Interstitial Doppler optical coherence tomography as a local tumor necrosis predictor in photodynamic therapy of prostatic carcinoma: an in vivo study.
We have tested the feasibility of real-time localized blood flow measurements, obtained with interstitial (IS) Doppler optical coherence tomography (DOCT), to predict photodynamic therapy (PDT)-induced tumor necrosis deep within solid Dunning rat prostate tumors. IS-DOCT was used to quantify the PDT-induced microvascular shutdown rate in s.c. Dunning prostate tumors (n=28). Photofrin (12.5 mg/kg) was administered 20 to 24 hours before tumor irradiation, with 635 nm surface irradiance of 8 to 133 mWcm(-2) for 25 minutes. High frequency ultrasound and calipers were used to measure the thickness of the skin covering the tumor and the location of the echogenic IS probe within it. A two-layer Monte Carlo model was used to calculate subsurface fluence rates within the IS-DOCT region of interest (ROI). Treatment efficacy was estimated by percent tumor necrosis within the ROI, as quantified by H&E staining, and correlated to the measured microvascular shutdown rate during PDT treatment. IS-DOCT measured significant PDT-induced vascular shutdown within the ROI in all tumors. A strong relationship (R2=0.723) exists between the percent tumor necrosis at 24 hours posttreatment and the vascular shutdown rate: slower shutdown corresponded to higher treatment efficacy, i.e., more necrosis. Controls (needle+light, no drug, n=3) showed minimal microvascular changes or necrosis (4%+/-1%). This study has correlated a biological end point with a direct and localized measurement of PDT-induced microvascular changes, suggesting a potential clinical role of on-line, real-time microvascular monitoring for optimizing treatment efficacy in individual patients.


Assessing effects of mechanical stimulation of fluid shear stress on inducing matrix Metalloproteinase-9 in cultured corneal epithelial cells.
Blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells. Therefore, we evaluated whether fluid shear stress affects matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human corneal epithelial cells (HCECs). No other study has shown the influence of fluid shear stress on HCECs regarding mRNA expression and the protein levels of MMPs. Cultured HCECs were exposed to shear stress (0, 1.2, 12 dyne/cm2) for 12 and 24 h with the parallel-plate type of flow chamber. Gene expression of MMPs and TIMPs was measured by real-time polymerase reaction. Concentrations of MMP-1 and MMP-9 in cell lysates were determined using bead-based amplified luminescent proximity homogenous assay-linked immunosorbent assay. The expression of MMP-9 and MMP-1 in HCECs exposed to low and high flow for 12 and 24 h, respectively, increased significantly compared with those under static conditions. The expression of MMP-9 in the cells exposed to high flow for 24 h increased significantly compared with those under static and low flow conditions. Levels of MMP-9 in cell lysates exposed to fluid flow for 24 h were elevated significantly with increasing shear stress. Fluid shear stress exerted on HCECs affected MMPs, which was associated with inflammation and pathogenesis. Mechanical stress induced by blinking might influence expression of MMPs on the ocular surface. Further studies are warranted to establish the molecular mechanism of shear stress-induced alternations of MMPs.


[Production of labelled gamma globulin for the detection of Chlamydia].
A method was worked out for the production of an antichlamydial fluorescent serum to be used in the direct immunofluorescence test. Used were the methods of culturing Chlamydia in chick embryos and cell cultures, light and electron microscopy, differential centrifugation and supercentrifugation, gel chromatography in Sepharose, ultracentrifugation in saccharose, hyperimmunization of guinea pigs, conjugation of gammaglobulin with fluorescein isothiocyanate, complement fixation, and the direct immunofluorescence itself. Applied was a new immunologic scheme for the production of fluorescent sera. The guinea pigs were hyperimmunized twice and three times at 30-day intervals with highly purified, highly concentrated and adjuvant-treated chlamydial suspensions. It was concluded that the main condition for the production of high titer labelled gammaglobulins was to obtain purified and concentrated chlamydial antigens and use these with an adjuvant. To indicate Chlamydia in testing the conjugates it is essential to prepare standard test lamellas infected at high multiplicity of purified and concentrated Chlamydia.


Three Research Strategies of Neuroscience and the Future of Legal Imaging Evidence.
Neuroscientific imaging evidence (NIE) has become an integral part of the criminal justice system in the United States. However, in most legal cases, NIE is submitted and used only to mitigate penalties because the court does not recognize it as substantial evidence, considering its lack of reliability. Nevertheless, we here discuss how neuroscience is expected to improve the use of NIE in the legal system. For this purpose, we classified the efforts of neuroscientists into three research strategies: cognitive subtraction, the data-driven approach, and the brain-manipulation approach. Cognitive subtraction is outdated and problematic; consequently, the court deemed it to be an inadequate approach in terms of legal evidence in 2012. In contrast, the data-driven and brain manipulation approaches, which are state-of-the-art approaches, have overcome the limitations of cognitive subtraction. The data-driven approach brings data science into the field and is benefiting immensely from the development of research platforms that allow automatized collection, analysis, and sharing of data. This broadens the scale of imaging evidence. The brain-manipulation approach uses high-functioning tools that facilitate non-invasive and precise human brain manipulation. These two approaches are expected to have synergistic effects. Neuroscience has strived to improve the evidential reliability of NIE, with considerable success. With the support of cutting-edge technologies, and the progress of these approaches, the evidential status of NIE will be improved and NIE will become an increasingly important part of legal practice.


Endoscopic Thoracic Sympathectomy in the Treatment of Vasospastic Angina Resistant to Medical Therapy.
In this study, we aimed to investigate the clinical follow-up results of endoscopic thoracic sympathectomy (ETS) in the treatment of vasospastic angina (VSA) resistant to maximal medical therapy. A total of 80 patients with VSA who presented to our hospital between 2010 and 2022 were included in our study. Among them, 6 patients who did not respond to medical therapy underwent ETS. In-hospital and long-term clinical outcomes of patients who underwent ETS were recorded. The median age of the patients with VSA was 57 [48-66] years, and 70% of the group were males. In the ETS group, compared to the non-ETS group, higher numbers of hospital admissions and coronary angiographies were observed before ETS (median 6 [5-6] versus 2 [1-3], P <.001; median 5 [3-6] versus 2 [1-3], P =.004, respectively). Additionally, while 2 patients (33.3%) in the ETS group had implantable cardioverter defib-rillator (ICD), only 2 patients (2.7%) in the non-ETS group had ICD (P =.027). Out of the 6 patients who underwent ETS, 2 were females, with a median age of 56 [45-63] years. Four patients underwent successful bilateral ETS, while 2 patients underwent unilateral ETS. During the follow-up period after ETS, only 3 patients experienced sporadic attacks (once in 28 months, twice in 41 months, and once in 9 years, respectively), while no attacks were observed in 3 patients during their median follow-up of 7 years. It appears that ETS is effective in preventing VSA attacks without any major complications.


A new type of mixed anionic framework in microporous rubidium copper vanadyl(V) phosphate, Rb2Cu(VO2)2-(PO4)2.
In dirubidium copper bis[vanadyl(V)] bis(phosphate), Rb(2)Cu(VO(2))(2)(PO(4))(2), three different oxo complexes form an anionic framework. VO(5) polyhedra in a trigonal bipyramidal configuration and PO(4) tetrahedra share vertices to form eight-membered rings, which lie in layers perpendicular to the a axis of the monoclinic unit cell. Cu atoms at centres of symmetry have square-planar coordination and link these layers along [100] to form a three-dimensional anionic framework, viz. [Cu(VO(2))(2)(PO(4))(2)](infinity)(2-). Intersecting channels in the [100], [001] and [011] directions contain Rb(+) cations. Topological relations between this new structure type and the crystal structures of A(VO(2))(PO(4)) (A = Ba, Sr or Pb) and BaCrF(2)LiF(4 )are discussed.


Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies-the German Cancer Consortium approach.
Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This review summarizes the current state of discussions of this cooperative approach providing a basis for further policy-making and suitable modification of processes.


Serological survey of leptospiral infection in kennelled dogs in Italy.
Two hundred and forty-five dogs were examined serologically for the presence of antibodies against different serovars of Leptospira interrogans. The dogs belonged to five different groups: group 1 was composed of clinically healthy pet dogs referred for a regular veterinary check-up visit or for vaccination; group 2 was composed of stray dogs; and groups 3, 4 and 5 were composed of dogs maintained in three different kennels which had varying standards of hygiene. Seventy-two out of the 245 dogs examined were seropositive for leptospirosis. In group 1, there were 3-4 per cent seropositive dogs; in group 2, 30.3 per cent; in group 3, 13.8 per cent; in group 4, 38.6 per cent; and in group 5, 49.2 per cent. This study demonstrates that leptospiral infection is common in dogs housed in kennels, despite most of them being vaccinated, and that crowding of animals into unsanitary quarters is associated with a high prevalence of infection. The most common infecting serovars found were bratislava and grippotyphosa, confirming recent observations that demonstrate a significant change in the epidemiology of canine leptospirosis.


The action of compound WA-335 on the central nervous system.
Compound WA-335 (9,10-dihydro-10-(-1-methyl-4-piperidylidene)9-anthrol) was studied with regard to its antidepressant and central antiserotonin action in mice and rats. WA-335 depresses reserpine-induced hypothermia, particularly in mice, but does not affect ptosis induced with this neuroleptic. The compound diminishes spontaneous motility in mice and rats, including mice stimulated with amphetamine. WA-335 acts synergistically with amphetamine in which it potentiates stereotyping and enhances motility. The compound has no influence on the action of L-DOPA and does not alter hypothermia or increase motility induced with this amino acid. WA-335 does not affect the drop in body temperature or stereotype induced with apomorphine. In mice, WA-335 inhibits motility elicited with L-5-hydroxytryptophan, and in rats as well as mice prevents occurrence of head-twitches due to activation of serotonin neurons. The compound has no effect on the righting reflex abolished with fenfluramine in frogs, and given together with reserpine slightly counteracts abolition of this reflex. WA-335 raises the level of serotonin in the brains of rats, and lowers the level of 5-hydroxyindoleacetic acid. In addition, WA-335 exhibits cholinolytic activity and abolishes the symptoms elicited with oxotremorin in mice and rats.


Substance use and its risk factors in Turkey: a nationally representative sample study.
Substance use is the most important modifiable factor in increased morbidity and premature mortality. The purpose of this study was to examine the psychological factors associated with substance use status in nationally representative sample. The data were from the Addiction Map of Turkey Study (TURBAHAR), in which 24,494 adults were recruited from 200 to 2000 participants in 26 provinces in Turkey. Chi-square tests and one-way ANOVAs were used to analyze the relationships between substance status and the risk factors. Multinomial Logistic regressions were used to calculate odds ratios. The prevalence of single substance use and polysubstance use at least once in their lifetime were 4.5% and 2.6%. Males, late emerging adults (24-29 years old) were more likely be a single substance use and polysubstance use. Having graduates diploma were more likely be a polysubstance use. Higher depression, anxiety, somatization, hostility, externally-oriented thinking, positive affect were associated with higher possibility of single and/or polysubstance use. Higher personal wellbeing scores and anxious attachment scores were associated with lower possibility of single and/or polysubstance use. Male, undergraduate and graduate, late emerging adults needs special attention. Many psychological variables are associated with substance use. Although not all have a high potency, they provide important information for subsequent treatment and diagnostic approaches.


Cross talk between the nuclease and helicase activities of Dna2: role of an essential iron-sulfur cluster domain.
Dna2 nuclease/helicase is a multitasking protein involved in DNA replication and recombinational repair, and it is important for preservation of genomic stability. Yeast Dna2 protein contains a conserved putative Fe-S (iron-sulfur) cluster signature motif spanning the nuclease active site. We show that this motif is indeed an Fe-S cluster domain. Mutation of cysteines involved in metal coordination greatly reduces not just the nuclease activity but also the ATPase activity of Dna2, suggesting that the nuclease and helicase activities are coupled. The affinity for DNA is not significantly reduced, but binding mode in the C to A mutants is altered. Remarkably, a point mutation (P504S), proximal to the Fe-S cluster domain, which renders cells temperature sensitive, closely mimics the global defects of the Fe-S cluster mutation itself. This points to an important role of this conserved proline residue in stabilizing the Fe-S cluster. The C to A mutants are deficient in DNA replication and repair in vivo, and, strikingly, the degree to which they are defective correlates directly with degree of loss of enzymatic activity. Taken together with previous results showing that mutations in the ATP domain affect nuclease function, our results provide a new mechanistic paradigm for coupling between nuclease and helicase modules fused in the same polypeptide.


Predictors of cognitive function in patients with hypothalamic hamartoma following stereotactic radiofrequency thermocoagulation surgery.
To determine the predictors of cognitive function in patients with drug-resistant gelastic seizures (GS) related to hypothalamic hamartoma (HH) before and after stereotactic radiofrequency thermocoagulation surgery (SRT). We studied 88 patients with HH who underwent SRT between October 1997 and December 2014. Patients received neuropsychological tests preoperatively and postoperatively. Based on the preoperative measures, patients were categorized as "high-functioning" (full-scale intelligence quotient [FSIQ] ≥70; n = 48) and "low-functioning" group (FSIQ <70; n = 40). Univariate and multivariate linear regression analyses determined the clinical, electroencephalography (EEG), and imaging factors associated with preoperative cognitive function as well as postoperative cognitive change. Eighty-seven patients (98.8%) were followed postoperatively for an average of 3.3 years, and 75 (85.2%) of them achieved GS remission at the last hospital visit. Neuropsychological performance was significantly improved after surgery in both groups. Multivariate linear regression analysis showed that a smaller HH size (p = 0.002) and a smaller number of antiepileptic drugs (p < 0.001) were preoperatively associated with better neuropsychological performance. Multivariate linear regression analysis showed that better postoperative improvement in cognition was associated with a shorter duration of epilepsy (p = 0.03). Cognitive impairment related to epileptic encephalopathy may improve following SRT in substantial proportions of HH patients. Reduced improvement in postoperative cognitive function in patients with longer duration of epilepsy warrants further studies to determine if earlier SRT provides a greater chance of postoperative cognitive improvement in patients with HH.


[Endocrinology of mastopathy and small breast cancer].
The role of hormones in the cancerogenesis of breast cancer is still discussed. It is not clear at the moment if sexual hormones are primarily or secondarily in wall in cancerogenesis. Beside the discussion it is clear that estrogen, progesterone, androgens, prolactin and thyroxin have influences on the physiology and pathophysiology of the breast tissue. Furthermore the isoforms of these hormones and also the sexual hormone, binding-protein could be of interest. At last also the receptor evaluation becomes of interest in the etiology and therapy of breast cancer.


On Bartlett's formulation of the Luria-Delbrück mutation model.
Current knowledge of microbial mutation rates was accumulated largely by means of fluctuation experiments. A mathematical model describing the cell dynamics in a fluctuation experiment is indispensable to the estimation of mutation rates through fluctuation experiments. In almost six decades the model formulated by Lea and Coulson dominated in research and application, although the model formulated by Bartlett is generally believed to describe the cell dynamics more faithfully. The neglect of the Bartlett formulation was mainly due to mathematical difficulties. The present investigation overcomes some of these difficulties, thereby paving the way for the application of the Bartlett formulation in estimating mutation rates. Specifically, the article offers an algorithm for computing the distribution function of the number of mutants under the Bartlett formulation. The article also provides algorithms for computing point and interval estimates of mutation rates that are based on the maximum-likelihood principle. In addition, the article examines and compares the asymptotic behavior of the distributions of the number of mutants under the two formulations.


Revealing the Dependency of Dye Adsorption and Photocatalytic Activity of ZnO Nanoparticles on Their Morphology and Defect States.
ZnO is an effective photocatalyst applied to the degradation of organic dyes in aqueous media. In this study, the UV-light and sunlight-driven photocatalytic activities of ZnO nanoparticles are evaluated. A handheld Lovibond photometer was purposefully calibrated in order to monitor the dye removal in outdoor conditions. The effect of ZnO defect states, i.e., the presence of zinc and oxygen defects on the photocatalytic activity was probed for two types of dyes: fuchsin and methylene blue. Three morphologies of ZnO nanoparticles were deliberately selected, i.e., spherical, facetted and a mix of spherical and facetted, ascertained via transmission electron microscopy. Aqueous and non-aqueous sol-gel routes were applied to their synthesis in order to tailor their size, morphology and defect states. Raman spectroscopy demonstrated that the spherical nanoparticles contained a high amount of oxygen vacancies and zinc interstitials. Photoluminescence spectroscopy revealed that the facetted nanoparticles harbored zinc vacancies in addition to oxygen vacancies. A mechanism for dye degradation based on the possible surface defects in facetted nanoparticles is proposed in this work. The reusability of these nanoparticles for five cycles of dye degradation was also analyzed. More specifically, facetted ZnO nanoparticles tend to exhibit higher efficiencies and reusability than spherical nanoparticles.


Pressure-volume curves in acute respiratory failure: automated low flow inflation versus occlusion.
Pressure-volume (P-V) curves of the respiratory system allow determination of compliance and lower and upper inflection points (LIP and UIP, respectively). To minimize lung trauma in mechanical ventilation the tidal volume should be limited to the P-V range between LIP and UIP. An automated low flow inflation (ALFI) technique, using a computer-controlled Servo Ventilator 900C, was compared with a more conventional technique using a series of about 20 different inflated volumes (Pst-V curve). The pressure in the distal lung (Pdist) was calculated by subtraction of resistive pressure drop in connecting tubes and airways. Compliance (Cdist), Pdist(LIP), and Pdist(UIP) were derived from the Pdist-V curve and compared with Cst, Pst(LIP), and Pst(UIP) derived from the Pst-V curve. Nineteen sedated, paralyzed patients (10 with ARDS and 9 with ARF) were studied. We found: Cdist = 2.3 + 0.98 x Cst ml/cm H2O (r = 0.98); Pdist(LIP) = 0.013 + 1.09 x Pst(LIP) cm H2O (r = 0.96). In patients with ARDS: Pdist(UIP) = 4.71 + 0.84 x Pst(UIP) cm H2O (r = 0.94). In ARF, we found differences in UIP between the methods, but discrepancies occurred above tidal volumes and had little practical importance. They may reflect that Pdist comprises dynamic phenomena contributing to pressure in the distal lung at large volumes. Compliance, but not LIP and UIP, could be accurately determined without subtraction of resistive pressure from the pressure measured in the ventilator. We conclude that ALFI, which is fully automated and needing no ventilator disconnection, gives useful clinical information.


Use of Psychrotolerant Lactic Acid Bacteria (Lactobacillus spp. and Leuconostoc spp.) Isolated from Chinese Traditional Paocai for the Quality Improvement of Paocai Products.
To improve the quality of Chinese traditional Paocai, two psychrotolerant lactic acid bacteria (LAB) strains were isolated from Paocai, and the quality of Chinese Paocai product using these two strains as starter cultures was compared to a control sample fermented with aged brine at 10 °C. The results suggested that the physicochemical and sensory features of Paocai fermented with psychrotolerant LAB were more suitable for industrial applications. The nitrite content of Paocai fermented with psychrotolerant LAB was 1 mg/kg, which was significantly lower than that of the control Paocai (P < 0.05). Low-temperature fermentation with the starter cultures of psychrotolerant LAB could effectively prevent overacidity and over-ripening of the Paocai products. Additionally, Paocai fermented with psychrotolerant LAB harbored relatively simple microbial flora as revealed by polymerase chain reaction-denaturing gradient gel electrophoresis. This study provides a basis for improving the quality of Chinese traditional Paocai and the large-scale production of low-temperature Chinese traditional Paocai products.


Tin Nanoclusters Confined in Nitrogenated Carbon for the Oxygen Reduction Reaction.
The oxygen reduction reaction is essential for fuel cells and metal-air batteries in renewable energy technologies. Developing platinum-group-metal (PGM)-free catalysts with comparable catalytic performance is highly desired for cost efficiency. Here, we report a tin (Sn) nanocluster confined catalyst for the electrochemical oxygen reduction. The catalyst was fabricated by confining 1-1.5 nm sized Sn nanoclusters in situ in microporous nitrogen-doped carbon polyhedra (SnxNC) with an average pore size of 0.7 nm. SnxNC exhibited high catalytic performance in acidic media, including positive onset and half-wave potentials, comparable to those of the state-of-the-art Pt/C and far exceeding those of the Sn single-atom catalyst. Combined structural and theoretical analyses reveal that the confined Sn nanoclusters, which have favorable oxygen adsorption behaviors, are responsible for the high catalytic performance, but not Sn single atoms.


The Influence of Acupuncture Parameters on Efficacy and the Possible Use of Acupuncture in Combination with or as a Substitute for Drug Therapy in Patients with Ulcerative Colitis.
Ulcerative colitis (UC) is an inflammatory disease of the colonic mucosa, which is accompanied by chronic, idiopathic characteristics. Acupuncture may be an effective therapy for UC. Here we focused on manual acupuncture and electroacupuncture (MA/EA), two widely used and studied acupuncture interventions, to probe the effects of acupuncture parameters on clinical efficacy in patients with UC and the use of MA/EA alone or with other drugs to support their wider adoption in clinical practice. The PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure Database, and Wanfang databases were searched from inception to April 27, 2021. Randomized clinical trials (RCTs) published in Chinese or English were included, and subgroup analyses were performed according to acupuncture parameter, acupuncture type, and control medicine type. The risk of bias was assessed using the Cochrane Risk of Bias tool and modified Jadad scale, and Review Manager 5.4 and Stata 14.0 were used to perform a meta-analysis. Sources of heterogeneity were explored; sensitivity analysis was performed; and the GRADE methodology was used to assess the evidence level. Sixteen studies (1454 individuals) were included. Retention of the needle [10-30 minutes (RR 1.18, 95% CI [1.11, 1.26], P < 0.01; heterogeneity: χ 2 = 6.25, df = 6 (P=0.40), I2 = 4%)], the frequency of MA [once every other day (RR 1.21, 95% CI [1.08, 1.35], P < 0.01; heterogeneity: χ 2 = 0.80, df = 1 (P=0.37), I2 = 0%)], and the length of treatment [8 weeks (RR 1.35, 95% CI [1.01, 1.81], P=0.04)] improved clinical efficacy at the end of treatment compared with medications alone. MA (RR 1.18, 95% CI [1.11, 1.25], P < 0.01; heterogeneity: χ 2 = 6.19, df = 7 (P=0.52), I2 = 0%) increased clinical efficacy compared with medications. Furthermore, MA plus medications (RR 1.26, 95% CI [1.13, 1.40], P < 0.01; heterogeneity: χ 2 = 0.95, df = 2 (P=0.62), I2 = 0%) and EA plus medications (RR 1.36, 95% CI [1.13, 1.63], P < 0.01; heterogeneity: χ 2 = 0.13, df = 1 (P=0.72), I2 = 0%) both dramatically improved clinical efficacy. The clinical efficacy of MA plus mesalazine or MA plus metronidazole and sulfasalazine was greater than with mesalazine or metronidazole and sulfasalazine alone. Similarly, EA plus sulfasalazine was more effective than sulfasalazine alone. MA/EA resulted in fewer adverse reactions than medical therapies. The use of MA plus medications significantly reduced Baron scores. GRADE evaluations indicated that the evidence strength was moderate to low but mostly low. Our study provides the latest evidence to allow us to speculate about the possible optimal MA parameters to treat patients with UC. The low number of adverse reactions and high efficacy make MA/EA a possible supplement to or replacement for traditional UC drugs. The variable parameter settings preferred by patients and acupuncturists may be an important factor limiting the wider clinical deployment of acupuncture as a potential UC therapy.


Childhood non-Hodgkin lymphomas in the United Kingdom: findings from the UK Children's Cancer Study Group.
To review the presenting clinical features and the histology of cases of non-Hodgkin lymphoma (NHL) entered into the United Kingdom Children's Cancer Study Group NHL Trial. Sections of biopsy specimens from all cases entered into the trial were stained with Giemsa and haematoxylin and eosin. All cases were stained immunohistochemically for CD45, CD3, CD45RO, CD20, and CD30. Sections were stained with either naphthol AS-D chloroacetate esterase or KP1 (CD68) to identify granulocytic tumours. In a minority of cases, additional immunohistochemical stains were performed when necessary to establish the diagnosis. The sections were reviewed by three pathologists. Of 308 cases analysed, 293 were categorised as NHL. There was only one case of low grade lymphoma in the series. Over 80% of the cases fell into the categories Burkitt lymphoma (42.2%), lymphoblastic lymphoma (27.2%) and anaplastic large cell lymphoma (15.1%). Cases of Burkitt lymphoma presented most often with abdominal tumours mainly of the ileocaecal region. Tumours of the oropharynx and nasopharynx were also common in this group. Of the 84 lymphoblastic lymphomas, 56 were of the T-cell phenotype, 12 of the B-cell phenotype and 16 of indeterminate lineage. Most of the T-lymphoblastic lymphomas showed mediastinal or pleural involvement. Infiltration of the skin and soft tissues was seen in 25% of lymphoblastic lymphoma of B or indeterminate phenotype. Forty six children were diagnosed as having anaplastic large cell lymphoma, the majority being of T or indeterminate lineage. Most patients presented with lymphadenopathy but involvement of the bones, soft tissues or skin was seen in seven patients and of the mediastinum and lungs in five. Childhood non-Hodgkin lymphomas are almost all high grade and frequently extranodal. They fall mainly into the categories Burkitt lymphoma, lymphoblastic lymphoma and anaplastic large cell lymphoma. The separation of these subcategories can be made on the basis of morphology and immunohistochemical features. The anatomical distribution of these different categories of non-Hodgkin lymphoma is distinctive.


[Structure and intramolecular dynamics of a photoactive pigment-protein eosin-casein complex].
The structure of eosin--casein complex was studied by triplet label method. Quantitative data on the quantum--mechanic exchange interaction between eosin centres and external quenchers were obtained. The dynamic state of water--protein matrix at -20 degrees to -180 degrees C with eosin as fluorescence and phosphorescence labels and natural chromophores of protein--tryptophane was studied.


Novel antifungal agents: a patent review (2011 - present).
Invasive fungal infections (IFI) have increased significantly over the past decades. The mortality rate of IFI is alarming, and early and accurate diagnosis is difficult. Most used antifungal drugs are not completely effective due to the development of increasing resistance and undesirable side effects which limit their use. In this scenario, new effective broad spectrum and safer antifungal drugs are urgently needed. This review summarizes the latest advances in the discovery of new antifungal compounds through the patents granted from 2011 to August 2013. In the 26 patents reviewed here, either derivatives of existing antifungal drugs or novel structures are included. New imidazoles, fluconazole analogs and adducts of azoles with 2,6-di-tert-butyl-4-methylphenol are described. The review also includes chitinases, β-1,3-D-glucan and chitin synthases inhibitors and novel structures. In the patents reviewed here, progress has been made to accomplish at least one of the necessary requirements for the development of novel antifungal agents, such as broad spectrum of activity, more favorable pharmacokinetic profile, good bioavailability and low adverse effects. However, in vivo activity, mechanisms of action, drug-drug interactions and other aspects that make a compound a good antifungal agent need further development.


Stepping strategies for regulating gait adaptability and stability.
Besides a stable gait pattern, gait in daily life requires the capability to adapt this pattern in response to environmental conditions. The purpose of this study was to elucidate the anticipatory strategies used by able-bodied people to attain an adaptive gait pattern, and how these strategies interact with strategies used to maintain gait stability. Ten healthy subjects walked in a Computer Assisted Rehabilitation ENvironment (CAREN). To provoke an adaptive gait pattern, subjects had to hit virtual targets, with markers guided by their knees, while walking on a self-paced treadmill. The effects of walking with and without this task on walking speed, step length, step frequency, step width and the margins of stability (MoS) were assessed. Furthermore, these trials were performed with and without additional continuous ML platform translations. When an adaptive gait pattern was required, subjects decreased step length (p<0.01), tended to increase step width (p=0.074), and decreased walking speed while maintaining similar step frequency compared to unconstrained walking. These adaptations resulted in the preservation of equal MoS between trials, despite the disturbing influence of the gait adaptability task. When the gait adaptability task was combined with the balance perturbation subjects further decreased step length, as evidenced by a significant interaction between both manipulations (p=0.012). In conclusion, able-bodied people reduce step length and increase step width during walking conditions requiring a high level of both stability and adaptability. Although an increase in step frequency has previously been found to enhance stability, a faster movement, which would coincide with a higher step frequency, hampers accuracy and may consequently limit gait adaptability.


Detection of isorhamnetin glycosides in extracts of apples (Malus domestica cv. "Brettacher") by HPLC-PDA and HPLC-APCI-MS/MS.
Extracts of apple fruits (Malus domestica cv. "Brettacher") were analysed by HPLC with photodiode array detection. An unknown peak was monitored displaying the same retention time as isorhamnetin 3-O-glucoside. Preliminary identification of the isorhamnetin aglycone was performed by comparison of UV spectral data of the unknown compound with a reference substance. Using atmospheric pressure chemical ionisation mass spectrometry in the negative ion mode, the presence of an isorhamnetin glycoside was supported by loss of 162 amu from the pseudomolecular ion (m/z 477). MS2 product ion analysis of the parent ion m/z 477 provided a fragmentation pattern identical to the reference. Collision-induced dissociation of the aglycone (m/z 315) in the MS3 product ion analysis allowed the differentiation of rhamnetin and isorhamnetin, and unambiguous assignment by comparison with standard compounds. A second isorhamnetin glycoside eluting prior to the glucoside was tentatively identified as isorhamnetin 3-O-galactoside. To the best of our knowledge, this is the first report of isorhamnetin glycosides in apple fruit extracts. Results are discussed with respect to chemotaxonomic relevance within the genera Malus and Pyrus, and especially in consideration of the control of the authenticity of apple products.


Analysis of differentially expressed genes related to cerebral ischaemia in young rats based on the Gene Expression Omnibus database.
The incidence rate of cerebral infarction in young people is increasing day by day, the age of onset tends to be younger, and its internal pathogenesis and mechanism are very complicated, which leads to greater difficulties in treatment. Therefore, it is essential to analyze the key pathway that affects the onset of cerebral infarction in young people from the perspective of genetics. To compare the differentially expressed genes in the brain tissue of young and aged rats with middle cerebral artery occlusion and to analyse their effect on the key signalling pathway involved in the development of cerebral ischaemia in young rats. The Gene Expression Omnibus 2R online analysis tool was used to analyse the differentially expressed genes in the GSE166162 dataset regarding the development of cerebral ischaemia in young and aged groups of rats. DAVID 6.8 software was further used to filter the differentially expressed genes. These genes were subjected to Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the key gene pathway that affects the occurrence of cerebral ischaemia in young rats. Thirty-five differentially expressed genes (such as Igf2, Col1a2, and Sfrp1) were obtained; 73 GO enrichment analysis pathways are mainly involved in biological processes such as drug response, amino acid stimulation response, blood vessel development, various signalling pathways, and enzyme regulation. They are involved in molecular functions such as drug binding, protein binding, dopamine binding, metal ion binding, and dopamine neurotransmitter receptor activity. KEGG pathway enrichment analysis showed a significantly enriched pathway: The cyclic adenosine monophosphate (c-AMP) signalling pathway. The c-AMP signalling pathway might be the key pathway in the intervention of cerebral infarction in young people.


Differences in glycinergic mIPSCs in the auditory brain stem of normal and congenitally deaf neonatal mice.
We have investigated the fundamental properties of central auditory glycinergic synapses in early postnatal development in normal and congenitally deaf (dn/dn) mice. Glycinergic miniature inhibitory postsynaptic currents (mIPSCs) were recorded using patch-clamp methods in neurons from a brain slice preparation of the medial nucleus of the trapezoid body (MNTB), at 12-14 days postnatal age. Our results show a number of significant differences between normal and deaf mice. The frequency of mIPSCs is greater (50%) in deaf versus normal mice. Mean mIPSC amplitude is smaller in deaf mice than in normal mice (mean mIPSC amplitude: deaf, 64 pA; normal, 106 pA). Peak-scaled fluctuation analysis of mIPSCs showed that mean single channel conductance is greater in the deaf mice (deaf, 64 pS; normal, 45 pS). The mean decay time course of mIPSCs is slower in MNTB neurons from deaf mice (mean half-width: deaf, 2.9 ms; normal, 2.3 ms). Light- and electron-microscopic immunolabeling results showed that MNTB neurons from deaf mice have more (30%) inhibitory synaptic sites (postsynaptic gephyrin clusters) than MNTB neurons in normal mice. Our results demonstrate substantial differences in glycinergic transmission in normal and congenitally deaf mice, supporting a role for activity during development in regulating both synaptic structure (connectivity) and the fundamental (quantal) properties of mIPSCs at central glycinergic synapses.


Gardner's syndrome with an unusual fibro-osseous lesion of the mandible.
A girl with a family history of Gardner's syndrome presented with an actively growing central lesion of the mandible and localized subcutaneous fibrous hyperplasia which required surgical intervention and bone grafting. The importance of this syndrome is the development of intestinal polyposis which become malignant. The presence of dentofacial stigmata and surface tumors should alert the dentist and physician to the possibility of Gardner's syndrome.


Metoprolol in the treatment and prophylaxis of paroxysmal reentrant supraventricular tachycardia.
The effect of metoprolol on paroxysmal reentrant supraventricular tachycardia was studied in 30 patients. In 16 cases (12 accessory pathway, 4 pure AV nodal reentry) programmed stimulation was performed before and after 0.1 mg/kg intravenous metoprolol. When administered during sustained tachycardia, metoprolol terminated the arrhythmia in 4 out of 12 cases. Metoprolol prolonged the AV nodal functional and effective refractory period and the A-H interval but had no effect on refractory periods and conduction intervals of accessory pathways. Following metoprolol no tachycardia could be initiated in five patients. Premature atrial pacing revealed widened tachycardia zones in 10 cases; premature ventricular pacing showed varying responses to the drug. Twenty two patients (13 accessory pathway, 9 pure AV nodal reentry) received two times 50 to two times 100 mg metoprolol orally per day and were followed for 4 weeks. Five patients did not complete the entire term, four because of frequent tachycardia and one because of side effects. Ten patients were free of arrhythmia, most over several months, and seven continued to have attacks. Plasma levels were higher on oral metoprolol. Intravenous testing had correctly predicted the response to oral metoprolol in seven out of eight patients. Higher plasma concentrations, suppression of premature beats, or the different patient population may explain the more favorable prophylactic action of oral metoprolol.


Performance of two alternative methods for Listeria detection throughout Serro Minas cheese ripening.
The ability of pathogens to survive cheese ripening is a food-security concern. Therefore, this study aimed to evaluate the performance of two alternative methods of analysis of Listeria during the ripening of artisanal Minas cheese. These methods were tested and compared with the conventional method: Lateral Flow System™, in cheeses produced on laboratory scale using raw milk collected from different farms and inoculated with Listeria innocua; and VIDAS(®)-LMO, in cheese samples collected from different manufacturers in Serro, Minas Gerais, Brazil. These samples were also characterized in terms of lactic acid bacteria, coliforms and physical-chemical analysis. In the inoculated samples, L. innocua was detected by Lateral Flow System™ method with 33% false-negative and 68% accuracy results. L. innocua was only detected in the inoculated samples by the conventional method at 60-days of cheese ripening. L. monocytogenes was not detected by the conventional and the VIDAS(®)-LMO methods in cheese samples collected from different manufacturers, which impairs evaluating the performance of this alternative method. We concluded that the conventional method provided a better recovery of L. innocua throughout cheese ripening, being able to detect L. innocua at 60-day, aging period which is required by the current legislation.


Tetramethylpyrazine Facilitates Functional Recovery after Spinal Cord Injury by Inhibiting MMP2, MMP9, and Vascular Endothelial Cell Apoptosis.
Spinal cord injury (SCI) is a major public health issue that leads to neurological dysfunctions and morbidities in patients. Tetramethylpyrazine (TMP) plays a neuroprotective role in SCI; however, the underlying mechanism has not been fully elucidated. In the present study, we aimed to investigate the mechanisms and therapeutic effects of TMP on SCI. A contusion SCI model was established that used a modified Allen's method. In the TMP group, TMP (200 mg/kg) was injected daily for 5 days post-injury, while in the Negative Control (NC) group, an equal volume of normal saline was injected. Hindlimb motor function was evaluated using the Basso, Beattie, Bresnahan (BBB) scale. The effects of TMP on protein levels of the matrix metalloproteinases 2 (MMP2) and 9 (MMP9), Bax and cleaved caspase-3 were determined by western blotting. Apoptotic changes in vascular endothelial cells were evaluated using immunofluorescence and TUNEL staining. Alterations in 3D vessel morphology after treatment with TMP were assessed by synchrotron radiation micro-CT (SRμCT). TMP treatment significantly improved recovery in hindlimb motor function and attenuated vascular endothelial cell apoptosis in rats with SCI. Additionally, TMP treatment markedly decreased the protein levels of MMP2 and MMP9, pro-apoptotic bax and cleaved caspase-3 while promoting angiogenesis, as evidenced by vessel visualization using SRμCT. These results indicate that TMP attenuated SCI-induced neurological impairments by the down-regulation of the expression of MMP2 and MMP9 proteins, the inhibition of vascular endothelial cell apoptosis, and the promotion of angiogenesis.


Synthesis and antimicrobial activity of some novel oxadiazole derivatives.
A series of 5-(3'-oxo-6'-(substituted aryl)-2',3',4',5'-tetrahydropyridazin-2'-ylmethyl )-2-substituted 1,3,4-oxadiazole has been synthesized. Appropriate aromatic hydrocarbon reacts with succinic anhydride in the presence of AICl3 to yield beta-aroyl propionic acid (1a). The corresponding acid is cyclized with hydrazine hydrate to give 6-(substituted aryl)-2,3,4,5-tetrahydro-3-pyridazinone (1b). This ntermediate after reaction with ethyl bromoacetate, was hydrazinolyzed into 3-oxo-6-(substituted aryl)-2, 3, 4, 5-tetrahydropyridazinyl acetohydrazide (1c). The resulting product was converted into 5-[3'-oxo-6'-(substituted aryl)-2',3',4',5'-tetrahydropyridazin-2'-ylmethyl]-2-substituted 1,3,4-oxadiazole (Scheme 1). All the final compounds were structurally elucidated on the basis of IR, H-NMR, MS data and elemental analysis and screened for antibacterial, antifungal and antitubercular activity. All the compounds are evaluated for their antibacterial activity against E. coli, S. aureus, Micrococcus luteus and Klebsiella pneumoniae by using cup plate technique in the nutrient agar at 100 microg/mL concentration. Antitubercular activity was determined using the BACTEC 460 system. Stock solutions of test compounds were prepared in DMSO. MIC of rifampin was calculated by established procedures. All the synthesized compounds were screened at 6.25 microg/mL against M. tuberculosis H37 Rv comparable with that of standard rifampicin and isoniazid. All the final compounds were evaluated for antifungal activity against C. albicans and C. neoformans by using cup-plate method in the Sabouraud agar media The zone of inhibition (mm) of each compound was determined and compared with standard drug fluconazole.


Pirfenidone, nintedanib and N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: A systematic review and meta-analysis.
The prevalence of idiopathic pulmonary fibrosis (IPF) is increasing every year. Pirfenidone and nintedanib were approved for treatment of IPF in 2014, but they received only a conditional recommendation for use and, thus, to date no drugs are strongly recommended for IPF. The aim of this study was to assess the effectiveness and safety of the currently approved drugs for IPF and N-acetylcysteine (NAC), the most debated drug in the last update of guidelines for IPF treatment. RCTs in IPF were identified searching from databases of published and unpublished studies. The influence of pirfenidone, nintedanib and NAC on clinical outcomes, safety, and mortality was assessed via pair-wise meta-analysis. Ten papers (3847 IPF patients; 2254 treated; 1593 placebo) were included in this study. Our results showed that both pirfenidone and nintedanib, but not NAC, were significantly effective in reducing FVC decline and the risk of FVC ≥10% decline in percent predicted over 12 months. Nintenadib significantly protected against the risk of acute exacerbation and mortality. Pirfenidone and nintedanib showed a similar and good safety profile, whereas NAC provided a signal for increased adverse events. The rank of effectiveness emerging from this meta-analysis represents an indirect indicator of potential differences between currently approved doses of pirfenidone and nintedanib. Direct comparisons are necessary to assess this matter, and well designed bench-to-bedside studies would permit to understand the potential of combined, sequential, or adjunctive treatment regimens in which perhaps NAC may have a role for specific clusters of IPF patients.


Day-old vaccination with live-in-oil vaccines: Newcastle disease (ND) and infectious bursal disease (IBD) in chicks and ND in turkey poults.
One-day-old broiler chicks were vaccinated with live Newcastle disease (ND) vaccine incorporated in oil alone or in killed-in-oil ND vaccine. Incorporation of live vaccine in oil emulsions was carried out just prior to vaccination. Live-in-oil ND vaccine containing 106.0 median embryo lethal doses (ELD50/dose induced the same protection following challenge and the same level of antibody at 42 days post-vaccination as did commercial killed-in-oil ND vaccine containing about 250 times as much antigen (108.4 ELD50/dose). Incorporation of live ND vaccine in killed-in-oil vaccine contributed markedly to protection rates and antibody levels, as compared to those obtained following vaccination with killed-in-oil vaccine only. One-day-old turkey poults also showed the advantage of incorporation of live ND vaccine in killed-in-oil vaccine when challenged 3 months post-vaccination. One-day-old broiler chicks, vaccinated with live ND and infectious bursal disease vaccine (IBD) incorporated in killed-in-oil combined ND + IBD vaccine, showed better protection against challenge with IBDV and higher antibody levels to NDV as compared to vaccination with killed-in-oil vaccine alone.


Transplantation of Adult Rat Schwann Cells into the Injured Spinal Cord.
Adult Schwann cells (SCs) can provide both a permissive substrate for axonal growth and a source of cells to ensheath and myelinate axons when transplanted into the injured spinal cord. Multiple studies have demonstrated that SC transplants can be used as part of a combinatorial approach to repairing the injured spinal cord. Here, we describe the protocols for collection and transplantation of adult rat primary SCs into the injured spinal cord. Protocols are included for the tissue culture procedures necessary for collection, quantification, and suspension of the cells for transplantation and for the surgical procedures for spinal cord injury at thoracic level nine (T9), reexposure of the injury site for delayed transplantation, and injection of the cells into the spinal cord.


Upper airway dynamic responses in children with the obstructive sleep apnea syndrome.
Normal children have a smaller upper airway than adults, but, nevertheless, snore less and have less apnea. We have previously shown that normal children have an upper airway that is resistant to collapse during sleep. We hypothesized that this resistance to collapse is due to preservation of upper airway neuromotor responses during sleep. Furthermore, we hypothesized that upper airway responses would be diminished in children with the obstructive sleep apnea syndrome (OSAS). We therefore compared the upper airway pressure-flow relationship during sleep between children with OSAS and controls. Measurements were made by correlating maximal inspiratory airflow with the level of nasal pressure applied via a mask. Neuromotor upper airway activation was assessed by evaluating the upper airway response to 1) hypercapnia and 2) intermittent, acute negative pressure. We found that children with OSAS had no significant response to either hypercapnia or negative pressure during sleep, compared with the normal children. After treatment of OSAS by tonsillectomy and adenoidectomy, there was a trend for normalization of upper airway responses. We conclude that upper airway dynamic responses are decreased in children with OSAS but recover after treatment. We speculate that the pharyngeal airway neuromotor responses present in normal children are a compensatory response for a relatively narrow upper airway. Further, we speculate that this compensatory response is lacking in children with OSAS, most likely due to either habituation to chronic respiratory abnormalities during sleep or to mechanical damage to the upper airway.


Discrimination, psychological functioning, and substance use among U.S. young adults aged 18-28, 2017.
This study aimed to test whether (a) discrimination is associated with past 30-day/current alcohol, cigarette, e-cigarette, alcohol, marijuana, and other illicit drug use among Black and White U.S. adults aged 18-28, (b) psychological distress (PD) and positive well-being (PW) are mediators of the discrimination-substance use relationships, and (c) the associations are moderated by race and sex. Using data from a 2017 U.S. nationally representative survey we conducted multiple-group moderated mediation analyses among 2,192 young adults aged 18-28 (508 Black males, 594 Black females, 533 White males, 557 White females). Black males had higher discrimination, Whites had higher PW, and females had higher PD scores. Discrimination was positively associated with PD and negatively associated with PW. Among all groups, discrimination was positively associated with other illicit drug (direct and indirect), and marijuana use through PD. Indirect effects were stronger among White males for other illicit drugs and Black males for marijuana. The indirect effect of discrimination and alcohol use through PW was positive for Black females and negative for all other groups examined. Among Black males only, discrimination was positively associated with cigarette and alcohol use through PD (positive) and cigarette smoking through PW (negative). This study highlights the negative influence of perceived discrimination on current licit and illicit substance use among Black and White young adults. Our results suggest that this relationship may be partially mediated by PD and PW, especially among Black male young adults. Future discrimination and substance use studies should consider potential mediation effects of poor mental health and differences by race and sex. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Mechanism of catalytic aziridination with manganese corrole: the often postulated high-valent Mn(V) imido is not the group transfer reagent.
The reaction of Arl=NTs (Ar = 2-(tert-butylsulfonyl)benzene and Ts = p-toluenesulfonyl) and (tpfc)Mn (tpfc=5,10,15-tris(pentafluorophenyl)corrole), 1, affords the high-valent (tpfc)MnV=NTs, 2, on stopped-flow time scale. The reaction proceeds via the adduct [(tpfc)MnIII(ArINTs)], 3, with formation constant K3 = (10 +/- 2) x 10(3) L mol-1. Subsequently, 3 undergoes unimolecular group transfer to give complex 2 with the rate constant k4 = 0.26 +/- 0.07 s-1 at 24.0 degrees C. The complex (tpfc)Mn catalyzes [NTs] group transfer from ArINTs to styrene substrates with low catalyst loading and without requirement of excess olefin. The catalytic aziridination reaction is most efficient in benzene because solvents such as toluene undergo a competing hydrogen atom transfer (HAT) reaction resulting in H2NTs and lowered aziridine yields. The high-valent manganese imido complex (tpfc)Mn=NTs does not transfer its [NTs] group to styrene. Double-labeling experiments with ArINTs and ArINTstBu (TstBu = (p-tert-butylphenyl)sulfonyl) establish the source of [NR] transfer as a "third oxidant", which is an adduct of Mn(V) imido, [(tpfc)Mn(NTstBu)(ArINTs)](4). Formation of this oxidant is rate limiting in catalysis.


Human body modeling method to simulate the biodynamic characteristics of spine in vivo with different sitting postures.
The aim of this study is to model the computational model of seated whole human body including skeleton, muscle, viscera, ligament, intervertebral disc, and skin to predict effect of the factors (sitting postures, muscle and skin, buttocks, viscera, arms, gravity, and boundary conditions) on the biodynamic characteristics of spine. Two finite element models of seated whole body and a large number of finite element models of different ligamentous motion segments were developed and validated. Static, modal, and transient dynamic analyses were performed. The predicted vertical resonant frequency of seated body model was in the range of vertical natural frequency of 4 to 7 Hz. Muscle, buttocks, viscera, and the boundary conditions of buttocks have influence on the vertical resonant frequency of spine. Muscle played a very important role in biodynamic response of spine. Compared with the vertical posture, the posture of lean forward or backward led to an increase in stress on anterior or lateral posterior of lumbar intervertebral discs. This indicated that keeping correct posture could reduce the injury of vibration on lumbar intervertebral disc under whole-body vibration. The driving posture not only reduced the load of spine but also increased the resonant frequency of spine.


Octahedral Ruthenium Complex with Exclusive Metal-Centered Chirality for Highly Effective Asymmetric Catalysis.
A novel ruthenium catalyst is introduced which contains solely achiral ligands and acquires its chirality entirely from octahedral centrochirality. The configurationally stable catalyst is demonstrated to catalyze the alkynylation of trifluoromethyl ketones with very high enantioselectivity (up to >99% ee) at low catalyst loadings (down to 0.2 mol%).


Development of guidelines for idiopathic normal-pressure hydrocephalus: introduction.
There are no currently accepted evidence-based guidelines for the diagnosis and management of the normal-pressure hydrocephalus (NPH) patient. As a result, an independent study group was assembled to address this issue and determine the feasibility of developing standardized guidelines, which would be acceptable in the United States and abroad and would be based on the available scientific evidence. The guidelines were to encompass value of clinical presentation, value of supplementary diagnostic tests, surgical management, and outcome assessment. Initially, a series of 10 questions were formulated in the areas of pathophysiology, diagnosis, and treatment to obtain a consensus by panels of experts (see Acknowledgments) assembled in San Antonio, TX, in September 2000. This workshop provided significant insight into the difficulties in developing NPH guidelines, and a consensus was reached as to those questions involving expert opinion. Subsequently, evidentiary tables were developed on the basis of the available evidence. Only those studies with 20 or more idiopathic NPH (INPH) patients were included. Sensitivity, specificity, and positive and negative predictive values for INPH diagnostic criteria were assessed, and guidelines were developed on the basis of the available evidence. Recommendations for classification of INPH and additional studies were documented. The development of the guidelines was made difficult because systematic studies of INPH and patient numbers were few. It was decided to maintain the classification of NPH into two major categories, INPH and those of known cause (secondary NPH). Many studies "mixed" these classifications, and as a result, they could not be used in the evidentiary tables. Despite these problems, evidence-based guidelines were developed, and it is hoped that they will be useful in guiding clinical management of the INPH patient.


Longitudinal field studies of infectious bronchitis virus and avian pneumovirus in broilers using type-specific polymerase chain reactions.
In longitudinal studies, 13 flocks were swabbed twice each week for the life of the flock (up to 46 days). The swabs were analyzed by type-specific reverse transcriptase polymerase chain reactions. Massachusetts type vaccinal infectious bronchitis virus (IBVs), applied at the hatchery, were usually maximal during the first week, as expected and, notably, remained detectable for 3 to 4 weeks, occasionally longer. IBV of the 793/B type (also known as 4/91 and CR88) was detected in 11/13 flocks (85%). The time of first detection of 793/B varied over several weeks and was sometimes within the first week in low amounts, which increased gradually. In some flocks, detection of 793/B remained intermittent. IBV types D274 and D1466 were each detected once, in the same flock, for short periods, in low amounts, and in the presence of higher amounts of 793/B. In swabs from a further 30 broiler flocks, plus those already mentioned, there was an incidence for 793/B, D274 and D1466 of 79, 10 and 2%, respectively. Avian pneumovirus (APV) (avian or turkey rhinotracheitis virus) vaccines, applied at the hatchery or later, were either not detected or were detected only after a delay of 1 to 3 weeks. In five flocks that received no APV-A vaccine and two flocks that received only APV type A vaccine, field infection by APV type B was detected but only during the last week or so of life. In six flocks that had received an APV-B vaccine, no field APV-B, differentiated from vaccinal APV-B by restriction enzyme analysis, was detected. In swabs from 30 other flocks, the great majority of which had not been vaccinated against APV, the incidence of APV types B and A was 50 and 3%, respectively. The results show (a) that vaccinal IBV can be detected for several weeks, (b) the dominance of the IBV 793/B type and


Childhood occipital epilepsy of Gastaut: a study of 33 patients.
To characterize the electroclinical features and evolution of childhood occipital epilepsy of Gastaut (COE-G). Children with electroclinical criteria of COE-G were retrospectively identified and followed-up clinically, and with sleep and awake EEGs between 1990 and 2007. We identified 33 patients with COE-G. In the same length of time, 201 children with Panayiotopoulos syndrome and 410 children with benign childhood epilepsy with centrotemporal spikes were registered. COE-G had a peak age at onset of 8.5 years. Visual manifestations were the most common ictal event. Ictal deviation of the eyes was frequent. Approximately half of the patients had migraine-like symptoms. In all patients the seizures occurred while awake, and 11 also had seizures during sleep. The majority of the patients had occipital spike-wave discharges when the eyes were closed that disappeared or attenuated when the eyes were opened. Prognosis was excellent in 80% of the cases. This study confirms the existence of COE-G, a rare but well-defined syndrome within the group of idiopathic focal epilepsies in childhood.


Antimicrobial and bactericidal activities of esters of 2-endo-hydroxy-1,8-cineole as new aroma chemicals.
Fourteen kinds of alkyl esters of 2-endo-hydroxy-1,8-cineole were synthesized, with yields of 57.8-98.0%. Each ester had a characteristic and unique odor. Especially, the tert-butyl acetate of 2-endo-hydroxy-1,8-cineole had the most interesting odor of all the synthetic esters. The antimicrobial and bactericidal activities of these synthetic esters against test bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas fluorescens) were examined using the broth dilution method. As a result, the tert-butyl acetate of 2-endo-hydroxy-1,8-cineole showed the highest antimicrobial and bactericidal activities against all kinds of the test bacteria.


New antithrombotics for the treatment of acute and chronic arterial ischemia.
The established antithrombotic agents are effective but they have limitations which have provided opportunities for the development of new antithrombotic compounds. Of these new agents, the antithrombin III-independent thrombin inhibitors and the platelet GPIIb/IIIa receptor antagonists are the most advanced in their development. Other new antithrombotic agents include the antithrombin III-independent factor Xa inhibitors, activated protein C, soluble thrombomodulin and tissue factor pathway inhibitor. Of the GPIIb/IIIa antagonists, the humanized 7E3 antibody and integrin have been evaluated in phase III studies. The 7E3 antibody was effective in preventing both short-term and longer-term complications of coronary angioplasty. The antithrombin III-independent thrombin inhibitors hirudin and hirulog have also been evaluated in phase III studies. The studies with hirudin as an adjuvant to coronary thrombolysis had to be terminated and restarted at lower dosages because of an unacceptable incidence at intracranial hemorrhage and the study with hirulog produced equivocal results.


The dark side of hippo signaling: A cancer promoter role.
The Hippo signaling pathway regulates organ size and tissue homeostasis. Given this role it is unsurprising that dysregulation of this pathway has implications for cancer progression. A convincing body of literature shows that the Hippo pathway serves a tumor suppressive function with its inactivation leading to massive overgrowth. However, additional studies have also shown that activation of Hippo signaling can promote tumor progression. It remains unknown how a single pathway can produce such diametrically opposed effects. This lack of knowledge is in part due to our inability to make meaningful comparisons from studies which have taken place in a variety of cell types, tissues, and organisms. Recently however, we have published 2 studies using the Drosophila wing disk to study the Hippo pathway and have found that Hippo pathway activation can promote cell migration and invasion while Hippo pathway inactivation leads to overgrowth. Thus we propose here that Drosophila can provide a research platform with which to begin addressing how the Hippo pathway can both enhance and suppress tumor progression due to published pro- and anti-tumor functionalities of the Hippo pathway in the same tissue.


Enhancing Clinical Trials Through Synergistic Gamma Power Analysis.
While the etiology of many neuropsychiatric disorders remains unknown, increasing evidence suggests that aberrant sensory processing plays a central role. For this class of disorders, which are characterized by affective, cognitive, and behavioral symptoms, electroencephalography remains the dominant tool for providing insight into the physiological and molecular underpinnings of the disease state and predicting the effectiveness of investigational new drugs. Within the spectrum of electrical activity present in the CNS, high-frequency oscillations in the gamma band are frequently altered in these patient populations. Measurement of gamma oscillation can be further classified into baseline and evoked, each of which offers a specific commentary on disease state. Baseline gamma analysis provides a surrogate of pharmacodynamics and predicting the time course effects of clinical candidate drugs, while alterations in evoked (time-locked) gamma power may serve as a disease biomarker and have utility in assessing patient response to new drugs. Together, these techniques offer complimentary methods of analysis for discrete realms of clinical and translational medicine. In terms of drug development, comprehensive analysis containing aspects of both baseline and evoked gamma oscillations may prove more useful in establishing better workflow and more accurate criteria for the testing of investigational new drugs.


The TRKB rs2289656 genetic polymorphism is associated with acute suicide attempts in depressed patients: A transversal case control study.
Suicide Attempts (SA) are the main complications of Major Depressive Episodes (MDE) and are difficult to predict. Suicide is associated with the expression of Receptor Tyrosin-Kinase B (TRKB), the receptor of the Brain Derived Neurotrophic Factor (BDNF) involved in MDE. However, the impact of its genetic polymorphisms as predictive factors of SA should be clarified. Our main aim is to assess the association of 8 TRKB genetic polymorphisms and SA in depressed patients. In 624 patients currently experiencing an MDE in the context of Major Depressive Disorder (MDD) (METADAP study), we assessed the association between 8 TRKB genetic polymorphisms (rs1778933, rs1187352, rs2289658, rs2289657, rs2289656, rs3824519, rs56142442 and rs1439050) and acute (previous month) or past (older than one month) SA. Bonferroni corrections and multivariate analysis adjusted for age, sex, level of education, marital status, Hamilton Depression Rating Scale score and previous MDE were used. The rs2289656 was associated with acute SA (CC = 28.5%, CT = 15.0% and TT = 11.5%, p = 0.0008). However, the other SNPs were not. Patients with the CC genotype had a higher rate of acute SA (28.5%) as compared to T carriers (14.6%) (adjusted OR = 2.2, CI95% [1.4; 3.5], p<0.0001). The TRKB rs2289656 CC genotype is associated with a 2.2 fold higher risk of acute SA in depressed patients. If this result could be confirmed, this TRKB SNP may be assessed to contribute to the prediction of SA in depressed patients.


Child Neurology: Bartonella henselae Neuroretinitis in 2 Patients.
Neuroretinitis due to Bartonella henselae infection is a rare cause of vision loss in children. Two pediatric cases of acute unilateral vision loss accompanied by edema of the optic nerve on fundoscopic examination are presented. Severe causes of vision loss were excluded. During the course of the disease, macular stellate exudates emerged on control fundoscopic examinations, and diagnosis of neuroretinitis was made. A causative agent was confirmed by serologic examination, as high titers of IgM and IgG antibodies to Bartonella henselae were detected. Both patients significantly recovered after oral antibiotic treatment.


EgRBP42 encoding an hnRNP-like RNA-binding protein from Elaeis guineensis Jacq. is responsive to abiotic stresses.
RNA-binding proteins (RBPs) have been implicated as regulatory proteins involved in the post-transcriptional processes of gene expression in plants under various stress conditions. In this study, we report the cloning and characterization of a gene, designated as EgRBP42, encoding a member of the plant heterogeneous nuclear ribonucleoprotein (hnRNP)-like RBP family from oil palm (Elaeis guineensis Jacq.). EgRBP42 consists of two N-terminal RNA recognition motifs and a glycine-rich domain at the C-terminus. The upstream region of EgRBP42 has multiple light-responsive, stress-responsive regulatory elements and regulatory elements associated with flower development. Real-time RT-PCR analysis of EgRBP42 showed that EgRBP42 was expressed in oil palm tissues tested, including leaf, shoot apical meristem, root, female inflorescence, male inflorescence and mesocarp with the lowest transcript level in the roots. EgRBP42 protein interacted with transcripts associated with transcription, translation and stress responses using pull-down assay and electrophoretic mobility shift assay. The accumulation of EgRBP42 and its interacting transcripts were induced by abiotic stresses, including salinity, drought, submergence, cold and heat stresses in leaf discs. Collectively, the data suggested that EgRBP42 is a RBP, which responds to various abiotic stresses and could be advantageous for oil palm under stress conditions. Key message EgRBP42 may be involved in the post-transcriptional regulation of stress-related genes important for plant stress response and adaptation.


Personality Development at Work: Workplace Conditions, Personality Changes, and the Corresponsive Principle.
Investigations concerning adult personality development have increasingly focused on factors that are associated with apparent personality trait changes. The current study contributes to this literature by replicating and extending previous research concerning personality trait development in young adulthood and perceptions of workplace conditions. Analyses were based on up to 442 individuals who participated in the ongoing Family Transitions Project (e.g., Conger & Conger, 2002). The current analyses included personality trait data from 1994 and 2003, high school grades and socioeconomic status indicators from 1994, and reports about work conditions in 2001, 2003, and 2005. Personality attributes were prospectively associated with work conditions and income. Findings also support the corresponsive principle of personality development (e.g., Roberts, Caspi, & Moffitt, 2003): Traits that were prospectively associated with particular workplace conditions often seemed to be accentuated by those conditions. Personality traits are prospectively associated with perceptions of the workplace. Workplace conditions are also associated with trait development.


Trade, intellectual property, and the public health bearing.
The objective of this article is to describe the current fracture between global trade and public health priorities, as well as examine opportunities for harmonisation. A literature review of public health, global trade, and intellectual property articles describes several issues with recommendations. Currently, there is mixed quality of research and a lack of health impact assessments to accompany the global trade agenda. Human rights concepts continue in debate as flexibilities to trade laws remain without organised surveillance or evaluation. There are specific, relevant recommendations to implement a trade agenda inclusive of public health leadership. Recent trade and intellctual property advances in public health collaborations should be supported and continued. Trade groups should produce impact assessments before decisions on policies are made, with quality to the research. Lastly, a global research and development treaty should be an open, accessed path.


Large-Scale Hexagonal-Patterned Growth of Aligned ZnO Nanorods for Nano-optoelectronics and Nanosensor Arrays.
An effective approach is demonstrated for growing large-area, hexagonally patterned, aligned ZnO nanorods. The synthesis uses a catalyst template produced by a self-assembled monolayer of submicron spheres and guided vapor-liquid-solid (VLS) growth on a single crystal alumina substrate. The ZnO nanorods have uniform shape and length, align vertically on the substrate, and are distributed according to the pattern defined by the catalyst template. The nanorods grow along [0001] with side surfaces defined by {21̄1̄0}. This approach opens the possibility of creating patterned one-dimensional nanostructures for applications as sensor arrays, piezoelectric antenna arrays, optoelectronic devices, and interconnects.


Comparison of the effects of efonidipine and amlodipine on aldosterone in patients with hypertension.
To prevent cardiovascular disease, targeting aldosterone synthesis and release may be clinically important. Aldosterone production in the adrenal gland is mediated mainly by the T-type calcium channel in vitro. Efonidipine inhibits both L- and T-type Ca channels. To compare the effects of efonidipine on neurohumoral factors with those of amlodipine, an L-type Ca channel blocker, we studied 40 essential hypertensive outpatients. Forty patients who had been administered amlodipine for more than 1 year were treated with efonidipine for 6 months in place of amlodipine. Substituting efonidipine for amlodipine had no significant effect on clinic systolic blood pressure or the plasma levels of brain natriuretic peptide, norepinephrine or active renin. However, the heart rate was significantly decreased (72.0+/-1.3 vs. 69.8+/-1.3 beats/min, p<0.01) and the plasma aldosterone level was also significantly decreased after efonidipine treatment (97.7+/-7.9 vs. 79.7+/-5.6 pg/mL, p<0.0001). Changes in the aldosterone level correlated with the baseline value before the replacement of amlodipine by efonidipine (r=-0.769, p<0.0001). These findings indicate that at the effective antihypertensive doses of efonidipine and amlodipine, efonidipine significantly decreases heart rate and plasma aldosterone level compared with those under amlodipine treatment in hypertensive patients.


Associations of anthropometry and lifestyle factors with HDL subspecies according to apolipoprotein C-III.
The presence of apoC-III on HDL impairs HDL's inverse association with coronary heart disease (CHD). Little is known about modifiable factors explaining variation in HDL subspecies defined according to apoC-III. The aim was to investigate cross-sectional associations of anthropometry and lifestyle with HDL subspecies in 3,631 participants from the Diet, Cancer, and Health study originally selected for a case-cohort study (36% women; age 50-65 years) who were all free of CHD. Greater adiposity and less activity were associated with higher HDL containing apoC-III and lower HDL lacking apoC-III. Per each 15 cm higher waist circumference, the level of HDL containing apoC-III was 2.8% higher (95% CI: 0.4, 5.3; P = 0.024) and the level of HDL not containing apoC-III was 4.7% lower (95% CI: -6.0, -3.4; P = <0.0001). Associations for physical activity were most robust to multivariable modeling. Each 20 metabolic equivalent task hours per week reported higher physical activity was associated with 0.9% (95% CI: -1.7, -0.1; P = 0.031) lower HDL containing apoC-III and 0.5% higher (95% CI: 0.1, 1.0; P = 0.029) HDL lacking apoC-III. Lower alcohol consumption was associated with lower HDL lacking apoC-III (percent difference per 15 g/day: 1.58 (95% CI: 0.84, 2.32; P = <0.0001). Adiposity and sedentary lifestyle were associated with a less favorable HDL subspecies profile.


Changes in bowel symptoms after different pelvic organ prolapse surgeries among elderly women at the 1-year follow up.
To investigate the prevalence of bowel symptoms in patients with pelvic organ prolapse (POP), to evaluate the changes in bowel symptoms after different POP surgeries, and to identify risk factors for unrelieved bowel symptoms. This was an observational prospective cohort study conducted at Peking University First Hospital from 2020 to 2021. Demographic, clinical, and therapeutic data were collected. Participants underwent POP Quantification examination and completed the Pelvic Floor Distress Inventory-20 questionnaire at baseline and 1 year postoperatively. The prevalence of bowel symptoms and bothersome bowel symptoms in women with POP was 46.38% and 24.40%, respectively. Surgical correction of prolapse was associated with significant relief in bowel symptoms (P < 0.05). Colpocleisis may relieve bowel symptoms better than reconstructive surgeries (41% vs. 31%, P = 0.048). However, 35% of women had at least one bowel symptom at the 1-year follow up. A long perineal body (Pb) and levator ani muscle injury were found to be predictors of unrelieved bowel symptoms in patients undergoing colpocleisis and those undergoing reconstructive surgery, respectively (odds ratio [OR] 2.306, 95% confidence interval [CI] 1.112-4.783, P = 0.025 and OR 3.245, 95% CI 1.266-8.317, P = 0.014, respectively), and perineoplasty was a protective factor for women who underwent colpocleisis (OR 0.102, 95% CI 0.025-0.417, P = 0.001) CONCLUSION: Women with POP have a high prevalence of bowel symptoms. Although bowel symptoms can be relieved after POP surgeries, one-third of women still experience bowel symptoms. A long Pb and levator ani muscle injury were associated with unrelieved bowel symptoms, while perineoplasty was a protective factor.


Lysostaphin: an antistaphylococcal agent.
Lysostaphin is a zinc metalloenzyme which has a specific lytic action against Staphylococcus aureus. Lysostaphin has activities of three enzymes namely, glycylglycine endopeptidase, endo-beta-N-acetyl glucosamidase and N-acteyl muramyl-L-alanine amidase. Glycylglycine endopeptidase specifically cleaves the glycine-glycine bonds, unique to the interpeptide cross-bridge of the S. aureus cell wall. Due to its unique specificity, lysostaphin could have high potential in the treatment of antibiotic-resistant staphylococcal infections. This review article presents a current understanding of the lysostaphin and its applications in therapeutic agent as a treatment against antibiotic-resistant S. aureus and methicillin-resistant S. aureus (MRSA) infections, either alone or in combination with other antibiotics.


Hopf bifurcation in a nonlocal nonlinear transport equation stemming from stochastic neural dynamics.
In this work, we provide three different numerical evidences for the occurrence of a Hopf bifurcation in a recently derived [De Masi et al., J. Stat. Phys. 158, 866-902 (2015) and Fournier and löcherbach, Ann. Inst. H. Poincaré Probab. Stat. 52, 1844-1876 (2016)] mean field limit of a stochastic network of excitatory spiking neurons. The mean field limit is a challenging nonlocal nonlinear transport equation with boundary conditions. The first evidence relies on the computation of the spectrum of the linearized equation. The second stems from the simulation of the full mean field. Finally, the last evidence comes from the simulation of the network for a large number of neurons. We provide a "recipe" to find such bifurcation which nicely complements the works in De Masi et al. [J. Stat. Phys. 158, 866-902 (2015)] and Fournier and löcherbach [Ann. Inst. H. Poincaré Probab. Stat. 52, 1844-1876 (2016)]. This suggests in return to revisit theoretically these mean field equations from a dynamical point of view. Finally, this work shows how the noise level impacts the transition from asynchronous activity to partial synchronization in excitatory globally pulse-coupled networks.


Genomic prediction for numerically small breeds, using models with pre-selected and differentially weighted markers.
Genomic prediction (GP) accuracy in numerically small breeds is limited by the small size of the reference population. Our objective was to test a multi-breed multiple genomic relationship matrices (GRM) GP model (MBMG) that weighs pre-selected markers separately, uses the remaining markers to explain the remaining genetic variance that can be explained by markers, and weighs information of breeds in the reference population by their genetic correlation with the validation breed. Genotype and phenotype data were used on 595 Jersey bulls from New Zealand and 5503 Holstein bulls from the Netherlands, all with deregressed proofs for stature. Different sets of markers were used, containing either pre-selected markers from a meta-genome-wide association analysis on stature, remaining markers or both. We implemented a multi-breed bivariate GREML model in which we fitted either a single multi-breed GRM (MBSG), or two distinct multi-breed GRM (MBMG), one made with pre-selected markers and the other with remaining markers. Accuracies of predicting stature for Jersey individuals using the multi-breed models (Holstein and Jersey combined reference population) was compared to those obtained using either the Jersey (within-breed) or Holstein (across-breed) reference population. All the models were subsequently fitted in the analysis of simulated phenotypes, with a simulated genetic correlation between breeds of 1, 0.5, and 0.25. The MBMG model always gave better prediction accuracies for stature compared to MBSG, within-, and across-breed GP models. For example, with MBSG, accuracies obtained by fitting 48,912 unselected markers (0.43), 357 pre-selected markers (0.38) or a combination of both (0.43), were lower than accuracies obtained by fitting pre-selected and unselected markers in separate GRM in MBMG (0.49). This improvement was further confirmed by results from a simulation study, with MBMG performing on average 23% better than MBSG with all markers fitted. With the MBMG model, it is possible to use information from numerically large breeds to improve prediction accuracy of numerically small breeds. The superiority of MBMG is mainly due to its ability to use information on pre-selected markers, explain the remaining genetic variance and weigh information from a different breed by the genetic correlation between breeds.


From Quellung to multiplex PCR, and back when needed, in pneumococcal serotyping.
All currently available vaccines against Streptococcus pneumoniae are based on selections of the over 90 different serotypes, which underlines the importance of serotyping for surveillance and vaccine efficacy monitoring. In this study, we modified and validated a PCR-based scheme for deducing the serotypes of the invasive pneumococci isolated in Finland. For validation, 170 isolates were serotyped using the new protocol with six sequential multiplex PCRs for the deduction of serotypes, supplemented with Quellung testing when needed. The results were compared with those obtained by traditional serotyping methods. We found that 98.8% (168/170) of the isolates were correctly serotyped by the new protocol. Subsequently, the scheme was taken into regular use for serotyping the invasive pneumococci isolated in Finland for serotype-specific surveillance purposes and has been applied in the serotyping of more than 1,500 invasive isolates so far. The sequential multiplex PCRs (mPCRs) have given a result for over 99% of the isolates and allowed us to both handle samples in bulk and noticeably reduce the cost of reagents. While serotyping primarily by PCR is precise and effective, Quellung testing remains the most reliable way to discover possible discrepancies between the DNA deduced and the phenotypic serotype of an isolate. Since implementing the protocol for regular use, two serotype 19F PCR-positive isolates were found to be serotype 19A by the Quellung reaction. While a rare occurrence, this is an important observation, which prompted a revision of our serotyping protocol to prevent possible underreporting of serotype 19A, a potential replacement serotype following large-scale vaccination.


Non-voltage-gated Ca2+ influx through mechanosensitive ion channels in aortic baroreceptor neurons.
The mechanisms underlying mechanotransduction in baroreceptor neurons (BRNs) are undefined. In this study, we specifically identified aortic baroreceptor neurons in primary neuronal cell cultures from nodose ganglia of rats. Aortic baroreceptor neurons were identified by labeling their soma with the fluorescent dye 1,1'-dioleyl-3,3,3',3'-tetramethylin-docarbocyanine (DiI) applied to the aortic arch. Using Ca2+ imaging with fura 2, we examined these BRNs for evidence of Ca2+ influx and determined its mechanosensitivity and voltage dependence. Mechanical stimuli were produced by ejecting buffer from a micropipette onto the cell surface with a pneumatic picopump, producing a shift in the center of mass of the cell that was related to intensity of stimulation. Ninety-three percent of DiI-labeled neurons responded to mechanical stimulation with an increase in [Ca2+]i. The magnitude of the increases in [Ca2+]i was directly related to the intensity of the stimulus and required the presence of external Ca2+. The trivalent cations Gd3+ or La3+ in equimolar concentrations (20 mumol/L) eliminated the K(+)-induced rises in [Ca2+]i, demonstrating that both trivalent cations are equally effective at blocking voltage-gated Ca2+ channels in these baroreceptor neurons. In contrast, the mechanically induced increases in [Ca2+]i were blocked by Gd3+ (20 mumol/L) only and not by La3+ (20 mumol/L). Stretch-activated channels (SACs) have been shown in other preparations to be blocked by Gd3+ specifically. Our data demonstrate that (1) BRNs, specifically identified as projecting to the aortic arch, have ion channels that are sensitive to mechanical stimuli; (2) mechanically induced Ca2+ influx in these cells is mediated by a Gd(3+)-sensitive ion channel and not by voltage-gated Ca2+ channels; (3) the magnitude of the Ca2+ influx is dependent on the intensity of the stimulus and the degree and duration of deformation; and (4) repeated stimuli of the same intensity result in comparable increases in [Ca2+]i. We conclude that mechanical stimulation increases Ca2+ influx into aortic BRNs independent of voltage-gated Ca2+ channels. The results suggest that Gd(3+)-sensitive SACs are the mechanoelectrical transducers in baroreceptors.


Colonoscopic polypectomy.
The colonoscopic management of 86 patients with polypoid lesions of bleeding from the colon of intermittent nature is discussed. There were 145 polyps found in 85 of these patients. Adenomatous polyps occurring in the sigmoid colon above the reach of the standard sigmoidoscope was the most common finding and pathological diagnosis. Adenocarcinoma of the colon occurred in two patients and invasive carcinoma of a polyp was found in three other patients. Five other patients had polyps that demonstrated a carcinoma in situ. The definitive treatment of these complicated polyps is outlined. The importance of barium enema examination on follow-up of polyp and carcinoma patients and on patients with polyps found at standard sigmoidoscopy is stressed. The possibility of colonoscopic follow-up in lieu of colectomy and ileoproctostomy is suggested for patients with multiple polyps of the colon who do not belong to the familial polyposis group.


Physicochemical control of adult stem cell differentiation: shedding light on potential molecular mechanisms.
Realization of the exciting potential for stem-cell-based biomedical and therapeutic applications, including tissue engineering, requires an understanding of the cell-cell and cell-environment interactions. To this end, recent efforts have been focused on the manipulation of adult stem cell differentiation using inductive soluble factors, designing suitable mechanical environments, and applying noninvasive physical forces. Although each of these different approaches has been successfully applied to regulate stem cell differentiation, it would be of great interest and importance to integrate and optimally combine a few or all of the physicochemical differentiation cues to induce synergistic stem cell differentiation. Furthermore, elucidation of molecular mechanisms that mediate the effects of multiple differentiation cues will enable the researcher to better manipulate stem cell behavior and response.


Combined methylmalonic acidemia and homocystinuria, cblC type. II. Complications, pathophysiology, and outcomes.
Combined methylmalonic acidemia and homocystinuria, cblC type, is stated to be the most common inborn error of intracellular cobalamin metabolism. The disorder can display a wide spectrum of clinical manifestations, spanning the prenatal period through late adulthood. While increased homocysteine concentrations and impaired methyl group metabolism may contribute to disease-related complications, the characteristic macular and retinal degeneration seen in many affected patients appears to be unique to cblC disease. The early detection of cblC disease by newborn screening mandates a careful assessment of therapeutic approaches and provides a new opportunity to improve the outcome of affected patients. The following article reviews the current knowledge on the complications, pathophysiology, and outcome of cblC disease in an effort to better guide clinical practice and future therapeutic trials.


Neuropsychological evidence for the crucial role of the right arcuate fasciculus in the face-based mentalizing network: A disconnection analysis.
Recent evidence from axonal stimulation mapping studies suggests that at least two white matter connectivities in the right hemisphere may be involved in face-based mentalizing, i.e. the ability to infer complex cognitive and affective states from human faces: the inferior fronto-occipital (IFOF) and the superior longitudinal/arcuate (SLF/AF) fasciculi. However, to date, only a handful of neuropsychological studies have focused on the white matter tracts subserving mentalizing in general, and face-based mentalizing in particular. Therefore, the main goal of this study was to confirm the abovementioned results by applying voxelwise and tractwise lesion-symptom analyses to a set of behavioral data obtained from a large and homogeneous group of neurological participants. More precisely, 122 patients operated on for diffuse low-grade glioma were assessed postoperatively with the well-validated "Reading the Mind in the Eyes" (RME) test. For each patient, the resection cavity and the residual tumor infiltration were mapped separately on the respective postoperative structural MRI. Behavioral data, previously controlled for sociodemographic factors, were then submitted to a standard voxel-based and to a less conservative, region-of-interest (ROI)-based, lesion-deficit analyses. Results were invariably the same: no anatomo-functional relationships were pinpointed by these investigations, making thus impossible the cortical topological localization of mentalizing deficits. In a second time, two kinds of tractwise lesion-symptom analyses based on the damaged volume and the disconnection probabilities of the white matter tracts, were performed. All results were corrected with the Bonferroni correction. Converging and strong evidence was found that resection-related disconnection of the right AF is especially deleterious for face-based mentalizing. More anecdotally, we identified the involvement of certain ventral tracts, especially the IFOF and the uncinate fasciculus (UF). Taken as a whole, the reported findings confirm the critical role of the right AF in mentalizing abilities. From a more clinical standpoint, they highlight the necessity to perform an intraoperative map of this connectivity during awake surgery in order to avoid long-lasting social cognition disorders.


Motivation and readiness for therapeutic community treatment among cocaine and other drug abusers.
There is currently little empirical research on the effect of motivation and readiness on the treatment of different groups of substance abusers. In the present study, the CMRS scales are used to assess motivation and readiness for treatment of a large sample of primary alcohol, marijuana, heroin, cocaine, and crack cocaine abusers admitted to a long-term residential therapeutic community. Findings show few significant differences in overall retention or initial motivation and readiness. Initial motivation and readiness scores persist as significant predictors of short-term retention in treatment across most groups. Findings support the TC perspective that the substance abuse problem is the person, not the drug of choice, and are consistent with prior research emphasizing the importance of dynamic rather than fixed variables as determinants of retention.


Efficacy of lixisenatide in patients with type 2 diabetes: A post hoc analysis of patients with diverse β-cell function in the GetGoal-M and GetGoal-S trials.
To evaluate the impact of β-cell function on the efficacy of lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist, in patients with type 2 diabetes (T2D). In this post hoc analysis, patients from the Phase 3 GetGoal-M and GetGoal-S clinical trials randomized to lixisenatide 20μg once daily were stratified into quartiles by baseline β-cell function, as measured by the secretory units of islet in transplantation (SUIT) index. Patients (N=437) were distributed evenly among SUIT index quartiles 1 to 4 (lowest to highest β-cell function). Clinical outcomes improved from baseline across all SUIT quartiles; mean changes at week 24 were: glycated hemoglobin (HbA1c; % [mmol/mol]), -0.99 (-10.8), -0.87 (-9.5), -0.86 (-9.4), -0.83 (-9.1); and postprandial plasma glucose (PPG; mmol/L), -7.9, -5.6, -5.5, -4.3 (overall effect P<0.0001). Furthermore, postprandial glucagon was reduced in all SUIT quartiles, while insulinogenic index improved only in patients with higher baseline SUIT (overall effect P=0.0286). No severe symptomatic hypoglycemic events were reported. Lixisenatide treatment resulted in reductions in HbA1c and PPG levels across all SUIT quartiles. This suggests that non-insulin-related actions of lixisenatide contribute to improved glycemic control in T2D.


Preparing New Nurses to Address Bullying: The Effect of an Online Educational Module on Learner Self-Efficacy.
Newly licensed nurses who start their careers in supportive, nurtur- ing environments are more likely to overcome challenges and successfully transition into professional practice (Spiva et al., 2013). Introduction of content about bullying in the workplace via an online educational module can be an effective strategy for the academic preparation of pre-licensure nursing students.


Determination of Ethyl Carbamate in Alcoholic Beverages and Fermented Foods Sold in Korea.
Ethyl carbamate (EC) classified as a probable human carcinogen (Group 2A) is naturally formed in alcoholic beverages and fermented foods during fermentation process and/or during storage. The objective of this study was to analyze EC in 34 food items including 14 alcoholic beverages and 20 fermented foods sold in Korea. Each food was collected from 18 supermarkets in 9 metropolitan cities in Korea, and then made into composite. According to food composition and alcohol content, samples were divided into four matrices such as apple juice, milk, Soju (liquor containing about 20% alcohol), and rice porridge. The maximum EC value of 151.06 µg/kg was found in Maesilju (liquor made from Maesil and Soju). Whisky and Bokbunjaju (Korean black raspberry wine) contained 9.90 µg/kg and 6.30 µg/kg, respectively. EC was not detected in other alcoholic beverages. Of 20 fermented foods, Japanese-style soy sauce had highest level of 15.59 µg/kg and traditional one contained 4.18 µg/kg. Soybean paste had 1.18 µg/kg, however, EC was not found in other fermented foods.


Characterization of antibody to the ferripyochelin-binding protein of Pseudomonas aeruginosa.
An outer membrane protein of Pseudomonas aeruginosa was previously shown to bind 59Fe-labeled pyochelin. Antibodies to the purified ferripyochelin-binding protein (FBP) were characterized by using a variety of assays. Anti-FBP cross-reacted with several P. aeruginosa isolates in an enzyme-linked immunosorbent assay. Anti-FBP significantly enhanced phagocytosis of P. aeruginosa by human polymorphonuclear leukocytes. In a serum bactericidal assay we observed no difference in viability between cells incubated with antiserum to FBP and cells incubated with preimmune serum. Anti-FBP immunoglobulin G inhibited both binding and uptake of 59Fe-labeled pyochelin by whole cells. Passive protection by anti-FBP was examined in experimental P. aeruginosa burn infections in mice. The protection provided by this antibody was strain dependent but lipopolysaccharide serotype independent.