Using Microbial Responses Viewer and a Regression Approach to Assess the Effect of pH, Activity of Water and Temperature on the Survival of Campylobacter spp.
This study aimed at developing a model for evaluating the survival of various Campylobacter jejuni strains under different conditions in culture media and poultry data from ComBase. Campylobacter data of culture media (116) and poultry (19) were collected from Microbial Responses Viewer, an additional tool of ComBase. The Weibull equation was selected as a suitable model for the analysis of survival data because of the nonlinearity of survival curves. Then, the fitting parameters (first reduction time and shape parameter) were analysed through a Kruskall-Wallis test and box-whisker plots, thus pointing out the existence of two classes of temperature (0-12 °C and 15-25 °C) and pH (4-6.5 and 7-7.5) acting on the viability of C. jejuni. Finally, a general regression model was used to build a comprehensive function; all factors were significant, but temperature was the most significant variable, followed by pH and water activity. In addition, desirability and prediction profiles highlighted a negative correlation of the first reduction time with temperature and a positive correlation with pH and water activity.


Structural changes of carbohydrate chains of human thyroglobulin accompanying malignant transformations of thyroid glands.
Carbohydrate moieties were released from human thyroglobulins prepared from normal and transformed, thyroid tissues by hydrazinolysis. The oligosaccharides thus prepared were fractionated by DEAE-cellulose, Bio-Gel P-4, concanavalin-A--Sepharose and Ricinus-communis-agglutinin--Sepharose columns and were characterized by exo-glycosidase and endo-glycosidase digestions, methylation analysis and 400-MHz 1H-NMR spectroscopy. These studies showed that the alterations accompanying malignancy occurred in complex-type carbohydrate chains and exhibited the following structural features: (a) a complex-type carbohydrate chain containing 1 phosphate in a diester linkage was present in all the malignant thyroglobulins. (b) Asialo-carbohydrate chains with biosynthetically incomplete structures were found in all of the malignant thyroglobulins. (c) Carbohydrate chains of higher molecular mass, which have repeating Gal-GlcNAc disaccharides and peripheral alpha-fucosyl residues were present in metastatic papillary carcinoma.


Fungal mn oxides supporting Mn(II) oxidase activity as effective Mn(II) sequestering materials.
We examined the Mn(II)-oxidizing ability of the biogenic Mn oxide (BMO) formed in cultures ofa Mn(II)-oxidizing fungus, Acremonium strictum strain KR21-2. The newly formed BMO effectively sequestered dissolved Mn(II) mainly by oxidizing Mn(II) to insoluble Mn under air-equilibrated conditions, and this ability lasted for at least 8 days. Deaerating the BMOs, poisoning them with NaN3, or heating them all readily weakened their Mn(II) oxidation ability, indicating the involvement of enzymatic Mn(II) oxidation. There was no Mn(II)-oxidizing ability observed for mycelia cultivated without Mn(II) or for residual mycelia after the BMO phase was dissolved, suggesting the need for the oxide phase. A sodium dodecyl sulphate-polyacrylamide gel electrophoresis assay demonstrated that the oxide phase embeds the Mn(II) oxidase and thereby maintains the enzymatic activity in BMOs. Freezing at -80 degrees C preserved the Mn(II)-oxidizing ability in BMOs for at least 4 weeks, while lyophilization caused a complete loss of this ability. Based on these results, we propose that fungal Mn oxides supporting Mn(II) oxidase activity are an effective Mn(II)-sequestering material capable of oxidizing Mn(II) continuously from solutions containing no additional nutrients to maintain biological activity.


Additive antiemetic efficacy of low-doses of the cannabinoid CB(1/2) receptor agonist Δ(9)-THC with ultralow-doses of the vanilloid TRPV1 receptor agonist resiniferatoxin in the least shrew (Cryptotis parva).
Previous studies have shown that cannabinoid CB1/2 and vanilloid TRPV1 agonists (delta-9-tetrahydrocannabinol (Δ(9)-THC) and resiniferatoxin (RTX), respectively) can attenuate the emetic effects of chemotherapeutic agents such as cisplatin. In this study we used the least shrew to demonstrate whether combinations of varying doses of Δ(9)-THC with resiniferatoxin can produce additive antiemetic efficacy against cisplatin-induced vomiting. RTX by itself caused vomiting in a bell-shaped dose-dependent manner with maximal vomiting at 18 μg/kg when administered subcutaneously (s.c.) but not intraperitoneally (i.p.). Δ(9)-THC up to 10 mg/kg provides only 80% protection of least shrews from cisplatin-induced emesis with an ID50 of 0.3-1.8 mg/kg. Combinations of 1 or 5 μg/kg RTX with varying doses of Δ(9)-THC completely suppressed both the frequency and the percentage of shrews vomiting with ID50 dose values 5-50 times lower than Δ(9)-THC doses tested alone against cisplatin. A less potent TRPV1 agonist, capsaicin, by itself did not cause emesis (i.p. or s.c.), but it did significantly reduce vomiting induced by cisplatin given after 30 min but not at 2 h. The TRPV1-receptor antagonist, ruthenium red, attenuated cisplatin-induced emesis at 5mg/kg; however, another TRPV1-receptor antagonist, capsazepine, did not. In summary, we present evidence that combination of CB1/2 and TRPV1 agonists have the capacity to completely abolish cisplatin-induced emesis at doses that are ineffective when used individually.


Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy.
Pegylated liposomal doxorubicin (Doxil, Caelyx) is a formulation of doxorubicin in poly(ethylene glycol)-coated (stealth) liposomes with a prolonged circulation time and unique toxicity profile. We review the preclinical and clinical pharmacology as well as recent clinical data obtained in specific cancer types. Doxil liposomes retain the drug payload during circulation and accumulate preferentially in tissues with increased microvascular permeability, as often is the case of tumors. Doxil toxicity profile is drastically different from that of doxorubicin, and is characterized by dominant and dose-limiting mucocutaneous toxicities, mild myelosuppression, minimal alopecia, and no apparent cardiac toxicity. Although the single maximum tolerated dose (MTD) of Doxil is actually lower than that of conventionally administered doxorubicin, the cumulative MTD dose of Doxil may be substantially greater than that of free doxorubicin. Doxil is probably one of the most active agents in AIDS-related Kaposi's sarcoma and has a definite role in management of recurrent ovarian cancer. The potential of Doxil in the treatment of other cancer types and the opportunities it offers in combination with other drugs and therapeutic modalities are under active investigation.


Harmonization of diffusion MRI data sets with adaptive dictionary learning.
Diffusion magnetic resonance imaging can indirectly infer the microstructure of tissues and provide metrics subject to normal variability in a population. Potentially abnormal values may yield essential information to support analysis of controls and patients cohorts, but subtle confounds could be mistaken for purely biologically driven variations amongst subjects. In this work, we propose a new harmonization algorithm based on adaptive dictionary learning to mitigate the unwanted variability caused by different scanner hardware while preserving the natural biological variability of the data. Our harmonization algorithm does not require paired training data sets, nor spatial registration or matching spatial resolution. Overcomplete dictionaries are learned iteratively from all data sets at the same time with an adaptive regularization criterion, removing variability attributable to the scanners in the process. The obtained mapping is applied directly in the native space of each subject toward a scanner-space. The method is evaluated with a public database which consists of two different protocols acquired on three different scanners. Results show that the effect size of the four studied diffusion metrics is preserved while removing variability attributable to the scanner. Experiments with alterations using a free water compartment, which is not simulated in the training data, shows that the modifications applied to the diffusion weighted images are preserved in the diffusion metrics after harmonization, while still reducing global variability at the same time. The algorithm could help multicenter studies pooling their data by removing scanner specific confounds, and increase statistical power in the process.


NMR metabolomics for evaluating passage number and harvesting effects on mammalian cell metabolome.
The variation in the extracellular metabolites of RAW 264.7 cells obtained from different passage numbers (passage 9, 12 and 14) was examined. The impact of different harvesting protocols (trypsinization and scraping) on recovery of intracellular metabolites was then assessed. The similarity and variation in the cell metabolome was investigated using 1H NMR metabolic profiling modeled using multivariate data analysis. The characterization and quantification of metabolites was performed to determine the passage-related and harvesting-dependent effects on impacted metabolic networks. The trypsinized RAW cells from lower passages gave higher intensities of most identified metabolites, including asparagine, serine and tryptophan. Principal component analysis revealed variation between cells from different passages and harvesting methods, as indicated by the formation of clusters in score plot. Analysis of S-plots revealed metabolites that acted as biomarkers in discriminating cells from different passages including acetate, serine, lactate and choline. Meanwhile lactate, glutamine and pyruvate served as biomarkers for differentiating trypsinized and scraped cells. In passage-dependent effects, glycolysis and TCA cycle were influential, whereas glycerophospholipid metabolism was affected by the harvesting method. Overall, it is proposed that typsinized RAW cells from lower passage numbers are more appropriate when conducting experiments related to NMR metabolomics.


Teaching the handicapped to eat in public places: acquisition, generalization and maintenance of restaurant skills.
This study examined classroom-based instruction in restaurant skills for handicapped persons. Three male students were taught each of four skill components in sequential order: locating, ordering, paying, and eating and exiting. Training was implemented in a multiple baseline design across subjects and consisted of modeling and role playing in conjunction with photo slide sequences and a simulated ordering counter. The use of a menu containing general item classes and a finger matching procedure for identifying errors in the delivery of change greatly reduced the reading and math skills necessary to enter and complete the program. Periodic probes were conducted in a McDonald's restaurant prior to, during, and up to one-year following the termination of training. In addition, two probes (overt and covert observation) were conducted in a Burger King restaurant to assess further generalization to a location different from the one depicted throughout training. Results showed that students' performance on restaurant probes improved as a result of training, generalized to novel settings, maintained over an extended period of time, and was comparable to that of a normative sample of nonretarded persons.


The role of skin biopsy in diagnosis of panniculitides.
Several factors hamper the clinical and histologic diagnosis of panniculitis. Clinically the patients tend to present with erythematous subcutaneous nodules with quite a monotonous appearance, without additional symptoms. Histopathologically, as the subcutaneous fat responds to a variety of insults in a limited number of forms, there are sometimes subtle pathologic differences among the conditions. Although the biopsy plays a critical role in the diagnostic process of a panniculitis, a series of prerequisites must be met in order to obtain as much information as possible from this procedure. If the biopsy is inadequate, i.e., does not include sufficient subcutaneous fat or the site of sampling site/biopsy timing is wrong, histopathologic assessment is limited and the correct diagnosis may be delayed and further sampling may be required. This article introduces the reader to the field of panniculitides under the histopathologic perspective through a brief description of the normal histology of subcutaneous fat. I also includes the definition of the types of fat necrosis, role of biopsy of panniculitis and its rules and pitfalls, up to a microscopic approach of a slide.


Relationship between individual quality of life and family quality of life for people with intellectual disability living in Italy.
There is substantial literature investigating quality of life (QoL) of individuals with intellectual disability (ID). QoL of families of people with ID is emerging as an important field of research. Despite this, there is a lack of studies regarding their relationship. The present paper aimed to study the relationship between QoL scores of individuals with ID and members of their families. Twenty-seven parents or relatives of 27 adults with ID were recruited by four different research centres across Tuscany (Italy) to be interviewed through the Italian adaptation of the Family Quality of Life Survey - 2006 (FQoLS-2006), a tool developed for use in a multiple-country study on family QoL. The FQoLS-2006 was translated and adapted to Italian through three revisions. The last was submitted to the authors of the original version, who also maintain an electronic data file and data archive for statistical evaluations in various countries. QoL of persons with ID was assessed through the administration of the Quality of Life - Instrument Package. QoL scores were analysed to describe population characteristics and to examine the relationships among measures of individual and family QoL using correlations (Pearson and Spearman). Findings showed that family ratings of QoL were generally low. Families interviewed reported a low level of QoL in 'Support from Others' and 'Community Interaction', while 'Family Relationships' and 'Health of the Family' rated higher. For individual QoL, individuals had the lowest scores in the area of 'Spiritual being' and higher scores in the area of 'Physical being'. Correlations examining possible relationships among Importance, Satisfaction and Opportunities found some statistically significant correlation coefficients between some aspects of the three main areas of individual QoL (Being, Belonging and Becoming) and the nine family domains. Most of these correlations regarded family 'Financial Well-Being', 'Family Relationships, 'Support from Service' and 'Support from Others' areas. The results of this study suggest that QoL is perceived somewhat differently by individuals with ID and by members of their families. This difference could negatively impact QoL of people with ID, if their views are not taken into account when planning for family support. The relationships between individual and family QoL appear to be quite complex, and such complexity needs to be clarified in future research.


Efficacy of different techniques of sinonasal irrigation after modified Lothrop procedure.
Postoperative irrigation after endoscopic sinus surgery and endoscopic modified Lothrop procedure is used to remove nasal crusts and to improve wound healing. To evaluate the optimal application protocol for irrigation of the frontal sinus, a prospective cadaver study was performed. An endoscopic modified Lothrop procedure and complete sphenoethmoidectomy were performed in 19 heads. Each was irrigated with a 1.5% solution of water and different colors using nasal spray and a squeeze bottle filled with 50, 100, and 200 mL. Intensity of local staining and percentage of area were documented using standardized videoendoscopy after irrigation in "bending over the sink" or "vertex to floor" position. Grading was performed by two independent observers for 23 anatomic regions, including the stained circumference of maxillary and frontal ostia. To evaluate the influence of the anatomy, acoustic rhinometry was performed. ANOVA was used to evaluate effects of application methods and head positions using GenStat 8.2 (Lawes Agricultural Trust, Rothamsted Experimental Station, Harpenden, U.K.) using an appropriate block structure. With regard to the frontal sinus, we were able to show clear superiority of the squeeze bottle technique filled with 200 mL and applied in the "vertex to floor position." In a relatively fit and flexible patient the vertex to floor position using a squeeze bottle technique is advocated. There may be some patients, however, for whom this position is not feasible. In these patients "bending over the sink," while inferior to the "vertex to floor" position, still ensures some irrigation of the frontal sinus.


Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations.
Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new intracranial hemorrhage (ICH) after brain arteriovenous malformation (BAVM) diagnosis would facilitate risk stratification and identify potential targets for therapeutic intervention. Patients with BAVM were longitudinally followed. Primary outcome was new ICH after diagnosis; censoring events were last follow-up or any BAVM treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes: interleukin-6 (IL-6-174G>C; IL-6-572G>C) and tumor necrosis factor-alpha (TNF-alpha-238G>A; TNF-alpha-308G>A). Association of genotype with risk of new ICH was screened using chi2; SNPs associated with new ICH were further characterized using Cox proportional hazards. We genotyped 280 patients (50% female; 59% white, mean+/-SD age at diagnosis 37+/-17 years; 40% presenting with ICH). TNF-alpha-238G>A was associated with increased risk of new ICH after diagnosis (chi2; P=0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new ICH was increased for patients with TNF-alpha-238 AG genotype (hazard ratio, 4.01; P=0.015). No other SNP was found to be associated with new ICH. A TNF-alpha SNP was associated with increased risk of new ICH in the natural course of BAVMs. The role of inflammatory cytokines in the pathogenesis of BAVM hemorrhage merits further study.


Clinical experience with naltrexone in suburban opioid addicts.
In a study of 160 patients (including 114 active heroin addicts and 42 former heroin addicts maintained on methadone, propoxyphene napsylate, or LAAM), subjects were retained on treatment with naltrexone for a mean of 50.7 days (range, 1-635). Clonidine or guanabenz acetate was used to detoxify subjects who received naltrexone within 10 days of their last dose of opioid. Because of the number of subjects dropping out of treatment after only a few days, it is recommended that there be an opioid-free period of 5 or more days for heroin-dependent subjects and 10 or more days for those on medical maintenance. A naloxone challenge should be administered at a dosage of 0.8 mg. Use of naltrexone combined with psychotherapy appears to promote long periods of opioid abstinence but does not prevent relapse after treatment. Trained clinicians utilizing an appropriate induction protocol can effectively treat volunteer opioid addicts with naltrexone.


Atomistic simulation of a model liquid crystal.
We present atomistic molecular dynamics computer simulations of the bulk phases of a model liquid crystal system based on 8CB. The model differs from real 8CB because it employs a united-atom description to eliminate all hydrogen atoms, and neglects all long-range electrostatic interactions. Despite this simplification, the pressure-temperature phase diagram shows an order-disorder transition, in which isotropic, smectic, and nematiclike behaviors are observed. A detailed analysis of the inter- and intramolecular structures of the ordered phases is given, together with an examination of finite size effects and the equilibration times of the system. It is shown that, whereas a system may appear to be thermodynamically and mechanically equilibrated after a period of 10-15 ns, it is possible for an imprint of the starting configuration to persist for much longer time scales. In the present case, however, such an imprint does not appear to affect the observed phase behavior.


Household air pollution from wood-burning cookstoves and C-reactive protein among women in rural Honduras.
Household air pollution from solid fuel combustion was estimated to cause 2.31 million deaths worldwide in 2019; cardiovascular disease is a substantial contributor to the global burden. We evaluated the cross-sectional association between household air pollution (24-h gravimetric kitchen and personal particulate matter (PM2.5) and black carbon (BC)) and C-reactive protein (CRP) measured in dried blood spots among 107 women in rural Honduras using wood-burning traditional or Justa (an engineered combustion chamber) stoves. A suite of 6 additional markers of systemic injury and inflammation were considered in secondary analyses. We adjusted for potential confounders and assessed effect modification of several cardiovascular-disease risk factors. The median (25th, 75th percentiles) 24-h-average personal PM2.5 concentration was 115 μg/m3 (65,154 μg/m3) for traditional stove users and 52 μg/m3 (39, 81 μg/m3) for Justa stove users; kitchen PM2.5 and BC had similar patterns. Higher concentrations of PM2.5 and BC were associated with higher levels of CRP (e.g., a 25% increase in personal PM2.5 was associated with a 10.5% increase in CRP [95% CI: 1.2-20.6]). In secondary analyses, results were generally consistent with a null association. Evidence for effect modification between pollutant measures and four different cardiovascular risk factors (e.g., high blood pressure) was inconsistent. These results support the growing evidence linking household air pollution and cardiovascular disease.


Absolute pitch correlates with high performance on interval naming tasks.
Absolute pitch, the rare ability to identify or produce a musical tone without a reference tone, has been shown to be advantageous in some musical tasks; however, its relevance in musical contexts primarily involving relative pitch has been questioned. To explore this issue, 36 trained musicians-18 absolute pitch possessors and 18 non-possessors with equivalent age of onset and duration of musical training-were tested on interval naming tasks requiring only relative pitch. The intervals to be named were either ascending or descending with separation ranging from 1 to 12 semitones and equally involved all 12 pitch classes. Three different conditions were employed; these used brief sine waves, piano tones, and piano tones preceded by a V7-I chord cadence so as to establish a tonal context. The possession of absolute pitch was strongly correlated with enhanced performance on all these tests of relative pitch. Furthermore, no evidence was found that this absolute pitch avantage depended on key, interval size, or musical context.


CA9-Related Acidic Microenvironment Mediates CD8+ T Cell Related Immunosuppression in Pancreatic Cancer.
This study aims to integrate pancreatic cancer TCGA, GEO, and single-cell RNA-sequencing (scRNA-seq) datasets, and explore the potential prognostic markers and underlying mechanisms of the immune microenvironment of pancreatic cancer through bioinformatics methods, in vitro and in vivo assays. Expression data and clinicopathological data of pancreatic cancer TCGA, GEO (GSE131050), single cell sequencing (PAAD_CRA001160) dataset were downloaded. We used R/Bioconductor edgeR for differential expression analysis. ClusterProfiler was utilized to perform GO enrichment analysis on differentially expressed genes. The online software CIBERSORT was used to reanalyze the mRNA expression data of pancreatic cancer. CellRanger, RunPCA, FindNeighbors, FindClusters, RunTSNE and RunUMAP were used to perform preprocessing, cell clustering and expression profile analysis on single-cell sequencing data sets. We analyzed intracellular pH with or without CA9 inhibitor SLC-0111. Indirect co-culture model of human pancreatic cancer cell lines and healthy individual-derived PBMCs were used to determine the effect of CA9-related Acidic Microenvironment on CD8+ T cells. The CIBERSORT analysis of TCGA pancreatic cancer transcriptome sequencing data showed that among the 22 immune microenvironment components, CD8+ T cell infiltration was significantly correlated with the prognosis of pancreatic cancer patients. The differential expression analysis of the TCGA data grouped by the level of CD8+ T cell infiltration indicates that the expression of carbonic anhydrase 9 (CA9) is the most significant, and the survival analysis suggests that CA9 is associated with the overall survival of pancreatic cancer. TCGA data and GEO data set GSE131050 expression correlation analysis suggests that CA9 and CD8 expression are closely related. Pancreatic cancer single-cell sequencing data set PAAD_CRA001160 analysis results show that CA9 is mainly expressed in pancreatic cancer cell clusters, and the expression of the cancer cell subgroup CA9 in the single-cell data set is correlated with CD8+ T cell infiltration. Pancreatic cancer cells may inhibit the infiltration of CD8+ T cells through CA9. Further exploration of its related mechanisms can be used to explore the immune escape pathway of pancreatic cancer and provides new perspectives immune targeted therapy.


Ultralow nanoscale wear through atom-by-atom attrition in silicon-containing diamond-like carbon.
Understanding friction and wear at the nanoscale is important for many applications that involve nanoscale components sliding on a surface, such as nanolithography, nanometrology and nanomanufacturing. Defects, cracks and other phenomena that influence material strength and wear at macroscopic scales are less important at the nanoscale, which is why nanowires can, for example, show higher strengths than bulk samples. The contact area between the materials must also be described differently at the nanoscale. Diamond-like carbon is routinely used as a surface coating in applications that require low friction and wear because it is resistant to wear at the macroscale, but there has been considerable debate about the wear mechanisms of diamond-like carbon at the nanoscale because it is difficult to fabricate diamond-like carbon structures with nanoscale fidelity. Here, we demonstrate the batch fabrication of ultrasharp diamond-like carbon tips that contain significant amounts of silicon on silicon microcantilevers for use in atomic force microscopy. This material is known to possess low friction in humid conditions, and we find that, at the nanoscale, it is three orders of magnitude more wear-resistant than silicon under ambient conditions. A wear rate of one atom per micrometre of sliding on SiO(2) is demonstrated. We find that the classical wear law of Archard does not hold at the nanoscale; instead, atom-by-atom attrition dominates the wear mechanisms at these length scales. We estimate that the effective energy barrier for the removal of a single atom is approximately 1 eV, with an effective activation volume of approximately 1 x 10(-28) m.


Expression of arginase II and related enzymes in the rat small intestine and kidney.
Arginase, which catalyzes the conversion of arginine to urea and ornithine, and consists of a liver-type (arginase I) and a non-hepatic type (arginase II). Arginine is also used for the synthesis of nitric oxide and creatine phosphate, while ornithine is used for the synthesis of polyamines and proline, and thus collagen. Arginase II mRNA and protein are abundant in the intestine (most abundant in the jejunum and less abundant in the ileum, duodenum, and colon) and kidney of the rat. In the kidney, the levels of arginase II mRNA do not change appreciably from 0 to 8 weeks of age. In contrast, arginase II mRNA and protein in the small intestine are not detectable at birth, appear at 3 weeks of age, the weaning period, and their levels increase up to 8 weeks. On the other hand, mRNAs for ornithine aminotransferase (OAT), ornithine decarboxylase, and ornithine carbamoyltransferase (OCT) are present at birth and their levels do not change much during development. Arginase II is elevated in response to a combination of bacterial lipopolysaccharide, dibutyryl cAMP, and dexamethasone in the kidney, but is not affected by these treatments in the small intestine. Immunohistochemical analysis of arginase II, OAT, and OCT in the jejunum revealed their co-localization in absorptive epithelial cells. These results show that the arginase II gene is regulated differentially in the small intestine and kidney, and suggest different roles of the enzyme in these two tissues. The co-localization of arginase II and the three ornithine-utilizing enzymes in the small intestine suggests that the enzyme is involved in the synthesis of proline, polyamines, and/or citrulline in this tissue.


Evaluation of a new approach for modelling the screw-bone interface in a locking plate fixation: a corroboration study.
Computational modelling of the screw-bone interface in fracture fixation constructs is challenging. While incorporating screw threads would be a more realistic representation of the physics, this approach can be computationally expensive. Several studies have instead suppressed the threads and modelled the screw shaft with fixed conditions assumed at the screw-bone interface. This study assessed the sensitivity of the computational results to modelling approaches at the screw-bone interface. A new approach for modelling this interface was proposed, and it was tested on two locking screw designs in a diaphyseal bridge plating configuration. Computational models of locked plating and far cortical locking constructs were generated and compared to in vitro models described in prior literature to corroborate the outcomes. The new approach led to closer agreement between the computational and the experimental stiffness data, while the fixed approach led to overestimation of the stiffness predictions. Using the new approach, the pattern of load distribution and the magnitude of the axial forces, experienced by each screw, were compared between the locked plating and far cortical locking constructs. The computational models suggested that under more severe loading conditions, far cortical locking screws might be under higher risk of screw pull-out than the locking screws. The proposed approach for modelling the screw-bone interface can be applied to any fixation involved application of screws.


Understanding In Vivo Mastication Behaviour and In Vitro Starch and Protein Digestibility of Pulsed Electric Field-Treated Black Beans after Cooking.
The aim of this study was to understand (i) the in vivo mastication behaviour of cooked black beans (chewing duration, texture perception, oral bolus particle size, microstructure, and salivary α-amylase) and (ii) the in vitro digestibility of starch and protein of in vivo-generated black bean oral bolus under simulated gastrointestinal condition. The beans were pre-treated using pulsed electric field (PEF) with and without calcium chloride (CaCl2) addition prior to cooking. The surface response model based on least square was used to optimise PEF processing condition in order to achieve the same texture properties of cooked legumes except for chewiness. In vivo mastication behaviour of the participants (n = 17) was characterized for the particle size of the resulting bolus, their salivary α-amylase activity, and the total chewing duration before the bolus was deemed ready for swallowing. In vitro starch and protein digestibility of the masticated bolus generated in vivo by each participant along the gastrointestinal phase were then studied. This study found two distinct groups of chewers-fast and slow chewers who masticated all black bean beans, on average, for <25 and >29 s, respectively, to achieve a bolus ready for swallowing. Longer durations of chewing resulted in boluses with small-sized particles (majorly composed of a higher number of broken-down cotyledons (2-5 mm2 particle size), fewer seed coats (5-13 mm2 particle size)), and higher activity of α-amylase. Therefore, slow chewers consistently exhibited a higher in vitro digestibility of both the starch and protein of processed black beans compared to fast chewers. Despite such distinct difference in the nutritional implication for both groups of chewers, the in vivo masticated oral bolus generated by fast chewers revealed that the processing conditions involving the PEF and addition of CaCl2 of black beans appeared to significantly (p < 0.05) enhance the in vitro digestibility of protein (by two-fold compared to untreated samples) without stimulating a considerable increase in the starch digestibility. These findings clearly demonstrated that the food structure of cooked black beans created through PEF treatment combined with masticatory action has the potential to modulate a faster hydrolysis of protein during gastrointestinal digestion, thus offering an opportunity to upgrade the quality of legume protein intake in the daily diet.


Neuroprotective effect of KR-31378, a novel potassium channel activator, on spinal cord ischemic injury in rabbits.
Neurologic deficits after the surgical repair of thoracic and thoracoabdominal aortic disease are devastating complications. Recently, pharmacologic preconditioning with potassium channel openers was reported to protect the spinal cord against neurologic injury in a model of spinal cord ischemia. A novel benzopyran derivative with an N-cyanoguanidine group, KR-31378, has been synthesized as a new therapeutic agent against ischemic injury. In the present study, we evaluated the protective effects of KR-31378 on spinal cord ischemic injury and compared its neuroprotective activities and hemodynamic stabilities with those of diazoxide. Thirty-four New Zealand white rabbits were randomly divided into four groups: ischemia group (n = 10, 25 min of aortic cross-clamping without any intervention), diazoxide group (n = 8, diazoxide [5 mg/kg] intravenously 15 min before the 25-min cross-clamping), KR20 group (n = 8, KR-31378 [20 mg/kg] intravenously 30 min before the 25-min cross-clamping), and the KR50 group (n = 8, KR-31378 [50 mg/kg] intravenously 30 min before the 25-min cross-clamping). Neurologic functions were evaluated for 72 h postoperatively using modified Tarlov's scores. All rabbits were sacrificed for histopathologic observations after finally scoring neurologic function. All rabbits but three survived. The rest were completely evaluated 72 h postoperatively. Unlike diazoxide-treated rabbits, KR-31378-treated rabbits showed relatively stable hemodynamics. Tarlov's score outcomes showed a marked improvement in the diazoxide group, in the KR20 group, and in the KR50 group compared to the ischemia group (p = .005, .002, and .001, respectively). However, Tarlov's scores in the KR50 group were not significantly different from those of the diazoxide group. Histopathologic data were not significantly different between the groups, but the degree of degenerative change in motor neurons showed a significant correlation with Tarlov's scores 3 days postoperatively (gamma = -.378, p = .036). Thus, the administration of KR-31378 before the aortic cross-clamping resulted in a significant improvement in neurologic outcome with stable hemodynamics in this rabbit model.


Effect of adenosine 5'-triphosphate on secretagogue-stimulated (14C)-aminopyrine accumulation by rabbit isolated gastric glands.
The effect of adenosine 5'-triphosphate (ATP) on gastric acid secretion stimulated by histamine, carbachol and dibutyryl-cAMP (db-cAMP) was studied using glands isolated from rabbit gastric mucosa. The (14C)-aminopyrine (AP) accumulation method was used as an index of acid production by the gastric glands. Histamine-stimulated AP accumulation was significantly inhibited by ATP (10 mumol/l-1 mmol/l). The inhibitory action of ATP appeared to be specific, inasmuch as this nucleotide had no significant effect on basal secretion or secretion stimulated by carbachol or db-cAMP. The antisecretory effect of ATP on histamine-stimulated glands was not affected by the P1-purinoceptor antagonist, theophylline. Pretreatment of glands with indomethacin, a well known prostaglandin synthesis inhibitor, led to a significant reduction of the inhibitory responses to ATP. These results show that ATP inhibits the histamine-stimulated AP accumulation by rabbit isolated gastric glands and suggest that this effect is not due to an ectoenzymatic conversion of ATP into adenosine but to a direct effect of ATP which may be mediated via a P2-purinoceptor subtype linked to prostaglandin production.


The effect of increased salt intake on blood pressure of chimpanzees.
A colony of 26 chimpanzees given a fruit and vegetable diet of very low Na and high K intake were maintained in long-standing, socially stable small groups for three years. Half of them had salt added progressively to their diet during 20 months. This addition of salt within the human dietetic range caused a highly significant rise in systolic, mean and diastolic blood pressure. The change reversed completely by six months after cessation of salt. The effect of salt differed between chimpanzees, some having a large blood pressure rise and others small or no rise. These results in the species phylogenetically closest to humans bear directly on causation of human hypertension, particularly in relation to migration of preliterate people, with low Na diet, to a Western urban lifestyle with increased salt intake. The hedonic liking for salt and avid ingestion was apt during human prehistory involving hunter-gatherer-scavenger existence in the interior of continents with a scarcity of salt, but is maladaptive in urban technological life with salt cheap and freely available.


Actin filament localization in normal and migrating rabbit corneal epithelium.
The molecular probe NBD phallacidin (7-nitro-benz-2-oxa-1, 3-diazolylphallacidin), which reacts specifically with filamentous actin (f-actin), was used to study the distribution of polymerized actin oligmers in normal and migrating rabbit corneal epithelial cells. In the normal cornea, the majority of the NBD phallacidin fluorescence was localized to the cortical or sub-plasma membrane area of the superficial and wing epithelial cells. Following full thickness corneal trephination injury, migrating corneal epithelial cell exhibited a marked increase in the cortical NBD phallacidin fluorescence. Transmission electron microscopy, using fixation techniques which revealed bundles of fine filaments (6nm underlying the plasma membrane of migrating epithelial cells, thus supporting the fluorescent results. These findings suggest that corneal re-epithelialization is characterized by a marked increase in the amount of filamentous actin within the migrating epithelial cells. We conclude that NBD phallacidin may be of value in analyzing changes in actin polymerization during wound healing.


When is the evidence conclusive? Analysis of systematic reviews for which Cochrane declared that conclusions will not change with further studies.
Some Cochrane reviews were declared stable or closed, that is, not in need of updating. For some of them, it has been declared that conclusions will not (or it is unlikely they will) change with further studies. We explored whether there is a discernable decision-making pattern for decisions about the conclusiveness and stabilization of these reviews. We analyzed Cochrane reviews published until April 2020 labeled as stable or closed. We extracted the rationale leading to the decision declaring that the conclusion is not expected to change with further studies. Furthermore, we assessed whether the reviews used GRADE analysis. We extracted data from summary of findings (SoF) tables on the direction of effect, statistical significance, and I2 values for the first and primary outcomes in SoFs, conclusions in the abstract and review, and implications for practice and future research. We included 40 stable/closed Cochrane reviews. Rationales for their stabilization did not enable any insight into the Cochrane's decision-making algorithm for considering the evidence as conclusive. Among 191 outcomes presented in the SoFs, 70% were rated with either low or very low certainty evidence. None of the reviews mentioned in the text that the review should be stabilized or closed, or that there is sufficient evidence on the subject. Reasons for stabilizing/closing Cochrane reviews were unclear, and we could not discern any pattern of "conclusive review" traits. Definition of systematic review conclusiveness is still lacking, which may contribute to research waste.


Arachidonate CYP hydroxylases of kidney contribute to formation of hypertension and maintenance of blood pressure.
To investigate the relationship of kidney-specific expression of cytochrome P-450 (CYP) 4A1 and the blood pressure. The specific sense and antisense CYP4A1 cDNA was administered respectively with the help of eukaryotic expression vector pcDNA3.1 to the Sprague-Dawley (SD) rats via sublingual vein (2 mg/kg). The systolic blood pressure of rats was assessed by the tail- cuff method, and the relative tissue expression of CYP4A1 was analyzed by Western blot and Northern blot at RNA and protein levels in the brain, heart, lung, liver, and kidney of control, sense, and anti-sense CYP4A1 cDNA-treated rats. Two weeks after the injection of the sense and antisense CYP4A1 cDNA recombinants respectively, the mean systolic pressure of the transgenic rats increased by 1.8 kPa +/- 0.3 kPa (13.2 mmHg +/- 2.5 mmHg) or decreased by 1.7 kPa +/- 0.3 kPa (13.0 mmHg +/- 2.2 mmHg) compared with control. At the levels of transcription and translation, the Northern and Western blots all demonstrated that CYP4A1 preferentially overexpressed in the kidney. The administration of sense and antisense CYP4A1 cDNA induced hypertension and hypotension, respectively, which indicated that renal arachidonate hydroxylase contributed to the formation of hypertension and maintenance of blood pressure in normotensive rats.


Respiratory Health Status of Workers that Exposed to Welding Fumes at Lumut Shipyard.
Welding fume exposure has led to the respiratory problems among welders including cough, phlegm, chest illnesses, nausea and fatigue. Inadequate ventilation during welding works causes the situation to worsen. Welding fumes can cause a decrease in lung function among welders. Chronic exposure will lead to other health effects especially COPD (Chronic Obstructive Pulmonary Disease). The objective of this study is to determine the exposure of welding fumes (Cd, Fe, Pb and Zn) towards respiratory health including lung function test (FEV1, FVC, FEV1/FVC, PEFR) of workers in Lumut shipyard, Perak. This research study the relationship between exposures of welding fumes towards lung function test among workers in Lumut shipyard, Perak. Lung function test was measured by spirometry among 30 welders and 31 non-welders. The concentration welding fume exposure was measured using OSHA ID-121 method. Sociodemographic data, respiratory symptoms and smoking habit data was analyzed based on the ATS 1987 questionnaire. The mean concentration for Pb in welding fumes was 2.752 mg m-3 which is above 0.5 mg m-3 PEL-TWA. The FEV1 and FVC readings showed significant different between welders and non-welders (p = 0.001). Cough and phlegm symptoms showed significant different between welders and non-welders (p = 0.001). Welders had higher prevalence in smoking habit than the non-welders. Chest illnesses symptom showed an association with the smoking habit (p = 0.01). There is relationship between welding fumes exposure on lung function test of workers in Lumut shipyard. Pb in welding fumes has high concentration and exceeded PEL-TWA level. The FEV1 and FVC in welders are lower than non-welder due to the fumes exposure. Welders showed higher respiratory symptoms than non-welders. Smoking habit is a contributing factor towards respiratory problem.


Site-directed serology with synthetic peptides representing the large glycoprotein G of respiratory syncytial virus.
A set of 23 nested 15-amino-acid-long peptides with overlaps of 5 amino acids, representing the complete extramembranous part of the large glycoprotein G of respiratory syncytial (RS) virus, was analyzed in ELISA against different sera containing virus-specific antibodies. Seven of the peptides reacted with rabbit hyperimmune sera against purified virions. In contrast, only one of these seven peptides reacted with murine monoclonal antibodies specific for G. In connection with RS virus infections in humans, increase of antibody titers against three peptides was found in about one-third of the cases. These three peptides were included among those identified by both murine and rabbit antibodies. The present findings may open possibilities for site-directed clinical serology in the case of RS virus infections.


Polyclonal human antibodies reduce bacterial attachment to soft contact lens and corneal cell surfaces.
Bacterial keratitis due to Pseudomonas aeruginosa is a potentially serious complication of extended-wear contact lens use. Adhesion of P. aeruginosa to soft contact lens materials or corneal endothelial cells in the presence of pooled human immunoglobulins and/or neutrophils in artificial tear fluid was studied in vitro as a potential method to treat contact lens-associated infection. Soft hydrophilic contact lens materials equilibrated in sterile saline were soaked in artificial tear fluid for 18 h prior to use. P. aeruginosa IFO 3455 was added to groups of lenses or confluent cultured bovine corneal endothelial cells with varying amounts of human polyclonal immunoglobulin (IgG) and human blood neutrophils or serum albumin as a control. After 2 or 4 h incubation, adherent viable bacteria on lenses were quantified. Fluorescence microscopy was used to assess bacterial adherence to bovine corneal endothelial cells in the presence and absence of IgG and neutrophils. Various concentrations of albumin had no effect on adhesion. Human immunoglobulin solutions (25 mg/ml) reduced P. aeruginosa adhesion by nearly 1 log and 2 logs after 2 and 4 h incubations, respectively. Neutrophils in combination with 25 mg/ml IgG reduced bacterial adhesion approximately 1 log over reduction in adhesion by neutrophils alone. Diluted human IgG (10 mg/ml) did not significantly decrease bacterial adhesion after 2 or 4 h, but did reduce adhesion in combination with human neutrophils at both time points. Similar reductions in amounts of fluorescently labeled bacteria adhered to cultured monolayers of corneal endothelial cells under these conditions were qualitatively observed.


Pharmacokinetic profile of recombinant human (rh) inhibin A and activin A in the immature rat. I. Serum profile of rh-inhibin A and rh-activin A in the immature female rat.
The serum pharmacokinetics of recombinant human inhibin A (rh-inhibin A) and rh-activin A were examined in immature female Sprague Dawley-derived rats after iv and sc injection of the drugs. After iv administration of rh-inhibin A (120 micrograms/kg), the serum concentrations were described by a biexponential equation. The weight-normalized clearance was 21.3 ml/min.kg, and the initial (t1/2 alpha) and terminal (t1/2 beta) half-lives were 2.9 min and 37.9 min, respectively. Subcutaneous administration of 120 micrograms/kg rh-inhibin A resulted in a peak serum concentration of 10.6 ng/ml at 30.8 min after injection. Approximately 24% of the sc administered material was absorbed. Serum concentrations of rh-activin A also declined biexponentially after iv injection of the drug (120 micrograms/kg). The clearance of rh-activin A was 5.1 ml/min.kg, the t1/2 alpha was 6.1 min, and the t1/2 beta was 46.3 min. The peak serum concentration of rh-activin A (104.7 ng/ml) was achieved 24.7 min after sc delivery of the drug. The bioavailability of the sc dose was 38%. Iodinated rh-inhibin A and rh-activin A were used to examine the serum forms and metabolites of the drugs. [125I]rh-inhibin A and [125I]rh-activin A associated with two serum-binding proteins. Within 2 min of iv injection, the labeled hormones bound follistatin and alpha-2-macroglobulin. Even though rh-inhibin A and rh-activin A are structurally similar and appear to bind to the same serum proteins, their disposition in the immature rat differ.


Basic principles and ecological consequences of changing water regimes on nitrogen cycling in fluvial systems.
Understanding the environmental consequences of changing water regimes is a daunting challenge for both resource managers and ecologists. Balancing human demands for fresh water with the needs of the environment for water in appropriate amounts and at the appropriate times are shaping the ways by which this natural resource will be used in the future. Based on past decisions that have rendered many freshwater resources unsuitable for use, we argue that river systems have a fundamental need for appropriate amounts and timing of water to maintain their biophysical integrity. Biophysical integrity is fundamental for the formulation of future sustainable management strategies. This article addresses three basic ecological principles driving the biogeochemical cycle of nitrogen in river systems. These are (1) how the mode of nitrogen delivery affects river ecosystem functioning, (2) how increasing contact between water and soil or sediment increases nitrogen retention and processing, and (3) the role of floods and droughts as important natural events that strongly influence pathways of nitrogen cycling in fluvial systems. New challenges related to the cumulative impact of water regime change, the scale of appraisal of these impacts, and the determination of the impacts due to natural and human changes are discussed. It is suggested that cost of long-term and long-distance cumulative impacts of hydrological changes should be evaluated against short-term economic benefits to determine the real environmental costs.


Deposition and resuspension of selected aerosols particles on electrically charged filter materials for respiratory protective devices.
The primary aim of the study was to analyse the non-steady state of filtration for selected electrostatic filter materials designed for use in respiratory protective devices. The obtained results showed that the filtration process in electrostatic filters was dependent in the main on the following factors: type of the filter material, electrostatic field strength of the material, and the charge of the aerosol. To a lesser degree the filtration process depended on the sign of the charge and the relative humidity of the air. A significant correlation was found between the increase in the penetration and the decrease in breathing resistance while the filter was being loaded. The effect of resuspension (tearing off and re-deposition of dust agglomerates inside the filter) on the filtration process very significant. It was also observed that under certain conditions electrostatic filter materials lost their protection properties.


The Effect of Decreased Audibility on MMSE Performance: A Measure Commonly Used for Diagnosing Dementia.
Hearing loss and dementia are both prevalent in late adulthood. The most common test used to determine cognitive status in late adulthood, the Mini-Mental State Examination (MMSE), is presented face to face, usually in the context of the physician's office in the presence of background noise. Despite the problems of hearing loss and cognitive problems in late life, there is an absence of evidence linking hearing-related deficits to performance on the MMSE and dementia diagnoses. This study examined the effect of decreased audibility on performance on the MMSE. A between-subjects design was implemented. Participants were randomly assigned to one of five degrees of simulated hearing loss conditions and were blinded to condition assignment. One hundred and twenty-five young normal-hearing participants were randomized into five conditions of varying degrees of simulated hearing loss. Performance on the MMSE was scored and cognitive status was categorized based on the scores. Analysis of variance with conditions as a between-subjects factor was conducted with post hoc multiple comparisons to determine the effect of audibility on performance. Reduced audibility significantly affected performance on the MMSE in a sample of young adults, resulting in greater apparent cognitive deficits as audibility decreased. Apparent cognitive deficits based on MMSE scores obtained in test conditions in which audibility is reduced could result in incorrectly identified cognitive loss if clinicians are not alert to hearing loss when patients are evaluated. Furthermore, health care providers should be cautious when using family report of cognitive impairment to diagnose dementia without accounting for hearing loss because the impression of family members may be based on misinterpretation of the effects of hearing loss.


Acute tumor lysis syndrome in patients with high-grade non-Hodgkin's lymphoma.
To identify patients with lymphoma at risk for tumor lysis after chemotherapy. The case records of 102 patients receiving combination chemotherapy for non-Hodgkin's lymphoma (intermediate to high-grade histology) were reviewed. Patients were considered to have "laboratory tumor lysis" if two of the following metabolic changes occurred within 4 days of treatment: a 25% increase in the serum phosphate, potassium, uric acid, or urea nitrogen concentrations, or a 25% decline in the serum calcium concentration. "Clinical tumor lysis" was defined as laboratory tumor lysis plus one of the following: a serum potassium level greater than 6 mmol/L, a creatinine level greater than 221 mumol/L, or a calcium level less than 1.5 mmol/L, the development of a life-threatening arrhythmia, or sudden death. Laboratory tumor lysis occurred in 42% of patients and clinical tumor lysis in 6%. There was no statistical difference in the frequency of either tumor lysis syndrome among lymphoma subgroups. Clinical tumor lysis occurred more frequently in patients with pretreatment renal insufficiency (serum creatinine level greater than 132 mumol/L) than in patients with normal renal function (36% versus 2%; p = 0.01). The development of azotemia correlated with high pretreatment serum lactate dehydrogenase concentrations (p < 0.01; r2 = 0.11). Clinically significant tumor lysis is a rare occurrence in patients with lymphoma when they are receiving allopurinol. However, tumor lysis can occur in patients with all types of moderate to high-grade non-Hodgkin's lymphoma. Patients with a high serum lactate dehydrogenase level or renal insufficiency are at increased risk for metabolic complications after chemotherapy and should be closely monitored.


Desaturation of Oleic and Linoleic Acids by Leaves of Dark- and Light-grown Maize Seedlings.
Oleate and linoleate desaturation in leaves of maize seedlings was largely independent of previous light treatment of the seedlings; there was no evidence of light-induced desaturase activities. These results are in sharp contrast to those observed with developing cucumber cotyledons in which pronounced increase in desaturation occurs after exposure of tissue to light. The rates of desaturation of oleate were about four times those of linoleate in both etiolated and 16-hour greened maize leaves. In both etiolated and greened tissues, about two-thirds of the label from oleate was esterified after 4 hours, half of which was in phosphatidylcholine. Phosphatidylcholine and diglyceride contained large proportions of [(14)C]linoleate formed from [(14)C]oleate but not [(14)C]linolenate. In monogalactolipid, about two-thirds of the labeled fatty acids were linolenate. In vivo desaturase activity was present in tissue of widely different levels of differentiation and chlorophyll content obtained from light-grown maize seedlings.


An Appraisal of the Prevalence and Attributes of Traumatic Dental Injuries in the Permanent Anterior Teeth among 7-14-Year-Old School Children of North East Delhi.
The aim of this study was to assess the prevalence, associated risk factors, characteristics, and pattern of traumatic dental injuries (TDIs) in the permanent anterior teeth among school children of North East Delhi area. A cross-sectional study was done in 3000 school-going children aged 7-14 years. A detailed case history and clinical examination were performed on the entire sample population. TDIs were recorded according to Andreasen's epidemiological classification of TDIs including World Health Organization codes. For finding the independent association of the significant variables with outcome, multivariable logistic regression analysis was used. A prevalence of 10.7% was observed in the sample being studied. Dental trauma was significantly (P < 0.05) associated with male gender, and high statistical significance (P < 0.001) was noted with age, participation in sports, lip seal, and overjet. Fall of the child while playing by himself/herself was the most common cause; afternoon and schools were the most common time and place of occurrence of TDIs, respectively. Single tooth enamel fractures in the left maxillary central incisors were most commonly seen. Adhesive restorations were the most frequent form of treatment required. Organizing studies addressing the prevention and treatment needs of TDIs and educational programs aimed toward parents and school teachers are of paramount importance. Furthermore, recognizing the tremendous treatment negligence is extremely critical to adequately analyze indifference of the people toward dental trauma and its consequences.


Universality of jamming criticality in overdamped shear-driven frictionless disks.
We investigate the criticality of the jamming transition for overdamped shear-driven frictionless disks in two dimensions for two different models of energy dissipation: (i) Durian's bubble model with dissipation proportional to the velocity difference of particles in contact, and (ii) Durian's "mean-field" approximation to (i), with dissipation due to the velocity difference between the particle and the average uniform shear flow velocity. By considering the finite-size behavior of pressure, the pressure analog of viscosity, and the macroscopic friction σ/p, we argue that these two models share the same critical behavior.


[Value of a scapular flap in the treatment of axillary hidradenitis. Apropos of a clinical case].
A severe case of axillary hidradenitis suppurativa, treated bilaterally by large excision followed by reconstruction with a pedicled scapular flap is presented. This reliable and thin fasciocutaneous flap provides good cover of large axillary defects with minimal donor site consequences. Its advantage is discussed versus the other surgical procedures used in this pathology for axillary reconstruction.


Behavior of Smooth Muscle Cells under Hypoxic Conditions: Possible Implications on the Varicose Vein Endothelium.
Varicose veins are a disease with high incidence and prevalence. In the venous wall, the smooth muscle cells (SMCs) act in the vascular homeostasis that secretes multiple substances in response to stimuli. Any alteration of these cells can modify the function and structure of the other venous layers such as the endothelium, resulting in increases in endothelial permeability and release of substances. Therefore, knowing the cellular and molecular mechanisms of varicose veins is imperative. The aims of this study are to understand how SMCs of patients with varicose veins subjected to saphenectomy of the great saphenous vein react under hypoxic cell conditions and to determine the role of vascular endothelial growth factor (VEGF) in this process. We obtained SMCs from human saphenous vein segments from patients with varicose veins (n=10) and from organ donors (n=6) undergoing surgery. Once expanded, the cells were subjected to hypoxic conditions in specific chambers, and expansion was examined through analyzing morphology and the expression of α-actin. Further gene expression studies of HIF-1α, EGLN3, VEGF, TGF-β1, eNOS, and Tie-2 were performed using RT-qPCR. This study reveals the reaction of venous cells to sustained hypoxia. As significant differential gene expression was observed, we were able to determine how venous cells are sensitive to hypoxia. We hypothesize that venous insufficiency leads to cellular hypoxia with homeostatic imbalance. VEGF plays a differential role that can be related to the cellular quiescence markers in varicose veins, which are possible therapeutic targets. Our results show how SMCs are sensitive to hypoxia with a different gene expression. Therefore, we can assume that the condition of venous insufficiency leads to a situation of sustained cellular hypoxia. This situation may explain the cellular response that occurs in the venous wall as a compensatory mechanism.


Study of endoscopic staple formation by specimen radiography on pulmonary wedges.
The advent in video-assisted thoracic surgery has rendered us to rely more and more on mechanical devices. We prospectively studied staple formation on resected lung specimen by radiography and attempted to correlate this with the clinical outcome. From February 1994 to January 1995, 36 consecutive pulmonary wedges (23 apical bullae, 12 pulmonary metastases, 1 tuberculoma) from 31 patients who had undergone resection by endoscopic staple-cutter (Endo GIA30, USSC) were examined by two-plane radiography for staple alignment and closure. Imperfect staple formation was found in 21 (58%) of resected specimens. The median size of the resected bullae is 4.2 mL (range, 2.0 to 58.8 mL) compared with 36 mL (range, 1.2 to 222.8 mL) in the resected metastases and tuberculoma specimen. Despite detecting more imperfect staples in the metastases group (77% vs 57%), there was little difference in the two groups with respect to postoperative chest drainage duration (median, 3 vs 2 days) or hospital stay (median, 2 vs 2 days). We conclude that the currently available endoscopic staplers are by no means perfect, especially for resection of larger specimens, even though this may not be apparent clinically. A continuous search for improvement in endoscopic staplers designed specifically for lung resection is needed.


Regional cerebral blood flow change in a case of Alzheimer's disease with musical hallucinations.
We examined alteration of regional cerebral blood flow (rCBF) in a case of Alzheimer's disease (AD) patient with musical hallucination. To detect regions related to musical hallucination, single-photon emission computed tomography (SPECT) imaging of the patient and nine sex, age, and cognitive function-matched AD patients without delusions and hallucinations were compared using statistical parametric mapping 99 (SPM99). In comparison with controls, the patient had increased rCBF in left temporal regions and left angular gyrus. This profile could be relevant to the neuroanatomical basis of musical hallucinations.


Sexual function in a woman with congenital bladder exstrophy and multiple pelvic reconstructive surgeries: a case report.
Bladder exstrophy is a rare congenital anomaly isolated to the fetal genitourinary tract. In our patient, this defect necessitated removal of her bladder in her childhood and a distal neovaginoplasty in adolescence. Despite these surgeries, as well as several procedures for pelvic organ prolapse, the patient reports excellent sexual function and ability to achieve vaginal orgasms. (i) To report on the sexual function of a woman without a bladder or urethra who has undergone multiple pelvic reconstructive surgeries; and (ii) to correlate her self-reported erotic areas with magnetic resonance imaging (MRI) assessment. The patient completed a detailed sexual history, the Female Sexual Function Index (FSFI), the Female Sexual Distress Scale (FSDS), the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12), and the Health Survey Short Form (SF-12). Photodocumentation of her erotic tissue was correlated with a pelvic MRI with contrast. The patient reports ability to achieve vaginal orgasms 100% of the time. Her FSFI score was 29.4/36 with maximum scores noted in arousal, lubrication, orgasm and satisfaction. Her FSDS score was 7/48, which implies no sexually related distress. Her PISQ-12 score was 10/48, demonstrating a small impact on her sexual function related to her pelvic organ prolapse. Her SF-12 scores were 36.6 and 57.9. Photography and mapping of her erotic areas illustrated the superficial and anterior locations of the vaginal opening to be the sites of orgasm. MRI correlated these exact locations with clitoral tissue. Intact sexual function is possible in patients after reconstructive surgery for congenital bladder exstrophy. Due to the superficial location of her clitoris and separation of the pubic rami associated with this anatomic variant, sexual function may be enhanced.


Decision analysis in aerospace medicine: costs and benefits of a hyperbaric facility in space.
Assembly and maintenance of the International Space Station (ISS) requires an unprecedented number of spacewalks, which expose astronauts to the risk of decompression sickness (DCS). We illustrate the use of decision analysis to compare a hyperbaric oxygen (HBO) chamber to currently available therapy for DCS treatment on the ISS. A decision-analytic model that simulates events over the lifespan of the ISS was constructed. Inputs to the model for probabilities, costs, and measures of morbidity and mortality were derived from a variety of sources, including a systematic literature review and an iterative consultation process with personnel at the Canadian Space Agency and the National Aeronautics and Space Administration (NASA). The decision model was analyzed using the methods of Monte-Carlo simulation and expected value calculation. Main outcome measures included the present value of costs and quality adjusted life years (QALYs), and the cumulative probability of mission-related events over the life cycle of the ISS. Sensitivity analysis was performed. The HBO chamber strategy is associated with a mean cost of -12.5 million dollarsw (a net cost saving of 12.5 million dollars) with a 95% CI (-112.8 million dollars, 51.3 million dollars). An HBO chamber reduces the likelihood of a premature shuttle return and a premature Soyuz return by 8% and 3%, respectively. The result is sensitive to the lifespan of the ISS. At a 50 million dollars cost, an HBO chamber is likely, though not certain, to result in cost savings. Decision analysis is a useful tool for use in priority setting in aerospace medicine.


Microwave-induced lethal heat stress: effects of phentolamine, prazosin and metoprolol.
Previous studies have shown that adrenergic antagonists can alter physiological responses to microwave-induced heating. In the present experiments, 33 ketamine-anesthetized Sprague-Dawley rats were exposed to 2450-MHz microwaves at an average power density of 60 mW/sq cm (whole-body average specific absorption rate of approximately 14 W/kg) until death occurred. The effects of intraarterial injections of the nonselective alpha-adrenoceptor antagonist phentolamine (10 mg/kg body weight), the alpha 1-adrenoceptor antagonist prazosin (5 mg/kg), and the beta 1-adrenoceptor antagonist metoprolol (2 mg/kg) on physiological responses (including changes in body temperature, heart rate, blood pressure, and respiratory rate) were examined. A group of saline-injected animals was included for comparison. There were no significant differences in lethal temperatures, survival times, or rates of temperature change among the different groups. In all groups, heart rate increased continuously during exposure; mean arterial blood pressure increased until colonic temperature reached 41-41.5 degrees C, and then decreased. These heart rate and blood pressure changes were similar to those that occur during environmental heat stress. Despite differences in absolute values of heart rate and mean arterial blood pressure among groups, there were no significant differences in changes from baseline levels among groups. From these results, taken together with previous findings in our laboratory, it may be hypothesized that selective alpha 1 blockade (without concurrent alpha 2 blockade) and beta 2 blockade (with or without concurrent beta 1 blockade) are effective in altering physiological responses to microwave exposure.


Adeno-associated virus Rep78 binds to E2-responsive element 1 of bovine papillomavirus type 1.
Adeno-associated virus type-2 (AAV-2) is a helper-dependent parvovirus that has been implicated in the inhibition of replication and oncogenic transformation of bovine papillomavirus type-1 (BPV-1) and other transforming DNA viruses. Previous studies have suggested that the Rep78 protein of AAV-2 is a key player mediating this effect. In this report we have analyzed the effect of AAV-2 Rep78 protein on the regulation of gene expression of a reporter gene under the control of the long control region (LCR) of BPV-1. Our results show that Rep78 is capable of down-regulating the promoter activity of the LCR in vivo in tissue culture cells. Inhibition of LCR activity in vivo suggested the need for Rep78 to bind to a region of the LCR promoter spanning the E2-responsive elements of BPV-1. This observation was further confirmed in vitro with gel shift assays showing specific binding of Rep78 to DNA oligonucleotides containing E2-responsive element 1 (E2RE1) sequences of BPV-1 LCR. Our results expand the understanding of the mechanism of trans-regulation mediated by Rep78 and involving this protein and DNA sequences with complex secondary structure.


External exposure model in the RESRAD computer code.
An external exposure model has been developed for the RESRAD computer code that provides flexibility in modeling soil contamination configurations for calculating external doses to exposed individuals. This model is based on the dose coefficients given in the U.S. Environmental Protection Agency's Federal Guidance Report No. 12 (FGR-12) and the point kernel method. It extends the applicability of FGR-12 data to include the effects of different source geometries, such as cover thickness, source thickness, source area, and shape of contaminated area of a specific site. A depth factor function was developed to express the dependence of the dose on the source thickness. A cover-and-depth factor function, derived from this depth factor function, takes into account the dependence of dose on the thickness of the source region and the thickness of the cover above the source region. To further extend the model for realistic geometries, area and shape factors were derived that depend not only on the lateral extent of the contamination, but also on source thickness, cover thickness, and radionuclides present. Results obtained with the model generally compare well with those from the Monte Carlo N-Particle transport code.


Respiratory hydrogen use by Salmonella enterica serovar Typhimurium is essential for virulence.
Based on available annotated gene sequence information, the enteric pathogen salmonella, like other enteric bacteria, contains three putative membrane-associated H2-using hydrogenase enzymes. These enzymes split molecular H2, releasing low-potential electrons that are used to reduce quinone or heme-containing components of the respiratory chain. Here we show that each of the three distinct membrane-associated hydrogenases of Salmonella enterica serovar Typhimurium is coupled to a respiratory pathway that uses oxygen as the terminal electron acceptor. Cells grown in a blood-based medium expressed four times the amount of hydrogenase (H2 oxidation) activity that cells grown on Luria Bertani medium did. Cells suspended in phosphate-buffered saline consumed 2 mol of H2 per mol of O2 used in the H2-O2 respiratory pathway, and the activity was inhibited by the respiration inhibitor cyanide. Molecular hydrogen levels averaging over 40 microM were measured in organs (i.e., livers and spleens) of live mice, and levels within the intestinal tract (the presumed origin of the gas) were four times greater than this. The half-saturation affinity of S. enterica serovar Typhimurium for H2 is only 2.1 microM, so it is expected that H2-utilizing hydrogenase enzymes are saturated with the reducing substrate in vivo. All three hydrogenase enzymes contribute to the virulence of the bacterium in a typhoid fever-mouse model, based on results from strains with mutations in each of the three hydrogenase genes. The introduced mutations are nonpolar, and growth of the mutant strains was like that of the parent strain. The combined removal of all three hydrogenases resulted in a strain that is avirulent and (in contrast to the parent strain) one that is unable to invade liver or spleen tissue. The introduction of one of the hydrogenase genes into the triple mutant strain on a low-copy-number plasmid resulted in a strain that was able to both oxidize H2 and cause morbidity in mice within 11 days of inoculation; therefore, the avirulent phenotype of the triple mutant is not due to an unknown spurious mutation. We conclude that H2 utilization in a respiratory fashion is required for energy production to permit salmonella growth and subsequent virulence during infection.


Conspecific exploration in the T-maze: abnormalities in S100 beta transgenic mice.
S100 beta, a calcium binding brain protein expressed by astrocytes, has been shown to be involved in higher neural processes, including hippocampal-dependent behavioral traits and hippocampal neuronal long-term potentiation (LTP) and depression (LTD), neurophysiological phenomena that may be involved in exploring, learning and remembering novel stimuli. In the present study, the exploratory behavior of previously generated transgenic mice overexpressing the protein are compared to that of normal control mice of identical genetic background and age in a T-maze. The test mice encountered a normal control and an S100 beta transgenic mouse (the choice mice) in the goal arms of the T-maze. We show that no test mice exhibited any preference for either genotype of choice mouse. However, there was a significant difference in the spatial and temporal exploratory pattern between control and S100 beta test mice, demonstrating that S100 beta overexpression significantly altered the behavior of the transgenic mice. We suggest that one probable factor underlying the abnormalities observed is impaired short-term memory.


Reactivity of HMB-45 monoclonal antibody with sweat-gland tumours of the skin.
HMB-45, a monoclonal antibody claimed to be specific for malignant melanoma, has been observed to react with normal eccrine sweat glands and occasionally with normal mammary and bronchial epithelium. In this study we show that HMB-45 also decorates cells in approximately 15% of various sweatgland tumours of the skin. This finding, along with the reported reactivity on mammary carcinomas further outlines the lack of absolute specificity of HMB-45 for cells of the melanocytic lineage.


Epstein-barr virus can infect B-chronic lymphocytic leukemia cells but it does not orchestrate the cell cycle regulatory proteins.
To understand the mechanism for the refractoriness of B-chronic lymphocytic leukemia (B-CLL) cells for Epstein-Barr virus (EBV)-induced immortalization. Cultures were initiated with EBV-infected tonsillar B and B-CLL cells. Expression of EBNA-2 and some of the key players regulating G1/S phase transition such as c-myc expression, phosphorylation of Rb protein, expression of G1 cyclins, and the cyclin-dependent kinase inhibitor p27 were followed. In line with earlier studies, EBV infection induced c-myc expression, pRb phosphorylation, D2 and D3 expression, and disappearance of p27 in normal B cells. In contrast, EBV-infected B-CLL cells remained resting and they did not express c-myc; cyclin D2, ppRb and cyclin D3 were seen only in occasional cells. Importantly, p27 expression was maintained. In B-CLL cells, the expression of the EBV-encoded nuclear proteins EBNAs is not followed by entrance to the cell cycle. Thus, the difference in the interaction of EBV-normal B cells and EBV-B-CLL cells is already apparent early after infection.


Effects of urinary bladder retroflexion and surgical technique on postoperative complication rates and long-term outcome in dogs with perineal hernia: 41 cases (2002-2009).
To evaluate the effects of urinary bladder retroflexion (UBR) and surgical technique on postoperative complication rates and long-term outcome in dogs with perineal hernia. Retrospective case series. 41 client-owned dogs with perineal hernia that underwent surgery between November 2002 and November 2009. Medical records were reviewed for information on dog signalment, history, physical examination findings, ultrasonographic findings, surgical techniques, intraoperative complications, duration of hospital stay, postoperative complications, and long-term outcome. 31 dogs had no UBR, and 10 dogs had UBR. Internal obturator muscle transposition (IOMT) was performed in 20 dogs, and a cystopexy or colopexy was performed before the IOMT (LapIOMT) in 21. Postoperative complications included tenesmus (n = 8) and urinary incontinence (1). Rates of postoperative complications were not significantly different between the no-UBR and UBR groups or between the IOMT and LapIOMT groups. Thirty-two dogs were free of clinical signs at the time of the study. The median disease-free interval did not differ significantly between dogs in the no-UBR and UBR groups, but it was significantly lower in the LapIOMT group than in the IOMT group. None of the 7 dogs with UBR that were treated without cystopexy developed recurrence of UBR. UBR was not associated with an increased rate of postoperative complications relative to no UBR and had no effect on the long-term outcome in dogs with perineal hernia. The use of IOMT alone may be recommended for clinical use because LapIOMT offered no clear advantage.


Optimal spliced alignments of short sequence reads.
Next generation sequencing technologies open exciting new possibilities for genome and transcriptome sequencing. While reads produced by these technologies are relatively short and error prone compared to the Sanger method their throughput is several magnitudes higher. To utilize such reads for transcriptome sequencing and gene structure identification, one needs to be able to accurately align the sequence reads over intron boundaries. This represents a significant challenge given their short length and inherent high error rate. We present a novel approach, called QPALMA, for computing accurate spliced alignments which takes advantage of the read's quality information as well as computational splice site predictions. Our method uses a training set of spliced reads with quality information and known alignments. It uses a large margin approach similar to support vector machines to estimate its parameters to maximize alignment accuracy. In computational experiments, we illustrate that the quality information as well as the splice site predictions help to improve the alignment quality. Finally, to facilitate mapping of massive amounts of sequencing data typically generated by the new technologies, we have combined our method with a fast mapping pipeline based on enhanced suffix arrays. Our algorithms were optimized and tested using reads produced with the Illumina Genome Analyzer for the model plant Arabidopsis thaliana. Datasets for training and evaluation, additional results and a stand-alone alignment tool implemented in C++ and python are available at http://www.fml.mpg.de/raetsch/projects/qpalma.


Familial outbreak of psittacosis as the first Chlamydia psittaci infection reported from Turkey.
Psittacosis, also known as parrot disease, parrot fever and ornithosis, can be transmitted to humans by inhaling dried excreta of infected birds like canaries, parakeets, parrots, pigeons and turkeys. Unless it is specifically thought of and investigated, the diagnosis of psittacosis can easily be missed and without identifying the exact etiology, the disease is usually treated as atypical pneumonia. We diagnosed psittacosis in a mother and her son with Friedreich ataxia, who took care of two parrots in their house. In addition to pneumonia, central nervous system and liver involvement were also identified in those patients. Since there was no any other case of psittacosis reported from Turkey, we thought to be important to report this mother and her son as first cases from Turkey.


Spectroscopic characterization of Be(2) (+) X (2)Sigma(u) (+) and the ionization energy of Be(2).
Rotationally resolved spectra for Be(2) (+) have been recorded using the pulsed-field ionization zero kinetic energy photoelectron technique. Vibrational levels in the range v(+)=0-6 were observed. The rotational selection rules confirmed that the ground state is (2)Sigma(u) (+), resulting from the removal of an electron from the sigma(u) antibonding orbital of Be(2). The bond energy and equilibrium distance for Be(2) (+) were found to be D(e) (+)=16 438(5) cm(-1) and R(e) (+)=2.211(8) A. The ionization energy for Be(2) [59 824(2) cm(-1)] was also refined by these measurements. Comparisons with high-level theoretical results indicate that the bonding in Be(2) (+) is adequately described by multi reference singles and doubles configuration interaction (MRDCI) calculations that employ moderate to large scale basis sets.


Lateral genetic transfer: open issues.
Lateral genetic transfer (LGT) is an important adaptive force in evolution, contributing to metabolic, physiological and ecological innovation in most prokaryotes and some eukaryotes. Genomic sequences and other data have begun to illuminate the processes, mechanisms, quantitative extent and impact of LGT in diverse organisms, populations, taxa and environments; deep questions are being posed, and the provisional answers sometimes challenge existing paradigms. At the same time, there is an enhanced appreciation of the imperfections, biases and blind spots in the data and in analytical approaches. Here we identify and consider significant open questions concerning the role of LGT in genome evolution.


An incremental response to high-dose therapy in multiple myeloma.
Results of conventional chemotherapy for multiple myeloma are disappointing. High-dose chemoradiotherapy with auto-transplantation is increasingly reported and some results are encouraging. We report the results of peripheral blood stem cell transplantation (PBSCT) for multiple myeloma at a single institution over a 6-year period. Forty patients, including 18 de novo patients, received debulking chemotherapy consisting of vincristine, adriamycin, and dexamethasone or methyl-prednisolone followed by stem cell mobilization with high-dose cyclophosphamide. Twenty-nine patients received PBSCT following high-dose chemoradiotherapy. Following PBSCT 92% of evaluable patients obtained at least a partial remission and 29% reached complete remission. Objective treatment responses, defined as at least a 50% reduction in serum paraprotein or marrow plasma cells, were observed following each treatment step of debulking chemotherapy, mobilization and PBSCT in 50, 42 and 71% of patients, respectively. The median overall survival from diagnosis in patients transplanted was 50 months and the median overall and progression-free survivals following transplant were 26 and 18 months, respectively. Median follow-up was 28 months. Overall treatment-related mortality was 20% but was significantly lower in de novo vs previously treated patients at 6 and 33% respectively (P = 0.027). De novo patients were more likely to obtain complete remission and had a longer overall survival following transplant but overall survival from diagnosis was similar to previously treated patients. A low serum B2M before mobilization predicted a longer progression-free survival. PBSCT needs to be considered early following diagnosis to maximise treatment response and reduce the high treatment-related mortality seen in heavily pretreated patients. In this treatment program a dose response effect in multiple myeloma was observed possibly suggesting that more intensive therapy than a single transplant may effect greater disease response.


Prolonged Withdrawal From Escalated Oxycodone Is Associated With Increased Expression of Glutamate Receptors in the Rat Hippocampus.
People suffering from opioid use disorder (OUD) exhibit cognitive dysfunctions. Here, we investigated potential changes in the expression of glutamate receptors in rat hippocampi at 2 h and 31 days after the last session of oxycodone self-administration (SA). RNA extracted from the hippocampus was used in quantitative polymerase chain reaction analyses. Rats, given long-access (9 h per day) to oxycodone (LgA), took significantly more drug than rats exposed to short-access (3 h per day) (ShA). In addition, LgA rats could be further divided into higher oxycodone taking (LgA-H) or lower oxycodone taking (LgA-L) groups, based on a cut-off of 50 infusions per day. LgA rats, but not ShA, rats exhibited incubation of oxycodone craving. In addition, LgA rats showed increased mRNA expression of GluA1-3 and GluN2a-c subunits as well as Grm3, Grm5, Grm6, and Grm8 subtypes of glutamate receptors after 31 days but not after 2 h of stopping the SA experiment. Changes in GluA1-3, Grm6, and Grm8 mRNA levels also correlated with increased lever pressing (incubation) after long periods of withdrawal from oxycodone. More studies are needed to elucidate the molecular mechanisms involved in altering the expression of these receptors during withdrawal from oxycodone and/or incubation of drug seeking.


High prevalence of asymptomatic deep vein thrombosis on admission in a medical unit among elderly patients.
The prevention of venous thromboembolism in medical patients remains questioned. All consecutive outpatients admitted in our medical unit were considered for inclusion in this study which aimed to estimate the prevalence of asymptomatic venous thrombosis on admission and the incidence during hospital stay. Exclusion criteria were: age <18 years, suspicion of venous thromboembolism, stay <4 days, ongoing anticoagulant therapy. Venous compression ultrasonography of the lower limbs was performed within 48 h. 234 patients were included. The prevalence of asymptomatic deep vein thrombosis on admission and the incidence during hospital follow-up were respectively 5.5% (95% confidence interval, 3.1 to 9.5%) and 2.6 per 1,000 person-days (95% confidence interval, 0.0 to 5.2). The prevalence and the incidence reached respectively 17.8% (95% confidence interval, 8.5 to 32.6%) and 6.0 per 1,000 person-days (95% confidence interval, 0.0 to 12.7) among patients over 80 years. A high prevalence of asymptomatic deep vein thrombosis on admission was suggested particularly among elderly medical patients.


Star Shaped Long Chain Branched Poly (lactic acid) Prepared by Melt Transesterification with Trimethylolpropane Triacrylate and Nano-ZnO.
Long chain branched poly (lactic acid) (LCBPLA) was prepared via transesterification between high molecular weight poly (lactic acid) (PLA) and low molar mass monomer trimethylolpropane triacrylate (TMPTA) during melt blending in the presence of zinc oxide nanoparticles (nano-ZnO) as a transesterification accelerant in a torque rheometer. Compared with the traditional processing methods, this novel way is high-efficiency, environmentally friendly, and gel-free. The results revealed that chain restructuring reactions occurred and TMPTA was grafted onto the PLA backbone. The topological structures of LCBPLA were verified and investigated in detail. It was found that the concentration of the accelerants and the sampling occasion had very important roles in the occurrence of branching structures. When the nano-ZnO dosage was 0.4 phr and PLA was sampled at the time corresponding to the reaction peak in the torque curve, PLA exhibited a star-shaped topological structure with a high branching degree which could obviously affect the melt strength, extrusion foaming performances, and crystallization behaviors. Compared with pristine PLA, LCBPLA showed a higher melt strength, smaller cell diameter, and slower crystallization speed owing to the synergistic effects of nano-ZnO and the long chain branches introduced by the transesterification reaction in the system. However, severe degradation of the LCBPLAs would take place under a mixing time that was too long and lots of short linear chains generated due to the excessive transesterification reaction, with a sharp decline in melt strength.


Pituitary incidentalomas in paediatric population: Incidence and characteristics.
To determine the incidence of pituitary incidentalomas in the paediatric population and among its different age subgroups as well as to identify the characteristics of these lesions. Additionally, we aim to give a perspective on the management and follow-up of these patients. We retrospectively studied MRI of children aged 18 years or below who underwent MRI with sellar region within their field of view between January 2010 and December 2018. Pituitary lesions were considered incidental according to the definition by the Endocrine Society. We reported the size, location and signal characteristics of each lesion. Medical charts of the subjects were reviewed for age, sex, the MRI indication and the hormonal assays levels. We identified 40 pituitary lesions of which 31 were incidental lesions. The incidence of pituitary incidentaloma in our cohort was 22 per 1000 patients with female predisposition ( 64.5%) and a mean age of 11 ± 6 years. Rathke's cleft cyst was the most prevalent lesion, accounting for 67.7% followed by cystic pituitary lesions and microadenomas. The most common indications for imaging were growth disturbance (12.9%) followed by headache (9.7%). Abnormal laboratory workup was present in 13% of the subjects. Incidental lesions were more common in the older age groups compared to young children. Incidental pituitary lesions in the paediatric population are relatively infrequent and increases with age. Rathke's cleft cyst is the most common incidentally encountered pituitary lesion followed by cystic pituitary lesions and microadenomas.


Long-Term Progression-Free and Overall Survival in Two Melanoma Patients Treated with Patient-Specific Therapeutic Vaccine Eltrapuldencel-T After Resection of a Solitary Liver Metastasis.
Hepatic metastases from melanoma are usually associated with recurrence and short survival, even in patients with a solitary metastasis. Two patients, one with melanoma of unknown primary and one with ocular melanoma, underwent resection of a solitary liver metastasis followed by treatment with eltrapuldencel-T, a patient-specific therapeutic vaccine consisting of autologous dendritic cells loaded with antigens from irradiated melanoma cells obtained from an autologous tumor cell line. Following surgical resection, the ocular melanoma patient remained progression free for more than 4.5 years and was known to be alive more than 8.5 years later, while the other patient, who previously had experienced lung and small bowel metastases, has remained disease free and is alive more than 12 years later. These two cases illustrate how immunotherapies designed to induce immune responses to tumor-associated antigens (TAA), as opposed to releasing previously existing responses to TAA that have been suppressed, may also enhance long-term disease control and survival.


Role of interferon-gamma against invasion by Toxoplasma gondii in a human monocytic cell line (THP1): involvement of the parasite's secretory phospholipase A2.
We examined the role of IFN gamma in protection against Toxoplasma gondii in the monocytoid cell line THP1. The addition of IFN gamma to cultured infected THP1 cells reduced the number of parasitized cells without altering intracellular multiplication during the first 24 hr. This reduction was potentiated by bacterial lipopolysaccharide (LPS). We also examined the role of an enzyme important for T. gondii cellular invasion, secretory phospholipase-A2 (sPLA2) and its relation with IFN gamma-induced protection. Treatment of cells or parasites with a specific inhibitor of sPLA2 significantly reduced the number of infected cells at 6 hr. The addition of exogenous sPLA2 from Naja naja venom did not interfere with the protective effect of IFN gamma and conferred protection when used alone. PLA2 activity was measured in supernatants of parasites maintained in the presence of IFN gamma, and the results suggested that IFN gamma opposes cell invasion by T. gondii by suppressing parasite production of PLA2.


How White American Children Develop Racial Biases in Emotion Reasoning.
For decades, affective scientists have examined how adults and children reason about others' emotions. Yet, our knowledge is limited regarding how emotion reasoning is impacted by race-that is, how individuals reason about emotions displayed by people of other racial groups. In this review, we examine the developmental origins of racial biases in emotion reasoning, focusing on how White Americans reason about emotions displayed by Black faces/people. We highlight how racial biases in emotion reasoning, which emerge as early as infancy, likely contribute to miscommunications, inaccurate social perceptions, and negative interracial interactions across the lifespan. We conclude by discussing promising interventions to reduce these biases as well as future research directions, highlighting how affective scientists can decenter Whiteness in their research designs. Together, this review highlights how emotion reasoning is a potentially affective component of racial bias among White Americans.


Magnetophoretic Mole-Ratio Method.
The principle of the mole-ratio method utilizing magnetophoretic velocimetry was demonstrated for the first time. The feasibility of the magnetophoretic mole-ratio method was studied for the determination of the stoichiometry of the complexes formed between a hydrophobic phosphate ligand adsorbed in mesoporous hydrophobic silica particles and paramagnetic metal ions of Co(II), Tb(III), and Dy(III) in aqueous solutions. The present method is a nonspectroscopic method and carried out by a simple magnetic device.


Investigating executive functions in youth with OCD and hoarding symptoms.
Executive functions (EF) deficits are hypothesized to be a core contributor to hoarding symptoms. EF have been studied in adult hoarding populations, but studies in youth are lacking. The current study compared multiple EF subdomains between youth with obsessive-compulsive disorder (OCD) and youth with OCD and hoarding symptoms. Forty youth (8-18 years old) with a primary diagnosis of OCD were recruited. Participants were divided by hoarding severity on the Child Saving Inventory (CSI) into either the "hoarding group" (upper 33.3%) or the "low-hoarding group" (lower 66.7%). Groups were compared on EF tasks of cognitive flexibility, decision-making, and inhibitory control. Youth in the hoarding group exhibited significantly higher cognitive flexibility and lowered perseveration than the low-hoarding group. Hoarding and low-hoarding groups did not differ in any other EF subdomain. Hoarding symptoms in youth with OCD were not associated with deficits in EF subdomains; instead, youth who hoard exhibited higher cognitive flexibility compared to youth with low hoarding symptoms.


Photoprotection by plant extracts: a new ecological means to reduce pesticide photodegradation.
A pesticide's reactivity toward light at the leaf surface after crop treatment is rarely considered, although such degradation reactions directly affect the pesticide's effectiveness. To overcome these limitations, the use of plant pigments was proposed as a new class of photoprotecting agent. The photoprotecting properties of seven plant pigments were tested under controlled conditions over herbicide sulcotrione. Grape wine extracts were tested over a panel of pesticides from distinct chemical families. The addition of plant extracts almost systematically reduced the pesticide's photoreactivity. The grape wine extracts improve at least by 38% the half-life of photolysis of almost all of the active ingredients tested, except for the herbicide triclopyr. Fustictree extract increases by 82% the photostability of the herbicide sulcotrione. Plant extracts mainly act as sunscreens; that is, the photostabilization of the active ingredient is due to the competitive energy absorption of UV photon. The use of natural plant extracts is a promising strategy to limit pesticide photodegradation. It is a way to develop sustainable and innovative technology for the plant protection industry, being beneficial from both economic and ecological points of view.


Predicting negative ureteroscopy for stone disease - Minimizing risk and cost.
Urolithiasis is common worldwide, with ureteric stones being a particular burden. Ureteroscopy (URS) is one of the most useful procedures in treating ureteric stones not passed spontaneously; this procedure has a complication risk of 4%. Negative URS, with described rates up to 15%, represents an avoidable patient risk and use of medical resources. To describe rates and identify predictive factors for negative URS and to define strategies which would minimize patient and financial burden from these unnecessary procedures. A retrospective cohort study analyzed patients who underwent URS in our Center to treat ureteric stones over a period of 2 years. Patient age, gender, and comorbidities, as well as laboratory and imaging findings, were analyzed. 262 patients underwent URS for ureteric stones. The female population was 50.8% with a mean age of 56.89 years. A total of 78 (29.8%) URS procedures were negative. Univariate analysis showed a higher prevalence of negative URS in female patients, as well as in primary, smaller, and radiolucent stones. At multivariate analysis, a logistic regression model correctly classified 76% of patients, with smaller stone size and radiolucency being significant predictors of negative URS. Our Center showed a high rate of negative URS, higher than commonly described in the literature. Female patients tend to have an even higher rate, possibly due to unnoticed passage of stones. Patients with small, radiolucent stones showed the highest rates of negative URS.