Dihydropyrimidine dehydrogenase deficiency in patients with severe toxicity after 5-fluorouracil: a retrospective single-center study.
5-Fluorouracil (5-FU) is an agent frequently used in the treatment of solid cancers. A deficiency in the enzyme that catabolizes 5-FU leads to severe toxicity. The gene responsible for this enzyme is DPYD, located on chromosome 1q22. The most prevalent alteration described is DPYD*2A, which leads to a splicing defect and thus skipping of the translation of an entire exon. The objectives of this retrospective study were to describe the frequencies of DPYD gene mutations in a Belgian population and to correlate them with the grade of toxicity. This was a retrospective, single-center study conducted at the University Hospitals Leuven, by reviewing a database of patients screened for DPYD gene mutations between May 2009 and June 2015 after prolonged grade 3-4 toxicity. Polymerase chain reaction sequencing of exons 2, 6, 10, 11, 13, 18, 19 and 22, and pyrosequencing of exon 14 were performed by an in-house laboratory. Of the 80 patients screened, 65 were heterozygous or compound heterozygous for DPYD and 3 had a homozygous mutation. The most prevalent mutation in our population was DPYD*9A. Despite previous reports, in our small retrospective study the most prevalent variation in patients with severe adverse events was DPYD*9A. As this variant has previously been reported to be benign, we suggest that screening for dihydropyrimidine dehydrogenase deficiency should be extended across multiple exons of the DPYD gene.


Tributaries as richness source for Oligochaeta assemblage (Annelida) of Neotropical dammed river.
Tributaries may serve as richness source for the river main channel and the zoobenthos community is a good tool to verify this kind of pattern. In this study, we aimed to characterize the benthic invertebrate assemblage in three tributaries associated to the Paraná River main channel, focusing in Oligochaeta community. We hypothesized that (i) in tributaries, Oligochaeta are richer than the main river (Paraná River) and (ii) dammed tributary (Paranapanema River) is poorly diverse than the others. Samples were conducted in Paranapanema, Baía and Ivinhema tributaries using a modified Petersen grab along three transects (samples conducted inside the tributary, in the mouth of each tributary and inside Paraná River). To analyze (i) the difference between the richness and density among the tributaries and the Paraná River and (ii) effect of each tributary transect on the Oligochaeta richness we used a nonparametric Kruskal-Wallis test. Changes in environmental variables and in richness and composition of Oligochaeta were summarized by Canonic Correspondence Analysis. It was registered 21 different benthic invertebrates taxa, being Oligochaeta assemblage with the highest density. Within Oligochaeta, Narapa bonettoi was the most abundant species, followed by Haplotaxis aedochaeta and Paranadrilus descolei. In our results we refused both hypotheses, because we did not found significant differences for richness and density between the tributaries and the main river, and also no difference between the three transects of each tributary were found. However, the tributaries less influenced by damming, especially the Baía recorded high richness. This corroborates their importance to diversity in the floodplain and the species of Oligochaeta reflect the peculiar characteristics of habitats within each tributaries.


Effects of anthocyanidin on the inhibition of proliferation and induction of apoptosis in human gastric adenocarcinoma cells.
Anthocyanins are naturally occurring reddish pigments that abundant in fruits and vegetables. To investigate the mechanistic basis for the anti-tumor properties of anthocyanins, five aglycone (cyanidin, delphinidin, malvidin, pelargonidin, and peonidin) and four glycosylated (cyanidin-3-glucoside, malvidin-3-glucoside, pelargonidin-3-glucoside and peonidin-3-glucoside) anthocyanins were used to examine their effects on cell cycle progression and induction of apoptosis in human gastric adenocarcinoma AGS cells. The data from cell viability assay showed that malvidin exhibited the most potent anti-proliferation effect on AGS cells in a time- and dose-dependent manner (P<0.05). This event is accompanied the arrest of AGS cells at the G0/G1 phase by malvidin at the tested concentrations of 0-200 microM. Cellular uptake of anthocyanin and anthocyanidin was confirmed by HPLC analysis and the intracellular accumulation of malvidin (24.9+/-1.1 microM/mg protein) was observed when treatment of AGS cells with malvidin for 12 h. In addition, an accumulation of AGS cells in sub-G1 phase (20% and 30% increase for 100 and 200 microM of malvidin, respectively) was observed as well as by the appearance of a fraction of cells with an aneudiploid DNA content. The occurrence of apoptosis induced by malvidin was confirmed by morphological and biochemical features, including apoptotic bodies formation, caspase-3 activation and poly(ADP-ribose) polymerase proteolysis. Furthermore, the mitochondrial membrane potential of apoptotic cells after treatment with malvidin was significantly lost and resulted in the elevation of Bax/Bcl-2 ratio for 1.6-fold against control for 100 microM treatment. In addition, the malvidin treatment significantly increased the p38 kinase expression and inhibited the ERK activity, and the effects of malvidin on caspase-3 activation were blocked, respectively, by the ERK and p38 inhibitors. These findings suggest that growth inhibition and cytotoxicity of AGS cells by malvidin is involved in the induction of apoptosis rather than necrosis.


Relationship between elevated levels of serum uric acid and saphenous vein graft disease.
Several studies have shown an association between elevated serum uric acid (SUA) levels and coronary heart disease and cardiovascular mortality. We investigated the relationship between SUA levels and the patency of saphenous vein grafts (SVG) after coronary artery bypass graft (CABG) surgery. The study included 192 patients (152 men, 40 women) who underwent elective coronary angiography after a mean of 5.6 years following CABG surgery, which involved the use of at least one SVG. The patients were divided into two groups depending on the extent of SVG patency. Stenosis of 50% or greater within the SVG was accepted as hemodynamically significant. Serum uric acid levels were determined with the enzymatic colorimetric method. Ninety patients (71 men, 19 women; mean age 62+/-8 years) were found to have patent SVG. Stenotic SVGs were detected in 102 patients (81 men, 21 women; mean age 62+/-10 years). The time interval between surgery and angiography was significantly longer in the stenotic group (p<0.001). Compared to patients without SVG disease, the mean SUA level was significantly higher in patients with SVG disease (4.9+/-1.2 mg/dl vs 5.8+/-1.4 mg/dl; p=0.02). Serum uric acid levels were similar in patients having stenosis in a single vein graft or multiple vein grafts (p=0.224). In multiple regression analysis, SVG disease was independently associated with SUA (p<0.001), diabetes mellitus (p=0.028), and smoking (p=0.039). Our results show that there is a significant association between increased SUA levels and SVG disease in patients undergoing CABG, which may justify the need for early screening for hyperuricemia and antiuricemic treatment.


Parental psychological violence and adolescent behavioral adjustment: the role of coping and social support.
The role of coping strategies (approach and avoidance) as a mediating factor between parental psychological violence and adolescent behavior problems, both internalized and externalized, as well as the protective role of social support were examined separately for boys and girls. A group of 278 adolescents (mean age: 14.2) were recruited in three high schools located in low, moderate, and high socioeconomic areas. Participants were in the seventh, eighth, and ninth grades, and each completed a self-administered questionnaire. The use of avoidant coping strategies partially mediated the link between parental psychological violence and behavior problems among girls. The use of approach coping strategies partially mediated the link between parental psychological violence and behavior problems among boys. In all cases, coping enhanced this link. No protective role of social support was found. On the contrary, this variable was found to increase the relationship between parental psychological violence and externalized behavior problems among boys. These findings suggest that interventions aimed at strengthening coping skills and social support in adolescents may not be effective in alleviating various behavioral symptoms associated with parental psychological violence. They highlight the importance of prevention of psychologically violent parental practices, instead of only reacting to the problem after it has occurred.


Stand dynamics modulate water cycling and mortality risk in droughted tropical forest.
Transpiration from the Amazon rainforest generates an essential water source at a global and local scale. However, changes in rainforest function with climate change can disrupt this process, causing significant reductions in precipitation across Amazonia, and potentially at a global scale. We report the only study of forest transpiration following a long-term (>10 year) experimental drought treatment in Amazonian forest. After 15 years of receiving half the normal rainfall, drought-related tree mortality caused total forest transpiration to decrease by 30%. However, the surviving droughted trees maintained or increased transpiration because of reduced competition for water and increased light availability, which is consistent with increased growth rates. Consequently, the amount of water supplied as rainfall reaching the soil and directly recycled as transpiration increased to 100%. This value was 25% greater than for adjacent nondroughted forest. If these drought conditions were accompanied by a modest increase in temperature (e.g., 1.5°C), water demand would exceed supply, making the forest more prone to increased tree mortality.


Mechanical properties of open-cell, self-expandable shape memory alloy carotid stents.
Mechanical properties of carotid stents are important for the selection of the implantable device. The efficacy of cell design is usually investigated on the basis of clinical follow-ups; however, for the specific carotid application the relative importance of the cell design on the stenting outcome is debated. Ideally, a carotid stent should have at the same time low bending stiffness (i.e., high flexibility) to correctly conform to the vessel curvatures in the stenotic region and high stiffness to sustain the vessel wall in the radial direction. In this study, experimental tests on six carotid open-cell design self-expandable stents were carried out to assess bending and radial stiffness. A four-point bending test was adopted to measure the bending stiffness. Radial stiffness was obtained by measuring the stent resistance to local compression in a V-shaped support. Geometrical features, such as the link positioning and their length, were examined as a possible determinant of the mechanical properties of the tested stents. The tested stents showed very different geometrical features and mechanical properties despite similar material and a common open-cell structure consisting in rings connected by roughly straight links. In particular, different strategies are evident regarding the link position. Three distinct behaviors were observed: stents with both low radial and bending stiffness, moderate bending and high radial stiffness, and high bending and moderate radial stiffness. In general, a large link length allows the stent to be more flexible under bending condition, whereas the mutual links positioning plays a key role in the radial stiffness of these devices. Furthermore, for a fixed strut layout, a correlation was found between the strut cross area, as well as metal-to-artery ratio and the resultant radial and bending stiffness.


Modulation of murine EL-4 thymic lymphoma cell proliferation and cytokine production by vitamin E succinate.
RRR-alpha-tocopheryl succinate (VES) was studied for effects on murine EL-4 cell proliferation and production of interleukin-2 (IL-2) and transforming growth factor-beta (TGF-beta). VES was biphasic in its actions: 0.1 microgram/ml enhanced EL-4 cell proliferation, whereas 10-20 microgram/ml inhibited cellular proliferation. Cell-conditioned media (CM) from EL-4 cells treated with 0.2 ng/ml phorbol myristate acetate (PMA) + 0.1 microgram/ml VES contained increased amounts of IL-2, as determined by the murine cytotoxic T cell IL-2-dependent CTLL-2 bioassay. VES at 0.1 microgram/ml or 0.1 microgram/ml VES + 0.2 ng/ml PMA induced the expression of IL-2 mRNA by EL-4 cells three to nine hours after treatment. CM from EL-4 cells treated with VES at 10-20 microgram/ml exhibited potent antiproliferative activity when tested in the TGF-beta-responsive mink lung cell (Mv1Lu) bioassay and showed reduced inhibitory effects when tested on TGF-beta receptor-negative mink lung (DRA-27) cells. CM from control-treated EL-4 cells exhibited no antiproliferative activity. The VES-induced antiproliferative activity was characterized as TGF-beta by neutralization analyses and immunoprecipitation of metabolically labeled proteins with TGF-beta-specific reagents. VES treatment of EL-4 cells had no effect on TGF-beta 1 mRNA expression while downregulating TGF-beta 3 mRNA expression. In summary, these studies showed that 0.1 microgram/ml VES enhanced cellular proliferation, in part, via increased IL-2 production, whereas 10-20 micrograms/ml VES inhibited cellular proliferation, in part, via the secretion of biologically active TGF-beta.


Effect of increased physical activity on growth and differentiation of regenerating rat soleus muscle.
Our purpose was to determine the effect of physical exercise on growth and differentiation during regeneration of a slow-twitch muscle. Degeneration/regeneration of the left soleus muscles of Wistar female rats was induced by injection of a snake venom. Muscular differentiation was studied by monitoring the sequential expression of the various myosin heavy chain isoforms (MHCs). Rats were assigned to one of two groups: cage sedentary (n = 14) or exercised (n = 16). The exercise programme began 1-day post-injection and the rats ran 1 h/day on a motorized treadmill. Then, 9 and 25 days after venom treatment, the soleus MHC phenotype as determined by immunohistology, electrophoresis and immunoblotting, was studied. At 25 days the expression of MHCs by regenerating soleus was not changed by the increased level of physical activity (P > 0.05). Exercised and sedentary regenerating muscles contained similar numbers of type-I fibres (100% of total fibres), levels of MHC-1 (85.4 and 89.5% of total MHCs), MHC-2a and M/HC-2x/d and their fibres expressed MHC-1 (100% of total fibres) and MHC-2 (45-50%) in the same way. Moreover, the masses of regenerating and nonregenerating soleus were significantly increased by physical exercise (P < 0.02). At 9 days no effect of muscular exercise was found. In conclusion, endurance exercise did not alter differentiation of regenerating soleus. Moreover regenerating soleus can respond to increased physical activity by enhancing its mass in the same way as mature muscle.


Longitudinal evaluation of laboratory-based serological assays for SARS-CoV-2 antibody detection.
Serological assays for SARS-CoV-2 infection are now widely available for use in diagnostic laboratories. Limited data are available on the performance characteristics in different settings, and at time periods remote from the initial infection. Validation of the Abbott (Architect SARS-CoV-2 IgG), DiaSorin (Liaison SARS-CoV-2 S1/S2 IgG) and Roche (Cobas Elecsys Anti-SARS-CoV-2) assays was undertaken utilising 217 serum samples from 131 participants up to 7 months following COVID-19 infection. The Abbott and DiaSorin assays were implemented into routine laboratory workflow, with outcomes reported for 2764 clinical specimens. Sensitivity and specificity were concordant with the range reported by the manufacturers for all assays. Sensitivity across the convalescent period was highest for the Roche at 95.2-100% (95% CI 81.0-100%), then the DiaSorin at 88.1-100% (95% CI 76.0-100%), followed by the Abbott 68.2-100% (95% CI 53.4-100%). Sensitivity of the Abbott assay fell from approximately 5 months; on this assay paired serum samples for 45 participants showed a significant drop in the signal-to-cut-off ratio and 10 sero-reversion events. When used in clinical practice, all samples testing positive by both DiaSorin and Abbott assays were confirmed as true positive results. In this low prevalence setting, despite high laboratory specificity, the positive predictive value of a single positive assay was low. Comprehensive validation of serological assays is necessary to determine the optimal assay for each diagnostic setting. In this low prevalence setting we found implementation of two assays with different antibody targets maximised sensitivity and specificity, with confirmatory testing necessary for any sample which was positive in only one assay.


Electroanalytical characteristics of antipsychotic drug ziprasidone and its determination in pharmaceuticals and serum samples on solid electrodes.
Ziprasidone is a psychotropic agent used for the treatment of schizophrenia. Its oxidation was investigated electrochemically at boron-doped diamond and glassy carbon electrodes using cyclic, differential pulse, and square wave voltammetry. The dependence of the peak current and peak potentials on pH, concentration, nature of the buffer, and scan rate were examined. The process was diffusion and adsorption controlled for boron-doped diamond and glassy carbon electrodes, respectively. The possible mechanism of oxidation was discussed with some model compounds that have indole and piperazine oxidations. A linear response was obtained between 8 x 10(-7) and 8 x 10(-5) M for the first peak in acetate buffer (pH 5.5) and between 2 x 10(-6) and 2 x 10(-4) M for the second peak in 0.1 M H(2)SO(4) with boron-doped diamond electrode for differential pulse and square wave voltammetric techniques. The reproducibility and accuracy of the proposed methods were found between 0.31 and 1.20, 99.27 and 100.22, respectively. The recovery studies were also achieved to check selectivity and accuracy of the methods. The proposed methods were applied for the determination of ziprasidone from pharmaceutical dosage forms and human serum samples without any time-consuming extraction, separation, evaporation or adsorption steps prior to drug assay except precipitation of the proteins using acetonitrile. The results were statistically compared with those obtained through an established LC-UV technique, no significant differences were been found between the voltammetric and LC methods.


[Drug-eluting stents: from the results of clinical studies to economic simulation models in the Italian reality].
Several studies with drug-eluting stents (DES) have demonstrated dramatic reductions in restenosis rates compared with bare metal stents (BMS). Although the clinical benefits of DES are increasingly evident, important concerns about their costs have been raised. Most data regarding the impact of restenosis on long-term costs after percutaneous coronary intervention (PCI) are derived from clinical trials. These studies demonstrate that there is no single cost or economic burden of restenosis; these values vary substantially according to the specific patient population under investigation and to the healthcare system reality where they are applied. In the present study we propose an economic interactive decision model which was applied to the Italian healthcare system, considering the different reimbursement rates of the Italian regions for DES and for both PCI and coronary artery bypass surgical interventions (CABG). The aim of this model was to simulate the impact of DES introduction after potential complete reimbursement by the national healthcare system, hypothesizing the usage of 1.4 stent per patient in case of single vessel disease and 2.4 stents in case of multivessel disease, and utilizing the TAXUS IV rate of revascularization for reintervention costs calculation and the ARTS-I study for CABG costs. For a low risk patients' population, the mean cost of a procedure with DES was 6% greater than utilizing BMS (xi 8125 for DES vs xi 7651 for BMS). However, this percentage was reduced in case of diabetic patients (+4%), long lesions (+2%) and was favourable for small vessels (-3%). In addition, in case of multivessel disease with conversion from CABG to DES, the 12 months cost per patients was reduced of around 30% (xi 10 170 for PCI vs xi 14 584 for CABG). This model suggests that national healthcare system may save 2.1% of the total costs (xi 18.60 millions) if 60% of revascularization procedures converts to total DES utilization and 15% from CABG to PCI with DES.


Enhanced UnaG With Minimal Labeling Artifact for Single-Molecule Localization Microscopy.
We introduced enhanced UnaG (eUnaG), a ligand-activatable fluorescent protein, for conventional and super-resolution imaging of subcellular structures in the mammalian cells. eUnaG is a V2L mutant of UnaG with twice brighter bulk fluorescence. We previously discovered the reversible fluorescence switching behavior of UnaG and demonstrated the high photon outputs and high localization numbers in single-molecule localization microscopy (SMLM). In this study, we showed that the fluorescence of eUnaG can be switched off under blue-light illumination, while a high concentration of fluorogenic ligands in the buffer can efficiently restore the fluorescence, as in UnaG. We demonstrated the capacity of eUnaG as an efficient protein label in mammalian cells, as well as for SMLM by utilizing its photoswitchable nature. While cytosolic UnaG proteins showed aggregated patches and fluorescence reduction at high expression levels, eUnaG-labeled protein targets successfully formed their proper structures in mammalian cells without notable distortion from the endogenous structure in the majority of transiently expressing cells. In particular, eUnaG preserved the vimentin filament structures much better than the UnaG. eUnaG provided similarly high single-molecule photon count distribution to UnaG, thus also similarly high resolution in the super-resolution images of various subcellular structures. The sampling coverage analysis of vimentin filaments in SMLM images showed the improvement of labeling efficiency of eUnaG. eUnaG is a high-performance fluorescent protein for fluorescence and single-molecule localization imaging in green emission with minimal labeling artifact.


Genetic difference between two Schistosoma japonicum isolates with contrasting cercarial shedding patterns revealed by whole genome sequencing.
Schistosoma japonicum is one of the major infectious agents of human schistosomiasis, mainly endemic in China and the Philippines. We have previously reported the finding of two schistosome isolates, each with a different cercarial emergence pattern adapted to their different hosts. However, there are currently no whole-genome sequencing studies to investigate the underlining genetics of the adaptive traits. We sampled schistosomes in 2013 and 2020 from a hilly area Shitai (ST) and a marshland area Hexian (HX) of Anhui, China. Ten to 15 male or female adult worms from each site/year were sent for whole genome sequencing. Genetics were analyzed, and selection signals along genomes were detected. Gene enrichment analysis was performed for the genome regions under selection. The results revealed considerable genetic differentiation between the two isolates. The genome "windows" affected by natural selection were fewer in ST (64 windows containing 78 genes) than in HX (318 windows containing 276 genes). Twelve significantly enriched genes were identified in ST, but none in HX. These genes were mainly related to specific DNA binding and intercellular signaling transduction. Some functional region changes identified along the genome of the hilly schistosome may be related to its unique late afternoon cercarial emergence.


A critical analysis of ICU/HC beds in South Africa: 2008-2009.
To determine the national distribution of intensive care unit (ICU)/high care (HC) beds and the implications for ICU bed availability in the envisaged national health insurance (NHI) scheme. A descriptive, non-interventional, observational study design was used. A desk-top audit of all public and private sector ICUs, including ICU/HC beds, in South Africa was undertaken for the period 2008 - 2009. For this study, both categories were analysed and referred to as ICU beds, as they reflect the critical care component of the health service in South Africa. In 2008 - 2009, there were 4 719 ICU beds in the private and public sectors in South Africa, with 75% (3 533) in the former and 25% (1 186) in the latter. The majority of ICU beds in the two sectors were located in three provinces: Gauteng (49%), KwaZulu-Natal (14%) and Western Cape (15%), representing 78% of ICU beds (3 703/4 719) and catering for 54% of the country's population. Eastern Cape had fewer than 300 beds, North West and Mpumalanga had fewer than 150 beds, and Limpopo and Northern Cape had 66 and 47 beds respectively. With the proposed NHI scheme, the number of ICU beds available would be 4 719, which would translate into a bed:population ratio of approximately 1:10 000. However, there are large variations across the provinces, which makes the availability of this level of care in some provinces non-existent. While increasing the number of ICU beds in the public sector will open critical care services to more users, the NHI scheme would not solve the huge discrepancies of access to ICUs, and availability of critical care staff, across the provinces.


Human-Cougar interactions in the wildland-urban interface of Colorado's front range.
As human populations continue to expand across the world, the need to understand and manage wildlife populations within the wildland-urban interface is becoming commonplace. This is especially true for large carnivores as these species are not always tolerated by the public and can pose a risk to human safety. Unfortunately, information on wildlife species within the wildland-urban interface is sparse, and knowledge from wildland ecosystems does not always translate well to human-dominated systems. Across western North America, cougars (Puma concolor) are routinely utilizing wildland-urban habitats while human use of these areas for homes and recreation is increasing. From 2007 to 2015, we studied cougar resource selection, human-cougar interaction, and cougar conflict management within the wildland-urban landscape of the northern Front Range in Colorado, USA. Resource selection of cougars within this landscape was typical of cougars in more remote settings but cougar interactions with humans tended to occur in locations cougars typically selected against, especially those in proximity to human structures. Within higher housing density areas, 83% of cougar use occurred at night, suggesting cougars generally avoided human activity by partitioning time. Only 24% of monitored cougars were reported for some type of conflict behavior but 39% of cougars sampled during feeding site investigations of GPS collar data were found to consume domestic prey items. Aversive conditioning was difficult to implement and generally ineffective for altering cougar behaviors but was thought to potentially have long-term benefits of reinforcing fear of humans in cougars within human-dominated areas experiencing little cougar hunting pressure. Cougars are able to exploit wildland-urban landscapes effectively, and conflict is relatively uncommon compared with the proportion of cougar use. Individual characteristics and behaviors of cougars within these areas are highly varied; therefore, conflict management is unique to each situation and should target individual behaviors. The ability of individual cougars to learn to exploit these environments with minimal human-cougar interactions suggests that maintaining older age structures, especially females, and providing a matrix of habitats, including large connected open-space areas, would be beneficial to cougars and effectively reduce the potential for conflict.


Role of neck ultrasonography in the follow-up of children operated on for thyroid papillary cancer.
The aim of this study was to evaluate the role of neck ultrasonography compared to (131)I whole-body scan (WBS) and circulating thyroglobulin (Tg) measurement after thyroid hormone withdrawal in the follow-up of children with thyroid papillary cancer, who had previously undergone total thyroidectomy for the diagnosis of neck lymph node metastases (LNM). Forty-five children were examined. Neck ultrasonography and diagnostic WBS were conclusive about the presence or absence of LNM in 35 patients. Diagnostic WBS revealed the presence of LNM in 6 cases not detected by neck ultrasonography; neck ultrasonography was positive in 3 cases that were negative at diagnostic WBS but confirmed by post-(131)I therapy WBS. One patient with suspicious neck lymphnodes at neck ultrasonography not confirmed by WBS was considered as a false-positive result of neck ultrasonography. Neck ultrasonography and thyroglobulin (Tg) were conclusive about the presence or absence of LNM in 29 patients. Tg was elevated in 10 subjects with negative neck ultrasonography (7 had also lung and/or mediastinic LNM). Tg was undetectable in 5 patients in whom the presence of LNM was confirmed by neck ultrasonography and WBS. In conclusion, our study in children demonstrates that neck ultrasonography can detect LNM that are not suspected by palpation, diagnostic WBS, or serum Tg determination. Furthermore, neck ultrasonography can pinpoint the anatomic site of the LNM.


Paediatric Spinal Deformity Surgery: Complications and Their Management.
Surgical correction of paediatric spinal deformity is associated with risks, adverse events, and complications that must be preoperatively discussed with patients and their families to inform treatment decisions, expectations, and long-term outcomes. The incidence of complications varies in relation to the underlying aetiology of spinal deformity and surgical procedure. Intraoperative complications include bleeding, neurological injury, and those related to positioning. Postoperative complications include persistent pain, surgical site infection, venous thromboembolism, pulmonary complications, superior mesenteric artery syndrome, and also pseudarthrosis and implant failure, proximal junctional kyphosis, crankshaft phenomenon, and adding-on deformity, which may necessitate revision surgery. Interventions included in enhanced recovery after surgery protocols may reduce the incidence of complications. Complications must be diagnosed, investigated and managed expeditiously to prevent further deterioration and to ensure optimal outcomes. This review summarises the complications associated with paediatric spinal deformity surgery and their management.


Characterizing Sex Differences in Physical Frailty Phenotypes in Heart Failure.
Although women with heart failure (HF) are potentially more likely to be physically frail compared with men with HF, the underlying contributors to this sex difference are poorly understood. The purpose of this study was to characterize sex differences in physical frailty phenotypes in HF. We prospectively enrolled adults with class I-IV HF. Physical frailty was measured with the frailty phenotype criteria. Symptoms of dyspnea, sleep-related impairment, pain interference, depression, and anxiety were assessed. Body composition was measured using dual-energy x-ray absorptiometry. Simple comparative statistics and stepwise regression modeling were used. The average age of the sample (n=115) was 63.6±15.7 years, 49% were women, and 73% had nonischemic cause. Forty-three percent of the sample was physically frail. Women had a 4.6 times greater odds of being physically frail compared with men, adjusting for covariates (odds ratio=4.63 [95% CI, 1.81-11.84], P=0.001). Both physically frail men and women were characterized by more type 2 diabetes, higher comorbidity burden, and worse dyspnea symptoms. Physically frail women had significantly worse symptoms compared with non-physically frail women but no difference in body composition characteristics. Physically frail men had significantly lower appendicular muscle mass, higher percent fat, lower hemoglobin, and more depressive symptoms compared with non-physically frail men. Women are significantly more likely to be physically frail compared with men in HF. Physical frailty in both women and men is characterized by comorbidities and worse symptoms; physical frailty in men is characterized by worse physiological characteristics.


Electroencephalogram Resting State Frequency Power Characteristics of Suicidal Behavior in Female Patients With Major Depressive Disorder.
Difficulties in predicting suicidal behavior hamper effective suicide prevention. Therefore, there is a great need for reliable biomarkers, and neuroimaging may help to identify such markers. Electroencephalography (EEG) was used to investigate resting state spatial-frequency power characteristics of female patients with major depressive disorder (MDD); 19 were recent suicide attempters (within the previous 30 days), 36 were suicide ideators, and 23 were nonsuicidal. Patients were enrolled at neuroCare Clinic Nijmegen (Nijmegen, the Netherlands) between May 2007 and November 2016, and the primary diagnosis of nonpsychotic MDD was confirmed using the Mini-International Neuropsychiatric Interview, DSM-IV criteria, and a score of ≥ 14 on the 21-item Beck Depression Inventory. Nonparametric, cluster-based permutation tests were applied to detect robust power differences between the study groups on the EEG broadband signal (2-100 Hz). Furthermore, a nonadaptive distributed source imaging method (eLORETA) was utilized to examine if these suicide-based frequency characteristics are localized in brain areas previously reported in the neuroimaging literature. When compared to nonsuicidal depressed patients, attempters and ideators displayed both decreased beta and low gamma activity in the frontal regions. Moreover, ideators had increased alpha activity over the posterior regions and increased high beta, low gamma activity over the left occipital region when compared to psychiatric controls. Attempters had reduced beta and low gamma activity over the right temporal region when compared to ideators. In addition, eLORETA localized attempter and ideator reduced frontal activity within the orbito-, medial-, middle-, superior-, and inferior-frontal areas and the anterior cingulate cortex. In attempters, reduced right temporal activity was localized within the right inferior-, middle-, and superior-temporal cortices and the fusiform gyrus. Frequency power characteristics of attempters and ideators are consistent with findings from the neuroimaging literature concerning suicide, implying EEG resting state assessment could become a potential biomarker to predict suicide risk.


The herpes simplex virus type 1 ribonucleotide reductase is required for acute retinal disease.
We have used a herpes simplex virus type 1 (HSV-1) ribonucleotide reductase (RR) null mutant (ICP6 delta) to determine if the HSV-1 RR is required for acute retinal disease. Injection of the ICP6 delta mutant into the vitreous induced mild transient signs of infection (vitreal infiltrate, retinal inflammation, and changes in retinal cytology). In contrast, the parental KOS and a revertant virus (ICP6 delta + 3.1) in which the RR gene had been restored, caused severe retinitis. Injection of media alone also induced mild transient signs of disease. Two months after infection, ICP6 delta injected eyes could not be distinguished from normal eyes. Repeated injection of ICP6 delta (3 times, 2 weeks apart) resulted in vitreal infiltrate near the site of injection but the retina did not appear damaged. The mutant, ICP6 delta, grew to peak titers 1 x 10(3) to 1 x 10(5)-fold lower and cleared faster than KOS or ICP6 delta + 3.1 in the injected eyes suggesting that the reduced virulence was due to reduced ability of the virus to grow. These results show that the viral RR is required for acute retinal disease.


Visual receptive fields sensitive to absolute and relative motion during tracking.
Some neurons in the visual cortex of awake monkeys visually tracking a moving target showed receptive fields that were excited only by stimulus motion relative to a background, while other neurons responded to any kind of stimulus motion. This result was found with two methods, one in which tracking eye movements were identical in both relative-motion and absolute-motion conditions, and another in which stimulus motions on the retina were identical in both conditions. This response pattern can differentiate translation of the retinal image during eye movement from motion of objects in the world.


[Clinical features of gas-forming liver abscesses: comparison between diabetic and nondiabetic patients].
Patients with diabetes mellitus (DM) are more likely to have a pyogenic liver abscess with gas formation, which is associated with higher morbidity and mortality. The morbidity and mortality in pyogenic liver abscess are also higher in DM patients than in non-DM patients. This study evaluated the morbidity, mortality, and clinical features in patients with gas-forming liver abscesses associated with DM. Among 379 cases of pyogenic liver abscess excluding malignancy from January 2001 through December 2009, 25 patients treated for pyogenic-gas-forming liver abscesses were reviewed retrospectively. We compared the morbidity, mortality, and clinical findings in patients with pyogenic-gas-forming liver abscesses between DM and non-DM patients. Gas formation was present in 25 (6.6%) of 379 cases with pyogenic liver abscess. DM was combined with gas-forming liver abscesses in 19 cases (76%). The most common organism responsible for the gas formation was Klebsiella pneumoniae (82%). Complications were present in 23 cases (92%) of gas-forming liver abscesses, with pulmonary complications (especially pleural effusion) being the most common (n=14, 61%). Four patients (16%) died of sepsis. Gas-forming liver abscesses are not uncommon in cases of pyogenic liver abscesses and are associated with high morbidity and mortality rates. The clinical manifestations and complications do not differ significantly between DM and non-DM patients.


Workplace cardiovascular risk reduction by healthcare professionals-a systematic review.
Cardiovascular disease has a significant impact on public health and is largely preventable by addressing modifiable risk factors. As most adults spend on average half of their waking hours at work, this provides a significant opportunity to address modifiable risk factors through health promotion interventions. Healthcare professionals have the knowledge and skills to provide workplace interventions aimed at cardiovascular risk reduction. This study was aimed to assess the literature regarding the effect of workplace interventions led by healthcare professionals on cardiovascular risk factors. Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, MEDLINE, PsycINFO and SPORTDiscus were systematically searched from inception to March 2021. Included studies evaluated impact of workplace interventions by healthcare professionals on cardiovascular health. Data on study design, baseline characteristics, interventions, outcomes and conclusions were extracted and qualitatively analysed. Forty-five studies representing 77 633 participants were included in the analysis. Healthcare professionals involved included: nurses, nurse practitioners, physicians, dietitians, pharmacists, physician assistants, medical technicians/emergency medical technicians and physiotherapists. Workplace interventions by healthcare professionals generally improved surrogate markers of cardiovascular health. Success varied based on provider and nature of the intervention. Addressing motivation and including follow-up were key factors for successful intervention to reduce cardiovascular risk factors. Workplace health promotion initiatives delivered by healthcare professionals may improve cardiovascular risk markers if they are evidence based and customized for target populations. More research is needed to determine clinical relevance of interventions and ideal interventions for specific employee groups.


Selection by genetic complementation and characterization of the gene coding for the yeast porphobilinogen deaminase.
The porphobilinogen deaminase (PBG-D) gene of Saccharomyces cerevisiae has been isolated by genetic complementation of a mutant GL7 (alpha hem 3) strain, previously shown to be defective in this haembiosynthetic enzyme [Gollub, Liu, Dayan, Adlersberg & Sprinson (1977) J. Biol. Chem. 252, 2846-2854]. The gene was selected from a yeast wild-type genomic DNA library ligated into the shuttle vector YEp13. The complementing gene restored growth of the hem 3 (PBG-D) mutant strain on media in the absence of exogeneous haem or fatty acid and sterol supplements. The recombinant plasmid was retained in the Hem+ transformant provided that selective pressure for plasmid-dependent growth was maintained. Transformation of the mutant strain (hem 3) restored the PBG-D activity to levels up to 10-fold those of the parental strain. The mutant strain GL7 does not show any measurable enzymic activity. Analysis of the plasmid designated YEpPBG-D (containing the PBG-D gene) by hybrid-selected translation revealed that it contained the coding information for a single protein of apparent Mr 43,000. The coding region was localized on an 1.5 kb endonuclease-EcoRI fragment (E4), within the 5.5 kb genomic insert in YEpPBG-D.


Extra-pair paternity as the result of reproductive transactions between paired mates.
Transactional ('optimal skew' or concessions') models of social evolution emphasize that dominant members of society can be favoured for donating parcels of reproduction to same-sexed subordinates in return for cooperation by the latter. We developed a mathematically similar model in which extra-pair paternity in broods receiving biparental care is viewed as emerging from a reproductive transaction between the paired mates. The model quantitatively predicted the maximum paternity that a male mate can demand before its female mate is favoured to break the pair bond and caring solitarily for a brood sired entirely by a neighbouring male. The model predicts that extra-pair paternity results when the neighbouring male is of sufficiently higher quality than the male mate. In such cases, the exact amount of extra-pair paternity will vary directly with the difference in quality between the two males and inversely with the value (fitness impact) of the male mate's parental care. Importantly, the transactional model provided a unified explanation for experimental and observational evidence that extra-pair paternity rises with decreasing quality of the male mate, increasing genetic variability among breeding males, increasing breeding density, increasing availability of food and decreasing involvement of the male mate in parental care.


Oxygen demand of calcium-tolerant adult cardiac myocytes.
Isolated Ca2+-tolerant myocytes are mechanically at rest. Therefore, minimal oxygen demands should be expected. If oxygen consumption is measured without mechanical agitation of the cells, consumption rates comparable to those of the arrested myocardium are measured. In the current literature, much higher values are usually reported. It is suggested that these are due to mechanical stimulation of the cells in stirred suspensions.


Fat-storing cells as liver-specific pericytes. Spatial dynamics of agonist-stimulated intracellular calcium transients.
Liver perisinusoidal fat-storing cells (FSC) show morphological and ultrastructural characteristics similar to pericytes regulating local blood flow in other organs. In the present study we have analyzed whether FSC respond to local vasoconstrictors such as thrombin, angiotensin-II, and endothelin-1 with an increase in intracellular free calcium concentration ([Ca2+]i) coupled with effective cell contraction. All agonists tested induced a rapid and dose-dependent increase in [Ca2+]i followed by a sustained phase lasting several minutes in confluent monolayers of Fura-2-loaded human FSC. Pharmacological studies performed using different Ca2+ channel blockers indicated that, at least for thrombin and angiotensin-II, the sustained phase is due to the opening of voltage-sensitive membrane Ca2+ channels. To analyze the temporal and spatial dynamics of Ca2+ release in response to these agonists, we performed experiments on individual Fura-2-loaded human FSC using a dual wavelength, radiometric video imaging system. The rise in [Ca2+]i was exclusively localized to the cytoplasm, particularly in the branching processes. Increases in [Ca2+]i more than four-fold were associated with a simultaneous and transient reduction of cell area indicating reversible cell contraction. Our results indicate that the Ca(2+)-dependent contraction of human FSC in vitro may reflect a potential role in regulating sinusoidal blood flow in vivo.


Evaluation of chemotherapy in the control of Schistosoma mansoni in Marquis Valley, Saint Lucia. II. Biological results.
Following the final chemotherapy campaign of a 4-year program, the biological assessment of transmission of Schistosoma mansoni was evaluated for 5 years. No infected Biomphalaria glabrata were found amongst 28,791 and 13,550 snails examined from flowing and static index sites, respectively. However, 89 infected snails of 16,602 examined (0.54%) were found from additional sites. Sentinel snails examined between March 1974 and October 1977 revealed no infections and their use was discontinued. Following an increase in transmission, routine focal mollusciciding at 4-weekly intervals was introduced in March 1980. The cost for eight applications was US $641, representing a cost per caput of $0.21. These figures, extrapolated to a full year's control, become $1,042 and $0.35, respectively. The maximum cost was for the molluscicide, which absorbed 71.5% of the total. The data suggest that the main transmission of S. mansoni occurs in the dry season, in flowing habitats, as it does elsewhere in St. Lucia.


Glucosamine-chondroitin sulphate accelerates tendon-to-bone healing in rabbits.
This study aims to investigate the contribution of glucosamine-chondroitin sulphate (GlcN-CS) to the healing of tendons within the bone tunnel. Tendon-to-bone healing was investigated in 28 New Zealand rabbits by re-attaching the extensor digitorum longus tendon into bone tunnel which was created in the proximal tibia. Rabbits were separated into two groups as treatment and control groups. Treatment group (n=14) received 210-250 mg/kg/day glucosamine sulphate and 170-200 mg/kg/day chondroitin sulphate, whereas control group (n=14) received equivalent dose of vehicle. Treatment and control groups were compared at sixth and 12th week after the procedure according to histological and biomechanical analysis. Yamakado scoring system was used to evaluate the histological changes. According to histological analysis, scores were significantly higher at both sixth and 12th week evaluations in the treatment group (p=0.029). Although not statistically significant, the ultimate pullout strength was higher in the treatment group at the 12th week evaluation (35.3 N/mm2 vs. 24.3 N/mm2) (p>0.05). However, stripping occurred at the muscle-tendon junction in the treatment group whereas tendons stripped from the bone tunnels in the control group. While no tendons in the treatment group stripped from the bone tunnels, we observed at sixth and 12th week evaluations that tendons in the control group stripped from the tunnels. Glucosamine-chondroitin sulphate treatment enhances tendon-to-bone healing by increasing hyaline cartilage formation and decreasing formation of capillary vessels.


6-Gingerol prevents MEHP-induced DNA damage in human umbilical vein endothelia cells.
Mono (2-ethylhexyl) phthalate (MEHP) is the principal metabolite of di (2-etylhexyl) phthalate, which is widely used as a plasticizer, especially in medical devices. MEHP has toxic effects on cardiovascular system. The aim of this study was to investigate the possibility that 6-gingerol may inhibit the oxidative DNA damage of MEHP in human umbilical vein endothelial cells (HUVECs) and the potential mechanism. The comet assay was used to monitor DNA strand breaks. We have shown that 6-gingerol significantly reduced the DNA strand breaks caused by MEHP. MEHP increased the levels of reactive oxygen species and malondialdehyde, decreased the level of glutathione and activity of superoxide dismutase, and altered the mitochondrial membrane potential. In addition, DNA damage-associated proteins (p53 and p-Chk2 (T68)) were significantly increased by the treatment of MEHP. Those effects can all be protected by 6-gingerol. The results firmly indicate that 6-gingerol may have a strong protective ability against the DNA damage caused by MEHP in HUVECs, and the mechanism may relate to the antioxidant activity.


Clinical aspects of congenital primary lymphedema.
Lymphedema is a specific type of edema with a chronic, progressive nature. The aim of the present study is to report clinical findings related to edema and its location in children with primary lymphedema. Sixty-eight children with congenital primary lymphedema were evaluated at the Godoy Clinic in São Jose do Rio Preto, Brazil, between 2014 and 2017. A retrospective, cross-sectional study was conducted involving the analysis of clinical data on the location of edema in 68 children with congenital primary lymphedema. We evaluated the charts of all children with this condition in the period analyzed, recording the affected limbs and conditions associated with lymphedema. Sixty-eight children, 37 girls (54.41%) and 31 boys (45.58%), were evaluated. We found that congenital primary lymphedema predominantly affects the lower limbs and is more prevalent in girls than boys.


A Rare Presentation of Concurrent Onset and Coexistence of Generalized Lichen Planus and Psoriasis in a Child.
Independently, psoriasis and lichen planus (LP) are common inflammatory skin conditions affecting around 2-3% and 1% of the population, respectively. However, the coexistence of both diseases is rare. Common immunological mechanisms with altered T-cell-mediated autoimmunity, cytokine milieu, and Koebner phenomenon play a role in their pathogenesis. As reviewed in the literature, psoriasis may independently be associated with other autoimmune conditions like vitiligo, alopecia areata, LP, and discoid lupus erythematosus. A rare co-occurrence of these two or three autoimmune diseases has been reported. Here, we report a case of a 10-year-old boy who presented with persistent nonpruritic multiple hyperpigmented scaly papules and plaques over the body since 6 months of age. Histopathology revealed features suggestive of both LP and psoriasis in the same section. A diagnosis of psoriasis-LP overlap was made, and the patient was managed with tab acitretin 25 mg daily and narrowband ultraviolet B (NBUVB) phototherapy with which he showed satisfactory clearance of the lesions.


Prevalence of Female Authors in Case Reports Published in the Medical Literature.
Underrepresentation of female authors in research publications is prevalent, but it is unclear whether this is attributable to sex disparities in research conduct or authorship practices. Case reports are a poorly understood component of the biomedical corpus, and the production of anecdotal observations is not confounded by factors associated with disparities in female representation in research publications. Whether female authorship disparities exist in nonresearch publications of clinical information is unknown. To examine the authorship of case reports and elucidate factors associated with sex disparity. Cross-sectional study of all case reports published by US authors in 2014 and 2015 indexed in PubMed performed from July 2015 to July 2018. The primary outcome measure was the proportion of female first authors. The secondary outcome measures were the proportion of female last authors and female authorship representation among different clinical specialties. Bibliometric data was abstracted from 20 427 case reports published across 2538 journals. A total of 7252 (36%) and 4825 (25%) case reports had a female first and last author, respectively. In comparison, 44% and 34% of US trainees and physicians, respectively, were female in 2015. Among adult case reports, female authorship was more prevalent in academic environments compared with community settings (34.0% vs 28.2% for female first authors and 23.4% vs 19.7% for female last authors). Across states, the proportions of female first authors and last authors were universally less than the proportions of female trainees and active female physicians, respectively. Female first authorship was associated with larger author teams (odds ratio [OR], 1.02; 95% CI, 1.01-1.03), an academic affiliation (OR, 1.16; 95% CI, 1.06-1.27), and a female last author (OR, 1.58; 95% CI, 1.47-1.70). Relative to general internal medicine, specialties dominated by male clinicians were less frequently associated with female first authors. Several exceptions displaying a relatively equivalent tendency for male and female first authorship included oncology (OR, 0.97; 95% CI, 0.81-1.16), ophthalmology (OR, 0.87; 95% CI, 0.72-1.05), and radiation oncology (OR, 0.94 95% CI, 0.56-1.56). The underrepresentation of women among first and last authors in publications of case reports underscores the pervasiveness of sex disparities in medicine. Collaboration and female mentors may be critical instruments in upsetting longstanding practices associated with sex bias. Not all clinical specialties were associated with lower-than-expected female authorship, and further exploration of specialty-specific norms in publication and mentorship may elucidate specific barriers to female authorship.


Electrical coupling between hippocampal neurons: contrasting roles of principal cell gap junctions and interneuron gap junctions.
There is considerable experimental evidence, anatomical and physiological, that gap junctions exist in the hippocampus. Electrical coupling through these gap junctions may be divided into three types: between principal neurons, between interneurons and at mixed chemical (glutamatergic)/electrical synapses. An approach, combining in vitro experimental with modeling techniques, sheds some light on the functional consequences of electrical coupling, for network oscillations and for seizures. Additionally, in vivo experiments, using mouse connexin knockouts, suggest that the presence of electrical coupling is important for optimal performance on selected behavioral tasks; however, the interpretation of such data, in cellular terms, has so far proven difficult. Given that invertebrate central pattern generators so often depend on both chemical and electrical synapses, our hypothesis is that hippocampus-mediated and -influenced behaviors will act likewise. Experiments, likely hard ones, will be required to test this intuition.


RhizoBindingSites, a Database of DNA-Binding Motifs in Nitrogen-Fixing Bacteria Inferred Using a Footprint Discovery Approach.
Basic knowledge of transcriptional regulation is needed to understand the mechanisms governing biological processes, i.e., nitrogen fixation by Rhizobiales bacteria in symbiosis with leguminous plants. The RhizoBindingSites database is a computer-assisted framework providing motif-gene-associated conserved sequences potentially implicated in transcriptional regulation in nine symbiotic species. A dyad analysis algorithm was used to deduce motifs in the upstream regulatory region of orthologous genes, and only motifs also located in the gene seed promoter with a p-value of 1e-4 were accepted. A genomic scan analysis of the upstoream sequences with these motifs was performed. These predicted binding sites were categorized according to low, medium and high homology between the matrix and the upstream regulatory sequence. On average, 62.7% of the genes had a motif, accounting for 80.44% of the genes per genome, with 19613 matrices (a matrix is a representation of a motif). The RhizoBindingSites database provides motif and gene information, motif conservation in the order Rhizobiales, matrices, motif logos, regulatory networks constructed from theoretical or experimental data, a criterion for selecting motifs and a guide for users. The RhizoBindingSites database is freely available online at rhizobindingsites.ccg.unam.mx.


A co-stimulatory trap set by myeloid leukemia cells.
The straightforward notion that tumor cells always exert immunosuppressive functions has been contradicted by the finding that myeloid leukemia cells can express potent co-stimulatory molecules. Indeed, the co-stimulatory support offered by leukemia cells can provoke helper T-cell responses. Unfavorably, this interaction allows leukemia cells to acquire immunosuppressive capacities.


Differential epigenetic factors in the prediction of cardiovascular risk in diabetic patients.
Hyperglycaemia can strongly alter the epigenetic signatures in many types of human vascular cells providing persistent perturbations of protein-protein interactions both in micro- and macro-domains. The establishment of these epigenetic changes may precede cardiovascular (CV) complications and help us to predict vascular lesions in diabetic patients. Importantly, these epigenetic marks may be transmitted across several generations (transgenerational effect) and increase the individual risk of disease. Aberrant DNA methylation and imbalance of histone modifications, mainly acetylation and methylation of H3, represent key determinants of vascular lesions and, thus, putative useful biomarkers for prevention and diagnosis of CV risk in diabetics. Moreover, a differential expression of some micro-RNAs (miRNAs), mainly miR-126, may be a useful prognostic biomarker for atherosclerosis development in asymptomatic subjects. Recently, also environmental-induced chemical perturbations in mRNA (epitranscriptome), mainly the N6-methyladenosine, have been associated with obesity and diabetes. Importantly, reversal of epigenetic changes by modulation of lifestyle and use of metformin, statins, fenofibrate, and apabetalone may offer useful therapeutic options to prevent or delay CV events in diabetics increasing the opportunity for personalized therapy. Network medicine is a promising molecular-bioinformatic approach to identify the signalling pathways underlying the pathogenesis of CV lesions in diabetic patients. Moreover, machine learning tools combined with tomography are advancing the individualized assessment of CV risk in these patients. We remark the need for combining epigenetics and advanced bioinformatic platforms to improve the prediction of vascular lesions in diabetics increasing the opportunity for CV precision medicine.


Oral lichen planus and dental implants--a retrospective study.
To examine whether oral lichen planus (OLP) affects the success rate of dental implants and if the manifestations of OLP are altered by implant-borne prostheses. OLP patients, treated in the oral medicine department, with (the study group) and without (control group) dental implants were included. Pocket depth, mobility, bleeding on probing, erythema, pain and radiolucency around the implants, as well as clinical findings and OLP symptoms were recorded. Follow-up ranged from 12-24 months. Ordinal variables and visual analog scale score were compared using the Mann-Whitney test. The significance of the trend within each of the groups was assed using the Friedman test. Categorical variables were compared using Pearson chi-squared test and Fisher's exact test. Fourteen patients in the study group with 1-15 implants per patient and 15 in the control group were included. No implant failures were recorded. Comparison between the clinical manifestations of OLP in both groups did not reveal any significant differences. Success of implant rehabilitation among treated OLP patients does not seem to be different from the success rate in the general population. Nor does implant placement influence the disease manifestations.


Cloning and characterization of cholesteryl ester transfer transfer protein isolated from the tree shrew.
To obtain the nucleotide sequence and deduced amino acid sequence of cholesteryl ester transfer protein (CETP) cDNA from the tree shrew (Tupaia glis). The cDNA sequence of the tree shrew CETP was obtained by utilizing the technique of switching mechanism at 5' end of RNA transcript (SMART) and rapid amplification of cDNA end (RACE) from the first strand of the cDNA. The amino acid sequence of CETP was deduced from the cDNA sequence and its primary and secondary structures were predicted. The sequence of CETP cDNA from tree shrew (GenBank accession number AF334033) covers 1636 bp, including 178 bp at the 3' end of the untranslated region and a 1458 bp fragment in a coding region, which provides the complete sequence of mature tree shrew CETP, although not the initiator methionine. The first 24 bp encodes a partial signal peptide. The mature protein consists of 477 amino acids and is longer than the human version by one amino acid (Gly318). Comparing this amino acid sequence with those of other animals' CETPs, the identity between tree shrew and human and rabbit CETP is 88% and 82%, respectively. The protein is extremely hydrophobic as it contains many hydrophobic residues, especially at the C-terminal, consistent with its function in the transfer of neutral lipids. The amino acid residues concerning with binding and transferring neutral lipids are highly conserved. There is a deletion of an N-linked glycosylation site at Asn342 in the tree shrew CETP protein that may participate in the removal of peripheral cholesterol and cholesteryl ester by increasing its activity of transferring cholesteryl ester. The possible glycosylation in the tree shrew CETP may be involved in the molecular mechanism of its insusceptibility to atherosclerosis.


Infectious and neoplastic disorders of the thyroid in AIDS patients: an autopsy study.
The course of human immunodeficiency virus infection and the acquired immunodeficiency syndrome can be complicated by a variety of endocrine abnormalities. This article describes the findings of a prospective autopsy study of the thyroid in 100 patients who died of complications of AIDS before the advent of the so-called highly active antiretroviral therapy [corrected]. A wide range of bacterial, fungal, viral, and neoplastic disorders were observed. Mycobacterium tuberculosis was recorded in 23% of the patients, cytomegalovirus in 17%, Cryptococcus in 5%, Mycobacterium avium in 5%, Pneumocystis in 4%, and other bacteria or fungi in 7%. Kaposi's sarcoma was recorded in 2% of patients and occult papillary carcinoma in 4%. Four patients had dual infections of the thyroid. The mean weight of the thyroid was lower than normal, and 1 case of thyroid follicular atrophy is presented. A review of the medical literature on thyroid disorders in HIV-infected patients is included. Physicians caring for HIV patients should be aware of the possibility of thyroid dysfunction in their patients.


A low-cost, in silico nutritional genomics course-based undergraduate research experience applicable to multiple disciplines.
This article describes the development and assessment of a Nutritional Genomics course, designed to be held in a regular classroom during normal class periods, with few extra costs to the students or the department. The course was run as an upper-level undergraduate and lower-level graduate student course. Student taking the course spent 11 weeks learning and then 4 weeks using various in silico methods to independently characterize genes of interest in the field. During the last 4 weeks of the course, students combined their methods to test a hypothesis they generated about a gene they have not yet studied and completed a final report in the form of a journal article. Two students have published or are in the process of publishing work from their final project. Validated surveys of genetic knowledge given at least 6 months following the course indicated a very high level of genetic knowledge retainment, and favorable attitudes toward genetics testing and medical use of genetics. Finally, self-perceived critical thinking skills were high, and students indicated that they perceived these skills to be gained by their participation in the course. Materials and syllabus provided in the manuscript makes this CURE easily transferrable to other disciplines.


Redox regulation of T-cell turnover by the p13 protein of human T-cell leukemia virus type 1: distinct effects in primary versus transformed cells.
The present study investigated the function of p13, a mitochondrial protein of human T-cell leukemia virus type 1 (HTLV-1). Although necessary for viral propagation in vivo, the mechanism of function of p13 is incompletely understood. Drawing from studies in isolated mitochondria, we analyzed the effects of p13 on mitochondrial reactive oxygen species (ROS) in transformed and primary T cells. In transformed cells (Jurkat, HeLa), p13 did not affect ROS unless the cells were subjected to glucose deprivation, which led to a p13-dependent increase in ROS and cell death. Using RNA interference we confirmed that expression of p13 also influences glucose starvation-induced cell death in the context of HTLV-1-infected cells. ROS measurements showed an increasing gradient from resting to mitogen-activated primary T cells to transformed T cells (Jurkat). Expression of p13 in primary T cells resulted in their activation, an effect that was abrogated by ROS scavengers. These findings suggest that p13 may have a distinct impact on cell turnover depending on the inherent ROS levels; in the context of the HTLV-1 propagation strategy, p13 could increase the pool of "normal" infected cells while culling cells acquiring a transformed phenotype, thus favoring lifelong persistence of the virus in the host.


Evaluation of serum concentrations of vascular endothelial growth factor (VEGF) in breast cancer patients.
The aim of the study was to assess the value of vascular endothelial growth factor (VEGF) measurements in breast cancer patients with respect to recognized clinicopathological prognostic factors. The study was conducted in 87 women with histologically confirmed breast cancer who underwent surgical treatment and 37 healthy women. Vascular endothelial growth factor concentration levels in the blood samples of patients were correlated with the size of the primary tumor, lymph nodes in the armpit, cancer stage, histological type, grading, multifocality, status of estrogen and progesterone receptors and HER-2 protein expression. Statistical analysis did not show any correlation between concentrations of VEGF and any of the selected parameters. The comparison of VEGF concentrations showed a slightly raised level of VEGF in women with the disease as opposed to the healthy subjects but the differences were not statistically significant (p = 0.472). Similar results were obtained for marker CEA (p = 0.09), while the level of Ca 15-3 in both groups differed significantly (p < 0.001) reaching higher values in the patients with diagnosed breast cancer. Vascular endothelial growth factor concentrations in breast cancer patients do not correlate with recognized clinicopathological prognostic factors and CEA and Ca 15-3 markers, which does not preclude the potential role of VEGF as an independent prognostic factor.


The F-prostaglandin receptor is a novel marker for tumor endothelial cells in renal cell carcinoma.
Tumor angiogenesis is necessary for tumor progression and metastasis; therefore, tumor blood vessels are potential therapeutic targets in anticancer therapy. We previously reported that tumor endothelial cells (TECs) exhibit different phenotypes compared with normal endothelial cells (NECs), and microarray analyses of mouse TECs and NECs have shown that several genes are upregulated in TECs compared with NECs. Among these genes, the expression levels of prostaglandin F receptor (PTGFR) mRNA, which encodes the prostaglandin F receptor (FP), were higher in TECs than in NECs. It has been reported that FP and its ligand, prostaglandin F(2α) , are involved in tumor angiogenesis. However, there have been no reports of the expression of PTGFR in the tumor vessels of renal cell carcinoma (RCC). Thus, we isolated human TECs (hTECs) from RCCs. The expression levels of PTGFR mRNA were also upregulated in hTECs. In addition, immunostaining showed that the PTGFR was expressed in human tumor blood vessels in vivo. These findings suggested that PTGFR is a novel TEC marker and that it may be a novel target for antiangiogenic therapy for RCC.


Pretreatment of guayule biomass using supercritical carbon dioxide-based method.
Guayule, a desert shrub harvested for commercial production of hypoallergenic latex and resins constitutes <20% of the biomass. Converting the remaining bagasse to biorefinery feedstock for value-added products is an optimal economic option. A supercritical CO(2)-based process had been developed previously for resin extraction. In this study, the feasibility of including a supercritical CO(2)-based bagasse pretreatment method was evaluated. The pretreatment involved: adding water to the bagasse, raising system temperature, pressurizing using supercritical CO(2), holding the system for a period of time, and exploding the bagasse. The pretreated biomass was subjected to enzyme hydrolysis. The yields of released sugars were used as pretreatment effectiveness indicators. Supercritical method outperformed other methods and gave much higher overall sugar yields for guayule (as high as 77% for glucose and 86% for total reducing sugars through both pretreatment and hydrolysis, as compared to 50% for glucose and 52% for total sugars with the dilute-acid pretreatment and 36% for glucose and 52% for total sugars with the delignification pretreatment). The enzymatic hydrolyzates were tested on the cellulase-producing fungus Trichoderma reesei Rut C-30. No inhibitory/toxic effects were apparent in terms of cell growth, sugar consumption, and cellulase and xylanase production. The supercritical CO(2)-based method was found to be very promising for pretreatment of waste biomass as the feedstock for subsequent enzymatic hydrolysis and fermentation to produce value-added bioproducts.


Adhesion of bioinspired micropatterned surfaces: effects of pillar radius, aspect ratio, and preload.
Inspired by biological attachment systems, micropatterned elastomeric surfaces with pillars of different heights (between 2.5 and 80 microm) and radii (between 2.5 and 25 microm) were fabricated. Their adhesion properties were systematically tested and compared with flat controls. Micropatterned surfaces with aspect ratios above 0.5 were found to be more compliant than flat surfaces. The adhesion significantly increases with decreasing pillar radius and increasing aspect ratio of the patterned features. A preload dependence of the adhesion force has been identified and demonstrated to be crucial for obtaining adhesives with tunable adherence.


Decreased numbers of monocytes in inflammatory exudates in systemic lupus erythematosus.
Rebuck skin windows and delayed hypersensitivity testing were performed on patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Patients with SLE had a decreased appearance of mononuclear/macrophage cells in the inflammatory exudate compared to patients with RA and normal controls. This abnormal response was unrelated to corticosteroid therapy, but appeared to correlate with activity of disease. Impaired ability to react to skin test antigens was also demonstrated in patients with SLE. The defective mononuclear/macrophage response in patients with SLE may contribute to the impaired cell-mediated immunity and increased susceptibility to infection which occur in this disorder.


Syndactyly type IV/hexadactyly of feet associated with unilateral absence of the tibia.
We report on a newborn girl with syndactyly type IV, hexadactyly of feet, and right tibial hemimelia. She has 5 other relatives with identical anomalies of the hands and feet transmitted as an autosomal dominant trait. Syndactyly type IV is rare as is absence of the tibia. We suggest the possibility that syndactyly type IV may be a more complex entity, including lower limb malformations, and transmitted as autosomal dominant with variable expressivity.


Sensitivity of Mammalian Cone Photoreceptors to Infrared Light.
Two-photon vision arises from the perception of pulsed infrared (IR) laser light as color corresponding to approximately half of the laser wavelength. The physical process responsible for two-photon vision in rods has been delineated and verified experimentally only recently. Here, we sought to determine whether IR light can also be perceived by mammalian cone photoreceptors via a similar activation mechanism. To investigate selectively mammalian cone signaling in mice, we used animals with disabled rod signal transduction. We found that, contrary to the expected progressive sensitivity decrease based on the one-photon cone visual pigment spectral template, the sensitivity of mouse cone photoreceptors decreases only up to 800 nm and then increases at 900 nm and 1000 nm. Similarly, in experiments with the parafoveal region of macaque retinas, we found that the spectral sensitivity of primate cones diverged above the predicted one-photon spectral sensitivity template beyond 800 nm. In both cases, efficient detection of IR light was dependent on minimizing the dispersion of the ultrashort light pulses, indicating a non-linear two-photon activation process. Together, our studies demonstrate that mammalian cones can be activated by near IR light by a nonlinear two-photon excitation. Our results pave the way for the creation of a two-photon IR-based ophthalmoscope for the simultaneous imaging and functional testing of human retinas as a novel tool for the diagnosis and treatment of a wide range of visual disorders.


Sofosbuvir-Velpatasvir (Epclusa)-Associated Photosensitivity in a Hepatitis C Patient: Case Report and Review of Photosensitivity to Hepatitis C Antiviral Agents.
Hepatitis C is a ribonucleic acid (RNA) virus, and its presence in individuals was previously considered to be a chronic condition. However, recent therapeutic advances with virus-directed treatment have resulted in a significant increase in cure rates as demonstrated by an absence of virus on repeat testing. Currently, several individual and combination antiviral therapies are available for the treatment of hepatitis C virus infection. However, each of the hepatitis C antiviral agents is associated with potential adverse skin effects whose incidence varies depending on the agent used for treatment. The cutaneous reactions, including photosensitivity, usually resolve once the antiviral treatment is completed. In this report, we discuss the case of a chronic hepatitis C patient who developed sofosbuvir-velpatasvir (Epclusa)-associated toxicity, while receiving the antiviral therapy. The 57-year-old man developed cutaneous phototoxicity when he started treatment with the drug. The adverse skin reaction promptly resolved once the treatment was completed. Clinicians who manage patients being treated with antiviral agents for hepatitis C infection should consider counseling these individuals regarding photoprotection including avoidance of sun exposure, daily sunscreen use, and wearing photoprotective clothing.


Cerebral amyloid angiopathy with and without hemorrhage: evidence for different disease phenotypes.
To gain insight into different cerebral amyloid angiopathy (CAA) phenotypes and mechanisms, we investigated cortical superficial siderosis (CSS), a new imaging marker of the disease, and its relation with APOE genotype in patients with pathologically proven CAA, who presented with and without intracerebral hemorrhage (ICH). MRI scans of 105 patients with CAA pathologic confirmation and MRI were analyzed for CSS (focal, ≤3 sulci; disseminates, ≥4 sulci) and other imaging markers. We compared pathologic, imaging, and APOE genotype data between subjects with vs without ICH, and investigated associations between CSS and APOE genotype. Our cohort consisted of 54 patients with CAA with symptomatic lobar ICH and 51 without ICH. APOE genotype was available in 53 patients. More than 90% of pathology samples in both groups had neuritic plaques, whereas neurofibrillary tangles were more commonly present in the patients without ICH (87% vs 42%, p < 0.0001). There was a trend for patients with CAA with ICH to more commonly have APOE ε2 (48.7% vs 21.4%, p = 0.075), whereas patients without ICH were more likely to be APOE ε4 carriers (85.7% vs 53.9%, p = 0.035). Disseminated CSS was considerably commoner in patients with ICH (33.3% vs 5.9%, p < 0.0001). In logistic regression, disseminated CSS was associated with APOE ε2 (but not APOE ε4) (odds ratio 5.83; 95% confidence interval 1.49-22.82, p = 0.011). This neuropathologically defined CAA cohort suggests that CSS and APOE ε2 are related to the hemorrhagic expression of the disease; APOE ε4 is enriched in nonhemorrhagic CAA. Our study emphasizes the concept of different CAA phenotypes, suggesting divergent pathophysiologic mechanisms.


RNAi mediated silencing of Nanog expression suppresses the growth of human colorectal cancer stem cells.
Colorectal cancer (CRC) is the third most common cancer in the world known for its poor recurrence-free prognosis. Previous studies have shown that it is closely linked with cancer stem cells (CSCs), which have self-renewal potential and the capacity to differentiate into diverse populations. Nanog is an important transcription factor that functions to maintain the self-renewal and proliferation of embryonic stem cells; however, many recent studies have shown that Nanog is also highly expressed in many cancer stem cells. To investigate whether Nanog plays a crucial role in maintaining the stemness of colorectal CSCs, RNA interference was used to downregulate Nanog expression in the CRC stem cell line, EpCAM+CD44+HCT-116 cells (CCSCs). We examined the anti-tumor function of Nanog in vitro and in vivo, using small interfering RNA. Our results revealed that the Nanog mRNA expression level in CCSCs was higher than that in HCT-116 cells. We found that the depletion of Nanog inhibited proliferation and promoted apoptosis in CCSCs. In addition, the invasive ability of CCSCs was markedly restricted when Nanog was silenced by small interfering RNA. Furthermore, we found that the silencing of Nanog decreased tumor size and weight and improved the survival rate of tumor-bearing mice. In conclusion, these findings collectively demonstrate that Nanog, which is highly expressed in CRC stem cells, is a key factor in the development of tumor growth, and it may serve as a potential marker of prognosis and a novel and effective therapeutic target for the treatment of CRC.


Informal "seed" systems and the management of gene flow in traditional agroecosystems: the case of cassava in Cauca, Colombia.
Our ability to manage gene flow within traditional agroecosystems and their repercussions requires understanding the biology of crops, including farming practices' role in crop ecology. That these practices' effects on crop population genetics have not been quantified bespeaks lack of an appropriate analytical framework. We use a model that construes seed-management practices as part of a crop's demography to describe the dynamics of cassava (Manihot esculenta Crantz) in Cauca, Colombia. We quantify several management practices for cassava--the first estimates of their kind for a vegetatively-propagated crop--describe their demographic repercussions, and compare them to those of maize, a sexually-reproduced grain crop. We discuss the implications for gene flow, the conservation of cassava diversity, and the biosafety of vegetatively-propagated crops in centers of diversity. Cassava populations are surprisingly open and dynamic: farmers exchange germplasm across localities, particularly improved varieties, and distribute it among neighbors at extremely high rates vis-à-vis maize. This implies that a large portion of cassava populations consists of non-local germplasm, often grown in mixed stands with local varieties. Gene flow from this germplasm into local seed banks and gene pools via pollen has been documented, but its extent remains uncertain. In sum, cassava's biology and vegetative propagation might facilitate pre-release confinement of genetically-modified varieties, as expected, but simultaneously contribute to their diffusion across traditional agroecosystems if released. Genetically-modified cassava is unlikely to displace landraces or compromise their diversity; but rapid diffusion of improved germplasm and subsequent incorporation into cassava landraces, seed banks or wild populations could obstruct the tracking and eradication of deleterious transgenes. Attempts to regulate traditional farming practices to reduce the risks could compromise cassava populations' adaptive potential and ultimately prove ineffectual.


Regulation of postsynaptic structure and function by an A-kinase anchoring protein-membrane-associated guanylate kinase scaffolding complex.
A-kinase anchoring protein (AKAP) 79/150 is a scaffold protein found in dendritic spines that recruits the cAMP-dependent protein kinase (PKA) and protein phosphatase 2B-calcineurin (CaN) to membrane-associated guanylate kinase (MAGUK)-linked AMPA receptors (AMPARs) to control receptor phosphorylation and synaptic plasticity. However, AKAP79/150 may also coordinate regulation of AMPAR activity with spine structure directly through MAGUK binding and membrane-cytoskeletal interactions of its N-terminal targeting domain. In cultured hippocampal neurons, we observed that rat AKAP150 expression was low early in development but then increased coincident with spine formation and maturation. Overexpression of human AKAP79 in immature or mature neurons increased the number of dendritic filopodia and spines and enlarged spine area. However, RNA interference knockdown of AKAP150 decreased dendritic spine area only in mature neurons. Importantly, AKAP79 overexpression in immature neurons increased AMPAR postsynaptic localization and activity. Neither the AKAP79 PKA nor CaN anchoring domain was required for increasing dendritic protrusion numbers, spine area, or AMPAR synaptic localization; however, an internal region identified as the MAGUK binding domain was found to be essential as shown by expression of a MAGUK binding mutant that formed mainly filopodia and decreased AMPAR synaptic localization and activity. Expression of the AKAP79 N-terminal targeting domain alone also increased filopodia numbers but not spine area. Overall, these results demonstrate a novel structural role for AKAP79/150 in which the N-terminal targeting domain induces dendritic filopodia and binding to MAGUKs promotes spine enlargement and AMPAR recruitment.


Factors associated with body image distortion in Korean adolescents.
Body image incorporates cognitive and affective components as well as behaviors related to own body perception. This study evaluated the occurrence of body image distortion and its correlates in Korean adolescents. In a school-based cross-sectional survey, a total of 2,117 adolescents were recruited. They filled out self-completing questionnaires on body image distortion, eating attitudes, and behaviors (Eating Attitude Test-26) and related factors. Body image distortions were found in 51.8 percent of adolescents. Univariate analyses showed that boys and older adolescents had higher rates of body image distortion. In the multivariate analyses, body image distortion was associated with high risk for eating disorders (odds ratio [OR] =1.69; 95% confidence interval [CI] 1.11-2.58; P=0.015) and being over weight (OR =33.27; 95% CI 15.51-71.35; P<0.001) or obese (OR =9.37; 95% CI 5.06-17.34; P<0.001). These results suggest that body image distortion is relatively common in Korean adolescents, which has implications for adolescents at risk of developing eating disorders.


Prevention of social stress-escalated cocaine self-administration by CRF-R1 antagonist in the rat VTA.
Intermittent exposure to social defeat stress can induce long-term neural plasticity that may influence escalated cocaine-taking behavior. Stressful encounters can lead to activation of dopamine neurons in the ventral tegmental area (VTA), which are modulated by corticotropin releasing factor (CRF) neurons. The study aims to prevent the effects of intermittently scheduled, brief social defeat stress on subsequent intravenous (IV) cocaine self-administration by pretreatment with a CRF receptor subtype 1 (CRF-R1) antagonist. Long-Evans rats were submitted to four intermittent social defeat experiences separated by 72 h over 10 days. Two experiments examined systemic or intra-VTA antagonism of CRF-R1 subtype during stress on the later expression of locomotor sensitization and cocaine self-administration during fixed (0.75 mg/kg/infusion) and progressive ratio schedules of reinforcement (0.3 mg/kg/infusion), including a continuous 24-h "binge" (0.3 mg/kg/infusion). Pretreatment with a CRF-R1 antagonist, CP 154,526, (20 mg/kg i.p.) prior to each social defeat episode prevented the development of stress-induced locomotor sensitization to a cocaine challenge and prevented escalated cocaine self-administration during a 24-h "binge". In addition, pretreatment with a CRF-R1 antagonist (0.3 μg/0.5 μl/side) into the VTA prior to each social defeat episode prevented stress-induced locomotor sensitization to a cocaine challenge and prevented escalated cocaine self-administration during a 24-h "binge". The current results suggest that CRF-R1 subtype in the VTA is critically involved in the development of stress-induced locomotor sensitization which may contribute to escalated cocaine self-administration during continuous access in a 24-h "binge".


A novel role for protein phosphatase 2A in the dopaminergic regulation of Na,K-ATPase.
Stimulation of dopaminergic type 1 (D(1)) receptors increases lung edema clearance by regulating Na,K-ATPase function in the alveolar epithelium. We studied the role of serine/threonine protein phosphatases in the Na,K-ATPase regulation by D(1) agonists in A549 cells. We found that low doses of the type 1/2A protein phosphatase inhibitor okadaic acid as well as SV40 small t antigen transiently transfected into A549 cells prevented the D(1) agonist-induced increase in Na,K-ATPase activity and translocation from intracellular pools to the plasma membrane. This was associated with a rapid and transient increase in protein phosphatase 2A activity. We conclude that D(1) stimulation regulates Na,K-ATPase activity by promoting recruitment of Na,K-ATPases from intracellular pools into the basolateral membranes of A549 cells via a type 2A protein phosphatase.


Oestrogen therapy in the peri-menopause: A practical approach.
The many preparations available for the treatment of women in the peri-menopause make the prescribing of a therapy both easy and difficult for the physician. It is easy because the number and variety of preparations available permit him, at least in theory, to prescribe an ideal, almost personalized, therapy for each patient, but the situation is difficult because he is required to understand and appreciate the individual properties of a large number of similar but different products. The oestrogen preparations available, the dosage schemes, and the modes of administration are the main aspects of therapy which will be discussed in this paper.


Intra-abdominal pressure increases peri-operatively in patients undergoing deep inferior epigastric perforator flap reconstruction: A prospective study linking high intra-abdominal pressure to non-fatal lung embolism within one patient.
The deep inferior epigastric perforator (DIEP) flap is the gold standard for autologous breast reconstruction. The procedure and peri-operative period are associated with the risk of severe post-operative complications, like venous thromboembolic events (VTE) and lung embolism. Whether the intra-abdominal pressure (IAP) increases after the closure of the abdominal defect, thereby potentially affecting the venous backflow and the risk of VTE, is currently not known. The primary aim is to test if the closure of the abdominal donor site increases the IAP in women undergoing secondary DIEP flap breast reconstruction. By using a Unometer, we measured the intravesical pressure as a surrogate marker for the IAP, at baseline, immediately after, and 24 h after abdominal skin closure, for 13 patients. The mean IAP increased from 6.1 mmHg (95% CI 4.6-7.7) at baseline to 9.0 mmHg (95% CI 8.0-10.0) immediately after skin closure [mean diff. 2.9 (95% CI 1.0-4.8) (p = 0.007)] and further up to 11.7 mmHg (95% CI 9.0-14.5) 24 h after closure [mean diff. 5.3 (95% CI 1.4-9.1) (p = 0.012)]. We found that IAP varies among the patients, regardless of the tightness of abdominal closure or rectus plication (n = 3). Immediately after closure, none of the isolated patients showed abnormal levels of IAP (>12 mmHg), while eight out of 12 isolated patients (67%) showed IAP levels above the normal range after 24 h. One patient developed a non-fatal lung embolism. The mean IAP increases significantly over the post-operative period after DIEP flap reconstruction, although abnormal IAP values are only seen 24 h after the closure of the skin.


Qualitative and quantitative evaluation of epoxy systems by Fourier transform infrared spectroscopy and the flexibilizing effect of mercaptans.
Epoxy systems are widely applied as adhesives in the aerospace industry. They have excellent adhesion properties, however, being thermosetting, epoxy systems show fracture brittleness characteristics. Polysulfide and polymercaptans are good options to increase the flexibility of the epoxy adhesive. Thermal analysis techniques are generally used to evaluate the curing degree of epoxy systems. In most cases, when infrared (IR) analysis is used, it is employed qualitatively. This paper presents the reaction study of a DGEBA epoxy prepolymer with diethylenetriamine (DETA) and linear and branched dodecyl mercaptans as flexibilizers. Conversion data and curing time were assessed qualitatively and quantitatively by Fourier Transform Infrared Spectroscopy (FT-IR) in the medium infrared region (MIR) and in the near infrared region, using near infrared reflectance accessory (NIRA). NIRA methodology showed satisfactory results, with errors between 3 and 7%, especially in samples with lower amine contents. Mechanical tests confirmed the flexibilization of the cured epoxy system by the addition of mercaptans, indicating a lower crosslinking degree in the matrix. Young's modulus (E) significantly decreased from 2017 MPa to 578 MPa with the addition of approximately 20 wt% of normal dodecyl mercaptan to the epoxy system.


Extracellular regulated kinase (ERK) interaction with actin and the calponin homology (CH) domain of actin-binding proteins.
An interaction between extracellular regulated kinase 1 (ERK1) and calponin has previously been reported (Menice, Hulvershorn, Adam, Wang and Morgan (1997) J. Biol. Chem. 272 (40), 25157-25161) and has been suggested to reflect a function of calponin as a signalling molecule. We report in this study that calponin binds to both ERK1 and ERK2 under native conditions as well as in an overlay assay. Using chymotryptic fragments of calponin, the binding site of ERK on calponin was identified as the calponin homology (CH) domain, an N-terminal region of calponin found in other actin-binding proteins. ERK also bound, in a gel overlay assay, alpha-actinin, a protein with two tandem CH domains, as well as a 27 kDa thermolysin product of alpha-actinin containing the CH domains of alpha-actinin. The CH domain of calponin could compete with intact calponin or alpha-actinin for ERK binding. Titration of acrylodan-labelled calponin with ERK gave a K(a) of 6x10(6) M(-1) and titration of acrylodan-labelled calponin with a peptide from the alphaL16 helix of ERK gave a K(a) of 1x10(6) M(-1). Recombinant ERK was found to co-sediment with purified actin and induced a fluorescence change in pyrene-labelled F-actin (K(a)=5x10(6) M(-1)). The interaction of ERK with CH domains points to a new potential function for CH domains. The interaction of ERK with actin raises the possibility that actin may provide a scaffold for ERK signalling complexes in both muscle and non-muscle cells.


Utility of monitoring mycophenolic acid in solid organ transplant patients.
To investigate whether monitoring concentrations of mycophenolic acid (MPA) in the serum or plasma of persons who receive a solid organ transplant will result in a lower incidence of transplant rejections and adverse events versus no monitoring of MPA. To investigate whether the incidence of rejection or adverse events differs according to MPA dose or frequency, type of MPA, the form of MPA monitored, the method of MPA monitoring, or sample characteristics. To assess whether monitoring is cost-effective versus no monitoring. The following databases were searched from their dates of inception (in brackets) until October 2007: MEDLINE (1966); BIOSIS Previews (1976); EMBASE (1980); Cochrane Database of Systematic Reviews (1995); and Cochrane Central Register of Controlled Trials (1995). Studies identified from the data sources went through two levels of screening (i.e., title and abstract, full text) and the ones that passed were abstracted. Criteria for abstraction included publication in the English language, study design (i.e., randomized controlled trial [RCT], observational study with comparison group, case series), and patient receipt of allograft solid organ transplant. Additionally, any form of MPA had to be measured at least once in the plasma or serum using any method of measurement (e.g., AUC0-12, C0). Furthermore, these measures had to be linked to a health outcome (e.g., transplant rejection). Certain biomarkers (e.g., serum creatinine, glomular filtration rate) and all adverse events were also considered health outcomes. The published evidence on MPA monitoring is inconclusive. Direct, head-to-head comparison of monitoring versus no monitoring is limited to one RCT in adult, kidney transplant patients. Inferences about monitoring can be made from some observational studies, although the evidence is equivocal for MPA dose and dose frequency, nonexistent for type of MPA, inconclusive for form of MPA monitored or method of monitoring, and nonexistent for cost-effectiveness. Some studies suggest gender and concomitant use of calcineurin inhibitors will affect pharmacokinetic parameters, but the impact of these findings has not been assessed in relation to monitoring versus no monitoring. The state of knowledge about therapeutic drug monitoring of MPA in solid organ transplants is still in its infancy. Until there is more evidence on the utility of routine MPA monitoring in solid organ transplant recipients, patients, clinicians, and other stakeholders (e.g., public and private insurers) will have to decide on a case by case basis whether the possible but uncertain benefits are worth the extra time and expense of monitoring.


Suppression of the transcription factor MSX1 gene delays bovine preimplantation embryo development in vitro.
This study was conducted to investigate the effect of suppressing transcription factor gene MSX1 on the development of in vitro produced bovine oocytes and embryos, and identify its potential target genes regulated by this gene. Injection of long double-stranded RNA (LdsRNA) and small interfering RNA (siRNA) at germinal vesicle stage oocyte reduced MSX1 mRNA expression by 73 and 37% respectively at metaphase II stage compared with non-injected controls. Similarly, injection of the same anti-sense oligomers at zygote stage reduced MSX1 mRNA expression by 52 and 33% at 8-cell stage compared with non-injected controls. Protein expression was also reduced in LdsRNA- and siRNA-injected groups compared with non-injected controls at both stages. Blastocysts rates were 33, 28, 20 and 18% in non-injected control, scrambled RNA (scRNA), LdsRNA- and siRNA-injected groups respectively. Cleavage rates were also significantly reduced in Smartpool siRNA (SpsiRNA)-injected group (53.76%) compared with scRNA-injected group (57.76%) and non-injected control group (61%). Large-scale gene expression analysis showed that 135 genes were differentially regulated in SpsiRNA-injected group compared with non-injected controls, of which 54 and 81 were down- and up-regulated respectively due to suppression of MSX1. Additionally, sequence homology mapping and gene enrichment analysis with known human pathway information identified several functional modules that were affected due to suppression of MSX1. In conclusion, suppression of MSX1 affects oocyte maturation, embryo cleavage rate and the expression of several genes, suggesting its potential role in the development of bovine preimplantation embryos.