Carbon nanoparticle induced cytotoxicity in human mesenchymal stem cells through upregulation of TNF3, NFKBIA and BCL2L1 genes.
Carbon based nanomaterials, including carbon nanotubes, graphene, nanodiamond and carbon nanoparticles, have emerged as potential candidates for a wide variety of applications because of their unusual electrical, mechanical, thermal and optical properties. However, our understanding of how increased usage of carbon based nanomaterials could lead to harmful effects in humans and other biological systems is inadequate. Our present investigation is focused on the cellular toxicity of carbon nanoparticles (CNPs) on human mesenchymal stem cells (hMSCs). Following exposure to CNPs, cell viability, nuclear morphological changes, apoptosis and cell cycle progression were monitored. Furthermore, the expression of genes involved in both cell death (e.g., P53, TNF3, CDKN1A, TNFRSF1A, TNFSF10, NFKBIA, BCL2L1) and cell cycle regulation (e.g., PCNA, EGR1, E2F1, CCNG1, CCND1, CCNC, CYCD3) were assessed using qPCR. Our results indicated that CNPs reduce cell viability and cause chromatin condensation and DNA fragmentation. Cell cycle analysis indicated that CNPs affect the cell cycle progression. However, the gene expression measurements confirmed that CNPs significantly upregulated the P53, TNF3, CDKNIA, and NFKBIA genes and downregulated the EGR1 gene in hMSCs. Our findings suggest that CNPs reduce cell viability by disrupting the expression of cell death genes in human mesenchymal stem cell (hMSC). The results of this investigation revealed that CNPs exhibited moderate toxicity on hMSCs.


Evidence that pyrophosphate acts as an extracellular signalling molecule to exert direct functional effects in primary cultures of osteoblasts and osteoclasts.
Extracellular pyrophosphate (PPi) is well known for its fundamental role as a physiochemical mineralisation inhibitor. However, information about its direct actions on bone cells remains limited. This study shows that PPi decreased osteoclast formation and resorptive activity by ≤50 %. These inhibitory actions were associated with reduced expression of genes involved in osteoclastogenesis (Tnfrsf11a, Dcstamp) and bone resorption (Ctsk, Car2, Acp5). In osteoblasts, PPi present for the entire (0-21 days) or latter stages of culture (7-21/14-21 days) decreased bone mineralisation by ≤95 %. However, PPi present for the differentiation phase only (0-7/0-14 days) increased bone formation (≤70 %). Prolonged treatment with PPi resulted in earlier matrix deposition and increased soluble collagen levels (≤2.3-fold). Expression of osteoblast (RUNX2, Bglap) and early osteocyte (E11, Dmp1) genes along with mineralisation inhibitors (Spp1, Mgp) was increased by PPi (≤3-fold). PPi levels are regulated by tissue non-specific alkaline phosphatase (TNAP) and ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1). PPi reduced NPP1 expression in both cell types whereas TNAP expression (≤2.5-fold) and activity (≤35 %) were increased in osteoblasts. Breakdown of extracellular ATP by NPP1 represents a key source of PPi. ATP release from osteoclasts and osteoblasts was decreased ≤60 % by PPi and by a selective TNAP inhibitor (CAS496014-12-2). Pertussis toxin, which prevents Gαi subunit activation, was used to investigate whether G-protein coupled receptor (GPCR) signalling mediates the effects of PPi. The actions of PPi on bone mineralisation, collagen production, ATP release, gene/protein expression and osteoclast formation were abolished or attenuated by pertussis toxin. Together these findings show that PPi, modulates differentiation, function and gene expression in osteoblasts and osteoclasts. The ability of PPi to alter ATP release and NPP1/TNAP expression and activity indicates that cells can detect PPi levels and respond accordingly. Our data also raise the possibility that some actions of PPi on bone cells could be mediated by a Gαi-linked GPCR.


Highly Diastereoselective Synthesis of Polycyclic Indolines through Formal [4+2] Propargylic Cycloaddition of Indoles with Ethynyl Benzoxazinanones.
A formal [4+2] propargylic annulation of indoles and pyrrole with ethynyl benzoxazinanones was described. This protocol provides a concise synthesis of tetrahydro-5H-indolo[2,3-b]quinolines and tetrahydro-3H-pyrrolo[3,2-b]quinoline, the core structures of alkaloid frameworks, featuring excellent yields, high diastereoselectivity, mild conditions and wide substrate scope.


[Transosseous repair of patellar tendon ruptures].
Restoration of active knee extension. Restoration of active knee stabilization. Avoiding secondary patella alta. Acute rupture of the patellar tendon within 3-5 days. Chronic rupture of the patellar tendon. Compromised general health status or associated injuries. Compromised local soft-tissue situation. Exposure of the ruptured tendon. Coronal drill hole through the distal third of the patella and coronal drill hole through the tibial tuberosity. After anatomic positioning of the patella (adjusting correct height), patellotibial fixation with monofil or woven (Labitzke) cerclage wire or PDS cord. Suture repair of the patellar tendon and repair of the ruptured medial and lateral retinaculum. Drain insertion. Wound closure in layers. Full load bearing in cylinder cast. Week 0-2: flexion restricted to 30 degrees , quadriceps muscle isometry. Week 2-4: flexion restricted to 60 degrees , strengthening of hip abductors and extensors. Week 4-6: flexion restricted to 90 degrees . After week 6: removal of cylinder cast. After week 12: return to sporting activities, removal of the cerclage wire. Good results after surgical therapy. Low rate of secondary rupture. Low rate of muscle weakness.


Circulating interferon-gamma and white matter brain damage in preterm infants.
The fetal inflammatory response has been suggested as causal in neonatal morbidity. Serial levels of circulating cytokines were evaluated in 74 infants with a mean gestational age (GA) of 27.1 wk. Pro-inflammatory [tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-1 beta, IL-2, IL-6, IL-8, IL-12] [corrected] and modulatory (IL-4, IL-10) cytokines were analyzed from cord blood, and at 6, 24 [corrected] and 72 h postnatal age. Measure of cytokine burden over time was assessed by calculating the area under curve (AUC) for analyzed levels (0-72 h). Premature rupture of membranes (PROM) was associated with higher levels of IL-2 at birth and at 6 h, of IFN-gamma at 6 and 24 h postnatal age and of TNF-alpha at 6 and 24 h. Levels of IFN-gamma at 6, 24, and 72 h were increased in infants developing white matter brain damage (WMD) compared with those without WMD. Infants with arterial hypotension requiring dopamine treatment had an increase in IL-6 with a peak at 6 h of age. Severe intraventricular hemorrhage (IVH) was associated with increase in AUC [(IL-6) and (IL-8), odds ratio (OR) 2.8 and 13.2 respectively], whereas white matter brain damage (WMD) [corrected] was associated with increase in AUC (IFN-gamma; OR, 26.0) [corrected] A fetal immune response with increased postnatal levels of IFN-gamma was associated with development of WMD. PROM was associated with a T-helper 1 cytokine response with increased levels of IFN-gamma. Type of inflammatory response appears of importance for subsequent morbidity.


Amyloid fiber formation in human γD-Crystallin induced by UV-B photodamage.
γD-Crystallin is an abundant structural protein of the lens that is found in native and modified forms in cataractous aggregates. We establish that UV-B irradiation of γD-Crystallin leads to structurally specific modifications and precipitation via two mechanisms: amorphous aggregates and amyloid fibers. UV-B radiation causes cleavage of the backbone, in large measure near the interdomain interface, where side chain oxidations are also concentrated. 2D IR spectroscopy and expressed protein ligation localize fiber formation exclusively to the C-terminal domain of γD-Crystallin. The native β-sandwich domains are not retained upon precipitation by either mechanism. The similarities between the amyloid forming pathways when induced by either UV-B radiation or low pH suggest that the propensity for the C-terminal β-sandwich domain to form amyloid β-sheets determines the misfolding pathway independent of the mechanism of denaturation.


Prevalence of mild cognitive impairment in an elderly community sample.
The term "mild cognitive impairment" refers to cognitive deficits which exceed normal physiological aging processes, but do not fulfill the criteria for dementia. While recent studies indicate that the respective deficits can be reliably assessed, different diagnostic criteria have prevented a wide application of this diagnosis in clinical practice. The aims of the present study were (1) to assess the prevalence rates of four current diagnostic concepts and (2) to investigate mild cognitive impairment with respect to psychological and sociodemographic variables. Data from 202 probands recruited from the interdisciplinary longitudinal study on adult development were analyzed. On the time of examination, probands were between 60 to 64 years old and in a good health. The following prevalence rates were determined: 13.5% for age-associated memory impairment (AAMI), 6.5% for age-consistent memory impairment (ACMI), 1.5% for late-life forgetfulness (LLF), and 23.5% for aging-associated cognitive decline (AACD). Complaints of cognitive deficits were significantly correlated with higher scores on depression and neuroticism scales but with none of the neuropsychological measures. Reduced performance in neuropsychological tests was associated with a lower educational level and socioeconomic status. We conclude that the prevalence rates of mild cognitive impairment are highly dependent on the diagnostic criteria applied. In this respect the self-report of cognitive decline might be a less useful criteria. Longitudinal studies are warranted to further elucidate the predictive value of these diagnostic criteria.


Evaluation of antinociceptive effects of Crassocephalum bauchiense Hutch (Asteraceae) leaf extract in rodents.
The leaves of Crassocephalum bauchiense have long been used in traditional Cameroonian medicine for the treatment of epilepsy, pain, inflammatory disorders, arthritis and intestinal pain. In this study, we attempted to identify the possible antinociceptive action of the aqueous extract and the alkaloid fraction prepared from the leaves of Crassocephalum baucheiense. Using acetic acid induced abdominal constrictions, formalin-, capsaisin- and glutamate-induced nociception, and hot plate assay procedures, the antinociceptive effects of the aqueous extract and the alkaloid fraction was assessed after oral administration in mice. Morphine sulfate was used as reference analgesic agent. Mice were submitted to the rota-rod task and open-field test in order to assess any non-specific muscle-relaxant or sedative effects of the extracts of Crassocephalum bauchiense. Male and female Swiss mice were used to assess acute toxicity of these extracts. The aqueous extract and the alkaloid fraction of Crassocephalum bauchiense produced a significant antinociceptive effects in the acetic acid, formalin, glutamate, capsaicin and hot plate tests. These antinociceptive effects of Crassocephalum bauchiense were significantly attenuated by pretreatment with naloxone. The extracts of Crassocephalum bauchiense did not alter the locomotion of animals in the open-field or rotarod tests, which suggest a lack of a central depressant effect. The animals did not exhibit any acute toxicity to the aqueous extract and the alkaloid fraction, so it was not possible to calculate the LD(50). The results confirm the popular use of Crassocephalum bauchiense as an antinociceptive, and contribute to the pharmacological knowledge of this species because it was shown that the aqueous extract and the alkaloid fraction of Crassocephalum bauchiense produced dose related antinociception in models of chemical and thermal nociception through mechanisms that involve an interaction with opioidergic pathway.


Cytogenetic biomonitoring of styrene-exposed plastic boat builders.
Earlier studies have produced evidence for an association between work-related styrene exposure and cytogenetic damage, while more recent studies have failed to show such an association. In the present study, chromosome aberrations (CA) and sister chromatid exchanges (SCE) were measured in peripheral blood lymphocytes of 46 male workers employed in a fiber-reinforced plastic boat building factory and exposed to styrene. Two groups of 23 workers each, characterized by different exposure levels (ranges: 2-120 mg/m3 and 86-1389 mg/m3 ambient air) were studied, fifty-one controls matched by sex, age and smoking habits were included. Randomized blood samples were analyzed for cytogenetic damage separately in two laboratories. Interlaboratory differences in the scoring of CA and SCE were noted. However, increases of the considered cytogenetic endpoints in exposed vs control groups were consistently observed in both laboratories. Multivariate statistical analysis of pooled data revealed increases of CA ranging between 19% (RR = 1.19; 95% C.I., 0.80-1.78; chromatid-type aberrations, low exposure group) and 144% (RR = 2.44; 95% C.I., 1.26-4.70; chromosome-type aberrations, high exposure group). Parallel excess of SCE in styrene exposed workers was also observed, although at a lesser extent (RR = 1.22; 95% C.I., 1.05-1.43, low exposure group; RR = 1.26; 95% C.I., 1.07-1.47, high exposure group). These findings suggest the presence of a causal association between occupational exposure to styrene and cytogenetic damage in the plastic boat building factory that was the object of the study.


Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis.
Current guidelines recommend the use of a combination of inhaled beta(2) agonists and anticholinergics, particularly for patients with acute severe or life threatening asthma in the emergency setting. However, this statement is based on a relatively small number of randomised controlled trials and related systematic reviews. A review was undertaken to incorporate the more recent evidence available about the effectiveness of treatment with a combination of beta(2) agonists and anticholinergics compared with beta(2) agonists alone in the treatment of acute asthma. A search was conducted of all randomised controlled trials published before April 2005. Data from 32 randomised controlled trials (n = 3611 subjects) showed significant reductions in hospital admissions in both children (RR = 0.73; 95% CI 0.63 to 0.85, p = 0.0001) and adults (RR = 0.68; 95% CI 0.53 to 0.86, p = 0.002) treated with inhaled anticholinergic agents. Combined treatment also produced a significant increase in spirometric parameters 60-120 minutes after the last treatment in both children (SMD = -0.54; 95% CI -0.28 to -0.81, p = 0.0001) and adults (SMD = -0.36; 95% CI -0.23 to -0.49, p = 0.00001). This review strongly suggests that the addition of multiple doses of inhaled ipratropium bromide to beta(2) agonists is indicated as the standard treatment in children, adolescents, and adults with moderate to severe exacerbations of asthma in the emergency setting.


A randomized, double-blind trial for stress ulcer prophylaxis shows no evidence of increased pneumonia.
H2-receptor antagonists are commonly used for stress ulcer prophylaxis on intensive care units. However, there is evidence that via the route of an elevated gastric pH, followed by bacterial overgrowth and subsequent tracheal aspiration, pneumonia could occur. In line with this assumption total gastrectomized patients should develop a very high incidence of pneumonia, which is actually not the case. We therefore formulated the hypothesis that stress ulcer prophylaxis with H2-receptor antagonists does not lead to an increased pneumonia rate. A total of 158 patients with mechanical ventilation > or =48 hours of a surgical intensive care unit were randomized to the following groups: A, placebo (n = 57); B, pirenzepine (3 x 10 mg intravenously, n = 44); and C, ranitidine (3 x 50 mg intravenously, n = 57). The pneumonia rate in ranitidine-, pirenzepine-, and placebo-treated patients is 10 of 57, 10 of 44, and 12 of 57, respectively. Pneumonia rate is not adversely affected by H2-receptor antagonists in stress ulcer prophylaxis.


Ketamine reduces amyloid β-protein degradation by suppressing neprilysin expression in primary cultured astrocytes.
Pathological accumulation of cortical amyloid β-protein (Aβ) is an early and consistent feature of Alzheimer's disease (AD). Aβ levels in the brain are determined by production and catabolism. Previous studies have suggested that deficits in the brain expression of neprilysin (NEP) and the insulin-degrading enzyme (IDE), which are both proteases involved in amyloid degradation, may promote Aβ deposition in patients with sporadic late-onset AD. Because the incidence of AD increases after surgical intervention, we examined whether ketamine, which is a general anaesthetic with neuroprotective properties for excitotoxic ischaemic damage, is associated with Aβ degradation by inducing NEP and IDE expression. The non-competitive N-methyl-d-aspartate receptor antagonist ketamine and MK801 significantly decreased the expression of NEP, but not IDE, in a concentration- and time-dependent manner through the dephosphorylation of p38 mitogen-activated protein kinase (MAPK) in cultured rat astrocytes. Furthermore, NEP-reduced reagents significantly suppressed the degradation of exogenous Aβ in cultured astrocytes. These results suggested that ketamine suppresses the Aβ degradation of NEP by reducing p38 MAPK-mediated pathway activity.


Early postnatal maternal deprivation in rats induces memory deficits in adult life that can be reversed by donepezil and galantamine.
Early postnatal maternal deprivation is known to cause long-lasting neurobiological effects. Here, we investigated whether some of the cognitive aspects of these deficits might be related to a disruption of the cholinergic system. Pregnant Wistar rats were individually housed and maintained on a 12:12h light/dark cycle with food and water freely available. The mothers were separated from their pups for 3h per day from postnatal day 1 (PND-1) to PND-10. To do that, the dams were moved to a different cage and the pups maintained in the original home cage, which was transferred to a different room kept at 32 degrees C. After they reached 120-150 days of age, maternal-deprived and non-deprived animals were either sacrificed for brain acetylcholinesterase measurement, or trained and tested in an object recognition task and in a social recognition task as described by Rossato et al. (2007) [Rossato, J.I., Bevilaqua, L. R.M., Myskiw, J.C., Medina, J.H., Izquierdo, I., Cammarota, M. 2007. On the role hippocampal synthesis in the consolidation and reconsolidation of object recognition memory. Learn. Mem. 14, 36-46] and Lévy et al. (2003) [Lévy, F., Melo. A.I., Galef. B.G. Jr., Madden, M., Fleming. A.S. 2003. Complete maternal deprivation affects social, but not spatial, learning in adult rats. Dev. Psychobiol. 43, 177-191], respectively. There was increased acetylcholinesterase activity in hippocampus and perirhinal cortex of the deprived animals. In addition, they showed a clear impairment in memory of the two recognition tasks measured 24h after training. Oral administration of the acetylcholinesterase inhibitors, donepezil or galantamine (1mg/kg) 30min before training reversed the memory impairments caused by maternal deprivation. The findings suggest that maternal deprivation affects memory processing at adulthood through a change in brain cholinergic systems.


Ossiculoplasty: A Prospective Study on 50 Patients Using Various Graft Materials.
With large number of grafts available for ossiculoplasty, choice becomes difficult. An ideal graft should be safe, easily available, cost efficient, with good hearing results, uptake and low extrusion rates. The ear nose and throat surgeon is still facing the indecision over type of graft to be selected. A prospective study was conducted in Department of Otorhinolaryngology, Rajindra Hospital, Patiala (August 2012-2014) on 50 patients 15-60 years, of either sex with ABG > 40 dB. Operative procedure planned and type of graft decided intraoperatively. Autografts included remodelled malleus, remodelled incus and tragal cartilage grafts. Synthetic (Teflon) grafts were PORP and TORP. Graft uptake/failure was noted at 1 and 3 months. PTA done at 3 months postoperatively. Net hearing gain (change in ABG) was calculated for various grafts used and analysed. Mean age was 35.26 ± 13 yrs, male and female 1:1. Most common involved ossicle was incus (100%) followed by stapes (36%) and malleus (34%). Autografts, 23, uptake in 20 (86.95%), failure 3 (13.04%) cases. Synthetic grafts, 27, uptake 18 (66.66%) and failure 9 (33.33%). 'p'value 0.09 (non significant). Mean hearing gain, autografts 14.47 ± 6.54 dB and synthetic grafts 14.57 ± 13.12 dB. 'p' value 0.976 (non significant). No significant difference seen in mean hearing gain and uptake/failure of autografts and synthetic grafts. Autografts being cost effective are preferred choice.


Publisher Correction: The composition of the perinatal intestinal microbiota in cattle.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.


Low uptake of continuous subcutaneous insulin infusion therapy in people with type 1 diabetes in Ireland: a retrospective cross-sectional study.
The uptake of continuous subcutaneous insulin infusion (CSII) therapy in those with type 1 diabetes varies internationally and is mainly determined by the national healthcare reimbursement systems. The aim of this study is to estimate national and regional uptake of CSII therapy in children, adolescents and adults with type 1 diabetes in Ireland. A retrospective cross-sectional study was conducted utilizing the national pharmacy claims database in 2016. Individuals using CSII were identified by dispensing of infusion sets. The uptake of CSII was calculated as the percentage of people with type 1 diabetes claiming CSII sets in 2016, both in children and adolescent (age < 18 years) and adult populations (≥ 18 years). Descriptive statistics including percentages with 95% confidence intervals (CIs) are presented, stratified by age-groups and geographical regions, and chi-square tests used for comparisons. Of 20,081 people with type 1 diabetes, 2111 (10.5, 95% CI: 10.1-10.9%) were using CSII in 2016. Uptake was five-fold higher in children and adolescents at 34.7% (95% CI: 32.9-36.5%) than in adults at 6.8% (95% CI: 6.4-7.2%). Significant geographical heterogeneity in CSII uptake was found, from 12.6 to 53.7% in children and adolescents (p < 0.001), and 2 to 9.6% in adults (p < 0.001). Uptake of CSII in people with type 1 diabetes is low in Ireland, particularly in those ≥18 years. Identification of barriers to uptake, particularly in this group, is required.


A new species of Oomyzus Rondani (Hymenoptera, Eulophidae) reared from the pupae of Coccinella septempunctata (Coleoptera, Coccinellidae) in China.
Oomyzus spiraculus Song, Fei & Cao sp. nov. (Hymenoptera, Eulophidae) is described and illustrated as a gregarious larval-pupal endoparasitoid of Coccinella septempunctata L. (Coleoptera, Coccinellidae). Differentiation between O. spiraculus and its similar species is discussed and a key to differentiate the female and male of these species is provided. DNA barcodes of O. spiraculus and O. scaposus are analyzed and compared.


Monoterpene indole alkaloids with diverse skeletons from the stems of Rauvolfia vomitoria and their acetylcholinesterase inhibitory activities.
Nine undescribed monoterpene indole alkaloids, rauvomitorine A-I, including an unprecedented C-9-methoxymethylene-sarpagine framework alkaloid, two rare suaveoline framework type alkaloids, and six yohimbine framework type alkaloids, as well as eleven known alkaloids, were isolated from the stems of Rauvolfia vomitoria Afzel. (Apocynaceae). The structures of the unreported alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis with Cu Kα radiation. Rauvomitorine A with an unreported framework type represents the first example of C-9-methoxymethylene-sarpagine alkaloids and its plausible biosynthetic pathway was proposed. All the isolated alkaloids were evaluated their acetylcholinesterase inhibitory (AChE) activities and cytotoxicity against five cancer cell lines and some of them exhibited potential anti-AChE activities with IC50 values ranging from 49.76 to 186.62 μM. Importantly, this is the first report of the AChE inhibitory activities on suaveoline framework type alkaloids, suggesting this type of alkaloids may be valuable sources for the discovery of AChE inhibitory agents. A preliminary structure-activity relationship for AChE inhibitory activities of the isolated alkaloids is also discussed, providing some clues to designing lead compounds for AChE inhibitors.


The in-vitro uptake of zinc by blood cells in rats with long-term inflammatory stress.
The aim of the present study was to investigate the in vitro uptake of zinc by blood cells, in an attempt to distinguish between those conditions in which low plasma zinc concentrations are due to inflammatory stress, and those which are due to true zinc deficiency. Inflammation induced by intramuscular injection of turpentine caused a significant reduction in plasma albumin concentrations, which persisted until the end of the study (2 weeks). It also caused a reduction in the plasma zinc concentration which was most marked during the first few days. A smaller difference persisted until the end of the study. When the serum zinc concentration was corrected for the hypoalbuminaemia, the changes in serum zinc concentration after the first 4 days of turpentine were small and mainly non-significant. The in vitro uptake of zinc by erythrocytes obtained from animals with inflammation did not increase, whereas the uptake was increased in cells obtained from animals with true zinc deficiency. Therefore this study suggests a method that can probably differentiate between an apparent zinc deficiency due to inflammatory stress and a real zinc deficiency, but additional experiments to validate this method should be performed.


Docetaxel plus cisplatin and bevacizumab for untreated patients with advanced/metastatic non-squamous non-small-cell lung cancer: a multicenter phase II study of the Hellenic Oncology Research Group.
The docetaxel/cisplatin (DC) combination is an active regimen against advanced/metastatic non-small-cell lung cancer (NSCLC), and bevacizumab (B) improves the efficacy of frontline chemotherapy. This phase II study was designed in order to explore the efficacy and safety of DCB regiment in this setting. Chemotherapy-naïve patients (n = 48) with measurable, histologically confirmed non-squamous, IIIB (wet)/IV NSCLC, and PS 0-2 were eligible. Patients received D (75 mg/m(2) IV), C (80 mg/m(2) IV), and B (15 mg/kg IV) every 3 weeks. Maintenance of bevacizumab was not mandatory. Complete and partial responses were achieved in two (4.2%) and 14 (29.2%) patients, respectively [overall response rate: 33.3%; 95% CI = 20.0-46.7%], whereas stable disease was documented in 14 [disease control rate = 62.5%; 95% CI = 48.8-76.2%]. The median progression-free survival was 4.4 months and the median overall survival 13.3 months. Treatment-related grade 3 or 4 hematologic adverse events were leukopenia, neutropenia, and anemia in 8.4, 18.7, and 2.1% of the patients, respectively. Febrile neutropenia occurred in three (6.3%) patients. Bleeding was documented in 4% of the patients, thrombotic episodes in 8%, and proteinuria in 3%. There was one treatment-related death. Frontline DCB in patients with advanced non-squamous NSCLC is an active regimen with manageable toxicity and merits to be further investigated.


Isolation and characterization of interferon-producing reticuloendothelial cells from mouse epidermis.
A homogeneous population of trypsin-resistant epidermal cells has been isolated from newborn ICR mice. These cells are characterized by adherence, receptors for Fc-IgG, ATPase activity, phagocytosis of latex particles and opsonized sheep erythrocytes, and secretion of lysozyme and interferon. The production of interferon by these cells suggests that they may be important in protection against viral infections of the skin as well as in regulation of immune responses. The ultrastructure of these trypsin-resistant epidermal cells shows striking similarity to that of reticuloendothelial cells.


Catastrophe modelling in the biological sciences.
Catastrophe Theory was developed in an attempt to provide a form of Mathematics particularly apt for applications in the biological sciences. It was claimed that while it could be applied in the more conventional "physical" way, it could also be applied in a new "metaphysical" way, derived from the Structuralism of Saussure in Linguistics and Lévi-Strauss in Anthropology. Since those early beginnings there have been many attempts to apply Catastrophe Theory to Biology, but these hopes cannot be said to have been fully realised. This paper will document and classify the work that has been done. It will be argued that, like other applied Mathematics, applied Catastrophe Theory works best where the underlying laws are securely known and precisely quantified, requiring those same guarantees as does any other branch of Mathematics when it confronts a real-life situation.


Effects of ageing on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxic effects on striatum and brainstem in the rat.
In 3- and 18-month-old male Wistar rats, levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA), dehydroascorbic acid (DHAA), noradrenaline (NA), uric acid, glutathione (GSH) and 1-methyl-4-phenylpyridinium ion (MPP+) were determined by HPLC in the striatum and/or in the brainstem 24 h after single injections of MPTP (12-35 mg/kg i.p.). Aged rats had lower baseline levels of AA and GSH, compared to young rats. In aged rats, MPTP 35 mg/kg induced a 70% death rate and a decrease in striatal DOPAC/DA ratio which was significantly correlated to MPP+ concentrations (r = -0.840, P < 0.005); in addition, MPTP did not increase AA oxidation. In the brainstem, the MPTP-induced decrease in NA levels and increase in uric acid levels were significantly correlated to the MPP+ concentrations (r = -0.709, P < 0.05, and r = +0.888, P < 0.001, respectively). In conclusion, evidence is given of a mechanism of toxicity of MPTP involving oxidative stress produced by xanthine oxidase; in addition, in aged rats the neuronal antioxidant system (levels of AA and GSH) is considerably lower than in young rats and may play an enabling role in the MPTP age-related neurotoxic effects on striatum and brainstem.


Genomic clustering within functionally related gene families in Ascomycota fungi.
Multiple mechanisms collaborate for proper regulation of gene expression. One layer of this regulation is through the clustering of functionally related genes at discrete loci throughout the genome. This phenomenon occurs extensively throughout Ascomycota fungi and is an organizing principle for many gene families whose proteins participate in diverse molecular functions throughout the cell. Members of this phylum include organisms that serve as model systems and those of interest medically, pharmaceutically, and for industrial and biotechnological applications. In this review, we discuss the prevalence of functional clustering through a broad range of organisms within the phylum. Position effects on transcription, genomic locations of clusters, transcriptional regulation of clusters, and selective pressures contributing to the formation and maintenance of clusters are addressed, as are common methods to identify and characterize clusters.


Biomass dynamics and water use efficiencies of five plant communities in the shortgrass steppe.
Standing crop biomass and water-use efficiency were estimated for five plant communities of the Central Plains Experimental Range in north central Colorado. Aboveground biomass by functional groups, surface litter amounts, and standing dead biomass were compared, as were vertical and size-class distributions of belowground biomass. Greater production and water-use efficiency values were found: (1) at coarse-textured sites, indicating the importance of the inverse texture effect, and (2) wherever site characteristics favored the establishment of lifeforms other than grasses, e.g., succulents, and shrubs. Seasonal aboveground biomass and water-use efficiencies for the grass component were similar among sites, even though the mixes of C3 and C4 grass species were different. Similar grass biomass values in very different communities suggested that high biomass and high water-use efficiencies were related less to grass types than to the abundance of non-grass life-forms.


Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at 2.0 A resolution.
Botulinum neurotoxin serotype B is a zinc protease that disrupts neurotransmitter release by cleaving synaptobrevin-II (Sb2), one of three SNARE proteins involved in neuronal synaptic vesicle fusion. The three-dimensional crystal structure of the apo botulinum neurotoxin serotype B catalytic domain (BoNT/B-LC) has been determined to 2.2 A resolution, and the complex of cleaved Sb2 with the catalytic domain (Sb2-BoNT/B-LC) has been determined to 2.0 A resolution. A comparison of the holotoxin catalytic domain and the isolated BoNT/B-LC structure shows a rearrangement of three active site loops. This rearrangement exposes the BoNT/B active site. The Sb2-BoNT/B-LC structure illustrates two distinct binding regions, which explains the specificity of each botulinum neurotoxin for its synaptic vesicle protein. This observation provides an explanation for the proposed cooperativity between binding of full-length substrate and catalysis and suggest a mechanism of synaptobrevin proteolysis employed by the clostridial neurotoxins.


Thyroid function in the elderly.
Many differences in thyroid function exist between elderly and younger populations. Although serum T4 levels probably do not change with age, serum T3 levels appear to decline. Hyperthyroidism in the geriatric population may be atypical and is characterized by anorexia and constipation. The pulse rate is often slower than in younger patients. Apathetic hyperthyroidism mainly occurs in older patients. The cause of hyperthyroidism is usually toxic multinodular goiter. Isolated T3 or T4 elevations may be seen. RAIU is often normal. Hypothyroidism is common in the elderly. TSH is a reliable indicator, but the significance of mild elevations (less than 20 microU/ml) is unclear. Serum antithyroid antibodies are unreliable in the definitive diagnosis of hypothyroidism. Acute and chronic illnesses occur frequently in older patients and have varied and important effects on thyroid function tests. Low T3 and both low T4 and low T3 are seen. High T4 syndrome may be more common in older patients than in younger patients. It is also seen in psychiatric populations. TSH levels are usually normal but may be mildly elevated.


Galactosemia unsolved.
Classic galactosemia is an enigmatic disorder that presents the challenge of unraveling the basis of the long-term complications of mental disability, speech defects, ovarian failure and neurologic syndromes which occur despite a galactose-restricted diet. A complete understanding of the pathobiochemistry and molecular genetics, and evaluation of the present theories for the poor long-term outcome, continuous intoxication, critical metabolite depletion and in utero damage is needed in order to design new therapeutic strategies. Answering this urgent question of how to treat galactosemic patients mandates enhanced clinical and basic research efforts.


Estimates of genetic relatedness among males in a polygynous wasp.
Cyclical oligogyny is considered to be the mechanism that is most likely to be responsible for stabilizing cooperation in polygynous, epiponine wasps, in which single-queen colonies produce new queens and multiple-queen colonies produce males. In contrast with the number of studies on relatedness among adult females, we know little about relatedness among males in polygynous epiponine wasps. We estimated worker and male relatedness in the Brazilian epiponine wasp Polybia paulista Ihering and found that colonies of P. paulista produced males when they contained multiple queens. Although average relatedness within males did not differ significantly from 0.5, the number of alleles observed suggests that there were more than one queen to produce males in each colony. Our data would be helpful to elucidate dynamics of the male production in a colony of epiponine wasps.


Molecular differences between stromal cell populations from deciduous and permanent human teeth.
Deciduous and permanent human teeth represent an excellent model system to study aging of stromal populations. Aging is tightly connected to self-renewal and proliferation and thus, mapping potential molecular differences in these characteristics between populations constitutes an important task. Using specifically designed microarray panels, Real-Time Quantitative Polymerase Chain Reaction (RT q-PCR), Western blot, immunohistochemistry and siRNA-mediated knock down experiments, we have detected a number of molecules that were differentially expressed in dental pulp from deciduous and permanent teeth extracted from young children and adults, respectively. Among the differentially regulated genes, high-mobility group AT-hook 2 (HMGA2), a stem cell-associated marker, stood out as a remarkable example with a robust expression in deciduous pulp cells. siRNA-mediated knock down of HMGA2 expression in cultured deciduous pulp cells caused a down-regulated expression of the pluripotency marker NANOG. This finding indicates that HMGA2 is a pulpal stem cell regulatory factor. In addition to this, we discovered that several proliferation-related genes, including CDC2A and CDK4, were up-regulated in deciduous pulp cells, while matrix genes COL1A1, fibronectin and several signaling molecules, such as VEGF, FGFr-1 and IGFr-1 were up-regulated in the pulp cells from permanent teeth. Taken together, our data suggest that deciduous pulp cells are more robust in self- renewal and proliferation, whereas adult dental pulp cells are more capable of signaling and matrix synthesis.


Respiratory Syncytial Virus Infection: An Update.
Respiratory syncytial virus (RSV) is a highly contagious respiratory virus that can cause mild to severe illness in children. It is the leading cause of lower respiratory tract infections (LRTI) in children under the age of one year, and it can also affect older children and adults, especially those with underlying medical conditions. In the post-COVID period, there seems to be an increase in the incidence, possibly due to 'immunity debt'. Symptoms of RSV infection in children may include fever, runny nose, and cough. In severe cases, it can lead to bronchiolitis (inflammation of the small airways in the lungs) or pneumonia (infection of the lungs). Most children with RSV infection recover within a week or two, but some may require hospitalization, especially those who are premature or have underlying medical conditions. As there is no specific treatment for RSV infection, supportive care is the mainstay of management. In severe cases, oxygen therapy or mechanical ventilation may be necessary. High flow nasal cannula seems to be beneficial. There have been promising advances in development of RSV vaccines; few trials in adults and pregnant women have reported encouraging results. The US FDA has approved two RSV vaccines for use in older adults (GSK's Arexvy and Pfizer's ABRYSVO).


Bifid Intratemporal facial nerves in an adult without other congenital anomalies.
To describe a case of bifid intratemporal facial nerves without associated middle or inner ear abnormalities encountered on computed tomography (CT) imaging during preoperative preparation for unilateral cochlear implant placement in an adult male with profound sensorineural hearing loss (SNHL). A rare case of bilateral bifid intratemporal facial nerves in an adult male is presented. The finding's impact on approach to safe cochlear implantation is discussed. Bifurcation of the intratemporal facial nerve is rarely seen and is usually associated with congenital middle or inner ear anomalies. A unique case of bilateral bifid intratemporal facial nerves without other middle or inner ear abnormalities was encountered incidentally on CT imaging during preparation for unilateral cochlear implant placement in an adult male with profound SNHL. The nerve was bifid along the mastoid segment with a nerve branch traversing through the facial recess precluding safe traditional approach to cochlear implant placement. Accessory stylomastoid foramina were noted bilaterally. Unilateral subtotal petrosectomy was performed with successful implantation and excellent hearing outcome. No additional clinical or radiographic otologic abnormalities were noted. Abnormal bifurcation of the facial nerve may occur in adults without other middle or inner ear anomalies. This case highlights the importance of independent imaging review by the surgeon and vigilance to potential rare anatomic aberrations of the facial nerve during cochlear implantation. IV.


The role of osteopontin and osteopontin aptamer (OPN-R3) in fibroblast activity.
Scarring is believed to be caused by both persistent inflammation and overexuberant fibroblast activation. Osteopontin (OPN) is a cytokine that promotes cell activation. The absence of OPN in vivo reduces dermal scarring. This suggests that OPN is involved in scar formation; however, how OPN exerts these pro-scarring effects is unknown. RNA aptamers are short RNA molecules that bind target proteins with high affinity. The aptamer OPN-R3 (R3) blocks OPN signaling. The role of R3 in preventing dermal fibrosis is unknown. Fibroblast migration was analyzed with the use of Boyden Chambers and HEMA-3 staining. Inverted confocal microscopy was used to assess fibroblast focal adhesion length. Adhesion was measured by incubating fluorescently stained fibroblasts on OPN coated 96-well plates. CellTiter 96 AQueous non-radioactive cell proliferation assay was utilized to investigate the proliferative activity of fibroblasts. Free floating collagen lattices were utilized to assess fibroblast contractility. Human dermal fibroblasts migrated significantly in response to OPN. OPN did not induce a significant increase in focal adhesion length compared with controls. Adhesion studies demonstrated that OPN increased fibroblast adhesion. Proliferation assays indicate that OPN increased fibroblast growth. OPN increased fibroblast contractility of collagen lattices. The addition of R3 significantly inhibited OPN-induced activity. OPN is associated with scar and exerts pro-scarring effects by increasing cellular migration, adhesion, proliferation, and contractility of human dermal fibroblasts. R3 prevents OPN mediated activity. OPN may be useful for promoting closure of non-healing wounds and the OPN specific aptamer, R3, may be useful for preventing fibrosis.


The Abbe island flap for the correction of whistle deformity.
An Abbe flap with the skin removed was used in four cases of whistle deformity after bilateral clefts. The Abbe flaps were converted into island flaps by incising the mucosa all around the pedicle. The results obtained were considered to be superior to those obtained by using neighbouring tissues from the upper lip as more bulk was supplied as well as a perfect lining for the reconstruction of the tubercle of the upper lip vermilion. The balance between the lips was improved. The technique is recommended for patients with severe shortage of vermilion in the midline.


Measuring the "Sandwich": Care for Children and Adults in the American Time Use Survey 2003-2012.
While the economic burden of simultaneously caring for young and old family members is widely recognized, it has yet to be accurately measured. Yet, such assessments are relevant both to public policies providing support to family caregivers and to private insurance markets for long-term care. This descriptive study presents a new method to address this problem: the construction of a crosswalk between time-use diaries and other types of surveys using lists of activities of daily living (ADLs) and instrumental activities of daily living (IADLs) for which assistance is required. Analysis of pooled data from American time use survey 2003-2012 provides some quantitative indicators, but understates the temporal burden of care and fails to distinguish types of care that involve personal interaction from those that do not. A crosswalk of time-use survey categories with the list-based approach typically applied in public health surveys clearly demonstrates the importance of clear definitions and also offers more precise measures. Depending on how sandwich caregiving was defined, the temporal burden for caregiving ranged from 11.2 to 60 h per week, clustering at around 20 h per week for most cases. This result demonstrates the magnitude of sandwich care demands and also underscores the need for improved care survey design. As shown in this study, such efforts should take into account the implications of disaggregating data by gender and age, and definitional variations that characterize existing datasets.


Nutritious crops producing multiple carotenoids--a metabolic balancing act.
Plants and microbes produce multiple carotenoid pigments with important nutritional roles in animals. By unraveling the basis of carotenoid biosynthesis it has become possible to modulate the key metabolic steps in plants and thus increase the nutritional value of staple crops, such as rice (Oryza sativa), maize (Zea mays) and potato (Solanum tuberosum). Multigene engineering has been used to modify three different metabolic pathways simultaneously, producing maize seeds with higher levels of carotenoids, folate and ascorbate. This strategy may allow the development of nutritionally enhanced staples providing adequate amounts of several unrelated nutrients. By focusing on different steps in the carotenoid biosynthesis pathway, it is also possible to generate plants with enhanced levels of several nutritionally-beneficial carotenoid molecules simultaneously.


Unreliable patient identification warrants ABO typing at admission to check existing records before transfusion.
This study describes patient identification errors leading to transfusional near-misses in blood issued by the Alps Mediterranean French Blood Establishment (EFSAM) to Marseille Public Hospitals (APHM) over an 18-month period. The EFSAM consolidates 14 blood banks in southeast France. It supplies 149 hospitals and maintains a centralized database on ABO types used at all area hospitals. As an added precaution against incompatible transfusion, the APHM requires ABO testing at each admission regardless of whether the patient has an ABO record. The study goal was to determine if admission testing was warranted. Discrepancies between ABO type determined by admission testing and records in the centralized database were investigated. The root cause for each discrepancy was classified as specimen collection or patient admission error. Causes of patient admission events were further subclassified as namesake (name similarity) or impersonation (identity fraud). The incidence of ABO discrepancies was 1:2334 including a 1:3329 incidence of patient admission events. Impersonation was the main cause of identity events accounting for 90.3% of cases. The APHM's ABO control policy prevented 19 incompatible transfusions. In relation to the 48,593 packed red cell units transfused, this would have corresponded to a risk of 1:2526. Collecting and storing ABO typing results in a centralized database is an essential public health tool. It allows crosschecking of current test results with past records and avoids redundant testing. However, as patient identification remains unreliable, ABO typing at each admission is still warranted to prevent transfusion errors.


Elicitation of defense related enzymes and resistance by L-methionine in pearl millet against downy mildew disease caused by Sclerospora graminicola.
Induction of resistance to downy mildew in pearl millet was studied after treatment with L-methionine. The disease severity was drastically reduced in the seedlings after treatment with L-methionine. Northern hybridization was used to study the transcript (mRNA) accumulation of defense response genes upon treatment with L-methionine in pearl millet seedlings and the mechanism during the induction of resistance. The gene activation patterns in the highly resistant cultivar IP18294 were compared with those exhibited by the susceptible cultivar 7042S at various time intervals to determine if differences in timing or levels of transcript accumulation could be correlated with the differences in the susceptibility of pearl millet to the downy mildew pathogen, Sclerospora graminicola. The mRNA levels of genes for Pr-1a, beta-1,3-glucanase, chitinase, peroxidase, lipoxygenases and chalcone synthase showed an increase after inoculation with S. graminicola. Significant gene activation was observed in the susceptible cultivar 7042S after treatment with L-methionine followed by challenge inoculation with the downy mildew pathogen which was comparable to the resistant cultivar.


Observation versus prophylactic Ladd procedure for asymptomatic intestinal rotational abnormalities in heterotaxy syndrome: A systematic review.
The management of intestinal rotational abnormalities (IRA) in heterotaxy syndrome (HS) remains inconsistent. Because of the high incidence of malrotation in HS, screening of asymptomatic patients is standard of care in some institutions. The Ladd procedure is the treatment for malrotation, and has been reported to have high complication rates in HS patients. We performed a systematic review of publications describing IRA in pediatric HS patients from January 1993 to present. The incidence of volvulus on surgical exploration was determined. Perioperative and long-term outcomes were analyzed to determine complication and mortality rates. Eleven retrospective studies describing 649 HS patients were identified. Of all patients with HS, 27% (176/649) underwent Ladd procedure. Only 1.2% (8/649) of HS patients included had volvulus. Postoperative complications occurred in 25 patients (14%), including a 10% incidence of small bowel obstruction. Perioperative and overall mortality rates after Ladd procedure were 3% and 21%, respectively. Six studies described mesenteric width, reporting 43% to have narrow mesentery. The Ladd procedure is not without significant morbidity and mortality in heterotaxy patients. Further prospective studies should investigate predictors of mesenteric width to spare the unnecessary morbidity of surgery in patients who are at low risk for volvulus.


Treatment and prognostic factors in patients with hepatocellular carcinoma.
Hepatocellular carcinoma is a leading cause of death from cancer worldwide. Survival of patients depends on tumor extension and liver function, but yet there is no consensual prognostic model. To evaluate the influence on survival of pretreatment parameters (clinico-laboratorial, liver function, tumor extension, Okuda and Cancer of the Liver Italian program (CLIP) staging) and treatment modalities. We retrospectively analyzed 207 patients, diagnosed between 1993 and 2003. The initial treatment was: surgery--six patients; radiofrequency ablation--21; percutaneous ethanol injection--29; transarterial chemoembolization--49; tamoxifen--49; supportive care alone--53. Factors determining survival were assessed by Kaplan-Meier method and Cox regression models. Median survival was 24 months. In univariate analysis, Child-Pugh classification and Model for end-stage liver disease (MELD) score, portal vein thrombosis (PVT), tumor size, number of lesions, Okuda and CLIP scores were all associated with prognosis (P < 0.001). Alpha-fetoprotein levels were not predictive of survival. Independent predictors of survival were ascites, bilirubin, PVT and therapeutic modalities (P < 0.001). In early stage hepatocellular carcinoma (HCC), survival was similar for both percutaneous ablation modalities, either radiofrequency or ethanol injection (P = NS). In advanced HCC, survival was better in patients receiving tamoxifen than supportive care alone (P < 0.001). This study reinforces the importance of baseline liver function (Child-Pugh classification and MELD score) in the survival of patients with HCC, although staging systems allowed the stratification of patients in different prognostic groups. Ascites, bilirubin and PVT were independent pretreatment predictors of survival. All treatments influenced the patient's outcome, whether in early or advanced stages.


Comment on "anharmonic properties of the vibrational quantum computer" [J. Chem. Phys. 126, 204102 (2007)].
Suitable molecules for quantum computing cannot be discussed in terms of anharmonicity and CNOT gates alone. The validity of the approximate approach [M. Zhao and D. Babikov, J. Chem. Phys.126, 204102 (2007)] is limited. Frequencies and anharmonicities cannot be used independent from the molecule. Hermite polynomials with the linear approximation for the dipole moment lead to oversimplified gates with potentially low intensities.


Extraoral removal of a lower third molar tooth.
This case report illustrates an example of when an extraoral approach was successfully used to remove a lower left third molar.


Metabolism-Associated Molecular Patterns (MAMPs).
Metabolic diseases pose a tremendous health threat in both developed and developing countries. The pathophysiology of metabolic diseases is complex but has been shown to be closely associated with sterile inflammation, which is initiated by various danger molecules derived from metabolic overload, such as oxidized low-density lipoproteins (OxLDLs), free fatty acids (FFAs), glucose, advanced glycation end products (AGEs), and cholesterol. These danger signals are sensed by pattern recognition receptors (PRRs) to activate proinflammatory signaling pathways and promote the release of proinflammatory mediators, leading to chronic low-grade inflammation. Although these harmful metabolic stimuli are generally regarded as damage-associated molecular patterns (DAMPs), a more specific definition and accurate classification for these DAMPs is still missing. In this opinion, we classify the harmful metabolic stimuli that can incite inflammatory responses and tissue damage via instigating PRRs as metabolism-associated molecular patterns (MAMPs), and we summarize their roles in metaflammation-mediated metabolic diseases.


miR-155 and miR-92 levels in ALL, post-transplant aGVHD, and CMV: possible new treatment options.
Acute lymphoblastic leukemia (ALL) is a malignancy that leads to altered blast cell proliferation, survival, and maturation and eventually to the lethal accumulation of leukemic cells. Recently, dysregulated expression of various micro-RNAs (miRNAs) has been reported in hematologic malignancies, especially ALL. Cytomegalovirus infection can induce ALL in otherwise healthy individuals, so a more detailed evaluation of its role in ALL-endemic areas like Iran is required. In this cross-sectional study, 70 newly diagnosed adults with ALL were recruited. The expression level of microRNA-155(miR-155) and microRNA-92(miR-92) was evaluated by real-time SYBR Green PCR. The correlations between the miRNAs mentioned above and the severity of disease, CMV infection, and acute graft vs. host disease after hematopoietic stem cell transplantation (HSCT) were assessed. B cell and T cell ALL distinction in the level of miRNAs was provided. After the statistical analysis, our results indicated a marked increase in the expression of miR-155 and miR-92 in ALL patients vs. healthy controls (*P = 0.002-*P = 0.03, respectively). Also, it was shown that the expression of miR-155 and miR-92 was higher in T cell ALL compared to B cell ALL (P = 0.01-P = 0.004, respectively), CMV seropositivity, and aGVHD. Our study suggests that the plasma signature of microRNA expression may act as a powerful marker for diagnosis and prognosis, providing knowledge outside cytogenetics. Elevation of miR-155 in plasma can be a beneficial therapeutic target for ALL patients, with consideration of higher plasma levels of miR-92 and miR-155 in CMV + and post-HSCT aGVHD patients.


Neuronal spike activity in the nucleus accumbens of behaving rats during ethanol self-administration.
Many lines of evidence support the importance of the nucleus accumbens (NAC) for ethanol-reinforced behavior. The nature of the neuronal activity that occurs in this region during ethanol self-administration is not known. We recorded from ensembles of single-units primarily located within the shell of the NAC during operant responding for oral ethanol solutions by well-trained rats. Of 90 units recorded from seven sessions from seven rats, 41 (46%) did not exhibit significant changes in relation to the experimental events. Of the 49 units (54%) that did exhibit significant phasic changes, alterations in firing rate occurred in relation to the following experimental events: operant response (63%), tone stimulus (20%), and ethanol delivery (63%). In addition, changes in spike activity during the intervals between the three experimental events were noted in 33% of the units. Most units (55% of responsive units) responded to multiple experimental events. Thus different but overlapping populations of neurons in the NAC represent each event that occurs along the temporal dimension of a single trial performed to obtain ethanol reward. The data suggest that the NAC plays a crucial role in linking together conditioned and unconditioned internal and external stimuli with motor plans to allow for ethanol-seeking behavior to occur.


The RNA-Binding Proteins OAS1, ZFP36L2, and DHX58 Are Involved in the Regulation of CD44 mRNA Splicing in Colorectal Cancer Cells.
Regulation of alternative splicing is carried out by RNA-binding proteins. Each alternative splicing event is controlled by several RNA-binding proteins, which in combination create the distribution of alternative splicing products in a given cell type. Transmembrane protein CD44 plays an important role at various stages of the metastatic cascade and is considered as a promising molecule for the therapy of tumor diseases and the construction of prognostic classifiers. However, the functions of specific isoforms of this protein may differ significantly. In this work, we performed a bioinformatic search of RNA-binding proteins that can determine the expression of clinically significant isoforms 3 and 4 of CD44 protein. The analysis revealed five RNA-binding proteins, three of which (OAS1, ZFP36L2, and DHX58) are shown for the first time as potential regulators of the studied process.


When Is Primary Metacarpal Corrective Osteotomy Recommended in Patients with Flatt Type IV Radial Polydactyly?
The aim of this study was to determine when primary metacarpal corrective osteotomy is recommended in patients with Flatt type IV radial polydactyly. A total of 78 patients with Flatt type IV radial polydactyly were included. The authors performed metacarpal osteotomy if the angulation of the metacarpophalangeal joint was not correctable by the intraoperative radial stress test. The authors measured the metacarpal deviation angle of the thumb in simple posteroanterior radiographs. The clinical outcomes were assessed using Japanese Society for Surgery of the Hand evaluation total score and the metacarpal deviation angle correction angle. These outcomes were compared between the patients who underwent metacarpal osteotomy and those who did not. Of the patients who did not undergo metacarpal osteotomy, the relationships between preoperative metacarpal deviation angle and the metacarpal deviation angle correction angle were formulated using segmented linear regression analysis. There were no significant differences in the demographic features and the value of preoperative metacarpal deviation angle between the two groups. However, the metacarpal deviation angle correction angle and Japanese Society for Surgery of the Hand evaluation total score were significantly higher in the patients who underwent metacarpal osteotomy. The segmented linear regression analysis demonstrated a breakpoint, indicating that the soft-tissue procedure alone does not sufficiently correct the metacarpal deviation angle. For the postoperative metacarpal deviation angle to be 5 degrees, the preoperative metacarpal deviation angle was calculated as 10.8 degrees. If the preoperative metacarpal deviation angle is greater than 10.8 degrees, metacarpal osteotomy can be considered even in patients with correctable metacarpophalangeal joint by intraoperative radial stress test. Therapeutic, III.


Overview of metabolomic aspects in postpartum depression.
Along with the typical biochemical alterations that occur during pregnancy, certain metabolic changes might be associated with the development of several psychiatric disorders, including postpartum depression (PPD), which is the most common type of psychiatric disorder during pregnancy or first postpartum year, and it develops in about 15% of women. Metabolomics is a rapidly developing discipline that deals with the metabolites as the final products of all genetically controlled biochemical pathways, highly influenced by external and internal changes. The aim of this paper was to review the published studies whose results suggest or deny a possible association between the fine regulation of the metabolome and PPD, enabling conclusions about whether metabolomics could be a useful tool in defining the biochemical pathways directly involved in the etiology, diagnosis and course of PPD. Beside numerous hormonal changes, a lot of different metabolic pathways have been discovered to be affected in women with PPD or associated with its development, including alterations in the energy metabolism, tryptophan and amino acid metabolism, steroid metabolism, purine cycle, as well as neurotransmitter metabolism. Additionally, metabolomics helped in defining the association between PPD and the exposure to various endocrine disrupting metabolites during pregnancy. Finally, metabolome reflects different PPD therapies and exposure of fetus or breastfed infants to pharmacotherapy prescribed to a mother suffering from PPD. This review can help in creating the picture about metabolomics' broad application in PPD studies, but it also implies that its potential is still not completely used.


Acoustic cardiography augments prolonged QRS duration for detecting left ventricular dysfunction.
Prolonged QRS duration has been used as a marker for left ventricular (LV) systolic dysfunction (SD) and is used in the evaluation of patients presenting with known or suspected heart failure. The goal of this study was to compare the abilities of QRS duration and simultaneous digital ECG and heart sounds, that is acoustic cardiographic, parameters to identify patients with LV dysfunction. Our learning population consisted of 171 patients with possible chronic compensated or mildly decompensated heart failure who presented to an ambulatory cardiology clinic for echocardiographic examination. We defined LVSD as a LV ejection fraction < 50%, and estimated LV filling pressures from diastolic measurements. These patients also had acoustic cardiographic recordings from which we obtained a variety of individual ECG and acoustic cardiographic parameters. We used the product of four of these parameters to obtain a diagnostic score for LV dysfunction. We then compared the diagnostic performances of QRS duration and the score on a test population of patients who presented to an emergency department with possible heart failure. In the learning population, the sensitivities/specificities of QRS duration > or =120 ms and the score for prediction of LVSD were 51%/92% and 77%/90%, respectively. In the test population, the score remained superior to QRS duration for detecting LVSD as well as acute decompensated heart failure. Improved identification of LVSD and clinical heart failure can be achieved with a cost-effective bedside screening tool with the simple combination of simultaneously acquired digital ECG and heart sound data.


Placental extract suppresses the formation of fibrotic deposits by tumor necrosis factor alpha and transforming growth factor beta-induced epithelial-mesenchymal transition in ARPE-19 cells.
Epithelial-mesenchymal transition (EMT) is involved in the development of proliferative vitreoretinopathy (PVR) and subsequent fibrosis. Previously, we demonstrated that placental extract ameliorates fibrosis in a mouse model of non-alcoholic steatohepatitis. In this study, we evaluated whether placental extract influences EMT and fibrosis through cytokine-induced EMT in the retinal pigment epithelial cells, in vitro. Placental extract did not inhibit EMT, but it suppressed excessive mesenchymal reactions and the subsequent fibrosis. These results suggest that placental extract effectively ameliorates EMT-associated fibrosis in PVR. This beneficial effect could be partially attributed to the suppression of excessive mesenchymal reactions.


Dynamic visual-vestibular integration during goal directed human locomotion.
Normal visual input plays a very dominant role during locomotion. Functionally, it can assist the central nervous system to overcome a destabilizing effect of abnormal or perturbed vestibular information. However, a recent study has shown a directional effect of transmastoidal galvanic vestibular stimulation (GVS) on gait trajectory when visual information is unreliable. The purpose of this study was to investigate how inputs from the visual and vestibular systems are weighted to optimize locomotor performance under impoverished visual conditions during goal directed locomotion. For unimodal stimulation, the visual input was manipulated using displacing prisms that caused 14 degrees horizontal displacement of perceived target location to the right or left. In addition, GVS (0.8 mAmp) was applied to manipulate vestibular system information during bimodal stimulation conditions. Two bimodal stimulation conditions were defined by the polarity of the galvanic current (anode on congruent and incongruent sides of prismatic deviation). The center of mass (CoM) displacement, head and trunk yaw angles and trunk roll angles were computed to analyze the global output as well as segmental coordination, as the participants walked towards the target. Although the performance was primarily guided by visual information, both congruent and incongruent GVS significantly altered CoM displacement. Similarly, the basic pattern of segmental responses during steering was maintained; however, the magnitude of the responses was altered. Spatio-temporal analysis demonstrated that during bimodal stimulation, the effect of GVS on global output tapered off as the participants approached the target. Results suggest a dynamic visual-vestibular interaction in which the gain of the vestibular input is initially upregulated in the presence of insufficient or impoverished visual information. However, there is a gradual habituation and the visual information, although insufficient, primarily dominates during goal directed locomotion. The experimental trajectories resembled mathematically simulated trajectories with a decaying GVS gain as opposed to a constant gain, further supporting the dynamic nature of sensory integration.


Association between preoperative neutrophil-lymphocyte ratio and mortality after plastic and reconstructive surgery.
Predictive factors associated with postoperative mortality have not been extensively studied in plastic and reconstructive surgery. Neutrophil-lymphocyte ratio (NLR), a systemic inflammation index, has been shown to have a predictive value in surgery. We aimed to evaluate association between preoperative NLR and postoperative outcomes in patients undergoing plastic and reconstructive surgery. From January 2011 to July 2019, we identified 7089 consecutive adult patients undergoing plastic and reconstructive surgery. The patients were divided according to median value of preoperative NLR of 1.84. The low NLR group was composed of 3535 patients (49.9%), and 3554 patients (50.1%) were in the high NLR group. The primary outcome was mortality during the first year, and overall mortality and acute kidney injury were also compared. In further analysis, outcomes were compared according to quartile of NLR, and a receiver operating characteristic curve was constructed to estimate the threshold associated with 1-year mortality. This observational study showed that mortality during the first year after plastic and reconstructive surgery was significantly increased in the high NLR group (0.7% vs. 3.5%; hazard ratio, 4.23; 95% confidence interval, 2.69-6.63; p < 0.001), and a graded association was observed between preoperative NLR and 1-year mortality. The estimated threshold of preoperative NLR was 2.5, with an area under curve of 0.788. Preoperative NLR may be associated with 1-year mortality after plastic and reconstructive surgery. Further studies are needed to confirm our findings.


"Costs" of reproduction in reptiles.
Many theoretical models of life-history evolution rely on the existence of trade-offs between current fecundity and probable future fecundity and survival. Such "costs" of reproduction have been demonstrated only rarely. Field and laboratory studies on six species of Australian scincid lizards show that gravid females are more vulnerable to predation than are non-gravid females, primarily because (i) they are physically burdened (running speeds are reduced by 20 to 30%), and (ii) they bask more often (in some species). However, food intake is not reduced in gravid animals. A review of published literature suggests that reproductive trade-offs are widespread among reptiles, but the nature of the reproductive "costs" may vary widely among related species. Within the range of annual survivorship rates of most lizard species, trade-offs between fecundity and survival are likely to be the main evolutionary determinants of optimal levels of "reproductive effort". Trade-offs between fecundity and bodily growth are less likely to be significant.


Developmental and aging changes in somatosensory, auditory and visual evoked potentials.
To assess developmental and aging changes in human sensory systems, components of short-latency somatosensory, brain-stem auditory and pattern-reversal visual evoked potentials, thought to originate in specific structures of these systems, were recorded in 286 normal subjects ranging in age from 4 to 95 years. Analysis was primarily restricted to peak and interpeak latencies; visual evoked potential amplitudes were also analyzed. Major results and conclusions are: (1) 'Developmental' changes (that is, decreases in latency attributable to decreased conduction time in younger subjects) were not seen in the median nerve, in brain-stem auditory pathways, or in some portions of visual cortex. Small developmental changes were seen in the somatosensory afferent pathway from the cervical spinal cord to thalamus, and large changes were seen in somatosensory and visual cortex. Cortical developmental changes appeared not to be complete until 17 years of age or later. (2) 'Aging' changes (that is, increases in latency attributable to increased conduction time in older subjects) were observed in the median nerve, cervical spinal cord, brain-stem auditory pathways, and somatosensory and visual cortex. (3) Visual evoked potential amplitudes tended to decrease with age, particularly during development; amplitude and latency effects were dissimilar for most components. (4) Males tended to show larger aging effects than females. (5) The results suggest that age-related changes in human sensory systems are not uniform, but rather are different in specific portions of these systems, different at particular epochs of the life span, and stronger in males than in females.


Diagnostic Value of Selected Echocardiographic Variables to Identify Pulmonary Hypertension in Dogs with Myxomatous Mitral Valve Disease.
Pulmonary hypertension (PH) is commonly associated with myxomatous mitral valve disease (MMVD). Because dogs with PH present without measureable tricuspid regurgitation (TR), it would be useful to investigate echocardiographic variables that can identify PH. To investigate associations between estimated systolic TR pressure gradient (TRPG) and dog characteristics and selected echocardiographic variables. 156 privately owned dogs. Prospective observational study comparing the estimations of TRPG with dog characteristics and selected echocardiographic variables in dogs with MMVD and measureable TR. Tricuspid regurgitation pressure gradient was significantly (P < .05) associated with body weight corrected right (RVIDDn) and left (LVIDDn) ventricular end-diastolic and systolic (LVIDSn) internal diameters, pulmonary arterial (PA) acceleration to deceleration time ratio (AT/DT), heart rate, left atrial to aortic root ratio (LA/Ao), and the presence of congestive heart failure. Four variables remained significant in the multiple regression analysis with TRPG as a dependent variable: modeled as linear variables LA/Ao (P < .0001) and RVIDDn (P = .041), modeled as second order polynomial variables: AT/DT (P = .0039) and LVIDDn (P < .0001) The adjusted R(2) -value for the final model was 0.45 and receiver operating characteristic curve analysis suggested the model's performance to predict PH, defined as 36, 45, and 55 mmHg as fair (area under the curve [AUC] = 0.80), good (AUC = 0.86), and excellent (AUC = 0.92), respectively. In dogs with MMVD, the presence of PH might be suspected with the combination of decreased PA AT/DT, increased RVIDDn and LA/Ao, and a small or great LVIDDn.


Estradiol target neurons in the hypothalamic arcuate nucleus and lateral ventromedial nucleus of young adult, reproductively senescent, and monosodium glutamate-lesioned female golden hamsters.
Histoautoradiographic methods were used to assess estrogen target neurons in the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus, lateral portion (LVM), comparing young adult and aged female golden hamsters. A subgroup of young adult females had ARC lesions induced by monosodium glutamate at neonatal day 8. All were ovariectomized to remove endogenous estrogens. Controls were given nonradioactive estradiol. After 3H-estradiol (3H-E2) was injected intravenously, hypothalami were removed, frozen, and processed for histoautoradiography. In the ARC and LVM the ratio of 3H-E2 labelled neurons to total neurons counted was significantly lower in the older animals. Young females with ARC lesions had very few 3H-E2 labelled neurons remaining in the ARC but had a normal complement in the LVM. Although 3H-E2 labelled ARC neurons were notably decreased in old females, those ARC neurons that were labelled in the old had virtually the same frequency distribution of the labelling index as in the young, suggesting no change in the average estrogen uptake per target cell.


Rapid methods for comparing the double-stranded RNA genome profiles of bluetongue virus.
Various double-stranded RNA extraction procedures, gel electrophoresis systems, and methods to detect the RNA bands in the gel were investigated to find the most rapid methods to obtain the genome profiles of bluetongue virus in small volumes (1-25 ml) of infected cell culture fluids. Rapid double-stranded RNA extraction procedures coupled with staining the acrylamide gel slabs with ethidium bromide or silver nitrate resulted in well-defined genome profiles from bluetongue virus infected cell cultures in 6-48 h. Radioactive labelling of viral RNA with 32P was time consuming, cumbersome and expensive. These techniques detect less than 0.5 micrograms of double-stranded RNA which can be obtained from one 1-ml well of a 24-well cluster plate of bluetongue virus infected cell monolayers. The methods were therefore suitable for rapid comparisons of the electropherotypes of multiple virus isolates.


The Hidden Pathways in Dense Energy Materials - Oxygen at Defects in Nanocrystalline Metals.
Highly abundant oxygen-rich line defects (blue) can act as fast oxygen transport paths. These defects show similar chemistry and therefore similar catalytic activity to the materials surface. These results provide the opportunity to design and produce simple scalable structures as catalysts, whose functionality derives from internal defects rather than from the materials surfaces.


Spatial Distribution and Temporal Patterns of Cassin's Auklet Foraging and Their Euphausiid Prey in a Variable Ocean Environment.
Krill (Euphausiids) play a vital ecosystem role in many of the world's most productive marine regions, providing an important trophic linkage. We introduce a robust modeling approach to link Cassin's auklet (Ptychoramphus aleuticus) abundance and distribution to large-scale and local oceanic and atmospheric conditions and relate these patterns to similarly modeled distributions of an important prey resource, krill. We carried out at-sea strip transect bird surveys and hydroacoustic assessments of euphausiids (2004-2013). Data informed separate, spatially-explicit predictive models of Cassin's auklet abundance (zero-inflated negative binomial regression) and krill biomass (two-part model) based on these surveys. We established the type of prey responsible for acoustic backscatter by conducting net tows of the upper 50 m during surveys. We determined the types of prey fed to Cassin's auklet chicks by collecting diet samples from provisioning adults. Using time-depth-recorders, we found Cassin's auklets utilized consistent areas in the upper water column, less than 30 m, where krill could be found (99.5% of dives were less than 30 m). Birds primarily preyed upon two species of euphausiids, Euphausia pacifica and Thysanoessa spinifera, which were available in the upper water column. Cassin's auklet abundance was best predicted by both large scale and localized oceanic processes (upwelling) while krill biomass was best predicted by local factors (temperature, salinity, and fluorescence) and both large scale and localized oceanic processes (upwelling). Models predicted varying krill and bird distribution by month and year. Our work informs the use of Cassin's auklet as a valuable indicator or krill abundance and distribution and strengthens our understanding of the link between Cassin's auklet and its primary prey. We expect future increases in frequency and magnitude of anomalous ocean conditions will result in decreased availability of krill leading to declines in the Farallon Islands population of Cassin's auklets.


Association between gastrointestinal symptoms and health-related quality of life after heart transplantation.
Heart transplantation (HTx) ameliorates the self-perceived health-related quality of life (HRQoL) of patients with terminal heart disease; gastrointestinal (GI) symptoms, due to obligatory immunosuppression, may contribute to impaired HRQoL post-HTx. In this cross-sectional, exploratory study we aimed to investigate association between GI symptoms and HRQoL. The study consisted of 167 patients who had undergone HTx between 1985 and 2006 in Finland. Short-Form 36 (SF-36) Quality of Life and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires were sent to the patients at the end of 2006 for capturing data on the HRQoL of HTx recipients. Higher or equal SF-36 scores describing the HRQoL dimensions compared with the Finnish age- and gender-matched reference population were as follows: physical functioning, 60.5%; role-physical, 67.5%; bodily pain, 62.6%; general health, 64.0%; vitality, 68.1%; social functioning, 68.1%; role-emotional, 70.0%; and mental health, 70.4%. The prevalence of troublesome GI symptoms (GSRS score >1) per GSRS dimension was 53.9% for diarrhea, 91.0% for indigestion, 60.6% for constipation, 73.4% for abdominal pain, 46.4% for reflux and 95.8% for any GI symptom. Diabetes contributed to the presence of diarrhea (odds ratio [OR]: 3.00; 95% confidence interval [CI]: 1.12 to 8.00), use of prednisolone to indigestion (OR: 3.21; 95% CI: 1.05 to 9.79) and increased age to constipation (OR: 1.04; 95% CI: 1.02 to 1.07). HRQoL after HTx is relatively good and comparable to the age- and gender-matched reference population. HRQoL is vulnerable to side-effects caused by the obligatory post-HTx immunosuppressive regimen, where GI symptoms play a major but clearly an underestimated role.


Assessment of automated cone-beam CT vessel identification software during transarterial hepatic embolisation: radiation dose, contrast medium volume, processing time, and operator perspectives compared to digital subtraction angiography.
To evaluate arterial cone-beam computed tomography (A-CBCT) automated analysis software for identification of vessels supplying tumours during transarterial hepatic embolisation (TAE). This study was approved by the institutional review board, with waiver of consent. Consecutive TAE procedures using arterial mapping software (AMS), and performed between February 2014 and August 2014, were reviewed. Hepatic arteries were imaged using digital subtraction angiography (DSA) as well as A-CBCT processed with AMS. Interventional radiologists reported1 potential embolisation target vessels computed using AMS versus DSA alone,2 modification of the embolisation plan based on AMS, and3 operator confidence related to technical success. Imaging set-up, processing time, radiation dose, and contrast media volume were recorded. Thirty of 34 consecutive procedures were evaluated retrospectively. At least one additional embolisation target vessel was identified using AMS in 13 procedures (43%, 95% confidence interval [CI]: 26-61%) and embolisation plan modified in 11 (37%, 95% CI: 19-54%). Radiologists reported AMS increased operator confidence and reduced the number of DSA acquisitions in 25 (83%, 95% CI: 70-97%) and 15 cases (50%, 95% CI: 32-68%), respectively. The average A-CBCT acquisition and processing time was 4 minutes 53 seconds and 3 minutes 45 seconds, respectively. A-CBCT contributed to 11% of the radiation dose and 18% of the contrast media volume. Physicians report increased tumour supplying vessel detection and intraprocedural confidence using AMS during TAE without substantial impact on radiation dose, contrast media volume, and procedure time.


Adeno-associated virus type 2 vectors: transduction and long-term expression in cerebellar Purkinje cells in vivo is mediated by the fibroblast growth factor receptor 1 : bFGFR-1 mediates AAV2 transduction of Purkinje cells.
The receptor for adeno-associated virus serotype 2 (AAV2) in Purkinje cells has not been identified, but based on work carried out in non-neuronal cell lines, heparan sulfate proteoglycan is thought to act as a primary receptor, with basic fibroblast growth factor receptor-1 being reported as a co-receptor. In this study, using antibody interference and protein competition strategies, we show specific reduction in Purkinje cell transduction by AAV2 vector in the presence of these inhibitors. We also demonstrate AAV2-mediated transgene expression in Purkinje cells in vivo that extends out to one year post-injection. These results provide new information on fibroblast growth factor receptor-1 involvement in AAV2-mediated transduction of Purkinje cells and have important implications for AAV-mediated treatment of various cerebellar disorders.


Bioelectric impedance measurements using synchronous sampling.
We have applied synchronous sampling to the demodulation of bioelectric impedance signals. This overcomes the need for analog demodulators in bioimpedance measurements. The sampling rate is determined by signal bandwidth, rather than by the highest frequency component before demodulation.


Immunoglobulin synthesis by lymphoid cells transformed in vitro by Abelson murine leukemia virus.
The majority of cell lines derived by infection of murine bone marrow cells with Abelson murine leukemia virus (A-MuLV) synthesize a mu chain but no detectable light chain. Aside from this mu-only phenotype, lines that make only light chain, both chains or no immunoglobulin-related polypeptides have also been found. Two lines have been studied in detail: one that makes only mu chain and one that makes only kappa light chain. Synthesis of both polypeptides can be increased by modifying the culture conditions so as to decrease the growth rate of the cells. Although some kappa chain secretion was observed, neither secreted nor surface mu was detected. We suggest that the mu- only phenotype may be an early normal step in the pathway of B lymphocyte maturation.


Functional carotid paragangliomas. Biochemical, ultrastructural, and histochemical correlation with clinical symptoms.
To our knowledge, this study is the first to correlate the results of biochemical, electron microscopic (EM), and histochemical analyses of tissues from functional paragangliomas of the upper carotid area with a patient's clinical symptoms. The tumor tissues from our two patients contained epinephrine, norepinephrine, and dopamine. Neurosecretory granules were identified in both tumors by EM and by the Grimelius silver stain. The patient with the most severe symptoms exhibited evidence of higher circulating levels of catecholamines by biochemical, EM, and histochemical analyses.


Current Swiss Techniques in Management of Lisfranc Injuries of the Foot.
The outcome after Lisfranc injuries correlates with anatomic and stable reduction. The best surgical treatment, particularly for the ligamentous Lisfranc injuries, remains controversial. Recent publications suggest that the ligamentous injuries may benefit from primary partial Lisfranc arthrodesis. Most surgeons agree that an appropriate reduction is better and easier achieved by open reduction and stable temporary screw or dorsal plate fixation or by open primary partial arthrodesis than by closed reduction or Kirschner wire fixation. Despite correct surgical technique and postoperative management, symptom-free recovery is uncommon. This article outlines current techniques in the management of Lisfranc injuries and resultant postoperative outcomes in a level I trauma center.


Preemptive interferon-α treatment could protect against relapse and improve long-term survival of ALL patients after allo-HSCT.
Relapse was the major cause of treatment failure in patients with acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of preemptive interferon-α (IFN-α) treatment in ALL patients who had minimal residual disease (MRD) after allo-HSCT. Multiparameter flow cytometry and polymerase chain reaction assays were applied for MRD monitoring. Recombinant human IFN-α-2b injections were administered subcutaneously twice weekly in every 4 weeks cycle. Twenty-four (35.3%), 5 (7.4%), 6 (8.8%), and 13 (19.1%) patients achieved MRD negativity at 1, 2, 3, and > 3 months, respectively, after treatment. Seven patients showed grade ≥ 3 toxicities after IFN-α treatment. The 4-year cumulative incidence of total acute graft-versus-host disease (aGVHD), severe aGVHD, total chronic GVHD (cGVHD), and severe cGVHD after treatment was 14.7%, 2.9%, 40.0%, and 7.5%, respectively. The 4-year cumulative incidences of relapse and non-relapse mortality after treatment was 31.9% and 6.0%, respectively. The 4-year probabilities of disease-free survival and overall survival after IFN-α treatment were 62.1% and 71.1%, respectively. Thus, preemptive IFN-α treatment could protect against relapse and improve long-term survival for ALL patients who had MRD after allo-HSCT. The study was registered at https://clinicaltrials.gov as #NCT02185261 (09/07/2014).


A potential cardiovascular mechanism for the behavioral effects of central and peripheral arginine vasotocin.
Few studies have attempted to separate the behavior modulating actions of central and peripheral arginine vasotocin/arginine vasopressin (AVT/AVP) from their roles in the endocrine and cardiovascular stress response. This series of experiments explored the relative contributions of AVT's central and peripheral mechanisms on altering behavior while simultaneously investigating AVT's effects on the behavioral, cardiovascular, and corticosteroid responses to acute stressors in European starlings (Sturnus vulgaris). Results illustrated peripheral AVT's ability to decrease feeding, drinking, preening, and overall activity. Effects on feeding, drinking, and preening were similar after AVT injection into the lateral ventricles, but the central effects were not blocked by dPTyr(Me)AVP, a selective AVT receptor blocker. This suggests that AVT's behavioral effects may not depend solely on a receptor mediated central mechanism. However, both central and peripheral AVT attenuated heart rate independent of increased plasma corticosterone. These data suggest that AVT's behavioral effects may be modulated by a corticosterone-independent cardiovascular mechanism.


Removal of chromium (VI) from water by porous carbon derived from corn straw: Influencing factors, regeneration and mechanism.
Porous carbon is one of the most widely used materials to remove Cr(VI) from polluted water. Here we reported one efficient porous carbon material prepared from corn straw. The results of Fourier transform infrared spectroscopy (FTIR), Energy dispersion spectrum (EDS), and X-ray photoelectron spectroscopy (XPS) indicated that the porous carbon surface had functional groups such as COOH, OH and COC, etc, which could be acted as active sites during the adsorption process. Brunauer-Emmett-Teller (BET) results showed that the surface area and total pore volume of the adsorbent were 2131.181 m2/g and 1.128 cm3/g, respectively. The percentages of micropore surface area and micropore volume achieved 91.93% and 80.43%, respectively. The maximum adsorption capacity of Cr(VI) was 175.44 mg/g at 25 °C with the well-developed microporous structure and abundant oxygen-containing functional groups of porous carbon. The adsorption process was well described by the pseudo-second order model and Langmuir adsorption isotherm model. It was mainly based on chemical adsorption of a single molecular layer, accompanied by ion exchange reaction, Cr(VI) reduction, and complexation, etc. The adsorbent exhibited excellent removal performance of Cr(VI) in the co-existing ions wastewater and electroplating wastewater, and could remain high removal performance for four adsorption-desorption cycles.


Effect of auricular acupressure for postpartum insomnia: an uncontrolled clinical trial.
This study examined the effects of auricular acupressure therapy on women with postpartum insomnia. Postpartum women generally have poor sleep quality because of frequent night-time breastfeeding during the first month after giving birth. A one-group pretest/post-test quasi-experiment was conducted. A convenience sampling method was used to recruit participants at a postpartum centre (doing-the-month centre) in Northern Taiwan, from January 2014-July 2014. Thirty women with postpartum insomnia received auricular acupressure therapy on one auricular point (Shenmen point pressing) four times a day for 14 days. The Chinese version of the Pittsburgh Sleep Quality Index was used to assess sleep quality before and after the 14-day treatment. After the 14-day auricular acupressure treatment, the Pittsburgh Sleep Quality Index total scores of the women decreased from 8·7 (pretest) to 5·57 (post-test, 36% reduction). Scores on the subscales of the Pittsburgh Sleep Quality Index, including sleep quality, sleep latency, sleep duration and sleep disturbance, also statistically improved (p < 0·05). Hormone changes and frequent breastfeeding were identified as characteristics that may exacerbate poor sleep quality of postpartum women, for whom the auricular acupressure intervention may effectively improve sleep quality. Auricular acupressure can be an alternative complementary therapy to aid postpartum women with insomnia in improving sleep quality.


Clinicopathological significance of androgen receptor expression in extramammary Paget disease: An analysis of 92 patients.
Extramammary Paget disease (EMPD) is a rare cutaneous malignant neoplasm arising in apocrine gland-rich areas. Although - like normal apocrine glands - EMPD frequently expresses androgen receptor (AR), the clinical significance of AR expression remains unclear. The present study investigated the clinicopathological impact of AR expression in EMPD. Immunohistochemistry for AR was performed in a retrospective cohort of 92 EMPD patients with 108 EMPD lesions, including 102 primary lesions, five lymph node [LN] metastases and one local recurrence. The total AR staining score was calculated as staining intensity score (IS 0-3) × positive-cell percentage score (PS 1-4). Expression levels were graded as Grade 1 (scores 0 and 1), Grade 2 (scores 2-4), and Grade 3 (scores 6-12). Higher expression grade was correlated with tumor thickness (P = 0.011), LN metastasis (P = 0.008), and higher EMPD stage (P = 0.023). Grade 1 EMPDs did not invade into the dermis and did not generate metastatic and/or recurrent lesions, whereas only Grade 2 or 3 EMPDs did so. AR expression in invasive components was significantly higher (P = 0.023) than in non-invasive components remaining within the epidermis. AR expression was further elevated in metastatic and/or recurrent lesions relative to locally invasive lesions (P = 0.014). These results clearly indicate that increased AR expression is associated with malignant progression of EMPD and that androgen blockade might be an effective therapy. Furthermore, AR expression assessed by immunohistochemistry may have potential for prediction of LN metastasis and local recurrence in EMPD.


What can be improved in learning to care for people with autism? A qualitative study based on clinical nursing simulation.
The aim of this study was to identify the main patterns of errors that 4th year nursing students made in simulated clinical practice with scenarios of care for people with Autism Spectrum Disorder (ASD). Clinical simulation currently plays a major role in the training of nursing students and provides the participants with the opportunity to practice and develop their clinical sills with a pediatric patient diagnosed with ASD. A retrospective longitudinal qualitative study was performed. Content analysis of the existing debriefing records from a period of 7 academic years (2016-2022) was carried out. The scenario was simulated by a standardized patient diagnosed with ASD, with 23 groups of nursing students. The results showed different patterns of errors. These patterns were grouped into 1 main category (weaknesses) and 5 major subcategories: clinical, communication, knowledge about ASD, emotions, and behavior towards parents. The most repeated errors were excessive use of verbal communication, abundant stimuli, low demand for information from primary caregivers, low demand for information about the child's emotions and interests, and a lack of knowledge of the profile of the child with ASD. From the findings of this study, we can highlight the lack of training that students received on the practical approach for providing care to these individuals. It has also been inferred in this study that clinical simulation is a tool that favors reflection and experiential learning for students when they are faced with caring for people with ASD.


Novel preparation of carbon-TiO2 composites.
Carbon-TiO2 sulfated composites were obtained from TiOSO4 · xH2O and glycerol as the TiO2 and carbon sources, respectively. The precursor xerogels were prepared in a one-step ultrasonic-assisted sol-gel reaction, followed by thermal treatment at 400°C under a nitrogen atmosphere to produce carbon-TiO2 sulfated composites. XRD, micro-Raman, SEM, and TEM studies showed that the composites consisted of nanocrystalline clusters of TiO2 and carbon. Ultrasonication in glycerol promoted the crystallinity of the xerogel precursors prior to thermal treatment. X-ray powder diffraction and Raman spectroscopy studies confirmed that glycerol also facilitated the formation of small crystallites. The band gaps of carbon-TiO2 composites with two different carbon loadings were found to be 3.06 eV and 2.69 eV. By contrast, the band gap of TiO2 prepared by our method was 3.53 eV. Calcination of the precursors led to an unusual increase in the specific surface and porosity of the composites compared to TiO2. The photocatalytic activities of the prepared composites were tested in a decomposition assay of Acid Orange 7. The reaction was monitored by UV-vis spectrophotometry and by LC-ESI-(Qq)-TOF-MS-DAD. Some intermediate species were identified by LC-ESI-QTOF-MS.