Retention of silicone oil droplets from ophthalmic viscosurgical devices in the drainage angle of 2 eyes.
We report the outcome in 2 eyes of 2 patients with retained silicone oil droplets in the anterior chamber drainage angle after the use of an ophthalmic viscosurgical device (OVD) during cataract surgery. Silicone oil droplets were observed when the OVD was injected into the anterior chamber during phacoemulsification. Despite removal by irrigation and aspiration, droplets were observed in the anterior chamber during the immediate postoperative period. At 15 months, they were observed in the drainage angle. The retained silicone did not produce untoward side effects in the eyes. Silicone oil is a common contaminant in OVDs but appears to be inert and harmless when retained in small amounts in the anterior chamber drainage angle.


Response of aquatic insects to an environmental gradient in Amazonian streams.
The increasing land use in the Amazon region has resulted in the widespread substitution of forest areas with pasture and bauxite mining. These land uses reduce the forest cover of streams and modify their characteristics, reducing the diversity of aquatic insect assemblages. In the present study, we aimed to identify the threshold of the assemblages of the larvae of insects of the orders Ephemeroptera, Plecoptera, and Trichoptera (collectively known as EPT), and adults of the order Odonata, along an environmental gradient of land use and land cover (LULC). We sampled 30 streams along an environmental gradient determined by the proportion of forest, pasture, and bauxite mining observed within the catchment of each stream. We identified 12 taxa associated with forest (nine positively and three negatively) and four negatively associated with pasture. However, no taxa were associated explicitly with the bauxite mining gradient. As forest is converted to pasture, the abundance and frequency of occurrence of the taxa sensitive to pasture are reduced, reflecting their environmental sensitivity and their potential as sentinels of preserved streams. The identification of the thresholds of the EPT and odonates taxa allowed us to determine which of these organisms are positively or negatively associated with the environmental gradient of LULC in Amazonian streams. We hope that the results of the present study can be applied in future biomonitoring programs, particularly for monitoring the response of aquatic insects to the degradation of streams.


Sequential intrastromal corneal ring segment and monofocal intraocular lens implantation for keratoconus and cataract: Long-term follow-up.
To evaluate the efficacy, safety, predictability, and stability of sequential Ferrara intrastromal corneal ring segment (ICRS) and intraocular lens (IOL) implantation in patients with keratoconus and cataract. Fernández-Vega Ophthalmological Institute, Oviedo, Spain. Retrospective case series. This study comprised patients with keratoconus and cataract who had ICRS implantation followed 6 months later by IOL implantation. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities and residual refractive errors, analyzed using vector analysis, were recorded preoperatively, 6 months after ICRS implantation, 6 months after IOL implantation, and 3 years and 5 years thereafter. Seventy eyes of 47 patients were studied. The mean UDVA was 1.08 logMAR ± 0.24 (SD) preoperatively, 0.95 ± 0.31 logMAR 6 months after ICRS implantation (P = .03), and 0.44 ± 0.29 logMAR 6 months after IOL implantation (P < .0001). The mean CDVA changed from 0.35 ± 0.23 logMAR before surgery to 0.28 ± 0.22 logMAR 6 months after ICRS implantation (P < .0001) and to 0.11 ± 0.16 logMAR 6 months after IOL implantation (P < .0001). The UDVA and CDVA were stable over the period after the second procedure (P > .05). The spherical equivalent (SE) and the refractive cylinder declined steeply after IOL implantation (P < .001) and then were stable (P > .05). Sequential ICRS and IOL implantation provided good visual and refractive outcomes and was an effective, safe, predictable, and stable procedure for the treatment of patients with keratoconus and cataract.


[Study on fibrolytic and hypotensive activity of earthworm homogenate of ultrafiltration separation from enzymolysis].
To study the fibrolytic and hypotensive activity of earthworm homogenate of ultrafiltration separation from simulated enzymolysis of gastrointestinal tract system. The before and after enzymolysis homogenate of fresh earthworm was seperated with different pore size PVDF ultrafiltration membrane and its fibrolytic and hypotensive activity was assayed. The fibrolytic activity of the total homogenate after enzymolysis overall changed little, but decreased in the the site of higher molecular weight and increased in the lower site of molecular weight; The ACE inhibitory activity improved, especially in the filtrate of the MW 4000 membrane. The fibrolytic activity of earthworm homogenate was not reduced by the digestive simulated enzymolysis, and the retention site of MW 10 000 membrane have more fibrolytic activity; The hypotensive activity of earthworm homogenate is enhanced by the digestive simulated enzymolysis. So the stronger activity could be obtained from enzymolysis.


Antibody-peptide-MHC fusion conjugates target non-cognate T cells to kill tumour cells.
Attempts to generate robust anti-tumour cytotoxic T lymphocyte (CTL) responses using immunotherapy are frequently thwarted by exhaustion and anergy of CTL recruited to tumour. One strategy to overcome this is to retarget a population of virus-specific CTL to kill tumour cells. Here, we describe a proof-of-principle study using a bispecific conjugate designed to retarget ovalbumin (OVA)-specific CTL to kill tumour cells via CD20. A single-chain trimer (SCT) consisting of MHCI H-2K(b)/SIINFEKL peptide/beta 2 microglobulin/BirA was expressed in bacteria, refolded and chemically conjugated to one (1:1; F2) or two (2:1; F3) anti-hCD20 Fab' fragments. In vitro, the [SCT × Fab'] (F2 and F3) redirected SIINFEKL-specific OT-I CTL to kill CD20(+) target cells, and in the presence of CD20(+) target cells to provide crosslinking, they were also able to induce proliferation of OT-I cells. In vivo, activated OT-I CTL could be retargeted to kill [SCT × Fab']-coated B cells from hCD20 transgenic (hCD20 Tg) mice and also EL4 and B16 mouse tumour cells expressing human CD20 (hCD20). Importantly, in a hCD20 Tg mouse model, [SCT × Fab'] administered systemically were able to retarget activated OT-I cells to deplete normal B cells, and their performance matched that of a bispecific antibody (BsAb) comprising anti-CD3 and anti-CD20. [SCT × Fab'] were also active therapeutically in an EL4 tumour model. Furthermore, measurement of serum cytokine levels suggests that [SCT × Fab'] are associated with a lower level of inflammatory cytokine release than the BsAb and so may be advantageous clinically in terms of reduced toxicity.


Ethanol physiology in the warehouse-staining fungus, Baudoinia compniacensis.
The fungus Baudoinia compniacensis colonizes the exterior surfaces of a range of materials, such as buildings, outdoor furnishings, fences, signs, and vegetation, in regions subject to periodic exposure to low levels of ethanol vapour, such as those in the vicinity of distillery aging warehouses and commercial bakeries. Here we investigated the basis of ethanol metabolism in Baudoinia and investigate the role of ethanol in cell germination and growth. Germination of mycelia of Baudoinia was enhanced by up to roughly 1d exposure to low ethanol concentrations, optimally 10ppm when delivered in vapour form and 5mm in liquid form. However, growth was strongly inhibited following exposure to higher ethanol concentrations for shorter durations (e.g., 1.7m for 6h). We found that ethanol was catabolized into central metabolism via alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ACDH). Isocitrate dehydrogenases (IDHs) were active in cells grown on glucose, but these enzymes were not expressed when ethanol was provided as a sole or companion carbon source. The glyoxylate cycle enzymes isocitrate lyase (ICL) and malate synthase (MS) activities observed in cells grown on acetate were comparable to those reported for other microorganisms. By replenishing tricarboxylic acid (TCA) cycle intermediates, it is likely that the functionality of the glyoxylate cycle is important in the establishment of luxuriant growth of Baudoinia compniacensis on ethanol-exposed, nutrient-deprived, exposed surfaces. In other fungi, such as Saccharomyces cerevisiae, ADH II catalyses the conversion of ethanol to acetaldehyde, which then can be metabolized via the TCA cycle. ADH II is known to be strongly repressed in the presence of glucose.


Lupus: novel therapies in clinical development.
There have been significant advancements in understanding the immunopathogenesis of systemic lupus erythematosus. However, the developments in therapeutics have been rather slow. Belimumab, a B lymphocyte stimulator (BLyS) inhibitor has been approved for the treatment of this disease after more than 50 years. Numerous biological agents are being developed which target the B cells, T cells, and various cytokines. Among anti-B cell therapy, drugs target CD20+ cells (ocrelizumab, SBI-087), CD22+ cells (epratuzumab) \or the receptors of tumor necrosis factor (TNF) superfamily (atacicept, LY2127399, A-623). Monoclonal antibodies targeting interferon alpha (IFN-α) and gamma (IFN-γ) and interleukins (IL-6, 10) are being investigated for SLE. Novel targets include toll like receptors, phosphodiesterases, CD40 ligand and retinoid receptors. This review discusses various drugs which are in different phases of clinical trials and hold promise for patients suffering from this chronic debilitating disease.


Factors relating to adolescent suicidal behavior: a cross-sectional Malaysian school survey.
This study was undertaken to examine factors relating to adolescent suicide behavior. This was a cross-sectional school survey of 4,500 adolescent students based on a structured questionnaire. Data were collected using the supervised self-administered questionnaire (modified version of the Youth Risk Behavior Surveillance in the Malaysian National Language, Bahasa Malaysia). Seven percent (312 of 4,454) of the adolescent students had seriously considered attempting suicide. Among the adolescents, 4.6% had attempted suicide at least once during the 12 months preceding the survey. Female adolescents were more likely to put their suicidal thoughts into suicidal action than were male adolescents. Malay and Indian people are more likely than the Chinese to respond, "Felt sad and hopeless." However, Malay adolescents had the lowest rate of attempted suicide. Based on multiple logistic regression, factors significantly related to urban adolescents' suicide behavior are "Felt sad or hopeless," "Number of days felt unsafe to go to school," "Riding with a driver who had been drinking alcohol," "Physical fight," and "Number of days absent from school." In comparison, factors relating to rural adolescents' suicide behavior are "Felt sad or hopeless," "Physical fight," "Physical fight resulting in injury," and "Drive a vehicle after drinking alcohol." Adolescent suicide behavior should be viewed as a serious problem. Measures can be taken to prevent suicide by looking at the factors significantly linked to suicidal behavior among adolescents. Steps can then be taken to identify adolescents who have serious suicidal ideation so that intervention can be taken to reduce the suicidal rate.


New nurses' perceptions of professional practice behaviours, quality of care, job satisfaction and career retention.
To test a model examining the effects of structural empowerment and support for professional practice on new graduate nurses' perceived professional practice behaviours, perceptions of care quality and subsequent job satisfaction and career turnover intentions. The nursing worklife model describes relationships between supportive nursing work environments and nurse and patient outcomes. The influence of support for professional practice on new nurses' perceptions of professional nursing behaviours within this model has not been tested. Structural equation modelling in Mplus was used to analyse data from a national survey of new nurses across Canada (n = 393). The hypothesised model was supported: χ²(122) = 346.726, P = 0.000; CFI = 0.917; TLI = 0.896; RMSEA = 0.069. Professional practice behaviour was an important mechanism through which empowerment and supportive professional practice environments influenced nurse-assessed quality of care, which was related to job satisfaction and lower intentions to leave nursing. Job satisfaction and career retention of new nurses are related to perceptions of work environment factors that support their professional practice behaviours and high-quality patient care. Nurse managers can support new graduate nurses' professional practice behaviour by providing empowering supportive professional practice environments.


Cardioprotective Strategies to Prevent Cancer Treatment-Related Cardiovascular Toxicity: a Review.
Patients with cancer have an elevated risk of cardiovascular disease. This review describes the cardiovascular risks of different cancer therapies and the evidence for cardioprotective strategies. Recent studies have provided additional support for the safety and efficacy of dexrazoxane and liposomal anthracycline formulations in certain high-risk patients receiving anthracyclines and for neurohormonal antagonist therapy in patients with breast cancer receiving sequential anthracyclines and trastuzumab. Ongoing studies are exploring the benefit of: (1) statins for anthracycline cardioprotection; (2) strict blood pressure control during vascular endothelial growth factor inhibitor treatment and; (3) dexrazoxane on long-term cardiac outcomes in pediatric populations. To date, there are no evidence-based cardioprotective strategies specifically for radiation-related heart and vascular disease, immunotherapy myocarditis, fluoropyrimidine cardiotoxicity, vascular endothelial growth factor inhibitor-related hypertension, BCR-Abl multikinase inhibitor vascular disease, and other established and emerging cancer therapeutics with cardiovascular effects. Current evidence supports specific cardioprotective strategies for high risk patients receiving anthracyclines or sequential anthracycline-trastuzumab therapy; however, major evidence gaps exist.


Allozymic and morphological differentiation in the South American frogs genus Eupsophus.
Four species of frogs genus Eupsophus were examined using electrophoresis at 19 loci, and 10 morphological characters employing discriminant analysis. The allozymic and morphological differentiation patterns do not agree. It is suggested that selective pressures are responsible for the incongruence of both sets of characters.


Modeling the progressive entrainment of bed sediment by viscous debris flows using the three-dimensional SC-HBP-SPH method.
Recent reports and experimental data closely indicate that bed-sediment entrainment by debris flows strongly impacts the evolution of the topographic signature of a valley. However, it is difficult to constrain the physics of the entrainment process in numerical models. The challenge is deeply embedded in the shape of the velocity profile, whose knowledge is fundamental for estimating debris-flow basal shear stress exerting on bed sediment. Most two-dimensional models are restricted because the depth-integrated shallow water assumption is problematic in this aspect. One alternative is to combine a three-dimensional, particle-based numerical model with a progressive entrainment law. In this paper, we propose a three-dimensional, surface cell (SC)-based smooth particle hydrodynamics (SPH) model for simulating bed-sediment entrainment by viscous debris flows. The dynamic behavior of a debris flow is simulated by the open-source DualSPHysics scheme, into which the Herschel-Bulkley-Papanastasiou (HBP) rheology model is incorporated. Subsequently, the bed surface is meshed, over which the particles belonging to a certain cell at each time step are identified to represent the basal velocity and flow depth using a novel SC-based algorithm. With the extracted velocities of these basal particles, the sediment entrainment rate of each cell can be estimated using the optimized progressive entrainment law. The proposed SC-HBP-SPH method is tested by means of a full-scale flume experiment carried out in a previous study. The results show that the proposed model can adequately describe and reproduce the complex dynamic process of bed-sediment entrainment by overriding debris flows.


(E)-2-hexenal fumigation control the gray mold on fruits via consuming glutathione of Botrytis cinerea.
(E)-2-hexenal fumigation inhibits the growth of Botrytis. cinerea, but the direct target and its effect on postharvest strawberry have not yet been discovered. In the present study, we applied increasing level of (E)-2-hexenal fumigation from 0.524 μM to 1048 μM to B. cinerea on strawberry and medium. Results showed that (E)-2-hexenal fumigation inhibited lesion diameter on strawberry by 13.96 %, 20.41 % and 100 % with the dosage increasing. On medium, (E)-2-hexenal fumigation increased both the ROS and mitochondria membrane potential level of B. cinerea. LC-MS/MS and FTIR results demonstrate a 1:1 Michael addition reaction between (E)-2-hexenal and glutathione with the product GSH-H in B. cinerea under (E)-2-hexenal fumigation. Furthermore, the consumption of glutathione and glutathione disulfide along with the production of GSH-H during fumigation in B. cinerea caused by (E)-2-hexenal were both concentration- and time-dependent. This study locates the direct target and discovered the functional model of (E)-2-hexenal to B. cinerea.


House dust mite sublingual immunotherapy is safe in patients with mild-to-moderate, persistent asthma: a clinical trial.
The safety of allergen immunotherapy (AIT) in asthma has not always been sufficiently documented; accordingly, fear of asthma exacerbations has made physicians somewhat reluctant to prescribe AIT in this context. In a double-blind, placebo-controlled, randomized clinical trial, house dust mite (HDM) sublingual AIT was found to be efficacious in moderate, persistent asthma. The trial's safety results are now reported in detail. Asthmatic adults were randomized 2 : 1 to twelve months of daily treatment with a sublingual solution of Dermatophagoides pteronyssinus and Dermatophagoides farinae extracts or a placebo. Adverse events (AEs) at least possibly related to the investigational product were classified by the investigators as adverse drug reactions (ADRs). Overall, the patients in the safety analysis set (n = 484; active treatment: n = 322; placebo: n = 162) had mostly well-controlled, persistent asthma [mild in 290 patients (59.9%), moderate in 183 (37.8%) and severe in 11 (2.3%)]. No treatment-related serious AEs were reported. A total of 87.0% and 75.9% of the patients in the active and placebo groups, respectively, experienced at least one AE (mostly mild), and 78.9% and 48.1% experienced an ADR (mostly mild or moderate oral reactions). The incidence of asthma exacerbations (symptoms requiring a short course of oral corticosteroids) during the study was similar in the active treatment group (3.7%) and the placebo group (4.3%). There were no significant intergroup differences or intragroup changes over time in respiratory AEs, lung function or asthma-related quality of life. HDM sublingual AIT was safe and well tolerated in adult patients with mild-to-moderate, persistent asthma (ClinicalTrials.gov: NCT00660452).


Testosterone and zinc supplementation in castrated rats: Effects on plasma leptin levels and relation with LH, FSH and testosterone.
The present study aims to examine how zinc and testosterone supplementation, in combination and separately, affect plasma LH, FSH and leptin levels in castrated rats. Eighty experimental animals used in the study were allocated to 8 groups, each containing an equal number of rats. Group 1, control group; Group 2, castration group; Group 3, testosterone group (5 mg/kg/day); Group 4, zinc-supplemented group (3 mg/kg/day); Group 5, testosterone and zinc-supplemented group; Group 6, zinc-supplemented castration group; Group 7, testosterone and castration group; and Group 8, zinc-supplemented, testosterone and castration group. Plasma zinc, leptin, LH, FSH and free and total testosterone levels were determined in the blood samples collected from the animals by decapitation. Group 2 had the highest leptin levels and together with group 6, it also showed the highest LH and FSH levels (p<0.01). The lowest leptin levels were observed in groups 3 and 7 (p<0.01). Leptin levels in groups 4 and 6 were higher than those in groups 1, 5 and 8 (p<0.01). LH levels in group 4 were lower than those in groups 2 and 6 and higher than those in all other groups (p<0.01). Free and total testosterone levels in groups 7 and 8 were lower than those in groups 3 and 5, but higher than those in all other groups (p<0.01). Plasma LH levels may be more effective than testosterone on plasma leptin and zinc may be an important mediator of the effect LH has on leptin.


Stomach distension increases efferent muscle sympathetic nerve activity and blood pressure in healthy humans.
Although the enteric nervous system is usually described as a separate and independent entity, animal studies show that gastric distension causes a reflex increase in arterial pressure and a sympathetically mediated increase in heart rate and peripheral vascular resistance. To assess the influence of gastric distension on sympathetic outflow and blood pressure, we recorded muscle sympathetic nerve activity (MSNA) from the peroneal nerve by microneurography in eight healthy volunteers. The stomach was distended by means of a barostat, using a single staircase protocol by which pressure was increased by 2 mmHg every 3 min. Gastric sensory function was assessed at each distension step by using a visual analog scale (VAS) for sensations of fullness, nausea and pain. For comparison, we also performed a cold pressor test. The MSNA increased on barostat-induced gastric distension with an almost concomitant elevation of blood pressure. The increase in both was proportional to the intragastric pressure and both decreased towards initial values after the end of distension. Heart rate increased inconsistently and only at higher distension pressures that were associated with high VAS scores. The opposite was found for the cold pressor test. The results of this study confirm the existence of a functional relationship between gastrointestinal distension and cardiovascular function. Decrease in this gastrovascular response may play a role in postprandial hypotension in the elderly, since the MSNA responses to simulated microgravity decrease with age.


Determination of isatin and monoamine neurotransmitters in rat brain with liquid chromatography using palladium hexacyanoferrate modified electrode.
The fabrication and application of a novel electrochemical detector (ED) with palladium hexacyanoferrate (PdHCF) chemically modified electrode (CME) for liquid chromatography (LC) were described. The electrochemical behaviors of isatin, monoamine neurotransmitters and their metabolites at this CME were investigated by cyclic voltammetry. It was found that the CME exhibited efficiently electrocatalytic of isatin and showed high sensitivity and stability for determination of monoamine neurotransmitters. The linear ranges were over three orders of magnitude and the detection limits were 2.5 x 10(-8) mol L(-1) for isatin, 2.5 x 10(-10) mol L(-1) for norepinephrine (NE), 2.5 x 10(-10) mol L(-1) for 5-hydroxyindoleacetic acid (5-HIAA), 5.0 x 10(-10) mol L(-1) for dopamine (DA), 1.0 x 10(-9)mol L(-1) for 3,4-dihydroxyphenylacetic acid (DOPAC), 1.2 x 10(-10) mol L(-1) for 5-hydroxytryptamine (5-HT) and 2.5 x 10(-9)mol L(-1) for homovanillic acid (HVA). Combined with microdialysis, the method was successfully applied to study the effect of isatin on the levels of monoamine neurotransmitters in experimental Parkinsonian rats. The results showed that isatin could significantly increase striatal monoamine neurotransmitters release to the basal level.


The nutrition of preterm infants.
Although great efforts have been made to improve neonatal nutrition in very low birthweight (VLBW) infants, many do not receive adequate nutrient intake and thus develop extrauterine growth restriction. In order to minimize the interruption of nutrients that occurs at birth, an "aggressive" nutritional approach has been proposed. Parenteral nutrition, which allows the infant's requirements for growth and development to be met, is indicated in infants for whom feeding via the enteral route is impossible, inadequate, or hazardous. In the last few years, great attention has been given to high amino acid supply in VLBW infants from the first day of life in order to avoid catabolism, establish anabolism, achieve in utero protein accretion rates, and promote linear growth. Whenever possible, enteral feeding should commence with human milk, which is the preferred feeding method for all infants, including those born preterm. In order to meet the unique nutritional requirements of VLBW infants and preserve the singular benefit of breastfeeding, human milk should be fortified to allow adequate growth and bone mineralization. When feeding of preterm infants with human milk is impossible or extremely limited, cow-milk-based formulas for preterm infants must be used.


Nitrogen deposition and climate effects on soil nitrogen availability: influences of habitat type and soil characteristics.
The amount of plant-available nitrogen (N) in soil is an important indicator of eutrophication of semi-natural habitats, but previous studies have shown contrasting effects of N deposition on mineralisable N in different habitats. The stock of readily mineralisable N (N(rm)) was measured in 665 locations across Britain from a range of intensively and extensively managed habitats, allowing N availability to be studied in relation to soil and vegetation type, and also to variation in climate and in reactive N deposition from the atmosphere. Mineralisable N contents were correlated with deposition in extensively managed habitats but not in intensively managed habitats. The following statements apply only to extensively managed habitats. All habitats showed a similar increase in N(rm) with N deposition. However, soil characteristics affected the relationship, and soil carbon content in particular was a major control on mineralisation. The N(rm) stock increased more with N deposition in organic than in mineral soils. The nitrate proportion of N(rm) also increased with N deposition but, conversely, this increase was greater in mineral than in organic soils. The measurements could be used as indicators of eutrophication, e.g. deposition rates of over 20 kg N ha(-1) y(-1) are associated with nitrate proportions of >41% in a mineral soil (2% carbon), and with N(rm) stocks of over 4.8 kg N ha(-1) in an organic soil (55% carbon). Both N(rm) and nitrate proportion increased with mean annual temperature of the sampling location, despite consistent incubation temperature, suggesting that increasing temperatures are likely to increase the eutrophying effects of N pollution on semi-natural ecosystems.


Impact of intracranial pressure and cerebral perfusion pressure on severe disability and mortality after head injury.
To investigate the relationships between intracranial pressure (ICP), cerebral perfusion pressure (CPP), and outcome after traumatic brain injury. A retrospective analysis of prospectively recorded data from 429 patients after head injury requiring intensive treatment on the Neuroscience Intensive Annex and the Neuro Critical Care Unit, Cambridge, UK. ICP, CPP, and arterial blood pressure (ABP) were continuously recorded. Mean values of pressures were compared to outcome assessed at 6 months after injury (using the Glasgow Outcome Scale). The mortality rate was greater in those having mean ICP greater than 20 mmHg (17% below versus 47% above; p < 0.0001). The mortality rate was dramatically increased for CPP below 55 mmHg (81% below versus 23% above; p < 0.0001). For values of CPP greater than 95 mmHg, favorable outcome was less frequent (50% below versus 28% above; p < 0.033). The rate of severe disability showed the tendency to increase with CPP ( r = 0.87; p = 0.02), suggesting that a higher CPP does not help in achieving favorable outcomes. ICP was greater in those who died in comparison to those who survived (27 +/- 19 mmHg versus 16 +/- 6 mmHg; p < 0.10 - 7), and CPP was lower (68 +/- 21 versus 76 +/- 10 mmHg; p < 0.0002). There was no difference between mean ICP and CPP in good/moderate and severe disability outcome groups. High ICP is strongly associated with fatal outcome. Excessive CPP seems to reduce the probability of achieving a favorable outcome following head trauma.


Use of a polyanionic carbomer, Carbopol971P, in combination with MF59, improves antibody responses to HIV-1 envelope glycoprotein.
Identification of optimal antigen(s) and adjuvant combination(s) to elicit potent, protective, and long-lasting immunity has been a major challenge for the development of effective vaccines against chronic viral pathogens, such as HIV-1, for which there are not yet any licensed vaccines. Here we describe the use of a novel adjuvant approach employing Carbopol 971P(®) NF (hereafter referred to as Carbopol971P), a cross-linked polyanionic carbomer, in combination with the Novartis proprietary oil-in-water adjuvant, MF59, as a potentially safe and effective adjuvant to augment humoral immune responses to the HIV-1 envelope glycoprotein (Env). Intramuscular immunization of small animals with recombinant Env glycoprotein (gp140) formulated in Carbopol971P plus MF59 gave significantly higher titers of binding and virus neutralizing antibodies as compared to immunization using gp140 with either MF59 or Carbopol971P alone. In addition, the antibodies generated were of higher avidity. Importantly, the use of Carbopol971P plus MF59 did not cause any serious adverse reactions or any obvious health problems in animals upon intramuscular administration. Hence, the Carbopol971P plus MF59 adjuvant formulation may provide a benefit for future vaccine applications.


DRB1*03:01 haplotypes: differential contribution to multiple sclerosis risk and specific association with the presence of intrathecal IgM bands.
Multiple sclerosis (MS) is a multifactorial disease with a genetic basis. The strongest associations with the disease lie in the Human Leukocyte Antigen (HLA) region. However, except for the DRB1*15:01 allele, the main risk factor associated to MS so far, no consistent effect has been described for any other variant. One example is HLA-DRB1*03:01, with a heterogeneous effect across populations and studies. We postulate that those discrepancies could be due to differences in the diverse haplotypes bearing that allele. Thus, we aimed at studying the association of DRB1*03:01 with MS susceptibility considering this allele globally and stratified by haplotypes. We also evaluated the association with the presence of oligoclonal IgM bands against myelin lipids (OCMB) in cerebrospinal fluid. Genotyping of HLA-B, -DRB1 and -DQA1 was performed in 1068 MS patients and 624 ethnically matched healthy controls. One hundred and thirty-nine MS patients were classified according to the presence (M+, 58 patients)/absence (M-, 81 patients) of OCMB. Comparisons between groups (MS patients vs. controls and M+ vs. M-) were performed with the chi-square test or the Fisher exact test. Association of DRB1*03:01 with MS susceptibility was observed but with different haplotypic contribution, being the ancestral haplotype (AH) 18.2 the one causing the highest risk. Comparisons between M+, M- and controls showed that the AH 18.2 was affecting only M+ individuals, conferring a risk similar to that caused by DRB1*15:01. The diverse DRB1*03:01-containing haplotypes contribute with different risk to MS susceptibility. The AH 18.2 causes the highest risk and affects only to individuals showing OCMB.


Pregnancy and infant loss support: a new, feminist, American, patient movement?
Using as examples three of the earliest pregnancy and infant loss organizations and multiple recent initiatives, I argue this is a unique patient movement, in part due to the particularities of pregnant patienthood. Although during the first 20 years of this distinctively US movement, pregnancy and infant loss support was hospital-based, there was remarkably little attention to the "medical" dimensions of these losses, e.g. etiology, diagnosis, prevention, and treatment. The thrust was instead on changing ideas and feelings. It is only since the turn of the century that bereaved parents have started to forge collaborations with physicians to work toward prevention. During the first phase (mid-1970s to mid-1990s), it was a women's movement, though it did not present itself as such, and although it was indebted to the feminist movement and included some feminist initiatives, the movement was dominated by a traditionally feminine ethos and included pro-life elements. During the second phase, as physicians and researchers have become more involved, leadership has become somewhat less female-centric while at the same time, more initiatives are explicitly feminist.


Initial presentation, management and follow-up data of 33 treated patients with hereditary tyrosinemia type 1 in the absence of newborn screening.
Hereditary tyrosinemia type 1 (HT1) is a rare autosomal recessive disorder of phenylalanine and tyrosine catabolism due to a deficiency of fumarylacetoacetate hydrolase. HT1 has a large clinical spectrum with acute forms presenting before six months of age, subacute forms with initial symptoms occurring between age 6 and 12 months, and chronic forms after 12 months of age. Without treatment, HT1 results in the accumulation of toxic metabolites leading to liver disease, proximal tubular dysfunction, and porphyria-like neurological crises. Since the early nineties, the outcome of HT1 has dramatically changed due to its treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC, nitisinone). In some countries, HT1 is included in the newborn screening program based on the analysis of succinylacetone concentration on dried blood spots. In the present study, we report clinical and laboratory parameters data on 33 HT1 patients focusing on clinical presentation and therapeutic management at the time of diagnosis. Eighteen patients were diagnosed with the acute form (median age at presentation 2.5 months), 6 with the subacute form (median age at presentation 10 months), and 5 with the chronic form of HT1 (median age at presentation 15 months). Four patients were diagnosed pre-symptomatically in the setting of a family history of HT1. Among the 29 symptomatic patients, hepatomegaly was found in 83% of patients and prolonged coagulation times due to hepatocellular insufficiency was observed in 93% of patients. HT1 diagnosis was confirmed by increased urine succinylacetone in all patients. All patients but 2 were treated with nitisinone immediately at diagnosis. During follow-up, 2 patients received liver transplant for high grade dysplasia or hepatocellular carcinoma, 10 patients exhibited some form of neurocognitive impairments. Our data confirm that HT1 is a severe treatable liver disease that should be detected at the earliest, ideally by newborn screening and appropriately treated.


Food consumption patterns in the Waterloo Region, Ontario, Canada: a cross-sectional telephone survey.
The demographics and lifestyles of Canadians are changing, thereby influencing food choices and food preparation in the home. Although different dietary practices are associated with increased risk of foodborne illness, our ability to evaluate food consumption trends and assess risks associated with foodborne illness is limited by lack of data on current eating habits and consumer food safety practices. The objective of this study was to describe, for the first time, the food consumption patterns in a Canadian-based population from a food safety perspective, in order to establish baseline data on actual food intake of individuals. A cross-sectional telephone survey of 2,332 randomly selected residents of Waterloo Region, Ontario, Canada (C-EnterNet pilot site) was conducted between November 2005 and March 2006. Food intake was assessed using a 7-day dietary recall method. Certain food items were consumed more than others among the same food groups, and consumption of many food items varied by gender and age. Specific foods considered high-risk for the transmission of certain enteric pathogens were significantly more likely to be consumed by males (i.e. unpasteurized juice, bean sprouts, and undercooked meat) and elderly individuals (i.e. undercooked eggs). The majority of households prepared and consumed most meals at home, allocating an average of 44 minutes to prepare a meal. Baseline data on actual food intake is useful to public health professionals and food safety risk assessors for developing communication messages to consumers and in foodborne outbreak investigations.


[Supported Housing - Development and Validation of the "Supported Housing Fidelity Scale" for People With Mental Health Problems].
For supported accommodation settings in mental health care, there is no comprehensive list of criteria for German-speaking countries available. The development and testing of a fidelity scale for independent housing is described. By means of a cross-country cooperation a fidelity scale was developed and was utilized in interviews with heads of 87 housing services and institutions in Germany and Switzerland. The fidelity scale consists of 31 items in 4 topic fields. Outreach services demonstrated a slightly higher fidelity compared to residential care. This was particularly true for the topic fields 'Housing conditions' and 'Inclusion orientation'. We found not differences in the topic fields 'Staff/team' and 'Support conditions'. With this fidelity scale there is a testable list of criteria for independent housing services in mental health care available for the first time in German-speaking countries.


An evaluation of the coronary constriction following propranolol.
This study attempts to determine whether a direct coronary vasoconstriction follows beta blockade with propranolol. Coronary blood flow was varied with the aid of a pump. When myocardial contractile force was plotted as a function of coronary blood flow a characteristic biphasic curve resulted. Autoperfusion without the pump resulted in a flow rate which fell on the knee of that curve. Any direct vasomotion therefore should shift that autoperfused flow rate off of that knee. When propranolol was given intravenously at 0.5 mg/kg a new contractile force--flow curve resulted but the autoperfused coronary blood flow remained at the knee of the curve. Since these data indicate that coronary flow fell precisely in proportion to myocardial metabolism it is concluded that all coronary vasoconstriction following propranolol is secondary to changes in metabolism.


Trace nutrients. 3 Magnesium, copper, zinc, vitamin B6, vitamin B12 and folic acid in the British household food supply.
1. Intakes of magnesium, copper, zinc, vitamin B6, vitamin B12 and folic acid in Britain were calculated by applying the values selected for the 4th edition of McCance and Widdowson's The Composition of Foods (Paul & Southgate, 1978) to the amounts of food recorded in the National Food Survey made during 1976 (Ministry of Agriculture, Fisheries and Food, 1977). 2. National average intakes were (/person per d): Mg 249 mg, Cu 1.51 mg, Zn 9.1 mg, vitamin B6 1.36 mg, vitamin B12 6.6 micrograms free folic acid 105 microgram and total folic acid 190 micrograms. Corresponding intakes (/person) in families with four or more children were 10-20% lower. 3. A comparison of intakes with those recommended in Canada (Department of National Health and Welfare, 1976) and the USA (National Research Council, 1974) or by WHO (1973) indicated that for folic acid average values were particularly low, and only for vitamin B12 were the recommendations significantly exceeded. 4. Contributions from alcoholic drinks and confectionery were also calculated and found, on average, to be significant for cu, vitamin B12 and folic acid. 5. The losses of B-vitamins which might occur on cooking are discussed.


[Gipospast-1 thermoelectric apparatus for local hypothermia].
A possibility of providing local hypothermia for human extremities over the area from 6.25 cm2 to 37.5 cm2 with temperature level up to 10 degrees C is shown. "Gipospast-1" is designed for accomplishing the local hypothermia. It was revealed that at such conditions the human organism reaction ensures a specific heat flow on the cooling surface to 0.02+/-0.04 W/cm2. The clinical trials of the apparatus confirmed its efficacy for removing the contractures of the facial muscles and for decreasing the spastics in paretic extremities of neurosurgical patients.


Small bowel tumors: spectrum of findings on 64-section CT enteroclysis with pathologic correlation.
Improvements in helical technology have made detection of benign and malignant small bowel tumors easier so that they are now frequently detected at an early stage. Sixty-four-section CT enteroclysis provides suggestive features that help determine the actual nature of a small bowel tumor in a large number of cases. Specific diagnosis of small bowel tumor is based on a combination of findings that are depicted owing to the use of the multiple capabilities of 64-section CT enteroclysis, allowing optimal planning prior to endoscopic or surgical resection.


Disturbance intensification is altering the trait composition of Caribbean reefs, locking them into a low functioning state.
Anthropogenic climate change is intensifying natural disturbance regimes, which negatively affects some species, while benefiting others. This could alter the trait composition of ecological communities and influence resilience to disturbance. We investigated how the frequency and intensification of the regional storm regime (and likely other disturbances) is altering coral species composition and in turn resistance and recovery. We developed regional databases of coral cover and composition (3144 reef locations from 1970 to 2017) and of the path and strength of cyclonic storms in the region (including 10,058 unique storm-reef intersections). We found that total living coral cover declined steadily through 2017 (the median annual loss rate was ~ 0.25% per year). Our results also indicate that despite the observed increase in the intensity of Atlantic cyclonic storms, their effect on coral cover has decreased markedly. This could be due in part to selection for disturbance-resistant taxa in response to the intensifying disturbance regime. We found that storms accelerated the loss of threatened acroporid corals but had no measurable effect on the cover of more resilient "weedy" corals, thereby increasing their relative cover. Although resistance to disturbance has increased, recovery rates have slowed due to the dominance of small, slow-growing species. This feedback loop is locking coral communities into a low-functioning state dominated by weedy species with limited ecological or societal value.


Nucleotide sequence of the coat protein gene of citrus tristeza virus: comparison of biologically diverse isolates collected in Israel.
The sequences of the coat protein genes of four seedling yellows (SY) and four non-SY (NSY) of citrus tristeza virus (CTV) isolates, which were collected in Israel over a period of 30 years, were analyzed. Pairwise comparisons showed extensive similarities in the nucleotide and amino acid sequences of six isolates designated the VT group. This group consists of three NSY isolates that cause a very mild CTV reaction on the sensitive combination of sweet orange (SwO) grafted on sour orange (SO), and three SY isolates that cause severe SY and SwO/SO reactions. MT, a CTV isolate that is consistently nontransmitted by Aphis gossypii, was found to be different in two amino acids (Val 103 and Glu 113) from each of the A. gossypii transmissible CTV isolates. Sequencing of the cDNA clones obtained from ST, a variably transmitted CTV isolate, showed extensive sequence variation among the tested clones. The sequence information indicates that the current CTV epidemics in Israel are caused by at least two CTV subspecies (VT and HT) displaying extensive differences in their coat protein genes.


Graph Measure Based Connectivity in Chronic Pain Patients: A Systematic Review.
Chronic pain affects 20 to 30% of the adult population worldwide and is consequently the leading cause of disability. Current developments in brain imaging technology are increasing the understanding of the pathophysiology of (chronic) pain and enabling the possibility to objectify pain. As a result, our view of the brain has evolved from a static organ to a dynamic organ that constitutes an adaptable network of linked regions. Graph theory has emerged as a framework to analyze such networks and can be applied to investigate a range of topological properties of both the functional and structural brain network or connectome, thus providing meaningful information about the organization of human brain networks. The aim of this systematic review is to determine whether connectivity differs between chronic pain patients and healthy controls by integrating previous studies that performed graph analyses on structural or functional connectivity. A secondary aim was to determine whether graph measures correlate to clinical outcomes. Systematic review. Relevant articles were searched for in PubMed and Web of Science. These were screened against certain criteria and assessed for quality. On a global level the transitivity, betweenness centrality, intramodular degree, and rich club organization differed between chronic pain patients and healthy controls, but the path length, modularity, degree, and (Hub Disruption Index [HDI] of) participation coefficient did not differ between both groups, along with the small-worldness. Conflicting evidence still remains about a number of global graph measures, namely the global efficiency, local efficiency, clustering coefficient, and HDI of degree. Significant correlations were found between several nodal and global graph measures on one hand, and clinical outcomes related to pain, disability, and motor control on the other hand. No clear conclusions could be made about the majority of the nodal measures, as they were often based on single studies. Differences between chronic pain patients and healthy controls were mostly observed for the global graph measures. Future research is still needed to validate the obtained findings and to expand this knowledge to the chronic pain populations that were not discussed in the included papers.


Incidence and Profile of Severe Cycling Injuries After Bikeway Infrastructure Changes.
The objective of this study was to evaluate whether bicycling infrastructure changes in the city of Minneapolis effectively reduced the incidence or severity of traumatic bicycling related injuries sustained by patients admitted to our Level 1 Trauma Center. Data for this retrospective cohort study was obtained from the trauma database at our institution and retrospective chart review. The total number of miles of bikeway in the city on a yearly basis was used to demonstrate the change in cycling infrastructure. Adjusted regression analysis demonstrated a significant reduction in ISS when total bike lane miles increased (Coef. - 0.04, P < 0.001). Increasing bike lane miles was also associated with a significant reduction in severe head injury (OR 0.99, P < 0.001) and ICU LOS (Coef. - 0.17, P = 0.013). The miles of bike lanes were not associated with any significant changes in mortality or mechanical ventilation days when adjusted for other factors. We were able to demonstrate a reduction in the severity of injuries incurred by cyclists in the setting of a significant increase in the total number of bicycle lane miles. Our data lends credence to the existing evidence that the addition of bicycle lane miles increases cyclist safety.


Surgical treatment of cutis verticis gyrata: a report of 2 cases.
Two cases of cutis verticis gyrata underwent partial excision supplemented by relaxation incisions under the folds with satisfactory results. This method may well be useful in treating selected cases of the primary type as well as those of secondary type.


Profile of microbial communities on carbonate stones of the medieval church of San Leonardo di Siponto (Italy) by Illumina-based deep sequencing.
Comprehensive studies of the biodiversity of the microbial epilithic community on monuments may provide critical insights for clarifying factors involved in the colonization processes. We carried out a high-throughput investigation of the communities colonizing the medieval church of San Leonardo di Siponto (Italy) by Illumina-based deep sequencing. The metagenomic analysis of sequences revealed the presence of Archaea, Bacteria, and Eukarya. Bacteria were Actinobacteria, Proteobacteria, Bacteroidetes, Cyanobacteria, Chloroflexi, Firmicutes and Candidatus Saccharibacteria. The predominant phylum was Actinobacteria, with the orders Actynomycetales and Rubrobacteriales, represented by the genera Pseudokineococcus, Sporichthya, Blastococcus, Arthrobacter, Geodermatophilus, Friedmanniella, Modestobacter, and Rubrobacter, respectively. Cyanobacteria sequences showing strong similarity with an uncultured bacterium sequence were identified. The presence of the green algae Oocystaceae and Trebuxiaceae was revealed. The microbial diversity was explored at qualitative and quantitative levels, evaluating the richness (the number of operational taxonomic units (OTUs)) and the abundance of reads associated with each OTU. The rarefaction curves approached saturation, suggesting that the majority of OTUs were recovered. The results highlighted a structured community, showing low diversity, made up of extremophile organisms adapted to desiccation and UV radiation. Notably, the microbiome appeared to be composed not only of microorganisms possibly involved in biodeterioration but also of carbonatogenic bacteria, such as those belonging to the genus Arthrobacter, which could be useful in bioconservation. Our investigation demonstrated that molecular tools, and in particular the easy-to-run next-generation sequencing, are powerful to perform a microbiological diagnosis in order to plan restoration and protection strategies.


Aqueous ethyl acetate as a novel solvent for the degreasing of black soldier fly (Hermetia illucens L.) larvae: degreasing rate, nutritional value evaluation of the degreased meal, and thermal properties.
The aim of this study was to select appropriate low-toxicity degreasing solvents to degrease black soldier fly (BSF, Hermetia illucens L.) larvae to prepare high-quality protein. Aqueous ethyl acetate was chosen as the solvent to extract BSF protein, and traditional solvents, such as petroleum ether, n-hexane, and isopropanol, were chosen as controls. The meal degreased by aqueous ethyl acetate (the volume ratio of ethyl acetate to water is 90 to 10, EA + W10) shows a high degreasing rate (29.04%), crude protein content (562.3 g kg-1 ), essential amino acid index (EAAI, 95.57), and digestible indispensable amino acid score (DIAAS, 85). The digestibility of the degreased meal samples in the simulated in vitro intestine can reach 76.52%. Thermodynamic analysis and the apparent morphology of the protein fragments showed that the meal degreased by EA + W10 exhibited thermodynamic stability, which suggests that using aqueous ethyl acetate as the degreasing solvent did not affect the nutritional value of the degreased meal. The results suggest that aqueous ethyl acetate (EA + W10) can be used as a novel solvent in the degreasing of BSF larvae meal to prepare high-quality protein with high EAAI and DIAAS and good digestibility. © 2019 Society of Chemical Industry.


Comparison of screening strategies to improve the diagnosis of latent tuberculosis infection in the HIV-positive population: a cohort study.
HIV is the most important risk factor for progression of latent tuberculosis infection (LTBI) to active tuberculosis (TB). Detection and treatment of LTBI is necessary to reduce the increasing burden of TB in the UK, but a unified LTBI screening approach has not been adopted. To compare the effectiveness of a TB risk-focused approach to LTBI screening in the HIV-positive population against current UK National Institute for Health and Clinical Excellence (NICE) guidance. Prospective cohort study. Two urban HIV treatment centres in London, UK. 114 HIV-infected individuals with defined TB risk factors were enrolled prospectively as part of ongoing studies into HIV and TB co-infection. The yield and case detection rate of LTBI cases within the research study were compared with those generated by the NICE criteria. 17/114 (14.9%, 95% CI 8.3 to 21.5) had evidence of LTBI. Limiting screening to those meeting NICE criteria for the general population (n=43) would have detected just over half of these, 9/43 (20.9%, 95% CI 8.3 to 33.5) and those meeting criteria for HIV co-infection (n=74) would only have captured 8/74(10.8%, 95% CI 3.6 to 18.1) cases. The case detection rates from the study and NICE approaches were not significantly different. LTBI was associated with the presence of multiple TB risk factors (p=0.002). Adoption of a TB risk-focused screening algorithm that does not use CD4 count stratification could prevent more cases of TB reactivation, without changing the case detection rate. These findings should be used to inform a large-scale study to create unified guidelines.


The Construction of Cucurbit[7]uril-Based Supramolecular Nanomedicine for Glioma Therapy.
Two supramolecular nanomedicines (CB[7]⊃DOX and CB[7]⊃CPT) based on the host-guest recognition between CB[7] and anticancer drugs were constructed. After supramolecular modification, the stability and water solubility of DOX and CPT were greatly improved, and the anticancer activities of chemotherapeutic drugs were effectively maintained. This work provided a simple but efficient method to enrich supramolecular nanomedicines for cancer therapy.


"Buried strip" versus "tube" in hypospadias repair: analysis of 82 consecutive cases.
The goal of this study was to analyze, discuss, and compare risks and results obtained with the "buried strip" and two "tube" techniques for hypospadias repair in a personal series. From 1976 through 1982, 82 patients underwent complete two-stage repair of hypospadias using either the Denis Browne procedure (23 patients) or the Belt-Fuqua technique (41) and Byars procedure (18), respectively. Only those patients with originally distal and mid shaft hypospadias plus chordee were included in this series. The mean age at the time of repair was 4.9 years, with a range of two to sixteen years. The overall complication rate was 13.4 per cent (11 of 82). The tube procedures alone had a complication rate of 6.8 per cent (4 of 59) compared with 30 per cent (7 of 23) with the Denis Browne technique. Complications noted were: fistulas 6 (Denis Browne 5, Belt-Fuqua 1); meatal stenosis 4 (Denis Browne 2, Byars 2); urethral stricture 1 (Belt-Fuqua). Our results confirm the general belief that tube techniques have a higher reliability than does the Denis Browne procedure. Each procedure improves with the experience of the surgeon, although the tube technique appears to cause less trouble in our hands. The running subcutaneous and intracutaneous sutures give a far smoother healing. We believe this study supports the virtues of two-stage tube repairs.


Heart failure after myocardial revascularization: risk markers.
We investigated the prognostic weight of several risk factors for heart failure in patients undergoing CABG. We followed 351 consecutive patients for 18+/-12 months after surgery to assess clinical outcome, presence and degree of heart failure. The risk of developing heart failure >class 2 at 1 year was investigated by logistic regression on the following preoperative variables: sex, age, left ventricular EF, QRS duration, previous MI, history of heart failure, atrial fibrillation (AF), hypertension, hypercholesterolemia, diabetes, previous stroke. Age was 70+/-8 years and EF was 54+/-12% at the time of surgery. Heart failure >class 2 occurred in 95/351 patients (27%) at follow up. Logistic regression identified QRS duration (OR=1.02), a history of stroke (OR=3.94), and diabetes (OR=1.98) as predictors of CHF at follow up. All the other variables were not risk markers for heart failure at logistic regression. Thirty five patients (10%) had QRS> or =140 ms before surgery; 51% of them had CHF at follow up compared to 24% of patients with QRS<140 ms (p<0.05). In the current surgical era, candidates to CABG (50% of patients older than 70 years) have a relevant likelihood of heart failure at follow up, despite myocardial revascularization. Risk stratification may rely upon inexpensive variables as previous stroke, diabetes, and QRS duration. A minority of patients (5%) could benefit from LV-based pacing, which should be considered at the same surgical time via an epicardial implantation.


Bronchial responsiveness and leucocyte reactivity after influenza vaccine in asthmatic patients.
The hypothesis was studied that an increased bronchial responsiveness (BR) after viral infections in asthmatics may be related to a change in cellular functions. Histamine threshold and histamine release from leucocytes were measured in asthmatic children and healthy controls before and after administration of a live attenuated or an inactivated influenza vaccine. Live influenza vaccine did increase bronchial responsiveness (BR) to histamine in asthmatic children but not in healthy controls. The inactivated vaccine did not give rise to an increased BR. The releasability of histamine from leucocytes was not increased as a result of the immunisation.


Neural substrates and behavioral profiles of romantic jealousy and its temporal dynamics.
Jealousy is not only a way of experiencing love but also a stabilizer of romantic relationships, although morbid romantic jealousy is maladaptive. Being engaged in a formal romantic relationship can tune one's romantic jealousy towards a specific target. Little is known about how the human brain processes romantic jealousy by now. Here, by combining scenario-based imagination and functional MRI, we investigated the behavioral and neural correlates of romantic jealousy and their development across stages (before vs. after being in a formal relationship). Romantic jealousy scenarios elicited activations primarily in the basal ganglia (BG) across stages, and were significantly higher after the relationship was established in both the behavioral rating and BG activation. The intensity of romantic jealousy was related to the intensity of romantic happiness, which mainly correlated with ventral medial prefrontal cortex activation. The increase in jealousy across stages was associated with the tendency for interpersonal aggression. These results bridge the gap between the theoretical conceptualization of romantic jealousy and its neural correlates and shed light on the dynamic changes in jealousy.


Mitral valve replacement in infants and children 5 years of age or younger: evolution in practice and outcome over three decades with a focus on supra-annular prosthesis implantation.
Successful mitral valve replacement in young children is limited by the lack of small prosthetic valves. Supra-annular prosthesis implantation can facilitate mitral valve replacement with a larger prosthesis in children with a small annulus, but little is known about its effect on the outcomes of mitral valve replacement in young children. One hundred eighteen children underwent mitral valve replacement at 5 years of age or younger from 1976-2006. Mitral valve replacement was supra-annular in 37 (32%) patients. Survival was 74% +/- 4% at 1 year and 56% +/- 5% at 10 years but improved over time (10-year survival of 83% +/- 7% from 1994-2006). Factors associated with worse survival included earlier mitral valve replacement date, age less than 1 year, complete atrioventricular canal, and additional procedures at mitral valve replacement, but not supra-annular mitral valve replacement. As survival improved during our more recent experience, the risks of supra-annular mitral valve replacement became apparent; survival was worse among patients with a supra-annular prosthesis after 1991. A pacemaker was placed in 18 (15%) patients within 1 month of mitral valve replacement and was less likely in patients who had undergone supra-annular mitral valve replacement. Among early survivors, freedom from redo mitral valve replacement was 72% +/- 5% at 5 years and 45% +/- 7% at 10 years. Twenty-one patients with a supra-annular prosthesis underwent redo mitral valve replacement. The second prosthesis was annular in 15 of these patients and upsized in all but 1, but 5 required pacemaker placement for heart block. Supra-annular mitral valve replacement was associated with worse survival than annular mitral valve replacement in our recent experience. Patients with supra-annular mitral valve replacement were less likely to have operative complete heart block but remained at risk when the prosthesis was subsequently replaced.


Nanoparticle agglomerates of indomethacin: The role of poloxamers and matrix former on their dissolution and aerosolisation efficiency.
Nanoparticles (NPs) were prepared and assembled to microsized agglomerates with and without matrix formers (mannitol and L-leucine) by coupling wet milling and spray drying to harmonise the advantages of NPs with handling and aerodynamics of microparticles without induction of amorphisation. Indomethacin was selected as poorly water-soluble drug and poloxamers with different ratios of hydrophilic to hydrophobic domains were evaluated as stabilisers comparatively to D-α-Tocopherol polyethylene-glycol succinate (TPGS). Particle size of nanosuspensions and morphology, size, crystal form, drug loading, redispersibility, in vitro dissolution, and in vitro aerosolisation of NP-agglomerates were determined. Molecular weight of stabilisers affected the rate but not the limit of NP size reduction and the length of hydrophilic segment in poloxamers was found important for the nanosuspension stabilisation. SEM revealed the structure of agglomerates consisting of nanocrystal assemblies. XRPD with DSC proved that NP agglomerates retained their crystallinity. NP-agglomerates exhibited enhanced dissolution compared to physical mixtures of drug and stabilisers while incorporation of matrix formers enabled redispersibility upon hydration and further increased the drug dissolution. Also, matrix formers resulted in significantly improved aerosolisation with higher fine particle fractions (49-62%) and smaller mass median aerodynamic diameters (<3.5 μm), compared to cases without matrix formers (34-43% and <4.5 μm).


Opiate (Enkephalin) receptors of neuroblastoma cells: occurrence in clusters on the cell surface.
A bioactive, fluorescent derivative of enkephalin, Tyr-D-Ala-Gly-Phe-Leu-Lys-rhodamine, was used to determine the distribution of opiate receptors in living neuroblastoma cells. The receptors appeared in clusters on the cell surface, and no internalization was detected. No specific fluorescence or clusters were observed in the presence of [D-Ala2, Leu5]enkephalin or at 4 degrees C, and the clusters were much reduced under ionic conditions (that is, with 100 millimolars sodium) that specifically decrease the binding of opiate agonists.


Sensorineural hearing loss of suspected autoimmune etiology: a report of three cases.
The present paper reports three cases of sensorineural hearing loss of suspected autoimmune origin. Cases 1 and 2 were bilateral sensorineural hearing loss which responded to steroid therapy. Case 3 was bilateral fluctuant sensorineural hearing loss in conjunction with systemic lupus erythematosus. The pathogenesis of autoimmune sensorineural hearing loss is not yet fully understood. In two patients, hearing levels improved or stabilized following the use of osmotic expanders. The clinical results suggest that endolymphatic hydrops may participate in autoimmune sensorineural hearing loss.


Effects of calcium-channel blockers on myocardial preservation during experimental acute myocardial infarction.
Calcium antagonists have become accepted agents for the attenuation of myocardial ischemia when it becomes manifest as angina pectoris. However, it is not known whether these agents can protect ischemic myocardium during the early evolution of an acute myocardial infarct. Calcium antagonists could potentially improve myocardial perfusion, by relieving coronary spasm or improving collateral blood flow, and reduce the energy demands of the ischemic myocardium either directly or by reducing heart rate or contractility. In some studies, calcium antagonists have decreased the rate of adenosine triphosphate depletion in ischemia and reduced functional or structural indexes of ischemic injury after relatively brief periods (up to 2 hours) of injury. We have assessed the ability of verapamil to protect severely ischemic myocardium in dogs with a 40-minute test period of circumflex occlusion followed by reperfusion. After 4 days of recovery, infarcts were sized by histologic methods. Untreated dogs had subendocardial infarcts (the more moderately ischemic subepicardial region being salvaged by reperfusion). Pretreatment with verapamil reduced the size of these subendocardial infarcts from 34 +/- 8 to 8 +/- 3% of the ischemic circumflex vascular bed (anatomic area at risk). Thus, verapamil prevented cell death in a substantial proportion of the severely ischemic subendocardial region that otherwise would have died as a result of the 40-minute test period of ischemia. To establish whether verapamil could prevent cell death for a longer period of time in the less severely ischemic subepicardial region, a 3-hour period of coronary occlusion with reperfusion was studied.


Plant Biology: The Making of an Epithelium.
The endodermis of plants is surrounded by an impermeable belt, the casparian strip, making it a highly selective barrier for nutrient uptake. Successful reprogramming of non-endodermal cells to form a casparian strip requires two signals produced by the vasculature.


Selective Synthesis of Partially Protected d-Talopyranosides and d-Gulopyranosides via Catalytic Asymmetric Dihydroxylation: Multiplier Effects of Substrate Control and Catalyst Control.
Highly selective syntheses of d-talopyranosides and d-gulopyranosides have been achieved by utilizing the multiplier effects of substrate control and catalyst control. Through the combination of an O-benzoyl-protected substrate and the AD-mix-β system, the d-talopyranoside was obtained in a ratio of 96:4. In contrast, the d-gulopyranoside was obtained in a ratio of 3:97 through the use of an O-tert-butyldimethylsilyl-protected substrate and AD-mix-α.


Allergic reactions to gadodiamide following interventional spinal procedures: a report of 4 cases.
Gadodiamide is currently considered a safe alternative for use in interventional spinal procedures in persons with a documented allergic response to iodine-based contrast dyes and with adequate renal function. The most common reactions to gadodiamide are nausea, emesis, and headache. These reactions usually are self-limited and are reported to occur in less than 1% of patients. We report the cases of 4 patients who developed an allergic reaction to gadodiamide, 3 of whom presented within the same week, after minimally invasive interventional spinal procedures at an outpatient private practice facility. Furthermore, 3 of the 4 patients had previously been exposed to gadodiamide during prior interventional spinal procedures without reaction, and the fourth patient had a reaction on the first exposure. The clinical presentation was manifested as a rash in 3 of the 4 patients, whereas the fourth patient experienced fevers and rigors along with rash. Because the injections of gadodiamide were not administered in succession, different vials of gadodiamide were used in each patient, and the injections were given by different clinicians at different spinal levels, we hypothesize that these patients experienced an allergic reaction, rather than contamination of the gadodiamide solution. These cases may call into question the safety of gadodiamide as an alternative contrast agent.


A prospective, longitudinal study of metabolic syndrome in patients with bipolar disorder and schizophrenia.
Although cross sectional studies have evaluated the prevalence of metabolic syndrome (MetS) in patients with bipolar patients (BPAD), data from longitudinal studies are limited. To assess the prevalence of MetS in patients with BPAD, to observe the change in prevalence rate over a period of 6 months, to assess the prevalence of sub-threshold MetS (i.e., patients fulfilling one or two criteria of MetS) and to compare patients with BPAD and schizophrenia on the above mentioned parameters. Seventy five patients with BPAD and 53 patients with schizophrenia were initially evaluated for MetS and then followed up for a period of 6 months. According to consensus definition, prevalence of MetS at baseline was 40% in BPAD group and 32% in schizophrenia group. Over 6 months of follow-up the prevalence of MetS increased by 8% and 9.4% in the BPAD and the schizophrenia groups respectively. There was no significant difference between the two groups on any of the assessments. Another 28-32% of patients in the BPAD group also fulfilled two criteria and 13-17% fulfilled at least one criterion of MetS at different points of assessment. Similarly, 19-26% of the patients with schizophrenia met at least two and 23-26% of the patients fulfilled at least one criterion of MetS. The study was limited by small sample size, inclusion and the relatively short follow-up period. 40% patients with BPAD and 32% with schizophrenia have MetS and the prevalence of MetS increases by 8-9.4% over 6 months.


Gamma-Aminobutyric Acid A Receptor Subunit Expression and Cellular Localization in the Human Parkinsonian Globus Pallidus.
The gamma-aminobutyric acid A (GABAA) receptor is an important mediator of cellular signaling in the globus pallidus and might be implicated in the pathophysiology of Parkinson disease (PD). The goal of the present study was to characterize GABAA receptor subunit expression in the normal and parkinsonian human globus pallidus. Postmortem brain specimens were obtained from 8 patients with pathological evidence of PD at autopsy and from 4 control patients without such evidence. These tissues were exposed to primary antibodies directed against the α1 and α3 subunits of the GABAA receptor and were visualized and quantified using fluorescence microscopy. No differences were found in the pallidal neuronal density in the control versus PD tissues. Projection neurons strongly expressed the α1, α3, and β2 GABAA receptor subunits. After normalizing the immunofluorescence intensities in the globus pallidus to those in the adjacent structures, no significant differences were found in GABAA receptor subunit expression in the globus pallidus between the PD specimens and the control specimens. Compensatory changes in GABAA receptor α1 and α3 subunit expression in response to PD-related signaling abnormalities in the globus pallidus did not occur in our PD cohort.


Effect of 3-isobutyl-1-methylxanthine on histamine-stimulated gastric secretion in dogs.
The effect of IMX on histamine-stimulated gastric secretion has been studied in dogs equipped with gastric cannulas. After determining the histamine dose response, IMX, histamine, and IMX plus histamine were given by a constant intravenous infusion for 3 h, and acid was collected at 15-min intervals. In a separate series of experiments a single dose of 100 mg of db-cAMP was given 1 h after initiation of infusion of IMX, histamine, and histamine plus IMX. Results show that IMX, a potent inhibitor of phosphodiesterase, is a weak stimulant of acid secretion, and augments histamine-stimulated secretion. However, during stimulated acid secretion, there were no significant changes in tissue cAMP levels, Administration of exogenous dib-cAMP did not produce any significant changes in acid secretion in dogs, but did contribute to elevated cAMP levels.


Estrogen receptor 2 polymorphism and carotid intima-media thickness.
The present study was designed to investigate the effects of estrogen receptor 2 gene (ESR2) rs1256049 polymorphism to carotid artery intima-media thickness (CIMT), as part of the Cardiovascular Risk in Young Finns Study. The frequencies of ESR2 genotypes G/G, G/A, and A/A were 85.1%, 14.3%, and 0.7%, respectively, in the whole study population (n = 2211). Compared with subjects with genotype GG, those with the A allele had higher mean CIMT (p = 0.004) and maximal CIMT (p = 0.005). In a Finnish population, the ESR2 rs1256049 polymorphism A allele is associated with preclinical atherosclerosis in young adulthood. Our results and those of others also suggest that some effects of this genetic variation may be population specific.


Obesity paradox as a new insight from postoperative complications in gastric cancer.
The obesity paradox is reported to exist in various diseases. However, obesity is a pivotal issue in gastric cancer (GC) patients because of the surgical difficulty related to postoperative abdominal infectious complications (PAIC). This study clarified the existence of the obesity paradox in GC. Between 1997 and 2015, 1536 consecutive patients underwent curative gastrectomy. Of all patients, 18.6% (285/1536) were obese and tended to have a better prognosis (P = 0.073). In patients without PAIC, obesity was a significant prognostic factor for 5-year overall survival (P = 0.017). PAIC was an independent poor prognostic factor in both obese and non-obese patients (P < 0.001; hazard ratio [HR] 4.22 and 1.82). In pStage II-III patients, there was a large and significant prognostic difference between non-PAIC and PAIC obese patients (P = 0.006; 5-year overall survival: 69.7% vs. 43.8%) related to the higher incidence of peritoneal recurrence in PAIC obese patients (P = 0.035; 31% vs. 10%). Whereas, there was a small prognostic difference between non-PAIC and PAIC non-obese patients (P = 0.102; 5-year overall survival: 56.5% vs. 51.9%). Although the obesity paradox is present in GC, PAIC had a more negative prognostic impact through peritoneal recurrence in obese GC patients.


Relationships between the resting-state network and the P3: Evidence from a scalp EEG study.
The P3 is an important event-related potential that can be used to identify neural activity related to the cognitive processes of the human brain. However, the relationships, especially the functional correlations, between resting-state brain activity and the P3 have not been well established. In this study, we investigated the relationships between P3 properties (i.e., amplitude and latency) and resting-state brain networks. The results indicated that P3 amplitude was significantly correlated with resting-state network topology, and in general, larger P3 amplitudes could be evoked when the resting-state brain network was more efficient. However, no significant relationships were found for the corresponding P3 latency. Additionally, the long-range connections between the prefrontal/frontal and parietal/occipital brain regions, which represent the synchronous activity of these areas, were functionally related to the P3 parameters, especially P3 amplitude. The findings of the current study may help us better understand inter-subject variation in the P3, which may be instructive for clinical diagnosis, cognitive neuroscience studies, and potential subject selection for brain-computer interface applications.


[Central neurocytomas: clinical and radiopathological correlations: about 12 cases].
Central neurocytomas are defined as neoplasms composed of round, uniform cells, with neural immunophenotypic profile and low proliferation index. They account for 0.5% of intracranial tumors. They usually occur near the foramen of Monro and can cause obstructive hydrocephaly. We conducted a retrospective data collection from records of 12 patients with central neurocytomas in the Anatomopathological Laboratory at the Mohammed VI University Hospital, Marrakech, between January 2006 and June 2015. This study aimed to report and describe the radiopathological features of this rare histologic type. The male/female sex-ratio was 1.4. The average age at diagnosis was 22.3 years. The revealing symptomatology was dominated by intracranial hypertension associated with decreased visual acuity and diplopia in all patients. Our study concerned about simple biopsy in one case, subtotal resection in seven cases and total resection in four cases. Histopathological examination showed tumor proliferation with endocrine architecture. Tumor cells are more often small and uniform. Mitotic index was low. Tumor proliferation was associated with fibrillary fundus and vascular network with three types of trees. Immunohistochemical examination was identical in all patients. It showed tumor cells positive for anti-synaptophysin antibodies, chromogranine and NSE. In all patients the radio-pathologic correlation suggested central neurocytoma (grade II - WHO 2016). This study highlights the anatomo-clinical, radiological and evolutionary features of these rare tumors.


Design and Rationale for a Phase II, Randomized, Open-Label, Two-Cohort Multicenter Interventional Study of Osimertinib with or Without Savolitinib in De Novo MET Aberrant, EGFR-Mutant Patients with Advanced Non-Small-Cell Lung Cancer: The FLOWERS Trial.
Epidermal growth factor receptor (EGFR) mutations are well-known genetic alterations in advanced non-small cell lung cancer (NSCLC) which are associated with remarkable survival benefits from first-line treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, around 30% of patients exhibit primary resistance to EGFR-TKIs therapy. Co-existing MET amplification/over-expression has showed shorter time to progression on EGFR-TKI monotherapy. Osimertinib (TAGRISSO, AZD9291) has been recommended in EGFR-mutant advanced NSCLC patients as first-line treatment. Savolitinib (AZD6094, HMPL-504) is a highly selective MET-TKI which has demonstrated anti-tumor activity in various cancers with MET alterations. This FLOWERS study, a phase II, randomized, open-label, 2-cohort multicenter trial aimed to evaluate the efficacy and safety of osimertinib with or without savolitinib as first-line therapy in patients with de novo MET amplified/over-expressed, EGFR-mutant positive, locally advanced or metastatic NSCLC. Approximately 44 patients will be randomized to receive osimertinib (80 mg once daily) monotherapy or osimertinib (80 mg once daily) and savolitinib (300 mg twice daily) combination therapy; patients in osimertinib monotherapy cohort confirmed as MET positive (MET-amplified/over-expressed) after disease progression will have the opportunity to receive the cross-over combination therapy as second-line treatment. Primary endpoint will be objective response rate. Key secondary endpoints will be progression-free survival, duration of response, disease control rate, overall survival, safety and tolerability. The results of the study will provide better perspectives on the efficacy and safety of EGFR-TKI plus MET-TKI combination therapy (osimertinib plus savolitinib) in patients with de novo MET-amplified/over-expressed, EGFR-mutant positive, treatment naïve, advanced NSCLC and offer a meaningful guidance in clinical practice (NCT05163249).


Successful use of levosimendan in a patient with peripartum cardiomyopathy.
This case represents the first reported use of levosimendan, a calcium-sensitizing drug with additional vasodilation properties, for treatment of a woman with peripartum cardiomyopathy. Levosimendan induced a steady decline of increased pulmonary capillary wedge pressure, followed by a definitive increase in cardiac stroke volume. The patient recovered from this serious episode of heart failure, and she ultimately regained left ventricular function. Acute heart failure is a life-threatening event that only rarely occurs during childbirth. We report a case of a woman who experienced cardiovascular collapse during vaginal delivery. We determined that she met current diagnostic criteria for peripartum cardiomyopathy, and we successfully treated her with levosimendan, a calcium-sensitizing drug with additional vasodilation properties.


Growth and development in children born very low birthweight.
To examine the relationships between growth (birth to age 2 years) and developmental outcomes in children born with very low birthweight (VLBW). Motor and mental development in children born with VLBW were regressed on anthropometric measurements at birth, 9 months and 2 years using multivariable regression. The Early Childhood Longitudinal Study-Birth Cohort, a longitudinal cohort, community sample, designed to be representative of children born across the USA. 950 children born with VLBW (<1500 g). Motor and cognitive scores on the Bayley Scales at 9 months and 24 months chronological age. A high proportion of children exhibited poor growth, with length-for-age z-scores <-2 (ie, stunting) in 21.3% of children at 9 months (adjusted for prematurity) and 34.2% of children at 2 years. Compared with children having z-scores >-2, children with growth shortfalls in head circumference, length and weight had a higher adjusted OR (aOR) of low Bayley motor scores at 9 months and 2 years (aOR ranging from 1.8 to 3.3, all p<0.05), while low Bayley cognitive scores were predicted by 9-month deficits in length and weight (aOR 2.0 and 2.4, respectively, both p<0.01) and 2-year deficits in length and head circumference (aOR 2.9 and 2.8, both p<0.05). Anthropometric measures of growth were linked to current and future neurodevelopmental outcomes in children born with VLBW. While careful length measures may be a particularly useful marker, deficits in all anthropometric measures were risk factors for developmental delays.


Acute kidney injury after burn surgery: Preoperative neutrophil/lymphocyte ratio as a predictive factor.
Severe inflammation and acute kidney injury (AKI) are serious adverse events after burn injuries. The neutrophil/lymphocyte ratio (NLR) is a marker of inflammation. We evaluated the independent risk factors for postoperative AKI, including NLR, in burn-injured patients. The preoperative, intraoperative, and postoperative variables of 473 burn-injured patients were collected. The risk factors for AKI after burn surgery were evaluated using univariate and multivariate logistic regression analyses. The receiver operating characteristic (ROC) curve analysis of preoperative NLR was performed. The 3-month mortality after surgery was also compared between AKI and non-AKI groups using Kaplan-Meier analysis with a log-rank test. Postoperative AKI occurred in 71 of 473 (15.0%) burn patients. The total body surface area burned (odds ratio (OR), 1.013; 95% confidence interval (CI), 1.001-1.026; P = 0.037), inhalation injury (OR, 1.821; 95% CI, 1.008-3.292; P = 0.047), and preoperative NLR (OR, 1.094; 95% CI, 1.064-1.125; P < 0.001) were risk factors for AKI after surgery. The area under the ROC curve was 0.767, with an optimal cut-off value of 11.7. Moreover, the 3-month mortality after surgery was significantly higher in the AKI group than in the non-AKI group (49.3% vs 14.9%, P < 0.001). Total body surface area burned, inhalation injury, and preoperative NLR are risk factors for AKI after burn surgery, which is associated with early postoperative mortality. Preoperative NLR can provide useful information for the early detection of postoperative AKI and subsequent mortality in burn-injured patients.


Case report: a camouflaged parathyroid carcinoma with initial misdiagnosis.
Parathyroid carcinoma is a rare malignancy with an increasing incidence. Most patients are characterized by the presence of severe primary hyperparathyroidism, especially hypercalcemia, while patients with normal level of serum calcium are extremely rare. Unfortunately, patients free of hypercalcemia are usually diagnosed at a later stage and suffer from a rather poor prognosis. We describe a patient diagnosed with intrathyroidal normocalcemic parathyroid carcinoma, whose preoperative ultrasonography suggests that the tumor is located inside the thyroid gland and present without obvious clinical manifestations, which makes it more challenging for diagnosis. Preoperative suspicion of malignancy is of great importance for advanced management while preoperative diagnosis is rather challenging with the limited contribution of imaging examinations. Any abnormality in serum level of calcium or parathormone may help to make an initial diagnosis especially when the level is extremely high. We introduce this case of initial misdiagnosis of an intrathyroidal parathyroid carcinoma, mimicking a suspicious thyroid nodule, to focus on the possible anomalous presentations of this rare condition and on its optimal management.


Environmental inactivation of Cryptosporidium parvum oocysts in waste stabilization ponds.
The survival of Cryptosporidium parvum oocysts in a waste stabilization pond system in northwestern Spain and the effects of sunlight and the depth and type of pond on oocyst viability were evaluated using an assay based on the exclusion or inclusion of two fluorogenic vital dyes, 4',6-diamidino-2-phenylindole (DAPI) and propidium iodide (PI). All tested factors had significant effects (P < 0.01) over time on C. parvum oocyst viability. Sunlight exposure was the most influential factor for oocyst inactivation. A 40% reduction was observed after 4 days exposure to sunlight conditions compared with dark conditions. The type of pond also caused a significant reduction in C. parvum oocyst viability (P < 0.01). Inactivation rates reflected that the facultative pond was the most aggressive environment for oocysts placed both at the surface (presence of sunlight) and at the bottom (absence of sunlight) of the pond, followed by the maturation pond and the anaerobic pond. The mean inactivation rates of oocysts in the ponds ranged from 0.0159 to 0.3025 day(-1).


Enzyme action in polymer and salt solutions. I. Stability of penicillin acylase in poly(ethylene glycol) and potassium phosphate solutions in relation to water activity.
The stability of penicillin acylase (penicillin aminohydrolase, EC 18.104.22.168) was studied in poly(ethylene glycol) and potassium phosphate solutions. Enzyme stability measured as the half-life of the enzymatic activity and the transition temperature determined by differential scanning calorimetry, correlated well. The enzyme stability could not be related to the water activity as a measure of solute-solvent interaction. It seems to be related more to the concentration of the solutes and much less to the molecular weight of poly(ethylene glycol). The stabilizing effect of poly(ethylene glycol) is also discussed in terms of poly(ethylene glycol)-protein interactions.


Treatment of metabolic alkalosis with peritoneal dialysis in a patient with renal failure.
Peritoneal dialysis using a chloride-rich dialysate succeeded in correcting systemic metabolic alkalosis in a patient with renal failure. The present approach may have a place in the therapy of metabolic alkalosis.


Assessment of a procedure for detecting minute levels of tooth erosion.
Over a period of some years, the components of a system for discerning erosion on children's teeth have been progressively developed, for use in an extensive project seeking correlations between erosion and various perceived risk factors. The aim was the detection of minute levels of erosion, based on mappings of the palatal surfaces of the maxillary central incisors in children. Significant challenges were encountered, the primary problem being the impracticality of placing control marks that would aid the realignment of successive measurements. The paper describes the erosion detection system and initial experiences based on the results of the first 100 subjects measured after 9 months. The procedures detected the occurrence of erosion of 50 microm magnitude on about one-quarter of the teeth over the 9 month period, at a precision estimated to be +/- 15 microm. The occurrence of some anomalous incidents prevented the procedure from being fully automatic, and it necessitated human examination of a graphical diagram derived from the surface matching program, but it was nevertheless superior to current practices of examining impressions or replicas entirely by eye.


Localisation de l'activite phospholipasique dans les tissus vegetaux. 1) Sur l'absence d'activité phospholipasique D dans les mitochondries et les plastes isolés.
Mitochondria and plastids isolated from various plant tissues by methods which exclude contamination by other cell organelles lack phospholipase D activity.


Fine-needle aspiration cytodiagnosis of endometriosis in cesarean section scar and rectus sheath mass lesions -- a study of seven cases.
The diagnosis of endometriosis is usually established by a biopsy. Since endometriotic lesions can present as a mass lesion, it seems feasible to investigate them by the noninvasive method of fine-needle aspiration cytology (FNAC). In this study, seven cases (5 from a cesarean scar and 2 from rectus sheath) are presented in which FNAC was indicative of endometriosis. The aspirate was obtained using a disposable 10 ml syringe and 22 gauge needle. The material was collected as syringe and needle washings in a cytology container in which 30% ethyl alcohol was present. From half of this material, filter preparations were made on size 3 mum filters and stained by Papanicolaou method, while the remaining aspirate was spun and a cell block was made from the sediment and sections cut and stained with hematoxylin-eosin stain. In all cases the cytologic preparations showed tubular structures indicative of endometrial tissue and stromal cells indicative of endometriosis. This was further confirmed on examination of cell blocks, which showed histologic features of endometriosis characterized by endometrial glands separated by endometrial stroma and rare siderophages. The seven cases described are interesting, since the cytohistological finding in FNAC sample and cell block not only were indicative of the diagnosis of endometriosis, but also obviated the need for an invasive surgical procedure.


Detection and Characterization of Bat Sarbecovirus Phylogenetically Related to SARS-CoV-2, Japan.
Epidemiology of bat Betacoronavirus, subgenus Sarbecovirus is largely unknown, especially outside China. We detected a sarbecovirus phylogenetically related to severe acute respiratory syndrome coronavirus 2 from Rhinolophus cornutus bats in Japan. The sarbecovirus' spike protein specifically recognizes angiotensin-converting enzyme 2 of R. cornutus, but not humans, as an entry receptor.


Gene-level analysis of rare variants in 379,066 whole exome sequences identifies an association of GIGYF1 loss of function with type 2 diabetes.
Sequencing of large cohorts offers an unprecedented opportunity to identify rare genetic variants and to find novel contributors to human disease. We used gene-based collapsing tests to identify genes associated with glucose, HbA1c and type 2 diabetes (T2D) diagnosis in 379,066 exome-sequenced participants in the UK Biobank. We identified associations for variants in GCK, HNF1A and PDX1, which are known to be involved in Mendelian forms of diabetes. Notably, we uncovered novel associations for GIGYF1, a gene not previously implicated by human genetics in diabetes. GIGYF1 predicted loss of function (pLOF) variants associated with increased levels of glucose (0.77 mmol/L increase, p = 4.42 × 10-12) and HbA1c (4.33 mmol/mol, p = 1.28 × 10-14) as well as T2D diagnosis (OR = 4.15, p = 6.14 × 10-11). Multiple rare variants contributed to these associations, including singleton variants. GIGYF1 pLOF also associated with decreased cholesterol levels as well as an increased risk of hypothyroidism. The association of GIGYF1 pLOF with T2D diagnosis replicated in an independent cohort from the Geisinger Health System. In addition, a common variant association for glucose and T2D was identified at the GIGYF1 locus. Our results highlight the role of GIGYF1 in regulating insulin signaling and protecting from diabetes.


Photometric detection at 405 nm in trace analysis by capillary isotachophoresis.
The possibilities of photometric detection at 405 nm were investigated for trace isotachophoretic analysis of various ionic constituents. Increased selectivity of the detection enabled, for example, the detection and determination of nitrophenols at 10(-8) M in a 25-microliter sample. 5-Nitrofurylacrylic acid, a wine stabilizer, could be detected with confidence at ca. 0.1 ppm in wine without any sample pretreatment. Approximately 250-fmol amounts of amino acids, labelled with 2,4-dinitrophenyl, were detectable with the technique employed. This is almost three decades lower in comparison to what is achievable with an high resolution universal detector. The adsorption of the analytes in the sample handling devices as well as in the separation compartment were problems in the analysis at this concentration level. The detection limit given above was achieved when these phenomena were suppressed by the addition of naphthalene-1,3,6-trisulphonate or pyrophosphate to the sample solution.


Birds and neotropical mistletoes: effects on seedling recruitment.
Two groups of neotropical mistletoes differ in fruit structure and consequently in the manner their seeds are deposited by avian frugivores. Birds defecate seeds of one group in clumps, but deposit seeds of the other group singly by regurgitation. A significant proportion of adult plants of both species were found growing alone, indicating a higher mortality with seed clumping.


Accounting- versus economic-based rates of return: implications for profitability measures in the pharmaceutical industry.
Accounting-based profits have indicated that pharmaceutical firms have achieved greater returns relative to other sectors. However, partially due to the theoretically inappropriate reporting of research and development (R&D) expenditures according to generally accepted accounting principles, evidence suggests that a substantial and upward bias is present in accounting-based rates of return for corporations with high levels of intangible assets. Given the intensity of R&D in pharmaceutical firms, accounting-based profit metrics in the drug sector may be affected to a greater extent than other industries. The aim of this work was to address measurement issues associated with corporate performance and factors that contribute to the bias within accounting-based rates of return. Seminal and broadly cited works on the subject of accounting- versus economic-based rates of return were reviewed from the economic and finance literature, with an emphasis placed on issues and scientific evidence directly related to the drug development process and pharmaceutical industry. With international convergence and harmonization of accounting standards being imminent, stricter adherence to theoretically sound economic principles is advocated, particularly those based on discounted cash-flow methods. Researchers, financial analysts, and policy makers must be cognizant of the biases and limitations present within numerous corporate performance measures. Furthermore, the development of more robust and valid economic models of the pharmaceutical industry is required to capture the unique dimensions of risk and return of the drug development process. Empiric work has illustrated that estimates of economic-based rates of return range from approximately 2 to approximately 11 percentage points below various accounting-based rates of return for drug companies. Because differences in the nature of risk and uncertainty borne by drug manufacturers versus other sectors make comparative assessments of performance challenging and often inappropriate, continued work in this area is warranted.


Epidermal-skin-test 1,000 (EST-1,000)--a new reconstructed epidermis for in vitro skin corrosivity testing.
The determination of a possible corrosive or irritative potential of certain products and ingredients is necessary for their classification and labeling requirements. Reconstructed skin as a model system provides fundamental advantages to single cell culture testing and leads to promising results as shown by different validation studies (for review: Fentem, J.H., Botham, P.A., 2002. ECVAM's activities in validating alternative tests for skin corrosion and irritation. ATLA 30(Suppl. 2), 61-67). In this study we introduce our new reconstructed epidermis "Epidermal-Skin-Test" (EST-1,000). This fully grown epidermis consists of proliferating as well as differentiating keratinocytes. EST-1,000 shows a high comparability to normal human skin as shown by histological and immunohistochemical data. Characteristic markers (KI-67, CK 1/10/5/14, transglutaminase, collagen IV, involucrin, beta 1 integrin) can be identified easily. The main focus of this work was to characterize EST-1,000 especially with respect to its barrier function by testing several substances of known corrosive potential. Skin corrosion was detected by the cytotoxic effect of the substances on a reconstructed epidermis after short-term application to the stratum corneum. The effect was determined by standard MTT assay and accompanying histological analysis. Hence EST-1,000 shows a very high predictive potential and closes the gap between animal testing and the established full-thickness model Advanced-Skin-Test 2,000 (AST-2,000) (Noll, M., Merkle, M.-L., Kandsberger, M., Matthes, T., Fuchs, H., Graeve, T., 1999. Reconstructed human skin (AST-2,000) as a tool for pharmaco-toxicology. ATLA 27, 302).