Cognitive functioning in patients with schizophrenia and bipolar disorder: a quantitative review.
Evidence suggests that cognitive functioning in bipolar disorder may be impaired even in euthymic states, but it is unclear if the pattern of deficits is similar to the deficits found in schizophrenia. The aim of this study was to review quantitatively the studies on cognitive performance in schizophrenia and bipolar disorder. Articles for consideration were identified through a literature search in MEDLINE and PsycLIT in the period between 1985 and October 2004, using the keywords "schizophrenia" combined with "bipolar disorder", or "manic-depress*" or "manic" combined with "cogniti*" or "neuropsycholog*". Thirty-one studies were included that: i) evaluated cognitive performance using standardized and reliable neuropsychological testing procedures; ii) compared adult patients with schizophrenia and with bipolar disorder; iii) reported test scores of both patient groups, or exact p-values, t-values, or F-values; and iv) were published as an original article in a peer-reviewed English language journal. Meta-analyses of all studies indicated that patients with bipolar disorder generally perform better than patients with schizophrenia, but the distribution of effect sizes showed substantial heterogeneity. Results based on a more homogeneous subset of studies that matched patient groups on clinical and demographic characteristics pointed in the same direction, with effect sizes in the moderate range. Patients with bipolar disorder show better cognitive performance than patients with schizophrenia, even when matched for clinical and demographic characteristics.


Pregnancy-induced nephropathy: the significance of focal segmental glomerulosclerosis.
The morphologic alterations of true preeclampsia are well described and distinct. Using available criteria to define reversible pregnancy-induced nephropathy (PIN), the pathologist can offer the clinician information useful in predicting remote renal function and hypertension. True PIN is a usually completely reversible lesion in the nullipara and carries little risk of future hypertension. Nephrosclerotic vascular lesions, however, whether arteriolar, interlobular, or glomerular and resembling focal segmental glomerulosclerosis (FSGS), signify underlying hypertensive disease. This review summarizes information concerning the nature of PIN and also surveys 20 biopsies in women who mainly had severe preeclampsia, often with persistent postpartum hypertension. This material was step-sectioned and specifically reviewed in an effort to find FSGS in women with PIN.


Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in schizophrenia.
Schizophrenia (SCZ) is a serious psychiatric condition with a 1% lifetime risk. SCZ is one of the top ten global causes of disabilities. Despite numerous attempts to understand the function of genetic factors in SCZ development, genetic components in SCZ pathophysiology remain unknown. The competing endogenous RNA (ceRNA) network has been demonstrated to be involved in the development of many kinds of diseases. The ceRNA hypothesis states that cross-talks between coding and non-coding RNAs, including long non-coding RNAs (lncRNAs), via miRNA complementary sequences known as miRNA response elements, creates a large regulatory network across the transcriptome. In the present study, we developed a lncRNA-related ceRNA network to elucidate molecular regulatory mechanisms involved in SCZ. Microarray datasets associated with brain regions (GSE53987) and lymphoblasts (LBs) derived from peripheral blood (sample set B from GSE73129) of SCZ patients and control subjects containing information about both mRNAs and lncRNAs were downloaded from the Gene Expression Omnibus database. The GSE53987 comprised 48 brain samples taken from SCZ patients (15 HPC: hippocampus, 15 BA46: Brodmann area 46, 18 STR: striatum) and 55 brain samples taken from control subjects (18 HPC, 19 BA46, 18 STR). The sample set B of GSE73129 comprised 30 LB samples (15 patients with SCZ and 15 controls). Differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the limma package of the R software. Using DIANA-LncBase, Human MicroRNA Disease Database (HMDD), and miRTarBase, the lncRNA- associated ceRNA network was generated. Pathway enrichment of DEmRNAs was performed using the Enrichr tool. We developed a protein-protein interaction network of DEmRNAs and identified the top five hub genes by the use of STRING and Cytoscape, respectively. Eventually, the hub genes, DElncRNAs, and predictive miRNAs were chosen to reconstruct the subceRNA networks. Our bioinformatics analysis showed that twelve key DEmRNAs, including BDNF, VEGFA, FGF2, FOS, CD44, SOX2, NRAS, SPARC, ZFP36, FGG, ELAVL1, and STARD13, participate in the ceRNA network in SCZ. We also identified DLX6-AS1, NEAT1, MINCR, LINC01094, DLGAP1-AS1, BABAM2-AS1, PAX8-AS1, ZFHX4-AS1, XIST, and MALAT1 as key DElncRNAs regulating the genes mentioned above. Furthermore, expression of 15 DEmRNAs (e.g., ADM and HLA-DRB1) and one DElncRNA (XIST) were changed in both the brain and LB, suggesting that they could be regarded as candidates for future biomarker studies. The study indicated that ceRNAs could be research candidates for investigating SCZ molecular pathways.


Direct measurement of ear canal volume in a pediatric population: can we explain its individual variation in terms of age and body weight?
The aim of this work was to measure the external auditory canal (EAC) volume in children directly and to analyze its variation according to age and body weight. This was a prospective study at a university-based, secondary referral hospital. Volumes of the bony and cartilaginous EACs were measured using a 1 ml tuberculin syringe filled with 95% ethyl alcohol before inserting ventilation tube(s). Three hundred thirty-eight ears from 194 children (107 boys and 87 girls) were enrolled in this study (mean age=58.8 ± 25.2 months). They were between the 10th and 90th percentiles for age and gender based on the 2007 growth chart for Korean children. EAC volume tended to increase with age. The volumes of cartilaginous and total EACs were significantly larger in boys than in girls. The volume of the bony EAC was significantly larger in right than in left ears. Under the assumption that EAC volume is a linear function of age as well as body weight, these factors explained less than one-third of overall variation. Preferably, the growth of EAC seemed to be not linear with aging in pediatric population. Our cubic model seemed to be more fit to the growth of EAC than simple linear model did and age and body weight alone were not clinically useful predictors of ear canal volume needed for the fitting of hearing aids in pediatric population. Because this variation can result in a large variation of real ear to coupler difference (RECD), this study supports that individual measurement of the RECD is crucial for fitting appropriate hearing aids in children.


Laryngoplasty: results and problems after the creation of a neoglottis.
Voice rehabilitation in the laryngectomy patient has been a major goal of reconstructive laryngeal surgery. 36 patients underwent laryngectomy with the creation of a phonatory neoglottis as outlined by Staffieri. In 13 patients good voice rehabilitation was achieved. In 23 patients who failed to develop voice production, altered swallowing function was the major problem.


Effects of long-term sildenafil treatment for pulmonary hypertension in infants with chronic lung disease.
To determine the clinical course and outcomes of infants with chronic lung disease (CLD) and pulmonary hypertension (PH) who received prolonged sildenafil therapy. We conducted a retrospective review of 25 patients <2 years of age with CLD in whom sildenafil was initiated for the treatment of PH while they were hospitalized from January 2004 to October 2007. Hemodynamic improvement was defined by a 20% decrease in the ratio of pulmonary to systemic systolic arterial pressure or improvement in the degree of ventricular septal flattening with serial echocardiograms. Chronic sildenafil therapy (dose range, 1.5-8.0 mg/kg/d) was initiated at a median of 171 days of age (range, 14-673 days of age) for a median duration of 241 days (range, 28-950 days). Twenty-two patients (88%) achieved hemodynamic improvement after a median treatment duration of 40 days (range, 6-600 days). Eleven of the 13 patients with interval estimates of systolic pulmonary artery pressure with echocardiogram showed clinically significant reductions in PH. Five patients (20%) died during the follow-up period. Adverse events leading to cessation or interruption of therapy occurred in 2 patients, 1 for recurrent erections, and the other had the medication held briefly because of intestinal pneumatosis. These data suggest that chronic sildenafil therapy is well-tolerated, safe, and effective for infants with PH and CLD.


Recurrent partial hydatidiform mole: report of a case.
The first case of recurrent partial hydatidiform mole is reported. Despite worsening of the associated embryopathy, there was no worsening of the histologic characteristics in terms of trophoblastic hyperplasia or behavior. More cases are needed to define the natural history of this recurrent form of trophoblastic neoplasia.


The use of systemic antibiotics in seven community hospitals in Northern Israel.
This study evaluated and compared the usage and costs of antibiotics in seven hospitals in the North of Israel and was the first of its kind. We also attempted to determine whether the presence of an Infectious Diseases Unit or Consultant affects antibiotic usage and costs.


Cellular mechanisms underlying acute graft rejection: time for reassessment.
Rejection of transplanted organs depends on an orchestrated immune response to histocompatibility antigens expressed by the grafted tissue. Effector mechanisms primarily responsible for the rejection process classically involve type 1 helper CD4(+) T cells, cytotoxic CD8(+) T cells and antibodies. Experimental studies revealed alternative mechanisms of rejection that implicate type 2 helper CD4(+) T cells and memory CD8(+) T cells as well as cells belonging to the innate immune system including natural killer cells, eosinophils and neutrophils. Furthermore, local inflammation associated with rejection is tightly regulated at the graft level by regulatory T cells and mast cells. The redundancy of rejection mechanisms explains the difficulty to induce transplantation tolerance and to develop reliable biomarkers for prediction of allograft outcome.


An instrument evaluation framework: description and application to assessments of hand function.
An instrument evaluation framework outlining a process for selecting measurement instruments for use in hand therapy is presented. Each section of the framework--including clinical utility, standardization, purpose, psychometric properties, and patient's perspective--is explained in detail. The framework is applied to four hand function assessments that measure functional limitation, specifically, the Test Evaluant les Membres Supèrieurs des Personnes Agèes (Upper Extremity Performance Evaluation Test for the Elderly; TEMPA), the Jebsen Test of Hand Function, the Smith Hand Function Test, and the Quantitative Test of Upper Extremity Function. The therapists who developed and applied the framework selected the TEMPA as the most appropriate measure for their setting. This framework will assist hand therapists in justifying the selection of measurement instruments and will facilitate a consistent, comprehensive, and critical evaluation approach.


Pesticide risk perceptions and the differences between farmers and extensionists: towards a knowledge-in-context model.
A growing body of literature analyzes farmer perceptions of pesticide risk, but much less attention has been given to differences in risk perception between farmers and technical experts. Furthermore, inconsistencies in knowledge have too easily been explained in terms of lack of knowledge rather than exploring the underlying reasons for particular forms of thinking about pesticide risks. By doing this, the division between expert and lay knowledge has been deepened rather than transcended. This study aims to understand differences and similarities among the perceptions of pesticide risks of farmers, farm workers, and technical experts such as extensionists, by applying a social science approach towards knowledge and risk attitudes. Semi-structured interviews and field observations were conducted to smallholders, farm workers, extensionists, health professionals and scientists involved in the use and handling of pesticides. Subsequently, a survey was carried out to quantify the farmers and extensionists' acceptance or rejection of typical assertions expressed previously in the semi-structured interviews. Smallholders showed to gain knowledge from their own experiences and to adapt pesticides practices, which is a potential basis for transforming notions of pesticide safety and risk reduction strategies. Though extensionists have received formal education, they sometimes develop ideas deviating from the technical perspective. The risk perception of the studied actors appeared to vary according to their role in the agricultural labor process; they varied much less than expected according to their schooling level. Commitment to the technical perspective is not dramatically different for extensionists on the one hand and farmers as well as farm workers on the other hand. Ideas about a supposed lack of knowledge by farmers and the need of formal training are too much driven by a deficit model of knowledge. Further research on risk perceptions of pesticides and training of rural people will benefit from the development of a knowledge-in-context model.


The effect of recombinant interleukin 2 in combination with mitomycin C on advanced cancer.
We recently discovered that the ability of cancer patients to generate lymphokine-activated killer (LAK) cells became remarkably augmented after mitomycin C (MMC) administration. Based on our clinical findings, we designed a treatment regimen comprised of MMC 12 mg/m2 given intravenously on day 1 and recombinant interleukin 2 (rIL 2) 700 U/m2 given intravenously every 12 hr from day 4 through day 8, when the generation of LAK cells had been shown to be markedly increased. Ten patients with various advanced carcinomas for which standard therapy had failed or no standard therapy was available, were treated with this regimen. Of these ten, three had a partial response and three others had a minor response. Fevers were common and anemia occurred in four patients, but nevertheless, severe toxicity was not encountered. These results indicated that rIL 2 in combination with MMC might be effective against advanced carcinoma without causing severe toxicity when these drugs are used in an appropriate combination.


Vitamin K-dependent carboxylase activity in fetal rat lung: developmental effects of dexamethasone and triiodothyronine.
Dexamethasone (Dex) and triiodothyronine (T3) were administered to pregnant rats during late gestation to evaluate potential developmental effects on fetal lung vitamin K-dependent carboxylation. Maternal rats were injected on the 2 d before study with Dex (0.2 mg/kg intraperitoneally), with T3 (0.7, 3.5, or 7 mg/kg intramuscularly), or with a combination of both hormones. Fetal lung microsomes were prepared at 18, 19, and 20 d of gestation, and carboxylase activity was assessed by measuring the incorporation of 14CO2 into a synthetic pentapeptide substrate. Dex alone resulted in a small but consistent increase in activity in all three gestational ages. T3 alone increased activity approximately 85% at 20 d of gestation. Treatment with a combination of Dex and T3 caused a 60% increase in vitamin K-dependent carboxylation at each gestational age. Decreased lung growth was noted with combination hormone treatment in all rats studied at 19 and 20 d of gestation. Lung growth expressed as lung wt/body wt was more sensitive to the effects of Dex plus T3 than was carboxylase activity. Decreased lung wt/body wt (decreased 25%) was noted with Dex plus T3 (0.7 mg/kg); however, no induction of carboxylase enzyme activity was evident at this dose. This study demonstrates that vitamin K-dependent carboxylase activity in fetal rat lung can be induced by the exogenous administration of Dex and T3 to pregnant rats. Fetal lung microsomes contain multiple endogenous substrates for the vitamin K-dependent carboxylase enzyme. These hormones play a significant developmental role not only in protein biosynthesis, but in posttranslational processing as well.(ABSTRACT TRUNCATED AT 250 WORDS)


Prodrugs of peptides. 6. Bioreversible derivatives of thyrotropin-releasing hormone (TRH) with increased lipophilicity and resistance to cleavage by the TRH-specific serum enzyme.
Bioreversible derivatization of TRH (pGlu-His-Pro-NH2) to protect the tripeptide against rapid enzymatic inactivation in the systemic circulation and to improve the lipophilicity of this highly hydrophilic peptide was performed by N-acylation of the imidazole group of the histidine residue with various chloroformates. Whereas TRH was rapidly hydrolyzed at its pGlu-His bond in human plasma by a TRH-specific pyroglutamyl aminopeptidase serum enzyme, the N-alkoxycarbonyl derivatives were resistant to cleavage by the enzyme. On the other hand, these derivatives are readily bioreversible as the parent TRH is formed quantitatively from the derivatives by spontaneous hydrolysis or by plasma esterase-catalyzed hydrolysis. In addition to protecting the parent TRH against rapid inactivation in the circulation and hence potentially prolonging the duration of action of TRH in vivo, the N-alkoxycarbonyl prodrug derivatives were much more lipophilic than TRH as assessed by octanol-buffer partitioning. This property may enhance prodrug penetration of the blood-brain barrier and various other biomembranes compared to the parent peptide.


Elimination of chemical shift artifacts of thoracic spine with contrast-enhanced FLAIR imaging with fat suppression at 3.0 T.
The purpose of this study was to assess the effect of chemical shift artifacts and fat suppression between contrast-enhanced T1-weighted fast spin-echo (FSE) sequence with fat suppression and contrast-enhanced T1-weighted fluid attenuated inversion recovery (FLAIR) sequence with fat suppression in magnetic resonance imaging (MRI) of the thoracic spine at 3.0T. Forty patients, who underwent MRI examination, were recruited and analyzed both qualitatively and quantitatively. Due to chemical shift artifacts in the T1-weighted FSE, 14 of the patients were found to be of non-diagnostic value. On the contrary, in 11 of those 14 patients, no chemical shift artifacts were observed in the T1-weighted FLAIR sequence. Regarding the efficiency of fat suppression, both sequences achieved successful fat suppression. Consequently, the use of T1-weighted FLAIR fat suppression after contrast administration sequence seems to eliminate or significantly reduce image quality deterioration stemming from chemical shift artifacts in thoracic spine examinations.


Individual resolvin E family members work distinctly and in a coordinated manner in the resolution of inflammation.
Three main E-type resolvins (RvEs): RvE1, RvE2, and RvE3, have roles in the resolution of inflammation as anti-inflammatory activities. To investigate the roles of each RvE in the resolution of inflammation, timing of interleukin (IL)- 10 release and IL-10 receptor expressions, and phagocytosis evoked by each RvE in differentiated human monocytes, macrophage-like U937 cells were examined. Here, we show that RvEs enhance the expression of IL-10, and IL-10 receptor-mediated signaling pathways and IL-10-mediated-signaling-independent resolution of inflammatory effects by activating the phagocytotic function. Thus, RvE2 mainly evoked an IL-10-mediated anti-inflammatory function, whereas RvE3 principally activated phagocytotic activity of macrophages, which may be involved in tissue repair. On the other hand, RvE1 showed both functions, although not prominent but rather acting as a relief mediator that takes over the RvE2 function and passes over to the RvE3 function. Therefore, each RvE may act as an important role/stage-specific mediator in a coordinated manner with other RvEs in the processes of the resolution of inflammation.


Red cell distribution width is associated with mortality in kidney transplant recipients.
Red cell distribution width (RDW), a parameter routinely reported as part of the complete blood count, is associated with increased morbidity and mortality risk in different patient populations. No published data are available about the association between RDW and mortality in kidney transplant recipients. We collected socio-demographic, clinical parameters, medical and transplant history and laboratory data at baseline in 723 prevalent kidney transplant recipients between June and October 2008 [mean age 51 ± 13 (SD) years, 56 % men, 21 % diabetics]. Associations between baseline RDW values and all-cause mortality over 3 years were examined in unadjusted and adjusted models. Increasing RDW was associated with increased mortality in both unadjusted [(HR(1 % increase) = 1.63; 95 % CI 1.41-1.89) and (HR(>median) = 2.74; 95 % CI 1.68-4.48)] and fully adjusted models [(HR(1 % increase) = 1.60; 95 % CI 1.27-1.89) and (HR(>median) = 1.33; 95 % CI 0.76-2.35)]. In reclassification analyses, RDW improved the predictive value of all-cause mortality prediction models [the net reclassification improvement (NRI) was 0.189; p < 0.001]. RDW, a cheap and readily available but largely neglected parameter independently, predicts mortality in prevalent kidney transplant recipients and could potentially been used in everyday risk assessment of kidney transplant recipients.


An active endoscopic robot based on wireless power transmission and electromagnetic localization.
Conventional endoscopes have the disadvantages of causing pain to patients because of their large dimensions and allowing incomplete inspection because of their limited power. An active inchworm-like endoscopic robot has been designed, which is based on electromagnetic localization and synthesis of magnetic field strength vectors. The efficiency of wireless power transmission can be kept above 0.9% when the power-receiving coil is at arbitrary position and orientation. The position error of localization is < 10 mm and the average error of orientation angle is 2 degrees. When the robot moves through part of the porcine colon, images are transmitted outwards continuously at a speed of 30 fps and the temperature rise of the colon is < 1 degrees C. By simulation, the electromagnetic exposures to the human body are lower than international standards. The endoscopic robot is a promising tool for use by doctors, although further experiments and improvements need to be done.


Developing an antibody-binding protein cage as a molecular recognition drug modular nanoplatform.
We genetically introduced the Fc-binding peptide (FcBP) into the loop of a self-assembled protein cage, ferritin, constituting four-fold symmetry at the surface to use it as a modular delivery nanoplatform. FcBP-presenting ferritin (FcBP-ferritin) formed very stable non-covalent complexes with both human and rabbit IgGs through the simple molecular recognition between the Fc region of the antibodies and the Fc-binding peptide clusters inserted onto the surface of FcBP-ferritin. This approach realized orientation-controlled display of antibodies on the surfaces of the protein cages simply by mixing without any complicated chemical conjugation. Using trastuzumab, a human anti-HER2 antibody used to treat patients with breast cancer, and a rabbit antibody to folate receptor, along with fluorescently labeled FcBP-ferritin, we demonstrated the specific binding of these complexes to breast cancer cells and folate receptor over-expressing cells, respectively, by fluorescent cell imaging. FcBP-ferritin may be potentially used as modular nanoplatforms for active targeted delivery vehicles or molecular imaging probes with a series of antibodies on demand.


New and reproducible technique for experimentally induced middle cerebral artery stenosis.
A reproducible technique has been developed to create reversible middle cerebral artery (MCA) stenosis in the cat. Under pentobarbital anesthesia, the right eye was enucleated, MCA dissected and a suture looped around the vessel. A short segment of thicker suture was set horizontally on the MCA. The looped suture was then tied and the segment suture removed, resulting in partial stenosis. The knot could be easily removed, restoring blood flow. Perfusion and diffusion-sensitive magnetic resonance (MR) images were obtained over the next 6 hours to document cerebral blood flow abnormalities and developing ischemic changes, respectively. Laser-Doppler was performed to further document reduced flow through the ipsilateral hemisphere following MCA stenosis. Histopathologic sections were assessed for ischemic damage. Our results show this to be a reliable model of MCA stenosis and reperfusion, which is suitable for the evaluation of acute cerebral perfusion abnormalities resulting from arterial stenosis.


Surgical approaches to cholangiocarcinoma at confluence of hepatic ducts.
Analysis of the surgical management of 94 consecutive patients with carcinoma at the confluence of the hepatic ducts showed that 20% of them (or 60% of those thought, after comprehensive pre-operative investigation, to have resectable lesions) underwent tumour resection--6 local resections and 12 liver resections. The 30-day hospital mortality was 11% and mean duration of survival was 17 months (7 patients are still alive, with a mean survival of 22.2 months). The quality of life was also much improved after resection. In patients treated with palliative surgery the hospital mortality was 33% and the mean survival was 8.5 months. The results support the treatment of bile-duct carcinoma at the hilum of the liver by resection and suggest that the use of drainage techniques, whether employed surgically or non-surgically, be reserved until the possibility of treatment by resection has been fully considered.


Decreased Na+-gradient-dependent D-glucose transport in brush-border membrane vesicles from rabbits with experimental Fanconi syndrome.
The effect of anhydro-4-epitetracycline on sodium gradient-dependent D-glucose transport of rabbit renal brush-border membrane vesicles was studied. The purity of isolated brush-border membrane vesicles as judged by enzyme activities was not different between normal control and anhydro-4-epitetracycline-administered rabbits. There was no difference in estimate of intravesicular volume, either. When NaCl was used for sodium gradient, the overshoot of D-glucose uptake into brush-border membrane vesicles isolated from anhydro-4-epitetracycline-treated rabbits was significantly smaller than that of normal control rabbits. In the cases of NaSCN or Na2SO4, the former was also smaller than the latter, but not significantly so. To avoid the possible effect of membrane potential on D-glucose uptake, the voltage-clamp method was applied. Even in the voltage-clamped condition, the overshoot of D-glucose uptake into vesicles from anhydro-4-epitetracycline-treated rabbits was decreased compared to that of normal rabbits. In vitro incubation of brush-border membrane vesicles with 20 mM anhydro-4-epitetracycline caused no alteration in sodium gradient-dependent D-glucose uptake. Our results demonstrate that there exists a disorder in sodium gradient-dependent D-glucose uptake of renal brush-border membrane in anhydro-4-epitetracycline-treated rabbits, and suggest that this disorder is one of the underlying mechanisms of experimental Fanconi syndrome.


LncRNA LINC00963 Promotes Tumorigenesis and Radioresistance in Breast Cancer by Sponging miR-324-3p and Inducing ACK1 Expression.
Upregulation of long non-coding RNA LINC00963 has been observed in several cancer types. In this study, we analyzed the clinical and biological significance of LINC00963 in breast cancer. The key microRNA (miR) mediating the action of LINC00963 was identified. We show that LINC00963 upregulation is correlated with aggressive parameters of breast cancer. Silencing of LINC00963 suppresses the proliferation and tumorigenesis of breast cancer cells, whereas LINC00963 overexpression exerts an opposite effect. Knockdown of LINC00963 enhances DNA damage and oxidative stress and sensitizes breast cancer cells to radiation. Mechanistically, LINC00963 antagonizes the repressive activity of miR-324-3p on ACK1 expression. Clinically, there is a negative correlation between miR-324-3p and LINC00963 expression in breast cancer tissues. Overexpression of LINC00963 or ACK1 rescues the inhibitory effects of miR-324-3p on breast cancer cell proliferation and radiosensitivity. In addition, knockdown of ACK1 attenuates LINC00963-dependent breast cancer growth and tumorigenesis. Taken together, LINC00963 promotes tumorigenesis and radioresistance in breast cancer through interplay with miR-324-3p and derepression of ACK1. LINC00963 may represent a potential target for the treatment of breast cancer.


Hypofractionated radiation therapy (66 Gy in 22 fractions at 3 Gy per fraction) for favorable-risk prostate cancer: long-term outcomes.
To report long-term outcomes of low- and intermediate-risk prostate cancer patients treated with high-dose hypofractionated radiation therapy (HypoRT). Patients with low- and intermediate-risk prostate cancer were treated using 3-dimensional conformal radiation therapy to a dose of 66 Gy in 22 daily fractions of 3 Gy without hormonal therapy. A uniform 7-mm margin was created around the prostate for the planning target volume, and treatment was prescribed to the isocenter. Treatment was delivered using daily ultrasound image-guided radiation therapy. Common Terminology Criteria for Adverse Events, version 3.0, was used to prospectively score toxicity. Biochemical failure was defined as the nadir prostate-specific antigen level plus 2 ng/mL. A total of 129 patients were treated between November 2002 and December 2005. With a median follow-up of 90 months, the 5- and 8-year actuarial biochemical control rates were 97% and 92%, respectively. The 5- and 8-year actuarial overall survival rates were 92% and 88%, respectively. Only 1 patient died from prostate cancer at 92 months after treatment, giving an 8-year actuarial cancer-specific survival of 98%. Radiation therapy was well tolerated, with 57% of patients not experiencing any acute gastrointestinal (GI) or genitourinary (GU) toxicity. For late toxicity, the worst grade ≥2 rate for GI and GU toxicity was 27% and 33%, respectively. There was no grade >3 toxicity. At last follow-up, the rate of grade ≥2 for both GI and GU toxicity was only 1.5%. Hypofractionation with 66 Gy in 22 fractions prescribed to the isocenter using 3-dimensional conformal radiation therapy produces excellent biochemical control rates, with moderate toxicity. However, this regimen cannot be extrapolated to the intensity modulated radiation therapy technique.


Mimetic gain in batesian and Müllerian mimicry.
Starting from field investigations and experiments on mimetic butterfly populations a model for two mimetic species is developed. The model comprises various features such as the growth rates and carrying capacities of the two species, their unpalatability to predators, the recruitment and the training of the predators and, most important, the similarity of the two mimetic species. The model ranges from pure Batesian to pure Müllerian mimicry over a spectrum of possible cases. The mimetic gain is introduced as the relative increase in equilibrium density in a mimetic situation as compared to a situation where mimicry is not present. The dependence of this quantity on parameters as growth rate, carrying capacity, unpalatability, and similarity is investigated using numerical methods.


Effects of d1-methadone and morphine on developing chick embryo.
Injections of methadone into the air space of fertile chicken eggs affected development of the embryo. Both methadone and morphine caused decreases in liver weight and brain protein, and morphine increased liver protein levels.


Peripheral nervous system involvement accompanies central nervous system involvement in anti-glial fibrillary acidic protein (GFAP) antibody-related disease.
Glial fibrillary acidic protein (GFAP) is expressed by astrocytes in the central nervous system (CNS), but also by immature and regenerative Schwann cells in the peripheral nervous system (PNS). GFAP antibodies (GFAP-Abs) in cerebrospinal fluid (CSF) have been mainly described in patients with meningoencephalomyelitis. We aimed to study PNS symptoms in patients with CSF GFAP-Abs. We retrospectively included all patients tested positive for GFAP-Abs in the CSF by immunohistochemistry and confirmed by cell-based assay expressing human GFAPα since 2017, from two French reference centers. In a cohort of 103 CSF GFAP-Abs patients, 25 (24%) presented with PNS involvement. Among them, the median age at onset was 48 years and 14/25 (56%) were female. Abnormal electroneuromyography was observed in 11/25 patients (44%), including eight isolated radiculopathies, one radiculopathy associated with polyneuropathy, one radiculopathy associated with sensory neuronopathy, and one demyelinating polyradiculoneuropathy. Cranial nerve involvement was observed in 18/25 patients (72%). All patients except one had an associated CNS involvement. The first manifestation of the disease concerned the PNS in three patients. First-line immunotherapy was administered to 18/24 patients (75%). The last follow-up modified Rankin Scale was ≤ 2 in 19/23 patients (83%). Patients with PNS involvement had significantly more bladder dysfunction than patients with isolated CNS involvement (68 vs 40.3%, p = 0.031). PNS involvement in GFAP-Abs autoimmunity is heterogeneous but not rare and is mostly represented by acute or subacute cranial nerve injury and/or lower limb radiculopathy. Rarely, PNS involvement can be the first manifestation revealing the disease.


Problems of controlling the optical thickness of infrared coatings during deposition.
Special problems that influence the accuracy of controlling the optical thickness of infrared coatings during deposition are discussed.


A review on LED technology in water photodisinfection.
The increase in efficiency achieved by UV LED devices has led to a compelling increase in research reports on UV LED water treatment for consumption in the past few years. This paper presents an in-depth review based on recent studies on the suitability and performance of UV LED-driven processes for water disinfection. The effect of different UV wavelengths and their combinations was analysed for the inactivation of various microorganisms and the inhibition of repair mechanisms. Whereas 265 nm UVC LED present a higher DNA damaging potential, 280 nm radiation is reported to repress photoreactivation and dark repair. No synergistic effects have been proved to exist when coupling UVB + UVC whereas sequential UVA-UVC radiation seemed to enhance inactivation. Benefits of pulsed over continuous radiation in terms of germicidal effects and energy consumption were also analysed, but with inconclusive results. However, pulsed radiation may be promising for improving thermal management. As a challenge, the use of UV LED sources introduces significant inhomogeneities in the light distribution, pushing for the development of adequate simulation methods to ensure that the minimum target dose required for the target microbes is achieved. Concerning energy consumption, selecting the optimal wavelength of the UV LED needs a compromise between the quantum efficiency of the process and the electricity-to-photon conversion. The expected development of the UV LED industry in the next few years points to UVC LED as a promising technology for water disinfection at a large scale that could be competitive in the market in the near future.


Prominent anterior QRS forces: clinical, electrocardiographic and prospective study.
Recent data suggest that the prominent anterior QRS forces (R greater than or equal to S in V1 and/or V2 leads), in the absence of posterior myocardial infarction, right ventricular hypertrophy, or WPW syndrome, are related to an intraventricular conduction disturbance, at times rate-dependent. We followed 240 subjects with prominent anterior QRS forces and without the above mentioned diseases (study group), (mean age: 44.6 +/- 16 years, mean follow-up: 8 +/- 2 years) and 240 subjects without the anterior displacement (control group), (mean age: 44.4 +/- 14 years, mean follow-up: 7.9 +/- 1.9 years). The age distribution, sex, prevalence of organic heart disease, and follow-up period did not show significant differences between the two groups. QRS duration, prevalence of left ventricular hypertrophy pattern, S1 S2 S3 morphology, terminal r wave in AVR and s wave in V6 were similar in the two groups. During the follow-up period the incidence of right and left bundle branch block and fascicular block was very similar in the two groups of patients. These data suggest that prominent anterior QRS forces do not appear to be related to an initial involvement of the main bundle branches and fascicles and do not increase the likelihood of appearance of an intraventricular block of more advanced degree. The clinical, ECG and prospective data are not helpful in localizing either the ventricle or the area of the ventricle affected by conduction disturbance responsible for the anterior displacement. Our data suggest that the prominent anterior QRS forces express a normal variant of ventricular depolarization and that this finding does not have, per se, any unfavourable clinical implication.


Correlation between digital clubbing and pulmonary function in cystic fibrosis.
The correlation between digital clubbing and certain pulmonary function derangements (hypoxemia and FEV(1)) was previously described. However, the relationship between digital clubbing and other measures of pulmonary function or the presence of liver disease in patients with cystic fibrosis (CF) is poorly defined. Hence we compared the digital clubbing index (CI: ratio of distal phalangeal depth to interphalangeal depth) of 100 patients with CF (43 males, 57 females; mean age, 15.7 +/- 7.3 years) with that of 100 age- and gender-matched healthy controls. Digital clubbing was defined as a CI > or = 1.00 (mean + 2.6 SD; 99% of normal subjects). The CI and its relationship to pulmonary function and to liver disease was then evaluated in the CF patients. Digital clubbing was present in 75/100 (75%) of CF patients but was absent in all controls (P < 0.0001). In CF patients, CI was inversely correlated with PaO(2) (r = -0.555; P < 0.001), FEV(1) (r = -0.499; P < 0.001), and FEF(25-75%) (r = -0.404; P < 0.001), and was positively correlated with RV (r = 0.285; P < 0.05) and the slope of phase 3 of single-breath nitrogen washout (SP3N(2)) (r = 0.532; P < 0.01). There was no significant correlation between CI and age (r = 0.020; P = 0.84), TLC (r = -0.097; P = 0.34), PaCO(2) (r = 0.167; P = 0.10), or history of liver disease (P = 0.08). We conclude that in CF, the degree of digital clubbing is related to degree of hypoxemia, airways obstruction, hyperinflation, and nonuniformity of ventilation.


Metronomic capecitabine with rapamycin exerts an immunosuppressive effect by inducing ferroptosis of CD4+ T cells after liver transplantation in rat.
Liver transplantation is one of the most effective treatments for hepatocellular carcinoma (HCC). The balance between inhibiting immune rejection and preventing tumor recurrence after liver transplantation is the key to determining the long-term prognosis of patients with HCC after liver transplantation. In our previous study, we found that capecitabine (CAP), an effective drug for the treatment of HCC, could exert an immunosuppressive effect after liver transplantation by inducing T cell ferroptosis. Recent studies have shown that ferroptosis is highly associated with autophagy. In this study, we confirmed that the autophagy inducer rapamycin (RAPA) combined with metronomic capecitabine (mCAP) inhibits glutathione peroxidase 4 (GPX4) and promotes ferroptosis in CD4+ T cells to exert immunosuppressive effects after rat liver transplantation. Compared with RAPA or mCAP alone, the combination of RAPA and mCAP could adequately reduce liver injury in rats with acute rejection after transplantation. The CD4+ T cell counts in peripheral blood, spleen, and transplanted liver of recipient rats significantly decreased, and the oxidative stress level and ferrous ion concentration of CD4+ T cells significantly increased in the combination group. In vitro, the combination of drugs significantly promoted autophagy, decreased GPX4 protein expression, and induced ferroptosis in CD4+ T cells. In conclusion, the autophagy inducer RAPA improved the mCAP-induced ferroptosis in CD4+ T cells. Our results support the concept of ferroptosis as an autophagy-dependent cell death and suggest that the combination of ferroptosis inducers and autophagy inducers is a new research direction for improving immunosuppressive regimens after liver transplantation.


Using indirect ELISA to assess different antigens for the serodiagnosis of Fasciola gigantica infection in cattle, sheep and donkeys.
An indirect enzyme-linked immunosorbent assay (iELISA) was evaluated for its diagnostic capability in detecting antibodies against Fasciola gigantica infection in cattle, sheep and donkeys sera using crude worm, excretory-secretory and glutathione S-transferase antigens prepared from adult liver fluke. Presence of F. gigantica worms at post-mortem examination of cattle, sheep and donkey's livers was taken as a gold standard for the evaluation of the assay. The diagnostic sensitivity, specificity and accuracy percentages of iELISA were determined for each antigen. Excretory-secretory antigen gave the best results for the serodiagnosis of F. gigantica infection in cattle, sheep and donkeys using iELISA with diagnostic sensitivity percentages of 93.3%, 94.9% and 93.3%, respectively, while the specificity percentages were 96.7%, 97.2% and 96.3%, respectively, whereas the accuracy percentages were 95%, 96% and 95.7%, respectively. The diagnostic sensitivity percentages of iELISA using crude worm antigen were 96.7%, 100% and 93.3%, respectively, while the specificity percentages were 80%, 83.3% and 85.2%, respectively, whereas the accuracy percentages were 88.3%, 86.7% and 87%, respectively. The diagnostic sensitivity percentages of iELISA using glutathione S-transferase antigen were 66.7%, 71.8% and 60%, respectively, while the specificity percentages were 70%, 77.8% and 77.8%, respectively, whereas the accuracy percentages were 68.3%, 74.7% and 73.9%, respectively. Conclusively, excretory-secretory antigen dependent iELISA can be used as a reliable serodiagnostic test for F. gigantica infection in cattle, sheep and donkeys.


Targeting proliferation and survival pathways in head and neck cancer for therapeutic benefit.
Head and neck squamous cell carcinomas (HNSCC) are common human malignancies with poor clinical outcomes. The 5-year survival rates for patients with advanced stage HNSCC have not changed appreciably in the past few decades, underscoring a dire need for improved therapeutic options. Recent studies have elucidated a key signaling axis, the EGFR-STAT3-Bcl-XL signaling axis, that is aberrantly activated in a majority of HNSCC and contributes to the proliferation and survival of malignant cells. Considerable effort is being placed on developing highly specific inhibitors of different components of this pathway. This review highlights the progress that is being made towards achieving potent inhibition of the EGFR-STAT3-Bcl-XL signaling axis in HNSCC and the promising therapeutic strategies that are currently under development for this disease.


Identification of new cytokine combinations for antigen-specific T-cell therapy products via a high-throughput multi-parameter assay.
Infusion of viral-specific T cells (VSTs) is an effective treatment for viral infection after stem cell transplant. Current manufacturing approaches are rapid, but growth conditions can still be further improved. To optimize VST cell products, the authors designed a high-throughput flow cytometry-based assay using 40 cytokine combinations in a 96-well plate to fully characterize T-cell viability, function, growth and differentiation. Peripheral blood mononuclear cells (PBMCs) from six consenting donors were seeded at 100 000 cells per well with pools of cytomegalovirus peptides from IE1 and pp65 and combinations of IL-15, IL-6, IL-21, interferon alpha, IL-12, IL-18, IL-4 and IL-7. Ten-day cultures were tested by 13-color flow cytometry to evaluate viable cell count, lymphocyte phenotype, memory markers and interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) expression. Combinations of IL-15/IL-6 and IL-4/IL-7 were optimal for the expansion of viral-specific CD3+ T cells, (18-fold and 14-fold, respectively, compared with unstimulated controls). CD8+ T cells expanded 24-fold in IL-15/IL-6 and 9-fold in IL-4/IL-7 cultures (P < 0.0001). CD4+ T cells expanded 27-fold in IL-4/IL-7 and 15-fold in IL-15/IL-6 (P < 0.0001). CD45RO+ CCR7- effector memory (CD45RO+ CCR7- CD3+), central memory (CD45RO+ CCR7+ CD3+), terminal effector (CD45RO- CCR7- CD3+), and naive (CD45RO- CCR7+ CD3+). T cells were the preponderant cells (76.8% and 72.3% in IL-15/IL-6 and IL-15/IL-7 cultures, respectively). Cells cultured in both cytokine conditions were potent, with 19.4% of CD3+ cells cultured in IL-15/IL-6 producing IFNγ (7.6% producing both TNFα and IFNγ) and 18.5% of CD3+ cells grown in IL-4/IL-7 producing IFNγ (9% producing both TNFα and IFNγ). This study shows the utility of this single-plate assay to rapidly identify optimal growth conditions for VST manufacture using only 107 PBMCs.


Late-Life Depression, Hippocampal Volumes, and Hypothalamic-Pituitary-Adrenal Axis Regulation: A Systematic Review and Meta-analysis.
We systematically reviewed and meta-analyzed the association of late-life depression (LLD) with hippocampal volume (HCV) and total brain volume (TBV), and of cortisol levels with HCV, including subgroup analyses of depression characteristics and methodological aspects. We searched PubMed and Embase for original studies that examined the cross-sectional relationship between LLD and HCV or TBV, and 46 studies fulfilled the inclusion criteria. Standardized mean differences (Hedges' g) between LLD and control subjects were calculated from crude or adjusted brain volumes using random effects. Standardized Fisher transformations of the correlations between cortisol levels and HCVs were calculated using random effects. We included 2702 LLD patients and 11,165 control subjects from 35 studies examining HCV. Relative to control subjects, patients had significantly smaller HCVs (standardized mean difference = -0.32 [95% confidence interval, -0.44 to -0.19]). Subgroup analyses showed that late-onset depression was more strongly associated with HCV than early-onset depression. In addition, effect sizes were larger for case-control studies, studies with lower quality, and studies with small sample size, and were almost absent in cohort studies and studies with larger sample sizes. For TBV, 2523 patients and 7880 control subjects from 31 studies were included. The standardized mean difference in TBV between LLD and control subjects was -0.10 (95% confidence interval, -0.16 to -0.04). Of the 12 studies included, higher levels of cortisol were associated with smaller HCV (correlation = -0.11 [95% confidence interval, -0.18 to -0.04]). While an overall measure of LLD may be associated with smaller HCVs, differentiating clinical aspects of LLD and examining methodological issues show that this relationship is not straightforward.


Potential of sperm small non-coding RNAs as biomarkers of testicular toxicity in a doxorubicin-induced mouse model.
Testicular toxicity is a major concern in cancer chemotherapy and drug development as it can result in infertility; however, there are no effective biomarkers for this adverse effect. To identify new biomarkers, we investigated the expression of small non-coding RNAs (sncRNAs) in a mouse model of doxorubicin (DXR)-induced testicular toxicity. First, we performed small RNA-seq analysis of sperm from DXR-treated or control mice and observed differential expression of many genome-derived sequences. We then performed real-time RT-PCR validation of these sequences and discovered that sncRNA detected by one primers, dxRN_3, showed similar differential expression as that seen in the RNA-seq experiment. These findings suggest that the sncRNAs present in sperm have potential as clinically acceptable biomarkers for testicular toxicity.


Evaluation of a carbon dioxide laser scalpel for disbudding Holstein calves: A pilot study.
Cautery hot-iron disbudding is a painful routine husbandry practice performed on many dairy farms and calf rearing facilities. Refinements to eliminate or reduce the pain associated with disbudding are desired. Carbon dioxide (CO2) laser scalpels cut and ablate tissue using high-power light energy. The objective of this study was to test the utility of a CO2 laser scalpel in bovine disbudding and to compare healing and pain measures with those of cautery hot-iron disbudding. Twelve Holstein bull calves (6-39 d of age) were enrolled in the study. Calves were randomly assigned into groups that were disbudded with a CO2 laser scalpel (n = 6) or cautery hot iron (n = 6). Calves were sedated with xylazine for the procedure and were given oral meloxicam and a local anesthetic block for analgesia. Outcome measures were maximum surface temperature by infrared thermography, mechanical nociception threshold (MNT) tests, and digital images for wound healing. The infrared thermography and MNT measures were collected before disbudding and out to 72 h postprocedure. Images for wound healing were collected before disbudding and at 6, 24, and 72 h and 7, 14, 28, and 42 d postdisbudding. Overall maximum surface temperatures were not different between groups (35.3 ± 0.3°C vs. 36.0 ± 0.3°C for laser and hot iron, respectively). No differences in overall MNT measures were noted between the laser calves (2.28 ± 0.19) and the hot-iron calves (2.42 ± 0.19 kg of force). All 6 calves in the laser group were completely healed by d 42, whereas only 4 out of 6 hot-iron calves were fully healed. These results suggest that disbudding calves using a CO2 laser scalpel may be painful based on the outcomes measured. Further research that focuses on pain associated with time points beyond those used in this study and that performs the procedure in unsedated calves is needed to fully evaluate its utility.


Early patellofemoral revision following total knee arthroplasty.
A consecutive series of 289 Miller-Galante (Zimmer, Warsaw, IN) total knee arthroplasties were studied, with particular reference to the patellofemoral joint. Sixteen knees were initially excluded; the remaining 273 arthroplasties were followed for 14 to 44 months. Thirty patients (11%) had patellofemoral pain. Twenty patients (7.3%) had revision patellofemoral surgery. Fourteen patients had revision surgery for patellar maltracking, of which 10 had resolution of their symptoms, 2 were improved, 1 had no change, and 1 developed a prosthetic infection. Six patients who had no evidence of patellar maltracking had revision surgery with a cemented metal-backed patellar component. Only two of these patients had symptom improvement from their revision surgery. A higher than usual incidence of patellar maltracking (5%) is reported. The first-generation Miller-Galante femoral component may contribute to the relative instability of patellofemoral tracking. Those patients with patellar maltracking were greatly improved by revision surgery; the results of revision surgery for anterior knee pain without associated patellar maltracking were disappointing.


Novel S-doped BiOBr nanosheets for the enhanced photocatalytic degradation of bisphenol A under visible light irradiation.
Bisphenol A (BPA), a typical endocrine disrupting chemical, is widespread in aqueous environment and cannot be efficiently treated by traditional water treatment technologies. Bismuth oxybromide (BiOBr) is a promising photocatalyst with a special layered structure. However, its band gap (2.8 eV) is not narrow enough for the efficient harvesting of visible light, severely restricting its practical use. Given that the band gap of Bi2S3 is only 1.3 eV, S-doping modification could be used to tailor the band structure of BiOBr. Here, series of S-doped BiOBr nanosheets was prepared through a facile hydrothermal procedure. The as-prepared S0.2-BiOBr nanosheets showed a narrower band gap of 2.33 eV. The intrinsic photocatalytic activity of S0.2-BiOBr sample for the degradation of BPA was 2.78 times higher than that of BiOBr under visible light degradation. Moreover, the mechanism of BPA degradation over the S-doped BiOBr under visible light irradiation was elucidated based on the experimental results and density functional theoretical calculations. Overall, a feasible and effective doping method was proposed to improve the utilization efficiency of visible light.


A case report on management of severe childhood pneumonia in low resource settings.
Pneumonia is a major cause of child mortality among children under five years, worldwide. Pneumonia infection may be caused by bacteria, viruses, or fungi in single or in both lungs. According to recent criteria developed by World Health Organization (WHO) in September (2013), pneumonia can be classified into severe pneumonia, pneumonia and no pneumonia. Most of the deaths occur from severe pneumonia and management of severe childhood pneumonia requires early identification, prompt referral and the availability of intensive quality of care. This case study aimed to represent the actual scenario of severe childhood pneumonia case management at community clinic. Considering that circumstances, International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) developed an innovative day care management approach as safe, effective and less expensive alternative to hospital management of severe childhood pneumonia. A twenty-seven months old boy came to the Health & Family Welfare Centre (HFWC) with severe breathing difficulty, cough, history of fever. The management described below was continued daily until there was clinical improvement; no fever, no fast breathing, no lower chest wall indrawing, no danger signs, no rales on auscultation and no hypoxemia. Considering the WHO case management protocol for severe pneumonia, day care management approach on community clinic recommends that diagnosis of severe pneumonia should be based primarily on visible clinical parameters. On that basis, severe childhood pneumonia can be successfully managed at community clinics including for children with hypoxemia who is required prolong (4-6 hours) oxygen therapy.


Comparing simultaneous integrated boost vs sequential boost in anal cancer patients: results of a retrospective observational study.
To evaluate clinical outcomes of simultaneous integrated boost (SIB) - intensity modulated radiotherapy (RT) in patients with non metastatic anal cancer compared to those of a set of patients treated with 3-dimensional conformal RT and sequential boost (SeqB). A retrospective cohort of 190 anal cancer patients treated at 3 academic centers with concurrent chemo-RT employing either SIB or SeqB was analysed. The SIB-group consisted of 87 patients, treated with 2 cycles of Mitomycin (MMC) and 5-Fluorouracil (5FU) using SIB-IMRT delivering 42-45Gy/28-30 fractions to the elective pelvic lymph nodes and 50.4-54Gy/28-30fractions to the primary tumor and involved nodes, based on pre-treatment staging. The SeqB group comprised 103 patients, treated with MMC associated to either 5FU or Capecitabine concurrent to RT with 36 Gy/20 fractions to a single volume including gross tumor, clinical nodes and elective nodal volumes and a SeqB to primary tumor and involved nodes of 23.4 Gy/13 fractions. We compared colostomy-free survival (CFS), overall survival (OS) and the cumulative incidence of colostomy for each radiation modality. Cox proportional-hazards model addressed factors influencing OS and CFS. Median follow up was 34 (range 9-102) and 31 months (range 2-101) in the SIB and SeqB groups. The 1- and 2-year cumulative incidences of colostomy were 8.2% (95%CI:3.6-15.2) and 15.0% (95%CI:8.1-23.9) in the SIB group and 13.9% (95%CI: 7.8-21.8) and 18.1% (95%CI:10.8-27.0) in the SeqB group. Two-year CFS and OS were 78.1% (95%CI:67.0-85.8) and 87.5% (95%CI:77.3-93.3) in the SIB group and 73.5% (95%CI:62.6-81.7) and 85.4% (95%CI:75.5-91.6) in the SeqB, respectively. A Cox proportional hazards regression model highlighted an adjusted hazard ratio (AdjHR) of 1.18 (95%CI: 0.67-2.09;p = 0.560), although AdjHR for the first 24 months was 0.95 (95%CI: 0.49-1.84;p = 0.877) for the SIB approach. SIB-based RT provides similar clinical outcomes compared to SeqB-based in the treatment of patients affected with non metastatic anal cancer.


Effects of Different Hay Feeders, Availability of Roughage on Abnormal Behaviors and Cortisol Circadian Rhythm in Horses Kept in Dry Lots.
Free choice forage could be the best option regarding horses' welfare but can lead to increased body weight (BW), and waste of hay. Automatic box feeders (BF) and slow feeders (SF) decrease food waste, but it is unknown how these affect the horses' time-budget (TB). This study compared the effects of feeding free choice hay (FC), to a SF and an automated BF on the horses' cortisol circadian rhythm (CCR) and behavior by 24-hours continuous behavioral sampling (CBS). The study was designed as a 3 × 3 Latin square design with 15 polo horses divided into 3 groups, for 15 days on each treatment. Every 15 days, BW was assessed, blood collected for CCR analysis, the behavior recorded during the last 24 hours of the last day of each treatment and the video analyzed with CBS. Time spent on all behaviors was evaluated and used for the determination of the animals' TB. The effects of the different feeders were analyzed with ANOVA. FC horses consumed and wasted more hay daily (16.6 ± 0.5kg) (P < .001), compared with BF (10.4 ± 0.5 kg), and SF (9.30 ± 0.45 kg). FC horses had higher weight gain (P < .001, 23.5 ± 4.6kg), compared to BF (1.2 ± 5.7 kg) and SF (0.37 ± 4.6) kg. FC and SF horses spent more than 50% of the TB foraging, generating a TB similar to grazing horses. BF horses spent less time eating (P < .001), increasing time spent standing, sniffing the ground, and practicing coprophagy (P < .050). BF horses showed the highest aggression (P < .043). CCR was not different among treatments.


The histone deacetylase inhibitor trichostatin A induces GADD45 gamma expression via Oct and NF-Y binding sites.
The GADD45gamma protein is a potential tumor suppressor whose expression is reduced in several tumors. However, very little is known about the regulation of its expression. We have determined that the most relevant region of its promoter lies between nucleotides -112 and -54, relative to the transcription start site. Putative Oct and NF-Y elements were found in this region and factors belonging to these families interacted with these elements in vitro and with the promoter in vivo. Mutation of these elements reduced the basal activity of the promoter, suggesting that both sites are essential for basal expression. These factors interact with chromatin modifying proteins and we found that histone deacetylase 1 or silencing mediator for retinoid and thyroid hormone receptor overexpression reduced the basal activity of the promoter. In contrast, forced expression of the histone acetylase protein PCAF or cell treatment with the HDAC inhibitor trichostatin A increased GADD45gamma mRNA levels and induced GADD45gamma promoter activity through its Oct and NF-Y elements. Moreover, ectopic expression of a dominant-negative version of NF-YA strongly inhibited trichostatin A-induced activation of the promoter. Our data strongly suggest that inhibition of deacetylase activity could potentially be used for treatment of tumors where GADD45gamma expression is reduced.


A novel surface plasmon resonance biosensor based on graphene oxide decorated with gold nanorod-antibody conjugates for determination of transferrin.
A surface plasmon resonance (SPR) biosensor based on graphene oxide (GO) decorated with gold nanorod (AuNR)-antibody conjugates was developed. Compared with traditional SPR biosensor, GO sheets were assembled on the amino-modified Au film via electrostatic interaction, and then AuNR-antibody conjugates were immobilized via carbodiimide-assisted amidation reaction. The abundant oxygen-containing functional groups, large specific surface area and friendly biocompatibility of GO sheets are beneficial to the immobilization of AuNR-antibody conjugates. Meanwhile, AuNRs are anchored to the GO surface through antibody and function as enhancers for the transferrin determination, which greatly enhance the sensitivity of the detection. As a result, the present biosensor shows a satisfactory response to transferrin in the concentration range of 0.0375-40.00 μg mL(-1). The lowest concentration of transferrin that can be determined by this method is about 32-fold lower than that obtained with the sensor based on Au film. This design affords a facile method of controlling the assembly of AuNRs on the GO sheets and can be easily extended to other protein detection by preparing corresponding AuNR-antibody conjugates.


The Parkinson's disease-associated protein α-synuclein inhibits hepatoma by exosome delivery.
Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer. However, their relevant pathogenesis is not clear. In the present study, we investigated the potential role of exosome-delivered α-synuclein (α-syn) in the regulation between PD and liver cancer. We cultured hepatocellular carcinoma (HCC) cells with exosomes derived from conditioned medium of the PD cellular model, and injected exosomes enriched with α-syn into the striatum of a liver cancer rat model. We found that α-syn-contained exosomes from the rotenone-induced cellular model of PD suppressed the growth, migration, and invasion of HCC cells. Integrin αVβ5 in exosomes from the rotenone-induced PD model was higher than that in the control, resulting in more α-syn-contained exosomes being taken up by HCC cells. Consistently, in vivo experiments with rat models also confirmed exosome-delivered α-syn inhibited liver cancer. These findings illustrate the important role of PD-associated protein α-syn inhibiting hepatoma by exosome delivery, suggesting a new mechanism underlying the link between these two diseases and therapeutics of liver cancer.


The perceived and built environment surrounding urban schools and physical activity among adolescent girls.
Neighborhood perceived/built environment and physical activity (PA) associations have been examined for adolescents around homes, but not surrounding schools. The purpose of this paper is to examine if positive perceptions/built environment in neighborhoods surrounding schools predict PA among low-income, urban adolescent girls. Measures include: minutes in moderate-vigorous PA (MVPA, ankle accelerometry), perceptions of the school environment (questionnaire), built environment (neighborhood audit). Analyses include multi-level models. Two hundred twenty-four sixth and seventh grade girls [mean(sd) age = 12.1(0.7) years] from 12 schools serving low-income, primarily African American communities; mean MVPA 35.4 min (mean days assessed = 5.8). Girls in schools with more positive perceptions of the neighborhood environment surrounding the school were less active (β = 7.2, p = 0.043). Having "places to go within walking distance" (perceptions) and number of food stores near school (built environment) positively relate to MVPA (β = 5.5, p = 0.042 and β = 0.59, p = 0.047). Among neighborhoods surrounding urban schools, positive perceptions do not predict PA; accessibility, via both perceived and built environment, support PA.


The importance of 'lumbar lordosis measurement device' application during pregnancy, and post-partum isometric exercise.
In this study, we measured the lumbar lordosis of normal pregnant women throughout their pregnancies and studied the efficacy and importance of the postpartum isometric exercise. 40 healthy primigravid patients were randomly assigned to one of the control and exercise groups. The lumbar lordotic deviation increased significantly throughout the pregnancy (p less than 0.05). Second postpartum day values of lumbar lordotic deviation and depth decreased compared to the third trimester values (p less than 0.05). Sixth postpartum week values of lumbar lordotic deviation and depth were found to be increased when compared to the first trimester values in the control and exercise group (p less than 0.05). On the other hand, the sixth week values in the exercise group are significantly lower compared to the control group (p less than 0.05). For these measurements we have used a 'Lumbar Lordosis Measurement Device' which was constructed in our institute. Muscle testing showed that isometric exercise improves the functional status of the affected muscles during pregnancy. We therefore conclude that the usage of 'LLMD' during the follow-up examination of pregnant women is essential to evaluate the posture of the patients. Isometric exercise is very important in order to obtain a normal posture and muscle tonus postpartumly.


Hydroxyethyl starch versus albumin in cardiopulmonary bypass prime solutions.
To compare hydroxyethyl starch (HES) with 25% albumin, 20 patients undergoing aortocoronary bypass were randomized into two groups: 10 received 1,000 ml of HES and 10 received 200 ml of 25% albumin in a bloodless priming solution for cardiopulmonary bypass (CPB). Platelet aggregation, antithrombin III, reptilase time, fibrinogen, plasminogen, fluid requirements, and hemodynamics were monitored. Platelet aggregation was abnormal in both groups, being relatively poorer in the albumin group. Both groups exhibited below normal antithrombin III and plasminogen levels, with significantly lower antithrombin III levels noted in the HES group postoperatively (41.9 +/- 11.8% versus 56.6 +/- 9.9%; p = 0.006). Compared with the albumin group, the HES group had slightly, but not significantly, elevated liver function test results, total volume replacement (9,173 +/- 2,046 ml versus 8,522 +/- 1,192 ml; p = 0.057), packed red blood cell usage (227 +/- 284 ml versus 75 +/- 168 ml; p = 0.066), and chest tube drainage (599 +/- 253 ml versus 454 +/- 174 ml; p = 0.144). In the HES group, 5% albumin requirement was greater (386 +/- 466 ml versus 50 +/- 158 ml; p = 0.002) and percent increase of body weight was higher (5.2 +/- 0.8% versus 2.3 +/- 0.6%; p = 0.05) postoperatively. Postoperative weight increase and colloid requirements plus trends toward larger blood loss and blood transfusions indicate possible further evaluation. However, results suggest that HES is a safe additive to priming solutions. Compared with albumin, HES has comparable changes in coagulation variables and slightly less severe derangements in platelet aggregation.


Rare presentation of definitive ocular tuberculosis in an immunocompetent young patient.
Ocular tuberculosis is not uncommon ocular presentation in our community nowadays. Rare presentations described mainly in the immunocompromised patients. The diagnosis of ocular TB is presumed in the vast majority of the cases of the intraocular TB. We are presenting a very rare presentation of definitive intraocular TB in a healthy 24-year-old male.


Protein adsorbents intended for use in aqueous two-phase systems.
Preparation of adsorbents with high partition coefficients in polyethylene glycol-dextran and polyethylene glycol-phosphate systems is described. These adsorbents may be used to carry to carry proteins away from the insoluble cell fragments generated during cell disruption. By chromatographic elution, proteins may be selectively desorbed in a reduced volume.


Structure-activity relationships of 1-alkyl-5-(3,4-dichlorophenyl)-5-{2-[3-(substituted)-1-azetidinyl]-ethyl}-2-piperidones. Part 2: Improving oral absorption.
A series of piperidone analogues of 1b-q, seeking replacements for the polar sulfamide moiety in clinical candidate UK-224,671 1a, possessing reduced H-bonding potential as a strategy to improve oral absorption, were prepared. These studies led to the successful identification of 1n, which demonstrated equivalent pharmacology and metabolic stability to 1a, and greatly improved oral absorption as assessed in rat PK studies.


Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses.
Companion diagnostics aim to identify patients that will respond to targeted therapies, therefore increasing the clinical efficacy of such drugs. Less is known about their influence on safety and tolerability of targeted anti-cancer agents. Randomized trials evaluating targeted agents for solid tumors approved by the US Food and Drug Administration since year 2000 were assessed. Odds ratios (OR) and and 95% confidence intervals (CI) were computed for treatment-related death, treatment-discontinuation related to toxicity and occurrence of any grade 3/4 adverse events (AEs). The 12 most commonly reported individual AEs were also explored. ORs were pooled in a meta-analysis. Analysis comprised 41 trials evaluating 28 targeted agents. Seventeen trials (41%) utilized companion diagnostics. Compared to control groups, targeted drugs in experimental arms were associated with increased odds of treatment discontinuation, grade 3/4 AEs, and toxic death irrespective of whether they utilized companion diagnostics or not. Compared to drugs without available companion diagnostics, agents with companion diagnostics had a lower magnitude of increased odds of treatment discontinuation (OR = 1.12 vs. 1.65, p < 0.001) and grade 3/4 AEs (OR = 1.09 vs. 2.10, p < 0.001), but no difference in risk of toxic death (OR = 1.40 vs. 1.27, p = 0.69). Differences between agents with and without companion diagnostics were greatest for diarrhea (OR = 1.29 vs. 2.43, p < 0.001), vomiting (OR = 0.86 vs. 1.44, p = 0.005), cutaneous toxicity (OR = 1.82 vs. 3.88, p < 0.001) and neuropathy (OR = 0.64 vs. 1.60, p < 0.001). Targeted drugs with companion diagnostics are associated with improved safety, and tolerability. Differences were most marked for gastrointestinal, cutaneous and neurological toxicity.


Synthesis of 2-(2,4-dihydroxyphenyl)thieno-1,3-thiazin-4-ones, their lipophilicity and anticancer activity in vitro.
A new one-step synthesis of novel biologically active 2-substituted 2,4-dihydroxyphenyl-4[Formula: see text]-thieno[3,2-[Formula: see text]][1,3]thiazin-4-ones and 4[Formula: see text]-thieno[2,3-[Formula: see text]][1,3]thiazin-4-ones has been elaborated and described. The compounds were prepared by the reaction of aryl-modified sulfinylbis [(2,4-dihydroxyphenyl)methanethione]s and the corresponding aminothiophenecarboxamides. The derivatives showed anticancer activity in vitro. These compounds inhibited the proliferation and viability of lung cancer A549, colon cancer HT-29 and glioma C6 cells in a concentration-dependent manner. Some of the derivatives had no influence on normal skin fibroblasts culture viability. Moreover, one compound (1b) showed the ability to inhibit DNA synthesis in cancer cells, especially in C6 cells, and was not toxic for normal oligodendrocytes and hepatocytes. Using reversed phase RP 18 HPLC and immobilised artificial membrane (IAM) chromatography the phase affinity of the compounds was determined. The influence of lipophilicity on the activity of compounds has been discussed.


Biomarkers to Evaluate Androgen Deprivation Therapy for Prostate Cancer and Risk of Alzheimer's Disease and Neurodegeneration: Old Drugs, New Concerns.
Androgen deprivation therapy (ADT) is a standard treatment for prostate cancer patients, routinely used in the palliative or in the curative setting in association with radiotherapy. Among the systemic long-term side effects of ADT, growing data suggest a potentially increased risk of dementia/Alzheimer's disease in prostate cancer patients treated with hormonal manipulation. While pre-clinical data suggest that androgen ablation may have neurotoxic effects due to Aβ accumulation and increased tau phosphorylation in small animal brains, clinical studies have measured the impact of ADT on long-term cognitive function, with conflicting results, and studies on biological changes after ADT are still lacking. The aim of this review is to report on the current evidence on the association between the ADT use and the risk of cognitive impairment in prostate cancer patients. We will focus on the contribution of Alzheimer's disease biomarkers, namely through imaging, to investigate potential ADT-induced brain modifications. The evidence from these preliminary studies shows brain changes in gray matter volume, cortical activation and metabolism associated with ADT, however with a large variability in biomarker selection, ADT duration and cognitive outcome. Importantly, no study investigated yet biomarkers of Alzheimer's disease pathology, namely amyloid and tau. These preliminary data emphasize the need for larger targeted investigations.


Enzymatic hydrolysis of ammonia-treated sugar beet pulp.
Sugar beet pulp is a carbohydrate-rich coproduct generated by the table sugar industry. Beet pulp has shown promise as a feedstock for ethanol production using enzymes to hydrolyze polymeric carbohydrates and engineered bacteria to ferment sugars to ethanol. In this study, sugar beet pulp underwent an ammonia pressurization depressurization (APD) pretreatment in which the pulp was exploded by the sudden evaporation of ammonia in a reactor vessel. APD was found to substantially increase hydrolysis efficiency of the cellulose component, but when hemicellulose- and pectin-degrading enzymes were added, treated pulp hydrolysis was no better than the untreated control.


A sandwich ELISA for measuring benzo[a]pyrene-albumin adducts in human plasma.
Exposure to polycyclic aromatic hydrocarbons has often been quantified via DNA or human serum albumin (HSA) adducts of the carcinogenic metabolite benzo[a]pyrene diol epoxide (BPDE). We previously reported a sandwich ELISA, using 8E11 as capture antibody and anti-HSA as detection antibody, that detected intact BPDE adducts in HSA isolated from plasma. After confirming that BPDE binds to HSA at His146 and Lys195, we modified the ELISA to measure intact BPDE-HSA directly in human plasma. To adjust for interference due to nonspecifically bound HSA on well surfaces and to cross-reactivity of the antibodies, the ELISA employs paired wells with and without addition of BPDE tetrols to deactivate 8E11. By performing assays in quadruplicate, a series of sample-specific adjustments and screening steps are used to reduce measurement errors that are a consequence of detecting low BPDE-HSA concentrations in the general population. ELISA measurements of BPDE-HSA in plasma from smoking and nonsmoking subjects (range 0.280-2.88 ng BPDE-HSA/mg HSA) and from highway workers with and without exposure to asphalt emissions (range 0.346-13.9 ng BPDE-HSA/mg HSA) detected differences in BPDE-HSA levels in the a priori expected directions.


Hospital costs for robot-assisted laparoscopic radical hysterectomy and pelvic lymphadenectomy.
To compare robot-assisted laparoscopy and laparotomy for radical hysterectomy and pelvic lymphadenectomy in terms of hospital costs. Consecutive women undergoing radical hysterectomy and pelvic lymphadenectomy as a sole procedure between January 2001 and February 2012 were included. We compared OR times, hospital stay, procedure specific costs, blood transfusions and cost for readmissions and re-interventions until three months after surgery for 231 women operated who received either an open (n=51) or a robot-assisted laparoscopic radical hysterectomy (n=180). The hospital internal charges and purchase costs were used for estimation. The specific robotic cost was based on an investment depreciation time of seven years, with 400 operations performed annually, costs for maintenance, robotic instruments, robot-specific assistant's instruments and robot draping. The estimated mean costs for an open radical hysterectomy was $12,986, for the first 30 robotic radical hysterectomies was $18,382, and for the last 30 was $12,759, with a break even in cost after 90 robotic procedures. The specific robot costs ($3469) was, for the last robot cohort, compensated mainly by an average of 22 min shorter OR time and 4.9 days shorter hospital stay. Given 400 robot operations annually, and only after a substantial implementation period, it is feasible to perform robot-assisted radical hysterectomy at an equal hospital cost compared with open surgery.


Dose-dependent cytotoxicity induced by pristine graphene oxide nanosheets for potential bone tissue regeneration.
This study was aimed to investigate the toxic effects of pristine graphene oxide (GO) nanosheets on bone-marrow-derived mesenchymal stem cells (BMSCs), a type of traditional seed cells in tissue regeneration engineering. First, a GO suspension was prepared and characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, and Raman shifts. Then, rat BMSCs were isolated and characterized. Subsequently, cell proliferation, membrane integrity, cell cycle, cell apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were measured. In addition, relevant proteins of the mitochondrial apoptotic pathway and autophagy were analyzed. Our results showed that a high concentration of GO inhibited cell viability and membrane integrity, while cell apoptosis and cell-cycle arrest were induced by GO. Further, GO significantly increased ROS generation and MMP loss with an upregulation of Cleaved Caspase-3, LC3-II/I, and Beclin-1 and a downregulation of Bcl-2 and Caspase3. We concluded that the toxic effects of GO on BMSCs occurred in a dose-dependent manner via the mitochondrial apoptotic pathway and autophagy.


Effects of improved blood glucose on insulin-induced hypoglycaemia, TRH, GnRH and exercise tests in insulin-dependent diabetes.
In order to evaluate effects of metabolic control on pituitary function in insulin-dependent diabetes exercise, hypoglycaemia (insulin tolerance test), thyrotrophin releasing hormone and gonadotrophin releasing hormone, tests were performed on 25 patients before (Study 1) and after 2 weeks of improved metabolic control (Study 2). Patients were sub-divided into C-peptide negative (CpN, 10 patients with no residual C-peptide secretion) and C-peptide positive (CpP, 15 patients with residual beta-cell function) groups for analysis of results. Exercise induced higher growth hormone responses in CpN patients independent of metabolic control (P less than 0.001). Thyrotrophin releasing hormone induced higher growth hormone responses in CpN patients; this response was threefold greater after improved control (P less than 0.005). Growth hormone and cortisol response to hypoglycaemia and thyroid stimulating hormone and prolactin secretion in response to thyrotrophin releasing hormone were unaffected by residual beta-cell function or metabolic control. Luteinizing hormone response to gonadotrophin releasing hormone in CpN patients was impaired and lower after improved control (P less than 0.002). The results indicate an association between residual pancreatic insulin secretory and hypothalamic/pituitary function, possibly reflecting central neurosecretion of insulin.


Synthesis, molecular structure and anticancer activity of 1-allyl-3-amino-2-(4-chloro-2-mercaptobenzenesulphonyl)guanidine derivatives.
A series of 3-allylamino-6-chloro-7-R-1,1-dioxo-1,4,2-benzodithiazines (2a-e) was obtained by the reaction of 6-chloro-3-methylthio-1,4,2-benzodithiazine-1,1-dioxides (1a-e) with allylamine. Selective hydrazinolysis of the allylaminobenzodithiazines (2a-e) gave the appropriate 1-allyl-3-amino-2-(4-chloro-2-mercaptobenzenesulphonyl)guanidines (3a-e) in good yields. The reaction of 3a with dimethylsulphate under alkaline conditions provided the methylthio derivative 4. The structures of these compounds were confirmed on the basis of elemental analysis, spectral data (IR, 1H- and 13C-NMR) and X-ray analysis. Screening data indicated that the compounds 3a and 3d exhibited significant in vitro activities against numerous human tumour cell lines, whereas compounds 3b and 3c showed a moderate activity.


Biochemical effects of dipyridamole on purine overproduction and excretion by mutant murine T-lymphoblasts.
A mutant murine T-cell line which overproduces purines and excretes massive quantities of inosine into the culture medium has served as a cell culture model for overproduction hyperuricemia (Ullman, B., Wormsted, M. A., Cohen, M. B., and Martin, D. W., Jr. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 5127-5131). Incubation of these cells with micromolar concentrations of dipyridamole, a potent inhibitor of nucleoside transport, prevents the excretion of inosine and depresses the rate of purine biosynthesis to that of wild type cells. These concentrations of dipyridamole have no effect on cellular growth rate or on the intracellular nucleoside triphosphate or phosphoribosylpyrophosphate pools. We suggest that dipyridamole might also be useful in ameliorating purine overproduction associated with hyperuricemia and gout.


Platelet transmission electron microscopy for the assessment of poor biological response to antiplatelet agent: pilot descriptive and prospective study - ELECTROSTROKE.
Ischaemic stroke is the leading cause of adult disability. Thus, a strategy based on an efficient antiplatelet therapy has been developed. The monitoring of antiplatelet therapy is now limited to high risk and poor prognosis patients. Indeed, the biological monitoring of the antiplatelet therapy with available platelet function assays do not provide a global integrative approach. Platelet transmission electron microscopy, recently validated for assessing distinct ultrastructural abnormalities is a reliable morphological platelet structural analysis tool which could be used to collect all the ultrastructural platelet characteristics and assess the degree of activation of platelets. Our pilot prospective and descriptive study will include 50 consecutive patients hospitalized for an ischaemic stroke. We expect to identify ultrastructural characteristics that will be correlated with the degree of platelet activation to guide clinicians in decision making regarding the antiplatelet therapy strategy. The French Ethics Committee (comité de protection des personnes d'Ile-de-France VII) approved the information notice that will be given to participants and the protocol of this trial (protocol No 21-031).The results of the trial will be disseminated through scientific publications. NCT05004233.


Differential effects of C- and N-terminal substance P metabolites on the release of amino acid neurotransmitters from the spinal cord: potential role in nociception.
Extensive evidence implicates Substance P [SP(1-11)] as a primary afferent neurotransmitter or modulator of nociceptive information, and there is increasing evidence that the excitatory amino acids aspartate (Asp) and glutamate (Glu) may also act as nociceptive neurotransmitters. We have previously demonstrated that nociceptive stimulation (metatarsal injection of formalin) caused a tetrodotoxin (TTX)-sensitive release of Asp and a TTX-insensitive release of Glu from the dorsal spinal cord. We have also shown release of Asp and Glu following the direct infusion of SP(1-11), suggesting that formalin-induced Asp or Glu changes could be secondary to an initial release of SP(1-11). In contrast to nociception, pretreatment with TTX, reported here, had no effect on the SP(1-11)-induced release of Asp, suggesting a presynaptic mechanism. Behavioral experiments, in both our laboratory, and others, now suggest that the N-terminal products of SP metabolism play a distinct role in the modulation of SP(1-11) nociception, possibly through an interaction with an opiate receptor. To test the hypothesis that N- and C-terminal fragments of SP produce opposite effects on biochemical events potentially involved in nociception, we compared the effects of infusion of the N-terminal metabolite SP(1-7) and the C-terminal metabolite SP(5-11) on changes in the ECF concentration of amino acids in the spinal cord as a measure of their apparent release, using microdialysis. Intradiaylsate infusion of SP(5-11) increased the release of Asp, Glu, asparagine (Asn), glycine (Gly), and taurine (Tau). The changes in Asp, Glu, and Tau were similar in direction and magnitude to changes produced by SP(1-11) or formalin injection, further supporting the hypothesis that the C-terminal is responsible for the nociceptive effects of SP(1-11). In contrast, infusion of SP(1-7) significantly decreased the release of Asn, Tau, Glu, and Gly. This inhibition of amino acid release is consistent with the hypothesis that N-terminal metabolites produce opposite effects to those of C-terminal metabolites of SP(1-11). The decreases in Glu, Asn, Gly, and Tau following SP(1-7) infusion were significantly reduced by i.p. or intradialysate naloxone. Systemic naloxone had no significant effects on the SP(5-11)-induced amino acid changes; however, it did inhibit the SP(1-11)-induced increase in Asp and Glu. Intradialysate naloxone had no effect on the SP(1-11)-induced increases.(ABSTRACT TRUNCATED AT 400 WORDS)


Comparison of the effects of perceived self-efficacy on coping with chronic cancer pain and coping with chronic low back pain.
The purposes of this study were to explore the differences between chronic cancer pain and chronic low back pain with respect to (a) the use of coping strategies to manage pain and (b) the relationship between self-efficacy for attenuating pain and pain outcomes. Descriptive correlational design. Eighty-five patients experiencing chronic low back pain (n = 85) and 88 patients with chronic cancer pain (n = 88) were recruited for this study. Modified Coping Strategies Questionnaire, self-efficacy expectancies, and the Brief Pain Inventory. The major findings of this study were that (a) patients with chronic cancer pain reported significantly lower pain intensity and pain interference than did patients with chronic low back pain; (b) the most frequently used coping strategies were almost the same between the low back pain group and the cancer pain group; (c) for both chronic cancer pain and chronic low back pain groups, patients' perceived self-efficacy was significantly inversely correlated with pain intensity and pain interference with daily life; and (d) patients' use of coping strategies was positively correlated with pain intensity and pain interference with daily life. These findings were discussed in terms of implications for clinical practice and future research.


Zymolyase-Treatment and Polymerase Chain Reaction Amplification from Genomic and Plasmid Templates from Yeast.
Here, we present a protocol for amplifying DNA fragments from the genome of, or plasmids transformed into, yeast strains that require the use of the lytic enzyme zymolyase to break open the yeast cells by digesting the cell wall. Yeast strains requiring such treatment include YM4271 and Y1HaS2, whereas other yeast strains (e.g., MaV103) might not require treatment with Zymolyase.


Oil extraction from tiger nut (Cyperus esculentus L.) using the combination of microwave-ultrasonic assisted aqueous enzymatic method - design, optimization and quality evaluation.
Microwave-ultrasonic assisted aqueous enzymatic extraction (MUAAEE) was applied to extract tiger nut oil (TNO). The conditions of MUAAEE were optimized by Plackett-Burman design followed Box-Behnken design. An oil recovery of 85.23% was achieved under optimum conditions of a 2% concentration of mixed enzyme including cellulase, pectinase and hemicellulase (1/1/1, w/w/w), particle size <600 μm, microwave power 300 W, ultrasonic power 460 W, radiation temperature 40 °C, time 30 min, enzymolysis temperature 45 °C, pH 4.9, liquid-to-solid ratio 10 mL/g and time 180 min. Oil by MUAAEE revealed the similar fatty acid compositions, triglyceride compositions, thermal behaviour and flavour compared with oil by Soxhlet extraction (SE), while the oil quality of MUAAEE is superior to that of SE. Scanning electron microscopy revealed that structural disruption of tiger nut caused by MUAAEE facilitated the oil extraction. Results suggest that MUAAEE could be an efficient and environment-friendly method for extraction of TNO.


Expression, nucleotide sequence and mutational analysis of two open reading frames in the nif gene region of Anabaena sp. strain PCC7120.
A 1.8 kb transcript corresponding to a region of the Anabaena 7120 chromosome 4 kb downstream of the nifHDK operon appears 12-18 h after heterocyst induction. The DNA corresponding to this transcript was sequenced and found to contain two open reading frames, designated ORF 1 and ORF 2. Two polypeptides, of 30 kDa and 13 kDa, encoded by these ORFs were expressed in Escherichia coli. An apparent start site for the transcript, detected by S1 nuclease protection, was located 42 bp upstream of the ATG start codon of ORF 1. ORF 2 shows strong sequence similarity to ORF 6 in the nif gene region of Azotobacter vinelandii. ORF 1 was interrupted using a 1.4 kb neomycin resistance cassette and the resulting mutant grew very slowly on medium lacking combined nitrogen. The mutant had 45% of wild-type acetylene reduction activity, which could be complemented by a 2.8 kb EcoRI fragment of wild-type Anabaena DNA containing only ORF 1 and ORF 2. Thus, one or both of these ORFs is required for efficient nitrogen fixation in Anabaena.


Cesarean section by choice: constructing a reproductive rights framework for the debate.
The question of cesarean section by choice (that is, cesarean delivery in the absence of medical indications) has been hotly debated by the obstetrical profession in recent years. The debate has focused around questions of risks and benefits, and has revolved around questions of obstetrical practice. In this paper, the question will be framed in a reproductive rights context. How does the phenomenon of CSBC (cesarean section by choice) impact women's empowerment? Which reproductive rights might be affected by this question, and what policies are related to its use? FIGO's 1998 statement "Ethical Aspects regarding Cesarean Delivery for Non-Medical Reasons" is revisited, and, in light of these considerations, its contents are endorsed once again.


Use of microcapsules with electrostatically immobilized bacterial cells or enzyme extract to remove nonylphenol in wastewater sludge.
We investigated the use of a high-voltage electrostatic system to immobilize bacterial cells or enzyme extract in alginate microcapsules for removing nonylphenol (NP) from wastewater sludge. With applied potential increased from 0 to 12kV, the gel bead diameter decreased from 950 to 250 μm. The amount of bacterial cells or enzyme extract immobilized in alginate microcapsules was greater than that in suspension, for improved tolerance to environmental loadings. Removal of NP at 2.0-20.0 mg L(-1) was greater with extract- than cell-containing microcapsules. The percentage of toxic chemicals (2.0 mg L(-1)) removed with alginate microcapsules, in descending order of magnitude, was bisphenol-F>bisphenol-A>NP>oxytetracycline>chlortetracycline>tetracycline>dibromodiphenyl ethers>tetrabromobisphenol-A>decabromodiphenyl ether.


Chlorpromazine eliminates acute myeloid leukemia cells by perturbing subcellular localization of FLT3-ITD and KIT-D816V.
Mutated receptor tyrosine kinases (MT-RTKs) such as internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3 ITD) and a point mutation KIT D816V are driver mutations for acute myeloid leukemia (AML). Clathrin assembly lymphoid myeloid leukemia protein (CALM) regulates intracellular transport of RTKs, however, the precise role for MT-RTKs remains elusive. We here show that CALM knock down leads to severely impaired FLT3 ITD- or KIT D814V-dependent cell growth compared to marginal influence on wild-type FLT3- or KIT-mediated cell growth. An antipsychotic drug chlorpromazine (CPZ) suppresses the growth of primary AML samples, and human CD34+CD38- AML cells including AML initiating cells with MT-RTKs in vitro and in vivo. Mechanistically, CPZ reduces CALM protein at post transcriptional level and perturbs the intracellular localization of MT-RTKs, thereby blocking their signaling. Our study presents a therapeutic strategy for AML with MT-RTKs by altering the intracellular localization of MT-RTKs using CPZ.


Idiopathic internal jugular vein thrombosis in a patient with severe dizziness.
Upper torso deep vein thrombosis usually occurs in association with an indwelling venous catheter and/or malignancy as part of a paraneoplastic syndrome. However, idiopathic internal jugular vein thrombosis is a rare but potentially fatal condition. We report a 59-year-old woman who presented with severe dizziness. Ultrasonography and contrast-enhanced multislice computed tomography revealed thrombi in the left internal jugular vein. This patient had no malignancy, coagulation disorder, or infection. A ventilation/perfusion scan of the lungs showed no evidence of pulmonary embolism. This is a rare case of idiopathic thrombosis of the internal jugular vein.


[Reflex mechanism for maintaining magnesium homeostasis].
Local stimulation of the liver with MgC12 solution in unanesthetized dogs evoked a reflex magnesiuretic response by changing the tubular processes in the kidneys. The presence of selectively magnesium-sensitive receptors in the liver is supposed. The information from these receptors was shown to spread along the vagus nerves.


Dispersed graphene materials of biomedical interest and their toxicological consequences.
Graphene is one-atom thick nanocarbon displaying a unique honeycomb structure and extensive conjugation. In addition to high surface area to mass ratio, it displays unique optical, thermal, electronic and mechanical properties. Atomic scale tunability of graphene has attracted immense research interest with a prospective utility in electronics, desalination, energy sectors, and beyond. Its intrinsic opto-thermal properties are appealing from the standpoint of multimodal drug delivery, imaging and biosensing applications. Hydrophobic basal plane of sheets can be efficiently loaded with aromatic molecules via non-specific forces. With intense biomedical interest, methods are evolving to produce defect-free and dispersion stable sheets. This review summarizes advancements in synthetic approaches and strategies of stabilizing graphene derivatives in aqueous medium. We have described the interaction of colloidal graphene with cellular and sub-cellular components, and subsequent physiological signaling. Finally, a systematic discussion is provided covering toxicological challenges and possible solutions on utilizing graphene formulations for high-end biomedical applications.


Plasma membrane/cell wall perturbation activates a novel cell cycle checkpoint during G1 in Saccharomyces cerevisiae.
Cellular wound healing or the repair of plasma membrane/cell wall damage (plasma membrane damage) occurs frequently in nature. Although various cellular perturbations, such as DNA damage, spindle misalignment, and impaired daughter cell formation, are monitored by cell cycle checkpoint mechanisms in budding yeast, whether plasma membrane damage is monitored by any of these checkpoints remains to be addressed. Here, we define the mechanism by which cells sense membrane damage and inhibit DNA replication. We found that the inhibition of DNA replication upon plasma membrane damage requires GSK3/Mck1-dependent degradation of Cdc6, a component of the prereplicative complex. Furthermore, the CDK inhibitor Sic1 is stabilized in response to plasma membrane damage, leading to cell integrity maintenance in parallel with the Mck1-Cdc6 pathway. Cells defective in both Cdc6 degradation and Sic1 stabilization failed to grow in the presence of plasma membrane damage. Taking these data together, we propose that plasma membrane damage triggers G1 arrest via Cdc6 degradation and Sic1 stabilization to promote the cellular wound healing process.


Investigation of oxidative stress defenses of Neisseria gonorrhoeae by using a human polymorphonuclear leukocyte survival assay.
Neisseria gonorrhoeae has well-characterized oxidative stress defense systems that protect against oxidative killing in in vitro assays. In contrast, mutant strains of N. gonorrhoeae lacking oxidative stress defenses are identical to the wild type when tested in an ex vivo survival assay using human polymorphonuclear leukocytes.