Effect of acclimation temperature on the elongation step of protein synthesis in different organs of rainbow trout.
Cytosolic extracts of liver, kidney, spleen, gill, red and white muscle from rainbow trout acclimated to 4 and 17 degrees C, respectively, have been investigated in vitro with respect to their enzymic activity in stimulating the growth of nascent peptide chains (labelled polyphenylalanine) at assay temperatures from 5 to 25 degrees C using polyuracil as messenger RNA. The elongation step of protein synthesis is characterized by a Q10 value of about 2.4 (range 10-25 degrees C) in all organs from both, 4 and 17 degrees C acclimated fish. Except for the red muscle, the organs of cold acclimated trout, however, exhibit significantly higher specific elongation rates (mol phenylalanine polymerized/(g wet weight X h)) at any experimental temperature than those of warm acclimated fish. This increase of the elongation rates varies between the organs and ranges from +29% (liver) to +60% in the gill. The specific acylation rate (mol phenylalanyl-tRNA formed/(g wet weight X h] surpasses the specific elongation rate by a factor of at least 8.5. Moreover, the specific acylation rate per mg protein is independent of acclimation temperature. It is concluded that the increased specific elongation rates in 4 degrees C acclimated trout are not due to altered pool sizes of the precursor phenylalanyl-tRNA, but reflect an effective enhancement of enzymic elongation factor activities. In accordance with data taken from literature, this finding suggests a compensatory enhancement of in vivo protein synthesis to occur in trout during cold acclimation.


Structural variations of the cell wall precursor lipid II in Gram-positive bacteria - Impact on binding and efficacy of antimicrobial peptides.
Antimicrobial peptides (AMPs) are natural antibiotics produced by virtually all living organisms. Typically, AMPs are cationic and amphiphilic and first contacts with target microbes involve interactions with negatively charged components of the cell envelope such as lipopolysaccharide (LPS), and wall- or lipoteichoic acids (WTA, LTA). The importance of charge-mediated interactions of AMPs with the cell envelope is reflected by effective microbial resistance mechanisms which are based on reduction of the overall charge of these polymers. The anionic polymers are linked in various ways to the stress-bearing polymer of the cell envelope, the peptidoglycan, which is made of a highly conserved building block, a disaccharide-pentapeptide moiety that also contains charged residues. This structural element, in spite of its conservation throughout the bacterial world, can undergo genus- and species-specific modifications that also impact significantly on the overall charge of the cell envelope and on the binding affinity of AMPs. The modification reactions involved largely occur on the membrane-bound peptidoglycan building block, the so-called lipid II, which is a most prominent target for AMPs. In this review, we focus on modifications of lipid II and peptidoglycan and discuss their consequences for the interactions with various classes of AMPs, such as defensins, lantibiotics and glyco-(lipo)-peptide antibiotics. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides.


A single universal scale of radical stabilization energies does not exist: global bond dissociation energies and radical thermochemistries are described by combining two universal scales.
Results from any single scale of radical stabilization energies are dependent on the species chosen for setting its zero. A scale of radical destabilization energies with a universal zero reference point is shown to exist, but it must be used in conjunction with a universal scale capable of describing the polarities of bonds broken and formed. The use of the two scales is demonstrated for calculating bond dissociation enthalpies, enthalpies of reactions, enthalpies of formation, and the magnitude of steric effects, resonance, and conjugation stabilization. Examples of applications include explanations of some observed effects in autoxidations and polymerizations.


Duodenal neuroendocrine tumors: Impact of tumor size and total number of lymph nodes examined.
The current study sought to investigate the impact of tumor size and total number of LN examined (TNLE) on the incidence of lymph node metastasis (LNM) among patients with duodenal neuroendocrine tumor (dNET). Patients who underwent curative resection for dNETs between 1997-2016 were identified from 8 high-volume US centers. Risk factors associated with overall survival and LNM were identified and the optimal cut-off of TNLE relative to LNM was determined. Among 162 patients who underwent resection of dNETs, median patient age was 59 (interquartile range [IQR], 51-68) years and median tumor size was 1.2 cm (IQR, 0.7-2.0 cm); a total of 101 (62.3%) patients underwent a concomitant LND at the time of surgery. Utilization of lymphadenectomy (LND) increased relative to tumor size (≤1 cm:52.2% vs 1-2 cm:61.4% vs >2 cm:93.8%; P < .05). Similarly, the incidence of LNM increased with dNET size (≤1 cm: 40.0% vs 1-2 cm:65.7% vs >2 cm:80.0%; P < .05). TNLE ≥ 8 had the highest discriminatory power relative to the incidence of LNM (area under the curve = 0.676). On multivariable analysis, while LNM was not associated with prognosis (hazard ratio [HR] = 0.9; 95% confidence intervals [95%CI], 0.4-2.3), G2/G3 tumor grade was (HR = 1.5; 95%CI, 1.0-2.1). While the incidence of LNM directly correlated with tumor size, patients with dNETs ≤ 1 cm had a 40% incidence of LNM. Regional lymphadenectomy of a least 8 LN was needed to stage patients accurately.


Mandibular metastasis in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) presenting initially as a bony metastasis is rare. Involvement of maxillofacial bones is even more rare and only 20 cases have been reported. A case of a 65-year-old male patient presenting with metastasis to the mandible from a primary HCC is described.


Association of organic solvents and occupational noise on hearing loss and tinnitus among adults in the U.S., 1999-2004.
Exposure to organic solvents and noise may be causal agents in the development of hearing loss and tinnitus. The objectives of the present study were to examine the association of organic solvents with hearing loss and tinnitus and to assess the interaction of organic solvent and occupational noise exposure on hearing loss and tinnitus. A secondary data analysis of data from the National Health and Nutrition Examination Survey and Occupational Information Network (O*NET) among a study population ranging from 1085 to 2471 study participants from 1999 to 2004. Multiple multivariate logistic regression models were used to assess the associations of individual organic solvent exposures as measured by blood biomarkers (1,4-dichlorobenzene, benzene, ethylbenzene, styrene, toluene, o-xylene, and m-/p-xylene) with self-reported hearing loss, audiometrically assessed hearing loss, and self-reported tinnitus. Models were adjusted for age, gender, race/ethnicity, diabetes, non-occupational noise exposure, smoking, and income. Organic solvents found to be statistically significantly associated with the outcome after adjusting for covariates were tested for interaction with occupational noise exposure. Solvent exposure was not statistically significantly associated with self-reported tinnitus. Benzene (OR 1.43, 95% CI 1.15-1.78), ethylbenzene (OR 1.24, 95% CI 1.02-1.50), and toluene (OR 1.27, 95% CI 1.06-1.52) concentrations were statistically significantly associated with increased adjusted odds of high-frequency hearing loss. No statistically significant interaction was observed between these solvents and occupational noise on high-frequency hearing loss. We found no evidence of an association between organic solvents and tinnitus; however, there was evidence of an association between organic solvent exposure and prevalence of high-frequency hearing loss.


Association between cardiometabolic index and atherosclerotic progression in patients with peripheral arterial disease.
Cardiometabolic index (CMI), calculated as a product of waist-to-height ratio and triglycerides-to-HDL cholesterol ratio, is a new index for discriminating diabetes mellitus. Patients with peripheral arterial disease (PAD) are prone to have other atherosclerotic diseases such as coronary artery disease and stroke. The purpose of this study was to clarify the relationships between CMI and indicators of atherosclerotic progression in patients with PAD. The subjects were 63 outpatients with PAD. Relationships of CMI with variables related to atherosclerotic progression were investigated using multivariate linear regression analysis and analysis of covariance with adjustment for age, sex and histories of smoking and alcohol drinking. Log-transformed CMI was significantly correlated with mean intima-media thickness of the common carotid artery (IMT) (standardized regression coefficient: 0.350, p < 0.01) and % decrease in ankle-brachial systolic pressure index (ABI) after treadmill exercise (standardized regression coefficient: 0.365, p < 0.01). Mean IMT and % decrease in ABI by treadmill exercise were significantly higher (p < 0.01) in the group of the 3rd tertile for CMI than in the group of its 1st tertile (mean ± SE: mean IMT (mm), 0.94 ± 0.06 (1st tertile) vs. 0.94 ± 0.06 (2nd tertile) vs. 1.19 ± 0.06 (3rd tertile); % decrease in ABI, 14.1 ± 3.4 [1st tertile] vs. 26.0 ± 3.5 [2nd tertile] vs. 30.0 ± 3.5 [3rd tertile]). CMI was shown to be associated with the degrees of atherosclerosis in the common carotid artery and ischemia in leg arteries and is therefore a useful discriminator of atherosclerotic progression in patients with PAD.


Long-term dermoscopic follow-up of melanocytic naevi: clinical outcome and patient compliance.
Digital dermoscopy for the follow-up of melanocytic naevi (MN) is becoming more common in dermatological private practice. To evaluate the clinical outcome, including the patient's compliance, in a long-term follow-up of single MN. Criteria for the selection of MN for follow-up: clinically suspicious without dermoscopically atypical features, or typical for the patient. Clinical outcome measures: number of detected malignant melanomas (MM) and/or atypical MN; quantity, quality, and differences in morphological changes between 'low-risk' patients (no MM in history and < 50 MN) and 'high-risk' patients (MM in history and/or > 50 MN). Compliance: the number of patients who joined a recommended follow-up scheme. No MM was found in 145 consecutive patients (mean age 28 years, 54% female) during a 4-year period (median follow-up per patient: 24 months; ranging 4-45; at least three visits). In five patients (3%), seven histologically proven atypical MN were shown on whole body examination at sites other than those documented. A total of 1968 images in 177 'low-risk' and 95 'high-risk' MN were analysed: 37% (n = 65) of 'low-risk' and 32% (n = 30) of 'high-risk' MN showed dermoscopic changes (difference not statistically significant), none were suspicious for MM. Compliance, evaluated within a separate database of 303 consecutive patients (mean age 32 years, 52% female) over a 6-month period, was only 46%, although recall letters were used. (i) In our setting of daily routines in dermatological private practices long-term follow-up of a single MN seems not to be helpful for the detection of MM. (ii) A whole body examination must be done at each visit. (iii) The clinician's experience of the type and number of possible morphological changes in MN is crucial in order to avoid unnecessary excisions. (iv) The patient's compliance might be an important problem. (v) Cost-effectiveness has yet to be analysed.


Forensic pathology services and autopsy law of Qatar.
This work presents information about the current practice of medico-legal services including forensic pathology services in the Islamic state of Qatar from the author's personal experience gained during a consultation visit to Hamad Medical Corporation Hospital of Qatar. Qatar enacted a comprehensive autopsy law (Law No. 8 of 2003) on the basis of tenets of Islam, incorporating modern trends and opinion. This deals with performance of hospital/clinical, forensic post-mortems and dissection of dead bodies for educational purposes.


From integrative signalling to metabolic disorders.
The adrenal cortex undergoes constant dynamic structural changes, a key element in ensuring integrative functionality of the gland. Studies have shown that the cellular environment can modulate cell functions such as proliferation and steroid secretion. For example, 3-day treatment with angiotensin II promotes protein synthesis with a concomitant decrease in proliferation of glomerulosa cells, when cultured on fibronectin, but not on collagen IV or laminin. These effects involve close interaction between cytoskeleton-associated proteins and activation of p42/p44mapk and p38 MAPK pathways. On the other hand, adrenocorticotropin hormone (ACTH), which is clearly the most potent stimulus of fasciculata cells, induces specific modulation of targeted proteins, when cells are cultured on collagen IV, but not on fibronectin or laminin. In particular, ACTH treatment leads to increased expression of Seladin-1 and induces the relocalization of Seladin-1 from the cytoplasm to the nucleus, both in vivo and in culture conditions, in adult rats and in human fetal adrenal glands. As a whole, these results indicate that Seladin-1, together with collagen IV, is able to modulate ACTH responsiveness. Hence, Seladin-1 may participate in the regulation of steroidogenesis when localized in the cytoplasm, while conversely protecting cells against oxidative stress generated by intense ACTH stimulation when massively localized in the nucleus.


Characterization of differentiation antigens of the mouse mammary epithelial cell (MME antigens) carried on the mouse milk fat globule.
The characterization of mouse mammary epithelial (MME) antigens from the mouse milk fat globule (MMFG) is described. Heterologous antisera against fat-free MMFG material identifies by indirect immunofluorescence techniques, cell-type-specific MME antigens on the surface of mouse mammary epithelial cells and MMFGs and not on cells of other tissues. Mammary epithelial cells of all mouse strains tested were positive. However, the intensity of staining differed. Specificity of anti-MME for MME antigens is demonstrated by competition and cross-absorption experiments. The MMFG is composed of 5 main proteinaceous components, 3 of which contain carbohydrate and which are shown to contain the specific MME antigens.


Amination degree of gelatin is critical for establishing structure-property-function relationships of biodegradable thermogels as intracameral drug delivery systems.
Glaucoma is a lifelong disorder that necessitates continuous medical therapy to manage its symptoms and preserve the vision of patients; accordingly, it is highly beneficial to develop a long-acting injectable depot system that can exhibit better drug delivery capability. This study aims to investigate the effect of the amination degree of gelatin on the carbodiimide-mediated grafting of thermo-responsive poly(N-isopropylacrylamide) segments onto biodegradable protein backbone molecules. Moreover, the potential applications of these carrier materials for intracameral pilocarpine administration in glaucomatous subjects will be considered. The gelatins with different amination degrees that are prepared by controlling the feed amount of adipic acid dihydrazide are further used for the synthesis of graft copolymers. The results of chemical characterization and electron microscopy studies showed that both grafting reaction effectiveness and gelling carrier ultrastructure vary in response to biomaterial amination. Compared to unmodified biopolymer thermogel without gel formation, graft copolymers that are composed of aminated gelatin networks showed a more remarkable temperature-triggered pilocarpine capture under physiological conditions. This could create more stable depot-forming carrier systems with improved in vivo pharmacological efficacy. Although the increase in amination degree enhances the biodegradation resistance of graft copolymers for achieving extended drug release profiles and provides significant therapeutic benefits, carriers with excess positive charges may potentiate the cytotoxic actions of oxidative stress signals and may cause damage in cellular barrier integrity. Consequently, unfavorable ocular tissue responses and poor treatment outcomes are observed in glaucomatous rabbits. For the first time, our findings suggest that the amination degree of gelatin performs a crucial function in guiding the development of structure-property-function relationships of biodegradable thermogels as intracameral drug delivery systems.


Prediction of deficits in behavioral self-regulation among persons with multiple sclerosis.
There is evidence that the lesions characteristic of multiple sclerosis (MS) may isolate prefrontal cortex from other regions of the brain. These findings are consistent with neuropsychological data that show many persons with MS to perform poorly on tests thought to assess the executive functions presumably mediated by the prefrontal area. Furthermore, prefrontal lesions have long been associated with the occurrence of various kinds of behavior pathology. These data prompted us to test the hypothesis that deficits in behavioral regulation typical of frontal lobe dysfunction might play a significant role in the occurrence of behavioral disturbances among persons with multiple sclerosis hospitalized for treatment with methylprednisolone and rehabilitation therapies. Twenty-three chronic progressive MS patients were compared with 23 healthy controls matched on age and education. Both groups were administered the Mini Mental State Exam (MMSE) and the Behavioral Dyscontrol Scale (BDS), a test based on Luria's studies of frontal lobe dysfunction that measures the capacity for regulation of purposeful activity. The MS patients performed more poorly than comparison subjects on the BDS, but not on the MMSE. The MS sample was then divided into two groups according to whether patients obtained low (n = 8) or high scores (n = 16) on the BDS. Compared with high-scoring patients, low-scoring patients showed greater behavioral inertia and greater disruption of the ability to regulate purposeful activity in the performance of activities of daily living. Behavioral disturbances in these individuals thus require careful assessment. Among those who show deficient capacity for behavioral control, the most efficacious interventions may involve the use of cueing, provision of structure, supervision, and environmental modifications.


Isolated endosomes from quiescent rat liver contain the signal transduction machinery. Differential distribution of activated Raf-1 and Mek in the endocytic compartment.
In this study we identify the molecules involved in the MAPK signal transduction pathway (Ras, Raf-1, Mek, Mek-P and MAPK) in highly purified endosomal fractions isolated from rat liver. Biochemical analysis shows that only the early-sorting endocytic compartment contains activated Raf-1 and Mek. Finally, the exogenous administration of EGF led to redistribution of Raf-1 from the caveolin-enriched plasma membrane into the endosomes.


Minimum nodal yield in oral squamous cell carcinoma: defining the standard of care in a multicenter international pooled validation study.
There is evidence to suggest that a nodal yield <18 is an independent prognostic factor in patients with clinically node negative (cN0) oral squamous cell carcinoma (SCC) treated with elective neck dissection (END). We sought to evaluate this hypothesis with external validation and to investigate for heterogeneity between institutions. We analyzed pooled individual data from 1,567 patients treated at nine comprehensive cancer centers worldwide between 1970 and 2011. Nodal yield was assessed with Cox proportional hazard models, stratified by study center, and adjusted for age, sex, pathological T and N stage, margin status, extracapsular nodal spread, time period of primary treatment, and adjuvant therapy. Two-stage random-effects meta-analyses were used to investigate for heterogeneity between institutions. In multivariable analyses of patients undergoing selective neck dissection, nodal yield <18 was associated with reduced overall survival [hazard ratio (HR) 1.69; 95 % confidence interval (CI) 1.22-2.34; p = 0.002] and disease-specific survival (HR 1.88; 95 % CI 1.21-2.91; p = 0.005), and increased risk of locoregional recurrence (HR 1.53; 95 % CI 1.04-2.26; p = 0.032). Despite significant differences between institutions in terms of patient clinicopathological factors, nodal yield, and outcomes, random-effects meta-analysis demonstrated no evidence of heterogeneity between centers in regards to the impact of nodal yield on disease-specific survival (p = 0.663; I (2) statistic = 0). Our data confirm that nodal yield is a robust independent prognostic factor in patients undergoing END for cN0 oral SCC, and may be applied irrespective of the underlying patient population and treating institution. A minimum adequate lymphadenectomy in this setting should include at least 18 nodes.


Association of Suicide Risk With Transition to Civilian Life Among US Military Service Members.
Although interest is high in addressing suicide mortality after the transition from military to civilian life, little is known about the risk factors associated with this transition. To support the ongoing suicide surveillance work of the US Department of Veterans Affairs (VA) Office of Mental Health and Suicide Prevention, examining these factors is important for targeting suicide prevention efforts. To examine the prevalence, patterns, and associated characteristics of suicide mortality among US service members after separation from military active status. This retrospective population-based cohort study obtained demographic and military service data from the VA/Department of Defense Identity Repository. Individuals who served on active duty in the US Army, Navy, Air Force, Marine Corps, or Coast Guard after September 11, 2001, and who separated from active status between January 1, 2010, and December 31, 2017, were included in the cohort. Data analyses were conducted from September 9, 2019, to April 1, 2020. Suicide mortality within 6 years after separation from military service. A total of 1 868 970 service members (1 572 523 men [84.1%]; mean [SD] age at separation, 30.9 [9.9] years) separated from the military during the study period. Through the end of the study period (December 31, 2017), 3030 suicides (2860 men and 170 women) were identified as having occurred within 6 years of separation from the military. Statistically significant differences in suicide risk were found by demographic and military service characteristics. Suicide rates after separation were time dependent, generally peaking 6 to 12 months after separation and declining only modestly over the study period. Male service members had a statistically significantly higher hazard of suicide than their female counterparts (hazard ratio [HR], 3.13; 95% CI, 2.68-3.69). Younger individuals (aged 17-19 years; HR, 4.46 [95% CI, 3.71-5.36]) had suicide hazard rates that were approximately 4.5 times higher than those who transitioned at an older age (≥40 years). Service branch remained a risk factor for suicide even 6 years after separation; those who separated from the Marine Corps (HR, 1.55; 95% CI, 1.36-1.78) and the Army (HR, 1.48; 95% CI, 1.31-1.67) had a higher hazard than those who transitioned from the Air Force. The hazard for those who separated from the active component was higher than for those who separated from the reserve component (HR, 1.29; 95% CI, 1.18-1.42). Service members with a shorter length of service had a higher hazard (HR, 1.26; 95% CI, 1.11-1.42) than those with a longer service history. Results of this study show that not all service members who recently transitioned from military life had the same risk of suicide. The data suggest that awareness of military service and demographic characteristics can help identify those most at risk for suicide to target prevention efforts.


[Vortioxetine: a new antidepressant to treat depressive episodes].
Vortioxetine is a new antidepressant, which mechanism of action is multimodal, targeting the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT3, 5-HT7 receptors and the serotonin transporter (5-HTT). Its efficacy and safety were assessed in fourteen studies including more than 3700 patients with a major depressive episode and treated with vortioxetine. In short-term studies (8 weeks), vortioxetine is more efficacious than placebo in decreasing depressive symptoms as measured by the MADRS total score, response rate (vortioxetine: 53.2% vs placebo: 35.2%) and remission rate (vortioxetine: 29.2% vs placebo: 19.3%). In a long-term study (52 weeks), vortioxetine is also superior to placebo in preventing relapses and recurrences. Moreover, in second line treatment, after failure of a first line selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrin reuptake inhibitor (SNRI), vortioxetine is superior to agomelatine in improving depressive symptoms and achieving response and remission. Furthermore, the positive effects of vortioxetine on improvement of cognitive symptoms of major depressive episodes are particularly well established in several clinical trials. The tolerability profile of vortioxetine is favourable. The recommended daily posology of vortioxetine is 10mg/d. Vortioxetine is a new antidepressant drug with a multimodal mechanism of action, well-documented efficacy and safety profiles.


Estimating Spatiotemporal Variability of Ambient Air Pollutant Concentrations with A Hierarchical Model.
Studies have linked exposure to air pollutants to short-term and sub-chronic health outcomes. However, individual-level air pollution exposure is difficult to measure at a high spatial and temporal resolution and for larger populations due to limitations in sampling techniques. We presented a hierarchical model to capture spatiotemporal variability of nitrogen dioxide (NO2) and nitrogen oxides (NOx) concentrations in Southern California by combining high temporal resolution data from routine monitoring stations with high spatial resolution data from investigator-initiated episodic measurements. In this model, the spatiotemporal field of concentrations was first decomposed into a mean and residual and the mean representing the seasonal trend was further decomposed into a constant and varying temporal basis functions. The mean of the spatially varying coefficients of temporal basis functions were modeled by local covariates using non-linear generalized additive model and least square fitting using measurements from both routine monitoring and additional episodic sampling locations, while the spatially-correlated residuals of the coefficients were co-kriged. We found traffic, land-use and wind accounted for a large portion of the variance (beyond 35%) for the long-term average trend of concentrations. Spatial residuals accounted for a large portion of the variance of the temporal components (about 30% for NO2 and 20% for NOx). Leave-one-out cross validation produced an R2 of 0.84 for NO2 and 0.81 for NOx when comparing the modeled weekly concentration with the observed trends at all routine monitoring stations.


Kluyveromyces lactis killer toxin inhibits adenylate cyclase of sensitive yeast cells.
K1 killer toxin secreted by the K1 strain of Saccharomyces cerevisiae, has been well characterized. It is a simple protein of molecular weight (MW) 11,470 (ref. 3), encoded by a double-stranded, linear RNA plasmid, called M RNA, of MW 1.1-1.7 x 10(6) (refs 4-6). It is lethal to sensitive Saccharomyces cerevisiae which does not carry M RNA. Leakage of K+ and ATP is the first distinct response in sensitive cells, and the toxic action is thought to be due to its action as a protonophore or K+ ionophore. Recently, a further killer toxin has been found in Kluyveromyces lactis IFO 1267, and it is associated with the presence of the double-stranded linear DNA plasmids, pGK1-1 (MW 5.4 x 10(6)) and pGK1-2 (MW 8.4 x 10(6)). It has been shown, by curing pGK1-1 or deletion mapping, that the structural gene for the killer toxin and immunity-determining gene reside on the smaller plasmid. Moreover, the plasmids could be transferred from K. lactis to S. cerevisiae by protoplast fusion and protoplast transformation. As the K. lactis toxin is encoded by a DNA plasmid and has a relatively wider action spectrum than K1 killer toxin, the mode of action of the toxin is highly interesting. Here we report that K. lactis toxin inhibits adenylate cyclase in sensitive yeast cells and brings about arrest of the cells at the G1 stage.


Liquid-liquid extraction of Pu(IV), U(VI) and Am(III) using malonamide in room temperature ionic liquid as diluent.
The extraction behavior of U(VI), Pu(IV) and Am(III) from nitric acid medium by a solution of N,N-dimethyl-N,N-dioctyl-2-(2-hexyloxyethyl)malonamide (DMDOHEMA) in the room temperature ionic liquid, 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (C(4)mimNTf(2)), was studied. The distribution ratio of these actinides in DMDOHEMA/C(4)mimNTf(2) was measured as a function of various parameters such as the concentration of nitric acid, DMDOHEMA, NTf(2)(-), alkyl chain length of ionic liquid. The extraction of actinides in the absence of DMDOHEMA was insignificant and the distribution ratio achieved in conjunction with C(4)mimNTf(2), was remarkable. The separation factor of U(VI) and Pu(IV) achieved with the use of DMDOHEMA, ionic liquid was compared with Am(III) and other fission products. The stoichiometry of the metal-solvate was determined to be 1:2 for U(VI) and Pu(IV) and 1:3 for Am(III).


Role of double-stranded RNA and Npro of classical swine fever virus in the activation of monocyte-derived dendritic cells.
Classical swine fever virus (CSFV) is a noncytopathogenic (ncp) positive-sense RNA virus that replicates in myeloid cells including macrophages and dendritic cells (DC). The virus does not induce type I interferon (IFN-alpha/beta), which in macrophages has been related to the presence of the viral Npro gene. In the present work, the role of viral double-stranded (ds)RNA and Npro in the virus-host cell interaction has been analyzed. Higher levels of detectable dsRNA were produced by a genetically engineered cytopathogenic (cp) CSFV compared with ncp CSFV, and cp CSFV induced IFN-alpha/beta in PK-15 cells. With DC, there was only a small difference in the levels of dsRNA between the cp and ncp viruses, and no IFN-alpha/beta was produced. However, the cp virus induced a higher degree of DC maturation, in terms of CD80/86 and MHC II expression. Npro deletion mutants induced an increase in DC maturation and IFN-alpha/beta production-for both ncp and cp viruses-despite reduced replication efficiency in the DC. Deletion of Npro did not influence dsRNA levels, indicating that the interference was downstream of dsRNA turnover regulation. In conclusion, the capacity of CSFV to replicate in myeloid DC, and prevent IFN-alpha/beta induction and DC maturation, requires both regulated dsRNA levels and the presence of viral Npro.


Gyrate atrophy of the choroid and retina: further experience with long-term reduction of ornithine levels in children.
To determine whether the long-term reduction of plasma ornithine levels by way of an arginine-restricted diet in patients with gyrate atrophy will slow the progression of this chorioretinal degeneration. Natural history study of 2 pairs of siblings with gyrate atrophy treated with an arginine-restricted diet. Fundus photography and electrophysical and psychophysical retinal function tests. After 16 to 17 years of receiving an arginine-restricted diet, the younger sibling in each pair, who was prescribed the diet at an earlier age than the older sibling, demonstrated a slower progression of lesions compared with the older sibling. If started at an early age, long-term substantial reduction of plasma ornithine levels may appreciably slow the progression of the chorioretinal lesions and, to a lesser extent, the progressive loss of retinal function in patients with gyrate atrophy.


Individual susceptibility of mice to a mutagen in both germ and somatic cells.
Male Swiss mice received simultaneously, by gavage, 500 mg methylurea/kg body weight and 25 mg sodium nitrite/kg body weight, and in a further experiment 330 mg of methylurea/kg and 17 mg sodium nitrite/kg, for 5 consecutive days. This treatment resulted in a dose-dependent mutagenic effect in both the dominant-lethal and the micro-nucleus tests. Furthermore, in both mammalian tests, some animals were more susceptible to the mutagenic compounds than were others. However, the liver microsomal metabolizing system did not seem to be responsible for this variation of mutagenic induction.


The impact of temporary deferral due to low hemoglobin: future return, time to return, and frequency of subsequent donation.
This study investigated the effects of a 6-month deferral due to low hemoglobin (Hb) on the subsequent donation patterns of Australian whole blood donors. The study was a retrospective cohort study of the donation patterns of all whole blood donors deferred for low Hb during a 2-month period compared with donors who were not deferred. Donations 3 years after eligibility to give blood were recorded. Analysis of proportion returning, time to return, and frequency of donation was performed using logistic regression, survival analysis, and negative binomial regression. Among first-time donors, 20.9% of low Hb-deferred donors returned during the follow-up period versus 69.9% of those not deferred. Among repeat donors, 64.0% of deferred donors returned versus 91.0% of those not deferred. Temporary deferral delayed time to first return (p < 0.001), reduced frequency of donation (2.4 donations per donor before deferral compared to 1.1 per donor in first year of follow-up), and increased the likelihood of dropping out in later years of follow-up. However, if a donor returned promptly once eligible and gave more donations in the first year, the negative impact on future donation patterns was diminished. High frequency of attendance before deferral was the strongest predictor of time to return and future donation frequency. Deferral for low Hb had a strong effect on first-time and repeat donors. This study highlights the influence of strong donation habits on return after deferral and the importance of encouraging donors to return promptly once eligible.


Variant morphology and arterial supply of diaphragmatic crura with probe patent foramen ovale.
Crura are the posterior pillars of the tendino-muscular partition between thoracic and abdominal cavity. This study highlights bilaterally an unfamiliar morphology of diaphragmatic crura with uncommon origin of inferior phrenic artery and accompanying atrial septal defect in a 63-years-old female cadaver with scoliosis. An attempt is made to portray the clinical implications of these variations. In addition authors have discussed the embryological and genetic basis of these variations. In the recent few decades, surgical correction of scoliosis involving intervention with the crura has gained pace. Knowledge about the normal as well as variant crural morphology is imperative for the surgeons to decide the correct approach during spinal corrective surgeries and for radiologist to prevent any diagnostic pitfall. Familiarity about the variant origin of inferior phrenic artery may prevent complications during treatment of pathological conditions related to inferior phrenic artery. Preoperative awareness about the coexisting atrial septal defect is vital for anesthesiologists promoting them to administer cardioprotective anesthetic drugs. To the best of our knowledge, description of such a combination of variations in anatomical literature is rare and scarcely reported. Awareness of these anatomical variations is relevant for operating surgeons, radiologists, anesthesiologists and anatomists.


MRA calibration and measurement capabilities--radioactivity.
The practical realisation of the Mutual Recognition Arrangement relies on its two main Appendices, B and C. Appendix B relates to the equivalence of national measurement standards. The dissemination of these standards is achieved by the provision of physical standards and measurement services, where the associated measurement values are traceable to the SI. Appendix C specifies the quantities and ranges for which participating institutes recognise the validity of calibration and measurement certificates issued by other participating institutes and these are detailed in the database devoted to these standards and services, commonly referred to as calibration and measurement capabilities. Each participating institute has the opportunity to submit entries, via its Regional Metrology Organisation (RMO), to the database but, in order for users to be able to make informed choices, it is important that the data are entered to a common standard. The Joint Committee of the RMOs and the Bureau International des Poids et Mesures is responsible for the coordination of data provided by the RMOs. It is for individual RMOs to ensure the correctness of their own entries and to review and comment on those from others. This paper details that process and describes the various entries in the tables. It also addresses some of the remaining issues that still need to be resolved, in particular, the magnitudes of uncertainties and the need for supporting comparisons, both of which still present some significant problems.


RAB-35 and ARF-6 GTPases Mediate Engulfment and Clearance Following Linker Cell-Type Death.
Clearance of dying cells is essential for development and homeostasis. Conserved genes mediate apoptotic cell removal, but whether these genes control non-apoptotic cell removal is a major open question. Linker cell-type death (LCD) is a prevalent non-apoptotic developmental cell death process with features conserved from C. elegans to vertebrates. Using microfluidics-based long-term in vivo imaging, we show that unlike apoptotic cells, the C. elegans linker cell, which dies by LCD, is competitively phagocytosed by two neighboring cells, resulting in cell splitting. Subsequent cell elimination does not require apoptotic engulfment genes. Rather, we find that RAB-35 GTPase is a key coordinator of competitive phagocytosis onset and cell degradation. RAB-35 binds CNT-1, an ARF-6 GTPase activating protein, and removes ARF-6, a degradation inhibitor, from phagosome membranes. This facilitates phosphatidylinositol-4,5-bisphosphate removal from phagosome membranes, promoting phagolysosome maturation. Our studies suggest that RAB-35 and ARF-6 drive a conserved program eliminating cells dying by LCD.


Immunobiological characterization of N -nitrosomethylurea-induced rat breast carcinomas: tumoral IL-10 expression as a possible immune escape mechanism.
Improvement of immunotherapy-based protocols in cancer requires a better understanding of tumor microenvironment and tumor-host interaction. Stromal and immune cells and molecules such as cytokines, chemokines, growth factors and metalloproteases mediate tumor-host interaction determining, at least in part, tumor development. In the present study, we used an immunohistochemical approach to explore leukocyte sub-populations, cytokine profiles and costimulatory molecule expression in rat N -Nitrosomethylurea (NMU)-induced breast tumors. Our results show a strong leukocyte infiltration mainly composed of macrophages and TCR alphabeta positive T cells. We observed a weak expression of costimulatory molecules (CD80, CD86) and an absence of inflammatory cytokines (IFNgamma, TNFalpha, IP-10) and lymphocyte activation markers (CD25). Interestingly, this immunosuppressed status could be a consequence of IL-10 expression by malignant cells, as demonstrated by immunohistology and western blot analysis, which seems to be an early event during mammary carcinogenesis. Analysis of a cell line derived from an NMU-induced rat breast tumor showed that this cell line also expresses IL-10. This study shows that the NMU model of rat breast cancer could be used to evaluate different immune based therapies as well as to study the role of IL-10 in breast cancer. Furthermore, this rat breast cancer model shows an immunohistological profile similar to that found in human cancer and the fact that it develops like spontaneously arising malignancies make it interesting as a cancer model in immunobiology.


The effects in rats and guinea pigs from six months exposures to sulfuric acid mist, ozone, and their combination.
Rats and guinea pigs were exposed to 0.5 ppm ozone, 10 mg/m3 sulfuric acid mist, or their combination for 6 hrs/day, 5 days/week for six months. Exposure-related microscopic alterations were seen in the lungs of guinea pigs exposed to ozone alone or in combination with sulfuric acid mist. No other microscopic lesions were present in either rats or guinea pigs. No biologically meaningful synergistic effects were noted in animals exposed to the combination of ozone and sulfuric mist.


Evolution of cooperation in multiplex networks through asymmetry between interaction and replacement.
Cooperation is the foundation of society and has been the subject of numerous studies over the past three decades. However, the mechanisms underlying the spread of cooperation within a group are not yet fully comprehended. We analyze cooperation in multiplex networks, a model that has recently gained attention for successfully capturing certain aspects of human social connections. Previous studies on the evolution of cooperation in multiplex networks have shown that cooperative behavior is promoted when the two key processes in evolution, interaction and strategy replacement, are performed with the same partner as much as possible, that is, symmetrically, in a variety of network structures. We focus on a particular type of symmetry, namely, symmetry in the scope of communication, to investigate whether cooperation is promoted or hindered when interactions and strategy replacements have different scopes. Through multiagent simulations, we found some cases where asymmetry can promote cooperation, contrasting with previous studies. These results hint toward the potential effectiveness of not only symmetrical but also asymmetrical approaches in fostering cooperation within particular groups under certain social conditions.


BK virus: I. Seroepidemiologic studies and serologic response to viral infection.
Sera of 656 patients in seven age groups were tested by hemagglutination=inhibition (HI) and complement=fixation (CF) tests for antibodies to BK virus. Both tests revealed that BK virus antibodies are common in the population of southern Germany, and that primary infection is apparently acquired during childhood. The highest rate of positive sera, 71% in the HI test and 56% in the CF test, was found in the 15-30 year old group. The antibody titers correlated in both serologic tests, but HI tests were more sensitive and reliable than CF tests. An indirect immunofluorescence assay for the detection of BK virus-specific IgM antibodies was also developed. Studying umbilical cord blood sera from 846 healthy donors, BK virus IgM antibodies were detected in 77 sera (9.1%).


Expression of vitamin D receptor, CYP27B1 and CYP24A1 hydroxylases and 1,25-dihydroxyvitamin D3 levels in stone formers.
The expression of vitamin D receptor (VDR) and 1,25-dihydroxyvitamin D3 [1,25(OH)D] levels exceed the values of controls in some but not all hypercalciuric stone formers (HSF). We aimed to evaluate serum 1,25(OH)D levels, the expression of VDR, CYP27B1, and CYP24A1 hydroxylases in HSF in comparison with normocalciuric stone formers (NSF) and healthy subjects (HS). Blood samples, 24-h urine collections and a 3-day dietary record were obtained from 30 participants from each of the groups. The expression of VDR, CYP27B1, and CYP24A1 was measured by flow cytometry. HSF presented significantly higher urinary volume, sodium, magnesium, oxalate, uric acid, and phosphorus than NSF and HS. Calcium intake was lower in HSF versus NSF and HS (442 ± 41 vs 594 ± 42 and 559 ± 41 mg/day, respectively, p = 0.027). Ionized calcium was significantly lower in HSF than NSF (1.29 ± 0.0 vs 1.31 ± 0.0 mmol/L, p < 0.01). Serum 1,25(OH)D was significantly higher in HSF and NSF than HS (22.5 ± 1.2; 22.2 ± 1.2 vs 17.4 ± 1.2 pg/ml, p = 0.007) but serum 25(OH)D, PTH, klotho and plasma FGF-23 did not differ between groups. VDR expression was higher in HSF and NSF than HS (80.8 ± 3.2; 78.7 ± 3.3 vs 68.6 ± 3.2%, p = 0.023). Although CYP27B1 and CYP24A1 expressions were similar among all groups, the ratio of 1,25(OH)D/CYP24A1 was higher in HSF and NSF than in HS (1.43 ± 0.25 and 0.56 ± 0.10 vs 0.34 ± 0.06, p = 0.00). Stone formers, regardless of urinary calcium excretion, had higher VDR expression and 1,25(OH)D levels than HS, even in ranges considered normal. Higher 1,25(OH)D/CYP24A1 ratio suggested a lower degradation of 1,25(OH)D by CYP24A1 in HSF and NSF.


The influence of the subjects' training state on the glycemic index.
To determine the glycemic index (GI) dependence on the training state of healthy adult males. Young, adult males of normal body mass index and normal glucose tolerance were tested twice with a 50 g reference glucose solution and twice with a breakfast cereal containing 50 g of available carbohydrates in a randomized order. Ten subjects were sedentary (SE), 12 were moderately trained (MT) and 12 were endurance trained (ET). Blood glucose, insulin and glucagon were measured. The GI differed significantly between SE and ET subjects (P=0.02, mean difference: 23 GI units, 95% CI=3-42 GI units). The GI of the MT subjects was intermediary, but did not differ significantly from the SE or ET subjects. The insulin index did not differ significantly between the groups (P=0.65). The GI of the commercially available breakfast cereal depended on the training state of the healthy males. The training state is the first reported factor influencing the GI that is subject specific rather than food specific.


Environmental Determination of Indigenous Bifidobacteria of the Human Intestine.
The environmental determination of indigenous (constantly present) bifidobacteria of the human large intestine is considered in this review. Environmental determination (from the Latin determinere, "I determine") is understood as a set of natural phenomena of a habitat (biotope) that determine the role of indigenous microorganisms in the microbiocenosis. Using the symbiotic approach, an attempt is made to identify the environmental conditions for the habitat of bifidobacteria and their physiological effects in the microsymbiocenosis. The features of indigenous bifidobacteria in terms of their nature have been established: evolutionary-genetic (phylogenetic remoteness, genome conservation, metabolic specialization), biochemical (lysozyme resistance, constitutive acetate production), and physiological (microbial "friend-foe" identification, immunoregulation), which are important in adaptation (persistence) and the provision of mutualistic effects and stability of the bifidoflora in the population.


Corticotropin-releasing factor and forskolin increase proopiomelanocortin messenger RNA levels in rat anterior and intermediate cells in vitro.
The effect of ovine corticotropin-releasing factor (CRF) on messenger ribonucleic acid (mRNA) level encoding proopiomelanocortin (POMC) was studied in serum-free primary cultures of intermediate (IL) and anterior lobe (AL) cells of rat pituitary. Levels of POMC mRNA were quantitated by hybridization to a 32P-labeled, single-stranded POMC complementary deoxyribonucleic acid (cDNA) probe. This effect was time dependent and after 48 h of treatment, POMC mRNA levels in IL cells and AL corticotrophs were increased by 116 +/- 9% and 118 +/- 2% of control values, respectively. Forskolin (1 microM) induced a similar increase in POMC mRNA in both pituitary cell types. These data suggest that CRF might stimulate the gene expression of POMC in pituitary melanotrope and corticotrope cells. Moreover, our findings are consistent with the role of cAMP as a second messenger for CRF in IL and AL corticotrophic cells.


An in silico approach for screening flavonoids as P-glycoprotein inhibitors based on a Bayesian-regularized neural network.
P-glycoprotein (P-gp), an ATP-binding cassette (ABC) transporter, functions as a biological barrier by extruding cytotoxic agents out of cells, resulting in an obstacle in chemotherapeutic treatment of cancer. In order to aid in the development of potential P-gp inhibitors, we constructed a quantitative structure-activity relationship (QSAR) model of flavonoids as P-gp inhibitors based on Bayesian-regularized neural network (BRNN). A dataset of 57 flavonoids collected from a literature binding to the C-terminal nucleotide-binding domain of mouse P-gp was compiled. The predictive ability of the model was assessed using a test set that was independent of the training set, which showed a standard error of prediction of 0.146+/-0.006 (data scaled from 0 to 1). Meanwhile, two other mathematical tools, back-propagation neural network (BPNN) and partial least squares (PLS) were also attempted to build QSAR models. The BRNN provided slightly better results for the test set compared to BPNN, but the difference was not significant according to F-statistic at p=0.05. The PLS failed to build a reliable model in the present study. Our study indicates that the BRNN-based in silico model has good potential in facilitating the prediction of P-gp flavonoid inhibitors and might be applied in further drug design.


Concept and development of a discharge alert filter for abnormal laboratory values coupled with computerized provider order entry: a tool for quality improvement and hospital risk management.
To develop a clinical decision support system activated at the time of discharge to reduce potentially inappropriate discharges from unidentified or unaddressed abnormal laboratory values. We identified 106 laboratory tests for possible inclusion in the discharge alert filter. We selected 7 labs as widely available, commonly obtained, and associated with high risk for potential morbidity or mortality within abnormal ranges. We identified trigger thresholds at levels that would capture significant laboratory abnormalities while avoiding excessive flag generation because of laboratory results that minimally deviate outside the normal reference range. We selected sodium (>155 or <125 mmol/L), potassium (<2.5 or >6 mEq/dL) phosphorous (<1.6 mg/dL), magnesium (<1.2 mg/dL), creatinine greater than 1.1 with a rise of 20% or more between the 2 most recent results, white blood cell count (>11,000 cells/mm with a rise of 20% or more between the 2 most recent results), and international normalized ratio greater than 4. A discharge alert filter that reliably and effectively identifies patients that may be discharged in unsafe situations because of unaddressed critical laboratory values can improve patient safety at discharge and potentially reduce the incidence of costly litigation. Further research is needed to validate whether the proposed discharge alert filter is effective at improving patient safety at discharge.


Characterization of cancer stem cell properties of CD24 and CD26-positive human malignant mesothelioma cells.
Malignant mesothelioma (MM) is an asbestos-related malignancy characterized by rapid growth and poor prognosis. In our previous study, we have demonstrated that several cancer stem cell (CSC) markers correlated with CSC properties in MM cells. Among these markers, we focused on two: CD24, the common CSC marker, and CD26, the additional CSC marker. We further analyzed the CSC properties of CD24 and CD26-positve MM cells. We established RNAi-knockdown cells and found that these markers were significantly correlated with chemoresistance, proliferation, and invasion potentials in vitro. Interestingly, while Meso-1 cells expressed both CD24 and CD26, the presence of each of these two markers was correlated with different CSC property. In addition, downstream signaling of these markers was explored by microarray analysis, which revealed that their expressions were correlated with several cancer-related genes. Furthermore, phosphorylation of ERK by EGF stimulation was significantly affected by the expression of CD26, but not CD24. These results suggest that CD24 and CD26 differentially regulate the CSC potentials of MM and could be promising targets for CSC-oriented therapy.


Multi-scale analysis of nickel ion tolerance mechanism for thermophilic Sulfobacillus thermosulfidooxidans in bioleaching.
Bioleaching is intensively investigated for recovering valuable metals such as Li, Co, Ni and Cu. Nickel ion stress threatens the health of microorganisms when Ni2+ starts to accumulate in the leachate during the bioleaching of materials that are rich in Ni, such as spent lithium-ion batteries. The possible mechanisms underlying the response of S. thermosulfidooxidans to nickel ion stress were analyzed using a multi-scale approach. Under the condition of nickel ion stress, high concentrations of nickel ions were immobilized by extracellular polymeric substances, while concentrations of nickel ions inside the cells remained low. The intracellular adenosine triphosphate (ATP) concentration and H+-ATPase activity increased to maintain normal cell growth and metabolic activities. Scavenging abilities of S. thermosulfidooxidans for hydrogen peroxide and superoxide anion were enhanced to reduce oxidative damage induced by nickel ion stress. There were 734 differentially expressed genes identified by RNA-seq under nickel ion stress. Most of them were involved in oxidative phosphorylation, glutathione metabolism and genetic information processing, responsible for intracellular energy utilization, intracellular antioxidant capacity and DNA damage repair, respectively. The results of this study are of major significance for in-depth understanding of the mechanisms of acidophilic microorganisms' resistance to metal ions.


Improved recombinant LC16m0 or LC16m8 vaccinia virus successfully expressing hepatitis B surface antigen.
An attempt was made to develop a safe, efficacious live recombinant vaccine using low neurovirulent strains of vaccinia virus: LC16m0 (m0) or LC16m8 (m8). Recombinant vaccinia virus (RVV) was constructed by inserting the hepatitis B surface antigen (HBsAg) gene fused to a 7.5 kDa protein promoter (7.5 kDa promoter) within the vaccinia virus thymidine kinase (TK) gene using the m0 or m8 strain as vectors. These RVVs expressed significant amounts of HBsAg (1.1 microgram/2 X 10(5) cells) consisting of 24.5 and 28 kDa (glycosylated) proteins. HBsAg produced by RVV (vaccinia HBsAg) had physical properties very similar to plasma-derived HBsAg. Considering the safety of RVVs from m0 or m8 that have been constructed with HBsAg without the addition of a promoter and the high induction of anti-HBs antibody with RVV from m0 strain in rabbits, the RVVs constructed in the present study are likely to form the basis of a safe live RVV vaccine for hepatitis B virus (HBV).


Recurrent initiation: a mechanism for triggering p53 pulses in response to DNA damage.
DNA damage initiates a series of p53 pulses. Although much is known about the interactions surrounding p53, little is known about which interactions contribute to p53's dynamical behavior. The simplest explanation is that these pulses are oscillations intrinsic to the p53/Mdm2 negative feedback loop. Here we present evidence that this simple mechanism is insufficient to explain p53 pulses; we show that p53 pulses are externally driven by pulses in the upstream signaling kinases, ATM and Chk2, and that the negative feedback between p53 and ATM, via Wip1, is essential for maintaining the uniform shape of p53 pulses. We propose that p53 pulses result from repeated initiation by ATM, which is reactivated by persistent DNA damage. Our study emphasizes the importance of collecting quantitative dynamic information at high temporal resolution for understanding the regulation of signaling pathways and opens new ways to manipulate p53 pulses to ask questions about their function in response to DNA damage.


Coupling and robustness of intra-cortical vascular territories.
Vascular domains have been described as being coupled to neuronal functional units enabling dynamic blood supply to the cerebral cyto-architecture. Recent experiments have shown that penetrating arterioles of the grey matter are the building blocks for such units. Nevertheless, vascular territories are still poorly known, as the collection and analysis of large three-dimensional micro-vascular networks are difficult. By using an exhaustive reconstruction of the micro-vascular network in an 18 mm(3) volume of marmoset cerebral cortex, we numerically computed the blood flow in each blood vessel. We thus defined arterial and venular territories and examined their overlap. A large part of the intracortical vascular network was found to be supplied by several arteries and drained by several venules. We quantified this multiple potential to compensate for deficiencies by introducing a new robustness parameter. Robustness proved to be positively correlated with cortical depth and a systematic investigation of coupling maps indicated local patterns of overlap between neighbouring arteries and neighbouring venules. However, arterio-venular coupling did not have a spatial pattern of overlap but showed locally preferential functional coupling, especially of one artery with two venules, supporting the notion of vascular units. We concluded that intra-cortical perfusion in the primate was characterised by both very narrow functional beds and a large capacity for compensatory redistribution, far beyond the nearest neighbour collaterals.


Baby Doe decisions: a hospital manager's perspective.
Profound changes have taken place in the treatment of seriously handicapped infants in hospitals. These changes are examined from the perspective of the hospital manager, looking at hospitals' response to the new challenges of handling "Baby Doe" types of cases, including the formation of Infant Care Review Committees in many hospitals.


Modern surgical therapy: limb salvage and the role of amputation for extremity soft-tissue sarcomas.
Historically the surgical management of extremity soft-tissue sarcomas (ESTS) commonly involved amputation. Nowadays limb-sparing, function-preserving surgery is the standard of care for ESTS. Adjuvant therapies such as radiation therapy and chemotherapy are used selectively in an effort to minimize both local recurrence and distant spread. Less common modalities, such as isolated limb perfusion, isolated limb infusion, and hyperthermia are being evaluated to potentially expand the cohort of individuals who may be eligible for limb-sparing surgery and to improve outcomes. This article reviews the standard and evolving approaches to the management of ESTS.


The complete mitochondrial genome of a stonefly species, Kamimuria chungnanshana Wu, 1948 (Plecoptera: Perlidae).
This study determined the complete mitochondrial (mt) genome of the stonefly, Kamimuria chungnanshana Wu, 1948. The mt genome is 15, 943 bp in size and contains 37 canonical genes which include 22 transfer RNA genes, 13 protein-coding genes, and two ribosomal RNA genes, the control region is 1062 bp in length. The phylogenetic tree shows that Kamimuria chungnanshana is sister group of Kamimuria wangi.


Prevalence of canine coronavirus (CCoV) in dog in Japan: detection of CCoV RNA and retrospective serological analysis.
We collected rectal swabs from dogs in Japan during 2011 to 2014, and canine coronavirus (CCoV) nucleocapsid gene was detected by RT-PCR. The relationship between CCoV infection and the manifestation of diarrhea symptoms was investigated, and a correlation was noted (df=1, χ(2)=8.90, P<0.005). The types of CCoV detected in samples from CCoV-infected dogs were CCoV-I in 88.9% and CCoV-II in 7.4%, respectively. We retrospectively investigated the seroprevalence of CCoV-I in dogs in Japan during 1998 to 2006. The sera were tested with a neutralizing antibody test. In the absence of CCoV-I laboratory strain, we used feline coronavirus (FCoV)-I that shares high sequence homology in the S protein with CCoV-I. 77.7% of the sera were positive for neutralizing anti-FCoV-I antibodies.


The stress-response dampening hypothesis: how self-esteem and stress act as mechanisms between negative parental bonds and alcohol-related problems in emerging adulthood.
The stress dampening model (Marlatt, 1987; Sayette, 1993; Sher, 1987) suggests certain individuals may use alcohol to escape from their negative life experiences. Pathological reasons for drinking (e.g., using alcohol as a means to cope) reflect the degree to which individuals are motivated to use alcohol in order to dampen or alleviate the stress they are experiencing (Johnson, Schwitters, Wilson, Nagoshi, & McClearn, 1985). Direct and mediational links among parental bonds (rejection, care, overprotection, autonomy, and neglect), self-esteem, stress, pathological reasons for drinking, and alcohol-related problems were explored. A Structural Equation Model with (405 students; 164 women, 241 men) college students was examined. Three path mediational analyses revealed several mediated pathways. Greater feelings of perceived father/mother neglectfulness (i.e., offspring feeling parents do not show up for them) were indirectly linked to more alcohol-related problems (e.g., indicative of alcohol use or dependence in emerging adulthood) through increased stress and pathological reasons for drinking. Furthermore, higher levels of father rejection (i.e., perception of feeling unwanted) were indirectly linked to more pathological reasons for drinking through low self-esteem and increased stress. However, greater feelings of mother care (affectionate and attentive) were indirectly linked to fewer pathological reasons for drinking through higher self-esteem and lower levels of stress. Moreover, high self-esteem was found to be indirectly linked to fewer alcohol-related problems through decreased stress and pathological reasons for drinking. These findings suggest several specific pathways for using alcohol to self-medicate (i.e., consume alcohol for a specific purpose) or dampen feelings of stress.


Requirement of β1 integrin for endothelium-dependent vasodilation and collateral formation in hindlimb ischemia.
An acute increase in blood flow triggers flow-mediated dilation (FMD), which is mainly mediated by endothelial nitric oxide synthase (eNOS). A long-term increase in blood flow chronically enlarges the arterial lumen, a process called arteriogenesis. In several common human diseases, these processes are disrupted for as yet unknown reasons. Here, we asked whether β1 integrin, a mechanosensory protein in endothelial cells, is required for FMD and arteriogenesis in the ischemic hindlimb. Permanent ligation of the femoral artery in C57BL/6 J mice enlarged pre-existing collateral arteries and increased numbers of arterioles in the thigh. In the lower leg, the numbers of capillaries increased. Notably, injection of β1 integrin-blocking antibody or tamoxifen-induced endothelial cell-specific deletion of the gene for β1 integrin (Itgb1) inhibited both arteriogenesis and angiogenesis. Using high frequency ultrasound, we demonstrated that β1 integrin-blocking antibody or endothelial cell-specific depletion of β1 integrin attenuated FMD of the femoral artery, and blocking of β1 integrin function did not further decrease FMD in eNOS-deficient mice. Our data suggest that endothelial β1 integrin is required for both acute and chronic widening of the arterial lumen in response to hindlimb ischemia, potentially via functional interaction with eNOS.


B cell activation and adjuvant activities of chemically synthesized analogues of the nonreducing sugar moiety of lipid A.
Immunological activities of synthetic lipid A analogues (derivatives of 3-O-tetradecanoyl D-glucosamine) were investigated. Compounds possessing a N-tetradecanoyloxytetradecanoyl group with or without a 4-O-phosphoryl group exhibited both mitogenic and polyclonal B cell activating activities. Among these, the phosphorylated compound exhibited strong activity. 4-O-phosphorylated analogues with a N-tetradecanoyl group or 6-O-tetradecanoyl group in addition to N-3-hydroxyacyl groups showed no activity. All the analogues tested showed adjuvant activity, which was determined by augmentation of IgM antibody response against sheep erythrocytes. Relationship between chemical structure and biological activities is also discussed.


Long-term follow-up of arrhythmias in pediatric orthotopic heart transplant recipients: incidence and correlation with rejection.
Arrhythmias in adult orthotopic heart transplant (OHT) recipients are common and have been used as predictors of rejection. Because of the paucity of information in pediatric OHT recipients, the purpose of this study was to determine the incidence and correlation of arrhythmias with rejection or with coronary artery disease (CAD) in children. We retrospectively reviewed the records, electrocardiograms (ECGs), and 24-hour ambulatory ECGs of patients who underwent OHT from January 1984 to December 1999. We excluded arrhythmias occurring in the first 2 weeks after OHT. Sixty-nine patients underwent OHT, received triple-immunosuppression therapy, were discharged home, and have been followed for a mean of 4.7 years (0.3-13 years). Each patient had an average of 10 ECGs and three 24-hour ECGs. Twenty-six patients had 33 arrhythmias: sinus bradycardia (n = 9), atrial tachycardia (n = 9), ventricular tachycardia (n = 3), and Wenckebach periodicity (n = 6). Sinus bradycardia was treated with theophylline in 8 patients, and 2 required pacemakers. Atrial tachycardias (atrial flutter in 4 patients and atrial ectopic tachycardia in 5) were treated with digoxin, propranolol, or procainamide. Ventricular tachycardia was treated with mexiletine, lidocaine, and amiodarone. There were 65 episodes of rejection, 20 of which were moderate/severe (> or =3B). Only Wenckebach was associated with the presence of either rejection or CAD (p < 0.05). We noted clinically significant arrhythmias in 38% of the pediatric OHT recipients. Sinus bradycardia, atrial tachyarrhythmias, and ventricular tachycardia occurred with the same frequency. Only new-onset Wenckebach periodicity was noted in the presence of either CAD or rejection. No arrhythmia was of negative predictive value for rejection or CAD. From this data, we suggest that new-onset Wenckebach prompt evaluation for rejection or CAD.


Changes in upper intestinal epithelial morphology and kinetics in the growing guinea pig.
Weaning, the process of intestinal adaptation from milk to solid diet, demands changes in gastrointestinal function. We aimed to measure upper intestinal mucosal morphology and cytokinetics during early life, to determine whether the marked changes seen at weaning in altricial species, such as rat and mouse also occur in the precocial guinea pig. A total of 79 animals was studied. Jejunal morphology was measured by microdissection and crypt cell production rate by a metaphase arrest technique in animals at 1, 7, 14, 21, and 28 days after birth. There was a 40% decline in villus height from 986 to 576 microns during the first 2 wk (p less than 0.001). Crypt depth increased by 25% from 148 to 199 microns (p less than 0.01). After an initial decline there was a significant increase in crypt:villus ratio from 6.7 to 8.2 (p less than 0.001), in crypt cell production rate from 3.9 to 5.6 cells/crypt/h (p less than 0.001), and net villus influx from 26.1 to 45.9 cells/villus/h (p less than 0.001) from 14 days onward. These proliferative changes were accounted for by an increase in the depth and number of crypts, and in crypt cell production rate, leading to an increase in net villus influx. In contrast with the rat and mouse they were gradual, occurred largely during the 3rd wk, and appeared to follow the cessation of breast feeding and commencement of solid food. It is suggested that the functional changes in the small intestine that occur during weaning in the guinea pig are neither due to rapid proliferation of a new epithelial cell population, nor precipitated by change in diet.


Cigarette smoke inhibits dynamic ciliary beat frequency in pediatric adenoid explants.
Environmental tobacco smoke exposure in children increases the incidence of upper respiratory infections, chronic sinusitis, and chronic otitis media. This study investigated the effects of ex vivo and in vitro smoke exposure on dynamic ciliary beat frequency (CBF) in pediatric adenoid explants. Blinded and controlled prospective study. Tertiary care pediatric hospital. Fifty-five children undergoing adenoidectomy for obstructive sleep apnea and adenotonsillar hypertrophy were enrolled in this study. Adenoids were surgically removed using currettage. Hair was collected for nicotine analysis. Tissue was sectioned into 1-mm strips and allowed to equilibrate in DMEM/F12 with 2% fetal bovine serum for 24 hours. Cilia-bearing explant tissues were treated with either DMEM/F12 media, 5% cigarette smoke extract (CSE), or 10% CSE for 24 hours. Cilia were then stimulated using either isoproterenol (10(-9) M) or methacholine (10(-6)M), and CBF was serially recorded using the Sisson-Ammons Video Analysis (SAVA) software. Children with hair nicotine levels ≥ 1 ng/mg consistent with secondhand smoke exposure display blunted dynamic CBF response ex vivo. Explants incubated with CSE in vitro demonstrate significant impairment of isoproterenol and methacholine-induced CBF. CBF of adenoid explants increases when stimulated with isoproterenol and methacholine. Ex vivo and in vitro smoke exposure blunted ciliostimulation of CBF in adenoid explants. Smoke exposure impairs ciliary function in the pediatric airway and could potentially contribute to disorders such as chronic rhinosinusitis and chronic otitis media.


Secretion pathway for the poly(3-hydroxybutyrate) depolymerase in Ralstonia pickettii T1.
The extracellular poly(3-hydroxybutyrate) depolymerase from Ralstonia pickettii T1 has been purified, its function and character investigated in detail, and its gene cloned and sequenced. However, the mechanism by which this enzyme is secreted has not been elucidated. A mutant unable to degrade poly(3-hydroxybutyrate), N17, was obtained with the random insertion of a mini-transposon, Tn5. Western analysis using antiserum against the poly(3-hydroxybutyrate) depolymerase of Ralstonia pickettii T1, revealed that N17 accumulated the poly(3-hydroxybutyrate) depolymerase in the periplasm and cytoplasm, and did not secrete the enzyme into the external medium. It was also found that 3-hydroxybutyrate-oligomer hydrolase was secreted but inactive. The disrupted gene in N17, depO, was analyzed by Southern hybridization and its nucleotide sequence was determined. One complete open reading frame was found in the cloned 2.3-kbp DNA fragment. From a BLAST search, this gene product was found to be homologous to PulO of Ralstonia eutropha JMP134 (60% identity) and XcpA of Pseudomonas aeruginosa (60% identity). These proteins are prepilin peptidase/N-metyltransferases, a component of the Type II secretion pathway. DepO also had the four cysteines highly conserved in most prepilin peptidases at the same positions. The transcript of depO was examined by Northern hybridization using depO as a probe. In the total RNA of Ralstonia pickettii T1 in the early stationary phase, a band at 2.6-kb was detected, suggesting depO to be a functional gene. In this study, it was found that poly(3-hydroxybutyrate) depolymerase was secreted by the Type II pathway.


[The mechanism of gefitinib resistance induced by hepatocyte growth factor in sensitive non-small cell lung cancer cells in vitro].
Previous studies have reported that Met might be related to gefitinib resistance in non-small cell lung cancer (NSCLC). The present study aims to explore the mechanism of hepatocyte growth factor (HGF)-induced gefitinib resistance in different gene types of sensitive NSCLC in vitro. The PC-9 and H292 cell lines were chosen and induced by HGF. The cell survival was measured using MTT assay, the cell cycle distribution was measured using PI assay, and cell apoptosis with an Annexin V-PE assay, respectively. The c-Met and p-Met protein expression was determined via Western blot analysis. Gefitinib inhibited the growth of PC-9 and H292 cells in a dose-dependent manner. The concentration-survival curves of both cell lines shifted to the right when induced with HGF. HGF did not affect PC-9 and H292 cell proliferation. The cell also had a higher cell survival rate when treated with HGF and gefitinib compared with that under gefitinib alone (P<0.05). The apoptotic rate and cell cycle progression showed no significant difference between the HG and G group (P>0.05). HGF stimulated Met phosphorylation in the PC-9 and H292 cells. Gefitinib inhibited the HGF-induced Met phosphorylation in PC-9 cells, but not in H292 cells. HGF induces gefitinib resistance in PC-9 and H292 cells. HGF-induced Met phosphorylation may be an important mechanism of gefitinib resistance in sensitive NSCLC.


Surgical management of peripheral artery pseudoaneurysm following orthopedic trauma: a report of 14 cases.
Purpose of this study was to report the etiology, diagnosis, surgical management, and outcome of pseudoaneurysm associated with orthopedic trauma. A retrospective review was conducted of all patients presenting to a Level 1 trauma center between 2013 and 2019. Clinical records were reviewed for the mechanism of primary injury, associated fracture pattern, time of presentation, site of involvement, etiology of the pseudoaneurysm, diagnosis, management, and complications. We identified 14 patients with pseudoaneurysm of peripheral arteries following orthopedic trauma. The mean interval between primary injury and the manifestation of clinical symptoms was 88.5 days (range, 16-304 days). There were 3 upper limb injuries and 11 lower limb injuries. The presenting symptoms were pain associated with excessive extremity swelling in most of the patients. A significant drop in hemoglobin (mean fall- 2.9 g/dL) was noted in nine patients. Most common artery involved was the superficial branch of femoral artery and posterior tibial artery followed by the brachial artery. Fractured bone spike was the cause of injury in eight patients and iatrogenic injury in six patients. Diagnosis was confirmed by CT angiography with duplex scan in eight patients, duplex scan alone in one patient, MRI along with duplex scan in one patient. The remaining four patients were diagnosed intraoperatively. Excision of the pseudoaneurysm and ligation of the involved minor arteries was done in eight patients. Surgical repair of the major artery with critical vascular injury was done in six patients. One patient underwent secondary amputation following the anastomotic blowout. Early diagnosis of pseudoaneurysm requires knowledge and a high index of suspicion. Surgical reconstruction of major arteries should always be done and ligation of major vessels can lead to catastrophes. Excision of pseudoaneurysm can be done when minor arteries are involved with the presence of good collateral circulation. Level IV Study.


Request of acute phase markers in primary care in Spain.
To study the inter-practice variability in Spain--by institution, management, and regional characteristics--of the frequency and appropriateness of test requests made by primary care practitioners for acute phase markers. Observational cross-sectional study. One hundred forty-one clinical laboratories were invited to participate by providing the number of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complete blood count (CBC) tests requested by general practitioners. We calculated the ratio of test requests per 1000 inhabitants, ratios of related test requests, and variability index (90th percentile/10th percentile). We compared the results among the different areas according to their setting, location, and management. We recruited 64 laboratories (14,846,065 inhabitants). There were almost twice as many ESR requests as CRP requests; the variability index for ESR was almost double that of CRP. Furthermore, the latter was underrequested in rural-urban areas compared with rural. The ESR/CBC and ESR/CRP ratios are lower in institutions with private management, and the number of ESR requested in institutions with private management are lower than that of public. The differences among Spanish regions were reported for ESR per 1000 inhabitants, ESR/CBC, and ESR/CRP. There was significant variability in the requests made by primary care practitioners for patients' acute phase markers. Rates were influenced by geographic location, hospital setting, and institution management. ESR was inappropriately overrequested; strong efforts should be made to adjust the requests of ESR and to standardize the use of CRP measurement.


Establishing regional specificity of neuroestrogen action.
The specificity of estrogen signaling in brain is defined at one level by the types and distributions of receptor molecules that are activated by estrogens. At another level, as our understanding of the neurobiology of the estrogen synthetic enzyme aromatase has grown, questions have emerged as to how neuroactive estrogens reach specific target receptors in functionally relevant concentrations. Here we explore the spatial specificity of neuroestrogen signaling with a focus on studies of songbirds to provide perspective on some as-yet unresolved questions. Studies conducted in both male and female songbirds have helped to clarify these interesting facets of neuroestrogen physiology.


Does exercise augment operant and Pavlovian extinction: A meta-analysis.
Exposure therapy, a behavioral approach to reduce symptomology in fear, anxiety, and drug-related psychiatric disorders, is based on learning and memory principles of extinction, and is subject to relapse. As such, it is important to find ways to enhance outcomes. One such way is through exercise. Identify if exercise augments extinction behavior, and whether this depends on the experimental paradigm used (i.e. operant or Pavlovian) and/or stimulus (i.e. appetitive or aversive). Additionally, determine which moderating variables influence the effects of exercise on extinction learning. A literature search was conducted and a Hedges' g calculation was employed to conduct a meta-analysis (metaSEM) using a structural equation modeling approach. This approach was chosen because of its ability to account for dependencies in effect sizes. We found a significant effect of exercise as an augmentation over extinction alone (g = 0.37, p < 0.001), with extinction paradigm (but not stimulus) producing a moderating effect (B = 0.43, p = 0.030). Data were then split by extinction paradigm, with operant extinction models having a significant effect (g = 0.55, p < 0.001), and number of extinction sessions moderating aggregate effects. Pavlovian models did not have significant overall effects (g = 0.11, p = 0.3976), but were moderated by the number of animals housed together and exercise after extinction. The effects of exercise on extinction learning are differentially modulated by the type of paradigm used, the number of extinction sessions, the timing of when exercise treatment was applied (after extinction), and the housing conditions.


Temperature and Humidity Effects on Hospital Morbidity in Darwin, Australia.
Many studies have explored the relationship between temperature and health in the context of a changing climate, but few have considered the effects of humidity, particularly in tropical locations, on human health and well-being. To investigate this potential relationship, this study assessed the main and interacting effects of daily temperature and humidity on hospital admission rates for selected heat-relevant diagnoses in Darwin, Australia. Univariate and bivariate Poisson generalized linear models were used to find statistically significant predictors and the admission rates within bins of predictors were compared to explore nonlinear effects. The analysis indicated that nighttime humidity was the most statistically significant predictor (P < 0.001), followed by daytime temperature and average daily humidity (P < 0.05). There was no evidence of a significant interaction between them or other predictors. The nighttime humidity effect appeared to be strongly nonlinear: Hot days appeared to have higher admission rates when they were preceded by high nighttime humidity. From this analysis, we suggest that heat-health policies in tropical regions similar to Darwin need to accommodate the effects of temperature and humidity at different times of day.


Understanding drugs and diseases by systems biology?
Systems biology aims to provide a holistic and in many cases dynamic picture of biological function and malfunction, in case of disease. Technology developments in the generation of genome-wide datasets and massive improvements in computer power now allow to obtain new insights into complex biological networks and to copy nature by computing these interactions and their kinetics and by generating in silico models of cells, tissues and organs. The expectations are high that systems biology will pave the way to the identification of novel disease genes, to the selection of successful drug candidates--that do not fail in clinical studies due to toxicity or lack of human efficacy--and finally to a more successful discovery of novel therapeutics. However, further research is necessary to fully unleash the potential of systems biology. Within this review we aim to highlight the most important and promising top-down and bottom-up systems biology applications in drug discovery.


A novel immunochemotherapy based on immunogenicity-activated and immunosuppression-reversed biomimetic nanoparticles.
Studies show that infiltrated myeloid-derived suppressor cells (MDSCs) are vital in the immunosuppressive tumor microenvironment and account for lymphoma refractoriness and recurrence. Here, we developed a biomimetic nanoplatform (PM-PLGA-DOX/GEM) in which platelet membranes (PM) wrap PLGA nanoparticles co-loaded with doxorubicin (DOX) and gemcitabine (GEM). PM-PLGA-DOX/GEM would accumulate in tumor tissues because of the enhanced permeation and retention (EPR) effect and the tumor cell-induced platelet aggregation (TCIPA) effect. GEM could eliminate the MDSCs in tumor tissues, thereby reversing the immunosuppressive tumor microenvironment. Furthermore, DOX could invoke the immunogenic cell death (ICD) of lymphoma cells. Consequently, numerous T cells were recruited and activated to improve the therapeutic effects. This study will offer a potential platform for clinical treatment of lymphoma and other solid tumors.


Solvolysis of the Tumor-Inhibiting Ru(III)-Complex trans-Tetrachlorobis(Indazole)Ruthenate(III).
The ruthenium(III) complex Hlnd trans-[RuCl(4),(ind)(2)], with two trans-standing indazole (ind) ligands bound to ruthenium via nitrogen, shows remarkable activity in different tumor models in vitro and in vivo. The solvolysis of the complex trans-[RuCl(4),(ind)(2)](-) has been investigated by means of spectroscopic techniques (UV/vis, NMR)in different solvents. We investigated the indazolium as well as the sodium salt, the latter showing improved solubility in water. In aqueous acetonitrile and ethanol the solvolysis results in one main solvento complex. The hydrolysis of the complex is more complicated and depends on the pH of the solution as well as on the buffer system.


Construction and evaluation of intrauterine adhesion model in rats by different methods of mechanical injury.
The study aimed to establish a stable and effective animal model for the experimental study of intrauterine adhesion (IUA) by evaluating various mechanical injury methods. A total of 140 female rats were divided into four groups according to the extent and area of endometrial injury: group A (excision area: 2.0 × 0.5 cm2), group B (excision area: 2.0 × 0.25 cm2), group C (endometrial curettage) and group D (sham operation). On the 3rd, 7th, 15th and 30th day after the operation, the tissue samples of each group were collected, and the uterine cavity stenosis and histological changes were recorded by HE and Masson staining. Immunohistochemistry of CD31 was applied to visualize microvessel density (MVD). The pregnancy rate and the number of gestational sacs were used to evaluate the reproductive outcome. The results showed that endometrium injured by small-area endometrial excision or simple curettage could be repaired. The ratio of fibrosis in groups A and B was higher than that in groups C and group D 30 days after modeling (P < 0.001). The number of endometrial glands and MVD in group A was significantly lower than those in groups B, C and D (P < 0.05). The pregnancy rate in group A was 20%, which was lower than that in groups B (33.3%), C (89%) and D (100%) (P < 0.05). Full-thickness endometrial excision has a high rate of success in constructing stable and effective IUA models in rats.


Acoustic impedance matching of medical ultrasound transducers.
Ultrasonic transducers for pulse-echo systems are studied both theoretically and experimentally. For the theoretical calculations the Mason model for thickness-mode disc transducers with and without backing and matching layers is used. By building several of the theoretically investigated transducer configurations it is shown that theory and experiment agree well. Thus the properties of a transducer can be predicted to a good approximation before its experimental realization. To find transducers with good sensitivity and short pulses, the pulse shape and frequency response for the following classes of transducers were studied both theoretically and experimentally: transducers with backing only, transducers with heavy backing and front matching layers, and air-backed transducers with front matching layers.


Reproductive outcome after early pregnancy loss treated with misoprostol versus surgical aspiration.
Does long-term reproductive outcome after early pregnancy loss (EPL) differ between women who are treated with misoprostol and surgical aspiration. A historic cohort study of all women who were diagnosed with early pregnancy loss (≤12 weeks), in a single medical centre, between September 2016 and August 2017, was conducted. The women were treated with either misoprostol or surgical aspiration according to their own preferences. Women who were lost to follow-up or did not attempt to conceive again were excluded. The primary outcome measure was the cumulative pregnancy rate within 12 months from intervention. Baseline characteristics were comparable between women who received misoprostol (n = 163) and women who underwent surgical aspiration (n = 122). Women who received misoprostol had a higher rate of interventions for retained products of conception (11.0% versus 3.3%, respectively; P = 0.015). The misoprostol and the surgical aspiration groups did not differ in rate of repeated miscarriages (17.8% versus 21.3%, respectively; P = 0.45), or pregnancy rate within 6 months (58.3% versus 50.0%, respectively; P = 0.16), 12 months (78.5% versus 78.7%, respectively; P = 0.97) and 24 months (92.0% versus 91.8%, respectively; P = 0.94). Live birth rate within 24 months was comparable (62.0% versus 58.2%, respectively; P = 0.52), as well as gestational age at birth (38.5 versus 38.6 weeks, respectively; P = 0.81) and birthweight (3295 versus 3161 g, respectively; P = 0.07). Long-term reproductive outcomes are comparable in women with EPL who are treated with either misoprostol or surgical aspiration. Our findings may help counselling patients facing EPL who have concerns about their future reproduction.


Plasmophore sensitized imaging of ammonia release from biological tissues using optodes.
A plasmophore sensitized optode was developed for imaging ammonia (NH(3)) concentrations in muscle tissues. The developed ammonia sensor and an equivalent non plasmophore version of the sensor were tested side by side to compare their limit of detection, dynamic range, reversibility and overall imaging quality. Bio-degradation patterns of ammonia release from lean porcine skeletal muscle were studied over a period of 11 days. We demonstrate that ammonia concentrations ranging from 10nM can be quantified reversibly with an optical resolution of 127 μm in a sample area of 25 mm × 35 mm. The plasmophore ammonia optode showed improved reversibility, less false pixels and a 2 nM ammonia detection limit compared to 200 nM for the non-plasmophore sensor. Main principles of the sensing mechanism include ammonia transfer over a gas permeable film, ammonia protonation, nonactin facilitated merocyanine-ammonium coextraction and plasmophore enhancement. The vast signal improvement is suggested to rely on solvatochroism, nanoparticle scattering and plasmonic interactions that are utilized constructively in a fluorescence ratio. In addition to fundamental medicinal and biological research applications in tissue physiology, reversible ammonia quantification will be possible for a majority of demanding imaging and non imaging applications such as monitoring of low ammonia background concentrations in air and non-invasive medicinal diagnosis through medical breath or saliva analysis. The nanoparticle doped sensor constitutes a highly competitive technique for ammonia sensing in complex matrixes and the general sensing scheme offers new possibilities for the development of artificial optical noses and tongues.


Artificial cells: prospects for biotechnology.
A variety of techniques can now be used to alter the genome of a cell. Although these techniques are very powerful, they have limitations related to cost and efficiency of scale. Artificial cells designed for specific applications combine properties of biological systems such as nanoscale efficiency, self-organization and adaptability at relatively low cost. Individual components needed for such structures have already been developed, and now the main challenge is to integrate them in functional microscopic compartments. It will then become possible to design and construct communities of artificial cells that can perform different tasks related to therapeutic and diagnostic applications.


Effect of Transfer Energy Capacitive and Resistive Therapy on Shoulder Pain, Disability, and Range of Motion in Patients With Adhesive Capsulitis: A Study Protocol for a Randomized Controlled Trial.
We describe a protocol to evaluate the effectiveness of transfer energy capacitive and resistive (TECAR) therapy on shoulder passive range of motion, shoulder pain, and disability index in patients with adhesive capsulitis. This study will be a double-blinded randomized clinical trial with a 1-month follow-up. For the purpose of this research, 30 patients with a 3-month history of shoulder pain and disability diagnosed as adhesive capsulitis will be selected and then randomized into 2 groups, including conventional physiotherapy consisting of electrophysical modalities and therapeutic exercises, which will be given to the control group. In the intervention group, after conventional physiotherapy, 10 minutes of TECAR therapy in resistive mode will be applied on both the anterior and inferior aspects of the shoulder joint. Outcome measures will be related to shoulder passive range of abduction, flexion, and external rotation that will be measured using a digital inclinometer, as well as shoulder pain and disability index that will be assessed by the validated questionnaire. Assessment will be done at baseline, 1 day after the intervention, and by passing 1 month. The statistical analysis will describe within-group and between-group comparisons; the findings will be illustrated in tables and charts. Given the reason that the effectiveness of TECAR therapy has not been widely evaluated in adhesive capsulitis, the findings of this pilot study would provide baseline information on the effectiveness and complications of this treatment method and possibly propose a more appropriate protocol for patients with adhesive capsulitis.


A DNA sequence which shows genomic variation in a, alpha and HO strains of Saccharomyces cerevisiae.
HindIII digested DNA from various mutant strains of Saccharomyces cerevisiae probed with a 340 bp nucleotide sequence in M13mp8 derived from a mouse liver cDNA clone p1581 showed strong hybridization to a 4.1 kb DNA fragment class. This was limited to the DNA of cells of alpha mating type but the fragments concerned apparently do not originate from chromosome III. The pattern of hybridization was modified in strains carrying the HO gene consistent with there being extra copies of the Bkm-homologous sequence in these cells. Northern analysis of RNA from cells synchronised in various stages of the mitotic and meiotic cell cycle probed with M13mp8/p1581 indicated related transcripts in meiotic cells.


Separation of oligogalacturonic acids by high-performance gel filtration chromatography on silica gel with diol radical.
Oligogalacturonic acids (OLGAs) ranging from two to nineteen residues in length were separated using high-performance gel filtration chromatography on a silica gel with diol radical. The optimum conditions (eluent, column temperature) for separation of OLGAs by high-performance gel filtration chromatography were investigated. The column used in this experiment allowed a high pressure of 4900 p.s.i. and a flow-rate of 2 ml/min. The stationary phase of silica gel stabilized the separation of OLGAs. The peaks of OLGAs separated using this column were assigned by comparing retention times with standards, and the molecular weights of the corresponding OLGAs were determined by fast atom bombardment mass spectrometry.


Comparison of forest stand height interpolation of GEDI and ICESat-2 LiDAR measurements over tropical and sub-tropical forests in India.
Forests absorb atmospheric carbon and hence play a vital role in carbon sequestration and climate regulation. Recent research emphasizes developing technology and methods to understand the carbon sequestration potential in various forest ecosystems. Forest stand height estimation is one of the crucial parameters in allometry that estimates forest biomass. An attempt is made in this study to map forest stand height in tropical and sub-tropical forests in India using recently launched spaceborne LiDAR platforms Ice Cloud and Elevation Satellite (ICESat-2) and Global Ecosystem Dynamics Investigation (GEDI). A geostatistical kriging approach is used to interpolate the forest stand height, and the generated stand height surface is validated using ground truth samples. The results showed that GEDI data performed better with an RMSE of 3.99 m and 2.62 m in tropical forests than the ICESat-2 data, which showed an RMSE of 5.71 m and 5.08 m, respectively. A similar pattern was observed in sub-tropical forests where GEDI modelled stand height outperformed ICESat-2 modelled stand height. This analysis demonstrates the potential of existing spaceborne LiDAR platforms in interpolating forest stand height at different forest types. Also, the research emphasizes the necessity of a high density of LiDAR footprints spread in both across- and along-track directions for accurate interpolation of forest stand height.


Nuclear localization of amyloid-β precursor protein-binding protein Fe65 is dependent on regulated intramembrane proteolysis.
Fe65 is an adaptor protein involved in both processing and signaling of the Alzheimer-associated amyloid-β precursor protein, APP. Here, the subcellular localization was further investigated using TAP-tagged Fe65 constructs expressed in human neuroblastoma cells. Our results indicate that PTB2 rather than the WW domain is important for the nuclear localization of Fe65. Electrophoretic mobility shift of Fe65 caused by phosphorylation was not detected in the nuclear fraction, suggesting that phosphorylation could restrict nuclear localization of Fe65. Furthermore, both ADAM10 and γ-secretase inhibitors decreased nuclear Fe65 in a similar way indicating an important role also of α-secretase in regulating nuclear translocation.


Radical-Dual-Difunctionalization and Trifluoromethylative Decarboxylation of Two Different Alkenes.
From a single alkene to two different alkenes! A convenient Fe-catalyzed A-D-A-T-type radical-dual-difunctionalization and cross-coupling of two different alkenes to provide chain elongated and trifluoromethylated aromatic alkenes has been developed.


Enhanced biomass production and pollutant removal by duckweed in mixotrophic conditions.
Duckweed is a potential biomass source for alternative energy production. This work reports the effects of trophic modes on growth rates, biomass accumulation, and removal rates of pollutant by duckweed. Glucose, fructose, galactose, sucrose, and maltose all supported heterotrophic and mixotrophic growth of duckweed. The mixotrophic growth rate was 4.98 and 6.22 times higher than those in heterotrophic and photoautotrophic conditions, respectively. Notably, mixotrophy produced more biomass than the simple sum of the biomass accumulation during heterotrophy and photoautotrophy. Mixotrophy was also superior in starch and protein production, as well as in removal rates of nutrients and organic carbon from the growth medium. However, the starch content of duckweed grown heterotrophically was 2.06 times higher than in mixotrophy, suggesting a combination of mixotrophy and heterotrophy as an effective strategy for starch-rich biomass production. This study thus provides a paradigm for future studies supporting duckweed-based biomass production and organic wastewater treatment.