Novel Software-Derived Workflow in Extracranial-Intracranial Bypass Surgery Validated by Transdural Indocyanine Green Videoangiography.
The introduction of image-guided methods to bypass surgery has resulted in optimized preoperative identification of the recipients and excellent patency rates. However, the recently presented methods have also been resource-consuming. In the present study, we have reported a cost-efficient planning workflow for extracranial-intracranial (EC-IC) revascularization combined with transdural indocyanine green videoangiography (tICG-VA). We performed a retrospective review at a single tertiary referral center from 2011 to 2018. A novel software-derived workflow was applied for 25 of 92 bypass procedures during the study period. The precision and accuracy were assessed using tICG-VA identification of the cortical recipients and a comparison of the virtual and actual data. The data from a control group of 25 traditionally planned procedures were also matched. The intraoperative transfer time of the calculated coordinates averaged 0.8 minute (range, 0.4-1.9 minutes). The definitive recipients matched the targeted branches in 80%, and a neighboring branch was used in 16%. Our workflow led to a significant craniotomy size reduction in the study group compared with that in the control group (P = 0.005). tICG-VA was successfully applied in 19 cases. An average of 2 potential recipient arteries were identified transdurally, resulting in tailored durotomy and 3 craniotomy adjustments. Follow-up patency results were available for 49 bypass surgeries, comprising 54 grafts. The overall patency rate was 91% at a median follow-up period of 26 months. No significant difference was found in the patency rate between the study and control groups (P = 0.317). Our clinical results have validated the presented planning and surgical workflow and support the routine implementation of tICG-VA for recipient identification before durotomy.


Late-onset malignant astrocytoma in a case of multiple sclerosis. Clinical, neuropathological, virological, and tissue culture studies.
An unusual case of concurrent MS and anaplastic astrocytoma is presented. MS was diagnosed in a female patient at the age of 22 years. A left side thalamotomy was performed for relief of severe intention tremor at age 28 and at age 32 she received immunosuppressive therapy for 1 year. At the age of 36 after a severe exacerbation of her symptoms a left side fronto-temporal tumor was diagnosed and a subtotal neurosurgical extirpation was performed. Histopathologically, the tumor was an anaplastic astrocytoma, which was further substantiated by electron microscopy and establishment of a permanent cell line in vitro. The cultured tumor cells were negative for measles virus by immunofluorescence. The relationship between the reactive astrocytes in MS plaques and astrocytic neoplasia is discussed.


Adaptation to hypoxia.
Many biochemical changes occur during acclimation to altitude. Some appear to be deleterious, but the increase in cytochrome-P 450 and the changes in the endoplasmic reticulum seem to be beneficial. The latter changes could reduce the capillary to oxidase gradient to compensate for the lower capillary oxygen tensions. The possibility of accelerating acclimation to hypoxia by using drugs which produce similar changes is being explored.


Angiotensin 1-7 mitigates rhabdomyolysis induced renal injury in rats via modulation of TLR-4/NF-kB/iNOS and Nrf-2/heme‑oxygenase-1 signaling pathways.
Rhabdomyolysis (RM) is a critical condition with a high mortality rate, but effective management is still deficient. Till date, there are no studies that have addressed the effect of angiotensin 1-7 in this condition, hence, the rationale of this study was to evaluate the potential protective effect of Angiotensin 1-7 (Ang1-7), on rhabdomyolysis (RM) induced kidney injury in rats and detecting the underlying mechanistic insights. Forty adult male albino rats were divided into groups; the control group, RM group, RM+Ang1-7 group, and RM+Ang1-7+ A779 group. Sera and urine samples were collected for analysis of renal and muscle injury markers. Kidney tissues were taken for estimation of oxidative, inflammatory, and apoptotic markers as well as angiotensin-II (Ang II) and Ang1-7. Renal histology and expression of inducible nitric oxide synthase-1 (iNOS), real-time PCR for angiotensin-converting enzyme-2 (ACE-2), nuclear erythroid factor-2 (Nrf-2), Toll like receptor 4 (TLR-4) and NF-kB in kidney tissues were also measured. Induction of RM caused renal oxidative stress injury, inflammation, apoptosis and marked deterioration in kidney functions as well as reduction of Ang1-7 and raised Angiotensin-II level in kidney tissues. Administration of Ang1-7 to the RM group reversed all the affected parameters which were blocked by A779 administration (Mas receptor blocker). We concluded that Ang1-7 could be a potential therapeutic agent that could mitigate RM-induced renal injury. The underlying mechanisms may involve Stimulation of the ACE-2/Ang1-7/MasR axis and modulation of TLR-4/NF-kB/iNOS and Nrf-2/heme‑oxygenase -1 pathways.


Biofunctionalization of synthetic bone substitutes with angiogenic stem cells: Influence on regeneration of critical-size bone defects in an in vivo murine model.
The aim of this study was to investigate the influence of human bone marrow-derived endothelial progenitor cells (EPC) on vascularization and bone regeneration in combination with a bone-substitute material (BSM) in a critical-size bone defect in a murine model. Critical-size bone defects were performed and the defects were filled according to the group membership. Eighteen rats were randomized in two experimental groups: BSM (BoneCeramic) with/without EPC biofunctionalization, and a control group without BSM and EPC. Calvaria bone defects were performed and the defects were filled according to the group membership. After 8 weeks, qualitative tissue response of newly formed bone mass was analyzed by histology, cone beam CT (CBCT) and micro-CT (μCT) scans. Occurrence of tumor masses due to EPC vascularization in peripheral organs was investigated microscopically in histological slides of liver and kidney. The combination of EPC and BSM showed smaller bone defects in the CT scans and the histological evaluation as the single use of BSM without EPC by trend (p = 0.067). Further, a higher amount of blood vessels could be found in histological slices of BSM in combination with EPC. No inflammatory response or tumor formation could be found. These findings confirm the biocompatibility of the used BSM and provide evidence that the combination of BSM with EPC might be effective for bone vascularization and regeneration. Using EPC in augmentation sites might overall lead to faster and better bone regeneration and should be further investigated in future studies.


[Diagnosis and tactics of managing a patient with central diabetes insipidus on the example of a clinical case].
Diagnosis and differential diagnosis of patients with diabetes insipidus is often a difficult task for the endocrinologist. This case report focuses on a patient with a long history of central idiopathic diabetes insipidus who had a substantial decrease in desmopressin requirements during the last year of follow-up. Conducting tests with osmotic stimulation (test with water deprivation, infusion test with hypertonic solution) made it possible to answer the question of the persistence of the disease, as well as to determine a further management plan, taking into account the physiological characteristics of our patient.


Ergonomic approach for pillow concept design.
Sleep quality is an essential factor to human beings for health. The current paper conducted four studies to provide a suitable pillow for promoting sleep quality. Study 1 investigated the natural positions of 40 subjects during sleep to derive key-points for a pillow design. The results suggested that the supine and lateral positions were alternatively 24 times a night, and the current pillows were too high for the supine position and too low for lateral positions. Study 2 measured body dimensions related to pillow design of 40 subjects to determine pillow sizes. The results suggested that the pillow height were quite different in supine position and lateral position and needed to take into consideration for a pillow design. Study 3 created a pillow design based on the results of above studies. The pillow was a U-form in the front of view in which the pillow height in the middle area was lower for the supine position, and both sides were higher for the lateral positions. Study 4 assessed sleep quality of 6 subjects by using the proposed pillows and the current pillows. The results showed that the newly designed pillow led to significantly higher sleep quality, and the new design received an innovation patent.


Role of Renal Sympathetic Nerves in GLP-1 (Glucagon-Like Peptide-1) Receptor Agonist Exendin-4-Mediated Diuresis and Natriuresis in Diet-Induced Obese Rats.
Background The gut-derived hormone GLP-1 (glucagon-like peptide-1) exerts beneficial effects against established risk factors for chronic kidney disease. GLP-1 influences renal function by stimulating diuresis and natriuresis and thus lowering arterial blood pressure. The role of the sympathetic nervous system has been implicated as an important link between obesity with elevated arterial pressure and chronic kidney disease. The primary aim of this study was to determine the contribution of renal sympathetic nerves on intrapelvic GLP-1-mediated diuresis and natriuresis in high-fat diet (HFD)-induced obese rats. Methods and Results Obesity was induced in rats by HFD for 12 weeks, followed by either surgical bilateral renal denervation or chronic subcutaneous endopeptidase neprilysin inhibition by sacubitril for a week. Diuretic and natriuretic responses to intrapelvic administration of the GLP-1R (GLP-1 receptor) agonist exendin-4 were monitored in anesthetized control and HFD rats. Renal GLP-1R expression and neprilysin expression and activity were measured. The effects of norepinephrine on the expression of GLP-1R and neprilysin in kidney epithelial LLC-PK1 cells were also examined. We found that diuretic and natriuretic responses to exendin-4 were significantly reduced in the HFD obese rats compared with the control rats (cumulative urine flow at 40 minutes, 387±32 versus 650±65 µL/gkw; cumulative sodium excretion at 40 minutes, 42±5 versus 75±10 µEq/gkw, P<0.05). These responses in the HFD rats were restored after ablation of renal nerves (cumulative urine flow at 40 minutes, 625±62 versus 387±32 µL/gkw; cumulative sodium excretion at 40 minutes, 70±9 versus 42±5 µEq/gkw, P<0.05). Renal denervation induced significant reductions in arterial pressure and heart rate responses to intrapelvic GLP-1 in the HFD rats. Renal denervation also significantly increased the GLP-1R expression and reduced neprilysin expression and activity in renal tissues from the HFD rats. Chronic subcutaneous neprilysin inhibition by sacubitril increased GLP-1-induced diuretic and natriuretic effects in the HFD rats. Finally, exposure of the renal epithelial cells to norepinephrine in vitro led to downregulation of GLP-1R expression but upregulation of neprilysin expression and activity. Conclusions These results suggest that renal sympathetic nerve activation contributes to the blunted diuretic and natriuretic effects of GLP-1 in HFD obese rats. This study provides significant novel insight into the potential renal nerve-neprilysin-GLP-1 pathway involved in renal dysfunction during obesity that leads to hypertension.


Prevention of the development of melphalan resistance in vitro by selenite.
Exposure of A2780 human ovarian tumor cells to a low concentration of melphalan in vitro for 7 d results in the development of melphalan resistance, which is dependent on elevated cellular levels of glutathione and glutathione S-transferase. The inclusion of selenite (at concentrations as low as 0.2 microM) during the exposure to melphalan completely prevented the development of resistance. Selenite did not prevent the melphalan-induced increase in glutathione, but it did prevent the increase in the activity of glutathione S-transferase. It also prevented the increase in the expression of the glutathione S-transferase gene, suggesting that this may be the mechanism by which it prevents the development of melphalan resistance. The results of this in vitro study suggest that selenite may prove to be useful in preventing the development of drug resistance in vivo.


Articulation error migration: a comparison of single word and connected speech samples.
In this study frequency and type of articulation error, including error migration, were compared between single word production and connected speech samples when vocabulary was held constant. Spontaneous single word and connected speech samples were obtained from 20 articulation disordered children ages 5-4 to 12-8 years. There were significantly more errors in connected speech samples than single word utterances. The difference between samples, i.e., error migration, is discussed, as is the predictive value for speech-language clinicians.


Searching for a DNAzyme Version of the Leadzyme.
The leadzyme refers to a small ribozyme that cleaves a RNA substrate in the presence of Pb(2+). In an optimized form, the enzyme strand contains only two unpaired nucleotides. Most RNA-cleaving DNAzymes are much longer. Two classical Pb(2+)-dependent DNAzymes, 8-17 and GR5, both contain around 15 nucleotides in the enzyme loop. This is also the size of most RNA-cleaving DNAzymes that use other metal ions for their activity. Such large enzyme loops make spectroscopic characterization difficult and so far no high-resolution structural information is available for active DNAzymes. The goal of this work is to search for DNAzymes with smaller enzyme loops. A simple replacement of the ribonucleotides in the leadzyme by deoxyribonucleotides failed to produce an active enzyme. A Pb(2+)-dependent in vitro selection combined with deep sequencing was then performed. After sequence alignment and DNA folding, a new DNAzyme named PbE22 was identified, which contains only 5 nucleotides in the enzyme catalytic loop. The biochemical characteristics of PbE22 were compared with those of the leadzyme and the two classical Pb(2+)-dependent DNAzymes. The rate of PbE22 rises with increase in Pb(2+) concentration, being 1.7 h(-1) in the presence of 100 μM Pb(2+) and reaching 3.5 h(-1) at 500 µM Pb(2+). The log of PbE22 rate rises linearly in a pH-dependent fashion (20 µM Pb(2+)) with a slope of 0.74. In addition, many other abundant sequences in the final library were studied. These sequences are quite varied in length and nucleotide composition, but some contain a few conserved nucleotides consistent with the GR5 structure. Interestingly, some sequences are active with Pb(2+) but none of them were active with even 50 mM Mg(2+), which is reminiscent of the difference between the GR5 and 8-17 DNAzymes.


IL-6: An endogenous activator of MMP-9 in preterm birth.
Preterm birth or PTB (<37 weeks) is a heterogeneous phenotype with numerous biological pathways. The lack of explanation due to complex pathways, inconsistent observations indicates the need for employing the role of genetic determinants to anticipate the danger of PTB. In this present study, we investigated the possible gene-gene interaction of five SNPs with PTB and its association with total MMP-9 levels. A total of 510 recruitments (250 terms and preterm each) were made and were genotyped by Restriction Fragment length polymorphism (RFLP). Generalized Multifactor Dimensionality Reduction (GMDR) method was carried out for determining gene-gene interaction. ANOVA and t-test were used to identify the association of IL-6 polymorphism with PTB alone and correspondingly with PTB and low birth weight infants (i.e. < 2500 kg). The combination of IL-6 and MMP-9 and MMP-1, MMP-8 and MMP-9 polymorphism was selected through GMDR analysis concerning mothers with preterm and term birth (accuracy 0.5921 and 0.8030 with Cross-Validation Consistency (CVC) 10/10 respectively). Increased expression of MMP-9 was reported in cases in those mothers carrying IL-6 G allele, which was profoundly associated with PTB independently. IL-6 polymorphisms showed synergistic effects in terms of increased total MMP-9 levels in the present study.


[Histiocytosis X in children--course of the disease and treatment].
A clinical analysis was carried out of the course of the disseminated form of the disease in 20 children aged from one month to 8 years (mean age 11 months). Unfavourable prognostic significance was confirmed of such factors as: child's age at the time of falling ill lower than two years, number of the involved organs and their dysfunction, and lacking reaction to treatment during the first three months of the disease.


Effect of Aging and Direction of Impulse in Suppression Head Impulse Test.
To identify differences in the vestibulo-ocular reflex (VOR) gain value and the peak saccade velocity in the suppression video head impulse test paradigms according to the age of the subject and the direction of the impulse. Retrospective chart analysis. Tertiary referral hospital. Between October 2017 and May 2019, we enrolled subjects who had previous histories of dizziness but no dizziness over the last 1 month. We conducted cervical vestibular-evoked myogenic potential and caloric tests, as well as video head impulse tests. We excluded the subjects who had abnormal cervical vestibular-evoked myogenic potential results (asymmetry ratio of greater than 30%) and abnormal caloric test results (caloric paresis of greater than 25%). We included 647 subjects aged 10 to 87 years. The mean VOR gain and peak saccade velocity were maintained in subjects less than 70 years old (VOR gain, 0.991 ± 0.08, peak saccade velocity, 348.47 ± 142.32). However, the decreases in VOR gain and peak saccade velocity were significant in subjects over 70 years old (VOR gain, 0.928 ± 0.09, peak saccade velocity, 315.51 ± 0.09; p < 0.001). The mean VOR gain of the rightward impulse (1.00 ± 0.09) was higher than the leftward impulse (0.96 ± 0.08, p < 0.001). Both the VOR gain and peak saccade velocity of suppression video head impulse test paradigms declined with increasing age over 70 years. In addition, the VOR gain of the rightward impulse was higher than the leftward impulse in the right-eye recordings.


CSF hypersecretion versus impaired CSF absorption in posthemorrhagic hydrocephalus: a systematic review.
The molecular mechanisms underlying development of posthemorrhagic hydrocephalus (PHH) remain elusive. The aim of this systematic review was to evaluate existing literature on increased CSF secretion and impaired CSF absorption as pathogenic contributors to CSF accumulation in neonatal and adult PHH. The systematic review was conducted in accordance with the PRISMA guidelines. Relevant studies published before March 11th, 2023, were identified from PubMed and reference lists. Studies were screened for eligibility using predefined inclusion and exclusion criteria. Data from eligible studies were extracted and potential sources of bias were evaluated. Nineteen studies quantified CSF production rates and/or CSF absorption capacity in human patients with PHH or animals with experimentally induced PHH. Increased CSF production was reported as early as 24 h and as late as 28 days post ictus in six out of eight studies quantifying CSF production rates in animals with experimentally induced PHH. Impaired CSF absorption was reported in all four studies quantifying CSF absorption capacity in human patients with PHH and in seven out of nine studies quantifying CSF absorption capacity in animals with experimentally induced PHH. Impaired CSF absorption was reported as early as 30 min and as late as 10 months post ictus. The pathological CSF accumulation in PHH likely arises from a combination of increased CSF secretion and impaired CSF absorption, which may manifest at different time scales following a hemorrhagic event. Emergent evidence on increased CSF secretion by the choroid plexus may herald a paradigm shift in our understanding of PHH.


Quantifying the spatial differentiation mechanism of land use degree.
The land use degree reflects the land use due to natural factors and human activities, and thus, its spatial differentiation analysis and the study of factors influencing it is of great importance. Although the mechanisms by which changes in factors affect land use have been extensively studied, the impact of factor variations on spatial differentiation of land use degree remains poorly understood. Therefore, in this study, we applied geographical detector, a new tool of spatial statistics, and used spatial autocorrelation and GIS spatial analyses to study the interactive effects of factors on land use degree and their changes in Sichuan, western China and identified the most appropriate characteristics and scope of factors. The land use degree showed an increasing trend. The geographical differentiation of land use was significant, with a high land use degree in the Chengdu Plain and its surrounding areas in the east, a low land use degree in the plateau area of western Sichuan and a significant aggregated distribution. Topographic relief, elevation, annual average temperature, geomorphic type, ≥10°C accumulated temperature, and other factors provided a good explanation for the variability in the land use degree. There were interactive effects of factors that influenced the land use degree. The synergistic effects of factors exhibited mutual and non-linear enhancement relationships, and the interaction of the factors enhanced the influence of individual factors. The most appropriate characteristics and scope of the main factors revealed by our study will contribute to a better understanding of the influences of factors on the changes in land use and their driving mechanisms.


Examining transcranial random noise stimulation as an add-on treatment for persistent symptoms in schizophrenia (STIM'Zo): a study protocol for a multicentre, double-blind, randomized sham-controlled clinical trial.
One out of three patients with schizophrenia failed to respond adequately to antipsychotics and continue to experience debilitating symptoms such as auditory hallucinations and negative symptoms. The development of additional therapeutic approaches for these persistent symptoms constitutes a major goal for patients. Here, we develop a randomized-controlled trial testing the efficacy of high-frequency transcranial random noise stimulation (hf-tRNS) for the treatment of resistant/persistent symptoms of schizophrenia in patients with various profiles of symptoms, cognitive deficits and illness duration. We also aim to investigate the biological and cognitive effects of hf-tRNS and to identify the predictors of clinical response. In a randomized, double-blind, 2-arm parallel-group, controlled, multicentre study, 144 patients with schizophrenia and persistent symptoms despite the prescription of at least one antipsychotic treatment will be randomly allocated to receive either active (n = 72) or sham (n = 72) hf-tRNS. hf-tRNS (100-500 Hz) will be delivered for 20 min with a current intensity of 2 mA and a 1-mA offset twice a day on 5 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Patients' symptoms will be assessed prior to hf-tRNS (baseline), after the 10 sessions, and at 1-, 3- and 6-month follow-up. The primary outcome will be the number of responders defined as a reduction of at least 25% from the baseline scores on the Positive and Negative Syndrome Scale (PANSS) after the 10 sessions. Secondary outcomes will include brain activity and connectivity, source monitoring performances, social cognition, other clinical (including auditory hallucinations) and biological variables, and attitude toward treatment. The results of this trial will constitute a first step toward establishing the usefulness of hf-tRNS in schizophrenia whatever the stage of the illness and the level of treatment resistance. We hypothesize a long-lasting effect of active hf-tRNS on the severity of schizophrenia symptoms as compared to sham. This trial will also have implications for the use of hf-tRNS as a preventive intervention of relapse in patients with schizophrenia. ClinicalTrials.gov NCT02744989. Prospectively registered on 20 April 2016.


Molecular dynamics simulations of adsorption and desorption of bone morphogenetic protein-2 on textured hydroxyapatite surfaces.
Interactions between bone morphogenetic protein-2 (BMP-2) and biomaterial surfaces are of great significance in the fields of regenerative medicine and bone tissue engineering. In this work, the adsorption and desorption behaviors of BMP-2 on a series of nano-textured hydroxyapatite (HAP) surfaces were systematically investigated by combined molecular dynamic (MD) simulations and steered molecular dynamic (SMD) simulations. The textured HAP surfaces exhibited nanostructured topographies and played a critical role in the mediation of dynamic behaviors of BMP-2. Compared to the HAP-flat model, the HAP-1:1 group (means ridge vs groove = 1:1) showed the excellent ability to capture BMP-2, less conformation change of BMP-2 molecule, and high cysteine-knot stability during the adsorption and desorption processes. These findings suggest that nano-textured HAP surfaces are more capable of loading BMP-2 molecules, and most importantly, they can help maintain a higher biological activity of BMP-2 cargos. In the present study, for the first time, we have deeply clarified the adsorption and desorption dynamics of BMP-2 on various nano-textured HAP surfaces at the atomic level, which can provide significant guidelines for the future design of BMP-2-based tissue engineering implants/scaffolds. STATEMENT OF SIGNIFICANCE: By using combined molecular dynamic (MD) simulations and steered molecular dynamic (SMD) simulations, the adsorption and desorption dynamics of bone morphogenetic protein-2 (BMP-2) dimer on a series of nano-textured hydroxyapatite (HAP) surfaces at the atomic level were presented in details for the first time. We have proved that the HAP-1:1 model (means ridge vs groove = 1:1) possessed excellent ability to capture BMP-2, less conformation change, and high cysteine-knot stability. As a result, the nano-textured topography of HAP-1:1 could maintain a relatively high biological activity of BMP-2 cargos. This work could provide theoretical guidelines for the design of BMP-2-based implants/scaffolds for bone tissue engineering.


The effect of panretinal photocoagulation on optic nerve cupping.
Panretinal photocoagulation (PRP) can produce damage to all layers of the retina, including the nerve fiber layer. The hypothesis that these changes in the nerve fiber layer may alter the contour of the optic disc and change the cup-to-disc (C/D) ratio was tested. In a masked retrospective study, the authors evaluated the stereoscopic disc photographs of 100 patients with proliferative diabetic retinopathy (PDR) before and 1 year after undergoing PRP. The fellow untreated eyes were used as controls. Neither argon nor xenon PRP produced a significant change in the C/D ratio.


Antifungal activity of Agapanthus africanus extractives.
The ethanolic extract of the rhizomes of Agapanthus africanus showed antifungal activity. In bioassay guided fractionation, n-butanol fraction exhibited significant activity against human pathogens. A saponin, (25R)-spirost-7-en-2alpha,3beta,5alpha-triol-3-O-[alpha-L-rhamnopyranosyl(1-->2)-[beta-D-galactopyranosyl (1-->3)] beta-D-glucopyranoside (1), responsible for the antifungal activity and having MIC value of 15.6 microg/ml against Trychophyton mentagrophytes and Sporothrix schenekii, was isolated and identified as active constituent of the plant.


Preliminary structure and predictive value of attenuated negative symptoms in 22q11.2 deletion syndrome.
Current research in schizophrenia suggests that negative symptoms cannot be considered a unitary construct and should be divided in two dimensions: lack of motivation and impoverishment of expression. In addition, negative symptoms are particularly related to decreased daily-life functioning. In the present study, we aimed to replicate these results in a sample of participants with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition associated with high risk of developing schizophrenia. We also expected to observe an association between the COMT Val/Met polymorphism and negative symptoms. We examined the factorial structure of negative symptoms in a sample of 47 individuals with 22q11DS using the Structured Interview for Prodromal Symptoms (SIPS) and the Positive and Negative Syndrome Scale (PANSS). We also performed stepwise regression analyses to investigate the associations between negative symptoms, adaptive skills and the COMT Val/Met polymorphism. Negative symptoms were explained by a two-factor solution, namely the "amotivation and social withdrawal" and the "emotional withdrawal and expression" dimensions. The motivational dimension was significantly associated with daily-life functioning. Met carriers were rated as experiencing significantly more symptoms of amotivation. The results are interpreted in the light of existing cognitive models in the field of motivation and schizophrenia.


Novel cytochromes P450 applications arising from the directed-evolution of recombinant micro-organisms.
Directed (forced) evolution of cytochromes P450 (overall 2700 CYP isoforms in non-recombinant biota) is a method that has been investigated in yeasts (and other micro-organisms) by aerobically growing brewers' yeast Saccharomyces cerevisiae in very high glucose (20%) media. Mitochondrial repression subverts cytochrome oxidase biosynthesis into manifest cytochromes P450 accumulation in brewers' yeast. A similar phenomenon is observed with the acridine-induced petit mutant. Cytochromes P450 EC 188.8.131.52 (and mimics) display a range of redox iron-mediated bioconversions in food processing, with mixed function oxidase (O2:mono-oxygenase) intervention results. Unfortunately these enzymes generate reactive oxygen species (ROS) through redox electron recycling, whilst isoform CYP 1A1 can activate precarcinogens such as benzo(a)pyrene to the ultimate (proximate) carcinogen that binds to nuclear DNA. In conclusion, another 5000 CYP isoforms, for example, might be identified in micro-organisms and many more made to order through recombinant DNA technology and utilized both in vitro and in vivo for aimed bioconversions in industry and in the environment, as part of the impact of greener-approach supporting strategies to minimize global pollution.


Low molecular weight heparin in children.
Low molecular weight heparins potentially have significant advantages over unfractionated heparin and oral anticoagulants for both the prevention and treatment of thromboembolic events in children. Compared to standard heparin, low molecular weight heparins have superior bioavailability, a longer half-life, and a dose-independent clearance, which results in a more predictable anticoagulant response. Low molecular weight heparins are administered subcutaneously and require minimal laboratory monitoring and dose adjustment, offering important benefits to children with poor venous access. In addition, complications including osteoporosis and heparin-induced thrombocytopenia are relatively rare with low molecular weight heparins compared to unfractionated heparin. based on the available data, low molecular weight heparins seem to be an efficient and safe alternative to standard anticoagulation therapy with unfractionated heparin and oral anticoagulants for both treatment and prevention of thromboembolic events in children of varying ages and underlying disorders.


Developmental changes in expression, subcellular distribution, and function of Drosophila N-cadherin, guided by a cell-intrinsic program during neuronal differentiation.
Cell adhesion molecules (CAMs) perform numerous functions during neural development. An individual CAM can play different roles during each stage of neuronal differentiation; however, little is known about how such functional switching is accomplished. Here we show that Drosophila N-cadherin (CadN) is required at multiple developmental stages within the same neuronal population and that its sub-cellular expression pattern changes between the different stages. During development of mushroom body neurons and motoneurons, CadN is expressed at high levels on growing axons, whereas expression becomes downregulated and restricted to synaptic sites in mature neurons. Phenotypic analysis of CadN mutants reveals that developing axons require CadN for axon guidance and fasciculation, whereas mature neurons for terminal growth and receptor clustering. Furthermore, we demonstrate that CadN downregulation can be achieved in cultured neurons without synaptic contact with other cells. Neuronal silencing experiments using Kir(2.1) indicate that neuronal excitability is also dispensable for CadN downregulation in vivo. Interestingly, downregulation of CadN can be prematurely induced by ectopic expression of a nonselective cation channel, dTRPA1, in developing neurons. Together, we suggest that switching of CadN expression during neuronal differentiation involves regulated cation influx within neurons.


Cardiovascular autonomic dysfunction in non-obese diabetic mice.
It is known that diabetes is associated with autonomic dysfunction; however, data about autonomic function in non-obese diabetic mice (NOD) remain scarce. We evaluated the autonomic profile of NOD mice. Female mice, 24-28 week old, were divided in two groups: NOD (n = 6) and control (n = 6, Swiss mice). NOD mice with glycemia ≥ 300 mg/dl were used. Heart rate variability (HRV) and arterial pressure variability (APV) in time and frequency domains, symbolic analysis of heart rate (HR) and baroreflex sensitivity were evaluated. HR and arterial pressure (AP) were similar between the groups; however, HRV (total variance of RR interval: NOD=21.07 ± 3.75 vs. C = 42.02 ± 6.54 ms(2)) and the vagal modulation index RMSSD were lower in NOD group (4.01 ± 0.32 vs. 8.28 ± 0.97 ms). Moreover, the absolute and normalized low-frequency (LF) components were also enhanced in NOD (normalized = 61.0 ± 4.0%) as compared to control mice (normalized = 20.0 ± 4.0%). Both the absolute and normalized high-frequency (HF) components were lower in NOD (normalized = 39.0 ± 4.0%) when compared to the control group (normalized = 80.0 ± 4.0). In the symbolic analysis the 0V pattern, an indication of sympathetic activity, was higher in NOD and 2 LV pattern, an indication of parasympathetic activity, was lower in the NOD than in the control group. Both bradycardic and tachycardic responses were decreased in NOD (3.01 ± 0.72 vs. 4.54 ± 0.36 bpm/mmHg and 2.49 ± 0.31 vs. C = 3.43 ± 0.33 bpm/mmHg) when compared to the control group. Correlation analysis showed negative correlations between vagal indexes (RMSSD, %HF and 2LV) and glycemic levels. In conclusion, NOD mice develop severe diabetes correlated with autonomic dysfunction.


Quality of life in adolescents and adults with CHARGE syndrome.
Health-related Quality of Life and the Impact of Childhood Neurologic Disability Scale were collected for 53 patients with CHARGE syndrome aged 13-39 years with a mean academic level of 4th grade. The most prevalent new and ongoing issues included bone health issues, sleep apnea, retinal detachment, anxiety, and aggression. Sleep issues were significantly correlated with anxiety, self-abuse, conduct problems, and autistic-like behaviors. Problems with overall health, behavior, and balance most affected the number of social activities in the individual's life. Sensory impairment most affected relationships with friends. Two contrasting case studies are presented and demonstrate that the quality of life exists on a broad spectrum in CHARGE syndrome, just as its physical features range from mild to very severe. A multitude of factors, including those beyond the physical manifestations, such as anxiety and sleep problems, influence quality of life and are important areas for intervention. © 2016 Wiley Periodicals, Inc.


Destination magnet: charting a course to excellence.
The Magnet Recognition Program for Excellence in Nursing Services, the Gold Star for Nursing, is a lofty but attainable goal. Oftentimes organizations are faced with the question, "Where do we start?" The answer more often than not includes involving staff development professionals. This article reviews the multiple phases of the Magnet journey as well as provides tips to facilitate a successful journey.


Conversion of the hydrochar recovered after levulinic acid production into activated carbon adsorbents.
Levulinic acid production by acid-catalyzed hydrothermal conversion of (ligno)cellulosic biomass generates significant amounts of carbonaceous hydrochar, which is currently considered a final waste. In this work, the hydrochar recovered after the levulinic acid production, was subjected to cascade pyrolysis and chemical activation treatments (by H3PO4 or KOH), to synthesize activated carbons. The pyrolysis post-treatment was already effective in improving the surface properties of the raw hydrochar (Specific Surface Area: 388 m2/g, VP: 0.22 cm3/g, VMESO: 0.07 cm3/g, VMICRO: 0.14 cm3/g), by removing volatile compounds. KOH activation resulted as the most appropriate for further improving the surface properties of the pyrolyzed hydrochar, showing the best surface properties (Specific Surface Area: 1421 m2/g, VP: 0.63 cm3/g, VMESO: 0.10 cm3/g, VMICRO: 0.52 cm3/g), which synergistically makes it a promising system towards adsorption of CO2 (∼90 mg/g) and methylene blue (∼248 mg/g). In addition, promising surface properties can be achieved after direct chemical activation of the raw hazelnut shells, preferably by H3PO4 (Specific Surface Area: 1918 m2/g, VP: 1.34 cm3/g, VMESO: 0.82 cm3/g, VMICRO: 0.50 cm3/g), but this choice is not the smartest, as it does not allow the valorization of the cellulose fraction to levulinic acid. Our approach paves the way for possible uses of these hydrochars originating from the levulinic acid chain for new environmental applications, thus smartly closing the biorefinery loop of the hazelnut shells.


Activation of neutrophil NADPH oxidase in a cell-free system. Partial purification of components and characterization of the activation process.
The superoxide-generating enzyme of human neutrophils, NADPH oxidase, is converted from an inactive to an active form upon stimulation of the neutrophil. This activation process was examined using a recently developed cell-free system in which dormant oxidase is activated by arachidonic acid in the presence of a soluble factor from the neutrophil (Curnutte, J. T. (1985) J. Clin. Invest. 75, 1740-1743). NADPH oxidase from unstimulated human neutrophils was detected only in the membrane fraction. The soluble activation factor was localized entirely to the cytosolic fraction and exhibited two peaks of activity when partially purified under nondenaturing conditions: a major peak with a molecular mass of approximately 250 kDa and a variable minor peak with a mass of approximately 40 kDa. Both forms activated NADPH oxidase in a similar manner and did not exhibit synergy when combined. The cytosolic factor is not protein kinase C (or another kinase) as both peaks of factor activity could be resolved from the protein kinase C peak and neither required calcium or ATP to activate the oxidase. Activation of NADPH oxidase did require the simultaneous presence of the membrane fraction, the cytosolic factor, arachidonic acid, and magnesium. Following activation, however, only the membrane fraction was then required for O2- production. Cytosolic factor levels were normal in five patients with either X-linked or autosomal recessive cytochrome b-negative chronic granulomatous disease. In contrast, the membrane fractions from each failed to generate O2-, indicating that the defects in these two genetic forms of chronic granulomatous disease reside either in the oxidase itself or in a membrane component required for activation.


Probability state modeling of memory CD8⁺ T-cell differentiation.
Flow cytometric analysis enables the simultaneous single-cell interrogation of multiple biomarkers for phenotypic and functional identification of heterogeneous populations. Analysis of polychromatic data has become increasingly complex with more measured parameters. Furthermore, manual gating of multiple populations using standard analysis techniques can lead to errors in data interpretation and difficulties in the standardization of analyses. To characterize high-dimensional cytometric data, we demonstrate the use of probability state modeling (PSM) to visualize the differentiation of effector/memory CD8⁺ T cells. With this model, four major CD8⁺ T-cell subsets can be easily identified using the combination of three markers, CD45RA, CCR7 (CD197), and CD28, with the selection markers CD3, CD4, CD8, and side scatter (SSC). PSM enables the translation of complex multicolor flow cytometric data to pathway-specific cell subtypes, the capability of developing averaged models of healthy donor populations, and the analysis of phenotypic heterogeneity. In this report, we also illustrate the heterogeneity in memory T-cell subpopulations as branched differentiation markers that include CD127, CD62L, CD27, and CD57.


Correlates of mothers' persistent depressive symptoms: a national study.
The purpose of this study was to examine the prevalence, persistence, and correlates of mothers' depressive symptoms over a 5-year period in a nationally representative sample of the United States population. Data from 2235 mothers in the National Survey of Families and Households, Wave I, 1987-1988, and Wave II, 1992-1994, were analyzed. Outcome measures were scores on the Center for Epidemiological Studies Depression Scale (CES-D, 12-item version) and a validated three-item depression screen. One fifth of study mothers had positive CES-D scores and almost half (48%) had negative CES-D scores in both waves. Wave I risk factors for persistent "positive" CES-D scores were maternal age less than 30 years (24%), African-American (33%), never married (26%) or divorced (32%), education less than high school (35%), and indigent (32%). Adjusted odds ratios (AOR) and 95% confidence intervals for persistent "positive" versus persistent "negative" CES-D scores were: age less than 30 years (Wave I), AOR = 1.64, (1.22-2.21); unmarried (Wave II), AOR = 2.60, (1.89-3.56); education less than high school (Wave II), AOR = 2.18, (1.41-3.38); and indigent (Wave II), AOR = 2.09 (1.36-3.21). About one fifth of the study sample reported high depressive symptoms twice over a 5-year period. Depression in women, especially mothers, is an urgent public health problem.


Heavy marijuana users show increased serum apolipoprotein C-III levels: evidence from proteomic analyses.
Marijuana (MJ) is the most commonly used illicit drug in the United States. Its abuse is associated with cognitive dysfunctions and increased resistance to blood flow in the cerebral vasculature. In addition, MJ abuse is associated with increased risks of potentially serious cardiovascular disorders. In the present study, we used the protein chip platform based on surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS) to test the possibility that MJ abuse might be associated with changes in serum protein levels. Indeed, MJ users showed significant increases in three protein peaks, which were identified as three isoforms of apolipoprotein (apo) C-III. Immunoprecipitation using an apoC-III antibody also validated the identification of the proteins. Marijuana-induced increases in apoC-III levels might occur through chronic stimulation of hepatic cannabinoid receptors (CB1 and/or CB2) by its active ingredient, Delta(9)tetrahydrocannibol (THC). Thus, chronic MJ abuse might cause increased transcription and/or translation of apoC-III in the liver with corresponding changes reflected in the plasma of these patients. In any case, because apoC-III is a cardiovascular risk factor, the increased levels observed in MJ users might explain, in part, the cardiac and cerebral abnormalities reported in these patients.


Efficacy and safety profile of neuroendoscopic hematoma evacuation combined with intraventricular lavage in severe intraventricular hemorrhage patients.
The present study was conducted to explore the effect of neuroendoscopic hematoma evacuation in severe intraventricular hemorrhage (IVH). Totally 81 patients with severe IVH in our hospital from November 2017 to March 2019 were divided into the intervention group (38 cases who received neuroendoscopic hematoma evacuation combined with intraventricular lavage) and the control group (40 cases who received trepanation drainage). The perioperative condition, hematoma clearance rate, Glasgow coma score (GCS), hematoma recurrence rate, and prognosis were observed and compared between the two groups after treatment. The operative time, time of cerebrospinal fluid drainage, and intracranial infection rate in the intervention group elicited superior results to those in the control group (p < .05). The clearance rate of hematoma in the intervention group was higher than that in the control group at 6 hr, 1, 3, and 7 days postoperatively (p < .05). The postoperative 3- and 7-day GCS scores in the intervention group were higher than those in the control group, and the recurrence rate of hematoma in the intervention group was significantly lower than that in the control group (p < .05), and the good/excellent rate of ADL in the intervention group was significantly higher than that in the control group (p < .05). Neuroendoscopic hematoma evacuation combined with intraventricular lavage showed evident beneficial outcomes in patients with severe IVH. It can effectively improve the perioperative condition and improve the hematoma clearance rate and is beneficial to the prognosis of patients with severe IVH.


Impacts on influenza A(H1N1)pdm09 infection from cross-protection of seasonal trivalent influenza vaccines and A(H1N1)pdm09 vaccines: systematic review and meta-analyses.
Cross-protection by seasonal trivalent influenza vaccines (TIVs) against pandemic influenza A H1N1 2009 (now known as A[H1N1]pdm09) infection is controversial; and the vaccine effectiveness (VE) of A(H1N1)pdm09 vaccines has important health-policy implications. Systematic reviews and meta-analyses are needed to assess the impacts of both seasonal TIVs and A(H1N1)pdm09 vaccines against A(H1N1)pdm09.We did a systematic literature search to identify observational and/or interventional studies reporting cross-protection of TIV and A(H1N1)pdm09 VE from when the pandemic started (2009) until July 2011. The studies fulfilling inclusion criteria were meta-analysed. For cross-protection and VE, respectively, we stratified by vaccine type, study design and endpoint. Seventeen studies (104,781 subjects) and 10 studies (2,906,860 subjects), respectively, reported cross-protection of seasonal TIV and VE of A(H1N1)pdm09 vaccines; six studies (17,229 subjects) reported on both. Thirteen studies (95,903 subjects) of cross-protection, eight studies (859,461 subjects) of VE, and five studies (9,643 subjects) of both were meta-analysed and revealed: (1) cross-protection for confirmed illness was 19% (95% confident interval=13-42%) based on 13 case-control studies with notable heterogeneity. A higher cross-protection of 34% (9-52%) was found in sensitivity analysis (excluding five studies with moderate/high risk of bias). Further exclusion of studies that recruited early in the pandemic (when non-recipients of TIV were more likely to have had non-pandemic influenza infection that may have been cross-protective) dramatically reduced heterogeneity. One RCT reported cross-protection of 38% (19-53%) for confirmed illness. One case-control study reported cross-protection of 50% (40-59%) against hospitalisation. (2) VE of A(H1N1)pdm09 for confirmed illness was 86% (73-93%) based on 11 case-control studies and 79% (22-94%) based on two cohort studies; VE against medically-attended ILI was 32% (8-50%) in one cohort study. TIVs provided moderate cross-protection against both laboratory-confirmed A(H1N1)pdm09 illness (based on eight case-control studies with low risk of bias and one RCT) and also hospitalisation. A finding of increased risk from seasonal vaccine was limited to cases recruited early in the pandemic. A(H1N1)pdm09 vaccines were highly effective against confirmed A(H1N1)pdm09 illness. Although cross-protection was less than the direct effect of strain-specific vaccination against A(H1N1)pdm09, TIV was generally beneficial before A(H1N1)pdm09 vaccine was available.


Comparative assessment of growth and biodegradation potential of soil isolate in the presence of pesticides.
In Pakistan, to increase agricultural production, higher amounts of fertilizers and pesticides are being used. The residues of the applied pesticides stay in the environment and therefore causing contamination of air, water and land. Moreover, agricultural industries are also contributing relatively high quantities of toxic pesticides into the environment. Since most of them have no treatment facilities. These pesticides may be toxic, mutagenic or carcinogenic. They may be bioaccumulated or biomagnified by the biota. Therefore its removal from environmental systems needs special attention. In this study, bacterial isolate, Pseudomonas, designated as IES-Ps-1, was used to assess its potential for pesticide removal from industrial wastewater using the biosimulator (activated sludge process). During experimental studies conducted in the flask as well as in biosimulator, it was observed that IES-Ps-1 grows normally at low concentrations of added insecticides when compared with the control test (without pesticide). However, at high concentrations the microbial count decreased but no death occurred and the culture remained in lag phase. In many cases, the growth of organisms in the presence of the particular substrate serves as an indication about its metabolic potential. However, to confirm these results, chemical oxygen demand (COD) and HPLC analysis were performed. Under aerobic culture conditions using mechanical aerators in biosimulator, almost complete removal of Cypermethrin at 20 mg/L dose occurred during 48 h. The study findings indicate that IES-Ps-1 strain, can be used for the treatment of the pesticide contaminated environment. Such study may be valuable to scientist and engineers, who are trying to develop methods for the treatment of toxic organic waste using the biological treatment process.


Small-Dosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1 and ABCG2), and Interaction (Atorvastatin and Grapefruit Juice) Profiles of 5 Probes for OATP2B1 and BCRP.
The aims of this study were (1) to investigate the effects of atorvastatin (10 mg, therapeutic dose) and grapefruit juice (GFJ), inhibitors of OATP2B1, on the pharmacokinetics of substrates for OATP2B1 and BCRP under oral small-dosing conditions (300 μg sulfasalazine, 250 μg rosuvastatin, 300 μg glibenclamide, 1200 μg celiprolol, and 600 μg sumatriptan), and (2) to evaluate the contribution of SLCO2B1*3 and ABCG2 c.421C>A polymorphisms to the pharmacokinetics of the 5 test drugs in 23 healthy volunteers. In the 3 phases, the test drugs were administered to volunteers with either water (control phase), atorvastatin, or GFJ. GFJ but not atorvastatin reduced the exposure of the test drugs significantly more than the control phase, suggesting that all 5 test drugs are substrates for OATP2B1. The SLCO2B1*3 genotype had no effect on the pharmacokinetics of the test drugs. In contrast, the exposure of sulfasalazine and rosuvastatin was significantly higher in ABCG2 421C/A than in ABCG2 421C/C individuals at all 3 phases, even under small-dosing conditions.


Impact of Psoriasis on Mortality Rate and Outcome in Myocardial Infarction.
Background Psoriasis is a frequent chronic inflammatory cytokine-mediated skin disease and was identified to be an independent risk factor for the occurrence of myocardial infarction (MI). However, data about the impact of psoriasis on mortality and other in-hospital adverse events in the setting of MI are sparse and inconsistent. Methods and Results The nationwide German inpatient sample of the years 2005 to 2016 was used for statistical analysis. Hospitalized patients with MI were stratified for the presence of psoriasis and the impact of psoriasis on in-hospital events was investigated. Overall, 3 307 703 patients with MI (37.6% females, 56.8% aged ≥70 years) were treated in Germany (2005-2016); among them 9028 (0.3%) were diagnosed with psoriasis. Patients with MI with psoriasis were significantly younger (68.0 [58.0-76.0] versus 73.0 [62.0-81.0] years; P<0.001) and showed significant lower in-hospital case-fatality rate (7.1% versus 12.4%; P<0.001), confirmed in the regression (odds ratio, 0.68; 95% CI, 0.63-0.74; P<0.001) adjusted for age, sex, and comorbidities. They more frequently revealed cardiovascular risk factors such as arterial hypertension (58.9% versus 55.0%; P<0.001), hyperlipidemia (44.4% versus 38.6%; P<0.001), smoking (14.3% versus 7.4%; P<0.001), diabetes mellitus (34.8% versus 30.4%; P<0.001) or obesity (17.9% versus 9.3%; P<0.001). While the rate of percutaneous coronary intervention (41.4 versus 42.0%; P=0.223) was comparable between both groups, coronary bypass surgery was more often performed in patients with MI with psoriasis (7.7% versus 4.7%; P<0.001). Conclusions Overall, only 0.3% of all MI cases were diagnosed with psoriasis, and patients with MI with psoriasis were in median 5 years younger than patients with MI without psoriasis. Psoriasis seems to enhance the prevalence of classical cardiovascular risk factors and might therefore explain the earlier time point for MI. Our data also showed in turn a lower in-hospital mortality rate in patients with MI with psoriasis, presumably driven by younger age.


Update on reslizumab for eosinophilic asthma.
Patients with severe eosinophilic asthma have an unmet need for novel and efficacious treatments. Reslizumab is one of the three monoclonal antibodies targeting the IL-5 pathway and has been found in Phase IIIb clinical trials to reduce asthma exacerbations, control asthma-related symptoms and improve pulmonary function in patients with eosinophilic asthma. In this article, we discuss the results of asthma clinical trials using reslizumab, beginning with a discussion of the relationship between eosinophils, IL-5 and asthma. We conducted PubMed searches using the terms 'reslizumab', 'anti-IL-5', 'eosinophilic asthma', 'IL-5 asthma'. We also searched ClinicalTrials.gov for 'reslizumab', 'reslizumab asthma', 'SCH 55700', 'SCH 55700 asthma', 'Cinquil' and 'Cinquil asthma'. Reslizumab and other anti-IL-5 therapies have seen success in recent trials through more stringent study participant selection targeting eosinophilic inflammation. This selection can now be based on simple blood counts. These drugs have shown a very good safety profile, but long-term safety data are not yet available. Approval for these drugs is eagerly awaited by clinicians and patients alike.


Leucopterin, the white pigment in butterfly wings: structural analysis by PDF fit, FIDEL fit, Rietveld refinement, solid-state NMR and DFT-D.
Leucopterin (C6H5N5O3) is the white pigment in the wings of Pieris brassicae butterflies, and other butterflies; it can also be found in wasps and other insects. Its crystal structure and its tautomeric form in the solid state were hitherto unknown. Leucopterin turned out to be a variable hydrate, with 0.5 to about 0.1 molecules of water per leucopterin molecule. Under ambient conditions, the preferred state is the hemihydrate. Initially, all attempts to grow single crystals suitable for X-ray diffraction were to no avail. Attempts to determine the crystal structure by powder diffraction using the direct-space method failed, because the trials did not include the correct, but rare, space group P2/c. Attempts were made to solve the crystal structure by a global fit to the pair distribution function (PDF-Global-Fit), as described by Prill and co-workers [Schlesinger et al. (2021). J. Appl. Cryst. 54, 776-786]. The approach worked well, but the correct structure was not found, because again the correct space group was not included. Finally, tiny single crystals of the hemihydrate could be obtained, which allowed at least the determination of the crystal symmetry and the positions of the C, N and O atoms. The tautomeric state of the hemihydrate was assessed by multinuclear solid-state NMR spectroscopy. 15N CPMAS spectra showed the presence of one NH2 and three NH groups, and one unprotonated N atom, which agreed with the 1H MAS and 13C CPMAS spectra. Independently, the tautomeric state was investigated by lattice-energy minimizations with dispersion-corrected density functional theory (DFT-D) on 17 different possible tautomers, which also included the prediction of the corresponding 1H, 13C and 15N chemical shifts in the solid. All methods showed the presence of the 2-amino-3,5,8-H tautomer. The DFT-D calculations also confirmed the crystal structure. Heating of the hemihydrate results in a slow release of water between 130 and 250 °C, as shown by differential thermal analysis and thermogravimetry (DTA-TG). Temperature-dependent powder X-ray diffraction (PXRD) showed an irreversible continuous shift of the reflections upon heating, which reveals that leucopterin is a variable hydrate. This observation was also confirmed by PXRD of samples obtained under various synthetic and drying conditions. The crystal structure of a sample with about 0.2 molecules of water per leucopterin was solved by a fit with deviating lattice parameters (FIDEL), as described by Habermehl et al. [Acta Cryst. (2022), B78, 195-213]. A local fit, starting from the structure of the hemihydrate, as well as a global fit, starting from random structures, were performed, followed by Rietveld refinements. Despite dehydration, the space group remains P2/c. In both structures (hemihydrate and variable hydrate), the leucopterin molecules are connected by 2-4 hydrogen bonds into chains, which are connected by further hydrogen bonds to neighbouring chains. The molecular packing is very efficient. The density of leucopterin hemihydrate is as high as 1.909 kg dm-3, which is one of the highest densities for organic compounds consisting of C, H, N and O only. The high density might explain the good light-scattering and opacity properties of the wings of Pieris brassicae and other butterflies.


Author Correction: Identification of a Novel Feruloyl Esterase by Functional Screening of a Soil Metagenomic Library.
The original version of this article unfortunately contained a mistake in the image and caption of Fig. 6. The corrected version of the image and caption is shown here.


Using Animation to Self-Report Health: A Randomized Experiment with Children.
The Child Health Utility-9D (CHU-9D) is the only generic preference-based measure specifically developed to elicit health-related quality of life directly from children aged 7-11 years. The aim of this study was to investigate whether the use of animation on a touch screen device (tablet) is a better way of collecting health status information from children aged 4-14 years compared to a traditional paper questionnaire. The specific research questions were firstly, do young children (4-7 years) find an animated questionnaire easier to understand; secondly, independent of age, is completion of an animated questionnaire easier for sick children in hospital settings; and thirdly, do children's preferences for the different formats of the questionnaire vary by the age of the child. Using a balanced cross-over trial, we administered different formats of the CHU-9D to 221 healthy children in a school setting and 217 children with health problems in a hospital setting. The study tested five versions of the CHU-9D questionnaire: paper text, tablet text, tablet still image, paper image and tablet animation. Our results indicated that the majority of the children aged 4-7 years found the CHU-9D questions easy to answer independent of the format of the questionnaire administered. Amongst children aged 7-14 with health problems, the format of questionnaire influenced understanding. Children aged 7-11 years found the tablet image and animation formats easier compared to text questionnaires, while the oldest children in hospital found text-based questionnaires easier compared to image and animation. Children in all three age groups preferred animation on a tablet to other methods of assessment. Our results highlight the potential for using an animated preference-based measure to assess the health of children as young as 4 years.


Acute effects of an endothelin-1 receptor antagonist bosentan at different stages of heart failure in conscious dogs.
Inhibition by endothelin antagonist is a potential therapy in heart failure. However, the effect of endothelin inhibition during the development of heart failure has not been evaluated. The goal of our study was to examine the acute hemodynamic effects of the mixed endothelin receptor antagonist bosentan in the control state and at different stages of heart failure induced by right ventricular pacing (250 bpm) in conscious dogs. Nine dogs were chronically instrumented for the measurements of left ventricular pressure and its first derivative (dP/dt), cardiac output, left ventricular regional wall thickness and aortic pressure. Bosentan (3 mg/kg, i.v. bolus) and placebo were given at control, at 1 week of pacing (stage of left ventricular dysfunction with perserved cardiac output) and at 3 weeks of pacing (phase of heart failure with low cardiac output). With the development of heart failure, baseline plasma endothelin level increased progressively. Placebo did not induce hemodynamic and plasma endothelin changes during the 30 min recording at any stage. At control, bosentan did not change hemodynamics. At 1 and 3 weeks of pacing, bosentan did not modify left ventricular myocardial function indices but reduced mean arterial pressure (by 7 +/- 2 and 8 +/- 1 mm Hg respectively, p < 0.005). Bosentan increased stroke volume at 3 weeks of pacing only. Endothelin inhibition by endothelin antagonist bosentan, decreases aortic pressure in both early left ventricular dysfunction and in heart failure in contrast with the control state. In the phase of heart failure with low cardiac output, bosentan increases stroke volume. In the early left ventricular dysfunction, bosentan, by reducing arterial pressure, may limit the deterioration of cardiac function through a reduction of the workload imposed on the heart.


Universal Fermi liquid crossover and quantum criticality in a mesoscopic system.
Quantum critical systems derive their finite-temperature properties from the influence of a zero-temperature quantum phase transition. The paradigm is essential for understanding unconventional high-Tc superconductors and the non-Fermi liquid properties of heavy fermion compounds. However, the microscopic origins of quantum phase transitions in complex materials are often debated. Here we demonstrate experimentally, with support from numerical renormalization group calculations, a universal crossover from quantum critical non-Fermi liquid behaviour to distinct Fermi liquid ground states in a highly controllable quantum dot device. Our device realizes the non-Fermi liquid two-channel Kondo state, based on a spin-1/2 impurity exchange-coupled equally to two independent electronic reservoirs. On detuning the exchange couplings we observe the Fermi liquid scale T*, at energies below which the spin is screened conventionally by the more strongly coupled channel. We extract a quadratic dependence of T* on gate voltage close to criticality, and validate an asymptotically exact description of the universal crossover between strongly correlated non-Fermi liquid and Fermi liquid states.


The molecular genealogy of sequential overlapping inversions implies both homologous chromosomes of a heterokaryotype in an inversion origin.
Cytological and molecular studies have revealed that inversion chromosomal polymorphism is widespread across taxa and that inversions are among the most common structural changes fixed between species. Two major mechanisms have been proposed for the origin of inversions considering that breaks occur at either repetitive or non-homologous sequences. While inversions originating through the first mechanism might have a multiple origin, those originating through the latter mechanism would have a unique origin. Variation at regions flanking inversion breakpoints can be informative on the origin and history of inversions given the reduced recombination in heterokaryotypes. Here, we have analyzed nucleotide variation at a fragment flanking the most centromere-proximal shared breakpoint of several sequential overlapping inversions of the E chromosome of Drosophila subobscura -inversions E1, E2, E9 and E3. The molecular genealogy inferred from variation at this shared fragment does not exhibit the branching pattern expected according to the sequential origin of inversions. The detected discordance between the molecular and cytological genealogies has led us to consider a novel possibility for the origin of an inversion, and more specifically that one of these inversions originated on a heterokaryotype for chromosomal arrangements. Based on this premise, we propose three new models for inversions origin.


Nano-TiO2 aggravates the adverse effect of pentachlorophenol on antioxidant and immune response in anti-predatory mussels.
Nano-TiO2 can act as a vector to organic compounds, such as pentachlorophenol (PCP) posing a potential threat to the marine ecosystems. Studies showed that nano pollutant toxicity can be modulated by abiotic factors, but little is known about the potential influence of biotic stressors (such as predators) on the physiological responses to pollutants in marine organisms. We explored the effects of n-TiO2 and PCP on the mussel Mytilus coruscus in the presence of its natural predator, the swimming crab Portunus trituberculatus. Exposure to n-TiO2, PCP, and predation risk showed interactive effects on antioxidant and immune parameters of the mussels. Elevated activities of catalase (CAT), glutathione peroxidase (GPX), acid phosphatase (ACP) and alkaline phosphatase (AKP), suppressed activity of superoxide dismutase (SOD), lower levels of glutathione (GSH) and increased malondialdehyde (MDA) levels indicated dysregulation of the antioxidant system and immune stress induced by single PCP or n-TiO2 exposure. Integrated biomarker (IBR) response values showed the effect of PCP was concentration dependent. Of the two used n-TiO2 sizes (25 and 100 nm), larger particles induced higher antioxidant and immune disturbances indicating higher toxicity possibly due to higher bioavailability. Compared to single PCP exposure, the combination of n-TiO2 and PCP enhanced the imbalance of SOD/CAT and GSH/GPX and led to elevated oxidative lesions and activation of immune-related enzymes. Overall, the combined impacts of pollutants and biotic stress exhibited a greater magnitude of adverse effects on antioxidant defense and immune parameters in mussels. The toxicological effects of PCP were exacerbated in the presence of n-TiO2, and the deleterious impact of these stressors was further amplified under predator-induced risk after prolonged (28 days) exposure. However, the underlying physiological regulatory mechanisms governing the interplay of these stressors and predatory cues on mussels remain elusive, warranting further investigation.


Skull changes with intrasellar cisternal herniation (empty sella).
Forty-seven cases with intrasellar cisternal herniation (empty sella) examined by plain X-ray of the skull and pneumoencephalography have been reviewed. Although the diagnosis may frequently be anticipated from the plain X-ray findings, further studies are necessary to establish the diagnosis. Also the type of herniation, whether horizontal, anterior or complete, may be anticipated from the appearance of the sella. Signs attributable to increased intracranial pressure, mainly erosion of the dorsum sellae, were found in about half of the cases.


On the reaction-diffusion type modelling of the self-propelled object motion.
In this study, we propose a mathematical model of self-propelled objects based on the Allen-Cahn type phase-field equation. We combine it with the equation for the concentration of surfactant used in previous studies to construct a model that can handle self-propelled object motion with shape change. A distinctive feature of our mathematical model is that it can represent both deformable self-propelled objects, such as droplets, and solid objects, such as camphor disks, by controlling a single parameter. Furthermore, we demonstrate that, by taking the singular limit, this phase-field based model can be reduced to a free boundary model, which is equivalent to the [Formula: see text]-gradient flow model of self-propelled objects derived by the variational principle from the interfacial energy, which gives a physical interpretation to the phase-field model.


Blood lead levels in schoolchildren living near an industrial zone in Cali, Colombia: the role of socioeconomic condition.
This study aimed to determine Blood Lead Levels (BLL) in schoolchildren 6-14 years old exposed to industrial sources of lead and evaluated the role of socioeconomic condition. A cross-sectional study was conducted in an area likely to be exposed to industrial pollutants in northern Cali (i.e., distance and wind direction) and in a "non-exposed" area. In children in two schools of corresponding study areas, venous samples (5 ml) were collected to determine BLL by graphite furnace absorption spectrometry. Using regression models, we evaluated the association between risk factors to BLL and the effect of modification with variables of socioeconomic condition. We enrolled 350 schoolchildren. Schoolchildren in the exposed area had higher prevalence of BLL of ≥ 5 μg/dl (44.2 vs. 8.2 %, p = 0.000) than those in non-exposed area. A positive association was found between exposure and BLL of ≥ 5 μg/dl (prevalence ratios (PR), 6.68; 95 % confidence interval (95 % CI), 3.95, 11.29). Demographic characteristics and socioeconomic condition such as age (PR, 1.45; 95 % CI, 1.03, 2.04), sex (PR, 1.84; 95 % CI, 1.30, 2.60), race (PR, 2.32; 95 % CI, 1.39, 3.89) and socioeconomic position (SEP; PR, 2.02; 95 % CI, 1.35, 3.04) were statistically significant and independently associated with BLL. There was a synergistic interaction between exposure to the industrial zone and SEP for higher BLL (coefficient, 0.80; 95 % CI, 0.17, 1.43). Residence in the northern urban area of Cali exposed to pollutants of an industrial zone is associated to an increased risk of higher BLL, especially among children from low SEC who are at greater risk of exposure and susceptibility.


Prevention of opportunistic infections in adult and adolescent patients with HIV infection. GESIDA/National AIDS Plan guidelines, 2004 [correction].
To provide an update of guidelines from the Spanish AIDS Study Group (GESIDA) and the National AIDS Plan (PNS) committee on the prevention of opportunistic infections in adult and adolescent HIV-infected patients. These consensus recommendations have been produced by a group of experts from GESIDA and/or the PNS after reviewing the earlier document and the scientific advances in this field in the last years. The system used by the Infectious Diseases Society of America and the United States Public Health Service has been used to classify the strength and quality of the data. This document provides a detailed review of the measures for the prevention of infections caused by viruses, bacteria, fungi and parasites in the context of HIV infection. Recommendations are given for preventing exposure and for primary and secondary prophylaxis for each group of pathogens. In addition, criteria are established for the withdrawal of prophylaxis in patients who respond well to highly active antiretroviral therapy (HAART). HAART is the best strategy for the prevention of opportunistic infections in HIV-positive patients. Nevertheless, prophylaxis is still necessary in countries with limited economic resources, in highly immunodepressed patients until HAART achieves beneficial effects, in patients who refuse to take or who cannot take HAART, in those in whom HAART is not effective, and in the small group of infected patients with inadequate recovery of CD4+ T lymphocyte counts despite good inhibition of HIV replication.


Accuracy of botulinum toxin type A injection into the gastrocnemius muscle of adults with spastic equinus: manual needle placement and electrical stimulation guidance compared using ultrasonography.
To investigate the accuracy of manual needle placement and electrical stimulation guidance, compared using ultrasonography, for injection of botulinum toxin type A into the gastrocnemius muscle of adults with spastic equinus. Prospective clinical study. A total of 81 adults with stroke who were scheduled to receive botulinum toxin type A injection into the gastrocnemius muscle. After randomization into two groups, each patient was injected into two sites at each head of the gastrocnemius muscle. The manual needle placement group (n = 42) underwent injections using anatomical landmarks and palpation. The electrical stimulation guidance group (n = 39) underwent injections under electrical stimulation guidance. The accuracy of needle placement and muscle thickness at each injection site were compared by means of ultrasonography. The overall accuracy of manual needle placement and electrical stimulation guidance, measured using ultrasonography, was significantly higher for the gastrocnemius medialis than for the lateralis (92.0% vs 79.0%). The gastrocnemius medialis was significantly thicker than the lateralis (mean 13.25 mm (standard deviation (SD) 1.86 mm) vs 10.84 mm (SD 1.52 mm). Electrical stimulation guidance may be useful for injections into the gastrocnemius lateralis of adults with spastic equinus. However, neither manual needle placement nor electrical stimulation guidance showed complete accuracy, when measured using ultrasonography.


Partition Coefficients and Diffusion Lengths of 222Rn in Some Polymers at Different Temperatures.
In this work, the partition coefficients K and diffusion lengths L D of radon in some polymers are experimentally determined for several temperatures in the range T = 5-31 °C. Some of the obtained values are compared to published data available for the given temperatures. It is shown that the temperature dependencies of the partition coefficients K ( T ) , the diffusion lengths L D ( T ) , and the permeabilities P ( T ) could be described analytically for the studied temperature range 5-31 °C. This allows estimation of these quantities in the given temperature range and quantitative description of the transport of radon in the studied polymers.


Adolescent units-an evidence-based approach to quality nursing in adolescent care.
Adolescence is a complex and critical period in psychosocial development. The interruptive process of hospitalisation may adversely affect the developmental period of adolescence and impact on psychological well being. As a result of increased attention to adolescents with cancer, the psychosocial management of this client group has become an integral component of cancer care. The unique needs of adolescents and the need to provide dedicated hospital facilities have been documented over the past four decades. However, despite the availability of policies and guidelines that stress the need for specific Adolescent Units, the vast majority of adolescents continue to be nursed inappropriately in adult or paediatric environments. Twenty-seven research articles are reviewed and the psychosocial factors that affect the quality of the hospital experience of the adolescent with cancer are identified. Relevant literature is reviewed and critiqued in order to provide an evidence-based approach to quality nursing in adolescent care.


Characterization of estrogen-induced progestin binding in cytosol of the R3327 prostatic carcinoma of the rat.
High affinity binding of the synthetic steroids methyltrienolone (R1881) and promegestone (R5020) to cytosol protein from the Dunning (R3327) experimental prostatic carcinoma of the rat was investigated. Animals bearing tumours of approx 1.5 cm mean diameter were either left untreated, or were administered diethylstilbestrol diphosphate (DESP) in the drinking water in doses close to those used clinically for the treatment of human prostatic carcinoma. Tumours were excised after 10-40 days, and binding of [3H]R1881 and [3H]R5020 to tumour cytosol was characterized using Scatchard analysis, sucrose density gradient centrifugation, and steroid competition, under conditions optimal for the conservation and assay of progesterone receptor. Both ligands were bound in much higher concentrations by cytosol from DESP-treated tumours than from untreated tumours. Binding was of high affinity (Kd congruent to 1 nM), was specific for progestins, and sedimented in peaks at approximately 8S and approximately 4S in sucrose density gradients. We conclude the DESP treatment of rats bearing the R3327 prostatic carcinoma induces synthesis of progesterone receptor in this tumour.


Priming of cytotoxic T lymphocytes at various stages of ontogeny with transfectoma cells expressing a chimeric Ig heavy chain gene bearing an influenza virus nucleoprotein peptide.
The amino acid residues 147-161 of the nucleoprotein (NP) of influenza virus represent a T cell epitope recognized by cytotoxic T cells (CTLs) in association with Kd class I molecules. When SP2/0 myeloma B cells are transfected with a chimeric heavy chain gene bearing this particular NP(147-161) peptide, they are lysed by CTLs specific for the NP(147-161) peptide. Cells that are transfected with this heavy chain chimera and the parental light chain secreted a soluble Ig-NP chimera and were also lysed by the CTLs. Herein, we present evidence that transfectoma cells are able to induce in vitro proliferation of NP specific CTL, whereas immobilized Ig-NP chimeras do not. Furthermore, the transfectoma cells expressing the chimeric heavy chain prime NP specific CTLs in adult as well as in newborn mice, while SP2/0 cells coated with NP(147-161) synthetic peptide do not. These data indicate that the NP peptide needs to be cleaved from the Ig context in order to be presented to T cells and that only endogenously generated NP peptide is immunogenic.


Cholesterol induces proliferation of chicken primordial germ cells.
Primordial germ cells (PGCs) are the precursors of sperm and eggs and may serve as suitable cells for use in research in developmental biology and transgenic animals. However, the long-term propagation of PGCs in vitro has so far been plagued by the loss of their germ cell characteristics. This is largely because of the scarcity of knowledge concerning cell division and proliferation in these cells and the poor optimization of the culture medium. The sonic hedgehog (SHH) signaling pathway is involved in proliferation of many types of cells, but little is known about its role in chicken PGCs. The results of the current study indicate that the proliferation of chicken PGCs increases significantly when cholesterol, a molecule that facilitates the trafficking of HH ligands, is supplemented in the culture medium. This effect was attenuated when an SHH antagonist, cyclopamine was added, suggesting the involvement of SHH signaling in this process. The characterization of PGCs treated with cholesterol has shown that these cells express germ-cell-related markers and retain their capability to colonize the embryonic gonad after re-introduction to vasculature of stage-15 HH embryos, indicating that proliferation of PGCs induced by cholesterol does not alter the germ cell characteristics of these cells.


Catalytic mechanism and allosteric regulation of an oligomeric (p)ppGpp synthetase by an alarmone.
Nucleotide-based second messengers serve in the response of living organisms to environmental changes. In bacteria and plant chloroplasts, guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) [collectively named "(p)ppGpp"] act as alarmones that globally reprogram cellular physiology during various stress conditions. Enzymes of the RelA/SpoT homology (RSH) family synthesize (p)ppGpp by transferring pyrophosphate from ATP to GDP or GTP. Little is known about the catalytic mechanism and regulation of alarmone synthesis. It also is unclear whether ppGpp and pppGpp execute different functions. Here, we unravel the mechanism and allosteric regulation of the highly cooperative alarmone synthetase small alarmone synthetase 1 (SAS1) from Bacillus subtilis. We determine that the catalytic pathway of (p)ppGpp synthesis involves a sequentially ordered substrate binding, activation of ATP in a strained conformation, and transfer of pyrophosphate through a nucleophilic substitution (SN2) reaction. We show that pppGpp-but not ppGpp-positively regulates SAS1 at an allosteric site. Although the physiological significance remains to be elucidated, we establish the structural and mechanistic basis for a biological activity in which ppGpp and pppGpp execute different functional roles.


Sex differences in the physiological adaptations to heat acclimation: a state-of-the-art review.
Over the last few decades, females have significantly increased their participation in athletic competitions and occupations (e.g. military, firefighters) in hot and thermally challenging environments. Heat acclimation, which involves repeated passive or active heat exposures that lead to physiological adaptations, is a tool commonly used to optimize performance in the heat. However, the scientific community's understanding of adaptations to heat acclimation are largely based on male data, complicating the generalizability to female populations. Though limited, current evidence suggests that females may require a greater number of heat acclimation sessions or greater thermal stress to achieve the same magnitude of physiological adaptations as males. The underlying mechanisms explaining the temporal sex differences in the physiological adaptations to heat acclimation are currently unclear. Therefore, the aims of this state-of-the-art review are to: (i) present a brief yet comprehensive synthesis of the current female and sex difference literature, (ii) highlight sex-dependent (e.g. anthropometric, menstrual cycle) and sex-independent factors (e.g. environmental conditions, fitness) influencing the physiological and performance adaptations to heat acclimation, and (iii) address key avenues for future research.


Pembrolizumab and lenvatinib in recurrent ovarian clear cell carcinoma resistant to chemotherapy.
Treatment of ovarian clear cell carcinoma (CCC) poses many challenges. Effective treatment options for recurrent and metastatic disease remain limited. A 70-year-old woman with recurrent metastatic ovarian CCC experienced durable response to the combination of pembrolizumab, a PD-1 targeting monoclonal antibody and lenvatinib, an oral multikinase inhibitor, after failing standard and experimental treatments. She experienced a 40.1% reduction of target lesions over 26 weeks of therapy. CA-125 trends confirmed serial CT scan findings of shrinking disease burden. She experienced overall mild side effects from the drug combination, and lenvatinib dosage was decreased from 20 to 10 mg/day over her 10 cycles. The combination of pembrolizumab and lenvatinib may represent a new treatment option for chemotherapy-resistant ovarian CCC.


Oligogalacturonide-accelerated healing of mechanical wounding in tomato fruit requires calcium-dependent systemic acquired resistance.
Mechanical wounding causes significant economic losses of fresh produce due to accelerated senescence and spoilage as well as loss of nutritional value. Here, pre-application of oligogalacturonides (OGs) enzymatically hydrolyzed from apple pectin effectively reduced the healing times of mechanical wounds from>24 h in mock groups to 12 h, and the Botrytis cinerea infection rate was reduced from 37.5% to 12.5%. OGs accordingly increased callose deposition; SlPR1, SlPAL and SlHCT gene expression; and phenylalanine ammonia-lyase (PAL) activity around the wounds. Inhibition of Ca2+ signaling using the inhibitor Ruthenium Red markedly inhibited OG accelerated healing of mechanical wounding on fruit. SlPG2, SlEXP1, and SlCEL2 mRNAs accumulation was reduced in OG-elicited tomato fruit compared to water-treated fruit with subsequent retardation of the fruit softening during ripening. These results indicated that apple pectin OGs accelerate wound healing and inhibit fruit softening by activating calcium signaling in tomato fruits during postharvest storage.


Italian multicentre study of carpal tunnel syndrome: study design. Italian CTS Study Group.
In September 1996, during a carpal tunnel syndrome (CTS) symposium, the Italian CTS Study Group was funded. The group designed a strict clinical and neurophysiological protocol for performing a wide multicentre study on idiopathic CTS in hands. In addition to the traditional evaluations, the group also adopted a validated patient-oriented measurement in order to obtain comprehensive and reliable data for the clinical picture. The study was designed to: (1) better assess the clinical picture of the CTS population, especially using new measurement tools (patient-oriented); (2) evaluate the sensitivity of an electrodiagnostic protocol; (3) re-evaluate the validity of a neurophysiological classification; and (4) evaluate the influence of social status and quantify some of the aspects regarding economic and social costs. The study design is described.


Injection drug use and HIV antiretroviral therapy discontinuation in a Canadian setting.
We investigated whether drug-related behaviors predicted antiretroviral therapy (ART) discontinuation among a cohort of injection drug users (IDU) in a Canadian setting. Cox regression analyses were used to investigate the impact of drug use patterns on rates of ART discontinuation among a sample of HIV-positive IDU in Vancouver, Canada between May 1996 and April 2008. In total, 408 HIV-positive IDU initiated ART during the study period, among whom 257 (63.0%) discontinued ART at least once. Rates of ART discontinuation were not significantly elevated among those who reported ongoing injection of heroin, cocaine, or other illicit drugs in comparison to those who reported not injecting drugs. However, public drug use was significantly predictive of ART discontinuation. Our findings may contribute to a reconsideration of the role of active drug use in determining retention in ART programs among IDU.


The nuclear power industry in the United States: status and projections.
One sixth of the electricity in the United States is now being generated in nuclear power plants, a remarkable achievement for a technology whose basic nuclear reaction was not even known 50 years ago. On the other hand, many of the nation's electric utilities are experiencing great difficulties completing the construction of their nuclear plants; 41 partially constructed plants have been abandoned. Those abandoned plants plus about 110 in operation and 15 still to be completed comprise the first generation of nuclear power plants in the United States. When, and even if, there will be a second generation is much in doubt. Data are presented to show that the absence of a second generation of nuclear plants will place large demands on the fossil fuels, with attendant high energy prices and high environmental costs the expected outcome. It appears that the future will bring large economic forces to start new orders for nuclear plants. On the other hand, the opposing institutional forces appear equally strong. Among the problems creating these institutional forces are the difficulty the United States is having in finding a politically acceptable approach to nuclear waste disposal and the vulnerability of power plant builders and operators to litigation and high financial risk. At present, the issue of a second generation of nuclear plants is stalemated.


Use of an attenuated live Salmonella Typhimurium vaccine on three breeding pig units: A longitudinal observational field study.
The study examined the effects of a licensed live Salmonella Typhimurium vaccine, administered to sows and gilts on three commercial pig units experiencing clinical salmonellosis associated with S. Typhimurium or its monophasic variant. After vaccination, clinical salmonellosis resolved and shedding of S. Typhimurium declined markedly and persistently on all breeding or breeding-finishing units, during the one- to two-year monitoring period. On two finishing units supplied in part by one of the vaccinated herds, pigs from the vaccinated herd were less likely to shed Salmonella than those from non-vaccinating herds, and Salmonella counts in faeces were also lower from the vaccine-linked animals. Non-Typhimurium Salmonella serovars were isolated typically in fewer than 10% of samples, and showed no clear temporal changes in frequency. Vaccination of dams alone with S. Typhimurium was associated with reduced shedding of closely-related serovars among all age groups in this commercial setting.


Spontaneous Urinary Bladder Perforation: An Unusual Presentation of Diabetes Mellitus.
Spontaneous urinary bladder perforation is a rare event, which requires immediate medical attention due to its extremely high morbidity and mortality. We report a case of a 36-year-old man who presented with acute-onset abdominal pain without any inciting events. His glucose level at the time of presentation was 1107 mg/dL. On initial abdominal imaging, it was believed that he had a large pelvic mass likely originating from the bladder. On further workup at our hospital, it was discovered that he had an intraperitoneal perforation after which he underwent an exploratory laparotomy and a cystorrhaphy.


Time dependence of residual tissue viability after myocardial infarction assessed by [18F]fluorodeoxyglucose and positron emission tomography.
Areas of myocardial infarction may retain glycolytic activity and this finding is indicative of tissue viability and predictive of functional recovery after revascularization. In order to assess the relation between the time elapsed from the occurrence of acute myocardial infarction and persistence of myocardial metabolic activity in the infarcted tissue, we prospectively studied 65 patients with previous myocardial infarction diagnosed clinically and by electrocardiographic (Q wave) and enzymatic criteria. All patients underwent coronary angiography and contrast left ventriculography, evaluation of regional myocardial glucose metabolism (in the fasting state) by positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), and assessment of myocardial perfusion by single photon emission computed tomography (SPECT) with technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI). Based on the regional metabolic and perfusion findings, patients were divided into 2 groups, depending on the absence (group 1, 26 patients) or presence (group 2, 39 patients) of [18F]FDG uptake in the underperfused regions. Areas of underperfusion at rest, consistent with the clinically identified myocardial infarction site, were observed in all patients. Severity of coronary artery disease, presence of collaterals, number of hypocontractile segments, and wall motion score did not differ significantly in the 2 groups. The time elapsed from the infarction was significantly greater (1,860 +/- 1,333 days) in group 1 than in group 2 (92 +/- 115 days; p < 0.0001). Exercise caused an increase in severity and/or extent of resting perfusion abnormalities in a greater proportion of patients of group 1 (53% vs 23%).(ABSTRACT TRUNCATED AT 250 WORDS)


Morphologic characterization of dome-shaped macula in myopic eyes with serous macular detachment.
To analyze dome-shaped maculas topographic features and related serous retinal detachment (SRD) in eyes with myopic staphyloma. Retrospective, observational case series. We reviewed the records of 48 eyes in 33 patients with dome-shaped maculas who were referred because of decreased vision. Ophthalmologic examination included axial length measurement, spectral domain optical coherence tomography (OCT), and fluorescein and indocyanine green angiography. The height of the macular bulge was measured, and the choroidal thickness was mapped. Patient mean age was 55.0 ± 13.6 years. Mean axial length was 27.49 ± 2.53 mm. Mean best-corrected visual acuity (BCVA) was 0.50 ± 0.33 logMAR. Three dome-shaped macula patterns were observed: round dome in 10/48 (20.8%) eyes; horizontal oval-shaped dome in 30/48 (62.5%) eyes; and vertical oval-shaped dome in 8/48 (16.7%) eyes. The mean macular bulge height was 407.7 ± 215.1 μm (120-1130) and was significantly greater in vertical oval-shaped domes. The mean central choroidal thickness (CCT) was 146.5 ± 56.0 μm, significantly greater than at 3 mm nasal and temporal to the fovea (P < 0.0001). The CCT was positively correlated to macular bulge height but not to BCVA. Foveal SRD was present in 25/48 eyes and significantly increased for macular bulge height greater than 350 μm (P = 0.0047). BCVA was significantly lower when SRD was present (P = 0.043). Most dome-shaped maculas did not display a round but a horizontal or vertical oval-shaped dome and could be missed on a single OCT scan. Chronic foveal SRD was associated with decreased vision and was more common when the macular bulge was highly elevated.


Purification and characterization of Escherichia coli RNase T.
RNase T, a nuclease thought to be involved in end-turnover of tRNA, has been purified about 4,000-fold from extracts of Escherichia coli. At this stage of purification, the enzyme was judged to be at least 95% pure based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The native molecular weight of RNase T determined from gel filtration and sedimentation analyses is about 50,000, whereas the monomer molecular weight determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis is 25,000, suggesting that the protein is an alpha 2 dimer. Purified RNase T is extremely sensitive to inactivation by oxidation, sulfhydryl group reagents, and temperature. The ribonuclease activity against tRNA-C-C-[14C]A is optimal at pH 8-9 in the presence of 2-5 mM MgCl2 and ionic strengths of less than 50mM. Although RNase T is highly specific for intact tRNA-C-C-A as a substrate and can hydrolyze all species in a mixed population of tRNA, it is inhibited by other RNAs, such as poly(A), rRNA, 5 S RNA, and tRNA-C-C. RNase T is an exoribonuclease which initiates attack at a free 3' terminus of tRNA and releases AMP; aminoacyl-tRNA is not a substrate. The role of RNase T in the end-turnover of tRNA and its possible involvement in other aspects of RNA metabolism are discussed.


Effects of interactions between different culture fractions of 'phosphobacteria' and Rhizobium on mycorrhizal infection, growth, and nodulation of Medicago sativa.
Interactions between cell-free culture supernatants, cells, and the whole cultures of Rhizobium and phosphobacteria with endomycorrhizal fungi and their effects on growth and nutrition of Medicago sativa grown in a low-phosphate soil were studied. A satisfactory nodulation was greatly dependent on the mycorrhizal symbiosis. Cell-free supernatants of Rhizobium and phosphobacteria improved plant growth, nodulation and mycorrhiza formation. The activity of phosphobacterial culture seemed to be due mainly to the supernatant and the possibility of plant hormones contained in this culture fraction being involved in such interactions is discussed. An increase of the overall pool of soluble P in soil by the inoculated phosphobacteria cells was not found in the conditions of this experiment. It was noteworthy that the best positive effect was achieved by the treatment which consisted of the whole cultures of Rhizobium, phosphobacteria, and the mycorrhizal fungi applied all together.


Regulation of Bcl-2 family proteins, neurotrophic factors, and APP processing in the neurorescue activity of propargylamine.
The anti-Parkinson drug, rasagiline (N-propargyl-(1R)-aminoindan) promotes neuronal survival, via neuroprotective activity related to its propargyl moiety (propargylamine). We have investigated the neurorescue effects of propargylamine, in a progressive neuronal death model, induced by long-term serum deprivation in human SH-SY5Y neuroblastoma cells. Propargylamine (0.1-10 microM) dose-dependently reduced the levels of the early apoptosis-associated phosphorylated protein, H2A-X (ser 139), as well as decreased the cleavage of caspase-3 and its substrate poly-ADP ribose polymerase (PARP). In addition, the compound markedly reversed the apoptotic effects induced by long-term serum withdrawal, including down-regulation of the antiapoptotic protein, Bcl-2, as well as up-regulation of the proapoptotic proteins, Bax, Bad, and Bim. Real-time RT-PCR demonstrated that propargylamine elevated gene expression levels of Bcl-2, and the neurotrophic factors glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) and reduced Bax gene expression. Serum deprivation increased mRNA and protein levels of holo-amyloid precursor protein (APP), which was markedly decreased by propargylamine. This was accompanied by inducing the release of the nonamyloidogenic alpha-secretase form of soluble APP (sAPPalpha) into the medium. Similar effects on cell survival and APP regulation/processing were demonstrated for rasagiline. These results indicate that both rasagiline and propargylamine possess neurorescue activity, associated with regulation of Bcl-2 family proteins, neurotrophic factors, and APP metabolism.