Use of advanced red blood cell and reticulocyte indices improves the accuracy in diagnosing iron deficiency in pregnant women at term.
Detection of iron deficiency during pregnancy with hemoglobin (Hb) and serum measurements is insignificant as the measurements may be affected by e.g. hemodilution or accelerated erythropoiesis. This study tests whether cell indices will give a more reliable measure of iron deficiency in pregnant women at term. The population was 202 pregnant women. Using the ADVIA 120 hematology system, Hb, mean cell volume (MCV), percentage of hypochromic red blood cells (%HYPOm) and reticulocytes (%HYPOr), and cellular hemoglobin in reticulocytes (CHr) were tested. Additionally, transferrin saturation (TfSat), ferritin, and transferrin receptor (TfR) were analyzed. Receiver operating characteristic (ROC) curves and area under the ROC curves (AUC) were used as statistical methods. When TfSat (< or = 11%) was used as the reference test for iron deficiency, %HYPOm and CHr had a sensitivity of 58.1% and 80.7%, while the specificities were 82.6% and 71.3%, respectively. Additionally, the AUC values were %HYPOr 0.80, CHr 0.79, ferritin 0.77, %HYPOm 0.75, TfR 0.67, MCV 0.63 and Hb 0.64. The results provided by the cell indices alone (%HYPOm or CHr) were in good agreement with the results based on the usage of a combination of three commonly used tests (Hb, MCV, ferritin). This study suggests that the most practical way to diagnose iron deficiency in pregnant women at term is to use cell indices such as CHr and %HYPOm provided by the automated hematological analyzer. Further studies are needed to determine the usefulness of the cell indices in diagnosing iron deficiency longitudinally during the course of pregnancy.


Changes in the composition of the bacterial flora on tray-packaged pork during chilled storage analyzed by PCR-DGGE and real-time PCR.
In this study, a polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) was used to investigate the changes in the composition of the bacterial population of tray-packaged pork during chilled storage. Relative quantitative real-time PCR was further used to evaluate the predominant spoilage bacteria obtained from DGGE analysis for their relative amount to the total bacteria in meat samples. DGGE analysis of the V3 and V6-V8 regions of the 16S rRNA gene showed that Pseudomonas were the predominant bacterial species at the end of the monitoring period. Real-time PCR expressed as the ΔΔC(T) method showed that the average 2(-ΔΔC)(T) values increased continually during the storage period from less than 0.001 at day 0 to 4.438 at the end of the monitoring, which indicated that the proportions of Pseudomonas within the total bacteria in meat samples increased. Both methods confirmed that Pseudomonas was the predominant spoilage bacteria. Practical Application: This study uses new techniques to identify bacteria in fresh retail pork and to follow changes in the bacterial population during 12 d refrigerated storage. Pseudomonads were found to increase with storage time, becoming the dominant flora after 12 d.


A retrospective study of chloral hydrate, meperidine, hydroxyzine, and midazolam regimens used to sedate children for dental care.
The purpose of this retrospective study was twofold: a) to examine the behavior and physiology of pre-school children each sedated with 1 of 3 drug regimens based on patient age, dental needs, and pre-operative clinical impression; and b) to determine the association between pre-operative behaviors to the behavior and physiology of the sedated children. Records of more than 600 patients sedated at Columbus Children's Hospital dental clinic over a two-year period were culled for patients who ranged in age from 2 to 5 years of age and had received one of three different drug regimens: a) chloral hydrate and hydroxyzine (CH-H), b) chloral hydrate, meperidine, and hydroxyzine (CH-D-H), or c) midazolam (M). A minimum of 300 patients (100/drug regimen) were randomly selected. The standard sedation sheet used in all sedations at the clinic included, among other factors, pre-operative assessments of patient behavior, interaction, and cooperation. Physiological and behavioral variables during the intraoperative sedation periods were also available. These periods included initial baseline vitals, vitals following drug administration, topical and local drug administration, rubber, dam placement, and a minimum of the first 15 minutes of restorative procedures. The three drug regimens were compared for these variables. Data were entered into SPSS for data analysis using one-way ANOVA, Chi-square, regression analysis, and descriptive statistics. The results indicated significant mean differences in patient age, weight, and duration by drug regimen (F = 20.3, P < 0.001; 16.2, P < 0.001; and 48.7, P < 0.001, respectively). ANOVA indicated a significant difference among drug regimens for percent of quiet, sleeping, and struggling behaviors. Quiet behavior accounted for 26%, 41%, and 67% of all behaviors for CH-H, CH-D-H, and M, respectively. Sleep accounted for 50%, 43%, 0.4% and struggling 11%, 8%, and 19% for CH-H, CH-D-H, and M, respectively. Pre-operative behaviors were also significantly different and patient cooperation was the only variable found minimally predictable of intra-operative behaviors (R = 0.32, P < 0.001). Significant differences among drug regimens were found for heart rate (HR) and mean arterial blood pressure (MAP) during certain procedures (e.g., CH-H produced lower MAP compared to the other drug regimens); however, all physiological variables were within normal limits for the children. Significant differences were found for behavioral and physiological variables among the drug regimens (e.g., CH-D-H produced significantly more quiet and sleeping behaviors than M). Prospective studies are needed to confirm these findings.


Use of fuzzy algorithms for phonetic and phonemic labeling of continuous speech.
A model for assigning phonetic and phonemic labels to speech segments is presented. The system executes fuzzy algorithms that assign degrees of worthiness to structured interpretations of syllabic segments extracted from the signal of a spoken sentence. The knowledge source is a series of syntactic rules whose syntactic categories are phonetic and phonemic features detected by a precategorical and a categorical classification of speech sounds. Rules inferred from experiments and results for male and female voices are presented.


Production of human lactoferrin in transgenic tobacco plants.
Production and characterization of human lactoferrin (hLf) in transgenic tobacco is reported. We have engineered two constructs containing either the native signal peptide from human lactoferrin or the signal peptide from sweet potato sporamin fused to human lactoferrin encoding cDNA. N-terminal sequences of rhLf purified from tobacco were identical to Lf from human milk for both constructs. The tobacco rhLf presents a molecular mass closely identical to native protein. Overall sugar composition shows the presence of plant specific xylose while sialic acid is absent. Binding parameters of the recombinant molecule to both Jurkat lymphoblastic T-cells or HT29-18-C1 enterocytes are similar to those of human lactoferrin isolated from milk.


Productivity and cost-effectiveness of short-rotation hardwoods on various land types in the southeastern USA.
Despite the growing need to produce energy crops, information on comprehensive feasibility of growing short-rotation woody crops (SRWCs) on non-contentious and less-utilized lands and lands transitioning from previous uses in the southeastern USA is limited. An assessment model (SRWC-PEAM) was developed and tested for assessing the feasibility of SRWCs on lands targeted for ecosystem-service enhancements based on land conditions, species, and stand and economic variables in the southeastern USA. Productivity and economic returns of sweetgum (Liquidambar styraciflua L.), sycamore (Platanus occidentalis L.), and poplar (Populus) stand differed due to land types, species' adaptability and biomass potential, and optimal land-type-based management schemes. Poplar stands had the greatest biomass and the highest returns on all land types although returns from the three species on most land types were poor using current reported regional delivered prices. Irrigating stands increased yields but returns were poorer than from non-irrigated stands due to high costs of irrigation. Longer rotations resulted in greater biomass and returns and were more crucial for irrigated stands. Significantly higher feedstock prices and productivities are requisite for SRWC viability in the southeastern USA. SRWC-PEAM is a web-based tool and can accommodate other SRWC species and assessment of environmental services associated with SRWCs.


A Case of Sheehan Syndrome 7 Years Postpartum with Transaminitis and Hyperlipidemia.
BACKGROUND Sheehan syndrome (pituitary necrosis after postpartum hemorrhage) can present in various ways, depending on the hormones that are deficient. There may be a long delay to diagnosis of over a decade because symptoms are often vague and pituitary dysfunction progresses gradually. We describe a case of a patient with acute presentation of Sheehan syndrome 7 years after the obstetric event and with no clear precipitating event. CASE REPORT A 46-year-old woman with a history of hyperlipidemia and transaminitis came to the clinic for evaluation of hypotension and syncope. She had a history of longstanding anhedonia, fatigue, and postpartum hemorrhage 7 years previously and had undergone medical evaluations with her primary doctor with no cause found. Laboratory results showed anemia, central hypothyroidism, and adrenal insufficiency. A diagnosis of Sheehan syndrome was made. CONCLUSIONS Sheehan syndrome is a rare condition of progressive pituitary dysfunction, which can present with nonspecific symptoms and a myriad of laboratory abnormalities until an adrenal crisis is triggered years after the precipitating event. Screening patients for hypopituitarism by free thyroxine levels and adrenocorticotropic hormone (ACTH) stimulation testing is vital for determining whether hypopituitarism is the cause in the appropriate clinical scenario. Use of thyroid-stimulating hormone levels and morning cortisol testing alone will miss this diagnosis, and free thyroxine levels and ACTH stimulation testing are vital.


Rapid memory reactivation revealed by oscillatory entrainment.
Episodic memory refers to humans' unique ability to mentally reconstruct past events. Neurocomputational models predict that remembering entails the reinstatement of brain activity that was present when an event was initially experienced [1-5], a claim that has recently gained support from functional imaging work in humans [6-14]. The nature of this reactivation, however, is still unclear. Cognitive models claim that retrieval is set off by an early reactivation of stored memory representations ("ecphory") [15-17]. However, reinstatement as found in imaging studies might also reflect postretrieval processes that operate on the products of retrieval and are thus a consequence rather than a precondition of remembering. Here, we used frequency entrainment as a novel method of tagging memories in the human electroencephalogram (EEG). Participants studied words presented on flickering backgrounds, entraining a steady-state brain response at either 6 or 10 Hz. We found that these frequency signatures rapidly reemerged during a later memory test when participants successfully recognized a word. An additional behavioral experiment suggested that this reactivation occurs in the absence of conscious memory for the frequencies entrained during study. The findings provide empirical evidence for the role of rapid, likely unconscious memory reactivation during retrieval.


Subtraction Images From Portal Venous Phase Gadoxetic Acid-Enhanced MRI for Observing Washout and Enhancing Capsule Features in LI-RADS Version 2018.
OBJECTIVE. The purpose of this study is to validate the use of subtraction images derived from gadoxetic acid-enhanced MRI for observation of washout and enhancing capsule in the diagnosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS. For 120 histologically verified HCCs in 115 high-risk patients, the presence of washout and enhancing capsule in the portal venous phase (PVP) on conventional MR images with and without corresponding subtraction images was determined by two independent observers. The incremental value of subtraction imaging in upgrading the categories outlined in the Liver Imaging Reporting and Data System (LI-RADS) version 2018 for the diagnosis of HCC was analyzed for different subgroups of patients classified on the basis of lesion size (< 10 mm, 10-19 mm, ≥ 20 mm), unenhanced T1-weighted signal intensity, and arterial phase hyperenhancement (APHE) of the lesions. RESULTS. When conventional PVP images were compared with the combination of conventional and subtraction PVP images, only T1-weighted isointensity or hyperintensity significantly increased the detection of washout (eight vs 15 of 18 lesions; p = 0.0233). Detection of enhancing capsule was significantly increased (p < 0.05) regardless of various factors, except for a lesion size of less than 2 cm (five vs nine of 36 lesions; p = 0.1336). Two lesions (one LI-RADS category 3 lesion and one LI-RADS category 4 lesion) with APHE were upgraded to category 5 on the basis of a review of PVP subtraction images. CONCLUSION. PVP subtraction imaging during gadoxetic acid-enhanced MRI can upgrade LI-RADS categories for the diagnosis of HCC because of its superior ability in depicting enhancing capsule and the incremental benefit of showing washout.


Systemic alterations in the metabolome of diabetic NOD mice delineate increased oxidative stress accompanied by reduced inflammation and hypertriglyceremia.
Nonobese diabetic (NOD) mice are a commonly used model of type 1 diabetes (T1D). However, not all animals will develop overt diabetes despite undergoing similar autoimmune insult. In this study, a comprehensive metabolomic approach, consisting of gas chromatography time-of-flight (GC-TOF) mass spectrometry (MS), ultra-high-performance liquid chromatography-accurate mass quadruple time-of-flight (UHPLC-qTOF) MS and targeted UHPLC-tandem mass spectrometry-based methodologies, was used to capture metabolic alterations in the metabolome and lipidome of plasma from NOD mice progressing or not progressing to T1D. Using this multi-platform approach, we identified >1,000 circulating lipids and metabolites in male and female progressor and nonprogressor animals (n = 71). Statistical and multivariate analyses were used to identify age- and sex-independent metabolic markers, which best differentiated metabolic profiles of progressors and nonprogressors. Key T1D-associated perturbations were related with 1) increases in oxidation products glucono-δ-lactone and galactonic acid and reductions in cysteine, methionine and threonic acid, suggesting increased oxidative stress; 2) reductions in circulating polyunsaturated fatty acids and lipid signaling mediators, most notably arachidonic acid (AA) and AA-derived eicosanoids, implying impaired states of systemic inflammation; 3) elevations in circulating triacylglyercides reflective of hypertriglyceridemia; and 4) reductions in major structural lipids, most notably lysophosphatidylcholines and phosphatidylcholines. Taken together, our results highlight the systemic perturbations that accompany a loss of glycemic control and development of overt T1D.


Helicobacter pylori RNA polymerase α-subunit C-terminal domain shows features unique to ɛ-proteobacteria and binds NikR/DNA complexes.
Bacterial RNA polymerase is a large, multi-subunit enzyme responsible for transcription of genomic information. The C-terminal domain of the α subunit of RNA polymerase (αCTD) functions as a DNA and protein recognition element localizing the polymerase on certain promoter sequences and is essential in all bacteria. Although αCTD is part of RNA polymerase, it is thought to have once been a separate transcription factor, and its primary role is the recruitment of RNA polymerase to various promoters. Despite the conservation of the subunits of RNA polymerase among bacteria, the mechanisms of regulation of transcription vary significantly. We have determined the tertiary structure of Helicobacter pylori αCTD. It is larger than other structurally determined αCTDs due to an extra, highly amphipathic helix near the C-terminal end. Residues within this helix are highly conserved among ɛ-proteobacteria. The surface of the domain that binds A/T rich DNA sequences is conserved and showed binding to DNA similar to αCTDs of other bacteria. Using several NikR dependent promoter sequences, we observed cooperative binding of H. pylori αCTD to NikR:DNA complexes. We also produced αCTD lacking the 19 C-terminal residues, which showed greatly decreased stability, but maintained the core domain structure and binding affinity to NikR:DNA at low temperatures. The modeling of H. pylori αCTD into the context of transcriptional complexes suggests that the additional amphipathic helix mediates interactions with transcriptional regulators.


Preterm low birthweight and the role of oral bacteria.
Preterm and low birthweight (PTLBW) continues to be a major cause of mortality and morbidity across the world. In recent years, maternal periodontal disease has been implicated as a risk factor for adverse pregnancy outcomes. There is conflicting evidence to support such an outcome as illustrated by descriptive, case control and randomised controlled trials involving pregnant women from across the world, using different measurement tools to determine the level of periodontal disease. Whilst considering the literature, there is evidence for both arguments, based on the effect of periodontal inflammatory by products. Bacteria associated with periodontal disease are not dissimilar to those known to be associated with genito-urinary bacterial infections and adverse pregnancy outcomes. Several groups have demonstrated the apparent translocation of Fusobacterium nucleatum, Prevotella nigrescens, Prevotella intermedia, Porphyromonus gingivalis, Treponema denticola to the foetal placental unit whereby a maternal or foetal response has been detected resulting in premature birth or low birthweight. The normal process of parturition involves a cascade of events including a build-up of inflammatory mediators as linked to inflammation, whereby the maternal environment becomes hostile and threatens the well-being of the infant, and the foetus expelled. The question remains therefore, is there a greater risk of delivering a PTLBW infant when the mother has detectable periodontal disease, or is the release of inflammatory mediators and their translocation via the haematogenous route sufficient to induce a poor pregnancy outcome? The data investigated would suggest that there is a positive outcome when certain oral gram-negative bacteria create a cumulative effect sufficient to trigger early delivery, which represents the final straw to result in preterm or low birthweight delivery. There is equally sufficient epidemiological evidence that does not support this outcome, but it is agreed that maintaining oral health during pregnancy is beneficial to the mother and her infant.


Subclinical symptoms in mood disorders: pathophysiological and therapeutic implications.
The aim of this review was to survey the available literature on prodromal and residual symptoms of unipolar major depression and bipolar disorder. Both a computerized (Medline) and a manual search of the literature were performed. In a substantial proportion of patients with affective disorders a prodromal phase can be identified. Most patients report residual symptoms despite successful treatment. Residual symptoms upon remission have a strong prognostic value. There appears to be a relationship between residual and prodromal symptomatology (the rollback phenomenon). Appraisal of subclinical symptomatology in mood disorders has important implications for pathophysiological models of disease and relapse prevention. In depression, specific treatment of residual symptoms may improve long-term outcome, by acting on those residual symptoms that progress to become prodromes of relapse. In bipolar disorder, decrease of subclinical fluctuations and improvement of level of functioning by specific therapeutic strategies may add to the benefits provided by lithium prophylaxis.


Graph Neural Networks and Structural Information on Ionic Liquids: A Cheminformatics Study on Molecular Physicochemical Property Prediction.
Ionic liquids (ILs) provide a promising solution in many industrial applications, such as solvents, absorbents, electrolytes, catalysts, lubricants, and many others. However, due to the enormous variety of their structures, uncovering or designing those with optimal attributes requires expensive and exhaustive simulations and experiments. For these reasons, searching for an efficient theoretical tool for finding the relationship between the IL structure and properties has been the subject of many research studies. Recently, special attention has been paid to machine learning tools, especially multilayer perceptron and convolutional neural networks, among many other algorithms in the field of artificial neural networks. For the latter, graph neural networks (GNNs) seem to be a powerful cheminformatic tool yet not well enough studied for dual molecular systems such as ILs. In this work, the usage of GNNs in structure-property studies is critically evaluated for predicting the density, viscosity, and surface tension of ILs. The problem of data availability and integrity is discussed to show how well GNNs deal with mislabeled chemical data. Providing more training data is proven to be more important than ensuring that they are immaculate. Great attention is paid to how GNNs process different ions to give graph transformations and electrostatic information. Clues on how GNNs should be applied to predict the properties of ILs are provided. Differences, especially regarding handling mislabeled data, favoring the use of GNNs over classical quantitative structure-property models are discussed.


The dynamics of vegetation diversity and biomass under traditional grazing in Ethiopia's Somali rangeland.
Traditional grazing management practices are central to rangeland productivity and biodiversity. However, the degradation of rangelands and loss of ecosystem services have raised concerns about the future of pastoralism as a form of land use. It is imperative to understand how these practices influence vegetation attributes, e.g., herbaceous species diversity and composition, growth forms (grass, forbs), life form (annuals, perennials), tree metrics (density, canopy cover, and biomass). This study evaluates vegetation shifts under three grazing management practices-enclosures, open grazing, and browsing lands-in the Somali pastoral ecosystem of Ethiopia. Enclosures exhibited the highest diversity in herbaceous species, with open grazing lands favoring forbs and annuals. Distinct compositional shifts in herbaceous species were observed across regimes, especially in grass and annuals. Enclosures had three times higher herbage biomass of open grazing and double that of browsing management practice. Conversely, browsing management practices presented optimal wood biomass, density, and canopy cover. The results highlight that a transition to combined enclosure and browsing practices can elevate plant production and diversity, benefiting the Somali rangeland economy. Consequently, dryland restoration should incorporate indigenous knowledge to ensure future rangeland sustainability and biodiversity preservation.


Turning a threat into an opportunity: British American Tobacco's weakening of the Protocol to Eliminate Illicit Trade in Tobacco Products.
Previous research has outlined transnational tobacco company (TTC) efforts to undermine implementation of the Protocol to Eliminate Illicit Trade in Tobacco Products (Protocol) and evidence of ongoing TTC complicity in the illicit tobacco trade (ITT). However, the industry's views on the Protocol and role in its development are not well understood. Systematic searching and analysis of leaked documents-approximately 15 000 from British American Tobacco (BAT) and 35 from Philip Morris International, triangulated via searches of online resources and interviews with five stakeholders across academia, international organisations, governments, civil society and the private sector. Evidence indicates that after privately viewing the Protocol as a significant threat (2003), BAT worked to influence its content, while publicly signalling support for it (2007-2012), and was largely satisfied with the final text. BAT successfully pushed for a non-prescriptive text which enabled further country-level TTC influence during the Protocol's implementation phase. The final text also reflected other BAT policy preferences, including preventing outright bans on duty-free sales and intermingling, and making it difficult to sanction and hold tobacco companies accountable for ongoing involvement in the ITT. TTC representatives were present during early Protocol negotiations, despite rules against this, and BAT obtained draft texts before they were public and paid at least one delegate to support its position. BAT's primary interest in shaping the Protocol was to minimise its financial and legal costs for BAT while maximising potential costs to small competitors. These findings raise concern about the Protocol's ability to control the ITT, particularly given TTCs' intention to influence ongoing national implementation. An effective Protocol is vital to controlling both the ITT and ongoing tobacco industry involvement in it and, in turn, governments' ability to increase tobacco taxes and thereby save lives.


Psychological distress among younger siblings of patients with homozygous sickle cell disease in the Jamaican cohort study.
The presence of a chronically ill family member may adversely affect the psychological health of siblings. This study used the General Health Questionnaire and the Modified Social Adjustment Scale to assess psychological distress in 20 younger siblings (4 AA, 16 AS genotypes), aged 16-19 years, of patients with homozygous sickle cell (SS) disease. The results were compared with those previously obtained in the 20 older siblings with SS disease and in 89 controls with a normal haemoglobin (AA) genotype. High levels of psychological distress occurred among all three groups. Greater psychological distress and poorer social adjustment occurred among siblings compared to AA controls but these differences disappeared after adjusting for the reduced age of siblings. The two measures were similar in SS patients and AA controls. The level of psychological distress among siblings of SS patients did not differ from that in SS patients or AA controls.


Access to prescription drugs among noninstitutionalized elderly people in west Texas.
The determinants of realized, perceived, and potential access to prescription drugs among an elderly population were studied. Data were derived from telephone interviews of 3498 noninstitutionalized elderly persons living in west Texas. Access indicators examined were whether the respondents were taking prescription drugs, had perceived problems in obtaining prescription drugs, had comprehensive prescription drug insurance, and had a usual pharmacy. On the basis of the behavioral model of health services, multivariate logistic regression analysis was performed to determine whether predisposing, enabling, and need factors were associated with each access indicator. Approximately 14% of the patients were not taking prescription drugs at the time of the interview. Of the patients who were taking prescription drugs, about 16% reported having problems obtaining prescription drugs and 24% primarily used a single pharmacy. Nearly 36% did not have comprehensive prescription drug coverage. Among the four indicators of prescription drug access, lack of prescription drug insurance was the most prevalent barrier. Employer-provided insurance improved access more than any other type of coverage. Elderly consumers taking more medications reported more problems accessing prescriptions than those taking fewer medications. Among the indicators of access to prescription drugs among noninstitutionalized elderly people in west Texas, lack of prescription drug insurance was the most prevalent barrier.


Relationship of dopamine D1 receptor binding in striatal and extrastriatal regions to cognitive functioning in healthy humans.
Dopamine (DA) availability in both striatal and extrastriatal brain regions has been implicated in cognitive performance. Given that different brain regions are neuroanatomically and functionally different, DA receptor binding in different brain regions may be selectively important to specific cognitive functions. Using PET and the radioligand SCH23390, we measured D1 receptor binding potential (BP(ND)) in dorsolateral prefrontal cortex (DLPFC), hippocampus (HC), as well as in sensorimotor (SMST), associative (AST), and limbic (LST) striatum in 20 healthy younger persons. Subjects completed tasks assessing executive functioning, episodic memory, speed, and general knowledge. Unlike previous reports, we found no linear or curvilinear relationships between D1 receptor binding in DLPFC and performance in any cognitive task. However, BP(ND) in HC was positively linked to executive performance as well as to speed and knowledge. With regard to the striatal subregions, D1 BP(ND) in SMST was more strongly related to speed compared to the other striatal subregions, whereas D1 BP(ND) in AST was more strongly linked to general knowledge. These findings provide support for the notion that D1 receptors in separate brain regions are differentially related to performance in tasks tapping various cognitive domains.


Dual function of Src in the maintenance of adherens junctions during tracheal epithelial morphogenesis.
The downregulation of E-cadherin by Src promotes epithelial to mesenchymal transition and tumorigenesis. However, a simple loss of cell adhesion is not sufficient to explain the diverse developmental roles of Src and metastatic behavior of viral Src-transformed cells. Here, we studied the functions of endogenous and activated forms of Drosophila Src in the context of tracheal epithelial development, during which extensive remodeling of adherens junctions takes place. We show that Src42A is selectively activated in the adherens junctions of epithelia undergoing morphogenesis. Src42A and Src64B are required for tracheal development and to increase the rate of adherens junction turnover. The activation of Src42A caused opposing effects: it reduced the E-cadherin protein level but stimulated transcription of the E-cadherin gene through the activation of Armadillo and TCF. This TCF-dependent pathway was essential for the maintenance of E-cadherin expression and for tissue integrity under conditions of high Src activity. Our data suggest that the two opposing outcomes of Src activation on E-cadherin facilitate the efficient exchange of adherens junctions, demonstrating the key role of Src in the maintenance of epithelial integrity.


Primary and secondary barriers to physically active healthy lifestyles for adults with learning disabilities.
Evidence shows that those with a learning disability are typically amongst the most inactive and sedentary members of the population, yet few studies have focused on the determinants of physical activity. The aim of the present study was to establish whether a group of 24 adults with mild and moderate learning disabilities receive adequate support to be able to make choices to lead a physically active lifestyle. A descriptive study was used based on interviews with 24 adults with learning disabilities (mean age of 34 years) triangulated by day time and residential care workers. Participants volunteered from two residential homes and one social education centre (SEC) in a city in the North of England. The participants face a set of primary barriers that prevent them from having a choice to adopt the Department of Health's recommendations for physical activity. Identified barriers included: unclear policy guidelines in residential and day service provision together with resourcing, transport and staffing constraints; participant income and expenditure; and limited options for physically active community leisure. These are barriers that are widely acknowledged and understood by day and residential staff and participants in the study, but are arguably poorly understood by policy makers, health promotion agencies, commissioners and providers of learning disability services. The current lack of resources and inadequately specified responsibilities associated with community care deny many people with learning disabilities real choices to live a physically active healthy lifestyle.


The influence of age on gait parameters during the transition from a wide to a narrow pathway.
The ability to negotiate pathways of different widths is a prerequisite of daily living. However, only a few studies have investigated changes in gait parameters in response to walking on narrow pathways. The aim of this study is to examine the influence of age on gait adjustments during the transition from a wide to a narrow pathway. Two-group repeated measures design. Gait Laboratory. Twenty healthy older participants (mean [M] = 74.3 years, Standard deviation [SD] = 7.2 years); 20 healthy young participants (M = 26.6 years, SD = 6.1 years). Making the transition from walking on a wide pathway (68 cm) to walking on a narrow pathway (15 cm). Step length, step time, step width, double support time and base of support. Healthy older participants were able to make the transition from a wide to a narrow pathway successfully. There was only one significant interaction, between age and base of support (p < 0.003). Older adults decreased their base of support only when negotiating the transition step, while young participants started decreasing their base of support prior to the negotiation of transition step (p < 0.01). Adjustments to the transition from a wide to a narrow pathway are largely unaffected by normal ageing. Difficulties in making the transition to a narrow pathway during walking should not be attributed to normal age-related changes.


An extensive and dynamic trans-omic network illustrating prominent regulatory mechanisms in response to insulin in the liver.
An effective combination of multi-omic datasets can enhance our understanding of complex biological phenomena. To build a context-dependent network with multiple omic layers, i.e., a trans-omic network, we perform phosphoproteomics, transcriptomics, proteomics, and metabolomics of murine liver for 4 h after insulin administration and integrate the resulting time series. Structural characteristics and dynamic nature of the network are analyzed to elucidate the impact of insulin. Early and prominent changes in protein phosphorylation and persistent and asynchronous changes in mRNA and protein levels through non-transcriptional mechanisms indicate enhanced crosstalk between phosphorylation-mediated signaling and protein expression regulation. Metabolic response shows different temporal regulation with transient increases at early time points across categories and enhanced response in the amino acid and nucleotide categories at later time points as a result of process convergence. This extensive and dynamic view of the trans-omic network elucidates prominent regulatory mechanisms that drive insulin responses through intricate interlayer coordination.


Comments about some species abundance patterns: classic, neutral, and niche partitioning models.
The literature on species abundance models is extensive and a great deal of new and important contributions have been published in the last three decades. Broadly speaking, one can recognize five families of species abundance models: i) purely statistical or classic models (Broken-stick, Log-normal, Logarithmic and Geometric series); ii) branching process (Zipf-Mandelbrot and Fractal branching models); iii) population dynamics (Neutral models included); iv) spatial distribution of individuals (Multifractal and HEAP models) and v) niche partitioning (Sugihara's breakage and Tokeshi models). Among these the neutral, the classic and the niche partitioning models have been the most applied to natural communities, the former having been more extensively discussed than the others in the last years. The objective of this paper is to comment some aspects of the classic, neutral and niche partitioning models in a way that the proposed distributions may contribute to the analysis of the empirical patterns of species abundance. In spite of the variety of models, the distributions in general vary between the log-normal and the logarithmic series. From these models the Power-Fraction, together with independent niche dimensions measures, are amenable to experimental tests and may offer answers on which resources are important in the structuring of biological communities.


Rationalizing structure and target relationships between current drugs.
A recent analysis of structure and target relationships between current drugs and bioactive compounds has revealed that only a small fraction of drugs that are active against the same or overlapping targets are involved in substructure relationships and/or share the same topology. By contrast, structurally related drugs displayed a tendency to preferentially act against different targets. For bioactive compounds, opposite trends were observed. These surprising findings arising from the global analysis have now been examined in detail by analyzing structure and target relationships between drugs at the level of individual targets and individual drugs and by comparing the results of local (target- or drug-based) and global relationship analysis. On the basis of target-based analysis, on average, only 14% of drugs active against a given target form well-defined structural relationships. In addition, drug-based analysis revealed that on average 72% of all structurally related drugs have no or at most 20% target overlap. Taken together, the results of our current analysis at the level of single targets and drugs rationalize their unexpected structure and target relationships in a consistent manner. These findings also have implications for ligand binding characteristics of popular drug targets and for frequently observed polypharmacological drug behavior.


Group B streptococcal disease: its diagnosis with the use of antigen detection, Gram's stain, and the presence of apnea, hypotension.
Antigen detection was found to be a rapid and useful technique in diagnosing group B streptococcal (GBS) infections. Of the two techniques described, latex agglutination was more sensitive than countercurrent immunoelectrophoresis. Concentrated urine was the best body fluid to test with 100% containing antigen. Though no false-positive reactions were noted, this is a potential problem. Gram-positive cocci in the gastric aspirate were associated with severe systemic infections with these organisms in almost half of the neonates with clinical signs of infection or respiratory distress syndrome (RDS). There was only a 4% infection rate in clinically similar neonates without Gram-positive cocci in the gastric aspirates. Apnea and/or hypotension was seen commonly in both early onset GBS pneumonia and RDS, making this finding alone of little clinical use.


[Immune complexes and R-proteins in yersinioses].
The intensity of the catabolism of cell receptors in yersiniosis patients has been studied. The dynamics of R-protein level reflects the relapsing character of the pathological process irrespective of the presence of clinically pronounced relapses and the form of the disease. The concentration of circulating immune complexes is elevated during the whole course of the disease and does not depend on its gravity and clinical form. The spectrum of immune complexes in the blood sera of yersiniosis patients is heterogeneous and changes in the course of the disease.


Activation of c-myc and c-K-ras oncogenes in primary rat tumors induced by ionizing radiation.
An activated K-ras oncogene was detected by transfection in NIH 3T3 cells and by Southern blot analysis in 6 of 12 rat skin tumors induced by ionizing radiation. The DNA from 10 of the 12 tumors also showed c-myc gene amplification and restriction polymorphisms. Evidence for tissue specificity was observed in patterns of oncogene activation, with each of three clear cell carcinomas exhibiting activation of both c-myc and K-ras oncogenes.


Demodex Mite, Rosacea and Skin Melanoma; Coincidence or Association?
To examine the possible associations between Demodex folliculorum and a number of skin diseases. Standardized skin surface biopsy samples were obtained from the cheeks of 144 patients with histopathologically proven basal cell carcinoma (BCC, n = 27), squamous cell carcinoma (SCC, n = 28), melanoma (n = 23), discoid lupus erythematosus (DLE, n = 32), and rosacea (n = 34). Thirty-four sex- and age-matched healthy volunteers served as controls. Mite density (per cm2) and infestation (density ≥ 5) were compared between the controls and patients. Mite infestation rates (%) did not differ significantly between the controls (20.6) and patients with BCC (22.2, p = 0.88), SCC (17.9, p = 0.79), melanoma (4.3, p = 0.08), and DLE (21.9, p = 0.90). Compared with the controls, the mite infestation rate was significantly higher in patients with rosacea (47.1, p = 0.02, odds ratio: 3.43, 95% confidence interval: 1.18-9.99). The mean mite density did not differ significantly between the controls (4.11 ± 2.17) and patients with BCC (5.34 ± 2.35, p = 0.75), SCC (3.57 ± 2.01, p = 0.38), and DLE (3.56 ± 1.34, p = 0.83), whereas it was significantly higher in patients with rosacea (8.78 ± 3.58, p = 0.02) and lower in patients with melanoma (1.89 ± 0.69, p = 0.02). D. folliculorum may be associated with rosacea and melanoma but not with BCC, SCC, or DLE.


Characterization of Syrian hamster adapted prions derived from L-type and C-type bovine spongiform encephalopathies.
Atypical forms of bovine spongiform encephalopathy (BSE) may be caused by different prions from classical BSE (C-BSE). In this study, we examined the susceptibility of mice overexpressing mouse and hamster chimeric prion protein (PrP) to L-type atypical BSE (L-BSE). None of the transgenic mice showed susceptibility to L-BSE, except mice overexpressing hamster PrP. We also examined the transmission properties of L-BSE in hamsters. The incubation period of hamsters intracerebrally inoculated with L-BSE was 576.8 days, and that of the subsequent passage was decreased to 208 days. Although the lesion and glycoform profiles and relative proteinase K resistant core fragment of the abnormal isoform of PrP (PrPcore) of L-BSE were similar to that of C-BSE, the deposition of the abnormal isoform of PrP (PrPSc) and the molecular weight of PrPcore of L-BSE was different from than that of C-BSE. In hamster models, some prion strain characteristics of L-BSE were indistinguishable from those of C-BSE.


Distinct roles of DMAP1 in mouse development.
DMAP1 (DNMT1-associated protein 1) is a member of the TIP60-p400 complex that maintains embryonic stem (ES) cell pluripotency and a complex containing the somatic form of DNA methyltransferase 1 (DNMT1s). DMAP1 interacts with DNMT1s through a domain that is absent in Dnmt1(V)(/)(V) mice expressing just the oocyte form (DNMT1o). A Dmap1-null allele was generated to study the role of DMAP1 in development. Consistent with the phenotypes of loss of other members of the TIP60-p400 complex, Dmap1(-/-) mice died during preimplantation in both Dnmt1(+/+) and Dnmt1(V)(/)(V) backgrounds. Unexpectedly, in the Dnmt1(V)(/)(V) background, Dmap1(+/-) parents produced mainly Dmap1(+/-) mice. Most Dmap1(+/+) progeny died during midgestation, with loss of DNA methylation on imprinted genes, suggesting that DMAP1 influences maintenance methylation mediated by DNMT1o. In this regard, a DMAP1-DNMT1o complex was detected in ES cells when DNMT1o was stably expressed but not when transiently expressed, indicating a novel interaction between DMAP1 and DNMT1o. These results suggest that DMAP1-DNMT1s and DMAP1-DNMT1o interactions are essential for normal development and that DMAP1-DNMT1o complexes are not readily formed in the embryo. Therefore, DMAP1 mediates distinct preimplantation epigenetic reprogramming processes: TIP60-p400 nucleosome remodeling and DNMT1 maintenance methylation.


CXCL12-induced glioblastoma cell migration requires intermediate conductance Ca2+-activated K+ channel activity.
The activation of ion channels is crucial during cell movement, including glioblastoma cell invasion in the brain parenchyma. In this context, we describe for the first time the contribution of intermediate conductance Ca(2+)-activated K (IK(Ca)) channel activity in the chemotactic response of human glioblastoma cell lines, primary cultures, and freshly dissociated tissues to CXC chemokine ligand 12 (CXCL12), a chemokine whose expression in glioblastoma has been correlated with its invasive capacity. We show that blockade of the IK(Ca) channel with its specific inhibitor 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) or IK(Ca) channel silencing by short hairpin RNA (shRNA) completely abolished CXCL12-induced cell migration. We further demonstrate that this is not a general mechanism in glioblastoma cell migration since epidermal growth factor (EGF), which also activates IK(Ca) channels in the glioblastoma-derived cell line GL15, stimulate cell chemotaxis even if the IK(Ca) channels have been blocked or silenced. Furthermore, we demonstrate that both CXCL12 and EGF induce Ca(2+) mobilization and IK(Ca) channel activation but only CXCL12 induces a long-term upregulation of the IK(Ca) channel activity. Furthermore, the Ca(2+)-chelating agent BAPTA-AM abolished the CXCL12-induced, but not the EGF-induced, glioblastoma cell chemotaxis. In addition, we demonstrate that the extracellular signal-regulated kinase (ERK)1/2 pathway is only partially implicated in the modulation of CXCL12-induced glioblastoma cell movement, whereas the phosphoinositol-3 kinase (PI3K) pathway is not involved. In contrast, EGF-induced glioblastoma migration requires both ERK1/2 and PI3K activity. All together these findings suggest that the efficacy of glioblastoma invasiveness might be related to an array of nonoverlapping mechanisms activated by different chemotactic agents.


The mitogenic effects of vasoactive neuropeptides on cultured smooth muscle cell lines.
In order to investigate the relationship between the biochemical pathways that characterize contraction and cell growth, we have studied both contraction, mitogenesis and protein synthesis induced by the vasoactive neuropeptides, substance P (SP), calcitonin gene related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) on four different established vascular and nonvascular smooth muscle cell lines. Contraction in vitro was evaluated by light microscopy and recorded photographically. Mitogenesis and protein synthesis were evaluated by [3H]-thymidine incorporation into cells and [3H]-amino acid incorporation into trichloroacetic acid precipitated materials, respectively. SP stimulated mitogenesis of A7r5 cells (embryonic rat aorta), but failed to induce significant contraction of these cells, whereas, SP induced contraction of cultured adult rat vascular smooth muscle cells (VSMC), but failed to stimulate mitogenesis. CGRP and VIP stimulated mitogenesis and protein synthesis, respectively, of DDT1MF-2 cells (hamster vas deferens), but neither induced contraction of this cell line. All three neuropeptides showed no effect on BC3H1 (mouse smooth muscle-like) cells. These results suggest that neuropeptides with vasoactive properties modulate different stages of cellular mitogenic responses which may be regulated by the degree of maturation of smooth muscle cell.


Deletion of GLUT1 in mouse lens epithelium leads to cataract formation.
The primary energy substrate of the lens is glucose and uptake of glucose from the aqueous humor is dependent on glucose transporters. GLUT1, the facilitated glucose transporter encoded by Slc2a1 is expressed in the epithelium of bovine, human and rat lenses. In the current study, we examined the expression of GLUT1 in the mouse lens and determined its role in maintaining lens transparency by studying effects of postnatal deletion of Slc2a1. In situ hybridization and immunofluorescence labeling were used to determine the expression and subcellular distribution of GLUT1 in the lens. Slc2a1 was knocked out of the lens epithelium by crossing transgenic mice expressing Cre recombinase under control of the GFAP promoter with Slc2a1loxP/loxP mice to generate Slc2a1loxP/loxP;GFAP-Cre+/0 (LensΔGlut1) mice. LensΔGlut1 mice developed visible lens opacities by around 3 months of age, which corresponded temporally with the total loss of detectable GLUT1 expression in the lens. Spectral domain optical coherence tomography (SD-OCT) imaging was used to monitor the formation of cataracts over time. SD-OCT imaging revealed that small nuclear cataracts were first apparent in the lenses of LensΔGlut1 mice beginning at about 2.7 months of age. Longitudinal SD-OCT imaging of LensΔGlut1 mice revealed disruption of mature secondary fiber cells after 3 months of age. Histological sections of eyes from LensΔGlut1 mice confirmed the disruption of the secondary fiber cells. The structural changes were most pronounced in fiber cells that had lost their organelles. In contrast, the histology of the lens epithelium in these mice appeared normal. Lactate and ATP were measured in lenses from LensΔGlut1 and control mice at 2 and 3 months of age. At 2 months of age, when GLUT1 was still detectable in the lens epithelium, albeit at low levels, the amount of lactate and ATP were not significantly different from controls. However, in lenses isolated from 3-month-old LensΔGlut1 mice, when GLUT1 was no longer detectable, levels of lactate and ATP were 50% lower than controls. Our findings demonstrate that in vivo, the transparency of mature lens fiber cells was dependent on glycolysis for ATP and the loss of GLUT1 transporters led to cataract formation. In contrast, lens epithelium and cortical fiber cells have mitochondria and could utilize other substrates to support their anabolic and catabolic needs.


[Evaluation of pulmonary arterial hypertension by phonoechocardiography and Doppler].
We discuss the value of the non-invasive methods such as phonomecanocardiography, echocardiography and Doppler in the assessment of pulmonary arterial hypertension (PAH) The phonocardiographic record, the yugular phlebogram and the precordiogram, have a good correlation with the systolic pressure of the pulmonary artery. The two-dimensional echocardiogram is the technique of choice to determine the state of the pulmonary artery bandages after surgery and is also useful in cases of pulmonary thromboembolisms. The most reliable non-invasive method to determine the severity of the PAH is the Doppler study of the outflow tract of the right ventricle and pulmonary artery.


Colony Size, Rather Than Geographic Origin of Stocks, Predicts Overwintering Success in Honey Bees (Hymenoptera: Apidae) in the Northeastern United States.
Honey bees (Apis mellifera L.) are key pollinators of agricultural crops. However, approximately 30% of managed colonies die each winter in the United States. There has been great interest in breeding for 'locally adapted stocks' which survive winter conditions in a particular region. Here, we evaluate the impact of geographic origin of stock on colony weight, population size, and overwintering survival. Comparing four different U.S. honey bee stocks (two bred in southern and two bred in northern regions) under standard beekeeping practices in three different apiary locations in central Pennsylvania, we examined possible adaptation of these stocks to temperate conditions. We confirmed the genotypic difference among the stocks from different geographic origins via microsatellite analysis. We found that stock or region of origin was not correlated with weight, population size, or overwintering success. However, overwintering success was influenced by the weight and population size the colonies reached prior to winter where higher colony weight is a strong predictor of overwintering survival. Although the number of locations used in this study was limited, the difference in average colony sizes from different locations may be attributable to the abundance and diversity of floral resources near the honey bee colonies. Our results suggest that 1) honey bees may use similar strategies to cope with environmental conditions in both southern and northern regions, 2) colonies must reach a population size threshold to survive adverse conditions (an example of the Allee effect), and 3) landscape nutrition is a key component to colony survival.


Air microbial contamination in dental clinics: comparison between active and passive methods.
The aim of this study was to evaluate the correlation between the microbial air contamination values obtained by active sampling (colony-forming units per cubic metre, CFU/m3) and by passive sampling (Index of microbial air contamination, IMA) and to calculate the corresponding equations. Air sampling was performed in ten dental clinics (DC), before (T0), during (T1) and after (T2) the clinical activity, for five consecutive days, once a month for a period of three months, for a total of 450 air samplings. The correlation was evaluated using the Spearman test, and a p value below 0.05 was considered statistically significant. A statistically significant correlation was found considering both the results obtained from the total observations and from the single sampling times, T0, T1 and T2. Different correlation patterns were observed stratifying by DC. Both methods were able to evaluate the microbial air quality and highlight critical situations; therefore, both can be used with this aim. However, in particular during the activity, passive sampling resulted more sensitive, and for its simplicity, economy and standardization by IMA, as suggested by several authors, can be suggested for routine monitoring.


Tubular Network Formation by Mixing Amphiphilic Polypeptides with Differing Hydrophilic Blocks.
Artificial tubular networks are promising structures for biomaterial applications because of their large surface areas. A tubular network was formed by co-assembling two different amphiphilic polypeptides, poly(ethylene glycol)-b-(l-Leu-Aib)6 (PL12) and polysarcosine-b-(l-Leu-Aib)6 (SL12). They both have the same hydrophobic 12-mer helical block (l-Leu-Aib)6 but different hydrophilic chains, poly(ethylene glycol) and polysarcosine. In water, both polypeptides self-assembled into a tubular structure having a uniform 80 nm diameter that was formed by packing among the hydrophobic L12 blocks. The SL12 nanotubes were short (200 nm), straight, and robust. PL12 formed long (>1 μm), bendable, and fusogenic nanotubes. The amphiphiles were then co-assembled with various mixing ratios to form tubular networks. Higher concentrations of PL12 made the nanotubes more bendable and fusogenic between open tube ends, which produced branching junctions under heat treatment.


beta-Lactamase activity in human pus.
Pus was obtained from patients with polymicrobial intraabdominal abscesses or polymicrobial empyema. Physical and chemical characteristics of 12 specimens were examined, and bacterial isolates were enumerated. Pus supernatant of six specimens rapidly inactivated penicillin, cephalothin, and cefazolin. Carbenicillin and ticarcillin were similarly degraded by supernatant of certain pus specimens. Cefoxitin, chloramphenicol, and clindamycin were not appreciably inactivated by pus supernatant. Degradation of penicillin and cephalosporin congeners in pus was due to the presence of beta-lactamase, as shown by chemical interaction with nitrocefin, chromatography, and inhibition by the beta-lactamase inhibitor clavulanic acid. Pus supernatant containing beta-lactamase activity reduced the bactericidal activity of carbenicillin against Bacteroides fragilis in whole pus in an abscess model in vitro. Bactericidal activity of clindamycin or cefoxitin was not impaired in pus containing beta-lactamase.


The mTOR inhibitor RAD001 sensitizes tumor cells to the cytotoxic effect of carboplatin in breast cancer in vitro.
The phosphatidylinositol 3-kinase (PI3K)/protein kinase B(AKT)/mammalian target of rapamycin (mTOR) signaling pathway is aberrantly activated in many types of cancer, including breast cancer. It is recognized that breast cancer cells develop resistance to a variety of standard therapies through the activation of this pathway. We hypothesized that targeting this signaling by the mTOR inhibitor RAD001 may potentiate the cytotoxicity of a conventional chemotherapeutic drug, carboplatin, and enhance the treatment efficacy for breast cancer. Cell proliferation was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; cell apoptosis with enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used for the analysis of cell cycle distribution and mitochondrial membrane function. Gene expression at the protein level was determined by Western blot. MTOR inhibitor RAD001 enhanced the sensitivity of breast cancer cells to carboplatin. RAD001 in combination with carboplatin resulted in synergistic inhibition of cell proliferation and caspase-independent apoptosis in these cells. Moreover, in MCF-7 and BT-474 cells, synergistic effects of this combination on G₂/M cell cycle arrest and regulation of different molecules responsible for cell cycle transition and apoptosis were observed. The p53 pathway was involved in the synergism of RAD001 and carboplatin on breast cancer cell proliferation and apoptosis, since the synergistic effect was demonstrated in all tested breast cancer cell lines with wild-type p53 and the use of p53 inhibitor partially antagonized the effect of RAD001 and carboplatin on p53 and p21 expression, as well as their inhibitory effect on cell proliferation. However, a synergistic effect of the combination of the two drugs on cell proliferation was observed in two p53-mutated cell lines with high AKT expression, suggesting that an alternative mechanism underlying the observed synergism exists. Our results suggest that the combination of RAD001 and carboplatin is a promising treatment approach for breast cancer. On the basis of these results, we have initiated a phase I/II clinical trial with the combination of carboplatin and RAD001 in patients with metastatic breast cancer.


Growth hormone modulation of the rat hepatic bile transporter system in endotoxin-induced cholestasis.
Treatment with high dose human GH, although an effective anabolic agent, has been associated with increased incidence of sepsis, inflammation, multiple organ failure, and death in critically ill patients. We hypothesized that GH might increase mortality by exacerbating cholestasis through modulation of bile acid transporter expression. High dose GH was continuously infused over 4 d into rats, and on the final day lipopolysaccharides were injected. Hepatic bile acid transporter expression was measured by Northern analysis and immunoblotting and compared with serum markers of cholestasis and endotoxinemia. Compared with non-GH-treated controls, GH increased endotoxin-induced markers of cholestasis and liver damage as well as augmented IL-6 induction. In endotoxinemia, GH treatment significantly induced multidrug resistance-associated protein 1 mRNA and protein and suppressed organic anion transporting polypeptides, Oatp1 and Oatp4, mRNA, suggesting impaired uptake of bilirubin and bile acids at the basolateral surface of the hepatocyte, which could contribute to the observed worsening of cholestasis by GH. This study of endotoxinemia may thus provide a mechanistic link between GH treatment and exacerbation of cholestasis through modulation of basolateral bile acid transporter expression in the rat hepatocyte.


Blocking of intracellular ROS production by phytoglycoprotein (30 kDa) causes anti-proliferation in bisphenol A-stimulated Chang liver cells.
Dioscorea batatas Decne (DBD) is traditionally used to heal inflammatory disease as a folk medicine. It was reported that a glycoprotein (DBD glycoprotein) with a molecular weight of 30 kDa was isolated from DBD and consists of carbohydrate (83.75%) and protein (16.25%) moieties. The previous results showed that it has a strong scavenging activity against hydroxyl radicals without any pro-oxidant activity in the cell-free system. The purpose of the present study was to show whether or not the DBD glycoprotein inhibits cell proliferation-related signal transduction stimulated by bisphenol A (BPA, an environmental hormone) in Chang liver cells. The results in this study indicated that DBD glycoprotein (200 microg ml(-1)) has suppressive effects on abnormal cell viability, production of intracellular reactive oxygen species (ROS) and nitric oxide (NO) in BPA (50 microM)-induced Chang liver cells by blocking the phosphorylation of mitogen-activated protein kinase (MAPK) and activating protein-1 (AP-1) activity. In addition, DBD glycoprotein (200 microg ml(-1)) normalized the activity of catalase (CAT) and glutathione peroxidase (GPx). Consequently, DBD glycoprotein inhibits the expression of proliferating cell nuclear antigen (PCNA, cell proliferation maker) stimulated by BPA. Therefore, it is speculated that DBD glycoprotein protects against carcinogenic events caused by BPA in Chang liver cells.


Human social genomics.
A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA) characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural "social signal transduction" pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving.


Social deprivation and the outcomes of crisis resolution and home treatment for people with mental health problems: a historical cohort study.
The development of crisis resolution and home treatment (CRHT) teams has been central to the UK Government's objective of reducing reliance on hospital-based care and is supported by a growing body of evidence. However, there has been no research specifically exploring the relationship between social deprivation and CRHT teams, in spite of evidence of an association between social deprivation and increased pressure on inpatient services. This article reports a study which tested the hypothesis that social deprivation is associated with the outcome of CRHT interventions. Using a historical cohort study design, we examined a total of 260 accepted referrals to a CRHT. Social deprivation was measured by the Index of Multiple Deprivation (Office of the Deputy Prime Minister 2004) as a predictor of CRHT interventions outcomes. CRHT outcomes were dichotomised into successful and unsuccessful and were defined with reference to the CRHT operational policy. Univariate analysis found that people who lived in more socially deprived areas had a poorer outcome, as did older people and those referred from the enhanced community mental health team (CMHT). Logistic regression analysis found that age and referral source were independently associated with outcome. Analysis of the demographic data also suggested a non-significant trend towards men having less successful outcomes. Further analysis exploring the characteristics of the different referral sources to the CRHT found that those referred from the enhanced CMHT were significantly more likely to be from the most deprived area. This suggested a relationship between an enhanced level of mental health need, social deprivation and poor outcome of CRHT intervention.


Expression and function of 5-HT4 receptors in the mouse enteric nervous system.
The aim of the current study was to identify enteric 5-HT(4) splice variants, locate enteric 5-HT(4) receptors, determine the relationship, if any, of the 5-HT(4) receptor to 5-HT(1P) activity, and to ascertain the function of 5-HT(4) receptors in enteric neurophysiology. 5-HT(4a), 5-HT(4b), 5-HT(4e), and 5-HT(4f) isoforms were found in mouse brain and gut. The ratio of 5-HT(4) expression to that of the neural marker, synaptophysin, was higher in gut than in brain but was similar in small and large intestines. Submucosal 5-HT(4) expression was higher than myenteric. Although transcripts encoding 5-HT(4a) and 5-HT(4b) isoforms were more abundant, those encoding 5-HT(4e) and 5-HT(4f) were myenteric plexus specific. In situ hybridization revealed the presence of transcripts encoding 5-HT(4) receptors in subsets of enteric neurons, interstitial cells of Cajal, and smooth muscle cells. IgY antibodies to mouse 5-HT(4) receptors were raised, affinity purified, and characterized. Nerve fibers in the circular muscle and the neuropil in ganglia of both plexuses were highly 5-HT(4) immunoreactive, although only a small subset of neurons contained 5-HT(4) immunoreactivity. No 5-HT(4)-immunoreactive nerves were detected in the mucosa. 5-HT and 5-HT(1P) agonists evoked a G protein-mediated long-lasting inward current that was neither mimicked by 5-HT(4) agonists nor blocked by 5-HT(4) antagonists. In contrast, the 5-HT(4) agonists renzapride and tegaserod increased the amplitudes of nicotinic evoked excitatory postsynaptic currents. Enteric neuronal 5-HT(4) receptors thus are presynaptic and probably exert their prokinetic effects by strengthening excitatory neurotransmission.


The post-chemotherapy changes of tumor physical microenvironment: Targeting extracellular matrix to address chemoresistance.
The tumor physical microenvironment (TPME) contributes to cancer chemoresistance in both mechanical and mechanobiological approaches. Along with chemotherapy, the tumor microenvironment undergoes dramatic changes, most of which can regulate TPME through extracellular matrix (ECM) remodeling and related signaling pathways. However, there is still no discussion about the post-chemotherapy TPME changes mediated by ECM remodeling, and consequent impact on chemoresistance. Herein, we summarize the TPME alterations induced by chemotherapy and corresponding influence on chemotherapy response of cancer cells in context of ECM. The response of cancer cell to chemotherapy, imposed by post-chemotherapy ECM, are discussed in both mechanical (ECM physical features) and mechanobiological (ECM-responsive signaling pathways) manner. In the end, we present ECM remodeling and related signaling pathways as two promising clinic strategies to relieve or overcome chemoresistance induced by TPME change, and summarize the corresponding therapeutic agents currently being tested in clinical trials.


[Unilateral versus bilateral neck exploration in the surgery of primary hyperparathyroidism].
The aim of this study is to know the indications, advantages and disadvantages of a unilateral neck exploration versus bilateral in the primary hyperparathyroidism (HPT) surgery. Since april 1990 to april 2002 we have operated 80 patients diagnosed of HPT. They where divided in different groups in function of the results of the clinic exploration intact paratohormone results (PTHi turbo). In 48 patients (60%) we have done an unilateral cervical surgical exploration (in 9 cases we have determined the PTHi turbo) with good postoperative results. In 32 patients we have realised a bilateral exploration with exposition of both recurrent nerves, based on the discordance between the image exploration and because we were not able to have the intro-operative dose of turbo of PTHi, which use parameter we defend because of its contrasted efficiency, with less surgical time and less iatrogenic possibilities.


Electrophysiological Evaluation of the Protective Effect of Dimethylthiourea against Retinal Photic Injury.
Purpose: The Protective Effect of Dimethylthiourea (DMTU) against photic injury of the retina was evaluated by electroretinogram (ERG).Methods: In the DMTU-treated group, 250, 500, or 750 mg/kg DMTU was administered intraperitoneally to albino rabbits at 24 hours and immediately before starting light exposure to the eye. In the control group, physiological saline was injected intraperitoneally instead of DMTU. Preservation rates of ERG a-, b- and c-wave amplitudes were defined as the percentages of the post-photic injury values to the pre-photic injury ones, and were compared between the control and the DMTU-treated groups.Results: In 750 mg/kg DMTU-treated group, the preservation rate of the a-wave was significantly higher than that in the control group 24 hours after the photic injury. While the preservation rate of the c-wave was remarkably low in the control group 24 hours after the photic injury, it was significantly higher in the 500 and 750 mg/kg DMTU-treated groups. Furthermore, better preservation rates of the c-wave were noted with higher doses of DMTU.Conclusion: These results suggest that DMTU protects against photic injury of the retinal pigment epithelium and photoreceptors.


Prospective, Randomized Study of Fibrinogen Concentrate Versus Cryoprecipitate for Correcting Hypofibrinogenemia in Cardiac Surgery Patients.
Cardiac surgery with cardiopulmonary bypass (CPB) is associated with hypofibrinogenemia and severe bleeding requiring transfusion. Guidelines recommend cryoprecipitate or fibrinogen concentrate (FC) for the treatment of acquired hypofibrinogenemia. This study compared cryoprecipitate and FC for the correction of acquired hypofibrinogenemia and the associated costs. A single-center, prospective, randomized study evaluating patients with hypofibrinogenemia after cardiac surgery. The primary endpoint was direct treatment cost. Secondary endpoints included the change in fibrinogen level after FC and/or cryoprecipitate dosing. A single-center study in Astana, Kazakhstan. Participants who underwent CPB from 2021 to 2022 and developed clinically significant bleeding and hypofibrinogenemia. Patients were randomized to receive cryoprecipitate or FC. Eighty-eight adult patients with acquired hypofibrinogenemia (<2.0 g/L) after CPB were randomized to receive cryoprecipitate (N = 40) or FC (N = 48), with similar demographics between groups. Overall, mean ± SD 9.33 ± 0.94 units (range, 8-10) cryoprecipitate or 1.40 ± 0.49 g (1-2) FC was administered to the 2 groups. From before administration to 24 hours after, mean plasma fibrinogen increased by a mean ± SD of 125 ± 65 and 96 ± 65 mg/dL in the cryoprecipitate and FC groups, respectively. At 48 hours after administration, there was no significant difference in fibrinogen levels between groups. The mean direct cost of treatment with FC was significantly lower than with cryoprecipitate (p < 0.0001): $1,505.06 ± $152.40 and $631.75 ± $223.67 per patient for cryoprecipitate and FC, respectively. Analysis of plasma fibrinogen concentration showed that cryoprecipitate and FC had comparable effectiveness. However, FC is advantageous over cryoprecipitate due to its ease of handling, lower cost, and high purity.


Dementias Platform UK Clinical Studies and Great Minds Register: protocol of a targeted brain health studies recontact database.
The case for de-risking neurodegenerative research and development through highly informative experimental medicine studies early in the disease process is strong. Such studies depend on the availability of genetic as well as high-granularity, longitudinal, phenotypic data in healthy ageing individuals who can be recruited into early phase trials on the basis of their perceived dementia risk. Until now the creation of such research infrastructure has been hampered by the lack of expense and time required to gather the rich longitudinal data needed for adequate risk stratification. Dementias Platform UK (DPUK) is a public-private partnership that brings together data from over 40 cohorts in a standardised framework, which represent an until now unavailable opportunity to create such a resource through a streamlined brain health recontact platform based on existing cohorts, as well as prospectively collected data. The DPUK recontact platform consists of an opt-in (Great Minds, GM) and an opt-out component (Clinical Studies Register, CSR). GM requires invited DPUK cohort participants to consent to targeted recontact at the GM website and then to provide self-reported demographic and medical history information relevant to recruitment into clinical studies. Participants complete prospective browser-based and smartphone-based cognitive tests and are given the option for remote genetic and actigraphy testing. The GM data are linked to the retrospective DPUK cohort dataset, including genotypic and longitudinal phenotypic data. The CSR is a solution for cohorts explicitly allowing targeted recontact. Approved studies provide prescreening criteria on the basis of the CSR/GM dataset, and individuals meeting these criteria are offered participation directly (GM) or through the parent DPUK cohort (CSR). Descriptive statistics will be used to summarise the outcomes relevant to the number of participants engaged with the register. Its sample size is not defined but is limited by the size of the DPUK parent cohorts. The database was approved by the South Central-Oxford C Research Ethics Committee, reference 18/SC/0268 on the 27th of June 2018 and amended on the 1st of November 2019. The availability of the register to researchers will be disseminated through DPUK's official communication channels as well as national and international scientific meetings.


Long-term survival in venous thromboembolic disease: rivaroxaban vs. warfarin - propensity score matching study.
Venous thromboembolic disease (VTE) is characterized by obstruction of venous blood flow by a thrombus. Survival data, frequency of disease recurrence, and bleeding rate in patients on anticoagulant therapy with warfarin compared to rivaroxaban in the Latin American population are limited in VTE. A retrospective cohort study with propensity score matching analysis was conducted in patients with pulmonary embolism and/or deep vein thrombosis anticoagulated with warfarin or rivaroxaban treated. Survival analysis was performed using a Kaplan-Meier curve for each of the intervention groups, and it was compared using a Log Rank test. Of 2193 potentially eligible patients with a suspected diagnosis of VTE, 505 patients entered the analysis; of these, 285 subjects were managed with warfarin and 220 anticoagulated with rivaroxaban. Major bleeding at 12 months occurred in 2.7% (6/220) of patients treated with Rivaroxaban, compared to 10.2% (29/285) in the Warfarin group in the unmatched population (p = 0.001). In the matched population, bleeding at 12 months occurred in 2.9% (6/209) of patients on Rivaroxaban and in 11.0% (23/209) of patients on Warfarin (p = 0.001). The survival rates at 6 months were 97.1% for Rivaroxaban and 97.6% for Warfarin (p = 0.76). At 12 months, the survival rates were 94.7% for Rivaroxaban and 95.7% for Warfarin (p = 0.61). In the treatment of VTE, there is no differences on 6 and 12-month survival or a reduction in the occurrence of new thromboembolic events when comparing rivaroxaban to warfarin. However, a lower risk of major bleeding is observed at 12 months with Rivaroxaban.


Selenium and glutathione peroxidase levels in patients with epidermoid carcinoma of the oral cavity and oropharynx.
Selenium ingestion may inhibit carcinogenesis. Epidemiologic studies have shown that age-adjusted death rates for cancer at most head and neck sites are lower in states where the soil and forage crops contain higher levels of selenium. The mode of action is incompletely understood, but may be mediated through an increase in the activity of the selenium dependent, antioxidant enzyme glutathione peroxidase (GSH-Px). The authors studied blood selenium levels and blood and tissue GSH-Px activities in 50 patients with untreated cancer of the oral cavity and oropharynx. Mean erythrocyte selenium and glutathione peroxidase were significantly depressed when compared to age-matched controls. Mean plasma selenium, on the other hand, was significantly elevated in the cancer patient group. Data from subsets within the cancer patient group were also discussed. GSH-Px activity did not differ in tumor and adjacent normal tissue. The concept of chemoprevention of carcinogenesis with inhibitory chemical compounds is particularly apropos to head and neck cancer control. Further work is indicated to determine if ingestion of supplemental selenium corrects the abnormalities identified here, and what affect, if any, this would have on the development and behavior of squamous cell cancers in the upper aerodigestive tract.


Basic concepts of heart-lung interactions during mechanical ventilation.
Critically ill patients with the need for mechanical ventilation show complex interactions between respiratory and cardiovascular physiology. These interactions are important as they may guide the clinician's therapeutic decisions and, possibly, affect patient outcome. The aim of the present review is to provide the practicing physician with an overview of the concepts of heart-lung interactions during mechanical ventilation. We outline the basic cardiac and respiratory physiology during spontaneous breathing and under mechanical ventilation. The main focus is on the interaction between positive pressure ventilation and its effects on right and left ventricular pre- and afterload and ventricular interdependence. Further we discuss different modalities to assess volume responsiveness, such as pulse pressure variation. We aim to familiarise the reader with cardiovascular side effects of mechanical ventilation when experiencing weaning problems or right heart failure.


Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection.
Focal cerebral ischemia and traumatic brain injury induce an escalating amount of cell death because of harmful mediators diffusing from the original lesion site. Evidence suggests that healthy cells surrounding these lesions attempt to protect themselves by producing endocannabinoids (eCBs) and activating cannabinoid receptors, the molecular target for marijuana-derived compounds. Indeed, activation of cannabinoid receptors reduces the production and diffusion of harmful mediators. Here, we provide evidence that an exception to this pattern is found in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. We show that cell damage induced by EAE does not lead to increase in eCBs, even though cannabinoid receptors are functional because synthetic cannabinoid agonists are known to confine EAE-induced lesions. This lack of eCB increase is likely due to IFN-gamma, which is released by primed T cells invading the CNS. We show that IFN-gamma disrupts the functionality of purinergic P2X7 receptors, a key step controlling eCB production by microglia, the main source of eCBs in brain. Accordingly, induction of EAE in P2X7-/- mice results in even lower eCB levels and more pronounced cell damage than in wild-type mice. Our data suggest that the high level of CNS IFN-gamma associated with EAE disrupts eCB-mediated neuroprotection while maintaining functional cannabinoid receptors, thus providing additional support for the use of cannabinoid-based medicine to treat multiple sclerosis.


Radiopaque Element to Evaluate Adequacy of Debridement of Bony Lesions.
A technique for using an x-ray detectable radiopaque element from a surgical sponge to assess the adequacy of debridement of carpal bone cysts, Kienböck disease (lunate avascular necrosis), enchondroma of the digits, and scaphoid nonunions is described. The technique is simple to perform, inexpensive, and presents minimal additional risk to the patient. The technique has been used over the past 16 years and has enabled adequate debridement of these hand and wrist maladies by radiographically demonstrating the adequacy of the debridement to be bone grafted. It avoids the problems associated with liquid contrast dye and has proven to be very safe, effective, and inexpensive.


Gender differences in acute stroke: Istanbul medical school stroke registry.
We aimed to investigate gender differences in Turkish stroke patients. Demographics, risk factors, clinical and etiologic subtypes, laboratory findings, clinical course, and in-hospital prognosis of 1 522 patients with ischemic stroke (IS) and 320 patients with intracerebral hemorrhage prospectively registered in the Istanbul Medical School Stroke Registry (1994-2004) were analyzed separately. The mean age of IS patients was higher in females (n : 751) (P<0.0001). In males, smoking, ischemic heart disease, peripheral arterial disease, posterior circulation syndromes, and strokes due to large-artery atherosclerosis were more common (P<0.0001 for each). Prestroke disability, atrial fibrillation (P<0.0001), hypertension (P=0.041), modified Rankin Scale (mRS) 3-5 at admission (P<0.0001), total anterior circulation syndrome (P<0.0001), and cardioembolic stroke (P<0.0001) were more frequent in females. Female gender was an independent predictor of poor outcome (mRS 3-6). Gender differences were observed exclusively in patients with IS. Although our patients were younger than those reported, gender differences were similar.


The biology and evolution of cohesive gel and shaped implants.
The introduction of the silicone gel implant in 1962 began the modern era of breast augmentation, and over the past 50 years, breast implants have evolved to encompass a wide array of commercially available implants today. In April 1992, the moratorium on silicone gel breast implants began, and much of the experience and development of the cohesive shaped implants occurred outside the United States. During this time, saline implants were used almost exclusively in North America, whereas silicone implants continued to be used throughout the rest of the world. In 2001, cohesive gel implants became available in the United States under an Investigational Device Exemption Study. Three companies have US Food and Drug Administration approval of fifth-generation implants: Sientra, Allergan, and Mentor. These implants are unique due to the texture of the shell, implant dimensions, gel-shell interaction, gel fill ratio, degree of cross-linking, and form stability. Although form stability is a relative term, it may best be reserved to describe the increased ability of the implant to maintain its basic, intended shape. The cross-linking, form stability, and cohesiveness of these fifth-generation implants provide surgeons with an innovative tool to more closely create a natural breast in both shape and softness.


Outcomes of treatment targeting syntax production in people with Broca's-type aphasia: evidence from psycholinguistic assessment tasks and everyday conversation.
Capturing evidence of the effects of therapy within everyday communication is the holy grail of aphasia treatment design and evaluation. Whilst impaired sentence production is a predominant symptom of Broca's-type aphasia, the effects of sentence production therapy on everyday conversation have not been investigated. Given the context-sensitive nature of spoken production by people with aphasia, it is difficult to extrapolate implications for everyday conversation based on results from task-based assessment (such as picture description, story retell or interview). Thus, there are strong theoretical and clinical motivations to investigate generalization from sentence production treatment to everyday conversation. To evaluate a theoretically driven treatment focused on the language production skills of participants with post-stroke Broca's aphasia and to track outcomes from psycholinguistic assessment tasks to everyday conversation. A case series design was utilized with pragmatic selection of participants with chronic aphasia undergoing the same assessment and treatment procedures. Nine participants with Broca's aphasia and their main conversation partners took part in the study. Treatment was implemented once weekly over 8 weeks and targeted production of basic syntax-two, three and four constituent constructions-through principles of mapping and reduced syntax treatment. Use of different possible exemplars for nouns, particularly pronouns, was trained together with use of both light and heavy verbs. Participants had the opportunity to 'top-up' therapy practise by completely a homework task that mirrored the therapy task. Syntactic well-formedness was assessed in samples of constrained sentence production, narrative retell and naturally occurring conversations at baseline, 1 week post-treatment, and 1 month post-treatment. Treatment showed strong direct effects in trained and untrained sentence construction tasks, with some generalization to narrative retell tasks. There was little evidence of change in everyday conversation. Improvement in language production in constrained assessment tasks may not impact on everyday conversations. Implications for further research are discussed, e.g. the need for bridging interventions between constrained and unconstrained contexts of language production. Clinical implications include the potential to streamline therapy planning and delivery by making use of rich, hybrid therapies to treat individuals with similar symptom profiles but with a range of underlying deficits.


Draft Genome Sequence of Methylomicrobium buryatense Strain 5G, a Haloalkaline-Tolerant Methanotrophic Bacterium.
Robust growth of the gammaproteobacterium Methylomicrobium buryatense strain 5G on methane makes it an attractive system for CH4-based biocatalysis. Here we present a draft genome sequence of the strain that will provide a valuable framework for metabolic engineering of the core pathways for the production of valuable chemicals from methane.


Pulmonary hypertension due to a pulmonary artery leiomyosarcoma: A case report.
Primary pulmonary artery sarcomas are very rare and their histologic type called leiomyosarcoma is even rarer. These tumors are frequently misdiagnosed as pulmonary thromboembolism in clinical settings. Many patients receive anticoagulant therapy without response, and many are diagnosed postmortem only. Most of the tumors reported in the literature have involved the right ventricular outflow tract and the main pulmonary trunk, often extending into the main pulmonary artery (MPA) branches. A 64-year-old woman presented with weakness, fatigue, malaise, dyspnea, and marked elevation of pulmonary artery pressure was admitted to our hospital. She was initially diagnosed with chronic pulmonary thromboembolism, and chest computed tomography (CT) scan revealed lobulated heterogeneous left hilar mass extended to precarinal and subcarinal space. Magnetic resonance imaging (MRI) demonstrated a polypoid lesion at the trunk with extension to left MPA and its first branch. The patient was operated, and a yellowish-shiny solid mass in pulmonary trunk was seen intra-operation and pulmonary endarterectomy was performed. Her tumor was pathologically diagnosed as pulmonary artery leiomyosarcoma. Clinicians must consider pulmonary artery sarcoma when making the differential diagnosis for patients with pulmonary artery masses. The clinical prediction scores and the CT and MRI findings can help identifying patients with pulmonary artery sarcoma.


Hepatic growth hormone signaling in the late gestation fetal rat.
The role of GH in the developing fetus is poorly understood. Several studies have demonstrated a limited role for GH in late fetal life. In fact, few data are available regarding GH signal transduction in the late gestation fetus. We therefore focused on a comparison of hepatic GH signaling in near-term fetal rats [embryonic day 19 (E19)] and adult rats using a combination of in vitro studies employing hepatocytes in primary culture and in vivo studies. We found that GH receptor (GHr) binding was comparable in fetal liver and adult liver. The long isoform of the GHr underwent tyrosine phosphorylation in response to GH stimulation of E19 fetal hepatocytes in a manner similar to that seen in cultured adult hepatocytes. Furthermore, downstream signaling via the Janus kinase-2 tyrosine kinase, STAT1 (signal transducer and activator of transcription), and STAT5 was also intact in both, as demonstrated by the tyrosine phosphorylation of these signaling proteins. To confirm the relevance of these findings to the in vivo situation, GH was directly administered by ip injection to E 19 fetal and adult rats. In both cases, tyrosine phosphorylation of STAT5 was markedly and rapidly induced. Finally, transfection of E19 fetal hepatocytes with GH-responsive reporter elements [Spi2.1(-275/+85)-CAT and 8xGHRE-TKCAT] demonstrated intact transcriptional regulation. Our data indicate that GHr abundance and activity as well as downstream GH signaling are similar in the late gestation fetal rat and in the adult and that these mechanisms appear capable of supporting physiological GH functions in the developing liver.


HIV incidence among injecting drug users in New York City syringe-exchange programmes.
There have been no studies showing that participation in programmes which provide legal access to drug-injection equipment leads to individual-level protection against incident HIV infection. We have compared HIV incidence among injecting drug users participating in syringe-exchange programmes in New York City with that among non-participants. We used meta-analytic techniques to combine HIV incidence data from injecting drug users in three studies: the Syringe Exchange Evaluation (n = 280), in which multiple interviews and saliva samples were collected from participants at exchange sites; the Vaccine Preparedness initiative cohort (n = 133 continuing exchanges and 188 non-exchangers, in which participants were interviewed and tested for HIV every 3 months; and very-high-seroprevalence cities in the National AIDS Demonstration Research (NADR) programme (n = 1029), in which street-recruited individuals were interviewed and tested for HIV every 6 months. In practice, participants in the NADR study had not used syringe exchanges. HIV incidence among continuing exchange-users in the Syringe Exchange Evaluation was 1.58 per 100 person-years at risk (95% CI 0.54, 4.65) and among continuing exchange-users in the Vaccine Preparedness Initiative it was 1.38 per 100 person-years at risk (0.23, 4.57). Incidence among non-users of the exchange in the Vaccine Preparedness Initiative was 5.26 per 100 person-years at risk (2.41, 11.49), and in the NADR cities, 6.23 per 100 person-years at risk (4.4, 8.6). In a pooled-data, multivariate proportional-hazards analysis, not using the exchanges was associated with a hazard ratio of 3.35 (95% CI 1.29, 8.65) for incident HIV infection compared with using the exchanges. We observed an individual-level protective effect against HIV infection associated with participation in a syringe-exchange programme. Sterile injection equipment should be legally provided to reduce the risk of HIV infection in persons who inject illicit drugs.


Celebrities and spiritual gurus: Comparing two biographical accounts of kidney transplantation and recovery.
As a kidney transplant recipient I have long been exposed to a shortage of renal narratives and to a dominant theme in those that exist: transplant as restitution or redemption. My lived experience has, however, shown me that post-transplant life is more complex. Even after transplantation, chronic kidney disease requires lifelong health care with varying degrees of impairment, resulting in ongoing liminality for those who experience it. Nonetheless, as a transplant recipient I find the restitution or redemptive narrative pervasive and difficult to escape. I examined two seemingly very dissimilar insider renal biographies, Janet Hermans's Perfect match: A kidney transplant reveals the ultimate second chance, and Steven Cojocaru's Glamour, interrupted: How I became the best-dressed patient in Hollywood, to explore how the narrators treat chronic kidney disease and transplantation. In addition to a close textual reading of the biographies, I used my own experience of meaning-making to problematize concepts around restitution or redemptive narratives. I found that the two biographies are, despite appearances and despite the attempts of one author to escape the redemptive form, very much the same type of narrative. The accounts end with the transplant, as is common, but the recipients' lives continue after this, as they learn to live with their transplants, and this is not addressed. Emphasising restitution or redemption might prevent an understanding of post-transplant liminality that has unique characteristics. The narrator evading this narrative form must come to terms with a changed identity and, sometimes, fight to evade the pervasive narratives others impose.


[Significance of cross-cultural experience for young psychiatrists--learning from "The Joint Workshop for Psychiatric Residents of Korea and Japan"].
Korea and Japan are geographically very close, and a variety of cultural exchanges have taken place in recorded history. However, Korea and Japan have been enriched by the influence of Western cultures along with modernization, and mutual exchanges between the two countries have thus decreased in numerous fields including mental health and psychiatry. Prof. Masahisa Nishizono and Prof. Byun-Kun Min, who are leaders in the field of psychiatry in both Japan and Korea, have established "The Joint Workshop for Psychiatric Residents of Korea and Japan", which has been held alternately in Fukuoka or Seoul every summer since 2000. This Joint Workshop provides young psychiatrists with real experiences and many opportunities to learn about transcultural psychiatry regarding both countries. The participants are able to obtain a better mutual understanding of psychiatric epidemiology, recent developments in biological psychiatry while also learning about different concepts regarding the stigma of mental disorders. All participants could also increase their knowledge about the traditional culture and social changes related to the field of psychiatry in both countries. The workshop has helped to build friendship and mutual cooperation between both nations. Contemporary societies are continually becoming more and more diversified and complicated. For young psychiatrists who have to treat patients with modern difficulties and various complicated problems, such cross-cultural experiences may be useful for establishing potentially new and effective treatments for such patients. Psychiatrists and mental health experts have tried to reduce of stigma and discrimination against people with mental disorders, but even today such stigma and discrimination continues to strongly exist. The author thinks that such cross-cultural experiences by the psychiatrists themselves may help to reduce such notions. The author would like to explore the role of cross-cultural experiences in the field of psychiatry.


Cystic lymphangioma of the pancreas.
Cystic lymphangioma of the pancreas is a rare condition. A 14-year-old girl presented with a cystic abdominal mass and abdominal pain. She was initially treated by biopsy and cyst drainage, and subsequently with partial excision of the cystic mass. The mass, which was a cystic lymphangioma involving the pancreas, recurred after each operation. Persisting symptoms led to a pylorus-preserving pancreatectomy and hepaticojejunostomy. Total excision is the only effective method of treating this benign tumour. The patient remains symptom free 2 1/2 years after pancreatectomy.