Structural properties of the synchronized cluster on complex networks.
We investigate how the largest synchronized connected component (LSCC) is formed and evolves to achieve a global synchronization on complex networks using Kuramoto model. In this study we use two different networks, Erdösi-Rényi network and Barabási-Albert network. From the finite-size scaling analysis, we find that the scaling exponents for the percolation order parameter and mean cluster size on both networks agree with the mean-field percolation theory, beta=gamma=1. We also find that the finite-size scaling exponent, nu, also agrees with the mean-field percolation result, nu=3. Moreover, we also show that the cluster size distributions are identical with the mean-field percolation distribution on both networks. Combining with the analysis for the merging clusters, we directly show that the LSCC on both networks evolves by merging clusters of various sizes.


TRANSPARENT TESTA2 regulates embryonic fatty acid biosynthesis by targeting FUSCA3 during the early developmental stage of Arabidopsis seeds.
TRANSPARENT TESTA2 (TT2) regulates the biosynthesis of proanthocyanidins in the seed coat of Arabidopsis. We recently found that TT2 also participates in inhibition of fatty acid (FA) biosynthesis in the seed embryo. However, the mechanism by which TT2 suppresses the accumulation of seed FA remains unclear. In this study, we show that TT2 is expressed in embryos at an early developmental stage. TT2 is directly bound to the regulatory region of FUSCA3 (FUS3), and mediates the expression of numerous genes in the FA biosynthesis pathway. These genes include BCCP2, CAC2, MOD1 and KASII, which encode proteins involved in the initial steps of FA chain formation, FAD2 and FAD3, which are responsible for FA desaturation, and FAE1, which catalyzes very-long-chain FA elongation. Loss of function of TT2 results in reduced expression of GLABRA2 but does not cause a significant reduction in the mucilage attached to the seed coats, which competes with FA for photosynthates. TT2 is expressed in both maternal seed coats and embryonic tissues, but proanthocyanidins are only found in wild-type seed coats and not in embryonic tissues. The amount of proanthocyanidins in the seed coat is negatively correlated with the amount of FAs in the embryo.


Granulomatosis with polyangiitis involving the epiglottis.
Granulomatosis with polyangiitis (GPA) frequently involves the upper respiratory tracts, but involvement of the epiglottis is extremely rare. This report describes a patient initially presenting with dysphagia and increasing stridor due to epiglottitis. Bronchoscopy showed swelling of the epiglottis with partly whitish nodular lesions, with biopsy specimens showing neutrophil infiltration and necrosis. Chest computed tomography showed multiple nodular consolidations in the bilateral lung parenchyma, and histological findings were consistent with vasculitis. The patient was diagnosed with GPA and responded well to treatment with prednisolone and cyclophosphamide. Although an uncommon manifestation, GPA should be included in the differential diagnosis of epiglottitis, especially in patients with lung parenchymal lesions suggestive of GPA.


DNA fragmentation in rat brain after intraperitoneal administration of kainate.
Cell death occurs in many neuropathological conditions. However, the mechanisms governing this process(es) remain generally unknown. In this report we studied whether excitotoxic neuronal death evoked by kainic acid (KA) in rat brain is associated with ladder-like DNA fragmentation. DNA was isolated from hippocampi, entorhinal and sensory cortices at various times following intraperitoneal KA (10 mg kg-1) injections. Typical oligonucleosome-sized DNA fragmentation was observed in all three structures at 18 h and 72 h following KA administration. These findings were further confirmed by in situ nick-translation. DNA fragmentation is believed to be diagnostic for apoptosis. The clear ladders of DNA fragmentation appeared after 18 h, although slight degradation was observed as early as 12 h after KA administration.


Primary Ovarian Insufficiency: Current Concepts.
A potential consequence of chemotherapy is the destruction of oocytes, resulting in primary ovarian insufficiency (POI) in young patients; this often results in secondary amenorrhea and necessitates hormone replacement therapy. Regardless of the etiology of POI, the chance of pregnancy is low in this patient population. Given the extent to which oocyte depletion or dysfunction is variable, there is the possibility of spontaneous ovulation on hormone replacement therapy and subsequent pregnancy, however. If pregnancy is not desired, contraception always should be discussed. In most patients, the etiology of POI will not be known, but the treatment for all patients includes estrogen and progesterone therapy, which ensures the development of secondary sex characteristics, acquisition of peak bone mass, and promotion of uterine growth and maturation. Early diagnosis, patient education, and emotional support are important to mitigate long-term sequelae.


Multiple hemangiomas involving the vertebral column.
Hemangiomas are benign, slow-growing skeletal and soft tissue tumors that commonly involve the bony spine. When found in the spine, they are usually asymptomatic, but can sometimes be associated with local pain and/or neurological deficits. We report the case of a middle-aged Indian male with multiple hemangiomas involving almost all the vertebrae contiguously from C2 to S1 vertebral levels. These were discovered incidentally when a magnetic resonance scan was performed for backache. To the best of our knowledge, such extensive involvement of the spine has not been reported previously.


Risperidone-induced mania: An emergent complication of treatment.
The occurrence of manic/hypomanic switch in patients being treated with risperidone has been reported by various authors, and they have described a variety of strategies for their management. In this report, we describe two cases of induction of elevated mood symptoms in patients treated with risperidone. We propose that the emergence of these symptoms may be a complication of treatment with this drug in susceptible individuals, of which the clinicians should be aware, mainly in those diagnosed with schizophrenia and bipolar disorder. We then discuss a few findings that might be useful in the management of such cases. We thereby also propose a mechanism for such an induction.


Bartonella henselae infection associated with autoimmune thyroiditis in a child.
Bartonella henselae was discovered a quarter of a century ago as the causative agent of cat-scratch disease. More recently, Bartonella has been found to be responsible for a broad range of clinical syndromes (prolonged fever, hepatosplenic disease, encephalopathies, ocular disease) and associated with autoimmune conditions. This is the first report of autoimmune thyroiditis related to B. henselae infection. We describe an 11-year-old boy who presented with goiter and weight loss. At the time of admission a 2 × 1 cm mildly tender right supraclavicular lymph node was noted in association with an erythematous papule at the same side of the neck. We describe an association of autoimmune hyperthyroidism (Hashitoxicosis) with B. henselae infection (cat-scratch disease) in a pediatric patient. Different types of infections are implicated in the pathogenesis of autoimmune thyroid disease through molecular mimicry or other mechanisms, despite their role is disputed. We speculated that autoimmune thyroiditis should be added to the spectrum of clinical syndromes that can be triggered by B. henselae.


Cytoskeleton vimentin disruption of mouse sertoli cells injured by nitrogen mustard in vitro.
Reproductive toxicity is one of the potential side effects of anticancer alkylating agents, with potential effects on vimentin intermediate filaments, one of the main components of the Sertoli cytoskeleton. Research suggests (Aumuller et al, 1988; Aumuller et al, 1992) that the highly organized and active Sertoli cytoskeleton is important in spermatogenesis. The aim of the current study was to investigate the effects of alkylating agents on vimentin filament expression in vitro. Sertoli cells, isolated from 20-day-old mice testes, were cultured for 5 days and then incubated with 0, 50, 100, and 200 micromol/L nitrogen mustard (HN2). Morphologic changes in Sertoli cells were observed per 30-minute interval at 12-hour exposure time points to 100 micromol/L HN2. Vimentin expression was investigated by immunocytochemistry at 6 hours and 24 hours posttreatment and reverse transcriptase polymerase chain reaction and Western blot at 12 hours posttreatment with 50, 100, and 200 micromol/L HN2. Exposure to HN2 resulted in a comparatively small Sertoli cell body with diminished cytoplasm. Sertoli cells were shrunk or detached. Cytoskeletal disruption increased with increasing HN2 concentration. The optical density values of vimentin antibody and expression of vimentin mRNA and protein were significantly decreased with increasing concentration of HN2. Significant treatment dose-dependent and time-dependent differences of vimentin mRNA and protein expression levels were also noted. Our data suggest that the change in the biochemical properties of vimentin may indicate that one of the mechanisms of reproductive toxicity resulting from HN2 is disruption of Sertoli cell vimentin filament structure, accompanied by a down-regulation of vimentin expression.


Reconfiguration of a smart surface using heteroclinic connections.
A reconfigurable smart surface with multiple equilibria is presented, modelled using discrete point masses and linear springs with geometric nonlinearity. An energy-efficient reconfiguration scheme is then investigated to connect equal-energy unstable (but actively controlled) equilibria. In principle, zero net energy input is required to transition the surface between these unstable states, compared to transitions between stable equilibria across a potential barrier. These transitions between equal-energy unstable states, therefore, form heteroclinic connections in the phase space of the problem. Moreover, the smart surface model developed can be considered as a unit module for a range of applications, including modules which can aggregate together to form larger distributed smart surface systems.


A Longitudinal Analysis of Stepfamily Relationship Quality and Adolescent Physical Health.
Approximately one third of youth are estimated to live with a biological parent and stepparent before reaching adulthood. Additional research is warranted whereby stepfamily processes are identified that drive variation in youth adjustment, particularly physical health. We examined stepfather-child, mother-child, and stepcouple relationship quality as predictors of levels and changes in adolescent physical health over time. We used a nationally representative sample of 1,233 adolescents living in biological mother-stepfather families from waves I (1994-1995) and II (1996) of the National Longitudinal Study of Adolescent to Adult Health. We incorporated measures of stepfather-child, mother-child, and stepcouple relationship quality, as well as adolescent reports of 10 physical health symptoms at waves I and II. Structural equation modeling was used to examine associations between wave I stepfamily relationships and adolescent physical symptoms at waves I and II. We used a zero-inflated negative binomial model to establish the validity of wave II adolescent physical symptoms as a predictor of an index of diagnosed chronic illnesses by wave IV (ages 26-32 years). Stepfather-child and mother-child relationship quality were negatively correlated with concurrent levels of adolescent physical symptoms. Stepfather-child relationship quality was negatively associated with change in adolescent physical symptoms over time. Adolescents with higher levels of physical symptoms at wave II were more likely to report chronic illnesses by adulthood. Stepfather-child relationship quality is a robust predictor of adolescent physical health throughout adolescence and is linked to chronic illness diagnoses in young adulthood. Future research should explore further the mechanisms that underlie this association.


Alterations in cellular retinol metabolism contribute to differential retinoid responsiveness in normal human mammary epithelial cells versus breast cancer cells.
The present study was undertaken to compare ROH growth responsiveness between normal human mammary epithelial cells (HMECs), estrogen receptor positive (MCF-7) and negative (MDA-MB-231) breast cancer cells, and assess whether this responsiveness is correlated with differences in ROH metabolism, particularly RA synthesis. HMECs were markedly more growth sensitive to a physiological dose of ROH than breast cancer cells, exhibiting a significant decrease in cell number by 48h and >70% decrease by 144h. In comparison, numbers of MCF-7s were only decreased 32% by 144h. MDA-MB-231 cells were not affected. However, HMECs and MCF-7 cells displayed similar growth responsiveness to 1 microM RA, while MDA-MB-231 cells were minimally affected. Although the initial rates and extent of ROH uptake were comparable among cell types, ROH levels in HMECs progressively decreased to 20% of the peak by 24h and < or = 10% by 72h. In contrast, ROH levels in the cancer cells remained relatively constant through 48 h. The decrease in HMEC ROH was attributable to greater metabolism as evidenced by rapid and predominant retinyl ester formation. HMECs also produced approximately 5 times more RA from ROH than MCF-7s and approximately 10 times more than MDA MB-231 cells. Our results demonstrate that normal HMECs are markedly more responsive to the growth inhibitory effects of ROH than breast cancer cells, and that this responsiveness is associated with greater ROH metabolism including greater RA synthesis. These data suggest that altered ROH metabolism may be a factor in breast cancer progression.


Seeking care for epilepsy and its impacts on households in a rural district in southern Malawi.
Epilepsy is a disability as defined in the 2012 Disability Act of the Government of Malawi. This article explores the health-seeking behaviour of people with epilepsy in a rural town in southern Malawi and how having a person with epilepsy impacts on the households' productivity. A snowball approach was used to identify persons with various forms of disabilities. The article is based on a bigger study carried out in Malawi which explored how persons with disabilities seek health care. In this bigger study, a total of 63 interviews were done with persons with disabilities or their guardians. Eight of the 63 interviews were with persons with epilepsy and this article is based on these interviews. The study found that persons with epilepsy seek both traditional and modern medicines to treat the condition. Informants mentioned that barriers to accessing western treatment include lack of medicines, congestion at health facilities, lack of knowledge about epilepsy, misdiagnosis by health workers and the belief that epilepsy caused by witchcraft cannot be treated by western medicine. The study also highlights the wider impacts of epilepsy on the household such as the failure of children to attend school, children dropping out of school, stigma and discrimination and households being driven deeper into poverty as a result of seeking care for members with epilepsy. The existing barriers to accessing treatment for epilepsy can be addressed by using a combination of public education, simple treatments and regular reviews. Ensuring constant availability of drugs for the treatment of epilepsy is key to effective treatment of the condition. This would contribute to closing the treatment gap for epilepsy as advocated by the Global Campaign against Epilepsy.


Cold stress reduces the acquisition of colostral immunoglobulin in piglets.
One-hundred and fourteen piglets were utilized in two experiments designed to determine the effect of a single or intermittent exposure to cold air on the acquisition of colostral gamma globulin. Piglets were allotted before nursing according to weight and sex to a thermoneutral (36 C) or a cold (10 C) treatment group. After nursing, gamma globulin in serum increased in both thermoneutral and cold-stressed piglets. However, the single 2.5-hr cold exposure near birth lowered (P less than .01) gamma globulin concentrations in serum at 14.5 hr of age and tended (P less than .10) to lower immunoglobulin levels at 24, 36 and 48 hr after thermal treatment. In the second experiment, three intermittent 1-hr exposures to 10 C during the first 15 hr of life consistently lowered serum gamma globulin by comparison with concentrations in the serum of piglets held at thermoneutrality (36 C), but these differences were not significant. Piglets dying before 21 days had lower (P less than .10 and P less than .01, Exp. 1 and Exp. 2, respectively) gamma globulin concentrations in the serum during the first day of life than did those piglets that survived. These data indicate that a single 2.5-hr exposure to cold air temperatures at birth reduces the subsequent acquisition of colostral immunoglobulin. A reduction in the amount of antigen-specific antibody from colostrum may contribute to preweaning mortality among young pigs.


The SOCS box domain of SOCS3: structure and interaction with the elonginBC-cullin5 ubiquitin ligase.
Suppressor of cytokine signalling 3 (SOCS3) is responsible for regulating the cellular response to a variety of cytokines, including interleukin 6 and leukaemia inhibitory factor. Identification of the SOCS box domain led to the hypothesis that SOCS3 can associate with functional E3 ubiquitin ligases and thereby induce the degradation of bound signalling proteins. This model relies upon an interaction between the SOCS box, elonginBC and a cullin protein that forms the E3 ligase scaffold. We have investigated this interaction in vitro using purified components and show that SOCS3 binds to elonginBC and cullin5 with high affinity. The SOCS3-elonginBC interaction was further characterised by determining the solution structure of the SOCS box-elonginBC ternary complex and by deletion and alanine scanning mutagenesis of the SOCS box. These studies revealed that conformational flexibility is a key feature of the SOCS-elonginBC interaction. In particular, the SOCS box is disordered in isolation and only becomes structured upon elonginBC association. The interaction depends upon the first 12 residues of the SOCS box domain and particularly on a deeply buried, conserved leucine. The SOCS box, when bound to elonginBC, binds tightly to cullin5 with 100 nM affinity. Domains upstream of the SOCS box are not required for elonginBC or cullin5 association, indicating that the SOCS box acts as an independent binding domain capable of recruiting elonginBC and cullin5 to promote E3 ligase formation.


[Epidemiology of Haemophilus influenzae type b infections (excluding meningitis) in 2 French departments].
The spectrum of severe Haemophilus influenzae type b disease exclusive of meningitis includes: epiglottitis, pneumonia, arthritis, septicemia, cellulitis and pericarditis. The results of a 7 year-epidemiologic study (Jan 1980 to Dec 1986) performed in 2 French departments are reported. Sixty-nine cases were detected, representing a yearly rate of 9/100,000 children aged 0 to 4 years. The real incidence is probably higher and was estimated as 11/100,000. In all of France, it corresponds to 382 annual cases and, more specifically to 60 to 70 annual cases of epiglottitis. No deaths were recorded and only 2 cases with minor sequelae were documented in this series. These results, as compared with those of previous studies, show that the incidence is lower than that in other countries, especially with regard to epiglottitis which is more frequent in North America and in Scandinavian countries.


The use of magnetic resonance imaging in diagnosing equine deep digital flexor tendinopathies--own experience.
Deep digital flexor tendinopathy is a common problem in horses of different athletic disciplines. Nowadays, the use of magnetic resonance imaging is considered to be a noninvasive and superior choice for recognizing bone and soft tissue pathologies especially related to difficult to access structures within the hoof capsule.


Female genital mutilation -- an exported medical hazard.
Female circumcision (FC) has remained a common practice in the countries where it has traditionally been performed. Following increased global mobility, it has also become a common medical issue in the predominantly non-Islamic countries where an increasing number of immigrants from regions where FC is still traditional, have settled. To investigate types of FC found in a group of immigrants from northern Africa with a current domicile in Scandinavia. To characterize these women with regard to education, socio-economic status and experienced complications and sequelae. To report attitudes to FC among the women and their husbands. An autoquestionnaire was distributed to 220 immigrant women (16-42 years old), who belonged to an African community in Scandinavia and who had all been circumcised. Information was also gathered concerning 76 of their daughters (aged 1-13 years). Of the women's husbands, 95 were asked about their attitudes to FC. Of the 140 women, who had been circumcised in their home country before they migrated, 78 (35%) had been clitoridectomized, 38 (17%) had been subjected to genital excision and 24 (11%) to infibulation. The corresponding percentages in the remaining women, who had had FC when returning home for a visit, were 0%, 14% and 22%, respectively. Of the daughters, 15 (19%) had been circumcised whilst living in Scandinavia; all had been clitoridectomized. Twenty-eight (13%) women reported having experienced late complications or post-FC sequelae. A positive attitude to stopping the tradition of FC was reported twice as often by the husbands (69%) as by the circumcised women (35%). Religion (95% of the responders were Muslims and 5% Christians), cultural tradition, and increased chance of marriage or of continued health were the reasons put forward in favor of the continuation of FC by 58%, 27%, 10% and 4 %, respectively. Five per cent could not supply an opinion. FC is performed in immigrant women even after settling in areas where this practise is legally banned. Circumcised immigrant women experience medical and sexual problems which have to be dealt with in their new domicile country. Many African Islamic women, who have migrated to Scandinavia, seem still to be in favour of the continuation of circumcision for varying reasons.


[Subungual glomus tumor. A case of unusual form].
The authors report a case of glomus tumour developing beneath the nail of the ring finger in a 95 year old woman. In contrast with other similar cases, the pain was moderate and had been present for 20 years. The bony phalanx was deformed. Microscopic examination confirmed the diagnosis of a glomus tumour developing in the soft tissues. The phalanx was amputated.


Y chromosome mediates ribosomal DNA silencing and modulates the chromatin state in Drosophila.
Although the Drosophila Y chromosome is degenerated, heterochromatic, and contains few genes, increasing evidence suggests that it plays an important role in regulating the expression of numerous autosomal and X-linked genes. Here we use 15 Y chromosomes originating from a single founder 550 generations ago to study the role of the Y chromosome in regulating rRNA gene transcription, position-effect variegation (PEV), and the link among rDNA copy number, global gene expression, and chromatin regulation. Based on patterns of rRNA gene transcription indicated by transcription of the retrotransposon R2 that specifically inserts into the 28S rRNA gene, we show that X-linked rDNA is silenced in males. The silencing of X-linked rDNA expression by the Y chromosome is consistent across populations and independent of genetic background. These Y chromosomes also vary more than threefold in rDNA locus size and cause dramatically different levels of PEV suppression. The degree of suppression is negatively associated with the number and fraction of rDNA units without transposon insertions, but not with total rDNA locus size. Gene expression profiling revealed hundreds of differentially expressed genes among these Y chromosome introgression lines, as well as a divergent global gene expression pattern between the low-PEV and high-PEV flies. Our findings suggest that the Y chromosome is involved in diverse phenomena related to transcriptional regulation including X-linked rDNA silencing and suppression of PEV phenotype. These results further expand our understanding of the role of the Y chromosome in modulating global gene expression, and suggest a link with modifications of the chromatin state.


Cathode Interface Compatibility of Amorphous LiMn2O4 (LMO) and Li7La3Zr2O12 (LLZO) Characterized with Thin-Film Solid-State Electrochemical Cells.
Solid-state lithium-ion batteries are a hopeful successor to traditional Li-ion cells that use liquid electrolytes. While a growing body of work has characterized the interfaces between various solid electrolytes and the lithium metal, interfaces with common cathode intercalation compounds are comparatively less understood. In this contribution, the influence of polarization and temperature on interfacial stability between LiMn2O4 (LMO) and Li7La3Zr2O12 (LLZO) are investigated. Sputtered thin-film LMO electrodes are utilized to permit high-capacity cycling while retaining a large ratio of interfacial area to electrode bulk. Electrochemical impedance spectroscopy (EIS) is compared across a set of full (LMO|LLZO|Li) and symmetric (LMO|LLZO|LMO, Li|LLZO|Li, and Au|LLZO|Au) cells to delineate impedance features that are specific to the evolution of the cathode interface. Additional X-ray photoelectron spectroscopy (XPS) provides evidence of a limited interfacial reaction between LMO and LLZO that coincides with an increase in the impedance of the LMO-LLZO interface.


[Fetal dystrophy--one of the feature of Turner syndrome].
Turner's syndrome is one of the most frequent diseases with accompanying growth deficiency, the developmental disorders being observed as early as in the fetal period. To determine the body mass of Turner's syndrome newborns delivered at term. A total of 474 female newborns with Turner's syndrome were studied, the pregnancies, mostly second ones, lasting 40 weeks on average but not less than 38 weeks. Turner's syndrome was confirmed by chromosome analysis. Body mass at birth (BM) was related to the norms for gestational age (GA) designed by Usher and McLean. Newborns, whose BM was lower than -2 SD for GA, were considered as small for gestational age (SGA). Mean body mass (+/-SD) at birth was 2963 +/- g and in 87% of newborns was below the normal value for gestational age. Mean body mass deficiency amounted to 611 g, but in 20% of newborns exceeded 1000 g. In 19% of newborns body mass was below -2 SD for gestational age which classified intrauterine dystrophy as one of the most frequent features of the Turner's syndrome. It might, furthermore, imply that intrauterine dystrophy could be associated with impaired gene expression, presumably on the X-chromosome.


Surgical correction of retinal folds involving the fovea.
Retinal folds are a rare complication after retinal detachment repair. Surgery is required if the fovea is involved. There are few surgical reports in the literature, describing various surgical approaches. The authors employed a surgical technique to treat retinal folds involving the fovea in a 59-year-old woman. Perimacular subretinal blebs were created with a 41-gauge cannula in conjunction with fluid-air exchange to coalesce the fluid at the macula. Perfluorocarbon liquid was injected to flatten the retina, and subretinal fluid drainage was performed through a peripheral retinotomy. The macula was successfully unfolded during surgery. Visual acuity improved from 20/800 to 20/50. After 3 months, mild changes at the outer nuclear layer were observed on optical coherence tomography, and autofluorescence showed tracks of hypoautofluorescence where the forced infusion of liquid started. The authors describe an effective surgical approach for the correction of retinal folds involving the fovea. Prompt treatment as well as gentle surgical manipulation are key points to obtain an improvement in visual acuity.


[Clinical, neurophysiologic and biopsy findings in neurotoxic amiodarone syndrome].
Three patients complained of proximal weakness and paraesthesia of the legs and difficulties in walking during amiodarone treatment. Examination showed signs of a predominantly distal sensory neuropathy, a proximal myopathy, and a cerebellar gait disorder. All had amiodarone dosages of 600 mg per day, amiodarone serum levels above 2.7 mg/l and a total amount of amiodarone ingestion of 300 to 500 g. The clinical symptoms subsided within six to eleven months after treatment was stopped. The neurophysiologic investigations showed slowing of sensory and motor nerve conduction velocities with dissociation of the action potentials and delay of SEP latencies. With discontinuation of the drug these abnormalities were progressive in one patient. The biopsy (muscle, nerve and skin) in the most severely affected patient showed numerous intracellular lysosomal inclusions in cells of different tissues. It is supposed that the storage of amiodarone in muscle cells results in a predominantly proximal myopathy whereas storage in Schwann cells results in a secondary neuropathy. A similar storage in Purkinje cells may be responsible for the cerebellar gait disorder. The clinical picture should be termed a neurotoxic amiodarone syndrome rather than amiodarone neuropathy.


Effects of chloroplast-cytoplasm exchange and lateral mass transfer on slow induction of chlorophyll fluorescence in Characeae.
Rapid cytoplasmic streaming in characean algae mediates communications between remote cell regions exposed to uneven irradiance. The metabolites exported from brightly illuminated chloroplasts spread along the internode with the liquid flow and cause transient changes in chlorophyll fluorescence at cell areas that are exposed to dim light or placed shortly in darkness. The largest distance to which the photometabolites can be transported has not yet been determined. Neither is it known if lateral transport has an influence on the induction of chlorophyll fluorescence. In this study, the relations between spatial connectivity of anchored chloroplasts in characean internodes and fluorescence induction curves were examined. Connectivity between remote cell parts was pronounced upon illumination of a cell spot at a distance up to 10 mm from the area of fluorescence measurement, provided the spot was located upstream in the cytoplasmic flow. Spatial interactions between distant cell sites were also manifested in strikingly different slow stages of fluorescence induction caused by narrow- and wide-field illumination. Cytochalasin D, cooling of bath solution, and inactivation of light-dependent envelope transporters were used to disturb cyclosis-mediated spatial interactions. Although fluorescence induction curves induced by narrow- and wide-field illumination differed greatly under control conditions, they became similar after the inhibition of cyclosis with cytochalasin D. The results indicate that cytoplasmic streaming not only drives the lateral translocation of photometabolites but also promotes the export of reducing power from illuminated chloroplasts due to flushing the chloroplast surface and keeping sharp concentration gradients.


Transition readiness of youth with co-occurring chronic health and mental health conditions: A mixed methods study.
A large proportion of youth with chronic conditions have mental health comorbidities. However, the effect of these comorbidities on paediatric-adult transition readiness, and the relevance of widely used tools for measuring transition readiness, are unknown. The objectives of this study were to describe and explore the transition readiness of youth with co-occurring chronic health and mental health conditions using a combination of quantitative data obtained from participants completing the Transition Readiness Assessment Questionnaire (TRAQ) and qualitative data. A three-phase sequential explanatory mixed methods design was employed, with the qualitative strand taking priority. First, the TRAQ scores (range 1-5) of youth with co-occurring conditions (n = 61) enroled in a multisite randomized controlled trial were measured, followed by qualitative interviews with a sample of youth (n = 9) to explain the quantitative results. Results from both strands were then integrated, yielding comprehensive insights. Median TRAQ scores ranged from 2.86 on the appointment keeping subscale to 5.00 on the talking with providers subscale. The qualitative results uncovered the complexities faced by this group concerning the impact of a mental health comorbidity on transition readiness and self-management skills across TRAQ domains. The integrated findings identified a diverse and highly individualized set of strengths and challenges amongst this group that did not align with overarching patterns as measured by the TRAQ. This mixed methods study generated novel understandings about how youth with co-occurring conditions develop competencies related to self-care, self-advocacy and self-management in preparation for paediatric-adult service transitions. Results demonstrated the assessment of transition readiness using a generic scale does not address the nuanced and complex needs of youth with co-occurring chronic health and mental health conditions. Our findings suggest tailoring transition readiness practices for this group based on youths' own goals, symptoms, coping mechanisms and resources. This study was conducted in collaboration with five young adult research partners (YARP) with lived experience transitioning from paediatric to adult health/mental health services. The YARP's contributions across study phases ensured the perspectives of young people were centred throughout data collection, analysis, interpretation and presentation of findings. All five YARP co-authored this manuscript.


Intestinal smooth muscle dysfunction develops postnatally in cystic fibrosis mice.
Intestinal dysmotility is one of the effects of cystic fibrosis (CF), but when and how this develops is not well understood. The goal of the present study was to use the Cftr knockout mouse to determine when in development circular smooth muscle of the small intestine becomes dysfunctional. Wild-type (WT) and CF mice were used at postnatal day 5 (P5) through adult. Pieces of small intestine were used to measure contractile activity of the circular muscle. Bacterial overgrowth was measured by quantitative polymerase chain reaction (PCR) of the bacterial 16S gene. Intestinal gene expression was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). Prostaglandin E2 (PGE2) and its metabolites were measured by enzyme immunoassay. CF circular muscle response to cholinergic stimulation was similar to WT at P5, became somewhat impaired at P7, and was severely impaired by P14. In the CF intestine, bacterial overgrowth occurred by P4 and was maintained into adulthood. Eicosanoid metabolic gene expression in the CF intestine did not differ from WT shortly after birth. The phospholipase A2 genes, Pla2g4c and Pla2g5 exhibited increased expression in CF mice at P24. Prostaglandin degradative genes, Hpgd and Ptgr1, showed lower expression in CF as compared with WT at P16 and P24, respectively. PGE2 levels were significantly greater in CF mice at most ages from P7 through adulthood. The results clearly demonstrate that lack of CFTR itself does not cause smooth muscle dysfunction, because the circular muscle from P5 CF mice had normal activity and dysfunction developed between P7 and P14.


The association of interleukin-6, interleukin-27, and body roundness index with gestational diabetes mellitus.
We aimed to investigate the relationship between GDM and IL-27, IL-6, and body roundness index (BRI), a new anthropometric measurement more sensitive than BMI in identifying obesity and predicting cardiometabolic outcomes. We enrolled 80 patients, 40 pregnant women with GDM and 40 healthy pregnant women at midgestation. The women's anthropometric measurements were recorded and serum markers and IL-6, IL-27 were analysed. At the time of delivery maternal, neonatal results were recorded. Women with GDM had significantly higher pregestational, midgestational and prepartum BMI and midgestational BRI; HOMA-IR; HbA1c; and IL-6 values and lower HDL values (p < .05). There was no statistically significant difference in IL-27 values between the groups (p = .939). In multivariate logistic regression analysis, HbA1c, IL-6 (>4.886 pg/mL), and BRI (>6.708) were found as independent risk factors associated with GDM (p < .05). Mean BRI was significantly associated with obesity (p < .001) and BRI higher than 6.708 was found to have 67.5% sensitivity and 80% specificity in the prediction of GDM. Women with GDM had elevated IL-6 levels, but no relationship was detected between IL-27 and GDM. BRI is a new anthropometric index that strongly correlated with BMI and seems to be a reliable alternative to BMI for the evaluation of obesity in GDM patients.IMPACT STATEMENTWhat's already known on this subject? Gestational diabetes mellitus (GDM) is the most common systemic disease in pregnancy. The risk of GDM was 3 times higher in obese pregnant women compared to normal weighted patients. IL-6 is an adipose-derived cytokine that was found to be associated with GDM. The body roundness index (BRI) is a new sensitive anthropometric index for detecting obesity and its secondary cardiometabolic results.What do the results of this study add? Our results showed that BRI was strongly correlated with obesity in GDM patients. HbA1c, IL-6 and BRI were found as independent risk factors associated with GDM. IL 27, a cytokine associated with inflammatory diseases, was not associated with GDM.What are the implications of these findings for clinical practice and/or further research? BRI could be a reliable alternative to BMI for the evaluation of obesity in pregnant women and predicting cardiometabolic outcomes.


Coexistence of myelomonocytic leukemia and monoclonal gammopathy or myeloma. Simultaneous presentation in three patients.
The coexistence of monoclonal gammopathy or myeloma and nonlymphoblastic leukemia is reported in three untreated patients. One patient had IgG kappa myeloma and monoblastic leukemia, whereas the two others had IgA paraprotein in association with chronic granulocytic and acute myelomonoblastic leukemia, respectively. Simultaneous presentation of monoclonal gammopathy or myeloma and nonlymphoblastic leukemia is rare, and this report reviews the possible pathogenesis of this phenomena.


Cellular pharmacology of potassium channel openers in vascular smooth muscle.
Potassium channel opening is a physiological mechanism which excitable cells exploit to maintain or restore their resting state. Thus drugs that open vascular potassium channels have the potential to restrain or prevent contractile responses to excitatory stimuli or clamp the vessel in a relaxed condition. Hence, potassium channel openers, such as aprikalim and levcromakalim, relax agonist precontracted vascular preparations in vitro and lower systemic and regional vascular resistances in intact animals. Glibenclamide, a blocker of ATP sensitive potassium (KATP) channels, antagonises these effects. The main vasorelaxant mechanism of the potassium channel openers is to increase the potassium efflux through opening plasmalemmal potassium channels, which repolarises and/or hyperpolarises the membrane. This effect lowers the opening probability of voltage dependent calcium channels, restrains agonist induced calcium release from intracellular sources through inhibition of inositol trisphosphate formation, decreases the sensitivity of intracellular contractile elements to calcium, and accelerates the clearance of intracellular calcium via the Na+/Ca+ exchanger. Experimental evidence indicates that mechanisms not linked to potassium channel opening may also contribute to the potassium channel opener induced vasorelaxation; these remain to be clearly defined (for example, inhibition of the refilling of intracellular calcium stores). Potassium channel openers displace the binding of 3H-P1075, a potent potassium channel opener, in myocytes and intact rings from the rat aorta. In patches from vascular myocytes, potassium channel openers primarily open a small conductance (10-20 pS) KATP channel which is gated by [ATP]i and particularly by nucleotide diphosphates and magnesium.(ABSTRACT TRUNCATED AT 250 WORDS)


Manganese-Enhanced Magnetic Resonance Imaging and Studies of Rat Behavior: Transient Motor Deficit in Skilled Reaching, Rears, and Activity in Rats After a Single Dose of MnCl2.
Manganese-enhanced magnetic resonance imaging (MEMRI) has been suggested to be a useful tool to visualize and map behavior-relevant neural populations at large scale in freely behaving rodents. A primary concern in MEMRI applications is Mn2+ toxicity. Although a few studies have specifically examined toxicity on gross motor behavior, Mn2+ toxicity on skilled motor behavior was not explored. Thus, the objective of this study was to combine manganese as a functional contrast agent with comprehensive behavior evaluation. We evaluated Mn2+ effect on skilled reach-to-eat action, locomotion, and balance using a single pellet reaching task, activity cage, and cylinder test, respectively. The tests used are sensitive to the pathophysiology of many neurological and neurodegenerative disorders of the motor system. The behavioral testing was done in combination with a moderate dose of manganese. Behavior was studied before and after a single, intravenous infusion of MnCl2 (48 mg/kg). The rats were imaged at 1, 3, 5, 7, and 14 days following infusion. The results show that MnCl2 infusion resulted in detectable abnormalities in skilled reaching, locomotion, and balance that recovered within 3 days compared with the infusion of saline. Because some tests and behavioral measures could not detect motor abnormalities of skilled movements, comprehensive evaluation of motor behavior is critical in assessing the effects of MnCl2. The relaxation mapping results suggest that the transport of Mn2+ into the brain is through the choroid plexus-cerebrospinal fluid system with the primary entry point and highest relaxation rates found in the pituitary gland. Relaxation rates in the pituitary gland correlated with measures of motor skill, suggesting that altered motor ability is related to the level of Mn circulating in the brain. Thus, combined MEMRI and behavioral studies that both achieve adequate image enhancement and are also free of motor skills deficits are difficult to achieve using a single systemic dose of MnCl2.


Genome-wide association studies of low back pain and lumbar spinal disorders using electronic health record data identify a locus associated with lumbar spinal stenosis.
Identifying genetic risk factors for lumbar spine disorders may lead to knowledge regarding underlying mechanisms and the development of new treatments. We conducted a genome-wide association study involving 100,811 participants with genotypes and longitudinal electronic health record data from the Electronic Medical Records and Genomics Network and Geisinger Health. Cases and controls were defined using validated algorithms and clinical diagnostic codes. Electronic health record-defined phenotypes included low back pain requiring healthcare utilization (LBP-HC), lumbosacral radicular syndrome (LSRS), and lumbar spinal stenosis (LSS). Genome-wide association study used logistic regression with additive genetic effects adjusting for age, sex, site-specific factors, and ancestry (principal components). A fixed-effect inverse-variance weighted meta-analysis was conducted. Genetic variants of genome-wide significance (P < 5 × 10-8) were carried forward for replication in an independent sample from UK Biobank. Phenotype prevalence was 48.8% for LBP-HC, 19.8% for LSRS, and 7.9% for LSS. No variants were significantly associated with LBP-HC. One locus was associated with LSRS (lead variant rs146153280:C>G, odds ratio [OR] = 1.17 for G, P = 2.1 × 10-9), but was not replicated. Another locus on chromosome 2 spanning GFPT1, NFU1, and AAK1 was associated with LSS (lead variant rs13427243:G>A, OR = 1.10 for A, P = 4.3 × 10-8) and replicated in UK Biobank (OR = 1.11, P = 5.4 × 10-5). This was the first genome-wide association study meta-analysis of lumbar spinal disorders using electronic health record data. We identified 2 novel associations with LSRS and LSS; the latter was replicated in an independent sample.


Effects of intracerebral microinjection of hydroxylated-[60]fullerene on brain monoamine concentrations and locomotor behavior in rats.
Fullerenes are condensed ring aromatic compounds with extended pi systems; they have unique cage structures. Current studies suggest that several fullerene derivatives have neuroprotective effects, and it is expected that fullerenes will be useful in drug delivery system and novel medical devices targeting the brain. However, little is known about the effects of fullerenes and its derivative on brain function. We examined the effect of fullerene(OH)24 on the central nervous system in this study. In a V79 colony assay, the IC50 of fullerene(OH)24 was 1.74 microg/ml. In an MTT assay, fullerene(OH)24 reduced proliferation of normal human astrocytes obviously. In an vivo study, 0.25 mg/kg(-1) of fullerene(OH)24 was injected into the lateral ventricle of rat brains. The intracerebral injection of fullerene(OH)24 remarkably decreased body weight and locomotor behavior of rats on day 1, but drastically increased locomotor behavior on day 7. The intracerebral injection of fullerene(OH)24 changed the monoamine concentration greatly on day 1 and slightly on day 30 after the injection. These results suggest that intracerebral injection of fullerene(OH)24 had strong and acute effects on the central nervous system, but that the effects were not permanent. In conclusion, we suggest that fullerene's derivative, fullerene(OH)24 had toxic effects on brain cells and that intracerebral injection of fullerene(OH)24 had acute harmful effects on brain monoamines neurotransmission and locomotor activity.


Adaptive optical phase estimation using time-symmetric quantum smoothing.
Quantum parameter estimation has many applications, from gravitational wave detection to quantum key distribution. The most commonly used technique for this type of estimation is quantum filtering, using only past observations. We present the first experimental demonstration of quantum smoothing, a time-symmetric technique that uses past and future observations, for quantum parameter estimation. We consider both adaptive and nonadaptive quantum smoothing, and show that both are better than their filtered counterparts. For the problem of estimating a stochastically varying phase shift on a coherent beam, our theory predicts that adaptive quantum smoothing (the best scheme) gives an estimate with a mean-square error up to 2sqrt[2] times smaller than nonadaptive filtering (the standard quantum limit). The experimentally measured improvement is 2.24+/-0.14.


Host-associated genetic differentiation in Thrips tabaci (Insecta; Thysanoptera), as determined from mtDNA sequence data.
We tested for host-associated genetic differentiation in 22 populations of Thrips tabaci collected from tobacco and leek, respectively. Clustering analyses and haplotype networks based on sequence variation at a fragment of the mitochondrial cytochrome oxidase I gene yielded three major evolutionary lineages; two were clearly associated with leek and the third with tobacco. These genetic findings corroborated recent experimental observations on the heterogeneity of T. tabaci populations with regard to host-plant preference and their capacity to be vectors for tomato spotted wilt virus. Estimated divergence times suggested an ancient divergence of these lineages dating back to the Miocene 28-21 million years ago. F(ST) values between these lineages ranged between 0.824 and 0.954 (P<0.001 for all comparisons), and sequence divergences ranged between 4 and 11%. Given these findings and by the standards of genetic and ecological differentiation in other published species groups, T. tabaci must be considered a complex of cryptic (sub)species.


Hepatitis A virus infection in Taipei City in 1989.
To evaluate the current status of hepatitis A virus (HAV) infection, a seroepidemiologic study to detect the prevalence of antibodies against HAV (anti-HAV) has conducted in Taipei City, from March to July, 1989. Serum specimens were collected from 602 male and 503 female apparently healthy children age 12 and under. The prevalence rate of anti-HAV was 27.5% in infants, and decreased to nearly 0% in preschool and early school children up to 10 years old. Compared to a previous study in the same area of Taipei in 1984, our study indicated a further and significant reduction in the prevalence of anti-HAV in almost every age group from 2 to 14 years of age. There was an average of a 5-year prevalence shift. These data suggest that there has been no significant endemic of HAV infection from 1984 to 1989. The antibody prevalence change in the different age groups represents an ongoing trend of HAV seroepidemiology in Taiwan where HAV infection is becoming rare. The age of primary infection in children has been extended to an older age group. The rarity of HAV infection in Taiwan has created a large and growing population of young adults susceptible to hepatitis A virus infection. The effective prevention of hepatitis A virus infection will become a major public health concern.


Nonaesthetic Applications for Botulinum Toxin in Plastic Surgery.
Since their introduction to clinical medicine in 1989, botulinum toxin injections have been used for many indications. First used for nonsurgical management of strabismus, botulinum toxin injections are now widely used in plastic and reconstructive surgery for aesthetic indications; however, nonaesthetic indications of botulinum toxin have grown tremendously over the past two decades and span numerous specialties, including urology, dermatology, ophthalmology, otolaryngology, gynecology, plastic surgery, general surgery, and neurology. The present review aims to highlight nonaesthetic indications of botulinum toxin that are most relevant to the plastic surgeon with an emphasis on evidence-based practice. A PubMed search with manual reference checking was conducted to find the most relevant and influential articles on the nonaesthetic uses of botulinum toxin within the realm of adult plastic surgery. Studies were then categorized into areas of use, and quality of evidence for each category was highlighted. Botulinum toxin has numerous nonaesthetic indications in plastic surgery, including for select pain-related disorders, skeletal muscle activity disorders, exocrine gland hyperfunction, wound healing, Raynaud phenomenon, abdominal wall reconstruction, and prosthetic breast reconstruction and augmentation. Although these indications have been widely reported, high-quality evidence supporting efficacy, optimal dose, and injection protocol with randomized controlled trials is lacking in many areas. Botulinum toxin is widely used in plastic surgery for a variety of nonaesthetic indications. Future studies should focus on investigating efficacy and best practice with high level of evidence research.


Time to Catheter Angiography for Gastrointestinal Bleeding after Prior Positive Investigation Does Not Affect Bleed Identification.
To determine, time to angiography for patients with positive gastrointestinal bleeding (GIB) on prior investigation (endoscopy [ES], nuclear medicine [NM] Tc99m red blood cells (RBC) scan, or computed tomography angiography), affects angiographic bleed identification. Visceral Angiograms performed from January 2012 to August 2017 were evaluated. Initial angiograms performed for GIB were included in the study. Exclusion criteria included recent abdominal surgery or procedure (30 days), empiric embolization (embolization without visualized active bleeding), and use of vasodilators, or subsequent angiogram. Timing and results of ES, NM Tc99m RBC scan, or computed tomography angiogram and catheter angiogram were recorded. In addition, age, gender, angiogram time, anti- platelet therapy, anti-coagulation therapy, bleed location, international normalized ratio, and units of packed RBCs received in the 24 h before catheter angiography were included in the study. One hundred and seventy angiograms were included in the final analysis. Forty-three angiograms resulted in the identification of an active bleed (68.9 years, and 67.4% male). All of these patients were embolized successfully. One hundred and twenty-seven angiograms failed to identify an active bleed (70.4 years, and 49.6% male). No significance was found across the two groups with respect to time from prior positive investigation. Receiver operating characteristic analysis demonstrated that units of packed RBCs received in the preceding 24 h were correlated with positive bleed identification on catheter angiography. Time to angiography from prior positive investigation, including ES, NM Tc99m RBC scan, or computed tomography angiogram does not correlate with positive angiographic outcomes. Increasing units of packed RBCs administered in the 24 h before angiogram do correlate with positive angiographic findings.


Insulin resistance and beta cell function as prognostic indicator in multi-organ dysfunction syndrome.
Insulin resistance (IR) is a major factor in the pathogenesis of sepsis. Critically ill patients with multi-organ dysfunction syndrome (MODS), diagnosed as per modified Acute Physiology and Chronic Health Evaluation II (modified APACHE II) score criteria and admitted to the medical ward in our hospital, were assessed for IR and beta cell function by using the homeostasis model assessment A (HOMA-A) and HOMA-B models, respectively. Of 80 consecutive patients, 60 were followed up to day 7; 16 patients died and 4 did not agree to follow up. The mean value of IR in all the 80 patients studied on the day 1 of hospitalization was 6.67 +/- 10.65. The initial high values of serum insulin and IR were significantly reduced (p < 0.05) as these patients recovered from their critical illness. Of those who died, the first day mean insulin levels were high (13.80 +/- 14.72 micro/ml as well as IR 5.14 +/- 6.76 values), but they had statistically low beta cell function (46.45 +/- 433.64%) as compared to those who recovered (227.60 +/- 430.36%; p < 0.05). This suggests that, beta cell overexhaustion occurs in critically ill patients, because it was required to overcome the prevailing state of IR and has more bearing in patients having less than 4 organ failures. beta cell failure ensued from the onset in those who were more moribund and had more than four organs failing or those who died. IR and beta cell function are reliable indicators of the state of severity of critical illness, and they corroborated with mortality in patients with MODS.


[Improved chance of survival for very small premature infants in Switzerland].
Extremely low birthweight infants are attracting increasing attention in the medical literature, mainly in audits from selected hospitals not representative of the entire population of a country. The Swiss Neonatology Group gathered selected data on mortality, morbidity and medical treatment of all liveborn infants weighing between 500 and 999 g at birth for the years 1979-81, 1983-85 and 1989-91. The results were compared and completed with information from the Swiss Office of Statistics. From 1979-81 to 1989-91 the incidence of extremely low birthweight infants increased from 1.3 to 2.2 per thousand livebirths. At the same time the survival rate increased from 23% to 53%, resulting in three times more infants being discharged from hospital in this weight group. The number of days of mechanical ventilation, which is an indicator of intensity of care, increased from 320 days to 1440 days per year. In contrast to mortality, morbidity scarcely decreased within this 12-year period and was still considerable in 1989-91. 57% of the survivors had chronic lung disease and 15% had sepsis. Intracranial hemorrhage was present in 35% of the survivors and 71% of the deaths. Retinopathy was noted in 38% of survivors. These facts, which are representative of the whole of Switzerland, show the increasing medical and economic significance of this patient group. Before the implications of this development can be fully assessed, extremely low birthweight infants must be followed up until adult life.


The in vivo time course for elimination of adrenalectomy-induced apoptotic profiles from the granule cell layer of the rat hippocampus.
Although apoptotic cellular degeneration has been reported to be extremely rapid with the use of in vitro models, the time needed to clear apoptotic neurons in the in vivo brain is unknown. In this study we used a simple morphological approach to solve this problem. Four days after adrenalectomy (ADX), all of the operated rats morphologically displayed hippocampal granule cell apoptosis that was prevented completely by corticosterone replacement immediately after ADX. Therefore, we intravenously injected the rats with corticosterone 4 d after ADX and subsequently maintained them on corticosterone replacement in saline drinking water. This corticosterone replacement could protect healthy granule cells promptly and continuously against hormone-deficient apoptosis, because the normal glucocorticoid receptor immunoreactivity within the granule cell nuclei, which disappeared after ADX, was identified 1 hr after corticosterone replacement was started, and this effect persisted for several days. However, this corticosterone treatment could not prevent the irreversible apoptosis of the already degenerated granule cells at various stages of the same progressive apoptotic process. Then we successively traced the disappearance of apoptotic granule cells throughout the hippocampus at different time points by Nissl and silver staining. Given that the apoptotic cells at the earliest stage of the degenerating process when the ADX rats received corticosterone injection were the last to disappear, the period from corticosterone injection until the disappearance of the last degenerating debris of apoptotic cells was taken to represent the time course for elimination of apoptotic neurons in vivo. We discovered that the elimination of apoptotic granule cells took 72 hr.


Children's Navigation of Contextual Cues in Peer Transgressions: The Role of Aggression Form, Transgressor Gender, and Transgressor Intention.
When faced with transgressions in their peer groups, children must navigate a series of situational cues (e.g., type of transgression, transgressor gender, transgressor intentionality) to evaluate the moral status of transgressions and to inform their subsequent behavior toward the transgressors. There is little research on which cues children prioritize when presented together, how reliance on these cues may be affected by certain biases (e.g., gender norms), or how the prioritization of these cues may change with age. To explore these questions, 138 5- to 7-year-olds (younger children) and 8- to 10-year-olds (older children) evaluated a series of boy and girl characters who partook in physical or relational aggression with ambiguous or purposeful intent. Children were asked to provide sociomoral evaluations (i.e., acceptability, punishment, and intention attribution judgments) and social preferences. Transgressor gender only impacted children's social preferences. Conversely, aggression form and transgressor intent shifted children's sociomoral judgments: they were harsher toward physical transgressors with purposeful intent over those with ambiguous intent but made similar evaluations for relational transgressors regardless of intentionality. The present results suggest that gender is perhaps not uniformly relevant to children across all contexts, as other cues were prioritized for children's sociomoral judgments. Since children likely have less familiarity with relational aggression compared to physical aggression, it follows that intent would only shift judgments about physical transgressors. This research provides insight about how children simultaneously navigate multiple cues in aggression contexts, which is likely reflective of their real-world experiences.


Renal arterial embolization: Indications, angiographic findings, and outcomes in a series of 170 patients.
The lack of overall experience and reporting on angiographic findings in previously published studies of renal arterial embolization (RAE) compelled us to report our overall experience on a series of patients. A retrospective study was performed analyzing data of patients enrolled for RAE between 2010 and 2019. History, physical examination, and laboratory data were reviewed for all patients. Abdominal ultrasound was the initial imaging study, and all patients underwent subsequent computed tomography or magnetic resonance imaging. The outcome of RAE was determined based on radiographic and clinical findings. Data from 202 patients were analyzed, with a mean age of 45 ± 15 years, and 71.3% of patients were male. Iatrogenic injury was the most common indication for RAE (54%), followed by renal tumors, trauma, and spontaneous, in 27.7%, 10.4%, and 8.4% of patients, respectively. Renal angiography revealing pseudoaneurysm alone or with other pathology in the lower pole of the kidney was the most common finding (40.6%), whereas no lesions were identified on angiography in 32 patients (15.8%), after which RAE was subsequently aborted. Renal arterial embolization was successful in 158 of 170 patients (92.9%) after 1 or more trials (maximum of 4). Microcoil alone or with other embolic materials was the most commonly used material for embolization (85%). Iatrogenic injury was the most common indication for RAE. Pseudoaneurysm alone or with other lesions was the most common lesion on renal angiography; however, angiography showed a negative result in 16% of patients, even those with symptoms. When lesions are present on angiography, the overall success of repeated trials of RAE reached 92.9%.


Spatial Memory Disturbance Following Transient Brain Ischemia is Associated with Vascular Remodeling in Hippocampus.
A number of studies have investigated the effects of ischemic injury on functional and cellular characteristics of hippocampus. There is only a limited study on vascular remodeling of it. The present study aimed at examining vascular remodeling in hippocampus and spatial memory disturbances after transient brain ischemia. Male Wistar rats were randomly divided into four groups, i.e. sham operated (SHAM), transient brain ischemia with 1 day reperfusion (IR1), 3 day reperfusion (IR3), and 10 days reperfusion (IR10) groups. Transient brain ischemia was induced by bilateral common carotid artery occlusion (BCCAO). The spatial memory test was performed using the Morris water maze (MWM) in SHAM and IR10 groups. The rats were euthanized at day 1, 3 or 10 after BCCAO depending on the groups. The mRNA expressions of SOD2, Bcl-2, NeuN, eNOS, endothelin-1 (ET-1), CD31, VE-cadherin and vascular remodeling of the hippocampus were examined. There were deteriorations of spatial learning ability in IR10 group. The percentages of SOD2 and Bcl-2, the expression of NeuN, decreased and the vascular remodeling was observed in the ischemic groups. The eNOS and CD31 expressions were less in IR10, the VE-cadherin expression was less in all ischemic groups than in SHAM group, while ET-1 expression in IR1 group was higher than any other groups. The spatial memory deterioration after BCCAO is associated with vascular remodeling in hippocampus, characterized by lumen narrowing and smooth muscle thickening of microvessels.


ProNGF derived from rat sciatic nerves downregulates neurite elongation and axon specification in PC12 cells.
Several reports have shown that a sciatic nerve conditioned media (CM) causes neuronal-like differentiation in PC12 cells. This differentiation is featured by neurite outgrowth, which are exclusively dendrites, without axon or sodium current induction. In previous studies, our group reported that the CM supplemented with a generic inhibitor for tyrosine kinase receptors (k252a) enhanced the CM-induced morphological differentiation upregulating neurite outgrowth, axonal formation and sodium current elicitation. Sodium currents were also induced by depletion of endogenous precursor of nerve growth factorr (proNGF) from the CM (pNGFd-CM). Given that sodium currents, neurite outgrowth and axon specification are important features of neuronal differentiation, in the current manuscript, first we investigated if proNGF was hindering the full PC12 cell neuronal-like differentiation. Second, we studied the effects of exogenous wild type (pNGFwt) and mutated (pNGFmut) proNGF isoforms over sodium currents and whether or not their addition to the pNGFd-CM would prevent sodium current elicitation. Third, we investigated if proNGF was exerting its negative regulation through the sortilin receptor, and for this, the proNGF action was blocked with neurotensin (NT), a factor known to compete with proNGF for sortilin. Thereby, here we show that pNGFd-CM enhanced cell differentiation, cell proportion with long neurites, total neurite length, induced axonal formation and sodium current elicitation. Interestingly, treatment of PC12 cells with wild type or mutated proNGF isoforms elicited sodium currents. Supplementing pNGFd-CM with pNGFmut reduced 35% the sodium currents. On the other hand, pNGFd-CM+pNGFwt induced larger sodium currents than pNGFd-CM. Finally, treatments with CM supplemented with NT showed that sortilin was mediating proNGF negative regulation, since its blocking induced similar effects than the pNGFd-CM treatment. Altogether, our results suggest that proNGF within the CM, is one of the main inhibitors of full neuronal differentiation, acting through sortilin receptor.


Modelling the spatial heterogeneity and molecular correlates of lymphocytic infiltration in triple-negative breast cancer.
Lymphocytic infiltration is associated with a favourable prognosis and predicts response to chemotherapy in many cancer types, including the aggressive triple-negative breast cancer (TNBC). However, it is not well understood owing to the high levels of spatial heterogeneity within tumours, which is difficult to analyse by traditional pathological assessment. This paper describes an unbiased methodology to statistically model the spatial distribution of lymphocytes among tumour cells based on automated analysis of haematoxylin-and-eosin-stained whole-tumour section images, which is applied to two independent TNBC cohorts of 181 patients with matched microarray gene expression data. The novelty of the proposed methodology is the fusion of image analysis and statistical modelling for an integrative understanding of intratumour heterogeneity of lymphocytic infiltration. Using this methodology, a quantitative measure of intratumour lymphocyte ratio is developed and found to be significantly associated with disease-specific survival in both TNBC cohorts independent to standard clinical parameters. The proposed image-based measure compares favourably to a number of gene expression signatures of immune infiltration. In addition, heterogeneous immune infiltration at the morphological level is reflected at the molecular scale and correlated with increased expression of CTLA4, the target of ipilimumab. Taken together, these results support the fusion of high-throughput image analysis and statistical modelling to offer reproducible and robust biomarkers for the objective identification of patients with poor prognosis and treatment options.


The future of cannabinoids as analgesic agents: a pharmacologic, pharmacokinetic, and pharmacodynamic overview.
For thousands of years, physicians and their patients employed cannabis as a therapeutic agent. Despite this extensive historical usage, in the Western world, cannabis fell into disfavor among medical professionals because the technology available in the 1800s and early 1900s did not permit reliable, standardized preparations to be developed. However, since the discovery and cloning of cannabinoid receptors (CB1 and CB2) in the 1990s, scientific interest in the area has burgeoned, and the complexities of this fascinating receptor system, and its endogenous ligands, have been actively explored. Recent studies reveal that cannabinoids have a rich pharmacology and may interact with a number of other receptor systems-as well as with other cannabinoids-to produce potential synergies. Cannabinoids-endocannabinoids, phytocannabinoids, and synthetic cannabinoids-affect numerous bodily functions and have indicated efficacy of varying degrees in a number of serious medical conditions. Nevertheless, despite promising preclinical and early clinical data, particularly in the areas of inflammation and nociception, development challenges abound. Tetrahydrocannabinol (THC) and other CB1 receptor agonists can have an undesirable CNS impact, and, in many cases, dose optimization may not be realizable before onset of excessive side effects. In addition, complex botanically derived cannabinoid products must satisfy the demanding criteria of the U.S. Food and Drug Association's approval process. Recent agency guidance suggests that these obstacles are not insurmountable, although cannabis herbal material ("medical marijuana") may present fatal uncertainties of quality control and dosage standardization. Therefore, formulation, composition, and delivery system issues will affect the extent to which a particular cannabinoid product may have a desirable risk-benefit profile and acceptable abuse liability potential. Cannabinoid receptor agonists and/or molecules that affect the modulation of endocannabinoid synthesis, metabolism, and transport may, in the future, offer extremely valuable tools for the treatment of a number of currently intractable disorders. Further research is warranted to explore the therapeutic potential of this area.


Patients unaware of their HIV infection until AIDS diagnosis in Sweden 1996-2002--a remaining problem in the highly active antiretroviral therapy era.
Our objective was to analyse the characteristics of patients who were unaware of their HIV infection until they developed AIDS, in the period after introduction of highly active antiretroviral therapy. The complete national register of HIV and AIDS cases reported to the Department of Epidemiology at the Swedish Institute for Infectious Disease Control 1996-2002 was searched for cases diagnosed with HIV less than three months before AIDS diagnosis (so-called "late testers"). Of a total of 487 patients with AIDS, reported during the seven-year period, 219 (45%) were late testers. Their proportion of all AIDS cases increased from 22% in 1996 to 58% in 2002. Heterosexual route of transmission, age greater than 40 years, and foreign origin were all significant risk factors for being a late tester. Intravenous drug users were associated with a highly significant reduced risk. The group without previously known HIV infection represents an increasing part of all cases of AIDS. From a disease control and from a medical perspective, it is important to study this group further and discover what measures are needed for earlier identification and access to medical care.


Genomic alterations of the c-myc protooncogene in relation to the overexpression of c-erbB2 and Ki-67 in human breast and cervix carcinomas.
Genomic alterations of c-myc (amplification, rearrangements and hypomethylation) were investigated in 30 breast carcinomas and 20 cervix carcinomas. In breast carcinomas c-myc alterations were compared with overexpression of the c-erbB2 protooncogene and the proliferation marker Ki-67. Alterations of c-myc were found in 50% of the breast carcinomas and in 25% of the cervix carcinomas. In 23% of the breast carcinomas c-erbB2 overexpression was associated with c-myc alterations. In 17% of the cases there was overexpression of c-erbB2 without detectable alterations of c-myc. Hence, in 67% of breast cancers alterations of c-myc and/or c-erbB2 have been found, while in 81% of the samples Ki-67 expression was increased. The results suggest that the study of c-myc alterations provides an important complement to that of other prognostic indicators of breast cancer such as c-erbB2 expression.


Microbiome: what intensivists should know.
The standard conditions of critical illness (including sepsis, acute respiratory distress syndrome, and multiorgan failure) cause enormous global mortality and a growing economic burden. Increasing evidence suggests that critical illness may be associated with loss of commensal microbes and overgrowth of potentially pathogenic and inflammatory bacteria. This state could be associated with poor outcomes. Therefore, microbiota-targeted interventions are potentially attractive novel treatment options. Although the precise mechanisms of microbiome-directed treatments such as prebiotics, probiotics, and fecal microbiota transplantation remain to be determined, they can be utilized in the Intensive Care Unit (ICU) setting. The current review aims to offer intensivists an evidenced-based approach on what we currently know about the role of the microbiome in critical illness and how the microbiome could be targeted in the clinical practice to improve ICU-related outcomes.


Immunoglobulin constant heavy G chain genes as risk factors in childhood allergies.
Several candidate genes have been found to be associated with the inflammatory response of IgE-mediated allergy, so also the immunoglobulin constant heavy G chain (IGHG) genes. The IGHG genes are situated close to the IGHE gene on chromosome 14q32, 5'mu, delta, gamma3, gamma1, alpha1, gamma2, gamma4, epsilon, alpha2, 3'. They are inherited in a Mendelian fashion and expressed randomly in allelic exclusion. The alternative and functionally different gamma3, gamma1 and gamma2 gene variants are found in four IGHG haplotypes, coding four B cell variants. The aim of this study was to assess the frequency of different IGHG genes in relation to phenotypes associated with allergy, in a case-control study. We identified the constant heavy-chain genes of IgG in 198 allergic and non-allergic children participating in the Phase II of the International Study of Asthma and Allergy in Children. The IGHG genes were assessed by the alternative serum IgG subclass allotypes expressing the alternative alleles of gamma3, gamma1 and gamma2 genes, using ELISA and double immunodiffusion. The IGHG*bfn haplotype (=B1 cells) and IGHG2*n allele dominated (51% vs. 24%, P=0.002) and the IGHG*bf-n haplotype (=B2 cells) was infrequent (16% vs. 52%, P < 0.001) in allergic children with a family history of allergy, clinical manifest allergy and positive skin prick test (SPT). The frequency of IGHG genes was similar in children with maternal and paternal heredity and in children with wheezing, eczema or rhinitis, as well as in children with different positive SPT. The IGHG*bfn haplotype with the IGHG2*n allele was strongly associated with heredity for allergy. The IGHG*bf-n haplotype was inversely related to allergy. Conclusions IgG allotypes, immunochemical and functional variants of IgG molecules from IGHG genes are associated with atopy. The IGHG*bfn haplotype (=B1 cells) with the IGHG2*n allele dominates, associated with an increased risk for atopy. In contrast, the IGHG*bf-n haplotype (=B2 cells) with the IGHG2*-n allele is associated with low risk.


Effects of climate change on Salmonella infections.
Climate change and global warming have been reported to increase spread of foodborne pathogens. To understand these effects on Salmonella infections, modeling approaches such as regression analysis and neural network (NN) were used. Monthly data for Salmonella outbreaks in Mississippi (MS), Tennessee (TN), and Alabama (AL) were analyzed from 2002 to 2011 using analysis of variance and time series analysis. Meteorological data were collected and the correlation with salmonellosis was examined using regression analysis and NN. A seasonal trend in Salmonella infections was observed (p<0.001). Strong positive correlation was found between high temperature and Salmonella infections in MS and for the combined states (MS, TN, AL) models (R(2)=0.554; R(2)=0.415, respectively). NN models showed a strong effect of rise in temperature on the Salmonella outbreaks. In this study, an increase of 1°F was shown to result in four cases increase of Salmonella in MS. However, no correlation between monthly average precipitation rate and Salmonella infections was observed. There is consistent evidence that gastrointestinal infection with bacterial pathogens is positively correlated with ambient temperature, as warmer temperatures enable more rapid replication. Warming trends in the United States and specifically in the southern states may increase rates of Salmonella infections.


Chemotherapy of Hodgkin's disease.
Chemotherapy is the main treatment for advanced Hodgkin's disease as demonstrated by the NCI MOPP study. The main prognostic factors have been identified. ABVD is partially non cross-resistant and permits the alteration of two regimens in order to achieve greater efficacy. The respective impact of conventional and high-dose chemotherapy for salvage treatment is being evaluated. Long-term hazards due to different regimens require continuous assessment so that the choice and modalities of chemotherapy in localized disease may be determined.


Recommendations for the clinical interpretation of genetic variants and presentation of results to patients with inherited bleeding disorders. A UK Haemophilia Centre Doctors' Organisation Good Practice Paper.
This paper sets out good practice for clinicians involved in interpreting variant reports for patients with inherited bleeding disorders. It is aimed primarily at doctors, nurses and allied healthcare professionals who may not have had specific training in genetic testing methodology or reporting. It deals with uncertainty in classification of variant pathogenicity and the handling of incidental findings.


Daytime warming has stronger negative effects on soil nematodes than night-time warming.
Warming of the climate system is unequivocal, that is, stronger warming during night-time than during daytime. Here we focus on how soil nematodes respond to the current asymmetric warming. A field infrared heating experiment was performed in the western of the Songnen Plain, Northeast China. Three warming modes, i.e. daytime warming, night-time warming and diurnal warming, were taken to perform the asymmetric warming condition. Our results showed that the daytime and diurnal warming treatment significantly decreased soil nematodes density, and night-time warming treatment marginally affected the density. The response of bacterivorous nematode and fungivorous nematode to experimental warming showed the same trend with the total density. Redundancy analysis revealed an opposite effect of soil moisture and soil temperature, and the most important of soil moisture and temperature in night-time among the measured environment factors, affecting soil nematode community. Our findings suggested that daily minimum temperature and warming induced drying are most important factors affecting soil nematode community under the current global asymmetric warming.


The Mediation Effect of Coping Style on the Relations between Personality and Life Satisfaction in Chinese Adolescents.
Previous findings showed the associations between each of the Big Five personality trait and adolescents' life satisfaction were different. Some traits (extraversion and neuroticism) correlated with adolescents' life satisfaction, while other traits did not have the same associations with adolescents' life satisfaction. In order to explain why the Big Five traits differed in their associations with adolescents' life satisfaction, the present study verified the relations between each of the Big Five personality traits and life satisfaction, and demonstrated the mediating effects of coping style on the relations between these personality traits and life satisfaction in a sample of 2,357 Chinese adolescents. The results demonstrated that four of the Big Five personality traits (extraversion, agreeableness, conscientiousness, and neuroticism) had significant associations with life satisfaction. Further, coping style partially mediated the relations between these four traits and life satisfaction, whereas coping style fully mediated the relation between openness to new experience and life satisfaction. The results implied a plausible explanation for why the Big Five traits differed in their associations with life satisfaction found among the previous literature: that there might be some partial or full mediation variables (such as coping style in this study) left unexamined. Theoretical and practical implications of this study on further research and educational practice are discussed.


Divalent cations in the envelope of a psychrophilic Achromobacter.
The function of Ca2+ in a psychrophilic Achromobacter, previously found to bind large amounts of these ions to its envelope, has been studied. Bacteria suspended in media of low ionic content showed decreases in wet weight, dry weight and growth capacity, and increases in light scattering and in the release of u.v.-absorbing substances into the medium. The permeability barrier to Ca2+ was also damaged, and there was a release of radioactivity from bacteria labelled with 45Ca2+. These events occurred at the optimum growth temperature, and took place at increased rates at higher temperatures. Damage was prevented to about the same extent by 0.1 mM-CaC12, BaC12 or MgC12 and by 10 mM-NaC1, KC1 or LiC1. Ion competition experiments showed that Ca2+ was preferentially taken up and retained in comparison with Ba2+, Mg2+ and Na+, in that order. Isolated envelopes gave similar results. The dry weight of envelopes was reduced by 35% when they were suspended in water at 40 degrees C. It is clear that the function of certain envelope components in Achromobacter is highly dependent on divalent cations; and that both the integrity of the permeability barrier and the stability of the envelope are affected at low ion concentrations.


[A case of pleomorphic adenocarcinoma of the ciliary body].
We performed local resection of a ciliary body tumor, which was diagnosed as pleomorphic adenocarcinoma arising from nonpigmented epithelium of the ciliary body. The patient was a 57-year-old male, and the tumor was found incidentally at an ophthalmologic examination. Since the possibility of malignant tumor could not be ruled out, local resection of the tumor was performed. The tumor developed from the pars plicata and the size was 5.5 x 6.0 x 7.5 mm. Histologically, the tumor cells displayed heteromorphism and revealed tubular and glandular structures which continued to the ciliary body epithelium. Melanin pigment was not observed, except in one small area of the tumor. The interstitium of the tumor tissue was stained with alcian blue, and a immunohistochemical study showed that tumor cells were positive for epithelial membrane antigen (EMA) and vimentin, but negative for S-100 protein and carcinoembryonic antigen (CEA). Electron microscopy revealed desmosomes between cells, and microvilli were observed at the margin of the glandular cavity structure. In this case, no severe complications occurred even after local resection and good visual function was maintained.


Tuning the Continuum of Structural States in the Native Ensemble of a Regulatory Protein.
The mesoscale nature of proteins allows for an efficient coupling between environmental cues and conformational changes, enabling their function as molecular transducers. Delineating the precise structural origins of such a connection and the expected spectroscopic response has, however, been challenging. In this work, we perform a combination of urea-temperature double perturbation experiments and theoretical modeling to probe the conformational landscape of Cnu, a natural thermosensor protein. We observe unique ensemble signatures that point to a continuum of conformational substates in the native ensemble and that respond intricately to perturbations upon monitoring secondary and tertiary structures, distances between an intrinsic FRET pair, and hydrodynamic volumes. Binding assays further reveal a weakening of the Cnu functional complex with temperature, highlighting the molecular origins of signal transduction critical for pathogenic response in enterobacteriaceae.


Identification of Ca2(+)-dependent cell adhesion molecules in Xenopus by the use of interspecies homology.
Ca2(+)-dependent cell adhesion molecules (CAMs) are transmembrane glycoproteins structurally and functionally related in mammalian and avian species. This suggests that Ca2(+)-dependent CAMs consist of an evolutionary conserved gene family. Antibodies or cDNA probes specific either to the extracellular part or the cytoplasmic domain of uvomorulin were compared for their ability to detect corresponding molecules in Xenopus. Only antibodies directed against the evolutionary highly conserved cytoplasmic domain afforded a clear membrane staining on sections of Xenopus embryos or on cultured Xenopus epithelial cells. However, these antibodies recognized different polypeptides of 156, 140 and 128 kDa in immunoblots prepared from cell lysates of epithelial, neural, muscle and embryonic tissues. In concordance with the antibody analysis, signals in Northern hybridizations were only obtained when the cDNA probe encoding the cytoplasmic domain of uvomorulin was used. Here again, this cDNA probe revealed different mRNA species of 4.3, 4.1, 3.8 and 3.2 kb in the studied cell types. These results provide further direct evidence that the Ca2(+)-dependent CAMs are evolutionary conserved. The variety of polypeptides and transcripts observed in Xenopus indicates that several members of this gene family were detected by the use of probes specific to conserved sequences. More important, with this approach we also identified members of this gene family in the early stages of Xenopus development. Since these proteins were present in mature eggs but not in oocytes, we assume a maternal store of Ca2(+)-dependent CAM RNAs whose translation might be initiated during egg maturation.


Ptaquiloside and Pterosin B Levels in Mature Green Fronds and Sprouts of Pteridium arachnoideum.
Pteridium arachnoideum, a fern of the Pteridium aquilinum species complex found in South America, is responsible for several different syndromes of poisoning. Cases of bovine enzootic hematuria and upper alimentary squamous cell carcinoma are both frequent occurrences in Brazil, whereas only bovine enzootic hematuria is noted with any frequency around the world. The reason for the high frequency of upper alimentary squamous cell carcinoma in Brazil is not currently known. One possible explanation may be the higher levels of ptaquiloside and pterosin B in Brazilian Pteridium than those present in the plant in other countries. However, these levels have not yet been determined in P. arachnoideum. Thus, the present study aimed to measure and compare ptaquiloside and pterosin B levels in mature green fronds and sprouts of P. arachnoideum collected from different locations in Brazil. Samples of P. arachnoideum were collected from the states of Minas Gerais and Rio Grande do Sul. A total of 28 mature leaf samples and 23 sprout samples were used. The mean concentrations of ptaquiloside and pterosin B present in the mature green fronds of P. arachnoideum ranged from 2.49 to 2.75 mg/g and 0.68 to 0.88 mg/g, respectively; in P. arachnoideum sprouts, mean concentrations of ptaquiloside and pterosin B ranged from 12.47 to 18.81 mg/g, and 4.03 to 10.42 mg/g for ptaquiloside and pterosin B, respectively. Thus, ptaquiloside and pterosin B levels in P. arachnoideum samples collected in Brazil were higher in sprouts than in mature green fronds, as observed in other countries. However, there was no variation in ptaquiloside levels among plants collected from different cities in Brazil. The high frequency of upper alimentary squamous cell carcinoma in Brazilian cattle may not be attributed to greater levels of ptaquiloside and pterosin B in P. arachnoideum than in other Pteridium species in other countries.


Increased prostate cancer specific mortality following radical prostatectomy in men presenting with voiding symptoms-A whole of population study.
Whole of population studies reporting long-term outcomes following radical prostatectomy (RP) are scarce. We aimed to evaluate the long-term outcomes in men with prostate cancer (PC) treated with RP in a whole of population cohort. A secondary objective was to evaluate the influence of mode of presentation on PC specific mortality (PCSM). A prospective database of all cases of RP performed in Victoria, Australia between 1995 and 2000 was established within the Victorian Cancer Registry. Specimen histopathology reports and prostate-specific antigen (PSA) values were obtained by record linkage to pathology laboratories. Mode of presentation was recorded as either PSA screened (PSA testing offered in absence of voiding symptoms) or symptomatic (diagnosis of PC following presentation with voiding symptoms). Multivariate Cox and competing risk regression models were fitted to analyze all-cause mortality, biochemical recurrence, and PCSM. Between 1995 and 2000, 2,154 men underwent RP in Victoria. During median follow up of 10.2 years (range 0.26-13.5 years), 74 men died from PC. In addition to Gleason score and pathological stage, symptomatic presentation was associated with PCSM. After adjusting for stage and PSA, no difference in PCSM was found between men with Gleason score ≤ 6 and Gleason score 3 + 4 = 7. Men with Gleason score 4 + 3 had significantly greater cumulative incidence of PCSM compared with men with Gleason score 3 + 4. Primary Gleason pattern in Gleason 7 PC is an important prognosticator of survival. Our findings suggest that concomitant voiding symptoms should be considered in the work-up and treatment of PC.


Effect of polysaccharide structure on mechanical and thermal properties of galactomannan-based films.
Films were prepared from guar gum and locust bean gum galactomannans. In addition, enzymatic modification was applied to guar gum to obtain structurally different galactomannans. Cohesive and flexible films were formed from galactomannans plasticized with 20-60% (w/w of polymer) glycerol or sorbitol. Galactomannans with lower galactose content (locust bean gum, modified guar gum) produced films with higher elongation at break and tensile strength. The mechanical properties of films were improved statistically significantly by decreasing the degree of polymerization of guar gum with mannanase treatments (4 h) of 2 and 10 nkat/g, whereas 50 nkat/g produced films with low elongation at break and tensile strength. Galactomannans with approximately 6 galactose units per 10 mannose backbone units resulted in films with 2 peaks in loss modulus spectra, whereas films from galactomannans with approximately 2 galactose groups per 10 mannose units behaved as a single phase in dynamic mechanical analysis.


Effects of Nasal Continuous Positive Airway Pressure and High-Flow Nasal Cannula on Sucking, Swallowing, and Breathing during Bottle-Feeding in Lambs.
The use of prolonged respiratory support under the form of high-flow nasal cannula (HFNC) or nasal continuous positive airway pressure (nCPAP) is frequent in newborn infants. Introduction of oral feeding under such nasal respiratory support is, however, highly controversial among neonatologists, due to the fear that it could disrupt sucking, swallowing, and breathing coordination and in turn induce cardiorespiratory events. The recent observation of tracheal aspirations during bottle-feeding in preterm infants under nCPAP justifies the use of animal models to perform more comprehensive physiological studies on the subject, in order to gain further insights for clinical studies. The objective of this study was to assess and compare the impact of HFNC and nCPAP on bottle-feeding in newborn lambs, in terms of bottle-feeding efficiency and safety as well as sucking-swallowing-breathing coordination. Eight full-term lambs were instrumented to record sucking, swallowing, and respiration as well as electrocardiogram and oxygenation. Lambs were bottle-fed in a standardized manner during three randomly ordered conditions, namely nCPAP 6 cmH2O, HFNC 7 L/min, and no respiratory support. Results revealed that nCPAP decreased feeding duration [25 vs. 31 s (control) vs. 57 s (HFNC), p = 0.03] and increased the rate of milk transfer [2.4 vs. 1.9 mL/s (control) vs.1.1 mL/s (HFNC), p = 0.03]. No other indices of bottle-feeding safety or sucking-swallowing-breathing coordination were significantly altered by HFNC or nCPAP. In conclusion, our results obtained in full-term newborn lambs suggest that: (i) nCPAP 6 cmH2O, but not HFNC 7 L/min, increases bottle-feeding efficiency; (ii) bottle-feeding is safe under nCPAP 6 cmH2O and HFNC 7 L/min, with no significant alteration in sucking-swallowing-breathing coordination. The present informative and reassuring data in full-term healthy lambs must be complemented by similar studies in preterm lambs, including mild-to-moderate respiratory distress alleviated by respiratory support in order to mimic preterm infants with bronchopulmonary dysplasia and pave the way for clinical studies.


The economic burden of switching targeted disease-modifying anti-rheumatic drugs among rheumatoid arthritis patients.
To estimate real world healthcare costs and resource utilization of rheumatoid arthritis (RA) patients associated with targeted disease modifying anti-rheumatic drugs (tDMARD) switching in general and switching to abatacept specifically. RA patients initiating a tDMARD were identified in IMS PharMetrics Plus health insurance claims data (2010-2016), and outcomes measured included monthly healthcare costs per patient (all-cause, RA-related) and resource utilization (inpatient stays, outpatient visits, emergency department [ED] visits). Generalized linear models were used to assess (i) average monthly costs per patient associated with tDMARD switching, and (ii) among switchers only, costs of switching to abatacept vs tumor necrosis factor inhibitors (TNFi) or other non-TNFi. Negative binomial regressions were used to determine incident rate ratios of resource utilization associated with switching to abatacept. Among 11,856 RA patients who initiated a tDMARD, 2,708 switched tDMARDs once and 814 switched twice (to a third tDMARD). Adjusted average monthly costs were higher among patients who switched to a second tDMARD vs non-switchers (all-cause: $4,785 vs $3,491, p < .001; RA-related: $3,364 vs $2,297, p < .001). Monthly RA-related costs were higher for patients switching to a third tDMARD compared to non-switchers remaining on their second tDMARD ($3,835 vs $3,383, p < .001). Switchers to abatacept had significantly lower RA-related monthly costs vs switchers to TNFi ($3,129 vs $3,436, p = .021), and numerically lower all-cause costs ($4,444 vs $4,741, p = 0.188). Switchers to TNFi relative to abatacept had more frequent inpatient stays after switch (incidence rate ratio (IRR) = 1.85, p = .031), and numerically higher ED visits (IRR = 1.32, p = .093). Outpatient visits were less frequent for TNFi switchers (IRR = 0.83, p < .001) compared to switchers to abatacept. Switching to another tDMARD was associated with higher healthcare costs. Switching to abatacept, however, was associated with lower RA-related costs, fewer inpatient stays, but more frequent outpatient visits compared to switching to a TNFi.


MRI-detection rate and incidence of lumbar bleeding sources in 190 patients with non-aneurysmal SAH.
Up to 15% of all spontaneous subarachnoid hemorrhages (SAH) have a non-aneurysmal SAH (NASAH). The evaluation of SAH patients with negative digital subtraction angiography (DSA) is sometimes a diagnostic challenge. Our goal in this study was to reassess the yield of standard MR-imaging of the complete spinal axis to rule out spinal bleeding sources in patients with NASAH. We retrospectively analyzed the spinal MRI findings in 190 patients with spontaneous NASAH, containing perimesencephalic (PM) and non-perimesencephalic (NPM) SAH, diagnosed by computer tomography (CT) and/or lumbar puncture (LP), and negative 2nd DSA. 190 NASAH patients were included in the study, divided into PM-SAH (n = 87; 46%) and NPM-SAH (n = 103; 54%). Overall, 23 (22%) patients had a CT negative SAH, diagnosed by positive LP. MR-imaging of the spinal axis detected two patients with lumbar ependymoma (n = 2; 1,05%). Both patients complained of radicular sciatic pain. The detection rate raised up to 25%, if only patients with radicular sciatic pain received an MRI. Routine radiological investigation of the complete spinal axis in NASAH patients is expensive and can not be recommended for standard procedure. However, patients with clinical signs of low-back/sciatic pain should be worked up for a spinal pathology.