 5-7.5 mg prednisolone daily for at least 2 years were randomized either to withdraw or to continue GC treatment. The patients were followed prospectively for 2 years with respect to disease activity [using the Disease Activity Score calculated for 28 joints, (DAS28)], functional ability [using the Health Assessment Questionnaire (HAQ) score] and bone mineral density (BMD) of the lumbar spine and hip. Only 11 patients out of 26 randomized to stop GC treatment and available for outcome measures succeeded in stopping the GC medication within 1 year. Fifteen patients failed withdrawal of GC because of increased joint symptoms. A higher mean DAS28 during the study was associated with loss of bone mass in the trochanter. The group that continued with unchanged GC treatment did not deteriorate in BMD during the 2 years but in fact Z-scores improved significantly. Our results indicate that low-dose GC treatment after several years has persisting anti-inflammatory effects in RA and no further negative impact on BMD. It thus seems to be more important to control disease activity than withdraw low-dose GC treatment in this population considering bone health.