Polyethylene glycol modification decreases the cardiac toxicity of carbonaceous dots in mouse and zebrafish models.
Carbonaceous dots (CDs), which have been used for diagnosis, drug delivery and gene delivery, are accumulated in heart at high concentrations. To improve their biocompatibility, polyethylene glycol-modified CDs (PEG-CDs) were prepared. In this study we compared the cardiac toxicity of CDs and PEG-CDs in mouse and zebrafish models. Mice were intravenously treated with CDs (size: 4.9 nm, 5 mg·kg(-1)·d(-1)) or PEG-CDs (size: 8.3 nm, 5 mg·kg(-1)·d(-1)) for 21 d. Their blood biochemistry indices, ECG, and histological examination were examined for evaluation of cardiac toxicity. CDs or PEG-CDs was added in incubator of cmlc2 transgenic Zebrafish embryos at 6 hpf, and the shape and size of embryos' hearts were observed at 48 hpf using a fluorescent microscope. Furthermore, whole-mount in situ hybridization was used to examine the expression of early cardiac marker gene (clml2) at 48 hpf. Administration of CDs or PEG-CDs in mice caused mild, but statistically insignificant reduction in serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels detected at 7 d, which were returned to the respective control levels at 21 d. Neither CDs nor PEG-CDs caused significant changes in the morphology of heart cells. Administration of CDs, but not PEG-CDs, in mice caused marked increase of heart rate. Both CDs and PEG-CDs did not affect other ECG parameters. In the zebrafish embryos, addition of CDs (20 μg/mL) caused heart development delay, whereas addition of CDs (80 μg/mL) led to heart malformation. In contrast, PEG-CDs caused considerably small changes in heart development, which was consistent with the results from the in situ hybridization experiments. CDs causes greater cardiac toxicity, especially regarding heart development. Polyethylene glycol modification can attenuate the cardiac toxicity of CDs.


Mother-infant interaction improves with a developmental intervention for mother-preterm infant dyads.
While premature infants have a high need for positive interactions, both infants and their mothers are challenged by the infant's biological immaturity. This randomized clinical trial of 198 premature infants born at 29-34 weeks gestation and their mothers examined the impact of the H-HOPE (Hospital to Home: Optimizing the Infant's Environment) intervention on mother-premature infant interaction patterns at 6-weeks corrected age (CA). Mothers had at least 2 social environmental risk factors such as minority status or less than high school education. Mother-infant dyads were randomly assigned to the H-HOPE intervention group or an attention control group. H-HOPE is an integrated intervention that included (1) twice-daily infant stimulation using the ATVV (auditory, tactile, visual, and vestibular-rocking stimulation) and (2) four maternal participatory guidance sessions plus two telephone calls by a nurse-community advocate team. Mother-infant interaction was assessed at 6-weeks CA using the Nursing Child Assessment Satellite Training-Feeding Scale (NCAST, 76 items) and the Dyadic Mutuality Code (DMC, 6-item contingency scale during a 5-min play session). NCAST and DMC scores for the Control and H-HOPE groups were compared using t-tests, chi-square tests and multivariable analysis. Compared with the Control group (n = 76), the H-HOPE group (n = 66) had higher overall NCAST scores and higher maternal Social-Emotional Growth Fostering Subscale scores. The H-HOPE group also had significantly higher scores for the overall infant subscale and the Infant Clarity of Cues Subscale (p < 0.05). H-HOPE dyads were also more likely to have high responsiveness during play as measured by the DMC (67.6% versus 58.1% of controls). After adjustment for significant maternal and infant characteristics, H-HOPE dyads had marginally higher scores during feeding on overall mother-infant interaction (β = 2.03, p = 0.06) and significantly higher scores on the infant subscale (β = 0.75, p = 0.05) when compared to controls. In the adjusted analysis, H-HOPE dyads had increased odds of high versus low mutual responsiveness during play (OR = 2.37, 95% CI = 0.97, 5.80). Intervening with both mother and infant is a promising approach to help premature infants achieve the social interaction patterns essential for optimal development.


Changes in renal and systemic hemodynamics after NO-synthase inhibition in males with family history of hypertension.
Nitric oxide (NO) plays an important role in the regulation of blood pressure and renal hemodynamics. To further investigate the role of NO in human hypertension, we studied the effect of systemic injection of N(G)-monomethyl-L-arginine (L-NMMA) on renal hemodynamics, urinary sodium excretion (FE(Na)), systemic hemodynamics and several vasoactive hormones in 5 healthy male subjects with (group H) and without (group N) family history of hypertension. An intravenous infusion of L-NMMA (3 mg/kg over 10 min) or placebo was given in a randomized, double-blinded manner. GFR and ERPF were measured by inulin- and PAH-clearances. Norepinephrine infusion (0.1 microg/kg/min over 60 min) served as vasoconstrictive control infusion. L-NMMA induced a significant decrease in ERPF (-135 +/- 49 vs. 7 +/- 31 ml/min/1.73 m(2) with placebo, p < 0.05), a decrease in FE(Na) (-1.2 +/- 0.6% with L-NMMA vs. 0.0 +/- 0.1% with placebo), and a significant increase in diastolic blood pressure (+7 +/- 1 vs. -2 +/- 1 mm Hg with placebo) in group N, only. A sustained drop in plasma renin activity (-0.1 +/- 0.1 vs. 0.3 +/- 0.1 ng/ml/h with placebo) could also be seen in this group, only. Subjects with family history of hypertension showed minor or even no response (changes in diastolic blood pressure: L-NMMA: 5 +/- 3 mm Hg, placebo: 0 +/- 2 mm Hg; changes in ERPF: L-NMMA: -89 +/- 57 ml/min/1.73 m(2), placebo: -34 +/- 28 ml/min/1.73 m(2); changes in plasma renin activity: L-NMMA: -0.0 +/- 0.3 ng/ml/h, placebo: -0.1 +/- 0.2 ng/ml/h). The vasoconstrictive effect of norepinephrine infusion did not differ between both groups. Our data indicate that systemic NO synthetase inhibition by L-NMMA results in a blunted effect on systemic blood pressure and the renal hemodynamic system in subjects with family history of hypertension.


[Cardinal errors in expert opinions for the statutory accident insurance].
Expert opinions are subject to restrictions and must abide by the rules laid down by the legal system, much more so than therapies. Cardinal errors in expert opinions for the statutory accident insurance (GUV) are sometimes mistakes which can be found in all forms of expert opinions but in some cases where special questions of social law and the statutory accident insurance are concerned. The first group of mistakes are the differences between the requirements of an expert and a therapist with respect to the certainty of expert opinions, the responsibility of the commissioning authority alone for the non-medical components of an expert opinion, the generally valid principle of only giving opinions on areas of proven expertise and the extremely important aspect of personal responsibility. The second group of mistakes involve specific questions for the statutory accident insurance, such as the principles of causality, the rules of evidence, the estimation of the consequences of an accident with respect to reduction in earning capacity (MdE) and the significance of pre-existing damage.


Irreversible fluorine covalent organic framework based probe nanoelectrospray ionization mass spectrometry for direct and rapid determination of perfluoroalkyl carboxylic acids.
Probe nanoelectrospray ionization mass spectrometry (PESI-MS) is practically desirable for rapid and ultra-sensitive analysis of trace contaminants in environment, but limited with the stable and selective probe coating. Herein, we show the design and preparation of irreversible fluorine-based covalent organic framework (TFPPA-F4) covalently bonded probe to couple with ESI-MS (TFPPA-F4-PESI-MS) for direct and rapid determination of perfluoroalkyl carboxylic acids (PFCAs) in environmental water. Chemical bonding coating of irreversible crystalline TFPPA-F4 not only improved stability of the probe, but also offered accessible multiple interactions including hydrophobic, hydrogen bonding and F-F interactions to promote the kinetics and selectivity for PFCAs. The proposed TFPPA-F4-PESI-MS realized rapid determination of PFCAs (about 4 min) with low limits of detection of 0.06-0.88 ng L-1 and wide linear range of 1-5000 ng L-1 (R2 of 0.9982-0.9998). Recoveries for the spiked lake and pond water were 85.9-111.1 %. TFPPA-F4 based probe can maintain the extraction performance after 100 times of extraction. This work shows the great potential of the irreversible covalent organic framework based PESI-MS in rapid and ultra-sensitive determination of contaminants in environmental samples.


Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity.
To reveal the influence of hypoxia on tumor cells and immune cells in primary IDH-wt glioblastoma patients. Single-cell RNA-seq data and bulk RNA-seq data were acquired from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, respectively. Hypoxia status and subtypes of tumor cells were identified based on single-sample Gene Set Enrichment Analysis (ssGSEA). Regulon network analysis of different subtypes under different conditions was conducted by SCENIC. Within tumor microenvironment, biological process activity analysis and cell-cell communication network were conducted to uncover the inner links between each cell subtype under different hypoxia status. Different types of tumor cell in GBM possessed different hypoxia status, and MES-like subtype was under a more severe hypoxia condition than other subtypes. Hypoxia also induced MES-like signature gene expression within each tumor cell, which could stimulate tumor cell proliferation and invasion by regulating cell-cell communication. Additionally, hypoxia inhibited immune cell activity in the tumor microenvironment by inducing macrophage phenotype polarization and upregulating immune-inhibited cell-cell interaction within immune cells. Interactions between tumor cells and immune cells under hypoxia status also promoted tumor progression. Hypoxia was a poor prognostic marker for primary IDH-wt GBM patients. Meanwhile, it could induce tumor cells' MES-like transformation trend and inhibit antitumor function of immune cells.


Association of weight-adjusted-waist index with non-alcoholic fatty liver disease and liver fibrosis: a cross-sectional study based on NHANES.
The purpose of this study was to explore the association of weight-adjusted-waist index (WWI) with non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. A cross-sectional study including 6587 participants was conducted in the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression was used to validate the association of WWI with NAFLD and liver fibrosis, and smoothed curve fitting and threshold effect models were used to validate non-linear relationships. Subgroup analyses were used to verify the stability of the relationship between the independent and dependent variables in different populations. There was a positive association of WWI with NAFLD and liver fibrosis. In the model adjusted for all covariates, the effect values of WWI with NAFLD and liver fibrosis were (OR = 3.44, 95% CI: 3.09-3.82) and (OR = 2.40, 95% CI: 2.05-2.79), respectively. This positive correlation became more significant as WWI increased when WWI was presented in quartiles (P for trend < 0.01). Smoothed curve fitting and threshold effects analysis suggested a non-linear correlation between WWI and NAFLD (LLR < 0.01), with the positive correlation between WWI and NAFLD becoming more significant when WWI was less than 11.44 [5.93 (95% CI: 5.04-6.98)]. However, there was a linear correlation between WWI and liver fibrosis (LLR = 0.291). When subgroup analyses were performed by indicators such as age, race and gender, we found that the positive association between WWI and the dependent variables (NAFLD and liver fibrosis) was more pronounced in white male participants aged < 40 years. Among adults in the United States, WWI was positively associated with the prevalence of NAFLD and liver fibrosis. Participants with a WWI less than 11.44 should be cautious about the possibility of an increased risk of NAFLD development due to a higher WWI. Meanwhile, white males younger than 40 years of age should be more cautious about the higher risk of NAFLD and liver fibrosis that might be associated with an increased WWI.


Kir2.1 channel: Macrophage plasticity in tumor microenvironment.
Diverse ion channels have dysregulated functional expression in the tumor microenvironment (TME). In this issue of Cell Metabolism, Chen et al. reveal that high intratumoral K+ ions restrict the plasticity of tumor-associated macrophages (TAMs). Inhibition of the Kir2.1 potassium channel induced metabolic reprogramming and repolarization of pro-tumor M2-TAMs to tumoricidal M1-like states.


Protective effects of isolecanoric acid on neurodegenerative in vitro models.
Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS), are neurodegenerative disorders characterized by loss of dopaminergic or motor neurons, respectively. Although understanding of the PD and ALS pathogenesis remains incomplete, increasing evidence from human and animal studies has suggested that aberrant GSK3β, oxidative stress and mitochondrial damage are involved in their pathogenesis. Using two different molecular models, treatment with L-BMAA for ALS and rotenone for PD the effect of isolecanoric acid, a natural product isolated from a fungal culture, was evaluated. Pre-treatment with this molecule caused inhibition of GSK3β and CK1, and a decrease in oxidative stress, mitochondrial damage, apoptosis and cell death. Taken together, these results indicated that isolecanoric acid might have a protective effect against the development of these neurodegenerative disorders.


Passive and active contributions to generated force and retraction in heart valve tissue engineering.
In tissue engineered heart valves, cell-mediated stress development during culture results in leaflet retraction at time of implantation. This tissue retraction is partly active due to traction forces exerted by the cells and partly passive due to release of residual stress in the extracellular matrix and the cells. Within this study, we unraveled the passive and active contributions of cells and matrix to generated force and retraction in engineered heart valve tissues. Tissue engineered rectangular strips, fabricated from PGA/P4HB scaffolds and seeded with human myofibroblasts, were cultured for 4 weeks, after which the cellular contribution was changed at different levels. Elimination of the active cellular traction forces was achieved with Cytochalasin D and inhibition of the Rho-associated kinase pathway. Both active and passive cellular contributions were eliminated by lysation and/or decellularization of the tissue. Maximum cell activity was reached by increasing the fetal bovine serum concentration to 50%. The generated force decreased ~20% after elimination of the active cellular component, ~25% when the passive cellular component was removed as well and remained unaffected by increased serum concentrations. Passive retraction accounted for ~60% of total retraction, of which ~15% was residual stress in the matrix and ~45% was passive cell retraction. Cell traction forces accounted for the remainder ~40% of the retraction. Full activation of the cells increased retraction by ~45%. These results illustrate the importance of the cells in the process of tissue retraction, not only actively retracting the tissue, but also in a passive manner to a large extent.


Distribution of mortality patterns in cats with naturally occurring trauma: A Veterinary Committee on Trauma registry study.
A greater understanding of the prognostic variables that affect the timing of death for cats with trauma may help clinicians select treatments and monitoring plans. This study investigated the mortality rate and its distribution pattern in a large population of cats to identify variables associated with the timing of trauma-related deaths. Clinical data was retrieved from the Veterinary Committee on Trauma database to determine mortality rates and timing of deaths, defined as early death (ED; <1 day post-presentation) or delayed death (DD; ≥1 day post-presentation). Multivariable logistic regression analyses were performed to identify characteristics and interventions that best predicted timing of death. Overall mortality rate for 6703 feline trauma patients with complete records was 17.2%, with 7.6% due to natural death and 92.3% due to euthanasia. Among the subset of 543 cats with trauma that died after presentation or required euthanasia due to a grave prognosis (representing an 8.1% mortality rate), EDs were more common (71.7%) than DD and the cause of death was not significantly associated with the timing of death. Clinical pathology parameters were unable to identify animals more likely to die or to require euthanasia due to a poor prognosis during hospitalisation. Factors that were significantly different for cats with ED vs. DD included the median cumulative results for the Modified Glasgow Coma Scale (MGCS) score and the Animal Trauma Triage (ATT) score, the presence of spinal trauma, administration of blood products and undertaking surgical procedures. An increased likelihood of DD rather than ED was associated with the administration of blood products (odds ratio [OR], 3.959; P = 0.019) vs. not, performing a surgical procedure (OR, 6.055; P < 0.001) vs. not, and a cumulative MGCS of 15-17 or 18 (OR, 1.947 and 3.115; P = 0.031 and P = 0.01, respectively) vs. a cumulative MGCS ≤ 11.


Non-invasive optical coherence tomography angiography: A comparison with fluorescein and indocyanine green angiography in normal adult dogs and cats.
While the retinal vasculature can be assessed by simple funduscopy, a more detailed assessment can be performed by conventional angiography using dyes such as fluorescein or indocyanine green. The development of optical coherence tomography angiography (OCT-A) allows a non-invasive detailed examination of posterior segment vasculature. The purpose of this prospective study was to compare imaging of posterior segment vasculature in normal dogs and cats using OCT-A, fluorescein angiography (FA), and indocyanine green angiography (ICGA). Eight adult funduscopically normal dogs and 13 funduscopically normal cats were included in the study. Retinal vasculature was assessed by OCT-A followed by ICGA then FA. Regular fundus imaging was also performed. High-resolution images of the different vascular layers within the retina and choroid could be acquired using OCT-A in both dogs and cats. The technique provided more detail than obtained with FA/ICGA. However, artifacts/errors can occur during OCT-A image acquisition/analysis/interpretation and must be considered. Furthermore, OCT-A only allows for a limited field of view compared to FA/ICGA. Optical coherence tomography angiography is a new non-invasive posterior segment imaging technique that is complementary to traditional dye-based angiographic techniques. Detailed imaging of the dog and cat posterior segment can be achieved under general anesthesia. OCT-A provides additional detail of the vasculature and can clearly demonstrate the anatomical depth of the imaged vessels. There are, however, some limitations to this new technique that may be overcome by future technological advances.


Confirmation of sub-cellular resolution using oversampling imaging mass spectrometry.
The use of oversampling in MALDI (matrix-assisted laser desorption/ionization) imaging mass spectrometry (IMS) to improve lateral resolution is a common practice. However, its application is still controversial and recent studies reported a spot size-dependent change in the relative intensity of the spectra. Previously, using oversampling, we described the lipidome of the human colon epithelium, a 20-30 μm wide cell monolayer; even assessing the changes occurring within this monolayer associated with complex biological processes. Interestingly, the K-means analysis of those experiments unveiled the presence of a third epithelial cluster that anatomically matched the nuclei position. Taking into account the nucleus size (9-12 μm of diameter) and its distinctive lipidome, we decided to test whether this cluster was really of nuclear origin. Hence, the spectra obtained directly from tissue sections were compared with those recorded from the nuclei isolated from colon biopsies. The highest correlation coefficient was obtained when comparing the spectrum of the isolated nuclei with that of the tissue nuclear cluster, demonstrating the successful identification of the nuclear lipidome in the MALDI-IMS experiments run using oversampling and a lateral resolution of 10 μm/pixel. Importantly, it was established that phosphatidylinositol 38:4 nuclear levels remained stable along the colon crypt. That is, it mimicked neither the regular decrease observed in the epithelium nor the regular increase observed in the stroma, eliminating the chance of inter-pixel contamination. Altogether, besides confirming the usefulness of the oversampling technique, these results strongly reinforce the pivotal role IMS may have in promising fields such as single-cell analysis. Graphical abstract.


Integrative analysis of transcriptome and proteome provides insights into adaptation to cadmium stress in Sedum plumbizincicola.
Sedum plumbizincicola, a cadmium (Cd) hyperaccumulating herbaceous plant, can accumulate large amounts of Cd in the above-ground tissues without being poisoned. However, the molecular mechanisms regulating the processes are not fully understood. In this study, Transcriptional and proteomic analyses were integrated to investigate the response of S. plumbizincicola plants to Cd stress and to identify key pathways that are potentially responsible for Cd tolerance and accumulation. A total of 630 DAPs (differentially abundant proteins, using fold change >1.5 and adjusted p-value <0.05) were identified from Tandem Mass Tag (TMT)- based quantitative proteomic profiling, which were enriched in processes including phenylpropanoid biosynthesis, protein processing in endoplasmic reticulum, and biosynthesis of secondary metabolites. Combined with the previous transcriptomic study, 209 genes and their corresponding proteins showed the identical expression pattern. The identified genes/proteins revealed the potential roles of several metabolism pathways, including phenylpropanoid biosynthesis, oxidative phosphorylation, phagosome, and glutathione metabolism, in mediating Cd tolerance and accumulation. Lignin staining and Cd accumulation assay of the transgenic lines over-expressing a selected Cd up-regulated gene SpFAOMT (Flavonoid 3',5'-methyltransferase) showed its functions in adapting to Cd stress, and provided insight into its role in lignin biosynthesis and Cd accumulation in S. plumbizincicola during Cd stress.


Von Recklinghausen's Disease Presenting as Otolaryngologic Emergency: A Rare Occurrence.
Type 1 Neurofibromatosis (NF1) is a rare autosomal dominant genetic disorder. There are seven clinical features of which two are necessary to diagnose it. Another important feature is plexiform neurofibroma which commonly presents as painful expansile lesion. Here we present a case of NF1 with huge swelling of left hemiface and chin following trauma over pre-existing swelling and presented as life threatening emergency and managed surgically.


Psychological and Non-Pharmacologic Treatments for Pain in Cancer Patients: A Systematic Review and Meta-Analysis.
Pain is the most fearful symptom in cancer. Although there is a relationship between psychosocial variables and oncologic pain, psychological and non-pharmacological treatments for pain management in cancer patients are not very widespread. To analyze the efficacy of psychological and non-pharmacological treatments for reducing pain in cancer patients. We performed a systematic review following the PRISMA protocol. In January 2021, data were extracted from PubMed, Web of Science and Scopus, including randomised controlled trials (RCT) published in the last five years (from 28 January, 2015 to December 15, 2020), in the English language and whose sample was patients with cancer pain. The database search used the following keywords: cancer, cancer-related pain, psychological intervention, non-pharmacologic intervention. The Cochrane risk of bias assess ment for randomised trials (RoB 2) was used for quality appraisal. After the inclusion and exclusion criteria were applied, ten papers were fully screened. The evidence suggested that the most effective interventions to reduce cancer pain were mindfulness-based cognitive therapy, guided imagery and progressive muscle relaxation and emotional and symptom focused engagement (EASE). Music therapy and brief cognitive behavioral strategies (CBS) require more research, while coping skills training and yoga did not show positive effects. Overall, we obtained a moderate size effect (d = 0.642, 95% CI: 0.125-1.158) favourable to psychological and non-pharmacologic treatments at post-treatment, which increased at follow-up (k = 5, d = 0.826, 95% CI: 0.141-1.511). This study provides insight into psychological interventions which might be applied and contribute to cancer-related pain reduction in adults. Although the results are not completely consistent, they may shed light on psychology applications in the oncology environment.


Death, dying, and the brain.
These cases have been cited and these issues presented to make the point that principles are often out of phase with perceptions. The argument is not that principles should cede to perceptions. This would imply resignation to the unlikelihood of moral development. Neither do we claim that perceptions should simply and generally capitulate to principles. This could mean an intolerable dictatorship of one philosophy over experience. Clinical ethics is the challenge to integrate principles and perceptions continuously and critically in resolving value conflicts about the best care of individual patients.


Chemical control of nitrification under rice in the central rainlands of the Sudan.
2-amino-4-chloro-6-methyl pyrimidine "AM" was used as a selective inhibitor of nitrifying organisms to prevent denitrification losses. Zero, 6, and 12 kg/ha of the chemical, 43 and 86 kg/ha urea-N or their equivalents were used in vitro and in vivo experiments. In the in vitro experiment, clear and significant inhibition lasted for 6 weeks. In both the pot and field experiments inhibition lasted shorter and only insignificant increases in yield and yield components were attained. The value of this chemical for rice under the soil and climatic conditions of the Central Rainlands seems to be small, though it seems promising for lighter (leaching) soils.


Osteocartilaginous metaplasia of the right atrium in male domestic sheep.
Among 53 clinically healthy male sheep with epididymitis, nine had minimal to severe firm nodular thickening of the right atrial wall at necropsy. The two most severely affected atria were about three times normal size. Histologically, the atrial masses consisted of partly mineralized cartilage nodules with lipid-filled cavities and basophilic to eosinophilic trabeculae. Further investigation failed to reveal clues as to etiopathogenesis of these lesions.


Symptom provocation in obsessive-compulsive disorder: A voxel-based meta-analysis and meta-analytic connectivity modeling.
Obsessive-compulsive disorder (OCD) is a heterogeneous psychiatric illness with a complex array of symptoms and potentially distinct neural underpinnings. We employed meta-analysis and connectivity modeling of symptom dimensions to delineate the circuit mechanisms of OCD. With the activation likelihood estimation (ALE) algorithm we performed meta-analysis of whole-brain functional magnetic resonance imaging (fMRI) studies of symptom provocation. We contrasted all OCD patients and controls in a primary analysis and divided the studies according to clinical symptoms in secondary meta-analyses. Finally, we employed meta-analytic connectivity modeling analyses (MACMs) to examine co-activation patterns of the brain regions revealed in the primary meta-analysis. A total of 14 experiments from 12 eligible studies with a total of 238 OCD patients (124 men) and 219 healthy controls (120 men) were included in the primary analysis. OCD patients showed higher activation in the right caudate body/putamen/insula and lower activation in the left orbitofrontal cortex (OFC), left inferior frontal gyrus (IFG), left caudate body/middle cingulate cortex (MCC), right middle temporal gyrus (MTG), middle occipital gyrus (MOG) and right lateral occipital gyrus (LOG). MACMs revealed significant co-activation between left IFG and left caudate body/MCC, left MOG and right LOG, right LOG and MTG. In the secondary meta-analyses, the washing subgroup showed higher activation in the right OFC, bilateral ACC, left MOG and right caudate body. OCD patients showed elevated dorsal striatal activation during symptom provocation. In contrast, the washing subgroup engaged higher activation in frontal, temporal and posterior cortical structures as well as right caudate body. Broadly consistent with the proposition of cortico-striatal-thalamic-cortical circuit dysfunction, these findings highlight potentially distinct neural circuits that may underlie the symptoms and potentially etiological subtypes of OCD.


Impairment by heparin of primary haemostasis and platelet [14C]5-hydroxytryptamine release.
Heparin was administered to 34 normal subjects by intravenous injection (100 mu/kg) and the template bleeding time was significantly increased both 10 min and 120 min following injection. Before heparin the bleeding time was 5-3 +/- 1.0 min (mean +/- 1 SD); 10 min after injection it was 9.8 +/- 5.6 min (P less than 0.001); and 120 min after injection it was 7.2 +/- 3.9 min (P less than 0.001). Increases in the bleeding time were unrelated to changes in platelet count, and independent of heparin's effect on plasma coagulation. In blood drawn 10 min and 120 min following heparin injection, there was significantly less [14C]5-HT released from platelet-rich plasma (PRP) in response to collagen, 0.41 mM epinephrine and 8 micron ADP, although in vitro addition of heparin (0.1 mu/ml, 0.5 mu/ml and 2.5 mu/ml) to baseline PRP of three subjects did not depress [14C]5-HT release. Our experiments suggest that intravenous administration of a therapeutic dose of heparin can cause a significant reversible inpairment of platelet haemostatic properties, possibly by an indirect mechanism.


Safety and Efficacy of Twice-Daily Pilocarpine HCl in Presbyopia: The Virgo Phase 3, Randomized, Double-Masked, Controlled Study.
To evaluate the safety, efficacy, and pharmacokinetics of pilocarpine hydrochloride 1.25% (Pilo hereafter) compared with vehicle when administered bilaterally, twice daily (6 hours apart) for 14 days in participants with presbyopia. Phase 3, randomized (1:1), controlled, double-masked, multicenter study. Participants (40-55 years of age) had objective and subjective evidence of presbyopia affecting daily activities with mesopic, high-contrast, binocular distance-corrected near visual acuity (DCNVA) of 20/40 to 20/100. The primary/key secondary endpoint was the proportion of participants gaining ≥3 lines in mesopic/photopic, high-contrast, binocular DCNVA on day 14 (last study visit), hour 9 (3 hours after the second dose), with no more than a 5-letter loss in mesopic/photopic corrected distance visual acuity with the same refractive correction. Key safety measures included treatment-emergent adverse events (TEAEs) and some ocular measurements. Pilocarpine plasma levels were assessed in approximately 10% of enrolled participants. Overall, 230 participants were randomized to Pilo twice daily (N = 114) and vehicle (N = 116). The proportion of participants achieving the primary and key secondary efficacy endpoints was statistically significantly greater with Pilo twice daily than vehicle, with between-treatment differences of 27.3% (95% CI = 17.3, 37.4) and 26.4% (95% CI = 16.8, 36.0), respectively. The most common TEAE was headache, reported in 10 participants (8.8%, Pilo group) and 4 participants (3.4%, vehicle group). Pilocarpine's accumulation index on day 14 was ≤1.11 after the second dose. Near-vision improvements were statistically greater with Pilo twice daily than with vehicle, without compromising distance acuity. The safety profile of Pilo twice daily was consistent with that of Pilo once daily, and systemic accumulation was minimal, supporting twice daily administration.


Androgens and estrogens: their interaction with stroma and epithelium of human benign prostatic hyperplasia and normal prostate.
Growth and integrity of human prostatic epithelium is strongly dependent upon the adjacent stroma. Furthermore, the human prostate is under the control of sex hormones. Both facts prompted us to compare epithelium with stroma of human benign prostatic hyperplasia (BPH) and normal prostate (NPR) concerning their metabolism, binding and tissue concentrations of androgens and estrogens. In vitro metabolism was analyzed by t.l.c., androgen and estrogen binding sites were determined by a charcoal adsorption technique, androgen and estrogen tissue concentrations were measured by RIA. The main results are--(1) Metabolism: BPH stroma shows 2-3 times higher 5 alpha-reductase activity than epithelium. This high 5 alpha-reductase activity in BPH stroma dictates the differences between unseparated BPH and NPR, in the former the 5 alpha-reductase activity being 2 times higher. The 3 alpha(beta)-hydroxysteroid dehydrogenase (HSDH) activity is more evenly distributed between stroma and epithelium of BPH and NPR. The ratios of 5 alpha-reductase to HSDH activity in the various tissue fractions indicate that the highest enzymatically regulated 5 alpha-dihydrotestosterone (DHT) enrichment must occur in BPH stroma. (2) Tissue concentrations: unseparated BPH contains 2.2 times more DHT than NPR. About 70% of the total DHT content is found in nuclear fractions, whereby the nuclear DHT content of BPH stroma is significantly higher than that of BPH epithelium. In addition, nuclei of BPH stroma contain significantly more estradiol than epithelial nuclei. (3) Binding: the androgen receptor is evenly distributed between epithelium and stroma of BPH, while the estrogen receptor is preferably assayed in BPH stroma. These studies indicate that the BPH stroma is not only a preferential tissue for 5 alpha-reductase activity and DHT enrichment but also for nuclear estradiol accumulation.


Enhancing the organic solvent resistance of ω-amine transaminase for enantioselective synthesis of (R)-(+)-1(1-naphthyl)-ethylamine.
Biocatalysis in high-concentration organic solvents has been applied to produce various industrial products with many advantages. However, using enzymes in organic solvents often suffers from inactivation or decreased catalytic activity and stability. An R-selective ω-amine transaminase from Aspergillus terreus (AtATA) exhibited activity toward 1-acetylnaphthalene. However, AtATA displayed unsatisfactory organic solvent resistance, which is required to enhance the solubility of the hydrophobic substrate 1-acetylnaphthalene. So, improving the tolerance of enzymes in organic solvents is essential. The method of regional random mutation combined with combinatorial mutation was used to improve the resistance of AtATA in organic solvents. Enzyme surface areas are structural elements that undergo reversible conformational transitions, thus affecting the stability of the enzyme in organic solvents. Herein, three surface areas containing three loops were selected as potential mutation regions. And the "best" mutant T23I/T200K/P260S (M3) was acquired. In different concentrations of dimethyl sulfoxide (DMSO), the catalytic efficiency (kcat /Km ) toward 1-acetylnaphthalene and the stability (half-life t1/2 ) were higher than the wild-type (WT) of AtATA. The results of decreased Root Mean Square Fluctuation (RMSF) values via 20-ns molecular dynamics (MD) simulations under 15%, 25%, 35%, and 45% DMSO revealed that mutant M3 had lower flexibility, acquiring a more stable protein structure and contributing to its organic solvents stability than WT. Furthermore, M3 was applied to convert 1-acetylnaphthalene for synthesizing (R)-(+)-1(1-naphthyl)-ethylamine ((R)-NEA), which was an intermediate of Cinacalcet Hydrochloride for the treatment of secondary hyperthyroidism and hypercalcemia. Moreover, in a 20-mL scale-up experiment, 10 mM 1-acetylnaphthalene can be converted to (R)-NEA with 85.2% yield and a strict R-stereoselectivity (enantiomeric excess (e.e.) value >99.5%) within 10 h under 25% DMSO. The beneficial mutation sites were identified to tailor AtATA's organic solvents stability via regional random mutation. The "best" mutant T23I/T200K/P260S (M3) holds great potential application for the synthesis of (R)-NEA.


Trends in mortality from primary liver cancer in England and Wales 1975-92: influence of oral contraceptives.
Numerous case-control studies have suggested a link between the oral contraceptive pill and liver cancer. The secular trends in liver cancer mortality rates for England and Wales from 1975 to 1992 were examined to determine whether an effect of the pill was apparent. Liver cancer mortality has remained constant in women in the age groups that have had major exposure to the pill.


Erythrobacter aureus sp. nov., a plant growth-promoting bacterium isolated from sediment in the Yellow Sea, China.
The application of plant growth-promoting (PGP) bacterium in agriculture is expanding rapidly in recent years. With the development of microbial technology, new bacterial species effective in promoting plant growth have been identified. In this study, a PGP bacterium was isolated from marine sediments of the Yellow Sea in China. The confrontation culture test and pot experiments showed that strain YH-07T inhibited the growth of Fusarium oxysporum f. sp. lycopersici (a plant pathogenic fungus), benefiting plant growth and reducing disease incidence of tomato wilt. We used polyphasic approaches including phenotypic, chemotaxonomic and phylogenetic information to determine its taxonomic status. In addition to profiling general features of the YH-07T genome, we identified genes related to PGP traits and genes involved in environmental stress tolerance. Metabolic assays showed that strain YH-07T could produce siderophores, solubilize phosphate, resist to salinity, and grow well within a wide range of temperature and pH, which is a promising PGP bacterium for future agricultural applications. These results provide evidence that strain YH-07T is a novel species of the genus Erythrobacter, for which the name Erythrobacter aureus sp. nov. is proposed. The type strain is YH-07T (= CGMCC 1.16784T = DSM 107319T).


COURAGE, ORBITA, and ISCHEMIA: Percutaneous Coronary Intervention for Stable Coronary Artery Disease.
This review article summarizes key landmark trials that have shaped understanding of the role of percutaneous coronary intervention (PCI) in stable coronary artery disease (CAD). The relationship between stenosis, ischemia, and angina is more complex than first imagined. Anginal relief remains the primary indication for PCI in stable CAD. The first placebo-controlled PCI trial showed a surprisingly small effect size, suggesting a significant placebo effect. PCI in stable CAD has not been shown to improve mortality or overall myocardial infarction rates, even in the presence of significant ischemia. Rather, risk reduction medical therapy remains the main intervention for improving outcomes.


Pheochromocytoma and pregnancy: report of three cases.
Three cases of pheochromocytoma associated with pregnancy are reported. Two patients had adrenal pheochromocytoma coexistent with normal pregnancy and one patient had a bladder pheochromocytoma coexistent with molar pregnancy (gestational trophoblastic disease). The diagnosis was made antenatally in the two normal pregnancy patients, both underwent planned tumor resection, one at mid-trimester, complicated by postoperative miscarriage, while the other had tumor resection during cesarean section at term. Bladder pheochromocytoma, preoperatively mistaken for invasive trophoblastic tumor, was resected at the time of planned abdominal hysterectomy for molar pregnancy, pheochromocytoma was recognized only after microscopic study of the resected bladder tumor. The three patients survived with no evidence of disease.


Postoperative paraplegia as a result of undiagnosed primitive neuroectodermal tumor, not epidural analgesia.
Postoperative paraplegia is a rare complication after epidural analgesia and often occurs with spinal hematoma or cord injury. We present the case of a 16-year-old girl who suffered from a tumor mass in the neck and abdomen who underwent gynecologic operation. Preoperatively, liver metastasis was found by computed tomography. Pathologic findings revealed that the abdominal mass was an ovarian dermoid cyst. After the operation, the patient complained of paraplegia while receiving epidural analgesia for postoperative pain control. A peripheral primitive neuroectodermal tumor in the thoracic and lumbar spines with spinal cord compression was later detected using magnetic resonance imaging. Learning from this case, we suggest that when a patient is preoperatively diagnosed with tumor metastasis, back pain and soreness, spinal cord compression from tumor metastasis should be excluded before epidural analgesia is implemented.


Anoxia-reoxygenation modulates cadmium-induced liver mitochondrial reactive oxygen species emission during oxidation of glycerol 3-phosphate.
Aquatic organisms are frequently exposed to multiple stressors including low dissolved oxygen (O2) and metals such as cadmium (Cd). Reduced O2 concentration and Cd exposure alter cellular function in part by impairing energy metabolism and dysregulating reactive oxygen species (ROS) homeostasis. However, little is known about the role of mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) in ROS homeostasis in fish and its response to environmental stress. In this study, mGPDH activity and the effects of anoxia-reoxygenation (A-RO) and Cd on ROS (as hydrogen peroxide, H2O2) emission in rainbow trout liver mitochondria during oxidation of glycerol 3-phosphate (G3P) were probed. Trout liver mitochondria exhibited low mGPDH activity that supported a low respiratory rate but substantial H2O2 emission rate. Cd evoked a low concentration stimulatory-high concentration inhibitory H2O2 emission pattern that was blunted by A-RO. At specific redox centers, Cd suppressed H2O2 emission from site IQ, but stimulated emission from sites IIIQo and GQ. In contrast, A-RO stimulated H2O2 emission from site IQ following 15 min exposure and augmented Cd-stimulated emission from site IIF after 30 min exposure but did not alter the rate of H2O2 emission from sites IIIQo and GQ. Additionally, Cd neither altered the activities of catalase, glutathione peroxidase, or thioredoxin reductase nor the concentrations of total glutathione, reduced glutathione, or oxidized glutathione. Overall, this study indicates that oxidation of G3P drives ROS production from mGPDH and complexes I, II and III, whereas Cd directly modulates redox sites but not antioxidant defense systems to alter mitochondrial H2O2 emission.


Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects.
Quercetin is a kind of flavonoid compounds that comes from nature and is widely existed in the daily diet. Previous studies have found that quercetin has many effects such as anti-inflammatory, anti-oxidation and anti-cancer. Both in vivo and in vitro experiments have demonstrated that quercetin can exert anti-tumor effects by altering cell cycle progression, inhibiting cell proliferation, promoting apoptosis, inhibiting angiogenesis and metastasis progression, and affecting autophagy. This review summarizes the evidence for the pharmacological potential and inhibition of quercetin on cancers, supporting the viewpoint that quercetin should be adequately considered as a therapeutic agent against various cancers.


Isolation and characterization of pHW15, a small cryptic plasmid from Rahnella genomospecies 2.
A small cryptic plasmid designated pHW15 was isolated from Rahnella genomospecies 2 WMR15 and its complete nucleotide sequence was determined. The plasmid contained 3002 bp with a G+C content of 47.4%. The origin of replication was identified by deletion analysis as a region of about 600 bp. This region had an identity of 70% to the replication origin of the ColE1 plasmid at the nucleotide level. Sequence analysis revealed the typical elements: RNA I, RNA II and their corresponding promoters, a sequence allowing hybridisation of RNA II to the DNA and favouring processing by RNaseH, a single-strand initiation determinant (ssi) that allows initiation of lagging-strand synthesis, and a terH sequence required for termination of lagging-strand synthesis. The plasmid contained three expressed open reading frames, one of which showed homology to a ColE1 plasmid-encoded protein. Furthermore, a multimer resolution site was identified by sequence analysis. Its deletion resulted in formation of plasmid multimers during growth leading to an increased plasmid loss rate.


Data on natural radionuclide's activity concentration of cement-based materials.
Cement based materials may contain varying levels of radionuclides, mainly 226Ra (from the 238U series), 232Th and 40K, which are used to determine the Activity Concentration Index ("ACI"). According to the European directive Euratom 2013/59 in these materials, the "ACI" must be < 1 to be suitable for their use in construction. In this paper, data on the activity concentration of natural radionuclides in cement-based materials (i.e. cements, additions, pigments and aggregates) as well as their chemical composition are presented. Radioactivity measurements have been determined by using gamma spectroscopy the chemical compositions have been determined by X-Ray Fluorescence. Data for cements measured shown that white cements present a lower concentration of activity than conventional CEM I. In addition, the CAC (Calcium aluminate cements) present high activity concentration in the 232Th series. Regarding additions, FA (Fly Ash) are those that present the highest concentration of activity in the 238U and 232Th series, while olive biomass ashes are those supplementary cementitious materials that show the highest concentration of activity for 40K. Some pigments used in mortar and concrete technology were also characterized. Granitic and volcanic rocks, potentially used as aggregates present much higher activity concentration than the siliceous aggregate.


Environmental assessment and durability performance of cement mortar incorporating sugarcane vinasse in replacement of water.
Sugarcane vinasse wastewater (SVW) is one of the most voluminous waste generated in the ethanol industry and usually applied in fertigation. It is characterized by presenting high COD and BOD; thus, continued disposal of vinasse results in negative environmental impacts. In this paper, we investigated the potential of SVW in replacement of water in mortar, rethinking about reuse of effluent, reduction of pollutants in the environment, and water consumption in civil construction. Mortar composites with 0, 20, 40, 60, 80, and 100% of water replaced by SVW were studied in order to determine the optimum content. Mortars with 60 to 100% of SVW result in improved workability and reduction in water demand. The mortars with 20, 40, and 60% SVW resulted in satisfactory mechanical properties, i.e., similar to the control mortar. However, XRD analysis of cement pastes showed that the SVW causes a delay in CH formation, reaching mechanical strength after 28 days. Durability tests results showed that SVW contributes to the mortar becoming more impermeable; therefore, less susceptible to weathering. This study provides an important evaluation of the potential of SVW for application in civil construction, indicating relevant results for replacement of water by liquid wastes in cementitious composites and reduction the use of natural resources.


Calibration of the Goldmann perimeter and accessories used in specific quantitative perimetry.
With known radiometric data of the components of the projection perimeter and its accessories it is possible to perform spectral sensitivity measurements which are essential for the performance of quantitative colour perimetry. The authors describes modifications made the Goldmann perimeter for the performance of such measurements. The calibration data of the perimeter and accessories are given. A good fit between the CIE scotopic spectral sensitivity curve (V' lambda) and our experimental results for a dark adapted eye serves as a control of the calibration.


Large Area Cryo-Planing of Vitrified Samples Using Broad-Beam Ion Milling.
On account of its excellent resolution and high throughput, cryoSEM imaging has recently seen resurgence. In this work, we report on the development of cryogenic triple ion gun milling (CryoTIGM™), a broad ion beam milling technique for cryo-planing of vitrified, "frozen-hydrated" specimens. We find that sections prepared with CryoTIGM™ are smooth over exceptionally large areas (~700,000 µm2), and reveal ultrastructural details in similar or better quality than freeze-fractured samples.


The impact of the lymph node ratio is greater than traditional lymph node status in stage III colorectal cancer patients.
The prognostic value of nodal status in colorectal cancer (CRC) patients may be influenced by the total number of lymph nodes (LNs) harvested. This study evaluates the impact of LN ratio (LNR) on CRC patients' outcome. A total of 612 stage III CRC patients who underwent curative-intent surgery between 2004 and 2008 were enrolled. The measured end point was postoperative disease-free survival (DFS) and overall survival (OS). The metastatic LN numbers were significantly higher in patients with more than 12 LN harvested (4.6 ± 5.81 vs. 2.7 ± 1.97, P < 0.001). The mean LNR was 22.9 ± 20 % (range = 2-100 %, median = 16.7 %). As the cutoff value of LNR was set above 17 %, the impact of the LNR on 5-year DFS became statistically significant. In univariate analysis, the 5-year DFS and OS for patients with high-LNR tumors was 54.4 and 57.3 %, respectively, significantly lower than those for patients with low-LNR tumors (72.8 and 76.4 %; P < 0.001). In multivariate analysis, the independent factors affecting the 5-year DFS and OS were tumor depth, carcinoembryonic antigen level, and LNR. The LNR, set at the median value or 17 %, could be an independent prognostic factor for stage III CRC patients.


Patient-centered empirical research on ethically relevant psychosocial and cultural aspects of cochlear, glaucoma and cardiovascular implants - a scoping review.
The significance of medical implants goes beyond technical functioning and reaches into everyday life, with consequences for individuals as well as society. Ethical aspects associated with the everyday use of implants are relevant for individuals' lifeworlds and need to be considered in implant care and in the course of technical developments. This scoping review aimed to provide a synthesis of the existing evidence regarding ethically relevant psychosocial and cultural aspects in cochlear, glaucoma and cardiovascular implants in patient-centered empirical research. Systematic literature searches were conducted in EBSCOhost, Philpapers, PsycNET, Pubmed, Web of Science and BELIT databases. Eligible studies were articles in German or English language published since 2000 dealing with ethically relevant aspects of cochlear, glaucoma and passive cardiovascular implants based on empirical findings from the perspective of (prospective) implant-wearers and their significant others. Following a descriptive-analytical approach, a data extraction form was developed and relevant data were extracted accordingly. We combined a basic numerical analysis of study characteristics with a thematically organized narrative synthesis of the data. Sixty-nine studies were included in the present analysis. Fifty were in the field of cochlear implants, sixteen in the field of passive cardiovascular implants and three in the field of glaucoma implants. Implant-related aspects were mainly found in connection with autonomy, freedom, identity, participation and justice, whereas little to no data was found with regards to ethical principles of privacy, safety or sustainability. Empirical research on ethical aspects of implant use in everyday life is highly relevant, but marked by ambiguity and unclarity in the operationalization of ethical terms and contextualization. A transparent orientation framework for the exploration and acknowledgment of ethical aspects in "lived experiences" may contribute to the improvement of individual care, healthcare programs and research quality in this area. Ethics-sensitive care requires creating awareness for cultural and identity-related issues, promoting health literacy to strengthen patient autonomy as well as adjusting healthcare programs accordingly. More consideration needs to be given to sustainability issues in implant development and care according to an approach of ethics-by-design.


A sixteen decimal places' accurate Darcy friction factor database using non-linear Colebrook's equation with a million nodes: A way forward to the soft computing techniques.
The Colebrook's equation is considered as an empirical model to accurately compute the Darcy friction factor in pipes under fully-developed turbulent flow. Due to non-linearity and implicitness of the Colebrook's equation, one needs to use numerical methods to acquire reasonably good approximation to the true friction factor values. However, such idea is not preferred by practitioners as it demands use of computers - also more computational time and effort. To overcome this, explicit equations that can describe Darcy friction factor directly in terms of the Reynolds number and relative roughness are essential. Using Fixed point iteration method in the MATLAB software, we have developed a 16 decimal places' accurate friction factor database for the Darcy friction factor for a 1000 by 1000 mesh of Reynolds number and relative roughness values. The accurate dataset described in this work will serve to be basis for the construction of new and more reliable explicit equations using regression modeling, artificial intelligence techniques and other soft computing methods.


[High level of satisfaction among patients despite persistent symptoms in the mid-long-term following surgery for lumbosacral radicular syndrome].
To determine the mid-long-term outcomes after surgery in patients with lumbosacral radicular syndrome (LRS) and to identify prognostic factors for persisting LRS symptoms. Descriptive retrospective and prospective. A total of 250 consecutive patients operated on by 7 neurosurgeons in four hospitals between May and December 2001 were selected from medical records. They were asked to take part in a telephone questionnaire at 6 and 19 months after operation. They had all undergone discectomy for LRS at L4-L5 or L5-S1 and were aged from 18 to 65. Of the 250 patients, 163 participated in the study: 63% reported that they still had LRS-related symptoms 19 months after surgery. However, severe leg pain had decreased in 83% of the patients. In general the patients were satisfied with their treatment. Female gender and an age of 51-65 were prognostic factors for persistent LRS symptoms. More than half of the patients reported LRS symptoms 19 months after surgery.


Transport of a soft cargo on a nanoscale ratchet.
Surface ratchets can guide droplet transport for microfluidic systems. Here, we demonstrated the actuation of microgels encapsulated in droplets using a unidirectional nanotextured surface, which moves droplets with low vibration amplitudes by a ratcheting mechanism. The nanofilm carries droplets along the ratchets with minimal drop shape deformation to move the encapsulated soft cargo, i.e., microscale hydrogels. The tilted nanorods of the nanofilm produce unidirectional wetting, thereby enabling droplet motion in a single direction. Maximum droplet translation speed on the nanofilm was determined to be 3.5 mm∕s, which offers a pathway towards high throughput microgel assembly applications to build complex constructs.


National Study of Triage and Access to Trauma Centers for Older Adults.
To identify predictors of undertriage among older injured Medicare beneficiaries, identify any regions in which undertriage is more likely to occur, and examine additional factors associated with undertriage at a national level. Using 2009 to 2014 Medicare claims data, we identified older adults (≥65 years) receiving a diagnosis of traumatic injury, and linked claims with trauma center designation records from the American Trauma Society. Undertriage was defined as nontrauma centers treatment with an Injury Severity Score greater than or equal to 16, consistent with the American College of Surgeons Committee on Trauma benchmark. We used multivariable logistic regression to estimate odds of undertriage by census region, adjusting for sex, race, age, Injury Severity Score, trauma center proximity, and mode of transportation. Forty-six percent of severely injured patients (n=125,731) were treated at a nontrauma center. Compared with that for patients in the Midwest, adjusted odds of undertriage were 100% higher for patients in Southern states (odds ratio [OR] 2.00; 95% confidence interval [CI] 2.00 to 2.04) and 78% higher in Western states (OR 1.78; 95% CI 1.73 to 1.82). Compared with that for patients aged 65 to 69 years, odds of undertriage gradually increased in all age groups, reaching 57% for patients older than 80 years (OR 1.57; 95% CI 1.52 to 1.61). Distance to a trauma center was associated with increasing odds of undertriage, with 37% higher odds (OR 1.37; 95% CI 1.15 to 1.40) for older adults living more than 30 miles from a trauma center compared with patients living within 15 miles. Nearly half of older adult trauma patients are undertriaged; it increases with age and distance to care and is most common in Southern and Western states. Improvements to field triage and trauma center access for older patients are urgently needed.


Diazepam self-administration and resistance to extinction.
Self-administration behavior was maintained by a unit dose of 0.03 mg/kg diazepam in 4 of 5 monkeys trained to respond on a lever by successive approximation using diazepam or saline. A dose-response function was determined using diazepam doses ranging between 0.01 and 0.3 mg/kg/infusion. Peak rates of responding occurred at doses of 0.01 or 0.03 mg/kg/infusion and drug intake was directly related to dose. When saline was substituted for diazepam either before or again after the dose-response function was determined, levels of responding remained unexpectedly high, even after as many as 16 consecutive sessions. The rates of responding maintained under extinction conditions appeared to be directly related to the amount of diazepam previously self-administered. For instance, monkeys which did not initially have high rates of responding for saline showed increases in responding after additional exposure to diazepam. Furthermore, the one monkey with low diazepam self-administration rates also had low rates of responding for saline. However, following a period of cocaine self-administration, responding declined in all monkeys when saline was substituted for cocaine. The data suggest that diazepam self-administration affects responding under extinction conditions, an effect which makes the interpretation of diazepam's reinforcing properties difficult.


Experimentally exposed toxic effects of long-term exposure to environmentally relevant concentrations of CIP in males and females of the silver catfish Rhamdia quelen.
Ciprofloxacin (CIP) is an antibiotic commonly used in human and veterinary medicine. It is present in the aquatic environment, but we still know very little about its effect on non-targeted organisms. This study aimed to evaluate the effects of long-term exposure to environmental CIP concentrations (1, 10, and 100 μg.L-1) in males and females of Rhamdia quelen. After 28 days of exposure, we collected the blood for the analysis of hematological and genotoxic biomarkers. Additionally, we measured 17 β-estradiol and 11 keto-testosterone levels. After the euthanasia, we collected the brain and the hypothalamus to analyze acetylcholinesterase (AChE) activity and neurotransmitters, respectively. The liver and gonads were assessed for biochemical, genotoxic, and histopathological biomarkers. At 100 μg.L-1 CIP, we observed genotoxicity in the blood, nuclear morphological changes, apoptosis, leukopenia, and a reduction of AChE in the brain. In the liver was observed oxidative stress and apoptosis. At 10 μg.L-1 CIP, leukopenia, morphological changes, and apoptosis were presented in the blood and a reduction of AChE in the brain. Apoptosis, leukocyte infiltration, steatosis, and necrosis occurred in the liver. Even at the lowest concentration (1 μg.L-1), adverse effects such as erythrocyte and liver genotoxicity, hepatocyte apoptosis, oxidative stress, and a decrease in somatic indexes were observed. The results showed the importance of monitoring CIP concentrations in the aquatic environment that cause sublethal effects on fish.


Xiaoyan lidan formula ameliorates α-naphthylisothiocyanate-induced intrahepatic cholestatic liver injury in rats as revealed by non-targeted and targeted metabolomics.
Intrahepatic cholestasis is a clinical syndrome of liver damage with systemic circulation and intrahepatic accumulation of excessive toxic bile acids without effective therapeutic methods so far. Xiaoyan Lidan Formula (XYLDF), a traditional Chinese prescription, has long been clinically applied for hepatobiliary disorders due to cholestasis. But its mechanism remains unknown. In this study, a non-targeted metabolomics approach based on UHPLC-Q-TOF-MS/MS combined with a bile acids (BAs) - targeted metabolomics approach based on UHPLC-MS/MS were performed to elucidate the functional mechanisms of XYLDF on α-naphthylisothiocyanate(ANIT)-induced intrahepatic cholestasis rats. The results showed that a total of 39 endogenous metabolites with significant difference (VIP > 1.00, P < 0.05) were identified as biomarkers of ANIT-induced intrahepatic cholestasis in rats. After treatment by XYLDF, 22 biomarkers were reversed to the control-like levels, which involved in primary BA biosynthesis, bile acid metabolism and excretion, steroids metabolism, retinol metabolism, starch and sucrose metabolism, inter conversions between pentose and glucoronate as well as arachidonic acid metabolism. Meanwhile, the results of contents variation of BAs in liver and serum showed that both hydrophilic and hydrophobic BAs were markedly increased in the model rats, while XYLDF treatment could restore the increase induced by ANIT, which suggested that one of the mechanisms of XYLDF on cholestasis referred to regulation of metabolic homeostasis of cholic acid.


Application and mechanism of nucleation-induced pelleting coagulation (NPC) in treatment of fracturing wastewater with high concentration of dissolved organic matter.
To improve the separation efficiency of fluffy flocs during coagulation of fracturing wastewater with high concentration of dissolved organic matter, a novel nucleation-induced pelleting coagulation (NPC) process is proposed based on pelleting coagulation in this study. In the NPC process, nucleation agents were added to act as pellet seeds to generate high-density pellet flocs. The results implied that the necessary condition for the NPC process was to control the metastable state, i.e. zeta potential around -10 mV after addition of the coagulant, polyaluminium chloride (PAC). Diatomite, which was added after rapid mixing, was used as the nucleation agent, and its optimal dosage was about 100 mg/L with particle size 100-200 μm. In addition, the dosage of the coagulant aid, polyacrylamide (PAM), significantly affected the performance of the NPC process, and the optimal PAM dosage was 10 mg/L in this study. It was found that 60 rpm (G = 55.1 s-1) was the optimal hydraulic condition for pellet growth during slow mixing. The pellet floc settling velocity reached 14.9 mm/s and the particle size (d50) reached 4.6 mm with an effective density of 0.021 g/cm3 at the optimal condition, which was one order higher than that of conventional aluminium flocs.


Inhibition of aldehyde dehydrogenases by methylene blue.
The effect of the redox dye methylene blue on the stability of NADH and on the activity of the enzyme aldehyde dehydrogenase (ALDH; EC 188.8.131.52) was examined. NADH was measured by HPLC with fluorometric or spectrophotometric detection. The ALDH activity assays were carried out by following the formation of 3,4-dihydroxyphenylacetic acid (DOPAC) from 3,4-dihydroxyphenylacetaldehyde (DOPAL) using HPLC and electrochemical detection. Incubation of NADH solutions in the presence of methylene blue resulted in a time-dependent direct oxidation of NADH. Methylene blue inhibited the human erythrocyte and leukocyte ALDHs and the rat liver mitochondrial low-Km ALDH in a concentration-dependent manner. The inactivation was reversible by dilution, and kinetic analysis indicated that methylene blue inhibits the rat liver mitochondrial low-Km and human erythrocyte ALDHs competitively with respect to DOPAL, while no effect of the NAD+ concentration was apparent. For the rat liver low-Km ALDH, a Ki of 8.4 +/- 2.8 microM (mean +/- SD; N = 5) was calculated. The inhibition of ALDH and the resulting decrease in the redox effect on the NAD system bound to alcohol dehydrogenase (EC 188.8.131.52) could explain the protective effect of methylene blue against metabolic redox effects of ethanol.


Efficacy and safety of iodized lecithin tablets versus spironolactone in alleviating central serous retinopathy among Chinese patients with uncontrolled diabetes.
To compare the effectiveness and safety of spironolactone versus lecithin-bound iodine in patients with central serous retinopathy (CSR). Chinese diabetes patients aged>18 years with CSR with persistent increased level of subretinal fluid (SRF) were enrolled. Subjects were randomized to receive either oral lecithin-bound iodine (390µg/kg/day) or oral spironolactone (50mg/day) for 6 months. A total of 200 patients were randomized and completed the study. Compared to spironolactone group, patients treated with lecithin-bound iodine had greater proportion of eye with complete resolution (87% vs 81%, p>0.005). Higher improvement in height of SRF was observed in lecithin-bound iodine-treated patients as compared with Spironolactone-treated patients (91.2[87.5] vs 142.5 [121.1]; p>0.005). However, no statistically significant difference was observed on none of comparisons. Compared to Spironolactone, the patients treated with lecithin-bound iodine had greater improvement in lesion size, central macular thickness and best-corrected visual acuity. However, no statistically significant difference was observed in any of parameter assessed. (p>0.005). The results of the present study suggested that the lecithin-bound iodine was found more effective (nnumerically) than spironolactone in Chinese diabetes patients with CSR.


Evaluation of Responsiveness to Reduced-Dose Rituximab in Corticotropin/Intravenous Immunoglobulin/Rituximab Combination Immunotherapy for Opsoclonus-Myoclonus Syndrome.
Rituximab (anti-CD20) has been used as B-cell-targeted intervention to treat opsoclonus-myoclonus syndrome. Due to isolated reports of chronic hypogammaglobulinemia and B lymphopenia following rituximab in several disorders, and rapid B-cell depletion after a few doses, we reduced the dosage 20% in our clinical practice. In this Institutional Review Board-approved retrospective study, 32 children with opsoclonus-myoclonus syndrome and cerebrospinal fluid B-cell expansion had received front-loaded adrenocorticotropic hormone, intravenous immunoglobulin, and rituximab combination immunotherapy for de novo opsoclonus-myoclonus syndrome. Parametric statistical analysis compared 10 children receiving 1200 mg/m2 of rituximab (300 mg/m2 × 4) and 22 receiving 1500 mg/m2 (375 mg/m2 × 4). Clinical response had been video documented and scored by a blinded observer. In both groups, motor severity (total score) lessened by ≥76% and cerebrospinal fluid B cells were similarly depleted (≥95%) six months after treatment. None of the treated patients remained unable to walk independently. Serum IgM depletion was analogous in the 1200 mg/m2 (-73%) and 1500 mg/m2 group (-64%). The relapse frequency was similar in both groups. Side effects were principally steroidal, tolerable, and transient. Circulating B-cell repopulation was comparable. The reduced-dose of rituximab in rituximab combination immunotherapy was as effective and well tolerated as the standard dose, and provided rapid, early therapeutic intervention in opsoclonus-myoclonus syndrome. Pending a long-term prospective study, these are proof-of-concept data in support of challenging the dose of rituximab in various disorders, which may have different dose requirements.


The use of carvone in consecutive patch testing.
Carvone (l-carvone) is a mint-tasting flavour additive that most of us is exposed to and can cause allergic contact reactions. To analyse the frequency and the relevance of positive carvone reactions in a dermatitis population. A retrospective analysis of dermatitis patients consecutively tested with carvone from 2017 to 2021. Data were retrieved from the department's patch-test database. Of 3554 patients tested with carvone, 28 (0.79%) had a positive reaction. Carvone-positive patients had higher mean age, were significantly more likely female (p < 0.001) and had often an intraoral/lip involvement (p < 0.001). In the carvone-positive group, 50% (n = 14) had a relevant reaction, and in 4 of 14, the relevance was first revealed after test reading. Of the carvone-positive patients, 18 of 28 did not have a coexisting allergy to a fragrance/flavour allergen and of these 44% had a relevant allergy. The study suggests that a significant fraction of relevant carvone contact allergies may be overlooked if the allergen is not tested. Furthermore, as the exposure is widespread, inclusion of carvone in the Swedish baseline series may be justified even if the contact allergy prevalence is below 1%.


Comparison between N13NH3-PET and 99mTc-Tetrofosmin-CZT SPECT in the evaluation of absolute myocardial blood flow and flow reserve.
PET/CT is the standard for quantitative assessments of myocardial blood flow (MBF), but it requires short-lived-tracers, costly, and not widely available. SPECT with Cadmium Zinc Telluride (CZT) detectors allows dynamic acquisition and quantitation of MBF. The study aims were to compare MBF measurements by 99mTc-tetrofosmin-CZT to N13NH3 PET/CT after regadenoson-induced coronary hyperemia and to evaluate the effect of attenuation correction (AC). 54 patients were evaluated at rest and during vasodilation by 99mTc-tetrofosmin-CZT and N13NH3 PET/CT within 2 weeks. MBF and MBF reserve (MFR) were measured by CZT with or without AC (NAC). The global rest MBF was 0.76 ± 0.19 mL/min/gr by PET and 0.76 ± 0.24 by AC-CZT (P = NS) and 1.14 ± 0.4 by NAC-CZT (P < 0.001 vs PET and AC-CZT). Stress MBF was higher when measured by PET than AC-CZT (1.87 ± 0.45 vs 1.62 ± 0.68 mL/min/gr, P < 0.0008), but lower than NAC-CZT (2.36 ± 1.1, P < 0.0003). The MBF reserve ratio (MFR) was higher by PET than AC-CZT (2.52 ± 0.56 vs 2.22 ± 1 (P < 0.009) and NAC-CZT (2.18 ± 1.0, P < 0.004). Linear regression was better between PET (MFR and stress MBF) and AC-CZT than between PET and NAC-CZT. ROC curve analysis showed the significant ability of AC-CZT to predict MFR < 2 and stress MBF < 1.7 (AUC = 0.75 and 0.82 respectively) and to differentiate between normal and CAD patients (AUC = 0.747 and 0.892 for MFR and stress MBF, respectively). Our data show a reasonable correlation between MBF and MFR measured by N13NH3-PET and 99mTc-Tetrofosmin-CZT SPECT. NAC-CZT overestimates MBF. AC is recommended when using CZT for measuring MBF.


Lycopene ε-cyclase mediated transition of α-carotene and β-carotene metabolic flow in carrot fleshy root.
The accumulation of carotenoids, such as xanthophylls, lycopene, and carotenes, is responsible for the color of carrot (Daucus carota subsp. sativus) fleshy roots. The potential role of DcLCYE, encoding a lycopene ε-cyclase associated with carrot root color, was investigated using cultivars with orange and red roots. The expression of DcLCYE in red carrot varieties was significantly lower than that in orange carrots at the mature stage. Furthermore, red carrots accumulated larger amounts of lycopene and lower levels of α-carotene. Sequence comparison and prokaryotic expression analysis revealed that amino acid differences in red carrots did not affect the cyclization function of DcLCYE. Analysis of the catalytic activity of DcLCYE revealed that it mainly formed ε-carotene, while a side activity on α-carotene and γ-carotene was also observed. Comparative analysis of the promoter region sequences indicated that differences in the promoter region may affect the transcription of DcLCYE. DcLCYE was overexpressed in the red carrot 'Benhongjinshi' under the control of the CaMV35S promoter. Lycopene in transgenic carrot roots was cyclized, resulting in the accumulation of higher levels of α-carotene and xanthophylls, while the β-carotene content was significantly decreased. The expression levels of other genes in the carotenoid pathway were simultaneously upregulated. Knockout of DcLCYE in the orange carrot 'Kurodagosun' by CRISPR/Cas9 technology resulted in a decrease in the α-carotene and xanthophyll contents. The relative expression levels of DcPSY1, DcPSY2, and DcCHXE were sharply increased in DcLCYE knockout mutants. The results of this study provide insights into the function of DcLCYE in carrots, which could serve as a basis for creating colorful carrot germplasms.


Clinical impact and cost-effectiveness of co-trimoxazole prophylaxis in patients with HIV/AIDS in Côte d'Ivoire: a trial-based analysis.
In 2000, WHO/UNAIDS recommended co-trimoxazole prophylaxis for persons at early stages of HIV infection (WHO stage > or = 2) in sub-Saharan Africa. To assess the cost-effectiveness of alternative strategies for initiation of co-trimoxazole in Côte d'Ivoire. Cost-effectiveness analysis with an HIV simulation model using clinical and cost data from a randomized trial of co-trimoxazole in HIV-infected adults. The study included HIV-infected patients in Côte d'Ivoire, with median age 33 years. Thirty-four percent were classified as WHO stage 2, 59% as stage 3, and 7% as stage 4. The mean CD4 cell count was 331 x 10(6) cells/l. The interventions were no prophylaxis, clinical criteria-based co-trimoxazole initiation (early: WHO stage > or = 2; late: WHO stage > or = 3), CD4-based co-trimoxazole initiation (< 500, < 200, < 50 x 10(6) CD4 cells/l). The outcome measures were life expectancy, lifetime costs, and incremental cost-effectiveness. The most effective strategy, initiation of co-trimoxazole prophylaxis at WHO stage > or = 2, increased undiscounted life expectancy by 5.2 months, discounted life expectancy by 4.4 months, and lifetime costs by US dollars 60, compared with no prophylaxis. Delaying prophylaxis initiation until WHO stage >or = 3 was less costly and less effective. All CD4-based strategies were dominated. The incremental cost-effectiveness of early versus late co-trimoxazole prophylaxis initiation was US dollars 200/year of life gained. Results were stable despite wide variations in plausible assumptions about bacterial resistance and the prophylaxis efficacy on co-trimoxazole-resistant strains. For HIV-infected adults in Côte d'Ivoire, co-trimoxazole prophylaxis is reasonably cost-effective and most effective if initiated when WHO stage > or = 2. Early co-trimoxazole prophylaxis will prevent complications prior to antiretroviral therapy initiation and should be considered an essential component of care for early HIV in sub-Saharan Africa.


Both gut microbiota and cytokines act to atherosclerosis in ApoE-/- mice.
Several studies have suggested a role for the gut microbiome and cytokines in atherosclerosis development, but combined analyses of the changes of the gut microbiota and cytokines have not been explored previously. We treated ApoE-/- and wild-type mice with a high-fat diet for 12 weeks. The gut microbiome and cytokine composition were analyzed using 16S ribosomal DNA sequencing and RayBio Quantibody Arrays, respectively. GO and KEGG analysis were performed to rationalize the potential mechanisms involved in the process of atherosclerosis. Gut bacterial characteristics in ApoE-/- mice were clearly separated and 21 gut bacterial clades were detected by the LEfSe analysis showing significant differences during the development of atherosclerosis. The relative abundance of Verrucomicrobia, Bacteroidaceae, Bacteroides, and Akkermansia showed significant positive correlations with serum total cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Additionally, the relative abundance of Ruminococcaceae was positive with the level of HDL and the abundance of Rikenellaceae showed a negative relationship with the level of TG and LDL. Thirteen differentially expressed proteins were identified with P-value < 0.05. CXCL5, FGF2, and E-Selectin were significantly negatively associated with Akkermansia and Verrucomicrobia. Additionally, CXCL5 was significantly negatively correlated with Bacteroides and Bacteroidaceae. Three "cellular component" subcategories, 24 ″molecular function" subcategories, 752 ″biological process" subcategories and 29 statistically remarkable KEGG pathway categories were identified. Gut microbiota changes of the mice having atherosclerosis and their relationship with the inflammatory status could be one of the major etiological mechanisms underlying atherosclerosis.


The Role of Children in Household Transmission of SARS-CoV-2 Across Four Waves of the Pandemic.
It is important to understand the dynamics of SARS-CoV-2 transmission in close-contact settings such as households. We hypothesized that children would most often acquire SARS-CoV-2 from a symptomatic adult caregiver. This prospective cohort study was conducted from April 2020 to July 2022 in a low-resource, urban settlement in Brazil. We recruited families who brought their children to a public clinic. We collected nasopharyngeal and oral swabs from household members and tracked symptoms and vaccination. In total, 1256 participants in 298 households were tested for SARS-CoV-2. A total of 4073 RT-PCR tests were run with 893 SARS-CoV-2 positive results (21.9%). SARS-CoV-2 cases were defined as isolated cases (N = 158) or well-defined transmission events (N = 175). The risk of household transmission was lower if the index case was a child (OR: 0.3 [95% CI: 0.16-0.55], P < .001) or was vaccinated (OR: 0.29 [95% CI: 0.1-0.85], P = .024), and higher if the index was symptomatic (OR: 2.53 [95% CI: 1.51-4.26], P < .001). The secondary attack rate for child index cases to child contacts was 0.29, whereas the secondary attack rate for adult index cases to child contacts was 0.47 (P = .08). In this community, children were significantly less infectious to their household contacts than adolescents or adults. Most children were infected by a symptomatic adult, usually their mother. There was a double benefit of vaccination as it protected the vaccine from severe illness and prevented onward transmission to household contacts. Our findings may also be valid for similar populations throughout Latin America.


Molecular Characterization of a Newly Identified Subfamily Member of Penaeidin from two Penaeid Shrimps, Fenneropenaeus indicus and Metapenaeus monoceros.
Penaeidins are a major group of antimicrobial peptides found in penaeid shrimps. This study reports a new isoform of penaeidin from the hemocytes of Indian white shrimp, Fenneropenaeus indicus (Fi-PEN, JX657680), and the pink shrimp, Metapenaeus monoceros (Mm-PEN, KF275674). Mm-PEN is also the first antimicrobial peptide to be identified from M. monoceros. The complete coding sequences of the newly identified Fi-PEN and Mm-PEN consisted of an ORF of 338 bp encoding 71 amino acids with a predicted molecular weight of 5.66 kDa and a pI of 9.38. The penaeidins had its characteristic signal peptide region (19 amino acids), which was followed by a mature peptide with a proline-rich domain (24 amino acids) at the N-terminal region and a cysteine-rich domain (28 amino acids) at the C-terminal region, designating it to penaeidin-3 subgroup. Structural analysis revealed an alpha-helix in its secondary structure and an extended structure at the proline-rich domain. The newly identified penaeidin isoform showed maximum similarity of 63 % to a penaeidin-3 isoform of P. monodon, which further proves it to be a new isoform. Phylogenetic analysis showed that it possessed similar evolutionary status like other penaeidins, which has subsequently diverged at different phases of evolution. The wide distribution of penaeidins in penaeid shrimps indicates the importance of these AMPs in the innate immunity.


Psychotherapy, neutrality, and the role of activism.
Was the sixties activist merely acting out unresolved Oedipal conflicts? Is the analyst who interprets the activist's neurotic conflicts actually "neutral"? Issues from the sixties debate are relevant to today's discussion of activism in public mental health. For instance, why, at a time of shrinking public service budgets and unprecedented suffering on the part of mental patients, have the providers and consumers of public mental health services not become more active in struggles to reorder our unfortunate social priorities? The discussion proceeds to an exploration of the therapeutic effect of activism.


Plasma intermedin levels in patients with acute myocardial infarction.
It has been shown that adrenomedullin (ADM) may function as a cardiovascular-regulatory peptide in humans. Intermedin (IMD) is a newly discovered peptide related to ADM and has a greater range of biological effects on the cardiovascular in animal experiments. The purpose of the study was to investigate the pathophysiological role of IMD in patients with acute myocardial infarction (AMI). The present study included twenty patients with acute ST-segment elevation myocardial infarction (STEMI), thirty-three with stable coronary heart disease (SCHD), and eighteen healthy controls. Plasma levels of IMD, malonaldehyde (MDA), and superoxide dismutase (SOD) and cardiac biomarkers were determined at one, two, four and seven days following AMI. Plasma IMD levels were significantly increased on day 1 in AMI patients when compared with SCHD subjects (P=0.014), and reached a peak of 181.88 ± 9.47 pg/ml at 96 h. Plasma IMD concentrations were correlated with MDA and SOD. Furthermore, patients with severe lesions in their coronary arteries tended to have higher plasma IMD levels (P<0.05) in AMI patients. A significant increase in plasma IMD following AMI may be associated with oxidative stress, and could be used as a marker to reflect the severity of the coronary stenosis.


[Complete cost of surgery for postpartum haemorrhage].
Reduction of maternal mortality is a major priority in the public health domain. One of the main causes of maternal mortality is postpartum haemorrhage. Because economic pressures favour the use of less expensive strategies, it is becoming now critical to know exactly the cost of the surgical procedures involved in the treatment of postpartum haemorrhage, in order to provide future guidelines in Implementing reforms in hospital. Evaluation was made on multiple data collected in the Gynecology-Obstetrics and Central Sterile Supplies departments of a tertiary care Hospital. Analysis of the production costs was made based on the actual costs. The receipts were figured on the basis of applicable reimbursement in France in 2005, taking into account the financial decisions of the producers. From January 2004 to December 2005, 262 patients were treated for postpartum hemorrhage and patients files were available for review in 255 cases. Of these, surgery was performed in 52 cases. The costs of surgery in the postpartum care ranged from 275.04 euro per manual exploration of the uterine cavity (n=8), 302.48 euro per exploration with valve (n=26), 601.55 euro per vascular ligation (n=3), 725.53 euro per vaginal packing or unpacking (n=10) to 875.06 euro per hysterectomy (n=5). Cleaning and sterilizing of surgical instruments represented a substantial burden, ranging from 7.5% to 11.4% of the total cost of surgery. The costs of surgery for postpartum haemorrhage have been calculated to provide future guidelines for the directions and follow-up of these activities in light of the T2A-EPRD and poles of activity. The actual costs could be used to determine the bases of one or more French DRGs (PMSI) "postpartum hemorrhage" evolution.


NanoZnO-modified titanium implants for enhanced anti-bacterial activity, osteogenesis and corrosion resistance.
Titanium (Ti) implants are widely used in dentistry and orthopedics owing to their excellent corrosion resistance, biocompatibility, and mechanical properties, which have gained increasing attention from the viewpoints of fundamental research and practical applications. Also, numerous studies have been carried out to fine-tune the micro/nanostructures of Ti and/or incorporate chemical elements to improve overall implant performance. Zinc oxide nanoparticles (nano-ZnO) are well-known for their good antibacterial properties and low cytotoxicity along with their ability to synergize with a variety of substances, which have received increasingly widespread attention as biomodification materials for implants. In this review, we summarize recent research progress on nano-ZnO modified Ti-implants. Their preparation methods of nano-ZnO modified Ti-implants are introduced, followed by a further presentation of the antibacterial, osteogenic, and anti-corrosion properties of these implants. Finally, challenges and future opportunities for nano-ZnO modified Ti-implants are proposed.


Drug metabolism biosensors: electrochemical reactivities of cytochrome P450cam immobilised in synthetic vesicular systems.
Biosensors containing cytochrome P450cam in a didodecyldimethylammonium bromide vesicular system were prepared by cross-linking onto a glassy carbon electrode (GCE) with glutaraldehyde in the presence of bovine serum albumin. Cyclic voltammetric responses of the sensor in air-free buffer solution showed that the sensor exhibited reversible electrochemistry due to direct electron exchange between the haem Fe(3+/2+) redox system and the GCE surface. In air-saturated solution containing camphor, the biosensor gave an irreversible electrocatalytic current which is compatible with the monooxygenation of the substrate. Steady state amperometric experiments with camphor, adamantanone and fenchone were performed with a biosensor prepared by cross-linking P450cam with glutaraldehyde onto a Pt disc electrode. The sensor was characterised by fast amperometric responses, attaining steady-state in about 20 s in a cobalt sepulchrate mediated electrochemical system. The kinetic parameters of the biosensor were analysed using the electrochemical Michaelis Menten equation. The estimated apparent Michaelis-Menten constant, Km, values for the biosensors were in the range of 1.41-3.9 mM.


A Concept of "Boundary Determination" by the Combination of a Local Flap and Free Tissue Transfer Useful for the Prevention of Postoperative Complications After Complex and Widespread Skull Base Reconstruction.
The transplanted tissue is sutured to the stumps of the bones in skull base reconstruction. Concerning reconstruction by free tissue transfer, it is difficult that the tissue is accurately sutured/fixed to a complex three-dimensional structure. The authors devised a technique in which free tissue transfer is combined with a local flap. A pericranial flap is sutured/fixed onto the irregular border between the cranial and nasal cavities. A free tissue graft is transplanted cranial or caudal to the determined border. Clinical presentation 1 is a patient with carcinoma of the frontal sinus (T4bN0M0). Resection of the frontal bone/nasal bone/medial and superior walls of the orbit, frontal lobectomy was performed. Clinical presentation 2 is a patient with carcinoma of the maxillary sinus (T4aN0M0). Extended total maxillectomy, simultaneous resection of the facial skin/temporal muscle were performed. There were no serious postoperative complications related to compression or occlusion of the cerebral parenchyma or paranasal sinus.


Clinical profiles and surgical outcomes of adult esotropia.
The aim of this study was to describe the clinical features and surgical outcomes of teenage and adult patients with esotropia undergoing strabismus surgery with adjustable sutures. Seventy-three patients were included in this retrospective, cohort study. Patients were stratified into group 1 (35 with childhood-onset esotropia [CET]) and group 2 (38 with adult-onset esophoria-tropia [EPT]). Preoperative immediate, 2-week, and 4-6-month postoperative measurements of ocular alignment, as well as fusional testing, were performed. Postoperative success was defined as distant (6 m) and near (33 cm) alignment within 12 prism diopters (PDs) of orthotropia in the primary position at 2 weeks and at 4-6 months with a single surgery. Patients with CET more frequently had hyperopia and amblyopia and were more likely to present for surgery because of psychosocial strabismus-related problems. Patients with EPT predominantly had myopia and were more likely to experience diplopia and asthenopia. In group 1, the mean preoperative distance deviation improved from 30 PDs to 4 PDs at 2 weeks and to 4 PDs at 4-6 months (p < 0.001). In group 2, mean preoperative distance alignment improved from 22 to 3 PDs at 2 weeks and to 3 PDs at 4-6 months (p < 0.001). The mean objective, single-surgery success rate at 2 weeks was 88% and 97% in groups 1 and 2, respectively. At 4-6 months, postoperative success was 71% in group 1 and 80% in group 2. The majority of patients reported subjective improvement. There are distinct preoperative differences between CET and EPT patients. Adjustable, strabismus surgery in this cohort is safe and effective in achieving subjective and objective success.


Theoretical feasibility of vasodilator-enhanced local tumor heating.
Normal arterioles, in contrast to the abnormal microvasculature of many solid tumors, provide a target for selective drug action which can enhance local heat treatment of the tumors. Measurements of tissue blood flow with radioactive microspheres and estimates of changes in blood flow with thermal clearance methods revealed that vasodilator drugs either decreased or did not alter blood flow in hamster melanoma, rat hepatoma and canine transmissible venereal tumor while increasing perfusion in adjacent normal tissues 2 to 4-fold. Solutions of the bio-heat transfer equation, which take into account such selective effects of vasodilators on blood flow in normal tissues, clearly demonstrate improved selective heating for spheroidal tumors over 2 cm in diameter. In the presence of vasodilator drug effect, steady-state center tumor temperatures of 45-50 degrees C can be achieved by increased power input, while surrounding normal tissues remain below 42 degrees C.


Ecoinformatics: supporting ecology as a data-intensive science.
Ecology is evolving rapidly and increasingly changing into a more open, accountable, interdisciplinary, collaborative and data-intensive science. Discovering, integrating and analyzing massive amounts of heterogeneous data are central to ecology as researchers address complex questions at scales from the gene to the biosphere. Ecoinformatics offers tools and approaches for managing ecological data and transforming the data into information and knowledge. Here, we review the state-of-the-art and recent advances in ecoinformatics that can benefit ecologists and environmental scientists as they tackle increasingly challenging questions that require voluminous amounts of data across disciplines and scales of space and time. We also highlight the challenges and opportunities that remain.


Ciliated hepatic foregut cyst: report of three cases and review of imaging features.
Ciliated hepatic foregut cysts (CHFCs) are rare cystic lesions which are most commonly asymptomatic. They can be clinically important as they may, on rare occasions, undergo malignant transformation or cause mass effect if significantly enlarged. Three cases of CHFCs are presented in this article and their imaging features are reviewed.


Modeling depression in animal models.
Animal models and preclinical tests have played large roles in the development of antidepressant drugs and are likely to continue to play important roles. In the present communication, the main animal models of depression have been described and reviewed. These models include the Flinders sensitive line (FSL) rat, the Wistar Kyoto (WKY) rat, the fawn-hooded (FH) rat, and the learned helpless (LH) rat. In addition, the materials used to assess the behavior of these rats, including swim tanks, drinking tubes, and an open field apparatus, have been discussed. Finally, the methods used in collecting the relevant behaviors in the animal models are described. These include the procedures used in the forced swim test and chronic mild stress protocols, including the sucrose preference test. It is concluded that the behavioral tests used to infer depressed-like behavior in rats will continue to provide useful data if the appropriate animals and proper methods are used.


Estimating biokinetic coefficients in the PACT™ system.
When powdered activated carbon (PAC) is continuously added to the aeration tank of an activated sludge reactor, the modification is called a PACT™ process (for powdered activated carbon treatment). The PAC provides many benefits, but complicates the determination of biological phenomena. Determination of bio-oxidation kinetics in a PACT system is a key to fully understanding enhanced biological mechanisms resulting from PAC addition. A model is developed to account for the main mechanisms involved in the PACT system -- adsorption, air stripping and bio-oxidation. The model enables the investigation of biokinetic information, including possible synergistic effects. Six parallel reactors were used to treat a synthetic waste; three activated sludge and three PACT. The PACT reactors provided significantly reduced effluent TOC (total organic carbon). Biokinetic coefficients were obtained from steady-state data using averaged reactor data and by using all data (22 points for each reactor). As expected, the PACT reactors resulted in a substantial reduction in the effluent concentration of non-biodegradable total organic carbon. The Monod equation's half-saturation coefficient (Ks) was reduced significantly in the PACT reactors, resulting in higher growth rates at lower concentrations. The maximum specific substrate utilization (qm) rate was also reduced about 25% using the averaged data and remained unchanged using all the data. The substrate utilization values are affected by errors in biomass determination and more research is needed to accurately determine biomass.


A comparison of accessibility of ribosomal proteins on free and membrane-bound ribosomes: the ribosomal proteins potentially involved in ribosome-membrane binding.
The relative accessibility of rat liver ribosomal proteins to reductive methylation was examined using membrane-bound and free ribosomes. Comparisons indicated that 12-13 large ribosomal proteins are masked by ribosomal association with membranes. These consisted of L8, L10, L17, L26-28, L31 and L36, and probably also include L4, L5, L7 and L29. These proteins seem to surround a region centered about L3 and may partly define a ribosomal channel through which the nascent peptide emerges. Approx. 10-20% of the large ribosomal subunit surface area is shielded by the membrane.


Responses of isolated and perfused dog coronary arteries to acetylcholine, norepinephrine, KCl, and diltiazem before and after removal of the endothelial cells by saponin.
The vascular responses to acetylcholine (ACh), norepinephrine (NE), KCl, and diltiazem were examined before and after removal of endothelial cells by an intraluminal bolus injection of saponin (1 mg) in isolated and perfused dog coronary arteries. Without any precontraction, ACh induced a long-lasting vasodilation in small doses (less than 1 microgram), and an initial brief vasoconstriction was occasionally accompanied in large doses. These vascular responses to ACh were not significantly affected by the pretreatment with propranolol (5 X 10(-6) mol/l). The endothelial removal by intraluminal saponin was confirmed electron microscopically. After 20-60 min of saponin treatment, the responses to drugs were observed and compared with the control. The ACh-induced vasodilation was significantly attenuated by saponin (P less than 0.01), but the ACh-induced vasoconstriction was not affected by it. The vasodilation was blocked by atropine. The NE- and KCl-induced vasoconstrictions and diltiazem-induced vasodilation were not affected by saponin treatment. It is suggested that: (1) ACh produced a vasodilation in the nonpreconstricted condition of dog coronary arteries; (2) the vasodilation caused by ACh is mostly endothelium-dependent, which is considered to be mediated by muscarinic receptors; and (3) the vascular responses to NE, KCl, and diltiazem and the vasoconstriction produced by ACh are not influenced by removal of the endothelium in a relatively large epicardial coronary artery of the dog.