Peripheral oxytocin receptors inhibit the nociceptive input signal to spinal dorsal horn wide-dynamic-range neurons.
Oxytocin (OT) has emerged as a mediator of endogenous analgesia in behavioral and electrophysiological experiments. In fact, OT receptors (OTRs) in the spinal dorsal horn participate in a selective inhibition of the neuronal activity mediated by Aδ and C fibers but not Aβ fibers. This study shows that OTRs are expressed in the terminal nerve endings and are able to inhibit nociceptive neuronal firing. Indeed, local peripheral OT blocked the first sensorial activity of Aδ and C fibers recorded in the spinal cord neurons. Furthermore, using the formalin behavioral nociceptive test, we demonstrated that only ipsilateral OTR activation inhibits pain behavior. Our data are reinforced by the fact that the OTR protein is expressed in the sciatic nerve. Consistent with this, immunofluorescence of primary afferent fibers suggest that OTRs could be located in nociceptive-specific terminals of the skin. Taken together, our results suggest that OTRs could be found in nociceptive terminals and that on activation they are able to inhibit nociceptive input.


2016 Neonatal Nurse Practitioner Workforce Survey: Report of Findings.
The National Association of Neonatal Nurse Practitioners (NANNP) conducted its second workforce survey of certified neonatal nurse practitioners in the fall of 2016. National Association of Neonatal Nurse Practitioners partnered with the National Certification Corporation and the American Association of Nurse Practitioners to conduct this electronic survey, containing 69 questions and focusing on practice sites and total compensation packages (including benefits) and workforce deficits.Findings indicate a rising neonatal nurse practitioners (NNPs) position vacancy rate across the country. Regional salary data indicated that the southeast had lower compensation rates for NNPs, with regions 4 and 11 (South) having the lowest rates. A promising trend indicated that new graduate NNPs with a doctorate are earning more. The study findings indicate that tailoring benefit packages to the age and years of experience for the individual NNP may aid in recruiting and retaining NNPs in practice. For experienced NNPs, altered shift lengths (shorter), higher employer matching rates in retirement plans, and less employee cost sharing for health insurance benefits are more appealing strategies.It is critical for NNPs to continually evaluate the profession's workforce data. There are more than 205,000 nurse practitioners practicing in the United States, with neonatal NPs making up approximately 3% of the larger whole. Increased participation in future surveys will assist in creating sustainable solutions to the workforce crisis facing the profession.


Kctd13 deletion reduces synaptic transmission via increased RhoA.
Copy-number variants of chromosome 16 region 16p11.2 are linked to neuropsychiatric disorders and are among the most prevalent in autism spectrum disorders. Of many 16p11.2 genes, Kctd13 has been implicated as a major driver of neurodevelopmental phenotypes. The function of KCTD13 in the mammalian brain, however, remains unknown. Here we delete the Kctd13 gene in mice and demonstrate reduced synaptic transmission. Reduced synaptic transmission correlates with increased levels of Ras homolog gene family, member A (RhoA), a KCTD13/CUL3 ubiquitin ligase substrate, and is reversed by RhoA inhibition, suggesting increased RhoA as an important mechanism. In contrast to a previous knockdown study, deletion of Kctd13 or kctd13 does not increase brain size or neurogenesis in mice or zebrafish, respectively. These findings implicate Kctd13 in the regulation of neuronal function relevant to neuropsychiatric disorders and clarify the role of Kctd13 in neurogenesis and brain size. Our data also reveal a potential role for RhoA as a therapeutic target in disorders associated with KCTD13 deletion.


Developing ICP-MS/MS for the detection and determination of synthetic DNA-protein crosslink models via phosphorus and sulfur detection.
Various endogenous and exogenous agents drive the un-directed formation of covalent bonds between proteins and DNA. These complex molecules are of great biological relevance, as can derive in mutations, but are difficult to study because of their heterogeneous chemical properties. New analytical approaches with sufficient detection capabilities to detect and quantify these compounds can help to standardize study models based on synthesized standards. The use of atomic spectrometry can provide quantitative information on the DNA-protein cross-link reaction yield along with basic stoichiometry of the products, based on internal elemental tags, sulfur from Cys and Met amino acids, and phosphorus from the DNA. A new instrumental approach to remove isobaric and polyatomic interferences from (31)P(+) and (32)S(+) was developed recently, with state-of-the-art for interference removal that captures (31)P(+) in Q1; it reacts with O2 in an octopole collision-reaction cell generating (47)PO(+), therefore allowing detection in Q3 without (31)NOH(+)/(48)Ca/(47)Ti interferences. Similarly, (32)S(+) is reacted to (48)SO(+), eliminating the polyatomic interferences at m/z = 32. In conjunction with the high resolving power of high-performance liquid chromatography (HPLC), this newer technology was applied by to the product purification of a DNA-protein cross link model and some preliminary structural studies.


Functional connectivity structure of cortical calcium dynamics in anesthetized and awake mice.
The interplay between hemodynamic-based markers of cortical activity (e.g. fMRI and optical intrinsic signal imaging), which are an indirect and relatively slow report of neural activity, and underlying synaptic electrical and metabolic activity through neurovascular coupling is a topic of ongoing research and debate. As application of resting state functional connectivity measures is extended further into topics such as brain development, aging and disease, the importance of understanding the fundamental physiological basis for functional connectivity will grow. Here we extend functional connectivity analysis from hemodynamic- to calcium-based imaging. Transgenic mice (n = 7) expressing a fluorescent calcium indicator (GCaMP6) driven by the Thy1 promoter in glutamatergic neurons were imaged transcranially in both anesthetized (using ketamine/xylazine) and awake states. Sequential LED illumination (λ = 454, 523, 595, 640nm) enabled concurrent imaging of both GCaMP6 fluorescence emission (corrected for hemoglobin absorption) and hemodynamics. Functional connectivity network maps were constructed for infraslow (0.009-0.08Hz), intermediate (0.08-0.4Hz), and high (0.4-4.0Hz) frequency bands. At infraslow and intermediate frequencies, commonly used in BOLD fMRI and fcOIS studies of functional connectivity and implicated in neurovascular coupling mechanisms, GCaMP6 and HbO2 functional connectivity structures were in high agreement, both qualitatively and also quantitatively through a measure of spatial similarity. The spontaneous dynamics of both contrasts had the highest correlation when the GCaMP6 signal was delayed with a ~0.6-1.5s temporal offset. Within the higher-frequency delta band, sensitive to slow wave sleep oscillations in non-REM sleep and anesthesia, we evaluate the speed with which the connectivity analysis stabilized and found that the functional connectivity maps captured putative network structure within time window lengths as short as 30 seconds. Homotopic GCaMP6 functional connectivity maps at 0.4-4.0Hz in the anesthetized states show a striking correlated and anti-correlated structure along the anterior to posterior axis. This structure is potentially explained in part by observed propagation of delta-band activity from frontal somatomotor regions to visuoparietal areas. During awake imaging, this spatio-temporal quality is altered, and a more complex and detailed functional connectivity structure is observed. The combined calcium/hemoglobin imaging technique described here will enable the dissociation of changes in ionic and hemodynamic functional structure and neurovascular coupling and provide a framework for subsequent studies of neurological disease such as stroke.


Haemophagocytic lymphohistiocytosis with lung cavity and lytic bone lesion in a 45 day infant.
Haemophagocytic lymphohistiocytosis (HLH) is a potentially fatal, hyper inflammatory condition which is caused by a highly stimulated but ineffective immune response. We are presenting here, a case of HLH which occurred in a 45 day infant. Presence of lung cavity and a lytic bone lesion in the skull, as was seen in this case, have not been reported in HLH in the literature. This raises a possibility of a simultaneous occurrence of HLH and Langerhans cell histiocytosis. In a child who presents with septicaemia but does not respond to treatment, the possibility of HLH needs to be considered.


Linear and nonlinear properties of heart rate control in infants at risk.
The aim of this study was to test whether the heart rate (HR) control in infants at risk differs in comparison with healthy infants. Twelve former preterm infants suffering from bronchopulmonary dysplasia and 18 control infants, matched for their postconceptional age, were examined polygraphically during quiet and active sleep. HR, low-frequency (LF) power, high-frequency (HF) power, total power, and the ratio of LF to HF power (LF/HF) of the instantaneous HR spectra were calculated for linear analysis. The largest Lyapunov exponent (LLE) of the R-R interval time series was calculated to determine a nonlinear property of HR. Infants at risk had significantly lower LF power (median: 0.51 x 10(-3) vs. 1.16 x 10(-3) Hz2) and lower LF/HF (median: 1.05 vs. 1.94) during quiet sleep. LLE was positive, revealing low-dimensional chaotic behavior of HR control, and did not differ between both groups (median: quiet sleep, 0.05 bit/s vs. 0.06 bit/s; active sleep, 0.16 bit/s vs. 0.15 bit/s). Sleep state-related changes in spectral parameters and LLE were similar in both groups. In infants at risk, the lower LF/HF during quiet sleep can be interpreted in terms of changes in the rhythmic components of the sympathovagal balance of the autonomic system, which is an expression of linear properties of HR control. Conversely, the lack of differences in LLE between both groups indicates similar nonlinear properties of the control system.


Psychotherapy: historical roots, universal elements, and cultural variations.
The authors review various forms of traditional psychotherapeutic interventions to trace the historical development of psychotherapy, which demonstrates a shift in focus from the supernatural world, to the natural world, to the physical person, then to the psychological person. The basic processes of identifying problems, providing explanations, and prescribing for change are observed among various kinds of treatment systems. Universal elements fundamental to successful treatment can be identified in each of these processes, and each is strongly modified by cultural factors. The authors conclude that the special cultural dimension of psychotherapy consists of defining cultural norms, reinforcing culturally sanctioned coping mechanisms, and providing "time out" from usual cultural expectations.


Endothelial RhoA GTPase is essential for in vitro endothelial functions but dispensable for physiological in vivo angiogenesis.
Imbalanced angiogenesis is a characteristic of several diseases. Rho GTPases regulate multiple cellular processes, such as cytoskeletal rearrangement, cell movement, microtubule dynamics, signal transduction and gene expression. Among the Rho GTPases, RhoA, Rac1 and Cdc42 are best characterized. The role of endothelial Rac1 and Cdc42 in embryonic development and retinal angiogenesis has been studied, however the role of endothelial RhoA is yet to be explored. Here, we aimed to identify the role of endothelial RhoA in endothelial cell functions, in embryonic and retinal development and explored compensatory mechanisms. In vitro, RhoA is involved in cell proliferation, migration and tube formation, triggered by the angiogenesis inducers Vascular Endothelial Growth Factor (VEGF) and Sphingosine-1 Phosphate (S1P). In vivo, through constitutive and inducible endothelial RhoA deficiency we tested the role of endothelial RhoA in embryonic development and retinal angiogenesis. Constitutive endothelial RhoA deficiency, although decreased survival, was not detrimental for embryonic development, while inducible endothelial RhoA deficiency presented only mild deficiencies in the retina. The redundant role of RhoA in vivo can be attributed to potential differences in the signaling cues regulating angiogenesis in physiological versus pathological conditions and to the alternative compensatory mechanisms that may be present in the in vivo setting.


What NMR can do in the biopharmaceutical industry.
Nuclear magnetic resonance (NMR) spectroscopy has a unique capability to probe the primary and higher order molecular structure and the structural dynamics of biomolecules at an atomic resolution, and this capability has been greatly fortified over the last five decades by an astonishing NMR instrumental and methodological development. Because of these factors, NMR has become a primary tool for the structure investigation of biomolecules, spawning a whole scientific subfield dedicated to the subject. This role of NMR is by now well established and broadly appreciated, especially in the context of academic research dealing with proteins that are purified and isotope-labeled in order to facilitate the necessary sophisticated multidimensional NMR measurements. However, the more recent industrial development, manufacturing, and quality control of biopharmaceuticals provide a different framework for NMR. For example, protein drug substances are not isotope-labeled and are present in a medium of excipients, which make structural NMR measurements much more difficult. On the other hand, biotechnology involves many other analytical requirements that can be efficiently addressed by NMR. In this respect the scope and limitations of NMR are less well understood. Having the non-expert reader in mind, herein we wish to highlight the ways in which modern NMR can effectively support biotechnological developments. Our focus will be on biosimilar proteins, pointing out certain cases where its use is probably essential. Based partly on literature data, and partly on our own hands-on experience, this paper is intended to be a guide for choosing the proper NMR approach for analytical questions concerning the structural comparability of therapeutic proteins, monitoring technology-related impurities, protein quantification, analysis of spent media, identification of extractable and leachable components, etc. Also, we focus on critical considerations, particularly those coming from drug authority guidelines, which limit the use of the well-established NMR tools in everyday practice.


Sociodemographic and mental health characteristics associated with changes in movement behaviours due to the COVID-19 pandemic in adolescents.
Control measures enacted to control the spread of COVID-19 appear to have impacted adolescent movement behaviours. It remains unclear how these changes relate to sociodemographic characteristics and indicators of mental health. Understanding these relationships can contribute to informing health promotion efforts. The purpose of this study is to examine sociodemographic and mental health characteristics associated with changes in movement behaviours (physical activity, screen time, sleep duration) due to the COVID-19 pandemic among adolescents. This cross-sectional study used May-June 2020 survey data and included 7349 students from Quebec, Ontario, and British Columbia (Canada). ANOVA, χ2 tests, and estimation of effect sizes using Cohen's d and h tests were performed between self-reported perceived changes (increase; decrease; no change) to physical activity, TV watching, social media use, and sleep duration as a result of the COVID-19 pandemic and gender, age, race/ethnicity, income, depression and anxiety symptoms, flourishing-languishing, and self-rated mental health. Over half of students reported increases in TV viewing and social media use and approximately 40% reported decrease in physical activity and increase in sleep duration due to the COVID-19 pandemic. More females (68.9%) than males (54.3%) reported increase in social media use (Cohen's h ≥ 0.2-0.5). No change from pre-COVID-19 social media use and sleep duration were associated with fewer depression and anxiety symptoms and better self-rated mental health compared to reports of an increase or decrease. These effect sizes ranged from small-to-moderate to moderate-to-large (Cohen's d/h ≥ 0.2-0.8). Decreased physical activity and sleep duration were associated with better psychological functioning with effects sizes of small-to-moderate. Compared to an increase or no change, decreased sleep had the largest effect size of less frequent depression symptoms (Cohen's d ≥ 0.5-0.8). Maintaining pre-COVID-19 screen time and sleep duration during early stages of the COVID-19 lockdown was generally beneficial to mental health, with sleep being particularly important in regards to symptoms of depression. Psychological functioning was more related to physical activity and sleep than screen time during the pandemic.


Voluntary Health Insurance expenditure in low- and middle-income countries: Exploring trends during 1995-2012 and policy implications for progress towards universal health coverage.
Most low- and middle-income countries (LMIC) rely significantly on private health expenditure in the form of out-of-pocket payments (OOP) and voluntary health insurance (VHI). This paper assesses VHI expenditure trends in LMIC and explores possible explanations. This illuminates challenges deriving from changes in VHI expenditure as countries aim to progress equitably towards universal health coverage (UHC). Health expenditure data was retrieved from the WHO Global Health Expenditure Database to calculate VHI, OOP and general government health (GGHE) expenditure as a share of total health expenditure (THE) for the period of 1995-2012. A literature analysis offered potential reasons for trends in countries and regions. In 2012, VHI as a percentage of THE (abbreviated as VHI%) was below 1 % in 49 out of 138 LMIC. Twenty-seven countries had no or more than five years of data missing. VHI% ranged from 1 to 5 % in 39 LMIC and was above 5 % in 23 LMIC. There is an upwards average trend in VHI% across all regions. However, increases in VHI% cannot be consistently linked with OOP falling or being redirected into private prepayment. There are various countries which exhibit rising VHI alongside a rise in OOP and fall in GGHE, which is a less desirable path in order to equitably progress towards UHC. Reasons for the VHI expenditure trends across LMIC include: external influences; government policies on the role of VHI and its regulation; and willingness and ability of the population to enrol in VHI schemes. Many countries have paid insufficient attention to the potentially risky role of VHI for equitable progress towards UHC. Expanding VHI markets bear the risk of increasing fragmentation and inequities. To avoid this, health financing strategies need to be clear regarding the role given to VHI on the path towards UHC.


Application of monoclonal antibody G250 recognizing carbonic anhydrase IX in renal cell carcinoma.
Monoclonal antibody G250 (mAbG250) recognizes a determinant on carbonic anhydrase IX (CAIX). CAIX is expressed by virtually all renal cell carcinomas of the clear cell type (ccRCC), but expression in normal tissues is restricted. The homogeneous CAIX expression in ccRCC and excellent targeting capability of mAbG250 in animal models led to the initiation of the clinical evaluation of mAbG250 in (metastatic) RCC (mRCC) patients. Clinical studies confirmed the outstanding targeting ability of mAbG250 and cG250 PET imaging, as diagnostic modality holds great promise for the future, both in detecting localized and advanced disease. Confirmation of the results obtained in the non-randomized clinical trials with unmodified cG250 is needed to substantiate the value of cG250 treatment in mRCC. cG250-Based radio immuno-therapy (RIT) holds promise for treatment of patients with small-volume disease, and adjuvant treatment with unmodified cG250 may be of value in selected cases. In the upcoming years, ongoing clinical trials should provide evidence for these assumptions. Lastly, whether cG250-based RIT can be combined with tyrosine kinase inhibitors, which constitutes the current standard treatment for mRCC, needs to be established.


Specificity of odorant-evoked inhibition in lobster olfactory receptor neurons.
Lobster olfactory receptor neurons, like those of many animals, use two modes of olfactory signaling, excitation and inhibition to code olfactory information. Inhibition appears to act through two distinct ionic mechanisms. Here we show that neither ionic mechanism is odor-specific, providing further support for the emerging understanding that there are no inhibitory odorants per se, but rather that the action of a particular odorant is inherent in the olfactory receptor cell on which an odorant acts.


Small Intestinal Adenocarcinoma Involving a Submucosal Ectopic Lymph Node: A Case Report.
An 83-year-old male with a 55-year history of Crohn's disease, ileocecectomy 40 years prior, and naturopathic treatment for 25 years, presented with nausea, vomiting, and abdominal pain. Computed tomography of abdomen and pelvis demonstrated partial small intestinal obstruction and a 4.4-cm solid left renal mass. After 3 months of recurrent intestinal obstruction and development of a pericolonic abscess, resection of the ileocolonic anastomosis, abscess, and partial nephrectomy were performed. Histopathology demonstrated chronic active enteritis with fistula tract formation, consistent with Crohn's disease, and moderately differentiated small intestinal adenocarcinoma extending from mucosa into subserosa. A submucosal intestinal lymph node-like structure containing adenocarcinoma demonstrated endothelial venules, open marginal and intermediate sinuses, multiple polarized germinal centers, and partial capsule, consistent with an ectopic lymph node, also called a tertiary lymphoid organ. Twenty mesenteric lymph nodes were negative for carcinoma. The renal mass was a papillary renal cell carcinoma, Stage I. Intestinal tertiary lymphoid organs form in chronic immune activation and have variable structures ranging from simple B and T cell clusters to organized groups with high endothelial venules and lymphatic vessels. Encapsulation of tertiary lymphoid organs is rare, with some sources claiming this entity is never encapsulated. To our knowledge, this is the first report of small intestinal adenocarcinoma involving a submucosal encapsulated tertiary lymphoid organ, the prognostic significance of which is uncertain. We suggest increased awareness of intestinal tertiary lymphoid organs as an entity and further studies to delineate the effect their involvement by adenocarcinoma imparts on survival.


Is male factor infertility associated with midlife low-grade inflammation? A population based study.
Male factor infertility is associated with an increased risk of disease and mortality, which has been related to markers of chronic systemic inflammation. The objective of this study was to investigate the association between male factor infertility and low-grade inflammation and furthermore to examine the lifetime prevalence of male factor infertility and overall infertility (also including female and couple infertility). The study population consisted of 2140 members of the Metropolit 1953 Danish Male Birth Cohort who had participated in the Copenhagen Aging and Midlife Biobank data collection in 2009-2011. Information on male factor infertility and overall infertility was obtained from a questionnaire, and low-grade inflammation was evaluated as the highest plasma levels of C-reactive protein, interleukin-6 and tumour necrosis factor-alpha in the population. The level of interleukin-6 was significantly higher among men with male factor infertility compared with other men adjusted for potential confounders. This was not found for the two other inflammatory markers. The lifetime prevalence of male factor infertility and overall infertility were 10.2% and 17.9%, respectively. The findings suggest that male factor infertility might be associated with an increased level of interleukin-6.


[Treatment of stroke in Europe: the Helsingborg Declaration].
Late in 1995, the Helsingborg Declaration was adopted, a European consensus text on the basic elements for policy in, and objectives of treatment of strokes. This declaration was prompted by the fact that the differences in incidence in different European countries, and the changes of the incidence in the course of the years suggest a great importance of environmental factors that can be influenced. The organizers of this consensus meeting might have enhanced the value of the document by more exactly indicating the (scientific) strength of the argumentation for each recommendation. Nevertheless, many of the recommendations are based on solid evidence. A plea is made to structure stroke care, measure the quality of care, facilitate early diagnosis and therapy after stroke, improve the possibilities for rehabilitation, and apply appropriate secondary prevention.


Multiple roles for u-turn/ventral veinless in the development of Drosophila PNS.
Most of the cells in the embryonic peripheral nervous system (PNS) of Drosophila are born in their final location. One known exception is the group of lateral chordotonal organs (lch5) whose precursors form in a dorsal position, yet the mature organs are located in the lateral PNS cluster. Mutations in the u-turn (ut) locus perturb the localization of lch5 neurons and result in a 'dorsal chordotonals' phenotype. We show that ut is allelic to ventral veinless (vvl), also known as drifter. VVL, a POU-domain transcription factor, has been shown to participate in the development of tracheae and CNS in the embryo, and in wing development in the adult; however, its role in PNS development has not been described. Characterization of the 'dorsal chordotonals' phenotype of vvl mutant embryos revealed that in the absence of VVL, cell fates within the lch5 lineage are determined properly and the entire organ is misplaced. Based on the positions of lch5 cells relative to each other in mutant embryos, and in normal embryos at different developmental stages, we propose a two-step model for lch5 localization. lch5 organs must first rotate to assume a correct polarity and are then stretched ventrally to their final position. In this process, VVL function is required in the ectoderm and possibly in the lch5 organs too. VVL is also expressed in developing external sensory organs in the embryo and in the adult. In the embryo, loss of VVL function results in increased apoptosis in specific es organs. Analysis of vvl mutant clones in adults revealed a requirement for VVL in the control of cell number within the bristle lineage.


The Temperature Dependence of Phytoplankton Stoichiometry: Investigating the Roles of Species Sorting and Local Adaptation.
The elemental composition of phytoplankton (C:N:P stoichiometry) is a critical factor regulating nutrient cycling, primary production and energy transfer through planktonic food webs. Our understanding of the multiple direct and indirect mechanisms through which temperature controls phytoplankton stoichiometry is however incomplete, increasing uncertainty in the impacts of global warming on the biogeochemical functioning of aquatic ecosystems. Here, we use a decade-long warming experiment in outdoor freshwater ponds to investigate how temperature-driven turnover in species composition and shifts in stoichiometric traits within species through local thermal adaptation contribute to the effects of warming on seston stoichiometry. We found that experimental warming increased seston C:P and N:P ratios, while the C:N ratio was unaffected by warming. Temperature was also the dominant driver of seasonal variation in seston stoichiometry, correlating positively with both C:P and N:P ratios. The taxonomic composition of the phytoplankton community differed substantially between the warmed and ambient treatments indicating that warming resulted in differential sorting of species from the regional pool. Furthermore, taxonomic composition also changed markedly over the year within each of the warmed and ambient treatments, highlighting substantial temporal turnover in species. To investigate whether local adaptation also played an important role in shaping the effects of warming on seston stoichiometry, we isolated multiple strains of the cosmopolitan alga, Chlamydomonas reinhardtii from across the warmed and ambient mesocosms. We found that warmed isolates had higher C:P and N:P ratios, shifts that were comparable in direction and magnitude to the effects of warming on seston stoichiometry. Our results suggest that both species sorting and local adaptation are likely to play important roles in shaping the effects of warming on bulk phytoplankton stoichiometry and indicate that major shifts in aquatic biogeochemistry should be expected in a warmer world.


Functionalized-ferroelectric-coating-driven enhanced biomineralization and protein-conformation on metallic implants.
In the context of bone regeneration, it is important to have platforms that with appropriate stimuli can support the attachment and direct the growth, proliferation and differentiation of cells. In the orthopedic field, metals and alloys are still the dominant materials used as implants, though their bioinert character leads to failure or to the need for multiple revision procedures. To respond to this situation here we exploit an alternative strategy for bone implants or repairs, based on charge mediating signals for bone regeneration, envisaged as a type of biological micro-electromechanical system (BioMEM). This strategy includes coating metallic 316L-type stainless steel substrates with ferroelectric LiTaO3 layers functionalized via electrical charging or UV-light irradiation. We show that the formation of surface calcium phosphates and protein adsorption are considerably enhanced for 316L-type stainless steel functionalized ferroelectric coatings. Our findings go beyond the current knowledge and demonstrate that the protein conformation is sensitive to the type of charge functionalization of the ferroelectric coatings. Our approach can be viewed as a set of guidelines for the development of electrically functionalized platforms that can stimulate tissue regeneration, promoting direct integration of the implant in the host tissue and hence contributing ultimately to reducing implant failure.


Decoding the regulatory network of early blood development from single-cell gene expression measurements.
Reconstruction of the molecular pathways controlling organ development has been hampered by a lack of methods to resolve embryonic progenitor cells. Here we describe a strategy to address this problem that combines gene expression profiling of large numbers of single cells with data analysis based on diffusion maps for dimensionality reduction and network synthesis from state transition graphs. Applying the approach to hematopoietic development in the mouse embryo, we map the progression of mesoderm toward blood using single-cell gene expression analysis of 3,934 cells with blood-forming potential captured at four time points between E7.0 and E8.5. Transitions between individual cellular states are then used as input to develop a single-cell network synthesis toolkit to generate a computationally executable transcriptional regulatory network model of blood development. Several model predictions concerning the roles of Sox and Hox factors are validated experimentally. Our results demonstrate that single-cell analysis of a developing organ coupled with computational approaches can reveal the transcriptional programs that underpin organogenesis.


Parents' information and support needs when their child is diagnosed with type 1 diabetes: a qualitative study.
The aim of this study was to describe and explore parents' information and support needs when their child is diagnosed with type 1 diabetes, including their views about the timing and chronology of current support provision. Our objective was to identify ways in which parents could be better supported in the future. Semi-structured interviews were conducted with 54 parents of children with type 1 diabetes in four paediatric diabetes clinics in Scotland. Data were analysed using an inductive, thematic approach. Parents described needing more reassurance after their child was diagnosed before being given complex information about diabetes management, so they would be better placed psychologically and emotionally to absorb this information. Parents also highlighted a need for more emotional and practical support from health professionals when they first began to implement diabetes regimens at home, tailored to their personal and domestic circumstances. However, some felt unable to ask for help or believed that health professionals were unable to offer empathetic support. Whilst some parents highlighted a need for support delivered by peer parents, others who had received peer support conveyed ambivalent views about the input and advice they had received. Our findings suggest that professionals should consider the timing and chronology of support provision to ensure that parents' emotional and informational needs are addressed when their child is diagnosed and that practical advice and further emotional support are provided thereafter, which takes account of their day-to-day experiences of caring for their child.


Quality of Life of Young Adult Survivors of Pediatric Burns Using World Health Organization Disability Assessment Scale II and Burn Specific Health Scale-Brief: A Comparison.
The objective was to determine long-term psychological distress and quality of life (QOL) in young adult survivors of pediatric burns using the World Health Organization Disability Assessment Scale II (WHODAS) and the Burn Specific Health Scale-Brief (BSHS-B). Fifty burn survivors 2.5 to 12.5 years postburn (16-21.5 years old; 56% male, 82% Hispanic) completed the WHODAS and BSHS-B. The WHODAS measures health and disability and the BSHS-B measures psychosocial and physical difficulties. Scores were calculated for each instrument, and then grouped by years postburn, TBSA, sex, burn age, and survey age to compare the effects of each. Next, the instruments were compared with each other. The WHODAS disability score mean was 14.4 ± 2.1. BSHS-B domain scores ranged from 3 to 3.7. In general, as TBSA burned increased, QOL decreased. Female burn survivors, survivors burned prior to school entry, and adolescents who had yet to transition into adulthood reported better QOL than their counterparts. In all domains except Participation, the WHODAS consistently identified more individuals with lower QOL than the BSHS-B. Young adult burn survivors' QOL features more disability than their nonburned counterparts, but score in the upper 25% for QOL on the BSHS-B. This analysis revealed the need for long-term psychosocial intervention for survivors with larger TBSA, males, those burned after school entry, and those transitioning into adulthood. Both instruments are useful tools for assessing burn survivors' QOL and both should be given as they discern different individuals. However, the WHODAS is more sensitive than the BSHS-B in identifying QOL issues.


Influence of the instrumented force shoe on gait pattern in patients with osteoarthritis of the knee.
Osteoarthritis (OA) of the knee is associated with alterations in gait. As an alternative to force plates, instrumented force shoes (IFSs) can be used to measure ground reaction forces. This study evaluated the influence of IFS on gait pattern in patients with knee OA. Twenty patients with knee OA walked in a gait laboratory on IFS and control shoes (CSs). An optoelectronic system and force plate were used to perform 3D gait analyses. A comparison of temporal-spatial gait parameters, kinematics, and kinetics was made between IFS and CS. Patients wearing IFS showed a decrease in walking velocity and cadence (8%), unchanged stride length, an increase in stance time (13%), stride time (11%) and step width (14%). No differences were found in knee adduction moment or knee kinematics. Small differences were found in foot and ankle kinematics (2-5°), knee transverse moments (5%), ankle frontal (3%) and sagittal moments (1%) and ground reaction force (1-6%). The gait of patients with knee OA was only mildly influenced by the IFS, due to increased shoe height and weight and a change in sole stiffness. The changes were small compared to normal variation and clinically relevant differences. Importantly, in OA patients no effect was found on the knee adduction moment.


Clarithromycin-induced hypersomnia in children.
Two cases of hypersomnia in children caused by therapeutic doses of oral clarithromycin are presented. Clarithromycin-induced hypersomnia in children has not been reported before. A 4-year-old girl and 13-year-old boy received clarithromycin as monotherapy. The girl fell into a deep sleep after every dose of the antibiotic. The boy reported daytime sleepiness and prolongation of night-time sleep during the antibiotic therapy. In both cases the hypersomnia receded after cessation of clarithromycin therapy. The onset of hypersomnia after clarithromycin intake, its remission once the drug was stopped, and the absence of other possible causative factors favored the diagnosis of clarithromycin-induced hypersomnia, further supported by the scores on Naranjo's Adverse Drug Reaction Probability Scale in both cases. Clinicians evaluating children receiving clarithromycin and exhibiting suddenly changed behavior should keep in mind that the antibiotic can produce uncommon adverse reactions.


Ab initio molecular dynamics simulations of the initial stages of solid-electrolyte interphase formation on lithium ion battery graphitic anodes.
The decomposition of ethylene carbonate (EC) during the initial growth of solid-electrolyte interphase (SEI) films at the solvent-graphitic anode interface is critical to lithium ion battery operations. Ab initio molecular dynamics simulations of explicit liquid EC/graphite interfaces are conducted to study these electrochemical reactions. We show that carbon edge terminations are crucial at this stage, and that achievable experimental conditions can lead to surprisingly fast EC breakdown mechanisms, yielding decomposition products seen in experiments but not previously predicted.


The importance of circadan rhythm alterations in erythrocyte deformability.
The hormone melatonin, secreted from the pineal gland at night and suppressed during the day, provides a circadian and seasonal signal to the organism. The impact of pharmacological doses of melatonin on erythrocyte deformability was investigated by our group in several studies in both in vitro and in vivo conditions. The aim of this study was to investigate the effects of alterations in the physiological melatonin levels via the circadian rhythm on erythrocyte deformability. 50 male rats weighing 250-300 g were divided in 5 groups. The rats were subjected to 12/12, 24/0, 0/24, 16/8 and 8/16 h of Light/Dark (L/D) cycle, respectively. The elongation indexes (EI) of the erythrocytes were measured by a laser diffractometer (Myrenne Rheodyne SSD) by using 30 microl of whole blood suspended in 2 ml of Dextran 60. There was no significant difference in the EI of the 24/0 h L/D group compared to the control (12/12), whereas the decrease of EI was statistically important in the 0/24 h L/D group (p = 0.009). This decrease in EI was also significant when this group was compared to the 24/0 h L/D group (p = 0.05). Furthermore, the EI was affected significantly by alterations in the circadian rhythm, compared to control (16/8, 8/16 h L/D; p = 0.05 and p = 0.007, respectively). As a result, the alterations in physiological melatonin levels via different circadian rhythms have significant impacts on the deformability of erythrocytes, which therefore may cause important cardiovascular implications in the people who are exposed to different light dark cycles. Furthermore, these data represents a new and a quite crucial open-field to be investigated and taken into account in in vivo hemorheological studies.


Effect of host microenvironment on the microcirculation of human colon adenocarcinoma.
It is generally accepted that the host microenvironment influences tumor biology. There are discrepancies in growth rate, metastatic potential, and efficacy of systemic treatment between ectopic and orthotopic tumors. Liver is the most common and critical site of distant metastasis of colorectal carcinoma. Tumorigenicity and efficacy of chemotherapeutic agents in colorectal tumors are different in liver and subcutaneous sites. Thus, we hypothesize that the liver (orthotopic) versus subcutaneous (ectopic) microenvironment would have different effects on the angiogenesis and maintenance of the microcirculation of colorectal tumor. To this end, we developed a new method to monitor and to quantify microcirculatory parameters in the tumor grown in the liver. Using this approach, we compared the microcirculation of LS174T, a human colon adenocarcinoma, metastasized to the liver with that of the host liver vessels and that of the same tumor grown in the subcutaneous space. In the liver metastasis model, 5 x 10(6) LS174T cells were injected into the spleen of nude mice. Four to eight weeks later, the liver with metastatic tumors was exteriorized and placed on a special stage and observed under an intravital fluorescence microscope. The dorsal skinfold chamber model was used to study the subcutaneous tumors. Red blood cell velocity, vessel diameter, density, permeability, and leukocyte-endothelial interactions were measured using fluorescence microscopy and image analysis. Vascular endothelial growth factor/ vascular permeability factor (VEGF/VPF) mRNA expression was determined by the Northern blot analysis. LS174T tumor foci in the liver had tortuous vascular architecture, heterogeneous blood flow, significantly lower vascular density, and significantly higher vascular permeability than normal liver tissue. Tumors grown in the liver had significantly lower vessel density, especially in the center coincident with central necrosis, than the subcutaneous tumors. The frequency distribution of vessel diameters of liver tumor was slightly shifted to smaller size compared with that of subcutaneous tumor. Leukocyte rolling in liver tumor was twofold lower than that in subcutaneous tumor. These physiological findings were consistent with the measurement of VEGF/VPF in that the VEGF/VPF mRNA level was lower in the liver tumor than that in the subcutaneous tumor. However, macromolecular vascular permeability in the liver tumor was significantly higher than in the subcutaneous tumor. Liver sinusoidal endothelial cells, the origin of liver tumor vessel endothelium, are known to be fenestrated and not to have a basement membrane, suggesting that the difference in endothelial cell origin may explain the difference in tumor vascular permeability in two sites. These findings demonstrate that liver microenvironment has different effects on some aspects of the tumor angiogenesis and microcirculation compared with the subcutaneous tissues. The new model/method described in this paper has significant implications in two research areas: 1) the liver microenvironment and its effect on tumor pathophysiology in conjunction with cytokine/ growth factor regulation and 2) the delivery of drugs, cells, and genes to liver tumors.


The Pregnancy Microbiome.
In recent years, microbiome research has revealed multiple essential roles of the microorganisms residing within the human body in host metabolism, immunity, and overall health. Numerous physiological and pathological states, including obesity and the metabolic syndrome, have been correlated with microbial changes, termed dysbiosis. Our microbiomes change in response to our environment, diet, weight, hormones, and other factors. It is, therefore, not surprising that there are also significant changes in the microbiome during pregnancy when dramatic weight gain and metabolic and immunological changes occur. In this review, we summarize the known changes in microbial composition throughout pregnancy at a variety of body sites, including the gut, vagina, oral cavity, and placenta, and we describe several studies that have linked pregnancy complications with microbial changes. Unlike the case of certain disease states, such as obesity, where dysbiosis is considered to have negative effects, we believe that the microbial alterations observed during pregnancy are vital for a healthy pregnancy. While more research in this field is required to reveal specific mechanisms and pathways regulating these alterations, the microbial changes during pregnancy are likely coordinated with the immune, endocrine, and metabolic states.


Prostaglandin E2 Inhibits Prostate Cancer Progression by Countervailing Tumor Microenvironment-Induced Impairment of Dendritic Cell Migration through LXRα/CCR7 Pathway.
Migration and homing of dendritic cells (DCs) to lymphoid organs are quite crucial for T cell-induced immune response against tumor. However, tumor microenvironment can make some tumor cells escape immune response by impairing DC migration. Prostaglandin E2 (PGE2) plays important roles in initiating and terminating inflammatory responses. In this study, we investigated whether PGE2 could inhibit murine prostate cancer progression by countervailing tumor microenvironment-induced impairment of dendritic cell migration. We found that murine prostate cancer cell line RM-1-conditioned medium impaired chemotactic movement of marrow-derived DCs and splenic cDCs toward CC chemokine receptor-7 (CCR7) ligand CCL19 in vitro and migration to draining lymph gland in vivo. Meanwhile, it also induced LXRα activation and CCR7 inhibition on maturing DCs. However, the treatment of PGE2 rescued this impairment of DC migration with upregulation of CCR7 and inhibition of LXRα. Further, it was observed that PGE2 also increased MMP9 expression and activated Notch1 signaling on DCs. In RM-1-bearing mouse model, PGE2 treatment was identified to inhibit tumor growth and induce more tumor-infiltrating T cells and CD11c dendritic cells in tumor sites. Therefore, our findings may demonstrate a new perspective for therapeutic interventions on prostate cancer immunoescape.


Tobacco Cessation in Oncology Care.
Globally, tobacco use is a major modifiable risk factor and leading cause of many forms of cancer and cancer death. Tobacco use contributes to poorer prognosis in cancer care. This article reviews the current state of tobacco cessation treatment in oncology. Effective behavioral and pharmacological treatments exist for tobacco cessation, but are not being widely used in oncology treatment settings. Comprehensive tobacco treatment increases success with quitting smoking and can improve oncological and overall health outcomes. This article describes the components of a model treatment program, which includes automatic referrals for all current tobacco users and recent quitters, motivational interviewing during initial and follow-up contacts, combined behavioral and pharmacological interventions for cessation, and systematic follow-up phone calls for relapse prevention.


Photoperiodism in Japanese quail (Coturnix coturnix japonica) with special reference to relative refractoriness.
Cloacal gland (an androgen dependent sex accessory) of Japanese quail exhibits full breeding condition as long as these were maintained under long days (LD 16:8). When shifted to short daylength (LD 6:18), scotosensitivity (cloacal gland regression) was observed up to 5 weeks, followed by scotorefractoriness (cloacal gland development). There was a regression in cloacal gland volume of the birds when shifted to intermediate daylength (LD 13.5:10.5 and 13:11) after 12 weeks of exposure to long days (relative refractoriness) but no regression when shifted to relatively short days (< 14 hr) after 3 weeks of exposure to long daylength. Birds maintained under constant short photoperiod (LD 6:18) exhibited cyclicity. Shift experiments (quail reared and maintained under continuous light; LL, were shifted to LD 16:8, 13:11 and 8:16, similarly quail maintained under LD 16:8 were shifted to rest three photoperiods and so on) made to compare the cloacal gland responses indicated that if the difference between two photoperiods (previous and shifted one) was more the percentage of difference in cloacal gland response was also high. Short daylength (LD 8:16) was always gonadoinhibitory for the quail previously exposed to any daylength (13L, 16L or 24L) and 16L and 24L were always stimulatory for the quail previously exposed to other daylength (8L, 13L, 16L). But, when the birds were shifted to 13L, photoresponses cannot be generalized and it depends on the photoperiod to which quail were exposed previously (i.e. photoperiodic history).


[Mechanism of glutathione oxidation by photosensitized retinal].
Sulphur radicals appearing in the retinal photosensitized glutathione oxidation have been recorded by spin trapping. There is no reaction in the absence of oxygen. That is why the single oxygen is supposed to take part in the reaction (IId type photosensitized reaction).


Laryngeal thrush.
Superficial fungal infection of the mucous membranes (thrush) isolated to the larynx is neither widely reported nor well recognized clinically. Therefore, it is often associated with ineffective treatment and delay in diagnosis, and sometimes associated with unneeded surgical intervention. Eight cases of thrush isolated to the larynx, with no oral or oropharyngeal manifestations, are presented. Four of these were isolated to the vocal folds alone. All patients were adults, and 4 were smokers. Hoarseness was always present. Pain was present inconsistently, and there was no dysphagia or odynophagia, in contrast to other forms of upper aerodigestive tract candidiasis. On average, diagnosis was not made until 6 months after the onset of symptoms. Possible causative factors included use of systemic steroids (3 cases), broad-spectrum antibiotics (1 case), or inhaled steroids (5 cases); diabetes (2 cases); and neutropenia (1 case). In 3 cases, all with thrush isolated to the vocal folds, inhaled steroids were the only causative factor identifiable--a feature reported only twice previously. Three patients underwent surgical procedures that might have been avoided had an accurate diagnosis been made. All patients responded readily to oral fluconazole and removal of predisposing factors where possible. The signs, symptoms, predisposing factors, and treatment are compared to those of 14 cases reported in the literature over 35 years.


Retroviral gene therapy with an immunoglobulin-antigen fusion construct protects from experimental autoimmune uveitis.
Immunoglobulins can serve as tolerogenic carriers for antigens, and B cells can function as tolerogenic antigen-presenting cells. We used this principle to design a strategy for gene therapy of experimental autoimmune uveitis, a cell-mediated autoimmune disease model for human uveitis induced with the uveitogenic interphotoreceptor retinoid-binding protein (IRBP). A retroviral vector was constructed containing a major uveitogenic IRBP epitope in frame with mouse IgG1 heavy chain. This construct was used to transduce peripheral B cells, which were infused into syngeneic recipients. A single infusion of transduced cells, 10 days before uveitogenic challenge, protected mice from clinical disease induced with the epitope or with the native IRBP protein. Protected mice had reduced antigen-specific responses, but showed no evidence for a classic Th1/Th2 response shift or for generalized anergy. Protection was not transferable, arguing against a mechanism dependent on regulatory cells. Importantly, the treatment was protective when initiated 7 days after uveitogenic immunization or concurrently with adoptive transfer of primed uveitogenic T cells. We suggest that this form of gene therapy can induce epitope-specific protection not only in naive, but also in already primed recipients, thus providing a protocol for treatment of established autoimmunity.


Role of connectivity in immune and neural network models: memory development and aging.
In this paper we analyzed how connectivity (defined as number of connections between network elements) can affect the memory capacity of a network-based model of the Immune System (IS) and of a model of the Nervous System (NS) synaptic plasticity (BCM model). The key point is the concept of competition between the characteristic variables that represent the response of such systems to environmental stimuli: the clonal concentrations for the IS, and the neuron responses for the BCM model. The memory states of both systems are characterized by a high selectivity to specific input patterns, reflecting a similar behaviour of their development rules. This selectivity property of memory states can be controlled by changing the degree of the internal connectivity in each system. We can explain the changes occurring in IS memory states during lifespan as due to a reshaping of its internal connectivity. This assumption is in agreement with experimental observations, reporting an increase of IS memory cells during lifespan. The change of connectivity in the BCM model leads to the introduction of quasilocal variables governing the plasticity of groups of synaptic junctions. This could be interpreted as the result of a refinement of neuron internal mechanisms during development, or it could be seen as a different learning rule deriving from the original BCM theory. We argue that connectivity seems to play an important role in a large class of biological systems controlled by competition mechanisms. Moreover, changes in connectivity may lead to changes in memory properties during development and aging.


Intense storms and the delivery of materials that relieve nutrient limitations in mangroves of an arid zone estuary.
Tropical cyclones can be devastating to ecosystems, but they can also result in pulses of fresh water and sediments delivered in floodwaters to the coastal zone. In the arid zone the pulses provided by cyclones may be particularly important for the maintenance of productivity. We examined the impacts of Cyclone Pancho on growth and nutrient limitations to growth in mangroves on the arid coast of Western Australia. We found that growth of trees was enhanced after the cyclone, more than doubling their rates of stem extension. Fertilisation studies showed that before the cyclone tree growth was nutrient limited. After the cyclone fertilisation treatments had no significant effect on growth, indicating nutrients had been delivered during the storm. Additionally, before the cyclone the efficiency of resorption of phosphorus and nitrogen from senescent leaves was higher than after the cyclone, suggesting that nutrient availability was enhanced. Analysis of stable isotopes of leaf tissue indicated that the cyclone was associated with small changes in water use efficiency, consistent with decreased soil salinity associated with the cyclone. There was, however, significant reductions in δ15N indicating enhanced N supply potentially from a new source. We conclude that in the arid zone, floodwater associated with cyclones is important for the delivery of nutrient subsidies that stimulate mangrove growth and that predicted future reductions in the frequency of cyclones will have negative impacts on the productivity of these ecosystems.


[High density lipoprotein cholesterol and iodine-accumulating function of thyroid gland in patients with alimentary obesity as well as patients with ischemic heart disease with excessive body mass].
Accumulation of 131I was decreased in patients with heart ischemic disease and excessive body mass whereas this decrease occurred more seldom in patients with metabolic-alimenatary obesity. Increase in the ratio of alpha-cholesterol/cholesterol in blood serum was more typical for the patients with heart ischemic disease as compared with corpulent patients. Deterioration of iodine-accumulating function of thyroid gland in the ischemic disease was accompanied by decrease in content of cholesterol as well as by increase of alpha-cholesterol. These alterations were not found in the patients with obesity. In the decrease of iodine-accumulating function of thyroid gland contents of cholesterol and alpha-cholesterol were dissimilarly altered in the patients with excessive body mass and heart ischemic disease as well as in the patients with metabolic-alimentary obesity.


Oxygen atom detection using third harmonic generation.
Atomic oxygen has been detected using the four-wave mixing technique of third harmonic generation (THG). Ground state O((3)P(j)) atoms, generated using a microwave discharge, were monitored by focusing a 391-nm dye laser beam into the post-discharge region and observing radiation at 130 nm, near resonant with the 3s (3)S(0)(1)? 2p(4)(3)P(j) transition, produced along the laser propagation direction. The observed concentration dependent frequency shifts of the laser excitation spectrum verified the assignment of THG. Oxygen atoms were also detected in the same manner following photodissociation of NO(2). An important point for diagnostic purposes is that both the VUV intensity and peak frequency shift are dependent on O atom concentration. The relationship between these variables was explored by employing chemical titrations to establish absolute concentration. The demonstrated sensitivity is 5 x 10(13) cm(-3), but this could be significantly improved. Implications for three-photon resonant multiphoton ionization detection as well as in situ monitoring of atomic oxygen metastable states ((1)D(2) and (1)S(0)) are discussed. Third harmonic generation provides state selective and low aperture detection with sensitivity comparable to other optical methods and shows promise as a general detection technique. Third harmonic generation, optical detection, four-wave mixing, oxygen, atomic detection, atomic spectroscopy, VUV radiation.


Antibacterial and antigelatinolytic effects of Satureja hortensis L. essential oil on epithelial cells exposed to Fusobacterium nucleatum.
The present report examined the effects of essential oils (EOs) from Satureja hortensis L. and Salvia fruticosa M. on the viability and outer membrane permeability of the periodontopathogen Fusobacterium nucleatum, a key bacteria in oral biofilms, as well as the inhibition of matrix metalloproteinase (MMP-2 and MMP-9) activities in epithelial cells exposed to such bacteria. Membrane permeability was tested by measuring the N-phenyl-1-naphthylamine uptake and bacterial viability by using the commercially available Live/Dead BacLight kit. In addition, gelatin zymography was performed to analyze the inhibition of F. nucleatum-induced MMP-2 and MMP-9 activities in HaCaT cells. We showed that 5, 10, and 25 μL/mL of Sat. hortensis L. EO decreased the ratio of live/dead bacteria and increased the outer membrane permeability in a range of time from 0 to 5 min. Treatments with 10 and 25 μL/mL of Sal. fruticosa M. also increased the membrane permeability and 5, 10, and 25 μL/mL of both EOs inhibited MMP-2 and MMP-9 activities in keratinocytes induced after exposure of 24 h to F. nucleatum. We conclude that antibacterial and antigelatinolytic activities of Sat. hortensis L. EO have potential for the treatment of periodontal inflammation.


Effects of Normovolemic Hemodilution on Survival of Skin Flaps: An Experimental Study.
BACKGROUND The aim of this study was to investigate the effects of various ratios of hemodilution on the survival of McFarlane's skin flaps. MATERIAL AND METHODS An experimental study was performed on 42 adult male Wistar rats (weighing 260 to 305 g) allocated to a control group without any volume loss and to 6 study groups with hemodilution ratios of 5%, 10%, 15%, 20%, 25%, and 30%. In all subjects, random-pattern McFarlane's skin flaps were uniformly elevated and re-sutured to the donor sites. The amount of necrosis was evaluated on the 7th day postoperatively and compared among the groups. RESULTS The amounts of flap necrosis in the groups with 5%, 10%, 15%, and 20% hemodilution ratios were significantly lower than that of the control group (p<0.001). In the 25% and 30% hemodilution groups, although there was less necrosis than in the control group, the differences were not statistically significant. Hematocrit levels, which initially decreased in conjunction with the hemodilution ratios, returned to normal levels on the 7th day after the operation. CONCLUSIONS Our results indicated that 20% or less of the total blood volume loss that may be compensated by the normovolemic hemodilution with dextran can improve flap survival.


An Assessment of Government Capacity Building to Restrict the Marketing of Unhealthy Food and Non-Alcoholic Beverage Products to Children in the Region of the Americas.
The Pan American Health Organization (PAHO) Strategic Plan 2020-2025 committed to reduce children's consumption of energy-dense nutrient-poor food and beverage products high in fat, sugar and salt (HFSS) and promote healthy eating patterns to reduce malnutrition in all forms. This paper describes the capacity-building needs in PAHO's Member States to restrict the marketing of HFSS food and beverages to children. We asked Ministries of Health officials or national institutes/departmental representatives (n = 35) to complete a 28-item web-based survey (January to July 2020). Capacity-building needs were assessed using an adapted version of the World Health Organization's government capacity-building framework with three modules: public health infrastructure, policies and information systems. Notable achievements for the PAHO's Plan of Action were identified. State representatives reported strong infrastructure and information systems; however, policy improvements are needed to increase comprehensive national responses. These include using a constitutional health and human rights approach within the policies, policies that document conflict of interest from non-state actors, and strengthening regulatory oversight for digital media platforms. These findings provide baseline data and we suggest priorities for further action to strengthen national governments' capacity-building and to accelerate the development, implementation, and monitoring systems to restrict the marketing of HFSS food and non-alcoholic beverages to children in the region of the Americas.


Augmenting atrazine and hexachlorobenzene degradation under different soil redox conditions in a bioelectrochemistry system and an analysis of the relevant microorganisms.
Soil microbial fuel cells (MFCs) are a sustainable technology that degrades organic pollutants while generating electricity. However, there have been no detailed studies of the mechanisms of pollutant degradation in soil MFCs. In this study, the effects of external resistance and electrode effectiveness on atrazine and hexachlorobenzene (HCB) degradation were evaluated, the performance of soil MFCs in the degradation of these pollutants under different soil redox conditions was assessed, and the associated microorganisms in the anode were investigated. With an external resistance of 20Ω, the degradation efficiencies of atrazine and HCB were 95% and 78%, respectively. The degradation efficiency, degradation rate increased with decreasing external resistance, while the half-life decreased. There were different degradation trends for different pollutants under different soil redox conditions. The fastest degradation rate of atrazine was in the upper MFC section (aerobic), whereas that of HCB was in the lower MFC section (anaerobic). The results showed that electrode effectiveness played a significant role in pollution degradation. In addition, the microbial community analysis demonstrated that Proteobacteria, especially Deltaproteobacteria involved in current generation was extremely abundant (27.49%) on soil MFC anodes, although the percentage abundances of atrazine degrading Rhodocyclaceae (8.77%), Desulfitobacterium (0.64%), and HCB degrading Desulfuromonas (0.73%), were considerably lower. The results of the study suggested that soil MFCs can enhance the degradation of atrazine and HCB, and bioelectrochemical reduction was the main mechanism for the pollutants degradation.


Adductor myocutaneous flap coverage for hip and pelvic disarticulations of sarcomas with buttock contamination.
Hip disarticulation and hemipelvectomy are alternatives to limb-salvage procedures for patients with extensive tumors of the upper thigh and buttocks. In cases when neither the conventional posterior gluteus maximus flap nor the anterior quadriceps flap can be used because of the location of the tumor, a medial adductor myocutaneous flap may be an alternative. The flap is outlined over the anteromedial thigh. The distal extent is at the level of the adductor hiatus. The common femoral vessels and nerve are traced, preserved, and protected. The adductor muscles then are divided above their insertions on the femur and preserved with the flap. En bloc removal of the tumor is performed by either hip disarticulation or hemipelvectomy. The long adductor myocutaneous flap is brought up laterally and proximally to close the wound. We reviewed four patients who underwent a medial adductor myocutaneous flap after either hip disarticulation or hemipelvectomy. The medical records and radiographs were analyzed. These patients were followed up for at least a year or until death. Wide surgical margins were achieved in all four patients and the flap remained viable, with no skin necrosis or flap breakdown. The patients were able to sit on the flap, and one patient was able to wear a prosthesis. In patients undergoing hip disarticulation or hemipelvectomy where tumor infiltration or inadvertent contamination by previous surgery will not allow the traditional posterior gluteus maximus or anterior quadriceps flap, this unconventional medial adductor myocutaneous flap is a feasible, technically simple option. Level IV therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Qualitative assessment of published studies on pulpotomy medicaments for primary molar teeth.
The aim of the present study was to perform a qualitative assessment of published clinical studies, using the Medline database between 2006 and 2016, on commonly used pulpotomy medicaments. Standardized criteria proposed by Fuks and Papagiannoulis in 2006 was used by three independent examiners who assessed a total of 64 studies and graded the papers as grades A (38-42), B1 (32-37), B2 (25-31), or C (<25) based on the score obtained. Dropout rates were calculated based on the initial sample and the final sample used for analysis. Only three papers were grade A, two of which were parts of the same clinical study with results presented at 24 and 42 months, respectively. Twelve papers were graded B1, 19 were graded B2, and 30 were graded C. The quality of evidence seemed greatest for formocresol (2 grade A, 21 grade B), followed by electro surgery (1 grade A study), calcium hydroxide (11 grade B studies), and ferric sulfate (11 grade B studies). The current qualitative assessment clearly highlights the inadequacies in the published studies, especially the study design and clinical and radiographic criteria, thus provides a basis for formulating specific guidelines for researchers embarking on conducting clinical trials on pulpotomy medicaments.


Treatment of large and giant residual and recurrent vestibular schwannomas.
This report is a retrospective analysis of the surgical outcome of 15 patients (8 females, 7 males; mean age, 37.8 years) with residual or recurrent vestibular schwannomas operated on between 1987 and 2005. These 15 patients were part of a larger series of 252 consecutive vestibular schwannoma excisions. Tumors were classified as large (10) when their diameter exceeded 3.5 cm and giant (5) when their diameter exceeded 4.5 cm. All patients had previously undergone surgery. Hearing was lost in all cases, 8 had complete facial nerve palsy, 6 had trigeminal nerve deficits, 5 had cranial nerve IX and X palsy, and 10 had ataxic gait. Twelve patients had hydrocephalus. The tumors were reoperated through the retrosigmoid-transmeatal approach. The mean postoperative follow-up was 4.9 years. Complete resection was achieved in all patients. The facial nerve was preserved in 6 of the 7 patients with preoperative facial function. Transient worsening of bulbar cranial nerves palsy occurred in 2 cases. Cerebrospinal fluid leakage occurred in 3 patients. There were no deaths, and the tumors were histologically benign. Surgical removal is the only treatment for these lesions. Total resection associated with a low morbidity rate is possible. Preservation of the facial nerve is difficult due to severe scar tissue.


Spanish nurses' experiences with personal protective equipment and perceptions of risk of contagion from COVID-19: A qualitative rapid appraisal.
Explore nurses' experiences and perception of risk regarding the use of personal protective equipment during the first wave of the pandemic in Spain. The contribution of our study is to use qualitative methods to understand nurses' experiences and perceptions of the risk of the contagion linked to the shortage of PPE during the first wave of the pandemic, whose explosive start strained health systems around the globe. Qualitative descriptive design according to the Rapid Research Evaluation and Appraisal model. Semi-structured videoconference interviews were conducted to explore the experiences of 29 nurses including staff nurses, nursing supervisors and nursing directors from hospital and community services of the Spanish health system. Interviews lasted 30-45 min and were conducted in May 2020. We carried out a thematic analysis using Dedoose. The COREQ checklist was used to report findings. We identified the following themes and subthemes: 1. Experiences with personal protective equipment: scarcity, inequality, reutilization, self-protection, delegation of responsibility, and gap between protocols and reality; 2. Perception of the risk of contagion: lack of credibility, lack of trust, lack of support, and meeting subjective needs. The scarcity of personal protective equipment and inequality in its distribution led nurses to take initiatives to feel more protected. Mid-ranking supervisors were caught between the responsibility of monitoring and rationing personal protective equipment and providing the necessary protection to nurses. The disjuncture between protocols and the available supply of personal protective equipment caused confusion. Lack of credibility, lack of trust and lack of support from management influenced participants' perception of the risk of contagion. Mid-ranking supervisors were often responsible for trying to alleviate fear among nursing staff. Understanding the factors involved in risk perception can be helpful to decision-makers who help protect nurses in clinical practice. These results can help administrators and policymakers because they point to the need for nurses to feel that their departments and centers look after their safety at work. Transparent communication and emotional support may contribute to their well-being in the face of risk.


Anisotropic optical properties of oriented silver nanorice and nanocarrots in stretched polymer films.
Stretching-induced orientation of both silver nanorice and silver nanocarrots dispersed in or deposited on the surface of poly(vinyl alcohol) (PVA) films was investigated using polarized UV-visible-near-infrared (NIR) spectroscopy and atomic force microscopy (AFM). The results show that the film stretching not only aligns the long axis of individual nanorice or nanocarrots preferentially along the stretching direction, but also induces assembly of these nanostructures into oriented arrays of random lengths in the deformation process. Consequently, the longitudinal surface plasmon resonance peaked at 820 nm for nanorice and 1050 nm for nanocarrots before stretching can be replaced by continuous extinction over the entire 800-1800 nm NIR spectral range after stretching. Stretched PVA films containing either silver nanorice or nanocarrots thus display polarization-dependent transmission of NIR light.


Moving the Target on the Optimal Adjuvant Strategy for Resected Pancreatic Cancers: A Systematic Review with Meta-Analysis.
Combination regimens have shown superiority over single agents in the adjuvant treatment of resected pancreatic cancer (PC), but there are no data supporting definition of the best regimen. This work aimed to compare the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel in PC patients. A meta-analysis was performed for direct comparison between trials comparing combination regimens and gemcitabine monotherapy. Subsequently, an indirect comparison was made between trials investigating the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel because of the same control arm (gemcitabine). A total of three studies met the selection criteria and were included in our indirect comparison. Indirect comparisons for efficacy outcomes showed a benefit in terms of DFS (disease-free survival)/EFS (event-free survival)/RFS (relapse-free survival) for both mFOLFIRINOX versus gemcitabine+capecitabine (HR 0.69, 95% CI 0.52-0.91) and versus gemcitabine+nab/paclitaxel (HR 0.67, 95% CI 0.50-0.90). No significant advantage was registered for OS (overall survival). Indirect comparisons for safety showed an increase in terms of G3-5 AEs (with the exception of neutropenia) for mFOLFIRINOX versus gemcitabine+capecitabine (RR 1.24, 95% CI 1.03-1.50), while no significant differences were observed versus gemcitabine+nab/paclitaxel. According to our results, mFOLFIRINOX is feasible and manageable and could represent a first option for fit PC resected patients.


Effects of Direct-To-Consumer Advertising on Patient Prescription Requests and Physician Prescribing: A Systematic Review of Psychiatry-Relevant Studies.
To systematically analyze the effects of direct-to-consumer advertising (DTCA) on patient requests for medication and physician prescribing across psychiatry-relevant studies. MEDLINE, PsycINFO, Thomson Reuters' ISI Web of Knowledge, and Google Scholar were searched (1999-2014) using variations of the terms direct-to-consumer advertising and psychiatric. Reference lists and an online repository of DTCA manuscripts were also scrutinized. English-language studies collecting data at the point of service, focusing on or including psychiatric medication, and assessing the effects of DTCA on patient and/or physician behavior were included. Of 989 articles identified, 69 received full-text review. Four studies across 5 manuscripts met inclusion criteria. Data were extracted on participants, study design, methodological quality, and results. Methodological quality of individual studies was assessed using adapted criteria from the Effective Public Health Practice Project. Confidence in conclusions across studies was determined using principles from the well-established GRADE system. Due to lack of replication across strong randomized controlled trials (RCTs), no conclusions merited high confidence. With moderate confidence, we concluded that DTCA requests (1) are granted most of the time (1 RCT, 3 observational), (2) prompt higher prescribing volume (1 RCT, 1 observational), (3) promote greater adherence to minimally acceptable treatment guidelines for patients with depression (1 RCT), and (4) stimulate overprescribing among patients with an adjustment disorder (1 RCT). Findings suggest that DTCA requests are typically accommodated, promote higher prescribing volume, and have competing effects on treatment quality. More methodologically strong studies are needed to increase confidence in conclusions.


20-Hydroxyeicosatetraenoic acid is formed in response to EGF and is a mitogen in rat proximal tubule.
Hydroxyeicosatetraenoic acid (20-HETE) is a major cytochrome P-450-arachidonic acid metabolite in the rat kidney, and its synthesis along the nephron is specifically localized to the proximal tubule, where receptor density for epidermal growth factor (EGF) is the highest. EGF stimulated endogenous 20-HETE formation in a concentration and time-dependent manner, i.e., from 1.6 to 2.6 +/- 0.3 and 3.0 +/- 0.6 pmol 20-HETE.mg-1.min-1 at 10(-8) and 10(-7) M EGF, respectively. The effect of 20-HETE on proximal tubular cell proliferation was examined using primary cultures of rat proximal tubular cells and proximal tubular-derived cell lines, LLC-PK1 and opossum kidney OK. In both cell lines, 20-HETE increased thymidine incorporation into DNA with maximal effect at 10(-9) M. Addition of 20-HETE to serum-deprived LLC-PK1 or OK cells for 48 h caused a concentration-dependent increase in cell number with maximal effect at 10(-9) M. This effect was specific, as structurally similar eicosanoids such as 20-COOH-arachidonic acid, 19(R)-HETE, and 19(S)-HETE did not increase cell number. In 4-day primary cultures of proximal tubular cells, EGF (10(-9) M) and 20-HETE (10(-9) M) increased bromodeoxyuridine (BrdU) incorporation by 40 and 28%, respectively. Addition of both resulted in a twofold increase in BrdU incorporation. Although 20-HETE synthesis in cultured cells is greatly diminished with time, significant picomolar concentrations can be obtained in 4-day cultures. Addition of 17-octadecynoic acid (17-ODYA), an inhibitor of 20-HETE synthesis, significantly inhibited EGF-stimulated BrdU incorporation. The demonstrations that EGF stimulates proximal tubular 20-HETE production and that the latter is a potent mitogen to these cells suggests that 20-HETE may act as a mediator of the EGF effect on cellular growth in the proximal tubule.


[A novel protein microarray detection technique based on biotin-avidin conjugation probe].
In this experiment, a novel biotin-avidin conjugation probe was synthesized and employed in the detection of reverse-phase protein microarray. Firstly, the proportion of the biotin-avidin conjugation probe was optimized. Then the rat IgG and goat anti-rat IgG system was served as a model to optimize the fabrication conditions of reverse-phase protein microarray, including the non-specific absorption of streptavidin-Cy3 molecules, spotting buffer as well as protein activities. At last, the biotin-avidin conjugation probe was applied to the detection of the reverse-phase protein microarray. The results show that the protein microarray prepared by using BSA spotting buffer could prevent non-specific absorptions of fluorescent molecules and improve the sensitivity, effectively. In addition, compared with traditional biotin-avidin system, the detection limit could be improved four times using the biotin-avidin conjugation probe. In conclusion, the biotin-avidin conjugation probe has its merits of easy synthesis, low price and could be further conjugated with other signal amplification techniques, which is promising to be used in the detection of protein microarray.


Neural Correlates of Causal Confounding.
As scientists, we are keenly aware that if putative causes perfectly covary, the independent influence of neither can be discerned-a "no confounding" constraint on inference, fundamental to philosophical and statistical perspectives on causation. Intriguingly, a substantial behavioral literature suggests that naïve human reasoners, adults and children, are tacitly sensitive to causal confounding. Here, a combination of fMRI and computational cognitive modeling was used to investigate neural substrates mediating such sensitivity. While being scanned, participants observed and judged the influences of various putative causes with confounded or nonconfounded, deterministic or stochastic, influences. During judgments requiring generalization of causal knowledge from a feedback-based learning context to a transfer probe, activity in the dorsomedial pFC was better accounted for by a Bayesian causal model, sensitive to both confounding and stochasticity, than a purely error-driven algorithm, sensitive only to stochasticity. Implications for the detection and estimation of distinct forms of uncertainty, and for a neural mediation of domain-general constraints on causal induction, are discussed.


Idling time of swimming bacteria near particulate surfaces contributes to apparent adsorption coefficients at the macroscopic scale under static conditions.
Static capillary assays were performed to observe the distribution of Escherichia coli and several mutant strains at the interface between an aqueous solution and a Gelrite particulate suspension, used as a model porous medium. Motile smooth-swimming mutant bacteria (E. coli HCB437) accumulated at the interface, but did not penetrate very far into the Gelrite suspension. Motile wild-type bacteria (E. coli HCB1) penetrated much further than the smooth-swimming mutant, but did not accumulate to the same extent at the interface. Nonmotile tumbly mutant bacteria (E. coli HCB359) did not accumulate or penetrate to a significant degree. Computer simulations using a Monte Carlo algorithm, with input parameters based on bacterial swimming properties in static bulk aqueous systems, appeared to underestimate the bacterial idling time associated with solid surfaces. To account for physicochemical, biological and geometrical influences, an additional component of the bacterial idling time was included. The third component of the idling time was further analyzed semiquantitatively with a 1-D population-scale transport model with first-order association (k(on)) and dissociation (k(off)) adsorption-like kinetics. Computer simulation results suggested that this additional bacterial idling time not only increased the magnitudes of k(on) and k(off), but also enhanced the ratio of k(on) to k(off). This further implies that motile bacteria may tend to accumulate at the boundaries of low-permeable regions in groundwater systems, which is beneficial for bioremediation of residual contamination that may not be accessible by conventional remediation approaches.


[Comparison of flat-panel radiography and computed radiography in urography].
To evaluate the diagnostic value of digital flat-panel radiography in uroradiology the i. v. urograms of patients who had been examined with computed radiography and digital flat-panel radiography were compared regarding image quality. 50 patients who underwent clinically indicated i. v. urography were examined with digital flat-panel radiography and computed radiography. In order to avoid unnecessary double exposure to X-rays, patients were examined either by flat-panel or computed radiography before injection of contrast media. Each further clinically indicated exposure after administration of contrast media was done by alternating the other examination technique. The digital images were compared by 4 radiologists regarding image quality for the detection of defined anatomic structures. Digital flat-panel radiography showed an image quality of the liver, spleen and both kidneys that was similar to computed radiography. The urinary tract, lumbar spine, pelvis and psoas muscle were significantly better visible on flat-panel radiography images. Compared to computed radiography there is no loss of image information by using digital flat-panel radiography in uroradiology. On the contrary, some anatomic structures on abdominal survey images show better image quality. In conclusion, digital flat-panel radiography has the potential to replace computed radiography in uroradiologic examinations.


Comparison of soil quality index using three methods.
Assessment of management-induced changes in soil quality is important to sustaining high crop yield. A large diversity of cultivated soils necessitate identification development of an appropriate soil quality index (SQI) based on relative soil properties and crop yield. Whereas numerous attempts have been made to estimate SQI for major soils across the World, there is no standard method established and thus, a strong need exists for developing a user-friendly and credible SQI through comparison of various available methods. Therefore, the objective of this article is to compare three widely used methods to estimate SQI using the data collected from 72 soil samples from three on-farm study sites in Ohio. Additionally, challenge lies in establishing a correlation between crop yield versus SQI calculated either depth wise or in combination of soil layers as standard methodology is not yet available and was not given much attention to date. Predominant soils of the study included one organic (Mc), and two mineral (CrB, Ko) soils. Three methods used to estimate SQI were: (i) simple additive SQI (SQI-1), (ii) weighted additive SQI (SQI-2), and (iii) statistically modeled SQI (SQI-3) based on principal component analysis (PCA). The SQI varied between treatments and soil types and ranged between 0-0.9 (1 being the maximum SQI). In general, SQIs did not significantly differ at depths under any method suggesting that soil quality did not significantly differ for different depths at the studied sites. Additionally, data indicate that SQI-3 was most strongly correlated with crop yield, the correlation coefficient ranged between 0.74-0.78. All three SQIs were significantly correlated (r = 0.92-0.97) to each other and with crop yield (r = 0.65-0.79). Separate analyses by crop variety revealed that correlation was low indicating that some key aspects of soil quality related to crop response are important requirements for estimating SQI.


Different paradigms of transcranial electrical stimulation induce structural changes in the CA1 region of the hippocampus in a rat model of Alzheimer's disease.
One of the prominent sign of Alzheimer's disease (AD) is structural changes in the hippocampus. Recently, the new methods used to treat this disease is transcranial electrical stimulation (tES). This study evaluated the effect of four primary standards of tES, including tDCS, tACS, tRNS, and tPCS on beta-amyloid 25-35 (Aβ25-35)-induced structural changes in the CA1 region of hippocampus in male rats. For this purpose, rats weighing 250-275 g were selected, the cannula was embedded reciprocally into the hippocampi. Aβ25-35 (5 μg/ 2.5 ml/ day) was infused reciprocally for four continuous days.Then, animals were then given tES for 6 days.Subsequently, structural changes in the hippocampal CA1 were evaluated using the stereological method. Aβ25-35 resulted in loss of neurons (P < 0.01) and decreased hippocampal volume (P < 0.05). However, the administration of tES paradigms prevented these changes. The results proposed that through the improvement of hippocampal cell number and volume, tES paradigms can retain efficiency in remediating structural impairments in AD. From this, it can be concluded that other tES paradigms besides tDCS can also be considered for the treatment of AD.


[Managed care--a possibility for German Health Insurance?].
Health services systems in nearly all developed countries face similar problems. This fact raises the question whether concepts used in different countries can be changed without affecting the historically grown foundations of national health services as have been accepted by majority. A group of experts of the German Medical Services of the Statutory Health Insurance were asked to analyse whether the managed care approach could play a substantial role in reforming the German "Bismarck model", given that the advisory responsibility of the social medical service for the sick funds is respected in such a consideration and that basic essentials of the system are maintained. The group concludes, in brief, that managed care and the "German model" are contradictory in respect of preconditions, aims and assumed results. Furthermore, the experts share the view that the "German model" incorporates sufficient to cope with its problems without changing the nature of health services, based on principles of solidarity in Germany. The system needs structural reforms rather than changes in monetary mechanisms.


Turbulence and capillary waves on bubbles.
We present a link between the theory of deep water waves and that of bubble surface perturbations. Theory correspondence is shown analytically for small wavelengths in the linear regime and investigated numerically in the nonlinear regime. To do so, we develop the second-order spatial perturbation equations for the Rayleigh-Plesset equation and solve them numerically. Our code is publicly available. Studying capillary waves on stable bubbles, we recreate the Kolmogorov-Zakharov spectrum predicted by weak turbulence theory, putting wave turbulence theory to use for bubbles. In this investigation, it seems that curvature does not affect turbulent properties. The calculated bubble surface responds qualitatively to low gravity experiments. The link demonstrated opens new possibilities for studying several bubble phenomena, including sonoluminescence and cavitation, using the extensive tools developed in the wave turbulence framework.


Five conversations: reflections of stakeholders on the impact of the ethnocultural communities facing AIDS study.
This paper reports on issues identified in conversations held between one of the Ethnocultural Communities Facing AIDS Study (ECFA) investigators and five stakeholders associated with this experiment in collaborative and participatory research. The stakeholders reflect on their experiences in partnering with university-based researchers, resistance in ethnocultural communities to being researched, and the next steps implicated by the research in question. The problem of HIV/AIDS in ethnocultural communities in Canada is, relative to the mainstream, also viewed as a symbol of disadvantage in these communities. The stakeholders suggest that to address these deeper concerns, there must be vital, dynamic, and enduring communication between researchers, community representatives, and government at all levels, in the process of identifying solutions and implementing them in the present.


Non-invasive brain stimulation in Stroke patients (NIBS): A prospective randomized open blinded end-point (PROBE) feasibility trial using transcranial direct current stimulation (tDCS) in post-stroke hemispatial neglect.
Up to 80% of people who experience a right-hemisphere stroke suffer from hemispatial neglect. This syndrome is debilitating and impedes rehabilitation. We carried out a clinical feasibility trial of transcranial direct current stimulation (tDCS) and a behavioural rehabilitation programme, alone or in combination, in patients with neglect. Patients >4 weeks post right hemisphere stroke were randomized to 10 sessions of tDCS, 10 sessions of a behavioural intervention, combined intervention, or a control task. Primary outcomes were recruitment and retention rates, with secondary outcomes effect sizes on measures of neglect and quality of life, assessed directly after the interventions, and at 6 months follow up. Of 288 confirmed stroke cases referred (representing 7% of confirmed strokes), we randomized 8% (0.6% of stroke cases overall). The largest number of exclusions (91/288 (34%)) were due to medical comorbidities that prevented patients from undergoing 10 intervention sessions. We recruited 24 patients over 29 months, with 87% completing immediate post-intervention and 67% 6 month evaluations. We established poor feasibility of a clinical trial requiring repeated hospital-based tDCS within a UK hospital healthcare setting, either with or without behavioural training, over a sustained time period. Future trials should consider intensity, duration and location of tDCS neglect interventions.Trial registration: ClinicalTrials.gov identifier: NCT02401724.


Development, utilisation, and importance of accident and emergency department derived assault data in violence management.
To develop formal processes for the collection, disclosure, and effective use of accident and emergency (A&E) department derived assault injury data for city violence reduction. Over a four year period, managed by a multi-agency steering group, A&E data collection, collation, and disclosure processes were developed, instituted, and refined. Consultations and negotiations between agencies identified the most effective and ethical methods, appropriate recipients, and the nature of the information of most use. Disclosure of A&E data to city authorities, the police, and local media drew substantial attention and crime prevention resources to the locations of violence. As a result, a police task force responsible for targeting city street crime was funded, which analysed both A&E and police information. Monthly, electronic transfer of raw, anonymous data to the task force crime analyst informed and prompted violence prevention initiatives by several agencies. Police mounted overt and covert interventions targeted at violence hotspot licensed premises and used the data to oppose, on injury grounds, drinks/entertainment licence applications. Transport authorities established new half hourly night time city centre bus services. The local authority mounted an assault awareness campaign in schools and public libraries, and licensing magistrates used the data to measure, for example, the impact of continuous 36 hour drinks licensing on public safety. The principal finding of this evaluation was that judicious sharing of unique information about locations and times of violence derived from A&E patients was a powerful and effective means of targeting police and other local resource to bring about violence reduction.


The influence of donor age, nerve growth factor, and cografting with drosophila cells on survival of peripherally grafted embryonic or fetal rat dorsal root ganglia.
Previous studies have shown that embryonic rat and human dorsal root ganglion (DRG) cells survive grafting to the cavity of extirpated adult rat DRG. Furthermore, grafted human embryonic neurons were shown to send axons peripherally and into the spinal cord, where they establish functional synaptic connections. This study analyzed the survival of orthotopically allografted rat DRG cells from embryonic stages 15 (E15) and 20 (E20), and the influence on their survival of nerve growth factor (NGF). NGF was delivered to the DRG transplants either by pump infusion or by cotransplantation of cells from Drosophila melanogaster, transgenic for human NGF. Lumbar DRGs of adult rats were removed and a collection of E15 or E20 DRGs placed in the cavity. One month after grafting the total number of DRG cells in the grafts was counted. Differentiation of subpopulations of DRG cells was estimated by counting cells immunostained for calcitonin gene-related peptide (CGRP), Griffonia simplicifolia agglutinin isolectin B4 (GSA), or heavy neurofilament protein (antibody RT97). The results show: i) similar survival of E15 and E20 grafts, with great variability in the survival of different subpopulations in E15 transplants, but a more consistent distribution of different phenotypes in E20 transplants; ii) infusion of NGF for 2 weeks increases the survival of E15 transplants, but has a negative effect on E20 transplants; iii) Drosophila cells transfected with human NGF gene survive peripheral xenografting and have a positive effect on the survival of the GSA- and CGRP-positive populations in E15 and E20 transplants; iv) Drosophila cells without the human NGF gene increase cell survival in E20 transplants. These data suggest that i) the effect of NGF is dependent on the embryonic stage of the transplants, ii) age-dependent sensitivity to NGF influences graft survival, and iii) transgenic Drosophila cells can be cotransplanted with embryonic neural tissue to the mammalian peripheral nervous system with a positive effect on the survival of neural grafts.


An investigation of the effect of trauma script exposure on risk-taking among patients with substance use disorders and posttraumatic stress disorder.
Studies show that patients with substance use disorders (SUD) and posttraumatic stress disorder (PTSD) are at high risk for engaging in risky behaviors. However, these studies do not speak to the context in which these behaviors are more likely to occur. This study examined whether SUD patients with current PTSD, compared to those without a history of PTSD, are more likely to exhibit risk-taking on a laboratory-based risk-taking task, the Iowa Gambling Task (IGT), following exposure to a personalized trauma script versus a neutral script. The sample consisted of 122 trauma-exposed SUD patients with and without PTSD. Participants were administered a series of diagnostic interviews and personalized trauma scripts were created. On separate days, participants were exposed to a neutral or trauma script, followed by the IGT. Contrary to expectations, PTSD-SUD patients exhibited significantly greater risk-taking after the neutral (vs. trauma) script than those without PTSD. Moreover, whereas SUD patients without PTSD evidenced stability in IGT performance across scripts, those with PTSD exhibited significantly lower risk-taking on the IGT following the trauma (vs. neutral) script. Results provide support for the context dependent nature of risk-taking in PTSD-SUD patients and suggest they may become more risk averse in the context of trauma-related distress.