Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats.
There is evidence from studies in humans and animals that a vulnerable period for chronic cannabinoid administration exists during certain phases of development. The present study tested the hypothesis that long-lasting interference of cannabinoids with the developing endogenous cannabinoid system during puberty causes persistent behavioral alterations in adult rats. Chronic treatment with the synthetic cannabinoid agonist WIN 55,212-2 (WIN) (1.2 mg/kg) or vehicle was extended over 25 days either throughout the rats' puberty or for a similar time period in adult rats. The rats received 20 injections intraperitoneally (i.p.), which were not delivered regularly. Adult rats were tested for object recognition memory, performance in a progressive ratio (PR) operant behavior task, locomotor activity, and prepulse inhibition (PPI) of the acoustic startle response (ASR). PPI was significantly disrupted only by chronic peripubertal cannabinoid treatment. This long-lasting PPI deficit was reversed by the acute administration of the dopamine antagonist haloperidol. Furthermore, we found deficits in recognition memory of pubertal-treated rats and these animals showed lower break points in a PR schedule, whereas food preference and locomotion were not affected. Adult chronic cannabinoid treatment had no effect on the behaviors tested. Therefore, we conclude that puberty in rats is a vulnerable period with respect to the adverse effects of cannabinoid treatment. Since PPI deficits, object recognition memory impairments, and anhedonia/avolition are among the endophenotypes of schizophrenia, we propose chronic cannabinoid administration during pubertal development as an animal model for some aspects of the etiology of schizophrenia.


Plasma and muscle free amino acids during continuous ambulatory peritoneal dialysis.
Free amino acids (AA) were determined in plasma and in muscle tissue of 29 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for 2 to 38 months. Muscle biopsies were taken in the morning after an overnight dwell with 1.36% glucose dialysis fluid. Muscle intracellular water was calculated using the chloride method. The intracellular (ic) and extracellular (ec) concentration and the ic/ec gradient for each AA was calculated and compared with values in matched healthy controls. Most of the essential and several non-essential AA were low in plasma. By contrast, none of the essential AA were low in muscle, and methionine was increased as were ornithine, asparagine, and aspartic acid; however, muscle taurine was markedly reduced. The ic/ec gradient was increased for most essential and several non-essential AA. In plasma, taurine precursors, methionine and cysteine, were not reduced and the ratios taurine/cysteine and taurine/methionine were low. Muscle taurine/methionine was also low. Thus, during CAPD muscle free AA are, in general, well maintained, suggesting that marked reductions of plasma AA levels in CAPD patients may reflect an ec to ic shift rather than depletion. The finding of low muscle taurine, but normal or increased cysteine and methionine pools, suggests that taurine depletion during CAPD is caused by blocked synthesis or low intake of taurine.


Age-dependent increase in the non-specific cholinesterase activity of the capillaries in the rat neostriatum.
Histochemically demonstrable non-specific cholinesterase activity in the capillaries of the neostriatum of 3-5-month-old rats was much weaker than that of 24-27-month-old rats. In the young adult rats the activity was electron microscopically localized mainly in endoplasmic reticulum and perinuclear cisternae of the endothelial cells, while capillaries of old rats showed a positive reaction also in the basal lamina and outer cell membranes of glial processes.


Concentrated Aqueous Sodium Tosylate as Green Medium for Alkene Oxidation and Nucleophilic Substitution Reactions.
A hydrotropic solution of highly concentrated sodium tosylate (NaOTs) can be used as a recyclable medium for the environmentally benign oxidation of conjugated alkenes with H2O2. Both uncatalyzed and metal-catalyzed reactions provided the corresponding oxidation products in higher yields than in pure water or many common organic solvents.


Calcitonin: a non-invasive giant cells therapy.
This paper reports four cases of central giant cell granuloma (CGCG) treated with calcitonin, attesting the efficacy and safety of its use as the chosen therapy for large CGCG. Four patients presenting CGCG treated with calcitonin were included in this study. Salmon calcitonin was administered for 6-28 months. It was observed determination of clear lesion limits for surgery, reduction and limitation of lesions. In aggressive cases, the calcitonin therapy was an excellent option, since it does not harm the patient, and a far less aggressive, complementary surgery may be performed in certain cases, avoiding life-long sequelae.


Modular Approach to Therapy for Anxiety, Depression, Trauma, or Conduct Problems in outpatient child and adolescent mental health services in New Zealand: study protocol for a randomized controlled trial.
Mental health disorders are common and disabling for young people because of the potential to disrupt key developmental tasks. Implementation of evidence-based psychosocial therapies in New Zealand is limited, owing to the inaccessibility, length, and cost of training in these therapies. Furthermore, most therapies address one problem area at a time, although comorbidity and changing clinical needs commonly occur in practice. A more flexible approach is needed. The Modular Approach to Therapy for Children with Anxiety, Depression, Trauma, or Conduct Problems (MATCH-ADTC) is designed to overcome these challenges; it provides a range of treatment modules addressing different problems, within a single training program. A clinical trial of MATCH-ADTC in the USA showed that MATCH-ADTC outperformed usual care and standard evidence-based treatment on several clinical measures. We aim to replicate these findings and evaluate the impact of providing training and supervision in MATCH-ADTC to: (1) improve clinical outcomes for youth attending mental health services; (2) increase the amount of evidence-based therapy content; (3) increase the efficiency of service delivery. This is an assessor-blinded multi-site effectiveness randomized controlled trial. Randomization occurs at two levels: (1) clinicians (≥60) are randomized to intervention or usual care; (2) youth participants (7-14 years old) accepted for treatment in child and adolescent mental health services (with a primary disorder that includes anxiety, depression, trauma-related symptoms, or disruptive behavior) are randomly allocated to receive MATCH-ADTC or usual care. Youth participants are recruited from 'mainstream', Māori-specific, and Pacific-specific child and adolescent mental health services. We originally planned to recruit 400 youth participants, but this has been revised to 200 participants. Centralized computer randomization ensures allocation concealment. The primary outcome measures are: (i) the difference in trajectory of change of clinical severity between groups (using the parent-rated Brief Problem Monitor); (ii) clinicians' use of evidence-based treatment procedures during therapy sessions; (iii) total time spent by clinicians delivering therapy. If MATCH-ADTC demonstrates effectiveness it could offer a practical efficient method to increase access to evidence-based therapies, and improve outcomes for youth attending secondary care services. Australian and New Zealand Clinical Trials Registry ACTRN12614000297628 .


Development of a single multiplex amplification refractory mutation system PCR for the detection of rifampin-resistant Mycobacterium tuberculosis.
A rapid and simple method for the detection of drug-resistant Mycobacterium tuberculosis is critical for the efficient treatment and control of this pathogen in developing country. Here we developed a single multiplex amplification refractory mutation system (M-ARMS) PCR, in which chimeric-primer and temperature switch PCR (TSP) strategy were included. Using this method, we detected rifampin resistance-associated mutations at codons 511, 516, 526 and 531 in the rifampin resistance-determining region of rpoB gene. The performance of M-ARMS-PCR assay was evaluated with 135 cultured isolates of M. tuberculosis. The sensitivity and specificity were 94.2% and 100%, respectively, compared with direct DNA sequencing, and 86.67% and 89.71%, respectively, compared with culture-based phenotypic drug susceptibility testing. Therefore, this newly-developed M-ARMS-PCR method is useful and efficient with an intended application in provincial Centers for Disease Control and Prevention for rapid detection of rifampin resistance-associated mutations.


Immunological studies on patients with optic neuritis without evidence of multiple sclerosis.
We studied 6 patients with idiopathic optic neuritis (ON) after a mean follow-up period of 12 years. No evidence of multiple sclerosis (MS) was found on clinical grounds, nor by magnetic resonance imaging (MRI) or evoked responses. Levels of spontaneous proliferation, serum gamma-interferon (IFN-gamma) and lymphocyte MHC locus II antigen were similar in ON and in 6 patients with progressive MS, but different in healthy controls. This suggests that similar immunological conditions in vivo prevail after an idiopathic ON and in MS. A normal PHA-induced interleukin-2 receptor expression and lymphocyte proliferation but a low IFN-gamma secretion and MHC locus II antigen expression were observed. This suggests that an ON and MS defect is expressed after an interleukin-2 receptor ligand but before IFN-gamma secretion. Our findings also suggest that immunological factors do not explain the neuropathological confinement of the lesions in ON but the protective influence may rather be exerted by some as yet undefined genetic influence or may be explained by the different etiology of ON and MS.


The neurological basis of motor asymmetry following unilateral 6-hydroxydopamine brain lesions in the rat: the effect of motor decortication.
The role of the motor cortex in the mediation of asymmetric movement after unilateral 6-hydroxydopamine (6-OHDA) brain lesions has been examined in the rat. The effect of unilateral and bilateral sensorimotor decortication upon spontaneous and drug (apomorphine and amphetamine)-induced motor asymmetry has been studied following unilateral injection of 6-OHDA into the lateral hypothalamus. Both bilateral decortication and unilateral decortication on the side of the 6-OHDA lesion caused a transient reversal of the spontaneous motor asymmetry normally seen in 6-OHDA lesioned animals. Neither unilateral nor bilateral sensorimotor decortication abolished drug-induced turning behaviour. It is postulated that subcortical basal ganglia efferent pathways may be involved in the mediation of motor asymmetry after unilateral 6-OHDA lesions of the nigrostriatal dopaminergic projection.


Effect of ursodeoxycholic acid after self-expandable metal stent placement in malignant distal biliary obstruction: a propensity score-matched cohort analysis.
Sludge occlusion is a primary reason for recurrent biliary obstruction (RBO) after self-expandable metallic stent (SEMS) placement. However, the efficacy of ursodeoxycholic acid (UDCA) for SEMS occlusion remains unexplored to date. This study aimed to evaluate the efficacy of UDCA after SEMS placement for malignant distal biliary obstruction (MDBO). Three hundred fifty-four patients were included, of which 60 received UDCA. Additionally, we conducted a propensity score-matched cohort analysis on 110 patients with SEMS placement for MDBO to reduce selection bias. Patients were categorized into 2 groups of 55 each, based on whether they received UDCA. In the UDCA group, the treatment was administered for more than a month. The primary endpoint was the time to RBO (TRBO) after SEMS placement. The secondary endpoint was to evaluate SEMS occlusion rate and early adverse events (AEs). The cumulative SEMS occlusion rate was 41.8% and 18.2% in the groups with and without UDCA, respectively (P = .0119). Median TRBO was significantly longer in the control group than in the UDCA group (528 vs 154 days, P = .0381). In the multivariate analysis, UDCA administration was identified as the independent risk factor for reducing TRBO (hazard ratio, 2.28; 95% confidence interval, 1.06-4.88; P = .0348). The overall early AE rate showed insignificant differences between groups. Administering UDCA after SEMS placement was not efficacious for prolonging the TRBO in MDBO. Moreover, administering UDCA beyond a month might increase the risk of stent sludge occlusion. (Clinical trial registration number: UMIN000046862.).


Simple ectopic kidney with renal artery originating from internal iliac bifurcation in a dog.
An ectopic left kidney together with an aberrant vascular structure were identified during a routine sterilization procedure in an eighteen-month-old female Akita Inu. Subsequently, ultrasound and computed tomography were performed to evaluate the clinical relevance. Based on these examinations' findings, a simple unilateral left-sided ectopic kidney with an abnormal course of the left renal artery as well as an earlier division of the right-sided renal artery were diagnosed. An ectopic kidney is clinically relevant differential diagnosis of secondary renal displacement or abdominal mass.


Gene therapy of malignant glioma: recent advances in experimental and clinical studies.
Recent advances in molecular tumor biology and gene technology have provided the possibility to treat patients with malignant brain tumors by altering gene expression in tumor cells. Tumor development and progression involves alterations in a wide spectrum of genes, therefore a variety of gene therapy approaches for malignant gliomas have been proposed. In this review article, we discuss some principles of current gene therapeutic strategies that are under investigation in laboratories and in clinics. In addition, some general issues that remain to be resolved for clinical application of gene therapy in patients with malignant gliomas will be addressed.


Tumor necrosis factor augments the immunogenicity and the production of L-ornithine by peritoneal macrophages.
The release of ornithine by macrophages and its correlation with their immunogenicity after treatment with recombinant human tumor necrosis factor-alpha (TNF) were analyzed. TNF was found to augment the capacity of peritoneal macrophages to convert 14C-labeled arginine into L-ornithine and to release L-ornithine into the culture medium. In agreement with the previous observation that L-ornithine potentiates immune responses in vivo, it was also found that treatment of peritoneal exudate cells with TNF augments the capacity of these cells to immunize mice in vivo for a subsequent secondary in vitro cytotoxic response against non-major-histocompatibility antigens.


Characterizing the heterogeneous metabolic progression in idiopathic REM sleep behavior disorder.
Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of synucleinopathies such as Parkinson's disease (PD). Positron emission tomography (PET) with 18F-FDG reveals metabolic perturbations, which are scored by spatial covariance analysis. However, the resultant pattern scores do not capture the spatially heterogeneous trajectories of metabolic changes between individual brain regions. Assuming metabolic progression occurs as a continuum from the healthy control (HC) condition to iRBD and then PD, we investigated spatial dynamics of progressively perturbed glucose metabolism in a cross-sectional study. 19 iRBD patients, 38 PD patients and 19 HC subjects underwent 18F-FDG PET. The images were spatially normalized, scaled to the global mean uptake, and automatically parcellated. We contrasted regional metabolism by group, and allocated the inferred progression to one of several possible trajectories. We further investigated the correlations between 18F-FDG uptake and the disease duration in the iRBD and PD groups, respectively. We also explored relationships between 18F-FDG uptake and the Unified Parkinson's Disease Rating Scale motor (UPDRS III) scores in the PD group. PD patients exhibited more extensive relative hyper- and hypo-metabolism than iRBD patients. We identified three dynamic metabolic trajectories, cross-sectional hypo- or hypermetabolism, cross-sectionally unchanged hypo- or hypermetabolism, cross-sectionally late hypo- or hypermetabolism, appearing only in the contrast of PD with iRBD. No correlation was found between relative 18F-FDG metabolism and disease duration in the iRBD group. Regional hyper- and hypo-metabolism in the PD patients correlated with disease duration or clinical UPDRS III scores. Cerebral metabolism changes heterogeneously in a continuum extending from HC to iRBD and PD groups in this preliminary study. The distinctive metabolic trajectories point towards a potential neuroimaging biomarker for conversion of iRBD to frank PD, which should be amenable to advanced pattern recognition analysis in future longitudinal studies.


Recent developments in colorimetric immunoassays using nanozymes and plasmonic nanoparticles.
Enzyme-linked immunosorbent assay (ELISA) is a popular detection technique for the screening and diagnosis of diseases. The sensitivity of ELISA can be increased by the incorporation of nanoparticles. Through this article, we discuss the utilization of nanoparticles in ELISA. Nanoparticles possess an intrinsic biological peroxidase-like activity which allows it to act as an enzyme mimic for the development of an improved analysis method. Different nanoparticles (gold nanoparticles, silver nanoparticles, etc.) carry different peroxidase-mimic characteristics. Besides this, nanoparticles can also perform as a colorimetric substrate in ELISA where it gives a more prominent color change compared to the commonly used colorimetric substrate TMB. This article also focuses on the mechanisms behind this color change including aggregation, in situ nanoparticle growth, seeding, and etching.


EM changes and other toxic effects of firemaster BP-6 (polybrominated biphenyls) in the mouse.
Groups of Swiss ICR mice were fed 1000 ppm polybrominated biphenyls (FireMaster BP-6) in rodent chow for 4, 8, 11, and 14 days. Control groups were fed standard rodent chow without FireMaster BP-6. Animals were killed at the end of each feeding period and the livers examined by electron microscopy. EM changes noted were progressive increase in size of hepatocytes, a decrease in rough endoplasmic reticulum, a marked increase in smooth endoplasmic reticulum, mitochondrial degeneration, increased lysosomes, and a decrease in glycogen. In addition, there was increasing proliferation of microvilli in bile canaliculi with increasing feeding times. A group of mice fed 1000 ppm FireMaster BP-6 in rodent chow for 11 days had livers with a mean of 13.93% of total body weight as compared with 6.49% for the control group (P=0.02). Tissue distribution following ingestion of 100 ppm FireMaster BP-6 for 14 days was studied. Twelve weeks post-feeding, the tissue concentrations of hexabromobiphenyl in order of highest concentration to lowest were as follows: perithymic fat, perirenal fat, adrenal glands, thymus gland, liver and stomach.


Zaprinast diminished pain and enhanced opioid analgesia in a rat neuropathic pain model.
The mechanism of neuropathic pain is complex and unclear. Based on our results, we postulate that an intensification of the kynurenine pathway occurs as a consequence of nerve injury. The G protein-coupled receptor 35 (GPR35) is important for kynurenine pathway activation. Cyclic GMP-specific phosphodiesterase inhibitors have also been shown to have beneficial effects on neuropathic pain. Therefore, the aims of our research were to elucidate how a substance that acts as both an agonist of GPR35 and an inhibitor of phosphodiesterase influences neuropathic pain in a rat model. Here, we demonstrated that preemptive and repeated intrathecal (i.t.) administration (16 h and 1 h before injury and then after nerve ligation daily for 7 days) of zaprinast (1 μg/5 μl) significantly attenuated mechanical (von Frey test) and thermal (cold plate test) hypersensitivity measured on day 7 after chronic constriction injury, and the effect of even a single injection lasted up to 24 h. Our data indicate that zaprinast diminished the number of IBA1-positive cells and consequently attenuated the levels of IL-1beta, IL-6, IL-18, and NOS2 in the lumbar spinal cord and/or dorsal root ganglia. Our results also demonstrated that zaprinast potentiated the analgesic properties of morphine and buprenorphine. In summary, in a neuropathic pain model, zaprinast significantly reduced pain symptoms and enhanced the effectiveness of opioids. Our data provide new evidence that modulation of both GPR35 and phosphodiesterase could be an important strategy for innovative pharmacological treatments designed to decrease hypersensitivity evoked by nerve injury.


Seasonal fluctuation in pathogenicity oFFusarium nivale (Gerlachia nivalis) to Lolium perenns L.
The changes in the degree of damage caused byFusarium nivale to Lolium perenne plants during different seasons around the year were observed, using the laboratory tests. The periods oF maximal and minimal pathogenicity of the fungus were determined. The graphic picture of seasonal changes in pathogenicity was constructed on the basis of results obtained for Argo variety and breeding population.


Metabolomic profiles of induced pluripotent stem cells derived from patients with rheumatoid arthritis and osteoarthritis.
Metabolomics is the systemic study of the unique fingerprints of metabolites involved in cellular processes and biochemical reactions. The metabolomic approach is useful in diagnosing and predicting the development of rheumatoid arthritis (RA) and osteoarthritis (OA) and is emerging as a useful tool for identifying disease biomarkers. The aim of this study was to compare the metabolic blueprint of fibroblast-like synoviocyte (FLS) cells and induced pluripotent stem cells (iPSCs) derived from RA and OA patients. Somatic cells of RA patients (n = 3) and OA patients (n = 3) were isolated, transduced with a lentiviral plasmid, and reprogrammed into iPSCs displaying pluripotency. Metabolic profiling of RA and OA patient-derived FLS cells and iPSCs was performed using liquid chromatography/mass spectrometry and statistical analysis. After normalization by the sum of the peak intensities through LC/MS, 37 metabolites were detected across RA and OA patients. The metabolites of RA and OA were distinguishable according to the PLS-DA analysis. LysoPC (20:4), 4-methoxychalcone, phosphorylcholine, and nicotinamide (NAM) were significantly higher in RA iPSCs than in OA iPSCs (p < 0.05). The NMNAT-3 enzyme, which catalyzes an important step in the biosynthesis of NAD+ from adenosine triphosphate, was also upregulated in RA iPSCs. Interestingly, the proliferation of RA iPSCs was significantly greater than OA iPSC proliferation (p < 0.05). NAM played a critical role in the proliferation of RA iPSCs but not in OA iPSCs. When iPSCs were treated with 100 nM of the NAM inhibitor tannic acid (TA), the proliferation of RA iPSCs was significantly reduced (p < 0.001). The metabolites of RA and OA FLS cells and RA and OA iPSCs were all clearly distinguishable from each other. NAM played a critical role in the proliferation of RA iPSCs but not in OA iPSCs. TA effectively inhibited the expression of NAM in RA iPSCs and is a possible effective treatment for RA patients.


Analysis of body mass index, weight loss and progression of idiopathic pulmonary fibrosis.
Nintedanib is an approved therapy for idiopathic pulmonary fibrosis (IPF). Some patients treated with nintedanib experience weight loss. Exploratory data suggest that low body mass index or weight loss are associated with worse outcomes in patients with IPF. We investigated whether BMI at baseline or weight loss over 52 weeks was associated with FVC decline, or influenced the effect of nintedanib, in patients with IPF. Using pooled data from the two INPULSIS trials, we analysed the rate of decline in FVC (mL/yr) over 52 weeks in patients treated with nintedanib and placebo in subgroups by baseline BMI (< 25; ≥25 to < 30; ≥30 kg/m2) and by weight loss over 52 weeks (≤5; > 5%) using random coefficient regression. In the placebo group, the mean rate of FVC decline over 52 weeks was numerically greater in patients with lower baseline BMI (- 283.3 [SE 22.4], - 207.9 [20.9] and - 104.5 [21.4] in patients with BMI < 25 kg/m2, ≥25 to < 30 kg/m2 and ≥ 30 kg/m2, respectively). Nintedanib reduced the rate of FVC decline versus placebo in all subgroups by BMI, with a consistent treatment effect across subgroups (interaction p = 0.31). In the placebo group, the mean rate of FVC decline was numerically greater in patients with > 5% than ≤5% weight loss over 52 weeks (- 312.7 [SE 32.2] versus - 199.5 [SE 14.4] mL/year). Nintedanib reduced the rate of FVC decline versus placebo in both subgroups by weight loss, with a greater treatment effect in patients with > 5% weight loss (interaction p = 0.0008). The adverse event profile of nintedanib was similar across subgroups. In patients with IPF, lower BMI and weight loss may be associated with faster decline in FVC. Nintedanib reduces the rate of FVC decline both in patients who lose weight on treatment and those who do not. ClinicalTrials.gov ; Nos. NCT01335464 and NCT01335477 ; URL: www.clinicaltrials.gov .


S-Nitrosylation in TNF superfamily signaling pathway: Implication in cancer.
One of the key features of tumor cells is the acquisition of resistance to apoptosis. Thus, novel therapeutic strategies that circumvent apoptotic resistance and result in tumor elimination are needed. One strategy to induce apoptosis is to activate death receptor signaling pathways. In the tumor microenvironment, stimulation of Fas, Death receptor 4 (DR4) and tumor necrosis factor receptor 1 (TNFR1) can initiate multiple signaling pathways driving either tumor promotion or elimination. Nitric oxide (NO) is an important signaling molecule now understood to play a dual role in cancer biology. More and more attention is directed toward the role displayed by S-nitrosylation, the incorporation of an NO moiety to a cysteine thiol group, in promoting cell death in tumor cells. Protein post-translation modification by S-nitrosylation has decisive roles in regulating signal-transduction pathways. In this review, we summarize several examples of protein modification by S-nitrosylation that regulate signaling pathways engaged by members of the TNF superfamily (Fas ligand (FasL), Tumor-necrosis-factor-related apoptosis inducing ligand (TRAIL) and TNFalpha (TNFα)) and the way it influences cell fate decisions.


Purification, characterization, and subsite affinities of Thermoactinomyces vulgaris R-47 maltooligosaccharide-metabolizing enzyme homologous to glucoamylases.
A maltooligosaccharide-metabolizing enzyme from Thermoactinomyces vulgaris R-47 (TGA) homologous to glucoamylases does not degrade starch efficiently unlike most glucoamylases such as fungal glucoamylases (Uotsu-Tomita et al., Appl. Microbiol. Biotechnol., 56, 465-473 (2001)). In this study, we purified and characterized TGA, and determined the subsite affinities of the enzyme. The optimal pH and temperature of the enzyme are 6.8 and 60 degrees C, respectively. Activity assays with 0.4% substrate showed that TGA was most active against maltotriose, but did not prefer soluble starch. Kinetic analysis using maltooligosaccharides ranging from maltose to maltoheptaose revealed that TGA has high catalytic efficiency for maltotriose and maltose. Based on the kinetics, subsite affinities were determined. The A1+A2 value of this enzyme was highly positive whereas A4-A6 values were negative and little affinity was detected at subsites 3 and 7. Thus, the subsite structure of TGA is different from that of any other GA. The results indicate that TGA is a metabolizing enzyme specific for small maltooligosaccharides.


Sex differences in ICI myocarditis: Hormones to the rescue.
Sex hormones may account for sex differences observed in the prevalence and susceptibility of ICI myocarditis (Zhang et al., this issue).


Vascular complication after insertion of a subcutaneous contraceptive implant.
Implanon is a reliable method of contraception widely used in France and around the world. Cases of difficulties encountered in inserting or removing the implant have been described. We report the first case of an insertion accident that led to occlusion of the right brachial artery and required exploratory vascular surgery.


Decreased levels of serum brain-derived neurotrophic factor in female patients with eating disorders.
Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays a role in the regulation of eating behavior. Because of its role in eating behavior, which is especially relevant to eating disorders, BDNF is an attractive candidate for investigation of potential biological markers of eating disorders such as bulimia nervosa (BN) and anorexia nervosa (AN). We enrolled 18 female patients with BN, 12 female patients with AN, and 21 age-matched female normal control subjects in this study. Eating-related psychopathology and depressive symptoms were evaluated using the Bulimic Investigatory Test, Edinburgh (BITE) and the Hamilton Depression Rating Scale (HDRS). Serum BDNF levels were measured by a sandwich enzyme-linked immunosorbent assay. Serum levels of BDNF in the patients with AN or BN were significantly (p<.0001) decreased compared with those of normal control subjects, and serum BDNF levels in the patients with AN were significantly (p=.027) lower than those in patients with BN. A significant positive correlation (r=.378, p=.006) between serum BDNF levels and body mass index in all of the subjects was detected. Furthermore, there was a significant positive correlation (r=.435, p=.015) between the BITE symptom scale score and HDRS in these patients. The present study suggests that BDNF may play a role in the pathophysiology of eating disorders.


Lumbar spinal ganglia enhancement after gadolinium chelate administration: a radio-histological correlation.
The aim of the present study was to assess the frequency of enhancement of lumbar spinal ganglia after Gadolinium chelate injection in patients without radiculopathy, and to correlate the enhancement with histology. This study is based on the analysis of MR lumbar examinations conducted on 18 patients without radicular symptoms, or previous surgery of the lumbar spine, or disease of the nervous system. The patients were imaged with a 1.5 T unit. Sagittal images were first obtained with a T1-weighted turbo spin-echo. Axial and sagittal images were then obtained with a T1-weighted turbo spin-echo, fat-saturated sequence after Gadolinium intravenous injection from the T12/L1 to the L5/S1 level. All 180 spinal ganglia demonstrated an important and homogeneous enhancement after Gadolinium injection. Four spinal ganglia obtained by dissection from four different fresh cadavers were studied by light microscopy to determine the potential relationship between contrast enhancement and presence and topography of vessels within the spinal ganglia. Vessels were particularly abundant at the peripheral zone of the spinal ganglia. The post-contrast enhancement of the spinal ganglia after Gadolinium administration has to be known and may be explained by the microvasculature pattern.


Adaptation of olfactory receptor abundances for efficient coding.
Olfactory receptor usage is highly heterogeneous, with some receptor types being orders of magnitude more abundant than others. We propose an explanation for this striking fact: the receptor distribution is tuned to maximally represent information about the olfactory environment in a regime of efficient coding that is sensitive to the global context of correlated sensor responses. This model predicts that in mammals, where olfactory sensory neurons are replaced regularly, receptor abundances should continuously adapt to odor statistics. Experimentally, increased exposure to odorants leads variously, but reproducibly, to increased, decreased, or unchanged abundances of different activated receptors. We demonstrate that this diversity of effects is required for efficient coding when sensors are broadly correlated, and provide an algorithm for predicting which olfactory receptors should increase or decrease in abundance following specific environmental changes. Finally, we give simple dynamical rules for neural birth and death processes that might underlie this adaptation.


Independent cellular effects of cold ischemia and reperfusion: experimental molecular study.
There is less information available on cell cultures on the exclusive effects of either duration of cold ischemia (CI) or rewarming-reperfusion in the kidney subjected to initial warm ischemia (WI). Therefore, the goals of our work were: (1) to evaluate the consequences on tubular cellular viability of different durations of CI on a kidney after an initial period of WI, and (2) to analyze the additional effect on tubular cell viability of rewarming of the same kidney. Sixteen mini-pig were used. All the animals were performed a right nephrectomy after 45-minute occlusion of the vascular pedicle. The kidneys were then divided into 2 groups (phase 1): cold storage in university of wisconsin (UW) solution for 3 hours (group A, n = 8) at 4°C, or cold storage in UW for 12 hours (group B, n = 8) at 4°C. Four organs of group A and four organs of group B were autotrasplanted (AT) and reperfused for 1 hour (phase 2). Nephrectomy was finally done. Biopsies were taken from all groups to perform cultures of proximal tubule epithelium cells. The biopsies were subjected to studies of cellular morphological viability (contrast phase microscopy [CPM]) and quantitative (confluence cell [CC]) parameters. Phase of pure CI effects (phase 1): Both CC rate and CPM parameters were significantly lower in group B compared with group A, where cell activity reached almost normal results. Phase of CI + AT (phase 2): At produced additional harmful effects in cell cultures compared with those obtained in phase 1, more evident in group B cells. The presence of cold storage followed by rewarming-reperfusion induces independent and cumulative detrimental effects in viability of renal proximal tubule cells. CI periods ≤ 3 hours may ameliorate the injuries secondary to reperfusion in comparison with longer CI periods.


Aerated biofiltration for simultaneous removal of iron and polycyclic aromatic hydrocarbons from groundwater.
Filters incorporating the principles of biological accumulation have been used in Europe to remove iron from drinking water for many years. The authors of this study hypothesized that a modified biological iron-removing filter could simultaneously degrade polycyclic aromatic hydrocarbons (PAHs) in groundwater impacted by former manufactured gas plant (MGP) operations. The MGP-impacted groundwater obtained for this study had an average total iron concentration of 3.8 mg/L and an average total dissolved PAH concentration of 3.0 mg/L. Naphthalene was the primary PAH, with an average concentration of 2.8 mg/L. The groundwater was passed intermittently through duplicate gravel-media columns at 15 to 30 cm/d for 2 months while filtered air was delivered countercurrently at 4 mL/min. The columns remained partially saturated throughout the study. Flooding, which would have indicated plugging of the columns, was not observed, and the pressure needed to aerate the columns remained constant. Total iron in the effluent was below the detection limit of 0.1 mg/L (97% removal) for 40 days of operation. Removal of total PAHs, primarily two- and three-ring compounds, averaged 99%. This single-stage treatment process represents an economical alternative to biological treatment systems currently available for MGP-impacted groundwater that require pretreatment to remove iron.


Impact of an exercise program in children with inflammatory bowel disease in remission.
The aim of our study was to investigate the impact of a structured exercise program on bone mineral density (BMD) and body composition parameters in children and adolescents with IBD in remission. Patients were recruited to participate in a 6-month exercise program. Total body less head (TLBH) dual energy X-ray absorptiometry (DXA) was used to measure BMD. The same method was used to assess fat mass (FM) and lean body mass (LBM) at baseline and at the completion of the program. Based on the baseline and endpoint TBLH DXA measurements, a total of 42 study participants (25 boys; aged 15.3 ± 2.08 years) experienced an increase in BMD (from 0.959 ± 0.023 g/cm2 to 0.988 ± 0.025 g/cm2, p < 0.001) and LBM (from 37.12 ± 1.43 kg to 38.75 ± 1.61 kg, p = 0.012). Age- and sex-based BMD Z-score increased significantly (from -0.35 ± 0.15 to -0.28 ± 0.17, p = 0.020), whilst LBM Z-score did not significantly change (from -1.78 ± 0.23 to -1.71 ± 1.49, p = 0.908). There was a significant improvement in BMD, age- and sex-based BMD Z-score, and LBM amongst study participants. Subgroup analysis showed that patients with CD and male study participants experienced significant improvement in all parameters, whilst patients with UC and IBD-U and female patients experienced improvement solely in BMD. Children and adolescents with IBD, regardless of disease activity, are under increased risk of secondary osteoporosis and lean body mass deficits. A 6-month home-based structured exercise program leads to a significant improvement in bone mineral density and lean body mass. Exercise therapy should be explored as a potentially adjacent to standard treatment modalities.


Recent developments in investigations of visual fields.
Methods are presented for screening and measuring central and peripheral visual fields as part of a vision examination. The paper describes static quantitative perimetry for single and multiple targets, the Visual Field Analyser, and kinetic and combined static and kinetic perimetry.


Artistic creativity and DBS: a case report.
Deep brain stimulation (DBS) is a treatment for patients with Parkinson's disease (PD) who are not adequately controlled with medications. An artist reported changes in her artistic creativity and art appreciation when treated with left DBS. We sought to study her artistic productions and her appreciation of art while both "on" and "off" left DBS. A 69-year-old right-handed woman with an approximate 20-year history of PD was referred to us for management of a left subthalamic region nucleus (STN) DBS placed at another institution 4 years prior. In Experiment 1 we had her rate several dimensions (Evocative Impact, Aesthetics, Novelty, Technique, Closure and Representation) of another artist's paintings. In Experiment 2, we tested her with the Abbreviated Torrance Test (of creativity) for Adults (ATTA). During testing the patient remained on her dopaminergic medication, but was tested on and off left DBS. On the judgment task while "on" left DBS, versus "off" DBS, there were significant reductions in her appreciation of artistic Closure and Technique. When "off" DBS her ATTA creativity index was above average, but when switched "on" her creativity index was below average. These results suggest the possibility that left ventral STN/SNR DBS reduces creativity as well as appreciation of art. The reason for these alterations is not known, but might be related to enhanced activation of the left hemisphere and reciprocal deactivation of the right hemisphere which mediates both visuospatial skills and global attention, both of which are important in artistic creativity and appreciation.


Optical clearing of the dura mater using glycerol: a reversible process to aid the post-mortem investigation of infant head injury.
In cases of suspected abusive head trauma, a thorough and systematic study of the cranium and its contents is essential, preferably using the best available methods for observing the brain and its coverings. Building upon recent developments in skull bone removal techniques in infant autopsies, we have assessed the use of two optical clearing agents (OCAs), glycerol and mannitol, on pediatric dura mater in an attempt to increase the transparency of this tissue and thereby enhance the post-mortem assessment of infant head injuries, particularly subdural hematomas. Extracorporeal testing revealed glycerol to be the more effective OCA. Therefore, in situ investigations were commenced using glycerol during 33 pediatric post-mortem examinations. An increase in the transparency of the dura was observed in 32 of the 33 cases, within 1 min of application of the OCA. In a 2 year old with cerebral palsy, only partial optical clearance of the dura was seen, most likely due to a significantly atrophic brain, prominent gelatinous leptomeninges, and abnormally thickened dura. This technique allowed for detection of minimal amounts of subdural bleeding over the convexities, before dissection of the dura, avoiding post-mortem blood spillage from artifactually disrupted bridging veins. Optical clearing of the dura aided in the evaluation of patterns of subdural hemorrhage in three cases of non-accidental head injury, three cases of peri-natal head injury and one case of overlaying, apparently resulting in minor crush injury to the head. We have demonstrated that glycerol is an effective and easy-to-use OCA to effect the readily reversible optical clearing of human infant calvarial dura at autopsy.


Selective inhibition of glial versus neuronal uptake of L-glutamic acid by SITS.
SITS, an inhibitor of anion exchange, was found to be a potent and selective inhibitor of L-glutamic acid uptake by cultured LRM55 glioma cells and rat brain astrocytes. Synaptosomal uptake of glutamate was relatively insensitive to inhibition by SITS. This differential effect indicates that the glutamate transport system in glia differs from that in neurons and that SITS may provide a tool for investigating the exclusive neuronal transport and metabolism of L-glutamic acid.


Withdrawal of antiepileptic drugs during presurgical video-EEG monitoring: an observational study for evaluation of current practice at a referral center for epilepsy.
Withdrawal of antiepileptic drugs (AEDs) before and during video-EEG-monitoring is commonly implemented to reduce time needed to register a sufficient number of seizures during presurgical evaluation. There are, however, few guidelines regarding withdrawal rate and observation time. We performed an observational study including sixty patients admitted to the national Norwegian epilepsy centre and registered tapering of AEDs and their effect on seizure rate and possible complications. The mean daily seizure rate before admission to the EMU was 0.4 (range 0.02-4) increasing to 1.1 (range 0-8) at the EMU. 29 patients (48%) followed a slow tapering rate whereas 31 (52%) had an intermediate tapering rate. There was no significant difference between the patients with a daily seizure rate during LTM of more or <0.7 seizures per day, an increase of seizure frequency from habitual to during LTM of more or <3.3 or 6.9 with regard to rate of tapering (slow vs intermediate) etiology or AED monotherapy vs polytherapy. Twenty-six patients (43%) had a sufficient number of seizures registered within 3 days to conclude regarding the presurgical evaluation. Two patients received escape treatment while 25 patients did have 24 h-seizure-clusters. There was no serious event. Less than 50% of the patients got a sufficient number of seizures for a conclusive result within 3 days. An increase in the registration period could increase the number of successful registrations.


Facial affect recognition in body dysmorphic disorder versus obsessive-compulsive disorder: An eye-tracking study.
Body dysmorphic disorder (BDD) is characterised by repetitive behaviours and/or mental acts occurring in response to preoccupations with perceived defects or flaws in physical appearance (American Psychiatric Association, 2013). This study aimed to investigate facial affect recognition in BDD using an integrated eye-tracking paradigm. Participants were 21 BDD patients, 19 obsessive-compulsive disorder (OCD) patients and 21 healthy controls (HC), who were age-, sex-, and IQ-matched. Stimuli were from the Pictures of Facial Affect (Ekman & Friesen, 1975), and outcome measures were affect recognition accuracy as well as spatial and temporal scanpath parameters. Relative to OCD and HC groups, BDD patients demonstrated significantly poorer facial affect perception and an angry recognition bias. An atypical scanning strategy encompassing significantly more blinks, fewer fixations of extended mean durations, higher mean saccade amplitudes, and less visual attention devoted to salient facial features was found. Patients with BDD were substantially impaired in the scanning of faces, and unable to extract affect-related information, likely indicating deficits in basic perceptual operations.


Arteriosclerotic changes in the myocardium, lung, and kidney in dogs with chronic congestive heart failure and myxomatous mitral valve disease.
The occurrence of small vessel arteriosclerosis in the myocardium, kidney, and lung in dogs with naturally occurring myxomatous mitral valve disease has not been previously investigated systematically. Twenty-one dogs with naturally occurring congestive heart failure and 21 age-matched, sex-matched, and weight-matched control dogs underwent extensive pathological and histopathological examination. Morphometry and scoring of tissue sections were used to measure arterial narrowing and fibrosis in the myocardium, kidney, and lung; and intimal thickness and plaque formation in the aorta and pulmonary artery. Dogs with congestive heart failure had significantly more arterial narrowing in the left ventricle (P < .003), lung (P < .0001), and kidney (P < .02); intimal-medial thickening in the pulmonary artery (P = .04); and fibrosis in the left ventricle (P < .0001) than control dogs. However, they did not have more plaque formation or intimal-medial thickening in the aorta than controls. There was significantly more arterial narrowing in papillary muscles than in all other locations in dogs with congestive heart failure (P < .002). In control dogs, arterial changes were less pronounced and did not differ in different locations. Dogs with naturally occurring myxomatous mitral valve disease have significantly more arterial changes in the myocardium, lung, and kidney, and significantly more fibrosis in the myocardium than control dogs. This could have important implications in the management of myxomatous mitral valve disease and raises interesting questions about the occurrence and importance of intramural small vessel disease in humans with primary mitral valve prolapse.


Black Mn-containing layered double hydroxide coated magnesium alloy for osteosarcoma therapy, bacteria killing, and bone regeneration.
Osteosarcoma (OS) tissue resection with distinctive bactericidal activity, followed by regeneration of bone defects, is a highly demanded clinical treatment. Biodegradable Mg-based implants with desirable osteopromotive and superior mechanical properties to polymers and ceramics are promising new platforms for treating bone-related diseases. Integration of biodegradation control, osteosarcoma destruction, anti-bacteria, and bone defect regeneration abilities on Mg-based implants by applying biosafe and facile strategy is a promising and challenging topic. Here, a black Mn-containing layered double hydroxide (LDH) nanosheet-modified Mg-based implants was developed. Benefiting from the distinctive capabilities of the constructed black LDH film, including near-infrared optical absorption and reactive oxygen species (ROS) generation in a tumor-specific microenvironment, the tumor cells and tissue could be effectively eliminated. Concomitant bacteria could be killed by localized hyperthermia. Furthermore, the enhanced corrosion resistance and synergistic biofunctions of Mn and Mg ions of the constructed black LDH-modified Mg implants significantly facilitated cell adhesion, spreading and proliferation and osteogenic differentiation in vitro, and accelerated bone regeneration in vivo. This work offers a new platform and feasible strategy for OS therapeutics and bone defect regeneration, which broadens the biomedical application of Mg-based alloys.


Experimental and theoretical investigation on the nonlinear optical properties of LDS 821 dye in different solvents and DNA.
Linear and nonlinear optical properties of near-infrared laser grade dye LDS 821 in different solvents and Salmon Deoxyribonucleic acid (DNA) were studied using spectroscopic and Z-scan techniques. UV-Vis absorption spectrum of the dye shows a bathochromic shift with a decrease in the solvent polarity parameter, and in DNA, the dye exhibits a hypochromic shift. The fluorescence spectrum of the dye does not show any notable correlation with the solvent polarity parameter, but in DNA, the fluorescence intensity of the dye decreases with the incremental addition of DNA. Molecular docking studies reveal that the dye intercalates on the major grooves of DNA. Nonlinear optical properties of the dye in different solvents and phosphate buffer solution with varying DNA concentrations were studied using the Z-scan technique using a Q-switched Nd: YAG laser operating at fundamental and second harmonics. A closed and open aperture Z-scan of dye in different solvents was carried out to estimate the nonlinear refractive index, excited-state absorption cross-section, and two-photon absorption coefficient (TPA). The variation in nonlinear optical properties of the dye in different solvents was due to solvent-induced structural modifications. Theoretical investigation on nonlinear optical properties of the dye in different solvents was carried out using density function theory. The theoretical first and second-order hyperpolarizability was calculated using B3LYP functional. The predicated nonlinear optical parameters of the dye in different solvents does not show any direct correlation with solvent polarity. Nonlinear absorption of the dye in phosphate buffer solution (PBS) and DNA were estimated. The nonlinear absorption of the dye in PBS decreases with the addition of DNA. Molecular docking studies were carried out to determine the structural changes induced in dye due to the intercalation with DNA.


Afferents and efferents of the vestibular nuclei: the necessity of context-specific interpretation.
A synopsis of physiological and anatomical results is presented that leads to the conclusion that experimental data have to be interpreted in a context meaningful for the system investigated. For example, since there is an obvious spatial relationship between semicircular canals and extraocular muscles, the interdependence between the three-neurone-arc circuitry, and vestibular and visual signals follows quite naturally from a common geometry inherent in the sensory and motor periphery. It is emphasized that signals related to compensatory eye movements have to be interpreted within a vestibular/eye muscle frame of reference. By the same argument, when dealing with the head-neck movement system, the appropriate reference frame will have to be applied to arrive at a meaningful interpretation of related sensorimotor functions. Thus, in general terms, each system has to be interpreted within its own meaningful biological context.


[Antioxidant effect of high-density lipoproteins in the peroxidation of low-density lipoproteins].
It has been shown that in the solution of low density lipoproteins (LDL) during their incubation at 37 degrees C the turbidity and concentration of malondialdehyde was increased, as compared to that observed at 4 degrees C. Both parameters were slowed down by the addition of high density lipoproteins (HDL) into the medium. The protective effect of HDL depended on the time of incubation and the concentration of HDL added. Delipidated HDL had no effect. Similar action of HDL was established in the experiments where the peroxidation in LDL was induced by the xanthine-xanthine oxidase. The data obtained demonstrate that HDL possess an antioxidant property that may play an important role in their antiatherogenic action.


A gel-forming beta-glucan isolated from the fruit bodies of the edible mushroom Pleurotus florida.
Glucans of basidiomycetes are considered to be an important class of polysaccharides, as they can act as biological response modifiers. We now isolate a gel-forming, water-soluble beta-glucan, with a molecular mass of 1.2 x 10(6)g/mol (HPSEC), from the fruit bodies of the edible mushroom Pleurotus florida, via alkaline extraction, followed by fractionation by freeze-thawing. Structural assignments were carried out using mono- and bi-dimensional nuclear magnetic resonance spectroscopy, monosaccharide composition, methylation analyses, and a controlled Smith degradation. It was a branched beta-glucan, with a main chain of (1-->3)-linked-Glcp residues, substituted at O-6 by single-unit Glcp side chains, on average to every fourth residue of the backbone.


Non-high-density lipoprotein cholesterol, guideline targets, and population percentiles for secondary prevention in 1.3 million adults: the VLDL-2 study (very large database of lipids).
This study sought to examine patient-level discordance between population percentiles of non-high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Non-HDL-C is an alternative to LDL-C for risk stratification and lipid-lowering therapy. The justification for the present guideline-based non-HDL-C cutpoints of 30 mg/dl higher than the LDL-C cutpoints remains largely untested. We assigned population percentiles to non-HDL-C and Friedewald-estimated LDL-C values of 1,310,440 U.S. adults with triglyceride levels <400 mg/dl who underwent lipid testing by vertical spin density gradient ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011. LDL-C cutpoints of 70, 100, 130, 160, and 190 mg/dl were in the same population percentiles as non-HDL-C values of 93, 125, 157, 190, and 223 mg/dl, respectively. Non-HDL-C values reclassified a significant proportion of patients within or to a higher treatment category compared with Friedewald LDL-C values, especially at LDL-C levels in the treatment range of high-risk patients and at triglyceride levels ≥150 mg/dl. Of patients with LDL-C levels <70 mg/dl, 15% had a non-HDL-C level ≥ 100 mg/dl (guideline-based cutpoint) and 25% had a non-HDL-C level ≥ 93 mg/dl (percentile-based cutpoint); if triglyceride levels were 150 to 199 mg/dl concurrently, these values were 22% and 50%, respectively. There is significant patient-level discordance between non-HDL-C and LDL-C percentiles at lower LDL-C and higher triglyceride levels, which has implications for the treatment of high-risk patients. Current non-HDL-C cutpoints for high-risk patients may need to be lowered to match percentiles of LDL-C cutpoints. Relatively small absolute reductions in non-HDL-C cutpoints result in substantial reclassification of patients to higher treatment categories with potential implications for risk assessment and treatment.


Treatment of L5178Y tumor-bearing BDF1 mice with a nonimmunogenic L-glutaminase-L-asparaginase.
An L-glutaminase-L-asparaginase from Achromobacter has been rendered nonimmunogenic by the covalent attachment of polyethylene glycol (PEG) to nonessential amine groups of the enzyme. PEG-L-glutaminase-L-asparaginase exhibits a greatly enhanced half-life in the bloodstream compared to the unmodified enzyme in normal mice, and is effective in prolonging the survival of BDF1 mice inoculated ip with L5178Y cells. PEG-L-glutaminase-L-asparaginase appears rapidly in the blood following ip injection.


Phenotypic and genotypic lineage switch of a lymphoma with shared chromosome translocation and T-cell receptor gamma gene rearrangement.
A case of non-Hodgkin's lymphoma showed a phenotypic and genotypic cell lineage switch twice during nine years of his clinical history; first, T-cell type, pleomorphic small cell lymphoma developed, followed by B-cell type, diffuse centroblastic/centrocytic lymphoma, and finally T-zone lymphoma without follicles again developed, from which AST-1 cultured cell line was established. Karyotype analysis demonstrated a shared abnormal chromosome, der(1)t(1;?)(p36;?), among the first relapsed B-cell tumor, the second relapsed T-cell tumor and AST-1 cell line. Furthermore, T-cell receptor (TCR) gamma gene rearrangement bands of the same size were observed in the first relapsed B-cell tumor and the second relapsed T-cell tumor as well as AST-1 cell line. These results suggested that both relapsed tumors of different cell lineages are derived from a common malignant clone, presumably a committed lymphoid stem cell. A unique translocation, t(2;14)(q37;q11.2), which may involve TCR delta/alpha gene complex, was observed in the second relapsed tumor and AST-1 cells. To attempt to isolate the breakpoint of this translocation, the configuration of TCR delta/alpha gene complex was studied. The result showed that two rearrangements of TCR alpha gene detected with J alpha probes were the products of the normal TCR rearrangement process, and were not involved in the translocation at this region. This patient, together with the AST-1 cell line, provided us a unique opportunity to study the development and clonal evolution of malignant lymphoma.


Association between Body Condition Score and Cancer Prognosis in Dogs with Lymphoma and Osteosarcoma.
In humans and rodents obesity appears to promote some cancers by increasing incidence, tumor aggressiveness, recurrence, and fatality. However, the relationship between obesity and cancer in dogs has not been thoroughly evaluated. Whether body condition score (BCS) at the time of lymphoma (LSA) or osteosarcoma (OSA) diagnosis in dogs is predictive of survival time (ST) or progression-free interval (PFI). We hypothesized that an overweight body state at the time of cancer diagnosis would be associated with negative outcomes. Dogs with LSA (n = 270) and OSA (n = 54) diagnosed and treated between 2000 and 2010. Retrospective case review. Signalment, body weight, BCS, cancer diagnosis and treatment, relevant clinicopathologic values, and survival data were collected. Dogs were grouped by BCS (underweight, ideal, and overweight) and ST and PFI were compared. Overall, 5.5% of dogs were underweight, 54.0% were ideal weight, and 40.4% were overweight at diagnosis. Underweight dogs with LSA had shorter ST (P = .017) than ideal or overweight dogs. BCS was not associated with ST for OSA (P = .474). Progression-free interval did not differ among BCS categories for either cancer. Obesity was not associated with adverse outcomes among dogs with LSA or OSA in this retrospective study; however, being underweight at the time of diagnosis of LSA was associated with shorter survival. More research is needed to elucidate the relationship between excessive body weight and cancer development and progression in dogs.


Amphetamine-type stimulants use and socio-economic factors associated with hepatitis C antibody positivity among border drug users in South of China.
Amphetamine-type stimulants (ATS) use has become popular in China. This study explored ATS use status and related risk factors of hepatitis C virus (HCV) infection among ATS users in Jinghong City, Xishuangbanna Prefecture, Yunnan Province, China. A cross-sectional study was conducted by questionnaires from January to July 2021 in border area in Yunnan. Respondent driving sampling and consecutive sampling was carried out among border drug users, and blood samples were tested for HCV antibodies. HCV infection and related risk factors among ATS users were measured. Descriptive, univariate and multivariate analysis were conducted separately by Software SPSS 26.0. The ATS users accounted for 85.82% (345/402) among drug users, while anti-HCV antibody prevalence was 6.38% (22/345) among ATS users. The combined use of other types of drugs (OR = 7.29, 95%CI: 1.982-26.81, P = 0.003), injection drug use (OR = 6.823, 95%CI: 1.898-24.525, P = 0.003), average monthly income (OR = 4.825, 95%CI: 1.325-17.566, P = 0.017) might increase the risk of HCV infection among ATS users. ATS users with high school or above had higher HCV infection rates than those with primary school or below (OR = 5.718, 95%CI: 1.172-27.908, P = 0.031). Taken together, among drug users using ATS in Jinghong City, Xishuangbanna Autonomous Prefecture, Yunnan Province, combined use of multiple drugs and intravenous drug use was the high risk factor for HCV infection. Therefore, corresponding education and intervention measures should be taken.


Contractile activity and motility responses of the dog heartworm Dirofilaria immitis to classical anthelmintics and other compounds.
A variety of compounds including classical anthelmintics and avermectin analogs were screened for their effects on movements of adult heartworms (HW) (Dirofilaria immitis). Contractile activity was measured by tension recording of spontaneous movements of intact HW coil preparations (6 min compound exposure) and motility was evaluated by observation of spontaneous, free movements in culture (3 and 7 days compound exposure). Results for female HW indicated that some compounds caused spastic paralysis of contractile activity and inhibition of motility in culture (bephenium, DL-tetramisole, and pyrantel); some caused only spastic paralysis of contractile activity (methyridine and disophenol); and some caused only inhibition of motility in culture (chlorpromazine, dithiazanine, 1-ethoxycarbonylmethyl-1-methylpyrrolidinium, and 4-methyltropolone). Effects on motility in culture appeared to be lethal. The following compounds lacked effects: amprolium, 2-amino-2-thiazoline, bithionol, bitoscanate, bitriben, hexachlorophene, ivermectin, and 10 H-phenothiazine. A group of avermectin analogs was screened for effects only on motility in culture of both adult female and male HW. Several of the analogs affected motility, but the effects appeared to be non-lethal. Microfilaria release into the culture media was suppressed by two of the analogs (an aglycone and avermectin B2). The HW maintenance system used in the present study facilitated screening of compounds for effects on this parasite.


Pediatric patient with restrictive cardiomyopathy on staged biventricular assist device support with Berlin Heart EXCOR® underwent heart transplantation successfully: the first case in Japan.
Pure restrictive cardiomyopathy is a strong risk factor for poor outcomes in children with cardiomyopathy on ventricular assist devices. Owing to concomitant right heart failure, children with end-staged restrictive cardiomyopathy who are supported with a ventricular assist device often require a biventricular assist device, which is another risk factor for waitlist mortality in heart transplantation candidates. Herein, we report the case of a 3-year-old boy with pure restrictive cardiomyopathy who successfully underwent heart transplantation after 12 months of support with staged biventricular assist devices. Owing to the progression of diastolic dysfunction, the left ventricular assist device could not provide adequate circulation support. Despite the provision of biventricular assist device support, the patient required a complex management strategy that involved balancing the left and right ventricular assist device supports. We were able to stabilize the patient by careful synchronization of the supports and proceeded to heart transplantation. TRIAL REGISTRATION: Clinical Registration No.: Institutional Review Board of Osaka University Hospital, approval no. 16105.


Breastfeeding Duration and Authoritative Feeding Practices in First-Time Mothers.
Longer breastfeeding duration appears to have a protective effect against childhood obesity. This effect may be partially mediated by maternal feeding practices during the first years of life. However, the few studies that have examined links between breastfeeding duration and subsequent feeding practices have yielded conflicting results. Using a large sample of first-time mothers and a newly validated, comprehensive measure of maternal feeding (the Feeding Practices and Structure Questionnaire), this study examined associations between breastfeeding duration and maternal feeding practices at child age 24 months. Mothers (n = 458) enrolled in the NOURISH trial provided data on breastfeeding at child age 4, 14, and 24 months, and on feeding practices at 24 months. Structural equation modeling was used to examine associations between breastfeeding duration and 5 nonresponsive and 4 structure-related "authoritative" feeding practices, adjusting for a range of maternal and child characteristics. The model showed acceptable fit (χ(2)/df = 1.68; root mean square error of approximation = .04, comparative fit index = .91, and Tucker-Lewis index = .89) and longer breastfeeding duration was negatively associated with 4 out of 5 nonresponsive feeding practices and positively associated with 3 out of 4 structure-related feeding practices. Overall, these results suggest that mothers who breastfeed longer reported using more appropriate feeding practices. These data demonstrate an association between longer breastfeeding duration and authoritative feeding practices characterized by responsiveness and structure, which may partly account for the apparent protective effect of breastfeeding on childhood obesity.


Isolation and characterization of UDP-galactose:N-acetylglucosamine 4 beta-galactosyltransferase activity induced in rat parotid glands treated with isoproterenol.
Chronic injection of the beta-adrenergic receptor agonist isoproterenol causes a 6- to 10-fold increase in the specific activity of the Golgi membrane marker enzyme UDP-galactose:D-glucose 4-beta-D-galactosyltransferase (EC 220.127.116.11) in rat parotid glands. Using a combination of size exclusion chromatography and affinity chromatography on alpha-lactalbumin-agarose, the Triton X-100-solubilized enzyme was purified to homogeneity from treated and control animals. The enzyme purified from both sources had a single Mr = 60,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme isolated from control and isoproterenol-treated animals had identical amino acid compositions and isoelectric points (pI = 5.9). Neutral sugar content as determined by the phenol-sulfuric acid assay was 10%. UDP-galactose:N-acetylglucosamine 4 beta-galactosyltransferase activity purified by alpha-lactalbumin column chromatography was inhibited by the presence of 200 mM N-acetylglucosamine and by the inclusion of alpha-lactalbumin in assays using 10 mM N-acetylglucosamine as acceptor. Increased enzyme activity was immune precipitated from Triton X-100-solubilized membrane prepared from isoproterenol-treated animals versus control animals. This was also true of protein synthesized by in vitro translation of poly(A+) RNA prepared from parotid glands, indicating an increase in mRNA levels for the enzyme. The molecular mass of the immune-precipitated, in vitro translation product was determined to be 45,000 Da.


Is routine antenatal booking vaginal examination necessary for reasons other than cervical cytology if ultrasound examination is planned?
Sixteen ovarian cysts, including one borderline ovarian malignancy, and ten trichomonal vaginal discharges but no cases of cervical incompetence or ectopic pregnancy had been detected at booking vaginal examination in 11,622 consecutive antenatal case records abstracted retrospectively. In an attitude survey of pregnant women 77% believed that vaginal examination was reassuring, 55% found it unpleasant, and 18% thought it could cause miscarriage. This, and a review of the literature, suggests that routine vaginal examination if ultrasound is planned has few advantages beyond the taking of a cervical smear.


Kinesin family member KIF18A is a critical cellular factor that regulates the differentiation and activation of dendritic cells.
KIF18A is a kinesin family member that is involved in various cellular processes including cell division, cell transformation, and carcinogenesis. However, its possible role in the regulation of host immunity has not been examined. The aim of this study is to investigate the functional role of KIF18A in the differentiation and activation of dendritic cells (DCs) that are the most efficient antigen-presenting cells. A bioinformatic analysis of the KIF18A gene family was performed to understand its sequence variability and evolutionary history. To inhibit KIF18A activity, a highly specific small molecule inhibitor for KIF18A, BTB-1 was used. DCs were differentiated from mouse bone marrow (BM) cells from 6 to 7 week old C57BL/6 mice with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). Expression of KIF18A was measured by Western blotting. The surface expression of differentiation and activation markers on DCs were analyzed by flow cytometry. The phylogenetic analysis revealed that the KIF18A gene family is remarkably conserved across vertebrates. Interestingly, the expression of KIF18A was increased as BM precursor cells differentiated into DCs. BTB-1 treatment strongly inhibited the differentiation of BM cells into DCs in a dose-dependent manner. Furthermore, treatment of immature DCs with BTB-1 significantly impaired the expression of activation markers on DCs including MHC class I, CD80, and CD86 upon TLR4 or TLR7 treatment. Our results reveal that KIF18A is a critical DC differentiation and activation regulator. Therefore, KIF18A could be a potential therapeutic target for immune-mediated disorders.


High resolution melting analysis as a new approach to discriminate gluten-containing cereals.
With this work, it is intended to propose a novel approach based on high resolution melting (HRM) analysis to detect wheat and discriminate it from other gluten-containing cereals. The method consisted of a real-time PCR assay targeting the gene encoding for the germ agglutinin isolectin A protein (Tri a 18 allergen), using the fluorescent Evagreen dye combined with HRM analysis. The results enabled wheat differentiation from other phylogenetically related cereals, namely barley, rye and oat with high level of confidence. Additionally, a quantitative real-time PCR approach was proposed, allowing detecting and quantifying wheat down to 20mg/kg in rice flour and 20pg of wheat DNA (∼1.1 DNA copies). Its application was successfully achieved in the analysis of processed foods to verify labelling compliance, being considered as a cost-effective tool for the specific detection of cereals in gluten-free foods.


Effects of hardness on the disintegration time and the dissolution rate of uncoated caffeine tablets.
The effects of hardness on disintegration and dissolution characteristics of uncoated caffeine tablets made at eight different pressure levels were studied. The disintegration times were determined using the J.P. VIII procedure with disks and the dissolution rate measurements were performed with the U.S.P.XVIII procedure (U.S.P. method) and the J.P. VIII disintegration test apparatus (J.P. method). A good correlation between the hardness and the disintegration times was obtained. The dissolution rate constants were determined from the equation of Noyes & Whitney (1897) and a good correlation between the hardness and the dissolution rate constants was obtained. The hardness governed the dissolution over all the stages from tablet to the smallest particles after the breakage by disintegration. The dissolution rates of the J.P. method were greater than those of the U.S.P. method.


Strength and Deformation Characteristics of Fiber and Cement-Modified Waste Slurry.
Using fiber and cement to modify waste slurry and apply it to roads is an effective way to recycle waste slurry. A new type of road material, fiber-cement-modified waste slurry (FRCS), was prepared in this study. The static and dynamic characteristics of the cement soil were studied using an unconfined compressive strength test and dynamic triaxial test. The results show that the optimum fiber content of FRCS is 0.75%. In the unconfined compressive strength test, under this fiber content, the unconfined compressive strength (UCS) of the FRCS is the largest, and the elastic modulus and modulus strength ratio are both the smallest, indicating that the tensile properties of the cement slurry have been enhanced. In the dynamic triaxial test, the hysteretic curve of the FRCS tends to be stable with the increase in the number of cycles, the dynamic elastic modulus of the FRCS decreases first and then increases with the increase in the dosage, while the damping ratio becomes stable after a rapid decline, and the fiber incorporation increases the cumulative strain of the soil-cement under low-stress cycles, indicating that the ductility of the FRCS is improved. In addition, a cumulative strain prediction model of the FRCS is established in this paper, which can provide a reference for the resource application of waste slurry in road engineering.


Synthesis and characterization of crystalline niobium and tantalum carbonyl complexes at room temperature.
A variety of homoleptic transition metal carbonyl complexes are known as bulk compounds for group 7-12 metals. These metals typically feature a maximum of 6 CO ligands to form complexes with 18 valence electrons. In contrast, group 3-5 metals, with fewer valence electrons, have been shown to form highly coordinated heptacarbonyl and octacarbonyl complexes-although they were only identified by gas-phase mass spectrometry and/or matrix isolation spectroscopy work. Now we have prepared heptacarbonyl cations of niobium and tantalum as crystalline salts that are stable at room temperature. The [M(CO)7]+ (M = Nb or Ta) complexes were formed by the oxidation of [M(CO)6]- with 2Ag+[Al(ORF)4]- (RF, C(CF3)3) under a CO atmosphere; their experimental characterization was supported by density functional theory calculations. Other unusual carbonyl compounds were also synthesized: two isostructural salts that contained the 84-valence-electron cluster cation [Ag6{Nb(CO)6}4]2+, the piano-stool complexes [(1,2-F2C6H4)M(CO)4]+ and two polymorphs of neutral Ta2(CO)12 with a long, unsupported Ta-Ta bond.


Application of density functional theory (DFT) to study the properties and degradation of natural estrogen hormones with chemical oxidizers.
Estrone (E1), 17β-estradiol (E2), estriol (E3), equilin (EQ) and 17α-estradiol (17α) estrogen hormones are released by humans and animals and have been detected in the environment and municipal wastewater treatment plants. The structural and electronic properties of natural hormone molecules are investigated by performing density functional theory calculations and used to predict their properties and chemical behavior. Quantitative structure property relationship (QSPR) approach is applied to correlate the estrogenicity associated with the natural estrogen hormones according to their molecular properties. The obtained relationship reveals the importance of the frontier molecular orbital energy in the interpretation of estrogenic activity of hormones, which is consistent with the previous research. Moreover, the obtained molecular descriptors also aid determination of the degradability of hormones, and to rationalize degradation pathways, with chemical oxidizers such as ozone and hydroxyl radical. Both types of interactions belong to the orbital-controlled reactions. The active sites determined by Fukui functions for the estrogen hormone molecules confirm the reaction pattern that initiates the attack of the aromatic ring for both ozone and hydroxyl radical. The reactive sites of the molecules are mapped with subsequent reaction intermediates and compared with experimental data obtained from the literature.


Oral treatment with RU 41.740 (Biostim) in patients with advanced colorectal cancer: influence on the blood lymphocyte population.
Twelve patients with advanced colorectal carcinoma received oral treatment with RU 41.740, an immunomodulatory drug obtained from Klebsiella pneumoniae. The patients received three courses of RU 41.740, each consisting of 8 mg daily for 7 consecutive days, with free intervals of 3 weeks. This treatment did not significantly change the distribution of various lymphocyte subsets in the blood or the NK activity of the lymphocytes. However, PHA reactivity of purified lymphocytes increased significantly and exhibited a 2-3-fold enhancement 3 weeks after the last course. Such an increase was not observed in lymphocyte preparations which were not depleted of monocytes. It is concluded that 41.740 may be immunopharmacologically active in man when administered by the oral route.


AAV9-NGLY1 gene replacement therapy improves phenotypic and biomarker endpoints in a rat model of NGLY1 Deficiency.
N-glycanase 1 (NGLY1) Deficiency is a progressive, ultra-rare, autosomal recessive disorder with no approved therapy and five core clinical features: severe global developmental delay, hyperkinetic movement disorder, elevated liver transaminases, alacrima, and peripheral neuropathy. Here, we confirmed and characterized the Ngly1 -/- / rat as a relevant disease model. GS-100, a gene therapy candidate, is a recombinant, single-stranded adeno-associated virus (AAV) 9 vector designed to deliver a functional copy of the human NGLY1 gene. Using the Ngly1 -/- rat, we tested different administration routes for GS-100: intracerebroventricular (ICV), intravenous (IV), or the dual route (IV + ICV). ICV and IV + ICV administration resulted in widespread biodistribution of human NGLY1 DNA and corresponding mRNA and protein expression in CNS tissues. GS-100 delivered by ICV or IV + ICV significantly reduced levels of the substrate biomarker N-acetylglucosamine-asparagine (GlcNAc-Asn or GNA) in CSF and brain tissue compared with untreated Ngly1-/- rats. ICV and IV + ICV administration of GS-100 resulted in behavioral improvements in rotarod and rearing tests, whereas IV-only administration did not. IV + ICV did not provide additional benefit compared with ICV administration alone. These data provide evidence that GS-100 could be an effective therapy for NGLY1 Deficiency using the ICV route of administration.


Effect of X-ray repair cross complementing group 1 polymorphisms on the efficacy of platinum-based chemotherapy in patients with nonsmall cell lung cancer.
X-ray repair cross complementing group 1 (XRCC1) has been indicated to be correlated with the efficacy of platinum-based chemotherapy. But study results were still debatable. Thus, a meta-analysis was conducted. A literature search was performed using the PubMed, EMBASE, CNKI, with the databases being last accessed on November 24, 2014. Odds ratios with 95% confidence intervals were used to assess the strength of the association. In this meta-analysis, we found that XRCC1 Arg194Trp polymorphism was significantly associated with the efficacy of platinum-based chemotherapy. However, XRCC1 Arg399Gln polymorphism showed no impact on the efficacy of platinum-based chemotherapy. This meta-analysis suggested that the XRCC1 Arg194Trp polymorphism may be associated with efficacy of platinum-based chemotherapy. Further studies with a larger sample size are needed to further assess this result.


Spectroscopic probing of organic molecules encapsulated in functionalized carbon nanotubes in solution.
Pyrene was introduced into cavities in functionalized single-walled and multiple-walled carbon nanotubes to be used as a molecular probe in the study of encapsulation. The solubility of these materials in common organic solvents allowed solution-phase absorption and emission spectroscopic measurements. The results, which are consistent with the formation of pyrene excimer, are explained in terms of high local pyrene concentrations and perhaps pyrene microcrystals inside the carbon nanotube cavities. The fluorescence decay results show that there is significant quenching of pyrene excited states by the hosting carbon nanotubes.


Influence of rat prenatal and postnatal exposure to a non-steroidal anti-inflammatory agent (flunoxaprofen) on cardiovascular function in the progeny.
The present experiments evaluated in rats the effects of prenatal and postnatal exposure to a non-steroidal antiinflammatory agent, flunoxaprofen (5-10 and 20 mg/kg/day by the oral route), on cardiovascular function in the pups. In both conscious and anaesthetized rats pre- and postnatal flunoxaprofen exposure at the 30th and 60th day of age, significantly (P less than .05) induced a decrease of pressor response to carotid-sinus baroreceptor stimulation and to L-noradrenaline (0.1-1 and 5 micrograms/kg iv), and an increase of the hypotensive responses to L-isoprenaline (0.01-0.1 and 1 microgram/kg iv) and acetylcholine (0.01-0.1 and 1 microgram/kg iv). These effects were not observed in rats on the 90th day of age. Moreover, pre- and postnatal flunoxaprofen exposure did not modify systolic arterial blood pressure of plasma levels of catecholamines and acetylcholinesterases. Our results also show that in normotensive rats flunoxaprofen exposure during pregnancy did not affect the body weight, systolic or diastolic blood pressure or heart rate of pregnant rats. It did not affect the length of gestation, number of pups per litter or pup body weight. No macroscopic teratogenic effects were observed.


A ratiometric fluorescent probe for detection of γ-glutamyl transpeptidase in blood serum and living cells.
γ-Glutamyl transpeptidase (GGT) is one of the biomarker of cancer, hepatitis, and numerous other diseases. The accurate analysis of GGT is useful for the early diagnosis of these diseases. In this work, Probe 1, a ratiometric fluorescent probe based on 2,3,5,6-tetrafluoroterephthalonitrile, was designed for GGT detection. The results indicated that Probe 1 can sensitively and selectively detect GGT in phosphate buffered solution and complex biological systems (e.g., blood serum). Furthermore, Probe 1 has been successfully applied for ratiometric imaging of GGT in cancer cells and normal cells.


In vitro antiparasitic activity of extracts of Cardiospermum halicacabum against third-stage larvae of Strongyloides stercoralis.
Extracts of Cardiospermum halicacabum, medicinal plant, were tested in vitro for their effectiveness against third-stage larvae of Strongyloidesstercoralis. Third-stage larvae of S. stercoralis were isolated from cultures of dog's feces using agar plate culture method. The larvae (1,000 larvae/ml), suspended in phosphate buffer saline solution, pH 7.4, were exposed to aqueous and alcohol extracts (2,000 microg/ml) of C. halicacabum at 37 degrees C with 5% CO2. Ivermectin (250 microg/ml) and piperazine (2,000 microg/ml) were also used as the reference drugs. The survival of Strongyloides larvae based on its motility was determined daily for 7 days. Strongyloides larvae were viable after contact with ivermectin, piperazine and C. halicacabum (aqueous and alcohol) solutions, but most of them were immobilized, after exposure to aqueous and alcohol extracts of C. halicacabum within 72 and 48 h, respectively, while ivermectin took from 72 to 144 h, and piperazine more than 7 days, to achieve the same rate of nonmotility. Clearly, the viability of S. stercoralis larvae was significantly reduced when exposed to extracts of C. halicacabum. Further study is needed on the antiparasitic activity of aqueous and alcohol extracts of C. halicacabum against S. stercoralis.


In vitro repair of psoralen-DNA cross-links by RecA, UvrABC, and the 5'-exonuclease of DNA polymerase I.
Psoralens produce DNA interstrand cross-links which are thought to be repaired via a sequential excision and recombination mechanism in Escherichia coli. The first round of incision by UvrABC has been characterized: it results in 11-base oligonucleotide cross-linked to an intact DNA strand (Van Houten, B., Gamper, B., Holbrook, S.R., Hearst, J.E., and Sancar, A. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 8077-8081). In the present work, DNA substrates containing 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT) cross-links in defined positions are constructed and used to analyze the other steps in repair. It is shown that RecA protein mediates strand transfer past an oligonucleotide cross-linked to a single-stranded DNA circle and that the resulting heteroduplex is a substrate for the UvrABC complex: it excises a double-stranded oligonucleotide which contains the HMT cross-link. It is also found that the first round of UvrABC incision does not lead directly to strand exchange but that an intervening step is needed. That step is carried out in vitro by the 5'-exonuclease activity of DNA polymerase I (pol I) which creates a single-stranded DNA region (a gap) at an incised cross-link such that RecA can initiate strand exchange. Studies using cross-linked oligonucleotides showed that the gap produced by pol I results from the inability of the polymerase to add nucleotides to a 3'-OH end two to three nucleotides away from the furan side of an HMT cross-link. Pol I can, however, extend a 3'-OH end next to the pyrone side of the cross-link. Since UvrABC incises predominantly the furan side of psoralen cross-links in duplex DNA, this discrepancy has important consequences for repair.


Cooperation between an academic subspecialty department and a community-based family medicine department: a developmental model.
While new, community-based family practice residency programs desperately need support from sister departments in academic centers, a variety of problems frequently prevents such cooperation. At the University of Wisconsin, Madison, the Department of Human Oncology, which is University Hospital-based, has worked to develop an appropriate educational program in oncology, together with and for the Department of Family Medicine and Practice, which is community-based. This paper, relating how and why these two departments have cooperated in this project, is presented to assist other departments in similar situations.


Assessing the effect of antihypertensives on plaque microbiota in patients with periodontitis and hypertension using 16S rRNA sequencing: A cross-sectional study.
Periodontitis is initiated or accelerated by dysbiosis of oral microorganisms. When hypertension is accompanied in periodontitis patients, changes of oral microbiota occur. Since there are no reports on antihypertensives, we assessed their effect on the oral microbial profiles of patients with periodontitis. This study involved 95 participants divided into two groups: those with periodontitis and hypertension (P_HT), and those with periodontitis and taking medications for hypertension (P_mHT). Plaque samples were collected from the buccal, supragingival, and subgingival sites of the oral cavities of these patients. DNA was extracted, and the V3-V4 region of the 16S ribosomal RNA was sequenced and analyzed. The P_HT and P_mHT groups were similar with respect to the alpha- and beta-diversity as well as the dominant phyla and genera, but differed in the relative abundance of bacterial species (85 species). In the P_mHT group, the relative abundance of major periodontal pathogens was greatly increased. In particular, Tannerella forsythia, Treponema denticola, and Fretibacterium fastidiosum increased nearly three times in the linear discriminant analysis score in the supragingival plaque. Also, there was an increase in the relative abundance of Prevotella spp., associated with periodontitis and nitrate reduction, which was also evident in the supragingival plaque. These findings indicate that antihypertensives induce dysbiotic changes in the oral microbiota of patients with periodontitis, which are associated with increases in the relative abundance of periodontal pathogens. Therefore, more active periodontal treatment and supportive periodontal therapy are required in patients taking antihypertensives.


Contemporary meta-analysis of short-term probiotic consumption on gastrointestinal transit.
To determine the efficacy of probiotic supplementation on intestinal transit time (ITT) in adults and to identify factors that influence these outcomes. We conducted a systematic review of randomized controlled trials of probiotic supplementation that measured ITT in adults. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference (SMD) of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses examined the impact of moderator variables on SMD of ITT. A total of 15 clinical trials with 17 treatment effects representing 675 subjects were included in this analysis. Probiotic supplementation was moderately efficacious in decreasing ITT compared to control, with an SMD of 0.38 (95%CI: 0.23-0.53, P < 0.001). Subgroup analyses demonstrated statistically greater reductions in ITT with probiotics in subjects with vs without constipation (SMD: 0.57 vs 0.22, P < 0.01) and in studies with high vs low study quality (SMD: 0.45 vs 0.00, P = 0.01). Constipation (R (2) = 38%, P < 0.01), higher study quality (R (2) = 31%, P = 0.01), older age (R (2) = 27%, P = 0.02), higher percentage of female subjects (R (2) = 26%, P = 0.02), and fewer probiotic strains (R (2) = 20%, P < 0.05) were predictive of decreased ITT with probiotics in meta-regression. Medium to large treatment effects were identified with B. lactis HN019 (SMD: 0.67, P < 0.001) and B. lactis DN-173 010 (SMD: 0.54, P < 0.01) while other probiotic strains yielded negligible reductions in ITT relative to control. Probiotic supplementation is moderately efficacious for reducing ITT in adults. Probiotics were most efficacious in constipated subjects, when evaluated in high-quality studies, and with certain probiotic strains.


Immunocytochemical and immunoelectron microscopic demonstration of cathepsin B in human malignant melanoma.
Proteases are known to enhance the spread of tumour cells. Possible sources of these proteases are the tumour cells themselves or fibroblasts in the tumour tissue. Immunological staining with anticathepsin B antibody indicates that the subcellular distribution of cathepsin B in tumour cell lines differs from that in normal liver. The aims of this study were: (i) to show whether different types of melanoma differ in their production of cathepsin B; (ii) to identify the cathepsin B-producing cells; and (iii) to determine the subcellular distribution of cathepsin B in melanoma cells. All types of melanomas contained cell regions stained with anticathepsin B antibody. The intensity of the stain and the number of cells reacting with anticathepsin B antibody depended on the size of the tumour but not on the type of melanoma. Epithelioid cells stained more intensely with anticathepsin B antibody than spindle-shaped cells. Cells staining with anticathepsin B antibody were almost exclusively tumour cells. Anticathepsin B stain was located mainly in vesicular structures which did not contain a filamentous matrix. Additional anticathepsin B stain was detected at the extracellular spaces. Hypomelanotic melanoma cells, mainly of the epithelioid type, produced most of the cathepsin B. Cathepsin B may be involved in both the degradation of possibly abnormal melanosomes and the focal degradation of the extracellular matrix.


Safety and efficiency modifications of SIV-based integrase-defective lentiviral vectors for immunization.
Integrase-defective lentiviral vectors (IDLVs) represent an attractive platform for vaccine development as a result of the ability to induce persistent humoral- and cellular-mediated immune responses against the encoded transgene. Compared with the parental integrating vector, the main advantages for using IDLV are the reduced hazard of insertional mutagenesis and the decreased risk for vector mobilization by wild-type viruses. Here we report on the development and use in the mouse immunogenicity model of simian immunodeficiency virus (SIV)-based IDLV containing a long deletion in the U3 region and with the 3' polypurine tract (PPT) removed from the transfer vector for improving safety and/or efficacy. Results show that a safer extended deletion of U3 sequences did not modify integrase-mediated or -independent integration efficiency. Interestingly, 3' PPT deletion impaired integrase-mediated integration but did not reduce illegitimate, integrase-independent integration efficiency, contrary to what was previously reported in the HIV system. Importantly, although the extended deletion in the U3 did not affect expression or immunogenicity from IDLV, deletion of 3' PPT considerably reduced both expression and immunogenicity of IDLV.


[A trial of assessment of the realization of the programme of stomatological health service for the Nowy Sacz Province in the years 1976-1986].
The epidemiological situation was evaluated in the Nowy Sacz Province in school children and adolescents aged 7, 12 and 14 years in urban and village areas in the school-years 1975-76 to 1985-86. The DMF index, the DMF pattern and the percent proportions of children receiving fluoride prevention of caries were calculated. The number of dentists employed during the period of 10 years was compared. The data are presented in tables. It was found that the proportion of children receiving health care for caries prevention has increased, the mean DMF value in children aged 12 years fell from 4.9 to 4, and favourable changes occurred in the DMF pattern.


Calculation of blood velocity and pressure in stenosed renal artery considered as a Venturi tube.
The authors propose using a Venturi tube as a model of stenosed renal artery; they can thus calculate blood velocity and pressure in the stenosed part from estimated renal flow, systemic pressure and the hydraulic characteristics of the model.


Seeing the forest and the trees: increasing nurse practitioner students' observational and mindfulness skills.
Accurate, objective observation is a critical component of clinical diagnosis and patient management, which in turn is essential for successful diagnostic reasoning by advanced practice nurses. The purpose of this quasi-experimental study was to enhance nurse practitioner students' observation and reflective thinking skills using Looking Is Not Seeing, a reflective practice/experiential learning technique that uses art objects to teach observation (Pellico, Friedlaender, & Fennie, 2009). Students' posttest observation and interpretation scores showed statistically significant improvement over pretest scores. Students' mindfulness scores and their own perceived observational and interpretive ability were statistically significantly higher after participating in the study. Building on the established record of successful visual literacy programs for nursing and medical students at other institutions, this research can help educators implement the Looking Is Not Seeing pedagogy.


Elucidating the adsorption of 2-Mercaptopyridine drug on the aluminum phosphide (Al12P12) nanocage: A DFT study.
Adsorption amplitude of the aluminum phosphide (Al12P12) nanocage toward the 2-Mercaptopyridine (MCP) drug was herein monitored based on density functional theory (DFT) calculations. The adsorption process through MCP⋅⋅⋅Al12P12 complex in various configurations was elucidated by means of adsorption (Eads) energies. According to the energetic affirmations, the Al12P12 nanocage demonstrated potential versatility toward adsorbing the MCP drug within the investigated configurations and exhibited significant negative adsorption energies up to -27.71 kcal/mol. Upon the results of SAPT analysis, the electrostatic forces showed the highest contributions to the overall adsorption process with energetic values up to -74.36 kcal/mol. Concurrently, variations of molecular orbitals distribution along with alterations in the energy gap (Egap) and Fermi level (EFL) of the studied nanocage were denoted after adsorbing the MCP drug. The favorable impact of water solvent within the MCP⋅⋅⋅Al12P12 complexes was unveiled and confirmed by negative solvation energy (ΔEsolv) values up to -17.75 kcal/mol. According to thermodynamic parameters, the spontaneous and exothermic natures of the considered adsorption process were proclaimed by negative values of ΔG and ΔH parameters. Significant changes in the IR and Raman peaks, along with the appearance of new peaks, were noticed, confirming the occurrence of the targeted adsorption process. Furthermore, the adsorption features of the MCP drug on the Al12N12 nanocage were elucidated and compared to the Al12P12 analog. The obtained results demonstrated the higher preferability of Al12P12 nanocage than the Al12N12 candidate towards adsorbing the MCP drug without structural distortion.


Outcomes in patients undergoing percutaneous ventricular assist device implantation for cardiogenic shock.
Percutaneous ventricular assist devices (PVADs) offer an important but resource-intensive option for management of severe cardiogenic shock (CS). Optimal selection of patients for PVAD support remains undefined. We investigated outcomes, including characteristics associated with in-hospital survival, during PVAD support for CS. We established a prospective quality improvement program among patients undergoing TandemHeart PVAD implantation for CS at Brigham and Women's Hospital (Boston, MA). We evaluated 65 consecutive patients between 2006 and 2014, analyzing demographic, clinical, laboratory, hemodynamic, and survival data. Thirty-two patients (49.2%) survived to hospital discharge, of which 12 received destination surgical therapy. Baseline characteristics associated with survival included younger age (47 ± 15 years vs 61 ± 11 years; p<0.001), non-ischemic cardiomyopathy (NICMP) vs ischemic CMP (survival 70.4% vs 34.2%, p=0.004), and, paradoxically, lower presenting left ventricular ejection fraction (LVEF) (survival 66.7% for LVEF ⩽15%, 41.2% for LVEF 16-25%, 25.0% for LVEF >25%; p=0.010). Younger age (p=0.026) and NICMP (p=0.034) remained independent predictors of survival. Twenty-four hours after PVAD placement, a more modest increase in cardiac index (⩽0.75 L/min/m(2)) was associated with higher in-hospital mortality (OR 6.3, 95% CI 1.8-22.1), as was lack of improvement in serum anion gap (⩽2 mEq/L; OR 5.1, 95% CI 1.6-16.6). Despite intensive care and provision of circulatory support, survival is poor in severe CS. Patients in CS with younger age and NICMP were more likely to survive to hospital discharge. Less robust hemodynamic improvement and persistent acidosis after 24 hours of PVAD support also identified patients less likely to survive.