Colorectal cancer with multiple metachronous metastasis achieving complete remission 14 years after surgical resection: report of a case.
A 63-year-old man underwent a colectomy for sigmoid colon cancer in 1997. The upper lobe of his left lung and his left adrenal gland were resected because of metachronous metastases, 7 and 10 years after the initial surgery, respectively. Recurrence of metastases to the middle lobe of the right lung and left adrenal gland were sequentially detected in 2007, and a multimodal therapy, consisting of the combination of radiotherapy and chemotherapy, was conducted since 2007. The chemotherapy included drugs such as FOLFOX, FOLFIRI, bevacizumab, capecitabine, and cetuximab. In 2011, the complete response of all metastatic lesions could be achieved, and no recurrence was detected for more than 1 year. In spite of repeated recurrences, by the combination of surgical resection, chemotherapy, and radiotherapy, the complete response could be achieved 14 years after the initial surgical resection, which can be attributed to the development of new treatment modalities and new agents for colorectal cancer.


Environmental fate and biodegradability of benzene derivatives as studied in a model aquatic ecosystem.
A model aquatic ecosystem is devised for studying relatively volatile organic compounds and simulating direct discharge of chemical wastes into aquatic ecosystems. Six simple benzene derivatives (aniline, anisole, benzoic acid, chlorobenzene, nitrobenzene, and phthalic anhydride) and other important specialty chemicals: hexachlorobenzene, pentachlorophenol, 2,6-diethylaniline, and 3,5,6-trichloro-2-pyridinol were also chosen for study of environmental behavior and fate in the model aquatic ecosystem. Quantitative relationships of the intrinsic molecular properties of the environmental micropollutants with biological responses are established, e.g., water solubility, partition coefficient, pi constant, sigma constant, ecological magnification, biodegradability index, and comparative detoxication mechanisms, respectively. Water solubility, pi constant, and sigma constant are the most significant factors and control the biological responses of the food chain members. Water solubility and pi constant control the degree of bioaccumulation, and sigma constant limits the metabolism of the xenobiotics via microsomal detoxication enzymes. These highly significant correlations should be useful for predicting environmental fate of organic chemicals.


Human corticotroph cell adenomas.
Sixty-one pituitary corticotroph adenomas from 47 patients with Cushing's disease, 10 with Nelson's syndrome, and four eucorticoid patients were studied by light microscopy, immunoperoxidase, and electron microscopy. Seventy nine percent of all tumors and 70% of Nelson's cases were microadenomas, sometimes minute. A contiguity between the posterior lobe and the adenoma was seen in ten cases. Spontaneous infarction of the tumor with remission of Cushing's syndrome occurred in one case. Light microscopy revealed that the adenoma cells were basophilic and contained PAS-positive granules also staining with Herlant tetrachrome and lead-hematoxylin. The granules stained positively with antiserum to adrenocorticotrophic hormone (ACTH), beta-lipotropic hormones (beta-LPH) and beta-endorphin. The most characteristic ultrastructural finding was the presence of perinuclear bundles of microfilaments found in all our cases. Oncocytic changes were seen in three tumors. Four silent corticotroph adenomas, two of them originally microadenomas that had enlarged to enclosed adenomas while being treated with bromocriptine for hyperprolactinemia and one a large diffuse invasive tumor, did not differ in their microscopic, immunocytological, or ultrastructural features.


Vitamin D receptor as a therapeutic target for benign prostatic hyperplasia.
The bioactive form of vitamin D, 1α, 25-dihydroxyvitamin D3 (1α, 25(OH)2D3), is a secosteroid hormone that binds to the vitamin D receptor (VDR), a member of the nuclear receptor super-family expressed in many cell types, and modulates a variety of biological functions. 1α, 25(OH)2D3 is essential for bone and mineral homeostasis, but also regulates growth and differentiation of multiple cell types, and displays immunoregulatory and anti-inflammatory activities. The antiproliferative, prodifferentiative, antibacterial, immunomodulatory and anti-inflammatory properties of synthetic VDR agonists could be exploited to treat a variety of chronic inflammatory and autoimmune diseases, including benign prostatic hyperplasia (BPH). It has been hypothesized that VDR may influence both the risk of a variety of diseases and their occurrence and prognosis. However, earlier studies investigating the associations between specific VDR polymorphisms and various diseases often show controversial results. We performed a systematic review of the current literature on vitamin D and BPH using the PubMed and Web of Knowledge databases. The aim of this review is to summarize the current knowledge on the utility of the VDR gene regarding prostate growth as well as the pathogenesis and treatment of BPH, a complex syndrome characterized by a static component related to prostate overgrowth, a dynamic component responsible for urinary storage symptoms, and an inflammatory component. Despite the massive advances in recent decades, further research is needed to fully characterize the exact underlying mechanisms of VDR action on BPH and to comprehend how these cellular changes translate into clinical development in physical concert.


Relation of perinatal risk and early parenting to executive control at the transition to school.
Executive control (EC) develops rapidly during the preschool years and is central to academic achievement and functional outcome. Although children with perinatal adversity are at known risk for EC impairments, little is known about the underlying nature of these impairments or the mechanisms that contribute to their development over time. Drawing on a cohort of 110 high-risk children born very preterm (VPT; < 33 weeks / < 1500 g) and 113 healthy full-term children, this study examined the implications of perinatal adversity and early parenting for children's EC as they transitioned to formal schooling. Parent supportive presence, intrusiveness, and parent-child synchrony were observed during a series of problem-solving tasks at ages 2 and 4 years. At age 6, children completed a comprehensive battery of EC tasks. Academic outcomes were assessed at age 9. The VPT group showed global EC impairments at age 6, although the unitary factor that best characterized the structure of EC was the same in both groups. High-risk dyads were characterized by more intrusive and less synchronous parent-child interactions in early childhood, which in turn predicted poorer child EC at age 6. EC partially mediated the relation of risk status to poorer academic achievement at age 9. Findings demonstrate the cumulative effects of perinatal adversity on children's EC in the crucial transition to schooling. They also highlight the importance of the parent-child relationship as a target for intervention efforts to help mitigate these effects.


Stereospecific analysis of triacylglycerols as a useful means to evaluate genuineness of pumpkin seed oils: lesson from virgin olive oil analyses.
In Slovenia two superb vegetable oils with high added nutritional value are produced: "Ekstra devisko oljcno olje Slovenske Istre (extra virgin olive oil from Slovene Istra)" and "Stajersko prekmursko bucno olje (pumpkin seed oil from Slovenia)". Their quality and genuineness must be monitored as adulteration can easily be undertaken. Olive oil genuineness determination experiences can show how analyses following an experience data-driven decision tree gathering several chemical determinations (fatty acids, (E)-isomers of fatty acids, sterol and tocopherol determinations) may be helpful in assessing the pumpkin seed oil from Slovenia genuineness. In the present work a set of HPLC triacylglycerol determinations was performed, based on the nine main triacylglycerols (LLLn, LLL, PLL, LOO, PLO, OOO, POO, SPL, and SLS) on a limited number of different pumpkin seed oils from northeastern Slovenia. The performed determinations showed that stereospecific analyses of triacylglycerols together with other chemical determinations can be useful in building a protocol for the evaluation of the genuineness of pumpkin seed oil from Slovenia.


A TEST OF THE CHITTY HYPOTHESIS: INHERITANCE OF LIFE-HISTORY TRAITS IN MEADOW VOLES MICROTUS PENNSYLVANICUS.
The Chitty hypothesis proposes that the demographic changes occurring in microtine cycles are mediated by natural selection operating on the genetic composition of the population. Implicit in this hypothesis is the assumption that a suite of life-history traits is simultaneously undergoing selection and that these traits are strongly heritable. We tested this in two ways: first, by determining whether the year-to-year differences in phenotypes in fluctuating meadow vole populations in the field are maintained in samples of young animals raised in the laboratory, and second, whether the variation seen in the field has a heritable basis as determined by half-sib analysis. Parents were obtained in the springs of successive years from a fluctuating meadow vole population. These animals were bred in small field enclosures, and their progeny were raised in the laboratory. Animals raised in the laboratory differed significantly from those in the natural field population. In the field, young from the year when population size was increasing grew more rapidly than those from the peak year; in the laboratory, the opposite occurred. The ages at sexual maturity showed similar differences. Heritability analysis was performed on body weight, growth rate, and age and weight at sexual maturity. Virtually all these traits showed significant dam effects, but small or nonexistant sire effects. Thus, most of the variation was nongenetic in origin; maternal and other environmental effects were of overriding importance. We conclude that the heritabilities of these traits in nature are usually lower than necessary for natural selection to operate in the time frames characteristic of microtine cycles.


Morphology and contractile gene expression of adipose-derived mesenchymal stem cells in response to short-term cyclic uniaxial strain and TGF-β1.
Previous studies have shown smooth muscle induction in adipose-derived mesenchymal stem cells (ASCs) caused by long-term cyclic stretch. Here we examined the capability of the short-term straining with time steps of 4, 8, 16 and 24 h alone or combined with TGF-β1 on smooth muscle induction of rabbit ASCs. Alterations in cell morphology were quantified through the cell shape index and orientation angle, and expression levels of α-SMA, SM22-α, h-caldesmon and calponin3 markers were examined using the real-time polymerase chain reaction (PCR) method. Moreover, F-actin cytoskeleton organization was observed by fluorescence staining. Mechanical strain either alone or combined with growth factor treatment caused significant up-regulation of both early and intermediate smooth muscle cells (SMCs) specific markers during the initial hours of stimulation peaking in 8 to 16 h. Furthermore, gradual alignment of cells perpendicular to the strain direction during loading time, and cell elongation resembling contractile SMC phenotype, together with alignment and reorganization of F-actin fibers were observed. Considering previously reported protein up-regulation in following days of straining, the effects of short-term cyclic stretch on smooth muscle induction of ASCs were revealed which can be helpful in achieving functional contractile SMCs through synergistic mechano-chemical regulation of ASCs as an appealing cell source for vascular tissue engineering.


[Risk factors analysis of postsurgical gastroparesis syndrome and its impact on the survival of gastric cancer after subtotal gastrectomy].
To investigate the risk factors of postsurgical gastroparesis syndrome (PGS) after subtotal gastrectomy in gastric cancer and the impact of PGS on prognosis. Clinical data of 422 patients who underwent subtotal gastrectomy for gastric cancer in the Central Hospital of Huzhou Sity from January 2004 to May 2010 were analyzed retrospectively. Risk factors of PGS were indentified and the recurrence-free survival was compared between the patients with and without PGS. PGS occurred in 42 patients (9.5%). Univariate analysis showed that: age over 65, combination of anxiety disorder, low-albuminemia in perioperative period, pyloric obstruction in preoperative period, high serume glucose level (≥ 11.2 mmol/L) in postoperative period, Billroth II (gastroenterostomy, operation time over 4 hours, using patient-controlled analgesia, or intravenous fluid over 3500 ml/d (all P<0.05) were prone to develop PGS. These might be potential clinical risk factors associated to PGS. Correlation analysis showed the number of clinical risk factors was positively correlated with the incidence of PGS (r=0.967, P<0.05). A total of 215 cases (50.9%) were followed up for 3-60 months. The mean recurrence-free survival time of patients with PGS was 26.1 months, which was shorter than that of those without PGS (33.4 months, P=0.029). Gastric cancer patients with the clinical risk factors mentioned above are prone to develop PGS after subtotal gastrectomy. PGS is associated with poor prognosis.


Obrieniolus, a new monotypic genus of Naupactini (Coleoptera, Curculionidae, Entiminae) from the Peruvian Andes and its phylogenetic placement.
A new monotypic genus of Naupactini (Coleoptera: Curculionidae), Obrieniolus del Río is described based on the new species Obrieniolus robustus del Río, endemic to Peru. This genus is easily recognized by the black, denuded and shiny integument, with imbricate microsculpture and the rounded body, with short, cordiform and moderately convex elytra. According to a cladistic analysis based on 69 continuous and discrete morphological characters, the new genus is the sister taxon of a group formed by Amitrus Schoenherr, Trichocyphus Heller, Amphideritus Schoenherr, Asymmathetes Wibmer & O'Brien and Galapaganus Lanteri. The paper includes habitus photographs, line drawings of genitalia, mouthparts, and other external features of taxonomic value, and a dichotomous key to the genera of Naupactini distributed in the South American Transition Zone.


Primary osteosarcoma of the penis.
We report a case of an 84-year-old man with extraskeletal osteosarcoma of the penis arising within heterotopic bone. Extraskeletal osteosarcoma of the penis is an exceedingly rare entity; only two other well-documented cases have been reported in the English-language literature.


Borehole flowmeter logging for the accurate design and analysis of tracer tests.
Tracer tests often give ambiguous interpretations that may be due to the erroneous location of sampling points and/or the lack of flow rate measurements through the sampler. To obtain more reliable tracer test results, we propose a methodology that optimizes the design and analysis of tracer tests in a cross borehole mode by using vertical borehole flow rate measurements. Experiments using this approach, herein defined as the Bh-flow tracer test, have been performed by implementing three sequential steps: (1) single-hole flowmeter test, (2) cross-hole flowmeter test, and (3) tracer test. At the experimental site, core logging, pumping tests, and static water-level measurements were previously carried out to determine stratigraphy, fracture characteristics, and bulk hydraulic conductivity. Single-hole flowmeter testing makes it possible to detect the presence of vertical flows as well as inflow and outflow zones, whereas cross-hole flowmeter testing detects the presence of connections along sets of flow conduits or discontinuities intercepted by boreholes. Finally, the specific pathways and rates of groundwater flow through selected flowpaths are determined by tracer testing. We conclude that the combined use of single and cross-borehole flowmeter tests is fundamental to the formulation of the tracer test strategy and interpretation of the tracer test results.


Safety and Efficacy of Alginate Adhesion Barrier Gel in Compromised Intestinal Anastomosis.
For any anti-adhesive barrier developed for abdominal surgery, the use under conditions in which anastomotic healing is compromised needs to be investigated. The current study evaluates the effect of a new ultrapure alginate gel on early healing of high-risk anastomoses in the ileum and compares this with the gold standard used in clinical practice. In 75 adult male Wistar rats, a 5 mm ileal segment was resected and continuity was restored by construction of an inverted anastomosis. Rats were divided randomly into a control group and groups receiving either alginate gel or a sodium hyaluronate carboxymethylcellulose (HA/CMC) film around the anastomosis (n = 25 each). Carprofen, given in a daily dose of 1.25 mg/kg, was used to compromise anastomotic healing. At day three, animals were killed and scored for signs of anastomotic leakage and the presence of adhesions. The incidence of adhesion formation was 95% in the HA/CMC film group, which was significantly higher than in the controls (64%, p = 0.010) and the alginate gel group (52%, p = 0.004). The adhesion score was nearly 40% lower in the alginate gel group compared with the HA/CMC film group. The incidence of ileal leakage in the HA/CMC film group (92%) was significantly higher than in the controls (68%, p = 0.016). Leakage rate did not differ between the alginate gel and control groups. There was no significant difference between groups in either incision bursting pressure or incision breaking strength. Ultrapure alginate gel does not interfere with repair of ileal anastomoses constructed under conditions in which chances of anastomotic dehiscence are high. The alginate gel performs better than the HA/CMC film.


Change of Cu,Zn-superoxide dismutase activity of guinea pig lung in experimental asthma.
Correlation between the level of reactive oxygen species (ROS) generated by airway inflammatory cells and superoxide dismutase (SOD) activity of pulmonary tissue during an asthma attach was investigated in a guinea pig model of allergic asthma. In addition, the influence of SOD inhibition by diethyldithiocarbamate (DDC, Cu-chelating agent) on the airway was investigated in terms of pulmonary function during an asthma attach. Relative to controls, the capacity of bronchoalveolar lavage fluid (BAL) cells to release ROS was significantly increased in guinea pigs sensitized with ovalbumin (OA) as the antigen, and significantly increased in guinea pigs with an asthma attack provoked by the inhalation of OA. SOD activity was increased significantly in the antigen-sensitized group. The asthma provocation group showed a tendency for increase in total SOD activity, compared with the sensitization group, whose increase was dependent on the increase in copper, zinc-SOD (Cu, Zn-SOD) activity. Pretreatment with DDC increased the severity and duration of the asthma attack. These results were indicated that Cu, Zn-SOD was closely involved in the asthma process, particularly in the scavenging of oxygen radicals secreted from BAL cells.


Total dislocation of the talus. Case report with a 13-year follow up and review of the literature.
Simultaneous dislocation of the talus from the tibiotalar, talocalcaneal, and talonavicular joints is uncommon and usually occurs from considerable violence. Total dislocation of the talus is frequently an open injury, or the skin may be tented over the dislocated talus leading to skin slough. Infection and avascular necrosis may follow. Treatment options include closed or open reduction, talectomy, and arthrodesis. The following case and literature review illustrate some of the problems encountered and factors that influence the outcome of this injury.


TWINS: improved spatial and angular phase calibration for holography.
We present TWINS (TWo INclining Slits), a method for characterizing phase spatial light modulators (SLMs), inspired by Young interferometry. TWINS is an elegant and versatile approach, using minimal equipment and alignment. It measures phase response locally rather than globally, both horizontally and vertically, with high resolution and at wide angles. It can also measure beam intensity profiles as directly seen by the SLM. TWINS characterizes the anisotropic aberrations in the mainstream models of liquid crystal phase SLMs, which is crucial to improve hologram quality. Compensating for anisotropic aberrations measured by TWINS improved the image quality of planar holograms by 10 dB.


Evaluation of a turbidimetric C-reactive protein assay to monitor early-onset neonatal sepsis in South Kivu (Democratic Republic of the Congo).
Neonatal sepsis, a condition defined as bacteremia within the first month of life accompanied by signs of systemic infection, is the most preventable cause of infant mortality in sub-Saharan Africa. Despite the development of new infection markers, C-reactive protein (CRP) is the most extensively studied acute phase reactant so far and the preferred index in many neonatal intensive care units (NICUs). The aim of the present study was to evaluate an affordable, non-commercial turbidimetric CRP assay for monitoring early-onset neonatal sepsis (EOS). A total of 148 neonates admitted at the NICU of the Hôpital Provincial Général de Référence de Bukavu to diagnose and to monitor EOS were enrolled in the study. CRP was assayed using a functional turbidimetric assay based on the interaction of CRP with phosphocholine containing particles (Intralipid®). In total, 62/148 (41.9%) cases were identified as blood culture-proven EOS. Different serum CRP slopes were observed among the different birth weight categories. Moreover, the serum (CRP 48 h-CRP 12 h) difference and the birth weight predicted the outcome of these septic newborns. Our turbidimetric CRP assay is a potential novel tool that can be used in the management of EOS in sub-Saharan Africa. The simplicity of the assay and the extremely low price make the CRP method very well suited for developing countries.


Antiretroviral therapy and the human immunodeficiency virus--improved survival but at what cost?
Patients infected with human immunodeficiency virus are living longer since the introduction of combination antiretroviral therapy more than a decade ago - but at what cost? Highly active antiretroviral therapy has been associated with lipodystrophy and associated metabolic derangements such as dyslipidaemia, insulin resistance and diabetes. These complications are likely to contribute to an increased risk of premature and accelerated atherosclerosis with growing concern about potential cardiovascular consequences.


Effect of antispasmodic agents, alone or in combination, in the treatment of Irritable Bowel Syndrome: systematic review and meta-analysis.
Irritable bowel syndrome (IBS) is characterized by recurrent abdominal pain, bloating, and changes in bowel habit. To determine the clinical effectiveness of the antispasmodic agents available in Mexico for the treatment of IBS. We carried out a systematic review and meta-analysis of randomized controlled clinical trials on antispasmodic agents for IBS treatment. Clinical trials identified from January 1960 to May 2011 were searched for in MEDLINE, the Cochrane Library, and in the ClinicalTrials.gov registry. Treatment response was evaluated by global improvement of symptoms or abdominal pain, abdominal distention/bloating, and frequency of adverse events. The effect of antispasmodics vs placebo was expressed in OR and 95% CI. Twenty-seven studies were identified, 23 of which fulfilled inclusion criteria. The studied agents were pinaverium bromide, mebeverine, otilonium, trimebutine, alverine, hyoscine, alverine/simethicone, pinaverium/simethicone, fenoverine, and dicyclomine. A total of 2585 patients were included in the meta-analysis. Global improvement was 1.55 (CI 95%: 1.33 to 1.83). Otilonium and the alverine/simethicone combination produced significant values in global improvement while the pinaverium/simethicone combination showed improvement in bloating. As for pain, 2394 patients were included with an OR of 1.52 (IC 95%: 1.28 a 1.80), favoring antispasmodics. Antispasmodics were more effective than placebo in IBS, without any significant adverse events. The addition of simethicone improved the properties of the antispasmodic agents, as seen with the alverine/simethicone and pinaverium/simethicone combinations.


A randomized, placebo-controlled phase ii study evaluating the reduction of neutropenia and febrile neutropenia in patients with colorectal cancer receiving pegfilgrastim with every-2-week chemotherapy.
Adding irinotecan and/or oxaliplatin to every-2-week 5-fluorouracil (5-FU)/leucovorin (LV) prolongs survival in patients with colorectal cancer (CRC) but increases neutropenia frequency. Pegfilgrastim is indicated to decrease infection as manifested by febrile neutropenia (FN) in patients receiving chemotherapy at > 14-day intervals. This randomized, placebo-controlled phase II study examined pegfilgrastim efficacy and safety in patients with CRC receiving every-2-week chemotherapy. Patients with CRC were randomized 1:1 to pegfilgrastim 6 mg or placebo administered per-cycle on day 4. Randomization was stratified by chemotherapy regimen (patients received every-2-week FOLFOX4 [5-FU/LV/oxaliplatin], FOLFIRI [5-FU/LV/irinotecan], or FOIL [5-FU/LV/oxaliplatin/irinotecan] at physician discretion). The primary endpoint was incidence of grade 3/4 neutropenia. Secondary endpoints included incidence of grade 3/4 FN and adverse events. After 4 cycles of study treatment, progression-free survival (PFS) and overall survival (OS) were followed for <or= 2 years in long-term follow-up. Of 241 eligible patients analyzed, 118 were in the placebo and 123 in the pegfilgrastim group. In the treatment period, the odds ratio for grade 3/4 neutropenia for pegfilgrastim versus placebo was 0.19 (95% CI, 0.10-0.37; P < .001); grade 3/4 FN incidence was also significantly lower in pegfilgrastim-treated patients (2%) compared with placebo-treated patients (8%; P = .04). Pegfilgrastim was well tolerated, with leukocyte counts remaining stable during cycles 2-4. In long-term follow-up, both treatment groups had similar PFS and OS. Pegfilgrastim was well tolerated in patients with CRC receiving every-2-week chemotherapy and significantly reduced neutropenia and FN compared with placebo, though FN was uncommon in both treatment groups. Results suggest that pegfilgrastim administration is feasible in CRC patients receiving every-2-week chemotherapy.


Endogenous skeletal muscle antioxidants.
Skeletal muscle is susceptible to oxidative deterioration due to a combination of lipid oxidation catalysts and membrane lipid systems that are high in unsaturated fatty acids. To prevent or delay oxidation reactions, several endogenous antioxidant systems are found in muscle tissue. These include alpha-tocopherol, histidine-containing dipeptides, and antioxidant enzymes such as glutathione peroxidase, superoxide dismutase, and catalase. The contribution of alpha-tocopherol to the oxidative stability of skeletal muscle is largely influenced by diet. Dietary supplementation of tocopherol has been shown to increase muscle alpha-tocopherol concentrations and inhibit both lipid oxidation and color deterioration. Dietary selenium supplementation has also been shown to increase the oxidative stability of muscle presumably by increasing the activity of glutathione peroxidase. The oxidative stability of skeletal muscle is also influenced by the histidine-containing dipeptides, carnosine and anserine. Whereas carnosine and anserine are affected by diet less than alpha-tocopherol and glutathione peroxidase, their concentrations vary widely with species and muscle type. In pigs, beef, and turkey muscle, carnosine concentrations are greater than anserine, while the opposite is true in rabbit, salmon, and chicken muscle. Anserine and carnosine are found in greater concentrations in muscle high in white fibers, with chicken white muscle containing over fivefold more anserine and carnosine than red muscle. Anserine and carnosine are thought to inhibit lipid oxidation by a combination of free radical scavenging and metal chelation.


NETWORK DIFFERENTIAL CONNECTIVITY ANALYSIS.
Identifying differences in networks has become a canonical problem in many biological applications. Existing methods try to accomplish this goal by either directly comparing the estimated structures of two networks, or testing the null hypothesis that the covariance or inverse covariance matrices in two populations are identical. However, estimation approaches do not provide measures of uncertainty, e.g., p-values, whereas existing testing approaches could lead to misleading results, as we illustrate in this paper. To address these shortcomings, we propose a qualitative hypothesis testing framework, which tests whether the connectivity structures in the two networks are the same. our framework is especially appropriate if the goal is to identify nodes or edges that are differentially connected. No existing approach could test such hypotheses and provide corresponding measures of uncertainty. Theoretically, we show that under appropriate conditions, our proposal correctly controls the type-I error rate in testing the qualitative hypothesis. Empirically, we demonstrate the performance of our proposal using simulation studies and applications in cancer genomics.


Partial characterization of the Nicotiana tabacum actin gene family: evidence for pollen-specific expression of one of the gene family members.
The actin gene family of Nicotiana tabacum has been partially characterised by Southern hybridisation and by isolating lambda EMBL4 recombinants from a genomic library having homology to the soybean actin gene, Sac3. The number of actin genes with homology to Sac3 is estimated at between 20 to 30, based on Southern hybridisation and library screening, though the total gene family may be larger. Twenty-four recombinant lambda clones were isolated, 18 had unique restriction profiles and from these, 2 clones, Tac9 and Tac25, were selected for further study. The region of Tac25 hybridizing to Sac3 was sequenced and shown to contain an open reading frame (ORF) with homology to actin. Partial sequencing of Tac9 revealed a sequence with homology to the third exon of Tac25 and Sac3. The two tobacco actin sequences were compared to other reported actin gene sequences; Tac25 was closely related to the allelic potato actins, Pac58 and Pac85, while Tac9 was more related to Pac79 than to other plant actins. Northern hybridisation analysis showed that while Tac9 detected actin transcripts in RNA from root, leaf, stigma and pollen, Tac25 transcripts were only detected in pollen RNA.


Synthesis and anticancer activities of a novel class of mono- and di-metallic Pt(II)(salicylaldiminato)(DMSO or Picolino)Cl complexes.
A series of novel Pt(ii) complexes [cis- and trans-Pt(ii)(salicylaldimine)(DMSO)Cl (), trans-Pt(ii)(salicylaldimine)(4-picoline)Cl (), Pt(ii)(salicylaldimine)Cl (), trans- and cis/trans-Pt2(ii)(salicylaldimine)(DMSO)2Cl2 (), trans-Pt2(ii)(salicylaldimine)(4-picoline)2Cl2 () was synthesized and characterized. The structures of -cis, -trans and were determined using a single crystal X-ray analysis. This class of Pt(ii) complexes has been studied for their in vitro cytotoxicity in multiple human cancer cell lines, including breast (MCF-7), liver (HepG2), lung (A549), colon (HCT116) and cervical (Hela) cancers. -trans, and -trans showed significant cytotoxicity to these cancer cells comparable to cisplatin. A time- and dose-dependent MTT assay revealed that these complexes can suppress cell viability and cell proliferation. Mechanistically these complexes induced pro-apoptotic gene expression such as BAX, PUMA and NOXA and thereby enhanced apoptosis. Moreover, PARP cleavage in a dose-dependent manner indicated their cytotoxic effect against cancer cells. Apoptosis of cancer cells occurred through apoptotic pathways as explained by the cytometry analysis. The DNA unwinding properties of these active Pt(ii) complexes were studied by gel electrophoresis using pBR322 plasmid DNA as a target. Changes in the morphology of cancer cells were also observed upon the addition of -trans, and -trans.


A Simultaneous Localization and Mapping System Using the Iterative Error State Kalman Filter Judgment Algorithm for Global Navigation Satellite System.
Outdoor autonomous mobile robots heavily rely on GPS data for localization. However, GPS data can be erroneous and signals can be interrupted in highly urbanized areas or areas with incomplete satellite coverage, leading to localization deviations. In this paper, we propose a SLAM (Simultaneous Localization and Mapping) system that combines the IESKF (Iterated Extended Kalman Filter) and a factor graph to address these issues. We perform IESKF filtering on LiDAR and inertial measurement unit (IMU) data at the front-end to achieve a more accurate estimation of local pose and incorporate the resulting laser inertial odometry into the back-end factor graph. Furthermore, we introduce a GPS signal filtering method based on GPS state and confidence to ensure that abnormal GPS data is not used in the back-end processing. In the back-end factor graph, we incorporate loop closure factors, IMU preintegration factors, and processed GPS factors. We conducted comparative experiments using the publicly available KITTI dataset and our own experimental platform to compare the proposed SLAM system with two commonly used SLAM systems: the filter-based SLAM system (FAST-LIO) and the graph optimization-based SLAM system (LIO-SAM). The experimental results demonstrate that the proposed SLAM system outperforms the other systems in terms of localization accuracy, especially in cases of GPS signal interruption.


[Increased expression of fatty acid binding protein 4 in lungs of preterm rats after hyperoxic lung injury].
To study the expression of fatty acid binding protein 4 (FABP4) in lungs and bronchoalveolar lavage fluid (BALF) of preterm rats exposed to 60% O2 and to elucidate the relationship between the changes of FABP4 expression and the pathogenesis of bronchopulmonary dysplasia (BPD). Hyperoxic lung injury was induced by exposing to 60% O2 in Spraque-Dawley rats within 6 hours after birth. Rats exposed to air were used as the control group. The lungs from groups aged postnatal days 3, 7 and 14 were removed and dissected from the main bronchi for analysis. Eight rats of each group were used to assess expression of FABP4 in lungs by immunohistochemistry and ELISA. Lung FABP4 mRNA levels were measured by semi-quantitative reverse transcription polymerase chain reaction. The levels of FABP4 in BALF were measured using ELISA. FABP4 immunoreactivity was detected in the majority of alveolar macrophages, bronchial epithelial cells and endothelial cells. FABP4 protein levels in lung tissues in the hyperoxic exposure group increased significantly compared with the control group on days 3, 7 and 14 after birth (P<0.05), and FABP4 mRNA levels in lung tissues also increased significantly in the hyperoxic exposure group compared with the control group on days 7 and 14 after birth (P<0.05). The hyperoxic exposure group demonstrated increased FABP4 levels in BALF compared with the control group on days 7 and 14 after birth (P<0.05). FABP4 levels increase in preterm rat lungs after hyperoxic lung injury, which may contribute to the pathogenesis of BPD.


Inaccuracy of lung adenocarcinoma subtyping using preoperative biopsy specimens.
The prognostic significance of the new classification of lung adenocarcinoma proposed in the 2015 World Health Organization guideline has been validated. This study aimed to compare the preoperative classification of the adenocarcinoma subtype based on computed tomography-guided 18-gauge core needle biopsy (CTNB) or radial probe endobronchial ultrasound (R-EBUS) specimens, with the postoperative classification based on the resected specimens. We retrospectively analyzed a consecutive series of 128 patients (60 CTNB and 68 R-EBUS) who underwent surgery for preoperatively confirmed lung adenocarcinoma between 2010 and 2014. Comprehensive histological subtyping was performed according to the 2015 World Health Organization classification system. Diagnostic concordance of subtypes between small biopsy and resection specimens was assessed. Concordant subtyping of adenocarcinomas between the predominant pattern on resections and biopsy sections was observed in 58.6% of cases (75 of 128; 95% confidence interval [CI], 49.9%-66.8%). Preoperative subtyping was accurate in only 30% of samples (3 of 10) with a predominance of solid patterns. None of the 5 micropapillary predominant cases was detected by CTNB or R-EBUS. For the concordance of the presence or absence of micropapillary/solid component, the sensitivity was as low as 16.5% (95% CI, 9.1%-26.5%). The detection rate by CTNB/R-EBUS increased with the increase in the percentage of micropapillary/solid component; however, even in the ≥40% micropapillary/solid group, only 24% of cases were detected by CTNB/R-EBUS. The accuracy of the estimation of adenocarcinoma histological subtype based on preoperative biopsy sections was unsatisfactory.


Effect of acyl-CoA oxidase activity on the accumulation of gamma-decalactone by the yeast Yarrowia lipolytica: a factorial approach.
beta-Oxidation is a cyclic pathway involved in the degradation of lipids. In yeast, it occurs in peroxisomes and the first step is catalyzed by an acyl-CoA oxidase (Aoxp). The yeast Yarrowia lipolytica possesses several genes (POX) coding for Aoxps. This study is based on the factorial analysis of results obtained with the many POX derivative strains that have been constructed previously. The effect of interactions between Aoxps on the acyl-CoA oxidase (Aox) activity was important even at the second order. We then investigated the effect of Aox activity on growth and lactone production. Aox activity was correlated with acidification of the medium by cells and with cellular growth but not with lactone production, although Aox activity on short chains was inversely correlated with lactone accumulation. Due to the poor correlation between Aox activity and lactone production, the modeling of this parameter gave no satisfactory results but growth depending on Aox activity was modeled.


Analysis of the Bile Salt Export Pump (ABCB11) Interactome Employing Complementary Approaches.
The bile salt export pump (BSEP, ABCB11) plays an essential role in the formation of bile. In hepatocytes, BSEP is localized within the apical (canalicular) membrane and a deficiency of canalicular BSEP function is associated with severe forms of cholestasis. Regulation of correct trafficking to the canalicular membrane and of activity is essential to ensure BSEP functionality and thus normal bile flow. However, little is known about the identity of interaction partners regulating function and localization of BSEP. In our study, interaction partners of BSEP were identified in a complementary approach: Firstly, BSEP interaction partners were co-immunoprecipitated from human liver samples and identified by mass spectrometry (MS). Secondly, a membrane yeast two-hybrid (MYTH) assay was used to determine protein interaction partners using a human liver cDNA library. A selection of interaction partners identified both by MYTH and MS were verified by in vitro interaction studies using purified proteins. By these complementary approaches, a set of ten novel BSEP interaction partners was identified. With the exception of radixin, all other interaction partners were integral or membrane-associated proteins including proteins of the early secretory pathway and the bile acyl-CoA synthetase, the second to last, ER-associated enzyme of bile salt synthesis.


Neutron tomographic imaging of bone-implant interface: Comparison with X-ray tomography.
Metal implants, in e.g. joint replacements, are generally considered to be a success. As mechanical stability is important for the longevity of a prosthesis, the biological reaction of the bone to the mechanical loading conditions after implantation and during remodelling determines its fate. The bone reaction at the implant interface can be studied using high-resolution imaging. However, commonly used X-ray imaging suffers from image artefacts in the close proximity of metal implants, which limit the possibility to closely examine the bone at the bone-implant interface. An alternative ex vivo 3D imaging method is offered by neutron tomography. Neutrons interact with matter differently than X-rays; therefore, this study explores if neutron tomography may be used to enrich studies on bone-implant interfaces. A stainless steel screw was implanted in a rat tibia and left to integrate for 6weeks. After extracting the tibia, the bone-screw construct was imaged using X-ray and neutron tomography at different resolutions. Artefacts were visible in all X-ray images in the close proximity of the implant, which limited the ability to accurately quantify the bone around the implant. In contrast, neutron images were free of metal artefacts, enabling full analysis of the bone-implant interface. Trabecular structural bone parameters were quantified in the metaphyseal bone away from the implant using all imaging modalities. The structural bone parameters were similar for all images except for the lowest resolution neutron images. This study presents the first proof-of-concept that neutron tomographic imaging can be used for ex-vivo evaluation of bone microstructure and that it constitutes a viable, new tool to study the bone-implant interface tissue remodelling.


Hypolipidemic activity of tincture of Crataegus in rats.
Tincture of Crataegus (TCR), an alcoholic extract of the berries of Crataegus oxyacantha, when administered to rats fed a hyperlipidemic diet (HLD), could prevent the elevation in plasma lipid levels. A significant decrease in lipid deposits in liver and aorta was also observed. Analysis of the plasma lipoprotein profile showed that TCR produced remarkable reduction in the increased levels of cholesterol, triglycerides and phospholipids in the low density lipoprotein (LDL) and very low density lipoprotein (VLDL) fractions in hyperlipidemic rats. Histological examination showed severe fatty vacuolation and degeneration of liver of HLD fed rats. TCR administration had an ameliorating effect on these changes. Agarose gel electrophoretic pattern of plasma lipoproteins also indicated that the drug brought down the raised levels of the atherogenic beta-lipoproteins in hyperlipidemic rats.


[Laparoscopic treatment of adnexal cystic masses].
Operative laparoscopy has become the gold standard for the surgical treatment of numerous gynecological benign conditions. In the case of ovarian cysts, however, the use of the laparoscopic approach has been debated due to the possibility of encountering an unexpected ovarian malignancy at the time of surgery. This would upstage a IA or IB ovarian malignancy to IC. In this review, the authors evaluate the preoperative parameters that could help in the selection of the patients who are candidate to a laparoscopic approach. In particular, the authors consider the age related risk of the patients, the use of sonography and color-Doppler velocimetry, the use of CA 125, and as a last diagnostic step, the findings at laparoscopy. In a personal series of 1.584 cysts in patients under 40 years of age, the first author encountered 7 unexpected borderline tumors and 1 mucinous G1 adenocarcinoma, while no malignancy was found in a group of strictly selected postmenopausal patients. These data have been compared with those found in scientific literature. There is no sound evidence that the stripping procedure determines a reduction of the ovarian reserve when performed with strict microsurgical principles. Recent evidence in the literature suggests that the decreased ovarian responsiveness reported by some authors following ovarian cystectomy may not be a consequence of surgery. The concern of a possible reduction of the ovarian reserve needs to be balanced with the benefits obtained with surgery. Finally, it should always be kept in mind the risk of an unexpected malignancy, even in cysts apparently benign, malignancy that can only be diagnosed through surgery obtaining a specimen for pathology.


A high-resolution two-dimensional imaging velocimeter.
Velocity interferometers are typically used to measure velocities of surfaces at a single point or along an imaged line as a function of time. We describe an optical arrangement that enables high-resolution measurements of the two-dimensional velocity field across a shock front or shocked interface. The technique is employed to measure microscopic fluctuations in shock fronts that have passed through materials being considered as ablators for indirect-drive inertial confinement fusion. With picosecond time resolution the instrument captures velocity modes with wavelengths as short as 2.5 microm at a resolution of approximately 10 m/s rms on velocity fields averaging many km/s over an 800 microm field of view.


The ParA/MinD family puts things in their place.
Bacteria must segregate their DNA and position a septum to grow and divide. In many bacteria, MinD is involved in spatial regulation of the cytokinetic Z ring, and ParAs are involved in chromosome and plasmid segregation. The use of the MinD/ParA family to provide positional information for spatial organization continues to expand with the recognition that orphan ParAs are required for segregating cytoplasmic protein clusters and the polar localization of chemotaxis proteins, conjugative transfer machinery, type IV pili, and cellulose synthesis. Also, some bacteria lacking MinD use orphan ParAs to regulate cell division. Positioning of MinD/ParA proteins is either due to self-organization on a surface or reliance on a landmark protein that functions as a molecular beacon.


Cell death triggering and effector recognition by Sw-5 SD-CNL proteins from resistant and susceptible tomato isolines to Tomato spotted wilt virus.
Only a limited number of dominant resistance genes acting against plant viruses have been cloned, and further functional studies of these have been almost entirely limited to the resistance genes Rx against Potato virus X (PVX) and N against Tobacco mosaic virus (TMV). Recently, the cell-to-cell movement protein (NSM ) of Tomato spotted wilt virus (TSWV) has been identified as the avirulence determinant (Avr) of Sw-5b-mediated resistance, a dominant resistance gene which belongs to the class of SD-CC-NB-LRR (Solanaceae domain-coiled coil-nucleotide-binding-leucine-rich repeat, SD-CNL) resistance genes. On transient expression of the NSM protein in tomato and transgenic Nicotiana benthamiana harbouring the Sw-5b gene, a hypersensitive cell death response (HR) is triggered. Here, it is shown that high accumulation of the Sw-5b protein in N. benthamiana leaves, achieved by co-expression of the Sw-5b protein with RNA silencing suppressors (RSSs), leads to auto-activity in the absence of NSM . In a similar approach, Sw-5a, the highest conserved paralogue of Sw-5b from Solanum peruvianum, also triggered HR by auto-activation, whereas the highest conserved orthologue from susceptible S. lycopersicum, named Sw-5aS , did not. However, neither of the last two homologues was able to trigger an NSM -dependent HR. Truncated and mutated versions of these Sw-5 proteins revealed that the NB-ARC [nucleotide-binding adaptor shared by Apaf-1 (from humans), R proteins and CED-4 (from nematodes)] domain is sufficient for the triggering of HR and seems to be suppressed by the SD-CC domain. Furthermore, a single mutation was sufficient to restore auto-activity within the NB-ARC domain of Sw-5aS . When the latter domain was fused to the Sw-5b LRR domain, NSM -dependent HR triggering was regained, but not in the presence of its own Sw-5aS LRR domain. Expression analysis in planta revealed a nucleocytoplasmic localization pattern of Sw-5b, in which the SD-CC domain seems to be required for nuclear translocation. Although the Sw-5 N-terminal CC domain, in contrast with Rx, contains an additional SD, most findings from this study support a conserved role of domains within NB-LRR (NLR) proteins against plant viruses.


Highly Ag+ selective tripodal gold(I) acetylide-based "off-on" luminescence chemosensors based on 3(ππ*) emission switching.
Newly prepared gold(I) acetylide-based luminescent cation sensors 1c and 1d, which bear a novel three-armed flexible conformation, together with control molecule 2c, were synthesized in four steps. 1c and 1d exhibit the π → π* absorption of the acetylide ligands in fluid solutions and produce the (3)(ππ*) emission of the acetylide ligands in the solid state and degassed THF solution. The (3)(ππ*) emission of 1c in DMSO can be turned on upon addition of Ag(+). The binding ratio between 1c and Ag(+) as well as the binding constant log K were determined as 1:1 and 4.35 ± 0.12 respectively by UV-vis titration experiments. The formation of [1c·Ag](+) adduct, which leads to the appearance of new up-field peaks, was confirmed by (1)H NMR spectroscopic titrations. The control (1)H NMR titration experiments for the acetylide-free analogue 1a and single-armed analogue 2c indicate the acetylide groups and tripodal structures are responsible for the binding of Ag(+). The control experiment for tripodal gold(I) acetylide analogue 1d suggests the change of PPh3 with P(2-Py)Ph2 induces similar binding affinity toward Ag(+) but less selectivity toward Ag(+). Free 1c also exhibits the anion binding affinity toward F(-), but the Ag(+) adduct [1c·Ag](+) shows less affinity toward F(-).


Sterols and terpenoids from Melia azedarach.
Three new sterols (1-3) including an unprecedented ring A-seco natural product (1), five new terpenoids (4-8), and 15 known compounds were isolated from the bark of Melia azedarach. Their structures were elucidated by means of spectroscopic data, and the structure of 1 was confirmed by X-ray crystallography.


Increase of endocan, a new marker for inflammation and endothelial dysfunction, in acute kidney injury.
In this study, the clinical relevance of the levels of serum endocan and 25-hydroxyvitamin D [25(OH)D] was investigated in patients with acute kidney injury (AKI). Endocan or the endothelial cell-specific molecule 1 is a soluble proteoglycan secreted by vascular endothelial cells. It plays a significant role in immunity, inflammation, and endothelial function. A total of 39 patients with AKI (19 females, 20 males) and 38 healthy individuals (18 females, 20 males) were included in the study. The levels of serum endocan, vitamin D, and other biochemical parameters were compared between the two groups. In the AKI group, the values of serum creatinine, endocan, parathormone, phosphorus, and uric acid were found to be higher, and the total protein, albumin, and calcium levels were lower compared to the control group. There was no difference between the two groups in terms of the serum vitamin D, magnesium, alkaline phosphatase, and gamma-glutamyl transferase. In patients with AKI, an increased endocan level is a significant marker of inflammation and endothelial injury. In addition, these patients experience vitamin D deficiency.


Analysis of the InsCor Score as a Predictor of Mortality in Patients Undergoing Coronary Artery Bypass Grafting.
Risk scores are important tools for predicting adverse events in cardiac surgery, but their accuracy varies when applied to different populations. The objective of this study is to evaluate the performance of the Brazilian score InsCor as a predictor of mortality after coronary artery bypass grafting (CABG) compared to the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Society of Thoracic Surgeons (STS) scores. This is an observational and retrospective study, with patients undergoing surgical myocardial revascularization in a cardiology hospital in Salvador (Bahia, Brazil), between 2010 and 2015. InsCor, STS, and EuroSCORE were compared for accuracy in predicting mortality within 30 days after surgery. Discrimination capacity of models was assessed using areas under receiver operating characteristic (ROC) curves. Significance level was 5%. Four hundred sixty-one patients were evaluated (mean age 63 [± 8.6] years, 77% men). Thirty-day mortality was 2.6%. InsCor classified 88, 210, and 163 patients as having low, medium, and high risk of death, respectively. According to EuroSCORE and STS, 379 and 430 patients were classified as having low risk and 77 and 29 as medium risk, respectively. Area under the ROC curve was 0.734 (P=0.002) for InsCor, 0.615 (P=0.027) for EuroSCORE, and 0.623 (P=0.033) for STS. ROC curve of InsCor maintained statistical significance after adjustment for other models. The InsCor score, derived from a Brazilian sample, showed good predictive accuracy of death up to 30 days in patients undergoing CABG in relation to STS and EuroSCORE scores.


Unusual bleeding of aneurysmal bone cyst in the upper thoracic spine.
Aneurysmal bone cyst (ABC) is a benign bone lesion and commonly affects young adolescents. It usually grows rapidly with hypervascularity. In the spine, it can cause extensive bone destruction and compress neural structures with eventual vertebral collapse. Operative management of such a lesion may be complicated by profuse hemorrhage. Herein, we report a 15-year-old boy who had an acute exacerbation of spinal cord compression because of an ABC in the upper thoracic region. With a two-staged operation that complicating with profuse intraoperative bleeding, decompressive curettage and stabilization of the vertebral column were assured. However, abrupt neurologic deterioration occurred because of rebleeding with spinal cord compression 1 month postoperatively. Secondary decompressive curettage and following local radiotherapy were undertaken to cure the disease. Neurological recovery and healing of spinal ABC could be expected if the lining of a cyst had been totally removed. At the 18-month follow-up examination, he was neurologically intact and without any backache, leg pain or gait disturbance.


Neural Plastic Effects of Cognitive Training on Aging Brain.
Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n = 109) and the Active Control Group (n = 100). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age.


Interaural intensity discrimination: insensitivity at 1000 Hz.
Recent data from three laboratories have replicated Mills' [J. Acoust. Soc. Am. 32, 132-134 (1960)] finding that interaural intensity discrimination is relatively poorer for tones of 1000 Hz than for tones of either higher or lower frequencies. To get a finer look at this frequency effect, interaural intensity difference thresholds were obtained from four subjects for tones of several frequencies around 1000 Hz. An adaptive two-interval forced-choice procedure was employed, in which the overall intensity of the signals was varied randomly in order to prevent subjects from listening to monaural loudness changes. Despite large intersubject differences in overall sensitivity to interaural intensity differences, all four subjects showed a local peak in their threshold functions at or near 1000 Hz. This curious "1000-Hz effect" might be explained by imagining that an interaural intensity comparator operates more efficiently as frequency increases, but that a peripheral interaural intensity difference to interaural-time difference conversion contributes to laterality judgments for low-frequency tones, thus acting to lower thresholds again for frequencies below 1000 Hz.


Prevalence of amyotrophic lateral sclerosis (ALS), United States, 2016.
Objective: To estimate the prevalence of amyotrophic lateral sclerosis (ALS) in the United States for 2016 using data from the National ALS Registry (Registry). Established in 2009, the Registry collects data on ALS patients in the U.S. to better describe the epidemiology of ALS, examine risk factors such as environmental and occupational exposures, and characterize the demographics of those living with the disease. Methods: To identify adult prevalent cases of ALS, the Registry compiles data from three national administrative databases (maintained by the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration). To ascertain cases not necessarily included in these databases and to better understand risk-factors associated with ALS and disease progression, the Registry also includes data collected from patients who voluntarily enroll via a web portal to complete online surveys. Results: In 2016, the Registry conservatively identified 16,424 adult persons who met the Registry definition of ALS for an age-adjusted prevalence rate of 5.2 per 100,000 U.S. population. The pattern of patient characteristics (e.g., age, sex, and race/ethnicity) has not changed from previous Registry reports. Overall, ALS was more common among whites, males, and persons aged 60-69 years. The age groups with the lowest number of ALS cases were persons aged 18-39 years. Males had a higher prevalence rate of ALS than females overall and across all data sources. Conclusions: Data collected by the National ALS Registry are being used to better describe the epidemiology and demographics of ALS in the U.S.


Onset of Inattention and Hyperactivity in Children and Adolescents With Epilepsy 6 months After the Diagnosis.
Complete or major symptoms of ADHD are often present in epilepsy. This study evaluated inattention and hyperactivity symptoms over the first 6 months in newly diagnosed pediatric epilepsy without comorbid ADHD. Children and adolescents with newly diagnosed epilepsy were followed for 6 months after starting antiseizure medications. The Nisonger Child Behavior Rating Form (NCBRF), Adverse Event Profile (AEP), and the Revised Wechsler Intelligence Scale for Children were used. There was a marked increase in attention difficulties while a moderate increase in hyperactivity levels. AEP scores, changes in non-verbal aspects of intelligence, levels of hyperactivity at the follow-up, and attention at baseline were significant predictors for inattention. In contrast, only levels of hyperactivity at the baseline and inattention at the follow-up were significant predictors for hyperactivity. Significant inattention and hyperactivity levels originated 6 months after the diagnosis of epilepsy and starting antiseizure medication.


Evaluation of Antibiotic Allergies in Surgical Patients.
Antibiotic administration in the perioperative period is the foundation of preventing surgical site infections. β-Lactam antibiotics, notably the first-generation cephalosporin cefazolin, are the drugs of choice for this indication. However, reported antibiotic allergies often result in the use of suboptimal alternative agents that can lead to an increased risk of infection and adverse effects. A comprehensive allergy history and risk stratification should be completed preoperatively to determine whether or not a patient can be rechallenged with a β-lactam antibiotic and what testing may be necessary prior to administration. Nursing staff can play a critical role in understanding the implications and management of reported antibiotic allergies in surgical patients in order to optimize patient care.


Renal elimination of organic anions in cholestasis.
The disposition of most drugs is highly dependent on specialized transporters. OAT1 and OAT3 are two organic anion transporters expressed in the basolateral membrane of renal proximal tubule cells, identified as contributors to xenobiotic and endogenous organic anion secretion. It is well known that cholestasis may cause renal damage. Impairment of kidney function produces modifications in the renal elimination of drugs. Recent studies have demonstrated that the renal abundance of OAT1 and OAT3 plays an important role in the renal elimination of organic anions in the presence of extrahepatic cholestasis. Time elapsed after obstructive cholestasis has an important impact on the regulation of both types of organic anion transporters. The renal expression of OAT1 and OAT3 should be taken into account in order to improve pharmacotherapeutic efficacy and to prevent drug toxicity during the onset of this hepatic disease.


Heterologous expression of five disulfide-bonded insecticidal spider peptides.
The genes of the five disulfide-bonded peptide toxins 1 and 2 (named Oxytoxins or Oxotoxins) from the spider Oxyopes lineatus were cloned into the expression vector pQE30 containing a 6His-tag and a Factor Xa proteolytic cleavage region. These two recombinant vectors were transfected into Escherichia coli BL21 cells and expressed under induction with isopropyl thiogalactoside (IPTG). The product of each gene was named HisrOxyTx1 or HisrOxyTx2, and the protein expression was ca 14 and 6 mg/L of culture medium, respectively. Either recombinant toxin HisrOxyTx1 or HisrOxyTx2 were found exclusively in inclusion bodies, which were solubilized using a chaotropic agent, and then, purified using affinity chromatography and reverse-phase HPLC (RP-HPLC). The HisrOxyTx1 and HisrOxyTx2 products, obtained from the affinity chromatographic step, showed several peptide fractions having the same molecular mass of 9913.1 and 8030.1 Da, respectively, indicating that both HisrOxyTx1 and HisrOxyTx2 were oxidized forming several distinct disulfide bridge arrangements. The isoforms of both HisrOxyTx1 and HisrOxyTx2 after DTT reduction eluted from the column as a single protein component of 9923 and 8040 Da, respectively. In vitro folding of either HisrOxyTx1 or HisrOxyTx2 yielded single oxidized components, which were cleaved independently by the proteolytic enzyme Factor Xa to give the recombinant peptides rOxyTx1 and rOxyTx2. The experimental molecular masses of rOxyTx1 and rOxyTx2 were 8059.0 and 6176.4 Da, respectively, which agree with their expected theoretical masses. The recombinant peptides rOxyTx1 and rOxyTx2 showed lower but comparable toxicity to the native toxins when injected into lepidopteran larvae; furthermore, rOxyTx1 was able to inhibit calcium ion currents on dorsal unpaired median (DUM) neurons from Periplaneta americana.


Bench-to-bedside review: human subjects research--are more standards needed?
There are many controversial issues surrounding ethics in study design and conduct of human subjects research. In this review we briefly touch on the origin of ethics in clinical research and how the current regulations and standards came into practice. We then discuss current controversies regarding informed consent, conflicts of interest, institutional review boards, and other relevant issues such as innovative procedures and quality improvement projects. The question of whether we need more standards is a very important yet challenging one to which there is no simple answer. We address this question by reviewing and commenting on relevant literature. We conclude that what is needed are not more standards per se, but rather refinement and uniformity of current standards, and their interpretation and application both to protect human subjects and to advance medicine.


Comparison of the induction of pulmonary neoplasms in Sprague-Dawley rats by fission neutrons and radon daughters.
Pulmonary carcinomas were recorded in a life-span experiment of male Sprague-Dawley rats exposed to fission neutrons. Mortality-corrected prevalences are obtained by the method of isotonic regression. In a second part of the paper a comparison is made with data obtained earlier for radon-daughter inhalations in the same strain of rats. A simultaneous maximum likelihood analysis is applied jointly to all experimental groups from the radon inhalation and the fission neutron study. The dependence of the resulting coefficients for the different groups on absorbed dose or inhalation dose permits a derivation of equivalence ratios. At low doses the equivalence ratio is 3 WLM (working level months) of radon-daughter exposure to 1 mGy of fission neutrons. At higher doses the equivalence ratio decreases. The neutron data are also utilized to derive mortality-corrected lifetime incidences of pulmonary carcinomas in the exposed animals. At low doses the relation is consistent with linearity, but sublinearity (dose exponent less than 1) cannot be excluded.


Acousto-optic measurements of tropospheric nitrogen dioxide column density by solar spectroscopy.
Measurements of column densities of atmospheric gases can be achieved by a solar spectroscopic method that uses differential optical absorption spectroscopy. Because of the scintillation of sunlight intensity in the atmosphere, the variation in intensity will introduce a low-frequency modification of the measured solar spectrum. A spectral capturing-type CCD spectrometer takes milliseconds to capture a solar spectrum, and the effect of sunlight scintillation is negligible. In contrast, without scintillation correction, a scanning-type spectrometer spending minutes to obtain a complete solar spectrum will introduce some amount of errors. We demonstrate an intensity-compensation technique in a scanning-type spectrometer, based on a solid-state acousto-optic tunable filter, for solar spectroscopic measurements.


"The nurse should consider.' Critical care ethical issues.
A hypothetical dilemma on resuscitation of an intensive care patient was presented to nurses at a workshop on ethics of critical care nursing. Nurses responded to separate questionnaires about what a charge nurse should do, and what they themselves would do in relation to ten considerations arising from the dilemma. Nurses were agreed that legal consequences, patient wishes and rights, and physician authority should and would be considered, and that peer influence should not. Nurses were divided in their attitudes to following procedure and personal moral beliefs, and to job risk. The most contentious issues were related to the nurse's role as a decision-making member of the health care team. Implications for regarding nurses as independent decision-makers are discussed.


AATF/Che-1-An RNA Binding Protein at the Nexus of DNA Damage Response and Ribosome Biogenesis.
The DNA damage response (DDR) is a complex signaling network that is activated upon genotoxic stress. It determines cellular fate by either activating cell cycle arrest or initiating apoptosis and thereby ensures genomic stability. The Apoptosis Antagonizing Transcription Factor (AATF/Che-1), an RNA polymerase II-interacting transcription factor and known downstream target of major DDR kinases, affects DDR signaling by inhibiting p53-mediated transcription of pro-apoptotic genes and promoting cell cycle arrest through various pathways instead. Specifically, AATF was shown to inhibit p53 expression at the transcriptional level and repress its pro-apoptotic activity by direct binding to p53 protein and transactivation of anti-apoptotic genes. Solid and hematological tumors of various organs exploit this function by overexpressing AATF. Both copy number gains and high expression levels of AATF were associated with worse prognosis or relapse of malignant tumors. Recently, a number of studies have enabled insights into the molecular mechanisms by which AATF affects both DDR and proliferation. AATF was found to directly localize to sites of DNA damage upon laser ablation and interact with DNA repair proteins. In addition, depletion of AATF resulted in increased DNA damage and decrease of both proliferative activity and genotoxic tolerance. Interestingly, considering the role of ribosomal stress in the regulation of p53, more recent work established AATF as ribosomal RNA binding protein and enabled insights into its role as an important factor for rRNA processing and ribosome biogenesis. This Mini Review summarizes recent findings on AATF and its important role in the DDR, malignancy, and ribosome biogenesis.


A retrospective comparison of the emergent use of fixed-dose four-factor prothrombin complex versus weight-based dosing for intracranial hemorrhage assessing medication delivery time and cost.
The goal of this study was to evaluate a low fixed-dose versus weight-based dosing strategy for four-factor prothrombin complex (4F-PCC) time to administration in intracranial hemorrhage (ICH) patients. A retrospective analysis was conducted at a single rural Tertiary referral center in patients ≥18 years old on warfarin with ICH who received 4F-PCC. Continuous variables were summarized using mean (±95% CI) and compared using two-tailed tests; p values ≤0.05 were considered statistically significant. A total of 46 ICH patients were reversed using 4F-PCC (Fixed, n = 27 and Weight, n = 19). Baseline characteristics were equivalent. Total units of 4F-PCC (mean dose units 2525.1 versus 1623.3) and dose per kg were significantly reduced in the fixed-dose group. Total time from order to delivery was significantly reduced with the fixed-dose strategy (mean time 43.0 versus 29.0 minutes). Hospital length of stay (LOS), intensive care unit LOS, and mortality were equivalent with a similar mechanism. International Normalized Ratio (INR) reversal success (≤1.5) and total INR change was comparable with no difference in adverse thromboses between groups. A fixed-dosed strategy reduced time to 4F-PCC administration for warfarin reversal in ICH, as compared to a weight-based strategy; with no increase in LOS, mortality, or need for additional dosing. This also resulted in significant cost savings.


Preoperative cutaneous hypersensitivity reaction related to postoperative complications following elective surgery.
Delayed cutaneous hypersensitivity testing (DCH) using the following antigens: Mumps, PPD, Candida and streptokinase/streptodornase was effectuated preoperatively in 339 surgical patients. DCH test results were evaluated as normal (N) when two or more antigens showed positive response (greater than 5 mm in diameter), relative anergic (RA) with one positive response and anergic (A) when no response was positive. Normal response was observed in 78%, RA in 13% and A in 9% of the patients. Complications in the 232 patients that were operated upon were seen in 51% of the A or RA patients while only 7.1% of the N patients developed complications. The mortality increased significantly from 2.2% in normal patients to 23.5% in the anergic group. Patients classified as anergic or relative anergic had significantly lower preoperative serum levels of prealbumin (p less than 0.001), retinolbinding protein (p less than 0.05) and albumin p less than 0.01) than the normal patients.


2'-nor-cGMP, a new cyclic derivative of 2'NDG, inhibits HSV-1 replication in vitro and in the mouse keratitis model.
The present study examined the antiherpetic effect of 2'-nor-cGMP, a new cyclic phosphate derivative of 2'NDG, in vitro and in the mouse keratitis model. The 50% inhibitory dose (ID50) was determined with HSV-1 RE strain in Vero cell monolayers for 2'-nor-cGMP (6.9 mcg./ml), 2'NDG (.06 mcg/ml), and trifluridine (F3T) (.72 mcg/ml). Balb C mice underwent bilateral ocular inoculation with HSV-1 RE strain, and then were treated with different therapeutic regimens. The antiviral efficacy of each drug was evaluated by ocular virus titers, clinical grading of epithelial keratitis, and histological evaluation of stromal keratitis. 2'-nor-cGMP was the most effective drug (P = .0001) in reducing ocular viral titers. Both 2'-nor-cGMP and 2'NDG were significantly more effective (P = .0001) than F3T in reducing epithelial keratitis, and as effective as F3T in reducing stromal keratitis.


An unusual presentation of ovarian teratoma: a case report.
Mature cystic teratomas account for 10-20% of all ovarian neoplasms and are the most common neoplasm in younger patients. Spontaneous rupture of the teratoma is rare and has been occasionally reported. Here we present an unusual case of left ovarian teratoma rupturing into sigmoid colon.


[Theoretical analysis of the multistability of pyramidal neurons].
The two-step switch off the long duration Ca action potential was observed recently in neocortex pyramids [1]. The phenomenon was interpreted as an evidence of the N-type Ca-channel distribution in isolated loci [1]. We demonstrate here that the two-step switch off can be imitated in the model with even channel distribution in a reconstructed pyramidal neuron as well. The first high plateau of the action potential corresponds to steady polarization of the whole membrane. The first switch off of the high plateau to the second low plateau corresponds to the switch off of the steady depolarization of the short basal dendrites. The steady depolarization of the long apical dendrite is more stable thus the switch off of the low plateau is a consequence of the apical dendrite repolarization. The model includes N-channel inactivation and a somatic shunt. The shunt may be artifactual, due to implement, or natural, due to postspike hyperpolarization. Recent experiments [2] have proved that the Ca-channels are located everywhere in the pyramidal cell.


Development, validation and practical use of a sensitive and specific radioimmunoassay for the determination of iloprost.
Iloprost is a potent, clinically effective PGI2-mimetic. Therapeutic plasma levels are in the low pg-range and currently analyses of biological samples are performed by GC/MS after antiserum-column extraction. Although this method exhibits high sensitivity and specificity it permits only limited numbers of samples to be analyzed owing to time-consuming work-up. The present report describes the development of a novel highly selective antiserum and its use for the RIA determination of iloprost in biological samples. An antiserum was raised against "iloprost-9-pentynyl"-BSA in rabbits. Iloprost-[3H]-methylester with a specific activity of 66.9 Ci/mmol was used as a tracer. RIA-analyses were carried out with 0.05-0.5 ml plasma adjusted to pH2 with 1 N HCl and extracted with 2.5 ml diethylether. Separation of antiserum bound and unbound iloprost was achieved by the charcoal method. Extraction recovery of iloprost was approximately 90% at pH less than or equal to 4. The detection limit of the novel assay was 1-2 pg/tube corresponding to 5-10 pg/ml plasma (if 0.1-0.2 ml plasma was used). Coefficients of variations were 8% and 2% (within-day, n = 3) and 17% and 12% (day-to-day, n = 5) at 50 and 100 pg/ml. RIA- and GC/MS-levels of iloprost measured in human samples were similar (p less than 0.001). Cross-reactivity HPLC-chromatograms of plasma extracts did not reveal any peak apart from iloprost. The RIA-method exhibits both a similar specificity and detection limit to GC/MS and will be used for further analyses.


Fatal Bleeding in Conjunction with Mandibular Medication-related Osteonecrosis of the Jaw (MRONJ).
Here, we report a case of fatal bleeding in conjunction with mandibular medicationrelated osteonecrosis of the jaw (MRONJ). A 75-year-old Japanese man was referred to our department with osteonecrosis of the jaw due to bisphosphonate (BP) for multiple bone metastases from prostate cancer. Aggressive surgical intervention was ruled out due to a poor prognosis in terms of life expectancy. Death occurred due to hemorrhagic shock resulting from massive oral bleeding caused by necrosis of the mandible. Numerous reports have suggested that jaw necrosis is induced not only by BP, but also RANKL antibody, steroids, and molecularly-targeted agents. This suggests that the number of cases of MRONJ is likely to increase among elderly patients in whom general health is already poor. The American Association of Oral and Maxillofacial Surgery recommends aggressive treatment only in cases of stage 3 disease. Therefore, such a therapeutic strategy may only be available for cases of jaw necrosis in which the general health status of the patient is otherwise good. To prevent a life-threatening outcome in cases of MRONJ, physicians, who are responsible for determining the drug strategy, should cooperate with oral surgeons in determining the best therapeutic strategy.


Study of the Incorporation of Biomass Bottom Ashes in Ceramic Materials for the Manufacture of Bricks and Evaluation of Their Leachates.
Scarcity of raw materials, reduction of greenhouse gas emissions and reduction of waste disposal in landfills are leading to the development of more sustainable building materials. Based on these lines, this work studies the incorporation of biomass bottom ashes into ceramic materials for brick manufacture, in order to reuse this currently unused waste and reduce clay extraction operations. To this end, different groups of samples were made with different combinations of clay and biomass bottom ashes, from 100% clay to 100% biomass bottom ashes. These samples were shaped, sintered and subjected to the usual physical tests in ceramics. In turn, the mechanical resistance, color and leaching of the contaminating elements present were studied. The physical and mechanical tests showed that the results of all the families were adequate, achieving compressive strengths of over 20 MPa and leaching of the contaminating elements acceptable by the regulations. Therefore, a sustainable range of ceramics was developed, with specific properties (porosity, density, resistance and color), with a waste that is currently unused and sustainable with the environment.


The Relationship of Serum S100B Levels with Infarction Size and Clinical Outcome in Acute Ischemic Stroke Patients.
S100B protein, which helps nerve development and differentiation, is produced by astrocytes and can be detected in peripheral circulation after brain damage. In this study, we aimed to investigate the relationship between the serum S100B protein level and the infarction volume and clinical outcome and also the early prognostic role of serum S100B protein in patients with ischemic stroke. Fifty patients admitted in the first 24-hour period of acute ischemic stroke were evaluated prospectively, and the findings were compared to those of the controls (n=26). S100B levels of the patients and neurological findings on days 1, 3, and 5 and their functional outcomes on the discharge day and at the first month were recorded by the same examiner. S100B levels were not affected by sex, age, or concomitant systemic diseases. The maximum levels of S100B were recorded on the 3rd day, and there was a correlation between infarct size and S100B levels. No correlation between the severity of stroke and S100B level was found. There was a poor correlation between the functional outcomes of the patients at the 1st month and S100B levels and on the 3rd day. The detection of high S100B levels in peripheral circulation after acute ischemic stroke and the correlations of S100B levels with infarct size (good) and disability (poor) imply that S100B protein may be used as a peripheral marker in acute ischemic stroke patients.


Fluorometric assay for anti-DNA antibodies: use of ethidium bromide as intercalating dye.
Autoantibodies against double-stranded DNA in the sera of patients with various autoimmune diseases have been examined by fluorometric assay using ethidium bromide as intercalating dye. Forty-three per cent of SLE patients, 14% of SLE patients with overlapping PSS, 20% of PSS patients and none of the RA and SS patients were positive for anti-DNA antibodies. The method was found to be more sensitive than immunoprecipitation techniques and comparable with the hemagglutination assay. The technique is simple, sensitive, specific and can be employed for the detection of low concentration of anti-DNA antibodies.


One-year clinical study on nifedipine in the treatment of pulmonary hypertension in chronic obstructive lung disease.
The advantages of long-term administration of vasodilators in the treatment of chronic cor pulmonale were investigated after informed consent in 60 patients with obstructive respiratory insufficiency (56 men, 4 women, mean age 63.5 +/- 1.5 years; mean pulmonary pressure 30.4 mm Hg). They were randomly divided into two groups of 30, a control group and a group treated with nifedipine, 10 mg three times a day. The following parameters were recorded every 3 months for a year: dyspnea, degree of right ventricular failure, number of days spent in hospital, survival and arterial blood gas tension. On the first day of study, no significant difference existed between the control and the treated groups. After 1 year 22 patients in the control group were still followed and 8 were dead. In the treated group 19 were followed, 7 were dead and 4 stopped treatment, generally due to ankle edema. At the end of the study, the only significant modification was improvement of the dyspnea in the nifedipine group (p less than 0.01). In conclusion, in spite of an improvement in the dyspnea index, clinical study for 1 year failed to demonstrate any objective benefit of nifedipine treatment.


Impact of Stress Levels on Eating Behaviors among College Students.
Weight gain is a common phenomenon among college students, especially those in their first year of university. Transitioning from high school to the college environment might increase perceived stress levels, thus affecting dietary behaviors and metabolism to promote overweight and obesity. The purpose of this study was to investigate the physical activities and dietary behaviors of college students in the context of their perceived stress levels. In addition, the demographic characteristics of the students were compared to ascertain their impact on dietary behaviors. Self-reported questionnaires were distributed to college students on campus in Korea. Perceived stress was measured by the 10-item Perceived Stress Scale (PSS-10), the scores for which were evaluated by independent t-tests to compare the dietary behaviors of the high- and low-perceived stress groups. Exploratory factor analysis was performed and Cronbach's alphas were computed to assess the validity and internal consistency of the PSS-10 measurement items. Differences in the physical activities and dietary behaviors of the college students based on demographics such as sex, academic year, and residence type were found. Several dietary behaviors were significantly different between students with low and high perceived stress levels. Students with high perceived stress levels exhibited increased unhealthy dietary behaviors such as ready-prepared meal consumption (p < 0.001). These results suggest that stress management should be offered to college students. In addition, programs should be provided to help first-year students adjust to the college environment in order to promote healthy dietary behaviors.


Flexible Semitransparent Energy Harvester with High Pressure Sensitivity and Power Density Based on Laterally Aligned PZT Single-Crystal Nanowires.
A flexible semitransparent energy harvester is assembled based on laterally aligned Pb(Zr0.52Ti0.48)O3 (PZT) single-crystal nanowires (NWs). Such a harvester presents the highest open-circuit voltage and a stable area power density of up to 10 V and 0.27 μW/cm2, respectively. A high pressure sensitivity of 0.14 V/kPa is obtained in the dynamic pressure sensing, much larger than the values reported in other energy harvesters based on piezoelectric single-crystal NWs. Furthermore, theoretical and finite element analyses also confirm that the piezoelectric voltage constant g33 of PZT NWs is competitive to the lead-based bulk single crystals and ceramics, and the enhanced pressure sensitivity and power density are substantially linked to the flexible structure with laterally aligned PZT NWs. The energy harvester in this work holds great potential in flexible and transparent sensing and self-powered systems.


Marrow transplantation for hematologic malignancies: a brief review of current status and future prospects.
The ability to transplant bone marrow makes it possible to treat patients with hematologic malignancies with doses of systemic radiotherapy or chemotherapy that would ordinarily result in fatal myelosuppression. With this approach, some otherwise incurable patients can be treated successfully. For most hematologic malignancies (acute nonlymphocytic leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and malignant lymphoma), if transplantation is delayed until patients have end-stage disease (drug-resistant relapse) or blast crisis, approximately 10 to 20% of patients can be saved. If transplantation is carried out earlier in the course of disease, the outcome improves considerably. Some of the major limitations of marrow transplantation are the need for an appropriate source of marrow, the severe myelosuppression seen in the immediate posttransplant period, the complications of graft-v-host disease (GVHD), and disease recurrence. The use of autologous marrow and the formation of a national donor registry may make transplantation more widely applicable. The availability of growth factors can hasten hematopoietic recovery, making the immediate posttransplant period safer. New immunosuppressive regimens and T-cell depletion of donor marrow can diminish the impact of GVHD. The need for better preparative regimens persists and has emerged as the major requirement for continued progress in marrow transplantation.


Capsular contracture in patients with prior breast augmentation undergoing breast conserving therapy and irradiation.
Radiation is considered to be a risk factor for developing capsular contracture in augmented women, but the studies reporting on this subject show conflicting results. In this systematic review we sought to understand the risk of capsular contracture in augmented patients with breast cancer treated with breast conserving surgery and radiotherapy. A search was conducted through PubMed for studies reporting on breast cancer, breast augmentation and radiotherapy, with capsular contracture as our primary outcome. To determine if specific risk factors were significant predictors of the development of capsular contracture, we performed uni- and multivariate analysis. Our search revealed 136 articles, of which 12 were deemed eligible. A total of 237 patients were included in the analysis. Univariate analysis revealed that whole breast irradiation (WBI) was significantly associated with a higher risk of contracture (p < .001), compared to treatment with accelerated partial breast irradiation (APBI). A higher radiotherapy dose regimen was also significantly associated with a risk of capsular contracture (p < .001). When performing the multivariate analysis only the effect of increasing radiation dose remained significant (p < .05). Neither the implant location nor the age of the implant had any significant effect on the development of contracture. In conclusion this review shows that WBI is associated with a higher risk of contracture compared to treatment with APBI. Because of the limitations of the studies included, further studies with larger patient cohorts are needed to establish this correlation and evaluate other potential risk factors.


Cosilencing Intestinal Transglutaminase-2 and Interleukin-15 Using Gelatin-Based Nanoparticles in an in Vitro Model of Celiac Disease.
In this study, we have developed a type B gelatin nanoparticle based siRNA delivery system for silencing of intestinal transglutaminase-2 (TG2) and interleukin-15 (IL-15) genes in cultured human intestinal epithelial cells (Caco-2) and murine alveolar macrophage cells (J774A.1). Small interfering RNA (siRNA) targeting the TG2 or IL-15 gene was encapsulated within gelatin nanoparticles using ethanol-water solvent displacement method. Size, charge, and morphology of gelatin nanoparticles were evaluated using a Zetasizer instrument and transmission electron microscopy. siRNA encapsulation efficiency was determined using an siRNA specific stem-loop quantitative polymerase chain reaction (qPCR) assay. Cellular uptake of siRNA-containing gelatin nanoparticles was determined using fluorescent microscopy and stem-loop qPCR assay. siRNA loading in the RISC (RNA-induced silencing complex) was determined by immunoprecipitation of argonaute 2 (AGO2) protein followed by stem-loop qPCR for siRNA quantification. Gene expression analysis of TG2, IL-15, and the proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), was performed using qPCR assays. Efficacy of silencing TG2 and IL-15 knockdown was evaluated in an in vitro model of celiac disease by utilizing immunogenic α-gliadin peptide p31-43 in cultured J774A.1 cells. siRNA-containing gelatin nanoparticles were spherical in shape with mean particle size and charge of 217 ± 8.39 nm and -6.2 ± 0.95 mV, respectively. siRNA loading efficiency within gelatin nanoparticles was found to be 89.3 ± 3.05%. Evaluations of cellular uptake using fluorescent microscopy showed rapid internalization of gelatin nanoparticles within 2 h of dosing, with cytosolic localization of delivered siRNA in Caco-2 cells. Gelatin nanoparticles showed greater intracellular siRNA exposure with a longer half-life, when compared to Lipofectamine-mediated siRNA delivery. Approximately 0.1% of total intracellular siRNA was associated in the RISC complex. A maximum knockdown of 60% was observed at 72 h post siRNA treatment for both TG2 and IL-15 genes, which corresponded to ∼200 copies of RISC associated siRNA. Further, efficacy of gelatin nanoparticle mediated knockdown of TG2 and IL-15 mRNA was tested in an in vitro model of celiac disease. Significant suppression in the levels of proinflammatory cytokines (TNF-α and IFN-γ) was observed in p31-43 stimulated J774A.1 cells upon either IL-15 or IL-15 + TG2 siRNA treatment. The results from this study indicate that gelatin nanoparticle mediated TG2 and IL-15 siRNA gene silencing is a very promising approach for the treatment of celiac disease.


Modeling of pH regulation in tumor cells: Direct interaction between proton-coupled lactate transporters and cancer-associated carbonic anhydrase.
The most aggressive tumor cells, which often reside in a hypoxic environment, can release vast amounts of lactate and protons via monocarboxylate transporters (MCTs). This additional proton efflux exacerbates extracellular acidification and supports the formation of a hostile environment. In the present study we propose a novel, data-based model for this proton-coupled lactate transport in cancer cells. The mathematical settings involve systems coupling nonlinear ordinary and stochastic differential equations describing the dynamics of intra- and extracellular proton and lactate concentrations. The data involve time series of intracellular proton concentrations of normoxic and hypoxic MCF-7 breast cancer cells. The good agreement of our final model with the data suggests the existence of proton pools near the cell membrane, which can be controlled by intracellular and extracellular carbonic anhydrases to drive proton-coupled lactate transport across the plasma membrane of hypoxic cancer cells.


A small yeast RNA selectively inhibits internal initiation of translation programmed by poliovirus RNA: specific interaction with cellular proteins that bind to the viral 5'-untranslated region.
We have purified, sequenced, and prepared a synthetic clone of a small (60-nucleotide) RNA molecule from the yeast Saccharomyces cerevisiae that had previously been isolated on the basis of its ability to selectively block the translation of poliovirus mRNA. RNA derived from the clone by transcription with T7 RNA polymerase appears to block translation initiation by internal ribosome entry (cap independent) but does not significantly affect cap-dependent translation. Deletion analysis of the poliovirus 5'-untranslated region (5'-UTR) has shown that yeast inhibitor RNA (I-RNA) requires internal ribosome entry site sequences to inhibit the translation of poliovirus RNA in vitro. Using a bicistronic RNA construct, we show that I-RNA preferentially inhibits translation by internal ribosome entry. Gel retardation and UV cross-linking studies demonstrate that I-RNA specifically binds proteins which interact with RNA secondary structures within the poliovirus 5'-UTR presumably involved in internal initiation. Specifically, purified I-RNA competes with virus RNA structures within the 5'-UTR which bind a cellular protein with an approximate molecular mass of 52 kDa. Finally, when transfected into HeLa cells, I-RNA efficiently inhibits the replication of poliovirus RNA presumably by inhibiting translation of the input virus RNA.


Comparison of surgical conditions following premedication with oral clonidine versus oral diazepam for endoscopic sinus surgery: A randomized, double-blinded study.
Endoscopic sinus surgery (ESS) provides a challenge and an opportunity to the anesthesiologists to prove their mettle and give the surgeons a surgical field which can make their delicate surgery safer,more precise and faster. The aim of the study was to evaluate the surgical field and the rate of blood loss in patients premedicated with oral clonidine versus oral diazepam for endoscopic sinus surgery. ASA I or II patients who were scheduled to undergo ESS were randomly allocated to group D (n = 30) or group C (n = 30). The patients' vital parameters, propofol infusion rate, and rate of blood loss were observed and calculated. The surgeon, who was blinded, rated the visibility of the surgical field from grade 0-5. In the clonidine group, the rate of blood loss, the surgical time, propofol infusion rate was found to be statistically lower as compared to the diazepam group. Also a higher number of patients in the clonidine group had a better surgical score (better surgical field) than the diazepam group and vice versa. Premedication with clonidine as compared to diazepam, provides a better surgical field with less blood loss in patients undergoing ESS.


Prodromal and autistic symptoms in schizotypal personality disorder and 22q11.2 deletion syndrome.
Despite clear diagnostic distinctions, schizophrenia and autism share symptoms on several dimensions. Recent research has suggested the two disorders overlap in etiology, particularly with respect to inherited and noninherited genetic factors. Studying the relationship between psychotic-like and autistic-like symptoms in risk groups such as 22q11 deletion syndrome (22q11DS) and schizotypal personality disorder (SPD) has the potential to shed light on such etiologic factors; thus, the current study examined prodromal symptoms and autistic features in samples of 22q11DS and SPD subjects using standardized diagnostic measures, including the Structured Interview for Prodromal Symptoms (SIPS) and the Autism Diagnostic Inventory-Revised (ADI-R). Results showed that SPD subjects manifested significantly more severe childhood and current social as well as stereotypic autistic features, as well as more severe positive prodromal symptoms. The two groups did not differ on negative, disorganized, or general prodromal symptoms, but were distinguishable based on correlations between prodromal and autistic features; the relationships between childhood autistic features and current prodromal symptoms were stronger for the SPD group. The results suggest that childhood autistic features are less continuous with subsequent prodromal signs in 22q11DS patients relative to those with SPD, and the findings highlight the importance of studying the overlap in diagnostic phenomenology in groups at risk for developing psychosis and/or autism.


Two sides of the same wing: ventral scales enhance dorsal wing color in the butterfly Speyeria mormonia.
Biological visual signals are often produced by complex interactions between light-absorbing and light-scattering structures, but for many signals, potential interactions between different light-interacting components have yet to be tested. Butterfly wings, for example, are thin enough that their two sides may not be optically isolated. We tested whether ventral wing scales of the Mormon fritillary, Speyeria mormonia, affect the appearance of dorsal orange patches, which are thought to be involved in sexual signaling. Using reflectance spectroscopy, we found that ventral scales, either silvered or non-silvered, make dorsal orange patches significantly brighter, with the silvered scales having the greater effect. Computational modeling indicates that both types of ventral scale enhance the chromatic perceptual signal of dorsal orange patches, with only the silvered scales also enhancing their achromatic perceptual signal. A lack of optical independence between the two sides of the wings of S. mormonia implies that the wing surfaces of butterflies have intertwined signaling functions and evolutionary histories.