The association among childhood maltreatment, somatic symptom intensity, depression, and somatoform dissociative symptoms in patients with fibromyalgia syndrome: a single-center cohort study.
Research demonstrates strong associations between childhood maltreatment and health problems that include dissociative symptoms and fibromyalgia syndrome (FMS). We assessed the associations among childhood maltreatment, somatic symptom severity, depression, and somatoform dissociative symptoms in all consecutive adult FMS patients of a tertiary referral pain medicine center between January 2010 and December 2011. Childhood maltreatment was assessed with the Childhood Trauma Questionnaire, somatoform dissociative symptoms with the Somatoform Dissociation Questionnaire, somatic symptom severity with the Patient Health Questionnaire-15 and depression by the Patient Health Questionnaire-2. A total of 117 patients (84% women) were included in the analysis, of whom 20.5% reported severe emotional abuse, 8.6% severe physical abuse, 12.8% severe sexual abuse, 25.6% severe emotional neglect, and 12.0% severe physical neglect in childhood and adolescence. On average, patients reported high levels of somatoform dissociative symptoms and moderate levels of somatic symptom severity and depression. Somatoform dissociative symptoms and emotional abuse were moderately correlated (r = .32). In hierarchical regression analysis, gender (p = .01) and somatic symptom severity (p < .0001) but not childhood maltreatment and depression were significant predictors of somatoform dissociative symptoms. Reports of somatoform dissociative symptoms by FMS patients might be attributed to their tendency to report multiple somatic symptoms.


Is metabolic syndrome a mild form of Cushing's syndrome?
The Metabolic Syndrome is a diagnosis of increasing prevalence that is noted to share multiple clinical features with Cushing's syndrome. Several studies suggest abnormalities in the Hypothalamic-Pituitary-Adrenal axis to be associated with this disease and tissue-specific hypercortisolemia is being investigated as a possible contributing factor. More research is needed to explore the relation between cortisol and the metabolic syndrome which, if confirmed, will have major therapeutic and public health implications.


Genetic insights into sepsis: what have we learned and how will it help?
Sepsis and septic shock, are complex disorders that are a major cause of mortality in the intensive care unit. In spite of major advances in our understanding of the pathophysiology of sepsis, accurate prediction of susceptibility to sepsis, multi-organ dysfunction, and death, even in the setting of a seemingly similar burden of infection, continues to challenge critical care clinicians. Evidence from family-based studies and recent gene-association studies suggest that a significant portion of the apparent variability in susceptibility is due to genetic factors. Common sequence variations in genes coding for innate immune effectors, inflammatory mediators, and modulators of coagulation have received particular attention. This review will summarize and integrate the results of studies testing for associations between sequence variations in genes from these functional classes and susceptibility to sepsis and related clinical outcomes. The important insights on sepsis pathophysiology provided by these studies will be discussed along with the relevance of these findings to the design of future diagnostic approaches and therapeutic trials.


A quantitative assessment of how Canadian intensivists believe they utilize oxygen in the intensive care unit.
To investigate attitudes and practices regarding oxygen therapy in intensive care units (ICUs) and to devise quantitative descriptive indices. Canadian university-affiliated adult ICUs. Fifty-two medical directors of ICUs in 48 institutions. Structured postal questionnaire returned by 48 participants. Attitudes, beliefs, and stated practices relating to oxygen use in ICUs were determined. Novel descriptors S-50min (minutes of oxygen saturation [Sao2] acceptable to >50% of respondents), F-50max (maximum F(IO)2 above which <50% of respondents would increase F(IO)2), and F-50min (minimum F(IO)2 below which <50% of respondents would decrease F(IO)2) were determined. All respondents believed that oxygen toxicity was a concern. Twenty-nine percent of respondents indicated that they did not always assess tissue oxygenation in critical cases. A stepwise reduction in acceptance of progressive desaturation and increasing duration of hypoxemia was found. Presented with a stable patient with Sao2 of 98%, the maximum level of F(IO)2 above which respondents stated that they would not increase the F(IO)2 was 0.41+/-0.17 (mean +/- SD). For stable patients with Sao2 of 85%, the minimum F(IO)2 below which respondents would not reduce F(IO)2 was 0.59+/-0.23 (mean +/- SD). F-50max was 0.8 vs. 0.5 for Sao2 of 80%-85% vs. 85%-90%, respectively; F-50min was 0.6 vs. 0.21 for Sao2 of 90%-95% vs. 95%-100%, respectively. Considerable variation exists in the attitudes, beliefs, and stated practices relating to the management of oxygen therapy in the ICU. These data are amenable to quantitative description and illustrate the necessity for documentation of actual practice and development of support systems for decision-making in this and similar areas.


A REMARKABLE NEW RED SEAWEED FROM NEW ZEALAND.
A remarkable new sublittoral red alga is described from New Zealand. A detailed account of its morphology is provided. A new genus, Pseudoanemonia, is proposed for it and the specific epithet P. tentacula. It is placed in a new family, Pseudoanemoniaceae.


Beta-Adrenergic receptors in rat fat cells and their relationship with lipolysis.
Norepinephrine stimulated lipolysis in rat fat cells while (-)-alprenolol completely inhibited this lipolysis. (-)-Alprenolol competed for (-)-[3H] dihydroalprenolol (DHA) binding sites on rat fat cells. The specific (-)-[3H]DHA binding sites identified by competition with (-)-alprenolol were found to be transferred to the solubilized supernatant during preparation of endogenous lipid droplets from the fat cells. Although the lipid droplets did not exhibit specific (-)-[3H]DHA binding, norepinephrine induced lipolysis in a cell-free system consisting of the lipid droplets and hormone-sensitive lipase (HSL). Norepinephrine-induced lipolysis in the cell-free system was inhibited by propranolol and (-)-alprenolol, but not by phenoxybenzamine. The lipolytic action of norepinephrine and the anti-lipolytic actions of propranolol and (-)-alprenolol disappeared after sonication of the lipid droplets in the cell-free system. These results suggest that the adrenergic receptor concerned with lipolysis in fat cells may not be a specific (-)-[3H]DHA binding site, but may be closely related to the lipid droplets.


Glucose-deprivation-induced [3H]D-aspartate release from isolated bovine and human retinae.
The glucose deprivation-induced release of [3H]D-aspartate was studied in bovine and human retinas in a superfusion apparatus. [3H]D-aspartate release was significantly increased upon omitting glucose in the superfusion buffer. This effect was dependent on external Ca2+ because L- and N-type Ca2+-channel blockers, such as diltiazem (1 microM), nitrendipine (1 microM), and omega-conotoxin (100 nM), significantly reduced the effect of glucose-deprivation induced release of [3H]D-aspartate. Furthermore, while glutamate receptor agonists (L-glutamate, N-methyl-D-aspartate, but not kainate) potentiated the effects of glucose deprivation, antagonists (MK-801, MCPG, ifenprodil, and L-AP3) at these receptors blocked the glucose deprivation-induced release process. Taken together, these studies have demonstrated that under conditions of glucose deprivation, as may happen during ischemic events in vivo, the retinal glutamatergic nerve endings and/or glial cells promote the efflux of [3H]D-aspartate into the extracellular environment. This process appears to be receptor-mediated and dependent on extracellular Ca2+ and is similar to previous reports pertaining to brain tissues.


Pictorial Guide for Rapid Identification of Common Adult Storage Insects.
To assist analysts with identification of the adult insects most commonly found in foods, detailed drawings of 21 such insects are provided. For each example, accompanying test summarizes the identifying characteristics and gives additional information about its name and habits. Larger scale drawings of adult antennae and mandibles are included with most examples.


Major increase in endopeptidase activity of human cathepsin B upon removal of occluding loop contacts.
The main feature distinguishing cathepsin B from other cysteine proteases of the papain family is the presence of a large insertion loop, termed the occluding loop, which occupies the S' subsites of the enzyme. The loop is held in place mainly by two contacts with the rest of the enzyme, involving residues His110 and Arg116 on the loop that form salt bridges with Asp22 and Asp224, respectively. The influence of this loop on the endopeptidase activity of cathepsin B has been investigated using site-directed mutagenesis and internally quenched fluorogenic (IQF) substrates. Wild-type cathepsin B displays poor activity against the substrates Abz-AFRSAAQ-EDDnp and Abz-QVVAGA-EDDnp as compared to cathepsin L and papain. Appreciable increases in kcat/KM were observed for cathepsin B containing the single mutations D22A, H110A, R116A, and D224A. The highest activity however is observed for mutants where both loop to enzyme contacts are disrupted. For the triple-mutant D22A/H110A/R116A, an optimum kcat/KM value of 12 x 10(5) M-1 s-1 was obtained for hydrolysis of Abz-AFRSAAQ-EDDnp, which corresponds to a 600-fold increase relative to wild-type cathepsin B and approaches the level of activity observed with cathepsin L or papain. By comparison, the mutations have little effect on the hydrolysis of Cbz-FR-MCA. The influence of the mutations on the pH dependency of activity also indicates that the complexity of pH activity profiles normally observed for cathepsin B is related to the presence of the occluding loop. The major increase in endopeptidase activity is attributed to an increase in loop "flexibility" and suggests that the occluding loop might move when an endopeptidase substrate binds to the enzyme. The possible contribution of these interactions in regulating endopeptidase activity and the implications for cathepsin B activity in physiological or pathological conditions are discussed.


miR-3132 upregulates surface TRAIL to induce apoptotic cell death in cancer cells.
TRAIL-based therapies are of significant clinical interest because of its unique ability to induce apoptosis in cancer cells while sparing normal and untransformed cells. This selective antitumor potential of the TRAIL pathway has been harnessed by development of therapeutics including recombinant (rh)TRAIL and TRAIL-receptor agonist antibodies such as mapatumumab and lexatumumab. While these TRAIL-based therapies have proven successful in preclinical studies and safe in early phase clinical trials, the limited serum half-life has been a hurdle for further clinical development. Here we characterize miR-3132, a novel and first-in class TRAIL-inducing miRNA with potent anti-proliferative and pro-apoptotic effects in cancer cell lines. Initial mechanistic studies indicate that miR-3132 engages the interferon signaling pathway to induce TRAIL and subsequent TRAIL-dependent apoptosis in cancer cell lines. Our data further suggests that the binding of miR-3132 to toll-like receptors could be the upstream pathway for the interferon response. The current study the first report to demonstrate miR-3132's in vitro efficacy and preliminary mechanism of action in cancer cell lines.


The relaxant effect of glyceryltrinitrate on isolated human peripheral vein and its relation to cyclic GMP metabolism.
The relaxant effect of glyceryltrinitrate (GTN) on human vena saphena magna was studied in vitro. Vessels contracted by serotonin (0.25 microM) and phenylephrine (0.1 mM) were relaxed to the same extent (EC50 = 10 microM) by GTN, whereas in 100 mM K+-depolarized vessels the relaxation was significantly lower. The relaxant effect produced by GTN was preceded by an elevation of cyclic guanosine-3',5'-monophosphate (cGMP). For 0.1 mM GTN there was a 3-fold increase in cGMP after 3 min. A correlation between relaxation and increase in cGMP was established. When GTN was combined with dipyridamole (5 microM) the relaxant effect of GTN was significantly greater (EC50 = 0.1 microM). Phosphodiesterase inhibition, as a possible mechanism behind the observed better relaxation for the combination (GTN+dipyridamole), is briefly discussed. In conclusion, the relaxant effect of GTN on isolated human vena saphena magna seems to be dependent on the contractile stimuli used, increased by the addition of DIP and to be mediated via cGMP.


[Hepatitis B and C in intravenous drug abusers in Switzerland].
Since the 1980s hepatitis B and C have spread greatly among intravenous drug consumers. This shows up today in a high prevalence for both pathogens. It is striking that many patients who have only consumed drugs intravenously for a few years have already been infected with hepatitis B or C. The clear reduction in the spread of HIV within the drug-using community achieved by targeted measures during recent years has not had a similar impact on hepatitis B and C. Given this background, optimising preventive efforts among intravenous drug users is of great importance. Structural steps for therapy and damage-reduction should be optimised even more. Moreover, individual protective behaviour among patients should be improved. Medical advice and care is of great importance in this case. New studies show that many intravenous drug consumers are insufficiently informed on the risks of infection from shared use of injection utensils (spoons, filters, etc.) or drug sharing with used needles. Moreover, many drug consumers are not vaccinated against hepatitis B. Medical advice on protective behaviour should address these problems more directly. In the future, other sustainable intervention programmes based on this approach will need to be developed.


Progression and cessation of collapse in osteonecrosis of the femoral head.
Thirty-five patients (54 hips) with osteonecrosis of the femoral head without collapse or only with a crescent sign were followed up for at least 5 years to clarify the natural course of osteonecrosis. During the followup, 28 hips (52%) in 21 patients collapsed including nine hips in nine patients with small necrotic lesions occupying less than the medial (2/3) of the weightbearing area. Cessation of collapse then was observed in 15 (14 patients) of the 28 hips (54%), especially in eight of the nine hips (89%) with small necrotic lesions. Of the 15 hips in 14 patients with cessation of collapse, 11 hips (73%) in 11 patients had less than 2 mm collapse and 10 hips in nine patients became asymptomatic. The analysis indicated that collapse of the femoral head does not necessarily determine a poor prognosis, and even after collapse occurs, subsequent cessation of collapse can be expected in a certain percentage of hips. Hips with less than 2 mm collapse and necrotic lesions occupying less than the medial (2/3) of the weightbearing area have a high chance of cessation of collapse and improvement of symptoms with no surgical intervention.


Update on selecting and adjusting antiplatelet therapy for prevention of noncardiogenic, recurrent ischemic stroke.
Antiplatelet therapy is a cornerstone of secondary prevention in patients with prior stroke or transient ischemic attack. Recent clinical trials and subanalyses of previous trials have influenced the selection of antiplatelet agents. Clinical decisions regarding the use of antiplatelet therapies have also been affected by recent advancements in our understanding of drug action, metabolism and drug-drug interactions. Aspirin has an established role in secondary prevention of stroke, although some patients are unable to tolerate it and others are resistant to its antiplatelet effects. Platelet function tests are available, but their routine use is not yet established. Clopidogrel and the combination of aspirin with extended-release dipyridamole both have established roles in secondary stroke prevention, but the optimal choice of agent is not always clear. Clinical trials of head-to-head comparisons will be discussed, as well as trials of combination therapies. In addition, several issues have surfaced recently impinging on the use of clopidogrel, especially relating to variable metabolism of the drug to its active metabolite and to interactions with proton pump inhibitors. The clinical implications of these issues will be discussed with respect to the secondary prevention of stroke.


Neurodevelopment Following Exposure to Antiseizure Medications in Utero: A Review.
Exposure in the womb to antiseizure medications and their potential impact on the brain of the developing child has long been researched. Despite this long period of interest, this review highlights that above the well-known risks associated with valproate exposure, there are more data required for conclusions regarding all other antiseizure medications. Limited experience with phenytoin and phenobarbital in monotherapy makes clearly defining the risk to later child postnatal functioning difficult, although the evidence of an impact is stronger for phenobarbital than for phenytoin. The widely prescribed lamotrigine is limited in its investigation in comparison to unexposed control children, and whilst it has been demonstrated to carry a lower risk than valproate for certain outcomes, whether it is associated with a more moderate impact on wider aspects of neurodevelopmental functioning is still to be understood. Data for levetiracetam, topiramate and oxcarbazepine are too limited to confidently draw conclusions for most neurodevelopmental outcomes. This slow accumulation of evidence impacts on the safest use of medications in pregnancy and makes counseling women regarding the risks and benefits of specific antiseizure medications difficult. Improved focus, funding, and research methodologies are urgently needed.


Identification and characterization of a tumor infiltrating CD56(+)/CD16 (-) NK cell subset with specificity for pancreatic and prostate cancer cell lines.
In a recent clinical trial, a patient exhibited regression of several pancreatic cancer metastases following the administration of the immune modulator Ipilimumab (anti-CTLA-4 antibody). We sought to characterize the immune cells responsible for this regression. Tumor infiltrating lymphocytes (TIL-2742) and an autologous tumor line (TC-2742) were expanded from a regressing metastatic lesion excised from this patient. Natural killer (NK) cells predominated in the TIL (92% CD56(+)) with few T cells (12% CD3(+)). A majority (88%) of the NK cells were CD56(bright)CD16(-). TIL-2742 secreted IFN-γ and GM-CSF following co-culture with TC-2742 and major histocompatibility complex mismatched pancreatic tumor lines. After sorting TIL-2742, the purified CD56(+)CD16(-)CD3(-) subset showed reactivity similar to TIL-2742 while the CD56(-)CD16(-)CD3(+) cells exhibited no tumor recognition. In co-culture assays, TIL-2742 and the NK subset expressed high reactivity to several pancreatic and prostate cancer cell lines and could lyse the autologous tumor as well as pancreas and prostate cancer lines. Reactivity was partially abrogated by blockade of TRAIL. We thus identified a unique subset of NK cells (CD56(bright)CD16(dim)) isolated from a regressing metastatic pancreatic cancer in a patient responding to Ipilimumab. This represents the first report of CD56(+)CD16(-) NK cells with apparent specificity for pancreatic and prostate cancer cell lines and associated with tumor regression following the treatment with an immune modulating agent.


Late cortical cerebellar atrophy. Clinical and oculographic features.
Ten patients with late cortical cerebellar atrophy documented with computerized tomography (CT) and magnetic resonance (MR) imaging presented a uniform pattern of oculomotor abnormalities. All had deficits in smooth pursuit and fixation suppression of the vestibulo-ocular reflex (VOR). The gain of the VOR was often increased but the dynamics of the VOR were not different from normals. Full-field optokinetic responses and visual-vestibular interaction mediated via the VOR velocity storage element were preserved. Just as in lower primates, the cerebellum in humans is a critical relay station for foveal pursuit and visual-vestibular interaction requiring foveal pursuit. Vestibular responses and visual-vestibular interaction mediated through the VOR velocity storage element are relatively independent of the cerebellum.


Clinical Clues of Pre-Symptomatic Pancreatic Ductal Adenocarcinoma Prior to Its Diagnosis: A Retrospective Review of CT Scans and Laboratory Tests.
Most pancreatic ductal adenocarcinoma cases are unresectable at the time of diagnosis. Only early diagnosis and curative resection can help prolong survival. We tried to find out useful clinical clues of pre-symptomatic area prior to pancreatic cancer diagnosis compared to normal controls. Of 4799 patients diagnosed with pancreatic cancer between 1995 and 2014 at the Samsung Medical Center, 51 were selected for study. They had no symptoms at diagnosis and underwent computed tomography 6 to 36 months prior to diagnosis for reasons other than cancer diagnosis. We selected 288 control subjects who underwent computed tomography during the same period. Data were retrospectively reviewed included various variables. Fasting blood sugar (171.8 ± 97.5 vs. 115.8 ± 34.8 units, p < 0.05), new onset diabetes mellitus within 3 years (12/51 (23.5%) vs. 17/181 (9.8%), p < 0.05), carbohydrate antigen 19-9 level (609.5 ± 2342.5 vs. 17.0 ± 26.2, p = 0.08), main pancreatic duct dilatation (26/51 (51.0%) vs. 57/181 (31.5%), p < 0.05) in computed tomography scan were higher in pancreatic cancer group than in normal group, respectively. In multi-variate analysis, carbohydrate antigen 19-9, new onset diabetes mellitus (<3 years), and segmental main pancreatic duct dilatation were independent risk factors for pancreatic cancer. Our study concluded that independent risk factors for pancreatic cancer were elevated carbohydrate antigen 19-9, new onset diabetes mellitus (<3 years), and local main pancreatic ductal dilatation on computed tomography scan.


Global Surgery Fellowship: A model for surgical care and education in resource-poor countries.
Surgical diseases have recently been shown to be a major cause of global morbidity and mortality. Effective methods to decrease the burden of surgical disease and provide care in resource-poor settings are unknown. An opportunity to meet this need exists through collaborative efforts to train local surgeons in specialty care, such as pediatric general surgery. We present a novel model for the provision of surgical care and education in a resource-poor setting via a collaborative Global Surgery Fellowship program. Through Partners in Health in Haiti, this program placed a fully trained pediatric surgeon at an established rural hospital, both to temporarily serve that community and to teach local surgeons pediatric surgical care. The Global Surgery Fellow performed the cases presented here during his term, between July 2009 and June 2010. A total of 147 operative procedures were performed on 131 patients over the course of 12 weeks in Haiti. A total of 134 of the 147 total cases performed (91.2%) were educational cases, in which the Fellow operated with and trained one or more of the following: American medical students, American residents, Haitian residents, or Haitian staff surgeons. The Global Surgery Fellowship model overcomes many of the traditional challenges to providing adequate surgical care in resource-poor countries. Specifically, it meets the challenge of providing a broad educational experience for many levels of local and foreign physicians, while working within an established locally run health care system. We believe that this model is generalizable to many resource-poor hospitals with permanent local staff that are open to collaboration.


Activation of the acute phase response and complement C3 in patients with IgA nephropathy.
Recently we showed systemic complement activation in patients with immunoglobulin A (IgA) nephropathy (measured by "activated C3" [actC3], in other words, neoantigens developing on breakdown products after C3 activation) and reported that plasma levels of actC3 can indicate disease activity and renal outcome. In this study we investigated whether plasma C3a and C-reactive protein (CRP), which require tests that are more readily available, have a similar diagnostic and predictive value. CRP was measured using a highly sensitive enzyme-linked immunosorbent assay and C3a using a specific immunoassay. CRP and C3a levels were significantly higher in 56 patients with IgA nephropathy as compared with 55 healthy controls. C3a levels in IgA nephropathy patients were also significantly increased in comparison with 42 patients with hypertension or nonimmune renal diseases. Neither C3a nor CRP levels correlated with those of actC3 in IgA nephropathy patients. We also compared 10 IgA nephropathy patients with stable, normal renal function with eight IgA nephropathy patients progressing from normal to impaired renal function during mean follow-ups of 7.1 and 5.1 years, respectively. Mean CRP but not C3a levels during the observation period were significantly higher in IgA nephropathy patients with disease progression than in those with stable renal function. Systemic complement activation can be detected by measurement of plasma C3a in IgA nephropathy, but C3a levels cannot substitute for actC3 in predicting renal prognosis. Subclinical induction of the acute phase response is also present in patients with progressive IgA nephropathy, but again its prognostic value is limited. Repeated determinations performed over prolonged time courses may possibly improve the prognostic value of CRP levels.


Idiopathic inflammatory myopathies: one year in review 2021
Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare and complex connective tissue diseases, mainly characterised by inflammatory involvement of skeletal muscles. Several other organs may be affected, particularly lungs, heart, skin, gastrointestinal tract and joints, often determining the morbidity and mortality associated with these autoimmune disorders. The course is generally chronic and the onset subacute. This latter aspect, together with the rarity of these conditions, can result in a clinical challenge for the physician with a considerable diagnostic delay. The scientific literature makes continuous advances in the understanding of these diseases, in particular with regards to the pathogenesis, serological findings, diagnostic strategies and therapeutic approaches. The aim of this review is to highlight the most relevant literature contributions published on this topic over the last year.


Treatment of hypogonadism in men with chronic kidney disease.
Hypogonadism is common among men with chronic kidney disease, but few studies have directly assessed the effects of testosterone replacement in this population. Limited information suggests that androgen replacement may improve libido and sexual function among men who are frankly hypogonadal. However, the threshold for normal sexual function is in the lower end of the normal range. Increasing serum testosterone above this level does not appear to have beneficial effects on sexual functioning. On the other hand, at least among healthy men, the dose-response curve for anabolic effects of testosterone administration appears to extend to testosterone levels on the high end of the normal range or above. Small studies have suggested that androgen treatment has anabolic effects among end-stage renal disease patients, even in the absence of hypogonadism. Androgens have potential side effects, and some preinitiation and subsequent assessment and monitoring are recommended to minimize these adverse effects. Recommendations for healthy older men appear to be reasonable for patients with chronic kidney disease. More research is needed to measure the effects of androgen therapy on various symptoms of hypogonadism as well as on overall quality of life, physical functioning, and survival among patients with chronic kidney disease.


Spectrometer baseline control via spatial filtering.
An absorptive half-moon aperture mask is experimentally explored as a broad-bandwidth means of eliminating spurious spectral features arising from reprocessed radiation in an infrared Fourier transform spectrometer. In the presence of the spatial filter, an order of magnitude improvement in the fidelity of the spectrometer baseline is observed. The method is readily accommodated within the context of commonly employed instrument configurations and leads to a factor of two reduction in optical throughput. A detailed discussion of the underlying mechanism and limitations of the method are provided.


Clinical evaluation of plasma free phenytoin measurement and factors influencing its protein binding.
The relationship between free phenytoin concentrations and clinical responses, and the factors influencing protein binding of phenytoin were investigated. A total of 119 plasma samples from 70 patients treated orally with phenytoin were analysed. The mean free phenytoin concentration was significantly higher in the patients who received phenytoin monotherapy and were classified as having a complete response (1.25 +/- 1.09 microg/ml) than that in the partial response group (0.59 +/- 0.07 microg/ml), whereas the mean total concentrations were not significantly different between the two groups. Samples were divided into three groups based on the free fraction of phenytoin, i.e. low, <5%; medium, 5%-10%; high, > 10%. The mean age (55.3 +/- 10.9 years) was significantly higher in the high group than in the low (42.7 +/- 21.2 years) and medium (42.8 +/- 16.0 years) groups. The mean creatinine clearance (CLcr) (55.3 +/- 10.9 ml/min) and serum albumin concentration (3.30 +/- 1.25 g/dl) were significantly lower in the high group than the low (88.3 +/- 29.0 ml/min and 4.08 +/- 0.50 g/dl, respectively) and medium (95.0 +/- 32.8 ml/min and 3.95 +/- 0.92 g/dl, respectively) groups. These results suggest that the free phenytoin concentration, rather than the total concentration, is more useful for monitoring antiepileptic effects in patients receiving phenytoin monotherapy. It was also found that the free phenytoin fraction was significantly influenced by aging, CLcr and serum albumin levels.


[Distribution of free equipment to intravenous drug addicts in Copenhagen].
Since HIV-infection was recognized in Denmark in the middle of the 80'ies, the authorities have tried to prevent spread of the infection by common educational information. Besides this, special interest was focussed on transmission between members in certain subgroups at high risk. Amongst these are intravenous drug users because of their common needle-sharing. Intravenous drug users constitute the second largest group of HIV infected individuals in Denmark as well as abroad, and it is from this primary high risk group that heterosexual transmission is most feared. In order to prevent this, the urgent need in stopping transmission among the members of the subpopulation itself as early as possible was realized. In order to achieve this, the municipalities of Copenhagen, Frederiksberg and Copenhagen County have distributed free needles and syringes from pharmacies during the past five years. The free needle arrangement is described in figures as well by interviews with a number of intravenous drug users seen as customers at Pharmacy of Istedgade, Copenhagen V. A total of 3 million needles and syringes have been distributed through the period and the arrangement seems to have been a success, although difficulties are great outside normal opening hours and for the imprisoned. Further and expanded distribution possibilities and new ways of thinking are recommended in order to achieve greater compliance amongst intravenous drug addicts.


Epigenetic drift, epigenetic clocks and cancer risk.
It is well-established that the DNA methylation landscape of normal cells undergoes a gradual modification with age, termed as 'epigenetic drift'. Here, we review the current state of knowledge of epigenetic drift and its potential role in cancer etiology. We propose a new terminology to help distinguish the different components of epigenetic drift, with the aim of clarifying the role of the epigenetic clock, mitotic clocks and active changes, which accumulate in response to environmental disease risk factors. We further highlight the growing evidence that epigenetic changes associated with cancer risk factors may play an important causal role in cancer development, and that monitoring these molecular changes in normal cells may offer novel risk prediction and disease prevention strategies.


Psychological Predictors of Health Anxiety in Response to the Zika Virus.
The threat of a United States (U.S.) Zika virus pandemic during 2015-2016 was associated with public anxiety. Such threats represent opportunities to examine hypotheses about health anxiety. The present study investigated psychological predictors of Zika-related anxiety during the 2015-2016 outbreak. U.S. adults (N = 216) completed a battery of measures assessing Zika-related anxiety as well as psychological variables hypothesized to predict anxious responding to the threat of a domestic Zika outbreak. Contrary to hypotheses, regression analyses indicated that only contamination severity overestimates and greater Zika knowledge significantly predicted Zika-related anxiety. Study limitations and clinical implications are discussed.


Pharmacokinetics of topical antifungal formulations.
The triad of infection--the dynamic equilibrium between pathogen, host, and drug--offers both opportunities and challenges for effectively delivering the right amount of drug to the right place for the right amount of time. The delivery system and drug must cooperate to achieve delivery and substantivity at the target site. Given the amount of variability introduced by the dosage form, it takes plenty of trial and error to get the right drug in the right vehicle so it can reach the targeted tissue. The deeper the target tissue, the greater the complexity of drug delivery and effect.


Incidence of Neisseria gonorrhoeae isolates negative by Syva direct fluorescent-antibody test but positive by Gen-Probe accuprobe test in a sexually transmitted disease clinic population.
To determine the accuracy of the Syva (Palo Alto, Calif.) direct fluorescent-antibody (DFA) test in comparison with the Gen-Probe (San Diego, Calif.) Accuprobe culture confirmation test, we tested 395 isolates of Neisseria gonorrhoeae from cultures obtained from patients attending a sexually transmitted disease clinic from 1 July 1991 through 30 June 1992. All isolates were tested for DFA reactivity with a polyclonal reagent (Difco Laboratories, Detroit, Mich.) and a monoclonal reagent (Syva, Inc., direct specimen test) and for specific molecular probe reactivity by the Gen-Probe Accuprobe culture confirmation test for N. gonorrhoeae. The 395 isolates gave positive results for the Gen-Probe culture confirmation test and the Difco polyclonal direct specimen test. However, 18 (4.6%) of the isolates were negative for N. gonorrhoeae by the Syva DFA test. With the exception of six beta-lactamase-positive isolates, all isolates that were negative by Syva DFA were sensitive to penicillin, tetracycline, spectinomycin, and ceftriaxone by disk-diffusion susceptibility testing. Auxotyping and serotyping studies indicated that strains negative by Syva DFA consisted of several variants. The frequency of N. gonorrhoeae isolates showing negative results by Syva DFA in this patient population ranged from 0 to 11.5%/month. Laboratories using only the Syva DFA test for confirmation of N. gonorrhoeae may incur a significant risk of misidentification.


Viral Parkinsonism: An underdiagnosed neurological complication of Dengue virus infection.
Dengue virus (DENV) is a flavivirus that is a significant cause of human disease costing billions of dollars per year in medical and mosquito control costs. It is estimated that up to 20% of DENV infections affect the brain. Incidence of DENV infections is increasing, which suggests more people are at risk of developing neurological complications. The most common neurological manifestations of DENV are encephalitis and encephalopathy, and movement disorders such as parkinsonism have been observed. Parkinsonism describes syndromes similar to Parkinson's Disease where tremors, stiffness, and slow movements are observed. Parkinsonism caused by viral infection is characterized by patients exhibiting at least two of the following symptoms: tremor, bradykinesia, rigidity, and postural instability. To investigate DENV-associated parkinsonism, case studies and reports of DENV-associated parkinsonism were obtained from peer-reviewed manuscripts and gray literature. Seven reports of clinically diagnosed DENV-associated parkinsonism and 15 cases of DENV encephalitis, where the patient met the case criteria for a diagnosis of viral parkinsonism were found. Clinically diagnosed DENV-associated parkinsonism patients were more likely to be male and exhibit expressionless face, speech problems, and lymphocytosis. Suspected patients were more likely to exhibit tremor, have thrombocytopenia and low hemoglobin. Viral parkinsonism can cause a permanent reduction in neurons with consequential cognitive and behavior changes, or it can leave a latent imprint in the brain that can cause neurological dysfunction decades after recovery. DENV-associated parkinsonism is underdiagnosed and better adherence to the case definition of viral parkinsonism is needed for proper management of potential sequalae especially if the patient has an ongoing or potential to develop a neurodegenerative disease.


Consolidation Tumor Ratio Combined With Pathological Features Could Predict Status of Lymph Nodes of Early-Stage Lung Adenocarcinoma.
Stage IA lung adenocarcinoma manifested as part-solid nodules (PSNs), has attracted immense attention owing to its unique characteristics and the definition of its invasiveness remains unclear. We sought to develop a nomogram for predicting the status of lymph nodes of this kind of nodules. A total of 2,504 patients between September 2018 to October 2020 with part-solid nodules in our center were reviewed. Their histopathological features were extracted from paraffin sections, whereas frozen sections were reviewed to confirm the consistency of frozen sections and paraffin sections. Univariate and multivariate logistic regression analyses and Akaike information criterion (AIC) variable selection were performed to assess the risk factors of lymph node metastasis and construct the nomogram. The nomogram was subjected to bootstrap internal validation and external validation. The concordance index (C-index) was applied to evaluate the predictive accuracy and discriminative ability. We enrolled 215 and 161 eligible patients in the training cohort and validation cohort, respectively. The sensitivity between frozen and paraffin sections on the presence of micropapillary/solid subtype was 78.4%. Multivariable analysis demonstrated that MVI, the presence of micropapillary/solid subtype, and CTR >0.61 were independently associated with lymph node metastasis (p < 0.01). Five risk factors were integrated into the nomogram. The nomogram demonstrated good accuracy in estimating the risk of lymph node metastasis, with a C-index of 0.945 (95% CI: 0.916-0.974) in the training cohort and a C-index of 0.975 (95% CI: 0.954-0.995) in the validation cohort. The model's calibration was excellent in both cohorts. The nomogram established showed excellent discrimination and calibration and could predict the status of lymph nodes for patients with ≤3 cm PSNs. Also, this prediction model has the prediction potential before the end of surgery.


Exploring the potential of the β-thiolactones in bioorganic chemistry.
A series of novel peptide-based β-thiolactones were synthesized and assayed for cytotoxicity against several human cancer cell lines, where they showed greater activity than the corresponding β-lactones and β-lactams. Several of the β-thiolactones prepared showed strong inhibitory activity in vitro against human cathepsins B and L.


Measurement of finite-frequency current statistics in a single-electron transistor.
Electron transport in nanoscale structures is strongly influenced by the Coulomb interaction that gives rise to correlations in the stream of charges and leaves clear fingerprints in the fluctuations of the electrical current. A complete understanding of the underlying physical processes requires measurements of the electrical fluctuations on all time and frequency scales, but experiments have so far been restricted to fixed frequency ranges, as broadband detection of current fluctuations is an inherently difficult experimental procedure. Here we demonstrate that the electrical fluctuations in a single-electron transistor can be accurately measured on all relevant frequencies using a nearby quantum point contact for on-chip real-time detection of the current pulses in the single-electron device. We have directly measured the frequency-dependent current statistics and, hereby, fully characterized the fundamental tunnelling processes in the single-electron transistor. Our experiment paves the way for future investigations of interaction and coherence-induced correlation effects in quantum transport.


The origins of duality of patterning in artificial whistled languages.
In human speech, a finite set of basic sounds is combined into a (potentially) unlimited set of well-formed morphemes. Hockett (1960) placed this phenomenon under the term 'duality of patterning' and included it as one of the basic design features of human language. Of the thirteen basic design features Hockett proposed, duality of patterning is the least studied and it is still unclear how it evolved in language. Recent work shedding light on this is summarized in this paper and experimental data is presented. This data shows that combinatorial structure can emerge in an artificial whistled language through cultural transmission as an adaptation to human cognitive biases and learning. In this work the method of experimental iterated learning (Kirby et al. 2008) is used, in which a participant is trained on the reproductions of the utterances the previous participant learned. Participants learn and recall a system of sounds that are produced with a slide whistle. Transmission from participant to participant causes the whistle systems to change and become more learnable and more structured. These findings follow from qualitative observations, quantitative measures and a follow-up experiment that tests how well participants can learn the emerged whistled languages by generalizing from a few examples.


DXA-measured visceral adipose tissue predicts impaired glucose tolerance and metabolic syndrome in obese Caucasian and African-American women.
New methods to measure visceral adipose tissue (VAT) by dual-energy X-ray absorptiometry (DXA) may help discern sex, race and phenotype differences in the role of VAT in cardiometabolic risk. This study was designed (1) to compare relationships of DXA-VAT, anthropometric and body composition variables with cardiometabolic risk factors in obese women; (2) to determine which variables most robustly predict impaired glucose tolerance (IGT) and metabolic syndrome (MetSx); and (3) to determine thresholds for DXA-VAT by race. VAT mass (g) and volume (cm(3)) were measured in 229 obese (body mass index (BMI), 30-49.9) women aged 21-69 years of European-American (EA=123) and African-American (AA=106) descent using the CoreScan algorithm on a Lunar iDXA scanner. Linear regression modeling and areas under the curve (AUC of ROC (receiver operating characteristic) curves) compared relationships with cardiometabolic risk. Bootstrapping with LASSO (least absolute shrinkage and selection operator) regression modeling determined thresholds and predictors of IGT and MetSx. DXA-VAT explained more of the variance in triglycerides, blood pressure, glucose and homeostatic model assessment-insulin resistance (HOMA-IR) compared with anthropometric and other body composition variables. DXA-VAT also had the highest AUC for IGT (0.767) and MetSx (0.749). Including race as a variable and the interaction between VAT and race in modeling did not significantly change the results. Thresholds at which the probability of developing IGT or MetSx was⩾50% were determined separately for AA women (IGT: 2120 cm(3); MetSx: 1320 cm(3)) and EA women (IGT: 2550 cm(3); MetSx: 1713 cm(3)). The odds for IGT or MetSx were fourfold greater with each standard deviation increase in DXA-VAT. DXA-VAT provides robust clinical information regarding cardiometabolic risk in AA and EA obese women and offers potential utility in the risk reduction interventions.


Mechanisms involved in governing adherence of Vibrio cholerae to granular starch.
Vibrio cholerae has been shown to adhere to cornstarch granules. The present work explored the mechanisms involved in this adhesion and the possibility of its occurrence in vivo. The findings suggest that both specific and nonspecific interactions are involved in the adhesion. Nonspecific hydrophobic interactions may play a role, since both V. cholerae and cornstarch granules exhibited hydrophobic properties when they were tested using a xylene-water system. In addition, the presence of bile acids reduced the adhesion. The adhesion also involves some specific carbohydrate-binding moieties on the cell surface, as reflected by reduced adhesion following pretreatment of the bacteria with proteinase K and sodium m-periodate. Further investigations supported these observations and showed that media containing low-molecular-weight carbohydrates had a significant inhibitory effect. Binding cell lysate to starch granules and removing the adhered proteins using either glucose or bile acids led to identification (by liquid chromatography-tandem mass spectrometry analysis) of several candidate V. cholerae outer membrane-associated starch-binding proteins. Different sets of proteins were isolated by removal in a glucose solution or bile acids. When the upper gastrointestinal tract conditions were simulated in vitro, both bile salts and the amylolytic activity of the pancreatic juices were found to have an inhibitory effect on the adherence of V. cholerae to starch. However, during acute diarrhea, this inhibitory effect may be significantly reduced due to dilution, suggesting that adhesion does occur in vivo. Such adhesion may contribute to the beneficial effects observed following administration of granular starch-based oral rehydration solutions to cholera patients.


Proximate Composition and Nutritional Attributes of Ready-to-Cook Catfish Products.
To increase the demand for U.S. farm-raised catfish, five healthy, convenient ready-to-cook products were developed to expand consumers' options beyond basic fresh or frozen fillets. Five new catfish products were produced, consisting of one hundred samples of each, including three size-types of Panko-breaded fish products (strips, center cuts of regular fillets, and center cuts from Delacata fillets) and two marinated products (sriracha and sesame-ginger). The breaded products were to be prepared by baking for convenience over traditional frying methods, while the marinated products were to be microwaved as healthy and convenient products. The nutrient content of the samples was analyzed, including protein, moisture, fat, fiber, ash, and carbohydrate, as well as minerals, amino acid, and fatty acid constituent content, with associated atherogenic index (AI) and thrombogenic index (TI), showing unique differences between the Panko-breaded and marinated products. In addition, a trend was observed showing an increase in moisture, protein, ash, and carbohydrate percentages, and a decrease in lipid content related to the volume-to-surface-area ratio, having the order of strips < standard fillets < Delacata fillets.


Identifying the effects of microsaccades in tripolar EEG signals.
Microsaccades are tiny, involuntary eye movements that occur during fixation, and they are necessary to human sight to maintain a sharp image and correct the effects of other fixational movements. Researchers have theorized and studied the effects of microsaccades on electroencephalography (EEG) signals to understand and eliminate the unwanted artifacts from EEG. The tripolar concentric ring electrode (TCRE) sensors are used to acquire TCRE EEG (tEEG). The tEEG detects extremely focal signals from directly below the TCRE sensor. We have noticed a slow wave frequency found in some tEEG recordings. Therefore, we conducted the current work to determine if there was a correlation between the slow wave in the tEEG and the microsaccades. This was done by analyzing the coherence of the frequency spectrums of both tEEG and eye movement in recordings where microsaccades are present. Our preliminary findings show that there is a correlation between the two.


[Infusion of propofol as anesthetic and antiemetic drug].
To determine the possible antiemetic effect of propofol as the single agent for intravenous anesthesia in children undergoing strabismus surgery, in comparison with other techniques. Eighty ASA I and II patients between 3 and 10 years, divided into 4 groups of 20, were studied prospectively. Groups I, II and III were premedicated with dehydrobenzylperidol (90 micrograms/kg) i.m. Group I then received sleep doses of thiopental and N2O. Group II received propofol, sleep doses, and N2O. Groups III and IV received sleep doses of propofol followed by intravenous perfusion (10 mg/kg/h). Half the patients in group I experienced postoperative vomiting, more than in groups II, III and IV (p < 0.05). The incidence of vomiting in group II was 30%. Groups III and IV experienced less vomiting (5-10%) than did groups I and II (p < 0.05). The incidence of bradycardia during surgery was higher in groups III and IV (p < 0.05); medical treatment was not required. Propofol used as the single agent for induction and maintenance of anesthesia offers clear advantages in reducing emesis after strabismus surgery.


Systematic review and meta-analysis of diagnostic and prognostic studies: a tutorial.
Systematic reviews with meta-analysis of studies on diagnostic tests or prognostic factors are research tools that are still being developed. The objective of the present paper is to describe the methodology of systematic review and meta-analysis of this type of studies, step by step. A literature review on the subject was made, the recommendations were compiled and the paper was organized in: a) Introduction, b) Details on the eight steps to be followed, c) Form of publication of a systematic review with meta-analysis, and d) Conclusion. The systematic review methods were thoroughly described with a critical analysis of the methods of statistical compilation of results, with emphasis on the utilization of the Summary Receiver Operator Characteristic curve. References for the details of each statistical technique used were provided in the meta-analysis. We concluded that systematic reviews with meta-analysis of diagnostic tests or prognostic factors are useful in data compilation of various studies on the same subject, since they reduce biases and increase the statistical power of the primary research.


Yellow fever vaccination during treatment with infliximab in a patient with ulcerative colitis: A case report.
We report the case of a 59-year-old patient who accidentally underwent live vaccination against yellow fever during continuous treatment with the TNF-α-antibody (AB) infliximab for ulcerative colitis. The clinical course showed fever of short duration and elevation of liver enzymes without further clinical complications. Yellow fever viremia was not detectable and protective antibodies were developed. A primary vaccination against yellow fever under infliximab has not been reported in the literature before, although vaccination is an important topic in IBD. Live vaccinations, like Stamaril(®) against yellow fever, are contraindicated during TNF-α-AB treatment. Treatment regimens containing TNF-α-AB are of growing importance, not only in gastroenterology, but also in rheumatology and dermatology. We discuss this topic by presenting our case and reviewing the current literature.


Effect of low-dose zearalenone exposure on reproductive capacity of male mice.
Zearalenone (ZEA), a kind of nonsteroidal mycotoxin with estrogenic effects, can influence animal reproductive capacity through interfering with estrogen signaling pathway. Previous studies have shown exposure to ZEA at high doses (higher than No-Observed Effect Level, NOEL) had a significant impact on mouse sperm quality and pregnant rate, but little is known about the effect of exposure to ZEA at low doses (lower than NOEL) on mouse reproductive capacity. This study evaluated the effects of exposure to low-dose ZEA on mouse spermatogenesis and semen quality. Male mice (CD-1) of 21days were exposed to ZEA at 20, or 40μg/kg body weight for 14, 28 or 42days. After exposure to ZEA for 14days, the spermatogenic cells in seminiferous tubules were declined dose-independently; however in groups treated by ZEA for 28days, the spermatogenic cells were declined dose-dependently. Moreover, after treatment for 28days or 42days, the DNA double stand break (DSB) in spermatogenic cells were increased in a dose-dependent manner in treated groups. Compared with the control group, the sperm concentration, viability, motility, and hyperactive rate in treated groups were decreased dose-dependently and time-dependently. Meanwhile, deformity and mortality rate of sperm in treated groups were increased remarkably dose-dependently too. In conclusion, low dose ZEA impaired male reproductive capacity especially in spermatogenesis and semen quality of mouse.


Genetic Markers for Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in the Asian Indian Population: Implications on Prevention.
This review attempts to collate all the studies performed in India or comprising a population originating from India and to find out if there is an association between the HLA (human leucocyte antigen) type of individual and development of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) subsequent to medication use. The authors performed a PubMed search of all articles published in English from 2009 to 2019 for articles that studied HLA type in patients who developed SJS/TEN after intake of a specific drug in the Asian Indian population or in individuals of Asian Indian origin. The selection criteria were satisfied by a total of 11 studies that reported HLA associations with specific drugs, which induced SJS/TEN, mainly anti-epileptic drugs, and cold medicine/non-steroidal anti-inflammatory drugs. These studies involved a small number of patients, and hence, there is limited evidence to conclude if these associations can be extrapolated to a larger population of the same ethnicity. Similar multi-center studies need to be conducted with a larger sample size to confirm these associations. This would have implications in policy making and for understanding the potential of using genetic markers as a screening tool before prescribing a drug to a patient, which might make them susceptible to developing a potentially life-threatening disease such as SJS/TEN. This is possibly the only mode of primary prevention for this potentially fatal severe cutaneous adverse drug reaction.


Endogenous liver carcinogenesis in the rat.
Carcinogenesis may be effected not only through exposure to exogenous stimuli but also by genetic and epigenetic influences derived from endogenous factors. In the latter case, the mechanisms are still largely obscure because of the limited availability of appropriate in vivo experimental models. However, continuous feeding of a diet deficient in choline and methionine is well known to cause hepatocellular carcinomas (HCC) in rats in the absence of any known exogenous carcinogens and can serve as a good research model. A semi-synthetic, choline-deficient, L-amino acid-defined (CDAA) diet, containing practically no choline and low methionine, induces HCC with a background of fatty liver and hepatocyte death, subsequent regeneration and fibrosis resulting in cirrhosis. Using the CDAA diet, we have revealed the participation of oxidative injury to DNA and other subcellular components and of alteration in intrahepatic signal transduction pathways in the mechanisms underlying this rat liver carcinogenesis model. In the present paper, the current understanding of endogenous rat liver carcinogenesis, due to dietary choline deficiency, is reviewed.


Novel α-Galactosidase A Mutation (K391E) in a Young Woman With Severe Cardiac and Renal Manifestations of Fabry Disease.
Fabry disease, an X-linked lysosomal storage disorder due to α-galactosidase A deficiency, is associated with dysfunction of various cell types and results in a systemic vasculopathy. We describe a 29-year-old woman with Fabry disease presenting with severe cardiac and renal manifestations. Gene analysis demonstrated a novel mutation (K391E) in the GLA gene. Enzyme replacement therapy (ERT) was started with agalsidase-β after confirming the diagnosis of Fabry disease, resulting in normalization of LV systolic function and improvement of renal function. As early therapy is crucial for preventing life-threatening sequelae, clinicians should consider Fabry disease in young patients presenting with cardiac and renal disease without any likely causes.


Isolation of two Drosophila melanogaster genes abundantly expressed in the ovary during vitelline membrane synthesis.
Several genomic clones were isolated from a Drosophila library screened with cDNA prepared from abundant adult female mRNA. Cytoplasmic dot hybridizations have shown that the genes in all of these clones are expressed only in posteclosion (stages 8-14) follicles. One set of overlapping clones (lambda 20, lambda 28, and lambda 30) was localized by in situ hybridization to 66D, a previously described locus for chorion genes. Restriction mapping demonstrated that these clones contained chorion genes which had been isolated previously. Another clone, lambda 7, was mapped to chromosomal region 26A. This clone carries genes that hybridized to mRNA species similar or identical in size to the known chorion genes encompassed by lambda 28. Furthermore, one of these genes shows homology to the 66D chorion locus, apparently with the s18-1 gene. R-loop and S1-nuclease mapping indicated that lambda 7 contains two genes of 700-800 base pairs in length. Dot hybridization of cytoplasmic RNA from egg chambers demonstrated that these genes are expressed predominantly during stages 9 + 10, the time of vitelline membrane synthesis. Analysis of DNA extracted from embryos and various female tissues by dot hybridization showed that lambda 7 sequences are not amplified in the mature ovary. These results suggest that the two genes carried by lambda 7 and derived from region 26A may code for protein components of the vitelline membrane. In addition it appears that some evolutionary relatedness exists between one of these genes and a member of the chorion multigene family.


A prospective study of nonmedical use of prescription opioids during adolescence and subsequent substance use disorder symptoms in early midlife.
This longitudinal study assesses characteristics associated with adolescents' nonmedical use of prescription opioids (NMUPO) including: frequency, co-ingestion, motives, specific opioid type; sequence of initiation of medical use of prescription opioids and NMUPO in relationship to subsequent substance use disorder (SUD) symptoms. Twenty-one independent national cohorts of U.S. high school seniors (n = 8,373) were surveyed and followed 17 years from adolescence to age 35. The majority of adolescents who engaged in NMUPO reported occasional/frequent NMUPO, non-pain relief motives for NMUPO, simultaneous co-ingestion involving NMUPO and other drugs, opioid analgesics with high misuse potential, and multiple types of opioid analgesics. Adolescents who reported NMUPO for pain relief, NMUPO involving opioid analgesics with high misuse potential, or multiple prescription opioids had significantly greater odds of SUD symptoms at age 35, relative to those who had no history of NMUPO during adolescence. In addition, medical use of prescription opioids after initiating NMUPO (or NMUPO only) during adolescence was associated with significantly greater odds of subsequent SUD symptoms at age 35 relative to those who reported the medical use of prescription opioids only or had no medical use or NMUPO during adolescence. This is the first U.S. national prospective study to examine the relationships between adolescents' NMUPO characteristics and later SUD symptoms in early midlife. Several characteristics (frequency, co-ingestion, motives, opioid type, and medical/NMUPO initiation history) were identified that could be used to screen and detect high-risk youth for indicated interventions to reduce prescription opioid misuse and SUDs.


Study of Sylvilagus rabbit TRIM5α species-specific domain: how ancient endoviruses could have shaped the antiviral repertoire in Lagomorpha.
Since the first report of the antiretroviral restriction factor TRIM5α in primates, several orthologs in other mammals have been described. Recent studies suggest that leporid retroviruses like RELIK, the first reported endogenous lentivirus ever, may have imposed positive selection in TRIM5α orthologs of the European rabbit and European brown hare. Considering that RELIK must already have been present in a common ancestor of the leporid genera Lepus, Sylvilagus and Oryctolagus, we extended the study of evolutionary patterns of TRIM5α to other members of the Leporidae family, particularly to the genus Sylvilagus. Therefore, we obtained the TRIM5α nucleotide sequences of additional subspecies and species of the three leporid genera. We also compared lagomorph TRIM5α deduced protein sequences and established TRIM5α gene and TRIM5α protein phylogenies. The deduced protein sequence of Iberian hare TRIM5α was 89% identical to European rabbit TRIM5α, although high divergence was observed at the PRYSPRY v1 region between rabbit and the identified alleles from this hare species (allele 1: 50% divergence; allele 2: 53% divergence). A high identity was expected between the Sylvilagus and Oryctolagus TRIM5α proteins and, in fact, the Sylvilagus TRIM5α was 91% identical to the Oryctolagus protein. Nevertheless, the PRYSPRY v1 region was only 50% similar between these genera. Selection analysis of Lagomorpha TRIM5α proteins identified 25 positively-selected codons, 11 of which are located in the PRYSPRY v1 region, responsible for species specific differences in viral capsid recognition. By extending Lagomorpha TRIM5α studies to an additional genus known to bear RELIK, we verified that the divergent species-specific pattern observed between the Oryctolagus and Lepus PRYSPRY-domains is also present in Sylvilagus TRIM5α. This work is one of the first known studies that compare the evolution of the antiretroviral restriction factor TRIM5α in different mammalian groups, Lagomorpha and Primates.


Sonic hedgehog is a regulator of extracellular glutamate levels and epilepsy.
Sonic hedgehog (Shh), both as a mitogen and as a morphogen, plays an important role in cell proliferation and differentiation during early development. Here, we show that Shh inhibits glutamate transporter activities in neurons, rapidly enhances extracellular glutamate levels, and affects the development of epilepsy. Shh is quickly released in response to epileptic, but not physiological, stimuli. Inhibition of neuronal glutamate transporters by Shh depends on heterotrimeric G protein subunit Gαi and enhances extracellular glutamate levels. Inhibiting Shh signaling greatly reduces epileptiform activities in both cell cultures and hippocampal slices. Moreover, pharmacological or genetic inhibition of Shh signaling markedly suppresses epileptic phenotypes in kindling or pilocarpine models. Our results suggest that Shh contributes to the development of epilepsy and suppression of its signaling prevents the development of the disease. Thus, Shh can act as a modulator of neuronal activity, rapidly regulating glutamate levels and promoting epilepsy.


[Retroperitoneal laparoscopic adrenalectomy for larger adrenal tumor].
To evaluate the feasibility and safety of retroperitoneal laparoscopic adrenalectomy for larger adrenal tumor. A retrospective cohort study of patients who underwent retroperitoneal laparoscopic adrenalectomy in a single unit from July 2004 to December 2008 was undertaken, in which 53 cases were divided into 2 groups according to size as estimated by group A [n=13; age: 45+/-18 years; size: (7.6+/-1.2) cm, maximum diameter of tumor larger than 6 cm] and group B [n=40; age: (49+/-12) years; size: (4.0+/-0.9) cm, between 3 and 6 cm]. All procedures were performed successfully. In comparison between the 2 groups ,the mean operative time [(127+/-77) min vs (107+/-47) min, P<0.05] and estimated blood loss [(167+/- 223) mL vs (65+/-60) mL,P<0.01] had significant difference. The intraoperative complications and blood transfusion rate in group A were higher than those of group B (23% vs 12.5% and 15% vs 2.5%),no difference was noted in their hospital stay after operation [(7.1+/-1.1) d vs (5.5+/-0.7) d, P>0.05]. Group A was followed up for 25+/-14 months,during which time no local recurrence was noted in 8 cases, 3 cases were missed ,and 2 cases were alive with hydronephrosis. Group B was followed up for 29+/-14 months, during which time 30 cases were free, 9 cases were lost, and 1 case was found with real disfunction. The pathology of most tumors in group A included medullary lipoma(30.8%), pheochromocytoma(23%) and ganglioneuroma(23%), the others included adenoma(32.5%), pheochromocytoma(25%) and ganglioneuroma(17.5%) in group B. Retroperitoneal laparoscopic adrenalectomy has best value in patients with larger adrenal tumor and it is a minimally invasive and safe procedure for skillful surgeons in the treatment of tumor size larger than 6 cm.


Synthesis, PASS-Predication and in Vitro Antimicrobial Activity of Benzyl 4-O-benzoyl-α-l-rhamnopyranoside Derivatives.
Benzyl α-l-rhamnopyranoside 4, obtained by both conventional and microwave assisted glycosidation techniques, was subjected to 2,3-O-isopropylidene protection to yield compound 5 which on benzoylation and subsequent deprotection of isopropylidene group gave the desired 4-O-benzoylrhamnopyranoside 7 in reasonable yield. Di-O-acetyl derivative of benzoate 7 was prepared to get newer rhamnopyranoside. The structure activity relationship (SAR) of the designed compounds was performed along with the prediction of activity spectra for substances (PASS) training set. Experimental studies based on antimicrobial activities verified the predictions obtained by the PASS software. Protected rhamnopyranosides 5 and 6 exhibited slight distortion from regular ¹C₄ conformation, probably due to the fusion of pyranose and isopropylidene ring. Synthesized rhamnopyranosides 4-8 were employed as test chemicals for in vitro antimicrobial evaluation against eight human pathogenic bacteria and two fungi. Antimicrobial and SAR study showed that the rhamnopyranosides were prone against fungal organisms as compared to that of the bacterial pathogens. Interestingly, PASS prediction of the rhamnopyranoside derivatives 4-8 were 0.49 < Pa < 0.60 (where Pa is probability 'to be active') as antibacterial and 0.65 < Pa < 0.73 as antifungal activities, which showed significant agreement with experimental data, suggesting rhamnopyranoside derivatives 4-8 were more active against pathogenic fungi as compared to human pathogenic bacteria thus, there is a more than 50% chance that the rhamnopyranoside derivative structures 4-8 have not been reported with antimicrobial activity, making it a possible valuable lead compound.


[Legionella pneumonia after the use of CPAP equipment].
Continuous positive airway pressure (CPAP) equipment can be colonised by Legionellae and might cause Legionella pneumonia in the user. However, there is no reported case of Legionella pneumonia related to CPAP equipment in which an identical Legionella was found in both the patient and the CPAP equipment. A 51-year-old man came to the Emergency Department with fever, confusion and dyspnoea that had been present for 3 days. His medical history included obstructive sleep apnoea, for which he had been using CPAP therapy at home for 10 weeks. The CPAP equipment showed signs of poor maintenance. Chest X-ray revealed a pulmonary consolidation. Laboratory investigation resulted in a positive urine antigen test for Legionella. Water from the CPAP equipment and sputum from the patient revealed Legionella pneumophila. Serotyping and sequence-based typing showed an identical L. pneumophila serotype 1 ST37. It is important to be aware that CPAP equipment can be colonised with Legionellae and might cause Legionella pneumonia. It is therefore necessary to ask about CPAP therapy in a patient with community-acquired pneumonia.


[Morphometric analysis of an Anoplocephala perfoliata population].
An Anoplocephala perfoliata population isolated from the caecum of a dead horse was analysed morphometrically. Besides the number of segments, length and width of strobila, the width of scolex and the last segment, in adult tapeworms the number of eggs per segment was counted. By the aid of these data the population was divided into 4 categories. The length of fixed tapeworms varied between 5.46 and 41.53 mm. There was an direct relation between length of the strobila and number of segments. Only 42 of 440 investigated tapeworms contained mature eggs in the uterus. The number of eggs varied between 125 and 4482. The beetle mite Scheloribates latipes could be infected successfully, 9 cysticercoids were isolated from their body cavity.


Cloning and analysis of the mobile element gypsy from D. virilis.
The homologue of the Drosophila melanogaster mobile element gypsy was cloned from the distantly related species D. virilis. It has three ORFs highly homologous to those of the element from D. melanogaster. gypsy from D. virilis appears to be actively transcribed and is capable of transposition. Comparison of the untranslated regions of both elements revealed conserved sequences including those which had previously been demonstrated to be important in transcription regulation. Distribution of gypsy among the different strains of D. virilis and different species within the D. virilis group was analyzed. Possible involvement of horizontal transmission in the process of spreading and evolution of gypsy is discussed.


Intramedium Interaction and the Third-Person Effect: How Partisans Respond to YouTube Ads and Comments.
As digital media technologies have evolved and become more powerful, the prevalence of mixed-media content-that is, content that mixes multiple media such as text and video-has increased considerably. Perhaps nowhere is this more apparent than YouTube, now the Web's third most trafficked site. YouTube provides for video sharing in an environment otherwise dominated by textual titles, descriptions, and comments. As such, it is an ideal venue in which to examine the impact of intramedium interaction on message evaluation. This study uses a survey experiment to test first-person and third-person evaluations of campaign ads from the Obama and Romney campaigns, and the comments posted about them on YouTube, using two real ads and one set of fake comments. Findings suggest that partisan perceptions of the manipulated ads transfer to the constant comments, and that the contextual cue of the YouTube environment reciprocally impacts partisan evaluation of the ads themselves.


Intranasal histamine challenge in normality and allergic rhinitis.
A series of investigations was performed in which histamine challenge was used to compare nasal responsiveness in 20 normal subjects and 20 with allergic rhinitis. There was found to be a lower threshold of reactivity (D100) to histamine in allergic subjects as measured by resistance changes (geometric mean, 0.53 mg/ml; normal subjects, 2.15: p = 0.022). This may represent increased number or sensitivity of histamine receptors on the nasal capacitance vessels. The loss of a laser Doppler response to a supramaximal histamine stimulus (normal subjects, 102% increase in flux at 3 minutes; p < 0.05) was observed in patients with allergic rhinitis and indicates either a down-regulation of the capillary system or an altered effect of histamine on superficial vessels, perhaps mediated by a shift in histamine receptor type. There was an observed increase in neutrophils at the mucosal surface under baseline conditions (rhinitis median, 49.6%; normal subjects, 32.72%: p < 0.05), which suggests an important primary role in the pathogenesis of this condition for this active cell. The observed increase in secretory volume response to histamine in allergic subjects, which persisted beyond 40 minutes after a single D100 challenge, may be related to an altered sensitivity of glandular tissue. There are important changes in nasal reactivity to histamine challenge in allergic rhinitis that may have implications for its pathogenesis.


Tensile set behavior of Foley catheter balloons.
The removal of indwelling urinary balloon catheters from patients is usually associated with many problems. The problems such as balloon deflation failure; encrustations on balloons, eyes, and lumen; and catheter associated infections are widely discussed in the literature. The tensile set exhibited by the catheter balloon material could also play a role and further complicate the removal process. This article addresses this issue by comparing the tensile set behavior of the balloon material from three commercially available Foley catheters. The balloon materials were subjected to aging in synthetic urine at 37 degrees C for 28 days to simulate clinical conditions. The deflation time of catheter balloons aged in similar conditions were also measured. It was found that different brands of catheters exhibited statistically significant differences in their properties. The tensile set data of the aged samples could be correlated with the deflation time of the balloons. The clinical significance of the tensile set is also highlighted.


Duocarmycins--natures prodrugs?
The duocarmycins and (+)-CC-1065 are amongst the most potent antitumour antibiotics discovered to date and yet have not progressed into the clinic. The natural products are extremely stable to nucleophilic attack until bound to their DNA target and are not substrates for any other biological nucleophile. The mechanism for this target activation of the duocarmycins is discussed with relation to both an acid-catalyzed activation and a binding-induced conformational change leading to ground state destabilization. It is suggested that targeting of the duocarmycins to their site of action in a tumour may be more important than introducing systemically-activated prodrugs as the natural product itself can be considered to be a type of prodrug, activated only on binding to its targets. Methods that have been used to target CC-1065 and the duocarmycins are reviewed as well as efforts towards systemically activated prodrugs. A simple analysis of the approaches that could be taken to vary the structure for targeting is suggested.


Total mesorectal excision in the treatment of rectal cancer: a review.
Despite the improvements in preoperative staging, surgical technique and adjuvant therapy, local recurrence remains a significant problem in rectal cancer surgery. Several patient- and tumour-related risk factors for the development of local recurrence have been identified and are being addressed by regimens of pre- or postoperative adjuvant therapy. Total mesorectal excision (TME) recently has been shown to result in a low recurrence rate even without the use of adjuvant therapy. Nevertheless, conclusive evidence in the form of a prospective randomized trial is to date not available. This paper describes the technique of TME and reviews the clinical and pathological data supporting its use in rectal cancer surgery.


Dissecting the Role of Circular RNAs in Sarcomas with Emphasis on Osteosarcomas.
Circular RNAs (circRNAs) are single-stranded RNAs generated from exons back-splicing from a single pre-mRNA, forming covalently closed loop structures which lack 5'-3'-polarity or polyadenylated tail. Ongoing research depicts that circRNAs play a pivotal role in tumorigenesis, tumor progression, metastatic potential and chemoresistance by regulating transcription, microRNA (miRNA) sponging, RNA-binding protein interactions, alternative splicing and to a lesser degree, protein coding. Sarcomas are rare malignant tumors stemming from mesenchymal cells. Due to their clinically insidious onset, they often present at advanced stage and their treatment may require aggressive chemotherapeutic or surgical options. This review is mainly focused on the regulatory functions of circRNAs on osteosarcoma progression and their potential role as biomarkers, an area which has prompted lately extensive research. The attributed oncogenic role of circRNAs on other mesenchymal tumors such as Kaposi Sarcoma (KS), Rhabdomyosarcoma (RMS) or Gastrointestinal Stromal Tumors (GISTs) is also described. The involvement of circRNAs on sarcoma oncogenesis and relevant emerging diagnostic, prognostic and therapeutic applications are expected to gain more research interest in the future.


Characterization of Japanese encephalitis virus infection in an immortalized mesencephalic cell line, CSM14.1.
Neurons are the major target cell of Japanese encephalitis virus (JEV). Rats intracerebrally inoculated with JEV show an age-dependent pattern of resistance to infection in which resistance is closely associated with neuronal maturation. However, because there is no reliable and convenient cell culture system that mimics the in vivo properties of JEV infection of immature and mature neurons, the mechanisms underlying this association remain poorly understood. The aim of the present study was to examine JEV infection in immortalized CSM14.1 rat neuronal cells, which can be induced to differentiate into neurons by culture under non-permissive conditions. JEV infected undifferentiated CSM14.1 cells more efficiently than differentiated cells, resulting in production of more progeny virus in the former setting than in the latter. An infectious virus recovery assay detected more internalized virions in undifferentiated cells. On the other hand, JEV infection of differentiated cells induced more rapid and stronger expression of interferon-β gene, along with smaller amounts of JEV RNA. Taken together, these results show that the initial phase of viral infection and the later IFN response play roles in the viral susceptibility of undifferentiated and differentiated CSM14.1 cells. Because CSM14.1 cells became more resistant to JEV infection as they mature, this culture system can be used as an in vitro model for studying age-dependent resistance of neurons to JEV infection.


[Legal and ethical limitations of competition in healthcare from a hospital owner's perspective].
Competition is tough and the cost pressure enormous. Vivantes will actively meet the challenges of the market to gain a strong market position. All measures to improve competitiveness will be taken on the basis of the communal mandate to provide prioritised medical care; quality standards need to be maintained. In times of tight budgets Vivantes uses the limited funds carefully and focuses on using them wherever they will be most beneficial. Vivantes will achieve its ambitious business objectives by concentrating services sensibly, using efficient structures and focussing on interlocking processes.


Cellular and whole-organism effects of prolonged versus acute heat stress in a montane, desert lizard.
Global climate change involves both prolonged periods of higher-than-normal temperatures and short but extreme heat waves. Both types of temperature increases are likely to be detrimental to ectotherms, and even if such temperature increases do not cause mortality directly, compensating for such temperature increases will likely entail costs to organisms. We tested the effects of prolonged periods of higher-than-average temperatures and short-term, acute heat stress in wild populations of greater short-horned lizards (Phrynosoma hernandesi), a temperate, montane lizard of the Colorado Plateau, UT, USA. We transplanted one group of lizards from a high- to a low-elevation site, exposing them to a prolonged period of warmer temperatures. These lizards, exposed to prolonged periods of higher-than-average temperatures, experienced no change in sprint speed, endurance, or heat shock protein (HSP) production after treatment compared to baseline levels; however, they had lower water content after the transplant to a warmer climate compared to before the transplant. We exposed a second group of lizards to acute heat stress by exposing them to thermally stressful temperatures for 4 h. These lizards, exposed to a short period of acute heat stress, had no change in endurance, water content, or HSP production following acute heat stress; however, lizards exposed to acute heat stress had slower sprint speeds than control lizards. Our results demonstrate that both prolonged temperature increases and acute heat stress, each of which are predicted to occur with climate change, had different cellular and/or whole organismal-level effects on lizards.


Methotrexate infusion and folinic acid as primary therapy for nonmetastatic and low-risk metastatic gestational trophoblastic tumors. 15 years of experience.
To investigate the efficacy and toxicity of methotrexate (MTX) given intravenously (i.v.) at a dose of 100 mg/m2 i.v. bolus and 200 mg/m2 infusion over 12 hours followed by folinic acid in the primary treatment of gestational trophoblastic tumors (GTTs). We reviewed the records of patients at the New England Trophoblastic Disease Center who had received MTX infusion at a dose of 100 mg/m2 i.v. bolus and 200 mg/m2 infusion over 12 hours followed by folinic acid as primary therapy for GTTs that did not resolve with uterine evacuation alone. Data on the patients' age, gravity and parity, disease stage (by FIGO and WHO criteria), antecedent pregnancy, presenting level of hCG, metastatic status, courses of chemotherapy required to achieve remission, toxicity related to chemotherapy treatments and time to normalization of hCG were recorded. One hundred ninety-two patients with persistent GTTs were treated with the MTX infusion protocol between December 1985 and December 2000. One hundred twenty-four patients (64.6%) achieved complete remission with the MTX infusion protocol. Complete remission was induced in 108 (87.1%) with a single course of chemotherapy; 12 others achieved remission with a single additional course of MTX. All patients found to be resistant to MTX therapy later achieved remission with other chemotherapy. Minimal toxicity was experienced during MTX treatment. MTX infusion with folinic acid is effective and well tolerated as primary single-agent therapy for nonmetastatic and low-risk metastatic GTT.


Comparative analysis of the effect of phenobarbital, dichlorodiphenyltrichloroethane, butylated hydroxytoluene and nafenopin on rat hepatocarcinogenesis.
In order to investigate whether different 'promoters' have the same qualitative and/or quantitative effects on rat hepatocarcinogenesis, 0.05% of phenobarbital (PB), 0.05% of dichlorodiphenyltrichloroethane (DDT), 0.5% butylated hydroxytoluene (BHT) and 0.1% of nafenopin (NAF) were chronically administered in the diet to rats previously submitted to an initiation by diethylnitrosamine and a selection with 2-acetylaminofluorene plus CC14. The animals were killed after 3, 6 and 14 weeks of 'promoters' administration to analyse their effect on premalignant lesions. The quantitative analysis of the gamma-glutamyltransferase positive lesions indicates that as compared to a control group receiving a basal diet after initiation and selection, PB, DDT and BHT enhance the development of these lesions whereas NAF inhibits it. Rats were also killed after 22 weeks of administration to analyse the incidence and the yield of liver cancer. As compared to the control group, PB, DDT and surprisingly NAF enhance the development of liver cancer whereas BHT does not. This suggests that the effect of potential 'promoters' should be analysed on cancer development rather than on premalignant lesions.


Low-frequency sonophoresis enhances rivastigmine permeation in vitro and in vivo.
We investigated the enhancement effect of low-frequency sonophoresis on transdermal permeation of rivastigmine in vitro and in vivo. The in vitro permeation study showed that sonophoresis increased steady-state transdermal flux 0.31 ± 0.03 μg x cm(-2) x h(-1) and the extent of rivastigmine permeation 6.00 ± 0.56 μg x cm(-2) though excised skin (both P < 0.01). In the in vivo experiment, the C(max) 0.83 ± 0.16 μg x mL(-1) and AUC(0 --> 24 h) 12.35 ± 1.99 μg x h x mL(-1) of the sonophoresis group was also significantly higher than that of the control group (both P < 0.01). These data suggest that low-frequency sonophoresis could be an effective method to enhance rivastigmine permeation.


Levothyroxin restores hypothyroidism-induced impairment of hippocampus-dependent learning and memory: Behavioral, electrophysiological, and molecular studies.
Hypothyroidism induces cognitive impairment in experimental animals and patients. Clinical reports are conflicting about the ability of thyroid hormone replacement therapy to fully restore the hypothyroidism-induced learning and memory impairment. In this study, we investigated the effects of L-thyroxin (thyroxin) treatment on hippocampus-dependent learning and memory in thyroidectomized adult rats. In the radial arm water maze (RAWM) task, thyroxin treated thyroidectomized animals made significantly fewer errors than the untreated hypothyroid animals in Trial 3 of the acquisition phase, short-term memory and long-term memory tests. In addition, the number of errors made by the thyroxin treated thyroidectomized animals was not different from that of the control group. Furthermore, the days-to-criterion (DTC) values for thyroxin treated thyroidectomized animals were not different from those of the control group but significantly lower than those of the untreated hypothyroid animals. In anesthetized rats, extracellular recording from hippocampal area CA1 of hypothyroid rats shows that thyroxin treatment restores impaired Late-phase long-term potentiation (L-LTP). Immunoblot analysis of signaling molecules, including cyclic-AMP response element binding protein (CREB), mitogen-activated protein kinases (MAPKp44/42; ERK1/2), in area CA1 revealed that thyroxin treatment reversed hypothyroidism-induced reduction of signaling molecules essential for learning and memory, and L-LTP. This study shows that thyroxin treatment reverses hypothyroidism-induced impairment of hippocampus-dependent cognition, and L-LTP, probably by restoring the levels of signaling molecule important for these processes.


The Position of the N Atom Plays a Significant Role for Excited-State Decay of Heterocycles.
We have employed combined electronic structure calculations and nonadiabatic dynamics simulations to study the S1 radiationless deactivation mechanism of pyrazole. In terms of MS-CASPT2 computed results, we propose that the 1πσ* state-driven nonadiabatic N-N dissociation is a major relaxation path; the ring-puckering deformation path as well as the 1πσ* state-driven N-H dissociation are less favorable. This excited-state decay mechanism is supported by MS-CASPT2 nonadiabatic dynamics simulations. The present study demonstrates that pyrazole has a different excited-state radiationless deactivation mechanism compared with its structural isomer imidazole, in which the 1πσ* state-driven nonadiabatic N-H dissociation plays a more important role. However, such a channel is suppressed in pyrazole; instead, the 1πσ* state-driven nonadiabatic N-N dissociation is dominant.


Integrated physiological and agronomic modelling of N capture and use within the plant.
Today farmers have several constraints to take into account in managing their crops: (i) competitiveness: productivity must be maintained or increased whereas inputs must be decreased, (ii) the environmental consequences of cultural practices: pesticide and fertilizer use must be decreased, and (iii) product quality must be improved and nitrogen nutrition is an important factor in harvest quality. These new constraints sometimes conflict: maximum yield is often obtained with large amounts of N, increasing the risks of N leaching. The determination of rates and dates for nitrogen application must become more precise in this context. Tools are required for the forecasting of crop requirements, the diagnosis of N deficiencies during the crop cycle and breeding of new adapted varieties. Models and diagnosis indicators have been developed to meet these needs, but those relating to nitrogen are often based on empirical relationships. Moreover, the available models and indicators often fail to account for cultivar-specific responses. The improvement of agronomic tools and the breeding of new varieties adapted to new cropping systems should be based on a thorough understanding of the key metabolic processes involved, and the relative contributions of these processes to yield determination in conditions of fluctuating N supply. For both purposes, more information is required about plant and crop N economy. In this paper, the way in which N absorption and use within the plant and crop, plant responses to deficiencies and excesses of nitrogen are taken into account in major agronomic models is described first. The level of sophistication of the modules comprising these models depends on operational objectives. Secondly, the ways in which the most recent molecular plant physiology findings can, and indeed should, be integrated into models at the crop and crop cycle levels are described. The potential value of this approach for improving current agronomic models and diagnostic tools, and for breeding more efficient varieties is also discussed.


Early parent-child relations and family functioning of preschool boys with pervasive hyperactivity.
This study examined the quality of parent-child relationships and family functioning of preschool children with early onset hyperactivity by comparing a community sample of 33 pervasively hyperactive preschool boys with a comparison sample of 34 boys. Mothers and children were assessed at home on a range of interview, parent questionnaire, and observational measures of parenting and family functioning. Results of the study showed that higher rates of reported lax disciplinary practices, less efficient parental coping, lower rates of father-child communication, and less synchronous mother-child interactions were significantly associated with hyperactivity following statistical adjustment for the effects of conduct problems and other confounding factors. The best parenting predictor of hyperactivity was maternal coping. The present findings suggest that the way in which parents interact with their preschool children may make a unique contribution to the development and ongoing behavioral difficulties experienced by children with pervasive hyperactivity. Findings also highlight the importance of considering the role of fathers in the behavioral development of boys with early tendencies to hyperactive and distractible behavior problems.


Novel path to IL-6 trans-signaling through thrombin-induced soluble IL-6 receptor release by platelets.
Interleukin (IL)-6 is a multifunctional cytokine with a critical role in inflammatory, immunoregulatory and haemopoietic responses. Its receptor consists of an ubiquitously expressed membrane transducing element (gp130) and of the specific element IL-6R-alpha (gp80), present only on hepatocytes and some leukocyte subsets. IL-6R-alpha also exists as soluble protein (sIL-6R) that, in the presence of IL-6, forms a complex able to bind gp130 and, thanks to the mechanism called trans-signaling, transduces IL-6 effect through tyrosine phosphorylation and activation of the signal transducer and transcription activator (STAT)-3. The aim of this study was to analyze the bidirectional relationships between platelet aggregation and IL-6-dependent effects. While platelets do not produce IL-6, we found that resting platelets express gp130, but not gp80, on their membranes. Upon activation by thrombin or calcium ionophore A23187, but not by ADP, the IL-6R-alpha is released in soluble form, while cangrelor, the specific inhibitor of P2Y12 receptor, can partially inhibit sIL-6R release. This sIL-6R is biologically active and, in the presence of IL-6, can trigger IL-6 trans-signaling, inducing an autocrine activation loop (as measured by an increase in gp80 and gp130 content) and STAT3 phosphorylation. On the other hand, IL-6 trans-signaling has no effect on platelet degranulation or aggregation by itself, nor on thrombin-induced platelet aggregation. Our data add an important piece to the puzzle of thrombosis and inflammation: in the presence of IL-6, which can be produced by stressed endothelial cells, the platelet-derived IL-6 trans-signaling could be crucial for the evolution of inflammation within a damaged vessel.


Sustainable water future with global implications: everyone's responsibility.
The current use and management of freshwater is not sustainable in many countries and regions of the world. If current trends are maintained, about two-thirds of the world's population will face moderate to severe water stress by 2025 compared to one-third at present. This water stress will hamper economic and social development unless action is taken to deal with the emerging problems. The Comprehensive Assessment of the Freshwater Resources of the World, prepared by the UN and the Stockholm Environment Institute, calls for immediate action to prevent further deterioration of freshwater resources. Although most problems related to water quantity and quality require national and regional solutions, only a global commitment can achieve the necessary agreement on principles, as well as financial means to attain sustainability. Due to the central and integrated role played by water in human activities, any measures taken need to incorporate a wide range of social, ecological and economic factors and needs. The Assessment thus addresses the many issues related to freshwater use, such as integrated land and water management at the watershed level, global food security, water supply and sanitation, ecosystem requirements, pollution, strengthening of major groups, and national water resource assessment capabilities and monitoring networks. Governments are urged to work towards a consensus regarding global principles and guidelines for integrated water management, and towards their implementation in local and regional water management situations. The alternative development options available to countries facing water stress, or the risk thereof, needs to be considered in all aspects of development planning.


Biosorptive Potential of Pseudomonas species RY12 Toward Zinc Heavy Metal in Agriculture Soil Irrigated with Contaminated Waste Water.
Industrial waste is mainly responsible for accumulating Zn (II) in the soil, which needs to be removed to avoid its bioaccumulation and hazardous effects on the environment. In a recent study, the potential of the RY12 strain was evaluated as a biosorbent of Zn (II) ions in an aqueous medium. Different microbiological techniques like biochemical, molecular characterization, and 16S rRNA gene sequencing were used for the identification of RY12. The impact of different parameters such as the initial zinc ion concentration, pH, temperature, and the removal of other metals such as manganese, lead, cobalt, silver, copper, mercury, and chromium was also evaluated on the reduction of Zn (II). Fourier Transform Infrared spectroscopy (FTIR) was also carried out to investigate the role of cellular surfaces in the sorption of Zn+2 ions. Both biochemical and phylogenetic analyses established that strain RY12 Pseudomonas sp. capable of reducing Zn+2 up to 89% at 28°C (pH = 6.5; initial Zn+2 concentration = 200 mg/L). The FTIR analysis revealed that the bacterial cell wall's amino, carboxyl, and phosphate groups were involved in the reaction with Zn (II). Our findings suggest that Pseudomonas sp. RY12 is a proficient bacterium for removing zinc from industrial waste and could be a valuable bioremediation agent.


[Effect of oxysophoridine on electric activities and its power spectrum of reticular formation in rats].
To observe the effect of oxysophoridine (OSR) on the EEG and its power spectrum of reticulum formation in mesencephalon of anaesthetized rat. Utilizing the technique of brain stereotactic apparatus, electrodes were implanted into reticulum formation of mesencephalon. Monopolar lead and computerized FFT technique were employed to record and analyse the index of EEG, power spectrum and frequency distribution in order to study the effect of oxysophoridine on the bioelectricity change of mesencephalon reticulum formation in rats. After administrating(icy) with oxysophoridine at the dose of 2.5,5, 10 mg/rat, the EEG of mesencephalon reticulum formation mainly characterized with low amplitude and slow waves accompanied by spindle-formed sleeping waves with a significant decrease of total power of EEG (P < 0.05) while the ratio of theta, alpha waves increased in total frequency of rats (P < 0.05). Oxysophoridine possesses central inhibitory effects and its inhibitory mechanism may associate with the reduction of bioelectricity in mesencephalon reticulum formation. Mesencephalon reticulum formation may serve as one part of the structure serving as the circuit conducting the central inhibitory effect of oxysophoridine. [Key words] oxysophoridine; reticulum formation; electroencephalogram (EEG) ; rats