The effect of valsartan and nebivolol treatment on ADMA and pentraxin-3 levels in hypertensive patients.
Long pentraxin 3 (PTX3) is a recently discovered multimeric inflammatory mediator that is structurally linked to short pentraxins, such as C-reactive protein (CRP) and serum amyloid P component. PTX3 is produced by a variety of tissues and cells, including vascular endothelial cells and macrophages. Because of its extrahepatic synthesis (in contrast to CRP), the PTX3 level is believed to be a true independent indicator of disease activity because PTX3 is produced at sites of inflammation and is intimately linked to endothelial dysfunction. PTX3 also has key functions in innate immunity and has been identified in atherosclerotic lesions. Previously, PTX3 was associated with myocyte damage in myocardial infarction (MI), mortality after MI, and unstable angina. Because PTX3 release is likely a specific response to vascular damage, PTX3 levels may provide more explicit information on development and progression of atherosclerosis than nonspecific markers like CRP and interleukin-6. Asymmetric dimethylarginine (ADMA) is a naturally occurring component of human blood plasma. More than one decade ago ADMA was first reported to exert biological effects by inhibiting nitric oxide synthesis. Many researchers today agree that ADMA may play a prominent role in the pathogenesis and in the progression of cardiovascular diseases. In this study PTX3 and ADMA levels investigated of valsartan and nebivolol's effect on newly diagnosed hypertensive patients.


Combined Signature of the Fecal Microbiome and Metabolome in Patients with Gout.
This study employed microbiome and metabolome analysis to explore the fecal signatures of gout patients. Fecal samples from 52 male individuals (26 healthy controls and 26 gout patients) were analyzed by 1H NMR spectroscopy and Illumina Miseq sequencing. The signatures of microbiome showed being up-regulation of opportunistic pathogens, such as Bacteroides, Porphyromonadaceae Rhodococcus, Erysipelatoclostridium and Anaerolineaceae. The signatures of metabolome were some altered metabolites which may involve uric acid excretion, purine metabolism, and inflammatory responses. Meanwhile, the correlation between discrepant metabolites and microbial taxa indicated that they could be the combined signatures of gout. This study suggests that the combined analysis of the fecal microbiome and metabolome may effectively characterize diseases.


Optimization of surgical intervention outside the epileptogenic zone in the Virtual Epileptic Patient (VEP).
Studies to improve the efficacy of epilepsy surgery have focused on better refining the localization of the epileptogenic zone (EZ) with the aim of effectively resecting it. However, in a considerable number of patients, EZs are distributed across multiple brain regions and may involve eloquent areas that cannot be removed due to the risk of neurological complications. There is a clear need for developing alternative approaches to induce seizure relief, but minimal impact on normal brain functions. Here, we develop a personalized in-silico network approach, that suggests effective and safe surgical interventions for each patient. Based on the clinically identified EZ, we employ modularity analysis to identify target brain regions and fiber tracts involved in seizure propagation. We then construct and simulate a patient-specific brain network model comprising phenomenological neural mass models at the nodes, and patient-specific structural brain connectivity using the neuroinformatics platform The Virtual Brain (TVB), in order to evaluate effectiveness and safety of the target zones (TZs). In particular, we assess safety via electrical stimulation for pre- and post-surgical condition to quantify the impact on the signal transmission properties of the network. We demonstrate the existence of a large repertoire of efficient surgical interventions resulting in reduction of degree of seizure spread, but only a small subset of them proves safe. The identification of novel surgical interventions through modularity analysis and brain network simulations may provide exciting solutions to the treatment of inoperable epilepsies.


Persistent Notochord in a Fetus with COL2A1 Mutation.
Multiple anomalies including micromelia, poor mineralization of the vertebrae, and a persistent notochord were identified on second trimester ultrasound in a fetus with a COL2A1 mutation. To our knowledge, this represents the first case of a persistent notochord associated with a COL2A1 mutation in humans. In this case report, we describe ultrasound and postmortem findings and review the pathogenesis associated with a persistent notochord.


Alcohol use initiation is associated with changes in personality trait trajectories from early adolescence to young adulthood.
Recent work has demonstrated the codevelopment of personality traits and alcohol use characteristics from early adolescence to young adulthood. Few studies, however, have tested whether alcohol use initiation impacts trajectories of personality over this time period. We examined the effect of alcohol use initiation on personality development from early adolescence to young adulthood. Participants were male (nmen = 2,350) and female (nwomen = 2,618) twins and adoptees from 3 community-based longitudinal studies conducted at the Minnesota Center for Twin and Family Research. Data on personality traits of Positive Emotionality (PEM; Well-being), Negative Emotionality (NEM; Stress Reaction, Alienation, and Aggression), and Constraint (CON; Control and Harm Avoidance)-assessed via the Multidimensional Personality Questionnaire (MPQ)-and age of first drink were collected for up to 4 waves spanning ages 10 to 32. Alcohol use initiation was associated with significant decreases in levels of Well-being and CON traits, most notably Control; and significant increases in levels of all NEM traits, particularly Aggression. In general, the effects of alcohol use initiation on personality traits were moderated by gender and enhanced among those with earlier age of first drink. From early adolescence to young adulthood, alcohol use initiation predicts deviations from normative patterns of personality maturation. Such findings offer a potential mechanism underlying the codevelopment of personality traits and alcohol use characteristics during this formative period of development.


Assessment of Ions released from Three Types of Orthodontic Brackets immersed in Different Mouthwashes: An in vitro Study.
Herbs are used widely in medicine. The purpose of the present study was to assess the ion release from gold-plated orthodontic bracket compared with other stainless steel brackets, and based on the findings of the study, the orthodontists can choose the most biocompatible brackets and mouthwashes useful in the clinical practice. A total of 150 orthodontic brackets from Orthotechnology™ Company, USA (50 stainless steel one-piece brackets, 50 stainless steel two-piece brackets, and 50 gold brackets) were immersed in four mouthwashes in addition to distilled water. Ten of each type of brackets in every media were immersed under 37°C for 45 days. Ions released in these mouthwashes were measured, and comparisons among different bracket types and among various mouthwashes were done by one-way analysis of variance (ANOVA) and then with Games-Howell tests. Increased amounts of ions released in herbal mouth-washes were recorded in gold and two-piece brackets in comparison with one-piece stainless steel brackets. Herbal mouthwashes must be used with caution as they showed an increased amount of ions released in comparison with chlorhexidine. One-piece stainless steel bracket system is the most compatible bracket type, as they released the least amount of ions. One-piece stainless steel brackets are better than two-piece brackets in terms of ions released.


Medication adherence among cardiac patients in Khartoum State, Sudan: a cross-sectional study.
Non-adherence to medication among cardiac patients is often the major risk factor for poor clinical outcomes, increased mortality rates and higher healthcare costs. The literature evaluating the prevalence of and reasons for non-adherence in resource-poor settings is extremely limited compared to resource-rich settings. There is a scarcity of data about medication adherence in Sudan hence this study was performed to identify prevalence, predictors and barriers of non-adherence to medication among cardiac patients in Khartoum State. A descriptive, cross-sectional survey was performed using a pre-tested, self-administered questionnaire on a sample of 433 randomly selected cardiac patients attending the largest three cardiac centres located in Khartoum State. Descriptive and multivariate logistic regression analyses were used for data analysis. The response rate was 89.1%. The mean (± SD) number of chronic diseases among respondents was 2.3 ( ± 1.3) and that of medication use was 4.2 ( ± 1.9). The mean ( ± SD) duration of medication use among participants was 6.4 ( ± 5.4) years. Optimal adherence was defined as having a score of greater than six on the eight-item Morisky medication adherence scale. Using this cut-off point, 49% (95% CI: 43.9-54.1) of respondents had optimal adherence and 51% (95% CI: 45.9-56.1) had poor adherence. Respondents with a high level of education, low and middle income levels, and those taking five or more medications daily were found to be significantly more non-adherent to medication use than those with low to intermediate education levels (p < 0.001), those with high income levels (p < 0.001), and those taking one to four medications daily (p = 0.039). The top four barriers for poor medication adherence among the study participants were the high cost of drugs, polypharmacy and lack of pharmacist and physician communication with patients about their drug therapy. The current findings highlight the need for urgent, multifaceted interventions, given the burden of cardiovascular diseases and the clinical and economic consequences of medication non-adherence. These interventions include affordable medications, easy-to-use medication regimens with fewer daily doses, ongoing communication between patients and healthcare providers, and improvement of the patient-provider partnership.


HSV, axonal transport and Alzheimer's disease: in vitro and in vivo evidence for causal relationships.
HSV, a neurotropic virus, travels within neuronal processes by fast axonal transport. During neuronal infection HSV travels retrograde from the sensory nerve terminus to the neuronal cell body, where it replicates or enters latency. During replication HSV travels anterograde from the cell body to the nerve terminus. Postmortem studies find a high frequency of HSV DNA in the trigeminal ganglia as well as the brain. Studies correlating HSV with Alzheimer's disease (AD) have been controversial. Here we review clinical evidence supporting such a link. Furthermore, the author describes experimental data showing physical interactions between nascent HSV particles and host transport machinery implicated in AD. The author concludes that the complexity of this relationship has been insufficiently explored, although the relative ease and nontoxicity of a potential anti-HSV treatment for AD demands further study.


[Use of interproximal enamel reduction in adult malocclusion patients with periodontitis].
To discuss the advantage of interproximal enamel reduction when it was applied to provide space needed in orthodontic treatment of malocclusion patients with periodontitis. Thirty four patients were chosen from those seeking for orthodontic treatment at Stomatology Department of the Third Hospital of Peking University from 2004 to 2009, which includes 9 males and 25 females, the average age was 25.4 years. All of them were diagnosed with periodontitis to some extend. The needed space for orthodontic treatment was achieved for each patient through the procedure of plaster model analysis and cephalometric tracing, then the treatment plan was given on the premise that interproximal enamel reduction was the first choice for creating spaces, the sites and amount of enamel reduction, any still-needed further extraction and the corresponding anchorage were determined. The fixed orthodontic treatment began after systematic periodontal treatment. Needle-shaped fine diamond drill was used for cutting 0.25-0.5mm interproximal enamel after arch alignment, NaF glycerol was used after polishing to decrease caries risk. The result was retained after orthodontic treatment. After 6-24 months' orthodontic treatment, the teeth were aligned, the interdental embrasures were shrunk or disappeared, normal overbite, overjet and posterior occlusion were achieved, and periodontal conditions were stable. No new caries were found in the areas of enamel reduction at the 0.5-2 years follow-up examination. There is clear superiority to apply interproximal enamel reduction to create space for orthodontic treatment in those patients with periodontitis. By this method, the difficulty and periodontal risk of orthodontic treatment will decrease, the treatment duration will be shorten, the gingival aesthetics will be improved, and the live-span of dentition will be elongated.


Evaluation of a vero cell toxicity test to detect EHEC infection.
An epidemiologic investigation was carried out in Modena (Italy) to evaluate the prevalence of faecal VEROtoxin (FVT) in diarrhoeal stool specimens. One thousand and sixty-six stool specimens, submitted to the Clinical Microbiology Laboratory of the University Hospital of Modena, were collected and faecal filtrates tested for neutralizable cytotoxin by a toxicity test on VERO cells. Cytopathic effect on VERO cells was produced by 301 stool specimens (28%); neutralizable VT was detected in 40 (13%) out of 301 positive samples (3.7% of 1066 specimens). The prevalent FVT type was VT2 (50%), followed by VT1 (32.5%) and VT1+2 (17.5%). We evaluated an assay that detects both VTs directly from stool specimens to demonstrate that enterohemorrhagic strains (EHEC) should be considerated a causative agent of sporadic non-bloody diarrhoea. Our results suggest that toxin neutralization assay is a sensitive and specific technique and may be used as an alternative method to diagnose diarrhoeal infections caused by EHEC.


Repeated consensus sequence and pseudopromoters in the four coordinately regulated tubulin genes of Chlamydomonas reinhardi.
The 5' coding and promoter regions of the four coordinately regulated tubulin genes of Chlamydomonas reinhardi have been mapped and sequenced. DNA sequencing data shows that the predicted N-terminal amino acid sequences of Chlamydomonas alpha- and beta-tubulins closely match that of tubulins of other eucaryotes. Within the alpha 1- and alpha 2-tubulin gene set and the beta 1- and beta 2-tubulin gene set, both nucleotide sequence and intron placement are highly conserved. Transcription initiation sites have been located by primer extension analysis at 140, 141, 159, and 132 base pairs upstream of the translation initiator codon for the alpha 1-, alpha 2-, beta 1-, and beta 2-tubulin genes, respectively. Among the structures with potential regulatory significance, the most striking is a 16-base-pair consensus sequence [GCTC(G/C)AAGGC(G/T)(G/C)--(C/A)(C/A)G] which is found in multiple copies immediately upstream of the TATA box in each of the four genes. An unexpected discovery is the presence of pseudopromoter regions in two of the transcribed tubulin genes. One pseudopromoter region is located 400 base pairs upstream of the authentic alpha 2-tubulin gene promoter, whereas the other is located within the transcribed 5' noncoding region of the beta 1-tubulin gene.


Contractile function, sarcolemma integrity, and the loss of dystrophin after skeletal muscle eccentric contraction-induced injury.
The purpose of this study was to evaluate the integrity of the muscle membrane and its associated cytoskeleton after a contraction-induced injury. A single eccentric contraction was performed in vivo on the tibialis anterior (TA) of male Sprague-Dawley rats at 900 degrees /s throughout a 90 degrees -arc of motion. Maximal tetanic tension (Po) of the TAs was assessed immediately and at 3, 7, and 21 days after the injury. To evaluate sarcolemmal integrity, we used an Evans blue dye (EBD) assay, and to assess structural changes, we used immunofluorescent labeling with antibodies against contractile (myosin, actin), cytoskeletal (alpha-actinin, desmin, dystrophin, beta-spectrin), integral membrane (alpha- and beta-dystroglycan, sarcoglycan), and extracellular (laminin, fibronectin) proteins. Immediately after injury, P0 was significantly reduced to 4.23 +/- 0.22 N, compared with 8.24 +/- 1.34 N in noninjured controls, and EBD was detected intracellularly in 54 +/- 22% of fibers from the injured TA, compared with 0% in noninjured controls. We found a significant association between EBD-positive fibers and the loss of complete dystrophin labeling. The loss of dystrophin was notable because organization of other components of the subsarcolemmal cytoskeleton was affected minimally (beta-spectrin) or not at all (alpha- and beta-dystroglycan). Labeling with specific antibodies indicated that dystrophin's COOH terminus was selectively more affected than its rod domain. Twenty-one days after injury, contractile properties were normal, fibers did not contain EBD, and dystrophin organization and protein level returned to normal. These data indicate the selective vulnerability of dystrophin after a single eccentric contraction-induced injury and suggest a critical role of dystrophin in force transduction.


Granulocyte-macrophage colony-stimulating factor receptor-targeted therapy of chemotherapy- and radiation-resistant human myeloid leukemias.
Contemporary therapies for acute myeloid leukemia (AML) commonly fail to cure patients because of the emergence of drug resistance. Drug resistance in AML is multifactorial but can be associated with the overexpression of transmembrane transporter molecules, including P-glycoprotein (Pgp) or the multidrug resistance-associated protein (MRP), or associated with inactivation of the p53 tumor suppressor gene, as well as overexpression of the anti-apoptotic protein bcl-2. We are investigating if novel recombinant biotherapeutics can circumvent these resistance mechanisms to effectively treat refractory AML. To target the lethal action of diphtheria toxin (DT) to high affinity granulocyte-macrophage colony-stimulating factor (GMCSF) receptors on AML blasts, we have produced a recombinant chimeric fusion toxin, DTctGMCSF. Since DTctGMCSF enters and kills its target cells by unique mechanisms (GMCSF-receptor binding and protein synthesis inhibition) and is not similar in structure to Pgp or MRP substrates, we postulated that it would be an active agent against therapy-resistant AML. DTctGMCSF was selectively cytotoxic (IC50 1-10ng/ml) to GMCSF-receptor positive AML cells expressing the Pgp- or MRP-associated multi-drug resistant phenotypes, despite high level resistance to conventional chemotherapeutic agents. DTctGMCSF also efficiently killed AML cells deficient in p53 expression, as well as radiation-resistant AML cells and mixed lineage leukemia cells expressing high levels of bcl-2. In addition, DTctGMCSF killed > 99% of primary leukemic progenitor cells from therapy-refractory AML patients under conditions that we have previously found to not adversely affect the proliferative capacity or differentiation of pluripotent normal hematopoietic progenitor cells. DTctGMCSF may prove useful in treating myeloid leukemias that are otherwise resistant to a wide range of conventional therapies.


Cytokinin oxidase activity and cytokinin content in roots of sunflower under water stress.
Contents of trans-zeatin riboside (ZR), dihydrozeatin riboside (DZR) and N6-(delta2-isopentenyl) adenosine (iPA) was quantified by an indirect ELISA using polyclonal antibodies, in the roots, xylem sap and leaves of pot grown sunflower plants subjected to water stress (RWC of leaves approximately 65 per cent). The delivery rates of all three cytokinins decreased significantly under stress. Cytokinin levels also decreased in roots and in leaves of stressed plants. Three-fold increase in cytokinin oxidase activity was observed in stressed roots after polymin P-ammonium sulphate fractionation. Further purification using Con A agarose resulted in elution of protein with cytokinin oxidase activity and was found to be 30 kDa protein on SDS-PAGE.


Infrared microspectroscopic imaging of biomineralized tissues using a mercury-cadmium-telluride focal-plane array detector.
A 64 x 64 mercury-cadmium-telluride focal-plane array detector attached to a Fourier transform infrared microscope was used to spectroscopically image 5 microm sections of canine alveolar bone tissue in the fingerprint region of the infrared spectrum. By ratioing the relative intensities of specific bands across the images, it is possible to obtain spatial distributions of the mineral-to-matrix ratio and mineral maturity as a function of distance from an osteon.


Leukotriene B4 receptor 1 expression on dendritic cells is required for the development of Th2 responses and allergen-induced airway hyperresponsiveness.
Dendritic cells (DC) are important APCs that control allergen-induced airway responses by interacting directly with T cells. Leukotriene B(4) (LTB(4)), interacting with its high-affinity receptor, LTB(4) receptor 1 (BLT1), is known to attract and activate leukocytes during inflammation. We have previously shown that BLT1 expression on Ag-primed T cells is required for the development of airway hyperresponsiveness (AHR; Miyahara et al. 2005. Am. J. Respir. Crit. Care Med. 172: 161-167). However, the role for the LTB(4)-BLT1 pathway in DC function in allergen-induced airway responses has not been defined. Bone marrow-derived DCs (BMDC) were generated. Naive BALB/c mice received OVA-pulsed BLT1-deficient (BLT1(-/-)) BMDCs or wild-type BMDCs intratracheally and were then challenged with OVA for 3 days. Airway responses were monitored 48 h after the last allergen challenge. BLT1(-/-) BMDCs showed normal maturation judged from surface expression of CD markers. Compared with recipients of wild-type BMDCs, mice that received BLT1(-/-) BMDCs developed significantly lower AHR to inhaled methacholine, lower goblet cell metaplasia, and eosinophilic infiltration in the airways and decreased levels of Th2 type cytokines in the bronchoalveolar lavage fluid. Migration of BLT1(-/-) BMDCs into peribronchial lymph nodes was significantly impaired compared with BLT1(+/+) BMDCs after intratracheal instillation. These data suggest that BLT1 expression on DCs is required for migration of DCs to regional lymph nodes as well as in the development of AHR and airway inflammation.


Burden of Early Life Obesity and Its Relationship with Protein Intake in Infancy: The Middle East Expert Consensus.
Adequate nutrition in early life is proposed to shape a child's future health by launching the growth trajectory in the proper direction, which helps to avoid negative metabolic programming effects. Protein intake during infancy and early childhood is of great importance, as it plays a key role in infant metabolic programming and the future risk of obesity. Breastfeeding provides the best nutrition in early life, with many benefits tailored for the baby, including the appropriate quantity and quality of proteins. Considering the high prevalence of childhood, and subsequent adult, obesity in the region, a virtual Middle East expert consensus meeting was held to discuss an effective approach for managing childhood obesity. Leading pediatric experts from Bahrain, Egypt, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates participated in the meeting. The experts discussed, debated, and agreed on certain directions, including the importance of educating parents, endorsing breastfeeding, and ensuring optimum quantity and quality intake of proteins in early life. This expert consensus may serve as the starting point for healthcare professionals in the region who are interested in shaping a healthy future for the generations to come.


The role of pentacyclic triterpenoids in the allelopathic effects of Alstonia scholaris.
Alstonia scholaris is a tropical evergreen tree native to South and Southeast Asia. Alstonia forests frequently lack understory species. However, potential mechanisms-particularly the allelochemicals involved-remain unclear. In the present study, we identified allelochemicals of A. scholaris, and clarified the role of allelopathic substances from A. scholaris in interactions with neighboring plants. We showed that the leaves, litter, and soil from A. scholaris inhibited growth of Bidens pilosa-a weed found growing abundantly near A. scholaris forests. The allelochemicals were identified as pentacyclic triterpenoids, including betulinic acid, oleanolic acid, and ursolic acid by using (1)H and (13)C-NMR spectroscopy. The half-maximal inhibitory concentration (IC50) for radicle growth of B. pilosa and Lactuca sativa ranged from 78.8 μM to 735.2 μM, and ursolic acid inhibited seed germination of B. pilosa. The triterpenoid concentrations in the leaves, litter, and soil were quantified with liquid chromatography-electrospray ionization/tandem mass spectrometry. Ursolic acid was present in forest soil at a concentration of 3,095 μg/g, i.e., exceeding the IC50. In the field, ursolic acid accumulated abundantly in the soil in A. scholaris forests, and suppressed weed growth during summer and winter. Our results indicate that A. scholaris pentacyclic triterpenoids influence the growth of neighboring weeds by inhibiting seed germination, radicle growth, and functioning of photosystem II.


[Sonographic diagnosis of channel pelvis].
This paper reports the findings in 22 primigravidae in whom Caesarian section was performed because of impaction of the head in mid-pelvis. 100 women who had normal deliveries served as controls. The routinely-determined external measurements of the pelvis were within the normal range in all women, whereas the distances between symphysis and the 3rd or 5th sacral vertebra were reduced in comparison with the conjugata externa in patients requiring Caesarian section. For an exact diagnosis ultrasound and X-ray pelvimetry was performed post sectionem. A reduced distance between the symphysis and the 3rd or 5th sacral vertebra was ascertained by both methods. Hence, a channel pelvis might be the main reason in these women for standstill in labour. The ultrasound and X-ray pelvimetry results were comparable.


The Neonatal Microbiome and Metagenomics: What Do We Know and What Is the Future?
The human microbiota includes the trillions of microorganisms living in the human body whereas the human microbiome includes the genes and gene products of this microbiota. Bacteria were historically largely considered to be pathogens that inevitably led to human disease. However, because of advances in both cultivation-based methods and the advent of metagenomics, bacteria are now recognized to be largely beneficial commensal organisms and thus, key to normal and healthy human development. This relatively new area of medical research has elucidated insights into diseases such as inflammatory bowel disease and obesity, as well as metabolic and atopic disorders. However, much remains unknown about the complexity of microbe-microbe and microbe-host interactions. Future efforts aimed at answering key questions pertaining to the early establishment of the microbiome, alongside what defines its dysbiosis, will likely lead to long-term health and mitigation of disease. Here, we review the relevant literature pertaining to modulations in the perinatal and neonatal microbiome, the impact of environmental and maternal factors in shaping the neonatal microbiome, and future questions and directions in the exciting emerging arena of metagenomic medicine.


[Philanthropic general hospitals: a new setting for psychiatric admissions].
To understand the process that led Brazilian philanthropic general hospitals to implement psychiatric units and to describe the main characteristics and therapeutic approaches of these services. Ten institutions in three Brazilian states (Minas Gerais, São Paulo e Santa Catarina) were assessed in 2002. Forty-three semi-structured interviews were carried out with health professionals who worked at the hospitals to collect data on service implementation process, therapeutic approaches and current situation. The interviews were audio-recorded and their content was analyzed. There was no mental hospital in the cities where the institutions were located. In five hospitals, psychiatric patients were admitted to general medical wards because there was no psychiatric unit. The therapeutic approach in six hospitals was based on psychopharmacological treatment. Due to lack of resources and more appropriate therapeutic planning, the admission of patients presenting psychomotor agitation increases resistance against psychiatric patients in general hospitals. Financial constraints regarding laboratory testing is still a challenge. There is no exchange between local authorities and hospital administrators of these institutions that are compelled to exceed the allowed number of admissions to meet the demand of neighboring cities. The need for mental health care to local populations combined with individual requests of local authorities and psychiatrists made possible the implementation of psychiatric units in these localities. In spite of the efforts and flexibility of health professional working in these institutions, there are some obstacles to be overcome: resistance of hospital community against psychiatric admissions, financial constraints, limited professional training in mental health and the lack of a therapeutic approach that goes beyond psychopharmacological treatment alone.


Spatial distribution of antibiotics and antibiotic resistance genes in tidal flat reclamation areas in China.
Tidal flat areas are important resources for land development and are becoming antibiotic resistance receivers that trigger major health concerns. The spatial distributions of forty-nine antibiotics, nine antibiotic resistance genes (ARGs), one mobile gene element (MGE) gene, and nine available metals in the soils and sediments along the coastlines of the Yellow Sea in China were quantified. Hierarchical linear model analysis was used to explore relationships between the antibiotics and ARGs across multiple effects resulting from human activities and environmental factors. Fish farm sediments and farmland soils showed high levels of quinolones (QNs) (maximum 637 ng·g-1), sulfonamides (SAs) (maximum 221 ng·g-1), and corresponding ARGs. Significant positive correlations (P from 5.47 × 10-14 to 0.0487) were observed between the antibiotics (QNs, SAs, and chlortetracycline) and their corresponding ARGs (qnrA, qnrD, aac(6')-Ib-cr, dfrA, sul2, and tetA), indicating the selective pressure from antibiotics in soils and sediments. Nine available metals had positive correlations with at least one ARG, indicating heavy metal pollution could enhance the ARGs. Sheep and poultry husbandry and marine aquaculture contribute the most to the antibiotic resistance in the coastlines. In conclusion, antibiotic pollutions have promoting effects at sub-inhibitory concentrations and more attention should be given to inhibit the enrichment of ARGs during tidal flat reclamation processes. The study also suggests the induction effects from metal pollutions, MGE spread, and the antibiotic pollutions from the usage in livestock and aquaculture.


Alpha 1-antichymotrypsin is present in and synthesized by the cornea.
The proteinase inhibitor alpha 1-antichymotrypsin is present in the epithelial, stromal and endothelial layers of the human cornea. This was determined by immunolocalization in corneal sections and by Western blot analysis of extracts from the three separated layers. The inhibitor was quantified in the extracts by immunodot blot analysis. The levels observed were 1.3 +/- 0.3 microgram/cornea for the epithelial layer, 22.8 +/- 3.8 micrograms/cornea for the stromal layer and an average of 0.17 micrograms/cornea for the endothelial layer. alpha 1-Antichymotrypsin is being synthesized by the cornea. Metabolically labeled inhibitor was immunoprecipitated from the three layers following organ culture of the intact cornea. Two major forms were detected. These were the native, mature 64 kDa form and a 50 kDa form which is either a degradation product or an incompletely glycosylated form. These results indicate that the cornea has the ability to locally control degradation through synthesis of this inhibitor. Local synthesis of this inhibitor releases the cornea from total dependance upon the vascular system for its supply of alpha 1-antichymotrypsin.


The decision to germinate is regulated by divergent molecular networks in spores and seeds.
Dispersal is a key step in land plant life cycles, usually via formation of spores or seeds. Regulation of spore- or seed-germination allows control over the timing of transition from one generation to the next, enabling plant dispersal. A combination of environmental and genetic factors determines when seed germination occurs. Endogenous hormones mediate this decision in response to the environment. Less is known about how spore germination is controlled in earlier-evolving nonseed plants. Here, we present an in-depth analysis of the environmental and hormonal regulation of spore germination in the model bryophyte Physcomitrella patens (Aphanoregma patens). Our data suggest that the environmental signals regulating germination are conserved, but also that downstream hormone integration pathways mediating these responses in seeds were acquired after the evolution of the bryophyte lineage. Moreover, the role of abscisic acid and diterpenes (gibberellins) in germination assumed much greater importance as land plant evolution progressed. We conclude that the endogenous hormone signalling networks mediating germination in response to the environment may have evolved independently in spores and seeds. This paves the way for future research about how the mechanisms of plant dispersal on land evolved.


Sparks and waves in a stochastic fire-diffuse-fire model of Ca2+ release.
Calcium ions are an important second messenger in living cells. Indeed, calcium signals in the form of waves have been the subject of much recent experimental interest. It is now well established that these waves are composed of elementary stochastic release events (calcium puffs or sparks) from spatially localized calcium stores. Here we develop a computationally inexpensive model of calcium release, based upon a stochastic generalization of the fire-diffuse-fire threshold model. Our model retains the discrete nature of calcium stores, but also incorporates a notion of release probability via the introduction of threshold noise. Numerical simulations of the model illustrate that stochastic calcium release leads to the spontaneous production of calcium sparks that may merge to form saltatory waves. In the parameter regime where deterministic waves exist, it is possible to identify a critical level of noise, defining a nonequilibrium phase transition between propagating and abortive structures. A statistical analysis shows that this transition is the same as for models in the directed percolation universality class. Moreover, in the regime where no initial structure can survive deterministically, threshold noise is shown to generate a form of array enhanced coherence resonance, whereby all calcium stores release periodically and simultaneously.


Taking population stratification into account by local permutations in rare-variant association studies on small samples.
Many methods for rare variant association studies require permutations to assess the significance of tests. Standard permutations assume that all individuals are exchangeable and do not take population stratification (PS), a known confounding factor in genetic studies, into account. We propose a novel strategy, LocPerm, in which individual phenotypes are permuted only with their closest ancestry-based neighbors. We performed a simulation study, focusing on small samples, to evaluate and compare LocPerm with standard permutations and classical adjustment on first principal components. Under the null hypothesis, LocPerm was the only method providing an acceptable type I error, regardless of sample size and level of stratification. The power of LocPerm was similar to that of standard permutation in the absence of PS, and remained stable in different PS scenarios. We conclude that LocPerm is a method of choice for taking PS and/or small sample size into account in rare variant association studies.


Postoperative pain management in frail older adults.
To evaluate the Frail Elder Pain Management Program (FEPMP) implemented for patients who had hip fracture repairs at a community hospital in 1995. Based on standards of geriatric and pain management practice, the FEPMP included education sessions, preprinted analgesic orders, pain flow sheets, written resources, and clinical support. A Logic Model reflected the program's conceptualization. Preexperimental pretest and posttest design. A random sample of 50 charts of patients aged 75 and older who had hip fracture repairs were audited from each of two periods: the preimplementation period (1994-95) and the postimplementation period (1997-98). A chart audit tool was developed, tested, and used. Data were analyzed using descriptive, parametric and nonparametric statistics. Surgeons' prescriptions and nurses' pain management practices improved significantly (p = .0001). Pain assessment modestly improved. Patient outcomes also improved. IMPLICATIONS FOR PRACTICE AND EDUCATION: A programmatic approach to pain management is effective for improving practice and outcomes for frail elders.


Cerebral processes related to visuomotor imagery and generation of simple finger movements studied with positron emission tomography.
Positron emission tomography was used to compare the functional anatomy of visual imagination and generation of movement. Subjects were asked to generate visual images of their finger movement in response to a preparatory signal. Four conditions were tested: in two, no actual movement was required; in the other two, a second signal prompted the subjects to execute the imagined movement. Which movement to imagine was either specified by the preparatory stimulus or freely selected by the subjects. Compared with a rest condition, tasks involving only imagination activated several cortical regions (inferoparietal cortex, presupplementary motor area, anterior cingulate cortex, premotor cortex, dorsolateral prefrontal cortex) contralateral to the imagined movement. Tasks involving both imagination and movement additionally increased activity in the ipsilateral cerebellum, thalamus, contralateral anteroparietal, and motor cortex and decreased activity in the inferior frontal cortex. These results support the hypothesis that distinct functional systems are involved in visuomotor imagination and generation of simple finger movements: associative parietofrontal areas are primarily related to visuomotor imagination, with inferior frontal cortex likely engaged in active motor suppression, and primary motor structures contribute mainly to movement execution.


[Effect of intra- and out-anorectal drainage in the prevention of anastomotic leakage after low anterior resection].
To investigate the effect of intra- and out-anorectal drainage in the prevention of anastomotic leakage after low anterior resection (LAR). Two hundred and thirty-five patients undergone LAR were divided into two groups according to two periods, the former group from Mar. 2003 to Aug. 2004 and the later group from Sep. 2004 to Nov. 2007. Technique advances were adopted in the later group, especially the routine intra- and out-anorectal drainage. Incidence of anastomotic leakage and clinicopathological data of two groups were compared. Anastomotic leakage occurred in 4 patients of the former group (4/89) and 1 of the later group (1/146). Logistic analysis found that intra- and out-anorectal drainage was the main issue which prevented anastomotic leakage. Intra- and out-anorectal drainage is useful for the prevention of anastomotic leakage after low anterior resection.


Biophysical characterization of the feline immunodeficiency virus p24 capsid protein conformation and in vitro capsid assembly.
The Feline Immunodeficiency Virus (FIV) capsid protein p24 oligomerizes to form a closed capsid that protects the viral genome. Because of its crucial role in the virion, FIV p24 is an interesting target for the development of therapeutic strategies, although little is known about its structure and assembly. We defined and optimized a protocol to overexpress recombinant FIV capsid protein in a bacterial system. Circular dichroism and isothermal titration calorimetry experiments showed that the structure of the purified FIV p24 protein was comprised mainly of α-helices. Dynamic light scattering (DLS) and cross-linking experiments demonstrated that p24 was monomeric at low concentration and dimeric at high concentration. We developed a protocol for the in vitro assembly of the FIV capsid. As with HIV, an increased ionic strength resulted in FIV p24 assembly in vitro. Assembly appeared to be dependent on temperature, salt concentration, and protein concentration. The FIV p24 assembly kinetics was monitored by DLS. A limit end-point diameter suggested assembly into objects of definite shapes. This was confirmed by electron microscopy, where FIV p24 assembled into spherical particles. Comparison of FIV p24 with other retroviral capsid proteins showed that FIV assembly is particular and requires further specific study.


[The value of platelet function tests].
Platelet function tests are used to detect patients with abnormal platelet function, which may be inborn or acquired or to detect increased platelet activation which may be accompanied by an increased risk of thrombosis. Platelet function tests are also used to monitor platelet function inhibitors as aspirin, clopidogrel or platelet membrane glycoprotein IIb/IIIa-inhibitors. Incorrect blood sampling is a major source of error in measuring platelet function. Global tests besides platelet count and bleeding time are thrombelastography, the platelet function analyzer (PFA) and possibly in the future the new Impact-system. Specific tests measure platelet spreading and adhesion to defined surfaces. In a series of methods platelets are counted before and after passage of a filter. Some of these tests are partially standardized. The most frequently measured platelet function is aggregation induced by ADP, collagen or other substances as first described by Gustav Born. Some newer methods to perform aggregometry are described. Platelet activation can be detected by measuring spontaneous aggregation as in the PAT-test. Prospective trials with this test have shown that enhanced spontaneous aggregation is a risk factor for new vascular occlusions in diabetics and for myocardial infarctions in healthy individuals. The Wu and Hoak-test and the measurement of released platelet factor 4 or betaglobulin are of limited value. Flow cytometric methods are frequently used to measure platelet activation markers as CD 62 and others. Platelet induced thrombin generation is an interesting function to measure drug effects. None of the presently available platelet function tests is well standardized, so there is much room for improvement.


Klippel-Trenaunay syndrome.
The association of three physical findings including capillary malformation, varicosities, and hypertrophy of bony and soft tissues corresponds to Klippel-Trenaunay syndrome. This triad of findings, described by the two French physicians Klippel and Trenaunay in 1900, differs from Parkes-Weber syndrome, in that Klippel-Trenaunay syndrome does not incorporate significant hemodynamic arteriovenous fistulas. Generally, management of this disease process should be individualized. Surgery should be considered in cases where skin ulcerations lead to persisting and recurrent bleeding, or where digital deformities lead to functional disabilities or where significant limb overgrowth leads to both functional and psychological impairment. Persistent hematochezia, hematuria, and vaginal and esophageal bleeding are considered indications for surgical intervention. Recurrent attacks of thrombophlebitis and cellulitis are treated medically with antiinflammatory agents and antibiotics. Otherwise, management of this syndrome is generally conservative, consisting of psychological encouragement, reassurance, and the continued use of graduated compressive stockings for varicosities and intermittent pneumatic compression pumps for lymphatic edema.


Comparison of SSS-CN and PHQ-15 in the evaluation of patients with suspected psychological disorders in cardiovascular medicine.
Somatic Symptom Scale-China (SSS-CN) has been applied to assess the presence and severity of somatization symptom disorders (SSD) in Chinese patients. However, there was no study comparing SSS-CN with Patient Health Questionnaire-15 (PHQ-15). The aim of this study was to compare the consistency of the SSS-CN with the PHQ-15 in evaluating SSD in patients with suspected psychological disorders in cardiovascular medicine and to explore the relationship between scores on the two SSD self-rating scales and scores on self-rating scales for anxiety or depression. In this study, 1,324 subjects were enrolled by using a "three-question method." Then, they completed four self-assessment scales, i.e., SSS-CN, PHQ-15, Patient Health Questionnaire-9 (PHQ-9), and General Anxiety Disorder-7 (GAD-7), in turn. The ability of SSS-CN to diagnose SSD was analyzed by the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) value, sensitivity, and specificity were calculated. Reliability analysis was performed with the Kappa statistic to determine consistency between SSS-CN and PHQ-15. The relationship between two qualitative variables was analyzed by Spearman correlation analysis. The proportions of SSD evaluated by SSS-CN and PHQ-15 were 83.2 and 87.0%, respectively. SSS-CN score was significantly correlated with PHQ-15 one (r = 0.709, p < 0.001). The AUC of the SSS-CN for the diagnosis of SSD was 0.891, with a high sensitivity and acceptable specificity. There was a moderate agreement between SSS-CN and PHQ-15 in assessing SSD, with a Kappa value of 0.512. Anxiety and/or depression were detected in about 70% of patients with SSD. There was significant correlation between the score of each SSD scale and that of GAD-7 or PHQ-9 (SSS-CN: r = 0.614 or 0.674; PHQ-15: r = 0.444 or 0.582, all p < 0.001). In addition, the SSS-CN score was more closely correlated with the GAD-7 or PHQ-9 score than the PHQ-15 score, and a higher proportion of patients with anxiety or depression was detected in those with moderate and severe SSD evaluated by SSS-CN. The SSS-CN could be one of the ideal scales for the rapid screening of patients with suspected psychological disorders in cardiovascular medicine.


Under the spotlight: understanding the role of the Chief Medical Officer in a pandemic.
As the COVID-19 pandemic took hold in 2020, Chief Medical Officers (CMOs) entered the public spotlight like never before. Amidst this increased visibility, the role is deeply contested. Much of the disagreement concerns whether CMOs should act independently of the government: while some argue CMOs should act as independent voices who work to shape government policy to protect public health, others stress that CMOs are civil servants whose job is to support the government. The scope and diversity of debates about the CMO role can be explained by its inherently contradictory nature, which requires incumbents to balance their commitments as physicians with their mandates as civil servants who advise and speak on the government's behalf. The long-haul COVID-19 pandemic has further tested the CMO role and has shone light on its varying remits and expectations across different jurisdictions, institutions and contexts. It is perhaps unsurprising, then, that calls to amend the CMO role have emerged in some jurisdictions during the pandemic. However, any discussions about changing the CMO role need a stronger understanding of how different institutional and individual approaches impact what incumbents feel able to do, say and achieve. Based on an ongoing comparative analysis of the position across five countries with Westminster-style political systems, we provide an overview of the CMO role, explain its prominence in a pandemic, examine some debates surrounding the role and discuss a few unanswered empirical questions before describing our ongoing study in greater detail.


A workflow for absolute quantitation of large therapeutic proteins in biological samples at intact level using LC-HRMS.
The commonly used LC-MS workflow to quantify protein therapeutics in biological samples is 'bottom-up' approach. In this study, the aim is to establish 'top-down' approach for absolute quantitation of therapeutic antibodies or proteins of similar sizes in biological samples at intact level. Using a recombinant human monoclonal antibody as the model molecule, we present a workflow to measure large therapeutic proteins in plasma at intact level based on deconvoluted high-resolution MS (HRMS) peaks. A novel MultiQuant™ software function was developed to automatically deconvolute the peaks and process the data. The workflow showed satisfying performance. This is a proof of concept study demonstrating the feasibility of bioanalysis of large therapeutic proteins at intact level using LC-HRMS.


Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood.
In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. Highly exposed individuals and their children have experienced endocrine-related health problems, though the underlying mechanism behind these remains unknown. We investigated whether PBB exposure is associated with variation in DNA methylation in peripheral blood samples from 658 participants of the Michigan PBB registry using the MethylationEPIC BeadChip, as well as investigated what the potential function of the affected regions are and whether these epigenetic marks are known to associate with endocrine system pathways. After multiple test correction (FDR <0.05), 1890 CpG sites associated with total PBB levels. These CpGs were not enriched in any particular biological pathway, but were enriched in enhancer and insulator regions, and depleted in regions near the transcription start site or in CpG islands (p < 0.05). They were also more likely to be in ARNT and ESR2 transcription factor binding sites (p = 3.27e-23 and p = 1.62e-6, respectively), and there was significant overlap between CpGs associated with PBB and CpGs associated with estrogen (p < 2.2e-16). PBB-associated CpGs were also enriched for CpGs known to be associated with gene expression in blood (eQTMs) (p < 0.05). These eQTMs were enriched for pathways related to immune function and endocrine-related autoimmune disease (FDR <0.05). These results indicate that exposure to PBB is associated with differences in epigenetic marks that suggest that it is acting similarly to estrogen and is associated with dysregulated immune system pathways.


Designing for and with People with Dementia using a Human Rights-Based Approach.
User-centered design is typically framed around meeting the preferences and needs of populations involved in the design process. However, when designing technology for people with disabilities, in particular dementia, there is also a moral imperative to ensure that human rights of this segment of the population are consciously integrated into the process and respectfully included in the product. We introduce a human rights-based user-centered design process which is informed by the United Nations Convention on the Rights of Persons with Disabilities (CRPD). We conducted two editions of a three-day-long design workshop during which undergraduate students and dementia advocates came together to design technology for people with dementia. This case study demonstrates our novel approach to user-centered design that centers human rights through different stages of the workshop and actively involves people with dementia in the design process.


Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis.
Alcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial. We investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose-response meta-regression models and investigated potential sources of heterogeneity. A total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose-risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin's and Non-Hodgkin's lymphomas were inversely associated. Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma.


Preliminary investigation of polymer-based in situ passive samplers for mercury and methylmercury.
Development of an in situ passive sampler for mercury (Hg), and its toxic form, methylmercury (MeHg), using simple polymer films, was explored for the potential to make an efficient and environmentally relevant monitoring tool for this widespread aquatic pollutant. The sulfur-containing polymers polysulfone (PS), and polyphenylene sulfide (PPS), were found to accumulate both MeHg and inorganic Hg (iHg), whereas polyethylene (PE) sorbed iHg but not MeHg, and polyoxymethylene (POM) and polyethersulfone (PES) films had low affinity for both Hg species. Uptake rates of Hg species into polymers were linear over two weeks, and dissolved organic matter at natural levels had no effect on partitioning of MeHg or iHg to the polymers. Sorption of MeHg to PS and PPS from three estuarine sediments correlated with uptake into diffusive gel-type samplers over time, and in PPS, with accumulation by the estuarine amphipod, Leptocheirus plumulosus. These polymers had lower MeHg adsorption rates, but are simpler to assemble, than diffusive gel-type samplers. Higher contaminant concentrations in polymer and gel-type samplers corresponded with porewater concentrations across sediments, suggesting they sample the dissolved MeHg pool, whereas MeHg levels in amphipods were more elevated with higher bulk sediment MeHg, which may reflect feeding strategy. While polymers with higher affinity for MeHg and iHg are needed for some environmental applications, this work suggests a simple sampling approach has potential for time-integrated, environmentally-meaningful MeHg monitoring in contaminated sediments.


Lack of evidence for pulmonary venous thrombosis in cryptogenic stroke: a magnetic resonance angiography study.
Even after extensive evaluation, the etiology of ischemic stroke remains undefined in a considerable proportion of cases, suggesting that causes of stroke may exist that have not yet been established. We tested the hypothesis that pulmonary venous thrombosis (PVT) is a potential source of brain embolism in patients with cryptogenic stroke. Within 7 days after mild to moderately severe ischemic stroke or transient ischemic attack, 18 patients (9 women, 9 men; mean age, 48 years) were studied in whom the etiology remained undefined despite complete workup. All patients received high-resolution pulmonary venography with the use of multiple-bolus, multiphase, 3-dimensional, gadolinium-enhanced MR angiography (MRA). Overall quality of the MRA was good in 14 and insufficient in 4 patients, mainly as a result of breathing artifacts. Visualization of the main and segmental veins and evaluability of their patency were good for most right pulmonary veins but often inadequate for left pulmonary veins, particularly for those in the left lower lobe. There was no evidence for PVT in any of the sufficiently visualized pulmonary veins. The results do not support the hypothesis of PVT as a contributor to the etiology of ischemic stroke. However, the study was limited regarding scan volume, spatial discrimination, patient selection, and delay between ischemia and MRA. Therefore, further investigations, including postmortem studies, are needed to resolve the question of whether PVT may contribute to ischemic stroke.


Analysis of a highly immunodominant epitope in the human immunodeficiency virus type 1 transmembrane glycoprotein, gp41, defined by a human monoclonal antibody.
A human monoclonal antibody, 41-7 [immunoglobulin G1(kappa)], directed against the transmembrane glycoprotein gp41 of the human immunodeficiency virus type 1 (HIV-1) has been produced by direct fusion of lymph node cells from an HIV-1-infected individual with a human B-lymphoblastoid cell line. The minimal essential epitope for 41-7 was mapped to a conserved seven-amino acid sequence, N-CSGKLIC-C, located within the N-terminal part of gp41. Antibodies blocking the binding of 41-7 could be detected in the serum of all HIV-1-infected individuals tested, irrespective of the stage of the infection. The epitope is located externally to the plasma membrane, and it is accessible to antibody in the native conformation of the glycoprotein. Despite this, no neutralizing activity of 41-7 could be demonstrated in vitro. These data indicate, directly and indirectly, that this immunodominant epitope on gp41, although exposed on the viral surface, elicits antibodies lacking antiviral activity and, hence, should be avoided in future vaccine candidates.


Synthetic pyrethroid effect on blood plasma biomarker enzymes and histological changes in Catla catla.
Alpha-cypermethrin is an isoform of cypermethrin; it is an active pyrethroid used extensively to control a wide range of pests in agriculture and animal breeding. In this study four groups of six fish were examined. The first group served as a control in fresh water alone, with no pyrethroid. The second, third and fourth groups were exposed to alpha-cypermethrin for 4, 8 and 96 h respectively. At the end of the each exposure period, the fish were sacrificed, and the required muscle tissues were collected for histological examination. The blood was drawn with heparinized needles and processed for serum enzymatic studies. Serum enzymes such as aspartate transaminase (AST), alanine transaminase (ALT), amylase, acid phosphatase (ACP) and gamma-glutamyl transpeptidase (GGT) were measured at 4, 8 and 96 h. AST enzyme activity was significantly increased at 4 h, whereas ALT and amylase enzyme activities were significantly reduced at all the time points. ACP enzyme activity was significantly reduced at 4 and 8 h, whereas GGT enzyme activity was significantly increased at all the time points. Hepatocyte cytoplasmic vacuolisation and degeneration, rupture of blood vessels, and necrosis was found at all time points. Congestion of blood vessels, bulging, distortion of filaments, erosion and disintegration of blood corpuscles and hyperplasia of epithelium were found in treated gills at 4, 8 and 96 h. Breakdown of muscle fibres, vacuolation and accumulation of lipids and melanin in white muscle were observed in treated fish muscle at 4, 8 and 96 h.


Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders.
A neurological disorder is any disorder or abnormality in the nervous system. Among different neurological disorders, Alzheimer's disease (AD) is recognized as the sixth leading cause of death globally. Considerable research has been conducted to find pioneer treatments for this devastating disorder among which cell therapy has attracted remarkable attentions over the last decade. Up to now, targeted differentiation into specific desirable cell types has remained a major obstacle to clinical application of cell therapy. Also, potential risks including uncontrolled growth of stem cells could be disastrous. In our novel protocol, we used basal forebrain cholinergic progenitor cells (BFCN) derived from human chorion-derived mesenchymal stem cells (hC-MSCs) which made it possible to obtain high-quality population of cholinergic neurons and in vivo in much shorter time period than previous established methods. Remarkably, the transplanted progenitors fully differentiated to cholinergic neurons which in turn integrated in higher cortical networks of host brains, resulting in significant improvement in cognitive assessments. This method may have profound implications in cell therapies for any other neurodegenerative disorders. Graphical Abstract .


Compatible and Incompatible Pollen-Styles Interaction in Pyrus communis L. Show Different Transglutaminase Features, Polyamine Pattern and Metabolomics Profiles.
Pollen-stigma interaction is a highly selective process, which leads to compatible or incompatible pollination, in the latter case, affecting quantitative and qualitative aspects of productivity in species of agronomic interest. While the genes and the corresponding protein partners involved in this highly specific pollen-stigma recognition have been studied, providing important insights into pollen-stigma recognition in self-incompatible (SI), many other factors involved in the SI response are not understood yet. This work concerns the study of transglutaminase (TGase), polyamines (PAs) pattern and metabolomic profiles following the pollination of Pyrus communis L. pistils with compatible and SI pollen in order to deepen their possible involvement in the reproduction of plants. Immunolocalization, abundance and activity of TGase as well as the content of free, soluble-conjugated and insoluble-bound PAs have been investigated. 1H NMR-profiling coupled with multivariate data treatment (PCA and PLS-DA) allowed to compare, for the first time, the metabolic patterns of not-pollinated and pollinated styles. Results clearly indicate that during the SI response TGase activity increases, resulting in the accumulation of PAs conjugated to hydroxycinnamic acids and other small molecules. Metabolomic analysis showed a remarkable differences between pollinated and not-pollinated styles, where, except for glucose, all the other metabolites where less concentrated. Moreover, styles pollinated with compatible pollen showed the highest amount of sucrose than SI pollinated ones, which, in turn, contained highest amount of all the other metabolites, including aromatic compounds, such as flavonoids and a cynnamoil derivative.


Effective dispersion in temporally fluctuating flow through a heterogeneous medium.
In this paper we investigate the effective transport of a passive solute in temporally fluctuating flow through a spatially heterogeneous medium. The Darcy equation for an incompressible fluid in the heterogeneous medium is solved with temporally fluctuating boundary conditions using perturbation theory. We distinguish between a spatial random process reflecting the medium heterogeneities and a temporal random process which models the fluctuations of the boundary conditions. By appropriately averaging over the corresponding random fields, we evaluate the second-order perturbation approximation to the time evolution of the "effective" and "ensemble" dispersion coefficients. Both quantities consist of three terms reflecting: (1) local dispersion; (2) dispersion caused by spatial heterogeneities (identical to the corresponding dispersion in steady random flow); (3) dispersion linked to the enhanced solute spreading caused by the interactions between temporal fluctuations, local dispersion, and spatial heterogeneity. The behavior of this latter contribution is complex due to the interplay of three different time scales (set by fluctuating boundary conditions, local dispersion, and advection). Temporal fluctuations of the velocity field lead to effective transverse dispersion coefficients that evolve in time to macroscopic values (i.e., independent of the local dispersion), which is consistent with observations in the field but was not predicted by theories based on steady flow. Due to their perturbative nature, the derived results are intrinsically limited to moderately fluctuating random velocity fields. However, numerical transport simulations indicate a wide range of applicability. The reported results support remediation techniques that attempt to enhance the mixing of injected reactants with contaminated ground water by temporal variations of injection and pumping rates.


Nanoencapsulation of Phenolic Extracts from Native Potato Clones (Solanum tuberosum spp. andigena) by Spray Drying.
Native potato clones grown in Peru contain bioactive compounds beneficial to human health. This study aimed to optimize the spray-drying nanoencapsulation of native potato phenolic extracts utilizing a central composite design and response surface methodology, obtaining the optimal treatment to an inlet temperature of 120 °C and an airflow of 141 L/h in the nano spray dryer B-90, which allowed maximizing the yield of encapsulation, antioxidant capacity (DPPH), encapsulation efficiency (EE), total phenolic compounds, and total flavonoids; on the other hand, it allowed minimizing hygroscopicity, water activity (Aw), and moisture. Instrumental characterization of the nanocapsules was also carried out, observing a gain in lightness, reddening of the color, and spherical nanoparticles of heterogeneous size (133.09-165.13 nm) with a negative ζ potential. Thermal, infrared, and morphological analyses confirmed the encapsulation of the core in the wall materials. Furthermore, an in vitro release study of phenolic compounds in an aqueous solution achieved a maximum value of 9.86 mg GAE/g after 12 h. Finally, the obtained nanocapsules could be used in the food and pharmaceutical industry.


Establishment and competitive exclusion of Yersinia enterocolitica in the gut of monoxenic and holoxenic chicks.
Newly hatched chicks subcutaneously injected with or orally exposed to Yersinia enterocolitica were colonized in the gastrointestinal tract by this bacteria. Colonization did not take place when chicks were exposed to less than 10(8) colony-forming units. In monoxenic chicks, major colonization was detected in the crop, ceca, and cloaca; fewer numbers colonized other regions of the gastrointestinal tract, and there was little evidence of bacteremia. None of the chicks exhibited clinical signs, although colonization was demonstrated throughout the gastrointestinal tract over the 28-day test period. Prior colonization by native gut microflora prevented subsequent colonization by Y. enterocolitica in holoxenic chicks.


Duodenum-preserving pancreatic head resection: A retrospective analysis of the Hamburg Modification.
Chronic pancreatitis remains a challenging inflammatory disease, causing progressive, irreversible fibrosis of the pancreatic parenchyma. Several surgical options for treatment have been established, but duodenum-preserving pancreatic head resections seem to be the most favorable option other than pancreatoduodenectomy. The aim of this retrospective analysis is to evaluate the outcomes of the Hamburg modification of duodenum-preserving pancreatic head resections. We retrospectively evaluated-for long-term outcomes concerning pain control, quality of life, and symptom control-500 consecutive patients suffering from painful chronic pancreatitis who had undergone the Hamburg modification of the duodenum-preserving pancreatic head resection. Additionally, the patients were compared with a database of 104 patients who underwent duodenum-preserving pancreatic head resections according to Beger or Frey. After a mean follow-up of 10 years, overall survival was 90% in those patients having undergone the Hamburg modification. Regarding analgetic medications, the median pain score for frequency of pain attacks, measured by a visual analog scale and inability to work, was 0 (0-100), and the global quality of life revealed a median of 92 (0-100). In addition, we found that a high rate of patients continued consuming alcohol after the operation (37.9%). The rate of redo surgery owing to the recurrence of chronic pancreatitis was 7.6% after this Hamburg modification. Duodenum-preserving pancreatic head resections provide adequate outcomes in terms of pain control, quality of life, and symptom control. In this retrospective analysis, the Hamburg modification was found to be a good alternative to other forms of duodenum-preserving pancreatic head resections. The choice of a certain modification of the duodenum-preserving pancreatic head resection may depend on the surgeon's expertise and the individual needs of the patient.


Fibroepithelial lesions; The WHO spectrum.
Fibroepithelial lesions of the breast comprise a morphologically and biologically heterogeneous group of biphasic tumors with epithelial and stromal components that demonstrate widely variable clinical behavior. Fibroadenomas are common benign tumors with a number of histologic variants, most of which pose no diagnostic challenge. Cellular and juvenile fibroadenomas can have overlapping features with phyllodes tumors and should be recognized. Phyllodes tumors constitute a spectrum of lesions with varying clinical behavior and are graded as benign, borderline or malignant based on a set of histologic features according to recommendations by the World Health Organization (WHO). Recent developments have significantly expanded our understanding of the pathogenesis of fibroepithelial lesions, highlighting fibroadenomas as true neoplasms and underscoring a commonality with phyllodes tumors in the form of recurrent MED12 exon 2 mutations. In addition, sequencing studies have elucidated pathways associated with phyllodes tumor progression. Accurate diagnosis and grading of phyllodes tumors are important for patient management and prognosis, as grade broadly correlates with increasing local recurrence risk, and essentially only malignant tumors metastasize. However, classification of fibroepithelial lesions in many cases remains challenging on both core biopsy and excision specimens. A commonly encountered problem at the benign end of the spectrum is the distinction of benign phyllodes tumor from cellular fibroadenoma, which is largely due to the subjective nature of histologic features used in diagnosis and histologic overlap between lesions. Grading is further complicated by the requirement to integrate multiple subjective and ill-defined parameters. On the opposite end of the histologic spectrum, malignant phyllodes tumors must be distinguished from more common metaplastic carcinomas and from primary or metastatic sarcomas, which can be especially difficult in core biopsies. Immunohistochemistry can be useful in the differential diagnosis but should be interpreted with attention to caveats. This review provides an overview and update on the spectrum of fibroepithelial lesions, with special emphasis on common problems and practical issues in diagnosis.


Clinical Results of Knot-tying Versus Knotless Suture Anchors in Arthroscopic Anteroinferior Labral Repair.
Background Arthroscopic repair of glenohumeral instability is becoming an increasingly common procedure. These repairs can be undertaken using knot-tying and knotless suture anchors; there is currently no clear consensus in the literature about what type of repair is most cost-effective and provides superior outcomes. The purpose of this study is to examine postoperative outcomes of patients undergoing arthroscopic anteroinferior labral repair (AALR) with either knot-tying or knotless anchors. Methods A single institution retrospective observational cohort study of 122 patients undergoing AALR from January 2014 to June 2021 was conducted. Univariate statistics were used to assess differences in demographics, operative characteristics, and postoperative outcomes between repair types; multivariate analysis was used to evaluate risk factors for recurrent instability and reoperation. Results Patients undergoing AALR with knotless anchors had a shorter case duration than those with knot-tying anchors (112.64 vs. 89.86 minutes, p<0.001). There were no significant differences between groups in the size of labral tear, presence of a glenoid bone defect, or Hill-Sachs lesion. After controlling for age, BMI, sex, glenoid bone defect, number of preoperative dislocations, and fixation type, only age (OR=0.896, p=0.010) and female sex (OR=5.341, p=0.008) were independent risk factors for recurrent instability and no factors were independent predictors of reoperation. Conclusion Patients undergoing AALR experienced similar rates of reoperation and recurrent instability regardless of whether a knot-tying or knotless repair was performed. The use of knotless suture anchors may improve cost-effectiveness due to decreased surgical time without diminishing postoperative outcomes.


Cytochemistry of the Golgi apparatus in developing ovarian germ cells of the Syrian hamster.
A cytochemical study of the Golgi apparatus in the developing oocyte of the golden hamster was carried out using the TPPase, AcPase and zinc iodide-osmium tetroxide (ZnOs) techniques. Tissue from both immature and sexually mature animals was investigated. Peak TPPase activity was found in pre-growth oocytes in ovaries from sexually mature adults. Some activity was also present in SER in the peripheral cytoplasm of growing oocytes. AcPase activity was found only after the onset of oocyte growth. It was present in Golgi cisternae and associated vesicles and in some profiles of peripheral SER. No structures corresponding to GERL were identified. Strong staining with ZnOs was seen, at all stages studied, in certain Golgi vesicles and short tubules but not in the cisternae unless the oocyte was atretic. Weaker ZnOs staining was characteristic of ER throughout the oocyte. With all techniques there was a falling off of reactivity as oocyte size increased. Within a single oocyte some Golgi bodies were negative while others were positive, with both TPPase and AcPase techniques. This suggests that two or more functional types of this organelle are present within the developing oocytes.


First American College of Surgeons National Surgical Quality Improvement Program Report from a Low-Middle-Income Country: A 1-Year Outcome Analysis of Neurosurgical Cases.
Low-middle-income countries (LMICs) share a substantial proportion of global surgical complications. This is compounded by the seemingly deficient documentation of postsurgical complications and the lack of a national average for comparison. In this context, the implementation of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) that compares hospital performance based on postsurgical complication data provided by a wide array of centers, could be a major initiative in a resource-challenged setting. Implementation of the NSQIP has provenly mitigated postoperative morbidity and mortality across many centers all over the world. To our knowledge, this report is the first from an LMIC to report its postoperative neurosurgical complications in comparison with international benchmarks. Our hospital joined the NSQIP in 2019. Through a standardized ACS protocol, ACS-trained surgical clinical reviewers (SCRs) reviewed and extracted data from randomly assigned neurosurgical patients' medical records from preoperative to postoperative (30-day) data using validated, standardized data definitions. SCRs entered deidentified data in an online Health Insurance Portability and Accountability Act web-based secure platform. The validated data were then consigned to the ACS NSQIP head office in the United States where the data were analyzed and compared with similar data from other centers registered with the NSQIP. In this way, our hospital was rated for each of the variables related to postsurgical complications after both spinal and cranial procedures, and the results were sent back to us in the form of text, tables, and graphs. Our initial report suggested a relatively higher odds ratio for sepsis and readmissions after spinal procedures at our hospital, and a similarly higher odds ratio for morbidity, sepsis, urinary tract infection, and surgical site infection for cranial procedures. For these variables, our hospital fell in the needs improvement category of the NSQIP. For the rest of the variables studied for both spinal and cranial procedures, the hospital fell in the as expected category of the NSQIP. Implementation of the NSQIP is an important first step in creating a culture of transparency, safety, and quality. This is the first report of NSQIP implementation in an LMIC, and we have shown comparable results to developed countries.


Staff and patient perspectives on the purpose of psychotropic prescribing in prisons: care or control?
The objective was to explore perspectives on reasons for psychotropic medication use in prisons. We recruited a purposive sample of healthcare staff and patients prescribed psychotropic medicines from four East of England prisons. Participants took part in qualitative, semistructured interviews, which were recorded, transcribed and analyzed thematically. While patients and healthcare staff viewed psychotropic medicines primarily as a treatment for reducing symptoms of mental illness, they were also used as a coping strategy and to reduce insomnia. Appropriate psychotropic prescribing was also thought to contribute towards the rehabilitation agenda and helped to maintain order in prisons. Staff voiced concerns regarding possible overreliance on psychotropic medicines. However, patients perceived insufficient access to alternative, nonpharmacological forms of treatment and support in prison. Psychotropic medicines are used for multiple purposes in prisons and are generally considered a useful resource. Nonetheless, further work may be needed to find the right balance between psychotropic medicines and alternative, nonpharmacological therapies.


Processing of multisensory spatial congruency can be dissociated from working memory and visuo-spatial attention.
Tactile stimuli at the same location as a visual target can increase activity in the contralateral occipital cortex compared with spatially incongruent bimodal stimulation. Does this cross-modal congruency effect in the visual cortex depend on available cognitive resources? Visual attention and working memory can modulate responses to visual stimuli in the occipital cortex, with attenuation in conditions of high-attentional or low-memory load. Here, we asked if these two cognitive factors affect multisensory processing in the visual cortex. Using functional magnetic resonance imaging in humans, we manipulated the load of working memory or visuo-spatial attention. Concurrently with these primary tasks we presented same-side (congruent) or opposite-side (incongruent) visuo-tactile stimuli. Both experiments revealed enhancement of brain activity for congruent vs incongruent bimodal stimulation in the contralateral occipital cortex. Critically, these cross-modal effects occurred irrespective of the level of load. We conclude that processing of visuo-tactile spatial congruency in the visual cortex does not depend on available visuo-spatial and memory resources.


A 73-year-old man with confusion, fever, and positive MPO-ANCA.
A 73-year-old man was admitted to the hospital because of progressive lethargy and fever. He had a history of hypertension since the age of 40, and was diagnosed as having a testicular tumor at the age of 50. On admission, he looked pale and stuporous. Laboratory examination revealed microscopic hematuria. The erythrocyte sedimentation rate was 110 mm/hr, and the serum CRP was 14.3 mg/dl. The titer of myeloperoxidase-antineutrophilic cytoplasmic antibodies (MPO-ANCA) was higher than 1:1000. On the sixth hospital day, he required ventilatory assistance because of aspiration pneumonia and was connected to a respirator. He was treated with intravenous corticosteroids, to which he responded in the short term with resolution of the fever and decrease in the serum CRP level, however, the consciousness disturbance persisted and the fever recurred soon thereafter. He developed gross hematuria and the renal function deteriorated. He eventually died of renal failure and pulmonary hemorrhage. Although his clinical course and laboratory findings were consistent with those of microscopic polyangitis, the pathological diagnosis was crescentic glomerulonephritis with no evidence of vasculitis.


Imagining counterfactual worlds in autism spectrum disorder.
Two experiments are presented that explore online counterfactual processing in autism spectrum disorder (ASD) using eye-tracking. Participants' eye movements were tracked while they read factual and counterfactual sentences in an anomaly detection task. In Experiment 1, the sentences depicted everyday counterfactual situations (e.g., If Joanne had remembered her umbrella, her hair would have been dry/wet when she arrived home). Sentences in Experiment 2 depicted counterfactual versions of real world events (e.g., If the Titanic had not hit an iceberg, it would have survived/sunk along with all the passengers). Results from both experiments suggest that counterfactual understanding is undiminished in adults with ASD. In fact, participants with ASD were faster than Typically Developing (TD) participants to detect anomalies within realistic, discourse-based counterfactuals (Experiment 1). Detection was comparable for TD and ASD groups when understanding could be grounded in knowledge about reality (Experiment 2), though the 2 groups used subtly different strategies for responding to and recovering from counterfactual inconsistent words. These data argue against general difficulties in global coherence and complex integration in ASD. (PsycINFO Database Record


Preparation and Characterization of Controlled-Release Avermectin/Castor Oil-Based Polyurethane Nanoemulsions.
Avermectin (AVM) is a low-toxic and high-active biopesticide, but it can be easily degraded by UV light. In this paper, biodegradable castor oil-based polyurethanes (CO-PU) are synthesized and used as carriers to fabricate a new kind of AVM/CO-PU nanoemulsion through an emulsion solvent evaporation method, and the chemical structure, colloidal property, AVM loading capacity, controlled-release behavior, foliar adhesion, and photostability of the AVM/CO-PU drug delivery systems are investigated. Results show that AVM is physically encapsulated in the CO-PU carrier nanospheres, the diameter of the AVM/CO-PU nanoparticles is <50 nm, and the AVM/CO-PU films are flat and smooth without any AVM aggregate. The drug loading capacity is up to 42.3 wt % with a high encapsulation efficiency of >85%. The release profiles indicate that the release rate is relatively high at the early stage and then slows, which can be adjusted by loaded AVM content, temperature, and pH of the release medium. The foliar pesticide retention of the AVM/CO-PU nanoemulsions is improved, and the photolysis rate of AVM in the AVM/CO-PU nanoparticles is significantly slower than that of the free AVM. A release mechanism of the AVM/CO-PU nanoemulsions is proposed, which is controlled by both diffusion and matrix erosion.


Particle and heavy metal accumulation by two plant species in a coal mining area of Odisha, India.
Mining activities lead to severe particulate matter (PM) pollution that consequently has a detrimental effect on ecosystem. A study was therefore conducted in a coal mining area of Odisha, India with an objective to assess the particulate matter pollution on the basis of differential aerodynamic size (PM10 and PM2.5) of the particles, the metallic (Zn and Fe) composition, and also to evaluate their nature of deposition on two identified plant species. The results suggest a significant variation in particle and heavy metal fractions in the ambient air of different sites (p < 0.05). Fe dominated the finer particle (PM2.5) fraction while Zn dominated the coarser counterpart (PM10) in the ambient air. When evaluated for the particle and heavy metal deposition on leaf surface, Shorea robusta performed better in trapping the coarser particles (PM10) while Holarrhena floribunda was found to be an efficient scrubber of the finer particles (PM2.5). Fe deposition on surface of leaves was comparatively higher than Zn irrespective of plant species or size fractions. Therefore, it is concluded that both S. robusta and H. floribunda should be planted in a schematic manner to tackle the particulate pollution in coal mining areas.


Differential expression of the major histocompatibility antigens and ICAM-1 on bile duct epithelial cells in biliary atresia.
Aberrant expression on biliary epithelial cells of the major histocompatibility complex (MHC) antigens in association with adhesion molecule intercellular adhesion molecule-1 (ICAM-1) may be crucial to the immunopathogenesis of biliary atresia. The patterns of MHC class I and II expression in relation to ICAM-1 expression as well as the associated lymphocyte subpopulations were studied in frozen section liver biopsies from six infants with biliary atresia. Intense ICAM-1 expression was found on all ductal epithelial cells in association with MHC I. No ductal epithelial cells demonstrated MHC II expression. Lymphocyte populations within the portal tracts all expressed LFA-1 and were predominantly CD4 positive (> 70%). CD8 positive cells accounted for less than 30%. The expression of ICAM-1 appears to be important in the pathogenesis of biliary atresia but is not linked to the expression of MHC II determinants. This result suggests that different regulatory mechanisms govern the expression of these important immunological receptors on biliary epithelial cells.


Crystal structures of the ADP and ATP bound forms of the Bacillus anti-sigma factor SpoIIAB in complex with the anti-anti-sigma SpoIIAA.
Cell type-specific transcription during Bacillus sporulation is established by sigma(F), the activity of which is controlled by a regulatory circuit involving the anti-sigma factor and serine kinase SpoIIAB, and the anti-anti-sigma SpoIIAA. When ATP is present in the nucleotide-binding site of SpoIIAB, SpoIIAA is phosphorylated, followed by dissociation. The nucleotide-binding site of SpoIIAB is left bound to ADP. SpoIIAB(ADP) can bind an unphosphorylated molecule of SpoIIAA as a stable binding partner. Thus, in this circuit, SpoIIAA plays a dual role as a substrate of the SpoIIAB kinase activity, as well as a tight binding inhibitor. Crystal structures of both the pre-phosphorylation complex and the inhibitory complex, SpoIIAB(ATP) and SpoIIAB(ADP) bound to SpoIIAA, respectively, have been determined. The structural differences between the two forms are subtle and confined to interactions with the phosphoryl groups of the nucleotides. The structures reveal details of the SpoIIAA:SpoIIAB interactions and how phosphorylated SpoIIAA dissociates from SpoIIAB(ADP). Finally, the results confirm and expand upon the docking model for SpoIIAA function as an anti-anti-sigma in releasing sigma(F) from SpoIIAB.


Innate and Adaptive Immune Responses in HELLP Syndrome.
Innate and adaptive immune involvement in hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome is an understudied field, although it is of high clinical importance. This syndrome implies a risk of serious morbidity and mortality to both the mother and the fetus during pregnancy. It was proposed that HELLP syndrome occurs in a circulatory inflammatory milieu, that might in turn participate in a complex interplay between the secreted inflammatory immunomodulators and immune cell surface receptors. Meanwhile, reported immune cell attenuation during HELLP may consequently lead to a prolonged immunoactivation and tissue damage. In this regard, learning more about the immune components of this syndrome should widen the understanding of the HELLP pathophysiology and eventually enable development of novel immune-based therapeutics. This review aims to summarize and discuss the recent and previous findings of the innate and adaptive immune responses during HELLP in order to update the current knowledge of the immune involvement in HELLP pathogenesis.


[Experimental animal model of multiple sclerosis--transverse investigation of MS pathogenesis for therapeutic intervention].
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) in which autoreactive T cells ignites downstream pathogenic cascades. The orphan nuclear receptor, NR4A2, is identified to be a selectively upregulated gene in peripheral blood T cells from relapsing-remitting MS patients. Furthermore, selective upregulation of NR4A2 is observed in peripheral blood T cells and CNS-infiltrating T cells upon immunization with myelin peptide in experimental autoimmune encephalomyelitis (EAE). Intriguingly, IL-17 -producing helper T cells exclusively express NR4A2, suggesting that NR4A2 expression represents a pathogenic T cells in autoimmunity. In addition, a NR4A2 blockade by RNA interference ameliorated EAE, implying the intrinsic roles of NR4A2 in MS/EAE, and could serve as a novel therapeutic target of the diseases.


[Management of bioterroristic attacks with dangerous infectious agents].
The ongoing discussion on threats by terrorist attacks leads to a realignment of tasks and responsibilities within the health care system. Especially the public health services are developing from exercising mainly an advisory function to becoming an integral part in disaster response to devastating biological scenarios. Recent risk assessment recommends authoritative integration of public health officials into disaster response planning and to define their role inside the command and control structures of disaster management. Interdisciplinary networks of public health services, medical treatment centres, emergency medical services, reference laboratories and hospital hygiene services have appeared to be successful in the management of life-threatening, contagious diseases and unexpected bioterrorist incidents as well. In March 2003 the "StAKoB" was established as a permanent working group of the centres for prepared ness and treatment. Major objectives of the working group are ex change of information, mutual support in cases of emergency and standardisation in staff training.


Effect of the insect growth regulator CGA-72662 (Larvadex) on broiler breeder production, hatchability, and subsequent chick performance.
Broiler breeders were fed CGA -72662 ( Larvadex ) at dosages of 0, 30, 300, and 3000 mg/kg (ppm) diet in a standard breeder diet from 25 to 65 weeks of age. The 3000 ppm level was reduced stepwise to 1000 ppm from 25 to 27 weeks due to a significant increase in male and female mortality. Feed consumption did not differ significantly due to treatment. However, birds fed 300 ppm exhibited significantly improved feed conversion and increased egg production on a hen-day basis compared to those fed 0 and 30 ppm with the 1000 ppm level intermediate. On an egg per hen-housed basis, birds fed 300 ppm produced significantly more eggs than those fed 0 ppm with 30 ppm intermediate. Hens fed 1000 ppm produced significantly fewer eggs than all other treatments due to higher initial mortality. Body weight gains for males and females among treatments were similar. Mortality was significantly greater at 1000 ppm than for all other treatments. Egg specific gravity at 50 and 60 weeks was not affected significantly by any treatment. Egg weight, when compared to the 0 ppm level, was decreased significantly at the 1000 ppm level at 50 weeks and by both 300 and 1000 ppm levels at 60 weeks. Egg shell weight was not affected significantly at 50 weeks, but was decreased significantly by both 300 and 1000 ppm Larvadex at 60 weeks. There were no significant effects due to treatment level on fertility, early deads , pipped eggs, hatchability of fertile eggs, or hatchability of eggs set.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of temperature on bone tissue: histological changes.
The analysis of burned human remains has been of great interest among forensic anthropologists largely due to the difficulty that their recovery, classification, reconstruction, and identification present. The main purpose of this analysis is to present histological methodology for the interpretation of bones altered by thermal processes. We include analyses of the microscopic changes among bones exposed to different temperatures, with the goal of establishing categories of histological morphology in relation to fire temperature. Samples of bone (ilium) were exposed systematically to controlled temperatures. Analysis of the resulting histological changes has allowed the formation of a clear four-stage classification of the alterations observed. This classification should prove useful in assessing bone changes in relation to temperature of exposure, particularly in cases where this temperature was previously not known.


The structure and formation of metacercarial cysts in the trematode family Microphallidae travassos 1920.
This study deals with the formation of the metacercarial cysts of four microphallid trematodes, Maritrema subdolum, M. arenaria, Levinseniella brachysoma and Microphallus claviformis. The first observable cyst was present around Maritrema arenaria 18 h p.i. (post-infection). The other species had not developed a cyst by day 8 p.i. but their cysts were apparent by day 16 p.i. These were bi-layered and that of M. subdolum was thicker than those of L. brachysoma and Microphallus claviformis of the same age. The structure of older cysts varied substantially between the four species. Microphallus claviformis and Maritrema subdolum cysts were fully formed at 30 days p.i. Like those of M. arenaria they were bi-layered, the outer layer (up to 3 microm thick) being electron-dense and the inner one (up to 7 microm thick) being less electron-dense. The cysts of fully formed L. brachysoma metacercariae were much more complex, composed of four layers, one of which was divisible into three sub-layers. It was concluded that the outer cyst layer was the product of secretory granules which were previously identified in cercarial tegument. The inner, thicker layer was derived from several sources. These included small tegument vesicles produced over the entire surface of the metacercariae, larger fragments of tegument released from the anterio-ventral region and material liberated from the metacercarial excretory bladder. This heterogeneous material accumulated in the cyst lumen for some time before becoming polymerized to form the thick inner layer or layers of the metacercarial cysts.


[Angelman syndrome and intracranial aneurysm: fortuitous association or commune genetic predisposition?].
Although the pathogenesis of cerebral aneurysms has been studied intensively, it is yet poorly understood. However, a genetic predisposition to this pathology has been often suspected. We describe a patient with both intracranial aneurysm and Angelman syndrome. Angelman syndrome is characterized by severe mental retardation, inappropriate laughter, absent speech, dysmorphic facial features and seizures. It is due to genetic abnormalities of chromosome 15. Cerebral aneurysms are sometimes associated with inherited diseases like autosomal dominant polycystic kidney disease. Moreover several candidate genes have been analysed, to search for genetic variants which might be associated with the occurrence of intracranial aneurysms. Our question is: is the association described in our observation fortuitous or do these diseases share a same genetic predisposition? Our observation also supports the hypothesis of a genetic participation in the genesis of cerebral aneurysms.


Prognostic influence of body mass index and body weight gain during adjuvant FOLFOX chemotherapy in Korean colorectal cancer patients.
Asian population has different body mass index (BMI) profile compared to Caucasian population. However, the effect of obesity and body weight gain in Asian colorectal cancer patients treated with adjuvant chemotherapy has not been studied thus far. We have analyzed the association between disease-free survival (DFS) and obesity/body weight change during treatment in Korean stage III or high-risk stage II colorectal cancer patients treated with adjuvant 5-fluorouracil/ leucovorin/oxaliplatin. BMI was classified according to WHO Asia-Pacific classification. Weight change was calculated by comparing body weights measured at the last chemotherapy cycle and before surgery. Among a total of 522 patients, 35.7 % of patients were obese (BMI ≥ 25 kg/m(2)) and 29.1 % were overweight (BMI, 23-24.9 kg/m(2)) before surgery. 18.0 % of patients gained ≥ 5 kg and 26.1 % gained 2-4.9 kg during the adjuvant chemotherapy period. Baseline BMI or body weight change was not associated with DFS in the overall study population. However, body weight gain (≥5 kg) was associated with inferior DFS (adjusted hazard ratio 2.04, 95 % confidence interval 1.02-4.08, p = 0.043) in overweight and obese patients (BMI ≥ 23.0 kg/m(2)). In Korean colorectal cancer patients treated with adjuvant FOLFOX chemotherapy, body weight gain during the treatment period has a negative prognostic influence in overweight and obese patients.


NMR studies of lipoprotein structure.
Early NMR structural studies of serum lipoproteins were based on (1)H, (13)C, (31)P, and (2)H studies of lipid components. From the early studies information on composition, lipid chain dynamics and order parameters, and monolayer organization resulted. More recently, selective or complete isotopic labeling techniques, combined with multidimensional NMR spectroscopy, have resulted in structural information of apoprotein fragments. Finally, use of heteronuclear three- and four-dimensional experiments have yielded solution structures and protein-lipid interactions of intact apolipoproteins C-I, C-II, and A-I.