Desorption electrospray ionization (DESI) source coupling ion mobility mass spectrometry for imaging fluoropezil (DC20) distribution in rat brain.
Fluoropezil (DC20) is a new selective acetylcholinesterase inhibitor, and it was developed for the treatment of Alzheimer's disease patients. In this study, a desorption electrospray ionization source coupling ion mobility mass spectrometry imaging (DESI/IMS-MSI) method was developed to explore the distribution of DC20 in brain tissue following oral administration. Rat brain coronal slices obtained 1 h and 3 h following drug dosing were used in the study. D6-DC20 was used as internal standard and sprayed by matrix sprayer on the brain slices to calibrate the matrix effect. Ion mobility separation was used to reduce the interference from background noise and the biological matrix. By optimizing DESI-MSI parameters for improved sensitivity, the limit of quantitation of the method was 1.45 pg/mm2 with a linear range from 1.45 to 72.7 pg/mm2. DESI-MSI data showed that DC20 could quickly enter and diffuse across whole brain and tended to be much more enriched in striatum than cerebral cortex and hippocampus, which was consistent with quantitative analysis using high-performance liquid chromatography-electrospray tandem mass spectrometry to measure DC20 concentration in each homogenized brain sub-region. The workflow of tissue imaging method optimization and strategy were established, and for the first time, the DESI-MSI technique and optimized method were used to explore the distribution characteristics of DC20 in rat brain, which could help elucidate pharmacological effect mechanisms and improve clinical outcomes.


High quality CdHgTe nanocrystals with strong near-infrared emission: relationship between composition and cytotoxic effects.
High quality CdHgTe quasi core/shell nanocrystals (NCs) were prepared via the one-step method. The relationship between the composition, structure, and property was systematically investigated by the combination of X-ray photoelectron spectroscopy (XPS), inductively coupled plasma atomic emission (ICP), and the photoluminescence (PL) measurements. The quantum yield (QY) was ~50% when the feed ratio of Cd(2+) to Hg(2+) was equal to 1. The PL property was further polished, and the QY was improved to ~80% through the variance of the prepared conditions such as the ratio of ligand to metal ion and HTe(-) to metal ion, pH value, and temperature. In addition, the cytotoxic effects of CdHgTe NCs were systematically studied. The results showed that, for Cd0.21Hg0.79Te NCs, its quasi core/shell structure was very stable and little cadmium ions were released. As a result, such NCs showed little cytotoxicity and would find applications in tissue imaging or detection.


[Association between subjective and objective sleepiness in obstructive sleep apnea hypopnea syndrome patients].
Objective: To examine the association between subjective sleepiness and objective sleepiness in Chinese obstructive sleep apnea hypopnea syndrome (OSAHS) patients. Methods: A total of 1 660 patients meeting the diagnostic criteria of OSAHS based on overnight polysomnography from West China Hospital, Sichuan University in the period from Jul 2010 to Jul 2014 were enrolled in the study. The Epworth Sleepiness Scale (ESS) and Multiple Sleep Latency Test (MSLT) were to evaluate subjective and objective sleepiness, respectively. The subjects were categorized into quartiles [A (0-4) (n=406), B (5-7) (n=325), C (8-12) (n=443), D(13-24) (n=486) groups] based on the ESS score distribution. Survival analysis was used to characterize the association between the ESS score and the mean sleep latency (MSL). Results: The apnea hypopnea index (AHI) in D group was higher than other three groups [(58.7±26.1) vs (36.8±24.2), (42.6±26.7), (45.7±26.6) events/h, all P<0.05]. The mean sleep latency in D group was shorter than other three groups [(8.0±4.6) vs (10.9±4.4), (10.3±4.8), (9.4±4.5) min, all P<0.05]. The Kaplan-Meier survivor functions across the ESS score quartiles were distinct and fourth quartiles were progressively associated with a greater tendency for falling asleep (χ(2)=77.76, P<0.001 by Log-rank test) in the daytime (The percentages of awaking patients in fourth quartiles were progressively lower at the same time). The adjusted hazard ratios for sleep onset during the MSLT for the group B, C and D were 1.05 (95%CI: 0.90-1.22), 1.22 (95%CI: 1.07-1.40), and 1.38 (95%CI: 1.20-1.60), respectively, comparing to group A. Conclusion: Subjective report of daytime sleepiness is consistent with the objective sleepiness in OSAHS patients.


Immobilization of Escherichia coli cells using porous support particles coated with cationic polymers.
The technique of cell immobilization using porous biomass support particles (BSPs), which is attractive from the point of view of simplicity and convenience, relies on the inherent ability of adhesive cells, as a consequence of their growth, to form films around the support material or the ability of flocculent cells to create flocs within the porous structure. In the present study, the immobilization of Escherichia coli cells using BSPs was investigated in shake-flask culture. The density of the cells immobilized within the BSPs was evaluated by measuring their intracellular lactate dehydrogenase (LDH) activity. Since E. coli K12 cells were not successfully retained within reticulated polyvinyl formal (PVF) resin BSPs with matrices of relatively small pores (pore diameter 60 microm), coating the surface of the BSPs with various polymers was examined as a way of promoting cell attachment. When positively charged polyamino acids such as poly-L-lysine, poly-L-arginine, poly-L-histidine, and poly-L-ornithine were adsorbed onto the particle surface, they were found to increase the immobilized cell density, while neutral and negatively charged polyamino acids including poly-L-asparagine and poly-L-glutamic acid were not effective. These results indicate that E. coli cells can be efficiently immobilized in PVF resin BSPs by electrostatic interaction between the negatively charged ions of the cell surface and the positively charged polymers adsorbed onto the BSP surface. A significantly high immobilized cell density was also achieved by coating the surface of the BSPs with the synthetic polymeric amine polyethyleneimine.


Where's the capital? A geographical essay.
This paper is inspired by Thomas Piketty's book Capital in the Twenty-First Century. Piketty does a wonderful job of tracing income and wealth over time, and relating changes to trends of economic and population growth, and drawing out the implications for inequality, inheritance and even democracy. But, he says relatively little about where capital is located, how capital accumulation in one place relies on activities elsewhere, how capital is urbanized with advanced capitalism and what life is like in spaces without capital. This paper asks 'where is the geography in Capital' or 'where is the geography of capital in Capital'? Following Piketty's lead, the paper develops its analysis through a number of important novels. It examines, first, the debate that Jane Austen ignored colonialism and slavery in her treatment of nineteenth century Britain, second, how Balzac and then Zola provide insight to the urban political economy of capital later in the century, and third, how Katherine Boo attends to inequality as the everyday suffering of the poor.


Acute cholecystitis and persistent liver necrosis in mice provoked by isothiocyanate.
Two known cholangiotoxic agents, alpha-naphthylisothiocyanate (ANIT) and p-phenylenediisothiocyanate (PDT), were administered in single doses to mice to study their effects on the gallbladder. Both compounds caused maximal bile duct necrosis and periportal hepatocytic necrosis at 24 hours. In contrast, the gallbladders were edematous but not necrotic at 24 hours after treatment. At 48 hours, and in some animals up to four days, severe cholecystitis was present, while bile ducts revealed progressive regeneration. The delay in the onset of gallbladder lesions was assumed to be the result of the toxic agent concentration in gallbladder bile after hepatic bile secretion was suppressed for 24 hours. The lesions provoked by PDT were similar to those induced by ANIT, except for a hemorrhagic component.


Pitting Oedema in a Patient with Lumbar Disc Herniation: Case report of an unusual association.
Oedema refers to the excessive accumulation of fluid within intercellular tissues as a result of disequilibrium between the capillary hydrostatic and oncotic pressure gradients. Lumbar disc herniation (LDH) commonly causes lower back pain and radicular leg pain. We report a 57-year-old female who presented to the neurosurgery clinic of the Bam University of Medical Sciences, Bam, Iran, in 2015 with pain and pitting oedema in the bilateral lower extremities. Magnetic resonance imaging confirmed a diagnosis of LDH of the L3-L4 and L4-L5 vertebrae. The patient subsequently underwent a bilateral laminotomy and foraminotomy of the involved vertebrae to relieve her pain. Following the surgery, there was a complete resolution of the LDH-related symptoms as well as the oedema. Although LDH has never before been associated with oedema, it may nevertheless cause lower limb oedema in exceptional and rare cases, as highlighted in this patient.


Investigating the effect of antiseptic solution on the release of interleukin-6 and transforming growth factor beta 1 from human gingival fibroblasts using wound healing assays.
This in vitro study evaluated the effect of different antiseptics and different concentrations thereof in a model of wound healing using human gingival fibroblasts. The fibroblasts were rinsed with four different antiseptic solutions: sodium hypochlorite (HYP), hydrogen peroxide (H2O2), chlorhexidine digluconate (CHX), and benzalkonium chloride (BC). The effect on the release of interleukin-6 (IL-6) and transforming growth factor beta 1 (TGF-β1) was investigated using enzyme-linked immunosorbent assays (ELISAs). In addition, the effects of the antiseptics on wound healing at 1, 12, 24, and 48 h were assessed through a wound healing assay. The viability of the fibroblasts rinsed with antiseptics was investigated with respect to the concentrations inhibiting cell growth by 50% (IC50), 25% (IC25), and ≤2% (IC2). A statistically significant increased release of IL-6 was obtained with BC IC25 and IC2 after 12, 24, and 48 h (P < 0.01). For TGF-β1, no significant release was found for CHX IC2 after 24 and 48 h or for IC50 and IC25 after 12 h. There was no significant effect on wound healing capacity for CHX or for BC IC25 and IC2. This study demonstrated that antiseptic rinses of human gingival fibroblasts alter the release of IL-6 and TGF-β1 and impact wound healing capacity, with both BC and CHX conferring neutral effects.


The frequency of adverse drug reactions as dependent upon age, sex and duration of hospitalization.
In 1972, 171 (18, 7%) of 914 patients showed evidence of an adverse drug reaction (ADR) in a prospective study of the division of internal medicine in a regional teaching hospital (Zieglerspital, Bern). The following factors correlated positively with frequency of ADR: 1. The duration of hospital stay. 2. The age between 60 and 80 years. 3. Female sex. 4. Previous ADR. The fact that most of the ADR occur within the first three weeks of a hospital stay, combined with point 1, suggests early ADR having some predictive value for duration of hospital stay. Statistical data of type, severity, duration and pathogenesis of ADR are given. The drugs involved are mentioned.


Thrombin activates nuclear factor-kappaB and potentiates endothelial cell activation by TNF.
Thrombin is the central bioregulatory enzyme in hemostasis and is generated in vascular beds in which inflammatory responses are ongoing. In this study, we examined the effect of thrombin, both alone and in combination with TNF, on gene expression in porcine aortic endothelial cells (EC). Thrombin (1-10 U/ml) induced increased mRNA levels of E-selectin, monocyte chemoattractant protein-1, IL-8, plasminogen activator inhibitor-1, and IkappaB-alpha. These effects were mimicked by a thrombin receptor-activating peptide; preincubation of thrombin with hirudin blocked the induction of mRNA, suggesting that the increased gene expression was due to thrombin-specific activity. Because these genes are known to contain nuclear-factor-kappaB (NF-kappaB)-binding elements in their promoter region, we next examined the ability of thrombin to activate this transcription factor. As detected by electrophoretic mobility shift assay, thrombin (10 U/ml) or thrombin receptor-activating peptide (100 microM) stimulated increased NF-kappaB-binding activity. Supershift analysis revealed that these complexes were comprised principally of the RelA (p65) and NF-kappaB1 (p50) Rel family members. Thrombin alone did not substantively increase protein levels of E-selectin despite the increase in E-selectin mRNA levels. However, thrombin (3-10 U/ml) stimulated a 10-fold enhancement in the ability of TNF (0.3-1.0 ng/ml) to induce E-selectin surface expression. Similar potentiation of TNF-induced NF-kappaB activity and E-selectin transcription by thrombin was observed in experiments utilizing luciferase reporter constructs expressed in bovine aortic EC. The ability of thrombin to potentiate TNF-induced EC activation thus provides an important mechanism by which products of the coagulation cascade may enhance cytokine-mediated inflammatory responses.


Moving from conceptual ambiguity to knowledgeable action: using a critical realist approach to studying moral distress.
Moral distress is a phenomenon that has been receiving increasing attention in nursing and other health care disciplines. Moral distress is a concept that entered the nursing literature - and subsequently the health care ethics lexicon - in 1984 as a result of the work done by American philosopher and bioethicist Andrew Jameton. Over the past decade, research into moral distress has extended beyond the profession of nursing as other health care disciplines have come to question the impact of moral constraint on individual practitioners, professional practice, and patient outcomes. Along with increased interest in the phenomenon of moral distress have come increasing critiques - critiques that in their essence point to a serious lack of conceptual clarity in the definition, study, and application of the concept. Foundational to gaining conceptual clarity in moral distress in order to develop strategies to prevent and ameliorate the experience is a careful revisiting of the epistemological assumptions underpinning our knowledge and use of the concept of moral distress. It is our contention that the conceptual challenges reveal flaws in the original understanding of moral distress that are based on an epistemological stance that holds a linear conception of cause and effect coupled with a simplistic perspective of 'constraint' and 'agency'. We need a more nuanced approach to our study of moral distress such that our ontological and epistemological stances help us to better appreciate the complexity of moral agents acting in organizational contexts. We believe that critical realism offers such a nuanced approach.


Cytogenetic and histologic findings in Wilms' tumor.
The cytogenetic abnormalities occurring in Wilms' tumors diagnosed and treated at the authors' institution were reviewed. Correlation with tumor histopathology, stage, and outcome were evaluated. Sixty-seven Wilms' tumors were encountered between 1984 and 1997. Tissue culture was obtained in 63 (94%) cases. Charts were reviewed retrospectively to obtain tumor histopathology, stage, and outcome. All tumors were examined in accordance with the National Wilms' Tumor Study (NWTS). Sixty-one were unilateral (54 unicentric, 7 multicentric), and 6 were bilateral (2 multicentric). Five Wilms' tumors showed anaplasia, whereas 62 showed favorable histology. Twenty children were stage I, 17 stage II, 20 stage III, 4 stage IV, and 6 stage V. Forty-eight (72%) tumors showed an abnormal karyotype. Chromosomal gain was more common than chromosomal loss, because hyperdiploidy was seen in 30 cases and hypodiploidy in 4. The most common aneuploidies were gains of chromosomes 6, 7, 8, 12, 13, and 18. In general, there was no correlation between specific chromosomal abnormalities with either tumor stage or histologic subtype. The only exceptions were anaplastic changes that were associated with poor prognosis and showed a variety of chromosomal changes including hyperdiploidy, hypodiploidy, and structural rearrangements. The 3 tumors causing mortality exhibited tetraploidy, hypodiploidy, and diploidy with a t(1p:11q) karyotype, respectively. Clonal progression was identified in Wilms' tumors when compared with its accompanying nephrogenic rest. A normal karyotype was seen more commonly in younger patients. Wilms' tumors display a variety of chromosomal abnormalities. These are particularly seen in anaplastic tumors and are less likely seen in younger patients. Overall, chromosomal gain was more common than loss with trisomies of chromosomes 12, 8, and 6 being the most frequently seen.


Spatial release from masking with noise-vocoded speech.
This study investigated how confusability between target and masking utterances affects the masking release achieved through spatial separation. Important distinguishing characteristics between competing voices were removed by processing speech with six-channel envelope vocoding, which simulates some aspects of listening with a cochlear implant. In the first experiment, vocoded target nonsense sentences were presented against two-talker vocoded maskers in conditions that provide different spatial impressions but not reliable cues that lead to traditional release from masking. Surprisingly, no benefit of spatial separation was found. The absence of spatial release was hypothesized to be the result of the highly positive target-to-masker ratios necessary to understand vocoded speech, which may have been sufficient to reduce confusability. In experiment 2, words excised from the vocoded nonsense sentences were presented against the same vocoded two-talker masker in a four-alternative forced-choice detection paradigm where threshold performance was achieved at negative target-to-masker ratios. Here, the spatial release from masking was more than 20 dB. The results suggest the importance of signal-to-noise ratio in the observation of "informational" masking and indicate that careful attention should be paid to this type of masking as implant processing improves and listeners begin to achieve success in poorer listening environments.


Transcriptional Signature of an Altered Purine Metabolism in the Skeletal Muscle of a Huntington's Disease Mouse Model.
Huntington's disease (HD) is a fatal neurodegenerative disorder, caused by a polyglutamine expansion in the huntingtin protein (HTT). HD has a peripheral component to its pathology: skeletal muscles are severely affected, leading to atrophy, and malfunction in both pre-clinical and clinical settings. We previously used two symptomatic HD mouse models to demonstrate the impairment of the contractile characteristics of the hind limb muscles, which was accompanied by a significant loss of function of motor units. The mice displayed a significant reduction in muscle force, likely because of deteriorations in energy metabolism, decreased oxidation, and altered purine metabolism. There is growing evidence suggesting that HD-related skeletal muscle malfunction might be partially or completely independent of CNS degeneration. The pathology might arise from mutant HTT within muscle (loss or gain of function). Hence, it is vital to identify novel peripheral biomarkers that will reflect HD skeletal muscle atrophy. These will be important for upcoming clinical trials that may target HD peripherally. In order to identify potential biomarkers that might reflect muscle metabolic changes, we used qPCR to validate key gene transcripts in different skeletal muscle types. Consequently, we report a number of transcript alterations that are linked to HD muscle pathology.


Lucidin type anthraquinone glycosides from Putoria calabrica.
Two new lucidin type anthraquinone glycosides, putorinoside A (1) and putorinoside B (2) were isolated from Putoria calabrica, in addition to two known anthraquinone glycosides, lucidin 3-O-beta-glucopyranoside (3) and lucidin 3-O-primeveroside (4). Based on spectroscopic data, putorinosides A and B were identified as 2-hydroxymethyl-1-methoxy-3,5,6-trihydroxyanthraquinone 3-O-beta-glucopyranoside and 2-hydroxymethyl-1-methoxy-3,6-dihydroxyanthraquinone 3-O-beta-glucopyranoside, respectively.


[Analysis of facial lesions on adult type atopic dermatitis with anti-fungus drug (terbinafine hydrochloride) -- analysis of serum anti-Malassezia IgE antibody titers and histamine release test].
Malassezia furfur has been described as an aggravating factor in facial lesions of atopic dermatitis, and oral antifungal agents have been reported to be effective against these lesions. We used terbinafine hydrochloride to treat 15 patients with adult-type atopic dermatitis and evaluated its efficacy by measuring the improvement in facial skin manifestations, serum IgE values, and serum anti-Malassezia IgE antibody titers. A histamine release test (HRT) for Malassezia. was also performed in 6 of the 15 patients. The facial skin manifestations improved in 8 (53.3%) of the 15 patients, and there were significant simultaneous decreases in their serum IgE values. The serum anti-Malassezia IgE antibody titer decreased significantly in all 15 patients. However, no significant correlation was observed between the HRT and the facial skin manifestations. We concluded that oral terbinafine hydrochloride is effective against the facial lesions of atopic dermatitis patients and this is possibly caused by decrease of Malassezia antigen in the facial lesions.


Effects of the Italian Law on Patient Safety and Health Professional Responsibilities Five Years after Its Approval by the Italian Parliament.
The application of the Italian law No. 24/2017, which focused on patient safety and medical liability, in the Italian National Health Service has been evaluated by a survey conducted five years after the promulgation of the law. The law required the establishment of healthcare risk management and patient safety centers in all Italian regions and the appointment of a Clinical Risk Manager (CRM) in all Italian public and private healthcare facilities. This study demonstrates that five years after the approval of the law, it has not yet been fully implemented. The survey revealed a lack of adequate permanent staff in all the Regional Centers, with two employees on average per Center. Few meetings were held with the Regional Healthcare System decision-makers with less than four meetings per year. This reduces the capacity to carry out functions. In addition, the role of the CRMs is weak in most healthcare facilities. More than 20% of CRMs have other roles in the same organization. Some important tasks have reduced application, e.g., assessment of the inappropriateness risk (reported only by 35.3% of CRM) and use of patient safety indicators for monitoring hospitals (20.6% of CRM). The function of the Regional Centers during the COVID-19 pandemic was limited despite the CRMs being very committed. The CRMs units undertake limited research and have reduced collaboration with citizen associations. Despite most of the CRMs believing that the law has had an important role in improving patient safety, 70% of them identified clinicians' resistance to change and lack of funding dedicated to implementing the law as the main barriers to the management of risk.


The association between erectile dysfunction and depressive symptoms in men treated for prostate cancer.
The relationship between erectile dysfunction (ED) and depressive symptoms is well established. However, this relationship is not well explored in men with prostate cancer. Limited data suggest men with prostate cancer may experience less ED bother than men with ED who do not have prostate cancer, implying that ED and depressive symptoms may not be associated in men with prostate cancer. To determine if ED is associated with depressive symptoms in men with prostate cancer. Assessments of quality-of-life (The Functional Assessment of Cancer Therapy [FACT-P]), anxiety/depression (Hospital Anxiety and Depression Scale [HADS]), and erectile function. Erectile function was measured with one question from the FACT-P similar to that used by the Massachusetts Male Aging Study. Men with prostate cancer, and naïve of hormone treatment, completed the study questionnaires at a single time point. The average age of the 339 men was 67±10 years. The average time since diagnosis was 3.9±3 years. When answering the question, "I am able to have and maintain an erection" on a 1 to 5 scale (5 representing the best function), the mean score was 2 indicating "a little bit." On univariate analysis, erectile function and depression were associated, r=-0.12, P<0.05. Other variables associated with depression were marital status, r=0.11, P<0.05; anxiety scores, r=0.56, P<0.01; and social support, r=-0.42, P<0.01. On multivariate analysis, erectile function remained a significant predictor of depression, beta=-0.10, P<0.05. Erectile function was associated with depressive symptoms in both univariate and multivariate analysis, indicating that ED is independently associated with depressive symptoms even though patients were approximately 4 years post diagnosis. These cross-sectional data suggest ED in men with prostate cancer can have lasting psychological effects.


[Computed tomography of the soft tissues of the shoulder. 1. Synovial reactions].
CT of the soft tissues of the shoulder without intra-articular contrast injections is useful for demonstrating effusions and synovial proliferation in the shoulder joint, in the bursa and in the synovial coverings of the long head of the biceps. The authors describe, for the first time, an intracapsular collection of fat in the posterior aspect of the capsule. This can be demonstrated via CT in 80% of the population. This fat line is displaced by even a few ml. of fluid in the presence of an effusion.


Small emergency departments: does size matter?
An emergency department provides care for a full spectrum of undifferentiated disorders and its size may influence how well it can do so. Outcomes research in emergency medicine is limited, although outcomes in severe trauma and acute coronary syndromes have been shown to be influenced by available facilities and expertise. A department can be too small to provide the full spectrum of emergency care, as has been documented with General Practice Casualty Units. Some research suggests that a critical mass is required to ensure acceptable outcomes. Small departments may operate in a hierarchical system, led by teaching hospitals setting practice standards. However, these may be opinion as much as evidence based and not broadly applicable as a universal practice standard. Small departments can be overwhelmed by trauma and other major cases or when the teaching hospital is unable to accept emergency patients or transfers because they are operating at capacity. Further outcomes research and audit of individual hospitals is required to determine a minimum optimum size for emergency departments.


Contact ulcers of the larynx. A reacquaintance with the pathology of an often underdiagnosed entity.
We reviewed the histologic features of 105 cases of contact ulcers of the larynx. Despite its characteristic clinical findings and correlative histopathology, the appropriate diagnosis was suggested in only one case. Instead, a descriptive diagnosis was most often rendered. Lesions for which this entity has been mistaken include pyogenic granuloma, hemangioma, hemangiopericytoma, Kaposi's sarcoma, angiosarcoma, spindle cell carcinoma, and granulomatous infectious diseases. Inappropriate diagnosis or failure to recognize the pathologic features of these lesions as correlating to a specific disease state deprives the patient of curative, well-established therapeutic procedures. We describe the histologic spectrum of contact ulcer of the larynx as well as its clinical findings, thereby familiarizing pathologists to an entity well recognized by otolaryngologists.


Non-interacting molecules as innate structural probes in surface plasmon resonance.
Determining the structural parameters of a molecular layer remains an unresolved problem in surface plasmon resonance (SPR). Given that molecular form and function are intimately coupled, a breakthrough in this area could be of considerable benefit to the study of protein and/or polymer-decorated material interfaces that are ubiquitous in biology and technology. Here, we describe how noninteracting molecules function as innate structural probes that "feel" the intrinsic exclusion volume of a surface-tethered molecular layer in SPR. Importantly, this is noninvasive and provides a means to bypass the refractive index (RI) constraint that convolutes and hinders SPR thickness measurements. To show proof-of-concept, we use BSA molecules in solution to measure the thicknesses of polyethylene glycol (PEG) molecular brushes as a function of molecular weight. The SPR-acquired brush thicknesses scale with PEG hydrodynamic diameter and are in good agreement with atomic force microscopy force-distance measurements. Theoretical treatments that account for changes in the evanescent field decay length at the metal-dielectric interface indicate that the method is most appropriate for low RI layers with an estimated maximal error of ±15% in the thickness due to the RI constraint. Such in situ thickness measurements can be easily incorporated into routine SPR binding assays for investigating mesoscopic structure-function correlations of diverse molecular layers (i.e., biointerfaces).


Glucose metabolism after pancreas transplantation: cyclosporine versus tacrolimus.
The results of the new immunosuppressants in simultaneous pancreas-kidney transplantation (SPK) concerning organ survival and rejection rates are excellent. Tacrolimus as well as cyclosporine are assumed to be diabetogenic; however, there are no comparative studies investigating their effects on glucose metabolism. One hundred thirty-six type 1 diabetic patients who had undergone successful SPK were investigated. Glucose and insulin levels during an oral glucose tolerance test as well as hemoglobin (Hb) A1c were analyzed. Investigations were performed early (3 months, n = 136) and late (3 years, n = 83) after transplantation. Graft recipients were grouped according to the first-line immunosuppression: group 1, cyclosporine; group 2, tacrolimus. There were no differences concerning age, gender, body mass index, and renal function between the groups. Early after transplantation, there was no difference between the groups concerning fasting glucose, HbA1c levels, basal and stimulated insulin secretion, and incidence of normal glucose tolerance. Late after transplantation, the incidence of a normal glucose tolerance tended to be lower (70% vs. 78%), whereas HbA1c (5.3% vs. 5.0%) and fasting glucose (81 vs. 78 mg/dL) levels tended to be higher in tacrolimus-treated patients. However, these differences were not significant. Insulin secretion was not reduced in the tacrolimus group. Concerning glucose metabolism and secretory capacity of the pancreas graft, no significant differences were found comparing tacrolimus- versus cyclosporine-treated graft recipients.


Functional alterations in macrophages after hypoxia selection.
Regions of low oxygen tension are common features of inflamed and infected tissues and provide physiologic selective pressure for the expansion of cells with enhanced hypoxia tolerance. The aim of this study was to investigate whether macrophages resistant to death induced by hypoxia were accompanied by functional alterations. A mouse macrophage cell line (J774 cells) was used to obtain subpopulations of death-resistant macrophages induced by long-term exposure to severe hypoxia (<1% O(2)). The results indicated that exposing J774 macrophages to periods of severe hypoxia results in the selection of cells with phenotypes associated with the modulation of heat-shock protein 70 kDa (HSP70) expression, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) production and reduced susceptibility to parasite Leishmania infection. Thus, we suggest that hypoxia-selected macrophages may influence the outcome of inflammation and infection.


Discovery of Novel Pseudomonas putida Flavin-Binding Fluorescent Protein Variants with Significantly Improved Quantum Yield.
Oxygen-independent, flavin-binding fluorescent proteins (FbFPs) are emerging as alternatives to green fluorescent protein (GFP), which has limited applicability in studying anaerobic microorganisms, such as human gastrointestinal bacteria, which grow in oxygen-deficient environments. However, the utility of these FbFPs has been compromised because of their poor fluorescence emission. To overcome this limitation, we have employed a high-throughput library screening strategy and engineered an FbFP derived from Pseudomonas putida (SB2) for enhanced quantum yield. Of the resulting SB2 variants, KOFP-7 exhibited a significantly improved quantum yield (0.61) compared to other reported engineered FbFPs, which was even higher than that of enhanced GFP (EGFP, 0.60), with significantly enhanced tolerance against a strong reducing agent.


The child patient and consent to treatment: legal overview.
The giving of consent by the patient before medical treatment is a central tenet of medical law. Although it may be fairly clear when an adult patient has given consent, the situation can be less clear, and more complex, when a child patient is involved. This article seeks to explore the legal issues and concepts that arise when treating a minor, and to show how the courts and legal process may become involved.


Anti-proliferative, anti-migration, and anti-invasion activity of novel hesperidin glycosides in non-small cell lung cancer A549 cells.
Several attempts have been made to synthesize and investigate modified flavonoids to improve their potential anticancer efficacy. This study aimed to determine the in vitro anti-viability, anti-migration, and anti-invasive effects of two novel hesperidin glycosides, hesperidin glucoside (HG1) and hesperidin maltoside (HG2), compared to original hesperidin and diosmin. Inhibitory effects on normal (MRC5) and cancer (A549) cell viability of hesperidin glycosides were investigated by the trypan blue and MTS assays. A scratch assay determined the suppressive effects on cancer cell migration, and inhibition of cancer cell invasion was investigated through Matrigel™. The selectivity index (SI), a marker of cell toxicity, was also determined for A549 relative to MRC5 cells. The cell viability trypan blue and MTS assays showed similar results of the inhibition of A549 cancer cells; HG1 and HG2 had lower IC50 than original hesperidin and diosmin. The SI of HG1 and HG2 was > 2 after 72-h culture. Investigation of cell migration showed that HG1 and HG2 inhibited the ability of gap closure in a time- and dose-dependent manner. The infiltration of the Matrigel™-coated filter by A549 cells was suppressed in the presence of HG1 and HG2. This result implied that HG1 and HG2 could inhibit cancer cell invasion. Our results suggest the inhibition of cancer cell migration and invasion in a time- and concentration-related manner with a favorable toxic profile. Moreover, HG1 and HG2 appeared potentially better agents than the original hesperidin for future anticancer development.


Transrectal ultrasonotomography of the canine prostate.
We developed a new scanner for transrectal ultrasonotomography of the canine prostate. Using this scanner, a clear horizontal tomogram of the canine prostate was obtained for cross sections at every 2 mm. Prostatic volume was estimated as the sum of the volume of each section. Accordingly, the weight of the canine prostate could be accurately calculated from the volume and the specific gravity of the prostate.


[Effect of immunization with Escherichia coli J5 on the course of experimental pyelonephritis in rats].
Among the germs of urinary tract infections is a great heterogenicity. Therefore, in search of vaccine candidates of pyelonephritis such germs must be checked the antigens of which to be occurred as much in other pyelonephritis germs as possible. E. coli J5 as a re-mutante of E. coli O111 has a core-antigen which is found in the most enterobacteria. We have examined whether a pyelonephritis in rats was prevented by prophylactic use of a E. coli J5 vaccine and if the course of the disease was influenced by vaccine treatment of animals with pyelonephritis, respectively. Neither a pyelonephritis was prevented nor an existing infection was influenced favourable by the vaccine of E. coli J5.


[Current situation in clinical trials with vaccines in the Czech Republic].
Clinical trials are an important part of clinical research. The conduction of clinical trials is strictly regulated and has to comply with an approved protocol. Local regulatory authorities, independent ethic committees, sponsors of clinical trials as well as the investigators are involved from the submission until the very end of the trial. All clinical trials performed in the Czech Republic have to be approved by the State Institute for Drug Control and by the Ethics Committee. The regulatory bodies and independent ethics committees evaluate and continuously supervise the justification and protocol of the clinical trial, quality of the investigational medicinal products and, primarily, the safety of the participants (patients and/or healthy volunteers) in clinical trials. In the Czech Republic there are many advanced clinical research centres, either located in private practices or within hospitals. The investigators are able to conduct a wide variety of clinical trials and recruit a high number of subjects for the trials, as well as to comply with the Good Clinical Practice guidelines and other regulatory requirements. The aim of this article is to summarise the current situation of clinical trials in the Czech Republic as well as the opportunities for getting involved in clinical trials and obligations arising for health professionals from such an involvement.


Gender Associated High Body Mass Index in Allergic Diseases.
The increasing prevalence of allergic diseases and atopy is affected by sex, age and lifestyle factors. Obesity and excess weight are reported to be potential risk factors for atopy and specifically for asthma symptoms in children and adults. To assess the relation between body mass index (BMI) and allergic diseases in patients of both genders, as well as association of BMI with atopy in healthy subjects. BMI (kg/m(2)), skin-prick test and total serum immunoglobulin E levels were assessed in 139 subjects: 109 were patients with allergic diseases (M to F ratio was 51:58) and 30 were healthy controls (M to F ratio was 6:24). The study population was grouped into asthma, asthmarhinitis, rhinitis, Urticaria oreczema and controls by BMI and sex. Females with the highest BMI were in asthma and urticaria/eczema group. Males with the highest BMI were in asthmarhinitis and urticariaeczema group. High BMI was associated with atopy in both genders of healthy controls. High levels of total IgE were in male allergic patients. High BMI was associated with asthma in females, urticaria/eczema in both genders and atopy in both genders of healthy controls. Higher levels of total IgE were concluded in male patients.


[Quality control of traditional Chinese medicines by the capillary electrophoresis fingerprint and capillary electrophoresis-mass spectrometry].
The quality control of traditional Chinese medicines by capillary electrophoresis (CE) fingerprint and CE-mass spectrometry(CE-MS) is reviewed. The optimum experimental conditions of CE, the research and appraisal methods of CE fingerprint for traditional Chinese medicines are also discussed . This review is based on the authors' work.


National Beef Quality Audit-2000: survey of targeted cattle and carcass characteristics related to quality, quantity, and value of fed steers and heifers.
The National Beef Quality Audit-2000 was conducted to assess the current status ofthe quality and consistency of U.S. fed steers and heifers. Between May and November 2000, survey teams assessed hide condition (n = 43,415 cattle for color, brands, mud/manure), bruises (n = 43,595 carcasses), offal and carcass condemnation (n = 8,588 cattle), and carcass quality and yield information (n = 9,396 carcasses) in 30 U.S. beef packing plants. Hide colors were black (45.1%), red (31.0%), yellow (8.0%), Holstein (5.7%), gray (4.0%), white (3.2%), brown (1.7%), and brindle (1.3%). Brand frequencies were no (49.3%), one (46.2%), and two or more (4.4%), and brands were located on the butt (36.3%), side (13.7%), and shoulder (3.6%). Most cattle had no (18.0%) or a small amount (55.8%) of mud/manure on their hides, and they had no (77.3%) horns. Most carcasses (53.3%) were not bruised, 30.9% had one bruise, and 15.8% had multiple bruises. Bruise location and incidence were round (14.9%), loin (25.9%), rib (19.4%), chuck (28.2%), and brisket, flank, and plate (11.6%). Condemnation item and incidence were liver (30.3%), lungs (13.8%), tripe (11.6%), heads (6.2%), tongues (7.0%), and carcasses (0.1%). Carcass evaluation revealed these traits and frequencies: steer (67.9%), heifer (31.8%), and bullock (0.3%) sex-classes; dark-cutters (2.3%); A (96.6%), B (2.5%), and C or older (0.9%) overall maturities; and native (90.1%), dairy-type (6.9%), and Bos indicus (3.0%) breed-types. Mean USDA yield grade traits were USDA yield grade (3.0), carcass weight (356.9 kg), adjusted fat thickness (1.2 cm), longissimus muscle area (84.5 cm2), and kidney, pelvic, and heart fat (2.4%). USDA yield grades were Yield Grade 1 (12.2%), Yield Grade 2 (37.4%), Yield Grade 3 (38.6%), Yield Grade 4 (10.4%), and Yield Grade 5 (1.3%). Mean USDA quality grade traits were USDA quality grade (Select85), marbling score (Small23), overall maturity (A66), lean maturity (A65), and skeletal maturity (A67). Marbling score distribution was Slightly Abundant or higher (2.3%), Moderate (4.8%), Modest (13.1%), Small (33.3%), Slight (43.3%), and Traces (3.4%). USDA quality grades were Prime (2.0%), Choice (49.1%), Select (42.3%), Standard (5.6%), and Commercial, Utility, Cutter, and Canner (0.9%). This information will help the beef industry measure progress compared to the past two surveys and will provide a benchmark for future educational and research activities.


Non-canonical eukaryotic glutaminyl- and glutamyl-tRNA synthetases form mitochondrial aminoacyl-tRNA in Trypanosoma brucei.
Glutaminyl-tRNA synthetase is thought to be absent from organelles. Instead, Gln-tRNA is formed via the transamidation pathway, the other route to this essential compound in protein biosynthesis. However, it was previously shown that glutaminyl-tRNA synthetase activity is present in Leishmania mitochondria. This work identifies genes encoding glutaminyl- and glutamyl-tRNA synthetase in the closely related organism Trypanosoma brucei. Down-regulation of their respective gene products by RNA interference showed that (i) they are essential for the growth of insect stage T. brucei and (ii) they are responsible for essentially all of the glutaminyl- and glutamyl-tRNA synthetase activity detected in both the cytosol and the mitochondria. In vitro aminoacylation experiments with the recombinant T. brucei enzymes and total tRNA confirmed the identity of the two aminoacyl-tRNA synthetases. Interestingly, T. brucei uses the same eukaryotic-type glutaminyl-tRNA synthetase to form mitochondrial and cytosolic Gln-tRNA. The formation of Glu-tRNA in mitochondria and the cytoplasm is catalyzed by a single eukaryotic-type discriminating glutamyl-tRNA synthetase. T. brucei, similar to Leishmania, imports all of its mitochondrial tRNAs from the cytosol. The use of these two eukaryotic-type enzymes in mitochondria may therefore reflect an adaptation to the situation in which the cytosol and mitochondria use the same set of tRNAs.


Improving machine learning force fields for molecular dynamics simulations with fine-grained force metrics.
Machine learning force fields (MLFFs) have gained popularity in recent years as they provide a cost-effective alternative to ab initio molecular dynamics (MD) simulations. Despite a small error on the test set, MLFFs inherently suffer from generalization and robustness issues during MD simulations. To alleviate these issues, we propose global force metrics and fine-grained metrics from element and conformation aspects to systematically measure MLFFs for every atom and every conformation of molecules. We selected three state-of-the-art MLFFs (ET, NequIP, and ViSNet) and comprehensively evaluated on aspirin, Ac-Ala3-NHMe, and Chignolin MD datasets with the number of atoms ranging from 21 to 166. Driven by the trained MLFFs on these molecules, we performed MD simulations from different initial conformations, analyzed the relationship between the force metrics and the stability of simulation trajectories, and investigated the reason for collapsed simulations. Finally, the performance of MLFFs and the stability of MD simulations can be further improved guided by the proposed force metrics for model training, specifically training MLFF models with these force metrics as loss functions, fine-tuning by reweighting samples in the original dataset, and continued training by recruiting additional unexplored data.


Characterization and mapping of monoclonal antibodies against the Sleeping disease virus, an aquatic alphavirus.
Sleeping disease virus (SDV) is an emerging pathogen in salmonid aquacultures, the impact of which is underestimated to date due to the lack of efficient diagnostic tools. To better characterize this new aquatic alphavirus and to make molecular tools available, a panel of monoclonal antibodies (mAbs) directed against SDV non-structural and structural proteins has been generated by immunizing mice with SDV-specific recombinant proteins overexpressed in Escherichia coli as antigens. So far, mAbs against nsP1, nsP3, E2 and E1 SDV proteins have been produced and their reactivity has been characterized by Western blot, radioimmunoprecipitation and indirect immunofluorescence assays. In addition, protein domains recognized by each mAb have been determined by immunofluorescence assay on truncated expressed SDV-derived proteins. Finally, one mAb directed against the E1 glycoprotein has been evaluated as a potential tool to be used in immunohistochemistry assay on experimentally infected trout.


Potent and reversible lentiviral vector restriction in murine induced pluripotent stem cells.
Retroviral vectors are derived from wild-type retroviruses, can be used to study retrovirus-host interactions and are effective tools in gene and cell therapy. However, numerous cell types are resistant or less permissive to retrovirus infection due to the presence of active defense mechanisms, or the absence of important cellular host co-factors. In contrast to multipotent stem cells, pluripotent stem cells (PSC) have potential to differentiate into all three germ layers. Much remains to be elucidated in the field of anti-viral immunity in stem cells, especially in PSC. In this study, we report that transduction with HIV-1-based, lentiviral vectors (LV) is impaired in murine PSC. Analyses of early retroviral events in induced pluripotent stem cells (iPSC) revealed that the restriction is independent of envelope choice and does not affect reverse transcription, but perturbs nuclear entry and proviral integration. Proteasomal inhibition by MG132 could not circumvent the restriction. However, prevention of cyclophilin A (CypA) binding to the HIV-1 capsid via use of either a CypA inhibitor (cyclosporine A) or CypA-independent capsid mutants improved transduction. In addition, application of higher vector doses also increased transduction. Our data revealed a CypA mediated restriction in iPSC, which was acquired during reprogramming, associated with pluripotency and relieved upon subsequent differentiation. We showed that murine PSC and iPSC are less susceptible to LV. The block observed in iPSC was CypA-dependent and resulted in reduced nuclear entry of viral DNA and proviral integration. Our study helps to improve transduction of murine pluripotent cells with HIV-1-based vectors and contributes to our understanding of retrovirus-host interactions in PSC.


[Erythrocyte sedimentation rate, fibrinemia, alpha-2 globulinemia, biological inflammation and the practitioner (author's transl)].
The authors found a significant statistical correlation (linear and Spearman) between erythrocyte sedimentation rate (ESR), plasma fibrinogen level, alpha-2-globulins level, platelets count, anemia and age, in 1 000 patients admitted to the Hôtel-Dieu of Marseille. The high degree of partial correlations obtained, confirmed that a direct and independent relationship exists between ESR-fibrinogen, ESR - alpha-2-globulin, fibrinogen - alpha-2-globulin. Determinations of plasma fibrinogen and alpha-2-globulin levels are they still useful in the survey of inflammatory diseases when ESR can be easily determined?


A post-Flexner comparative case study of medical training responses to health system needs in Brazil and Germany.
Health systems need medical professionals who can and will work in outpatient settings, such as general practitioner practices or health centres. However, medical students complete only a small portion of their medical training there. Furthermore, this type of training is sometimes seen as inferior to training in academic medical centres and university hospitals. Hence, the healthcare system's demand and the execution of medical curricula do not match. Robust concepts for better alignment of both these parts are lacking. This study aims to (1) describe decentral learning environments in the context of traditional medical curricula and (2) derive ideas for implementing such scenarios further in existing curricula in response to particular medicosocietal needs.This study is designed as qualitative cross-national comparative education research. It comprises three steps: first, two author teams consisting of course managers from Brazil and Germany write a report on change management efforts in their respective faculty. Both teams then compare and comment on the other's report. Emerging similarities and discrepancies are categorised. Third, a cross-national analysis is conducted on the category system.Stakeholders of medical education (medical students, teaching faculty, teachers in decentral learning environments) have differing standards, ideals and goals that are influenced by their own socialisation-prominently, Flexner's view of university hospital training as optimal training. We reiterate that both central and decentral learning environments provide meaningful complementary learning opportunities. Medical students must be prepared to navigate social aspects of learning and accept responsibility for communities. They are uniquely positioned to serve as visionaries and university ambassadors to communities. As such, they can bridge the gap between university hospitals and decentral learning environments.


A Framework for the Development of maternal quality of care indicators.
In collaboration with the California Department of Health Maternal and Child Health Branch, the authors formed a Working Group to identify potential clinical indicators that could be used to inform decision making regarding maternal health care quality. To develop potential indicators for the assessment of maternal health care quality. A Working Group was convened to review information from the published literature and expert opinion. Selection of potential indicators was guided by the following goals: 1) To identify key areas for routine aggregate monitoring; 2) To include perspectives of relevant stakeholders in maternal health care services; 3) To include measures that are comprehensive and reflect a balance between maternal and fetal interests; and 4) To develop measures that would be valid, generalizable, mutable, and feasible. Ninety potential indicators were identified. Each underwent a thorough review based on: its definition, objective, and validity; its contribution to innovation; the cost and timeliness of implementation; its feasibility, acceptability, and potential effectiveness; and its compatibility with ethics, values, and social policy. This process yielded 24 final indicators from the following categories: Health Status and Access (e.g., availability of 24 h inpatient anesthesia); Preconception and Interconception Care (e.g., Pap smear use); Antenatal Care (e.g., hospitalization for uncontrolled diabetes or pyelonephritis); Labor and Delivery Care (e.g., chorioamnionitis or obstetrical hemorrhage), and Postpartum Care (e.g., rate of postpartum visits). These potential indicators, representative of the women's health continuum, can serve as a foundation to structure the development of consensus and methods for maternal health care quality assessment.


Evolution of DMSP (dimethylsulfoniopropionate) biosynthesis pathway: Origin and phylogenetic distribution in polyploid Spartina (Poaceae, Chloridoideae).
DMSP (dimethylsulfoniopropionate) is an ecologically important sulfur metabolite commonly produced by marine algae and by some higher plant lineages, including the polyploid salt marsh genus Spartina (Poaceae). The molecular mechanisms and genes involved in the DMSP biosynthesis pathways are still unknown. In this study, we performed comparative analyses of DMSP amounts and molecular phylogenetic analyses to decipher the origin of DMSP in Spartina that represents one of the major source of terrestrial DMSP in coastal marshes. DMSP content was explored in 14 Spartina species using 1H Nuclear Magnetic Resonance (NMR) spectroscopy and Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS). Putative genes encoding the four enzymatic steps of the DMSP biosynthesis pathway in Spartina were examined and their evolutionary dynamics were studied. We found that the hexaploid lineage containing S. alterniflora, S. foliosa and S. maritima and their derived hybrids and allopolyploids are all able to produce DMSP, in contrast to species in the tetraploid clade. Thus, examination of DMSP synthesis in a phylogenetic context implicated a single origin of this physiological innovation, which occurred in the ancestor of the hexaploid Spartina lineage, 3-6MYA. Candidate genes specific to the Spartina DMSP biosynthesis pathway were also retrieved from Spartina transcriptomes, and provide a framework for future investigations to decipher the molecular mechanisms involved in this plant phenotypic novelty that has major ecological impacts in saltmarsh ecosystems.


Highly Reliable Silver Nanowire Transparent Electrode Employing Selectively Patterned Barrier Shaped by Self-Masked Photolithography.
The transparent electrode based on silver nanowire (AgNW) networks is one promising alternative of indium tin oxide film in particular for advanced flexible and printable electronics. However, the widespread application of AgNW electrode is hindered by its poor long-term reliability. Although the reliability can be improved by applying traditional overcoating layer or the core-shell structure, the transmittance or conductivity is inevitably undermined. In this paper, a novel patterned barrier of photoresist in situ assembled on the nanowire surface realized the reliability enhancement by simply employing AgNWs themselves as the mask in the photolithography process. The patterned barrier selectively covered the nanowires, while keeping the high transmittance and conductivity unchanged and improving the adhesion of AgNW networks on substrate. After 720 h storage in 85 °C/85% relative humidity (RH) environment, the resistance of electrode with patterned barrier only increased by 0.72 times. This study proposes a new way, i.e., the in situ patterned barrier containing light-sensitive substance, to selectively protect AgNW networks, which can be expanded to various metallic networks including nanowires, nanorods, nanocables, electrospun nanofibers, and so on.


Risks and benefits of oral contraceptive pills.
In the more than 40 years since the combined oral contraceptive pill was first marketed, much information has been obtained as to its risks. Considerably less publicity has been given to the balancing benefits that have also emerged. There has been an increasing realization that the risks are focused in those women with recognised risk factors, meaning that the remainder can use the product with increasing reassurance. The doses of both hormones have also been lowered considerably since the early years. Thus, it can be a rational decision by a fully informed woman to use this form of contraception.


Activating TiO2 Nanoparticles: Gallium-68 Serves as a High-Yield Photon Emitter for Cerenkov-Induced Photodynamic Therapy.
The classical photodynamic therapy (PDT) requires external light to activate photosensitizers for cancer treatment. However, limited tissue penetration of light has been a long-standing challenge for PDT to cure malignant tumors in deep tissues. Recently, Cerenkov radiation (CR) emitted by radiotracers such as 18F-fluorodeoxyglucose (18F-FDG) has become an alternative and promising internal light source. Nevertheless, fluorine-18 (F-18) only releases 1.3 photons per decay in average; consequently, injection dose of F-18 goes beyond 10-30 times more than usual to acquire therapeutic efficacy because of its low Cerenkov productivity. Gallium-68 (Ga-68) is a favorable CR source owing to its ready availability from generator and 30-time higher Cerenkov productivity. Herein, we report, for the first time, the use of Ga-68 as a CR source to activate dextran-modified TiO2 nanoparticles (D-TiO2 NPs) for CR-induced PDT. Compared with 18F-FDG, 68Ga-labeled bovine serum albumin (68Ga-BSA) inhibited the growth of 4T1 cells and exhibited significantly stronger DNA damage to tumor cells. In vivo studies showed that the tumor growth was almost completely inhibited when tumor-bearing mice were treated with a combination of D-TiO2 NPs and 68Ga-BSA. This study proved that Ga-68 is a more potent radionuclide for PDT than F-18 both in vitro and in vivo offered a promising strategy of using a diagnostic dose of radioactivity to achieve depth-independent cancer therapy without using any external light source.


[Once in a blue moon: coronavirus disease complicates pregnancy in a patient with unknown pulmonary hypertension and subsequent left ventricular dysfunction].
During COVID-19 pandemic, several clinical manifestations have been described beyond respiratory compromise that characterizes the viral disease. Cardiovascular manifestations are one of the main complications. In this case, we report an unusual association between the novo diagnosis of pulmonary arterial hypertension in a pregnant patient with SARS Cov-2, with subsquent development of left ventricular dysfunction.


The cysteine residues of recombinant human gastric lipase.
Recombinant human gastric lipase (rHGL) and three of its cysteine mutants (cysteine 227, 236, and 244 substitued for threonine or serine) were expressed in the baculovirus/insect cell system and purified to homogeneity by performing a two-step procedure. Substituting Ser for Cys 227 and Cys 236 resulted in mutant lipases with a significantly lower level of activity (30% and 22%, respectively) on a short chain triglyceride (tribuyrin) substrate, while the mutation at position 244 only slightly reduced the activity. Using 4, 4'-dithiopyridine (4-PDS) as a sulfhydryl reagent on the above mutants, it was possible to clearly identify the single sulfhydryl residue at position 244 and consequently, the disulfide bridge at position 227-236. No potential disulfide bridges were formed during the protein folding between cysteines 227-244 or between cysteines 236-244, as thought to occur in the case of rabbit gastric lipase (RGL). The present results are consistent with the recently determined 3D-structure of rHGL.


Primaquine for radical cure of Plasmodium vivax and Plasmodium ovale malaria: an observational survey (2008-2010).
Since 2008, the French guidelines have promoted the systematic use of 30 mg/day of primaquine for the radical cure of Plasmodium vivax and Plamodium ovale infections. We observed three relapses in 10 patients with P vivax acquired in French Guiana. No relapses were seen in West African P ovale patients.


Chronic suppurative otitis media and its association with socio-econonic factors among rural primary school children of bangladesh.
Chronic Suppurative Otitis Media (CSOM) is a common community health disorder of children in all developing countries like Bangladesh which causes significant impact in speech, cognitive, educational and psychological development. The aim of the study was to determine the prevalence of CSOM and its association with certain socio-economic factors and health related practice and believes among rural primary school children of Bangladesh. The study was done among 1468 rural school going children (Boys:Girls, 1:1.23) aged between 4 and 12 years (mean 8.8 ± 1.66) in five randomly selected rural primary school of Palash Upazilla of Narsingdi district, Bangladesh. They had underwent ENT check up by the doctors trained in ENT and their guardians were interviewed regarding their socioeconomic status, health related practices and beliefs and other related issues using a pre tested protocol. Total 77 (5.2%) cases of CSOM were detected with girl's predominance (5.7 vs. 4.7%). Our study revealed statistically significant association of CSOM with yearly income of guardian (P < 0.005), maternal education (P < 0.001), bathing habit (P < 0.001), ear cleaning habit (P < 0.05), pattern of primary medical consultation (P < 0.05). Disease prevalence was also found higher among the dwellers of kachha house. So, this preventable burning problem of CSOM can be resolved by collective effort by incorporating primary ear care program with primary health care system among the vulnerable children of rural area along with their socio-economic development. Thus, future citizens can be safeguarded from developing CSOM, hearing impairment and its resultant complications.


Controlled crack propagation for atomic precision handling of wafer-scale two-dimensional materials.
Although flakes of two-dimensional (2D) heterostructures at the micrometer scale can be formed with adhesive-tape exfoliation methods, isolation of 2D flakes into monolayers is extremely time consuming because it is a trial-and-error process. Controlling the number of 2D layers through direct growth also presents difficulty because of the high nucleation barrier on 2D materials. We demonstrate a layer-resolved 2D material splitting technique that permits high-throughput production of multiple monolayers of wafer-scale (5-centimeter diameter) 2D materials by splitting single stacks of thick 2D materials grown on a single wafer. Wafer-scale uniformity of hexagonal boron nitride, tungsten disulfide, tungsten diselenide, molybdenum disulfide, and molybdenum diselenide monolayers was verified by photoluminescence response and by substantial retention of electronic conductivity. We fabricated wafer-scale van der Waals heterostructures, including field-effect transistors, with single-atom thickness resolution.


The in vitro effect of gefitinib ('Iressa') alone and in combination with cytotoxic chemotherapy on human solid tumours.
Activation of the epidermal growth factor receptor (EGFR) triggers downstream signaling pathways that regulate many cellular processes involved in tumour survival and growth. Gefitinib ('Iressa') is an orally active tyrosine kinase inhibitor (TKI) targeted to the ATP-binding domain of EGFR (HER1; erbB1). In this study we have used a standardised ATP-based tumour chemosensitivity assay (ATP-TCA) to measure the activity of gefitinib alone or in combination with different cytotoxic drugs (cisplatin, gemcitabine, oxaliplatin and treosulfan) against a variety of solid tumours (n = 86), including breast, colorectal, oesophageal and ovarian cancer, carcinoma of unknown primary site, cutaneous and uveal melanoma, non-small cell lung cancer (NSCLC) and sarcoma. The IC50 and IC90 were calculated for each single agent or combination. To allow comparison between samples the IndexSUM was calculated based on the percentage tumour growth inhibition (TGI) at each test drug concentration (TDC). Gefitinib was tested at concentrations ranging from 0.0625-2 microM (TDC = 0.446 microg/ml). This study represents the first use of a TKI in the assay. There was heterogeneity in the degree of TGI observed when tumours were tested against single agent gefitinib. 7% (6/86) of tumours exhibited considerable inhibition, but most showed a more modest response resulting in a low TGI. The median IC50 value for single agent gefitinib in all tumours tested was 3.98 microM. Interestingly, gefitinib had both positive and negative effects when used in combination with different cytotoxics. In 59% (45/76) of tumours tested, the addition of gefitinib appeared to potentiate the effect of the cytotoxic agent or combination (of these, 11% (5/45) had a >50% decrease in their IndexSUM). In 38% of tumours (29/76), the TGI was decreased when the combination of gefitinib + cytotoxic was used in comparison to the cytotoxic alone. In the remaining 3% (2/76) there was no change observed. The in vitro model suggests that gefitinib may have differential effects in response to concomitant cytotoxic chemotherapy with the agents tested during this study. The mechanism involved may relate to the effect of TKIs on growth rate versus their effect on the ability of the cell to survive the stimulus to apoptosis produced by chemotherapy.


Protein interacting with C‑kinase 1 modulates exocytosis and KATP conductance in pancreatic β cells.
It has been previously identified that α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) are expressed in pancreatic β cells and regulate exocytosis and insulin release. It is known that protein interacting with C‑kinase 1 (PICK1) regulates trafficking and synaptic targeting of AMPARs in the central nervous system. However, it is unknown whether PICK1 regulates glutamate‑induced insulin release in β cells. The present study demonstrated that glutamate‑induced exocytosis was increased in β cells derived from PICK1‑knockout mice. In agreement with this result, adding PICK1 in β cells reduced glutamate‑induced exocytosis, whereas adding EVKI, a peptide that interrupts the interaction between AMPARs and PICK1, increased the exocytosis of β cells with the application of glutamate. Furthermore, the conductance of ATP‑sensitive potassium (KATP) channels was reduced in PICK1‑knockout mice, which was reversed by the overexpression of PICK1. In addition, PICK1 application reduced voltage oscillation induced by the closure of KATP. Taken together, the results indicate that PICK1 regulates glutamate‑induced exocytosis in β cells.


Antioxidant potential of Juglans nigra, black walnut, husks extracted using supercritical carbon dioxide with an ethanol modifier.
The black walnut, Junglas nigra, is indigenous to eastern North America, and abscission of its fruit occurs around October. The fruit consists of a husk, a hard shell, and kernel. The husk is commonly discarded in processing, though it contains phenolic compounds that exhibit antioxidant and antimicrobial properties. For this study, black walnut husks were extracted using supercritical carbon dioxide with an ethanol modifier. The effects of temperature, ethanol concentration, and drying of walnut husks prior to extraction upon antioxidant potential were evaluated using a factorial design of experiments. The solvent density was held constant at 0.75 g/mL. The optimal extraction conditions were found to be 68°C and 20 wt-% ethanol in supercritical carbon dioxide. At these conditions, the antioxidant potential as measured by the ferric reducing ability of plasma (FRAP) assay was 0.027 mmol trolox equivalent/g (mmol TE/g) for dried walnut husk and 0.054 mmol TE/g for walnut husks that were not dried. Antioxidant potential was also evaluated using the total phenolic content (TPC) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assays and the FRAP assay was found to linearly correlate to the TPC assay.


Cognitive impairment and BDNF serum levels.
To investigate the alterations of brain-derived neurotrophic factor (BNDF) serum levels in subjects with different intensity of cognitive impairment and different neurodegenerative processes. Serum BDNF levels were analyzed by ELISA kit in 378 subjects: 134 Alzheimer's disease (AD) patients, 115 amnestic mild cognitive impairment (MCI) patients, and 129 controls divided into two groups: neurodegenerative control group (ND), consisting of 49 Parkinson's disease patients without any cognitive complaints, and cognitively normal control group (CN), consisting of 80 subjects without any neurological disorders. AD patients had significantly lower (p<0.001) BDNF serum levels compared to MCI, CN and ND controls. Age and education had significant influence on BDNF serum levels regardless the diagnosis or group assignment. We have found no influence of depression on BDNF serum levels either in our group as a whole, or in each group assessed separately. We found significant correlation between BDNF serum levels and cognitive impairments. After multiple comparisons between the groups, we found that, after adjustment for confounding factors (age, gender, education, depression, cognitive impairment), BDNF serum levels were the lowest in AD group (p=0.05). Advanced age and low educational level are associated with decreased BDNF serum levels. Decreased BDNF serum levels correspond to the severity of cognitive impairment. There is no correlation between BDNF serum levels and depressive symptoms.


Multiple noncontiguous injuries of the spine in a child: atlantooccipital dislocation and seat-belt injury of the lumbar spine.
Multiple noncontiguous injuries of nonadjoining regions of the spine in children are rare. Such injuries can be overlooked as the neurological deficit caused by one injury can be masked by the other. The combination of atlantooccipital dislocation and a seat-belt injury of the spine in children is rare. We describe an unusual case of atlantooccipital dislocation in combination with a seat-belt injury of the lumbar spine in a surviving child. Early halo-vest immobilization was an effective treatment in this patient. Although survival with atlantooccipital injuries is becoming common, severe and persistent neurological deficits can result in high morbidity. A brief description of the pathomechanics, diagnosis and treatment of the atlantooccipital dislocation and lumbar seat-belt injury is given.


Adolescent and adult rats' aversion to flavors previously paired with nicotine.
Despite the high prevalence of adolescent smoking, few studies have examined nicotine sensitivity during this developmental period. In the present study we examined adolescent and adult rats' preference/aversion for a flavor previously paired with nicotine. Paired (nicotine + Kool-Aid) and unpaired (Kool-Aid) solutions were presented in the home cage on alternating nights, with water given during the light phase for six days. A choice test was conducted 24 hr after the last night of conditioning, with both flavors presented simultaneously during the dark cycle. On test day, although the flavor previously paired with nicotine was not preferred at either age, adolescent rats consumed significantly more of the paired flavor than adults. These results suggest that adolescent rats are less sensitive to the aversive properties of nicotine. This finding taken together with adolescents' increased sensitivity to the rewarding properties of nicotine, may result in an increased vulnerability to nicotine dependence.


Tissue-specific expression of multiple gamma-glutamyl transpeptidase mRNAs in rat epithelia.
gamma-Glutamyl transpeptidase (GGT) is an enzyme that plays a key role in interorgan glutathione transport. Three mRNAs (mRNAI, mRNAII, and mRNAIII) are known to encode the GGT precursor; they are initiated on three separate promoters on the single GGT gene. In this work, we identified by Northern blot and RNase H analysis a new GGT mRNA (mRNAIV). This mRNA differs from the others in its 5'-noncoding sequence. This mRNA species is the predominant GGT mRNA expressed in HTC hepatoma cells and in the small intestine in which its level increases from the base to the apex of the microvillus. The analysis of the GGT gene expression pattern in kidney, mammary gland, small intestine, liver, preneoplastic liver, and HTC hepatoma cells reveals a strong tissue or cell specificity. The mRNAIII was found in all the tissues and cells; in contrast, the expression of mRNAI, mRNAII, and mRNAIV is limited in normal tissues to the kidney and to the small intestine, the two tissues that display the highest enzyme activity. The synthesis of these three mRNAs is linked to the development of the kidney proximal tubule and to the differentiation of the enterocyte. The tissue and cell specificity of the GGT gene expression is based upon the use of multiple promoters that are controlled independently by specific cell factors.


Isolation and identification of surface-bound acetone enolate on Ni(111).
A surface-bound acetone enolate species has been synthesized on Ni(111) between 260 and 340 K by two different routes catalyzed by surface Ni and O atoms: deprotonation of acetone and deacetylation of acetylacetone. The reaction pathways and surface species have been identified using reflection absorption infrared spectroscopy (RAIRS) in combination with isotopic substitution and density functional theory (DFT) calculations. Acetone enolate exhibits characteristic vibrational absorption bands at 1260, 1353, and 1545 cm-1 arising from mixed modes that involve CC stretching, CH3 bending, and CO stretching. This work conclusively proves the existence of stable acetone enolate species on a metal single-crystal surface and provides its first detailed characterization.


Pseudoepitheliomatous hyperplasia mimicking ocular surface squamous neoplasia following cultivated limbal epithelium transplantation.
A 12-year-old girl with total limbal stem cell deficiency in the right eye following chemical burns underwent autologous cultivated limbal epithelium transplantation from the healthy left eye. Postoperatively at 6 weeks a mass at the limbus was noted, which increased in size and involved infero-nasal limbus extending over 5 mm on bulbar conjunctiva. It was a gelatinous, placoid freely movable mass with irregular surface, multiple intralesional cysts without feeder vessels or intrinsic vascularization and stained brilliantly with rose bengal. Histopathology following excision biopsy showed hyperplastic epithelium with stratified columnar cells and goblet cells. At the last follow-up, 6 months following cultivated limbal epithelium transplantation the ocular surface was stable without any recurrence of the lesion. We herein report a rare complication of epithelial hyperplasia presenting as leukoplakia following cultivated limbal epithelium transplantation mimicking ocular surface squamous neoplasia.


Direct ex vivo analysis of activated, Fas-sensitive autoreactive T cells in human autoimmune disease.
The frequency of clonally expanded and persistent T cells recognizing the immunodominant autoantigenic peptide of myelin basic protein (MBP)p85-99 was directly measured ex vivo in subjects with typical relapsing remitting multiple sclerosis (MS). T cells expressing mRNA transcripts encoding T cell receptor (TCR)-alpha and -beta chains found in T cell clones previously isolated from these subjects recognizing the MBPp85-99 epitope were examined. In contrast to frequencies of 1 in 10(5)-10(6) as measured by limiting dilution analysis, estimates of the T cell frequencies expressing MBPp85-99-associated TCR chain transcripts were as high as 1 in 300. These high frequencies were confirmed by performing PCR on single T cells isolated by flow cytometry. MBPp85-99 TCR transcripts were present in IL-2 receptor alpha-positive T cells which were induced to undergo Fas-mediated cell death upon antigen stimulation. These data demonstrate that at least a subpopulation of patients with MS can have a very high frequency of activated autoreactive T cells.


Perturbation model to predict the effect of spatially varying absorptive inhomogeneities in diffusing media.
We develop a perturbation model to predict the effect of a spatially varying absorptive inhomogeneities in a diffusing slab. The model is based on a perturbation solution of diffusion equation derived for a refractive index mismatch between the scattering slab and the surrounding medium, through the use of the extrapolated boundary conditions. We show that the model allows to compute the time-dependent relative change in the transmitted signal resulting from the presence of the inclusion. We derive simplified expressions for the perturbed time-resolved transmittance that allows to implement an efficient fitting procedure for obtaining the optical properties of the absorptive inclusion. The accuracy of the predictions of the model was investigated through comparison with the results of the Finite Element Method to solve the time-dependent diffusion equation numerically. The procedure is used to obtain the absorption perturbation parameter of an absorptive inclusion characterized by spatially dependent Gaussian distribution of its absorption coefficient located at the midplane of a scattering slab.


Liver Transplant for Nonhepatocellular Carcinoma Malignancy.
Liver transplant is now an acceptable and effective treatment for specific nonhepatocellular malignancies. Worldwide, hilar cholangiocarcinoma accounts for 3% of all primary gastrointestinal malignancies and for 10% of primary hepatobiliary malignancies. For patients who have early-stage, unresectable cholangiocarcinoma, liver transplant preceded by neoadjuvant radiotherapy can result in tumor-free margins, accomplish a radical resection, and treat the underlying primary sclerosing cholangitis when present. Hepatic epithelioid hemangioendothelioma is a rare tumor of vascular origin with a variable malignant potential. Excellent results have been reported with liver transplant for patients with unresectable hepatic epithelioid hemangioendothelioma, with 1-year and 10-year survival rates of 96% and 72%. Hepatoblastoma is the most common primary hepatic malignancy in children. The long-term survival rate after transplant ranges from 66% to 77% in patients with unresectable tumors and good response to chemotherapy. Metastatic liver disease is not an indication for liver transplant, with the exception of cases in which the primary tumor is a neuroendocrine tumor. Indication for liver transplant for hepatic metastasis from neuroendocrine tumors is mainly for patients with unresectable tumors and for palliation of medically uncontrollable symptoms. Posttransplant survival in those patients with low tumor activity index is excellent, despite recurrence of the tumor. Some recent data on liver transplant for unresectable hepatic metastases from colorectal cancer have reported limited survival benefits compared with previous reports. However, due to the high rate of tumor recurrence in a very short time after liver transplant, especially in the era of organ shortage, this indication has not been favored by the transplant community. The indications for liver transplant for nonhepatocellular carcinoma malignancy and its limitations have evolved dramatically over the past decades and will continue to be redefined through future research and investigations.


Automated protein sequence database classification. II. Delineation Of domain boundaries from sequence similarities.
Decomposing each protein into modular domains is a basic prerequisite to classify accurately structural units in biological molecules. Boundaries between domains are indicated by two similar amino acid sequence segments located within the same protein (repeats) or within homologous proteins at notably different distances from their respective N- or C-termini. We have developed an automated method that combines such positional constraints derived from various detected pairwise sequence similarities to delineate the modular organization of proteins. The procedure has been applied to a non-redundant data set of 26 990 proteins whose sequences were taken from the PIR and SWISS-PROT databanks and shared <60% sequence identity amongst pairs. The resultant clustering, delineation and multiple alignment of 24 380 sequence fragments yielded a new database of 4364 domain families. Comparison of the domain collection with that of PRODOM indicates a clear improvement in the number and size of domain families, domain boundaries and multiple sequence alignments. The accuracy and sensitivity of the method are illustrated by results obtained for ankyrin-like repeats and EGF-like modules. The resulting database, called DOMO, is available through the database search routine SRS at Infobiogen (http://www.infobiogen.fr/srs5/), EBI (http://srs.ebi.ac.uk:5000/) and EMBL (http://www.embl-heidelberg.de/srs5/) World Wide Web sites. email@example.com


[Progress in the application of laparoscopic and endoscopic cooperative surgery in gastrointestinal stromal tumors].
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor among gastrointestinal tumors, with an inherent potential for malignancy. The primary approach to addressing GIST remains surgical intervention. Laparoscopic and endoscopic cooperative surgery (LECS) has emerged as an innovative treatment approach for GIST. LECS includes various techniques, such as classic LECS, inverted LECS, and laparoscopic-assisted endoscopic full-thickness resection, all of which aim to combine the advantages of laparoscopy and endoscopy. This treatment offers benefits such as accurate localization, complete lesion removal, and a good prognosis. Generally, LECS can be used for GIST with a tumor diameter less than 50 mm, which cannot be completely removed through traditional endoscopic surgery. The clinical application of LECS deserves further exploration and expansion in the future, ultimately benefiting patients.


Insulin Signaling Regulates the FoxM1/PLK1/CENP-A Pathway to Promote Adaptive Pancreatic β Cell Proliferation.
Investigation of cell-cycle kinetics in mammalian pancreatic β cells has mostly focused on transition from the quiescent (G0) to G1 phase. Here, we report that centromere protein A (CENP-A), which is required for chromosome segregation during the M-phase, is necessary for adaptive β cell proliferation. Receptor-mediated insulin signaling promotes DNA-binding activity of FoxM1 to regulate expression of CENP-A and polo-like kinase-1 (PLK1) by modulating cyclin-dependent kinase-1/2. CENP-A deposition at the centromere is augmented by PLK1 to promote mitosis, while knocking down CENP-A limits β cell proliferation and survival. CENP-A deficiency in β cells leads to impaired adaptive proliferation in response to pregnancy, acute and chronic insulin resistance, and aging in mice. Insulin-stimulated CENP-A/PLK1 protein expression is blunted in islets from patients with type 2 diabetes. These data implicate the insulin-FoxM1/PLK1/CENP-A pathway-regulated mitotic cell-cycle progression as an essential component in the β cell adaptation to delay and/or prevent progression to diabetes.


Comparison of ximelagatran, an oral direct thrombin inhibitor, with enoxaparin for the prevention of venous thromboembolism following total hip replacement. A randomized, double-blind study.
Prophylaxis is recommended following total joint replacement because of the high risk of venous thromboembolism (VTE). Postoperative low-molecular-weight heparin (LMWH) reduces the incidence of venographically detected deep vein thrombosis (DVT) to about 10-15% in total hip replacement (THR) patients. Ximelagatran is a novel, oral direct thrombin inhibitor that selectively and competitively inhibits both free and clot-bound thrombin. We compared the efficacy and safety of ximelagatran with those of enoxaparin for the prevention of VTE in patients undergoing THR. This was a prospective, randomized, multicenter, double-blind study conducted principally in the USA and Canada. Patients received fixed-dose oral ximelagatran 24 mg bid or subcutaneous enoxaparin 30 mg bid and matched placebo for 7-12 days; both regimens were initiated the morning after surgery. The incidence of VTE (by postoperative day 12) included thrombosis determined by mandatory venography of the leg on which surgery was performed and symptomatic, objectively proven DVT or pulmonary embolism (PE). VTE and bleeding events were interpreted by an independent central adjudication committee for primary analysis. Of the 1838 patients randomized, 1557 had either adequate venography or symptomatic, proven VTE (efficacy population). Overall rate of venography acceptable for evaluation was 85.4%. Overall rates of total VTE were 7.9% (62 of 782 patients) in the ximelagatran group and 4.6% (36 of 775 patients) in the enoxaparin group, with an absolute difference of 3.3% and a 95% confidence interval for the difference of 0.9% to 5.7%. Proximal DVT and/or PE occurred in 3.6% (28 of 782 patients) in the ximelagatran group and 1.2% (nine of 774 patients) in the enoxaparin group. Major bleeding events were observed in 0.8% (seven of 906) of the ximelagatran-treated patients and in 0.9% (eight of 910) of the enoxaparin-treated patients (P > 0.95). Non-inferiority of ximelagatran 24 mg bid based on a prespecified margin of 5% was not met, resulting in superiority of the enoxaparin regimen. Both ximelagatran and enoxaparin decreased the overall rate of VTE compared with that reported historically. However, in this study, enoxaparin 30 mg bid was more effective than ximelagatran 24 mg bid for prevention of VTE in THR. Oral ximelagatran was used without coagulation monitoring, was well tolerated, and had bleeding rates comparable to those of enoxaparin. Further refinement by testing a higher dose of ximelagatran in the patients undergoing THR is warranted.


Pulmonary Aspects of Exercise and Sports.
Although the lungs are a critical component of exercise performance, their response to exercise and other environmental stresses is often overlooked when evaluating pulmonary performance during high workloads. Exercise can produce capillary leakage, particularly when left atrial pressure increases related to left ventricular (LV) systolic or diastolic failure. Diastolic LV dysfunction that results in elevated left atrial pressure during exercise is particularly likely to result in pulmonary edema and capillary hemorrhage. Data from race horses, endurance athletes, and triathletes support the concept that the lungs can react to exercise and immersion stress with pulmonary edema and pulmonary hemorrhage. Immersion in water by swimmers and divers can also increase stress on pulmonary capillaries and result in pulmonary edema. Swimming-induced pulmonary edema and immersion pulmonary edema in scuba divers are well-documented events caused by the fluid shifts that occur with immersion, elevated pulmonary venous pressure during extreme exercise, and negative alveolar pressure due to inhalation resistance. Prevention strategies include avoiding extreme exercise, avoiding over hydration, and assuring that inspiratory resistance is minimized.


Short term effects of different omega-3 fatty acid formulation on lipid metabolism in mice fed high or low fat diet.
Bioactivities of Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) depend on their chemical forms. The present study was to investigate short term effects of triglyceride (TG), ethyl ester (EE), free fatty acid (FFA) and phospholipid (PL) forms of omega-3 fatty acid (FA) on lipid metabolism in mice, fed high fat or low fat diet. Male Balb/c mice were fed with 0.7% different Omega-3 fatty acid formulation: DHA bound free fatty acid (DHA-FFA), DHA bound triglyceride (DHA-TG), DHA bound ethyl ester (DHA-EE) and DHA bound phospholipid (DHA-PL) for 1 week, with dietary fat levels at 5% and 22.5%. Serum and hepatic lipid concentrations were analyzed, as well as the fatty acid composition of liver and brain. At low fat level, serum total cholesterol (TC) level in mice fed diets with DHA-FFA, DHA-EE and DHA-PL were significantly lower than that in the control group (P < 0.05). Hepatic TG level decreased significantly in mice fed diets with DHA-TG (P < 0.05), DHA-EE (P < 0.05) and DHA-PL (P < 0.05), while TC level in liver was significantly lower in mice fed diets with TG and EE compared with the control group (P < 0.05). At high fat level, mice fed diets with DHA-EE and DHA-PL had significantly lower hepatic TC level compared with the control diet (P < 0.05). Hepatic PL concentration experienced a significant increase in mice fed the diet with PL at high fat level (P < 0.05). Furthermore, both at low and high fat levels, hepatic DHA level significantly increased and AA level significantly decreased in all forms of DHA groups (P < 0.05), compared to control groups at two different fat levels, respectively. Additionally, cerebral DHA level in mice fed diets with DHA-FFA, DHA-EE and DHA-PL significantly increased compared with the control at high fat level (P < 0.05), but no significant differences were observed among dietary treatments for mice fed diets with low fat level. The present study suggested that not only total dietary fat content but also the molecular forms of omega-3 fatty acids contributed to lipid metabolism in mice. DHA-PL showed effective bioactivity in decreasing hepatic and serum TC, TG levels and increasing omega-3 concentration in liver and brain.


Characterization of mannanase from a novel mannanase-producing bacterium.
Locust bean gum (LBG) was employed to screen mannanase-producing bacteria. The bacterium with highest mannanase ability was identified as Paenibacillus cookii. It revealed highest activity (6.67 U/mL) when cultivated in 0.1% LBG with 1.5% soytone and 0.5% tryptone after 4 days incubation at 27 °C. Its mannanase was purified to electrophoretical homogeneity after DEAE-Sepharose and Sephacryl S-100 separation. The purified mannanase, with an N-terminus of GLFGINAY, had pH and temperature optimum at 5.0 and 50 °C, respectively, and was stable at pH 5.0-7.0, ≤ 50 °C. It was strongly activated by β-mercaptoethanol, dithiothreitol, cysteine, and glutathione, but inhibited by Hg(2+), Cu(2+), Zn(2+), Fe(3+), PMSF, iodoacetic acid, and EDTA. According to substrate specificity study, the purified mannanase had high specificity to LBG and konjac.


Antisense hairpin loop oligonucleotides as inhibitors of expression of multidrug resistance-associated protein 1: their stability in fetal calf serum and human plasma.
Multidrug resistance-associated protein (MRP1) is a transmembrane pump protein responsible for the efflux of chemotherapeutic drugs, an important cause of anticancer treatment failure. Trying to circumvent MRP-mediated resistance we designed and synthesized hairpin loops forming antisense oligodeoxyribonucleotides (ODNs), both phosphodiesters (PO-ODNs) and their phosphorothioate analogues (PS-ODNs), to reduce the protein expression by targeting its mRNA in a sequence specific manner. Melting temperature measurements as well as polyacrylamide gel electrophoresis supported the preferential formation of a secondary structure, which was expected to protect ODNs against 3'-exonuclease degradation. ODNs and PS-ODNs designed in this work were successfully tested as antisense inhibitors of the expression of MRP1 in the leukaemia HL60/ADR cell line. Foreseeing the necessity to perform clinical studies with such ODNs we investigated their stability against the 3'-exonuclease activity of fetal calf serum and human plasma. Under the conditions, corresponding to physiological ones, we observed high stability of hairpin loop forming ODNs, especially those containing longer (e.g. 7 base pair) stems. Comparative studies on the stability of chemically unmodified hairpin loop forming ODNs and their PS-counterparts indicated that endonuclease activity did not play any important role in the process of their nucleolytic degradation. Our studies provide strong evidence for high stability of chemically unmodified hairpin loop ODNs, making them an attractive alternative to phosphorothioate analogues commonly used in antisense strategy.


Clinical credibility and trustworthiness are key characteristics used to identify colleagues from whom to seek information.
To explore the use of information by nurses making decisions in clinically uncertain situations in one aspect of critical care nursing practice (enteral feeding). In this paper, we report the characteristics, which participants identified as important, of the people from whom they sought information for the purpose of making clinical decisions. Registered nurses have a plethora of information sources available to assist them in making clinical decisions. Identifying and selecting the best information to support these decisions can be difficult and is influenced by factors such as accessibility, usefulness and variations in quality of the information. An instrumental case study design using multiple case study analysis. Twenty-two critical care nurses from two intensive care units contributed to the data through multiple methods of data collection including concurrent verbal protocols (think aloud), retrospective probing and focus group interviews. Nurses preferentially used colleagues as a source of information when faced with uncertainty about their clinical practice. Most participants placed greater emphasis on evaluating the individual providing the information rather than on evaluating the information itself. Key features used for identifying an individual as a source of information included experience, clinical role, trust and approachability. Establishing clearly what clinical credibility means, and to what extent trustworthiness and expertise play a role in the establishment of credibility, is an important debate for nursing. We need to carefully consider what defines the construct of clinical credibility and how this aligns with the concept of clinical currency, to allow clinicians to determine in others the characteristics associated with clinical credibility to access quality information through social interaction. Processes to focus on determining the quality of information obtained from colleagues should be emphasised. What these processes are and how they could be implemented into clinical practice remains unknown and is highlighted as an area for future research.


Repeat immigration: A previously unobserved source of heterogeneity?
Register data allow for nuanced analyses of heterogeneities between sub-groups which are not observable in other data sources. One heterogeneity for which register data is particularly useful is in identifying unique migration histories of immigrant populations, a group of interest across disciplines. Years since migration is a commonly used measure of integration in studies seeking to understand the outcomes of immigrants. This study constructs detailed migration histories to test whether misclassified migrations may mask important heterogeneities. In doing so, we identify a previously understudied group of migrants called repeat immigrants, and show that they differ systematically from permanent immigrants. In addition, we quantify the degree to which migration information is misreported in the registers. The analysis is carried out in two steps. First, we estimate income trajectories for repeat immigrants and permanent immigrants to understand the degree to which they differ. Second, we test data validity by cross-referencing migration information with changes in income to determine whether there are inconsistencies indicating misreporting. From the first part of the analysis, the results indicate that repeat immigrants systematically differ from permanent immigrants in terms of income trajectories. Furthermore, income trajectories differ based on the way in which years since migration is calculated. The second part of the analysis suggests that misreported migration events, while present, are negligible. Repeat immigrants differ in terms of income trajectories, and may differ in terms of other outcomes as well. Furthermore, this study underlines that Swedish registers provide a reliable data source to analyze groups which are unidentifiable in other data sources.


7,9-Bis(hy-droxy-meth-yl)-7H-purine-2,6,8(1H,3H,9H)trione.
The structure of the title uric acid derivative, C(7)H(8)N(4)O(5), from human kidney stones, is characterized by the C and O atoms of one of the two hy-droxy-methyl groups being disordered nearly equally over three different sites. In the crystal, mol-ecules are connected by a three-dimensional hydrogen-bonding scheme though they look stacked in planes nearly parallel to ([Formula: see text]04).