Echocardiographic risk stratification of fetuses with sacrococcygeal teratoma and twin-reversed arterial perfusion.
To evaluate pre-intervention echocardiographic parameters of cardiac function in fetuses who survive without hydrops as compared to fetuses who develop hydrops or perinatal death in the setting of sacrococcygeal teratoma (SCT) and twin-reversed arterial perfusion sequence (TRAP). Clinical, echocardiographic and sonographic data of fetuses with SCT or TRAP during 1999-2009 were reviewed retrospectively. Measurements of cardiothoracic ratio (CTR), cardiac dimension Z-scores, combined ventricular output (CVO), valvular regurgitation, and cardiovascular profile scores (CVPS) were obtained. In total, 19 fetuses (11 SCT, 8 TRAP) met the inclusion criteria and 26 detailed fetal echocardiographic studies were reviewed. Outcome was poor in 7 pregnancies (group A) and good in 12 (group B). Group A had worse CVPS (8.5 vs. 10, p < 0.01) and higher CTR (0.37 vs. 0.30, p = 0.04). At least one of the following was present in each group A fetus: CTR >0.5, CVO >550 ml/min/kg, tricuspid or mitral regurgitation, or mitral valve Z-score >2. No group B fetus had any of these abnormalities. No fetus in either group had abnormal venous Doppler waveforms at presentation. Fetal echocardiography can identify abnormalities of cardiac size and systolic, but not diastolic, function in all fetuses who subsequently died or developed hydrops.


Effect of freezing and thawing rates on denaturation of proteins in aqueous solutions.
The freeze denaturation of model proteins, LDH, ADH, and catalase, was investigated in absence of cryoprotectants using a microcryostage under well-controlled freezing and thawing rates. Most of the experimental data were obtained from a study using a dilute solution with an enzyme concentration of 0.025 g/l. The dependence of activity recovery of proteins on the freezing and thawing rates showed a reciprocal and independent effect, that is, slow freezing (at a freezing rate about 1 degrees C/min) and fast thawing (at a thawing rate >10 degrees C/min) produced higher activity recovery, whereas fast freezing with slow thawing resulted in more severe damage to proteins. With minimizing the freezing concentration and pH change of buffer solution by using a potassium phosphate buffer, this phenomenon could be ascribed to surface-induced denaturation during freezing and thawing process. Upon the fast freezing (e.g., when the freezing rate >20 degrees C/min), small ice crystals and a relatively large surface area of ice-liquid interface are formed, which increases the exposure of protein molecules to the ice-liquid interface and hence increases the damage to the proteins. During thawing, additional damage to proteins is caused by recrystallization process. Recrystallization exerts additional interfacial tension or shear on the entrapped proteins and hence causes additional damage to the latter. When buffer solutes participated during freezing, the activity recovery of proteins after freezing and thawing decreased due to the change of buffer solution pH during freezing. However, the patterns of the dependence on freezing and thawing rates of activity recovery did not change except for that at extreme low freezing rates (<0.5 degrees C/min). The results exhibited that the freezing damage of protein in aqueous solutions could be reduced by changing the buffer type and composition and by optimizing the freezing-thawing protocol.


Safety and efficacy of CT-P13 in Japanese patients with rheumatoid arthritis in an extension phase or after switching from infliximab.
This study aimed to evaluate the safety of CT-P13 in patients with rheumatoid arthritis (RA) during long-term treatment or after switching from innovator infliximab (IFX). Patients who completed 54 weeks of treatment in a phase I/II study (PI/II) received CT-P13 at an initial dose of 3 mg/kg at Week 62, with dose increases permitted up to 10 mg/kg. The primary endpoint was adverse event (AE) incidence. Thirty-four of 38 patients in the maintenance group and 29 of 33 in the switch group reported at least one AE. Safety profiles in both groups were similar to those in PI/II. Eleven of 28 patients who were positive for anti-drug antibodies (ADA) at Week 62 discontinued the study before Week 110. Forty-one of 43 ADA-negative patients remained negative, and 10 of 28 ADA-positive patients became negative during the study. The mean DAS28 (ESR) at Week 134 was 3.166 in the maintenance group and 3.955 in the switch group. CT-P13 was well tolerated in patients who maintained the treatment after 54 weeks and in patients who switched to CT-P13 after 54 weeks of IFX treatment. The study also demonstrated a stable clinical efficacy of CT-P13 in RA patients.


Application of the Scale for the Assessment of Feeding Interaction (SVIA) to Children With Autism Spectrum Disorder.
Background and Objectives: Feeding problems occur more frequently among children with Autism spectrum disorder (ASD). The aim of this study was to analyse eating difficulties of ASD children through the direct observation of the caregiver-child co-regulation system. Methods: We compared 60 ASD children with a control group of 50 typically developing Italian children on the Scale for the Assessment of Feeding Interaction (SVIA). The Brief Autism Mealtime Behaviour Inventory (BAMBI) was used to define the presence of an eating disorder. Results: The ASD group showed higher scores on all dimensions of the SVIA compared to the control group. The SVIA and the BAMBI showed significant correlations. In a second step, the ASD sample was divided into two subgroups, children with and without feeding difficulties. The comparison between the ASD subgroups with the control group on the SVIA scales showed significant differences on all dimensions. Finally, significant differences emerged between the two ASD subgroups in three SVIA dimensions. Conclusion: These data suggest the importance of direct observation of feeding in the assessment of children with ASD. The SVIA seems to be able to point out some feeding difficulties in these subjects and to discriminate ASD with and without an eating disorder. Critical aspects of the application of SVIA to autistic children are discussed.


Lessons from the bare lymphocyte syndrome: molecular mechanisms regulating MHC class II expression.
Major histocompatibility complex class II (MHCII) molecules drive the development, activation and homeostasis of CD4* T-helper cells. They play a central role in key processes of the adaptive immune system, such as the generation of T-cell-mediated immune responses, the regulation of antibody production and the development and maintenance of tol erance. It is thus not surprising that the absence of MHCII expression results in a severe primary immunodeficiency disease (the bare lymphocyte syndrome (BLS)). The genetic defects responsible for BLS do not lie within the MHCII locus, but in genes encoding transcription factors required for MHCII expression. A great deal of our current knowledge about the mechanisms regulating expression of MHCII genes has been derived from the study of BLS. Four different MHCII regulatory genes have been identified. These genes encode RFXANK, RFXS, RFXAP and CIITA. The first three are subunits of RFX, a ubiquitously expressed factor that binds to the promoters of all MHCII genes. RFX binds co-operatively with other factors to form a highly stable multiprotein complex referred to as the MHCII enhanceosome. This enhanceosome serves as a landing pad for the co-activator CIITA, which is recruited via protein-protein interactions CIITA is the master control factor for MHCII expression. The highly regulated expression pattern of CIITA ultimately dictates the cell type specificity, induction and level of MHCII expression.


Safety of intravenous iron in hemodialysis patients.
Among end-stage renal disease patients maintained by hemodialysis, anemia has been managed primarily through erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron. Following concerns about the cardiovascular (CV) safety of ESAs and changes in the reimbursement policies in Medicare's ESRD program, the use of IV iron has increased. IV iron supplementation promotes hemoglobin production and reduces ESA requirements, yet there exists relatively little evidence on the long-term safety of iron supplementation in hemodialysis patients. Labile iron can induce oxidative stress and is also essential in bacterial growth, leading to concerns about IV iron use and risk of CV events and infections in hemodialysis patients. Existing randomized controlled trials provide little evidence about safety due to insufficient power and short follow-up; recent observational studies have been inconsistent, but some have associated iron exposure with increased risk of infections and CV events. Given the widespread use and potential safety concerns related to IV iron, well-designed large prospective studies are needed to assess to identify optimal strategies for iron administration that maximize its benefits while avoiding potential risks.


Food marketing to children through toys: response of restaurants to the first U.S. toy ordinance.
On August 9, 2010, Santa Clara County CA became the first U.S. jurisdiction to implement an ordinance that prohibits the distribution of toys and other incentives to children in conjunction with meals, foods, or beverages that do not meet minimal nutritional criteria. Restaurants had many different options for complying with this ordinance, such as introducing more healthful menu options, reformulating current menu items, or changing marketing or toy distribution practices. To assess how ordinance-affected restaurants changed their child menus, marketing, and toy distribution practices relative to non-affected restaurants. Children's menu items and child-directed marketing and toy distribution practices were examined before and at two time points after ordinance implementation (from July through November 2010) at ordinance-affected fast-food restaurants compared with demographically matched unaffected same-chain restaurants using the Children's Menu Assessment tool. Affected restaurants showed a 2.8- to 3.4-fold improvement in Children's Menu Assessment scores from pre- to post-ordinance with minimal changes at unaffected restaurants. Response to the ordinance varied by restaurant. Improvements were seen in on-site nutritional guidance; promotion of healthy meals, beverages, and side items; and toy marketing and distribution activities. The ordinance appears to have positively influenced marketing of healthful menu items and toys as well as toy distribution practices at ordinance-affected restaurants, but did not affect the number of healthful food items offered.


[Placental morphology in pregnancy complicated with iron-deficiency anemia].
Iron-deficiency anemia in pregnant females negatively affects pregnancy, delivery, neonatal infants. Anemia-caused placental changes found during pregnancy are characterized by imbalance between the processes of adaptation and dysadaptation in response to the developed hypoxia in the pregnant-placenta-fetus system and placental tissue ischemia. When iron-deficiency anemia had developed before pregnancy, placental morphological changes show the signs of chronic placental insufficiency. The developed therapy for anaemia with Ferro-Folgama corrects all the elements of the pregnant-placenta-fetus system.


Correlation of Vascularization and Inflammation with Severity of Oral Leukoplakia.
Changes in submucosal vascularization and inflammation, determined by immunohistochemistry staining, were shown to be correlated with the development of dysplasia and invasiveness of epithelial cells in premalignant and malignant lesions. This study evaluated changes in sections routinely stained with Hematoxylin and Eosin (H&E) in order to investigate vascular density and intensity of inflammatory cells infiltration during the progression of oral leukoplakia with mild dysplasia to Squamous Cell Carcinoma (SCC).The aim of the research was to determine whether changes in sub-mucosal vascularity and inflammatory infiltration of leukoplakia in routine H&E-stained sections could contribute to the assessment of severity of the lesion. In this cross-sectional, comparative and descriptive study, vascular density and inflammation intensity of 125 available samples of H&E-stained sections, consisting of 35 cases of mild and moderate dysplasia, 38 severe dysplasia and carcinoma in situ, and 52 SCC, were investigated. To analyze the data, chi-square test, Mann-Whitney test, Kruskal-Wallis test, Tukey's post hoc test, and cumulative ordinal logistic regression were conducted. There was a significantly higher vascular density in cases with severe dysplasia, in situ carcinoma, and SCC compared to those with mild to moderate dysplasia (P<0.0001). However, the difference in vascularity was not statically significant between severe dysplasia, carcinoma in situ, and SCC (P=0.78). Intensity of inflammatory cells infiltration in the underlying connective tissue was significantly different among the three groups (P<0.0001), and the highest intensity of inflammatory cells infiltration was seen in the SCC group. Increased submucosal vascularization and inflammatory cells infiltration can contribute further to predicting more aggressive epithelial dysplasia.


Lower eyelid and cheek reconstruction by a temporally extended V-Y cheek flap.
Reconstruction of medium and large cheek defects involving the whole length of the lower eyelid and suborbital region is a challenging procedure. Several cervicofacial flaps are well described in the literature; most of them require extensive undermining and retroauricular and cervical incisions. A case is presented of an 84-year-old woman, a smoker, with a recurrent squamous cell carcinoma on the left suborbital region. Excision resulted in a 5.5 × 3.5-cm defect of the suborbital region and the whole length of the lower eyelid. Considering that the patient was an elderly smoker, a simple technique was sought. Reconstruction was achieved by a wide temporally extended V-Y cheek flap. The extension was used to reconstruct the eyelid and the main flap to cover the cheek defect. The procedure necessitated minimal undermining and was done under local anesthesia with an excellent functional and cosmetic result.


Modification of Surface and Subsurface Properties of AA1050 Alloy by Shot Peening.
AA1050 Al alloy samples were shot-peened using stainless-steel shots at shot peening (SP) pressures of 0.1 and 0.5 MPa and surface cover rates of 100% and 1000% using a custom-designed SP system. The hardness of shot-peened samples was around twice that of unpeened samples. Hardness increased with peening pressure, whereas the higher cover rate did not lead to hardness improvement. Micro-crack formation and embedment of shots occurred by SP, while average surface roughness increased up to 9 µm at the higher peening pressure and cover rate, indicating surface deterioration. The areal coverage of the embedded shots ranged from 1% to 5% depending on the peening parameters, and the number and the mean size of the embedded shots increased at the higher SP pressure and cover rate. As evidenced and discussed through the surface and cross-sectional SEM images, the main deformation mechanisms during SP were schematically described as crater formation, folding, micro-crack formation, and material removal. Overall, shot-peened samples demonstrated improved mechanical properties, whereas sample surface integrity only deteriorated notably during SP at the higher pressure, suggesting that selecting optimal peening parameters is key to the safe use of SP. The implemented methodology can be used to modify similar soft alloys within confined compromises in surface features.


Electrical Tunability of Domain Wall Conductivity in LiNbO3 Thin Films.
Domain wall nanoelectronics is a rapidly evolving field, which explores the diverse electronic properties of the ferroelectric domain walls for application in low-dimensional electronic systems. One of the most prominent features of the ferroelectric domain walls is their electrical conductivity. Here, using a combination of scanning probe and scanning transmission electron microscopy, the mechanism of the tunable conducting behavior of the domain walls in the sub-micrometer thick films of the technologically important ferroelectric LiNbO3 is explored. It is found that the electric bias generates stable domains with strongly inclined domain boundaries with the inclination angle reaching 20° with respect to the polar axis. The head-to-head domain boundaries exhibit high conductance, which can be modulated by application of the sub-coercive voltage. Electron microscopy visualization of the electrically written domains and piezoresponse force microscopy imaging of the very same domains reveals that the gradual and reversible transition between the conducting and insulating states of the domain walls results from the electrically induced wall bending near the sample surface. The observed modulation of the wall conductance is corroborated by the phase-field modeling. The results open a possibility for exploiting the conducting domain walls as the electrically controllable functional elements in the multilevel logic nanoelectronics devices.


Oilseed rape (Brassica napus) resistance to growth of Leptosphaeria maculans in leaves of young plants contributes to quantitative resistance in stems of adult plants.
Key message: One QTL for resistance against Leptosphaeria maculans growth in leaves of young plants in controlled environments overlapped with one QTL detected in adult plants in field experiments. The fungal pathogen Leptosphaeria maculans initially infects leaves of oilseed rape (Brassica napus) in autumn in Europe and then grows systemically from leaf lesions along the leaf petiole to the stem, where it causes damaging phoma stem canker (blackleg) in summer before harvest. Due to the difficulties of investigating resistance to L. maculans growth in leaves and petioles under field conditions, identification of quantitative resistance typically relies on end of season stem canker assessment on adult plants. To investigate whether quantitative resistance can be detected in young plants, we first selected nine representative DH (doubled haploid) lines from an oilseed rape DY ('Darmor-bzh' × 'Yudal') mapping population segregating for quantitative resistance against L. maculans for controlled environment experiment (CE). We observed a significant correlation between distance grown by L. maculans along the leaf petiole towards the stem (r = 0.91) in CE experiments and the severity of phoma stem canker in field experiments. To further investigate quantitative trait loci (QTL) related to resistance against growth of L. maculans in leaves of young plants in CE experiments, we selected 190 DH lines and compared the QTL detected in CE experiments with QTL related to stem canker severity in stems of adult plants in field experiments. Five QTL for resistance to L. maculans growth along the leaf petiole were detected; collectively they explained 35% of the variance. Two of these were also detected in leaf lesion area assessments and each explained 10-12% of the variance. One QTL on A02 co-localized with a QTL detected in stems of adult plants in field experiments. This suggests that resistance to the growth of L. maculans from leaves along the petioles towards the stems contributes to the quantitative resistance assessed in stems of adult plants in field experiments at the end of the growing season.


Pre-stimulus bioelectrical activity in light-adapted ERG under blue versus white background.
To compare the baseline signal between two conditions used to generate the photopic negative response (PhNR) of the full-field electroretinogram (ERG): red flash on a blue background (RoB) and white flash on a white background (LA3). The secondary purpose is to identify how the level of pre-stimulus signal affects obtaining an unambiguous PhNR component. A retrospective chart review was conducted on four cohorts of patients undergoing routine ERG testing. In each group, LA3 was recorded the same way while RoB was generated differently using various luminances of red and blue light. The background bioelectrical activity 30 ms before the flash was extracted, and the root mean square (RMS) of the signal was calculated and compared between RoB and LA3 using Wilcoxon test. Pre-stimulus noise was significantly higher under RoB stimulation versus LA3 in all four conditions for both right and left eyes (ratio RoB/LA3 RMS 1.70 and 1.57 respectively, p < 0.033). There was also no significant difference between the RMS of either LA3 or RoB across protocols, indicating that the baseline noise across cohorts were comparable. Additionally, pre-stimulus noise was higher in signals where PhNR was not clearly identifiable as an ERG component versus signals with the presence of unambiguous PhNR component under RoB in all four groups for both eyes (p < 0.05), whereas the difference under LA3 was less pronounced. Our study suggests that LA3 produces less background bioelectrical activity, likely due to decreased facial muscle activity. As it seems that the pre-stimulus signal level affects PhNR recordability, LA3 may also produce a better-quality signal compared to RoB. Therefore, until conditions for a comparable bioelectrical activity under RoB are established, we believe that LA3 should be considered at least as a supplementary method to evaluate retinal ganglion cell function by ERG.


Change in subjective social status following HIV diagnosis and associated effects on mental and physical health among HIV-positive gay men in Australia.
This study investigates the impact of HIV diagnosis on subjective social status and if changes are linked to health outcomes. Two measures of subjective social status, socio-economic and standing in the community were examined in 342 Australian HIV-positive gay men in 2014. Participants recalled ratings at diagnosis were compared with current ratings. Self-reported mental (psychological distress, self-esteem, positive mental health and satisfaction with life) and physical health (self-rated health, CD4 count, viral load). Half of the participants reported improvements in subjective socio-economic status (59%) or standing in the community (52%) since diagnosis, yet one quarter reported socio-economic status (25%) or standing in the community had decreased (23%). Increases in either measure of subjective social status were linked to higher self-esteem, positive mental health, satisfaction with life and better self-rated health. Decreases in subjective social status, however, were strongly linked to poorer outcomes on all mental health measures. Decreases in standing in the community were also associated with poorer physical self-rated health. Most participants reported their subjective social status were the same or better since diagnosis. Changes in subjective social status following diagnosis were strongly linked to mental health outcomes. Those who reported a decrease in subjective social status were particularly vulnerable to mental health problems.


Enumeration, isolation, and species identification of mycoplasmas in saliva sampled from the normal and pathological human oral cavity and antibody response to an oral mycoplasma (Mycoplasma salivarium).
Saliva samples collected from 393 subjects with and without oral diseases were examined for concentrations of mycoplasmas and Mycoplasma species. Mycoplasmas were isolated from 383 (97%) of the 393 subjects. Viable counts ranged from zero to 7.6 X 10(7) CFU/ml (median, 6.9 X 10(4)) and were significantly (P less than 0.01) higher in diseased subjects, except for those with arthrosis temporomandibularis, than in controls. Of 1,400 isolates, 897 (64%), 442 (30%), and 8 (1%) were identified as Mycoplasma salivarium, M. orale, and M. hominis, respectively, and the remaining 73 isolates (5%) were unidentifiable. More than two-thirds of the isolates from diseased subjects versus only half from controls were identified as M. salivarium. In diseased subjects other than those with ostitis (especially those with arthrosis temporomandibularis), the incidence of M. salivarium was higher than that of M. orale, whereas the former occurred about as frequently as the latter in the controls. Antibodies to M. salivarium were also measured in sera from some subjects by the metabolism inhibition test. Sera with metabolism inhibition titers of 16 or greater were rated positive. There was no significant difference in the prevalence of antibodies between diseased subjects (60%) and controls (40%), but the mean titers (97 to 220) of all positive sera from diseased subjects were two to four times those for sera from controls. In addition, a fourfold or greater rise or fall of antibody titers to the organism was shown in paired sera from some subjects. On the basis of these results, M. salivarium was strongly suggested to participate etiologically in some cases of oral infection.


The dynamics of scarlet fever epidemics in England and Wales in the 19th century.
There was a marked rise in scarlet fever mortality in England and Wales in the mid-nineteenth century and spectral analysis of the registration details, 1847-80, shows that the interepidemic interval was 5-6 years, but after 1880 the endemic level fell and the fatal epidemics disappeared. The dynamics of the scarlet fever epidemics can be represented by a linearized mathematical model and because the system is lightly damped, it could be driven by an oscillation in susceptibility. Epidemics were significantly correlated with dry conditions in spring/summer (P < 0.001), suggesting that these produced a low amplitude oscillation in susceptibility which drove the system. Epidemics also correlated (P < 0.001) with an oscillation in wheat prices but at a lag of 3 years, suggesting that malnutrition during pregnancy caused increased susceptibility in the subsequent children which interacted synergistically with seasonal dry conditions. Scarlet fever mortality was sharply reduced after 1880 in parallel with falling wheat prices suggesting that the remarkable period of high scarlet fever mortality (1840-80) was dependent on poor nutritive levels during that time.


Cecilie Greig memorial lecture 2002. Myocardial protection: an expanding or contracting discipline?
For the past thirty years cardiac surgeons have had a unique opportunity to study the consequences of myocardial ischemia and reperfusion. With the advent of an ability to intervene in acute myocardial syndromes, cardiologists have vigorously joined that effort as have fundamental scientists. Exogenous myocardial protective strategies have emerged as have novel strategies that take advantage of endogenous mechanisms of myocardial protection. As a consequence of improved myocardial protection, operative mortality and morbidity, in particular the low output syndrome, have diminished. However, despite important increases in the knowledge base referable to myocardial ischemia and reperfusion, major advances in myocardial protection have slowed in the past several years. This article explores potential untapped options for augmenting myocardial protection and focuses on the potential adverse interactions between cardiopulmonary bypass and myocardial protection as a prime target for future investigations leading to improved myocardial management during heart operations.


Genomic and Metabolic Characterization of Plant Growth-Promoting Rhizobacteria Isolated from Nodules of Clovers Grown in Non-Farmed Soil.
The rhizosphere microbiota, which includes plant growth-promoting rhizobacteria (PGPR), is essential for nutrient acquisition, protection against pathogens, and abiotic stress tolerance in plants. However, agricultural practices affect the composition and functions of microbiota, reducing their beneficial effects on plant growth and health. Among PGPR, rhizobia form mutually beneficial symbiosis with legumes. In this study, we characterized 16 clover nodule isolates from non-farmed soil to explore their plant growth-promoting (PGP) potential, hypothesizing that these bacteria may possess unique, unaltered PGP traits, compared to those affected by common agricultural practices. Biolog profiling revealed their versatile metabolic capabilities, enabling them to utilize a wide range of carbon and energy sources. All isolates were effective phosphate solubilizers, and individual strains exhibited 1-aminocyclopropane-1-carboxylate deaminase and metal ion chelation activities. Metabolically active strains showed improved performance in symbiotic interactions with plants. Comparative genomics revealed that the genomes of five nodule isolates contained a significantly enriched fraction of unique genes associated with quorum sensing and aromatic compound degradation. As the potential of PGPR in agriculture grows, we emphasize the importance of the molecular and metabolic characterization of PGP traits as a fundamental step towards their subsequent application in the field as an alternative to chemical fertilizers and supplements.


Effect of carrot intake on cholesterol metabolism and on antioxidant status in cholesterol-fed rat.
Vegetables are major dietary sources of fibers and antioxidants such as carotenoids, polyphenols and vitamin C which contribute to explain their protective effects against cardiovascular diseases. We investigated in the rat the effects of a 3-week supplementation of the diet with carrot (15% dry matter) on lipid metabolism and antioxidant status. A significant decrease of cholesterol level in liver (-44%; P= 0.0007) was observed together with a reduction of the level of liver triglycerides (-40%; P= 0.0005). Fecal total steroids excretion increased by 30% upon feeding the carrot diet as compared to the control. The secretion of bile acids was maintained, whereas the cholesterol apparent absorption was reduced in rats fed carrot diet. Carrot consumption also improved the antioxidant status. It significantly decreased the urinary excretion of thiobarbituric acid reactive substances (TBARS), reduced the TBARS levels in heart, increased the vitamin E plasmatic level and tended to increase the ferric reducing ability of plasma (FRAP) as compared to the controls. The carrot diet provided carotenoid antioxidants: 5.1 mg beta-carotene, 1.6 mg alpha-carotene and 0.25mg lutein per 100 g diet. No carotenoids were found in plasma whereas the three carotenoids were detected in the plasma of the rats fed the carrot diet at 125, 41, 43 nmol/L respective concentrations. beta-Carotene was also detected in liver and heart. Carrot consumption modifies cholesterol absorption and bile acids excretion and increases antioxidant status and these effects could be interesting for cardiovascular protection.


Neuropilin2 regulates the guidance of post-crossing spinal commissural axons in a subtype-specific manner.
Spinal commissural axons represent a model system for deciphering the molecular logic that regulates the guidance of midline-crossing axons in the developing central nervous system (CNS). Whether the same or specific sets of guidance signals control the navigation of molecularly distinct subtypes of these axons remains an open and largely unexplored question. Although it is well established that post-crossing commissural axons alter their responsiveness to midline-associated guidance cues, our understanding of the repulsive mechanisms that drive the post-crossing segments of these axons away from the midline and whether the underlying guidance systems operate in a commissural axon subtype-specific manner, remains fragmentary at best. Here, we utilize axonally targeted transgenic reporter mice to visualize genetically distinct dorsal interneuron (dI)1 and dI4 commissural axons and show that the repulsive class 3 semaphorin (Sema3) guidance receptor Neuropilin 2 (Npn2), is selectively expressed on the dI1 population and is required for the guidance of post-crossing dI1, but not dI4, axons. Consistent with these observations, the midline-associated Npn2 ligands, Sema3F and Sema3B, promote the collapse of dI1, but not dI4, axon-associated growth cones in vitro. We also identify, for the first time, a discrete GABAergic population of ventral commissural neurons/axons in the embryonic mouse spinal cord that expresses Npn2, and show that Npn2 is required for the proper guidance of their post-crossing axons. Together, our findings indicate that Npn2 is selectively expressed in distinct populations of commissural neurons in both the dorsal and ventral spinal cord, and suggest that Sema3-Npn2 signaling regulates the guidance of post-crossing commissural axons in a population-specific manner.


Problems in the treatment of peptic ulcer.
Although apparently very successful, the treatment of peptic ulcers remains unsatisfactory because therapy is still symptomatic. Consequently, debate continues about the proper objectives of therapy. Some clinicians consider it best to treat the patients' subjective symptoms, while others focus on the "objective" sign of mucosal ulceration. The latter seems more appropriate, since mucosal ulceration may result in lethal complications. It is therefore necessary not only to heal ulcers, but to keep them healed. The choice of optimal treatment of present ulcer relapse is determined not only by therapeutic success, but also by the frequency and severity of the iatrogenic diseases produced by the treatment. At the present time, maintenance treatment of proven efficacy is provided only by H2 receptor antagonists and is superior to operative therapy because it is accompanied by a lesser incidence of death and adverse reactions.


Comparison of efficacy and safety between PD-1 inhibitors and PD-L1 inhibitors plus platinum-etoposide as first-line treatment for extensive-stage small-cell lung cancer: a multicenter, real-world analysis.
Immunotherapy in combination with platinum-etoposide (EP) chemotherapy has been approved as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, real-world (RW) data regarding the use of immune checkpoint inhibitors (ICIs) in ES-SCLC are lacking. We aimed to assess the differences between programmed death protein 1 (PD-1) inhibitors and programmed death ligand 1 (PD-L1) inhibitors, both in conjunction with EP chemotherapy, as first-line treatment for ES SCLC. We conducted a real-world, multicenter, retrospective cohort, controlled study to compare the prognosis, efficacy, and safety of PD-1 and PD-L1 inhibitors in ES-SCLC patients when used along with chemotherapy. Each patient received up to six cycles of etoposide, carboplatin, or cisplatin combined with ICI drugs, including PD-1 and PD-L1 inhibitors. The primary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS). The secondary endpoints were the investigator-assessed objective response rate (ORR) and disease control rate (DCR) according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Between January 2017 and December 2021, 194 patients with ES-SCLC from three clinical centers in a PLA general hospital were included in our study, including 93 patients in the PD-1 group and 101 patients in the PD-L1 group. At the time of data cutoff, progression-free survival in the PD-1 group (median PFS, 6.8 months; 95% CI, 5.3-8.1) was similar to that in the PD-L1 group (median PFS, 6.4 months; 95% CI, 5.5-7.5); the stratified hazard ratio for PFS was 1.12 (95% CI, 0.83-1.53; P = 0.452). The median OS was similar in the PD-1 and PD-L1 groups (15.8 m vs. 17.7 m, P = 0.566); the hazard ratio was 0.90 (95% CI, 0.62-1.30, P = 0.566). The two groups had comparable investigator-assessed confirmed objective response rates (ORR) (76.3% vs. 76.2%). Adverse effect (AE)-related discontinuation occurred in 4 (4.3%) patients in the PD-1 group and 2 (2.0%) patients in the PD-L1 group. Deaths due to AEs of any cause occurred in 2 (2.2%) patients in the PD-1 inhibitor group and 1 (1.0%) patient in the PD-L1 inhibitor group. Our research revealed that there were no significant differences in efficacy or prognosis between PD-1 inhibitor + EP chemotherapy and PD-L1 inhibitor + EP chemotherapy. The two groups seemed to have comparable safety profiles, but the number of discontinuation or death events was too small to draw a firm conclusion.


Evaluation of sodium hypochlorite as a denture cleanser: a clinical study.
To evaluate the effect of sodium hypochlorite (NaOCl) on biofilms, colour stability (ΔE) and surface roughness (Ra) of complete dentures and patient acceptability. Denture cleansers should be able to reduce the accumulation of biofilms without affecting the acrylic resin properties. Patient satisfaction is important to maintaining their daily use. Fifteen participants were instructed to keep their dentures immersed daily in a 0.5% NaOCl solution for 3 min over 90 days. Swabs were taken from dentures and inoculated on CHROMagar and blood agar. The number of colony-forming units (cfu) was counted after a 48-h incubation period. ΔE was assessed using the CIE L*a*b* system. Ra was measured using a profilometer. Patient acceptability was checked based on their degree of satisfaction. Cell counts, ΔE and Ra were analysed using anova, Friedman's and Kruskal-Wallis tests, respectively (α = 0.05). A significant reduction in the total number of microorganisms (p = 0.001) and Candida spp. was noticed. No significant differences were found for ΔE (p = 0.68) and for Ra (p = 0.47). The level of the patient satisfaction increased throughout the follow-up period. The 0.5% NaOCl solution was effective in reducing microorganisms without significant changes in colour or roughness of denture resin. The participants reported satisfaction with the cleaning results.


Metabolism of tryptophan by Pseudomonas aureofaciens and its relationship to pyrrolnitrin biosynthesis.
Studies on the metabolism of tryptophan in Pseudomonas aureofaciens ATCC 15926 revealed different metabolic routes for the L- and D-isomer besides the biosynthetic pathway for pyrrolnitrin synthesis. L-Tryptophan catabolism follows the aromatic route via anthranilic acid. Tryptophan 2,3-dioxygenase were induced by L-tryptophan. Kynureninase and anthranilate 1,2-dioxygenase were induced by L-tryptophan, L-kynurenine and anthranilic acid. Anthranilate 1,2-dioxygenase was absent from a mutant strain of P. aureofaciens ATCC 19526 which produced about 30-fold increased amounts of pyrrolnitrin. The Km values of tryptophan 2,3-dioxygenase and kynureninase did not differ substantially between the two strains. Kynurenine 3-monooxygenase, 3-hydroxyanthranilate 3,4-dioxygenase, tryptophanase and indolyl-3-alkane alpha-hydroxylase activities were not detected. D- and L-tryptophan were converted to indole-3-acetic acid. This additional catabolic pathway was well as tryptophan racemase activity was constitutive and present in both strains.


Comparison of Dual-antiplatelet Therapy to Mono-antiplatelet Therapy After Transcatheter Aortic Valve Implantation: Systematic Review and Meta-analysis.
Post-transcatheter aortic valve implantation (TAVI) dual-antiplatelet therapy (DAPT) with acetylsalicylic acid and clopidogrel is common practice to reduce ischemic complications despite the lack of clinical trial evidence demonstrating superiority over mono-antiplatelet therapy (MAPT). A systematic search was conducted to retrieve studies that investigated DAPT vs MAPT in patients who have undergone TAVI. Outcomes of interest included both ischemic and bleeding events at 30 days and 6 months. Four studies met inclusion criteria-2 randomized control trials and 2 observational studies, with 286 patients in the DAPT group and 354 patients in the MAPT group. For the primary outcome of a combined end point of 30-day major stroke, spontaneous myocardial infarction (MI), all-cause mortality, and combined lethal and major bleeding, there was a trend toward increased harm in the DAPT group (29%) compared with the MAPT group (16%), with an odds ratio (OR) of 1.88 (P = 0.05). Secondary outcome analysis revealed that there was no significant difference between groups regarding 30-day stroke, 30-day spontaneous MI, and 30-day all-cause mortality. Patients who received DAPT had a significant increase in combined 30-day lethal and major bleeding (OR, 2.62; P = 0.008). Further analysis revealed that increased adverse events were driven by observational studies, with no difference in outcomes between groups in randomized controlled trials. DAPT in patients who have undergone TAVI demonstrated no benefit over MAPT in reduction of ischemic events, with a trend toward increased harm because of bleeding. Future considerations should be given to MAPT with clopidogrel alone, as well as the omission of clopidogrel loading before the procedure.


Early formative objective structured clinical examinations for students in the pre-clinical years of medical education: A non-randomized controlled prospective pilot study.
The value of formative objective structured clinical examinations (OSCEs) during the pre-clinical years of medical education remains unclear. We aimed to assess the effectiveness of a formative OSCE program for medical students in their pre-clinical years on subsequent performance in summative OSCE. We conducted a non-randomized controlled prospective pilot study that included all medical students from the last year of the pre-clinical cycle of the Université Paris-Cité Medical School, France, in 2021. The intervention group received the formative OSCE program, which consisted of four OSCE sessions, followed by debriefing and feedback, whereas the control group received the standard teaching program. The main objective of this formative OSCE program was to develop skills in taking a structured medical history and communication. All participants took a final summative OSCE. The primary endpoint was the summative OSCE mark in each group. A questionnaire was also administered to the intervention-group students to collect their feedback. A qualitative analysis, using a convenience sample, was conducted by gathering data pertaining to the process through on-site participative observation of the formative OSCE program. Twenty students were included in the intervention group; 776 in the control group. We observed a significant improvement with each successive formative OSCE session in communication skills and in taking a structured medical history (p<0.0001 for both skills). Students from the intervention group performed better in a summative OSCE that assessed the structuring of a medical history (median mark 16/20, IQR [15; 17] versus 14/20, [13; 16], respectively, p = 0.012). Adjusted analyses gave similar results. The students from the intervention group reported a feeling of improved competence and a reduced level of stress at the time of the evaluation, supported by the qualitative data showing the benefits of the formative sessions. Our findings suggest that an early formative OSCE program is suitable for the pre-clinical years of medical education and is associated with improved student performance in domains targeted by the program.


A home-based protocol of electrical muscle stimulation for quadriceps muscle strength in older adults with osteoarthritis of the knee.
To determine whether home-based neuromuscular electrical stimulation (NMES) applied to the quadriceps femoris (QF) muscle increases strength, physical activity, and physical performance in older adults with knee osteoarthritis (OA). Thirty-four adults (> 60 yrs) with radiographically confirmed symptomatic knee OA were randomized to NMES plus education or education only (EDU). The primary outcome was isometric QF peak torque (PTIso), with secondary outcomes of daily step counts, total activity vector magnitude, 100-foot walk-turn-walk, timed stair climb, chair rise, and pain. The NMES group used a portable electrical muscle stimulator 3 days a week for unilateral QF training with incremental increases in the intensity of isometric contraction to 30-40% of maximum over 12 weeks. Both groups received the 12-week Arthritis Self-Management course and were followed an additional 12 weeks. The stimulated knee-extensor showed a 9.1% increase in 120 degrees PTIso compared to a 7% loss in the EDU group (time x group interaction for 120 degrees PTIso; p = 0.04). The chair rise time decreased by 11% in the NMES group, whereas the EDU group saw a 7% reduction (p = 0.01, time; p = 0.9, group). Similarly, both groups improved their walk time by approximately 7% (p = 0.02, time; p = 0.61 group). Severity of pain reported following intervention did not differ between groups. In older adults with knee OA, a home-based NMES protocol appears to be a promising therapy for increasing QF strength in adults with knee OA without exacerbating painful symptoms.


ATP-sensitive K+ transport in adrenal chromaffin granules.
In the present study the influx of 86Rb+, a K+ analogue, was studied in mitochondria, microsomes and chromaffin granules prepared from adrenal gland medulla. The most active electrogenic 86Rb+ transport was found in the membrane fraction identified as chromaffin granules by marker enzyme estimation. The transport was found to be sensitive to ATP, ATP gamma S, ADP and to the triazine dyes, but not to AMP and cAMP. The inhibition induced by ATP was observed in the absence of externally added Mg2+, suggesting that a free nucleotide, rather than the ATP-Mg complex, was required for inhibition. Furthermore, the 86Rb+ influx was found to be inhibited by Mg2+ alone, but not by Ca2+ and antidiabetic sulfonylureas. The 86Rb+ influx was not stimulated by potassium channel openers. In conclusion, our results indicate that an electrogenic, ATP-sensitive potassium transport system operates in the chromaffin granule membrane.


Wave number-spiral acoustic tweezers for dynamic and reconfigurable manipulation of particles and cells.
Acoustic tweezers have recently raised great interest across many fields including biology, chemistry, engineering, and medicine, as they can perform contactless, label-free, biocompatible, and precise manipulation of particles and cells. Here, we present wave number-spiral acoustic tweezers, which are capable of dynamically reshaping surface acoustic wave (SAW) wavefields to various pressure distributions to facilitate dynamic and programmable particle/cell manipulation. SAWs propagating in multiple directions can be simultaneously and independently controlled by simply modulating the multitone excitation signals. This allows for dynamic reshaping of SAW wavefields to desired distributions, thus achieving programmable particle/cell manipulation. We experimentally demonstrated the multiple functions of wave number-spiral acoustic tweezers, among which are multiconfiguration patterning; parallel merging; pattern translation, transformation, and rotation; and dynamic translation of single microparticles along complex paths. This wave number-spiral design has the potential to revolutionize future acoustic tweezers development and advance many applications, including microscale assembly, bioprinting, and cell-cell interaction research.


Shaggy photoreceptors with subfoveal fluid associated with a distant choroidal melanoma.
Purpose. To describe the enhanced depth imaging optical coherence tomography (EDI-OCT) findings in a patient with an extra macula choroidal melanoma before and after treatment. Methods. Observational case report. Results. A 45 year-old Caucasian male patient was referred to retina clinic for management of choroidal melanoma. Examination revealed a nasal choroidal melanoma while EDI-OCT illustrated subfoveal fluid pocket with elongated shaggy photoreceptors distant and separate from the tumor. The patient was treated with plaque brachytherapy and intravitreal bevacizumab. One week after plaque removal, there was a dramatic reduction in the shaggy photoreceptors. Conclusion. Choroidal melanomas have effects that are not localized to the area of the tumor. This loculated pocket of subretinal fluid and coinciding changes to photoreceptor morphology may be related to global changes in choroidal function or release of tumor related cytokines.


Efficacy of human resource development program for young industry personnel who will be involved in future medical device development.
Training next-generation personnel from small/medium enterprises (SMEs) is an urgent issue in promoting medical device research and development (R&D). Since 2014 we have engaged in governmentally funded human resource development program for medical/non-medical SMEs, and have assessed its effectiveness by analyzing self-evaluation of achievement level (SEAL) data obtained before and after the training course. Human resource development experts interviewed 34 key opinion leaders with deep knowledge of medical device R&D from industry, government, and academia. The skills required for R&D personnel were written down, and a set of skills was created by making a greatest common measure in the list of common elements among them. Using that skill sets, skill evaluations were conducted on trainees at "Osaka University Training Course," twice before participation and after completion of the entire program using SEAL assessment. There were 97 men and 25 women, with one-third in the'30 s. Among them, 61 participants (50%) were from R&D divisions, and 32 (26%) were from business/sales divisions. 94 (77%) were from medical SMEs, and 28 (23%) were from non-medical SMEs (new entry). After completing the training course, significant growth was observed in every item of both Soft and Hard skill sets. Especially in new entry SME members, a striking improvement was observed in practical medical knowledge to enhance communication with medical doctors (p < 0.0001). Our training course, though 7-day-short in total, showed that both Soft and Hard skills could be improved in young medical/non-medical SME members. Further assessment is needed to establish the necessary skill sets for our future partners from industries, to foster the creation of innovative medical devices through med-tech collaboration.


Graded-index plastic optical fiber composed of methyl methacrylate and vinyl phenylacetate copolymers.
Graded-index plastic optical fiber whose transmission attenuation is 143 dB/km at 651-nm wavelength was fabricated by heat-drawing the corresponding GI preform rod. This rod is prepared by the interfacial-gel copolymerization technique of methyl methacrylate (MMA) and vinyl phenylacetate (VPAc). The total scattering loss of the GI preform rod is ~60 dB/km at 633 nm. The graded-index profiles of the optical fibers are almost the same as those of the corresponding preforms with cladding sheaths. The index distributions of their core regions are quadratic against the distance from the center axis. The numerical aperture estimated from the index difference is ~0.20.


Identification of Small-Molecule Positive Modulators of Calcitonin-like Receptor-Based Receptors.
Class B G protein-coupled receptors are highly therapeutically relevant but challenges remain in identifying suitable small-molecule drugs. The calcitonin-like receptor (CLR) in particular is linked to conditions such as migraine, cardiovascular disease, and inflammatory bowel disease. The CLR cannot act as a cell-surface receptor alone but rather must couple to one of three receptor activity-modifying proteins (RAMPs), forming heterodimeric receptors for the peptides adrenomedullin and calcitonin gene-related peptide. These peptides have extended binding sites across their receptors. This is one reason why there are few small-molecule ligands that can modulate these receptors. Here we describe small molecules that are able to positively modulate the signaling of the CLR with all three RAMPs but are not active at the related calcitonin receptor. These compounds were selected from a β-arrestin recruitment screen, coupled with rounds of medicinal chemistry to improve their activity. Translational potential is shown as the compounds can positively modulate cAMP signaling in a vascular cell line model. Binding experiments do not support an extracellular domain binding site; however, molecular modeling reveals potential allosteric binding sites in multiple receptor regions. These are the first small-molecule positive modulators described for the CLR:RAMP complexes.


Magnitude and distribution of acute, self-reported gastrointestinal illness in a Canadian community.
To estimate the magnitude and distribution of self-reported, acute gastrointestinal illness in a Canadian-based population, we conducted a retrospective, cross-sectional telephone survey of approximately 3500 randomly selected residents of the city of Hamilton (Ontario, Canada) from February 2001 to February 2002. The observed monthly prevalence was 10% (95 % CI 9.94-10.14) and the incidence rate was 1.3 (95 % CI 1.1-1.4) episodes per person-year; this is within the range of estimates from other developed countries. The prevalence was higher in females and in those aged < 10 years and 20-24 years. Overall, prevalence peaked in April and October, but a different temporal distribution was observed for those aged < 10 years. Although these data were derived from one community, they demonstrate that the epidemiology of acute gastrointestinal illness in a Canadian-based population is similar to that reported for other developed countries.


Computer-aided diagnostic scheme for the detection of lung nodules on chest radiographs: localized search method based on anatomical classification.
We developed an advanced computer-aided diagnostic (CAD) scheme for the detection of various types of lung nodules on chest radiographs intended for implementation in clinical situations. We used 924 digitized chest images (992 noncalcified nodules) which had a 500 x 500 matrix size with a 1024 gray scale. The images were divided randomly into two sets which were used for training and testing of the computerized scheme. In this scheme, the lung field was first segmented by use of a ribcage detection technique, and then a large search area (448 x 448 matrix size) within the chest image was automatically determined by taking into account the locations of a midline and a top edge of the segmented ribcage. In order to detect lung nodule candidates based on a localized search method, we divided the entire search area into 7 x 7 regions of interest (ROIs: 64 x 64 matrix size). In the next step, each ROI was classified anatomically into apical, peripheral, hilar, and diaphragm/heart regions by use of its image features. Identification of lung nodule candidates and extraction of image features were applied for each localized region (128 x 128 matrix size), each having its central part (64 x 64 matrix size) located at a position corresponding to a ROI that was classified anatomically in the previous step. Initial candidates were identified by use of the nodule-enhanced image obtained with the average radial-gradient filtering technique, in which the filter size was varied adaptively depending on the location and the anatomical classification of the ROI. We extracted 57 image features from the original and nodule-enhanced images based on geometric, gray-level, background structure, and edge-gradient features. In addition, 14 image features were obtained from the corresponding locations in the contralateral subtraction image. A total of 71 image features were employed for three sequential artificial neural networks (ANNs) in order to reduce the number of false-positive candidates. All parameters for ANNs, i.e., the number of iterations, slope of sigmoid functions, learning rate, and threshold values for removing the false positives, were determined automatically by use of a bootstrap technique with training cases. We employed four different combinations of training and test image data sets which was selected randomly from the 924 cases. By use of our localized search method based on anatomical classification, the average sensitivity was increased to 92.5% with 59.3 false positives per image at the level of initial detection for four different sets of test cases, whereas our previous technique achieved an 82.8% of sensitivity with 56.8 false positives per image. The computer performance in the final step obtained from four different data sets indicated that the average sensitivity in detecting lung nodules was 70.1% with 5.0 false positives per image for testing cases and 70.4% sensitivity with 4.2 false positives per image for training cases. The advanced CAD scheme involving the localized search method with anatomical classification provided improved detection of pulmonary nodules on chest radiographs for 924 lung nodule cases.


Human Wharton's jelly stem cells inhibit endometriosis through apoptosis induction.
Endometriosis is a relatively benign disease characterized by endometrial tumors and uterus stroma. Apoptosis suppression is one of the most important pathological processes of endometriosis. Recently, several studies reported that human Wharton's jelly stem cells (hWJSCs) can inhibit growth and proliferation of various cancer cells through induction of apoptosis. Therefore, the aim of the present study was to investigate the effects of hWJSCs conditioned medium (hWJSC-CM) and cell-free lysate (hWJSC-CL) on endometriosis cells in vitro. In the present study, effects of different concentrations of hWJSC-CM and hWJSC-CL on viability and proliferation, morphological alterations, colony formation, migration, invasion, and apoptosis of endometriosis cells were evaluated. Our results showed that hWJSC-CM and hWJSC-CL decrease viability and proliferation, colony formation, migration, and invasion, as well as increase morphological alterations and apoptosis of endometriosis cells, in a concentration- and time-dependent manner. Decreased migration and invasion of treated endometriosis cells with hWJSC-CM and hWJSC-CL may be due to decrease of MMP-2 and MMP-9 gene expression. Moreover, induction of apoptosis in treated endometriosis cells can be due to regulation of apoptosis-related genes expression, including BAX, BCL-2, SMAC, and SURVIVIN. The results of the present study suggest that hWJSC-CM and hWJSC-CL can inhibit endometriosis cells at a mild-to-moderate level through various physiological mechanisms. However, further studies on animal models are necessary to achieve more accurate results.


Analysis of Operating Room Personnel Perspectives to Enhance Medical Student Readiness for Surgery.
We sought to better define surgical etiquette and elucidate operating room (OR) personnel expectations of medical students to determine areas for medical education improvement. A questionnaire probing medical student performance regarding elements of OR etiquette was developed. Questions were designed to obtain structured feedback through Likert scales and open-ended responses. Descriptive and thematic analysis was conducted on Likert scale and free-text responses, respectively. Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ. Tertiary academic center. A questionnaire was distributed to nurses, surgical and anesthesia faculty and residents. The survey was distributed via email amongst various hospitals, predominantly our home institution. We received 126 complete responses. About half of respondents (46.3%) self-identified as female. Most respondents were part of the surgical team (74.7%), with most (57.8%) from attending physicians. A majority of respondents agreed that medical students responded well to feedback. Roughly half of respondents agreed that medical students understand their role, maintain sterility, and assist in delivery of effective patient care. More than half of respondents did not believe that medical students understand traffic patterns. The majority of respondents indicated that medical students are not appropriately prepared with basic surgical skills prior to entering the OR. Two-thirds of respondents did not feel that medical students contribute towards maintaining safety in the OR. We identified 4 themes from free text responses: students should assume an active role in the OR, utilize situational awareness, understand sterility and OR workflow, and have knowledge of basic operative technique and anatomy. Medical students are not meeting OR personnel expectations and may benefit from early educational interventions to optimize the OR as a learning environment.


Predictors of death and mode of death during long-term follow-up among patients with unconfirmed acute myocardial infarction.
Among patients hospitalized with a suspected acute coronary syndrome, a minority will eventually develop a confirmed acute myocardial infarction (AMI). In the remaining patients, coronary artery disease is the underlying cause in a large proportion. The aim of the study was to determine risk indicators for death and the mode of death during 5 years of follow-up among patients hospitalized and surviving hospitalization, who presented with initially suspected AMI, but in whom infarction was not confirmed. Consecutive patients who fulfilled the above criteria and were discharged from Sahlgrenska Hospital alive during 1986 and 1987 were followed for 5 years. In all, 1,227 patients, of whom 396 (34%) died during the 5 years of follow-up, fulfilled the criteria. The following factors appeared to be independent risk indicators for death: age (p < 0.001); male gender (p < 0.001); a history of either current smoking (p < 0.001), congestive heart failure (p < 0.01), or myocardial infarction (p < 0.05); congestive heart failure during hospital stay (p < 0.01); and prescription of digitalis at discharge (p < 0.05). Among patients who died, only 63% were judged to have been dying a cardiac death. Among patients hospitalized with suspected acute coronary syndrome and discharged from hospital without a confirmed AMI, one third had died during the 5 years of follow-up. Risk indicators for death were related to age, male gender, history of current smoking, congestive heart failure or previous AMI, congestive heart failure in hospital, and digitalis medication at discharge.


Health Care Utilization and Costs of Patients With Prostate Cancer in China Based on National Health Insurance Database From 2015 to 2017.
In terms of medical costs, prostate cancer is on the increase as one of the most costly cancers, posing a tremendous economic burden, but evidence on the health care utilization and medical expenditure of prostate cancer has been absent in China. This study aimed to analyze health care utilization and direct medical costs of patients with prostate cancer in China. Health care service data with a national representative sample of basic medical insurance beneficiaries between 2015 and 2017 were obtained from the China Health Insurance Association database. We conducted descriptive and statistical analyses of health care utilization, annual direct medical costs, and composition based on cancer-related medical records. Health care utilization was measured by the number of hospital visits and the length of stay. A total of 3,936 patients with prostate cancer and 24,686 cancer-related visits between 2015 and 2017 were identified in the database. The number of annual outpatient and inpatient visits per patient differed significantly from 2015 to 2017. There was no obvious change in length of stay and annual direct medical costs from 2015 to 2017. The number of annual visits per patient (outpatient: 3.0 vs. 4.0, P < 0.01; inpatient: 1.5 vs. 2.0, P < 0.001) and the annual medical direct costs per patient (US$2,300.1 vs. US$3,543.3, P < 0.001) of patients covered by the Urban Rural Resident Basic Medical Insurance (URRBMI) were both lower than those of patients covered by the Urban Employee Basic Medical Insurance (UEBMI), and the median out-of-pocket expense of URRBMI was higher than that of UEBMI (US$926.6 vs. US$594.0, P < 0.001). The annual direct medical costs of patients with prostate cancer in Western regions were significantly lower than those of patients in Eastern and Central regions (East: US$4011.9; Central: US$3458.6; West: US$2115.5) (P < 0.001). There was an imbalanced distribution of health care utilization among regions in China. The direct medical costs of Chinese patients with prostate cancer remained stable, but the gap in health care utilization and medical costs between two different insurance schemes and among regions still needed to be further addressed.


Anti-osteoporosis effects of mammalian lignans and their precursors from flaxseed and safflower seed using zebrafish model.
Secoisolariciresinol diglucoside (SDG) and tracheloside (TCL) are the main lignan components of flaxseed cake and safflower seed cake, which are by-products of oil extraction. Both SDG and TCL are metabolized into mammalian lignan enterolactone (EL) with the involvement of intestinal bacteria. In this research, we evaluated the anti-osteoporosis effects of SDG and the in vivo metabolites EL and enterodiol (ED) prepared in our previous work, as well as the newly isolated chemical constituents from safflower seed, including TCL, the lactone ring opening product of TCL (OTCL) and two alkaloids on the alloxan-induced zebrafish model. All the compounds showed significant anti-osteoporosis effects at 80 µM, with p < 0.05 for EL and p < 0.001 for other compounds compared with the model. SDG and TCL showed the most significant and concentration-dependent effects, with p < 0.001 compared with model at 20 µM. The alkaloids, N-coumaroylserotonin glucoside and N-feruloylserotonin glucoside, also showed anti-osteoporosis at 20 µM with p < 0.01, whereas EL, ED, and OTCL showed no significant effects. Quantitative real-time polymerase chain reaction revealed that SDG and TCL upregulated the expression of osteogenic genes Runx2, SP7, OPG, Col1a1a, Alp, ON, OPN, and OCN in alloxan-treated zebrafish. The in vivo metabolite of lignans, EL, showed significant anti-inflammatory effect (p < 0.01) at 20 µM, which might also help to combat osteoporosis and other complications caused by excessive immune response in the body. The results provided scientific data for using the oil extraction by-products as sources of anti-osteoporosis compounds. PRACTICAL APPLICATION: This study found that lignans in flaxseed cake and safflower seed cake exhibited anti-osteoporosis effects by upregulating the expression of osteogenic genes, making the oil extraction by-products sources of anti-osteoporosis compounds.


Recyclability of Photoinduced Cross-Linked EPM Rubber with Anthracene-Grafted Groups: Problems and Their Solutions.
In this paper, we present the formation of reversible covalently cross-linked networks in ethylene propylene rubber with grafted anthracene groups (EPM-g-AN) based on the principles of photoinduced anthracene dimerization. First, an industrial-grade EPM rubber grafted with maleic anhydride functional groups (EPM-g-MA) was modified with 9-anthracenemethanol. By irradiating EPM-g-AN with UV light (365 nm), the anthracene moieties dimerize via [4 + 4]cycloaddition, forming a covalent network. The network cleavage proceeds at high temperatures (>170 °C), even if with considerable (chemical) degradation. Furthermore, one of the degradation routes has been identified by 1H NMR to occur via the ester bond cleavage releasing 9-anthracenemethanol. Nevertheless, the reversibility of cross-linking has been achieved by performing the reverse reaction in decalin. The UV-vis spectroscopy clearly shows that the de-cross-linking process in these conditions is due to the anthracene dimer cleavage. Although the recovery in mechanical properties upon recycling is yet to be optimized, the disclosed results pave the way toward the use of anthracene chemistry in thermally reversible networks with possible industrial perspective applications.


Effector function of human tumor-specific CD8 T cells in melanoma lesions: a state of local functional tolerance.
Although tumor-specific CD8 T-cell responses often develop in cancer patients, they rarely result in tumor eradication. We aimed at studying directly the functional efficacy of tumor-specific CD8 T cells at the site of immune attack. Tumor lesions in lymphoid and nonlymphoid tissues (metastatic lymph nodes and soft tissue/visceral metastases, respectively) were collected from stage III/IV melanoma patients and investigated for the presence and function of CD8 T cells specific for the tumor differentiation antigen Melan-A/MART-1. Comparative analysis was conducted with peripheral blood T cells. We provide evidence that in vivo-priming selects, within the available naive Melan-A/MART-1-specific CD8 T-cell repertoire, cells with high T-cell receptor avidity that can efficiently kill melanoma cells in vitro. In vivo, primed Melan-A/MART-1-specific CD8 T cells accumulate at high frequency in both lymphoid and nonlymphoid tumor lesions. Unexpectedly, however, whereas primed Melan-A/MART-1-specific CD8 T cells that circulate in the blood display robust inflammatory and cytotoxic functions, those that reside in tumor lesions (particularly in metastatic lymph nodes) are functionally tolerant. We show that both the lymph node and the tumor environments blunt T-cell effector functions and offer a rationale for the failure of tumor-specific responses to effectively counter tumor progression.


Singlet oxygen photosensitization by EGFP and its chromophore HBDI.
The photosensitization of reactive oxygen species and, in particular, singlet oxygen by proteins from the green fluorescent protein (GFP) family influences important processes such as photobleaching and genetically targeted chromophore-assisted light inactivation. In this article, we report an investigation of singlet oxygen photoproduction by GFPs using time-resolved detection of the NIR phosphorescence of singlet oxygen at 1275 nm. We have detected singlet oxygen generated by enhanced (E)GFP, and measured a lifetime of 4 micros in deuterated solution. By comparison with the model compound of the EGFP fluorophore 4-hydroxybenzylidene-1,2-dimethylimidazoline (HBDI), our results confirm that the beta-can of EGFP provides shielding of the fluorophore and reduces the production of this reactive oxygen species. In addition, our results yield new information about the triplet state of these proteins. The quantum yield for singlet oxygen photosensitization by the model chromophore HBDI is 0.004.


[Automobile transport medicine--experience and prospects].
Results of complex long-standing research served as a basis to present social and medical reasons for official acknowledgement of automobile transport medicine in Russia and ways to improve traffic safety.


MicroRNA-202 inhibits cell proliferation, migration and invasion of glioma by directly targeting metadherin.
Glioma is the most common and aggressive type of primary malignant brain tumour. Increasing evidence has revealed that microRNAs play important roles in multiple biological processes related to glioma occurrence, development, diagnosis, treatment and prognosis. MicroRNA-202 (miR-202) has been studied in several types of human cancer, whereas the biological roles of miR-202 in glioma remain unknown. The present study, aimed to investigate the expression, clinical significance and biological roles of miR-202 in glioma, as well as its underlying molecular mechanism. We found that miR-202 was significantly downregulated in glioma tissues and cell lines. Low miR-202 expression was associated with Karnofsky performance status (KPS) score and World Health Organization (WHO) grade of glioma patients. Functional assays revealed that ectopic expression of miR-202 inhibited cell proliferation, migration and invasion of glioma. In addition, metadherin (MTDH) was identified as a direct target gene of miR-202 in glioma through bioinformatic analysis, luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Furthermore, MTDH expression was upregulated and negatively correlated with miR-202 expression in clinical glioma tissues. MTDH knockdown had similar roles to miR-202 overexpression in glioma cells. Rescue experiments revealed that upregulation of MTDH reversed the suppression of glioma cell growth and metastasis by miR-202. Moreover, miR-202 impaired the PI3K/Akt and Wnt/β-catenin pathways. These results highlight the tumour-suppressive effect of miR-202 in glioma, thereby suggesting that miR-202 may be a potential therapeutic target for the treatment of patients with this malignancy.


Towards a unified Latin American Natural Products Database: LANaPD.
Around the world, the number of compound databases of natural products in the public domain is rising. This is in line with the increasing synergistic combination of natural product research and chemoinformatics. Toward this global endeavor, countries in Latin America are assembling, curating, and analyzing the contents and diversity of natural products available in their geographical regions. In this manuscript we collect and analyze the efforts that countries in Latin America have made so far to build natural product databases. We further encourage the scientific community in particular in Latin America, to continue their efforts to building quality natural product databases and, whenever possible, to make them publicly accessible. It is proposed that all compound collections could be assembled into a unified resource called LANaPD: Latin American Natural Products Database. Opportunities and challenges to build, distribute and maintain LANaPD are also discussed.


Critical Issues for the Translation of Cardioprotection.
The translation from numerous successful animal experiments on cardioprotection beyond that by reperfusion to clinical practice has to date been disappointing. Animal experiments often use reductionist approaches and are mostly performed in young and healthy animals which lack the risk factors, comorbidities, and comedications which are characteristics of patients suffering an acute myocardial infarction or undergoing cardiovascular surgery. Conceptually, it is still unclear by how much the time window for successful reperfusion is extended by preconditioning, and how long the duration of ischemia can be so that adjunct cardioprotection by postconditioning at reperfusion still protects. Experimental studies addressing long-term effects of adjunct cardioprotection beyond infarct size reduction, that is, on repair, remodeling, and mortality, are lacking. Technically, reproducibility and robustness of experimental studies are often limited. Grave faults in design and conduct of clinical trials have also substantially contributed to the failure of translation of cardioprotection to clinical practice. Cardiovascular surgery with ischemic cardioplegic arrest is only a surrogate of acute myocardial infarction and confounded by the choice of anesthesia, hypothermia, cardioplegia, and traumatic myocardial injury. Trials in patients with acute myocardial infarction have been performed on agents/interventions with no or inconsistent previous animal data and in patients who had either some reperfusion already at admission or were reperfused too late to expect any myocardial salvage. Of greatest concern is the lack of adequate phase II dosing and timing studies when rushing from promising proof-of-concept trials with surrogate end points such as infarct size to larger clinical outcome trials. Future trials must focus on interventions/agents with robust preclinical evidence, have solid phase II dosing and timing data, and recruit patients who have truly a chance to benefit from adjunct cardioprotection.


Effects of different hydraulic models on predicting longitudinal profiles of reactive pollutants in activated sludge reactors.
This paper presents effects of dispersion on predicting longitudinal ammonia concentration profiles in activated sludge bioreactor located at "Wschod" WWTP in Gdansk. The aim of this study was to use the one-dimensional advection-dispersion Equation (ADE) to simulate the flow conditions (based on the inert tracer concentrations in selected points) and longitudinal profile of reactive pollutant (based on the ammonia concentration profiles in selected points). The simulation results were compared with the predictions obtained using a traditional "tanks-in-series" (TIS) approach, commonly used in designing biological reactors. The use of dispersion coefficient calculated from an empirical formula resulted in substantial differences in the tracer concentration distributions in two sampling points in the bioreactor. Simulations using the one-dimensional ADE and TIS model, with the nitrification rate incorporated as the source term, revealed that the hydraulic model plays a minor role compared to the biochemical transformations in predicting the longitudinal ammonia concentration profiles.


Monitoring community responses to the SARS epidemic in Hong Kong: from day 10 to day 62.
To report the evolution in perceptions and behaviours of the general public in response to the severe acute respiratory syndrome (SARS) epidemic in Hong Kong. Ten similar and sequential telephone surveys were conducted during outbreak of SARS, which are classified as belonging to the first and second phases of the epidemic. Hong Kong, China. 1397 Hong Kong residents between 18 and 60 years of age. Perceptions and behaviours to SARS and its prevention. Most of the respondents believed that SARS could be transmitted via direct body contact and droplets. About half of respondents believed that SARS was curable, which increased in the initial phase and decreased in the second phase. Perceived chance of infection was low (9%) but fear of infection in public places was high (48%). Perceived efficacy of hygiene measures (wearing a mask: 82%, hand washing: 93%, and home disinfection: 75%) remained high in both phases and the perceived efficacy of avoiding crowded place, and using public transportation, etc, increased initially and decreased in the second phase. In parallel, use of the three hygiene measures increased significantly in the first phase and remained high for wearing a mask and washing hands in the second phase. Percentages of people avoiding crowded place and public transportation significantly increased initially and decreased in the second phase. SARS related perceptions and behaviours evolved rapidly during the epidemic and Hong Kong residents quickly adopted appropriate SARS prevention measures. Timely dissemination of information seems effective in public health crises management.


Restorative management of severely ankylosed primary molars.
Severe dentoalveolar ankylosis is an etiological factor for malocclusion. When infraocclusion occurs early, it progresses with time, leading to severe consequences in young children because of compensatory supra-eruption of the antagonist tooth and mesialization of adjacent teeth. Early diagnosis allows for interception of the problem and may prevent orthodontic treatment. The purpose of this manuscript is to report two cases of infraocclusion of primary mandibular second molars that were diagnosed early and were treated with composite resin crowns. The use of indirect composite restorations for ankylosed teeth is a good option for primary teeth with a moderate/ severe degree of ankylosis.


Development of a grassland integrity index based on breeding bird assemblages.
We utilized landscape and breeding bird assemblage data from three Breeding Bird Survey (BBS) routes sampled from 1965-1995 to develop and test a grassland integrity index (GII) in a mixed-grass prairie area of Oklahoma. The overall study region is extensively fragmented from long-term agricultural activity, and native habitat remnants have been degraded by recent encroachment of woody vegetation, namely eastern red cedar (Juniperus virginiana L.). The 50 individual bird survey points along the BBS routes, known as stops, were used as sample sites. Our process first focused on developing a grassland disturbance index (GDI) as a measure of cumulative landscape disturbances for these sites. The GDI was based on five key landscape variables identified in an earlier species-level study of long-term avian community dynamics: total tree, shrub, and herbaceous vegetation cover indices, overall mean landscape patch size, and grassland patch core size. The GII was then developed based on breeding bird assemblage data. Assemblages were based on commonly used response guilds reflective of five avian life history parameters: foraging mode/location, nesting location, habitat specificity, migratory pattern, and dietary guild. We tested the response of 78 candidate assemblage metrics to the GDI, and eliminated those with no or poor response or with high correlations (redundant), resulting in 13 metrics for use in the final index. Individual metric scores were scaled to fall between 0 and 10, and the cumulative index to range from 0 to 100. Although broader application and refinement are possible, the avian-based GII has an advantage over labor-intensive, habitat-based monitoring in that the GII is derived from readily available long-term BBS data. Therefore, the GII shows promise as an inexpensive tool that could easily be applied over other areas to monitor changes in regional grassland conditions.


The analysis of decomposition methods for support vector machines.
The support vector machine (SVM) is a new and promising technique for pattern recognition. It requires the solution of a large dense quadratic programming problem. Traditional optimization methods cannot be directly applied due to memory restrictions. Up to now, very few methods can handle the memory problem and an important one is the "decomposition method." However, there is no convergence proof so far. In this paper, we connect this method to projected gradient methods and provide theoretical proofs for a version of decomposition methods. An extension to bound-constrained formulation of SVM is also provided.We then show that this convergence proof is valid for general decomposition methods if their working set selection meets a simple requirement.


Lack of prion infectivity in fixed heart tissue from patients with Creutzfeldt-Jakob disease or amyloid heart disease.
In most forms of prion disease, infectivity is present primarily in the central nervous system or immune system organs such as spleen and lymph node. However, a transgenic mouse model of prion disease has demonstrated that prion infectivity can also be present as amyloid deposits in heart tissue. Deposition of infectious prions as amyloid in human heart tissue would be a significant public health concern. Although abnormal disease-associated prion protein (PrP(Sc)) has not been detected in heart tissue from several amyloid heart disease patients, it has been observed in the heart tissue of a patient with sporadic Creutzfeldt-Jakob Disease (sCJD), the most common form of human prion disease. In order to determine whether prion infectivity can be found in heart tissue, we have inoculated formaldehyde fixed brain and heart tissue from two sCJD patients, as well as prion protein positive fixed heart tissue from two amyloid heart disease patients, into transgenic mice overexpressing the human prion protein. Although the sCJD brain samples led to clinical or subclinical prion infection and deposition of PrP(Sc) in the brain, none of the inoculated heart samples resulted in disease or the accumulation of PrP(Sc). Thus, our results suggest that prion infectivity is not likely present in cardiac tissue from sCJD or amyloid heart disease patients.


[Thymus structure after polyoxydonium administration].
This investigation was aimed at the evaluation of nature and sequence of thymus structural changes in 25 mice following their treatment with immunomodulating drug, polyoxydonium. Morphometric study has established that the structural reorganization of thymus in mice that was induced by therapeutic doses of polyoxydonium (120 mg per animal once a day for 3 days) had a cyclic course. 4 days after the start of an experiment small increase in the cortical volume was detected. Simultaneously, the surface area, occupied in the sections of the organ by medulla, was found to be significantly decreased in experimental animals. By the end of the first week, there was a decline in a surface area, occupied by the thymic cortex, while afterwards this parameter started to increase, reaching its maximum at 14 days after polyoxydonium treatment. By the end of the experiments (30 days) practically no differences were detected in the areas that were occupied in thymus sections by the cortex and medulla, between the treated animals and those of control groups.


Food allergy and adult migraine: double-blind and mediator confirmation of an allergic etiology.
Foods as a cause for migraine attacks were evaluated in 43 adults with recurrent migraine. Skin testing, elimination diets, double-blind challenges, and measurements of plasma histamine were performed. Thirteen subjects experienced 66% or greater reduction in headache frequency during a diet trial. Six subjects became headache free. Eleven of 16 skin test-positive patients responded to diet manipulation, while only two of 27 skin test-negatives did (P less than .005). Seven subjects agreed to double-blind challenges. In five of seven, at least one food provoked migraine. Placebo challenges did not provoke migraine. In three subjects, plasma histamine rose during migraine provoking challenges. The relationship between food ingestion and migraine is based in part on allergic mechanism. Tests for IgE-specific food allergy appear helpful in selecting patients likely to benefit from diet therapy.


Thalassaemia is a tropical disease.
Genes for thalassaemias, sickle cell disorders and Glucose-6- phosphate dehydrogenase (G6PD) deficiency are known to be associated with prevalent malaria infection. The prevalence in the heterozygote state for sickle cell anaemia (SCA), G6PD and alpha thalassaemia is between 25-30% in Nigerians but the prevalence for the beta thalassaemia trait (BTT) is low. Under-diagnosis of BTT may arise from the similarity in its clinical manifestation to that of SCA which is of high prevalence in Nigeria and secondly because the hypochromia and microcytosis associated with it may be misdiagnosed as iron deficiency anaemia. There is therefore the need to review this disorder in the light of the wide use of automation in processing a full blood count which will include red cell indices, a good screening method for the thalassaemias. This expectedly will aid easy and early diagnosis of the disorder.


Seeing objects in motion.
This paper reports estimates of the conjoint spatiotemporal tuning functions of the neural mechanisms of the human vision system which detect image motion. The functions were derived from measurements of the minimum contrast necessary to detect the direction of drift of a sinusoidal grating, in the presence of phase-reversed masking gratings of various spatial and temporal frequencies. A mask of similar spatial and temporal frequencies to the test grating reduces sensitivity considerably, whereas one differing greatly in spatial or temporal frequency has little or no effect. The results show that for test gratings drifting at 8 Hz, the tuning function is bandpass in both space and time, peaked at the temporal and spatial frequency (SF) of the test (SFs were 0.1, 1 or 5 c deg-1; c represents cycles throughout). For a grating of 5 c deg-1 drifting at 0.3 Hz, the function is bandpass in space but lowpass in time. Fourier transform of the frequency results yields a function in space-time which we term the 'spatiotemporal receptive field'. For movement detectors (bandpass in space and time) the fields comprise alternating ridges of opposing polarity, elongated in space-time along the preferred velocity axis of the detector. We suggest that this organization explains how detectors analyse form and motion concurrently and accounts, at least in part, for a variety of perceptual phenomena, including summation, reduction of motion smear, metacontrast, stroboscopic motion and spatiotemporal interpolation.


Coping with food allergy: exploring the role of the online support group.
The aims of this study were to explore the reasons for participation in an online support group for individuals affected by food allergy, its perceived advantages and disadvantages as well as impact on the relationship with healthcare providers. A total of 32 members of the Food Allergy Survivors Together (F.A.S.T.) online support group completed an online structured interview and responses were analysed using thematic analysis. Group members identified a range of benefits, including accessibility, receipt of social support as well as guidance on coping strategies. The only disadvantages identified revolved around the accuracy and trust in information exchanged via the group bulletin board. Group participation did appear to impact on relationships with healthcare providers with several members reporting greater empowerment through decision-making, though in contrast some experienced difficulties in discussing their online support experiences and information obtained with their healthcare providers.


Histone-like protein in the Archaebacterium Sulfolobus acidocaldarius.
The Archaebacterium Thermoplasma acidophilum contains a basic chromosomal protein remarkably similar to the histones of eukaryotes. Therefore, it was of interest to examine a different Archaebacterium for similar proteins. We chose to examine Sulfolobus acidocaldarius because it is thermophilic, like T. acidophilum, but nevertheless the two organisms are not particularly closely related. Two major chromosomal proteins were found in S. acidocaldarius. The smaller of these was soluble in 0.2 M H2SO4 and had a molecular weight of 14500. The larger was acid-insoluble and had a molecular weight of about 36000. Together, the proteins protected about 5% of the DNA against nuclease digestion and stabilized about 50% against thermal denaturation. Overall, the properties of these proteins were intermediate between those of the Escherichia coli protein HU and T. acidophilum protein HTa.


Manx shearwater (Puffinus puffinus) rafting behaviour revealed by GPS tracking and behavioural observations.
Before visiting or leaving their remote island colonies, seabirds often engage in a behaviour termed 'rafting', where birds sit, often in groups, on the water close to the colony. Despite rafting being a widespread behaviour across many seabird taxa, the functional significance of rafting remains unknown. Here we combine global positioning system (GPS) tracks, observational and wind condition data to investigate correlates of rafting behaviour in Manx shearwaters (Puffinus puffinus) at a large colony on Skomer Island, Wales. We test (1) the influence of wind direction on rafting location and (2) whether raft size changes with respect to wind speed. Our approach further allows us to describe day-night trends in (3) raft distance from shore through time; (4) the number of birds present in the nearshore waters through time; and (5) spatial patterns of Manx shearwater rafts in marine waters adjacent to the breeding colony. We find no evidence that wind direction, for our study period, influences Manx shearwater rafting location, yet raft size marginally increases on windier days. We further find rafting birds closer to the shore at night than during the day. Thus, before sunset, birds form a "halo" around Skomer Island, but this halo disappears during the night as more individuals return from foraging trips and raft nearer the colony on Skomer Island. The halo pattern reforms before sunrise as rafts move away from land and birds leave for foraging. Our results suggest that wind conditions may not be as ecologically significant for rafting locations as previously suspected, but rafting behaviour may be especially important for avoiding predators and cleaning feathers.


Machine Learning of Designed Translational Control Allows Predictive Pathway Optimization in Escherichia coli.
The field of synthetic biology aims to make the design of biological systems predictable, shrinking the huge design space to practical numbers for testing. When designing microbial cell factories, most optimization efforts have focused on enzyme and strain selection/engineering, pathway regulation, and process development. In silico tools for the predictive design of bacterial ribosome binding sites (RBSs) and RBS libraries now allow translational tuning of biochemical pathways; however, methods for predicting optimal RBS combinations in multigene pathways are desirable. Here we present the implementation of machine learning algorithms to model the RBS sequence-phenotype relationship from representative subsets of large combinatorial RBS libraries allowing the accurate prediction of optimal high-producers. Applied to a recombinant monoterpenoid production pathway in Escherichia coli, our approach was able to boost production titers by over 60% when screening under 3% of a library. To facilitate library screening, a multiwell plate fermentation procedure was developed, allowing increased screening throughput with sufficient resolution to discriminate between high and low producers. High producers from one library did not translate during scale-up, but the reduced screening requirements allowed rapid rescreening at the larger scale. This methodology is potentially compatible with any biochemical pathway and provides a powerful tool toward predictive design of bacterial production chassis.


Evaluation of complication rates of pediatric spinal procedures in which a polyethylene glycol sealant was used.
Cerebrospinal fluid leakage following durotomy in spinal surgery can lead to significant patient morbidity and mortality, including meningitis and even death. Usage of a polyethylene glycol (PEG) sealant in combination with standard closure techniques has been shown to be effective in preventing CSF leaks in animal models and adult patients, but the results of its use have not been reported in the pediatric population. A retrospective analysis was performed of pediatric neurosurgery patients (0-18 years of age) treated at The Johns Hopkins Hospital from 2003 to 2010. There were 93 spinal surgery patients identified in whom PEG was applied. The incidence of CSF leakage, meningitis, and neurological injury was recorded. There were 54 males and 39 females in this study with an average age of 8.7 years. Of the identified patients, 16.1%, 28%, and 55.9% underwent surgery in the cervical region, thoracic region, and lumbar region, respectively. At 90-day follow-up, 5 patients (5.4%) had a CSF leak, 4 patients (4.3%) required a reoperation, and 1 patient (1.1%) had meningitis within this time period. No deaths or associated neurological deficits were observed. The use of a PEG sealant to augment dural closure in pediatric spine surgery appears to be a safe adjunct to standard dural closure in pediatric spine patients.


Human Trafficking: ACOG COMMITTEE OPINION, Number 787.
Human trafficking, or modern-day slavery, is a global problem with broad reach that is often underrecognized in the United States. Victims of trafficking have been found in a wide range of legal and illegal business settings, and this frequently hidden population is most often exploited in the commercial sex industry, agriculture, factories, hotels, restaurants, as domestic workers, and by marriage brokers and some adoption firms. Human trafficking disproportionately affects underserved women and children, with more than 70% of trafficking cases involving women and girls and more than 90% of victims trafficked into the sex industry. Obstetrician-gynecologists and other women's health care providers are well-situated to identify and assist victims of human trafficking. Many trafficked individuals present to outpatient obstetrics and gynecology clinics, community health centers, family planning clinics, urgent care centers, and adolescent medicine clinics, and one half of all female victims of sex trafficking have visited the emergency department while involved in sex trafficking. Obstetrician-gynecologists and other women's health care providers should be aware of human trafficking, recognize signs of human trafficking, and be prepared to assist patients who are victims or who have been victims of human trafficking. This Committee Opinion has been updated to include screening questions and indicators to identify victims of human trafficking, additional information regarding reporting obligations for suspected human trafficking, and additional resources for survivors of human trafficking.


Plasmonic labeling of subcellular compartments in cancer cells: multiplexing with fine-tuned gold and silver nanoshells.
Fine-tuned gold and silver nanoshells were produced via an entirely reformulated synthesis. The new method yielded ultramonodisperse samples, with polydispersity indexes (PI) as low as 0.02 and narrow extinction bands suited for multiplex analysis. A library of nanoshell samples with localized surface plasmon resonances (LSPR) spanning across the visible range was synthesized. Hyperspectral analysis revealed that the average scattering spectrum of 100 nanoshells matched closely to the spectrum of a single nanoshell, indicating an unprecedented low level of nanoparticle-to-nanoparticle variation for this type of system. A cell labeling experiment, targeting different subcellular compartments in MCF-7 human breast cancer cells, demonstrated that these monodisperse nanoparticles can be used as a multiplex platform for single cell analysis at the intracellular and extracellular level. Antibody-coated gold nanoshells targeted the plasma membrane, while silver nanoshells coated with a nuclear localization signal (NLS) targeted the nuclear membrane. A fluorescence counterstaining experiment, as well as single cell hyperspectral microscopy showed the excellent selectivity and specificity of each type of nanoparticle for its designed subcellular compartment. A time-lapse photodegradation experiment confirmed the enhanced stability of the nanoshells over fluorescent labeling and their capabilities for long-term live cell imaging.