Fluorescent sensing and selective Pb(II) extraction by a dansylamide ion-exchanger.
The (bis)dansylated sulfonamide 1,2-C6H4(NHSO2C10H6-5-N(CH3)2)2 (1) extracted Pb(II) selectively from water into 1,2-dichloroethane via an ion-exchange mechanism and showed fluorescence quenching upon Pb(II) extraction. The distribution ratios for metal extraction (determined by ICP-MS) for Pb(II) were 133-1410 times higher than those for other metal cations [Co(II), Ni(II), Cu(II), Zn(II), and Cd(II)] under identical conditions. Fluorescence quenching was observed upon Pb(II) extraction, which was dependent on Pb(II) concentration. The monodansylated control, C6H5NHSO2C10H6-5-N(CH3)2 (2), showed neither extraction nor quenching, indicating that the fluorescence effects are a direct result of Pb coordination to 1. The observed selectivity for Pb(II) is ascribed to the formation of a low-coordinate binary Pb(II)-Sulfonamido complex in the organic phase.


Spontaneous spinal epidural hematoma developing after percutaneous coronary intervention: early diagnosis, early intervention, and good outcome.
A 56-year-old female patient hospitalized with diagnosis of acute coronary syndrome underwent early coronary intervention. Anticoagulant and antithrombotic treatment was administered, including acetylsalicylic acid, clopidogrel, and heparin in periprocedural period. Severe back pain and rapidly progressing paraplegia developed in early period of follow-up. The patient underwent surgery immediately after diagnosis of spontaneous spinal epidural hematoma (SSEH) causing pressure, and decompression was performed. The patient rapidly improved without recurrence through early diagnosis and early surgical intervention. A common problem encountered by interventional cardiologists is back pain in patients who have undergone interventions in the femoral region and have lain in the same position for an extended period. Clinical onset of SSEH includes similar complaints, a fact of which cardiologists should be aware. Early diagnosis and early intervention may provide a good outcome, as is reported in the present case.


Hematopoietic Stem Cell Transplantation: A Bioethical Lens.
Hematopoietic stem cell transplantation (HSCT) is one of a range of therapeutic options available to patients suffering from various diseases. HSCT procedure involves important ethical and legal aspects that can occur at every phase of the procedure: the clinical choice of whether to perform the procedure, pretransplantation preparation regimens, donor selection, stem cell harvest procedure, transplantation phase, and short-term and long-term follow-up care. In this discussion paper, we outline the ethical issue-facing physicians involved in HSCT. Currently, HSCT is a widely accepted treatment for many life-threatening diseases. It thus represents a real therapeutic hope for many patients. It does, however, carry a burden of possible morbidity and mortality. Consequently, there are substantial information and communication issues involved in the consent process for HSCT. In the final decision, the judgements of different parties, such as patients, family members, and healthcare professionals, intersect and overlap and this is particularly true when the patient is a minor. Finally, HSCT is a very expensive procedure. The social and economic concerns of HSCT are discussed within the actual contextual framework of the dramatic increase in healthcare costs and inequalities in healthcare in relation to socioeconomic status, educational status, and ethnicity.


A training intervention for supervisors to support a work-life policy implementation.
Effective policy implementation is essential for a healthy workplace. The Ryan-Kossek 2008 model for work-life policy adoption suggests that supervisors as gatekeepers between employer and employee need to know how to support and communicate benefit regulations. This article describes a workplace intervention on a national employee benefit, Family and Medical Leave Act (FMLA), and evaluates the effectiveness of the intervention on supervisor knowledge, awareness, and experience with FMLA. The intervention consisted of computer-based training (CBT) and a survey measuring awareness and experience with FMLA. The training was administered to 793 county government supervisors in the state of Oregon, USA. More than 35% of supervisors reported no previous training on FMLA and the training pre-test revealed a lack of knowledge regarding benefit coverage and employer responsibilities. The CBT achieved: (1) a significant learning effect and large effect size of d = 2.0, (2) a positive reaction to the training and its design, and (3) evidence of increased knowledge and awareness regarding FMLA. CBT is an effective strategy to increase supervisors' knowledge and awareness to support policy implementation. The lack of supervisor training and knowledge of an important but complex employee benefit exposes a serious impediment to effective policy implementation and may lead to negative outcomes for the organization and the employee, supporting the Ryan-Kossek model. The results further demonstrate that long-time employees need supplementary training on complex workplace policies such as FMLA.


Burning pain: axonal dysfunction in erythromelalgia.
Erythromelalgia (EM) is a rare neurovascular disorder characterized by intermittent severe burning pain, erythema, and warmth in the extremities on heat stimuli. To investigate the underlying pathophysiology, peripheral axonal excitability studies were performed and changes with heating and therapy explored. Multiple excitability indices (stimulus-response curve, strength-duration time constant (SDTC), threshold electrotonus, and recovery cycle) were investigated in 23 (9 EMSCN9A+ and 14 EMSCN9A-) genetically characterized patients with EM stimulating median motor and sensory axons at the wrist. At rest, patients with EM showed a higher threshold and rheobase (P < 0.001) compared with controls. Threshold electrotonus and current-voltage relationships demonstrated greater changes of thresholds in both depolarizing and hyperpolarizing preconditioning electrotonus in both EM cohorts compared with controls in sensory axons (P < 0.005). When average temperature was raised from 31.5°C to 36.3°C in EMSCN9A+ patients, excitability changes showed depolarization, specifically SDTC significantly increased, in contrast to the effects of temperature previously established in healthy subjects (P < 0.05). With treatment, 4 EMSCN9A+ patients (4/9) reported improvement with mexiletine, associated with reduction in SDTC in motor and sensory axons. This is the first study of primary EM using threshold tracking techniques to demonstrate alterations in peripheral axonal membrane function. Taken together, these changes may be attributed to systemic neurovascular abnormalities in EM, with chronic postischaemic resting membrane potential hyperpolarization due to Na/K pump overactivity. With heating, a trigger of acute symptoms, axonal depolarization developed, corresponding to acute axonal ischaemia. This study has provided novel insights into EM pathophysiology.


Mechano-biology of skeletal muscle hypertrophy and regeneration: possible mechanism of stretch-induced activation of resident myogenic stem cells.
In undamaged postnatal muscle fibers with normal contraction and relaxation activities, quiescent satellite cells of resident myogenic stem cells are interposed between the overlying external lamina and the sarcolemma of a subjacent mature muscle fiber. When muscle is injured, exercised, overused or mechanically stretched, these cells are activated to enter the cell proliferation cycle, divide, differentiate, and fuse with the adjacent muscle fiber, and are responsible for regeneration and work-induced hypertrophy of muscle fibers. Therefore, a mechanism must exist to translate mechanical changes in muscle tissue into chemical signals that can activate satellite cells. Recent studies of satellite cells or single muscle fibers in culture and in vivo demonstrated the essential role of hepatocyte growth factor (HGF) and nitric oxide (NO) radical in the activation pathway. These experiments have also reported that mechanically stretching satellite cells or living skeletal muscles triggers the activation by rapid release of HGF from its extracellular tethering and the subsequent presentation to the receptor c-met. HGF release has been shown to rely on calcium-calmodulin formation and NO radical production in satellite cells and/or muscle fibers in response to the mechanical perturbation, and depend on the subsequent up-regulation of matrix metalloproteinase (MMP) activity. These results indicate that the activation mechanism is a cascade of events including calcium ion influx, calcium-calmodulin formation, NO synthase activation, NO radical production, MMP activation, HGF release and binding to c-met. Better understanding of 'mechano-biology' on the satellite cell activation is essential for designing procedures that could enhance muscle growth and repair activities in meat-animal agriculture and also in neuromuscular disease and aging in humans.


Hydrogel/nanoadjuvant-mediated combined cell vaccines for cancer immunotherapy.
Combined cell vaccines of tumor whole cells and dendritic cells (DCs) provide an effective individualized immunotherapy for malignant tumors. We propose an innovative strategy termed "biomaterial-mediated combined cell vaccines for immunotherapy," which combines tumor cell and DC vaccines with a cyclodextrin-polyethylene glycol hydrogel and a cytosine-phosphate-guanine (CpG) nanoadjuvant. The nanoadjuvant promotes antigen presentation and amplifies immune-eliciting potency by co-delivery of antigens and adjuvants. The hydrogel scaffold provides a better growth microenvironment for injected exogenous DCs and recruits endogenous DCs to maintain their viability for synergistic effect. The results indicated that, relative to live tumor cells, the immunogenically dying tumor cells activated DC maturation effectively with the auxiliary effect of immune adjuvant CpG nanoparticles. The increased T cell percentage, proliferation ability, cytokine secretion, and cytotoxic effect revealed the enhanced immunogenicity of the combined cell vaccines. The combined hydrogel/nanoadjuvant system showed the best efficiency in inhibiting tumor growth. Moreover, vaccination with a single dose of hydrogel-based combined vaccines significantly delayed the development of tumors. The biomaterial-mediated combined cell vaccines remarkably increased the infiltration of effector T cells, alleviated the intratumoral immunosuppressive microenvironment, and maximized the immune effect of the vaccines, thus improving cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Cell-based vaccines, including tumor whole-cell vaccine or DC vaccine, have attracted wide attention as an effective method for cancer immunotherapy. However, it is difficult to gain satisfactory outcomes in clinical trials because of the low immunogenicity of tumor whole cell vaccine and the short-term survival of transferred DC vaccine. Therefore, improving the ability of cell-based vaccines to induce a strong and durable immune response is the primary objective for vaccine development. Biomaterial-mediated combined cell vaccines is an innovative strategy for cancer immunotherapy. The combined hydrogel/ nanoadjuvant system comprises immunogenically dying tumor cells, DCs, and nanoadjuvants. Nanoadjuvant-loaded immunogenically dying tumor cells can induce efficient immune response as the tumor cell vaccine. The hydrogel-based combined tumor cell/DC vaccine could be used for individualized immunotherapy.


[Safety and the Short-Term Efficacy of Venetoclax Combined with Azacitidine Followed by Cladribine in Children with Refractory/Relapsed Acute Myeloid Leukemia].
To investigate the safety and the short-term efficacy of venetoclax combined with azacitidine followed by cladribine (VAC regimen) in children with refractory/ relapsed acute myeloid leukemia (AML). The clinical data, treatment outcomes, complications, and blood product consumption of 6 children with refractory/relapsed AML treated with VAC regimen in the Children's Hospital of Soochow University from August 2021 to December 2021 were retrospectively analyzed. Among the 6 children, there were 1 male and 5 females. 5 cases were refractory AML, and 1 case was relapsed AML, which recurred again 16 months after allogeneic hematopoietic stem cell transplantation. 4 children were accompanied by chromosomes or genes that predicted poor prognosis, such as RUNX1, FLT3-ITD, KMT2A exon 2-exon 8 dup, MLL-AF6, 7q-, KMT2A exon 2-exon 10 dup, etc. After received VAC regimen, 4 cases achieved CR+CRi, 1 case achieved PR (only MRD did not relieve, MRD was 0.59%), and 1 case was NR (but the proportion of bone marrow blasts decreased). All 6 patients had grade Ⅳ neutropenia, and 4 patients had grade Ⅳ thrombocytopenia. During the period of neutropenia, none of the 6 children developed symptoms of infection such as fever, cough, and diarrhea. No treatment-related death occurred. Venetoclax combined with azacitidine followed by cladribine provides a new treatment option for patients with relapsed/refractory AML who have poor efficacy in early induction remission theragy, showing good efficacy and safety.


Regional cerebral glucose metabolism in dementia with Lewy bodies and Alzheimer's disease: a comparative study using positron emission tomography.
Regional cerebral metabolic rate of glucose (rCMRglc) was studied in 19 patients with a clinical diagnosis of dementia with Lewy bodies (DLB) and 19 patients with a clinical diagnosis of Alzheimer's disease (AD), using [18F]fluorodeoxyglucose ([18F]FDG) and positron emission tomography (PET). The two groups were matched with age, gender, disease duration and severity of cognitive disturbances. In 'dementia with Lewy bodies' (DLB) patients, when compared with AD patients, significant rCMRglc decreases were distributed in the temporo-parieto-occipital association cortices and the cerebellar hemispheres. In contrast, the medial temporal and cingulate rCMRglc were significantly lower in AD patients than those in DLB patients. These different regional emphases of glucose hypometabolism are consistent with the pathological and neurochemical differences between DLB and AD and explain the different clinical features of the two diseases.


[Estimation of diffuse bone marrow infiltration of the spine in multiple myeloma: correlation of MRT with histological results].
To determine the detection of diffuse bone marrow infiltration with MRI in comparison with histopathological findings. MRI was performed on 45 patients with histologically proven multiple myeloma and on 30 healthy individuals. Three experienced radiologists read separately Tl-weighted SE sequences, STIR sequences and the combination of Tl-weighted SE and STIR sequences of the spine. Additionally, Tl-weighted SE sequences were obtained after gadolinium administration and the percentage increase in signal intensity was calculated. Bone marrow histology was used as gold standard for assessing the grade of infiltration. A dichotomous decision (infiltration yes/no) was made when assessing the MRI examinations. For the visual detection of diffuse infiltration, the best sensitivity was found with Tl-weighted SE sequences, achieving 71 % on average. The specificity was 89 %. The STIR sequences showed a sensitivity of 61 % and a specificity of 98 %, and the combination of Tl-weighted/STIR-sequences achieved a sensitivity of 65 % and a specificity of 94 %. In comparison with the histological findings, the sensitivity of the Tl-weighted sequences was 35 % for low-grade, 89 % for moderate and 100 % for high-grade infiltration. The application of contrast material with calculation of the percentage signal increase improved the detection by 7 %. The sensitivity of the visual detection of diffuse multiple myeloma with unenhanced MRI is limited for low-grade or moderate infiltration, whereas the sensitivity for high grade infiltration is reliable. The specificity is high and the diagnostic confidence improves after application of contrast material with calculation of the percentage increase in signal intensity.


[Perinatal audit: the most important legal aspects].
In The Netherlands a perinatal audit system is being prepared. Perinatal audit is seen as a powerful means of identifying substandard factors in perinatal care and of increasing the quality of care with better grounding. The proposed system does not raise insurmountable legal problems. However, certain legal aspects should be given specific attention. These aspects include the rights of patients with respect to privacy and information and the protection of health professionals against use of information from the audit system for reasons other than quality purposes. Legislation from other countries may inspire legislative developments in The Netherlands in this area.


The incidence of Echinococcus infection in dogs, sheep and goats slaughtered in Ibadan, Nigeria.
An investigation was conducted to determine the incidence of Echinococcus infection among dogs and slaughtered sheep and goats in Ibadan Municipality. Of 102 dogs examined, forty-nine (48%) had Echinococcus-like ova. Parasite eggs from four (3.9%) of these animals produced Echinococcus larvae when cultured while twenty (19.6%) of the faecal samples had proglottides. Two hundred and fifteen sheep and goats were examined at four different abattoirs. Only 28% had hydatid cysts.


Increased activity of the glucose cycle in the liver: early characteristic of type 2 diabetes.
The aims were to assess in the mild, lean, type 2 diabetics the activity of the hepatic futile cycle (glucose cycling) in the basal state and during an infusion of glucose and the overall contribution of futile cycling and the relative contributions of the liver and the periphery to excessive hyperglycemia during a glucose challenge. To determine hepatic futile cycling, we studied seven healthy controls (C) and eight mild, lean, type 2 diabetics with decreased oral glucose tolerance test and blood glucose of 123 +/- 4 mg/dl. Experiments included an equilibration period, followed by a 2-hr infusion of glucose at 2 mg/kg of body weight per min. In each subject, two such experiments were performed randomly with infusions of [2-3H]glucose or [3-3H]glucose to calculate, respectively, total glucose output or total glucose phosphorylation and glucose production or irreversible glucose loss. Futile cycling equals the difference between glucose turnover measured by the two tracers. In controls basal glucose production was 2.0 +/- 0.09 mg/kg per min, and it decreased by 75% during glucose infusion; futile cycling could not be detected. Plasma glucose increased by 30% and plasma C-peptide by 88%. In the diabetics total glucose output (2.41 +/- 0.17 mg/kg per min) was larger than glucose production (2.12 +/- 0.16 mg/kg per min), indicating a glucose cycle. During the glucose infusion, glucose production in the diabetics as well as in the controls decreased by 75% (to 0.6 mg/kg per min) despite higher than normal plasma glucose and C-peptide; futile cycling amounted to 0.6 mg/kg per min, which is half of the total glucose output; increase of glucose uptake was essentially only due to phosphorylation of glucose because irreversible uptake increased only marginally; and most glucose taken up by the liver during the glucose challenge reenters the blood stream without being oxidized or polymerized. These findings, when compared to our previous work in which controls were infused with glucose at 4 mg/kg per min, indicate that excessive hyperglycemia in the diabetics during glucose infusion is due to a decrease in irreversible glucose uptake (impaired phosphorylation and futile cycling) and to a decrease in suppression of glucose production. The relative contributions of the liver and periphery to hyperglycemia seem to be almost equivalent. The mechanism behind the increased glucose cycle activity is not clear; it may be due to a relative decrease of glycogen synthase or increase in glucose-6-phosphatase or both.


Stem cell-derived nodal-like cardiomyocytes as a novel pharmacologic tool: insights from sinoatrial node development and function.
Since the first reports on the isolation and differentiation of stem cells, and in particular since the early success in driving these cells down a cardiac lineage, there has been interest in the potential of such preparations in cardiac regenerative therapy. Much of the focus of such research has been on improving mechanical function after myocardial infarction; however, electrophysiologic studies of these preparations have revealed a heterogeneous mix of action potential characteristics, including some described as "pacemaker" or "nodal-like," which in turn led to interest in the therapeutic potential of these preparations in the treatment of rhythm disorders; several proof-of-concept studies have used these cells to create a biologic alternative to electronic pacemakers. Further, there are additional potential applications of a preparation of pacemaker cells derived from stem cells, for example, in high-throughput screens of new chronotropic agents. All such applications require reasonably efficient methods for selecting or enriching the "nodal-like" cells, however, which in turn depends on first defining what constitutes a nodal-like cell since not all pacemaking cells are necessarily of nodal lineage. This review discusses the current state of the field in terms of characterizing sinoatrial-like cardiomyocytes derived from embryonic and induced pluripotent stem cells, markers that might be appropriate based on the current knowledge of the gene program leading to sinoatrial node development, what functional characteristics might be expected and desired based on studies of the sinoatrial node, and recent efforts at enrichment and selection of nodal-like cells.


A hydraulic model is compatible with rapid changes in leaf elongation under fluctuating evaporative demand and soil water status.
Plants are constantly facing rapid changes in evaporative demand and soil water content, which affect their water status and growth. In apparent contradiction to a hydraulic hypothesis, leaf elongation rate (LER) declined in the morning and recovered upon soil rehydration considerably quicker than transpiration rate and leaf water potential (typical half-times of 30 min versus 1-2 h). The morning decline of LER began at very low light and transpiration and closely followed the stomatal opening of leaves receiving direct light, which represent a small fraction of leaf area. A simulation model in maize (Zea mays) suggests that these findings are still compatible with a hydraulic hypothesis. The small water flux linked to stomatal aperture would be sufficient to decrease water potentials of the xylem and growing tissues, thereby causing a rapid decline of simulated LER, while the simulated water potential of mature tissues declines more slowly due to a high hydraulic capacitance. The model also captured growth patterns in the evening or upon soil rehydration. Changes in plant hydraulic conductance partly counteracted those of transpiration. Root hydraulic conductivity increased continuously in the morning, consistent with the transcript abundance of Zea maize Plasma Membrane Intrinsic Protein aquaporins. Transgenic lines underproducing abscisic acid, with lower hydraulic conductivity and higher stomatal conductance, had a LER declining more rapidly than wild-type plants. Whole-genome transcriptome and phosphoproteome analyses suggested that the hydraulic processes proposed here might be associated with other rapidly occurring mechanisms. Overall, the mechanisms and model presented here may be an essential component of drought tolerance in naturally fluctuating evaporative demand and soil moisture.


Synopsis of partial-body radiation diagnostic biomarkers and medical management of radiation injury workshop.
Radiation exposures from accidents, nuclear detonations or terrorist incidents are unlikely to be homogeneous; however, current biodosimetric approaches are developed and validated primarily in whole-body irradiation models. A workshop was held at the Armed Forces Radiobiology Research Institute in May 2008 to draw attention to the need for partial-body biodosimetry, to discuss current knowledge, and to identify the gaps to be filled. A panel of international experts and the workshop attendees discussed the requirements and concepts for a path forward. This report addresses eight key areas identified by the Workshop Program Committee for future focus: (1) improved cytogenetics, (2) clinical signs and symptoms, (3) cutaneous bioindicators, (4) organ-specific biomarkers, (5) biophysical markers of dose, (6) integrated diagnostic approaches, (7) confounding factors, and (8) requirements for post-event medical follow-up. For each area, the status, advantages and limitations of existing approaches and suggestions for new directions are presented.


Disagreement in primary study selection between systematic reviews on negative pressure wound therapy.
Primary study selection between systematic reviews is inconsistent, and reviews on the same topic may reach different conclusions. Our main objective was to compare systematic reviews on negative pressure wound therapy (NPWT) regarding their agreement in primary study selection. This retrospective analysis was conducted within the framework of a systematic review (a full review and a subsequent rapid report) on NPWT prepared by the Institute for Quality and Efficiency in Health Care (IQWiG). For the IQWiG review and rapid report, 4 bibliographic databases (MEDLINE, EMBASE, The Cochrane Library, and CINAHL) were searched to identify systematic reviews and primary studies on NPWT versus conventional wound therapy in patients with acute or chronic wounds. All databases were searched from inception to December 2006. For the present analysis, reviews on NPWT were classified as eligible systematic reviews if multiple sources were systematically searched and the search strategy was documented. To ensure comparability between reviews, only reviews published in or after December 2004 and only studies published before June 2004 were considered. Eligible reviews were compared in respect of the methodology applied and the selection of primary studies. A total of 5 systematic reviews (including the IQWiG review) and 16 primary studies were analysed. The reviews included between 4 and 13 primary studies published before June 2004. Two reviews considered only randomised controlled trials (RCTs). Three reviews considered both RCTs and non-RCTs. The overall agreement in study selection between reviews was 96% for RCTs (24 of 25 options) and 57% for non-RCTs (12 of 21 options). Due to considerable disagreement in the citation and selection of non-RCTs, we contacted the review authors for clarification (this was not initially planned); all authors or institutions responded. According to published information and the additional information provided, most differences between reviews arose from variations in inclusion criteria or inter-author study classification, as well as from different reporting styles (citation or non-citation) for excluded studies. The citation and selection of primary studies differ between systematic reviews on NPWT, particularly with regard to non-RCTs. Uniform methodological and reporting standards need to be applied to ensure comparability between reviews as well as the validity of their conclusions.


Three-Dimensional Remodeling of SARS-CoV2-Infected Cells Revealed by Cryogenic Soft X-ray Tomography.
Plus-strand RNA viruses are proficient at remodeling host cell membranes for optimal viral genome replication and the production of infectious progeny. These ultrastructural alterations result in the formation of viral membranous organelles and may be observed by different imaging techniques, providing nanometric resolution. Guided by confocal and electron microscopy, this study describes the generation of wide-field volumes using cryogenic soft-X-ray tomography (cryo-SXT) on SARS-CoV-2-infected human lung adenocarcinoma cells. Confocal microscopy showed accumulation of double-stranded RNA (dsRNA) and nucleocapsid (N) protein in compact perinuclear structures, preferentially found around centrosomes at late stages of the infection. Transmission electron microscopy (TEM) showed accumulation of membranous structures in the vicinity of the infected cell nucleus, forming a viral replication organelle containing characteristic double-membrane vesicles and virus-like particles within larger vesicular structures. Cryo-SXT revealed viral replication organelles very similar to those observed by TEM but indicated that the vesicular organelle observed in TEM sections is indeed a vesiculo-tubular network that is enlarged and elongated at late stages of the infection. Overall, our data provide additional insight into the molecular architecture of the SARS-CoV-2 replication organelle.


Physician practices in the diagnosis and treatment of infectious diseases in home care settings: A questionnaire study.
To elucidate the current practices of infectious disease management in home care settings in Japan, we sent a questionnaire to 36 physicians working at 13 clinics that specialize in providing care to patients in their homes or residential care facilities. The questionnaire described three hypothetical scenarios (aspiration pneumonia, pyelonephritis, and neoplastic fever) in older patients with terminal cancer, and 25 respondents answered questions on testing and treatment strategies. Most respondents chose to obtain cultures for aspiration pneumonia (sputum) and for pyelonephritis (urine), although fewer respondents chose to obtain blood cultures. For neoplastic fever, most of respondents elected to continue observation without antibiotic treatment. The most frequently selected antibiotics were cephalosporins and quinolones. The results indicated that most respondents would perform bacterial culture tests before prescribing antibiotics and observe patients when bacterial infections are not suspected. Standardized guidelines are needed to optimize infectious disease management in home care.


Protective effect of adenosine receptors against lipopolysaccharide-induced acute lung injury.
Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) affect 200,000 people a year in the USA. Pulmonary vascular and specifically endothelial cell (EC) barrier compromise is a hallmark of these diseases. We have recently shown that extracellular adenosine enhances human pulmonary (EC) barrier via activation of adenosine receptors (ARs) in cell cultures. On the basis of these data, we hypothesized that activation of ARs might exert barrier-protective effects in a model of ALI/ARDS in mice. To test this hypothesis, we examined the effects of pre- and posttreatment of adenosine and 5'-N-ethylcarboxamidoadenosine (NECA), a nonselective stable AR agonist, on LPS-induced lung injury. Mice were given vehicle or LPS intratracheally followed by adenosine, NECA, or vehicle instilled via the internal jugular vein. Postexperiment cell counts, Evans Blue Dye albumin (EBDA) extravasation, levels of proteins, and inflammatory cytokines were analyzed. Harvested lungs were used for histology and myeloperoxidase studies. Mice challenged with LPS alone demonstrated an inflammatory response typical of ALI. Cell counts, EBDA extravasation, as well as levels of proteins and inflammatory cytokines were decreased in adenosine-treated mice. Histology displayed reduced infiltration of neutrophils. NECA had a similar effect on LPS-induced vascular barrier compromise. Importantly, posttreatment with adenosine or NECA recovers lung vascular barrier and reduces inflammation induced by LPS challenge. Furthermore, adenosine significantly attenuated protein degradation of A2A and A3 receptors induced by LPS. Collectively, our results demonstrate that activation of ARs protects and restores vascular barrier functions and reduces inflammation in LPS-induced ALI.


Harnessing Nucleophilicity of Allenol Ester with p-Quinone Methides via Gold Catalysis: Application to the Synthesis of Diarylmethine-Substituted Enones.
A gold(I)-catalyzed protocol for intermolecular 1,6-conjugate addition of nucleophilic allenol ester generated in situ through [3,3]-sigmatropic rearrangement with p-quinone methides ( p-QMs) has been developed. The gold catalyst plays a dual role by the π-acid-triggered activation of alkynes and at the same time as a Lewis acid for activation of p-QMs toward nucleophilic attack. This method enables rapid access to a wide range of densely functionalized diarylmethine-substituted enones, a Morita-Baylis-Hillman (MBH) product with high selectivity, excellent yields, and broad substrate scope.


Interplays of different types of epitranscriptomic mRNA modifications.
Eukaryotic mRNAs are modified by several chemical marks which have significant impacts on mRNA biology, gene expression, and cellular metabolism as well as on the survival and development of the whole organism. The most abundant and well-studied mRNA base modifications are m6A and ADAR RNA editing. Recent studies have also identified additional mRNA marks such as m6Am, m5C, m1A and Ψ and studied their roles. Each type of modification is deposited by a specific writer, many types of modification are recognized and interpreted by several different readers and some types of modifications can be removed by eraser enzymes. Several works have addressed the functional relationships between some of the modifications. In this review we provide an overview on the current status of research on the different types of mRNA modifications and about the crosstalk between different marks and its functional consequences.


[The use of fractionation in a polyethylene glycol-dextran two-phase system for the testing and purification of restriction endonucleases].
A simple procedure was developed for testing and purification of restriction endonucleases Msp I, Pst I, Bam HI, Pvu I, Pvu II that includes biomass destruction, fractionation of cell-free extracts in the aqueous two-phase (polyethylene glycol-dextran) system and chromatography oh phosphocellulose. Optimal conditions for the fractionation of Msp I, Pst I, Bam HI, Pvu II, EcoR I, EcoR II, BspR I, Alu I were chosen. For separation of Pvu I and Pvu II gel filtration through biogel A-0.5 m was additionally introduced.


Responsive medical professionalism: integrating education, practice, and community in a market-driven era.
Revolutionary changes in the nature and form of medical practice institutions are likely to reverberate backward into medical education as leaders of the new practice organizations demand that the educational mission be responsive to their needs, and as these demands are increasingly backed by market power. In the face of this pressure, medical education's traditional response--that it should have autonomy in defining its mission--is no longer viable. Instead, more explicit, formal, and systemic linkages between practice and educational institutions are inevitable. The crucial question is whether these linkages will reflect the values of the market, oriented by economic self-interest, or the values of medical professionalism, oriented by the obligation to sacrifice economic self-interest in the service of patients. The authors maintain that the realization of the normative ideal of professionalism in medical education within the emerging market environment requires that a vision be articulated that is distinct from that of either autonomy or the market, and that combined lay-professional institutions be established to integrate--and perhaps merge--education and practice, and to foster responsiveness to lay values and community needs. The authors conclude by briefly describing examples of current efforts in this direction.


The Use of Sign Language Pronouns by Native-Signing Children with Autism.
We report the first study on pronoun use by an under-studied research population, children with autism spectrum disorder (ASD) exposed to American Sign Language from birth by their deaf parents. Personal pronouns cause difficulties for hearing children with ASD, who sometimes reverse or avoid them. Unlike speech pronouns, sign pronouns are indexical points to self and other. Despite this transparency, we find evidence from an elicitation task and parental report that signing children with ASD avoid sign pronouns in favor of names. An analysis of spontaneous usage showed that all children demonstrated the ability to point, but only children with better-developed sign language produced pronouns. Differences in language abilities and self-representation may explain these phenomena in sign and speech.


Increased prevalence of gastroesophageal reflux symptoms in patients with COPD.
To determine the prevalence of gastroesophageal reflux (GER) symptoms in patients with COPD and the association of GER symptoms with the severity of airways obstruction as assessed by pulmonary function tests (PFTs). Prospective questionnaire-based, cross-sectional analytic survey. Outpatient pulmonary and general medicine clinics at a Veterans Administration hospital. Patients with mild-to-severe COPD (n = 100) were defined based on American Thoracic Society criteria. The control group (n = 51) consisted of patients in the general medicine clinic without respiratory complaints or prior diagnosis of asthma or COPD. Both groups completed a modified version of the Mayo Clinic GER questionnaire. Compared to control subjects, a greater proportion of COPD patients had significant GER symptoms defined as heartburn and/or regurgitation once or more per week (19% vs 0%, respectively; p < 0.001), chronic cough (32% vs 16%; p = 0.03), and dysphagia (17% vs 4%; p = 0.02). Among patients with COPD and significant GER symptoms, 26% reported respiratory symptoms associated with reflux events, whereas control subjects denied an association. Significant GER symptoms were more prevalent in COPD patients with FEV(1) < or %, as compared with patients with FEV(1) > 50% of predicted (23% vs 9%, respectively; p = 0.08). In contrast, PFT results were similar among COPD patients with and without GER symptoms. An increased number of patients with COPD utilized antireflux medications, compared to control subjects (50% vs 27%, respectively; p = 0.008). The questionnaire demonstrated a higher prevalence of weekly GER symptoms in patients with COPD, as compared to control subjects. There was a trend toward higher prevalence of GER symptoms in patients with severe COPD; however, this difference did not reach statistical significance. We speculate that although GER may not worsen pulmonary function, greater expiratory airflow limitation may worsen GER symptoms in patients with COPD.


Pesticide-associated pemphigus vulgaris.
We present a 40-year-old man with occupation-induced pemphigus vulgaris (PV). He developed PV within days of a one-time heavy exposure to fumes of burning glyphosate, a broad-spectrum nonselective pesticide. This exposure suggests acute cutaneous contact as a stimulus in the development of his pemphigus. While the patient initially required mycophenolate mofetil and prednisone therapy, he has since eliminated contact with pesticides and has been successfully tapered off systemic medication. We discuss the case and review concepts of inducible PV by pesticides and physical cutaneous injury.


Subunit interactions and composition of the fructose 6-phosphate catalytic site and the fructose 2,6-bisphosphate allosteric site of mammalian phosphofructokinase.
Mammalian phosphofructokinase originated by duplication, fusion, and divergence of a primitive prokaryotic gene, with the duplicated fructose 6-phosphate catalytic site in the C-terminal half becoming an allosteric site for the activator fructose 2,6-bisphosphate. It has been suggested that both sites are shared across the interface between subunits aligned in an antiparallel orientation, the N-terminal half of one subunit facing the C-terminal half of the other. The composition of these binding sites and the way in which subunits interact to form the dimer within the tetrameric enzyme have been reexamined by systematic point mutations to alanine of key amino acid residues of human muscle phosphofructokinase. We found that residues His-199, His-298, Arg-201, and Arg-292 contribute to the catalytic site and not to the allosteric site, because their mutation decreased the affinity for fructose 6-phosphate without affecting the activation by fructose 2,6-bisphosphate or its binding affinity. In contrast, residues Arg-566, Arg-655, and His-661 were critical components of the fructose bisphosphate allosteric site, because their mutation strongly reduced the action and affinity of the activator, with no alteration of substrate binding to the active site. Our results suggest that mammalian phosphofructokinase subunits associate with the N-terminal halves facing each other to form the two catalytic sites/dimer and the C-terminal halves forming the allosteric sites. Additionally, mutation of certain residues eliminated activation by fructose 1,6-bisphosphate, but not its binding, with little effect on activation by fructose 2,6-bisphosphate, indicating a divergence in the signal transduction route despite their binding to the same site.


Impact of psychosocial factors on functional improvement in Latino older adults after Tai Chi exercise.
Increasing evidence underscores the health benefits of Tai Chi (TC), although there is limited evidence of benefits among racial and ethnic minorities. This study investigated the impact of psychosocial status on balance among 23 Latino seniors after a twice-a-week, 12-week TC exercise program. Functional status was measured at baseline, immediately after, and three months following the TC exercise program, using the Timed Up and Go Test and Tinetti Falls Efficacy Scale. Psychosocial status was measured at baseline by the Center for Epidemiologic Studies Depression Scale and Norbeck Social Support Questionnaire. Both measures of functional status improved and were sustained after three months of TC. Greater improvement was significantly related to a higher level of baseline social support. More depressed seniors reported less fear of falling after TC. Depression and social support are important moderators of functional improvement after TC among Latino seniors.


Improving quality through identifying inappropriate care: the use of guideline-based utilization review protocols in the Washington State Workers' Compensation System.
Utilization review (UR) is widely instituted to ensure that medical treatment is clinically necessary and appropriate. UR programs have been criticized for their failure to promote quality and for relying on proprietary review criteria that are rarely subject to external, independent evaluation or validation. In fashioning its UR program for workers' compensation, the Washington State Department of Labor and Industries sought to address these shortcomings. Working collaboratively with the state medical association, the Department of Labor and Industries developed treatment guidelines and then used these guidelines to formulate review criteria for UR. From 1993 through 1998, 100,005 UR reviews were conducted, half of which used the guideline-based review criteria. We analyzed these reviews to examine the patterns of denied requests. The overall denial rate for the guideline-based reviews was 7.3%. The highest denial rates were for thoracic outlet syndrome surgery (19.1%) and lumbar fusion (17.7%). The use of guideline-based UR protocols may improve the effectiveness of UR as a tool to identify potentially inappropriate care.


Imbalance of desmoplastic stromal cell numbers drives aggressive cancer processes.
Epithelial tissues have sparse stroma, in contrast to their corresponding tumours. The effect of cancer cells on stromal cells is well recognized. Increasingly, stromal components, such as endothelial and immune cells, are considered indispensable for cancer progression. The role of desmoplastic stroma, in contrast, is poorly understood. Targeting such cellular components within the tumour is attractive. Recent evidence strongly points towards a dynamic stromal cell participation in cancer progression that impacts patient prognosis. The role of specific desmoplastic stromal cells, such as stellate cells and myofibroblasts in pancreatic, oesophageal and skin cancers, was studied in bio-engineered, physiomimetic organotypic cultures and by regression analysis. For pancreatic cancer, the maximal effect on increasing cancer cell proliferation and invasion, as well as decreasing cancer cell apoptosis, occurs when stromal (pancreatic stellate cells) cells constitute the majority of the cellular population (maximal effect at a stromal cell proportion of 0.66-0.83), accompanied by change in expression of key molecules such as E-cadherin and β-catenin. Gene-expression microarrays, across three tumour types, indicate that stromal cells consistently and significantly alter global cancer cell functions such as cell cycle, cell-cell signalling, cell movement, cell death and inflammatory response. However, these changes are mediated through cancer type-specific alteration of expression, with very few common targets across tumour types. As highlighted by these in vitro data, the reciprocal relationship of E-cadherin and polymeric immunoglobulin receptor (PIGR) expression in cancer cells could be shown, in vivo, to be dependent on the stromal content of human pancreatic cancer. These studies demonstrate that context-specific cancer-stroma crosstalk requires to be precisely defined for effective therapeutic targeting. These data may be relevant to non-malignant processes where epithelial cells interact with stromal cells, such as chronic inflammatory and fibrotic conditions.


Human cytoplasmic actin proteins are encoded by a multigene family.
We characterized nine human actin genes that we isolated (Engel et al., Proc. Natl. Acad. Sci. U.S.A. 78:4674-4678, 1981) from a library of cloned human DNA. Measurements of the thermal stability of hybrids formed between each cloned actin gene and alpha-, beta-, and gamma-actin mRNA demonstrated that only one of the clones is most homologous to sarcomeric actin mRNA, whereas the remaining eight clones are most homologous to cytoplasmic actin mRNA. By the following criteria we show that these nine clones represent nine different actin gene loci rather than different alleles or different parts of a single gene: (i) the restriction enzyme maps of the coding regions are dissimilar; (ii) each clone contains sufficient coding region to encode all or most of an entire actin gene; and (iii) each clone contains sequences homologous to both the 5' and 3' ends of the coding region of a cloned chicken beta-actin cDNA. We conclude, therefore, that the human cytoplasmic actin proteins are encoded by a multigene family.


A longitudinal study of radiation-induced changes in tumor vasculature by contrast-enhanced magnetic resonance imaging.
Dynamic contrast-enhanced MRI with two different-sized contrast agents, Gd-DTPA and Gadomer-17, was used to study the effects of radiation on the pharmacokinetics of the paramagnetic enhancement of water relaxation in the rat R3230 AC adenocarcinoma tumor model. The kinetics of enhancement was analyzed by a two-compartment pharmacokinetic model to derive parameters related to vascular volume (V(b)) and permeability (K(2)). Rats implanted with tumors were divided into two groups; one received 5 Gy and the other received 20 Gy (137)Cs gamma rays. Sequential dynamic contrast-enhanced MRI studies were performed, one before irradiation, one at day 1 after irradiation, and another at day 3 after irradiation, to investigate the effect of the radiation dose and the changes that occurred over time. The analysis was performed on a pixel-by-pixel basis to study the heterogeneity within the tumor. The pixel distribution profiles of V(b) and K(2) from each tumor were obtained to assess the regional radiation-induced effects on vascular volume and permeability. No significant change in vascular volume was detected with either Gd-DTPA or Gadomer-17 after irradiation of the tumor; however, a small dependence of K(2) on the radiation dose was observed. After low-dose (5 Gy) irradiation, the mean value of K(2) decreased by 46% at day 1 compared to the baseline, presumably due to cell swelling, and decreased further by 67% from the baseline on day 3. When the dose was increased to 20 Gy, the mean value of K(2) measured with Gadomer-17 did not show any significant changes at either day 1 or day 3 after irradiation. The value of K(2) measured with Gd-DTPA did not show any significant changes after either the low or the high radiation dose.


An Evaluation of the Belief in Science Scale.
The Belief in Science Scale (BISS) is a unidimensional measure that assesses the degree to which science is valued as a source of superior knowledge. Due to increased academic interest in the concept of belief in science, the BISS has emerged as an important measurement instrument. Noting an absence of validation evidence, the present paper, via two studies, evaluated the scale's factorial structure. Both studies drew on data collected from previous research. Study 1 (N = 686), using parallel analysis and exploratory factor analysis, identified a unidimensional solution accounting for 56.43% of the observed variance. Study 2 (N = 535), using an independent sample, tested the unidimensional solution using confirmatory factor analysis (CFA). Data-model fit was good (marginal for RMSEA): CFI = 0.93, TLI = 0.91, RMSEA = 0.09 (90% CI of 0.08 to 0.10), SRMR = 0.04. Invariance testing across gender supported invariance of form, factor structure, and item intercepts for this one-factor model. BISS at the overall level correlated negatively with the reality testing dimension of the Inventory of Personality Organization (IPO-RT), demonstrating convergent validity. Researchers often use the IPO-RT as an indirect index of preference for experiential processing (intuitive thinking). In this context, only BISS scores above the median (second quartile) produced a reduction in experiential-based thinking. The authors discuss these findings in the context of belief in science as a psychometric construct.


High-fidelity characterization on anisotropic thermal conductivity of carbon nanotube sheets and on their effects of thermal enhancement of nanocomposites.
Some assemblies of nanomaterials, like carbon nanotube (CNT) sheet or film, always show outstanding and anisotropic thermal properties. However, there is still a lack of comprehensive thermal conductivity (κ) characterizations on CNT sheets, as well as a lack of estimations of their true contributions on thermal enhancement of polymer composites when used as additives. Always, these characterizations were hindered by the low heat capacity, anisotropic thermal properties or low electrical conductivity of assemblies and their nanocomposites. The transient κ measurement and calculations were also hampered by accurate determination of parameters, like specific heat capacity, density and cross-section, which could be difficult and controversial for nanomaterials, like CNT sheets. Here, to measure anisotropic κ of CNT sheets directly with high fidelity, we modified the conventional steady-state method by measuring under vacuum and by infrared camera, and then comparing temperature profiles on both reference standard material and a CNT sheet sample. The highly anisotropic thermal conductivities of CNT sheets were characterized comprehensively, with κ/ρ in alignment direction as ∼95 mW m2 K-1 kg-1. Furthermore, by comparing the measured thermal properties of different CNT-epoxy resin composites, the heat conduction pathway created by the CNT hierarchical network was demonstrated to remain intact after the in situ polymerization and curing process. The reliable and direct κ measurement rituals used here, dedicated to nanomaterials, will be also essential to assist in assemblies' application to heat dissipation and composite thermal enhancement.


Helminth infection impairs the immunogenicity of a Plasmodium falciparum DNA vaccine, but not irradiated sporozoites, in mice.
Development of an effective vaccine against malaria remains a priority. However, a significant number of individuals living in tropical areas are also likely to be co-infected with helminths, which are known to adversely affect immune responses to a number of different existing vaccines. Here we compare the response to two prototype malaria vaccines: a transmission blocking DNA vaccine based on Pfs25, and a pre-erythrocytic malaria vaccine based on irradiated sporozoites in mice infected with the intestinal nematode Heligmosomoides polygyrus. Following primary immunization with Pfs25 DNA vaccine, levels of total IgG, as well as IgG1, IgG2a, IgG2b (all P=0.0002), and IgG3 (P=0.03) Pfs25 antibodies were significantly lower in H. polygyrus-infected mice versus worm-free controls. Similar results were observed even after two additional boosts, while clearance of worms with anthelmintic treatment 3 weeks prior to primary immunization significantly reversed the inhibitory effect of helminth infection. In contrast, helminth infection had no inhibitory effect on immunization with irradiated sporozoites. Mean anti-CSP antibody responses were similar between H. polygyrus-infected and worm-free control mice following immunization with a single dose (65,000 sporozoites) of live radiation attenuated (irradiated) Plasmodium yoelii sporozoites (17X, non-lethal strain), and protection upon sporozoite challenge was equivalent between groups. These results indicate that helminth infection may adversely affect certain anti-malarial vaccine strategies, and highlight the importance of these interactions for malaria vaccine development.


Attention and the readiness for action.
The initiation of voluntary action is preceded by up to 2s of preparatory neural activity, originating in premotor and supplementary motor regions of the brain. The function of this extended period of pre-movement activity is unclear. Although recent studies have suggested that pre-movement activity is influenced by attention to action, little is understood about the specific processes that are involved in this preparatory period prior to voluntary action. We recorded readiness potentials averaged from EEG activity as participants made voluntary self-paced finger movements. We manipulated the processing resources available for action preparation using concurrent perceptual load and cognitive working memory load tasks. Results showed that pre-movement activity was significantly reduced only under conditions of high working memory load, when resources for planning action were limited by the concurrent cognitive load task. In contrast, limiting attentional resources in the perceptual load task had no effect on pre-movement readiness activity. This suggests that movement preparatory processes involve mechanisms of cognitive control that are also required for working memory, and not more general engagement of selective attentional resources. We propose that the extended period of pre-movement neural activity preceding voluntary action reflects the engagement of cognitive control mechanisms for endogenously orienting attention in time, in readiness for the initiation of voluntary action.


Autism spectrum disorders: Integration of the genome, transcriptome and the environment.
Autism spectrum disorders denote a series of lifelong neurodevelopmental conditions characterized by an impaired social communication profile and often repetitive, stereotyped behavior. Recent years have seen the complex genetic architecture of the disease being progressively unraveled with advancements in gene finding technology and next generation sequencing methods. However, a complete elucidation of the molecular mechanisms behind autism is necessary for potential diagnostic and therapeutic applications. A multidisciplinary approach should be adopted where the focus is not only on the 'genetics' of autism but also on the combinational roles of epigenetics, transcriptomics, immune system disruption and environmental factors that could all influence the etiopathogenesis of the disease. ASD is a clinically heterogeneous disorder with great genetic complexity; only through an integrated multidimensional effort can modern autism research progress further.


Psychoeducational Interventions for Supporters of Women with Breast Cancer: an Integrative Review.
The purpose of this review was to identify and evaluate psychoeducational intervention studies addressing the psychological adjustment needs of family members, spouses, and friends (supporters) providing support to women with early-stage breast cancer with the goal of guiding future research and practice. This is an integrative review initiated by a systematic search conducted within the PubMed, CINAHL, and PsycINFO databases among literature published from 2003 to 2014. Articles were retained for evaluation if the sample was from a western culture, and outcomes were reported separately for supporters of women with early-stage breast cancer after receipt of a psychosocial/educational intervention. Studies using qualitative, pilot, and pre-experimental designs were included for review. Six studies meeting the inclusion criteria were identified. Of these, three were randomized controlled trials (one pilot) and three used a pre-experimental, single-group design. All of the interventions demonstrated some efficacy; however, limitations in design, sample, and reporting of outcomes were identified. The pre-experimental and pilot design of the majority of the research identified in this review limits the ability to make firm recommendations for translation to clinical practice although the psychoeducational interventions appear clinically useful. Future research should define samples of supporters consistently across studies, report behavioral and psychological outcomes separately for individuals with differing relationships with the affected woman, increase racial diversity among samples, consider time and cost when designing psychoeducational interventions, and focus interventions on specific characteristics and needs of the diverse groups of individuals who provide support for women with early-stage breast cancer.


CHRFAM7A: A human specific fusion gene, accounts for the translational gap for cholinergic strategies in Alzheimer's disease.
Cholinergic neuronal loss is one of the hallmarks of AD related neurodegeneration; however, preclinical promise of α7 nAChR drugs failed to translate into humans. CHRFAM7A, a uniquely human fusion gene, is a negative regulator of α7 nAChR and was unaccounted for in preclinical models. Molecular methods: Function of CHRFAM7A alleles was studied in vitro in two disease relevant phenotypic readouts: electrophysiology and Aβ uptake. Genome edited human induced pluripotent stem cells (iPSC) were used as a model system with the human context. Double blind pharmacogenetic study: We performed double-blind pharmacogenetic analysis on the effect of AChEI therapy based on CHRFAM7A carrier status in two paradigms: response to drug initiation and DMT effect. Mini Mental Status Examination (MMSE) was used as outcome measure. Change in MMSE score from baseline was compared by 2-tailed T-test. Longitudinal analysis of clinical outcome (MMSE) was performed using a fitted general linear model, based on an assumed autoregressive covariance structure. Model independent variables included age, sex, and medication regimen at the time of the first utilized outcome measure (AChEI alone or AChEI plus memantine), APOE4 carrier status (0, 1 or 2 alleles as categorical variables) and CHRFAM7A genotype. The direct and inverted alleles have distinct phenotypes. Functional CHRFAM7A allele classifies the population as 25% non-carriers and 75% carriers. Induced pluripotent stem cell (iPSC) models α7 nAChR mediated Aβ neurotoxicity. Pharmacological readout translates into both first exposure (p = 0.037) and disease modifying effect (p = 0.0048) in two double blind pharmacogenetic studies. CHRFAM7A accounts for the translational gap in cholinergic strategies in AD. Clinical trials not accounting for this uniquely human genetic factor may have rejected drug candidates that would benefit 25% of AD. Reanalyses of the completed trials using this pharmacogenetic paradigm may identify effective therapy.


Objective and Subjective Eating Speeds Are Related to Body Composition and Shape in Female College Students.
Eating speed reportedly relates to body composition and shape. Little is known about the relationship between the objectively assessed eating speed and the body composition and shape. This study examined relationships between eating speed as assessed both objectively and subjectively, and body composition and shape. The following variables of body composition and shape were measured in 84 female college students: body mass, relative body fat mass (%Fat), body mass index (BMI), and circumferences of the waist, abdomen and hip. After measuring the body composition and shape, subjects consumed a 174-kcal salmon rice ball. The following chewing variables were measured by observing videotape recordings of the subjects' faces: number of chews per bite, total number of chews, total meal duration, number of bites, and chewing rate. The subjects were categorized into three groups (fast, moderate and slow) according to their own subjective assessments of the actual eating speed. In objective assessments of the eating speed, the total number of chews and the total meal duration were significantly negatively correlated with the body mass, %Fat, BMI, and circumferences of the waist, abdomen and hip. In subjective eating-speed assessments, the body mass, %Fat, BMI, and circumferences of the waist, abdomen and hip were greater in the fast eating group than in the slow eating group. Both the objectively and subjectively assessed eating speeds are related to the body composition and shape. The present study supports that fast eating may relate to gains in body mass and/or fat mass.


The impact of clickers in nursing education: a review of literature.
Learner participation and engagement has proven effective and essential across educational settings. Clickers, also known as classroom response systems (CRS), are widely used across disciplines, and their effectiveness has been demonstrated in higher education. However, few studies have been conducted on clicker use in nursing education. The purpose of this article is to examine the literature on how clickers can best be used to promote learner engagement among undergraduate nursing students and to better classroom education. This literature review addresses three key characteristics of clicker use in nursing, medical, pharmacy, and paramedic education found in fifteen empirical studies: interactivity and participation; satisfaction and learning outcomes; and formative assessment and contingent teaching. Nurse educators must take advantage of the latest technology such as clickers to provide more effective and efficient education.


In-line skate and rollerskate injuries in childhood.
To describe the estimated frequency and types of injuries associated with in-line skates in U.S. children and to compare in-line skating injuries to rollerskating injuries. National case series. Emergency departments of hospitals participating in the United States Consumer Product Safety Commission (USCPSC) National Electronic Injury Surveillance System. Persons with injuries associated with the use of in-line skates or rollerskates reported to the USCPSC in 1992 and 1993. There were an estimated 66,465 injuries associated with in-line skates; the incidence of injury was highest in children 11 and 12 years old. An estimated 40,730 in-line skate injuries involved children < 20 years old. The mean age of injured children was 11.8 years (median, 12 years); 68% were boys. Fractures (45%) were the most common injury; 66% of fractures involved the distal forearm. Five percent had head injuries. Two and one half percent required hospital admission; 90% of children admitted had a fracture and 11% had a head or face injury. There were an estimated 147,928 rollerskating injuries among children < 20 years old; the mean age was 10.5 years (median 10 years) (P < 0.001 vs in-line skates). Thirty-two percent were to boys (P < 0.001 vs in-line skates). Fractures were the most common injury; forearm fractures accounted for 72% (P < 0.001 vs in-line skates). Five percent had head injuries. One and one half percent were admitted to the hospital (P < 0.001 vs in-line skates). In 1993, the injury rate among children for in-line skates was 31/100,000, and the injury rate for rollerskates was 95/100,000. Injuries associated with in-line skates are highest among preadolescents. Injuries associated with in-line skate use are less common than injuries associated with rollerskate use. Distal forearm fractures are the most common injuries related to both in-line skate and rollerskate use. Exposure data and analysis of the efficacy of protective gear, including wrist guards and helmets, are needed.


Cardiac robustness regulated by reactive sulfur species.
The human myocardium contains robust cells that constantly beat from birth to death without being replaced, even when exposed to various environmental stresses. Myocardial robustness is thought to depend primarily on the strength of the reducing power to protect the heart from oxidative stress. Myocardial antioxidant systems are controlled by redox reactions, primarily via the redox reaction of Cys sulfhydryl groups, such as found in thioredoxin and glutathione. However, the specific molecular entities that regulate myocardial reducing power have long been debated. Recently, reactive sulfide species, with excellent electron transfer ability, consisting of a series of multiple sulfur atoms, i.e., Cys persulfide and Cys polysulfides, have been found to play an essential role in maintaining mitochondrial quality and function, as well as myocardial robustness. This review presents the latest findings on the molecular mechanisms underlying mitochondrial energy metabolism and the maintenance of quality control by reactive sulfide species and provides a new insight for the prevention of chronic heart failure.


Dysregulation of the orexin/hypocretin system is not limited to narcolepsy but has far-reaching implications for neurological disorders.
Neuropeptides orexin A and B (OX-A/B, also called hypocretin 1 and 2) are released selectively by a population of neurons which projects widely into the entire central nervous system but is localized in a restricted area of the tuberal region of the hypothalamus, caudal to the paraventricular nucleus. The OX system prominently targets brain structures involved in the regulation of wake-sleep state switching, and also orchestrates multiple physiological functions. The degeneration and dysregulation of the OX system promotes narcoleptic phenotypes both in humans and animals. Hence, this review begins with the already proven involvement of OX in narcolepsy, but it mainly discusses the new pre-clinical and clinical insights of the role of OX in three major neurological disorders characterized by sleep impairment which have been recently associated with OX dysfunction, such as Alzheimer's disease, stroke and Prader Willi syndrome, and have been emerged over the past 10 years to be strongly associated with the OX dysfunction and should be more considered in the future. In the light of the impairment of the OX system in these neurological disorders, it is conceivable to speculate that the integrity of the OX system is necessary for a healthy functioning body.


Decreased cerebrospinal fluid hypocretin-1 levels near the onset of narcolepsy in 2 prepubertal children.
We present 2 cases of narcolepsy with prepubertal onset. Although excessive daytime sleepiness and cataplexy had appeared early in both patients, the presence of sleep-onset rapid eye movement periods was detected several months after the onset of hypersomnia. The levels of hypocretin in the cerebrospinal fluid were reduced when measured 3 weeks (Patient 1) and 2 months (Patient 2) after the appearance of hypersomnia, before the presence of sleep-onset rapid eye movement periods was confirmed. Because the symptoms of narcolepsy in children are often obscure and easily mistaken as other diseases, and the electrophysiologic studies may not be specific in the early stage, the definite diagnosis tends to be delayed. Measurement of hypocretin-1 levels in the cerebrospinal fluid is useful for the early diagnosis of narcolepsy with prepubertal onset.


Iron whiskers on asteroid Itokawa indicate sulfide destruction by space weathering.
Extraterrestrial iron sulfide is a major mineral reservoir of the cosmochemically and astrobiologically important elements iron and sulfur. Sulfur depletion on asteroids is a long-standing, yet unresolved phenomenon that is of fundamental importance for asteroid evolution and sulfur delivery to the Earth. Understanding the chemistry of such environments requires insight into the behavior of iron sulfides exposed to space. Here we show that troilite (FeS) grains recovered from the regolith of asteroid 25143 Itokawa have lost sulfur during long-term space exposure. We report the wide-spread occurrence of metallic iron whiskers as a decomposition product formed through irradiation of the sulfide by energetic ions of the solar wind. Whisker growth by ion irradiation is a novel and unexpected aspect of space weathering. It implies that sulfur loss occurs rapidly and, furthermore, that ion irradiation plays an important role in the redistribution of sulfur between solids and gas of the interstellar medium.


Developing a taxonomy of hazards and hazard mitigation strategies for Motorised mobility scooter users.
The increased use of motorised mobility scooters (MMSs) presents a road safety challenge as using a MMS has risks for the user, pedestrians, and other road users. In relation to enhancing MMS driving safety, much of the training and available literature focuses on training vehicular control. Equally important is the need to investigate higher-order cognitive skills involved in driving MMSs, particularly hazard perception. Through a large questionnaire study with MMS users, we develop a taxonomy of the types of hazard MMS users encounter when crossing roads and strategies that are used to negotiate these hazards. Whilst MMS experience modulated hazard perception and strategy use, a core set of hazards and strategies were identified that have policy and practice implications for training interventions and the built environment. Exploration of the advantages and disadvantages of MMS use indicated its impact on various wellbeing outcomes as well as some potential barriers to use.


[Wilms' tumor with an unusual presentation].
The case history of a 8 year old boy is described who presented with haematuria without other signs or symptoms. No abdominal mass could be palpated. Excretory urography revealed a tumor in the right pyelum . Histological examination confirmed the diagnosis. The tumor was mainly located in the submucosal area of the right pyelum and proximal ureter.


Solitary Plasmacytoma of the Mandible: An Uncommon Entity.
Plasma cell dyscrasias are characterized by a monoclonal neoplastic proliferation of plasma cells. Solitary bone plasmacytoma (SBP) is a local form of the disease with the vertebrae and long bones being the most frequently encountered sites. Its prevalence in the maxillofacial area is extremely rare. A 70-year-old Caucasian male patient was referred for the extraction of his mobile premolar tooth with a poorly-defined radiolucent lesion. Histopathological analysis revealed an SBP and no distant lesion or serum M protein was noted on radiological and hematological examinations. The patient was under follow-up care with no recurrence at 2 years of follow up. Diagnosis of an SBP is based on local radiological and neurological symptoms and similar systemic manifestations of multiple myeloma that are also distinctive for SBP. Skeletal radiological analysis including CT and PET-CT, bone marrow biopsy, and serum protein electrophoresis are essential for confirmation of the diagnosis. Although surgery, chemotherapy, and radiation, or a combination of these modalities, have been successfully used in the treatment of SBP, it should be managed in relation to its possible long-term evolution.


Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial.
Between 1983 and 1986, the National Institute for Cancer Research in Genoa and affiliated institutions conducted a randomized study to compare two different ways of combining chemotherapy (CT) and radiation therapy (RT). One hundred sixteen patients were randomized to receive neoadjuvant CT followed by definitive RT (treatment arm A) or alternating CT and RT. In treatment arm A, RT consisted of 70 Gy to the involved areas and 50 Gy to the uninvolved neck at 2 Gy/fraction, five fractions per week. In treatment arm B, RT consisted of 60 Gy to involved areas and 50 Gy to the uninvolved neck in three courses of 20 Gy each, 2 Gy/fraction, ten fractions/2 weeks alternated with four courses of CT. CT consisted of vinblastine 6 mg/m2 intravenously followed 6 hours later by bleomycin 30 IU intramuscularly, day 1; methotrexate 200 mg intravenously, day 2; leucovorin rescue, day 3. CT was repeated every 2 weeks up to four courses. The same CT was used in both treatment arms of the study. Fifty-five patients were entered in treatment arm A and 61 in treatment arm B. Complete responses were 7/48 and 19/57 in treatment arms A and B, respectively (P less than 0.03). Four-year progression-free survival was 4% in treatment arm A and 12% in treatment arm B (P less than 0.02), and four-year survival was 10% in A and 22% in B (P less than 0.02). Mucosal tolerance was significantly worse in treatment arm B (P less than 0.00004). The subgroup analysis shows the major improvement of alternating CT and RT in patients with the worst prognostic characteristics.


Effect of vitamin D supplementation on N-glycan branching and cellular immunophenotypes in MS.
To investigate the effect of cholecalciferol (vitamin D3) supplementation on peripheral immune cell frequency and N-glycan branching in patients with relapsing-remitting multiple sclerosis (RRMS). Exploratory analysis of high-dose (20 400 IU) and low-dose (400 IU) vitamin D3 supplementation taken every other day of an 18-month randomized controlled clinical trial including 38 RRMS patients on stable immunomodulatory therapy (NCT01440062). We investigated cholecalciferol treatment effects on N-glycan branching using L-PHA stain (phaseolus vulgaris leukoagglutinin) at 6 months and frequencies of T-, B-, and NK-cell subpopulations at 12 months with flow cytometry. High-dose supplementation did not change CD3+ T cell subsets, CD19+ B cells subsets, and NK cells frequencies, except for CD8+ T regulatory cells, which were reduced in the low-dose arm compared to the high-dose arm at 12 months. High-dose supplementation decreased N-glycan branching on T and NK cells, measured as L-PHA mean fluorescence intensity (MFI). A reduction of N-glycan branching in B cells was not significant. In contrast, low-dose supplementation did not affect N-glycan branching. Changes in N-glycan branching did not correlate with cell frequencies. Immunomodulatory effect of vitamin D may involve regulation of N-glycan branching in vivo. Vitamin D3 supplementation did at large not affect the frequencies of peripheral immune cells.


Oral health in young adults with long-term, controlled asthma.
To study oral health in young adults with long-term, controlled asthma. Twenty 18- to 24-year-olds with a mean duration of asthma of 13.5 [standard deviation (SD) 5.4] years and 20 matched healthy controls were included. A clinical examination was performed and the prevalences of caries, erosions, gingival inflammation, cervicular fluid and periodontal pockets and the plaque formation rate were registered. The salivary flow rate and the numbers of mutans Streptococci and Lactobacilli in saliva were determined. Plaque pH was measured after a sucrose rinse for up to 40 min at two approximal sites. The participants were interviewed regarding dietary and oral hygiene habits. The mean (SD) DFS, including manifest and initial caries, was 8.6 (10.6) in the asthma group and 4.0 (5.2) in the control group (P = 0.09). Initial caries lesions were more common in the asthma group than in the control group: 6.0 (8.1) and 1.3 (2.0), respectively (P = 0.02). The asthma group had more gingivitis (P = 0.01) and a lower stimulated salivary secretion rate than the controls (P = 0.01). The asthmatics also had a somewhat, although not statistically significant, lower initial pH value in plaque and a more pronounced pH drop compared with the controls. In the asthma group, 65% reported frequent mouthbreathing, compared with 10% of the controls (P = 0.01). No differences were found in tooth-brushing or dietary habits between the groups. Young adults with long-term, controlled asthma had more initial caries, more gingival inflammation and a lower stimulated salivary secretion rate than individuals without asthma.


Maternal PTSD and corresponding neural activity mediate effects of child exposure to violence on child PTSD symptoms.
The aim of this study was to examine the relationship of maternal interpersonal violence-related posttraumatic stress disorder (IPV-PTSD), associated neural activity in response to mother-child relational stimuli, and child psychopathology indicators at child ages 12-42 months and one year later. The study tested the hypothesis that decreased maternal neural activity in regions that subserve emotion regulation would be associated with child symptoms associated with emotional dysregulation at both time points. Functional magnetic resonance imaging of 42 mothers with or without violence-exposure and associated IPV-PTSD were assessed. Their child's life-events and symptoms/behaviors indicative of high-risk subsequent PTSD diagnosis on a maternal-report questionnaire were measured one year later. Maternal IPV-PTSD severity was significantly associated with decreased ventromedial prefrontal cortex (vmPFC) activation in response to mother-child relational stimuli. Maternal IPV-PTSD severity and decreased vmPFC activation were then significantly associated with a child attachment disturbance at 12-42 months and symptoms/behaviors one year later, that were correlated with emotional dysregulation and risk for child PTSD. Maternal IPV-PTSD and child exposure to IPV were both predictive of child PTSD symptoms with maternal IPV-PTSD likely mediating the effects of child IPV exposure on child PTSD symptoms. These findings suggest that maternal IPV-PTSD severity and associated decreased vmPFC activity in response to mother-child relational stimuli are predictors of child psychopathology by age 12-42 months and one-year later. Significant findings in this paper may well be useful in understanding how maternal top-down cortico-limbic dysregulation promotes intergenerational transmission of IPV and related psychopathology and, thus should be targeted in treatment.


Dose-effect study of the serotonin agonist R-8-OH-DPAT on opioid-induced respiratory depression in blesbok (Damaliscus pygargus philipsi) and impala (Aepyceros melampus).
To determine whether the R-enantiomer of 8-hydroxy-2-(di-n-propylamino) tetralin (R-8-OH-DPAT) alleviates respiratory depression in antelope species immobilized with etorphine. The experiment also aimed to establish the most clinically effective dose of this serotonin 5- HT1A receptor agonist. A group of six female blesbok and six female impala. Each animal was subjected to four immobilization treatments in a prospective four-way crossover design-control treatment consisting of only etorphine at 0.09 mg kg-1 and three treatments consisting of etorphine at 0.09 mg kg-1 combined with 0.005, 0.02 and 0.07 mg kg-1 of R-8-OH-DPAT, respectively. Induction, quality of immobilization and recovery were monitored in each treatment. Physiological variables including heart rate, respiratory rate, arterial blood pressure and blood gases were measured for 35 minutes during immobilization. A linear mixed model was used to assess the effects of treatments over the recumbency period. R-8-OH-DPAT did not influence induction, immobilization or recovery scores. Respiratory rate in blesbok was increased in the medium- and high-dosage R-8-OH-DPAT treatment group. However, this increased respiratory rate did not translate into improvements of arterial partial pressure of oxygen (PaO2) values in the blesbok. The medium and higher dosages of R-8-OH-DPAT in impala led to an improved PaO2 as well as to decreased opioid-induced tachycardia during the first 10 minutes of immobilization. Previous reports indicated that the racemic mixture of 8-OH-DPAT injected intravenously had a positive effect on blood-gas values in etorphine-treated hypoxemic goats. In this experiment, similar effects could be seen in impala at the higher dosage rates of R-8-OH-DPAT. However, failure to achieve an improvement of blood-gas values in blesbok was an unexpected result. It could be speculated that the dosage, species-specific differences of serotonin receptors or the use of the R-enantiomer of 8-OH-DPAT might play a role.


Phakomatosis Pigmentovascularis: A Clinical Profile of 11 Indian Patients.
Phakomatosis pigmentovascularis (PPV) is a rare congenital syndrome characterized by the simultaneous presence of capillary malformation and pigmentary nevi. The objective of our study was to describe the clinical characteristics of a series of Indian patients presenting with this rare entity. It was a record-based descriptive case series. A total of 11 patients with PPV (9 females, 2 males, age range: 7 days to 45 years; mean 11.6 years) were studied. Port wine stain was present in 10 (91%) patients and one patient (9%) had cutis marmorata telangiectatica congenita. Isolated nevi of Ota and Mongolian spots were seen in 4 (36%) patients each. Simultaneous presence of both Mongolian spots and nevus of Ota was present in 1 (9%) patient. The combination of Mongolian spots and bilateral palatal hyper-melanosis was noticed in 2 (18%) patients. Café au lait macule was present in one patient. Bilateral ocular melanosis was found in 3 (27%) patients. Unilateral ocular melanosis was noticed in 4 (36%) patients. Two patients (18%) had history of seizure disorder and intracranial vascular anomalies on MRI imaging. Two patients (18%) had features of Klippel-Trenaunay syndrome. According to the traditional classification, three patients had PPV type 2b, one patient had PPV type 5b, and seven patients had PPV type 2a. According to the Happle's classification, 10 patients had PPV of cesio flammea type, and one patient had PPV of cesio marmorata type. We could not perform genetic study of the patients. Our findings emphasize the importance of detailed systemic evaluation including ocular examination and brain imaging in every patient of PPV.


Attenuation of Oxytocin and Serotonin 2A Receptor Signaling through Novel Heteroreceptor Formation.
The oxytocin receptor (OTR) and the 5-hydroxytryptamine 2A receptor (5-HTR2A) are expressed in similar brain regions modulating central pathways critical for social and cognition-related behaviors. Signaling crosstalk between their endogenous ligands, oxytocin (OT) and serotonin (5-hydroxytryptamine, 5-HT), highlights the complex interplay between these two neurotransmitter systems and may be indicative of the formation of heteroreceptor complexes with subsequent downstream signaling changes. In this study, we assess the possible formation of OTR-5HTR2A heteromers in living cells and the functional downstream consequences of this receptor-receptor interaction. First, we demonstrated the existence of a physical interaction between the OTR and 5-HTR2Ain vitro, using a flow cytometry-based FRET approach and confocal microscopy. Furthermore, we investigated the formation of this specific heteroreceptor complex ex vivo in the brain sections using the Proximity Ligation Assay (PLA). The OTR-5HTR2A heteroreceptor complexes were identified in limbic regions (including hippocampus, cingulate cortex, and nucleus accumbens), key regions associated with cognition and social-related behaviors. Next, functional cellular-based assays to assess the OTR-5HTR2A downstream signaling crosstalk showed a reduction in potency and efficacy of OT and OTR synthetic agonists, carbetocin and WAY267464, on OTR-mediated Gαq signaling. Similarly, the activation of 5-HTR2A by the endogenous agonist, 5-HT, also revealed attenuation in Gαq-mediated signaling. Finally, altered receptor trafficking within the cell was demonstrated, indicative of cotrafficking of the OTR/5-HTR2A pair. Overall, these results constitute a novel mechanism of specific interaction between the OT and 5-HT neurotransmitters via OTR-5HTR2A heteroreceptor formation and provide potential new therapeutic strategies in the treatment of social and cognition-related diseases.


An Unusual Case of Intraabdominal Abscess After a Colonoscopy With Polypectomy.
The use of colonoscopies in the screening of colorectal cancers has helped in the early detection and treatment of these cancers. Less than 0.5% of patients develop colonoscopy complications, mostly bleeding, and less frequently, perforations. There have been very few reported cases of micro-perforations following colonoscopies. We present a case of a 66-year-old female smoker who had undergone a screening colonoscopy for colorectal cancer with two polyps removed 3 weeks prior, who was brought to the hospital because of altered mental status and hypotension. A computed tomography (CT) scan of the abdomen and pelvis with contrast demonstrated intraabdominal abscess which was drained by interventional radiology. A culture of the pus grew Streptococcus constellatus, a pus-forming bacterium. She was treated with ceftriaxone and metronidazole for a total of 6 weeks, and a repeat CT of abdomen and pelvis demonstrated complete resolution. The only contributing factor to the formation of the intraabdominal abscess was a screening colonoscopy with polypectomy, which might have caused micro-perforations in the colon with the seeding of Streptococcus constellatus. The occurrence of intraabdominal abscess following a colonoscopy is very rare, and requires a high index of suspicion in patients who present with sepsis following colonoscopies.


Biological and cytoselective anticancer properties of copper(II)-polypyridyl complexes modulated by auxiliary methylated glycine ligand.
A series of ternary copper(II)-1,10-phenanthroline complexes with glycine and methylated glycine derivatives, [Cu(phen)(aa)(H(2)O)]NO(3)·xH(2)O 1-4 (amino acid (aa): glycine (gly), 1; DL: -alanine (DL: -ala), 2; 2,2-dimethylglycine (C-dmg), 3; sarcosine (sar), 4), were synthesized and characterized by FTIR, elemental analysis, electrospray ionization-mass spectra (ESI-MS), UV-visible spectroscopy and molar conductivity measurement. The determined X-ray crystallographic structures of 2 and 3 show each to consist of distorted square pyramidal [Cu(phen)(aa)(H(2)O)](+) cation, a nitrate counter anion, and with or without lattice water, similar to previously reported structure of [Cu(phen)(gly)(H(2)O)]NO(3)·1½H(2)O. It is found that 1-4 exist as 1:1 electrolytes in aqueous solution, and the cationic copper(II) complexes are at least stable up to 24 h. Positive-ion ESI-MS spectra show existence of only undissociated [Cu(phen)(aa)](+) species. Electron paramagnetic resonance, gel electrophoresis, fluorescence quenching, and restriction enzyme inhibition assay were used to study the binding interaction, binding affinity and selectivity of these complexes for various types of B-form DNA duplexes and G-quadruplex. All complexes can bind selectively to DNA by intercalation and electrostatic forces, and inhibit topoisomerase I. The effect of the methyl substituents of the coordinated amino acid in the above complexes on these biological properties are presented and discussed. The IC(50) values (24 h) of 1-4 for nasopharyngeal cancer cell line HK1 are in the range 2.2-5.2 μM while the corresponding values for normal cell line NP69 are greater than 13.0 μM. All complexes, at 5 μM, induced 41-60 % apoptotic cell death in HK1 cells but no significant cell death in NP69 cells.


Amphidoma languida (Amphidomatacea, Dinophyceae) with a novel azaspiracid toxin profile identified as the cause of molluscan contamination at the Atlantic coast of southern Spain.
Azaspiracids (AZA) are a group of food poisoning phycotoxins that are known to accumulate in shellfish. They are produced by some species of the planktonic dinophycean taxon Amphidomataceae. Azaspiracids have been first discovered in Ireland but are now reported in shellfish from numerous global sites thus showing a wide distribution. In shellfish samples collected in 2009 near Huelva (Spain), AZA was also found along the Andalusian Atlantic coast for the first time. Analysis using LC-MS/MS revealed the presence of two different AZA analogues in different bivalve shellfish species (Chamelea gallina, Cerastoderma edule, Donax trunculus, and Solen vagina). In a number of samples, AZA levels exceeded the EU regulatory level of 160μg AZA-1 eq. kg-1 (reaching maximum levels of >500μg AZA-1 eq. kg-1 in Chamelea gallina and >250μg AZA-1 eq. kg-1 in Donax trunculus) causing closures of some local shellfish production areas. One dinophyte strain established from the local plankton during the AZA contamination period and determined as Amphidoma languida was in fact toxigenic, and its AZA profile disclosed it as the causative species: it contained AZA-2 as the main compound and the new compound AZA-43 initially detected in the shellfish. AZA-43 had the same mass as AZA-3, but produced different collision induced dissociation (CID) spectra. High resolution mass spectrometric measurements indicated that there is an unsaturation in the H, I ring system of AZA-43 distinguishing it from the classical AZA such as AZA-1, -2, and -3. Furthermore, the Spanish strain was different from the previously reported AZA profile of the species that consist of AZA-38 and AZ-39. In molecular phylogenetics, the Andalusian strain formed a monophyletic group together with other strains of Am. languida, but ITS sequences data revealed surprisingly high intragenomic variability. The first Andalusian case of AZA contamination of shellfish above the EU regulatory limit reported here clearly revealed the risk of azaspiracid poisoning (AZP) for this area and also for the Atlantic coast of Iberia and North Africa. The present study underlines the need for continuous monitoring of AZA and the organisms producing such toxins.


[Premortal data in the process of skeletal remains identification].
The basic task of a forensic examiner during the exhumation of mass graves or in mass accidents is to establish identity of a person. The results obtained through these procedures depend on the level of perceptibility of post mortal changes and they are compared with premortal data obtained from family members of those missing or killed. Experience with exhumations has shown significant differences between the results obtained through exhumation and the premortal data. The aim of the study was to suggest the existance of the difference between premortal data and the results obtained by exhumation regarding the some parameters, as well as to direct premortal data colection to the specific skeletal forms. We performed comparative analysis of the results of exhumation of skeletal remains in a mass grave and the premortal data concerning the identified persons. The least number of individuals in this mass grave was calculated according to the upper parts of the right femur and it helped in calculating the smallest number of individuals in mass graves to be 48. A total of 27 persons were identified. Sex was determined by metrics and morphology of the pelvis. Personal age in the moment of death was determined by morphology features of groin symphisis and morphology of sternal edge of ribs and other parts of scelets observations. The hight was calculated as average results of length of long bones and Rollet coefficients. There was a complete match in terms of sex and age matched within an interval that could be established based on the skeletal remains. All the other parameters were different, however, which made identification significantly more difficult. The premortal data is an important element of identification process and it should be obtained by the forensic doctor and directed towards more detailed examination of the skeletal system.


Redox buffering by melanin and Fe(II) in Cryptococcus neoformans.
Melanin is a fungal extracellular redox buffer which, in principle, can neutralize antimicrobial oxidants generated by immunologic effector cells, but its source of reducing equivalents is not known. We wondered whether Fe(II) generated by the external ferric reductase of fungi might have the physiologic function of reducing fungal melanin and thereby promoting pathogenesis. We observed that exposure of a melanin film electrode to reductants decreased the open-circuit potential (OCP) and reduced the area of a cyclic voltammetric reduction wave whereas exposure to oxidants produced the opposite effects. Exposure to 10, 100, 1,000 or 10,000 microM Fe(II) decreased the OCP of melanin by 0.015, 0.038, 0.100, and 0.120 V, respectively, relative to a silver-silver chloride standard, and decreased the area of the cyclic voltammetric reduction wave by 27, 35, 50, and 83%, respectively. Moreover, exposure to Fe(II) increased the buffering capacity by 44%, while exposure to millimolar dithionite did not increase the buffering capacity. The ratio of the amount of bound iron to the amount of the incremental increase in the following oxidation wave was approximately 1.0, suggesting that bound iron participates in buffering. Light absorption by melanin suspensions was decreased 14% by treatment with Fe(II), consistent with reduction of melanin. Light absorption by suspensions of melanized Cryptococcus neoformans was decreased 1.3% by treatment with Fe(II) (P < 0.05). Cultures of C. neoformans generated between 2 and 160 microM Fe(II) in culture supernatant, depending upon the strain and the conditions [the higher values were achieved by a constitutive ferric reductase mutant in high concentrations of Fe(III)]. We infer that Fe(II) can reduce melanin under physiologic conditions; moreover, it binds to melanin and cooperatively increases redox buffering. The data support a model for physiologic redox cycling of fungal melanin, whereby electrons exported by the yeast to form extracellular Fe(II) maintain the reducing capacity of the extracellular redox buffer.


Spironolactone and risk of upper gastrointestinal events: population based case-control study.
To confirm and quantify any association between spironolactone and upper gastrointestinal bleeding and ulcers. Population based case-control study. A primary care information database in the Netherlands. All people on the database who were aged 18 or more between 1 January 1996 and 30 September 2003. Patients with a history of alcoholism or gastrointestinal cancer were excluded. Ten controls were matched to each case of gastroduodenal ulcer or upper gastrointestinal bleeding by age (year of birth), sex, and index date. The occurrence of an upper gastrointestinal event (bleeding or ulcers), adjusted for potential confounders with conditional logistic regression analysis. Within the source population of 306 645 patients, 523 cases of gastric or duodenal ulcer or upper gastrointestinal bleeding were identified and matched to 5230 controls. Current use of spironolactone was associated with a 2.7-fold (95% confidence interval 1.2 to 6.0) increased risk of a gastrointestinal event. The risk of gastroduodenal ulcers or upper gastrointestinal bleeding is significantly increased in patients using spironolactone.


Clinical and course indicators of bipolar disorder type I with and without opioid dependence.
The existing evidence about the clinical situations of the bipolar patients with opioid dependence is scarce. The present study was carried out to compare the clinical features and course of the bipolar disorder type I regarding the two subgroups of opioid dependent and non-dependent. There were 178 adult patients with bipolar disorder type I consecutively referred to the Iran Hospital of Psychiatry, Tehran, Iran, from January 2008 to January 2009 who enrolled in the study. The Persian Structured Clinical Interview for DSM-IV axis I disorders (SCID-I), HDRS-17, and Y-MRS were administered for all patients. Other clinical information was gathered through the face-to-face interviews with the probands and the hospital records. The T test, Chi square test and logistic regression were used to analyze the data. The mean age of probands were 33.6 ± 11.1 years old and they were mostly male. Among the evaluated indices, the factors gender, anxiety disorders comorbidity, non-adherence, and positive family history were different significantly and independently from the other studied factors between opioid dependent and non-dependent bipolar patients. Despite some differences, the opioid dependent and non-dependent bipolar patients did not have any significant difference regarding most of the examined clinical and course indices.