Differential expression of synaptophysin and synaptoporin mRNAs in the postnatal rat central nervous system.
Synaptophysin and synaptoporin are two homologous integral membrane proteins of small synaptic vesicles. Here, the distribution of the corresponding transcripts in the CNS of the rat was investigated by in situ hybridization using sequence-specific oligonucleotide probes. Synaptophysin mRNA was abundantly distributed through all major brain regions, whereas synaptoporin transcripts displayed a more restricted localization in telencephalic structures. Resolution at the cellular level disclosed a differential labeling of distinct cell types in different areas, suggesting that synaptophysin and synaptoporin are expressed by specific subpopulations of central neurons. Consistent with this conclusion, relative synaptoporin mRNA contents were found to vary between different brain regions during postnatal development, whereas synaptophysin transcripts showed a more uniform increase during the same period.


Clinical validation of genetic variants associated with in vitro chemotherapy-related lymphoblastoid cell toxicity.
Hematotoxicity is one of the major side effects of chemotherapy. The aim of this study was to examine the association between single nucleotide polymorphisms (SNPs) and hematotoxicity in breast cancer patients in a subset of patients of the SUCCESS prospective phase III chemotherapy study. All patients (n = 1678) received three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by three cycles of docetaxel or docetaxel/gemcitabine, depending on randomization. Germline DNA was genotyped for 246 SNPs selected from a previous genome-wide association study (GWAS) in a panel of lymphoblastoid cell lines, with gemcitabine toxicity as the phenotype. All SNPs were tested for their value in predicting grade 3 or 4 neutropenic or leukopenic events (NLEs). Their prognostic value in relation to overall survival and disease-free survival was also tested. None of the SNPs was found to be predictive for NLEs during treatment with docetaxel/gemcitabine. Two SNPs in and close to the PIGB gene significantly improved the prediction of NLEs after FEC, in addition to the factors of age and body surface area. The top SNP (rs12050587) had an odds ratio of 1.38 per minor allele (95% confidence interval, 1.17 to 1.62). No associations were identified for predicting disease-free or overall survival. Genetic variance in the PIGB gene may play a role in determining interindividual differences in relation to hematotoxicity after FEC chemotherapy.


Behavioral similarities and differences among alcohol-preferring and -nonpreferring rats: confirmation by factor analysis and extension to additional groups.
Thirteen behavioral variables from six tasks were measured in alcohol-preferring (AA, FH, and P) and -nonpreferring (ANA, FRL, and NP) rat lines/strains and subjected to Factor Analysis. Four Independent factors accounted for > 90% of the variance. Defecation in the open field and ultrasonic vocalizations after an air puff were negatively correlated with alcohol intake and preference, whereas the increase in daily fluid intake in the presence of saccharin was positively correlated. Other factors could be labeled Activity, Emotionality, and immobility Factors, and each was independent of the Alcohol Factor. When an additional alcohol-preferring rat line (HAD) and two additional nonpreferring groups (LAD and ACI) were tested, they were found to differ on most behaviors that were associated with alcohol intake and preference in the Factor Analysis; vocalizations and saccharin-induced increase in fluid intake, but not defection. A new Factor Analysis was then performed incorporating these three new groups and including five new behavioral measures. The following measures had high loadings on the Alcohol Factor: alcohol intake under choice conditions; alcohol preference; forced alcohol intake; alcohol acceptance (forced alcohol intake/basal water intake x 100); ultrasonic vocalization; saccharin intake; saccharin-induced increase in daily fluid intake; defecation in the open field test; and immobility in a modified forced swim test. These findings indicate that there are indeed certain behavioral characteristics that are common among alcohol-preferring rat lines/strains, but there are also substantial group differences on other behavioral measures. For those behavioral measures reflecting emotionality (defecation and ultrasonic vocalization) that loaded highly on the Alcohol Factor, the alcohol-preferring rats had lower scores.


[Biodegradation of oil hydrocarbons by Candida yeast].
Capability of 14 yeast species to utilize oil hydrocarbons has been analyzed. All strains utilized oil hydrocarbons as a single carbon source. Four strains-destructors that are characterized by higher growth in the presence oil in cultivation medium have been chosen among them. Peroxisomes participation in utilization of oil hydrocarbons by strains-destructors has been shown. Availability of peroxisome key enzymes are characteristic of these strains grown in cultivation medium with oil. Numerous peroxisomes available in the cells of some strains grown in oil cultivation medium have been demonstrated. Utilization of a wide spectrum of oil hydrocarbons has been revealed in all four strains. Two strains are promising to be used for environment purification from oil pollution.


Twenty-Five Years of Intracranial Pressure Monitoring After Severe Traumatic Brain Injury: A Retrospective, Single-Center Analysis.
Intracranial pressure (ICP) is a clinically important variable after severe traumatic brain injury (TBI) and has been monitored, along with clinical outcome, for over 25 yr in Addenbrooke's hospital, Cambridge, United Kingdom. This time period has also seen changes in management strategies with the implementation of protocolled specialist neurocritical care, expansion of neuromonitoring techniques, and adjustments of clinical treatment targets. To describe the changes in intracranial monitoring variables over the past 25 yr. Data from 1146 TBI patients requiring ICP monitoring were analyzed. Monitored variables included ICP, cerebral perfusion pressure (CPP), and the cerebral pressure reactivity index (PRx). Data were stratified into 5-yr epochs spanning the 25 yr from 1992 to 2017. CPP increased sharply with specialist neurocritical care management (P < 0.0001) (introduction of a specific TBI management algorithm) before stabilizing from 2000 onwards. ICP decreased significantly over the 25 yr of monitoring from an average of 19 to 12 mmHg (P < 0.0001) but PRx remained unchanged. The mean number of ICP plateau waves and the number of patients developing refractory intracranial hypertension both decreased significantly. Mortality did not significantly change in the cohort (22%). We demonstrate the evolving trends in neurophysiological monitoring over the past 25 yr from a single, academic neurocritical care unit. ICP and CPP were responsive to the introduction of an ICP/CPP protocol while PRx has remained unchanged.


Multimedia & PBPK modelling with MERLIN-Expo versus biomonitoring for assessing Pb exposure of pre-school children in a residential setting.
This paper reports on a case study - conducted within the European FP7 project "4FUN" - focusing on exposure of pre-school children to lead resulting from past emissions by non-ferrous smelters in Belgium (Northern Campine area). Exposure scenarios were constructed and simulated with the MERLIN-Expo tool to estimate external Pb exposure as well as the Pb body burden in children living in the vicinity of the former industrial sites as compared to children living in adjacent areas and a reference area. Simulations were run for several scenarios ranging from very simple to rather complex in order to study the effect of different simulation approaches (e.g., deterministic vs. probabilistic, individual vs. aggregated population exposure) and different exposure scenarios (e.g., with vs. without considering local food consumption or time activity patterns) on the model outcomes (predicted concentrations of Pb in environmental and human matrices). This paper discusses the two most complex scenarios, namely exposure at the aggregated population level and at the individual level for a random sub-sample of subjects, respectively. In the final and most realistic exposure scenario, simulating individual lead exposure, model predictions were shown to be higher than the biomonitoring data. Blood Pb levels in children, irrespective of the area they lived in, were overpredicted by MERLIN-Expo with a factor of about 2 on average. The model predictions for individual children overlap with the prediction interval calculated by MERLIN-Expo based on population averages, demonstrating the use of probabilistic approaches in risk assessment. While these results constitute a first verification of the model performance of MERLIN-Expo dealing with inorganic pollutants in a complex real-world exposure scenario and a demonstration of the robustness of the modelling tool, further validation and benchmarking efforts are required for a larger number of inorganic pollutants and different exposure settings.


Process evaluation of an intensified preventive intervention to reduce cardiovascular risk in general practices in deprived neighbourhoods.
A RCT, conducted to examine the effectiveness of a structured collaboration in general practice to provide intensified preventive care in patients at high cardiovascular risk yielded no effect in the total group but differences across healthcare centres and ethnic groups become apparent. We conducted a process evaluation to explain these differences. We assessed the reach of the target group and whether key intervention components (individual educational sessions, structured team meetings, and risk assessments) were performed as planned (maximum score for protocol completion is 11). The reach was initially 91%, but only a minority of patients completed the intervention activities as planned. The average score of the number of intervention components was low (5.66 out of 11 (sd 2.8)) and varied between centres (4.84 to 7.40) and ethnic groups (4.89 to 7.38), with team meetings as the least implemented activity conform plan. This study indicates that adding a practice nurse and a peer health educator to the general practice did not seem to result in the desired collaboration between the healthcare personnel. Further research is needed to investigate the reasons behind the low participation rate of the patients in the intervention.


Ratiometric temperature sensing with fluorescent thermochromic switches.
The connection of fluorescent chromophores to switchable heterocycles translates into molecular probes with ratiometric response to temperature. The opening and closing of their heterocyclic component equilibrates two emissive species with resolved fluorescence. Their relative emission intensities change monotonically with temperature to enable the visualization of thermal distributions at the microscale.


Impact of SNPs on CpG Islands in the MYC and HRAS oncogenes and in a wide variety of tumor suppressor genes: A multi-cancer approach.
Single nucleotide polymorphisms (SNPs) that occur within CpG Islands may lead to increased hypermethylation if a SNP allele has the potential to form a CpG dinucleotide, as well as potentially lead to hypomethylation if a SNP allele eliminates a CpG dinucleotide. We analyzed CpG-related SNP allele frequencies in whole genome sequences (WGS) across 5 TCGA cancer datasets, thereby exploiting a more recent appreciation for signaling pathway degeneracy in cancer. The cancer data sets were analyzed for SNPs in CpG islands associated with the oncogenes, HRAS and MYC, and in the CpG islands associated with the tumor suppressor genes, APC, DCC, and RB1. We determined that one SNP allele (rs3824120) in a CpG island associated with MYC which eliminated a CpG was more common in the cancer datasets than in the 100Genomes databases (p < 0.01). For HRAS, 2 SNP alleles (rs112690925, rs7939028) that created CpG's occurred significantly less frequently in the cancer data sets than in the general SNP databases (e.g., rs7939028, p < 0.0002, in comparison with AllSNPs(142)). Also, one SNP allele (rs4940177) that created a CpG in a CpG island associated with the DCC tumor suppressor gene, was more common in the cancer datasets (p < 0.0007). To understand a broader picture of the potential of SNP alleles to create CpG's in CpG islands of tumor suppressor genes, we developed a scripted algorithm to assess the SNP alleles associated with the CpG islands of 43 tumor suppressor genes. The following tumor suppressor genes have the possibility of significant, percent increases in their CpG counts, depending on which SNP allele(s) is present: VHL, BRCA1, BRCA2, CHEK2, PTEN and RB1.


Trends in HIV incidence in homosexual men in developed countries.
To describe trends in HIV notifications and in other measures of HIV incidence in homosexual men in developed countries. A literature search was conducted using PubMed. In addition to the peer-reviewed literature, data on HIV surveillance trends were sought by searching websites of surveillance authorities in developed countries. The availability of long-term HIV surveillance data varied considerably. However, in almost all jurisdictions in which such data were available, notifications of new HIV diagnoses among homosexual men have increased, mostly since the late 1990s. The magnitude of this increase varied, but was more than 50% in many countries. There were much fewer data available on trends in direct measures of HIV incidence in homosexual men, and increases in HIV testing rates may have contributed to the increases in HIV diagnoses in many countries. However, since the late 1990s, several clinic- and community-based cohort studies in Europe and North America reported increasing incidence. There were increases in HIV notifications in homosexual men in almost all developed countries, starting in the late 1990s and continuing to 2006. Although increases in HIV testing probably contributed to the increases in some settings, limited cohort data do support the existence of a true increase in HIV incidence in European and North American countries. Improved monitoring of HIV incidence in homosexual men at the population level is required to allow more timely assessment of the drivers underlying such trends.


Cancer and disability benefits: a synthesis of qualitative findings on advice and support.
Following the Supportive and Palliative Care Guidance, a call was made for a meta-ethnography on social support services for people affected by cancer. We responded by focusing on the topic of financial advice and support. After a scoping exercise revealed little qualitative evidence, we adopted the chief aim of identifying issues for research. Over 50 keywords relating to patient finances, cancer and qualitative research were entered into electronic search databases and combined. Because of the nature of the literature found, we synthesized primary data into themes and discussion, rather than second-order constructs into third-order constructs, as is common in meta-ethnography. Most of the literature found serves pragmatic, campaigning and/or service-development objectives. Also, most relates to disability benefits rather than insurance, tax and other issues. Five themes emerged: patients' struggles to obtain financial advice and benefits; tests/rules for disability benefits; issues relating to 'Special Rules'; intervention by benefit advisers; and intervention by health/social-care professionals. Struggles with the benefit system emerged as the fundamental theme. We conclude that patients need sensitive, proactive services to assist with benefit claims, and a benefit system that seems supportive rather than obstructive. Numerous under-researched topics were identified, including the need for general financial advice, help for carers, and cultural issues.


The role of surgery in metastatic squamous cell carcinoma of the penis.
Prognosis of penile squamous cell cancer (PeSCC) depends on the involvement of the groin(s) as first step. We introduce the current available evidences that should rule the use of surgery in the management of PeSCC. Prophylactic inguinal node dissection in patients with no palpable nodes associates with immediate and long-term side-effects in up to 70% of patients. Recent findings support selective intervention based on early identification of dynamic sentinel node biopsy (DSNB) with false negative rate of 4-12%. Adequate node retrieval and extending surgery to the pelvis have been addressed as important key factors as staging and therapeutic factors in patients with nodal metastases. Pelvic dissections could be spared only in patients with small (< 3 cm), limited (< 3 nodes) and no extranodal extension. Bilateral pelvic dissection should be recommended in case of involvement of bilateral nodes of at least four. Cisplatin-based neo-adjuvant chemotherapy has a moderate activity, whereas adjuvant chemotherapy associates with prolonged survival in a proportion of patients. In case of nodal metastases, surgery still represents the most effective treatment. Preventive surgery could be driven by DSNB, which needs an accurate multistep pathway. Extent of surgery is of paramount importance, and inguinal only and unilateral dissections should be reserved to selected patients with the most favorable features. Definitive conclusions concerning perioperative chemotherapy cannot be drawn.


Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study.
Atherosclerosis is the most common complication of diabetes. Correction of hyperglycaemia helps to prevent microvascular complications but has little effect on macrovascular disease. Post-hoc analyses of diabetic subpopulations in lipid intervention trials suggest that correction of lipoprotein abnormalities will lead to a decrease in coronary-artery disease. The Diabetes Atherosclerosis Intervention Study (DAIS) was specifically designed to assess the effects of correcting lipoprotein abnormalities on coronary atherosclerosis in type 2 diabetes. 731 men and women with type 2 diabetes were screened by metabolic and angiographic criteria. 418 were randomly assigned micronised fenofibrate (200 mg/day) or placebo for at least 3 years. They were in good glycaemic control (mean haemoglobin A1c 7.5%), had mild lipoprotein abnormalities, typical of type 2 diabetes, and at least one visible coronary lesion. Half had no previous clinical coronary disease. Initial and final angiograms followed a standard protocol and were analysed by a computer-assisted quantitative approach. Missing data for the primary endpoints (minimum lumen diameter, mean segment diameter, and mean percentage stenosis) were imputed. Analyses were by intention to treat. Total plasma cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations all changed significantly more from baseline in the fenofibrate group (n=207) than in the placebo group (n=211). The fenofibrate group showed a significantly smaller increase in percentage diameter stenosis than the placebo group (mean 2.11 [SE 0.594] vs 3.65 [0.608]%, p=0.02), a significantly smaller decrease in minimum lumen diameter (-0.06 [0.016] vs -0.10 [0.016] mm, p=0.029), and a non-significantly smaller decrease in mean segment diameter (-0.06 [0.017] vs -0.08 [0.018] mm, p=0.171). The trial was not powered to examine clinical endpoints, but there were fewer in the fenofibrate group than the placebo group (38 vs 50). DAIS suggests that treatment with fenofibrate reduces the angiographic progression of coronary-artery disease in type 2 diabetes. This effect is related, at least partly, to the correction of lipoprotein abnormalities, even those previously judged not to need treatment.


Ornamental Flowers Grown in Human Surroundings as a Source of Anthocyanins with High Anti-Inflammatory Properties.
Flowers have always accompanied people thanks to their manifold aesthetic properties. Some species have also become a component of the human diet. Recent years have seen an increased interest in edible flowers and, consequently, research has been undertaken to determine their chemical composition. Dyes that are abundantly contained in flowers, whose role is to attract pollinating animals, are recognized substances with health-promoting properties. Anthocyanins are a group of dyes that are very common in petals and other parts of flowers. Studies carried out in the twentieth and twenty-first century on flowers growing in temperate climates have found very strong antioxidant and anti-inflammatory properties of anthocyanins. Therefore, flowers used by humans for centuries to decorate their surroundings may become an easily available source of nutrients and health-promoting substances. This paper discusses the health-promoting properties of anthocyanins and collects literature on anthocyanin content in edible flowers commonly grown on balconies, terraces, and roofs in countries of temperate climate.


Human Herpesvirus 6 and Malignancy: A Review.
In order to determine the role of human herpesvirus 6 (HHV-6) in human disease, several confounding factors, including methods of detection, types of controls, and the ubiquitous nature of the virus, must be considered. This is particularly problematic in the case of cancer, in which rates of detection vary greatly among studies. To determine what part, if any, HHV-6 plays in oncogenesis, a review of the literature was performed. There is evidence that HHV-6 is present in certain types of cancer; however, detection of the virus within tumor cells is insufficient for assigning a direct role of HHV-6 in tumorigenesis. Findings supportive of a causal role for a virus in cancer include presence of the virus in a large proportion of cases, presence of the virus in most tumor cells, and virus-induced in-vitro cell transformation. HHV-6, if not directly oncogenic, may act as a contributory factor that indirectly enhances tumor cell growth, in some cases by cooperation with other viruses. Another possibility is that HHV-6 may merely be an opportunistic virus that thrives in the immunodeficient tumor microenvironment. Although many studies have been carried out, it is still premature to definitively implicate HHV-6 in several human cancers. In some instances, evidence suggests that HHV-6 may cooperate with other viruses, including EBV, HPV, and HHV-8, in the development of cancer, and HHV-6 may have a role in such conditions as nodular sclerosis Hodgkin lymphoma, gastrointestinal cancer, glial tumors, and oral cancers. However, further studies will be required to determine the exact contributions of HHV-6 to tumorigenesis.


Longitudinal associations of volunteering, grandparenting, and family care with processing speed: A gender perspective on prosocial activity and cognitive aging in the second half of life.
An active lifestyle has been associated with better cognitive performance in many studies. However, most studies have focused on leisure activities or paid work, with less consideration of the kind of prosocial activities, many people engage in, including volunteering, grandparenting, and family care. In the present study, based on four waves of the German Ageing Survey (N = 6,915, aged 40-85 at baseline), we used parallel growth curves to investigate the longitudinal association of level and change in volunteering, grandparenting, and family care with level and change in processing speed. Given the gendered nature of engagement in these activities over the life span, we tested for gender differences in the associations. Only volunteering was reliably associated with higher speed of processing at baseline, no consistent longitudinal associations were found. Our results show that although prosocial activities are of great societal importance, expectations of large rewards in terms of cognitive health may be exaggerated. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Swimming mechanics and propulsive efficiency in the chambered nautilus.
The chambered nautilus (Nautilus pompilius) encounters severe environmental hypoxia during diurnal vertical movements in the ocean. The metabolic cost of locomotion (Cmet) and swimming performance depend on how efficiently momentum is imparted to the water and how long on-board oxygen stores last. While propulsive efficiency is generally thought to be relatively low in jet propelled animals, the low Cmet in Nautilus indicates that this is not the case. We measured the wake structure in Nautilus during jet propulsion swimming, to determine their propulsive efficiency. Animals swam with either an anterior-first or posterior-first orientation. With increasing swimming speed, whole cycle propulsive efficiency increased during posterior-first swimming but decreased during anterior-first swimming, reaching a maximum of 0.76. The highest propulsive efficiencies were achieved by using an asymmetrical contractile cycle in which the fluid ejection phase was relatively longer than the refilling phase, reducing the volume flow rate of the ejected fluid. Our results demonstrate that a relatively high whole cycle propulsive efficiency underlies the low Cmet in Nautilus, representing a strategy to reduce the metabolic demands in an animal that spends a significant part of its daily life in a hypoxic environment.


Transmission of human papillomavirus type 11 infection by desquamated cornified cells.
While much is known about the human papillomavirus (HPV) productive cycle, the mechanisms of virion transmission from person to person are poorly understood. The keratinocyte is the target cell of HPV infection. As keratinocytes differentiate, nuclei are lost and the cornified cell envelope develops. Layers of these desquamated cornified cells (DCCs) are continuously shed from the stratum corneum. Release of HPV requires the cornified cell envelope, a normally very durable structure, to break apart, liberating the contents of the cell. In differentiated keratinocytes infected with HPV 11, the cornified cell envelope is abnormally thin and fragile. In this study, DCCs from HPV 11-infected genital epithelium were used to investigate the mechanisms of viral transmission. First, HPV 11-infected tissue was examined for the presence of virions by transmission electron microscopy. Virions were observed in the nuclei of differentiated keratinocytes. In addition, virions were detected in the cytoplasm of DCCs that had undergone nuclear dissolution. Rarely, virions were observed outside of cells. Next, infectivity of intact and ruptured DCCs was tested in an assay performed in the athymic mouse xenograft system. High-titer cesium chloride gradient-purified HPV 11 virions infected 100% of recovered xenografts. Using intact DCCs derived from HPV 11-infected tissue, 62.5% of recovered xenografts were infected. To test the effects of mechanical stress on infectivity, DCCs were ruptured by sonication and used in the infectivity assay. The infectivity rate increased to 90%. We conclude that DCCs serve as vehicles for efficient, concentrated delivery of virions in HPV 11 infection.


A gene regulatory network for Müllerian duct regression.
Mammalian embryos initially develop progenitor tissues for both male and female reproductive tract organs, known as the Wolffian ducts and the Müllerian ducts, respectively. Ultimately, each individual develops a single set of male or female reproductive tract organs. Therefore, an essential step for sex differentiation is the regression of one duct and growth and differentiation of the other duct. In males, this requires Müllerian duct regression and Wolffian duct growth and differentiation. Müllerian duct regression is induced by the expression of Amh, encoding anti-Müllerian hormone, from the fetal testes. Subsequently, receptor-mediated signal transduction in mesenchymal cells surrounding the Müllerian duct epithelium leads to duct elimination. The genes that induce Amh transcription and the downstream signaling that results from Amh activity form a pathway. However, the molecular details of this pathway are currently unknown. A set of essential genes for AMH pathway function has been identified. More recently, transcriptome analysis of male and female Müllerian duct mesenchyme at an initial stage of regression has identified new genes that may mediate elimination of the Müllerian system. The evidence taken together can be used to generate an initial gene regulatory network describing the Amh pathway for Müllerian duct regression. An Amh gene regulatory network will be a useful tool to study Müllerian duct regression, sex differentiation, and its relationship to environmental influences.


Microbial control of silicate weathering in organic-rich ground water.
An in situ microcosm study of the influence of surface-adhering bacteria on silicate diagenesis in a shallow petroleum-contaminated aquifer showed that minerals were colonized by indigenous bacteria and chemically weathered at a rate faster than theoretically predicted. Feldspar and quartz fragments were placed in anoxic, organic-rich ground water, left for 14 months, recovered, and compared to unreacted controls with scanning electron microscopy. Ground-water geochemistry was characterized before and after the experiment. Localized mineral etching probably occurred in a reaction zone at the bacteria-mineral interface where high concentrations of organic acids, formed by bacteria during metabolism of hydrocarbon, selectively mobilized silica and aluminum from the mineral surface.


The Qrc membrane complex, related to the alternative complex III, is a menaquinone reductase involved in sulfate respiration.
Biological sulfate reduction is a process with high environmental significance due to its major contribution to the carbon and sulfur cycles in anaerobic environments. However, the respiratory chain of sulfate-reducing bacteria is still poorly understood. Here we describe a new respiratory complex that was isolated as a major protein present in the membranes of Desulfovibrio vulgaris Hildenborough. The complex, which was named Qrc, is the first representative of a new family of redox complexes. It has three subunits related to the complex iron-sulfur molybdoenzyme family and a multiheme cytochrome c and binds six hemes c, one [3Fe-4S](+1/0) cluster, and several interacting [4Fe-4S](2+/1+) clusters but no molybdenum. Qrc is related to the alternative complex III, and we show that it has the reverse catalytic activity, acting as a Type I cytochrome c(3):menaquinone oxidoreductase. The qrc genes are found in the genomes of deltaproteobacterial sulfate reducers, which have periplasmic hydrogenases and formate dehydrogenases that lack a membrane subunit for reduction of the quinone pool. In these organisms, Qrc acts as a menaquinone reductase with electrons from periplasmic hydrogen or formate oxidation. Binding of a menaquinone analogue affects the EPR spectrum of the [3Fe-4S](+1/0) cluster, indicating the presence of a quinone-binding site close to the periplasmic subunits. Qrc is the first respiratory complex from sulfate reducers to have its physiological function clearly elucidated.


The interpretation of biological motion.
The term biological motion has been coined by Johansson (1973) to refer to the ambulatory patterns of terrestrial bipeds and quadripeds. In this paper a computational theory of the visual perception of biological motion is proposed. The specific problem addressed is how the three-dimensional structure and motions of animal limbs may be computed from the two dimensional motions of their projected images. It is noted that the limbs of animals typically do not move arbitrarily during ambulation. Rather, for anatomical reasons, they typically move in single planes for extended periods of time. This simple anatomical constraint is exploited as the basis for utilizing a "planarity assumption" in the interpretation of biological motion. The analysis proposed is: (1) divide the image into groups of two or three elements each; (2) test each group for pairwise-rigid planar motion; (3) combine the results from (2). Fundamental to the analysis are two "structure from planar motion" propositions. The first states that the structure and motion of two points rigidly linked and rotating in a plane is recoverable from three orthographic projections. The second states that the structure and motion of three points forming two hinged rods constrained to move in a plane is recoverable from two orthographic projections. The psychological relevance of the analysis and possible interactions with top down recognition processes are discussed.


Targeting GSTP1-1 induces JNK activation and leads to apoptosis in cisplatin-sensitive and -resistant human osteosarcoma cell lines.
The effect of the glutathione transferase P1-1 (GSTP1-1) targeting has been investigated in both sensitive (U-2OS) and cisplatin-resistant (U-2OS/CDDP4 μg) human osteosarcoma cell lines. Despite the different enzyme's content, inhibition of GSTP1-1 by 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) causes the activation of c-Jun N-terminal kinase (JNK) and apoptosis in both cell lines. However, different time courses of JNK activation and cell responses are observed. Whereas in the U-2OS/CDDP4 μg cell line drug treatment results in an early increase of caspase activity and secondary necrosis, in the U-2OS cells it mainly causes an early cell cycle arrest followed by apoptosis. In order to elucidate the action mechanism of NBDHEX we performed a proteomic investigation by label-free nLC-MS(E). The high-throughput analysis associated with a bioinformatic tool suggested the involvement of the TNF receptor associated factor (TRAF) family in the cellular response to the drug treatment. We report experimental evidence of the interaction between GSTP1-1 and TRAF2 and we demonstrate that NBDHEX is able to dissociate the GSTP1-1 : TRAF2 complex. This restores the TRAF2 : ASK1 signaling, thereby leading to the simultaneous and prolonged activation of JNK and p38. These mitogen-activated protein kinases (MAPKs) mediate different effects: JNK is crucial for apoptosis, whereas p38 causes an increase in the p21 level and a concomitant cell cycle arrest. Our study shows that GSTP1-1 plays an important regulatory role in TRAF signaling of osteosarcoma and discloses new features of the action mechanism of NBDHEX that suggest potentially practical consequences of these findings.


Predictors of time to recovery in infants with probable serious bacterial infection.
Serious bacterial infections continue to be an important cause of death and illness among infants in developing countries. Time to recovery could be considered a surrogate marker of severity of the infection. We therefore aimed to identify clinical and laboratory predictors of time to recovery in infants with probable serious bacterial infection (PSBI). We used the dataset of 700 infants (7-120 days) enrolled in a randomised controlled trial in India in which 10mg of oral zinc or placebo was given to infants with PSBI. PSBI was defined as signs/symptoms of possible serious bacterial infection along with baseline C-reactive protein(CRP) level >12mg/L. Time to recovery was defined as time from enrolment to the end of a 2-day period with no symptoms/signs of PSBI and daily weight gain of at least 10g over 2 succesive days on exclusive oral feeding. Cox proportional hazard regression was used to measure the associations between relevant variables and time to recovery. Infants who were formula fed prior to illness episode had 33% longer time to recovery (HR-0.67, 95%CI-0.52, 0.87) than those who were not. Being underweight (HR-0.84, 95%CI-0.70, 0.99), lethargic (HR-0.77, 95%CI-0.62, 0.96) and irritable (HR-0.81, 95%CI-0.66, 0.99) were independent predictors of time to recovery. Baseline CRP was significantly associated with time to recovery (P<0.001), higher CRP was associated with longer time to recovery and this association was nearly linear. Simple clinical and laboratory parameters such as formula feeding prior to the illness, being underweight, lethargic, irritable and having elevated CRP levels could be used for early identification of infants with PSBI at risk for protracted illness and could guide prompt referral to higher centers in resource limited settings. This also provides prognostic information to clinicians and family as longer recovery time has economic and social implications on the family in our setting. ClinicalTrials.gov NCT00347386.


Cognitive ability, expertise, and age differences in following air-traffic control instructions.
Differences in cognitive ability and domain-specific expertise may help explain age differences in pilot performance. Pilots heard air-traffic controller messages and then executed them while "flying" in a simulator. Messages varied in length and speech rate. Age was associated with lower accuracy, but the expected Age x Message Difficulty interactions were not obtained. Expertise, as indexed by pilot ratings, was associated with higher accuracy; yet expertise did not reduce age differences in accuracy. The effect of age on communication task accuracy was largely explainable as an age-associated decrease in working memory span, which in turn was explainable as decreases in both speed and interference control. Results are discussed within frameworks of deliberate practice and cognitive mediation of age differences.


[Clinical applicability of the term 'transient neurological attack'].
Transient neurological symptoms not fulfilling the criteria for TIA are a problem often encountered in clinical practice. In a large cohort from the Rotterdam study, it was found that these 'transient neurological attacks' (TNA) increase the risk of future cardiovascular events and dementia. However, the group of patients diagnosed with TNA concerns a heterogeneous group with a wide variety of non-focal symptoms. A considerable proportion is probably not caused by vascular (atherothrombotic) disease. Therefore, in our opinion, the reported higher risk for cardiovascular events and dementia should not lead to treatment aimed at secondary prevention in the TNA group as a whole, as it is customary in TIA patients. However, the increased risk for cardiovascular disease, as found in this study, emphasises the need for a thorough search for a possible vascular cause of the symptoms and the presence of cardiovascular risk factors in this complicated group of patients.


Telepsychiatry services for Korean immigrants.
Asian Americans often face cultural and language barriers when obtaining mental health treatment. With the small number of Asian mental health providers, it is difficult to ensure the linguistic and ethnic matching of providers and patients. Telepsychiatry holds great promise to address the unique needs of Asian Americans. We developed a project to establish telepsychiatry services that connect Korean mental health patients in Georgia with a linguistically and culturally competent psychiatrist in California and assessed the level of acceptability of psychiatric treatment via real-time teleconferencing among these patients. Upon the completion of the program, 16 patients (5 men, 11 women) completed a questionnaire that measured their acceptability of the telepsychiatry service. The findings indicate a high level of acceptance of the program among Korean patients. The quantitative and qualitative data show that they especially appreciated the cultural sensitivity of the consultation and the comfortable interaction with the provider. However, challenges such as technical issues of teleconferencing may negatively affect the quality of the clinical interaction. Our study expands the knowledge base regarding the acceptability of such services to a population that experiences disparities in mental health care. Future research should extend telepsychiatry services to other Asian population groups that experience lower access to mental health services.


Vaginal eroticism: a replication study.
Vaginal eroticism was investigated in a group of 27 coitally experienced volunteers by means of systematic digital stimulation of both vaginal walls. Erogenous zones were found in all subjects, mainly located on the upper anterior wall and the lower posterior one. An orgasmic response was elicited by stimulation of these zones in 89% of the subjects. This study supports previous findings regarding vaginal eroticism. It does not support the existence of the discrete anatomical structure called the Grafenberg spot. It supports the contention that there are two distinct types of female orgasm, vaginally evoked and clitorally evoked. It also supports the finding that some women expel a fluid through the urethra at the time of orgasm. In this particular case the fluid was chemically indistinguishable from urine.


Situational characteristics of young adults' eating occasions: a real-time data collection using Personal Digital Assistants.
To examine (i) situational characteristics of young adults' eating occasions, including away-from-home eating, social influences and multi-tasking, and (ii) how these characteristics are associated with specific foods/beverages consumed. Participants logged numerous characteristics of eating occasions (n 1237) in real time over 7 d. Minneapolis/St. Paul metropolitan area (Minnesota, USA). Forty-eight participants, aged 18-23 years. Half of all eating occasions (46 %) occurred alone, 26 % occurred while watching television and 36 % involved other multi-tasking. Most participants (63 %) did not think about their food choices in advance of eating occasions. Eating that occurred in the absence of television viewing and/or other multi-tasking was less likely to include sweetened beverages and more likely to include items like water, fruit, vegetables, cereal, grains and entrées. Eating occasions occurring alone, and/or those occurring at home, were more likely to include snack foods that required little preparation (e.g. cookies, baked goods) and less likely to include more traditional meal items (e.g. fruits, vegetables, entrée items). Overall, a large proportion of young adults' eating occasions occurred alone, while engaging in other activities and with little advanced planning. Although many young adults' eating occasions consist of a wide range of highly processed, energy-dense, convenience products, more traditional meal settings (i.e. eating at home with others in the absence of multi-tasking) may result in more structured mealtimes and better food choices, such as more fruits and vegetables. Effective behavioural strategies promoting positive eating patterns, including home meal preparation, are urgently needed among young adults.


[Work ability, psycho-physical health, burnout, and age among nursery school and kindergarten teachers: a cross-sectional study].
Although well-being and psychophysical health of nursery school and kindergarten teachers have important implications also on the health and well-being of their recipients, studies dedicated to these workers are quite rare, particularly in Italy. The aim of the study was to observe psychophysical health conditions in a sample of nursery school and kindergarten teachers employed in the Education Services Division of the Municipality of Turin. The study was cross-sectional; 884 self-reporting questionnaires were distributed and 734 teachers (representing 53% of those employed at the Education Services of the Municipality of Turin) correctly filled out the questionnaire. Respectively 53.4% and 50% of participants reported medium or high levels of emotional exhaustion and depersonalization, while 18.5% showed low levels of personal accomplishment. Responders reported moderate levels of work ability in 38.9% and poor levels in 5.6%. The majority of the respondents (98.7%) did not report depressive symptoms; 42.9% of the sample suffered moderate to severe limiting musculoskeletal pain. Age and profession were associated with emotional exhaustion, personal accomplishment, and musculoskeletal pain. However, work ability and depression were only associated with age. No associations were found with depersonalization. The present study shows that health conditions of nursery school and kindergarten teachers were critical and that age contributed to the explanation of these conditions.


The F-loop of the GABA A receptor gamma2 subunit contributes to benzodiazepine modulation.
GABA(A) receptors can be modulated by benzodiazepines, although these compounds do not directly activate or inhibit the receptors. The prototypic benzodiazepine, diazepam, potentiates responses to GABA in GABA(A) receptors that contain a gamma subunit. Here we have used mutagenesis, radioligand binding, voltage clamp electrophysiology, and homology modeling to probe the role of the F-loop residues Asp(192)-Arg(197) in the GABA(A) receptor gamma(2) subunit in diazepam potentiation of the GABA response. Substitution of all of these residues with Ala and/or a residue with similar chemical properties to the wild type residue decreased the level of diazepam potentiation, and one mutation (D192A) resulted in its complete ablation. None of the mutations changed the GABA EC(50) or the [(3)H]flumazenil binding affinity, suggesting they do not affect GABA or benzodiazepine binding characteristics; we therefore propose that they are involved in the diazepam-mediated conformational change that results in an increased response to GABA. Homology models of the receptor binding pocket in agonist-bound and unbound states suggest that the F-loop is flexible and has different orientations in the two states. Considering our data in relation to these models, we find that the F-loop residues could contribute to hydrogen bond networks and hydrophobic interactions with neighboring residues that change during receptor activation.


Genetic Diversity and Genome-Wide Association Study for the Phenology Response of Winter Wheats of North America, Western Asia, and Europe.
Wheat is a staple food in many areas around the World. In the 20th century, breeders and scientists were able to boost wheat yield considerably. However, a yield plateau has become a concern and is threatening food security. Investments in cutting-edge technologies, including genomics and precision phenology measurements, can provide valuable tools to drive crop improvement. The objectives of this study were to (i) investigate the genetic diversity in a set of winter wheat lines, (ii) characterize their phenological response under different vernalization and photoperiod conditions, and (iii) identify effective markers associated with the phenological traits. A total of 249 adapted genotypes of different geographical origin were genotyped using the 35K Axiom® Wheat Breeder's Array. A total of 11,476 SNPs were used for genetic analysis. The set showed an average polymorphism information content of 0.37 and a genetic diversity of 0.43. A population structure analysis revealed three distinct subpopulations mainly related to their geographical origin (Europe, North America, and Western Asia). The lines of CGIAR origin showed the largest diversity and the lowest genetic distance to all other subpopulations. The phenology of the set was studied under controlled conditions using four combinations of long (19 h light) and short photoperiod (13 h light) and long vernalization (49 days at 5 °C) and no vernalization. With this, phenological traits such as earliness per se (Eps), relative response to vernalization (RRV), and relative response to photoperiod (RRP) were calculated. The phenotypic variation of growing degree days was significant in all phenology combinations. RRV ranged from 0 to 0.56, while RRP was higher with an overall average of 0.25. The GWAS analysis detected 30 marker-trait associations linked to five phenological traits. The highest significant marker was detected on chromosome 2D with a value of -log10(p) = 11.69. Only four loci known to regulate flowering exceeded the Bonferroni correction threshold of -log10(p) > 5.1. These results outline a solid foundation to address global food security and offer tremendous opportunities for advancing crop improvement strategies.


Derivation of a finite-element model of lingual deformation during swallowing from the mechanics of mesoscale myofiber tracts obtained by MRI.
To demonstrate the relationship between lingual myoarchitecture and mechanics during swallowing, we performed a finite-element (FE) simulation of lingual deformation employing mesh aligned with the vector coordinates of myofiber tracts obtained by diffusion tensor imaging with tractography in humans. Material properties of individual elements were depicted in terms of Hill's three-component phenomenological model, assuming that the FE mesh was composed of anisotropic muscle and isotropic connective tissue. Moreover, the mechanical model accounted for elastic constraints by passive and active elements from the superior and inferior directions and the effect of out-of-plane muscles and connective tissue. Passive bolus effects were negligible. Myofiber tract activation was simulated over 500 ms in 1-ms steps following lingual tip association with the hard palate and incorporated specifically the accommodative and propulsive phases of the swallow. Examining the displacement field, active and passive muscle stress, elemental stretch, and strain rate relative to changes of global shape, we demonstrate that lingual reconfiguration during these swallow phases is characterized by (in sequence) the following: 1) lingual tip elevation and shortening in the anterior-posterior direction; 2) inferior displacement related to hyoglossus contraction at its inferior-most position; and 3) dominant clockwise rotation related to regional contraction of the genioglossus and contraction of the hyoglossus following anterior displacement. These simulations demonstrate that lingual deformation during the indicated phases of swallowing requires temporally patterned activation of intrinsic and extrinsic muscles and delineate a method to ascertain the mechanics of normal and pathological swallowing.


Reversible hydrogenation and bandgap opening of graphene and graphite surfaces probed by scanning tunneling spectroscopy.
The effects of hydrogenation on the topography and electronic properties of graphene and graphite surfaces are studied by scanning tunneling microscopy and spectroscopy. The surfaces are chemically modified using an Ar/H(2) plasma. By analyzing thousands of scanning tunneling spectroscopy measurements it is determined that the hydrogen chemisorption on the surface of graphite/graphene opens on average an energy bandgap of 0.4 eV around the Fermi level. Although the plasma treatment modifies the surface topography in an irreversible way, the change in the electronic properties can be reversed by moderate thermal annealing and the samples can be hydrogenated again to yield a similar, but slightly reduced, semiconducting behavior after the second hydrogenation.


Isolation and characterization of Burkholderia rinojensis sp. nov., a non-Burkholderia cepacia complex soil bacterium with insecticidal and miticidal activities.
Isolate A396, a bacterium isolated from a Japanese soil sample demonstrated strong insecticidal and miticidal activities in laboratory bioassays. The isolate was characterized through biochemical methods, fatty acid methyl ester (FAME) analysis, sequencing of 16S rRNA, multilocus sequence typing and analysis, and DNA-DNA hybridization. FAME analysis matched A396 to Burkholderia cenocepacia, but this result was not confirmed by 16S rRNA or DNA-DNA hybridization. 16S rRNA sequencing indicated closest matches with B. glumae and B. plantarii. DNA-DNA hybridization experiments with B. plantarii, B. glumae, B. multivorans, and B. cenocepacia confirmed the low genetic similarity (11.5 to 37.4%) with known members of the genus. PCR-based screening showed that A396 lacks markers associated with members of the B. cepacia complex. Bioassay results indicated two mechanisms of action: through ingestion and contact. The isolate effectively controlled beet armyworms (Spodoptera exigua; BAW) and two-spotted spider mites (Tetranychus urticae; TSSM). In diet overlay bioassays with BAW, 1% to 4% (vol/vol) dilution of the whole-cell broth caused 97% to 100% mortality 4 days postexposure, and leaf disc treatment bioassays attained 75% ± 22% mortality 3 days postexposure. Contact bioassays led to 50% larval mortality, as well as discoloration, stunting, and failure to molt. TSSM mortality reached 93% in treated leaf discs. Activity was maintained in cell-free supernatants and after heat treatment (60°C for 2 h), indicating that a secondary metabolite or excreted thermostable enzyme might be responsible for the activity. Based on these results, we describe the novel species Burkholderia rinojensis, a good candidate for the development of a biocontrol product against insect and mite pests.


Increased brown adipose tissue thermogenesis in obese (ob/ob) mice fed a palatable diet.
Feeding female genetically obese (ob/ob) mice a palatable "cafeteria" diet results in increased sympathetic nervous system activity in brown adipose tissue and hypertrophy and increased thermogenesis of this tissue. There is an associated increase in the capacity of the ob/ob mouse to respond thermogenically to noradrenaline, prolongation of its survival in the cold, and an increase in body temperature at all times of day. Thus the cafeteria diet overcomes the usual refractoriness of brown adipose tissue of the ob/ob mouse to noradrenaline and to sympathetic stimulation, increases the low capacity for a thermogenic response to noradrenaline, almost normalizes resistance to cold, and increases the "set point" at which the ob/ob mouse regulates its body temperature. It is concluded that the repetitive sympathetic nervous stimulation engendered by the high-fat cafeteria diet has a trophic action on brown adipose tissue that improves its atrophied functional state and that the low sympathetic nervous system activity usually seen in brown adipose tissue of ob/ob mice eating chow under animal house conditions results in secondary atrophy of the tissue. The results point to a central location for the defect in the ob/ob mouse, perhaps in the control of the sympathetic nervous system in relation to diet availability and composition and to environmental temperature.


Patterns of care for Multiple Sclerosis in a setting of universal care access: A cross-sectional study.
Current guidelines recommend regular neurological MS care in persons diagnosed with MS, but little is known about implementation of this recommendation or potential access barriers. This study examined disease-specific and sociodemographic differences between MS patients in Neurological Care (NeC), General Practitioner Care (GPC), or no Physician Care (NoPC) to identify group differences and characteristics that may suggest care access barriers. Patient-reported data were analyzed from 1038 Swiss Multiple Sclerosis Registry participants by means of multivariable regression to identify systematic differences across the three care groups. Assessments included comprehensive data on clinical, sociodemographic, and geographic factors. 89% reported being in regular care by a neurologist (56% in private practices, 44% in hospitals), 5% were in GPC, and 6% reported No Physician Care (NoPC). Compared with the NeC group, patients not seeing a neurologist included two subgroups, one consisting of persons with a primary progressive MS (PPMS) and/or an extended MS history. The second subgroup included persons with a recent MS diagnosis within the last 2 years. Within the NeC group, the patients seen in private practices were of older age and more frequently female compared to those at clinics, but no differences were detected with regard to disability status, MS type, or treatment patterns. Access to neurological care is high in Switzerland. Given the emerging paradigm for early treatment and new drugs for progressive MS, regular neurology visits should be promoted among patient groups currently less in neurological care such as persons with PPMS or recently diagnosed.


DNA-induced fusion between lipid domains of peptide-lipid hybrid vesicles.
Peptide-lipid hybrid vesicles were prepared with complementary DNA strands in their lipid domains. Hybridization of the complementary DNA strands induced the controlled fusion of the vesicles during repeated heating and cooling cycles. Vesicle fusion was indicated by a decrease in the efficiency of Förster resonance energy transfer between lipid-localized probes (from 72 to 42%) and transmission electron microscopy analysis. We suggest that this approach is a general strategy for the creation of polymersomes with membrane-fusion functionality.


Introducing a Navigation Algorithm for Reducing the Spread of Diseases in Public Transport Networks.
Reducing passenger flow through highly frequented bottlenecks in public transportation networks is a well-known urban planning problem. This issue has become even more relevant since the outbreak of the SARS-CoV-2 pandemic and the necessity for minimum distances between passengers. We propose an approach that allows to dynamically navigate passengers around dangerously crowded stations to better distribute the passenger load across an entire urban public transport network. This is achieved through the introduction of new constraints into routing requests, that enable the avoidance of specific nodes in a network. These requests consider walks, bikes, metros, subways, trams and buses as possible modes of transportation. An implementation of the approach is provided in cooperation with the Munich Travel Corporation (MVG) for the city of Munich, to simulate the effects on a real city's urban traffic flow. Among other factors, the impact on the travel time was simulated given that the two major exchange points in the network were to be avoided. With an increase from 26.5 to 26.8 minutes on the average travel time, the simulation suggests that the time penalty might be worth the safety benefits.


When to Transfer: Predictors of Pediatric High Flow Nasal Cannula Failure at a Community Hospital.
To identify risk factors of high flow nasal cannula (HFNC) failure at a US pediatric hospital without a co-located ICU. Retrospective cohort study of patients aged 0 to 18 years who were started on HFNC in the emergency department or inpatient unit at a community hospital over a 16-month period. Children with chronic medical conditions were excluded. Outcome was HFNC failure, defined as HFNC need greater than floor limit, noninvasive positive pressure, or mechanical ventilation. In bivariate analysis, we compared demographic and clinical factors between those with and without failure. We included variables in a multivariable model on the basis of statistical significance. We used Poisson regression with robust error variance to calculate the adjusted relative risk (aRR) of failure for each variable. Of 195 children, 51% had HFNC failure. In adjusted analysis, failure was higher in all age groups <12 months as compared with older children. For example, children aged 3 to 5 months had a higher risk of failure compared with patients 12 months or older (aRR 1.85, confidence interval [CI] 1.34-2.54). Patients with an asthma exacerbation had a higher risk of failure (aRR 1.39, CI 1.03-1.88). Patients whose respiratory rate or heart rate did not improve also had a higher risk of failure (aRR 1.73, CI 1.24-2.41; aRR 1.47, CI 1.14-1.90). Patients who were younger, had asthma, and did not have improved respiratory rate or heart rate after HFNC were more likely to experience HFNC failure.


Dieting practices and body image perception among Lebanese university students.
Dieting is becoming a popular phenomenon among university students to achieve or maintain a healthy weight. The purpose of this study is to obtain a preliminary understanding of what dieting practices university students use in order to achieve their desirable body weight and to determine the magnitude of body dissatisfaction in relation to weight status among a sample of students (n=252) from the Lebanese American University in Beirut, Lebanon. Students filled out a self-reported questionnaire that included questions on their dieting and physical activity practices in addition to the body shape questionnaire (BSQ). Weight and height were measured to calculate body mass index. Percentage body fat was measured using Tanita scale body fat analyzer 300A. The outcome of this study showed that smoking and unhealthy dieting practices were not common among students (only 26% reported smoking, 8% reported taking laxatives and 4% taking diet pills). Half of the students reported practicing regular physical activity. Multivitamin intake was also not popular among students. BSQ scores indicate that the majority of students were not worried about their body image perception (64% reported not being worried, 19% were slightly worried, 12% were moderately worried and 5% were extremely worried). A gender difference was observed in the BSQ scores, as 89% of the "extremely worried" students were females. Collectively, results indicate that unhealthy dieting practices are uncommon among students. However, developing health promotion awareness' programs to promote good self image within the concept of a realistic healthy weight will be beneficial, especially among females.


The Expanding Role of Advanced Practice Providers in Urologic Procedural Care.
To understand the role of Advanced Practice Providers (APPs) in urologic procedural care and its change over time. As the population ages and the urologic workforce struggles to meet patient access demands, the role of APPs in the provision of all aspects of urologic care is increasing. However, little is currently known about their role in procedural care. Commonly performed urologic procedures were linked to Current Procedural Terminology (CPT) codes from 1994 to 2012. National Medicare Part B beneficiary claims frequency was identified using Physician Supplier Procedure Summary Master Files. Trends were studied for APPs, urologists, and all other providers nationally across numerous procedures spanning complexity, acuity, and technical skill set requirements. Between 1994 and 2012, annual Medicare claims for urologic procedures by APPs increased dramatically. Cystoscopy increased from 24 to 1820 (+7483%), transrectal prostate biopsy from 17 to 834 (+4806%), complex Foley catheter placement from 471 to 2929 (+522%), urodynamics testing from 41 to 9358 (+22,727%), and renal ultrasound from 18 to 4500 (+24,900%) CONCLUSION: We found dramatic growth in the provision of urologic procedural care by APPs over the past 2 decades. These data reinforce the known expansion of the APP role in urology and support the timeliness of ongoing collaborative multidisciplinary educational efforts to address unmet needs in education, training, and guideline formation to maximize access to urologic procedural services.


Diagnosis of eosinophilic esophagitis in an infant undergoing milk oral immunotherapy - a case report.
Although the standard of care for cow's milk (CM) allergy is strict food avoidance, oral immunotherapy (OIT) is being widely investigated as an alternative management option in certain cases. Immediate adverse reactions to OIT have been described, but its long-term effects are much less often reported. We present the case of a girl diagnosed with IgE-mediated CM allergy that was proposed for our CM OIT protocol at the age of 3 years. The first sessions (dose escalation up to 5 ml) were well tolerated, however eight hours after her daily morning dose of 5 ml CM the child developed late episodes of vomiting. No other symptoms, particularly immediately after CM ingestion, were reported. These episodes became progressively worse and on the third day she presented mild dehydration and blood eosinophilia. After OIT interruption, a progressive clinical improvement was observed. An esophageal endoscopy was performed, showing signs of eosinophilic esophagitis (EoE) with peak 20 eosinophils/hpf. After treatment with topical swallowed fluticasone (500 mcg bid) and a CM-free diet for 4 months, the child was asymptomatic and endoscopy and biopsy findings were normal.The long-term effects of milk OIT are still in part unknown. We hypothesize that eosinophilic esophagitis may have been a consequence of OIT in this case. The findings seem to indicate that food allergy may play a role in the pathogenesis of esophageal eosinophilia and stress the importance of a well programmed long-term follow-up of patients that have undergone milk OIT.


Vgl1, a multi-KH domain protein, is a novel component of the fission yeast stress granules required for cell survival under thermal stress.
Multiple KH-domain proteins, collectively known as vigilins, are evolutionarily highly conserved proteins that are present in eukaryotic organisms from yeast to metazoa. Proposed roles for vigilins include chromosome segregation, messenger RNA (mRNA) metabolism, translation and tRNA transport. As a step toward understanding its biological function, we have identified the fission yeast vigilin, designated Vgl1, and have investigated its role in cellular response to environmental stress. Unlike its counterpart in Saccharomyces cerevisiae, we found no indication that Vgl1 is required for the maintenance of cell ploidy in Schizosaccharomyces pombe. Instead, Vgl1 is required for cell survival under thermal stress, and vgl1Δ mutants lose their viability more rapidly than wild-type cells when incubated at high temperature. As for Scp160 in S. cerevisiae, Vgl1 bound polysomes accumulated at endoplasmic reticulum (ER) but in a microtubule-independent manner. Under thermal stress, Vgl1 is rapidly relocalized from the ER to cytoplasmic foci that are distinct from P-bodies but contain stress granule markers such as poly(A)-binding protein and components of the translation initiation factor eIF3. Together, these observations demonstrated in S. pombe the presence of RNA granules with similar composition as mammalian stress granules and identified Vgl1 as a novel component that required for cell survival under thermal stress.


Interpolation and Averaging of Diffusion MRI Multi-Compartment Models.
Multi-compartment models (MCM) are increasingly used to characterize the brain white matter microstructure from diffusion-weighted imaging (DWI). Their use in clinical studies is however limited by the inability to resample an MCM image towards a common reference frame, or to construct atlases from such brain microstructure models. We propose to solve this problem by first identifying that these two tasks amount to the same problem. We propose to tackle it by viewing it as a simplification problem, solved thanks to spectral clustering and the definition of semi-metrics between several usual compartments encountered in the MCM literature. This generic framework is evaluated for two models: the multi-tensor model where individual fibers are modeled as individual tensors and the diffusion direction imaging (DDI) model that differentiates intra- and extra-axonal components of each fiber. Results on simulated data, simulated transformations and real data show the ability of our method to well interpolate MCM images of these types. We finally present as an application an MCM template of normal controls constructed using our approach.


Investigating the Potential Use of Andrographolide as a Coadjuvant in Sickle Cell Anemia Therapy.
Andrographolide is one of the main active principles of Andrographolide paniculata and has been extensively explored for its therapeutic use. Current studies focus on phytotherapeutics-based adjuvant therapy to symptomatically treat sickle cell anemia (SCA) as there is no specific drug/gene therapy available to date. The present study aimed to explore the potential of andrographolide as an adjuvant therapy for SCA in the presence or absence of hydroxyurea (HU), a key drug for SCA treatment. A panel of ex vivo and in vivo experimentations was performed to explore the antisickling activity of andrographolide, followed by evaluating pharmacokinetic and pharmacodynamic (PK/PD) activities in the presence of HU. Andrographolide showed significant antisickling activity using blood from SCA patients (ex vivo) and did not show any deleterious effect to cause hemolysis using rat blood (ex vivo). It displayed a substantial decrease in HU-induced decline in splenic lymphocyte proliferation and cytokine level (TNF-α and IFN-γ) using rat splenocytes (ex vivo). Concomitant oral administration of andrographolide with HU in rats for 15 days exhibited a noticeable improvement in the RBC count and hemoglobin levels comparable to the efficacy of l-glutamine (in vivo). Simultaneous administration of andrographolide with HU caused no marked effect on any pharmacokinetic parameters of HU except the highest plasma concentration of HU and its corresponding time point, which significantly dropped and delayed, respectively (in vivo). No considerable effect of andrographolide was observed on urease and horseradish peroxidase activity (in vitro). Overall, results suggest that andrographolide has several beneficial actions to be an adjuvant therapy to symptomatically manage SCA, but it should be avoided during the prescribed therapy of HU.


Influence of a diet regimen on glucose homeostasis and serum lipid levels of male elite athletes.
Physical training affects carbohydrate metabolism and results in an increased insulin-stimulated glucose disposal. To investigate if carbohydrate and lipid metabolism would be affected by nutritional factors in optimally trained elite athletes, during a 1-year period we studies elite ice-hockey players on two Swedish top-performance teams. Players on one team were subjected to extensive dietary monitoring and intervention, whereas players on the second team continued their ordinary diet. Blood levels of insulin, C-peptide, glucose, hemoglobin A1C (HbA1c), lipids, and lipoproteins were measured repeatedly. Basal insulin levels and insulin resistance (IR) were significantly lower among athletes on both teams compared with a sedentary group, and muscle weight and body mass index were significantly higher. During the course of the study in the intervention group, insulin levels decreased (3.6 +/- 0.3 v 6.2 +/- 0.6 [mean +/- SEM], P <.05) in conjunction with a decreased relative fat energy content, but returned toward baseline levels when relative fat energy content increased. IR decreased in parallel (0.59 +/- 0.05 v l.12 +/- 0.12, P <.05) and followed a similar pattern, reverting toward baseline levels. Also, levels of HbA1c changed during dietary manipulation. No changes in these parameters were observed among the elite players from the team not participating in the diet regimen. In contrast to the parameters for glucose homeostasis, no significant changes were found in serum lipid or lipoprotein levels in either team during the course of the study. The results verify the presence of an improved carbohydrate metabolism in elite athletes. The observed changes in glycemic control and glucose homeostasis as a consequence of dietary modification demonstrate further that nutritional factors may affect carbohydrate metabolism also in well-trained athletes.


Histopathology of papilloma virus infection of the cervix uteri: the history, taxonomy, nomenclature and reporting of koilocytic dysplasias.
Papilloma virus infections of the squamous cervix are common and determine the incidence of koilocytes in cervical smears and biopsies. Typical exophytic condyloma acuminatum accounts for few of the infections. Most are "flat condylomata" (flat koilocytosis)--slightly raised plaques of flat profile. Superficial koilocytosis, dyskeratosis and often disturbed deep cells are their main histological features. The association between koilocytosis and dysplasia is considered and the different taxonomic approaches to the koilodysplastic states are compared. Equivalence is established between different nomenclatures by reference to the familiar dysplastic grades. Methods of reporting koilodysplasias are given and a prognostically difficult state of "full thickness" or "plenary" koilocytosis is described. In applying the "high technology" of nucleic acid hybridisation to confirm the lesion specificity of papilloma virus strains the lesions must be well defined and clearly identified by precise nomenclature: the nature and nomenclature of the lesions is critically discussed.


[Active management of labor].
The active management of labour in the National Maternity Hospital in Dublin has the general aim that labour will not last longer than 12 hours. Since the outstanding cause of dystocia is inefficient uterine action the proper use of oxytocin has a position of great importance, especially in primigravidae. In 1984 under this procedure perinatal mortality was 12/1000 and the rate of caesarean sections 4.2 per cent. Total births--7853.


Reboxetine modulates the firing pattern of dopamine cells in the ventral tegmental area and selectively increases dopamine availability in the prefrontal cortex.
Central dopaminergic neurons have been suggested to be involved in the pathophysiology of several psychiatric disorders, including depression, and appear to be modulated by noradrenergic activity both at the nerve terminal level and at the somatodendritic level. In recent years reboxetine, a selective noradrenaline reuptake inhibitor that differs from tricyclic antidepressants by its low affinity for muscarinic, cholinergic and alpha(1)-adrenergic receptors, has been introduced clinically. In the present study the effect of reboxetine on the function of the mesolimbocortical dopamine system was investigated by means of single cell recording and microdialysis in rats following administration of reboxetine in doses that appear to yield clinically relevant plasma concentrations. Reboxetine (0.625--20 mg/kg intravenously) induced an increase in burst firing, but not in average firing frequency of dopamine (DA) cells in the ventral tegmental area (VTA). Moreover, reboxetine (0.15--13.5 mg/kg intraperitoneally) caused a significantly enhanced DA output in the medial prefrontal cortex, whereas no effect was observed in the nucleus accumbens. Local administration of reboxetine (333 microM, 60 min), by means of reversed microdialysis into these brain regions, caused a significant increase in DA output in both brain regions. However, local administration of reboxetine into the VTA (333 microM, 60 min) did not affect DA availability in these terminal areas. Our results imply that clinical treatment with reboxetine may result in facilitation of both prefrontal DA output and the excitability of VTA DA neurons, effects that may contribute to its antidepressant action, especially on drive and motivation.


[Ratio of concentration of ions of uni- and bivalent metals in the tissues of developing chick embryos and 1-day-old chickens].
The ratio of concentrations Na+/K+ decreases in the brain and liver and increases in the cardiac muscle during the chick embryogenesis. The maximum concentration of Ca2+ was noted in the tissues under study on 14th day of chick embryonic development and its content decreased reliably at the subsequent stages. The concentration of Mg2+ in the tissues under study decreased during the embryogenesis as well.


Twelve tips on how to set up postgraduate training via remote clinical supervision.
Doctors-in-training can now be supervised remotely by specialist clinicians using information and communication technology. This provides an intermediate stage of professional development between on-site supervision and independent medical practice. Remote supervision could increase training capacity, particularly in underserved areas and ensure doctors are willing and able to practice where they are needed once qualified. Remotely supervised doctors learn via virtual autonomy in clinical decision making and working at the limits of their abilities. It suits experienced registrars with resilience, insight into their strengths and weaknesses, capacity to self-monitor and correct, and willingness to seek help. These doctors benefit from remote supervisors who facilitate their learning, monitor their well-being, and support them holistically. Educational organisations need to oversee remote placements and match the right registrar, to the right placement with the right supervisor. We outline in our twelve tips how to set up remote supervision in order to maximise the educational benefits and minimise the risks.


[Splenic disorders in internal medicines].
The spleen is the largest lymphopoietic organ, containing 25% of total lymphoid mass. It participates in cellular and humoral immunity and intervenes in the renovation of red cells and the elimination of bacteria. Splenic functions are reduced when the spleen is absent, which entails, amongst other complications, greater susceptibility to suffering from sepsis due to encapsulated organisms. We present 6 clinical cases admitted to the Internal Medicine serve with splenic pathology and we make a review of the approach to be used. The spectrum of splenic lesions in internal medicine is very wide. On occasions, a splenic pathology can be suspected due to clinical history, physical exploration or because of cytopenias in the analyses. Different complementary tests are available for completing study of these lesions. A splenectomy can be carried out in case of diagnostic doubt, with the most frequent diagnoses being hepatic cirrhosis and lymphoma/leukaemia.


Rapid Screening of Mentha spicata Essential Oil and L-Menthol in Mentha piperita Essential Oil by ATR-FTIR Spectroscopy Coupled with Multivariate Analyses.
Mentha piperita essential oil (EO) has high economic importance because of its wide usage area and health-beneficial properties. Besides health-beneficial properties, Mentha piperita EO has great importance in the flavor and food industries because of its unique sensory and quality properties. High-valued essential oils are prone to being adulterated with economic motivations. This kind of adulteration deteriorates the quality of authentic essential oil, injures the consumers, and causes negative effects on the whole supply chain from producer to the consumer. The current research used fast, economic, robust, reliable, and effective ATR-FTIR spectroscopy coupled chemometrics of hierarchical cluster analysis(HCA), principal component analysis (PCA), partial least squares regression (PLSR) and principal component regression (PCR) for monitoring of Mentha spicata EO and L-menthol adulteration in Mentha piperita EOs. Adulterant contents (Mentha spicata and L-menthol) were successfully calculated using PLSR and PCR models. Standard error of the cross-validation SECV values changed between 0.06 and 2.14. Additionally, bias and press values showed alteration between 0.06 and1.43 and 0.03 and 41.15, respectively. Authentic Mentha piperita was successfully distinguished from adulterated samples, Mentha spicata and L-menthol, by HCA and PCA analysis. The results showed that attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, coupled with chemometrics could be effectively used for monitoring various adulterants in essential oils.


Ruxolitinib attenuates acute rejection and can serve as an immune induction therapy in heart transplantation.
The benefits of IL2RA antagonists in heart transplant patients are controversial. We aimed to elucidate the effects of IL2RA antagonists and identify targets that could be better than IL2RA antagonists. By using single-cell RNA sequencing of immune cells at different time points in patients receiving IL2RA antagonists, we identified nineteen types of cells. We revealed higher IL2RA expression in regulatory T cells (Tregs), suggesting that IL2RA antagonists attenuated IL-2-induced Treg activation. CD4_C04_IFNGR1 and CD8_C05_IFITM2 which had more cytotoxic effects, remained elevated at later time points. IFNGR1 was upregulated in these two subtypes, but was not expressed in Treg. Ruxolitinib targeted the pathways of IFNGR1 (JAK1/2) while not affecting the pathway of IL-2-induced Tregs activation (JAK3). Ruxolitinib showed prolonged survival compared to IL2RA mAb-treated mice. Our study provided dynamic changes of immune cells after IL2RA antagonists treatment at single-cell resolution. Ruxolitinib has potential as a new immunoinduction therapy without affecting Treg.


Targeting TLR/IL-1R signalling in human diseases.
The members of Toll-like receptor/interleukin (IL)-1 receptor (TLR/IL-1R) superfamily play a fundamental role in the immune response. These receptors detect microbial components and trigger complex signalling pathways that result in increased expression of multiple inflammatory genes. On the other hand, an aberrant activation of TLR/IL-1R signalling can promote the onset of inflammatory and autoimmune diseases, raising the interest in the development of therapeutic strategies for the control of their function. In this review, we illustrate the structural and functional features of TLR/IL-1R proteins and discuss some recent advances in the approaches undertaken to develop anti-inflammatory therapeutic drugs. In particular, we will focus on inhibitors, such as decoy peptides and synthetic mimetics, that interfere with protein-protein interactions between signalling molecules of the TLR/IL-1R superfamily. Given their central role in innate and adaptive immune responses, it is foreseen that pharmaceutical modulation of TLR/IL-1R signalling pathways by these drugs might yield clinical benefits in the treatment of inflammatory and autoimmune diseases.


Expression of tumor necrosis factor-α-induced protein 8 in stage III gastric cancer and the correlation with DcR3 and ERK1/2.
Tumor necrosis factor (TNF)-α-induced protein 8 (TIPE) is a recently identified protein that is considered to be associated with various malignancies, including esophageal, breast and pancreatic cancer; however, the importance of TIPE in gastric cancer (GC) remains unknown. Decoy receptor 3 (DcR3) is a member of the tumor necrosis factor receptor superfamily that is expressed in digestive system neoplasms. The expression of DcR3 is regulated by the mitogen-activated protein kinase (MAPK)/MAPK kinase/extracellular signal-regulated kinase (ERK) signaling pathway. Reverse transcription-polymerase chain reaction was performed to detect the expression of TIPE, ERK and DcR3 in the pathological and tumor-adjacent normal gastric tissues of 30 patients that demonstrated stage III gastric adenocarcinoma. The expression and distribution of the TIPE protein was examined using immunohistochemistry, and the clinical significance and expression levels of DcR3 and ERK1/2 were evaluated. The expression of TIPE, ERK1/2 and DcR3 in the tumor tissues of GC was significantly increased compared with paracarcinoma tissues (P<0.05). In addition, TIPE expression positively correlated with DcR3 and ERK1 levels (r=0.538 and r=0.462, respectively; P<0.05). There was no statistical difference between tumor tissues from patients with varying age, gender, differentiation or lymph node metastasis (P>0.05). TIPE may be vital in the progression of GC. TIPE may be associated with the expression of DcR3 and ERK1/2, which may be involved in the cell apoptosis of GC. The present study elucidates the potential function of TIPE as a novel marker and therapeutic target for GC.


Is Autonomy Always Beneficial for Work Engagement? A Six-year Four-Wave Follow-Up Study.
Work engagement is expected to result from job resources such as autonomy. However, previous results have yielded that the autonomy-work engagement relationship is not always particularly strong. Whereas previous longitudinal studies have examined this relationship as an average at a specific point in time, this study examined whether this relationship is different within individuals from one time to another over the years. Furthermore, experiences of work engagement are expected to affect how employees benefit from autonomy, but no studies have so far investigated whether the initial level of work engagement affects the autonomy-work engagement relationship. This study aimed to first identify the different kinds of longitudinal relationship patterns between autonomy and work engagement, and then to investigate whether the identified relationship patterns differ in terms of the initial mean level of work engagement. The four-wave study was conducted among Finnish managers (n = 329) over a period of six years. Multilevel regression mixture analysis identified five relationship patterns. Four of the patterns showed a positive predictive relationship between autonomy and work engagement. However, the relationship was statistically significant in only one of these patterns. Furthermore, when the initial mean level of work engagement was high, autonomy related more strongly to work engagement. However, an atypical pattern was identified that showed a negative association between autonomy and work engagement. In this pattern, the mean level of work engagement was low. Consequently, autonomy may not always enhance work engagement; sometimes this relationship may even be negative.


[Biological and molecular characteristics of uropathogenic Escherichia coli strains isolated in the city of Rio de Janeiro].
Uropathogenic Escherichia coli strains isolated from individuals living in different areas of the city of Rio de Janeiro were characterized according to serotype, hemolytic properties, hemagglutination properties, antimicrobial susceptibility and isoenzymatic profile. The molecular approach used, together with investigation of urovirulence markers, enabled detection of great diversity among the isolates. However, closer relationships were observed between epidemiologically related Escherichia coli samples.


Nuclear-to-cytoplasmic relocalization of the proliferating cell nuclear antigen (PCNA) during differentiation involves a chromosome region maintenance 1 (CRM1)-dependent export and is a prerequisite for PCNA antiapoptotic activity in mature neutrophils.
Neutrophils are deprived of proliferative capacity and have a tightly controlled lifespan to avoid their persistence at the site of injury. We have recently described that the proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repair of proliferating cells, is a key regulator of neutrophil survival. In neutrophils, PCNA was localized exclusively in the cytoplasm due to its nuclear-to-cytoplasmic relocalization during granulocytic differentiation. We showed here that leptomycin B, an inhibitor of the chromosome region maintenance 1 (CRM1) exportin, inhibited PCNA relocalization during granulocytic differentiation of HL-60 and NB4 promyelocytic cell lines and of human CD34(+) primary cells. Using enhanced green fluorescent protein fusion constructs, we have demonstrated that PCNA relocalization involved a nuclear export signal (NES) located from Ile-11 to Ile-23 in the PCNA sequence. However, this NES, located at the inner face of the PCNA trimer, was not functional in wild-type PCNA, but instead, was fully active and leptomycin B-sensitive in the monomeric PCNAY114A mutant. To test whether a defect in PCNA cytoplasmic relocalization would affect its antiapoptotic activity in mature neutrophils, a chimeric PCNA fused with the SV40 nuclear localization sequence (NLS) was generated to preclude its cytoplasmic localization. As expected, neutrophil-differentiated PLB985 cells expressing ectopic SV40NLS-PCNA had an increased nuclear PCNA as compared with cells expressing wild-type PCNA. Accordingly, the nuclear PCNA mutant did not show any antiapoptotic activity as compared with wild-type PCNA. Nuclear-to-cytoplasmic relocalization that occurred during myeloid differentiation is essential for PCNA antiapoptotic activity in mature neutrophils and is dependent on the newly identified monomerization-dependent PCNA NES.


Does primary brachial plexus surgery alter palliative tendon transfer surgery outcomes in children with obstetric paralysis?
The surgical management of obstetrical brachial plexus palsy can generally be divided into two groups; early reconstructions in which the plexus or affected nerves are addressed and late or palliative reconstructions in which the residual deformities are addressed. Tendon transfers are the mainstay of palliative surgery. Occasionally, surgeons are required to utilise already denervated and subsequently reinnervated muscles as motors. This study aimed to compare the outcomes of tendon transfers for residual shoulder dysfunction in patients who had undergone early nerve surgery to the outcomes in patients who had not. A total of 91 patients with obstetric paralysis-related shoulder abduction and external rotation deficits who underwent a modified Hoffer transfer of the latissimus dorsi/teres major to the greater tubercle of the humerus tendon between 2002 and 2009 were retrospectively analysed. The patients who had undergone neural surgery during infancy were compared to those who had not in terms of their preoperative and postoperative shoulder abduction and external rotation active ranges of motion. In the early surgery groups, only the postoperative external rotation angles showed statistically significant differences (25 degrees and 75 degrees for total and upper type palsies, respectively). Within the palliative surgery-only groups, there were no significant differences between the preoperative and postoperative abduction and external rotation angles. The significant differences between the early surgery groups and the palliative surgery groups with total palsy during the preoperative period diminished postoperatively (p < 0.05 and p > 0.05, respectively) for abduction but not for external rotation. Within the upper type palsy groups, there were no significant differences between the preoperative and postoperative abduction and external rotation angles. In this study, it was found that in patients with total paralysis, satisfactory shoulder abduction values can be achieved with tendon transfers regardless of a previous history of neural surgery even if the preoperative values differ.


An accurate method for the determination of complex coefficients of single crystal piezoelectric resonators II: design of measurement and experiments.
In this paper, we present the design of measurements for single crystals by using the general results in Part I of this paper. The selection of impedance measurement or admittance measurement for both bar and plate type resonators is dependent on whether the cutting orientation l is parallel to or perpendicular to the electric field direction n. Two matrices A and B, which are defined in part I of this paper, are major tools used for the measurement design. For different cutting orientations, the elements in matrix A are associated with different elastic and piezoelectric constants. Matrix B reveals what vibration modes can be excited electrically and how to excite them. With the aid of matrices A and B, the design of measurement becomes straightforward. The measurement for a rhombohedral class (3m) LiNbO3 single crystal is used as an example to demonstrate the experiment and calculation procedures. It is found that by using either three thin bars and one plate or three plates and one thin bar we can completely characterize the complex materials constants of a LiNbO3 single crystal.


Replacement of dietary fish oil with increasing levels of linseed oil: modification of flesh fatty acid compositions in Atlantic salmon (Salmo salar) using a fish oil finishing diet.
Five groups of salmon, of initial mean weight 127 +/- 3 g, were fed increasing levels of dietary linseed oil (LO) in a regression design. The control diet contained capelin oil (FO) only, and the same oil was blended with LO to provide the experimental diets. After an initial period of 40 wk, all groups were switched to a finishing diet containing only FO for a further 24 wk. Growth and flesh lipid contents were not affected by dietary treatment. The FA compositions of flesh total lipids were linearly correlated with dietary FA compositions (r2 = 0.88-1.00, P < 0.0001). LO included at 50% of added dietary lipids reduced flesh DHA and EPA (20:5n-3) concentrations to 65 and 58%, respectively, of the concentrations in fish fed FO. Feeding 100% LO reduced flesh DHA and EPA concentrations to 38 and 30%, respectively, of the values in fish fed FO. Differences between diet and flesh FA concentrations showed that 16:0, 18:1n-9, and especially DHA were preferentially retained in flesh, whereas 18:2n-6, 18:3n-3, and 22:1n-11 were selected against and presumably utilized for energy. In fish previously fed 50 and 100% LO, feeding a finishing diet containing FO for 16 wk restored flesh DHA and EPA concentrations, to approximately 80% of the values in fish fed FO throughout. Flesh DHA and EPA concentrations in fish fed up to 50% LO were above recommended intake values for humans for these EFA. This study suggests that LO can be used as a substitute for FO in seawater salmon feeds and that any reductions in DHA and EPA can be largely overcome with a finishing diet high in FO before harvest.


Cell Biology of Coral Symbiosis: Foundational Study Can Inform Solutions to the Coral Reef Crisis.
Coral reefs are faced with almost complete destruction by the end of the century due to global warming unless humanity can cap global temperature rise. There is now a race to develop a diverse set of solutions to save coral reefs. In this perspective, a case is made for understanding the cell biology of coral-dinoflagellate symbiosis to help inform development of solutions for saving reefs. Laboratory model systems for the study of coral symbiosis, including the sea anemone Exaiptasia pallida, are featured as valuable tools in the fight to save corals. The roles of host innate immunity and inter-partner nutrient dynamics in the onset, ongoing maintenance, and dysregulation of symbiosis are reviewed and discussed. Key innate immune genes and pathways, such as glycan-lectin interactions, the sphingosine rheostat, and the cytokine transforming growth factor beta are shown to modulate a host immune response in the symbiotic state. An upset in the homeostatic inorganic nutrient balance during heat stress and high exogenous nutrient availability is credited with driving the partnership toward dysregulation and coral bleaching. Specific examples are given where knowledge of the cell biology of symbiosis is informing the development of solutions, including studies showing clear limitations in the value of partner switching and acclimatization protocols. Finally, emphasis is placed on rapid advancement of knowledge to try to meet the urgent need for solutions. This includes real-time open communication with colleagues on successes and failures, sharing of resources and information, and working together in the spirit of a collective mission to save coral reefs.


Posterior uterine wall rupture during labour.
Vaginal births after Caesarean section (VBAC) are well-accepted procedures when pregnant women do not have any contra-indications. The possibilities of the uterine dehisence and rupture during VBAC should always be considered. This occurrence is usually related to the previous scar tissue and subsequent risk is acceptable. Nevertheless, rupture that occurs in presumably normal tissue areas of the uterus instead of in scar tissue areas with resultant perinatal death is extremely rare. We present a 31 year old woman who had posterior uterine rupture when she tried VBAC at 38 weeks gestation. During the course of VBAC, she had a smooth labour course without use of any augmentation medication, but her condition was complicated with uterine rupture without any premonitory signal. It resulted in maternal shock and sequentially the death of the newborn 7 days after delivery. By reviewing this case report, we should keep in mind that prompt response to every woman during labour is of paramount importance to avoid repeating the occurrence of uterine rupture, partly because uterine rupture could occur without prominent signals and partly because subsequent dangers seem to be those created by acts of omission. Finally, the benefits and safety of VBAC have not been undermined because this patient is an isolated and extremely rare case.


Comparative study on guidelines in determining HBV phases in Iranian patients.
The aim of this study was to compare the different phases of chronic Hepatitis B virus (HBV) infection with different values for normal ALT. For many years, the upper limit of 40 IU was considered normal for ALT for both sexes, but in recent years this value is challenged and some guidelines have lowered their limit. In this cross-sectional study, 2000 HBsAg positive patients who were referred to Taleghani Hospital, Tehran, Iran, from 2011 through 2018 were classified in four groups according to American Association of the study of the liver disease (AASLD), European Association of the study of the liver (EASL) /Asian-Pacific Association of the study of the liver (APASL) and American Collage of Gastroenterology (ACG) guidelines. The frequency of each group based on 3 different guidelines was compared. In HBeAg positive patients (n=100), the percentage of immune tolerance phase was 43% according to AASLD cutoff for normal ALT (35 IU for men, 25 IU for women), while it was 68% and 28% with regard to EASL/APASL and ACG (30 IU for men, 19 IU for women) cutoffs respectively. In HBeAg negative patients (n=1900), 66.68% were inactive carriers according to AASLD, but the percentage changed to 82.89% and 52.42% considering EASL/APASL and ACG values, respectively. Using ACG and to a lesser extent AASLD cutoff for ALT, many patients shift from immune tolerance and inactive carrier state into the immune active phase. Thus, more patients are candidates for treatment or intensive workup to determine the extent of liver damage.