The genetics of cortical myelination in young adults and its relationships to cerebral surface area, cortical thickness, and intelligence: A magnetic resonance imaging study of twins and families.
The cerebral cortex contains a significant quantity of intracortical myelin, but the genetics of cortical myelination (CM) in humans is not well understood. Relatively novel MRI-derived measures now enable the investigation of cortical myelination in large samples. In this study, we use a genetically-informative neuroimaging sample of 1096 young adult subjects from the Human Connectome Project in order to investigate genetic and environmental variation in CM and its relationships with cerebral surface area (SA) and cortical thickness (CT). We found that genetic factors account for approximately 50% of the observed individual differences in mean cortical myelin, 75% of the variation in total SA, and 85% of the variance in global mean CT. Although significant genetic influences were found throughout the cortex, both CM and SA demonstrated a posterior predominance, with disproportionately strong effects in the parietal and occipital lobes and significantly overlapping heritability maps (p < 0.001). Yet despite showing similar spatial heritability patterns, we found evidence that CM is genetically independent from SA at both global and vertex levels; genetically-mediated relationships between CM and CT were similarly small in magnitude. We also found small but statistically significant genetic associations between NIH Toolbox Total Cognition score and CM in the temporal lobe and insula. SA-cognition and CT-cognition correlations were less widespread compared to CM and both patterns were similar to those reported in prior studies.


Biosynthesis of phyto-functionalized silver nanoparticles using olive fruit extract and evaluation of their antibacterial and antioxidant properties.
The green synthesis of nanomaterials is of utmost interest as it offers an eco-friendly approach over chemical synthetic routes. However, the reported biosynthesis methods are often time-consuming and require heating or mechanical stirring. The current study reports a facile one-pot biosynthesis of silver nanoparticles (AgNPs) mediated by olive fruit extract (OFE) and sunlight irradiation of only 20 s. OFE acts as both a reducing and a capping agent for the formation of OFE-capped AgNPs (AgNPs@OFE). The as-synthesized NPs were systematically characterized by UV-vis spectrometry, Fourier transform infrared (FTIR) spectroscopy, scanning electrochemical microscopy with energy-dispersive X-ray (SEM-EDX), X-ray diffraction (XRD), dynamic light scattering (DLS), and cyclic voltammetry. SEM images confirmed the successful formation of monodispersed spherical AgNPs@OFE of approximately 77 nm. FTIR spectroscopy suggested the involvement of functional groups of phytochemicals from the OFE in the capping and reduction of Ag+ to Ag. The particles revealed excellent colloidal stability as evidenced from the high zeta potential (ZP) value (-40 mV). Interestingly, using the disk diffusion method, AgNPs@OFE revealed higher inhibition efficiency against Gram-negative bacteria (Escherichia coli, Klebsiella oxytoca, and extensively drug-resistant (XDR) Salmonella typhi) than Gram-positive bacteria (Staphylococcus aureus), with Escherichia coli showing the highest inhibition zone of 27 mm. In addition, AgNPs@OFE exhibited maximum potent antioxidant scavenging potential against H2O2, followed by DPPH, O2 -, and OH- free radicals. Overall, OFE can be considered an effective source for the sustainable production of stable AgNPs with potential antioxidant and antibacterial activities for biomedical applications.


Mass spectrometry of a human tumor glycolipid antigen being defined by mouse monoclonal antibody NS-19-9.
With an antibody-to-chromatogram binding assay to follow the preparation a glycolipid was isolated from human pancreatic carcinoma using a mouse monoclonal antibody of apparent specificity for gastrointestinal tumors. Direct probe mass spectrometry of three derivatives established the sugar sequence as NeuAc-hexose-(fucose)N-acetylhexosamine-hexose-hexose and the ceramide to be composed mainly of phytosphingosine and 16-24 carbon 2-hydroxy fatty acids. NMR spectroscopy of two of the derivatives made likely the presence of the sequence Gal beta 1 leads to 3GlcNAc(4 comes from 1 alpha Fuc)beta 1 leads to, which is the blood group Lewis a determinant. This is in agreement with recent results from degradation studies.


Testing a cascade model of linkage between child abuse and negative mental health among battered women in Japan.
This study examined the following hypotheses: (1) a child abuse history (CAH), domestic violence (DV), and child abuse by an intimate partner might have a crucial and specific influence but act differently on women's negative mental health; (2) CAH, DV, child abuse by an intimate partner, and negative mental health might be predictors of maternal child abuse, with complex interactions. A self-administered questionnaire survey was conducted among a sample of mothers (N=304) and their children (N=498) staying in 83 Mother-Child Homes in Japan to assess the women's CAH and DV experiences, along with their current mental health problems, including dissociated, depressed, and traumatic symptoms. A structural equation modeling (SEM) was adapted to test whether a complex theoretical model fits the actual relationship among a set of observed measures. Our model confirmed the linkage with broader aspects of violence within the family such as CAH and DV, focusing on women's mental health problems reported by them. In addition, CAH, DV, child abuse by intimate partner, and maternal mental health might have a crucial and specific but act influence on maternal child abuse.


Proanthocyanidins from the bark of Metasequoia glyptostroboides ameliorate allergic contact dermatitis through directly inhibiting T cells activation and Th1/Th17 responses.
The leaves and bark of Metasequoia glyptostroboides are used as anti-microbic, analgesic and anti-inflammatory drug for dermatic diseases in Chinese folk medicine. However, the pharmacological effects and material basis responsible for the therapeutic use of this herb have not yet been well studied. The objectives of this study were to evaluate the anti-inflammatory effects of the proanthocyanidin fraction from the bark of M. glyptostroboides (MGEB) and to elucidate its immunological mechanisms. The anti-inflammatory activity of MGEB was evaluated using 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD) in mice. Its potential mechanisms were further investigated by determining its effects on Con A-induced T cell activation and Th1/Th17 responses in vitro. Both intraperitoneal injection and oral administration of MGEB significantly reduced the ear swelling in DNFB-induced ACD mice. MGEB inhibited Con A-induced proliferation and the expression levels of cell surface molecules CD69 and CD25 of T cells in vitro. MGEB also significantly decreased the production of Th1/Th17 specific cytokines (IL-2, IFN-γ and IL-17) and down-regulated their mRNA expression levels in activated T-cells. MGEB could ameliorate ACD, at least in part, through directly inhibiting T cells activation and Th1/Th17 responses.


Folic acid increases global DNA methylation and reduces inflammation to prevent Helicobacter-associated gastric cancer in mice.
Previous studies have suggested that dietary folic acid (FA) can protect against certain types of cancers. However, the findings have varied, and the mechanisms by which FA exerts chemopreventive effects remain to be clarified. We examined the effects of FA supplementation on DNA methylation, gene expression, and gastric dysplasia in a transgenic mouse model that is etiologically and histologically well matched with human gastric cancers. Hypergastrinemic mice infected with Helicobacter felis were studied at multiple stages of gastric dysplasia and early cancer with FA supplementation initiated both at weaning and later in life. Global DNA methylation was assessed by a methylation sensitive cytosine incorporation assay, bisulfite pyrosequencing of B1 repetitive elements, and immunohistochemistry with anti-5-methylcytosine. We also profiled gene expression in the same tissues. We found a decrease in global DNA methylation and tissue folate and an increase in serum homocysteine with progression of gastric dysplasia. FA supplementation prevented this loss of global DNA methylation and markedly reduced gastric dysplasia and mucosal inflammation. FA protected against the loss of global DNA methylation both in the dysplastic gastric epithelial cells and in gastric stromal myofibroblasts. In addition, FA supplementation had an anti-inflammatory effect, as indicated by expression profiling and immunohistochemistry for lymphocyte markers. We conclude that FA supplementation is chemopreventive in this model of Helicobacter-associated gastric cancer. The beneficial effect of FA is likely due to its ability to prevent global loss of methylation and suppress inflammation.


Effects of tone repetition on auditory evoked neuromagnetic fields.
To investigate the impact of stimulus repetition on neuromagnetic auditory evoked fields (AEF) in the context of permanently varying auditory stimulation and uniform stimulation. Left-hemispheric AEF of 16 healthy subjects were recorded on a 31-channel system. In one condition subjects were stimulated with trains of 5 identical tones, in another condition the pitch of the stimuli varied from 800 to 1250 Hz in 50 Hz steps and every 10th stimulus was followed by an identical stimulus. Evoked cortical activity was estimated by calculation of the signal:noise ratio and by dipole reconstruction. If the stimuli were permanently varied, tone repetition elicited a neuromagnetic mismatch negativity (MMNm) in about half of the subjects, while the AEF component N100m was not significantly affected. If trains of uniform stimuli were applied, a significant decrease of the N100m dipole moment was observed from the first to the second stimulation only. The N100m dipole location in mediolateral direction, however, varied at least between the first 3 stimulus positions. An MMNm can be elicited by tone repetition even at interstimulus intervals extending the so-called temporal window of integration. The data on repeated stimulation with uniform tones reveal a dissociation between effects on N100m dipole moment and location.


Metal bioaccumulation in edible target tissues of mullet (Mugil liza) from a tropical bay in Southeastern Brazil.
The present study aimed to investigate metal bioaccumulation in mullet (M. liza) from a tropical bay located in Southeastern Brazil, comparing a previously considered reference site to a known contaminated area of the bay, as well as to conduct human health risk assessments with regard to the consumption of this species. The metal concentrations were compared to the maximum residue level (MRL) in foods established by the different national and international regulatory agencies, and the Provisional Tolerable Daily Intake (PTDI) was determined and compared to reference values. Chromium (Cr), Zinc (Zn), Copper (Cu), Manganese (Mn), Nickel (Ni), Cadmium (Cd) and Lead (Pb) concentrations were determined in the gills, muscle and liver of 28 mullet by ICP-MS after acid digestion. Certain metals exceeded MRL guidelines established by different regulatory agencies, indicating human health risks associated to these metals. PTDI values, however, did not exceed corresponding metal values proposed by the World Health Organization. The metal concentrations found in the mullet samples indicate that the previously considered reference site is now showing signs of anthropogenic contamination.


Spondylodiscitis: diagnosis and treatment.
We present our experience in the diagnosis and treatment of spondylodiscitis. 27 patients with spondylodiscitis were studied. There were 15 men and 12 women, with ages ranging from 26 to 85 years. Of the 27 cases, there were 21 patients with pyogenic spondylodiscitis, 6 patients with tuberculosis spondylodiscitis, and 8 patients with diabetes mellitus complication. Two patients presented with tetraparesis, 13 with paraparesis, and 1 with hemiparesis. Seventeen patients underwent surgical treatment, among whom surgical intervention with instrumentation was performed on 5 patients, and emergency operation was performed on 6 patients. Fourteen patients were judged as "excellent," 8 patients as "good," and 4 patients as "no change." One patient died because of infection by penicillin-resistant Staphylococcus pneumoniae. It is very difficult to diagnose spondylodiscitis at the first medical examination. Most spondylodiscitis patients often first visit a department of internal medicine. We strongly recommend that all doctors, especially doctors examining diabetes mellitus patients daily, should be well informed of spondylodiscitis in order to improve its diagnosis.


Convergent Genetic and Expression Datasets Highlight TREM2 in Parkinson's Disease Susceptibility.
A rare TREM2 missense mutation (rs75932628-T) was reported to confer a significant Alzheimer's disease (AD) risk. A recent study indicated no evidence of the involvement of this variant in Parkinson's disease (PD). Here, we used the genetic and expression data to reinvestigate the potential association between TREM2 and PD susceptibility. In stage 1, using 10 independent studies (N = 89,157; 8787 cases and 80,370 controls), we conducted a subgroup meta-analysis. We identified a significant association between rs75932628 and PD (P = 3.10E-03, odds ratio (OR) = 3.88, 95 % confidence interval (CI) 1.58-9.54) in No-Northern Europe subgroup, and significantly increased PD risks (P = 0.01 for Mann-Whitney test) in No-Northern Europe subgroup than in Northern Europe subgroup. In stage 2, we used the summary results from a large-scale PD genome-wide association study (GWAS; N = 108,990; 13,708 cases and 95,282 controls) to search for other TREM2 variants contributing to PD susceptibility. We identified 14 single-nucleotide polymorphisms (SNPs) associated with PD within 50-kb upstream and downstream range of TREM2. In stage 3, using two brain expression GWAS datasets (N = 773), we identified 6 of the 14 SNPs regulating increased expression of TREM2. In stage 4, using the whole human genome microarray data (N = 50), we further identified significantly increased expression of TREM2 in PD cases compared with controls in human prefrontal cortex. In summary, convergent genetic and expression datasets demonstrate that TREM2 is a potent risk factor for PD and may be a therapeutic target in PD and other neurodegenerative diseases.


Fine Motor Skill Decline After Brain Radiation Therapy-A Multivariate Normal Tissue Complication Probability Study of a Prospective Trial.
Brain radiation therapy can impair fine motor skills (FMS). Fine motor skills are essential for activities of daily living, enabling hand-eye coordination for manipulative movements. We developed normal tissue complication probability (NTCP) models for the decline in FMS after fractionated brain radiation therapy (RT). On a prospective trial, 44 patients with primary brain tumors received fractioned RT; underwent high-resolution volumetric magnetic resonance imaging, diffusion tensor imaging, and comprehensive FMS assessments (Delis-Kaplan Executive Function System Trail Making Test Motor Speed [DKEFS-MS]; and Grooved Pegboard dominant/nondominant hands) at baseline and 6 months postRT. Regions of interest subserving motor function (including cortex, superficial white matter, thalamus, basal ganglia, cerebellum, and white matter tracts) were autosegmented using validated methods and manually verified. Dosimetric and clinical variables were included in multivariate NTCP models using automated bootstrapped logistic regression, least absolute shrinkage and selection operator logistic regression, and random forests with nested cross-validation. Half of the patients showed a decline on grooved pegboard test of nondominant hands, 17 of 42 (40.4%) on grooved pegboard test of -dominant hands, and 11 of 44 (25%) on DKEFS-MS. Automated bootstrapped logistic regression selected a 1-term model including maximum dose to dominant postcentral white matter. The least absolute shrinkage and selection operator logistic regression selected this term and steroid use. The top 5 variables in the random forest were all dosimetric: maximum dose to dominant thalamus, mean dose to dominant caudate, mean and maximum dose to the dominant corticospinal tract, and maximum dose to dominant postcentral white matter. This technique performed best with an area under the curve of 0.69 (95% CI, 0.68-0.70) on nested cross-validation. We present the first NTCP models for FMS impairment after brain RT. Dose to several supratentorial motor-associated regions of interest correlated with a decline in dominant-hand fine motor dexterity in patients with primary brain tumors in multivariate models, outperforming clinical variables. These data can guide prospective fine motor-sparing strategies for brain RT.


Preparation of alkaline earth phosphates with sol containing sodium alginate and sodium diphosphate.
Magnesium hydrogen phosphate, calcium hydroxyapatite, and strontium hydroxyapatite were successfully prepared from sol consisting of sodium alginate and Na4P2O7 with Mg2+, Ca2+, and Sr2+ in the corresponding nitrates, respectively. It is revealed that the order of the addition of those substrates and the role of sodium alginate are important factors for the preparation of desired phosphate compounds. According to the previous paper on the preparation of calcium hydroxyapatite, sodium alginate was mixed with aqueous Na4P2O7, followed by the addition of the aqueous divalent cations, resulting in the poor formation of the target phosphates. However, as a revised sol-gel technique, sodium alginate was added to the mixture of Na4P2O7 and aqueous Mg2+ and Sr2+, resulting in a rather favorable formation of MgHPO4 and strontium hydroxyapatite, respectively, while the sol thus obtained was stable within a few days. However for aqueous Ca2+, calcium hydroxyapatite could not be obtained through the revised sol-gel technique. In the preparation of magnesium hydrogen phosphate, sodium alginate contributes mainly to the sol formation of the precursor. The ion exchange between Na+ in sodium alginate and aqueous Ca2+ was important for the preparation of calcium hydroxyapatite. In contrast, the reaction of sodium alginate with the mixture of Na4P2O7 and aqueous Sr2+ afforded strontium hydroxyapatite at the specific ratio of those three substrates. The structure of calcium and strontium phosphates prepared from the revised sol-gel process evidently depended on the amount of sodium alginate introduced into the mixture of Na4P2O7 and the corresponding divalent cations.


alpha-Isopropylmalate synthase from Alcaligenes eutrophus H 16. II. Substrate specificity and kinetics.
The purified isopropylmalate synthase of Alcaligenes eutrophus H 16 reacted with the following alpha-keto acids and acyl-coenzyme A derivatives (in the sequence of decreasing affinities): alpha-ketoisovalerate, alpha-keto-n-valerate, alpha-ketobutyrate and pyruvate; acetyl-CoA, propionyl-CoA, butyryl-CoA, malonyl-CoA, valeryl-CoA, and crotonyl0CoA. alpha-Ketoisocaproate, however, is a strong inhibitor of the enzyme. All reactions catalyzed by isopropylmalate synthase were inhibited to the same extent by the endproduct L-leucine. The substrate saturation curves of alpha-ketoisovalerate or other alpha-keto acids and of acetyl-coenzyme A or other acyl-CoA derivatives had intermediary plateau regions; the Hill coefficient alternated between nH-values higher and lower than 1.0, indicating changes from positive to negative and from negative to positive cooperativity for the substrates. The products, isopropylmalate and free coenzyme A, showed competitive inhibition patterns against both substrates (alpha-ketoisovalerate and acetyl-CoA). Free coenzyme A (1 micronM) inactivated the enzyme irreversibly. The 3'-phosphate of coenzyme A and the free carboxyl group of alpha-ketoisovalerate were involved in optimal binding of these substrates, but 3'-dephospho-acetyl-coenzyme A and the methylester of alpha-keto-isovalerate were also converted by this enzyme. A CH3--CH2-grouping of the alpha-keto acids seemed to be necessary for binding this substrate.


Prenatal protein deprivation increases defects of the corpus callosum in BALB/c laboratory mice.
The development of two forebrain fiber tracts, the anterior commissure (CA) and corpus callosum (CC), was examined in BALB/cCF laboratory mice in relation to the maternal dietary protein concentration during gestation. The diets contained either 8 or 27% casein. The BALB/c strain was used because it is prone to having a corpus callosum which is either deficient in size or absent. Female mice were assigned to the low-protein diet either 2 weeks prior to mating (chronic malnutrition) or on the seventh day of gestation (acute malnutrition), and fetal brain development was assessed at 18.5 days after conception. Protein deficiency increased the number of animals which did not have a corpus callosum present in a midsagittal section. In those animals in which the structure was present, it was evident that the cross-sectional area was smaller in the chronically deprived animals than in the control group. In addition to CC area, both CA area and brain weight were reduced by protein deprivation. When brain weight was used as a covariate in an analysis of covariance the effect on CA area was no longer apparent. Part of the effect on the corpus callosum was, however, independent of the effect on brain weight and CA area.


Additional evidence supports association of common genetic variants in VTI1A and ETFA with increased risk of glioma susceptibility.
VTI1A and ETFA were identified recently as susceptibility genes for non-glioblastoma (GBM) of glioma risk in European populations, but the genetic etiology and pathogenesis of glioma have not been fully elucidated. Here, we aimed to investigate whether common genetic variants in VTI1A and ETFA predispose Han Chinese individuals to glioma. The association of thirteen common tagging single nucleotide polymorphisms (SNPs) in VTI1A and ETFA genes with glioma were assessed in a hospital-based case-control study including 473 non-GBM of glioma patients and 1046 cancer-free controls. Two SNPs (rs11196067 in VTI1A and rs1801591 in ETFA) were found to be significantly associated with non-GBM of glioma risk (rs11196067, adjusted P=0.00018, adjusted odds ratio (OR)=1.37, 95% confidence interval (CI)=1.16-1.61; rs1801591, adjusted P=0.000022, adjusted OR=1.72, 95% CI=1.34-2.20). In further stratified analysis, they were both more pronounced in the adult subgroup. In haplotype-based analysis, two haplotypes were identified to be significant association with glioma. The haplotype "TGA" (P=0.002) in VTI1A and the haplotype "ACA" (P<0.001) in ETFA had a 1.5-fold and 3-fold increased glioma risk respectively, compared with corresponding non-carriers. In summary, our results indicate that genetic variants in VTI1A and ETFA may modify individual susceptibility to non-GBM of glioma in the Han Chinese population and support the role of the VTI1A and ETFA genes in the occurrence of glioma.


Paternalism, participation and partnership - the evolution of patient centeredness in the consultation.
There is much discussion at present on the need for a more patient-centered health service. However, it is not always clear what exactly this means for patients or healthcare providers. Furthermore many current trends in healthcare and society may in fact move the consultation further from the patient-centered model. In this article I shall critically review the current state of the consultation. This article is based on a critical review of the literature. I shall firstly outline what is meant by the terms 'patient centeredness' and 'participation'. I shall then examine what wider factors may facilitate or impede effective communication within the consultation. Patient centeredness and participation is challenged by several factors including the 'co-modification' of healthcare, the information revolution, the tension between choice and continuity, the process of medicalisation, population health strategies and the availability of resources. I will argue that precisely because of these wider trends in society the consultation is now more important than ever as a point of access, communication, understanding and delivery of healthcare. The structure and aims of the consultation must be re-visited in the light of the rapid pace of change in service delivery. As such, healthcare professionals may need to advocate for the continuing role of the patient-centered consultation.


Altered immune system in offspring of rat maternal vertical sleeve gastrectomy.
Obesity in women results in reduced fertility and increased complications during pregnancy. Vertical sleeve gastrectomy (VSG) effectively reduces weight, type 2 diabetes, and dyslipidemia, but is also associated with preterm and small-for-gestational age births. The mechanism by which VSG influences fetal development remains unknown. Here we hypothesize that previously reported immune changes during rat VSG pregnancy are reflected long term in the immune system of the offspring. Offspring of VSG and sham dams were evaluated at postnatal day (PND) 21 and PND60. At PND21, VSG pups have lower numbers of circulating B lymphocytes compared with sham pups (P < 0.05) and have lower transcription of lymphocyte marker Ptprc (P < 0.01) in the spleen, while other lymphocyte populations measured are not different. Total plasma IgG is higher (P < 0.01) and C-reactive protein is lower (P < 0.05) in VSG offspring compared with sham offspring at PND21. The central nervous system of VSG pups is also affected at PND21, having higher expression of Il1b mRNA (P < 0.05) and higher immunoreactivity of microglia marker, IBA1, in the hypothalamus. At PND60, the immune-hematological differences are not present; however, mRNA expression of Il1b is elevated (P < 0.001) in the spleen of VSG offspring along with markers of T cells. These data suggest that the immune system of VSG offspring is compromised early in life, but rebounds after weaning and may even become hyperactive. Future work is needed to determine whether the immune system of VSG offspring is capable of mounting a proper defense and whether other aspects of development are affected.


Toxic Effect of Streptozotocin on Cultured Mouse Hippocampal Neurons.
In primary dissociated hippocampal cell cultures from 18-day-old mouse embryos, streptozotocin in concentrations of 2-5 mM produced a dose-dependent cytotoxic effect on day 3 in vitro, whereas on day 11 of culturing, the neurons were resistant to streptozotocin. The neurons in the 3-day cultures were functionally immature, which was seen from their weak spontaneous bioelectric activity in the form of rare single action potentials; by day 11 of culturing, the neurons reached a high level of differentiation and their functional properties acquired a character of network burst activity. Thus, streptozotocin had the most pronounced cytotoxic effect on immature hippocampal neurons in vitro.


Treatment results for simultaneous primary squamous cell carcinomas of the head and neck.
Forty patients with simultaneous multiple primaries of the head and neck were treated with curative intent between June 1964 and April 1983. The primary sites were treated with radiation therapy alone or in combination with surgery. Surgery was used to salvage local failures of radiation treatment. Neck disease was treated with radiation therapy alone or with neck dissection added after completion of radiation therapy to the primary lesions. Minimum follow-up was 2 years with a range of 2 to 20 years. For the 32 patients whose primary tumors were treated with radiation alone, the 2-year local control rates for the 53 individual tumors evaluated were as follows: T1, 18/21; T2, 16/23; and T3-T4, 1/9. In the T3-T4 group, there was only one successful surgical salvage. Local control rates for disease at all primary sites in each patient according to highest T-stage were as follows: T1, 4/5; T2, 9/15; and T3-T4, 1/9. Eight patients whose primary tumors were treated with radiation and surgery are discussed. The absolute disease-free survival rate at 2 years for 40 patients was 42%. Complications of treatment are described.


Enkephalin affects ion transport via the enteric nervous system in guinea-pig ileum.
The endogenous opioid enkephalin drives ion transport towards absorption. To determine the site and mechanism of this effect, fractionated stripping of guinea-pig ileum was carried out. The muscularis propria, including myenteric plexus, was removed by partial stripping. The submucosa, including the submucosal plexus, plus the muscularis mucosae were removed by total stripping. For binding studies, epithelial cells were removed by the method of Weiser leaving the lamina propria mucosae with the mucosal plexus. Radio-receptor-assay with (3H)2-D-ala-5-D-leu-enkephalin revealed enkephalin binding sites in the submucosa plus muscularis mucosae (KD = 3.6 nmol l-1; Vmax = 7.3 fmol mg-1) and in the lamina propria mucosae (KD = 4.2 nmol l-1; Vmax = 5.1 fmol mg-1. The binding was stereospecific in both layers. No binding was detected on epithelial cells. In the Ussing chamber, partially stripped ileum exhibited spontaneous ISC which was abolished by addition of tetrodotoxin (TTX) or by total stripping indicating that this ISC was neuronally stimulated by the submucosal plexus. Electrogenic chloride secretion was identified as contributing to this ISC, since the TTX-sensitive part of ISC in the partially stripped ileum was lacking in Cl- and HCO3-free medium, reappeared after addition of Cl consistent with Michaelis-Menten kinetics (Km = 19 nmol l-1) and was reversed by serosal addition of bumetanide. In addition, enkephalin increased electroneutral NaCl-absorption as obtained by Na- and Cl-flux measurements. Enkephalin decreased this spontaneous neuronally stimulated electrogenic Cl-secretion in the partially stripped ileum, but had no effect in totally stripped ileum if ISC was stimulated at the cellular level by theophylline or PGE1. We conclude that ganglia located in the submucosal plexus regulate intestinal ion transport. Enkephalin acts by presynaptic inhibition via receptors on these neurons in the submucosa and/or via receptors on their neurites in the lamina propria mucosae.


MiR-223/Ect2/p21 signaling regulates osteosarcoma cell cycle progression and proliferation.
Osteosarcoma is one of the most common tumors. The mechanisms of formation and development of osteosarcoma have been studied for a long time. Recently, more and more evidence showed that miRNAs play important roles in regulating tumor growth. In this study we found that miRNA-223 was downregulated in both osteosarcoma patients' tumor tissues and osteosarcoma cell lines. Overexpression of miRNA-233 greatly inhibited the proliferation of Saos-2 cells. Cell cycle analysis by flow cytometry showed the arrest of cell cycle progression at the G1 phase. Further mechanistic study indicated that Ect2 was directly targeted by miR-223. Downregulation of Ect2 by miR-223 induces the expression of p21, p27 and the phospharylation of retinoblastoma, which are involved in the G1 block. We concluded that miR-223 functions as a tumor suppresser in osteosarcoma and miR-223/Ect2/p21 signaling is an important pathway that regulates the osteosarcoma cell cycle progression and proliferaion.


MK-0873, a PDE4 inhibitor, does not influence the pharmacokinetics of theophylline in healthy male volunteers.
MK-0873 is a novel selective phosphodiesterase-4 inhibitor, which has been in development for the treatment of chronic obstructive pulmonary disease (COPD). In this indication, theophylline is still an important treatment, despite its relatively small therapeutic window. In view of this, it is important to investigate whether MK-0873 could affect the pharmacokinetics, safety and tolerability of theophylline, when both drugs are given concomitantly. The objective of this study was to investigate the effect of multiple doses of oral MK-0873, a selective phosphodiesterase-4 inhibitor, on the pharmacokinetics, safety and tolerability profile of orally administered theophylline in healthy volunteers. Eight healthy, non-smoking male subjects participated in this randomized, open-label, 2-period, cross-over study. In one period subjects received an oral dose of 2.5mg MK-0873 for 6 days co-administered with a single oral dose of 250 mg theophylline on day 5. The other period consisted of a single dose of 250 mg theophylline on day 1. In each period, blood samples were collected at predefined time points to evaluate theophylline pharmacokinetics. All subjects completed the study. The study medications were generally well tolerated and no clinically relevant changes were observed in either treatment periods. No significant difference was found in the AUC 0-infinity (77.7 vs. 83.8h ng/ml; p=0.280) and Cmax (6.70 vs. 7.77 ng/ml; p=0.125) of theophylline between the MK-0873+theophylline and theophylline only treatment, and bioequivalence was demonstrated for AUC0-infinity (geometric mean ratio with 90% confidence interval: 0.930 (0.826, 1.047)). In this study, in a limited number of subjects, co-administration of oral MK-0873 did not affect the pharmacokinetics, safety, and tolerability of oral theophylline in non-smoking healthy male subjects.


Research progress of novel magnetic two-dimensional carbon composites in photocatalytic degradation of pollutants: a review.
With the improvement of economic level and the development of science and technology, the problem of water pollution needs to be solved now. Various water pollutants have a negative impact on nature and restrict its development. In recent years, photocatalysis is considered to be a promising wastewater treatment method. Two-dimensional carbon materials have become the hotspot of photocatalytic degradation of pollutants because of their excellent conductivity, large specific surface area, and good hydrophilicity. Nevertheless, it is very hard for these photocatalysts based on carbon materials to separate and recover from the system. For solving such a problem, the composition with magnetic components is an effective way which can facilitate separation and keep the catalytic activity of the samples. In this review, the main roles of magnetic carbon-based composites in the field of pollutant degradation are introduced, and their synthesis technology, classification, and application are summarized. In the end, the current challenges and prospects in this field are involved, aiming to provide useful insights and enlightments into the fields of pollutant treatment and photocatalytic degradation.


Numerical integration of autonomous and non-autonomous non-linear size-structured population models.
We present an efficiency study for autonomous and non-autonomous non-linear size-structured population models. The study considers three numerical methods: a characteristics scheme, the Lax-Wendroff method and the box method, which are completely described in the paper. Five test problems are considered with diverse degree of complexity: non-trivial equilibrium, periodic solutions and diverse growth functions. The study of the efficiency takes into account the properties of the numerical schemes (such as the stability) and uses a multiple regression analysis to determine the constants of the leading terms of the corresponding global errors. We show how the tables of errors and cpu-times can be used to explain the meaning of the efficiency results. In addition, we present the convergence analysis of the box method.


Palladium-Catalyzed Enantioselective C-H Aminocarbonylation: Synthesis of Chiral Isoquinolinones.
A Pd-catalyzed enantioselective C-H carbonylation by desymmetrization was developed with commercially available L-pyroglutamic acid as chiral ligand. Isoquinolinones were successfully obtained with good yields and high enantioselectivities. Mechanistic studies and DFT calculations provided a reasonable reaction pathway.


An in vitro assessment of novel chitosan/bimetallic PtAu nanocomposites as delivery vehicles for doxorubicin.
To synthesize and functionalize platinum (core)-gold (shell) bimetallic nanoparticles (PtAuBNps) with chitosan and doxorubicin to display favorable pharmacokinetics, biodegradability, biological activity and safety in vitro. PtAuBNps and their drug nanocomposites were morphologically and physico-chemically characterized. Binding studies determined the efficiency and stability of the platform. In vitro release kinetics were evaluated under simulated environments, cytotoxicity profiles through MTT and Sulforodhamine B assays and apoptosis induction using the dual EtBr/AO staining. The results obtained indicate that functionalized PtAuBNps displayed favorable physio-chemical attributes, high binding capabilities, pH-triggered drug release through zero-order release kinetics, cell-specific cytotoxicity and good colloidal stability. The positive attributes of this novel delivery system bodes well for future in vivo studies.


Repeated intraperitoneal injections of saline attenuate the antibody response to a subsequent intraperitoneal injection of antigen.
The results of two experiments with male C3H/HeJ mice indicated that repeated intraperitoneal (ip) injections of sterile saline over a 2-week period resulted in an attenuated antibody response to the subsequent ip injection of a soluble protein antigen, keyhole limpet hemocyanin. There were no differences among experimental groups that received a different number of preimmunization injections of saline, and comparable effects were obtained simply by the daily handling of mice. Neither repeated ip injections nor handling altered preimmunization (baseline) corticosterone levels, and only previously unmanipulated mice showed an elevation in corticosterone levels 30 min after ip immunization. These latter results suggest that the depressed IgM and IgG responses were not due to the immunosuppressive effects of endogenously elevated adrenocortical steroids.


A Phase I Study to Evaluate the Pharmacokinetics and Safety of Cabotegravir in Adults With Severe Renal Impairment and Healthy Matched Control Participants.
This study investigates the impact of severe renal impairment on the pharmacokinetics of cabotegravir, an investigational HIV-1 integrase inhibitor. This was a phase I, open-label, parallel-group, multicenter study conducted in 8 participants with severe renal impairment (creatinine clearance <30 mL/min; no renal replacement therapy) and 8 healthy participants (creatinine clearance >90 mL/min; 2 women/group; 6 men/group) matched for sex, age (±10 years), and body mass index (±25%). Participants received a single 30-mg oral cabotegravir tablet to determine total and unbound plasma cabotegravir concentrations. Arithmetic and geometric least squares means were calculated, and cabotegravir noncompartmental pharmacokinetic parameters were compared using geometric least squares mean ratios with 90% confidence intervals. Safety was assessed throughout the study. Geometric least squares mean ratios (90% confidence intervals) were 0.97 (0.84-1.14) for area under the plasma concentration-time curve extrapolated to infinity, 1.01 (0.87-1.17) for maximum observed plasma concentration, 1.31 (0.84-2.03) for unbound cabotegravir 2 hours after dosing, and 1.51 (1.19-1.92) for unbound cabotegravir 24 hours after dosing. All adverse events were grade 1, except grade 3 lipase elevation in a participant with renal impairment. Severe renal impairment did not impact plasma cabotegravir exposure, and cabotegravir may be administered without dose adjustment in renal impairment among patients not receiving renal replacement.


ISPRM discussion paper: proposing dimensions for an International Classification System for Service Organization in Health-related Rehabilitation.
Rehabilitation is 1 of 4 main health strategies. The World Report on Disability identifies deficits in rehabilitation care for people with disabilities as an important barrier to full inclusion in society or to achieve optimal functioning. In order to overcome such deficits, to close gaps in national and/or regional rehabilitation systems, and to develop appropriate rehabilitation services, it is crucial to define uniform criteria and a widely accepted language to describe and classify rehabilitation services. The aim of this paper was therefore to develop a list of dimensions and categories to describe the organization of health-related rehabilitation services. The classification is based on a series of expert workshops including members of the International and European Society of Physical Medicine and Rehabilitation. The proposed classification has 2 levels (dimensions and categories). The upper level distinguishes 3 dimensions: the service provider (with 9 categories), the funding of the service (with 3 categories), and the service delivery (8 subcategories). A further specification of the categories in a 3-level classification (including value sets) is needed. This paper is an intermediate step towards development of a classification system with distinct categories and dimensions.


Effects of ultra-high-temperature processes on metabolite changes in milk.
Processing can affect milk properties and alter the composition of milk metabolites, which has corresponding effects on milk flavor and quality. It is quite important to study the safe quality control of milk processing. Therefore, the purpose of this study was to identify metabolites at different steps of ultra-high-temperature-sterilized (UHT) milk processing using gas chromatography-mass spectrometry (GC-MS). These steps included raw milk, pasteurized milk (80°C for 15 s), semi-finished milk (after pasteurizing, it was homogenized at 75°C with pressure of 250 bar), UHT milk (at 140°C for 10 s), and finished milk (homogenized UHT milk). A total of 66 metabolites were identified across all samples, including 30 metabolites in the chloroform layers of the milk samples and 41 metabolites in the water layers; 5 metabolites were found in both layers. The metabolites were primarily fatty acids, amino acids, sugars, and organic acids. For example, pasteurized and ultra-high-temperature-sterilized kinds of milk had lactose contents similar to those of raw milk, with increases in saturated fatty acids such as hexadecanoic acid and octadecanoic acid. Additionally, these findings indicated that these methods of processing can affect the contents of some components of milk. Therefore, from the perspective of milk's nutritional value and consumer health, the excessive heating of dairy products should be avoided and the milk heat treatment process should be standardized from the source.


Adrenal insufficiency is common amongst kidney transplant recipients receiving maintenance prednisolone and can be predicted using morning cortisol.
Long-term glucocorticoid therapy is a key component of immunosuppression for kidney transplant recipients (KTRs), leading to significant cumulative glucocorticoid exposure. The aims of this study are to investigate the prevalence of adrenal insufficiency (AI) in KTRs taking prednisolone and to develop a screening algorithm to identify patients at the highest risk of AI. In this cross-sectional cohort study, 67 KTRs receiving prednisolone underwent a short synacthen test (SST) and measurement of cumulative glucocorticoid exposure. A total of 72% (n = 48) of participants failed the SST. Participants with AI had a higher daily prednisolone dose (4.9 versus 4.2 mg/day; P = .002) and greater cumulative glucocorticoid exposure (289 versus 111 mg/kg; P = .03) than those with intact adrenal function. Participants with AI had lower baseline cortisol than participants with intact adrenal function (143 versus 303 nmol/L; P < .001). Morning cortisol of >288 nmol/L predicted a normal SST with 100% specificity [95% confidence interval (CI) 92-100] and 70% sensitivity (95% CI 56-78%), therefore excluding AI. Our results suggest KTRs are at a higher risk for AI than previously reported. A morning serum cortisol measurement is a useful screening tool in this cohort, reducing the need for stimulatory testing by 44%. KTRs with AI need education regarding glucocorticoid sick rules, similar to patients with other forms of AI.


Compound heterozygosity for novel variations of the NHLRC1 Gene in a family with Lafora disease.
NHLRC1 gene mutations are present in a varied proportion of patients with Lafora disease (LD). Compound heterozygosity for novel variations of the gene has been reported in progressive Lafora myoclonic epilepsy of Lafora pedigree. The clinical data of the cases were collected for diagnosis, and the genetic spectrum of the family was confirmed. For molecular diagnosis, whole-exome sequencing (WES) of the pedigree was performed. A novel biallelic compound heterozygous c.333dupC chr6-18122504 (p.(Gly112ArgfsTer44)) and c.612dupT chr6-18122225 (p.(Gly205Trpfs*29)) mutation in the NHLRC1 gene was identified in our progressive myoclonic epilepsy of Lafora pedigree. The genetic analysis was useful for the diagnosis of LD. Genetic analysis is recommended for patients and close relatives, and tissue biopsy is an alternative.


Clinical Characteristics, Surgical Treatment, and Risk Factor Analysis of Postoperative Functional Outcome in Patients with Intracranial Hemangioblastoma.
This study aims to present the clinical characteristics and surgical treatment in patients with intracranial hemangioblastomas and to investigate risk factors for postoperative functional outcomes. Patients with intracranial hemangioblastomas who received surgical treatment in our institute between 2011 and 2020 were included. We retrospectively reviewed and analyzed the clinical characteristics, surgical treatment, and postoperative functional status. Risk factors for postoperative functional outcomes were further analyzed using univariate and multivariate analysis. We identified 48 patients with 82 intracranial hemangioblastomas resected in this study. There were 22 females and 26 males, and the mean age was 39.3 ± 15.3 years. Total resection was achieved in all the cases. After primary surgery, immediate functional status was improved in 20 patients (41.7%), stable in 9 patients (18.8%), and worsened in 19 patients (39.6%). Forty-two patients (89.4%) had favorable functional status (Karnofsky Performance Scale ≥80) at long-term follow-up. Through univariate and multivariate analysis, body mass index, number of resected tumors per operation, and intraoperative blood loss were independent risk factors for the immediate functional outcome (P = 0.006, P = 0.023, P = 0.038, respectively). Preoperative hydrocephalus was significantly associated with unfavorable long-term functional status (P = 0.047). Generally, patients can benefit from surgical removal of intracranial hemangioblastomas with favorable functional outcomes. Body mass index, number of resected tumors per operation, and intraoperative blood loss can be used as risk factors for immediate functional outcomes after surgery, and preoperative hydrocephalus for long-term functional status.


Transcription stimulates recombination. II. Generalized transduction of Escherichia coli by phages T1 and T4.
Phage Mu was inserted in the trpE gene of one donor Escherichia coli strain and in the lac promoter of another. Strains with Mu prophage mutations which permitted transcription of genes whose transcription had been polarly blocked by the Mu insertion were isolated and called "bypass" strains. The transducing phages T1am, and T1am,ST, and, in one instance, T4GT7 were grown on both the bypass and the original strains. After growth on the bypass strains transducing phages were able to transduce Trp+ and Lac+, respectively, to a variety of Trp- and Lac- strains more efficiently than after growth on nonbypass strains. These results support the idea that crossovers required for generalized transduction occur more efficiently if the specific region is transcribed by both interacting parental molecules.


A purified recombinant organophosphorus acid anhydrase protects mice against soman.
Since pharmacologic treatments of organophosphorus anticholinesterases (OPs) are nearing their practical limit other types of treatment are being sought. One approach is the prophylactic administration of scavengers that will detoxify OPs before they reach their critical target site. Using mice that were sensitized to OPs by depletion of their serum carboxylesterase with cresylbenzodioxaphosphorin oxide (CBDP), we have shown that animals pretreated intravenously with a purified organophosphorus acid anhydride hydrolase (parathionase) (0.10 mg per g body wt.) are not measureably affected by up to 34.4 micrograms soman per kg, a dose more than double that which is lethal to untreated animals. This result indicates that this approach is worthy of exploration and development for protecting military personnel and agricultural workers against OP intoxication.


Priming correct information reduces the misinformation effect.
The misinformation effect is a well-established phenomenon in the false memory literature, although the mechanisms that underlie it are debated. In the present study, we explored one aspect of the controversy, the fate of the original memory. We began from an activation-based view of memory, capitalizing on the well-understood processes of associative priming and spreading activation, to test the hypothesis that true and suggested information can coexist in memory. After exposure to misinformation, participants were unknowingly primed with associates of either the true or a suggested item. Misled participants who were primed for the true item performed better on a final memory test than did misled participants primed for neutral information. The results indicated that true and suggested information coexist and that retrieval is influenced by each concept's activation level at test. Implications for theories of the misinformation effect were discussed.


Isolation and Genomic Characterization of a Duck-Origin GPV-Related Parvovirus from Cherry Valley Ducklings in China.
A newly emerged duck parvovirus, which causes beak atrophy and dwarfism syndrome (BADS) in Cherry Valley ducks, has appeared in Northern China since March 2015. To explore the genetic diversity among waterfowl parvovirus isolates, the complete genome of an identified isolate designated SDLC01 was sequenced and analyzed in the present study. Genomic sequence analysis showed that SDLC01 shared 90.8%-94.6% of nucleotide identity with goose parvovirus (GPV) isolates and 78.6%-81.6% of nucleotide identity with classical Muscovy duck parvovirus (MDPV) isolates. Phylogenetic analysis of 443 nucleotides (nt) of the fragment A showed that SDLC01 was highly similar to a mule duck isolate (strain D146/02) and close to European GPV isolates but separate from Asian GPV isolates. Analysis of the left inverted terminal repeat regions revealed that SDLC01 had two major segments deleted between positions 160-176 and 306-322 nt compared with field GPV and MDPV isolates. Phylogenetic analysis of Rep and VP1 encoded by two major open reading frames of parvoviruses revealed that SDLC01 was distinct from all GPV and MDPV isolates. The viral pathogenicity and genome characterization of SDLC01 suggest that the novel GPV (N-GPV) is the causative agent of BADS and belongs to a distinct GPV-related subgroup. Furthermore, N-GPV sequences were detected in diseased ducks by polymerase chain reaction and viral proliferation was demonstrated in duck embryos and duck embryo fibroblast cells.


Long-term outcome of vincristine-aspirin-ticlopidine (VAT) therapy for vascular tumors associated with Kasabach-Merritt phenomenon.
. This study aimed to clarify the combinatorial treatment effect of agents as aspirin and ticlopidine associated with vincristine in the management of Kasabach-Merritt phenomenon (KMP), a severe thrombocytopenic coagulopathy that occurs in the presence of an enlarging vascular tumor such as kaposiform hemangioendothelioma (KHE) and tufted angioma (TA). . A retrospective review was conducted of medical records of all children with diagnosis of KHE or TA associated with KMP treated with vincristine-aspirin-ticlopidine (VAT) therapy at two different institutions in the same country from 1994 to 2011. Clinical features, response to VAT therapy and outcomes were recorded. . Eleven patients (mean age 11 months, range 0-36), including seven females (64%) and four males (36%), were identified. Seven patients underwent incisional biopsy and two different histologies were found, KHE in four patients and TA in three patients. Tumors were located in the head and neck (n = 5), chest wall (n = 2), arm (n = 2) and retroperitoneum (n = 2). Mean platelet level was 10,200/mm(3) (range 4,000-21,000). A plaque-like lesion with ecchymosis was the most common cutaneous manifestation (63%). All patients underwent VAT therapy. Mean duration of treatment was 3.9 months for vincristine, 13.9 months for aspirin, and 13.4 months for ticlopidine. All patients are alive with a mean follow-up of 4.5 years (range, 2-17). . Antiaggregant therapy is helpful in combination with vincristine in the treatment of KMP associated with KHE and TA. Prognosis is excellent if severe thrombocytopenia is controlled despite failure in reduction of tumor size.


Barakol suppresses norepinephrine-induced inhibition of spontaneous longitudinal smooth muscle contractions in isolated rat small intestine.
The present study aimed to investigate the purgative effects of barakol, the purified extract of Cassia siamea Lam., on the longitudinal smooth muscle contractions of the rat ileum. The extract increased the force of spontaneous muscle contractions in a concentration-dependent manner (EC50=0.3 mM). Saxitoxin (0.3 microM) abolished the stimulatory effects of barakol, a result indicating a neural mechanism of action. In addition, atropine (10 microM) but not propanolol (10 microM) or phentolamine (10 microM), partially inhibited barakol-induced smooth muscle contractions suggesting that cholinergic nerves were involved. The motor effects of barakol were further examined in muscle strips treated with catecholamines to suppress spontaneous contractile activity and decrease muscle tone. Norepinephrine or dopamine (10 microM) decreased the amplitude of spontaneous contractions by 72% and 18%, respectively. Pretreatment of the tissues with barakol (1 mM) significantly decreased the inhibitory effect of norepinephrine by 60%, but not that of dopamine. Its ability to potentiate atropine- and saxitoxin-sensitive contractions and inhibit the antimotility actions of norepinephrine suggests that barakol may increase longitudinal smooth muscle contractions by decreasing the inhibitory effect of norepinephrine on excitatory cholinergic motor neurons. Barakol may produce a purgative action in small intestine which may be clinically important in patients with intestinal hypomotility disorders.


Familial uterine hernia syndrome: report of an Arab family with four affected males.
We report an Arab Bedouin family including four males with uterine hernia syndrome. All had a male chromosome constitution and phenotype, inguinal herniae, cryptochidism, and persistence of Müllerian derivatives. Histopathological studies confirmed the presence of both testicular tissue and Müllerian derivatives. The presence of two affected brothers and two affected maternal uncles suggests X-linked inheritance. Autosomal recessive determination with male sex limitation is also a possibility based on parental consanguinity in one sibship.


The association between hip/groin pain and hip strength in football players: An exploratory analysis of the FORCe cohort.
Explore associations between peak hip strength in football players with hip/groin pain and healthy controls. Cross-sectional study. Male and female sub-elite football players (soccer and Australian football) with hip/groin pain >6-month duration and players without hip/groin pain were recruited across Melbourne and Brisbane, Australia. Demographic information and two questionnaires; the Copenhagen Hip and Groin Outcome Score and the International Hip Outcome Tool 33 were collected. Hand-held dynamometry was used to measure isometric hip strength for flexion, extension, abduction, adduction, internal rotation, and external rotation. Linear mixed effects models were used to compare strength measures between groups. 190 football players with hip/groin pain (mean ± standard deviation age, 27.8 ± 6.3 years) and 64 controls (age, 27.3 ± 5.6 years) were included in this study. Of these, 291 symptomatic limbs and 128 control limbs were used for analyses. Symptomatic players had lower peak hip adduction (adjusted mean difference = -0.18: 95 % confidence interval -0.27 to -0.08, P : 0.001), external rotation (-0.06: 95 % confidence interval -0.09 to -0.02, P : 0.003), and internal rotation strength (-0.06: 95 % confidence interval -0.10 to -0.03, P : 0.001) compared to controls. A sport-specific interaction was observed for hip abduction strength. When separated by football code, abduction strength was lower in symptomatic Australian football players compared to their same sport peers (-0.20: 95 % confidence interval -0.33 to -0.06, P : 0.004), but not in symptomatic soccer players (-0.05: 95 % confidence interval -0.15 to 0.06, P : 0.382). Hip adduction, internal rotation, and external rotation strength appears lower in football players with hip/groin pain independent of sex and football code. Hip abduction strength was lower in symptomatic Australian football players but not in soccer players.


Polymeric drug nanoparticles prepared by an aerosol flow reactor method.
Our purpose was to study the possibility of using a novel method, namely, aerosol flow reactor method, for the preparation of drug-containing nanoparticles with varying amounts of drug and polymer. The physical properties of the prepared nanoparticles were analyzed. The nanoparticle size distributions were measured using differential mobility analyzer. The structure of the prepared nanoparticles was assessed by x-ray diffraction, differential scanning calorimetry, and electron microscopy. Drug release from the nanoparticles was analyzed. The spherical particles produced showed a unimodal and lognormal size distribution, and the geometric number mean size of the nanoparticles could be varied between 90 and 200 nm. When the amount of drug in the polymeric matrix was small, the nanoparticles had a homogeneous, amorphous structure. Drug crystals were formed when the amount of drug was increased over the solubility limit of the drug into the polymer. The amounts of drug and polymer controlled the drug release from the nanoparticles. The aerosol flow reactor method was found to be able to produce homogeneous amorphous matrix-type nanoparticles that can directly be collected as dry powder.


[Ultrastructural mechanisms of serotonin demyelination].
The effect of serotonin on dog white matter ultrastructure in the CNS was investigated. The intracysternal injection of this amine (6 microgram in 0.1 ml of physiological saline) induced significant lesions in the myelin and glia of the spinal cord white matter areas adjacent to the cerebrospinal fluid tracts. A loss of the regular structure and stratification of the myelin lamellae, as well as rupture and lysis of the myelin membranes, and their demyelination occurred. There was vacuolar dystrophy of oligodendrocytes; the astrocytes remained practically unchanged. After local intracranial injection of this amine (2 microgram in 0.01 ml of physiological saline) similar lesions were observed in the white matter of the cerebral hemisphere; in addition signs of inflammatory reaction were revealed at the late period of investigation. In control animals injected with physiological saline the changes were observed later and in gliocytes only. A conclusion was drawn that serotonin was capable of injuring the myelin and glia.


Scrushy plots a comeback. As HealthSouth works hard to put a fraud scandal in the past, its acquitted founder studies how he can regain the company.
The jury ruled that Richard Scrushy is not guilty. So now HealthSouth's deposed leader wants to reclaim the company he founded, even if current management and investors don't want him. "I have a hard time believing he's going to get back in there," says Larry Scanlan, left, of Navigant Consulting. Others are more blunt: "We have less than zero support for his return," says a principal at the largest single owner of HealthSouth shares.


In vitro and computational insights revealing the potential inhibitory effect of Tanshinone IIA against influenza A virus.
Seasonal human influenza is a serious respiratory infection caused by influenza viruses that can be found all over the world. Type A influenza is a contagious viral infection that, if left untreated, can lead to life-threatening consequences. Fortunately, the plant kingdom has many potent medicines with broad-spectrum antiviral activity. Herein, six plant constituents, namely Tanshinone IIA 1, Carnosic acid 2, Rosmarinic acid 3, Glycyrrhetinic acid 4, Baicalein 5, and Salvianolic acid B 6, were screened for their antiviral activities against H1N1 virus using in vitro and in silico approaches. Hence, their anti-influenza activities were tested in vitro to determine inhibitory concentration 50 (IC50) values after measuring their CC50 values using MTT assay on MDCK cells. Interestingly, Tanshinone IIA (TAN) 1 was the most promising member with CC50 = 9.678 μg/ml. Moreover, the plaque reduction assay carried on TAN 1 revealed promising viral inhibition percentages of 97.9%, 95.8%, 94.4%, and 91.7% using concentrations 0.05 μg/μl, 0.025 μg/μl, 0.0125 μg/μl, and 0.006 μg/μl, respectively. Furthermore, in silico molecular docking disclosed the superior affinities of Salvianolic acid B (SAL) 6 towards both surface glycoproteins of influenza A virus (namely, hemagglutinin (HA) and neuraminidase (NA)). The docked complexes of both SAL and TAN inside HA and NA receptor pockets were selected for 100 ns MD simulations followed by MM-GBSA binding free energy calculation to confirm the docking results and give more insights regarding the stability of both compounds inside influenza mentioned receptors, respectively. The selection criteria of the previously mentioned complexes were based on the fact that SAL showed the highest docking scores on both viral HA and NA glycoproteins whereas TAN achieved the best inhibitory activity on the other hand. Finally, we urge more advanced preclinical and clinical research, particularly for TAN, which could be used to treat the human influenza A virus effectively.


Immunohistochemical expression of folate receptor alpha in colorectal carcinoma: patterns and biological significance.
Folate receptor alpha (FRalpha) has emerged as a potential cancer therapy target with several folate-linked therapeutic agents currently undergoing clinical trials. In addition, FRalpha expression in tumors may offer prognostic significance. Most studies on FRalpha expression used reverse transcriptase polymerase chain reaction or cytofluorimetric assays. The applicability of such methods to paraffin-embedded tissues is limited. The aims of this study were to assess the feasibility of immunohistochemistry in detecting FRalpha expression and to assess the patterns and clinical significance of FRalpha expression in colorectal tissues. We used tissue microarrays containing 152 normal colorectal mucosa samples, 42 adenomas, 177 primary, and 52 metastatic colorectal carcinomas. Our results showed that staining for FRalpha on colorectal tissues was simple and easy to read. FRalpha positivity was more frequent in carcinomas (33% in primaries and 44% in metastases) than in normal mucosa or adenoma (7% in both) (P < .001). Positive staining in primary carcinomas correlated with younger age (n = 130) (P = .008), presence of distant metastasis (n = 130) (P = .043), and non-high-frequency microsatellite instability status (as detected by the standard polymerase chain reaction method using the 5 National Cancer Institute-recommended markers) (n = 77) (P = .006). Positive staining in primary carcinomas also correlated with a worse 5-year disease-specific survival (P = .04) on univariate but not multivariate analysis. Thus, our data show that there is selective expression of FRalpha in some colorectal cancers, providing a foundation for investigating the use of folate conjugates for imaging and therapy of colorectal tumors. Furthermore, our results suggest that a possible association exists between FRalpha expression and the microsatellite instability status in colorectal carcinoma. The significance of such an association as well as the prognostic value of FRalpha expression deserves further exploration.


Formation of bromo-substituted triclosan during chlorination by chlorine in the presence of trace levels of bromide.
The side reactions of triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether, TC) and chlorine in the presence of sodium chloride were investigated. In the absence of sodium chloride, three chloro-derivatives of TC, 2',3,4,4'-tetrachloro-2-hydroxydiphenyl ether (3-Cl-TC), 2',4,4',5-tetrachloro-2-hydroxydiphenyl ether (5-Cl-TC), and 2',3,4,4',5-pentachloro-2-hydroxydiphenyl ether (3,5-Cl(2)-TC) were formed, whereas in the presence of sodium chloride, 3-bromo-2',4,4'-trichloro-2-hydroxydiphenyl ether (3-Br-TC), 5-bromo-2',4,4'-trichloro-2-hydroxydiphenyl ether (5-Br-TC), (3 or 5)-bromo-2',4,4',(5 or 3)-chloro-2-hydroxydiphenyl ether ((3,5)-(BrCl)-TC), and 3,5-dibromo-2',4,4'-trichloro-2-hydroxydiphenyl ether (3,5-Br(2)-TC) were additionally formed. Radiochemical neutron activation analysis indicated that 1g of commercially available sodium chloride contained 73 microg of bromide and the bromide ion was determined to be the source of the side reactions. The rate of decrease of TC due to reaction with chlorine was greatly accelerated by the presence of bromide ion in the system: the rate with only 1 x 10(-5) M bromide ion was three times the rate in the absence of bromide.


The Alabama Preterm Birth Project: placental histology in recurrent spontaneous and indicated preterm birth.
For unknown reasons, a previous preterm birth (PTB) is a major risk factor for PTB in the current pregnancy. Our goal is to evaluate placental histology for clues related to the recurrent nature of PTB. Four hundred fifty-seven mother/infant dyads delivering between 23 and 32 weeks were first classified as having a spontaneous (S) or indicated (I) PTB, and then sorted into the following mutually exclusive categories by pregnancy history: 1) nulliparous; 2) having no previous PTB; 3) having any previous IPTB; or 4) having a previous SPTB. The placentas were evaluated for acute inflammation in the free membranes, umbilical cord, and chorionic plate, chronic inflammation in the membranes and decidua basalis, thrombosis in the chorionic plate and umbilical cord, and diffuse decidual leukocytoclastic necrosis (DDLN), a lesion associated with decreased placental perfusion. Women who had a SPTB were far more likely (85.5 vs 14.4 P < .0001) to have a SPTB in the previous pregnancy, while women with an IPTB were significantly more likely to have had a previous IPTB (89.7 vs 10.3 P < .0001). Nulliparas and women with previous term births each had about 64% SPTB and 36% IPTB. Acute inflammation at any site was present in 73.9% of SPTB versus 8.0% of IPTB (P < .0001). Chorionic plate thrombosis was also more common in SPTB than IPTB (16.2 vs 7.6, P = .01). Chronic inflammation at any site was more common in IPTB than SPTB (21.0 vs 12.7%, P = .02), as was DDLN (46.5 vs 16.1, P < .0001). When classified by SPTB and IPTB in the current pregnancy, the histologic results were not further influenced by the previous pregnancy history. SPTB and IPTB are strongly repetitive. Women with SPTB are significantly more likely to have acute inflammation in the free membranes, chorionic plate, and cord, and chorionic plate thrombosis, while women with an IPTB are significantly more likely to have chronic inflammation and especially DDLN. Past obstetric history does not further influence the placental histology.


Review of the molecular development of the thumb: digit primera.
The thumb, or digit 1, is not a typical digit. In addition to its unusual mobility and function, its formation is also unusual. It is the last digit to form and the most commonly targeted when limb development is disrupted. The thumb domain is defined by the overlapping expression of HOXA13, TBX5, GLI3R, and HOXD13 and, importantly, by an absence of other distal HOXD transcription factors. This brief review, combining developmental biology and clinical genetics, discusses the current understanding of how the thumb domain is established.


Syntheses and cell-based phenotypic screen of novel 7-amino pyrido[2,3-d]pyrimidine-6-carbonitrile derivatives as potential antiproliferative agents.
A series of N-3-substituted 7-aminopyrido[2,3-d]pyrimidin-6-carbonitrile derivatives was readily synthesized and their anti-proliferative activities on five types of tumor cells were evaluated through a cell-based phenotypic screening approach. Compound 3k was found to be potent on human colon cancer SW620 cells with an IC(50) value of 12.5 mM. Structural optimization of compound 3k led to compound 4a with improved anti-proliferative potency on SW620 cells with an IC(50) value of 6.9 mM. Further cell-cycle analyses suggested that compound 4a induced apoptosis of SW620 cells in a concentration-dependent manner.


Obstetric and psychological effects of psychoprophylactic preparation for childbirth.
Medical records, personal interviews about the childbirth experience, and self-administered attitudinal and socioeconomic data were obtained 1 to 3 days post partum in a large metropolitan hospital, for 249 women, 95 of whom had taken psychoprophylaxis training for childbirth prior to delivery. When controlled by parity, psychoprophylactic preparation was not related to any obstetric differences except for lower levels of anesthesia for both primiparas and multiparas and lower levels of analgesia among multiparas only. Preparation was significantly related to lower levels of pain and higher levels of enjoyment during childbirth, and these psychological benefits did not diminish when controlled for parity, socioeconomic status, and four sets of psychological and attitudinal characteristics.


Relationships of the stand-up time to falls and fractures in patients with rheumatoid arthritis: Results from the CHIKARA study.
Patients with rheumatoid arthritis (RA) have a higher risk of falls and fractures due to muscle weakness and painful joints of the lower extremities. Evaluation of muscle functions is important to predict falls and fractures. The aim was to investigate the relationships of muscle functions with falls and fractures in RA patients. Stand-up muscle power, speed, and stabilizing time were evaluated by a muscle function analyzer in 90 RA patients in the CHIKARA study (UMIN000023744). The relationships of the muscle functions with falls, fractures, body composition, Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR), modified Health Assessment Questionnaire (mHAQ) scores, Steinbrocker class, stage, sarcopenia, and frailty were investigated in a cross-sectional study. Each parameter of muscle function was related to age, falls, frailty, and the leg muscle score. However, only stabilizing time was related with fractures (r = .217, P = .04). When stabilizing time was ≥ 1.13 and ≥1.36 seconds, the odds ratios for falls and fractures were increased 6.2-fold compared to < 1.13 seconds (95% CI: 1.2-20.1, P = .002) and 11.4-fold compared to <1.36 seconds (95% CI: 1.7-92.5, P = .071), respectively. Sarcopenia and skeletal muscle mass were not significantly related to each muscle function. There was a negative correlation between DAS28-ESR and power. Steinbrocker class and mHAQ had negative correlations with power and speed. Sarcopenia and skeletal muscle mass were not adequate indicators of muscle functions in RA patients. Analyzing muscle functions is helpful to predict falls and fractures. Patients with extended stabilizing times should recognize the increased risk of falls and fractures.


The potential of stem cells in the treatment of cardiovascular diseases.
Although the adult mammalian heart was once believed to be a post-mitotic organ without any capacity for regeneration, recent findings have challenged this dogma. A modified view assigns to the mammalian heart a measurable capacity for regeneration throughout life. The ultimate goals of the cardiac regeneration field have been pursued by multiple strategies, including understanding the developmental biology of cardiomyocytes and cardiac stem and progenitor cells, applying chemical genetics, and engineering biomaterials and delivery methods that facilitate cell transplantation. Successful stimulation of endogenous regenerative capacity in injured adult mammalian hearts can benefit from studies of natural cardiac regeneration.


Numerical Study on the Seismic Performance of Cold-Formed Steel Shear Walls with Steel Sheathing and Gypsum Board.
The cold-formed steel shear wall with steel sheathing has gained increasing popularity due to its excellent shear capacity. To extend the applicability of this system to multi-story residences, aside from experimental investigations on the shear walls, it is essential to conduct a comprehensive study on the seismic performance of buildings. In this paper, numerical simulations were conducted on specimens subjected to monotonic and cyclic loading. Subsequently, seismic analysis of mid-rise building models was also carried out to investigate the influence of the proposed shear wall on building seismic performance. The research findings indicate that this study's modeling method can effectively simulate the shear performance of the proposed shear wall under monotonic and cyclic loading. In addition, the proposed shear wall significantly enhances the structural stiffness and improves the seismic performance of the structure under seismic action.


Conditioning effect on the long latency potentials in the lower limb to transcranial magnetic stimulation.
We used an electrical conditioning stimulation followed by transcranial magnetic stimulation (TMS) to facilitate the occurrence of long latency potentials (LLPs) in order to study the relationship between primary motor evoked potentials (MEPs) and LLPs in the lower limbs. The study group included 6 healthy subjects, 1 patient with right thalamic infarction, and 3 patients with spinal cord injuries. The subjects were subjected to electrical conditioning (C) stimulation delivered to the left big toe at 250 Hz in a train of pulses of 20 ms duration prior to TMS (T) from 0 to 150 ms at an increment of 10 ms. The surface electromyographic signals were recorded at the tibialis anterior and gastrocnemius medialis for 400 ms. The C-T test facilitated both primary MEPs and LLPs with a pattern similar to the primary MEPs of its antagonist. There was no facilitation of the primary MEPs or LLPs in the affected limb of patients with thalamic or spinal cord lesions. At appropriate C-T interval, LLPs could be consistently provoked by TMS. The LLPs were absent in the patients with thalamic infarction and spinal cord injuries. It suggests that LLPs might be provoked through a supraspinal control.


Decomposition of energetic chemicals contaminated with iron or stainless steel.
Contamination of chemicals or reaction mixtures with iron or stainless steel is likely to take place during chemical processing. If energetic and thermally unstable chemicals are involved in a manufacturing process, contamination with iron or stainless steel can impact the decomposition characteristics of these chemicals and, subsequently, the safety of the processes, and should be investigated. The goal of this project was to undertake a systematic approach to study the impact of iron or stainless steel contamination on the decomposition characteristics of different chemical classes. Differential scanning calorimetry (DSC) was used to study the decomposition reaction by testing each chemical pure, and in mixtures with iron and stainless steel. The following classes of energetic chemicals were investigated: nitrobenzenes, tetrazoles, hydrazines, hydroxylamines and oximes, sulfonic acid derivatives and monomers. The following non-energetic groups were investigated for contributing effects: halogens, hydroxyls, amines, amides, nitriles, sulfonic acid esters, carbonyl halides and salts of hydrochloric acid. Based on the results obtained, conclusions were drawn regarding the sensitivity of the decomposition reaction to contamination with iron and stainless steel for the chemical classes listed above. It was demonstrated that the most sensitive classes are hydrazines and hydroxylamines/oximes. Contamination of these chemicals with iron or stainless steel not only destabilizes them, leading to decomposition at significantly lower temperatures, but also sometimes causes increased severity of the decomposition. The sensitivity of nitrobenzenes to contamination with iron or stainless steel depended upon the presence of other contributing groups: the presence of such groups as acid chlorides or chlorine/fluorine significantly increased the effect of contamination on decomposition characteristics of nitrobenzenes. The decomposition of sulfonic acid derivatives and tetrazoles was not impacted by presence of iron or stainless steel.


Repeat stereotactic radiosurgery for locally recurrent brain metastases previously treated with stereotactic radiosurgery: A systematic review and meta-analysis of efficacy and safety.
To perform a systematic review and meta-analysis of outcomes for patients with locally recurrent brain metastases treated with a repeat course of stereotactic radiosurgery (rSRS). Primary outcomes were 1-year local control(LC) and radionecrosis (RN). Secondary outcomes were 1-year overall survival (OS) and 1-year distant brain control (DBC). Weighted random effects meta-analyses utilizing the DerSimonian and Laird methods were conducted to characterize summary effect sizes. Mixed effects regression models were utilized to analyze potential correlations between prognostic factors and outcomes. In total, 347 patients with 462 brain metastases treated with rSRS were included. Estimated 1-year LC, OS, and DBC rates were 69.0% (95% CI: 61.0-77.0%), 49.7% (95% CI: 28.9-70.6%), and 41.6% (95% CI: 33.0-50.4%), respectively. The estimated RN rate was 16.1% (95% CI: 6.3-25.9%). Every 1 Gy increase in prescription dose was estimated to result in roughly 5% increase in 1-year LC (p = 0.14). rSRS was well-tolerated with reasonable 1-year LC and OS. Dose escalation may result in improved LC.


Genetic variants in microRNA biogenesis pathway genes are associated with semen quality in a Han-Chinese population.
MicroRNA biogenesis genes have been confirmed involved in lots of diseases. This study evaluated the role of genetic variants in microRNA biogenesis genes in semen quality and idiopathic male infertility. Seven single-nucleotide polymorphisms (SNP) of DICER1 (rs13078, rs1057035 and rs12323635) and DROSHA (rs10719, rs2291109, rs17409893 and rs642321) were determined by TaqMan probes and SNPstream in 667 eligible infertile men and 419 fertile controls. Semen quality analysis was performed by computer-assisted sperm analysis. It was found that genetic variants of rs12323635 was associated with idiopathic male infertility. Additionally, in strategy analysis, the rs12323635 C allele might decrease the risk of oligozoospermia (OR 0.42, 95% CI 0.26-0.66; P=0.0002). The rs642321 TT genotype may have a higher risk of oligozoospermia (OR 2.38, 95% CI 1.34-4.25; P=0.003). These significant differences were retained after Bonferroni correction. The results showed that variants of DICER1 and DROSHA may modify the risk of abnormal semen parameters, which could result in male infertility. MicroRNA have been confirmed involved in lots of diseases. To our knowledge, few studies have elucidated the role of genetic variants in microRNA biogenesis genes in semen quality and idiopathic male infertility, although microRNA is indispensable in normal spermatogenesis. In this original study, we evaluated the potential impact of the polymorphisms in microRNA biogenesis genes on the risk of abnormal semen quality based on 667 infertile patients and 419 controls, and provided the first evidence that polymorphism in rs12323635 in DICER1 may modify the risk of abnormal semen parameters, which could result in male infertility.


The parieto-rubro-olivary pathway in the cat.
Stimulation of the parietal association cortex as well as the frontal motor cortex elicited clearly extracellular unitary activities or field potentials in the ipsilateral inferior olive in the cat. The parietal-induced responses came out generally at a longer and more variable latency than the frontal-induced ones. This suggested the existence of an indirect pathway from the parietal association cortex to the inferior olive. The recording sites for the parietal-induced responses were located not only in the dorsal lamella but also in the ventral lamella of the principal olive and in the medial accessory olive. Such olivary sites were exclusively in the rostral half of the inferior olive, and these areas in the olive were considered to give projection fibres predominantly to the hemispherical parts of the cerebe-lar cortex (neocerebellum). Small neuronal cells were labelled with horseradish peroxidase (HRP) homolaterally in the midbrain tegmentum, after HRP was injected through recording glass microelectrodes into the inferior olive where only the parietal-induced responses were evidently recorded. These small cells were distributed in the rostral one-third of the red nucleus and/or around the adjacent midbrain reticular formation close to the lateral border of the red nucleus. In referring to recent anatomical and physiological data, such small neurones labelled with HRP could be identified as the parvocellular red nucleus neurones. The present results indicate the existence of the parieto-rubro-olivary pathway system in the cat and suggest, in association with our previous studies, that the parvocellular red nucleus neurones participate in control of highly co-ordinated posture and movement predominantly through the neocerebellum.


Past, present, and future of pancreatic surgery.
The advances in the surgical treatment of pancreatic disease in the 20th century were built on careful anatomic and physiologic studies dating to the early 1800s. Operations for neoplastic diseases developed in the 1930s by Whipple, Trimble, and others allowed pancreatic malignancies to be removed with ever increasing safety. Endocrine tumors of the pancreas were described and treated surgically. Patients with pancreatitis now have a number of surgical alternatives available for their individual circumstances. The future of surgery for pancreatic disease lies in the results of the human genome project and the fields of genomics and proteomics that resulted. The rapidity with which knowledge of gene expression is advancing owing to new technologies such as the microarray biochip is amazing. The future of pancreatic surgery is bright.


Frailty assessment as independent prognostic factor for patients ≥65 years undergoing urgent cholecystectomy for acute cholecystitis.
To evaluate, in a prospective observational cohort study of adults ≥65 years old, the frailty status at the emergency department (ED) admission for the in-hospital death risk stratification of patients needing urgent cholecystectomy. Clinical variables and frailty status assessed in the ED were evaluated for the association with major complications and the need for open surgery. The parameters evaluated were frailty, comorbidities, physiological parameters, surgical approach, and laboratory values at admission. Logistic regression analysis was used to identify independent risk factors for poor outcomes. The study enrolled 358 patients aged ≥65 years [median age 74 years]; 190 males (53.1%)]. Overall, 259 patients (72.4%) were classified as non-frail, and 99 (27.6%) as frail. The covariate-adjusted analysis revealed that frailty (P< 0.001), and open surgery (P = 0.015) were independent predictors of major complications. Frailty, peritonitis, constipation at ED admission, and Charlson Comorbidity Index ≥ 4 were associated with higher odds of open surgical approach (2.06 [1.23 - 3.45], 2.49 [1.13 - 5.48], 11.59 [2.26 - 59.55], 2.45 [1.49 - 4.02]; respectively). In patients aged ≥65 years undergoing urgent cholecystectomy, the evaluation of functional status in the ED could predict the risk of open surgical approach and major complications. Frail patients have an increased risk both for major complications and need for "open" surgical approach.


A short enantioselective synthesis of N-Boc-(2R,3R)-3-methyl-3-hydroxypipecolic acid from geraniol.
The asymmetric synthesis of (2R,3R)-3-methyl-3-hydroxypipecolic acid, a key intermediate in the synthesis of dual MMP-13/aggrecanase inhibitors, is described. The title compound is prepared in seven steps with an overall yield of 41% starting from geraniol. Key steps in the synthesis include Sharpless asymmetric epoxidation, which establishes the chiral centers, and a one-pot oxidative olefin cleavage/reductive amination sequence that closes the piperidine ring.


Predicting Ebola virus disease risk and the role of African bat birthing.
Ebola virus disease (EVD) presents a threat to public health throughout equatorial Africa. Despite numerous 'spillover' events into humans and apes, the maintenance reservoirs and mechanism of spillover are poorly understood. Evidence suggests fruit bats play a role in both instances, yet data remain sparse and bats exhibit a wide range of life history traits. Here we pool sparse data and use a mechanistic approach to examine how birthing cycles of African fruit bats, molossid bats, and non-molossid microbats inform the spatio-temporal occurrence of EVD spillover. We create ensemble niche models to predict spatio-temporally varying bat birthing and model outbreaks as spatio-temporal Poisson point processes. We predict three distinct annual birthing patterns among African bats along a latitudinal gradient. Of the EVD spillover models tested, the best by quasi-Akaike information criterion (qAIC) and by out of sample prediction included significant African bat birth-related terms. Temporal bat birthing terms fit in the best models for both human and animal outbreaks were consistent with hypothesized viral dynamics in bat populations, but purely spatial models also performed well. Our best model predicted risk of EVD spillover at locations of the two 2018 EVD outbreaks in the Democratic Republic of the Congo was within the top 12-35% and 0.1% of all 25 × 25 km spatial cells analyzed in sub-Saharan Africa. Results suggest that sparse data can be leveraged to help understand complex systems.


Thermal Injection Measurement (TIM) Adds Accuracy to Injections and Can Assess Cold Chain Management.
Inaccurate assessment of injected drug delivery may increase cost and morbidity or reduce efficacy. Yet currently most injections are evaluated solely by the formation of a visible wheal that might not truly estimate the actual area of effect. We hypothesized that thermal injection measurement (TIM) might verify appropriate temperature at the time of injection, as required for some temperature-sensitive vaccines and provide more accurate information about the area of delivery. 0.1 mL of either iced (n = 11) or room temperature (n = 17) methylene blue solution was injected subcutaneously in mice under anesthesia and photos taken with an iPhone 7 built-in camera and Thermal Seek Camera phone plug-in. After 5 min, true values were determined at necropsy. TIM was closer in value to the measured area at necropsy than the area of the visualized skin wheal at both ice temperature and room temperature. The difference between the true value and thermal area assessment of iced solution averaged 0.15 cm2 as compared with the difference between the true value and wheal size, which averaged 0.27 cm2 (P = 0.04). At room temperature, this was maintained for thermal and visible wheal differences, 0.23 cm2 and 0.65 cm2, respectively (P = 0.0006). TIM can assess temperature at the time of injection and is more accurate than visual inspection. TIM could be applied to colorless injections and areas that are hard to visualize such as scar. As a portable phone plug-in, it might be a useful adjunct to aid the evaluation of injected drug delivery including in resource-limited settings.


Robotic versus open radical hysterectomy: a comparative study at a single institution.
To compare the short-term surgical outcome of patients undergoing robotic radical hysterectomy (RRH) versus open radical hysterectomy (ORH) for the treatment of early stage cervical cancer. IRB approval was obtained for a retrospective chart review of all radical hysterectomies (RHs) for Stage I and II cervical cancer performed at Brigham and Women's Hospital between August 1, 2004 and August 1, 2007. Prior to August 1, 2006 all procedures were ORHs. After this date, all procedures were RRHs. Demographic data, operative data and short-term outcomes were compared. Statistical analysis using t-tests and Fisher's Exact test were performed with SAS software. A total of 48 RHs were identified, including 16 RRHs and 32 ORHs. The groups did not differ significantly in age, body mass index, stage, or histology. Mean operative time was significantly longer for RRH than ORH (4:50 vs 3:39 h, p=0.0002). The mean estimated blood loss was significantly less for RRH than ORH (81.9 vs 665.6 mL, p<0.0001). The mean number of lymph nodes resected did not differ between RRHs and ORHs (15.6 vs 17.1, p=0.532). There were no intra-operative complications in the RRH group and one ureteral transection in the ORH group. Three RRH patients (18.8%) suffered post-operative complications which included a vaginal cuff infected hematoma, a transient ureterovaginal fistula, and a pelvic lymphocele, in comparison to seven in the ORH group (21.9%) which included 3 wound infections, two patients with pulmonary emboli, a partial small bowel obstruction with a mesenteric abscess, and a post-operative ileus (p=0.999). Mean length of stay was significantly shorter for the RRH group (1.7 vs. 4.9 days, p<0.0001). RRH results in lower blood loss and shorter length of stay, compared to ORH. Intra-operative and post-operative complication rates are comparable. RRH is a promising new surgical technique that deserves further study.


Cyberbullying detection: advanced preprocessing techniques & deep learning architecture for Roman Urdu data.
Social media have become a very viable medium for communication, collaboration, exchange of information, knowledge, and ideas. However, due to anonymity preservation, the incidents of hate speech and cyberbullying have been diversified across the globe. This intimidating problem has recently sought the attention of researchers and scholars worldwide and studies have been undertaken to formulate solution strategies for automatic detection of cyberaggression and hate speech, varying from machine learning models with vast features to more complex deep neural network models and different SN platforms. However, the existing research is directed towards mature languages and highlights a huge gap in newly embraced resource poor languages. One such language that has been recently adopted worldwide and more specifically by south Asian countries for communication on social media is Roman Urdu i-e Urdu language written using Roman scripting. To address this research gap, we have performed extensive preprocessing on Roman Urdu microtext. This typically involves formation of Roman Urdu slang- phrase dictionary and mapping slangs after tokenization. We have also eliminated cyberbullying domain specific stop words for dimensionality reduction of corpus. The unstructured data were further processed to handle encoded text formats and metadata/non-linguistic features. Furthermore, we performed extensive experiments by implementing RNN-LSTM, RNN-BiLSTM and CNN models varying epochs executions, model layers and tuning hyperparameters to analyze and uncover cyberbullying textual patterns in Roman Urdu. The efficiency and performance of models were evaluated using different metrics to present the comparative analysis. Results highlight that RNN-LSTM and RNN-BiLSTM performed best and achieved validation accuracy of 85.5 and 85% whereas F1 score was 0.7 and 0.67 respectively over aggression class.


Field metabolic rates and water influxes of two sympatric Gerbillidae:Gerbillus allenbyi andG. pyramidum.
Two primarily granivorous rodents of Old World deserts,Gerbillus allenbyi (mean adult body mass=26 g) andG. pyramidum (mean adult body mass=40 g), coexist in sandy habitats in the northwestern Negev desert. Both species are burrow dwellers and are nocturnal; however, in their overall distributions,G. pyramidum occurs in more extreme deserts than doesG. allenbyi. In comparing field metabolic rate (FMR) and water influx of the twoGerbillus species, we considered two alternative hypotheses: (1) given the difference in their overall distributions,G. pyramidum has a lower FMR and water influx thanG. allenbyi, and (2) given the similarity in their diets, and that we worked with sympatric populations, FMR and water influx are similar. The latter alternative proved to be correct. Field metabolic rates in summer were 7.29 kJ · g-0.51 · day-1 forG. allenbyi and 7.74 kJ · g-0.51 · day-1 forG. pyramidum, values that were 69.3% and 74.5%, respectively, of those predicted for rodents of their body masses. Summer water influx ofG. allenbyi was 0.167 ml · g-0.90 · day-1 and that ofG. pyramidum was 0.144 ml · g-0.90 · day-1; these values were 79.4% and 68.6%, respectively, of water influxes predicted for rodents of their body masses. When compared allometrically, there were no interspecific differences in any of the measurements.


Comparative study of the percutaneous permeation and bioaccumulation of a cyclic siloxane using frozen-thawed and nonfrozen ex vivo human skin.
Literature shows contradictory information regarding the effect of freezing the excise skin ex vivo on the diffusion of substances into the skin. Few studies indicate that storing the human or animal skin in a frozen state decreases the barrier properties after thawing. Therefore, to understand the properties of frozen skin, we evaluated the effect of storage of ex vivo human skin (2 weeks at -20 °C) on the penetration of stratum corneum and permeation into deeper skin layers (epidermis, and dermis) as well as to the receptor fluid by octamethylcyclotetrasiloxane (D4) a representative test compound of cyclic siloxanes. The main research were preceded by checking the integrity of nonfrozen ex vivo human skin in comparison to the frozen-thawed one by using the Electrical Resistance technique (ER) and the fluorescence microscopy. Samples collected in the skin absorption experiment were analyzed by gas chromatography equipped with a flame ionization detector (GC-FID). The results of this study demonstrated that freezing of excised ex vivo human skin at -20 °C for up to 14 days does not alter the permeability of D4 in a statistically significant manner. Thus, our results confirmed the validity of using skin storage conditions for testing the penetration and permeation of xenobiotics recommended by the OECD, EMA, and WHO guidelines.


Translational activation of the lck proto-oncogene.
The lck proto-oncogene, a member of the src gene family, encodes a lymphocyte-specific protein tyrosine kinase (p56lck) that is implicated in the pathogenesis of lymphoid neoplasia. We report here that 5' lck sequence elements, containing AUG codons, significantly reduce the in vivo efficiency of p56lck translation from the normal messenger RNA. This result provides a quantitative explanation for the overexpression of p56lck in two retrovirally-induced murine lymphomas that express abnormal lck transcripts from which the physiological 5' translational control region has been deleted and non AUG-containing viral sequences substituted. In contrast to other mammalian genes, most proto-oncogenes contain AUG codons 5' to the authentic initiation codon, suggesting that cells can regulate translational start sites in these mRNAs. Abrogation of translational control may be a general mechanism of proto-oncogene activation in malignancy.


Severe sprains of the sub-axial cervical spine in adolescents: a diagnostic and therapeutic challenge: a report of three cases.
Sub-axial cervical spine(C spine) distraction flexion injuries, known as cervical sprains, have been divided into either "benign" or "severe" sprains depending on the integrity of the posterior longitudinal ligament (PLL) of the spinal column. It is a very uncommon injury and rarely reported in the literature. Most of the reports in the literature discuss this injury in the adult age group and so the adolescent age group was also considered to follow the same model of progression of mechanical instability depending on the degree and extent of structures injured, including the PLL as a cutoff factor between a "stable" and an "unstable" injury. We report three cases of adolescents with severe cervical sprains at the C2-C3 level and argue the integrity of PLL as a determinant factor in the sagittal stability of the C spine in this age group.


Induction of the Drosophila heat shock response in isolated polytene nuclei.
When Drosophila salivary glands are disrupted in cytoplasm from heat-shocked Drosophila Kc cells in culture, puffs are induced in the polytene nuclei at the heat shock loci. The in vitro response increases with time of incubation, reaching in vivo levels after 2 hr, and is sensitive to alpha-amanitin. Cytoplasm from control Kc cells induces poorly, but prolonged exposure to air or the addition of hydrogen peroxide stimulates induction to the levels observed with cytoplasm from heat-shocked Kc cells. Autoradiography confirms that the heat shock loci induced to puff in vitro are the most actively transcribing sites in the genome.