A straightforward and efficient analytical pipeline for metaproteome characterization.
The massive characterization of host-associated and environmental microbial communities has represented a real breakthrough in the life sciences in the last years. In this context, metaproteomics specifically enables the transition from assessing the genomic potential to actually measuring the functional expression of a microbiome. However, significant research efforts are still required to develop analysis pipelines optimized for metaproteome characterization. This work presents an efficient analytical pipeline for shotgun metaproteomic analysis, combining bead-beating/freeze-thawing for protein extraction, filter-aided sample preparation for cleanup and digestion, and single-run liquid chromatography-tandem mass spectrometry for peptide separation and identification. The overall procedure is more time-effective and less labor-intensive when compared to state-of-the-art metaproteomic techniques. The pipeline was first evaluated using mock microbial mixtures containing different types of bacteria and yeasts, enabling the identification of up to over 15,000 non-redundant peptide sequences per run with a linear dynamic range from 10(4) to 10(8) colony-forming units. The pipeline was then applied to the mouse fecal metaproteome, leading to the overall identification of over 13,000 non-redundant microbial peptides with a false discovery rate of <1%, belonging to over 600 different microbial species and 250 functionally relevant protein families. An extensive mapping of the main microbial metabolic pathways actively functioning in the gut microbiome was also achieved. The analytical pipeline presented here may be successfully used for the in-depth and time-effective characterization of complex microbial communities, such as the gut microbiome, and represents a useful tool for the microbiome research community.


Psychological well-being of Cambodian women in resettlement.
Current literature focuses on immediate needs of refugees as they flee acute crises. However, the search for refuge extends beyond immediate migration. Refugees confront many issues in resettlement. The experience of traumatic pain and multiple losses coupled with the struggle for survival in a foreign community places them at risk for diminished health and psychological well-being. The notion of recovery extends to the period of resettlement. It is imperative that nursing professionals examine assumptive biases that hinder the care and recovery of refugees. This article seeks to heighten professional awareness about issues that confront Cambodian women in resettlement by examining these biases.


Two healing patterns correlate with different adult neural connectivity patterns in regenerating embryonic Xenopus retina.
Nasal and temporal one-third-sized eye fragments, formed by ablation at stage 32-33 of Xenopus laevis embryos, heal and, in about 50% of the cases, survive to make eyes in the postmetamorphic animal which have mappable visuotectal projections. The majority of nasal one-third eyes have duplicate projections whereas the majority of temporal one-third eyes have unduplicated projections. Most nasal one-third eye fragments and a minority of temporal eye fragments heal by the extrusion of cells from the center of the cut edge into the region of the ablation, forming a tongue of cells between the distal cut edges. This healing pattern is correlated with duplicated visuotectal projections. Most temporal one-third fragments and a minority of nasal one-third fragments heal by rounding up; that is, the distal cut edges collapse to meet in the region of the ablation. This healing pattern is correlated with the formation of unduplicated visuotectal projections. During tongue formation, neurons and undifferentiated cells are transferred from the original fragment into the tongue in a disorderly array, but quickly re-form normal retinal order. We propose that the tongue cells retain their original determination to connect to the same tectal positions as the fragment from which they originated, despite their new positions, and that this mosaicism, coupled with cell movement into the tongue, established duplicate visuotectal projections.


The protective effect of glucose, but not 3-O-methyl glucose, against alloxan-induced diabetes depends upon the route of hexose administration.
It is well established that pretreatment with glucose prevents the development of alloxan-induced diabetes in rodents. This was confirmed in the present study, and a protective effect against the development of hyperglycemia, after alloxan administration (75 mg/kg body weight), in male NMRI mice was observed when glucose was injected i.v. 10 or 20 min before alloxan injection. However, when glucose was administered i.p., a protective effect was only observed when glucose was given 20 min before alloxan, despite the fact that the serum glucose concentrations at the time of the alloxan injection were similar in the i.v.- and i.p.-injected animals. Administration of 3-O-methyl glucose by i.v. and i.p. routes protected against the effects of alloxan to the same extent. When alloxan was administered at a lower dose (65 mg/kg body weight) both i.v. and i.p. administration of glucose 10 min before alloxan, protected against the development of hyperglycemia. It is concluded that the route of administration of glucose, but not of 3-O-methyl glucose, affects its protective action against alloxan-induced diabetes. The present findings suggest that an important feature of the glucose mediated protection against alloxan-induced diabetes is the metabolism of glucose within the B-cells, rather than via extracellular effects on the B-cell plasma membrane.


Fully Automated Segmentation of Connective Tissue Compartments for CT-Based Body Composition Analysis: A Deep Learning Approach.
Body composition comprises prognostic information in patients with various malignancies and can be opportunistically determined from routine computed tomography (CT) scans. However, accurate assessment of patients with alterations, for example, due to ascites or anasarca, and accurate identification of intermuscular fat remain challenging. In this study, we aimed to develop a fully automated and highly accurate segmentation tool for connective tissue compartments from abdominal CT scans using the open-source Convolutional Neural Network (CNN) DeepMedic. In this retrospective study, a CNN was developed using data of 1143 consecutive patients undergoing either preinterventional CT for transcatheter aortic valve implantation (TAVI) (82%) or diagnostic CT for liver cirrhosis with portosystemic shunting (PTSS) (18%). All analyses were performed on single-slice images at the L3/L4 level. The data were subdivided into subsets of training (70%), validation (15%), and test data (15%), balanced for TAVI and PTSS patients. To demonstrate the generalizability of the applied method with respect to nonspecific clinical routine data, the model with the highest performance in TAVI and PTSS patients was further tested on 100 randomly selected patients who underwent CT for routine diagnostic purposes at a hospital of maximum care, including critically ill patients. The applicability of the method to native CT examinations was additionally tested on 50 patients. Compared with the ground truth of the test data, the presented method achieved highly accurate segmentation results (subcutaneous adipose tissue [SAT], Dice score [DSC]: 0.98 ± 0.01; visceral adipose tissue [VAT], DSC: 0.96 ± 0.04; skeletal muscles [SM], DSC: 0.95 ± 0.02) and showed excellent generalizability on the routine CT diagnostic patients (SAT, DSC: 0.97 ± 0.04; VAT, DSC: 0.95 ± 0.05; SM, DSC: 0.95 ± 0.04) and also on native CT scans (SAT, DSC: 0.99 ± 0.01; VAT, DSC: 0.97 ± 0.03; SM, DSC: 0.97 ± 0.02). Fully automated determination of body composition based on CT can be performed with excellent results using the open-source CNN DeepMedic. The trained model is made usable for research by a deployable and sharable application.


Expression of stathmin in human uterus and decidualizing endometrial stromal cells.
The cytosolic phosphoprotein stathmin is upregulated at the site of embryo implantation in the rodents. However, stathmin expression in the human uterus has not yet been investigated. The distribution of uterine and placental stathmin was analyzed by immunohistochemistry, while stathmin mRNA expression was detected in endometrial tissues by the reverse transcriptase-PCR. Cultured endometrial stromal cells were used to investigate whether stathmin plays a role in decidualization. Stathmin is expressed specifically in the glandular epithelium and the stromal cells of human endometrial tissue. It is also expressed by cytotrophoblasts and extravillous trophoblasts, but not by syncytiotrophoblasts or decidual tissues during the first trimester of pregnancy. When stromal cells isolated from normal endometrial tissues were cultured and stimulated to decidualize by progesterone (P4) plus estrogen or dibutyryl cyclic 3',5'-AMP, their total and phosphorylated stathmin levels decreased. Knocking down stathmin expression in the cultured stromal cells using small interfering RNA, before the cells were exposed to the decidualizing agents, significantly suppressed decidualization, as indicated by the decreased expression of IGF-binding protein-1 and prolactin. Stathmin is differently expressed in human endometrial and placental cells and may participate in the decidualization of endometrial stromal cells.


Perceptual learning with a sodium depletion procedure.
Rats in a state of salt need prefer a flavor that has previously been paired with saline (Experiment 1). In Experiments 2 and 3, rats exposed to 2 saline concentrations, presented either concurrently or on separate trials, and each paired with a different flavor, showed a preference for the flavor that had been associated with the stronger saline. This effect was substantial, however, only in those rats that had experienced the concurrent exposure schedule. This effect cannot be attributed to a difference in the strength of within-compound associations produced by the 2 preexposure schedules (Experiment 4). It is suggested that concurrent preexposure can engage a learning process that enhances the discriminability of the preexposed stimuli.


Resolving the lineage relationship between malignant cells and vascular cells in glioblastomas.
Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.


A joint experimental and theoretical study on structural, electronic, and magnetic properties of MnGen - (n = 3-14) clusters.
A systematic structure and property investigation of MnGen - (n = 3-14) was conducted by means of density functional theory coupled with mass-selected anion photoelectron spectroscopy. This combined theoretical and experimental study allows global minimum and coexistence structures to be identified. It is found that the pentagonal bipyramid shape is the basic framework for the nascent growth process of MnGen - (n = 3-10), and from n = 10, the endohedral structures can be found. For n = 12, the anion MnGe12 - cluster probably includes two isomers: a major isomer with a puckered hexagonal prism geometry and a minor isomer with a distorted icosahedron geometry. Specifically, the puckered hexagonal prism isomer follows the Wade-Mingos rules and can be suggested as a new kind of superatom with the magnetic property. Furthermore, the results of adaptive natural density partitioning and deformation density analyses suggest a polar covalent interaction between Ge and Mn for endohedral clusters of MnGe12 -. The spin density and natural population analysis indicate that MnGen - clusters have high magnetic moments localized on Mn. The density of states diagram visually shows the significant spin polarization for endohedral structures and reveals the weak interaction between the Ge 4p orbital and the 4s, 3d orbitals of Mn.


Pediatric movement disorders: an update.
Pediatric movement disorders the represent a broad range of disorders, the majority of which are intermittent and hyperkinetic. The goal of this review is to discuss recent findings in several under-recognized conditions (motor stereotypy disorder, restless legs syndrome, and infantile masturbation) as well as the area of autoimmune movement disorders [Sydenham's chorea and PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection)]. Advances to be discussed include clarification of symptoms, diagnostic clues, epidemiology, pathogenesis, and treatment. Significant progress has been made in the study of several paroxysmal movement disorders. Motor stereotypies can occur in typical children and persist over time. Infantile masturbation is often misdiagnosed for seizures or dystonia. Restless leg syndrome is a relatively common problem in children and established criteria are available. Advances have been made in the hallmark autoimmune disorder Sydenham's chorea, but PANDAS remains controversial.


Effect of autoclaving of a lactose-containing diet on cholesterol and bile acid metabolism of conventional and germ-free rats.
Feeding of lactose in amounts comparable to the adult human intake in developed countries (6% of diet, and in later studies 10%) had no major effect on cholesterol and bile acid metabolism of germ-free and conventional rats. However, when lactose-containing casein-starch diets were sterilized by autoclaving, changes in intestinal and/or fecal bile acids were found. Both germ-free and conventional rats demonstrated some increase in intestinal beta-muricholic acid concentrations ascribable to the mere presence of lactose in the diet. Autoclaving of the diet produced additional changes, especially in the fecal bile acid pattern of conventional rats. Here the ratio between the beta-muricholic-derived secondary bile acids hyodeoxycholic and omega-muricholic acids changed from the usual 5:3 to approximately 1:10, with omega-muricholic acid becoming the major fecal bile acid. These changes point to a notable effect of lactose-derived products, formed during steam-sterilization, on the microbial modification of intestinal bile acids in the lower gut. Similar changes have been observed after oral administration of aureomycin and other, unrelated antibiotics that inhibit growth of gram positive organisms.


Navigating maternity health care: a survey of the Canadian prairie newcomer experience.
Immigration to Canada has significantly increased in recent years, particularly in the Prairie Provinces. There is evidence that pregnant newcomer women often encounter challenges when attempting to navigate the health system. Our aim was to explore newcomer women's experiences in Canada regarding pregnancy, delivery and postpartum care and to assess the degree to which Canada provides equitable access to pregnancy and delivery services. Data were obtained from the Canadian Maternity Experiences Survey. Women (N = 6,241) participated in structured computer-assisted telephone interviews. Women from Alberta, Saskatchewan and Manitoba were included in this analysis. A total of 140 newcomers (arriving in Canada after 1996) and 1137 Canadian-born women met inclusion criteria. Newcomers were more likely to be university graduates, but had lower incomes than Canadian-born women. No differences were found in newcomer ability to access acceptable prenatal care, although fewer received information regarding emotional and physical changes during pregnancy. Rates of C-sections were higher for newcomers than Canadian-born women (36.1% vs. 24.7%, p = 0.02). Newcomers were also more likely to be placed in stirrups for birth and have an assisted birth. Although newcomers residing in Prairie Provinces receive adequate maternity care, improvements are needed with respect to provision of information related to postpartum depression and informed choice around the need for C-sections.


Leiomyosarcoma of the penis. Case report and review of the literature.
The twenty-third case of penile leiomyosarcoma in the literature is reported, and all cases are reviewed. Clinically and pathologically these tumors fall into two groups, superficial and deep. Superficial tumors grow slowly, and tend to recur locally, but have a high salvage rate and good prognosis. The recommended treatment is local excision with negative margins. Recurrences are usually amenable either to re-excision or amputation with some degree of success. Deep tumors exhibit a more aggressive behavior, and have a poorer prognosis. Despite radical surgery the salvage rate is low, and most patients die from disseminated disease one or two years after diagnosis. Metastases to inguinal lymph nodes are uncommon, and should be treated aggressively in the absence of distant metastases. The role of adjuvant radiotherapy and chemotherapy in treating deep tumors should be investigated.


Evolving Trends in Endodontic Research: An Assessment of Published Articles in 2 Leading Endodontic Journals.
The aim of this study was to evaluate and analyze the evolving trends in endodontic research in 2 leading endodontic journals (ie, Journal of Endodontics and International Endodontic Journal) in articles published from January 2009 to December 2013. The differences in content between this period and a 10-year earlier period from January 1999 to December 2003 were also evaluated. Each journal's content was accessed through the web edition. For each article, the following parameters were recorded: number of authors, article type, number of affiliations, field of study, source of article, and geographic origin. The recorded data were analyzed using both descriptive and analytic statistics. During 2009-2013 (second period), the mean number of authors per article increased significantly compared with 1999-2003 (first period). The main volume of the literature in both periods and journals was original research articles. The number of published reviews increased significantly from the first to the second study period in contrast to case reports/clinical articles, which presented a significant decrease. "Endodontic materials" was the most prevalent thematic category in both study periods. The number of published articles related to "biology" and "chemical preparation and disinfection" increased significantly from the first to the second study period. On the contrary, the number of articles regarding "obturation and microleakage" presented a considerable decrease at the same time. The United States was the leading country in the number of publications in the first period followed by Brazil. In the second period, this rank was reversed with Brazil becoming the leading country followed by the United States. In the last 15 years, the progress of the specialty of endodontology was apparent as shown through the trends and shifts in research orientation in published articles in the 2 leading endodontic journals. The results of the present reviewing process encourage both journals to publish well-designed research projects with a high degree of difficulty, thus contributing to a more evidence-based approach of endodontology.


Effectiveness and feasibility of robotic gastric neurostimulator placement in patients with refractory gastroparesis.
Gastric neurostimulation (GNS) with Enterra® therapy device (Medtronic, Minneapolis, MN) appears as the last resort for patients with refractory gastroparesis. Currently, the device has Humanitarian Use status by Food and Drug Administration, thereby requiring further investigation. We aim to describe its feasibility and clinical outcomes using robotic technique. From June 2014 to September 2016, 15 consecutive patients underwent robotic insertion of Enterra® device. Patient demographics, comorbidities, and clinical outcomes including mortality, length of stay, readmission rates, reoperation and complications were retrospectively collected. Patients were also assessed based on a validated 14-point questionnaire regarding satisfaction with the operation, quality of life and symptomatic relief. Mean age was 41.6 years ± 13.8 and there were 11 females (73.3%). No mortality was reported. The annual hospital admissions were reduced after GNS (2.5 ± 4.1 vs. 3.6 ± 4.4, p = 0.004). The frequency of bloating (p = 0.029) and severity of emesis (p = 0.038), early satiety (p = 0.042) and bloating (p = 0.031) were reduced after GNS. The severity and frequency total scores were also improved after GNS (12.6 ± 1.4 vs. 18.1 ± 2.7, p = 0.008 and 12.9 ± 2.2 vs. 16.1 ± 1.1, p = 0.016, respectively). This is the first report describing the clinical experience with robotic insertion of GNS device. This approach is safe and feasible and seems to have similar long-term outcomes as laparoscopic technique. Potential advantages to robotic technique include enhanced dexterity and suturing of the device within gastric wall. Further experience with large prospective studies and randomized clinical trials may be warranted.


Complete conversion of all typical glycosylated protopanaxatriol ginsenosides to aglycon protopanaxatriol by combined bacterial β-glycosidases.
Aglycon protopanaxatriol (APPT) has valuable pharmacological effects such as anti-inflammatory and anti-stress activities. However, the complete conversion of all typical glycosylated protopanaxatriol ginsenosides to APPT has not been achieved to date. β-Glycosidase from the hyperthermophilic bacterium Dictyoglomus turgidum (DT-bgl) hydrolyzes the glucose residues at C-6 and the inner glucose at C-20 in protopanaxatriol (PPT), but not the outer rhamnose residues at C-6. In contrast, β-glycosidase from the hyperthermophilic bacterium Pyrococcus furiosus (PF-bgl) hydrolyzes the outer rhamnose residue at C-6 but not the inner glucose residues at C-6 and C-20 in PPT. Thus, the combined use of DT-bgl and PF-bgl resulted in the complete the conversion of all typical glycosylated PPT ginsenosides, including R1, R2, Re, Rg1, Rg2, Rh1, Rf, F1, F3, and F5, to APPT. DT-bgl combined with PF-bgl completely hydrolyzed 1.0 mg ml-1 R1 and 1.0 mg ml-1 total PPT-type ginsenosides in Panax notoginseng root extract to 0.5 and 0.63 mg ml-1 APPT for 4 and 3 h, with molar conversions of 100% and productivities of 125 and 210 mg l-1 h-1, respectively. To the best of our knowledge, this is the first report of the complete conversion of all typical glycosylated PPT ginsenosides to APPT and the highest productivity of APPT obtained from ginseng extract achieved to date.


Comparison of effects of yoga & physical exercise in athletes.
The effect of pranayama a controlled breathing practice, on exercise tests was studied in athletes in two phases; sub-maximal and maximal exercise tests. At the end of phase I (one year) both the groups (control and experimental) achieved significantly higher work rate and reduction in oxygen consumption per unit work. There was a significant reduction in blood lactate and an increase in P/L ratio in the experimental group, at rest. At the end of phase II (two years), the oxygen consumption per unit work was found to be significantly reduced and the work rate significantly increased in the experimental group. Blood lactate decreased significantly at rest in the experimental group only. Pyruvate and pyruvate-lactate ratio increased significantly in both the groups after exercise and at rest in the experimental group. The results in both phases showed that the subjects who practised pranayama could achieve higher work rates with reduced oxygen consumption per unit work and without increase in blood lactate levels. The blood lactate levels were significantly low at rest.


Volume displaced by diaphragm motion in emphysema.
To examine the effect of hyperinflation on the volume displaced by diaphragm motion (DeltaVdi), we compared nine subjects with emphysema and severe hyperinflation [residual volume (RV)/total lung capacity (TLC) 0.65 +/- 0.08; mean +/- SD] with 10 healthy controls. Posteroanterior and lateral chest X rays at RV, functional residual capacity, one-half inspiratory capacity, and TLC were used to measure the length of diaphragm apposed to ribcage (Lap), cross-sectional area of the pulmonary ribcage, DeltaVdi, and volume beneath the lung-apposed dome of the diaphragm. Emphysema subjects, relative to controls, had increased Lap at comparable lung volumes (4.3 vs. 1.0 cm near predicted TLC, 95% confidence interval 3.4-5.2 vs. 0-2.1), pulmonary rib cage cross-sectional area (emphysema/controls 1.22 +/- 0.03, P < 0.001 at functional residual capacity), and DeltaVdi/DeltaLap (0.25 vs. 0.14 liters/cm, P < 0.05). During a vital capacity inspiration, relative to controls, DeltaVdi was normal in five (1.94 +/- 0.51 liters) and decreased in four (0.51 +/- 0.40 liters) emphysema subjects, and volume beneath the dome did not increase in emphysema (0 +/- 0.36 vs. 0.82 +/- 0.80 liters, P < 0.05). We conclude that DeltaVdi can be normal in emphysema because 1) hyperinflation is shared between ribcage and diaphragm, preserving Lap, and 2) the diaphragm remains flat during inspiration.


Between sexual and apomictic: unexpectedly variable sporogenesis and production of viable polyhaploids in the pentaploid fern of the Dryopteris affinis agg. (Dryopteridaceae).
In ferns, apomixis is an important mode of asexual reproduction. Although the mechanisms of fern reproduction have been studied thoroughly, most previous work has focused on cases in which ferns reproduce either exclusively sexually or exclusively asexually. Reproduction of ferns with potentially mixed systems and inheritance of apomixis remains largely unknown. This study addresses reproduction of the pentaploid Dryopteris × critica, a hybrid of triploid apomictic D. borreri and tetraploid sexual D. filix-mas. Spore size, abortion percentage and number of spores per sporangium were examined in pentaploid plants of D. × critica grown in an experimental garden. The sporangial content of leaf segments was cultivated on an agar medium, and DNA ploidy levels were estimated by DAPI flow cytometry in 259 gametophytes or sporophytes arising from the F2 generation of the pentaploid hybrid. The hybrid is partly fertile (89-94% of aborted spores) and shows unstable sporogenesis with sexual and apomictic reproduction combined. The number of spores per sporangium varied from approx. 31 to 64. Within a single sporangium it was possible to detect formation of either only aborted spores or various mixtures of aborted and well-developed reduced spores and unreduced diplospores. The spores germinated in viable gametophytes with two ploidy levels: pentaploid (5x, from unreduced spores) and half of that (approx. 2·5x, from reduced spores). Moreover, 2-15% of gametophytes (both 2·5x and 5x) formed a viable sporophyte of the same ploidy level due to apogamy. This study documents the mixed reproductive mode of a hybrid between apomictic and sexual ferns. Both sexual reduced and apomictic unreduced spores can be produced by a single individual, and even within a single sporangium. Both types of spores give rise to viable F2 generation gametophytes and sporophytes.


The role of lumbosacral paraspinal muscle degeneration and low vertebral bone mineral density on distal instrumentation-related problems following long-instrumented spinal fusion for degenerative lumbar scoliosis: a retrospective cohort study.
This study aimed to confirm the role of paraspinal muscle degeneration and low vertebral bone mineral density (vBMD) of the lumbosacral region in the development of distal instrumentation-related problems (DIPs) in degenerative lumbar scoliosis (DLS) patients undergoing long-instrumented spinal fusion. From 2013 to 2019, 125 DLS patients with 24-month follow-up after long-instrumented spinal fusion in Beijing Chao-Yang Hospital were retrospectively recruited and divided into DIP and non-DIP groups. Demographic characteristics, surgical data, and radiographic parameters were statistically compared between the groups. Degeneration of the paraspinal muscle was evaluated using the relative gross cross-sectional area (rGCSA), relative functional cross-sectional area (rFCSA), ratio of the rFCSA to rGCSA, gross muscle-fat index, and functional muscle-fat index of the multifidus (MF), erector spinae (ES), paraspinal extensor muscle (PSE), and psoas major determined by preoperative magnetic resonance imaging (MRI). The vBMD of the lumbosacral region and lower instrumented vertebra (LIV) was assessed using Hounsfield unit (HU) values determined by computed tomography (CT) scans. The DeLong test was performed to select MRI and CT scan variables. Multivariable logistic regression analysis was applied to determine the independent predictive factors of DIPs. The incidence of DIPs was 16.0% (20/105). There were no significant differences in demographic characteristics or surgical data between the groups. The rFCSAs of the MF (65.74±21.51 vs. 92.37±21.68; P<0.001), ES (82.67±21.44 vs. 111.48±24.21; P<0.001) and PSE (144.31±36.12 vs. 208.48±41.57; P<0.001) and the HU values of the lumbosacral region (103.80±22.64 vs.. 132.19±19.17; P<0.001) and LIV (111.70±23.23 vs. 128.69±20.70; P=0.005) were significantly lower in the DIP group. Significantly less preoperative pelvic tilt and greater postoperative lumbosacral lordosis and sagittal vertical axis (SVA) values were observed in the DIP group. The rFCSA of the PSE, the HU value of the lumbosacral region, and the postoperative SVA value were detected as independent predictive factors of DIPs. Lower muscularity of the PSE, a lower vBMD of the lumbosacral region, and postoperative sagittal malalignment were independent predictive factors of DIPs. Surgeons should emphasize the preoperative evaluation of paraspinal muscle and bone mass in DLS patients.


Lipid status and long-chain polyunsaturated fatty acid concentrations in adults and adolescents with phenylketonuria on phenylalanine-restricted diet.
Blood lipid studies are reported in 25 adults and 2 adolescents with PKU who had been on phenylalanine-restricted diets for a mean period of 22.6 years (range 7-39 years). Measurements included plasma concentrations of phenylalanine, cholesterol, lipoproteins, triglycerides and fatty acid profiles, including the analysis of seven fatty acids in plasma and red blood cells. Lipid screening identified 7 subjects with significantly elevated cholesterol/HDL ratios ranging from 5.6 to 10.3. Triglyceridaemia was documented in 5 of these 7, with concentrations ranging between 0.24 and 4.5 mmol/L (219-402 mg/dl) with a mean of 3.5 mmol/L (310 mg/dl). The fatty acid analyses demonstrated slight but statistically significant reductions in the concentrations of long-chain polyunsaturated fatty acids (LCPUFA), including plasma docosahexaenoic (DHA) and arachidonic acid (AA), and red blood cell DHA concentrations. The pattern resembles that reported previously in children, but alterations in the mean levels are less severe. In six of the adult patients plasma DHA or AA concentrations were less than 50% of controls. Since DHA and AA have important physiological roles, including brain and retinal function, it is recommended that blood lipid concentrations be monitored in all patients with PKU, including adults, and that DHA and AA supplementation be provided, particularly in those patients in whom the blood concentrations of these substances are reduced significantly.


Proteus vertebral osteomyelitis.
Proteus organisms are rare causes of osteomyelitis. Vertebral osteomyelitis caused by this organism has only been reported in 21 cases over the last 75 years. Although Staphylococcus aureus is the most common cause of vertebral osteomyelitis, rare causes such as P. mirabilis may need to be considered in the context of recent urinary tract infection or urological surgery. Therefore biopsy should be undertaken to establish the causative organism and determine appropriate antibiotic susceptibility.


Phase-field study of three-dimensional steady-state growth shapes in directional solidification.
We use a quantitative phase-field approach to study directional solidification in various three-dimensional geometries for realistic parameters of a transparent binary alloy. The geometries are designed to study the steady-state growth of spatially extended hexagonal arrays, linear arrays in thin samples, and axisymmetric shapes constrained in a tube. As a basis to address issues of dynamical pattern selection, the phase-field simulations are specifically geared to identify ranges of primary spacings for the formation of the classically observed "fingers" (deep cells) with blunt tips and "needles" with parabolic tips. Three distinct growth regimes are identified that include a low-velocity regime with only fingers forming, a second intermediate-velocity regime characterized by coexistence of fingers and needles that exist on separate branches of steady-state growth solutions for small and large spacings, respectively, and a third high-velocity regime where those two branches merge into a single one. Along the latter, the growth shape changes continuously from fingerlike to needlelike with increasing spacing. These regimes are strongly influenced by crystalline anisotropy with the third regime extending to lower velocity for larger anisotropy. Remarkably, however, steady-state shapes and tip undercoolings are only weakly dependent on the growth geometry. Those results are used to test existing theories of directional finger growth as well as to interpret the hysteretic nature of the cell-to-dendrite transition.


[Ocular injuries in mild facial trauma].
Ocular contusions are common and cause significant morbidity. The mechanism of ocular contusion is a decrease in the length of the anterioposterior axis whereas the transversal axis increases. Epidemiology data shows that young men are most injured in relation with sports, aggression, work, or car or work accidents. Injury to the ocular surface (conjunctiva and cornea) is minor. The iris is very frail, usually leading to hyphema which can progress to glaucoma. A cataract can appear after a contusion but usually years after the trauma. Final visual acuity can be compromised by retinal contusion or retinal detachment (due to a retinal dehiscence or post-traumatic dialysis). The worst outcome is optic neuropathy. The most difficult task is to predict visual acuity after the initial ocular lesion.


[Adverse events of biologic therapies].
Biological therapies have revolutionized the management and the outcome of patients with inflammatory rheumatic diseases. The prescription and the number of patients under biotherapies have greatly increased. Unfortunately, these treatments are occasionally accompanied by side effects usually reversible upon treatment discontinuation. Some are preventable or can be reduced, including through the screening and prevention (tuberculosis screening, vaccination…). It is important to be aware of these different side effects to adapt the prescription of biologics according to the patient's profile (history of infection, malignancy, heart failure…). It is also critical to involve the patients into the decision-making and thus, to inform them thoroughly.


alpha-Melanocyte-stimulating hormone (alpha-MSH) and melanin-concentrating hormone (MCH) modify monoaminergic levels in the preoptic area of the rat.
The effect of perfusion of melanin-concentrating hormone (MCH) or alpha-melanocyte-stimulating hormone (alpha-MSH) (100 ng/microliter) in the ventromedial nucleus (VMN) or medial preoptic area (MPOA) on monoaminergic levels of female rats was measured using microdialysis and HPLC-electrochemical detection. In the MPOA, alpha-MSH raised 5-HIAA concentration, whereas MCH reduced both 5-HT and 5-HIAA. Neither peptide had any effect in the VMN. The opposite effects of the peptides on the serotonergic system might be responsible for their antagonistic or opposite actions previously reported on several CNS functions. Dopamine may mediate the similar effects of the two peptides, because alpha-MSH inhibits dopaminergic release in the MPOA (but not VMN) and MCH tends to follow the same pattern.


Utility of numerical and visual analog scales for evaluating the post-operative pain in rural patients.
Visual analog scales (VAS) and numeric analog scales (NAS) are used to assess post-operative pain, but few studies indicate their usefulness in rural illiterate population in India. This study was designed to 1) Compare the impact of literacy on the ability to indicate pain rating on VAS and NAS in post-operative rural patients. 2) Assess the level of agreement between the pain scales. Cross sectional, hospital based study. Informed consent was obtained from patients prior to undergoing surgical procedures in a teaching hospital. Post surgery, patients who were conscious and coherent, were asked to rate pain on both VAS and NAS. The pain ratings were obtained within 24 hours of surgery and within 5 minutes of each other. Percentages, chi square test, regression analysis. A total of 105 patients participated in the study. 43 (41%) of the sample was illiterate. 82 (78.1%) were able to rate pain on VAS while 81 (77.1%) were able to rate pain on NAS. There was no significant association between pain ratings and type of surgery, duration of surgery and nature of anaesthesia. In multivariate analysis, age, sex and literacy had no significant association with the ability to rate pain on VAS (P value 0.652, 0.967, 0.328 respectively). Similarly, no significant association was obtained between age, sex and literacy and ability to rate pain on NAS (P value 0.713, 0.405, 0.875 respectively). Correlation coefficient between the scales was 0.693. VAS and NAS can be used interchangeably in Indian rural population as post-operative pain assessment tools irrespective of literacy status.


Impairment of reactivity to lepromin by mycobacterial antigens related to, or identical with, Mycobacterium leprae.
Three hundred and twenty young children were injected with Bacillus Calmette-Guerin (BCG) saline, or with one of the mycobacterial cytoplasmic antigens related with Mycobacterium leprae. At an appropriate time thereafter they were tested for dermal hypersensitivity to the antigens and for reactions to lepromin. Whereas all the antigens induced cell-mediated immunity, the incidence and intensity of late response to lepromin were significantly reduced in children preinjected with the cytoplasmic mycobacterial antigens, as contrasted with increased lepromin reactivity in the BCG group and with the findings in saline-injected children.


[Pain in patients with cancer].
All cancer patients will inevitably experience pain during their illness, whether it is cured or not: acute pain induced by the treatment and examinations required for diagnosis; chronic pain associated with the evolution of the disease or sequelae caused by treatment. These pains must be treated imperatively as accompanying symptoms. The practitioner should be able to analyse the components, the physiopathological, the cause(s) and the way in which they occurred. Treatment will then be prescribed, adapted and monitored according to stringent criteria so that optimal efficacy is achieved with a minimum of side effects.


Genotoxicity of tobacco smoke-derived aromatic amines and bladder cancer: current state of knowledge and future research directions.
Bladder cancer is a significant public health problem, worldwide. In the United States, bladder cancer is the fourth most common cancer in men, and its recurrence rate is the highest among all malignancies. Tobacco smoking is the leading risk factor for bladder cancer. The risk of bladder cancer is directly related to the intensity and duration of smoking, while quitting smoking reduces this risk. The increased risk of smokers for developing bladder cancer is attributable to their exposure to aromatic amines, which constitute a family of known bladder carcinogens present in tobacco smoke. The underlying mechanism of action of aromatic amines in the genesis of bladder cancer is not, however, fully delineated. Research has identified a genotoxic mode of action, specifically DNA adduction and mutagenicity, for aromatic amines, which may account for their carcinogenicity. The present review summarizes our current knowledge on the DNA adduction and mutagenicity of aromatic amines in relation to smoking-associated bladder cancer. For illustrative purposes, representative results from published research on aromatic amine-induced DNA adduction and mutagenesis are discussed. The direction of future research on the underlying mechanisms of tobacco smoke-associated bladder carcinogenesis is also outlined. Understanding the molecular mechanisms of bladder carcinogenesis is essential for improving future strategies for prevention, early detection, treatment, and prognosis of this malignancy.


A blinded randomised trial of acupuncture (manual and electroacupuncture) compared with a non-penetrating sham for the symptoms of osteoarthritis of the knee.
To compare the effect of acupuncture (manual and electroacupuncture) with that of a non-penetrating sham ('placebo' needle) in patients with osteoarthritic knee pain and disability who are blind to the treatment allocation. Acupuncture naïve patients with symptomatic and radiological evidence of osteoarthritis of the knee were randomly allocated to a course of either acupuncture or non-penetrating sham acupuncture using a sheathed 'placebo' needle system. Acupuncture points for pain and stiffness were selected according to acupuncture theory for treating Bi syndrome. Both manual and electrical stimulation were used. Response was assessed using the WOMAC index for osteoarthritis of the knee, self reported pain scale, the EuroQol score and plasma beta-endorphin. The effectiveness of blinding was assessed. There were 34 patients in each group. The primary end point was the change in WOMAC pain score after the course of treatment. Comparison between the two treatment groups found a significantly greater improvement with acupuncture (mean difference 60, 95% CI 5 to 116, P= 0.035) than with sham. Within the acupuncture group there was a significant improvement in pain (baseline 294, mean change 95, 95% CI 60 to 130, P<0.001) which was not seen by those who had sham acupuncture (baseline 261, mean change 35, 95% CI -10 to 80, P=0.12). Similar effects within group, but not between groups, were seen with the secondary end points of WOMAC stiffness, WOMAC function, and self reported pain. One month after treatment the between group pain difference had been lost (mean difference 46; 95% CI -9 to 100, P=0.10) although the acupuncture group was still benefiting compared to baseline (mean difference 59; 95% CI 16 to 102, P=0.009). The EuroQol score, a generic measure of health related quality of life, was not altered by the treatments. A minority of patients correctly guessed their treatment group (41% in the acupuncture group and 44% in the control group). Plasma beta-endorphin levels were not affected by either treatment. Acupuncture gives symptomatic improvement for patients with osteoarthritis of the knee, and is significantly superior to non-penetrating sham acupuncture. The study did not confirm earlier reports of release of plasma beta-endorphin during acupuncture.


Use of linezolid in children: an overview of recent advances.
Linezolid is the first member of a new generation of antibiotics, the synthetic oxazolidinones, to become available, with a broad spectrum of in vitro activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and vancomycin-resistant E. faecium. Linezolid is showing great promise currently for the treatment of multiresistant gram-positive bacterial infections, especially complicated skin infections, catheter-induced bacteremia or nosocomial pneumonia both in the community and in a hospital setting, in children and in adults. Although most recent reports are favorable and anticipatory of a more extensive use of linezolid in appropriately selected pediatric population groups in the near future, following treatment failure of conventional antimicrobial agents, more clinical trials are, however, required to investigate the safety profile and tolerability of this new antibiotic in the pediatric population.


The role of P2X receptors in bone biology.
Bone is a highly dynamic organ, being constantly modeled and remodeled in order to adapt to the changing need throughout life. Bone turnover involves the coordinated actions of bone formation and bone degradation. Over the past decade great effort has been put into the examination of how P2X receptors regulate bone metabolism and especially for the P2X7 receptor an impressive amount of evidence has now documented its expression in osteoblasts, osteoclasts, and osteocytes as well as important functional roles in proliferation, differentiation, and function of the cells of bone. Key evidence has come from studies on murine knockout models and from pharmacologic studies on cells and animals. More recently, the role of P2X receptors in human bone diseases has been documented. Loss-of-functions polymorphisms in the P2X7 receptorare associated with bone loss and increased fracture risk. Very recently a report from a genetic study in multiple myeloma demonstrated that decreased P2X7 receptor function was associated with increased risk of developing multiple myeloma. In contrast, the risk of developing myeloma bone disease and subsequent vertebral fractures was increased in subjects carrying P2X7 receptor gain-of-function alleles as compared to subjects only carrying loss-of-function or normal functioning alleles. It is evident that P2X receptors are important in regulating bone turnover and maintaining bone mass, and thereby holding great potential as novel drug targets for treatment of bone diseases. However, further research is needed before we fully understand the roles and effects of P2X receptors in bone.


A rare conjunctival Spitz nevus: a case report and literature review.
A conjunctival Spitz nevus is a very rare, benign melanocytic lesion, which can be mistaken for a malignant melanoma. We present a case of a 28-year old man, who suffered from a rapidly growing, non-pigmented mass in the left caruncular area, extending to the nasal conjunctiva. The lesion was excised and pathologic examination showed nests of large, polygonal, non-pigmented epithelioid cells, located in the stroma. The overlying epithelium showed focal erosions. At the base, there was a lymphocytic infiltrate. Immunohistochemical techniques, with stainings for S-100 protein, HMB-45 and MIB-1, were used for further investigation and showed the melanocytic origin of the lesion (S-100 staining) as well as many cells in cell cycle (MIB-1 staining). However, no mitoses were seen. The clinical image, combined with pathologic and immunohistochemical findings, provided the diagnosis of a Spitz nevus localised in the conjunctiva. Although the cutaneous location of Spitz nevi is well known, conjunctival Spitz nevi are very rare and because of their mucosal origin, some of the histological features are different.


Material Properties of Rat Middle Cerebral Arteries at High Strain Rates.
Traumatic brain injury (TBI), resulting from either impact- or nonimpact blast-related mechanisms, is a devastating cause of death and disability. The cerebral blood vessels, which provide critical support for brain tissue in both health and disease, are commonly injured in TBI. However, little is known about how vessels respond to traumatic loading, particularly at rates relevant to blast. To better understand vessel responses to trauma, the objective of this project was to characterize the high-rate response of passive cerebral arteries. Rat middle cerebral arteries (MCAs) were isolated and subjected to high-rate deformation in the axial direction. Vessels were perfused at physiological pressures and stretched to failure at strain rates ranging from approximately 100 to 1300 s-1. Although both in vivo stiffness and failure stress increased significantly with strain rate, failure stretch did not depend on rate.


The role of EEG in patients with suspected epilepsy.
Despite the advances in imaging, EEG remains a critical test for the diagnosis of epilepsy. Not only can it confirm the diagnosis, but it can also clarify the type of epilepsy. There are many different types of EEG recordings depending on duration, the presence of video, and inpatient or outpatient setting, each with its pros and cons. Interictal epileptiform abnormalities are very specific to epilepsy, but they can be over-interpreted by inexperienced readers. In addition to diagnosis of epilepsy, EEG also has a role in the decision to discontinue treatment in seizure-free patients, and in assessing critically ill patients for possible status epilepticus and encephalopathies. EEG reports should be relatively standardized and clear to the clinician who requested the EEG.


Altered basal C-peptide/insulin molar ratios in obese patients with fatty liver.
To elucidate if the presence of fatty liver in obesity influences hepatic insulin extraction under basal conditions, serum immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) were measured in 20 obese patients with normal glucose tolerance and in 8 normal subjects. The obese patients were subdivided into two groups matched for age and body weight according to the presence or absence of fatty liver: 8 obese patients without fatty liver (OBN) and 14 with fatty liver (OBF). Basal levels of IRI and CPR were significantly greater in the obese patients than in the normals, but were similar in the two obese groups. In the OBF group, the CPR/IRI molar ratios, a relative measure of hepatic insulin uptake, were significantly lower than in the other two groups, while the ratios of the normal and OBN groups were similar. The CPR/IRI molar ratios in all obese patients correlated well with the degree of fatty liver (r = 0.785, p less than 0.001). These results suggest that hepatic insulin extraction in a subgroup of obese patients is either reduced or indistinguishable from that of non-obese subjects, and that basal CPR/IRI molar ratio may serve as a useful indicator of the presence of fatty liver in simple obesity.


A Priori Theoretical Model for Discovery of Environmentally Sustainable Perfluorinated Compounds.
Since SF6 is the most potent greenhouse gas, the search for a viable alternative is taking on great urgency for several decades but without success. The demanding combination of performance, safety, and environmental properties for the new chemistry superior to SF6 was thought to be nearly impossible to achieve. In contrast to the commonly used mixtures with two or three individual gases, a hybrid model has been proposed to create the new perfluorinated compounds with multiple unsaturated chemical bonds by means of full or partial integration of the parent molecules. A unique combination of a series of paradoxical properties that is high in dielectric strength and stability, low in boiling point, and significantly lower in global warming potential is achieved for the first time. The present a priori theoretical predictions shed new lights on the rational molecular design of the perfluorinated compounds and will greatly inspire experimental synthesis and field tests on the new chemistry for dielectric use.


In vitro and in vivo modifications of recombinant and human IgG antibodies.
Tremendous knowledge has been gained in the understanding of various modifications of IgG antibodies, driven mainly by the fact that antibodies are one of the most important groups of therapeutic molecules and because of the development of advanced analytical techniques. Recombinant monoclonal antibody (mAb) therapeutics expressed in mammalian cell lines and endogenous IgG molecules secreted by B cells in the human body share some modifications, but each have some unique modifications. Modifications that are common to recombinant mAb and endogenous IgG molecules are considered to pose a lower risk of immunogenicity. On the other hand, modifications that are unique to recombinant mAbs could potentially pose higher risk. The focus of this review is the comparison of frequently observed modifications of recombinant monoclonal antibodies to those of endogenous IgG molecules.


Reelin protects against pathological α-synuclein accumulation and dopaminergic neurodegeneration after environmental enrichment in Parkinson's disease.
Two of the primary features of Parkinson's disease (PD) are the accumulation of α-synuclein (α-Syn) and the depletion of lysosomal-associated membrane protein 1 (LAMP1) in the brain. Beneficial effects of environmental enrichment (EE) have been reported on the activation of lysosomal function and the amelioration of PD symptoms. Furthermore, Reelin could be a novel therapeutic target in PD. Hence, in this study, we validated the effects of EE on the activation of LAMP1 via Reelin in PD. Heterogeneous α-Syn (A53T)-overexpressing transgenic mice (age 6 and 16 months) were exposed to EE for 8 weeks. After motor and cognitive tests, brain tissues were obtained from mice and subjected to immunohistochemistry and molecular analyses. EE ameliorated motor and non-motor symptoms, protected dopamine neurons, and reduced pathological α-Syn accumulation in the early stage of PD. Striatal Reelin levels were altered depending on the disease stage and regulated by EE in PD mice. To elucidate the underlying mechanism of the effect of EE on PD, we performed further molecular and cellular analyses using activated preformed fibril (PFF)-induced SH-SY5Y cells, an in vitro model of PD, which were treated with recombinant Reelin protein and a Reelin blocker, CR-50. The CR-50 increased pathological α-Syn accumulation and accelerated dopamine neuronal degeneration by decreasing LAMP1 in the PFF-induced PD model. Our results showed that Reelin increased LAMP1 after EE and decreased pathological α-Syn accumulation, thus protecting dopamine neurons from degeneration in the striatum and substantia nigra, and ameliorating neurobehavioral deficits. These results suggest that Reelin is a promising target in treating histopathological changes and improving behavioral symptoms associated with PD.


Characterization of a blend-biosurfactant of glycolipid and lipopeptide produced by Bacillus subtilis TU2 isolated from underground oil-extraction wastewater.
Biosurfactants have versatile properties and potential industrial applications. A new producer, B. subtilis TU2, was isolated from the underground oil-extraction wastewater of Shengli Oilfield, China. Preliminary flask culture showed that the titer of biosurfactant obtained from the broth of TU2 was ~1.5 g/l at 48 h (718 mg/l after purification), with a reduced surface tension of 32.5 mN/m. The critical micelle concentration was measured as 50 mg/l and the surface tension maintained stability in solution with 50 g/l NaCl and 16 g/l CaCl(2) after 5 days of incubation at 70°C. FT-IR spectra exhibited the structure information of both glycolipid and lipopeptide. MALDI-TOF-MS analyses confirmed that the biosurfactant produced by B. subtilis TU2 was a blend of glycolipid and lipopeptide, including rhamnolipid, surfactin, and fengycin. The blended biosurfactant showed 86% of oil-washing efficiency and fine emulsification activity on crude oil, suggesting its potential application in enhanced oil recovery.


Effects of opioid prescription medication dependence and detoxification on pain perceptions and self-reports.
The purpose of this work is to document whether prescription opioid medications used for pain enhanced or worsened pain syndromes from medical conditions in patients who received a diagnosis of prescription opioid dependence as determined by a diagnosis by Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria. Further, whether detoxification improved or worsened pain perceptions and self-reports in patients who chronically administered prescription opioid medications. Our study consisted of a retrospective sample of patients taken from the Addiction Treatment Unit at St Lawrence Hospital in Lansing, MI. Patients were selected from those who voluntarily sought detoxification from opioid medications in an inpatient setting. Selection criteria for the study consisted of a DSM-IV diagnosis of opioid prescription medication dependence, willingness to undergo medical detoxification, cooperation with self-report scales, and abstinence from opioid medications. Study patients were randomly selected from discharges in patient census for the years 2001 to 2003. The significant findings were that self-reported pain scores improved during the detoxification from admission to discharge, from a mean of 5.5 at admission to mean of 3.4 at discharge (0 is no pain and 10 is the most pain). The detoxification period extended to an average of 5 days. Whereas oxycodone CR (OxyContin) produced higher levels of self-reported pain at admission than at discharge, and these patients experienced significant levels of pain reduction with decremental opioid doses as with other opioid medications. Patients with a DSM-IV diagnosis of prescription opioid dependence reported (self) less pain with detoxification and abstinence from the opioid medications.


Better Understanding the Potential Importance of Florida Roadside Breeding Habitat for the Monarch.
The North American monarch butterfly (Danaus plexippus) population has declined significantly over the past two decades. Among the many other factors, loss of breeding habitat has been implicated as a potential leading driver. In response, wildlife agencies and conservation practitioners have made a strong push to restore and conserve milkweeds on both wild and managed landscapes including agricultural lands as well as transportation and utility rights-of-way. Roadsides in particular have been emphasized as a targeted landscape for monarch habitat restoration. While much attention has been focused on habitat in California, along the I-35 corridor from Texas to Minnesota, and more broadly across the agricultural Midwest, research on the occurrence of roadside breeding habitat and the development of best vegetative management practices conducted in the Deep South has been limited. We sampled roadside verges in north-central Florida for the presence of two early season milkweed species, that are particularly important for early season monarch recolonization, Asclepias tuberosa and Asclepias humistrata. Our findings suggest that roadsides harbor extensive populations of the target milkweeds with the vast majority of plants occurring on the back slope of the verge. Alterations to current roadside mowing frequency and scope are needed to effectively conserve these populations and ensure that they are available for use by the monarch.


Toward the design of efficient transglycosidases: the case of the GH1 of Thermus thermophilus.
Using the information available in the sequences of well-characterized transglycosidases found in plants, mutations were introduced in the glycoside hydrolase of the bacterium Thermus thermophilus, with the aim of turning it into an efficient transglycosidase. All mutants happen to have fair catalytic efficiencies, being at worst 25 times less efficient than the wild type. Noteworthy, W120F, one of our high transglycosylation yield (≈ 50%) mutants, is only two times less efficient than the wild type. Interestingly, while in the wild type the sidechain of the acid-base is only found able to sample a pair of equivalent conformations during 0.5-μs-long molecular dynamics simulations, its flexibility is much higher in the case of the high transglycosylation yield mutants. Our results thus suggest that engineering the flexibility of the acid-base of a retaining glycoside hydrolase could be a general way to turn it into an efficient transglycosidase.


The absence of introns within a human fibroblast interferon gene.
Experiments in which immobilised restriction fragments of genomic DNA were hybridised with a cloned human fibroblast interferon cDNA indicate that the homologous chromosomal genes exist in only one basic arrangement. This is in marked contrast to recent studies by Nagata et al. (1) showing that there are at least eight gene arrangements for human leukocyte interferon. Having isolated a chromosomal human fibroblast interferon gene from a gene bank, we conclude from nucleotide sequencing studies that there is a complete absence of introns within the RNA-coding region. In view of a similar observation recently made for a human leukocyte interferon gene (1), it would appear as if interferon genes in general are unlike the vast majority of eukaryote genes in this respect.


[Treatment of coronary disease with elantan. Results of a multicenter study].
10,229 patients with coronary heart disease (CHD) took part in a multicenter study to verify the efficacy and tolerance of a 14 days lasting therapy with elantan under practical conditions. The majority of patients with an average age of 59 +/- 10 years (58.8% men, 40.3% women) had suffered about four years on CHD and had already been treated with coronary efficient drugs. The 14-day therapy with elantan 20 in a dosage of 3 X 1 tabl./day showed a cure rate of 79.9% in patients who had already been treated, a complete remission of the angina pectoris attacks being achieved in 50% and a reduction of the frequency of the attacks in a further 29.9%. The reduced frequency of the attacks was associated with a reduced consumption of acute nitrates (nitroglycerine capsules). With the smaller group of patients who were being treated for angina pectoris for the first time, the therapy with elantan was characterized by a cure rate of 91%.


[Neoadjuvant therapy for resectable esophageal cancer].
Surgical excision remains the only therapeutic approach with curative potential in patients with localized esophageal cancer. Due to the presence of lymph node metastases upon diagnosis in a large percentage of patients with locally advanced tumors and/or the presence of considerable co-morbidity, only a limited number of patients are amenable to surgery. These facts have prompted us to evaluate approaches including perioperative therapy modalities. By means of a computer-supported search (MEDLINE, ASCO Proceedings) as well as a manual literature search, randomized clinical trials and meta-analyses evaluating preoperative therapy plus surgery in patients with resectable esophageal cancer were identified. Twenty-three randomized clinical studies and five meta-analyses were identified. Interpretation--especially of the older studies--however, is hampered by the lack of a stringent application of modern examination techniques allowing for exact specification of tumor stage (resectable/locally advanced) as well as the inclusion of patients with different histological entities (squamous cell/adenocarcinoma), different surgical techniques and the low number of patients. There were no significant differences for the following perioperative therapy modalities regarding tumor-related mortality: preoperative radiotherapy versus postoperative radiotherapy, preoperative and postoperative radiotherapy versus postoperative radiotherapy (higher mortality in preoperative and postoperative radiotherapy arm), preoperative radiotherapy versus surgery, preoperative chemotherapy versus surgery, preoperative and postoperative chemotherapy versus surgery. In terms of 3-year mortality, statistically significant differences could be found for the following therapy modalities: preoperative radiochemotherapy versus surgery (preoperative therapy superior), preoperative chemotherapy versus preoperative radiotherapy (preoperative radiotherapy superior). Judging from these data, no clear recommendation for a standard multimodality approach outside clinical studies can be given for patients with resectable esophageal cancer. Neoadjuvant therapy, therefore, can only be recommended in centers with a maximum surgical expertise and in the context of multidisciplinary study protocols.


Vocal learning as a preadaptation for the evolution of human beat perception and synchronization.
The human capacity to synchronize movements to an auditory beat is central to musical behaviour and to debates over the evolution of human musicality. Have humans evolved any neural specializations for music processing, or does music rely entirely on brain circuits that evolved for other reasons? The vocal learning and rhythmic synchronization hypothesis proposes that our ability to move in time with an auditory beat in a precise, predictive and tempo-flexible manner originated in the neural circuitry for complex vocal learning. In the 15 years, since the hypothesis was proposed a variety of studies have supported it. However, one study has provided a significant challenge to the hypothesis. Furthermore, it is increasingly clear that vocal learning is not a binary trait animals have or lack, but varies more continuously across species. In the light of these developments and of recent progress in the neurobiology of beat processing and of vocal learning, the current paper revises the vocal learning hypothesis. It argues that an advanced form of vocal learning acts as a preadaptation for sporadic beat perception and synchronization (BPS), providing intrinsic rewards for predicting the temporal structure of complex acoustic sequences. It further proposes that in humans, mechanisms of gene-culture coevolution transformed this preadaptation into a genuine neural adaptation for sustained BPS. The larger significance of this proposal is that it outlines a hypothesis of cognitive gene-culture coevolution which makes testable predictions for neuroscience, cross-species studies and genetics. This article is part of the theme issue 'Synchrony and rhythm interaction: from the brain to behavioural ecology'.


A comparison of the posterolateral and anterolateral approaches to total hip arthroplasty.
A comparative statistical analysis was performed weighing the relative merits of two surgical approaches for total hip arthroplasty--the Watson-Jones anterolateral approach and the gluteus maximus splitting posterolateral approach. Intraoperative and clinical records were evaluated for 175 patients undergoing total hip arthroplasty between 1975 and 1979--100 by a posterolateral approach and 75 by an anterolateral approach. Minimum follow-up period was two years. Mean operative times for the posterolateral and anterolateral approaches were 62 minutes and 140 minutes, respectively. The posterolateral group had a mean blood loss of 433 ml, with 35% requiring an average transfusion of 2.5 units. The anterolateral group had a mean blood loss of 767 ml, with 78% requiring an average transfusion of 2.5 units. The average lengths of hospitalization for posterolateral and anterolateral groups were 13 and 15 days, respectively. The time to independent cane ambulation was significantly less in the posterolateral group. The rate of post-operative complications was similar in each group. However, in the posterolateral group there were four dislocations, three loosened femoral components, one deep-wound infection, and one pulmonary embolus, while the anterolateral group suffered one dislocation, no prosthesis loosening, no deep-wound infections, and three pulmonary emboli. Although the posterolateral approach was associated with a lower perioperative morbidity than the anterolateral approach, the latter exhibited fewer dislocations and loosened acetabular components.


Current outlook of childhood cancer epidemiology in a middle-income country under a public health insurance program.
In Mexico, childhood cancer (0-18 years) is treated in a multidisciplinary way while providing care for more than half of the affected children through a public medical insurance. This insurance is given to all children who do not have any health care coverage in Mexico. This program is offered to the poorest of all Mexicans. All the children with this disease are submitted to pathology diagnosis and treatment according to national treatment protocols from 57 accredited medical institutions. From 2007 to 2015, a total of 24,039 children with cancer have been registered; the male gender predominates by 55%. The highest incidence was in the group aged between 0 and 4 years. Every year, there has been an increment in registration. In 2015, there were 3,433 new patients with an incidence of 150.1/million. In the same year, the incidence for all types of leukemia increased to 89.5/million. But for acute lymphoblastic leukemia, the incidence was found to be 79.8/million, which is extremely high. The mortality rate for all these patients in 2015 was 5.3/100,000. However, with regard to children aged between 15 and 18 years, the mortality rate was 8.5/100,000. Abandonment rate was 10%, and there were nine state institutions that had a mortality rate between 25% and 50% among their patients. Coincidentally, as per the Human Development Index, the parameters for education, health, and income were low for those nine institutions. The purpose of this work is to show the epidemiology and the burden we are facing due to this disease.


A review of acute appendicitis seen in the Taiping District Hospital from July to December, 1990.
In a retrospective study, 455 people were found to have been admitted to the Surgical Unit of the Taiping District Hospital, suspected of acute appendicitis in the study period from 1 July to 31 December 1990. However, only 147 (32.3%) were clinically confirmed to have appendicitis and underwent appendicectomy. Out of these, 120 (81.6%) cases were subjected to detailed analysis. The study showed that the commonest age group affected was the 10 to 20 year old. Males were slightly more often affected but there seemed to be an equal distribution among the major races. The diagnostic accuracy, that is the operated cases that were actually acute appendicitis, was 92.5%. The perforation rate was 31.5%. Fifty-five percent of patients developed some post-operative complications, of which the commonest was fever.


Community attitudes to remunerated blood donation in Australia: results from a national telephone survey.
Blood in Australia is sourced through voluntary, non-remunerated donations. With periodic shortages in supply, increasing demand for blood products and a donor base that is perceived to be unsustainable, remuneration has been proposed as a means to improve donation rates. To examine community attitudes to remunerated blood donation in Australia. A national random telephone survey of Australian adults age 18-70 was conducted (n = 1024). Associations were tested using a chi-square (χ(2)) test for linear distribution. Reimbursement for the cost of travel to donate blood was supported by more respondents (46%) than reimbursement for time (19%). Non-donors were more likely to support a payment compared to donors (P = 0.002). Twelve per cent of respondents thought they would be more likely to donate if remunerated while 10% thought they would be less likely. The majority (76%) thought that a payment would not change whether or not they would donate, while 85% thought that it would make other people more likely to donate. The average amount considered to be reasonable reimbursement was AU$30. Despite the common perception that other people would be motivated to donate blood with the introduction of a financial incentive, remuneration may provide minimal incentive in Australia and is unlikely to increase donor participation for the time being.


Qualitative Evaluation of the Africa Malaria Task Force Symposia Effectiveness on African Partner Nations' Malaria Vector Management Capacity.
Creating health alliances to build meaningful networks is critical to combating regional and global burdens of disease. These alliances work by uniting support for elimination efforts through cooperative engagement at the national and international levels. The reduction in malaria-related morbidity and mortality in Africa since 2001 is in part because of investments of international organizations and governments in national level malaria control and prevention-related programs and research. Investment in malaria reduction networks has contributed to this success by strengthening support to overcome the conditions that restrict or prevent change through local laboratory and epidemiological capacity building, thereby resulting in a decrease in burden of disease, increase in economic prosperity, and improvements in stability worldwide.The reformation of local military efforts to combat disease through incorporation into health security alliance networks by the provision of training and financial support is key to reinforcing this success at the national level. One such example of this is the U.S. Africa Command (USAFRICOM) established and partner nation (PN) led Africa Malaria Task Force (AMTF) program. USAFRICOM's mission for AMTF as a health security alliance was to develop sustainable African-led malaria diagnostic, vector surveillance and control capabilities, and to increase collaborations among AMTF military PNs by enabling national and international-level network capacity. The overall objective of this evaluation of the AMTF program was to assess the implementation effectiveness of two AMTF supported symposia in improving the individual, organizational, and institutional diagnostic capacity of the Ghanaian, Ivorian, and Senegalese armed forces. The specific aims of this process evaluation were to identify procedural, contextual, and capacity-related factors that influence the effect of the symposia events on laboratory capabilities at the individual, organizational, and institutional levels through a two-phased formative evaluation approach utilizing qualitative methodologies. Findings indicate that the AMTF program symposia positively encouraged malaria prevention and control efforts in all three countries included in the evaluation. Conclusions suggest that learning about the different types of malaria prevention and control efforts underway in other countries helped to contextualize the burden of malaria-related morbidity and mortality not only within their respective countries, but also across the African continent. Participation in the AMTF Symposia and Key Leader Events helped military leadership clarify the purpose and intention of their military objectives related to systemic malaria prevention and control while purposefully contributing to national land international-level malaria reduction capacity.


Centrifugal telencephalic afferent connections to the main and accessory olfactory bulbs.
Parallel to the olfactory system, most mammals possess an accessory olfactory or vomeronasal system. The olfactory and vomeronasal epithelia project to the main and accessory olfactory bulbs, which in turn project to adjacent areas of the telencephalon, respectively. New data indicate that projections arising from the main and accessory olfactory bulbs partially converge in the rostral telencephalon and are non-overlapping at caudal telencephalic levels. Therefore, the basal telencephalon should be reclassified in olfactory, vomeronasal, and mixed areas. On the other hand, it has been demonstrated that virtually all olfactory- and vomeronasal-recipient structures send reciprocal projections to the main and accessory olfactory bulbs, respectively. Further, non-chemosensory recipient structures also projects centrifugally to the olfactory bulbs. These feed-back projections appear to be essential modulating processing of chemosensory information. The present work aims at characterizing centrifugal projections to the main and accessory olfactory bulbs arising from olfactory, vomeronasal, mixed, and non-chemosensory recipient telencephalic areas. This issue has been addressed by using tracer injections in the rat and mouse brain. Tracer injections were delivered into the main and accessory olfactory bulbs as well as in olfactory, vomeronasal, mixed, and non-chemosensory recipient telencephalic structures. The results confirm that olfactory- and vomeronasal-recipient structures project to the main and accessory olfactory bulbs, respectively. Interestingly, olfactory (e.g., piriform cortex), vomeronasal (e.g., posteromedial cortical amygdala), mixed (e.g., the anterior medial amygdaloid nucleus), and non-chemosensory-recipient (e.g., the nucleus of the diagonal band) structures project to the main and to the accessory olfactory bulbs thus providing the possibility of simultaneous modulation and interaction of both systems at different stages of chemosensory processing.


The development of subcutaneous emphysema after delivery on a specially designed chair.
A case of a 23-year-old woman, with an uncomplicated term pregnancy, who developed subcutaneous emphysema 12 hours after the delivery on a specially designed chair is reported. Subcutaneous emphysema is an uncommon delivery complication, with a favourable outcome. The pathophysiology and treatment modalities of this rare phenomenon are discussed.


Allosteric effects of G protein overexpression on the binding of beta-adrenergic ligands with distinct inverse efficacies.
Allosteric models of G protein-coupled receptors predict that G protein influences the spontaneous isomerization between inactive (R) and active (R*) conformations. Since inverse agonists have been proposed to preferentially bind to the inactive and uncoupled form(s), changes in the G protein content should influence the binding properties of these ligands. To test this hypothesis, we systematically assessed the effect of G proteins on the binding of beta(2)-adrenergic ligands with distinct levels of inverse efficacy. Recombinant baculoviruses encoding the human beta(2)-adrenoreceptor (beta(2)AR) were expressed alone or in combination with G protein subunits in Sf9 cells. Coexpression with the G protein alpha s beta 1 gamma 2 did not influence the relative efficacy of the ligands to inhibit the adenylyl cyclase but induced considerable decrease in number of sites detected by [(3)H]ICI 118551, [(3)H]propranolol, and (125)I-cyanopindolol. This loss was proportional to the inverse efficacy of the ligand used as the radiotracer in the assay. The addition of Gpp(NH)p inhibited the effects of G protein overexpression indicating that the G proteins acted allosterically. Consistent with this notion, Western blot analysis revealed that coexpression with the G proteins was not accompanied by a loss of immunoreactive beta(2)AR. Such allosteric effects of the G proteins were also observed in mammalian cells expressing endogenous level of G proteins indicating that the phenomenon is not unique to overexpression systems. Taken together, these results demonstrate that the apparent receptor number detected by radiolabeled inverse agonists is affected by the content in G proteins as a result of their influence on R/R* isomerization.


Two different point mutations in ABL gene ATP-binding domain conferring Primary Imatinib resistance in a Chronic Myeloid Leukemia (CML) patient: A case report.
Imatinib (Gleevec) is the effective therapy for BCR-ABL positive CML patients. Point mutations have been detected in ATP-binding domain of ABL gene which disturbs the binding of Gleevec to this target leading to resistance. Detection of mutations is helpful in clinical management of imatinib resistance. We established a very sensitive (ASO) PCR to detect mutations in an imatinib-resistant CML patient. Mutations C944T and T1052C were detected which cause complete partial imatinib resistance, respectively. This is the first report of multiple point mutations conferring primary imatinib resistance in same patient at the same time. Understanding the biological reasons of primary imatinib resistance is one of the emerging issues of pharmacogenomics and will be helpful in understanding primary resistance of molecularly-targeted cancer therapies. It will also be of great utilization in clinical management of imatinib resistance. Moreover, this ASO-PCR assay is very effective in detecting mutations related to imatinib resistance.


Should the drinking water of Truro, Nova Scotia, be fluoridated? Water fluoridation in the 1990s.
An epidemiological assessment of differences in caries and fluorosis prevalences between children in Truro (< 0.1 ppm) and Kentville (fluoridated at 1.1 ppm in 1991), Nova Scotia, Canada, was completed in 1991. Out of a total of 429 children, in grades 5 and 6, in the two towns in 1991, 219 (51%) were examined. Parents answered a self-administered questionnaire investigating the sources of drinking water used by the children since birth, residence history, use of fluoride supplements, dentifrices, and other fluoride products during the first 6 yr of the life. The examination criteria differentiated between non-cavitated and cavitated carious lesions. Dental fluorosis was measured using the TSIF index. Examiner agreement was excellent. Of the children examined, 80 (36.5%) drank water (fluoridated or non-fluoridated) from municipal water systems during the first 6 yr of life. The children were assigned into five groups based upon residence history and exposure to fluoridated water during the first 6 yr of life. The percentage difference in mean DMFS scores between children in the fluoridated and non-fluoridated groups is 17% (delta DMFS1 = 0.7) when non-cavitated carious lesions are included and 39% (delta DMFS2 = 1.1) when they are excluded. The differences are not statistically significant. The significant risk factors associated with the DMFS1 and DMFS2 scores identified by a stepwise multiple regression analysis are: education level of the father, gender, and number of years of reported use of toothpaste during the first 6 yr of life. Dental fluorosis (mainly TSIF score of 1) was present in 41.5% and 69.2% of the children in the non-fluoridated and fluoridated groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Dog growls express various contextual and affective content for human listeners.
Vocal expressions of emotions follow simple rules to encode the inner state of the caller into acoustic parameters, not just within species, but also in cross-species communication. Humans use these structural rules to attribute emotions to dog vocalizations, especially to barks, which match with their contexts. In contrast, humans were found to be unable to differentiate between playful and threatening growls, probably because single growls' aggression level was assessed based on acoustic size cues. To resolve this contradiction, we played back natural growl bouts from three social contexts (food guarding, threatening and playing) to humans, who had to rate the emotional load and guess the context of the playbacks. Listeners attributed emotions to growls according to their social contexts. Within threatening and playful contexts, bouts with shorter, slower pulsing growls and showing smaller apparent body size were rated to be less aggressive and fearful, but more playful and happy. Participants associated the correct contexts with the growls above chance. Moreover, women and participants experienced with dogs scored higher in this task. Our results indicate that dogs may communicate honestly their size and inner state in a serious contest situation, while manipulatively in more uncertain defensive and playful contexts.


A Hyper-Crosslinked Carbohydrate Polymer Scaffold Facilitates Lineage Commitment and Maintains a Reserve Pool of Proliferating Cardiovascular Progenitors.
Cardiovascular progenitor cells (CPCs) have been cultured on various scaffolds to resolve the challenge of cell retention after transplantation and to improve functional outcome after cell-based cardiac therapy. Previous studies have reported successful culture of fully differentiated cardiomyocytes on scaffolds of various types, and ongoing efforts are focused on optimizing the mix of cardiomyocytes and endothelial cells as well as on the identification of a source of progenitors capable of reversing cardiovascular damage. A scaffold culture that fosters cell differentiation into cardiomyocytes and endothelial cells while maintaining a progenitor reserve would benefit allogeneic cell transplantation. Isl-1 + c-Kit + CPCs were isolated as clonal populations from human and sheep heart tissue. After hyper-crosslinked carbohydrate polymer scaffold culture, cells were assessed for differentiation, intracellular signaling, cell cycling, and growth factor/chemokine expression using real time polymerase chain reaction, flow cytometry, immunohistochemistry, and calcium staining. Insulin-like growth factor 1, hepatocyte growth factor, and stromal cell derived factor 1α paracrine factors were induced, protein kinase B signaling was activated, extracellular signal-regulated kinase phosphorylation was reduced and differentiation into both cardiomyocytes and endothelial cells was induced by scaffold-based cell culture. Interestingly, movement of CPCs out of the G1 phase of the cell cycle and increased expression of pluripotency genes PLOU5F1 (Oct4) and T (Brachyury) within a portion of the cultured population occurred, which suggests the maintenance of a progenitor population. Two-color immunostaining and 3-color fluorescence-activated cell sorting analysis confirmed the presence of both Isl-1 expressing undifferentiated cells and differentiated cells identified by troponin T and von Willebrand factor expression. Ki-67 labeling verified the presence of proliferating cells that remained in situ alongside the differentiated functional derivatives. Cloned Isl-1 + c-kit + CPCs maintained on a hyper-cross linked polymer scaffold retain dual potential for proliferation and differentiation, providing a scaffold-based stem cell source for transplantation of committed and proliferating cardiovascular progenitors for functional testing in preclinical models of cell-based repair.


Multifocal cutaneous tuberculosis coexisting with pulmonary tuberculosis.
Tuberculosis (TB) is caused by Mycobacterium tuberculosis and it can affect multiple organ systems. Cutaneous TB, a less common type of extrapulmonary TB can coexist with TB of other organs. Here, we describe a case of multifocal cutaneous TB suggestive of two different morphological types with concomitant miliary pulmonary TB.


Liver levels of retinol in unselected necropsy specimens: a prevalence survey of vitamin A deficiency in Recife, Brazil.
Total retinol was analyzed in 517 necropsy specimens from children 0 to 14 yr of age, deceased of various causes in Recife, Brazil, and from eight persons, 10 to 59 yr of age, who died violently. Age and nutritional status, in that order, were found to be the major determinants of the prevalence of low reserves, children less than 1 yr of age showing the highest prevalence of deficient values. These data were extrapolated to the live population less than 5 yr of age, categorized by age and nutritional status. By using the criteria that liver reserves of vitamin A less than 5 and 20 micrograms/g denote states of high risk and inadequacy, respectively, approximately 3 and 17% of children 0 to 4 yr of age in the live population of Recife were estimated to fall in the high risk and inadequate status group, respectively. None of the persons who died violently was at high risk and only one had inadequate reserves. These estimates agree with previous prevalence figures from clinical and biochemical surveys. Thus, the direct assessment of concentrations of vitamin A in the liver at necropsy is a simple, inexpensive, and noninvasive procedure for estimating the vitamin A status of children.


Frontal sinus destruction from allergic eosinophilic fungal rhinosinusitis.
Extensive fungal infections of the paranasal sinuses are most often associated with immunocompromised patients or poorly controlled diabetics. Seldom do young, otherwise healthy patients present with advanced disease destroying bone and compressing the dura and frontal lobe posteriorly. A case of eosinophilic fungal rhinosinusitis which grew Curvularia lunata in culture is reported. Bone destruction can be common as an expanding inflammatory mass pushes and weakens surrounding bone. The destruction of the frontal sinus with the compression of the dura into the anterior cranial fossa of a 26-year-old requires drainage, reconstruction, and medical management. Our experience with the disease and our approach is reviewed.


Rootstock-Mediated Effects on Cabernet Sauvignon Performance: Vine Growth, Berry Ripening, Flavonoids, and Aromatic Profiles.
Rootstocks are widely used in viticulture due to their resistance to biotic and abiotic stress. Additionally, rootstocks can affect vine growth and berry quality. This study evaluated the effects of eight rootstocks (101-14, 110R, 5A, 5BB, Ganzin 1, Harmony, Riparia Gloire, and SO4) on the vine growth, berry ripening, and flavonoids and aromatic profiles of Cabernet Sauvignon in two consecutive seasons (2015⁻2016). With few exceptions, minor differences were observed among grafted and own-rooted vines. Own-rooted vines produced the least pruning weight but the highest yield. 101-14, 5BB, and SO4 slightly reduced total soluble solids, but increased acidity, showing tendencies for retarding maturation. Ganzin 1 inhibited the accumulation of flavan-3-ols in berry skins. Furthermore, concentrations and proportions of epicatechin-3-O-galate were decreased by rootstocks, except for 110R. 5A, Harmony, and Riparia Gloire enhanced flavonol concentrations. SO4 slightly decreased most of the individual anthocyanin concentrations. With respect to volatile compounds, 110R, Riparia Gloire, and SO4 induced reductions in concentrations of total esters, whilst 101-14, Ganzin 1, 110R, and 5BB led to increases in the concentrations of C13-norisoprenoids. Therefore, with respect to the negative effects of SO4 on berry ripening and the accumulation of anthocyanin and volatile esters, SO4 is not recommended in practice.


The effect of heat treatment and skimming on precipitate formation in caprine and bovine milks.
Caprine and bovine milks have a similar overall gross composition, but vary considerably in the ratios of their casein components. These differences in colloidal casein micelles could affect directly or indirectly the heat stability of caprine and bovine milks at their natural pH. In the present work, the differences in colloidal stability of caprine and bovine milk have been studied by analysing the effect of heat treatment and skimming on precipitation of proteins. Raw and heated milk samples (70 °C/5 min, 80°C/5 min and 90°C/5 min) were centrifuged at 600, 2000, and 4500 g . The amount of precipitate formed after skimming was measured and the protein composition of both precipitates and supernatants analysed using the SDS-PAGE (sodium dodecyl sulphate polyacrylamide gel electrophoresis) and densitometry. In caprine milk, the heat treatment prior to skimming had a statistically significant effect on protein precipitation. Centrifugal force had a statistically significant effect on amount of precipitate for both milks, but the amount was 2 to 4 times higher for caprine milk. When defatting the milk for electrophoresis, a centrifugal force of 600 g appeared to be the most appropriate, in order to avoid protein loss and a possible error in the interpretation of results. Results of this study could also serve as the basis for further investigations on adjusting the skimming conditions for caprine milk in industrial dairy processing environment.


New perspectives on perfluorochemical ecotoxicology: inhibition and induction of an efflux transporter in the marine mussel, Mytilus californianus.
The toxicological effects of perfluoroalkyl acids on the p-glycoprotein (p-gp) cellular efflux transporter were investigated using the marine mussel Mytilus californianus as a model system. Four of the perfluoroalkyl acids studied exhibit chemosensitizing behavior, significantly inhibiting p-gp transporter activity. The inhibitory potency is maximal for the longer chain acids perfluorononanoate (PFNA) and perfluorodecanoate (PFDA), with average IC50 values of 4.8 and 7.1 microM, respectively. Results indicate that PFNA inhibits p-gp by an indirect mechanism, and this inhibition is reversible and accompanied by a rapid loss of PFNA from the tissue. In addition, PFNA induces expression of the p-gp transporter after a 2-h exposure, a stress response that may result in a metabolic cost to the organism. Given that most organisms, including humans, share efflux transporters as a first line of defense against toxicants, the results of this study may have broader implications for the ecotoxicology of perfluoroalkyl acids.


Thyroid cancer: current molecular perspectives.
The thyroid cancer is a rare oncological entity, representing no more than 1% of all human malignant neoplasms. Recently, it has been demonstrated a sharp increase in incidence of differentiated thyroid carcinoma, equally occurring in both sexes. So far, multiple genetic alterations have been identified in differentiated thyroid carcinoma, leading to investigate the clinical utility of genetic studies. In particular, molecular genetic approaches searching for gene mutations in the material collected by fine needle ago-biopsy may have a particular utility in small nodules and in those specimens with an indeterminate cytology. The expansion of knowledge about genetic mutations occurring in different thyroid tumors has characterized recent years, allowing the identification of a correlation between specific mutations and phenotypic characteristics of thyroid cancers, essential for their prognosis. This review will briefly report on the histological features and the new entity represented by thyroid microcarcinoma and will focus on both environmental and genetic aspects associated with the occurrence of thyroid cancer.


Ocular injury progression and cornea histopathology from chloropicrin vapor exposure: Relevant clinical biomarkers in mice.
Ocular tissue is highly sensitive to chemical exposures. Chloropicrin (CP), a choking agent employed during World War I and currently a popular pesticide and fumigating agent, is a potential chemical threat agent. Accidental, occupational, or intentional exposure to CP results in severe ocular injury, especially to the cornea; however, studies on ocular injury progression and underlying mechanisms in a relevant in vivo animal model are lacking. This has impaired the development of effective therapies to treat the acute and long-term ocular toxicity of CP. To study the in vivo clinical and biological effects of CP ocular exposure, we tested different CP exposure doses and durations in mice. These exposures will aid in the study of acute ocular injury and its progression as well as identify a moderate dose to develop a relevant rodent ocular injury model with CP. The left eyes of male BALB/c mice were exposed to CP (20% CP for 0.5 or 1 min or 10% CP for 1 min) using a vapor cap, with the right eyes serving as controls. Injury progression was evaluated for 25 days post-exposure. CP-exposure caused a significant corneal ulceration and eyelid swelling which resolved by day 14 post exposure. In addition, CP-exposure caused significant corneal opacity and neovascularization. Development of hydrops (severe corneal edema with corneal bullae) and hyphema (blood accumulation in the anterior chamber) was observed as advanced CP effects. Mice were euthanized at day 25 post-CP-exposure, and the eyes were harvested to further study the corneal injury. Histopathological analyses showed a significant CP-induced decrease in corneal epithelial thickness and increased stromal thickness with more pronounced damage, including stromal fibrosis, edema, neovascularization, trapped epithelial cells, anterior and posterior synechiae, and infiltration of inflammatory cells. Loss of the corneal endothelial cells and Descemet's membrane could be associated with the CP-induced corneal edema and hydrops which could lead to long term term pathological conditions. Although exposure to 20% CP for 1 min caused more eyelid swelling, ulceration, and hyphema, similar effects were observed with all CP exposures. These novel findings following CP ocular exposure in a mouse model outline the corneal histopathologic changes that associate with the continuing ocular clinical effects. The data are useful in designing further studies to identify and correlate the clinical and biological markers of CP ocular injury progression with acute and long-term toxic effects on cornea and other ocular tissues. We take a crucial step towards CP ocular injury model development and in pathophysiological studies to identify molecular targets for therapeutic interventions.