A Mixed Methods Study of Contraceptive Effectiveness in a Relationship Context Among Young Adult, Primarily Low-Income African American Women.
Unintended pregnancy is an important public health issue. Rates of unintended pregnancy are disproportionately higher among women from racial and ethnic minority groups among whom rates of contraceptive use are lower. Women's multifaceted feelings about pregnancy and perceptions of their intimate relationships may influence contraceptive behavior. We used mixed methods to examine women's perceptions of pregnancy, motherhood, and contraceptives within the context of their intimate relationships. A convenience sample of 130 primarily low-income African American women ages 18-29 completed a cross-sectional, computerized survey; 12 women provided in-depth qualitative interview data. Generalized linear mixed models were used to identify associations between study variables and contraceptive effectiveness. Interview data were analyzed using qualitative descriptive methods and integrated with quantitative data. Higher positive pregnancy attitude [odds ratio (OR) 0.78; 95 % confidence interval (CI) 0.63, 0.98], lower contraceptive attitude (OR 1.17; 95 % CI 1.01, 1.36), and more than one recent sexual partner (OR 0.03; 95 % CI <0.01, 0.60) were associated with less effective contraceptive use. Qualitative results included three themes: You get pregnant that's on you; Motherhood means everything; and Make sure you're stable. Women's qualitative reports primarily supported but occasionally diverged from quantitative findings, reflecting discrepancies from their stated ideals, personal goals, and behavior. The incongruities between women's ideals and their actual contraceptive behavior demonstrate the complexity of making reproductive decisions based on existing life circumstances and challenges. Health care providers should have broad understanding of women's pregnancy goals in order to recommend the most appropriate contraceptive methods and pre-conception counseling.


A global analysis of Caenorhabditis elegans operons.
The nematode worm Caenorhabditis elegans and its relatives are unique among animals in having operons. Operons are regulated multigene transcription units, in which polycistronic pre-messenger RNA (pre-mRNA coding for multiple peptides) is processed to monocistronic mRNAs. This occurs by 3' end formation and trans-splicing using the specialized SL2 small nuclear ribonucleoprotein particle for downstream mRNAs. Previously, the correlation between downstream location in an operon and SL2 trans-splicing has been strong, but anecdotal. Although only 28 operons have been reported, the complete sequence of the C. elegans genome reveals numerous gene clusters. To determine how many of these clusters represent operons, we probed full-genome microarrays for SL2-containing mRNAs. We found significant enrichment for about 1,200 genes, including most of a group of several hundred genes represented by complementary DNAs that contain SL2 sequence. Analysis of their genomic arrangements indicates that >90% are downstream genes, falling in 790 distinct operons. Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes. Numerous examples of co-transcription of genes encoding functionally related proteins are evident. Inspection of the operon list should reveal previously unknown functional relationships.


Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn's disease and ulcerative colitis?
The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide. We review novel biologic agents targeting the T-helper 17 axis, including therapies directed towards interleukin (IL)-17 (secukinumab, ixekizumab, bimekizumab), IL-17R (brodalumab), IL-12/23p40 (ustekinumab, briakinumab) and IL-23p19 (guselkumab, tildrakizumab, brazikumab, risankizumab, mirikizumab). We also present an overview of biologics active against type I and II interferons, including sifalumumab, rontalizumab, anifrolumab and fontolizumab. Emerging strategies to interfere with cellular adhesion processes involved in lymphocyte recruitment are discussed, including both integrin blockade (natalizumab, vedolizumab, etrolizumab) and sphingosine-1-phosphate receptor inhibition (fingolimod, ozanimod). We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib) and second-generation selective JAK inhibitors (decernotinib, filgotinib, upadacitinib). New biologics targeting B-cells (including ocrelizumab, veltuzumab, tabalumab and atacicept) and the development of novel strategies for regulatory T-cell modulation (including low-dose IL-2 therapy and Tregitopes) are also discussed. Finally, we explore recent biotechnological advances such as the development of bispecific antibodies (ABT-122, COVA322), and their application to the treatment of IMIDs.


Endogenous sex hormone levels and cognitive function in aging men: is there an optimal level?
To determine whether endogenous sex hormone levels are associated with cognitive functioning in men. Cognitive performance was assessed in 400 independently living men between ages 40 and 80 in a population-based cross-sectional study. Compound scores were calculated for memory function, processing capacity/speed, and executive function. The Mini-Mental State Examination was used as a measure of global cognitive function. The adjusted association of testosterone (T) and estradiol (E2) (total, bioavailable) with neuropsychological test scores in the total group and in subgroups was assessed by linear and logistic regression analysis. Curvilinear associations were observed between T and memory performance and processing capacity/speed, suggesting optimal sex hormone levels. No association between E2 and cognitive functioning was found. After the population was subdivided into four age decades, a linear association of T with cognitive functioning in the oldest age category remained. No association was found in the other age decades. Lower bioavailable T levels were associated with lower scores on processing capacity/speed and executive function; beta (95% CI) values were 0.36 (0.07 to 0.66) and 0.17 (-0.01 to 0.35). Similar results were observed for total T. Higher testosterone (T) levels are associated with better cognitive performance in the oldest age category. Apparent curvilinear associations between T and certain cognitive functions in men suggest an optimal hormone level for particular cognitive tasks and are explained by linear associations in the oldest age category.


Disparate Metabolomics Data Reassembler: A Novel Algorithm for Agglomerating Incongruent LC-MS Metabolomics Datasets.
In the past decade, the field of LC-MS-based metabolomics has transformed from an obscure specialty into a major "-omics" platform for studying metabolic processes and biomolecular characterization. However, as a whole the field is still very fractured, as the nature of the instrumentation and the information produced by the platform essentially creates incompatible "islands" of datasets. This lack of data coherency results in the inability to accumulate a critical mass of metabolomics data that has enabled other -omics platforms to make impactful discoveries and meaningful advances. As such, we have developed a novel algorithm, called Disparate Metabolomics Data Reassembler (DIMEDR), which attempts to bridge the inconsistencies between incongruent LC-MS metabolomics datasets of the same biological sample type. A single "primary" dataset is postprocessed via traditional means of peak identification, alignment, and grouping. DIMEDR utilizes this primary dataset as a progenitor template by which data from subsequent disparate datasets are reassembled and integrated into a unified framework that maximizes spectral feature similarity across all samples. This is accomplished by a novel procedure for universal retention time correction and comparison via identification of ubiquitous features in the initial primary dataset, which are subsequently utilized as endogenous internal standards during integration. For demonstration purposes, two human and two mouse urine metabolomics datasets from four unrelated studies acquired over 4 years were unified via DIMEDR, which enabled meaningful analysis across otherwise incomparable and unrelated datasets.


Newly synthesized peripherally octa-substituted zinc phthalocyanines carrying halogen terminated phenoxy-phenoxy moiety: comparative photochemical and photophysical features.
This study reports the 3 new phthalonitrile derivatives, namely 4, 5 Bis-[4-(4-bromophenoxy) phenoxy] phthalonitrile ( 1 ), 4,5 Bis-[4-(4-chlorophenoxy) phenoxy]phthalonitrile ( 2 ), and 4, 5 Bis[4-(4-fluorophenoxy) phenoxy] phthalonitrile ( 3 ). Their octa-substituted zinc phthalocyanines ( 4 , 5 , 6 ) are reported for the first time in this study. The resulting compounds were characterized by utilizing some spectroscopic methods, such as UV-Vis, 1HNMR, FT-IR spectroscopy, as well as mass spectraand elemental analysis. To show photosynthesizer's potential, emission (F F ), singlet oxygen (1O2), and photodegradation quantum yields (F∆, Fd) of octa-peripherally phthalocyanines (Pcs) were performed in the solutions, such as biocompatible solvent DMSO (dimethyl sulfoxide) as well as DMF (dimethylformamide) and THF (tetrahydrofuran). Solvent and octa-peripherally binding effect of the halogen (Br, Cl, F) terminated phenoxy-phenoxy groups on phthalocyanine rings for photophysicochemical properties ( 4 , 5 , and 6 ) were compared with the tetra-peripherally and tetra nonperipherally substituted derivatives. The new dyes ( 4 to 6 ) may be evaluated in photodynamic therapy (PDT) of cancer as photosensitizers due to efficient 1O2 from 0.55 to 0.75.


NASPGHAN Clinical Report on Postoperative Recurrence in Pediatric Crohn Disease.
Pediatric Crohn disease is characterized by clinical and endoscopic relapses. The inflammatory process is considered to be progressive and may lead to strictures, fistulas, and penetrating disease that may require surgery. In addition, medically refractory disease may be treated by surgical resection of inflamed bowel in an effort to reverse growth failure. The need for surgery in childhood suggests severe disease and these patients have an increased risk for recurrent disease and potentially more surgery. Data show that up to 55% of patients had clinical recurrence in the first 2 years after initial surgery. The current clinical report on postoperative recurrence in pediatric Crohn disease reviews the risk factors for early surgery and postoperative recurrence, operative risk factors for recurrence, and prevention and monitoring strategies for postoperative recurrence. We also propose an algorithm for postoperative management in pediatric Crohn disease.


A Randomized Controlled Trial of the Collaborative Assessment and Management of Suicidality (CAMS) Versus Treatment as Usual (TAU) for Suicidal College Students.
This randomized controlled trial compared the Collaborative Assessment and Management of Suicidality (CAMS) and Treatment as Usual (TAU) for suicidal college students within a feasibility trial. Sixty-two suicidal college students were randomized to CAMS (n = 33) or TAU (n = 29). We hypothesized that those receiving CAMS would show more improvement in suicide-related measures, and effects would be moderated by borderline personality disorder (BPD), prior suicide attempts, and age. Both treatment groups showed improvements in all outcome variables; CAMS had a significantly higher impact on depression and suicidal ideation when measured weekly during care and was more likely than TAU to decrease hopelessness among students with fewer BPD features, no suicide attempt history, and older age. Conversely, TAU did better for students with BPD features and history of multiple suicide attempts.


Sediminibacterium goheungense sp. nov., isolated from a freshwater reservoir.
A novel bacterial strain designated HME7863(T) was isolated from a freshwater reservoir in Goheung, Republic of Korea. Cells of strain HME7863(T) were Gram-staining-negative, strictly aerobic, orange-pigmented, rod-shaped and motile by gliding. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain HME7863(T) formed a lineage within the genus Sediminibacterium. Strain HME7863(T) was closely related to Sediminibacterium ginsengisoli DCY13(T) (96.9 % sequence similarity) and Sediminibacterium salmoneum NJ-44(T) (96.4 %). The major cellular fatty acids were iso-C15 : 1 G, iso-C15 : 0, iso-C17 : 0 3-OH and iso-C16 : 0 3-OH. Polar lipid analysis revealed the presence of phosphatidylethanolamine, five unidentified aminolipids, two unidentified aminophospholipids, one unidentified phospholipid and two unidentified polar lipids. The only respiratory quinone was MK-7. The DNA G+C content was 40.5 mol%. On the basis of the evidence presented in this study, strain HME7863(T) represents a novel species of the genus Sediminibacterium, for which the name Sediminibacterium goheungense sp. nov., is proposed. The type strain is HME7863(T) ( = KCTC 23945(T) = CECT 8100(T)).


Construction of a collagen-based, split-thickness cornea substitute.
Tissue-engineered corneas may become a promising alternative to allografts in the treatment of serious cornea defects because of the tunable characteristics of the biomaterials, biomimetic designs, and incorporation of patient's own cells. In this study, collagen foam was coated with a fibrous mat to mimic the stromal layer and the Bowman's layer. The stromal layer substitute was made of N-ethyl-N-(3-dimethyl aminopropyl)carbodiimide/N-hydroxysuccinimide-cross-linked collagen-chondroitin sulfate foam and seeded with primary human corneal keratocytes (HK). Retinal pigment epithelium (RPE) cells served as the epithelial layer after seeding on a dehydrothermally cross-linked collagen type I fibrous mat deposited directly on top of the foams by electrospinning. The physical characterization and the in vitro studies showed that the designed cornea replacement was suitable for cell attachment and growth, and co-culture of the two cell types induced more extracellular matrix (ECM) deposition than the single cell-seeded constructs. The fiber layer was shown to be successful in separating the HK and RPE cells, and still allowed them to maintain cell-cell communication as the increase in ECM deposition and the maintenance of the high transparency (~80%) suggested. This split-thickness corneal substitute was also shown to be readily suturable without any major tears at the end of a short co-culture of 30 days.


Basics of breastfeeding. Part I: Infant feeding patterns past and present.
One of the great medical advances of the past decade has been the scientific validation of the importance of species-specific milk. This "discovery" has led to a growing general awareness of the value, during the first year of life, of the milk of the baby's own mother for optimal physical and emotional development. These benefits of breastfeeding may last a lifetime. The need to understand and assist the mother in maintaining this relationship presents a major challenge to the nurse. Beginning with this issue of JOGN and continuing in two subsequent issues a series of six articles is being presented that gives an overview of breastfeeding, from historical perspectives to specific problems nursing mothers may encounter. The initial installment consists of "Infant Feeding Patterns Past and Present" and "The Anatomy and Psychophysiology of Lactation." Following in September/October and November/December will be "The Biologic Specificity of Breast Milk," "Preparation for Breastfeeding and Early Optimal Functioning," "Self-Care for Continued Breastfeeding," and "Some Breastfeeding Problems and Solutions." The cultural pattern of breastfeeding in ancient and contemporary cultures are compared, and changes during the Industrial Revolution that led to the decline in breastfeeding are outlined. Also described are the consequences of the trend away from breastfeeding in Third World countries and current breastfeeding patterns in the United States.


A large increase of Salmonella infections in 2003 in The Netherlands: hot summer or side effect of the avian influenza outbreak?
In June 2003, the Dutch National Salmonella Centre reported a significant excess isolation rate of Salmonella Enteritidis when compared with earlier years in most regional public health laboratories. By the end of 2003, this amounted to an extra 540 laboratory confirmed cases for the whole of the Netherlands, which implies an estimated 7500 extra cases of gastroenteritis caused by S. Enteritidis in the general population, an increase of 50% on previous years. The hot summer could not explain the findings. Strong evidence has been found to suggest that the increase in importation of salmonella contaminated eggs, as a side effect of a concurrent avian influenza outbreak, was the most probable reason for this excess.


Rapid and selective modification of phosphoserine residues catalysed by Ba2+ ions for their detection during peptide microsequencing.
The beta-elimination of phosphoserine residues by dilute alkali is catalysed by the presence of group II metal ions. The use of 0.1 M-Ba (OH)2 catalysed the rate of beta-elimination of phosphoserine by more than two orders of magnitude compared with the use of NaOH at the same OH-ion concentration. Serine and threonine residues are unaffected by this treatment. Free thiol groups and disulphide bonds are labile to these conditions, but carboxymethylcysteine is stable. The rate of beta-elimination of O-glycosidically linked moieties is not catalysed under these conditions, and the rate of reaction is thus two orders of magnitude slower than for phosphoserine. This specific catalysis was readily exploited in the rapid and selective modification of phosphoserine residues under mildly alkaline conditions with the nucleophile methylamine via the alpha beta-desaturated dehydroalanine intermediate to yield the beta-methylaminoalanine residue. This modified residue could be easily detected on sequence analysis and in amino acid compositions.


Thoracic sympathectomy for hyperhidrosis: from surgical indications to clinical results.
Sympathectomy and its variations have been performed in thoracic surgery for more than 100 years. However, its indications have undergone profound modifications in this period. Likewise, since then the surgical technique has also evolved dramatically up to the minimally invasive techniques worldwide accessible in present days. Currently, primary hyperhidrosis is, by far, the main indication for thoracic sympathectomy and this procedure is usually carried out thoracoscopically with excellent results. However, until today, hyperhidrosis is a part of thoracic surgery still surrounded by controversy, persisting as an open field over which some confusion still resides regarding its pathophysiology, terms definitions and operative approaches. The aim of this article is to provide a wide but easily comprehensible review of the theme, discussing and clarifying the major concepts with respect to its clinical presentation, all the presently available treatment options and strategies with their potential benefits and risks, the adequate patient selection for sympathectomy, as well as the postoperative clinical results.


Female influence over offspring paternity in the red flour beetle Tribolium castaneum.
In animals having internal fertilization, both sexes can potentially influence the post-copulatory processes of sperm transfer, sperm storage and sperm use for fertilization. In this experiment, we investigated whether Tribolium castaneum females can influence male paternity success following consecutive matings with two different males. We compared second male paternity success (P2) between females exposed to carbon dioxide (CO2) and control females kept in air, in both cases for 30 min between two matings. CO2 exposure inhibits muscular activity and has previously been shown to decrease sperm storage by T. castaneum females. Females exposed to CO2 after their first mating showed significantly higher P2 than control females during the later portion of a one-month oviposition period. These results are consistent with reduced storage of first male sperm by CO2-exposed females. Also, T. castaneum females showed considerable variation in spermathecal morphology, and P2 decreased with increasing spermathecal tubule volume. These results demonstrate that T. castaneum females can influence male paternity success, and suggest that differential sperm storage may be an important mechanism of post-copulatory female choice.


[Research progress on phenotype and genotype of hyperphenylalaninemia].
Hyperphenylalaninemia(HPA), an autosomal recessive disease, is the most common inborn error of amino acid metabolism, caused by the deficiency of phenylalanine hydroxylase(PAH) or tetrahydrobiopterin(BH4) which induced by mutations of genes. The accumulation of the clinical database and genetic information will enhance the development of novel personalized medicine and to provide more accurate and timely diagnostic and therapeutic approaches for HPA. This paper summarizes the correlations between HPA metabolism and PAH, BH4, pathogenic genes and their distributions in HPA, as well as the phenotypes and genotypes of HPA, so as to provide reference for personalized medicine for HPA.


Monoclonal antibody identification of a potentially lithogenic protein extracted from human renal calculi.
In an attempt to identify potentially lithogenic proteins, a detergent soluble extract of human renal calculi was used to produce a unique monoclonal antibody. The monoclonal antibody was found to detect the presence of a specific epitope in 77% of individually extracted kidney stones from our patients' stone bank at The Long Island Kidney Stone Unit, State University of New York, Stony Brook. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoprecipitation, and Western Blot analysis revealed this monoclonal antibody to be specific to a protein of 83,000 dalton molecular weight. A secondary source of protein reactive to the monoclonal antibody was subjected to enzyme kinetic studies, those studies suggested that the 83,000 dalton protein is a member of the protein-glutamine gammaglutamyltransferase (transglutaminase) family of enzymes. It was not determined in the present investigation whether a member of this family of enzymes initiates or is necessary for lithiasis.


Phosphorus recovery from wastewater through struvite formation in fluidized bed reactors: a sustainable approach.
Recovery of phosphate as struvite (MgNH4PO4.6H2O), before it forms and accumulates on wastewater treatment equipment, solves wastewater treatment problems and also provides environmentally sustainable, renewable nutrient source for the agriculture sector. A pilot-scale fluidized bed reactor was used to recover phosphate through crystallization of struvite, from anaerobic digester centrate at the Lulu Island Wastewater Treatment Plant, Richmond, British Columbia, Canada. The desired degree of phosphate removal was achieved by maintaining operating pH (8.0-8.2), and recycle ratio 5-9, to control the supersaturation conditions inside the reactor. The performance of the system was found to be optimal when in-reactor supersaturation ratio was 2-6. Among several other operating parameters, apparent upflow velocity and magnesium to phosphate molar ratio were also found important to maintain system performance, both in terms of efficiency of phosphate removal and recovery as struvite pellets. A narrow window of upflow velocity (400-410 cm/min) was found to be effective in removing 75-85% phosphate. TOC level inside the rector was found to affect the performance to some extent. The precipitation potential of struvite could be successfully predicted using a thermodynamic solubility product value of 10(-13.36) and its temperature dependence in PHREEQC.


[Neuroendocrine tumors and liver transplantation: review based on a case report].
A case of orthotopic liver transplantation (OLT) for secondary Neuroendocrine Tumor (NET), whose primary site was not detected at the time of surgery, is reported. The primary pancreatic lesion was found 20 months later in association with recurrence of neoplasm in the graft and with a paraneoplastic syndrome peculiar of glucagonoma. The patient started octreoide therapy with a decrease of the glucagone level but without reduction of the tumor size, nor disappearance of the clinical syndrome. A few months later the primary lesion was surgically removed, but her general condition deteriorated and the patient died waiting for liver retransplantation. A discussion about the management and the diagnostic tools for preoperative staging of these neoplasms and their ability to identify the primitive and secondary location of neuroendocrine tumors is presented.


Response of early-weaned pigs to an enterotoxigenic Escherichia coli (K88) challenge when fed diets containing spray-dried porcine plasma or pea protein isolate plus egg yolk antibody, zinc oxide, fumaric acid, or antibiotic.
The effect of feeding diets containing either spray-dried porcine plasma (SDPP) or pea protein-isolate (PPI) supplemented with either egg yolk antibodies (EYA) from hens immunized with enterotoxigenic Escherichia coli (ETEC) (K88 and F18) antigens, ZnO, fumaric acid (FA), or carbadox (AB) on pig performance, incidence of scours, and gut morphology was studied in a 14-d experiment. Ninety 10-d-old weaned pigs were assigned to six dietary treatments in a completely randomized design to give five pens per treatment with three pigs per pen. The diets were SDPP without EYA (SDPP - EYA), PPI without EYA (PPI - EYA), PPI with EYA (PPI + EYA), PPI with ZnO (PPI + ZnO), PPI with FA (PPI + FA), or PPI with AB (PPI + AB). Diets were formulated to similar nutrient levels, with AB, EYA, FA, and ZnO at 0.25, 0.5, 2.0, and 0.4% of the diet, respectively. Pigs were weighed and bled on d 0, 7, and 14 to determine plasma urea N (PUN). Pigs were orally challenged with a 6-mL dose of 10(10) cfu/mL ETEC (K88) on d 7. On d 14, three pigs per treatment were killed to obtain sections of the small intestine for histological measurements. Weekly feed intake, BW changes, and gain:feed were determined. Incidence of scours and scour scores were monitored and fecal swabs were taken before and after ETEC challenge for PCR test to detect ETEC (K88). Feeding SDPP or supplementing PPI-based diets with EYA, ZnO, FA, or AB did not affect (P > 0.05) ADG, ADFI (as-fed basis), or gain:feed throughout the study. However, pigs fed PPI - EYA tended to have lower (P = 0.08) ADFI during wk 2 (137.9 g/d) and lower (P < 0.10) ADG from d 0 to 14 (100.1 g/d) than those fed the SDPP - EYA (156.6 g/d), PPI + EYA (151.2 g/d), PPI + ZnO (158.9 g/ d), PPI + FA (155.4 g/d), and PPI + AB (152.6 g/d) diets. Although scours was evident in all pigs 8 h after the ETEC challenge, it lasted only 3 to 5 d in pigs fed SDPP or PPI supplemented with EYA, ZnO, FA, or AB. Pigs fed PPI - EYA continued to have severe diarrhea, resulting in 40% mortality vs. 13% or less in the other groups. The PCR results showed that 81% of PPI-fed pigs continued to shed ETEC K88 7 d after ETEC challenge. Pigs fed PPI-EYA had shorter villi (P < 0.05), reduced villi:crypt ratio (P < 0.003), and higher intestinal pH (P < 0.001) and PUN (P < 0.001) than those fed SDPP or PPI supplemented with EYA, ZnO, FA, and AB. In conclusion, SDPP, EYA, ZnO, FA, and AB may have provided passive control to ETEC (K88) infection and potentially enabled young pigs to efficiently utilize a PPI-based diet.


Adherence to a Mediterranean Diet Protects from Cognitive Decline in the Invecchiare in Chianti Study of Aging.
Following a Mediterranean diet high in plant-based foods and fish, low in meat and dairy foods, and with moderate alcohol intake has been shown to promote healthy aging. Therefore, we examined the association between a Mediterranean diet and trajectories of cognitive performance in the InCHIANTI study. Subjects (N = 832) were examined every 2⁻3 years up to 18 years with an average follow-up period of 10.1 years. Cognitive performance was assessed using the Mini Mental State Examination (MMSE) at every visit. Dietary habits were assessed using a validated food frequency questionnaire and adherence to Mediterranean diet was computed on a scale of 0-9 and categorized into three groups of low (≤3), medium (4⁻5), and high (≥6). Those in the highest adherence group (OR = 0.48, 95% CI: 0.29⁻0.79) and medium adherence group (OR = 0.64, 95% CI: 0.41⁻0.99) were less likely to experience cognitive decline. The annual average decline in MMSE scores was 0.4 units, for those in the high and medium adherence group this decline was attenuated by 0.34 units (p < 0.001) and 0.16 units (p = 0.03), respectively. Our findings suggest that adherence to a Mediterranean diet can have long-lasting protective effects on cognitive decline and may be an effective strategy for the prevent or delay dementia.


Evaluation of subchronic repeated administration toxicity of ammonium nitrate in rats.
Ammonium nitrate is a chemical mostly used in agriculture and munitions to produce fertilizers and explosives, respectively. Its annual production and consumption exceed ten million tons. Despite is diverse uses, large production and consumption, and occupational risk, information on the toxicity that results from oral exposure to ammonium nitrate is limited. In this study, the safety of ammonium nitrate was therefore evaluated by observing its subchronic toxicity in rats. Ammonium nitrate (0, 100, 300 and 1000 mg/kg/day) was orally administered by gavage to rats at 5 times/week for 13 weeks. Reversibility of the effects of 1000 mg/kg/day was assessed in rats after 2 weeks. Mortality, clinical signs, body weight, and food consumption were monitored. Hematology, serum chemistry, urinalysis, organ weight, necropsy, and histopathology were performed. Salivation was intermittently observed in both sexes receiving 300 and 1000 mg/kg/day ammonium nitrate, which normalized 2 weeks post-treatment. Urine volume increased in both sexes receiving 1000 mg/kg/day ammonium nitrate. Urine pH decreased in both sexes of all dosing groups when compared with the concurrent control group. Urinary changes normalized 2 weeks post-treatment. Blood urea nitrogen levels increased in males receiving 1000 mg/kg/day, but normalized 2 weeks later. Potassium level in males and sodium and chloride levels in both sexes receiving 1000 mg/kg/day ammonium nitrate decreased, but normalized 2 weeks later. Hypertrophy of zona glomerulosa in the adrenals was observed in both sexes receiving 1000 mg/kg/day and in females receiving 300 mg/kg/day ammonium nitrate. After a 2-week recovery period, the same lesion was observed in one female receiving 1000 mg/kg/day ammonium nitrate. Our results indicate that ammonium nitrate induces reversible salivation, increases BUN levels, induces acidic diuresis with decreases in sodium, potassium, and chloride levels, and induces ZG hypertrophy. These results shed light on the toxicity profile of ammonium nitrate.


Introducing Overlapping Grain Boundaries in Chemical Vapor Deposited Hexagonal Boron Nitride Monolayer Films.
We demonstrate the growth of overlapping grain boundaries in continuous, polycrystalline hexagonal boron nitride (h-BN) monolayer films via scalable catalytic chemical vapor deposition. Unlike the commonly reported atomically stitched grain boundaries, these overlapping grain boundaries do not consist of defect lines within the monolayer films but are composed of self-sealing bilayer regions of limited width. We characterize this overlapping h-BN grain boundary structure in detail by complementary (scanning) transmission electron microscopy techniques and propose a catalytic growth mechanism linked to the subsurface/bulk of the process catalyst and its boron and nitrogen solubilities. Our data suggest that the overlapping grain boundaries are comparatively resilient against deleterious pinhole formation associated with grain boundary defect lines and thus may reduce detrimental breakdown effects when polycrystalline h-BN monolayer films are used as ultrathin dielectrics, barrier layers, or separation membranes.


Comparison of aortic and carotid arterial stiffness parameters in patients with verified coronary artery disease.
Arterial stiffness parameters are commonly used to determine the development of atherosclerotic disease. The independent predictive value of aortic stiffness has been demonstrated for coronary events. The aim of our study was to compare regional and local arterial functional parameters measured by 2 different noninvasive methods in patients with verified coronary artery disease (CAD). We also compared and contrasted these stiffness parameters to the coronary SYNTAX score in patients who had undergone coronary angiography. In this study, 125 CAD patients were involved, and similar noninvasive measurements were performed on 125 healthy subjects. The regional velocity of the aortic pulse wave (PWVao) was measured by a novel oscillometric device, and the common carotid artery was studied by a Doppler echo-tracking system to determine the local carotid pulse wave velocity (PWVcar). The augmentation index (AIx), which varies proportionately with the resistance of the small arteries, was recorded simultaneously. In the CAD group, the PWVao and aortic augmentation index (Alxao) values increased significantly (10.1 ± 2.3 m/sec and 34.2% ± 14.6%) compared to the control group (9.6 ± 1.5 m/sec and 30.9% ± 12%; P < 0.05). We observed similar significant increases in the local stiffness parameters (PWVcar and carotid augmentation index [Alxcar]) in patients with verified CAD. Further, we found a strong correlation for PWV and AIx values that were measured with the Arteriograph and those obtained using the echo-tracking method (r = 0.57, P < 0.001 for PWV; and r = 0.65, P < 0.001 for AIx values). Our results indicate that local and regional arterial stiffness parameters provide similar information on impaired arterial stiffening in patients with verified CAD.


Application of array-based age prediction models to post-mortem tissue samples.
Since DNA methylation at specific CpG sites exhibits a strong age association, researchers have developed numerous age prediction models based on the methylation BeadChip array. These models harness epigenetic clocks that hold the potential to narrow down the search range for unknown suspects and unidentified victims. This study collected 180 post-mortem tissue samples comprising nine tissue types (blood, brain, heart, lung, liver, kidney, muscle, epidermis, and dermis) from autopsies of 20 Koreans aged 18-78. Subsequently, DNA methylation profiling was conducted using the Infinium MethylationEPIC array. We tested several array-based age prediction models using the data obtained from various tissues. The pan-tissue clock exhibited a moderately accurate prediction across all nine tissue types (MAE = 8.7 years, r = 0.88). Notably, the DNAm ages of the Hannum clock, the skin & blood clock, and the Zhang clock strongly correlated with the actual age in blood samples (MAE < approximately 5 years, r > 0.9). PhenoAge yielded an MAE of 10.1 years and an r-value of 0.92. The muscle-specific epigenetic clock, the MEAT package, demonstrated high prediction accuracy in muscle samples (MAE = 4.7 years, r = 0.93). Those previously reported array-based age prediction models were mainly constructed in Europeans but performed well in Koreans. In addition, tests involving various quantities of DNA and fragmented DNA have shown that DNA quantity and quality affected methylation measurements and age prediction results. However, robust age prediction models exist under low amounts of DNA and fragmented DNA conditions.


Detection of group B Streptococcus by immunoassay following enrichment in LIM-selective broth medium.
Rapid immunoassays have been developed to decrease the time to detection of Group B Streptococcus (GBS) carriage in pregnant women. In this study, a total of 162 pregnant women, considered to be high-risk obstetric patients, were seen in the Family Care Center at Memorial Hospital of Rhode Island, a 300-bed teaching hospital associated with Brown University Medical School. Vaginal and rectal specimens were taken and tested for GBS by using two rapid enzyme immunoassays (EIAs) that were compared with culture. Quidel and Hybritech ICON Group B strep tests were run following 4 h incubation in the selective enrichment LIM Group B strep broth; cultures were done both directly and after enrichment. Results with both EIAs were identical, with overall sensitivity, specificity, and positive and negative predictive values of 38%, 98%, 88%, and 84% respectively. However, when women having positive cultures were separated into moderately to heavily colonized (> or = 3 +) and lightly colonized (< or = 2 +) populations, the sensitivities were 82% and 19%, respectively. Although GBS assays are useful in the rapid diagnosis of heavily colonized women, culture following enrichment remains the most sensitive method for a lightly colonized population.


Induction of leukemic-cell-specific cytotoxic T lymphocytes by autologous monocyte-derived dendritic cells presenting leukemic cell antigens.
Leukemic-dendritic cells (leukemic-DCs) have certain limitations, which include difficult generation in 30-40% of patients, and low levels of expression of several key molecules. Therefore, an alternative approach using monocyte-derived DCs pulsed with tumor antigens is required. We investigated the possibility of immunotherapy for AML using leukemic-cell-specific cytotoxic T lymphocytes that were stimulated in vitro by autologous DCs pulsed with tumor antigens. To generate DCs, CD14(+) cells were isolated from peripheral blood mononuclear cells using magnetic-activated cell sorting, and cultured in the presence of GM-CSF and IL-4. On day 6, maturation of DCs was induced by addition of cytokine cocktail (TNF-alpha, IL-1beta, IL-6, and prostaglandin E(2)) for 2 days, and then the mature DCs were pulsed with whole leukemic cell lysates or apoptotic leukemic cells. There were no differences in the phenotypic expressions of mature DCs generated by pulsing with or without leukemic antigens. The mature DCs pulsed with tumor cell lysates or apoptotic leukemic cells showed a higher allostimulatory capacity for allogeneic CD3(+) T cells as compared with mature non-pulsed DCs. Autologous CD3(+) T cells stimulated by the mature pulsed DCs showed more potent cytotoxic activities against autologous leukemic cells than those stimulated by mature non-pulsed DCs. These results suggest that use of DCs pulsed with leukemic cell lysates or apoptotic leukemic cells is a feasible alternative immunotherapeutic approach to overcome the limitations of leukemic-DCs for the treatment of AML patients.


The effects of forced-egg retention on the blood-feeding behavior and reproductive potential of Culex pipiens (Diptera: Culicidae).
High rates of West Nile virus (WNV) transmission to humans are associated with exceptionally hot and dry summers. This is paradoxical since the eggs of Culex vectors of WNV depend on the persistence of containers with water, which decline during droughts. We examined the effects of forced-egg retention on the reproductive success of female Culex pipiens as well as behavioral responses, such as likelihood of secondary blood meals. As controls we examined the effects of female age and delayed mating. We found that early mating is essential to achieve reproductive success and, consistent with an "all-or-none" ovipositing strategy, C. pipiens females are able to retain considerable reproductive potential while searching for oviposition sites. Specifically, although forced-egg retention resulted in significant decreases in fitness, the decline was moderate for 5 weeks and most can be accounted for by increases in female age. Consequently, no females took blood more than once per gonotrophic cycle, which eliminates the possibility that heightened vectorial capacity due to multiple blood-feedings increases WNV transmission during periods of drought. Instead, our findings suggest that during droughts populations of C. pipiens have time to locate the remaining water holes, which are associated with human populations and WNV-competent bird species.


[Analysis of 208 flexible bronchoscopies performed in an intensive care unit].
To describe the main indications, clinical results and complications associated with fibrobronchoscopy in the Intensive Care Unit (ICU). A retrospective, single-center observational study was carried out. Setting. Seventeen beds in a medical/surgical ICU. Patients. Consecutive patients undergoing fibrobronchoscopy during their stay in the ICU over a period of 5 years. Flexible bronchoscopy performed by an intensivist. Main variables of interest. Flexible bronchoscopy indications and complications derived from the procedure. A total of 208 flexible bronchoscopies were carried out in 192 patients admitted to the ICU. Most of the procedures (193 [92.8%]) were performed in mechanically ventilated patients. The average patient age was 58 ± 16 years, with an APACHE II score at admission of 19 ± 7. The most frequent indication for flexible bronchoscopy was diagnostic confirmation of initially suspected pneumonia (148 procedures), with positive bronchoalveolar lavage findings in 46%. The most frequent therapeutic indication was the resolution of atelectasis (28 procedures). Other indications were the diagnosis and treatment of pulmonary hemorrhage, the aspiration of secretions, control of percutaneous tracheotomy, and difficult airway management. The complications described during the procedures were supraventricular tachycardia (3.8%), transient hypoxemia (6.7%), and slight bleeding of the bronchial mucosal membrane (2.4%). A microbiological diagnosis of pneumonia and the resolution of atelectasis are the most frequent indications for flexible bronchoscopy in critically ill patients. Flexible bronchoscopy performed by an intensivist in ICU is a safe procedure.


Pathogenesis of the hepatorenal syndrome.
This review examines current understanding about the patient with moderately advanced cirrhosis of the liver and his or her transition to hepatorenal syndrome (HRS). Special emphasis is given to three areas of ongoing research. Atrial natriuretic factor's role in the pathogenesis of salt and water retention is examined, as well as its role in determining volume status in these patients. The current literature regarding prostaglandins (PGs) is reviewed, with emphasis on how vasodilatory PGs appear first to help maintain homeostasis in advanced cirrhosis and how vasoconstrictor thromboxane may then be involved in the transition to HRS. Finally, new findings regarding the liver hormone glomerulopressin are examined, and how deficient release of this may lead to the decrease in glomerular filtration rate seen in HRS.


Mutations in PIK3R1 cause SHORT syndrome.
SHORT syndrome is a rare, multisystem disease characterized by short stature, anterior-chamber eye anomalies, characteristic facial features, lipodystrophy, hernias, hyperextensibility, and delayed dentition. As part of the FORGE (Finding of Rare Disease Genes) Canada Consortium, we studied individuals with clinical features of SHORT syndrome to identify the genetic etiology of this rare disease. Whole-exome sequencing in a family trio of an affected child and unaffected parents identified a de novo frameshift insertion, c.1906_1907insC (p.Asn636Thrfs*18), in exon 14 of PIK3R1. Heterozygous mutations in exon 14 of PIK3R1 were subsequently identified by Sanger sequencing in three additional affected individuals and two affected family members. One of these mutations, c.1945C>T (p.Arg649Trp), was confirmed to be a de novo mutation in one affected individual and was also identified and shown to segregate with the phenotype in an unrelated family. The other mutation, a de novo truncating mutation (c.1971T>G [p.Tyr657*]), was identified in another affected individual. PIK3R1 is involved in the phosphatidylinositol 3 kinase (PI3K) signaling cascade and, as such, plays an important role in cell growth, proliferation, and survival. Functional studies on lymphoblastoid cells with the PIK3R1 c.1906_1907insC mutation showed decreased phosphorylation of the downstream S6 target of the PI3K-AKT-mTOR pathway. Our findings show that PIK3R1 mutations are the major cause of SHORT syndrome and suggest that the molecular mechanism of disease might involve downregulation of the PI3K-AKT-mTOR pathway.


Where do we stand now? Mouse early embryo patterning meeting in Freiburg, Germany (2005).
Mechanism underlying mammalian preimplantation development has long been a subject of controversy and the central question has been if any "determinants" play a key role in a manner comparable to the non-mammalian "model" system. During the last decade, this issue has been revived (Pearson, 2002; Rossant and Tam, 2004) by claims that the axes of the mouse blastocyst are anticipated at the egg ("prepatterning model"; Gardner, 1997; Gardner, 2001; Piotrowska et al., 2001; Piotrowska and Zernicka-Goetz, 2001; Zernicka-Goetz, 2005), suggesting that a mechanism comparable to that operating in non-mammals may be at work. However, recent studies by other laboratories do not support these claims ("regulative model"; Alarcon and Marikawa, 2003; Chroscicka et al., 2004; Hiiragi and Solter, 2004; Alarcon and Marikawa, 2005; Louvet-Vallee et al., 2005; Motosugi et al., 2005) and the issue is currently under hot debate (Vogel, 2005). Deepening our knowledge of this issue will not only provide an essential basis for understanding mammalian development, but also directly apply to ongoing clinical practices such as intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis (PGD). These practices were originally supported by a classical premise that mammalian preimplantation embryos are highly regulative (Tarkowski, 1959; Tarkowski, 1961; Tarkowski and Wroblewska, 1967; Rossant, 1976), in keeping with the "regulative model". However, if the "prepatterning model" is correct, the latter will require critical reassessment.


Rhizophagy Cycle: An Oxidative Process in Plants for Nutrient Extraction from Symbiotic Microbes.
In this paper, we describe a mechanism for the transfer of nutrients from symbiotic microbes (bacteria and fungi) to host plant roots that we term the 'rhizophagy cycle.' In the rhizophagy cycle, microbes alternate between a root intracellular endophytic phase and a free-living soil phase. Microbes acquire soil nutrients in the free-living soil phase; nutrients are extracted through exposure to host-produced reactive oxygen in the intracellular endophytic phase. We conducted experiments on several seed-vectored microbes in several host species. We found that initially the symbiotic microbes grow on the rhizoplane in the exudate zone adjacent the root meristem. Microbes enter root tip meristem cells-locating within the periplasmic spaces between cell wall and plasma membrane. In the periplasmic spaces of root cells, microbes convert to wall-less protoplast forms. As root cells mature, microbes continue to be subjected to reactive oxygen (superoxide) produced by NADPH oxidases (NOX) on the root cell plasma membranes. Reactive oxygen degrades some of the intracellular microbes, also likely inducing electrolyte leakage from microbes-effectively extracting nutrients from microbes. Surviving bacteria in root epidermal cells trigger root hair elongation and as hairs elongate bacteria exit at the hair tips, reforming cell walls and cell shapes as microbes emerge into the rhizosphere where they may obtain additional nutrients. Precisely what nutrients are transferred through rhizophagy or how important this process is for nutrient acquisition is still unknown.


Dust measurements in the coma of comet 81P/Wild 2 by the Dust Flux Monitor Instrument.
We present measurements of the dust particle flux and mass distribution from the Stardust Dust Flux Monitor Instrument (DFMI) throughout the flyby of comet 81P/Wild 2. In the particle mass regime from 10(-14) to 10(-7) kilograms, the spacecraft encountered regions of intense swarms of particles, together with bursts of activity corresponding to clouds of particles only a few hundred meters across. This fine-scale structure can be explained by particle fragmentation. We estimate that 2800 +/- 500 particles of diameter 15 micrometers or larger impacted the aerogel collectors, the largest being approximately 6 x 10(-7) kilograms, which dominates the total collected mass.


Medulloblastoma-derived tumor stem-like cells acquired resistance to TRAIL-induced apoptosis and radiosensitivity.
Medulloblastoma (MB) is the most malignant primary brain tumor in early childhood that contains cellular and functional heterogeneity. Recent evidence has demonstrated that the tumor stem cells (TSC) may explain the radiochemoresistance of brain tumors, including MB. The aim of the present study is to investigate the possible role of TNF-related apoptosis-inducing ligand (TRAIL) in viability and tumorigenicity of MB cells and MB-derived TSC. MB-associated TSC were isolated and cultured by serum-free medium with bFGF and EGF. The parental MB cells and MB-TSC cells were treated with TRAIL in different concentrations and assessed for cell viability, invasion ability, colony forming ability, and radiotherapy effect. We enrich a subpopulation of MB-TSC cells using tumor spheroid formation approach. MB-TSC display enhanced self-renewal and highly expressed "stemness" genes (CD133, Sox-2, Bmi1, Nestin). Additionally, MB-TSC showed significant resistance to TRAIL-induced apoptosis and radiosensitivity compared to the parental MB cells due antiapoptotic gene (c-FLIP, Caspase 8, Bcl-2, and Bax) upregulation. Our data suggest that MB-TSC are resistant to TRAIL-induced apoptosis and tumorigenic properties. Understanding the molecular mechanisms by which to operate the physiological characteristics in MB-TSC cells offers attractive approach for MB treatment.


[Drugs for heart rate control and non-antiarrhythmic drugs in atrial fibrillation].
Multiple drugs are helpful for rate control in different tachyarrhythmias, in particular atrial fibrillation (AF). Betablockers (betaB) and calcium channel blockers have been used as monotherapy or as adjunctive therapy to antiarrhythmics for mantaining an acceptable ventricular rate. In recent years new concepts about auricular remodelation process as a consequence of AF has shown benefits with drugs as angiotensin-renin system blockers (ARSB) like angiotensin conversing enzime inhibitors (ACEI) and angiotensin receptor blockers (ARB). In this article it will be reviewed the benefits of rate control in AF by using betaB and calcium channel blockers and also the benefits in atrial remodelation process and the prevention of AF with ARSB drugs.


Gastrointestinal symptoms during exercise in Enduro athletes: prevalence and speculations on the aetiology.
A study of the prevalence of gastrointestinal symptoms during exercise was carried out on athletes who participated in the recent Enduro event in Dunedin. Of 119 competitors, 70 (59%) responded to our questionnaire and demonstrated a prevalence of gastrointestinal symptoms of 81%. Upper gastrointestinal symptoms were noticed in 58% with lower gastrointestinal symptoms, tending to be more severe and significant to the athlete, noticed in 61%. Speculations on the aetiology of these symptoms are included. The demonstrated high prevalence of symptoms during exercise and the relative lack of knowledge in this area provides a fertile ground for further objective research.


Nephrocystin-4 is required for pronephric duct-dependent cloaca formation in zebrafish.
NPHP4 mutations cause nephronophthisis, an autosomal recessive cystic kidney disease associated with renal fibrosis and kidney failure. The NPHP4 gene product nephrocystin-4 interacts with other nephrocystins, cytoskeletal and ciliary proteins; however, the molecular and cellular functions of nephrocystin-4 have remained elusive. Here we demonstrate that nephrocystin-4 is required for normal cloaca formation during zebrafish embryogenesis. Time-lapse imaging of the developing zebrafish pronephros revealed that tubular epithelial cells at the distal pronephros actively migrate between the yolk sac extension and the blood island towards the ventral fin fold to join the proctodeum and to form the cloaca. Nphp4-deficient pronephric duct cells failed to connect with their ectodermal counterparts, and instead formed a vesicle at the obstructed end of the pronephric duct. Nephrocystin-4 interacts with nephrocystin-1 and Par6. Depletion of zebrafish NPHP1 (nphp1) increased the incidence of cyst formation and randomization of the normal body axis, but did not augment cloaca malformation in nphp4-deficient zebrafish embryos. However, simultaneous depletion of zebrafish Par6 (pard6) aggravated cloaca formation defects in nphp4-depleted embryos, suggesting that nphp4 orchestrates directed cell migration and cloaca formation through interaction with the Par protein complex.


Disruption of CD40-CD40 ligand pathway inhibits the development of intestinal muscle hypercontractility and protective immunity in nematode infection.
In our previous studies, we demonstrated that during Trichinella spiralis infection, T helper (Th) 2 cells contribute to the development of intestinal muscle hypercontractility and worm expulsion from the gut via STAT6. In addition, we have linked the altered muscle contractility to the eviction of the parasite and thereby to the host defense. However, the initial events linking infection to the development of muscle hypercontractility are poorly understood. In this study, we examined the contribution of CD40-CD40 ligand (CD40L) interaction in the development of intestinal muscle hypercontractility, in monocyte chemoattractant protein-1 (MCP-1) production, and in the Th2 response in CD40 ligand-deficient (CD40L -/-) mice infected with T. spiralis. Expulsion of intestinal worms was substantially delayed in CD40L -/- mice compared with the wild-type mice after T. spiralis infection. Consistent with delayed worm expulsion, there was a significant attenuation of intestinal muscle contractility in CD40L -/- mice. Infected CD40L -/- mice also exhibited marked impairment in the production of MCP-1, IL-4, IL-13, IgG1, IgE, and mouse mucosal MCP 1 (MMCP-1), and in goblet cell response. These results demonstrate that CD40-CD40 ligand interaction plays an important role in MCP-1 production, Th2 response, intestinal muscle hypercontractility, and worm expulsion in nematode infection. The present data suggest that the early events leading to the generation of Th2 response include CD40-CD40 ligand interaction, which subsequently influences the production of Th2 cytokines, most likely via upregulation of MCP-1.


Young men's intimate partner violence and relationship functioning: long-term outcomes associated with suicide attempt and aggression in adolescence.
Longitudinal research supports that suicidal thoughts and behaviors in adolescence predict maladjustment in young adulthood. Prior research supports links between suicide attempt and aggression, perhaps because of a propensity for impulsive behavior in states of high negative affect that underlies both problems. Such vulnerability may increase risk for intimate partner violence and generally poor young adulthood relational adjustment. A total of 153 men participated in annual assessments from ages 10-32 years and with a romantic partner at three assessments from ages 18-25 years. Multi-method/multi-informant constructs were formed for parent/family risk factors, adolescent psychopathology (e.g. suicide-attempt history, mother-, father-, teacher- and self-reported physical aggression) and young adulthood relational distress (jealousy and low relationship satisfaction) and maladaptive relationship behavior (observed, self- and partner-reported physical and psychological aggression toward a partner, partner-reported injury, official domestic violence arrest records and relationship instability). Across informants, adolescent aggression was correlated with suicide-attempt history. With few exceptions, aggression and a suicide attempt in adolescence each predicted negative romantic relationship outcomes after controlling for measured confounds. Adolescent aggression predicted young adulthood aggression toward a partner, in part, via relationship dissatisfaction. Boys' aggression and suicide-attempt history in adolescence each predict poor relationship outcomes, including partner violence, in young adulthood. Findings are consistent with the theory of a trait-like vulnerability, such as impulsive aggression, that undermines adaptation across multiple domains in adolescence and young adulthood. Prevention and intervention approaches can target common causes of diverse public health problems.


Vitamin D receptor rs3782905 and vitamin D binding protein rs7041 polymorphisms are associated with hepatocellular carcinoma susceptibility in cirrhotic HCV patients.
The severity of chronic hepatitis C and susceptibility to hepatocellular carcinoma (HCC) are associated with genetic variations within vitamin D receptor (VDR) in several populations. This study aims to determine the significance of the VDRs (rs2228570, rs3782905, rs11568820) and DBP (rs7041) for the susceptibility to HCC in Egyptian patients with chronic HCV infection and their effect on the progression of liver cirrhosis to carcinogenesis. Single nucleotide polymorphisms (SNPs) VDR (rs2228570, rs3782905), and DBP rs7041 were genotyped using restriction fragment length-PCR (RFLP-PCR) technique and VDR rs11568820 was genotyped using single strand polymorphism PCR (SSP PCR). These SNPs genotypes, haplotypes and linkage disequilibrium analyses were examined in 299 Egyptian individuals (100 HCV-cirrhotic patients, 99 HCC- HCV patients, and 100 healthy controls). The VDR rs2228570 CC genotype, VDR rs3782905 GC and CC genotypes, and DBP rs7041 GG genotype are significantly higher in HCC. It is noteworthy that, VDR rs3782905 CC and DBP rs7041 TG genotypes are higher in HCV induced liver cirrhosis than with HCC progression in HCV infected patients. Furthermore, among patients, the relationship between these SNPs and smoking status, gender, and HCC susceptibility was reported. Among the four investigated SNPs, there are associations between VDR rs3782905 and DBP rs7041 and the HCC progression in Egyptian patients chronically infected with HCV. These SNPs are considered as risk factors in HCV induced liver cirrhosis and HCC. The combinations of these SNPs with smoking status and gender are statistically linked to a high risk of HCC. Future research with a larger sample size of subjects with HCV infection is advised, because chronic liver disease induced by HCV infection is the primary cause of HCC in Egypt. We recommend screening of these SNPs for prediction of LC and HCC development in HCV infected patients, which may improve the used therapeutic protocol. These results suggest that VDR polymorphisms may be potential determinants for HCC susceptibility in Egyptian HCV patients.


The Bethesda System for Reporting Thyroid Fine-Needle Aspiration Cytology: A Kuwaiti Experience - A Cytohistopathological Study of 374 Cases.
The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) identifies 6 diagnostic categories in which the risk of malignancy increases respectively. The aim of our study was to assess TBSRTC reporting in our hospital and to evaluate its specificity based on cytohistological correlation. A histological diagnosis was available in 374 (110 males and 264 females) out of 7,809 thyroid aspirates examined at Mubarak Al-Kabeer Hospital, Kuwait, from 2004 to 2012. The aspirates were classified in accordance with TBSRTC. Thyroid aspirates were classified as nondiagnostic (n = 18; 4.8%), benign (n = 114; 30.5%); atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS; n = 59; 15.8%), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN; n = 17; 4.5%), suspicious for malignancy (SM; n = 80; 21.4%), or malignant (n = 86; 23.0%). In 75 of 86 malignant cases, a papillary carcinoma was detected. There were 3 (1.6%) false-positive aspirates and the sensitivity, specificity, negative predictive value, and positive predictive value were 91.0, 61.9, 84.2, and 75.3%, respectively. Our results are fairly comparable to those of various previous studies in the SM, AUS/FLUS, and SFN categories. The higher rates observed in the nondiagnostic and benign categories were possibly due to limited guided aspirations and a lack of on-site evaluation for all cases.


The Drosophila protein, Nausicaa, regulates lamellipodial actin dynamics in a Cortactin-dependent manner.
Drosophila CG10915 is an uncharacterized protein coding gene with sequence similarity to human Cortactin-binding protein 2 (CTTNBP2) and Cortactin-binding protein 2 N-terminal-like (CTTNBP2NL). Here, we have named this gene Nausicaa (naus) and characterize it through a combination of quantitative live-cell total internal reflection fluorescence microscopy, electron microscopy, RNAi depletion and genetics. We found that Naus co-localizes with F-actin and Cortactin in the lamellipodia of Drosophila S2R+ and D25c2 cells and this localization is lost following Cortactin or Arp2/3 depletion or by mutations that disrupt a conserved proline patch found in its mammalian homologs. Using permeabilization activated reduction in fluorescence and fluorescence recovery after photobleaching, we find that depletion of Cortactin alters Naus dynamics leading to a decrease in its half-life. Furthermore, we discovered that Naus depletion in S2R+ cells led to a decrease in actin retrograde flow and a lamellipodia characterized by long, unbranched filaments. We demonstrate that these alterations to the dynamics and underlying actin architecture also affect D25c2 cell migration and decrease arborization in Drosophila neurons. We present the hypothesis that Naus functions to slow Cortactin's disassociation from Arp2/3 nucleated branch junctions, thereby increasing both branch nucleation and junction stability.


Rapid and efficient Pd-catalyzed Sonogashira coupling of aryl chlorides.
An efficient and effective microwave-assisted cross-coupling of terminal alkynes with various aryl chlorides including sterically hindered, electron-rich, electron-neutral, and electron-deficient aryl chloride is developed. It proceeds faster and generally gives good to excellent yields and also can be extended successfully to the Suzuki coupling and Buchwald-Hartwig amination, as well as the Heck coupling with inert aryl chlorides. The short reaction times and simple reaction conditions coupling with a broad substrate scope render this method particularly attractive for the efficient preparation of biologically and medicinally interesting molecules.


Parenthood, Childlessness, and Well-Being: A Life Course Perspective.
This article reviews recent research (1999 - 2009) on the effects of parenthood on wellbeing. We use a life course framework to consider how parenting and childlessness influence well-being throughout the adult life course. We place particular emphasis on social contexts and how the impact of parenthood on well-being depends on marital status, gender, race/ethnicity, and socioeconomic status. We also consider how recent demographic shifts lead to new family arrangements that have implications for parenthood and well-being. These include stepparenting, parenting of grandchildren, and childlessness across the life course.


Umbilical Venous Catheters and Peripherally Inserted Central Catheters: Are They Equally Safe in VLBW Infants? A Non-Randomized Single Center Study.
Background and Objective: Peripherally inserted central catheters (PICC) and umbilical venous catheters (UVC) are frequently used for vascular access in neonatal intensive care units (NICUs). While there is a significant need for these devices for critically ill neonates, there are many complications associated with their use. We aimed at investigating the incidence of UVC and PICC complications in very low birth weight (VLBW) infants. Materials and Methods: This is an observational study performed with neonates of the tertiary General Hospital of Piraeus, Greece, during an 18 month-period. Seventy-one neonates were recruited and divided into two groups: 34 neonates with PICC and 37 neonates with UVC. We recorded: Catheter dwell time, the causes of catheter removal, other complications, infections, and catheter tip colonization rates. Results: No significant statistical differences were noticed between the 2 study groups with regards to demographic characteristics, causes for catheter removal, catheter indwelling time or the incidence of nosocomial infection. Eleven UVC tips and no PICC tips were proved colonized (p = 0.001) following catheter removal. Conclusions: The incidence of complications associated with the use of UVCs and PICCs in VLBW infants did not significantly differ in our study. Their use seems to be equally safe. Further studies, with larger samples, are necessary to confirm our results.


Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol.
Development of physiologically relevant test methods to analyse potential irritant effects to the respiratory tract caused by e-cigarette aerosols is required. This paper reports the method development and optimisation of an acute in vitro MTT cytotoxicity assay using human 3D reconstructed airway tissues and an aerosol exposure system. The EpiAirway™ tissue is a highly differentiated in vitro human airway culture derived from primary human tracheal/bronchial epithelial cells grown at the air-liquid interface, which can be exposed to aerosols generated by the VITROCELL® smoking robot. Method development was supported by understanding the compatibility of these tissues within the VITROCELL® system, in terms of airflow (L/min), vacuum rate (mL/min) and exposure time. Dosimetry tools (QCM) were used to measure deposited mass, to confirm the provision of e-cigarette aerosol to the tissues. EpiAirway™ tissues were exposed to cigarette smoke and aerosol generated from two commercial e-cigarettes for up to 6 h. Cigarette smoke reduced cell viability in a time dependent manner to 12% at 6 h. E-cigarette aerosol showed no such decrease in cell viability and displayed similar results to that of the untreated air controls. Applicability of the EpiAirway™ model and exposure system was demonstrated, showing little cytotoxicity from e-cigarette aerosol and different aerosol formulations when compared directly with reference cigarette smoke, over the same exposure time.


Flavanol-rich cocoa drink lowers plasma F(2)-isoprostane concentrations in humans.
Flavan-3-ols are potent antioxidants in vitro, but convincing evidence for antioxidant action in vivo is lacking. We examined whether an oxidative stress-mediated increase in plasma F(2)-isoprostanes is counteracted by a flavanol-rich cocoa beverage. Twenty volunteers were examined in a comparative randomized double-blind crossover design with respect to ingestion of high-flavanol cocoa drink (HFCD; 187 mg flavan-3-ols/100 ml) vs. low-flavanol cocoa drink (LFCD; 14 mg/100 ml). With 10 individuals, the treatment was combined with strenuous physical exercise. Total (esterified plus nonesterified) F(2)-isoprostanes were analyzed by GC/MS. LFCD caused a slight increase in the mean (+/- SEM) plasma concentrations of F(2)-isoprostanes 2 and 4 h after intake (2.16 +/- 0.19 nM at 4 h vs. 1.76 +/- 0.11 nM at 0 h, n = 10), which may be attributable to postprandial oxidative stress. This increase did not occur with HFCD (1.57 +/- 0.06 nM at 4 h vs. 1.65 +/- 0.10 nM at 0 h, n = 10). The difference in F(2)-isoprostanes 2 and 4 h after intake of HFCD vs. LFCD became statistically significant when the intake was combined with physical exercise (P < 0.01, ANOVA). We conclude that dietary flavanols, using cocoa drink as example, can lower the plasma level of F(2)-isoprostanes, indicators of in vivo lipid peroxidation.


The Relationship of Intensive Care Nurses' Attitudes Towards Organ Donation With Their Attitudes Towards Euthanasia and Moral Sensitivity.
Determination of the relationship between nurses' attitudes towards issues, such as end-of-life care that is specific to intensive care, euthanasia, and organ donation and their moral sensitivity levels is one of the important points for working out ethical problems encountered in intensive care units and increasing the quality of care. This study was conducted to determine the relationship between the attitudes of intensive care nurses towards organ donation, euthanasia, and terminal patients and their moral sensitivity. The study was completed with 175 nurses who agreed to participate in the study. Informed consent of the participants was obtained. While nurses' attitudes towards euthanasia, death, and caring for the dying patient did not correlate with their moral sensitivities, their attitudes towards organ donation did.


Comparison Of Different Methods Of Controlling Pain During Debonding Of Orthodontic Brackets.
To compare the efficacy of finger pressure and plastic wafers in terms of pain control during debonding. This cross sectional study was conducted at the Department of Orthodontics, Armed Forces Institute of Dentistry, Rawalpindi, Pakistan, from January to June 2020, and comprised patients of either gender aged 13-21 years who had completed fixed orthodontic treatment with 0.022 brackets of Roth prescription and required debonding. The patients was divided into two equal groups. In group A, teeth were stabilised with finger pressure with cotton between the finger and teeth, and then debonding was done using open mouth technique. In group B, teeth were stabilised using a plastic wafer between maxillary and mandibular teeth, and then debonding was done using closed mouth technique. Pain was assessed using a visual analogue scale VAS. Data was analysed using SPSS 23. Of the 110 patients, each of the 2 groups had 55(50%) subjects. Overall, there were 35(32%) males and 75(68%) females. The mean age of the sample was 16±2.4 years. Mean pain scores among the males was 32.0±7.68 compared to 34.067±12.59 among the females (p>0.05). Subjects in group B had significantly less pain than those in group A (p<0.05). Plastic wafer was found to be more effective in terms of controlling pain during debonding compared to finger pressure.


Medical therapy of gastroesophageal reflux disease in secondary and tertiary care settings.
Gastroesophageal reflux disease (GERD) is common. Many patients with recurring or troublesome symptoms are referred for endoscopic examination. Patients seen in secondary care usually have failed OTC or primary care anti-reflux therapy. Acid suppression is the mainstay of healing and maintenance therapy. Increasingly proton pump inhibitors (PPIs) are preferred above H2 receptor antagonists (H2RAs), not only for the more severe end of the GERD spectrum but also for patients with mild degrees of esophagitis. Not all patients respond symptomatically to acid suppression, not even with high dose PPI. Prokinetics are mainly useful in the milder degrees of GERD. It is still not clear whether a particular symptom cluster can be recognized for which prokinetics are especially useful. The concept of "step-up versus step-down" approach remains in need for proper validation. Switching from PPIs to cisapride for "step-down" maintenance appears inadequate in practice. All current therapies have shortcomings; H2RAs insufficiently block meal-stimulated acid secretion; long-term strong acid suppression worsens Helicobacter pylori-associated inflammation in the corpus and may accelerate development of atrophy; PPI-potency is substantially weaker in non-H. pylori infected individuals. Optimization of individualized therapy will require more potent and more precisely targeted motility modulating drugs and superior acid/peptic inhibiting pharmaceuticals.


Assessment of template-based protein structure predictions in CASP10.
Template-based modeling (TBM) is a major component of the critical assessment of protein structure prediction (CASP). In CASP10, some 41,740 predicted models submitted by 150 predictor groups were assessed as TBM predictions. The accuracy of protein structure prediction was assessed by geometric comparison with experimental X-ray crystal and NMR structures using a composite score that included both global alignment metrics and distance-matrix-based metrics. These included GDT-HA and GDC-all global alignment scores, and the superimposition-independent LDDT distance-matrix-based score. In addition, a superimposition-independent RPF metric, similar to that described previously for comparing protein models against experimental NMR data, was used for comparing predicted protein structure models against experimental protein structures. To score well on all four of these metrics, models must feature accurate predictions of both backbone and side-chain conformations. Performance rankings were determined independently for server and the combined server plus human-curated predictor groups. Final rankings were made using paired head-to-head Student's t-test analysis of raw metric scores among the top 25 performing groups in each category.


Bioengineering of a Nisin A-producing Lactococcus lactis to create isogenic strains producing the natural variants Nisin F, Q and Z.
Nisin is the prototypical example of the lantibiotic family of antimicrobial peptides and has been employed as a food preservative for over half a century. It has also attracted attention due to its potency against a number of multidrug-resistant clinical pathogens. Nisin A is the originally isolated form of Nisin and a further five natural variants have been described which differ by up to 10 amino acids (of 34 in total in Nisin A). Nisins A, Z, F and Q are produced by Lactococcus lactis, while Nisins U and U2 are produced by Streptococcus sp. In this study we bioengineered the nisA gene of a Nisin A producer to generate genes encoding Nisins Z, F, Q, U and U2. We determined that while active Nisin Z, F and Q can be produced against this genetic background, active forms of Nisin U and U2 are not generated. Minimum inhibitory concentration studies with Nisin A, Z, F and Q variants against a series of different clinically significant pathogens establish differences in specific activities against selected targets. Nisin F was most impressive, being the most active, or one of the most active, against the MRSA strain ST 525, EC 676, EC 725, VISA 22900, VISA 22781, hVISA 35197, Staphylococcus aureus 8325-4 and L. lactis HP. Nisin Z was most active against ST 299, hVISA 32683 and, together with Nisin F, HP but had contrastingly poor activity against ST 525, EC 676 and 8325-4. Nisin F, Q and A exhibited similar potency against VISA 22900. This was the only target against which Nisin Q and Nisin A were among the most active variants.


Characterization of an immunoprotective protein complex of Anaplasma marginale by cloning and expression of the gene coding for polypeptide Am105L.
Immunization with an Anaplasma marginale surface protein complex containing two polypeptides (Am105U and Am105L), each having a molecular weight of 105,000, protected cattle against challenge with virulent organisms. These polypeptides were immunoprecipitated together from detergent extracts of A. marginale by a neutralizing monoclonal antibody. After surface radioiodination of intact parasites, both Am105U and Am105L contained the radiolabel. To define the structural and antigenic relationships between Am105U and Am105L and to determine individual efficacies as protective immunogens, we cloned and expressed A. marginale DNA in Escherichia coli. We identified recombinant bacteria which expressed a novel protein of 105,000 molecular weight as a major cellular component. The recombinant protein was structurally and antigenically homologous to Am105L. There were multiple, partially homologous copies of the cloned DNA sequence in the rickettsial genome.


Evaluation of an in-house ELISA using the intermediate species Leptospira fainei for diagnosis of leptospirosis.
Leptospirosis is recognized as an emerging zoonotic disease generally affecting urban slums in developing countries and tropical regions. A combination of non-specific symptoms, low awareness among the medical community and a lack of readily available diagnostic tests have made leptospirosis an underdiagnosed disease. In this study, we tested an in-house ELISA with formalin-treated and boiled bacteria from the intermediate species Leptospira fainei as an antigen to detect Leptospira-specific IgM antibodies. A total of 819 serum samples, tested by a microscopic agglutination test (MAT) as a reference test, were used to evaluate the ELISA. Compared with positive and negative sera, the ELISA showed 94 % sensitivity and 99 % specificity. Positive and negative likelihood ratios were 94 and 0.06, respectively. No cross-reactivity was observed in sera from subjects with dengue and syphilis infections. The kappa value was 0.92 (95 % confidence interval 0.88-0.96), which indicated excellent agreement between the MAT and ELISA. The overall performance of this in-house ELISA suggests applicability as a rapid screening test for the diagnosis of leptospirosis in resource-limited settings and in hospitals and laboratories where a MAT is not available.


Connectomic markers of disease expression, genetic risk and resilience in bipolar disorder.
Bipolar disorder (BD) is characterized by emotional dysregulation and cognitive deficits associated with abnormal connectivity between subcortical-primarily emotional processing regions-and prefrontal regulatory areas. Given the significant contribution of genetic factors to BD, studies in unaffected first-degree relatives can identify neural mechanisms of genetic risk but also resilience, thus paving the way for preventive interventions. Dynamic causal modeling (DCM) and random-effects Bayesian model selection were used to define and assess connectomic phenotypes linked to facial affect processing and working memory in a demographically matched sample of first-degree relatives carefully selected for resilience (n=25), euthymic patients with BD (n=41) and unrelated healthy controls (n=46). During facial affect processing, patients and relatives showed similarly increased frontolimbic connectivity; resilient relatives, however, evidenced additional adaptive hyperconnectivity within the ventral visual stream. During working memory processing, patients displayed widespread hypoconnectivity within the corresponding network. In contrast, working memory network connectivity in resilient relatives was comparable to that of controls. Our results indicate that frontolimbic dysfunction during affect processing could represent a marker of genetic risk to BD, and diffuse hypoconnectivity within the working memory network a marker of disease expression. The association of hyperconnectivity within the affect-processing network with resilience to BD suggests adaptive plasticity that allows for compensatory changes and encourages further investigation of this phenotype in genetic and early intervention studies.


Patient reported outcomes are associated with physical activity level in adults with congenital heart disease.
In general, adults with congenital heart disease (CHD) have impaired exercise capacity, and approximately 50% do not reach current recommendations on physical activity. Herein we analysed factors associated with physical activity level (PAL) in adults with CHD by using patient-reported outcomes (PRO). Patients with CHD (n=471) were randomly selected from the national register on CHD and categorized according to complexity of lesions - simple (n=172, 39.1±14.6years), moderate (n=212, 39±14.1years), and severe (n=87, 31.7±10.7years). Participants completed a standardized questionnaire measuring PRO-domains including PAL. Variables associated with PAL were tested in multivariate logistic regression. PAL was categorized into high (≥3 METs ≥2.5h/week, n=192) and low (≥3 METs <2.5h/week, n=279). Patients with low PAL were older (42.6 vs. 35.8years, p≤0.001), had more prescribed medications (51% vs. 39%, p=0.009), more symptoms (25% vs. 16%, p=0.02) and comorbidity (45% vs. 34% p=0.02). Patients with low PAL rated a lower quality of life (76.6 vs. 83.4, p<0.001), satisfaction with life (25.6 vs. 27.3, p=0.003), a lower Physical Component Summary score (PCS) (78.1 vs. 90.5, p<0.001) and Mental Component Summary score (MCS) (73.5 vs. 79.5, p<0.001). Complexity of heart lesion was not associated with PAL. The included PROs - separately tested in the model, together with age were associated with PAL. PCS and MCS are stronger associated with PAL than age and medical factors. The use of these PROs could therefore provide valuable information of benefit for individualized advice regarding physical activity to patients with CHD.


Diazepam inhibits forskolin-stimulated adenylyl cyclase activity in human tumour cells.
Previous studies have shown that the benzodiazepine agonist, diazepam, suppresses adenylyl cyclase activity in rat brain, via a G protein-coupled benzodiazepine receptor. Since diazepam binding sites are also present in diverse non-neuronal tissues including tumour cells, its effects on adenylyl cyclase activity were examined in membranes from human MCF-7 (breast cancer) and M-6 (melanoma) cells. Diazepam caused a biphasic and concentration-dependent inhibition of forskolin-stimulated adenylyl cyclase activity in MCF-7 membranes. The first phase of inhibition, at picomolar to nanomolar drug concentrations (EC50=5.7 x 10(-12)M), is similar to the receptor mediated phase observed in the rat brain. At micromolar concentrations of diazepam (EC50= 1.8 x 10(-4)M), the steep decrease in adenylyl cyclase activity may involve a direct action on the enzyme itself, as detected previously in rat brain membranes. Diazepam-induced suppression of adenylyl cyclase activity was also detected in M-6 membranes. However, in contrast to MCF-7 findings, only micromolar concentrations of diazepam (EC50=5.2 x 10(-4)M) inhibited enzyme activity in M-6 membranes. These findings suggest that G protein-coupled benzodiazepine receptors, which mediate inhibition of the adenylyl cyclase-cAMP pathway in the brain, are also expressed in MCF-7 cells.


Solubilization and other studies on adenylate cyclase of baker's yeast.
1. Adenylate cyclase of Saccharomyces cerevisiae was sedimented from mechanically disintegrated preparations of yeast over an unusually wide range of centrifugal forces. 2. The enzyme was readily solubilized by Ficoll and by Lubrol PX. Lubrol caused a 2-fold activation. 3. Both particle-bound and Lubrol-solubilized enzyme had an apparent Km for ATP of 1.6 mM in the presence of 0.4 mM-cyclic AMP and 5 mM-MnCl2 at pH 6.2 and 30 degrees C. 4. The Lubrol-solubilized enzyme behaved on gel filtration as a monodisperse protein with an apparent mol.wt. of about 450000.


Subgroup effects despite homogeneous heterogeneity test results.
Statistical tests of heterogeneity are very popular in meta-analyses, as heterogeneity might indicate subgroup effects. Lack of demonstrable statistical heterogeneity, however, might obscure clinical heterogeneity, meaning clinically relevant subgroup effects. A qualitative, visual method to explore the potential for subgroup effects was provided by a modification of the forest plot, i.e., adding a vertical axis indicating the proportion of a subgroup variable in the individual trials. Such a plot was used to assess the potential for clinically relevant subgroup effects and was illustrated by a clinical example on the effects of antibiotics in children with acute otitis media. Statistical tests did not indicate heterogeneity in the meta-analysis on the effects of amoxicillin on acute otitis media (Q = 3.29, p = 0.51; I2 = 0%; T2 = 0). Nevertheless, in a modified forest plot, in which the individual trials were ordered by the proportion of children with bilateral otitis, a clear relation between bilaterality and treatment effects was observed (which was also found in an individual patient data meta-analysis of the included trials: p-value for interaction 0.021). A modification of the forest plot, by including an additional (vertical) axis indicating the proportion of a certain subgroup variable, is a qualitative, visual, and easy-to-interpret method to explore potential subgroup effects in studies included in meta-analyses.


Analysis of the Use of Cylindrospermopsin and/or Microcystin-Contaminated Water in the Growth, Mineral Content, and Contamination of Spinacia oleracea and Lactuca sativa.
Cyanobacteria and cyanotoxins constitute a serious environmental and human health problem. Moreover, concerns are raised with the use of contaminated water in agriculture and vegetable production as this can lead to food contamination and human exposure to toxins as well as impairment in crop development and productivity. The objective of this work was to assess the susceptibility of two green vegetables, spinach and lettuce, to the cyanotoxins microcystin (MC) and cylindrospermopsin (CYN), individually and in mixture. The study consisted of growing both vegetables in hydroponics, under controlled conditions, for 21 days in nutrient medium doped with MC or CYN at 10 μg/L and 50 μg/L, or CYN/MC mixture at 5 + 5 μg/L and 25 + 25 μg/L. Extracts from M. aeruginosa and C. ovalisporum were used as sources of toxins. The study revealed growth inhibition of the aerial part (Leaves) in both species when treated with 50µg/L of MC, CYN and CYN/MC mixture. MC showed to be more harmful to plant growth than CYN. Moreover spinach leaves growth was inhibited by both 5 + 5 and 25 + 25 µg/L CYN/MC mixtures, whereas lettuce leaves growth was inhibited only by 25 + 25 µg/L CYN/MC mixture. Overall, growth data evidence increased sensitivity of spinach to cyanotoxins in comparison to lettuce. On the other hand, plants exposed to CYN/MC mixture showed differential accumulation of CYN and MC. In addition, CYN, but not MC, was translocated from the roots to the leaves. CYN and MC affected the levels of minerals particularly in plant roots. The elements most affected were Ca, K and Mg. However, in leaves K was the mineral that was affected by exposure to cyanotoxins.


[Antihypertensive effects of valsartan. National multicentric study].
Valsartan is an angiotensin AT1 receptor antagonist. Clinical studies have shown that this is an effective and well tolerated drug. To compare valsartan with other commonly used antihypertensives in a National multicentric study. Between 1997 and 1998, a pharmacological surveillance of patients with mild or moderate hypertension, coming from different regions of the country, was carried out. Patients were followed during 8 weeks. In the group treated with valsartan, the initial dose was 80 mg/day. After four weeks of therapy, and according to patient's response the dose of valsartan or of the other antihypertensives was modified. Five hundred ninety three patients, aged 59 years old as a mean, were included in the study. Of these 434 (265 female) received valsartan and 159 (101 female) other antihypertensive drugs. Fifteen percent of patients treated with valsartan and 25% of patients with other medications required a dose change at four weeks, due to lack of response (p < 0.01). At week eight, 1.5% of patients with valsartan and 17.4% of patients with other medications reported adverse effects such as cough, headache, edema or flushing (p < 0.01). In this Chilean observational multicentric study, valsartan proved to be more effective and to cause less adverse effects than commonly used medications in hypertensive patients.


[Conceptual framework of gambling and gambling-related harms].
Gambling is a legitimate leisure activity in many countries that many people use. However, some of them suffer significant harm because of gambling. This may involve economic, social, physical or mental harm. These harms are not only suffered by the individual gambler, but affect the family, the community and society. The aim of this text is to propose a conceptual framework for understanding the determinants of gambling and its related harms and thus, contribute to the development of prevention policies to reduce its impact on health. The framework proposed in this manuscript places present evidence in the model of health inequalities, analyzing the effect of the socioeconomic and political context, the axes of inequalities, individual and social factors, and the health system in generating the health inequalities of gambling suffered by the most vulnerable groups. The evidence gathered in this framework suggests that health determinants lead to health inequality in relation to gambling and its associated harms.


A new approach based on Machine Learning for predicting corneal curvature (K1) and astigmatism in patients with keratoconus after intracorneal ring implantation.
Keratoconus (KC) is the most common type of corneal ectasia. A corneal transplantation was the treatment of choice until the last decade. However, intra-corneal ring implantation has become more and more common, and it is commonly used to treat KC thus avoiding a corneal transplantation. This work proposes a new approach based on Machine Learning to predict the vision gain of KC patients after ring implantation. That vision gain is assessed by means of the corneal curvature and the astigmatism. Different models were proposed; the best results were achieved by an artificial neural network based on the Multilayer Perceptron. The error provided by the best model was 0.97D of corneal curvature and 0.93D of astigmatism.


Traveling and standing waves mediate pattern formation in cellular protrusions.
The mechanisms regulating protrusions during amoeboid migration exhibit excitability. Theoretical studies have suggested the possible coexistence of traveling and standing waves in excitable systems. Here, we demonstrate the direct transformation of a traveling into a standing wave and establish conditions for the stability of this conversion. This theory combines excitable wave stopping and the emergence of a family of standing waves at zero velocity, without altering diffusion parameters. Experimentally, we show the existence of this phenomenon on the cell cortex of some Dictyostelium and mammalian mutant strains. We further predict a template that encompasses a spectrum of protrusive phenotypes, including pseudopodia and filopodia, through transitions between traveling and standing waves, allowing the cell to switch between excitability and bistability. Overall, this suggests that a previously-unidentified method of pattern formation, in which traveling waves spread, stop, and turn into standing waves that rearrange to form stable patterns, governs cell motility.


Development of label-free molecular beacons based on abasic site-binding fluorescence molecules.
Here we report on a class of label-free molecular beacons (MBs) based on a non-covalent interaction with abasic site (AP site)-binding fluorescence molecules. In contrast to conventional MBs that require the chemical labelling with fluorophores and quenchers, our MB simply contains the AP site in the stem moiety, so that a small molecule specifically binds to the AP site. This binding event is accompanied by a significant quenching of its fluorescence, and thus a closed state of the AP site-containing MB (APMB) shows almost no fluorescence. Upon hybridization with a complementary DNA, APMB undergoes a conformational change to take an open state, resulting in an effective fluorescence enhancement due to a release of the molecule from the AP site. These sensing functions of APMB are discussed with a view towards further development of gene detection chemistry based on DNA-binding small molecules.


Sidewall functionalization of single-walled carbon nanotubes by addition of dichlorocarbene.
We report the sidewall functionalization of soluble HiPco single-walled carbon nanotubes (SWNTs) by addition of dichlorocarbene. The dichlorocarbene-functionalized SWNTs [(s-SWNT)CCl(2)] retain their solubility in organic solvents such as tetrahydrofuran and dichlorobenzene. The degree of dichlorocarbene functionalization was varied between 12% and 23% by using different amounts of the dichlorocarbene precursor. Because the addition of dichlorocarbene saturates the carbon atoms on the sidewall of the SWNTs and effectively replaces the delocalized partial double bonds with a cyclopropane functionality, the optical spectra of the SWNTs change dramatically. We estimate that the saturation of 25% of the pi-network electronic structure of the SWNTs is sufficient to remove all vestiges of the interband transitions in the infrared spectrum. The transitions at the Fermi level in the metallic SWNTs that appear in the far-infrared (FIR) region of the spectrum show a dramatic decrease of intensity on dichlorocarbene functionalization. The FIR region of the spectrum allows a clear differentiation between the covalent and the ionic chemistry of SWNTs. In contrast with covalent functionalization, we show that reaction of the SWNTs with bromine vapor leads to a strong increase in absorptions at the Fermi level that is observable in the FIR due to hole doping of the semiconducting SWNTs. Thermal treatment of the (s-SWNT)CCl(2) above 300 degrees C resulted in the breakage of C-Cl bonds, but did not restore the original electronic structure of the SWNTs.


Chronic pruritus associated with Helicobacter pylori.
Helicobacter pylori is an established cause of gastritis and has been implicated in extradigestive diseases. To investigate the role of H. pylori in patients with unexplained refractory pruritus. Ten patients with severe pruritus unresponsive to conventional therapy were evaluated for active H. pylori infection by H. pylori serology followed by either esophagogastroduodenoscopy (EGD) or urea breath test. Of the 10 patients, 8 were found to have active infection. All 10 received anti-H. pylori antibiotic therapy and were reevaluated for relief of pruritus. Of 8 patients with active H. pylori infection, 87.5% (7/8) had some type of pruritus relief after triple therapy. Of these, 62.5% (5/8) had complete relief and 25% (2/8) had temporary relief of pruritus. The remaining 12.5% (1/8) did not respond. Two control patients without active H. pylori infection had no relief of pruritus with therapy. We have identified a population of patients with refractory pruritus and active H. pylori infection whose pruritus resolved after eradication of H. pylori.


Effectiveness and Safety of Apixaban Versus Warfarin in Obese Patients with Nonvalvular Atrial Fibrillation Enrolled in Medicare and Veteran Affairs.
Real-world studies have evaluated the use of anticoagulants in obese patients with nonvalvular atrial fibrillation (NVAF), but they have been limited by sample size or the use of diagnosis codes on claims to define obesity. This retrospective study used body weight data of ≥100 kg or a body mass index of ≥30 kg/m2 to identify elderly (aged ≥65 years) NVAF patients with obesity in dually enrolled Veterans Affairs and fee-for-service Medicare patients. It evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients that initiated apixaban versus warfarin. Stabilized inverse probability treatment weighting was used to balance the baseline characteristics between patients prescribed apixaban and warfarin in obese patients. Cox models were used to evaluate the relative risk of stroke/SE and MB. Overall, 35.9% (n = 26,522) of the NVAF population were obese, of which 13,604 apixaban and 12,918 warfarin patients were included. After inverse probability treatment weighting, patient characteristics were balanced. The mean age was 75 years, the mean CHA2DS2-VASc score (Congestive Heart Failure, Hypertension, Age ≥75 [Doubled], Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack [Doubled], Vascular Disease, Age 65-74, Female) was 3.8, the mean HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) Score was ∼2.6, and >98% of patients were males. Obese apixaban patients were associated with a similar risk of stroke/SE (hazard ratio: 0.82; 95% confidence interval: 0.66 to 1.03) and a significantly lower risk of MB (hazard ratio: 0.62; 95% confidence interval: 0.54 to 0.70) versus warfarin. No significant interaction was observed between treatment and obesity status (nonobese, obese/nonmorbid, obese/morbid) for stroke/SE (interaction p = 0.602) or MB (interaction p = 0.385). In obese patients with NVAF, apixaban was associated with a similar risk of stroke/SE and a significantly lower risk of MB versus warfarin.