Identification of cytotoxin-producing Klebsiella oxytoca strains isolated from clinical samples with cell culture assays.
Klebsiella oxytoca is an opportunistic pathogen which damages intestinal epithelium through producing cytotoxin tilivalline. This toxin plays a role in the pathogenesis of bacteria and is the main virulence factor which leads to antibiotic-associated hemorrhagic colitis progress. In this study, we collected a total of 75 K. oxytoca strains isolated from the stool, urine, blood, wounds, and sputum and evaluated them in terms of the production of toxins; we detected their cytotoxic effects on HEp-2 cells. Of all the isolates, five K. oxytoca strains isolated from the stool cultures, two strains isolated from the blood cultures, one strains isolated from the wound cultures, and one strains isolated from the urine cultures had cytotoxic effects on HEp-2 cells. The strains isolated from sputum cultures had no cytotoxic effects on HEp-2 cells. In the current study, the majority of strains isolated from the stool of the patients included cytopathic effects on HEp-2 cells.


Impact of diabetes on clinical outcomes after revascularization with the dual therapy CD34 antibody-covered sirolimus-eluting Combo stent and the sirolimus-eluting Orsiro stent.
To compare the efficacy and safety of the dual therapy CD34 antibody-covered sirolimus-eluting Combo stent (DTS) and the sirolimus-eluting Orsiro stent (SES) in patients with and without diabetes mellitus (DM) included in the Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) X study. The incidence of target lesion failure (TLF) after treatment with modern drug-eluting stents has been reported to be significantly higher in patients with DM when compared to patients without DM. Thus, whether the results from the SORT OUT X study apply to patients with and without DM remains unknown. In total 3146 patients were randomized to stent implantation with DTS (n = 1578; DM: n = 279) or SES (n = 1568; DM: n = 271). The primary end point, TLF, was a composite of cardiac death, target-lesion myocardial infarction (MI), or target lesion revascularization (TLR) within 1 year. At 1 year, the rate of TLF was increased in the DTS group compared to the SES group, both among patients with DM (9.3% vs. 4.8%; risk difference: 4.5%; incidence rate ratio: 1.99, 95% confidence interval [CI]: 1.02-3.90) and without DM (5.7% vs. 3.5%; incidence rate ratio: 1.67, 95% CI: 1.15-2.42). The differences were mainly explained by higher rates of TLR. Compared to the SES, the DTS was associated with an increased risk of TLF at 12 months in patients with and without DM. The differences were mainly explained by higher rates of TLR, whereas rates of cardiac death and target lesion MI did not differ significantly between the two stent groups in patients with or without DM.


Experimental allergic myositis: strain 13 guinea pig immunised with rabbit myosin B fraction.
Of 32 guinea pigs (Hartley and strain 13), 20 were immunised with whole muscle homogenate, microsome or myosin B fraction of rabbit skeletal muscle with Freund's complete adjuvant (FCA); the purified myosin fraction was also used as an antigen in four animals at a concentration lower than other antigens; four were injected with normal saline and FCA; other four had no injection. Five histological changes, namely necrosis, phagocytosis, central nuclei, inflammation and vacuoles, in the quadriceps femoris muscle were compared by quantitative analysis. The group immunised with myosin B fraction showed necrosis, phagocytosis and inflammation more frequently than those immunised with other preparations (p less than 0.05). The changes were more frequent in the strain 13 than in Hartley (p less than 0.05).


Cooperative interaction between organic and inorganic moieties in hybrid silica nanohelices for enantioselective interaction.
Hybrid nanometric helical structures formed by the molecular assemblies of dicationic gemini surfactants with tartrate counterions covered with helical silica walls interact differently with matching or mismatching enantiomers of the tartrate. The difference of the interaction is based on the cooperativity between the chiral crystalline gemini surfactant molecular organization/conformation and the rigid chiral nanospace formed by the helical silica wall.


Plutonium determination in seawater by inductively coupled plasma mass spectrometry: A review.
Knowing the concentration and isotopic ratio of Pu in seawater is of critical importance for assessing Pu contamination and investigating oceanic processes. In recent decades, the concentration of (239+240)Pu in seawater, particularly for surface seawater, has presented an exponential decreasing trend with time; thus determination of Pu in seawater has become a challenge nowadays. Here, we have summarized and critically discussed a variety of reported analytical methods for Pu determination in seawater sample based on inductively coupled plasma mass spectrometry (ICP-MS) analytical technique for rapid ultra-trace detection of Pu. Generally, pretreatments for seawater sample include co-precipitation, valence adjustment and chemical separation and purification procedures, all of which are comprehensively reviewed. Overall, the selected anion-exchange, extraction resins and operation condition are important for decontamination of interference from matrix elements and achieving satisfactory chemical yields. In addition, other mass spectrometric and radiometric detections are briefly addressed and compared with the focus on assessing ICP-MS. Finally, we discuss some issues and prospects in determination and application of Pu isotopes in seawater samples for future research.


Isolating and targeting a highly active, stochastic dendritic cell subpopulation for improved immune responses.
Dendritic cell (DC) activation via pathogen-associated molecular patterns (PAMPs) is critical for antigen presentation and development of adaptive immune responses, but the stochastic distribution of DC responses to PAMP signaling, especially during the initial stages of immune activation, is poorly understood. In this study, we isolate a unique DC subpopulation via preferential phagocytosis of microparticles (MPs) and characterize this subpopulation of "first responders" (FRs). We present results that show these cells (1) can be isolated and studied via both increased accumulation of the micron-sized particles and combinations of cell surface markers, (2) show increased responses to PAMPs, (3) facilitate adaptive immune responses by providing the initial paracrine signaling, and (4) can be selectively targeted by vaccines to modulate both antibody and T cell responses in vivo. This study presents insights into a temporally controlled, distinctive cell population that influences downstream immune responses. Furthermore, it demonstrates potential for improving vaccine designs via FR targeting.


Target-specific oral anticoagulants in atrial fibrillation: results of phase III trials and comments on sub-analyses.
Dabigatran, rivaroxaban, apixaban and edoxaban administered in fixed doses and without routine laboratory monitoring have been compared to warfarin for the prevention of stoke in patients with nonvalvular atrial fibrillation (AF). Phase III data is currently available for dabigatran, rivaroxaban and apixaban. It is derived from three randomized controlled trials: RE-LY, ROCKET AF and ARISTOTLE. Dabigatran and apixaban appeared to be superior to warfarin for the primary endpoint of stroke or systemic embolism, while rivaroxaban was deemed non-inferior. The risk of major bleeding was modestly decreased overall with the new agents, while the risk of intracranial hemorrhage was substantially reduced. The results of ENGAGE AF-TIMI 48 comparing edoxaban to warfarin are still pending. Large, well designed clinical trials support the use of three new target-specific oral anticoagulants for the prevention of stroke in individuals with nonvalvular AF.


Assessment of Aortic Stenosis Severity: A Multimodality Approach.
Severe aortic stenosis (AS) is associated with a progressive cardiac remodeling that ultimately leads to heart failure and death if the valve is not replaced. The confirmation of AS severity is therefore crucial to adequately manage patients with AS. Transthoracic echocardiography is the first-line examination to confirm AS severity, but it may be inconclusive in discordant cases. In this setting, AS severity should be confirmed using a multimodality imaging approach. This review gives an overview of how to assess and/or confirm AS severity, especially in case of discordance.


Peritoneal dialysate-range hypertonic glucose promotes T-cell IL-17 production that induces mesothelial inflammation.
Peritoneal dialysis (PD) employs hypertonic glucose to remove excess water and uremic waste. Peritoneal membrane failure limits its long-term use. T-cell cytokines promote this decline. T-cell differentiation is critically determined by the microenvironment. We here study how PD-range hypertonic glucose regulates T-cell polarization and IL-17 production. In the human peritoneal cavity, CD3+ cell numbers increased in PD. Single cell RNA sequencing detected expression of T helper (Th) 17 signature genes RORC and IL23R. In vitro, PD-range glucose stimulated spontaneous and amplified cytokine-induced Th17 polarization. Osmotic controls l-glucose and d-mannose demonstrate that induction of IL-17A is a substance-independent, tonicity dose-dependent process. PD-range glucose upregulated glycolysis and increased the proportion of dysfunctional mitochondria. Blockade of reactive-oxygen species (ROS) prevented IL-17A induction in response to PD-range glucose. Peritoneal mesothelium cultured with IL-17A or IL17F produced pro-inflammatory cytokines IL-6, CCL2, and CX3CL1. In PD patients, peritoneal IL-17A positively correlated with CX3CL1 concentrations. PD-range glucose-stimulated, but neither identically treated Il17a-/- Il17f-/- nor T cells cultured with the ROS scavenger N-acetylcysteine enhanced mesothelial CX3CL1 expression. Our data delineate PD-range hypertonic glucose as a novel inducer of Th17 polarization in a mitochondrial-ROS-dependent manner. Modulation of tonicity-mediated effects of PD solutions may improve membrane survival.


Lack of correlation between antiobesity policy and obesity growth rates: review and analysis.
To review federal, state, and local antiobesity policies and to assess their relationships with obesity growth rates. We performed a literature review, acquired data from governmental Internet sources, and assessed the statistical correlation between state antiobesity policies and the concavity in obesity growth rates. State-by-state antiobesity policies in 3 categories-taxation of sugared beverages and snacks, physical education and physical activity in schools, and funding for bicycle trails-were found to have no significant immediate correlation with the change in obesity growth rates. Ineffective antiobesity legislation may be attributable to shortcomings in policy implementation. Behavioral economics and addressing large-scale cultural issues may have critical roles in promoting more healthful lifestyles. We propose that a systems-based paradigm evaluating complex interactions among pathophysiological, cultural, political, economic, and behavioral components can improve antiobesity policy implementation and should therefore be a research focus.


Electrical stimulation of primary motor cortex within the central sulcus for intractable neuropathic pain.
To assess the pain-relieving effects of motor cortex electrical stimulation (MCS) within the central sulcus and the predictive factors retrospectively. Thirty-four patients with intractable neuropathic pain underwent MCS; 19 patients had cerebral lesions, and 15 had non-cerebral lesions. In selected 12 patients, test electrodes were implanted within the central sulcus and on the precentral gyrus. Twelve patients received both MCS and repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex. Pain reduction of > or =50% was observed in 12 of 32 (36%) patients with > or =12 months follow-ups (2 patients were excluded because of short follow-up). In 10 of the 12 patients who received test electrodes within the central sulcus and on the precentral gyrus, the optimal stimulation was MCS within the central sulcus. In 4 of these (40%) patients, positive effects were maintained at follow-ups. The pain reduction of rTMS significantly correlated with that of MCS during test stimulation. The test stimulation within the central sulcus was more effective than that of the precentral gyrus. In the selected patients, chronic stimulation within the central sulcus did not significantly improve long-term results. The present findings suggest that an intra-central sulcus is one of the favorable targets for MCS.


The Westheimer function as an indicator of fixation locus.
The dimensions of the Westheimer function are stable across populations and in time and vary with the eccentricity of fixation. The function is thus useful to assess whether an individual is fixing centrally and if not to estimate the degree of eccentricity of fixation. We identified both summation and inhibition-like regions in a 66-year-old woman with senile macular degeneration and estimated that the extent of eccentric fixation was approximately 4 degrees.


Single nucleotide polymorphisms in the NOS2 and NOS3 genes are associated with exhaled nitric oxide.
Polymorphisms in nitric oxide synthase genes (NOS1, NOS2, and NOS3) have been suggested to have a major impact on fraction of exhaled nitric oxide (FENO), a biomarker of airway inflammation. However, the genetic contribution of NOS polymorphisms to FENO is not fully understood. The aim of this study was to investigate comprehensively the association between single nucleotide polymorphisms (SNPs) in all three NOS genes and FENO in an adult population, and to assess whether such associations are modified by asthma or atopy. In 1737 adults from a Swedish general population sample, FENO was measured and genetic variation in the NOS genes was assessed using 49 SNPs. The genetic effect of NOS polymorphisms on FENO, asthma, and atopy was estimated using multiple regression methods. In a multi-SNP model based on stepwise regression analysis, two SNPs in NOS2 and one in NOS3 showed independent associations with levels of FENO. For NOS2 SNP rs9901734, subjects had 5.3% (95% CI 1.0% to 9.7%) higher levels of FENO per G allele, and for rs3729508, subjects with CC or CT genotypes had 9.4% (95% CI 3.1% to 15.2%) higher levels compared with TT. For NOS3 SNP rs7830, subjects with GT or TT had 5.6% (95% CI 0.4% to 11.1%) higher levels than GG; the genetic effect of this SNP was stronger in asthmatics (21.9%, 95% CI 4.6% to 42.0%). These results suggest that NOS2 is the major NOS gene determining variability in exhaled nitric oxide in the healthy adult population, while NOS3 may play a more important role in asthmatic adults.


PMVEMA-coated upconverting nanoparticles for upconversion-linked immunoassay of cardiac troponin.
Surface engineering of upconverting nanoparticles (UCNPs) is crucial for their bioanalytical applications. Here, an antibody specific to cardiac troponin I (cTnI), an important biomarker for acute myocardial infection, was covalently immobilized on the surface of UCNPs to prepare a label for the detection of cTnI biomarker in an upconversion-linked immunoassay (ULISA). Core-shell UCNPs (NaYF4:Yb,Tm@NaYF4) were first coated with poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) and then conjugated to antibodies. The morphology (size and uniformity), hydrodynamic diameter, chemical composition, and amount of coating on the of UCNPs, as well as their upconversion luminescence, colloidal stability, and leaching of Y3+ ions into the surrounding media, were determined. The developed ULISA allowed reaching a limit of detection (LOD) of 0.13 ng/ml and 0.25 ng/ml of cTnI in plasma and serum, respectively, which represents 12- and 2-fold improvement to conventional enzyme-linked immunosorbent based on the same immunoreagents.


Reimagining Relationships: Multispecies Justice as a Frame for the COVID-19 Pandemic.
COVID-19 catalyzed a renewed focus on the interconnected nature of human health. Together with the climate crisis, it highlighted not only intra-human connections but the entanglement of human health with the health of non-human animals, plants, and ecological systems more broadly. In this article, we challenge the persistent notion that humans are ontologically distinct from the rest of nature and the ethics that flow from this understanding. Imposing this privileged view of humans has devastating consequences for beings other than humans and for humans and impedes effective responses to crises. We situate the COVID-19 pandemic within the "polycrisis," and argue that one component of addressing multidimensional crises must involve fully embracing a relational ontology and ethics. We discuss two approaches to relationality, one articulated by ecofeminists and the second inhering in an Indigenous Māori worldview. Two dominant approaches, One Health and Planetary Health, purport to take account of relational ontologies in their approaches to health, but, we argue, persist in casting the more-than-human world in an instrumental role to secure human health. We suggest that Multispecies Justice, which draws on ecofeminist and Indigenous approaches, affords a fully relational approach to health and well-being. We explore the implications of relationality, and suggest fresh ways of understanding humans' connections with the more-than-human world.


Sexual and drug use risk behaviors among children and youth in street circumstances in Porto Alegre, Brazil.
We conducted a cross-sectional study to assess sexual and drug use risk in 161 children and youth in street circumstances in Porto Alegre, Brazil. Median age was 14 and 79% were male. Overall, 59% reported ever having had sex; a significantly higher proportion of males (66%) compared to females (30%). Overall, 39% reported illicit drug use in the last year, and only 1.2% reported injection drug use. In multivariate analyses, correlates of unsafe sex included younger age of sexual debut, and having a steady sex partner. Independent correlates of illicit drug use included lack of family contact, increased hours in the street daily, having had an HIV test, and older age. A high proportion of children and youth in street circumstances reported high risk sex and drug exposures, confirming their vulnerability to HIV/STD. Services Centers, such as where this research was carried out, offer an opportunity for interventions.


Deterministic center of pressure patterns characterize postural instability in Parkinson's disease.
Static posturographic recordings were obtained from six Parkinson's patients and six age-matched, healthy control participants. The availability of vision and visuo-spatial cognitive load were manipulated. Postural sway patterns were analyzed using recurrence quantification analysis (RQA), which revealed differences in center of pressure (COP) dynamics between Parkinson's and control participants. AP COP trajectories for the Parkinson's group were not only significantly more variable than for the control group, but also exhibited distinct patterns of temporal dynamics. The visual manipulation did not differentially affect the two groups. No cognitive load effects were found. The results are generally consistent with the hypothesis that pathological physiological systems exhibit a tendency for less flexible, more deterministic dynamic patterns.


Recurrent cavernous haemangioma of the extensor tendons of the hand.
Haemangiomas arising from tendons are very uncommon and are not usually considered in the differential diagnosis of lesions of tendons. The following report is of specific interest for it presents a case of recurrent haemangioma of the extensor tendons of the hand which could be excised and the hand reconstructed at the same operative procedure.


Determination of lamivudine and zidovudine permeability using a different ex vivo method in Franz cells.
The major processes that control the absorption of orally administered drugs are dissolution and gastrointestinal permeation. These processes depend on two main properties: solubility and permeability. Based on these characteristics, the Biopharmaceutical Classification System (BCS) was proposed as a tool to assist in biowaiver and bioavailability prediction of drugs. The purpose of the present study was to evaluate the permeability of lamivudine (3TC) and zidovudine (AZT) using a different ex vivo method in Franz cells. A segment of jejunum was inserted in a Franz cells apparatus, in order to assess drug permeability in the apical-basolateral (A-B) and basolateral-apical (B-A) directions. Each drug was added to the donor chamber, collected from the acceptor chamber and analyzed by HPLC. Fluorescein (FLU) and metoprolol (METO) were used as low and high permeability markers, respectively. The apparent permeability (Papp) results for the A-B direction were: Papp FLU A-B=0.54×10(-4)cm·s(-1), Papp METO A-B=7.99×10(-4)cm·s(-1), Papp 3TC A-B=4.58×10(-4)cm·s(-1) and Papp AZT A-B=5.34×10(-4)cm·s(-1). For the B-A direction, the Papp results were: Papp FLU B-A=0.56×10(-4)cm·s(-1), Papp METO B-A=0.25×10(-4)cm·s(-1), Papp 3TC B-A=0.24×10(-4)cm·s(-1) and Papp AZT B-A=0.19×10(-4)cm·s(-1). For the A-B direction, the Papp results of fluorescein and metoprolol show low and high permeability, respectively, indicating that the membranes were appropriate for permeability studies. For the A-B direction, the Papp results of 3TC and AZT suggest that these antiretroviral drugs have permeability values close to metoprolol. Nevertheless, for the B-A direction the Papp results do not suggest efflux mechanism for any of the drugs. Thereby, the different ex vivo methods using Franz cells can be successfully applied in drug permeability studies, in particular for drug biopharmaceutical classification.


Sonographic demonstration of renal arterial calcification simulating multiple renal calculi.
A case of arterial calcification simulating renal calculi during ultrasound examination is described. The differential diagnosis of echogenic foci with acoustic shadowing is discussed.


Systemic lupus erythematosus in pregnancy.
Most literature on pregnancies in patients with systemic lupus erythematosus (SLE) is retrospective and selective. This report is a detailed, prospective analysis of 13 pregnancies in eight women with SLE. Pregnancy was best tolerated by mothers without significant nephropathy or cardiopathy who had been in clinical remission for more than three months prior to conception. Management was aided by serial evaluation of complement (C3 and C4) levels and careful supervision of immunosuppressive therapy when indicated. Although fetal status was closely monitored, premature deliveries and spontaneous abortions occurred frequently. No malformations or adverse sequelae were noted in surviving infants exposed to immunosuppressive agents during gestation.


Iridoids from Avicennia marina.
Three new iridoid glucosides, 10-O-[(E)-cinnamoyl]-geniposidic acid, 10-O-[(E)-p-coumaroyl]-geniposidic acid, 10-O-[(E)-caffeoyl]-geniposidic acid and the known iridoid glucoside, 2'-O-[(E)-cinnamoyl]-mussaenosidic acid have been isolated from Avicennia marina. The structures were determined primarily by NMR spectroscopy. The assignment of NMR signals was performed by means of 1H-1H COSY, HMQC and HMBC experiments.


Exploring psychiatric prescribing practices: the relationship between the role of the provider and the appropriateness of prescribing.
The prescribing habits of psychiatrists and neurologists in a large, urban Veterans Administration medical center were surveyed. It was determined that these physicians prescribed a large amount of nonpsychotropic medication, and the rationale for this practice was explored and is presented. Patient expectations in this population derived from certain established sociocultural biases toward the medical profession appeared to significantly influence prescribing practices. Such prescribing behavior suggests that the psychiatrist in this setting is often required to assume the role of primary care provider as part of a larger patient therapist relationship.


Grinding of alumina ceramic with microtextured brazed diamond end grinding wheels.
Brazed monolayer diamond grinding wheels have advantages of a high abrasive bonding strength, high protrusion, and a large chip disposal space. However, it is difficult to prepare ordered and fine-grained brazed diamond grinding wheels. This study presents a new method for grain-arranged, brazed diamond grinding wheels with microtextures with similar performance to ordered and fine-grained brazed diamond grinding wheels. First, coarse diamond grains (18/20 mesh) were orderly brazed to fabricate the end grinding wheels. Next, a series of microtextures were ablated on the diamond grains using a pulsed laser, and two types of textured end grinding wheels-TG-G (ablated microgrooves only) and TG-GH (ablated microgrooves and microholes)-were prepared. Then, an experiment involving the grinding of alumina ceramics was performed, and the grinding characteristics and grinding mechanism were analyzed. The results indicated that compared with untextured diamond end grinding wheels (TG), the textured diamond grinding wheels (TG-G and TG-GH) significantly reduced the grinding force and the roughness of the machined surface. The local stress concentration at the microtextures promoted the formation of microcracks in the diamond grains of TG-G and TG-GH, and the self-sharpness of the grinding wheel was significantly improved. The brittle fracture mode of ceramic materials in grinding included intergranular fracture and transgranular fracture. Ironing pressure action was a key material-removal mechanism. It had an important influence on the cutting force and plasticity characteristics of the TG machined surface. For the surfaces processed by TG-G and TG-GH, the effect of ironing was weakened, while shearing played a more important role. The TG-GH grinding wheel ablated with microgrooves and microholes was superior to the TG-G grinding wheel ablated with only microgrooves, with regard to the grinding force, roughness, and self-sharpening.


Persistent subretinal fluid after surgery for rhegmatogenous retinal detachment: hypothesis and review.
Persistent subretinal fluid after rhegmatogenous retinal detachment (RRD) surgery is responsible for delayed recovery, and may affect the final visual outcome. Cause, consequences, and treatment remain elusive. Literature review and case series. We reviewed the pathophysiological principles and therapeutic options from the literature, and we report the results from a subretinal fluid cytology study. Nine eyes from nine patients with macula-involving RRD underwent surgical repair. The cellular content of subretinal fluid (SRF) was studied by electron microscopy and anti-rhodopsin immunostaining. All eyes were assessed postoperatively with optical coherence tomography for the detection of persistent submacular fluid (PSF) (Ethics Committee Ghent University Hospital, registration number B6702006169). Certain patient characteristics as well as surgical methods were implicated. PSF appears to occur more frequently in patients with longstanding detachments treated with buckling surgery. Several therapeutic options have been suggested but safety and efficacy remain unclear. We found PSF in three eyes on postoperative OCT scans, which corresponded to the three cell-rich subretinal samples. PSF after successful RRD repair seems to be related to fluid composition. We hypothesize, in the absence of an effective treatment, that a modified surgical drainage, including a washout of the subretinal space, could evacuate the subretinal fluid more completely, and may prevent this complication.


Occurrence of dispensing errors and efforts to reduce medication errors at the Central Arkansas Veteran's Healthcare System.
Medical errors have received national attention in the past few years, largely due to the Institute of Medicine's (IOM) 1999 report, which found that over one million injuries and nearly 100,000 deaths occur annually in the US as a result of medical errors. The purpose of this study was to examine the type and severity of dispensing errors reported by pharmacy services at the Central Arkansas Veteran's Healthcare System from October 1997 through September 2001 and to examine the efforts implemented by the Central Arkansas Veteran's Healthcare System to reduce overall medication-related errors. Dispensing error reports for the Central Arkansas Veteran's Healthcare System were obtained for October 1997 to September 2001. Dispensing errors were tabulated in the Statistical Package for the Social Sciences (SPSS) according to the pharmacy section, type of error (wrong drug, wrong dose, wrong patient and 'other') and severity of error (minor, significant, major and unrated). Data were explored using descriptive statistics, chi2, independent sample t-tests and Pearson's correlation. Information on error reduction efforts was obtained from pharmacy administrative services. A total of 82 dispensing errors were reported from eight different pharmacy sections for the time period examined. Errors included 31 wrong drugs, 21 wrong doses, 24 wrong patients and six 'other' errors. The number of errors, according to severity, included 29 unrated, 30 minor, 21 significant and two major errors. Both major errors were due to wrong drug selection. In total, the highest number of errors occurred at the North Little Rock Ambulatory Care Pharmacy (39 errors) and the Little Rock Ambulatory Care Pharmacy (24 errors). Wrong drug and wrong dose dispensing errors were not significantly different among the pharmacy sections. Wrong patient selection was significantly different among pharmacy service sections. Wrong patient selection, wrong drug, and wrong dose were all significantly correlated with unrated severity, minor severity, and significant severity. Significant correlations were also found between wrong drug, wrong dose and wrong patient selection. There were no significant correlations between wrong patient selection and major severity, or other errors. chi2 analysis found significant differences in expected frequency among errors for wrong drug, wrong dosage, wrong patient and other errors. Significant differences were also found in expected frequencies between unrated, minor, significant and major errors. Although the major dispensing errors were not statistically different according to pharmacy services sections and not significantly correlated with any other categories, they both involved the selection of the wrong drug, which was also the most common error. In contrast, the selection of the wrong patient, the second most common error, was statistically different among pharmacy sections and was significantly correlated with all other dispensing type and severity of error except major severity and other errors. Focusing error reduction efforts on selection of the correct drug and correct patient would likely yield the best results in reducing dispensing errors since these errors combined accounted for 55 (67.1%) of the 82 reported errors.


Involvement of hypothalamic adrenaline in the clonidine withdrawal syndrome in normotensive and spontaneously hypertensive rats.
1. The concentrations of adrenaline and other catecholamines (noradrenaline and its major metabolite DHPG, dopamine and its major metabolite DOPAC) were measured in the hypothalamus and medulla oblongata of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) which had received a continuous subcutaneous infusion of clonidine (10 micrograms/kg per h) for 10 days, and also in WKY and SHR rats which were killed 15-18 h after the cessation of the 10-day infusion. 2. The concentrations of adrenaline in the hypothalamus and medulla oblongata/pons of the clonidine treated WKY and SHR rats were not different from their respective controls. However, the adrenaline concentrations in the hypothalamus (but not the medulla oblongata) were significantly decreased in the post-infusion WKY and SHR. 3. These results suggest that hypothalamic adrenergic mechanisms may have a common involvement in the post-clonidine infusion syndromes displayed by the WKY and SHR strains.


MDCT: cardiology indications.
In the past 2 years mechanical multidetector-row CT (MDCT) systems with simultaneous acquisition of four slices and half-second scanner rotation have become widely available. Data acquisition with these scanners allows for considerably faster coverage of the heart volume compared with single-slice scanning. This increased scan speed can be used for retrospective gating together with 1-mm collimated slice widths and allows coverage of the entire cardiac volume in one breath hold. Initial results from studies in correlation with intracoronary ultrasound suggest that MDTC technology not only offers the possibility to visualize intracoronary stenoses non-invasively but also to differentiate plaque morphology. This is especially the case with the next generation of 16-row multidetector CT. An increased number of simultaneously acquired slices and sub-millimeter collimation for cardiac applications allows true isotropic scanning with high temporal resolution. Contrast-enhanced MDTC is a promising non-invasive technique for the detection, visualization, and characterization of stenotic artery disease. It could act as a gate keeper prior to cardiac catherization and finally replace conventional diagnostic modalities.


Rare Mucor circinelloides and Fusarium infection in latissimus free flap reconstruction after devastating foot injury in non-neutropenic patient.
Nowadays, free flap reconstruction in devastating lower limb trauma is a standard procedure in reconstructive surgery. The greatest factor directly affecting limb salvage is still the risk of infectious complications, whether local or systemic. Fungal wound infections are not among the most common infection complications in surgery, but their low incidence is compensated for by their fulminant and serious course, as well as severe local tissue destruction and strong angio-invasive potential together with the possibility of dissemination. In this case study, we present an example of a devastating lower leg injury, solved using latissimus free flap reconstruction, with subsequent difficult and prolonged healing, due to an invasive filamentous fungi infection. In the final part of the article, we focus briefly on the occurrence of similar cases in the literature.


Top 50 most cited articles on primary tumors of the spine.
Citation analysis was performed in order to identify the top 50 most cited articles pertaining to the field of primary spinal tumors. This collection of articles highlights important trends in the neurosurgical literature. We searched the Thomson Reuters Web of Knowledge in order to identify articles pertaining to primary tumors of the spine. Impertinent articles were removed. The top 50 most cited articles were identified. Thereafter, article characteristics were determined including article type, article topic, level of evidence, and citation rate. The selected articles were published between 1951 and 2008. The most productive year was 1997 with 6 publications. The top 50 articles were published in twenty-two different journals, most commonly in Neurosurgery (12), Journal of Neurosurgery (8), and Spine (6). The most frequently cited article was by Tomita et al. written in 1997 which described total en bloc spondylectomy as a novel surgical technique in management of primary tumors of the vertebral column. We identified the 50 most-cited articles in the field of primary spinal tumors. This collection of articles serves as a reference for recognizing impactful studies in the field.


Effect of bradykinin to cyclic AMP levels and response of murine lymphocytes.
No information is available on the pharmacological effect of bradykinin to lymphocytes and immunological responses of them. In this study it was clarified that bradykinin as well as histamine elevated cyclic adenosine 3',5' monophosphate (cAMP) levels of murine splenic or lymph node lymphocytes and mature thymocytes (cortisone-resistant thymus), but did not increase cAMP levels of immature thymocytes as well as histamine. The increased cAMP ratios in T cell-enriched splenic lymphocytes by the impulse of bradykinin were higher than that in splenic and lymph node lymphoid cells by the stimulation of bradykinin. It was also demonstrated that bradykinin as well as histamine suppressed DNA synthesis by mitogenic (PHA-P, Con-A) stimulation of splenic lymphocytes, but not a effect to the response of lymphocytes by mitogenic (LPS) stimulation was observed. These facts suggest that bradykinin may play an important role in the regulation of immunologic lymphocyte responses.


Ultrasound evaluation of elbow fractures in children.
Elbow fractures are a common pathology in any pediatric emergency unit. X-ray of the elbow is the standard diagnostic procedure. Previous studies have shown that fractures can also be visualized by ultrasound (US). The aim of our study was to evaluate the diagnostic accuracy of US in comparison to X-rays in diagnosing pediatric elbow fractures. Sixty-seven patients aged 1-13 years with clinically suspected elbow fracture were first examined by US followed by standard two-plane radiographs. US examination was done with a 12-MHz linear probe from seven longitudinal positions across the distal humerus and additionally from longitudinal positions across the radial head and olecranon. The sonographic and radiological findings were compared in a contingency table, and sensitivity, specificity, and positive and negative predictive values of the US diagnostic procedure were calculated. With X-ray, we found 48 patients with an elbow fracture and 19 patients with no fracture. With US, we found 46 patients with an elbow fracture and 21 patients with no fracture. In comparison to X-ray diagnosis, we calculated for US diagnosis a sensitivity of 97.9 %, a specificity of 95 %, a negative predictive value of 95 %, and a positive predictive value of 97.9 %. Typical elbow fractures in children could also be visualized by US. A positive fat pad sign, in particular, serves as a strong indicator for elbow joint fractures and can be identified very sensitively by US. We confirm US as a valuable primary screening tool for elbow injuries in children. In the absence of US signs of fracture and in sonographically confirmed non-displaced fractures, standard X-rays are dispensable, thereby minimizing the X-ray burden in children without loss of diagnostic safety.


Quadriceps myositis: an appraisal of the diagnostic criteria of quadriceps myopathy.
A patient with the clinical picture of quadriceps myopathy was shown to have an underlying myositis. Review of the literature showed myositis to be a rare cause of the 'quadriceps syndrome' but it is important to identify this group because they are potentially treatable with corticosteroids.


Enzyme catalytic amplification of miRNA-155 detection with graphene quantum dot-based electrochemical biosensor.
A specific and sensitive method was developed for quantitative detection of miRNA by integrating horseradish peroxidase (HRP)-assisted catalytic reaction with a simple electrochemical RNA biosensor. The electrochemical biosensor was constructed by a double-stranded DNA structure. The structure was formed by the hybridization of thiol-tethered oligodeoxynucleotide probes (capture DNA), assembled on the gold electrode surface, with target DNA and aminated indicator probe (NH2-DNA). After the construction of the double-stranded DNA structure, the activated carboxyl groups of graphene quantum dots (GQDs) assembled on NH2-DNA. GQDs were used as a new platform for HRP immobilization through noncovalent assembly. HRP modified biosensor can effectively catalyze the hydrogen peroxide (H2O2)-mediated oxidation of 3,3',5,5'-tetramethylbenzidine (TMB), accompanied by a change from colorless to blue in solution color and an increased electrochemical current signal. Due to GQDs and enzyme catalysis, the proposed biosensor could sensitively detect miRNA-155 from 1 fM to 100 pM with a detection limit of 0.14 fM. High performance of the biosensor is attributed to the large surface-to-volume ratio, excellent compatibility of GQDs. For these advantages, the proposed method holds great potential for analysis of other interesting tumor makers.


Evaluation of cerebral infarction by computed tomography with special emphasis on microinfarction.
Computed tomography has proved to be the most effective mode of evaluating cerebral infarction in 143 documented cases. This was especially true when multiple focal infarcts were present. The incidence of contrast enhancement in acute infarcts was 88%. Concomitant acute and old infarcts were observed in 20% of cases. In the acute stage of stroke, radionuclide studies are preferable to contrast angiography since the latter may aggravate the pre-existing focal ischemia. Follow-up CT and radionuclide scans were extremely useful in confirming the diagnosis and demonstrating various postinfarction sequelae.


Quaternary (Fe/Ni)(P/S) mesoporous nanorods templated on stainless steel mesh lead to stable oxygen evolution reaction for over two months.
Synthesis of mesoporous (Fe/Ni)(P/S) dendritic nanorods on commercial 304L stainless steel mesh (SSM) was accomplished by initial anodic oxidation and subsequent co-sulfuration/phosphorization process. The mesoporous (Fe/Ni)(P/S) dendritic nanorods were obtained as a freestanding and stable catalyst for oxygen evolution reaction (OER). The mechanism of formation of mesoprous structure with nanorods is due to in-situ removal of Cr atoms (from the hard template of SSM) while the O2 bubbles released during OER served as dynamic bubble template (soft template). The as-prepared sample exhibited overpotentials of 173 mV at 10 mA cm-2 and 270 mV at 100 mA cm-2, which exceeded those that were recently reported using surface modified stainless steel-based catalysts for OER in alkaline condition. Moreover, the (Fe/Ni)(P/S) nanorods showed a remarkable Tafel slope of 65.7 mV dec-1 with stable activity beyond two months with only 2.5% fluctuation. The above outstanding performance could be attributed to the unique morphology with highly exposed active sites and the control of electronic structure by co-treatment with P and S. This work presents an efficient way to modify SSM for use as an inexpensive and durable OER catalyst.


The integrated model of serotonin transporter gene variation (5HTTLPR) and the glial cell transporter in stress vulnerability and depression.
The serotonin transporter gene (SLC6A4) promoter polymorphism (5HTTLPR) has been associated with individual stress responses such that individuals with childhood abuse history have higher rates of depression in later life if they are homozygous short (s/s) of the gene. It is hypothesized that these findings could be explained by an integrated model of a role of the glial cell transporter and a functional difference of 5HTTLPR in the capacity of absorbing serotonin from the synapse. A hypothetical integrated model of the SLC6A4 function and the role of glial cells are put forward to explain accumulating results of recent investigations exploring the relationship between the gene and the diverse mental activities including depression and stress response. A model based on SLC6A4 variation is proposed to explain individual differences in stress vulnerability/resilience. The role of the glial cell transporter surrounding the synapse is integrated in the model to understand the modulation of the neurotransmission. It is hypothesized that a synapse with less serotonin transporter contributes to unstable processing in neurotransmission as compared to a synapse with more serotonin transporter. As such, based on functional differences of 5HTTLPR in the expression of the serotonin transporter, it is asserted that individuals with the s/s genotype process neurotransmission differently and in a reactive way. This integrated model of 5HTTLPR and glial cells suggests that the efficacy of serotonin reuptake in the synapse may play a crucial role in variability of neurotransmission, which can lead to differences in the stress response and the pathophysiology of depression.


Keloid formation after pediatric male genital surgeries: an uncommon and difficult problem to manage.
Penile and genital keloids are uncommon despite frequent surgeries in the genital area. Keloid scar pathogenesis is not well understood, and a uniform effective therapeutic regimen for keloids has not yet been established. In the present study, the clinical features and subsequent management in cases of severe keloid formation after pediatric genital surgery are described. A retrospective review of keloid cases that had developed after genital procedures between 2000 and 2017 was conducted. Pre-operative characteristics, operative procedures, postoperative management, and follow-up were reviewed for each case. All cases were managed by a multidisciplinary team that included plastic surgeons and dermatologists. Six cases developed genital keloids. The mean age at surgery was 5.6 years (± standard deviation 4.6 years). Procedures included phalloplasties, penile curvature correction, penoscrotal transposition, redo hypospadias repair, and circumcision. Treatment options included excision of the keloid ± topical steroid injections and postoperative use of silicone gel. Two cases of severe keloid lesions developed after using posterior auricular grafts. Ultimately, a successful outcome was achieved in all cases. Genital keloids are rare and difficult to treat. Many therapeutic options are available with varying degrees of proven clinical success. As a result, pediatric urologists must be aware of advances in other fields such as plastic surgery and dermatology to treat and ideally prevent the occurrence of this serious complication.


In vitro production of steroid cataract in bovine lens. Part II: measurement of sodium-potassium adenosine triphosphatase activity.
Fresh calf lesnses incubated in nutritive media containing dexamethasone phosphate or ouabain in concentrations ranging from 1 X 10(-4) M to 1 X 10(-8) M developed cortical opacification and showed significant inhibition of Na(+)-K(+) ATP'ase activity. Over a 3-day incubation period the decrease in Na+-K+ ATP'ase activity correlated well with the observed decrease in light transmission. The degree of enzyme inhibition and decrease in light transmission varied directly with the concentration of dexamethasone phosphate and ouabain, with significant changes observed at 'physiologic' and 'pharmacologic' concentrations of these agents. Lenses incubated for 4 days in dexamethasone phosphate or ouabain showed substantial increases in water content as well as an increase in Na+ and a decrease in K+ concentration. These data suggest that inhibition of the cation pump may play a significant role in the formation of steroid cataract in vitro.


Bioinformatics and biological reality.
Many bioinformaticians seem to shy away from believing that we can have knowledge about a mind-independent biological reality. This paper attempts to show that this tendency is neither well-founded nor harmless. Even though most bioinformaticians work only with terms and concepts, they cannot altogether disregard the question whether these terms and concepts have any real referents. The paper consists of three parts. Part I clarifies three different positions in the philosophy of science with which it would be good for the philosophical outlook of bioinformaticians to become familiar, and it defends one of them, Karl Popper's epistemological realism. Part II discusses a distinction which is necessary for epistemological realism and is of practical importance for bioinformatics, the distinction between the use and mention of terms and concepts. Part III, finally, contains some brief concluding words about realism, both in general and in relation to bioinformatics.


Flexible thermoplastic resin to add retention to tooth-supported stereolithographic surgical guides.
Surgical guides produced by stereolithography use hard resin. The hard resin prevents seating beyond the height of contour, hence these guides are not intrinsically retentive. By covering the guide with a flexible thermoplastic material that extends into the undercuts, the resulting guide now has a retentive feature. This allows it to maintain its position during surgery yet it can easily be removed and repositioned.


Comparison of Vascular Perturbations in an Aβ-Injected Animal Model and in AD Brain.
The validity of amyloid-β peptide (Aβ(1-42)) intrahippocampal injection, as an animal model of Alzheimer's disease (AD), has previously been considered in terms of inflammatory reactivity and neuronal damage. In this work, we have extended the testing of the animal model to vasculature by comparison of selected properties of microvessels in vivo with those in human AD brain tissue. The injection of Aβ(1-42), relative to control PBS (phosphate buffered saline), increased the mean number of microvessels and diminished the mean length of microvessels in the molecular layer of dentate gyrus. The animal model showed Aβ(1-42), but not PBS, injection was associated with abnormalities in morphology of microvessels which were characterized as looping, fragmented, knob-like, uneven, and constricted. In particular, numbers of constricted microvessels, defined as vessels with diameters less than 3 μm, were considerably enhanced for Aβ(1-42), compared to PBS, injection. In comparison, human AD brain demonstrated an elevated number of microvessels with a diminished mean length relative to nondemented (ND) brain. Additionally, microvessel perturbations in AD brain showed a similar pattern of morphological abnormalities to those observed in Aβ(1-42)-injected rat hippocampus. Constricted microvessels were a prominent feature of AD brain but were rarely observed in ND tissue. These results provide the first evidence that a peptide-injection animal model exhibits a commonality in perturbations of microvessels compared with those evident in AD brain.


Lowering detection limits for 1,2,3-trichloropropane in water using solid phase extraction coupled to purge and trap sample introduction in an isotope dilution GC-MS method.
Purge and trap sample introduction (PTI) has been the premier sampling and preconcentration technique for gas chromatographic determination of volatile organic compounds (VOCs) in drinking water for almost 50 years. PTI affords sub parts-per-billion (ppb) detection limits for purgeable VOCs including fixed gases and higher boiling hydrocarbons and halocarbons. In this study the coupling of solid phase extraction (SPE) to PTI was investigated as a means to substantially increase enrichment and lower detection limits for the emerging contaminant, 1,2,3-trichloropropane (TCP). Water samples (500 mL) were dechlorinated, preserved with a biocide, and spiked with the isotope labeled internal standard, d5-TCP. The entire 500 mL sample was extracted with activated carbon or carbon molecular sieve SPE cartridges, and then eluted with dichloromethane -- excess solvent was removed in a nitrogen evaporator and diethylene glycol "keeper" remaining was dispersed in 5 mL of water for PTI GC-MS analysis. The experimental Method Detection Limit (MDL) for TCP was 0.11 ng/L (ppt) and accuracy was 95-103% in sub-ppt determinations. Groundwater samples including impaired California sources and treated water (n = 21) were analyzed with results ranging from below the method reporting limit (0.30 ng/L) to > 250 ng/L. Coupling of SPE with PTI may provide similar reductions in detection limits for other VOCs with appropriate physical-chemical properties.


Pharmacology and preclinical validation of a novel anticancer compound targeting PEPCK-M.
Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the decarboxylation of oxaloacetate to phosphoenolpyruvate. The mitochondrial isozyme, PEPCK-M is highly expressed in cancer cells, where it plays a role in nutrient stress response. To date, pharmacological strategies to target this pathway have not been pursued. A compound embodying a 3-alkyl-1,8-dibenzylxanthine nucleus (iPEPCK-2), was synthesized and successfully probed in silico on a PEPCK-M structural model. Potency and target engagement in vitro and in vivo were evaluated by kinetic and cellular thermal shift assays (CETSA). The compound and its target were validated in tumor growth models in vitro and in murine xenografts. Cross-inhibitory capacity and increased potency as compared to 3-MPA were confirmed in vitro and in vivo. Treatment with iPEPCK-2 inhibited cell growth and survival, especially in poor-nutrient environment, consistent with an impact on colony formation in soft agar. Finally, daily administration of the PEPCK-M inhibitor successfully inhibited tumor growth in two murine xenograft models as compared to vehicle, without weight loss, or any sign of apparent toxicity. We conclude that iPEPCK-2 is a compelling anticancer drug targeting PEPCK-M, a hallmark gene product involved in metabolic adaptations of the tumor.


Increased expression of 5-HT1B receptors in rat nucleus accumbens via virally mediated gene transfer increases voluntary alcohol consumption.
Serotonin 5-HT(1B) receptors have been linked to alcoholism in humans and alcohol consumption in rodents. We hypothesize that these receptors, which are located on the axon terminals of nucleus accumbens' (NAcc) projection neurons, modulate alcohol reward mechanisms. To test this hypothesis, we measured ethanol consumption by rats that received bilateral microinjections of a viral vector producing 5-HT(1B) overexpression (HA1B/GFP). Other groups received either control (GFP-only) herpes simplex viral vectors into the medial NAcc shell or were handled briefly with no surgery. All animals were housed singly and had continuous access to water, 6% ethanol, and 12% ethanol in their home cages both before and after surgery. There were no differences in the amount or rate of weight gain, amount of food eaten, or total fluid consumed. There were also no differences in the amount of ethanol consumed between groups prior to surgery. However, after surgery, the HA1B/GFP group consumed twice as much ethanol as the other groups. The main effect of total ethanol consumption was significant (p<.05); the control groups did not differ from each other. Whereas there were no between-group differences in 6% ethanol consumption, there was a large increase in the amount of 12% ethanol consumed by the HA1B/GFP-expressing animals compared to the two control groups as well as to their own presurgery intake (p<.05). We hypothesize that increased 5-HT(1B) expression in NAcc led to either greater reward or reduced aversive effects from the 12% ethanol, thereby leading to increased voluntary ethanol consumption.


The Association of Outdoor Walking Per Week with Mental Health and Costs of Psychotropic Drugs in Adults.
Regular walking confers many physical health benefits, including a reduced risk of disease-specific and all-cause mortality and better physical fitness. However, less is known about its role in mental health. Thus, the aims of this study were to determine the associations of outdoor walking per week with costs of psychotropic drugs used and mental health in adults. 500 adults aged 18 to 64 years in Hangzhou (China) reported sex, age, the name of the psychotropic drugs used and their dosage, and outdoor walking during the past 7 days. The cost that a person spends on buying psychotropic drugs for a month was considered psychotropic drugs costs. Overall mental health was assessed using the Chinese Version of the 12-Item General Health Questionnaire. The levels of walking in participants taking psychotropic were significantly lower than participants who did not taking psychotropic (p = 0.002). There was a significant negative correlation between mental health scores and minutes of walking per week and a significant positive correlation between the number of psychotropic drugs used and walking per week (p < 0.05). However, no particular associations were found between costs of psychotropic drug used and walking per week. Outdoor walking is prospectively associated with better overall mental health in adults. Then, awareness should be raised about the possible positive effects of outdoor walking on the mental health of adults.


The management of transitional cell carcinoma (TCC) in a European regional renal transplant population.
In the West, transitional cell carcinoma (TCC) in renal transplant patients is uncommon, but aggressive. Conversely, it appears to be frequent in the Far East, necessitating aggressive surgical approaches such as prophylactic nephroureterectomy. There are few European case series to date. TCC in the present population was predominantly low-grade and superficial, with no progression in patients with those tumours. Endoscopic management was sufficient for most patients. The behaviour of TCC in the present population was much less aggressive than that described in the Far East. Altering immunosuppression regimes may have a role to play in managing bladder cancer in renal transplant patients. To examine the clinical characteristics, management and long-term outcomes of patients with transitional cell carcinoma (TCC) who also have had renal transplantation. A retrospective case note review was performed for the 15-year period 1995-2009. Searches from three different urological centres in the UK, using multiple sources, yielded 1647 patients with renal transplants, 12 of whom had TCC. Eight cases were identified who developed de novo TCC after transplantation (0.48%). Four patients had pre-existing TCC who then had renal transplantation. The current literature was reviewed. In the eight de novo TCC cases, the bladder was the site in all with no upper tract TCC; seven were superficial (pTa/T1) and five were low grade (G1/2). The mean time to development of TCC after transplant was 5 years, with a mean follow-up of 11 years. There was no progression in low-grade superficial disease that was managed endoscopically. The 5- and 10-year overall survival was 83% and 72%, respectively. In patients with pre-existing TCC prophylactic bilateral nephroureterectomy before transplantation was performed once. There was progression of superficial disease whilst on immunosuppression in one patient. Sirolimus was used in patients with TCC and reports suggest this may have a role to play in modifying malignancy in this setting. The number of patients involved in studies particularly focusing on TCC in renal transplantation is small (136 patients), with 60% from China/Taiwan where there is a high incidence of upper tract TCC and high-grade muscle-invasive disease. Although this is one of the largest European case series of renal transplant patients with TCC, the numbers are small making clear conclusions difficult. The frequency of TCC in our renal transplant population is low, consistent with previous studies. However, contrary to prior studies, TCC after renal transplantation in this European population was predominantly superficial, low-grade, non-progressive and confined to the bladder. Altering immunosuppression regimes in patients with TCC may have a role to play, although further work is required to clarify and substantiate this.


A method of estimating radial distribution function of protein particles in membranes from freeze-fracture electron micrographs.
A computational method for estimating the radial distribution function of particles seen in electron micrographs of freeze-fractured membranes is presented. The method overcomes the previous difficulty of measurements of this quantity from freeze-fracture electron micrographs--the systematic error due to the finite size of the sample areas in the freeze-fracture. By multiplying the measurements by weights specific to the shape of the sample area, the method lessens the errors due to the boundaries of the area and allows a synthesis of the average radial distribution function from counts over many small separate areas.


A Paired Phase and Magnitude Reconstruction for Advanced Diffusion-Weighted Imaging.
Multi-shot interleaved echo planer imaging (Ms-iEPI) can obtain diffusion-weighted images (DWI) with high spatial resolution and low distortion, but suffers from ghost artifacts introduced by phase variations between shots. In this work, we aim at solving the ms-iEPI DWI reconstructions under inter-shot motions and ultra-high b-values. An iteratively joint estimation model with paired phase and magnitude priors is proposed to regularize the reconstruction (PAIR). The former prior is low-rankness in the k-space domain. The latter explores similar edges among multi-b-value and multi-direction DWI with weighted total variation in the image domain. The weighted total variation transfers edge information from the high SNR images (b-value = 0) to DWI reconstructions, achieving simultaneously noise suppression and image edges preservation. Results on simulated and in vivo data show that PAIR can remove inter-shot motion artifacts very well (8 shots) and suppress the noise under the ultra-high b-value (4000 s/mm2) significantly. The joint estimation model PAIR with complementary priors has a good performance on challenging reconstructions under inter-shot motions and a low signal-to-noise ratio. PAIR has potential in advanced clinical DWI applications and microstructure research.


Human amnesia and the medial temporal lobe illuminated by neuropsychological and neurohistological findings for patient E.P.
We present neurohistological information for a case of bilateral, symmetrical damage to the medial temporal lobe and well-documented memory impairment. E.P. developed profound memory impairment at age 70 y and then was studied for 14 y He had no capacity for learning facts and events and had retrograde amnesia covering several decades. He also had a modest impairment of semantic knowledge. Neurohistological analysis revealed bilaterally symmetrical lesions of the medial temporal lobe that eliminated the temporal pole, the amygdala, the entorhinal cortex, the hippocampus, the perirhinal cortex, and rostral parahippocampal cortex. The lesion also extended laterally to involve the fusiform gyrus substantially. Last, the superior, inferior, and middle temporal gyri were atrophic, and subjacent white matter was gliotic. Several considerations indicate that E.P.'s severe memory impairment was caused by his medial temporal lesions, whereas his impaired semantic knowledge was caused by lateral temporal damage. His lateral temporal damage also may have contributed to his extensive retrograde amnesia. The findings illuminate the anatomical relationship between memory, perception, and semantic knowledge.


Determination of picomole quantities of hydroperoxides by a coupled glutathione peroxidase and glutathione disulfide specific glutathione reductase assay.
A procedure to quantitate picomole amounts of hydroperoxides based on GSSG formation is described. Hydroperoxides are incubated with GSH and glutathione peroxidase, and the GSSG formed is measured by a GSSG-specific glutathione reductase recycling assay. Prior to analysis the remaining GSH is removed with N-ethylmaleimide. N-Ethylmaleimide inhibition of the recycling assay is prevented by alkaline hydrolysis of the N-ethylmaleimide, without GSSG hydrolysis, at pH 11. The method is rapid, 30 min, with a limit of detection of 142 pmol calculated by linear regression analysis. Stoichiometric amounts of GSSG are produced in response to hydroperoxides. An application of the method is shown with air oxidation of arachidonic acid solutions over 4 h at room temperature. The method is sufficiently sensitive to quantitate the low amounts of hydroperoxides present in fresh arachidonic acid samples.


Skin penetration and UV-damage prevention by nanoberries.
Ethanolic extract from blueberry (Vaccinium myrtillus) is rich in anthocyanins and thus exhibits antioxidant activity. On the other hand, ultradeformable liposomes are capable of penetrating to the impermeable barrier of skin. Nanoberries are ultradeformable liposomes carrying blueberry extract. In this study, their capacity to penetrate the stratum corneum and photodamage prevention were tested, with the aim of developing a topical formulation for skin protection from environmental damage. Nanoberries were prepared by lipid film resuspension with ethanolic extract from blueberry, followed by sonication and incorporation to a gel. Size, zeta potential, deformability, rheology, and viscoelasticity were determined. Toxicity was assessed in vivo in zebrafish model, while in vitro cytotoxicity assay was performed on HaCaT and HEK-293T cell lines. Skin penetration was evaluated with the Saarbrücken penetration model followed by tape stripping, cryosection, or optical sectioning. UV-damage protection and photoprotection were determined by ad hoc methods with UVA, UVB, and UVC radiation on HaCaT cells. Wound assay was performed on HaCaT cells. Nanoberries of about 100 nm, with differential elastic properties, did penetrate the stratum corneum, with low toxicity. When HaCaT cells were exposed to UV radiation in the presence of nanoberries, their viability was maintained. Nanoberries could be effective to protect the skin from sun photodamage.


Cancer: Bad Luck or Punishment?
Contrasting opinions on the role of extrinsic and intrinsic factors in cancer etiology (Tomasetti, C., and Vogelstein, B. (2015) Science, 347, 78-81; Wu, S., et al. (2016) Nature, 529, 43-47) variously define priorities in the war on cancer. The correlation between the lifetime risk of several types of cancer and the total number of divisions of normal self-renewing cells revealed by the authors has given them grounds to put forward the "bad luck" hypothesis. It assumes that ~70% of cancer variability is attributed to random errors arising during DNA replication in normal, noncancerous stem cells, i.e. to internal factors, which is impossible either to expect or to prevent. This assumption caused many critical responses that emphasize, on the contrary, the defining role of extrinsic factors in cancer etiology. The analysis of epidemiological and genetic data presented in this work testifies in favor of the "bad luck" hypothesis.


Ascaris suum: continuous perfusion of the pseudocoelom and nutrient absorption.
A double-cannulation apparatus was constructed for continuous perfusion of the pseudocoelom of adult Ascaris suum while maintaining the intact parasite in a controlled incubation chamber. Peristaltic pumps maintained a constant flow rate of artificial perienteric fluid through the incubation chamber (1 ml/min) and through the parasite (100 microliters/min). Based on protein determinations, perienteric fluid was removed from the pseudocoelom within 35 min of initiation of perfusion (3.5 ml). A nonabsorbable dye, Blue Dextran, was detected first in the perfusate 4 min (400 microliters) after initiation of infusion into the pseudocoelom, and was maintained at a constant concentration in the perfusate by 8 min after initiation of dye infusion. Removal of the dye from the pseudocoelom was accomplished within 8 min (800 microliters) after the cessation of dye infusion. Occlusion of the digestive tract had no effect (P less than 0.05) on the short-term (3 hr) absorption of 3H-labeled cholesterol, [14C]-3-o-methylglucose or [14C]glucose from the incubation medium into the perienteric cavity. Concentrations of isotopes in the pseudocoelom reached steady-state levels within 60 min of the initiation of incubation, but remained low (greater than 0.5%) when compared to medium concentration. Similarly, the time course of the accumulation of [14C]glucose into individual tissue components did not differ in intact worms with or without patent intestinal tracts. Thus, the cuticular/muscle tissue largely appears to be the primary route of absorption of cholesterol and glucose in adult A. suum.(ABSTRACT TRUNCATED AT 250 WORDS)


Metabolic signatures provide novel insights to Picrorhiza kurroa adaptation along the altitude in Himalayan region.
Along the altitude, environmental conditions vary significantly that might influence plant performance and distribution. Adaptation to these changing conditions is a complex biological process that involves reprogramming of genes, proteins and metabolites. The metabolic response of medicinal plants along the altitude has been less explored yet. In the present study, we investigated the adaptation strategies of Picrorhiza kurroa Royle ex Benth. along the altitude in organ specific manner using metabolomic approach. Picrorhiza kurroa plants at flowering stage were randomly sampled from three altitudes viz. 3400, 3800 and 4100 masl in the Himalayan region. Leaf, root and rhizome were used for LC-MS based non-targeted metabolite profiling and targeted analysis of sugars, amino acids, picrosides and their corresponding phenolic acids. A total of 220, primary and secondary metabolites (SMs) were identified (p < 0.05) representing an extensive inventory of metabolites and their spatial distribution in P. kurroa. Differential accumulation of metabolites suggests source-sink carbon partitioning, occurrence of partial TCA cycle, ascorbate metabolism, purine catabolism and salvage route, pyrimidine synthesis, lipid alteration besides gibberellins and cytokinin inhibition might be an adaptive strategy to alpine environmental stress along the altitude. Further, marked differences of organ and altitude specific SMs reflect alteration in secondary metabolic pathways. Significant accumulation of picrosides suggests their probable role in P. kurroa adaptation. This study provides a platform that would be useful in deciphering the role of metabolites considered to be involved in plant adaptation.


YY1 functions with INO80 to activate transcription.
Ubiquitously expressed transcription factor Yin-Yang-1 (YY1) controls expression of many genes. YY1 is tightly associated with the human ATP-dependent INO80-like chromatin-remodeling complex (INO80). INO80 is recruited by YY1 to YY1-activated genes, where it functions as an essential coactivator. Binding of YY1 to its DNA sites in target genes requires INO80, suggesting that YY1 uses the INO80 complex not only to activate transcription but also to gain access to target promoters.


Intracellular electrolytes and water analysis in dystrophic canine muscles.
Skeletal muscles from normal dogs and labrador retrievers with a hereditary muscular dystrophy were examined morphologically and histochemically and were analysed for sodium (Na+), potassium (K+) and chloride (Cl-) ions and total muscle water. The partition of total muscle water and electrolytes between intracellular and extracellular phases was calculated on the basis of the chloride space method as the estimate of extracellular fluid volume. Muscle samples from dystrophic dogs contained significantly increased concentrations of Na+, Cl-, total muscle water, and a significant reduction in the level of K+ compared with normal values. There was a significant increase in the intracellular water and Na+ levels with a concomitant reduction of intracellular K+ content. Most dystrophic muscle samples had a pronounced type 2 fibre deficiency and a marked increase in numbers of fibres with internalised nuclei.


Ageing, age-related diseases and oxidative stress: What to do next?
Among other mechanisms, oxidative stress has been postulated to play an important role in the rate of ageing. Oxidative damage contributes to the hallmarks of ageing and essential components in pathological pathways which are thought to drive multiple age-related diseases. Nonetheless, results from studies testing the hypothesis of oxidative stress in ageing and diseases showed controversial results. While observational studies mainly found detrimental effects of high oxidative stress levels on disease status, randomized clinical trials examining the effect of antioxidant supplementation on disease status generally showed null effects. However, re-evaluations of these counterinitiative observations are required considering the lack of reliability and specificity of traditionally used biomarkers for measuring oxidative stress. To facilitate these re-evaluations, this review summarizes the basic knowledge of oxidative stress and the present findings regarding the role of oxidative damage in ageing and age-related diseases. Meanwhile, two approaches are highlighted, namely proper participants selection, together with the development of reliable biomarkers. We propose that oxidized vitamin E metabolites may be used to accurately monitor individual functional antioxidant level, which might serve as promising key solutions for future elucidating the impact of oxidative stress on ageing and age-related diseases.


Ivermectin adsorption by commercial charcoal in batch and fixed-bed operations.
Emerging contaminants were used during the COVID-19 pandemic, including ivermectin. Studies that limit the optimal adsorption parameters of ivermectin are scarce in the literature. In this study, we analyzed the adsorption of ivermectin with a high surface area and porosity charcoal. Isotherms were better fitted to the Koble-Corrigan model. The maximum capacity was 203 μg g-1 at 328 K. Thermodynamics indicated a spontaneous and endothermic behavior. The equilibrium was quickly reached within the first few minutes regardless of the ivermectin concentration. The linear driving force (LDF) model fitted the kinetic data (qexp = 164.8 μg g-1; qpred = 148.1 μg g-1) at 100 μg L-1 of ivermectin. The model coefficient (KLDF) and diffusivity (Ds) increased with increasing drug concentration. Two sloped curves were obtained in the column experiments, with a breakthrough time of 415 min and 970 min. The capacity of the column (qeq) was 76 μg g-1. The length of the mass transfer zone was 9.04 and 14.13 cm. Therefore, it can be concluded that the adsorption of ivermectin is highly sensitive to changes in pH, being favored in conditions close to neutrality. Commercial activated charcoal was highly efficient in removing the studied compound showing high affinity with very fast kinetics and a good performance in continuous operation mode.


Clinical Outcomes And Risk Factors In Patients Circumcised By Chinese Shang Ring: A Prospective Study Based On Age And Types Of Penile Disease.
To explore the efficacy of circumcision with Chinese Shang Ring (CSR) in the different cohorts so that can obtain the best applicable population and manage complications better. This study consisted of 657 patients who were circumcised with CSR in our institute between August 2017 and August 2018. All cases were followed up at post-operation for 3 to 15 months. The surgery time (ST), wound healing time (WHT), satisfaction with the appearance of postoperative penis and complications were collected and comparatively analyzed. Multivariate analysis was used to determine the independent risk factors associated with efficacy, which were presented by odd ratios and its 95% confidence index. All cases wore the CSR successfully. The ST and WHT respectively were 5.75 ± 2.27 mins and 21.15 ± 5.05 days. The long-term complications, total complications (TC), satisfaction and successful circumcision (SC) respectively were 5.30%, 11.70%, 97.70% and 94.70%. For TC and SC, there was a difference between phimosis and redundant foreskin (21.30% vs 6.20%, P<0.001 and 89.20% vs 97.8%, P<0.001, respectively). In terms of satisfaction and SC, adolescents were higher than children (98.70% vs 94.70%, P=0.035 and 96.80% vs 90.10%, P=0.024, respectively) but was similar to adults (98.70% vs 100.00%, P=0.071 and 96.80% vs 98.00%, P=0.257, respectively). The degree of pain and the incidence of wound dehiscence in adults was higher than adolescents (P<0.05). The phimosis (OR= 1.47, 95% CI=1.26-1.79, P<0.001) and childhood (OR= 1.13, 95% CI =1.06-1.36, P<0.001) were associated with poor efficacy. The curative effect of circumcision by CSR in adolescents was similar to adults, both higher than that of children. However, adults have more severe pain and a higher probability of wound dehiscence in the later stage than adolescents. So, adolescence is probably the best time to be circumcised with CSR.


Phospholipase C cDNAs from sponge and hydra: antiquity of genes involved in the inositol phospholipid signaling pathway.
To know whether or not the set of genes involved in the inositol phospholipid signaling pathway already existed in the early evolution of animals, we carried out cloning of cDNAs encoding phospholipase Cs (PLCs) from Ephydatia fluviatilis (freshwater sponge) and Hydra magnipapillata strain 105 (hydra). We isolated two PLC cDNAs, PLC-betaS and PLC-gammaS, from sponge and three cDNAs, PLC-betaH1, PLC-betaH2, and PLC-deltaH, from hydra. From the domain organization and the divergence pattern in the PLC family tree, the sponge PLC-betaS and PLC-gammaS and the hydra PLC-deltaH are possibly homologous to the vertebrate PLC-beta, PLC-gamma and PLC-delta subtypes, respectively. A detailed phylogenetic analysis suggests that the hydra PLC-betaH1 and PLC-betaH2 are homologs of the vertebrate PLC-beta1/2/3/Drosophila PLC21 and the vertebrate PLC-beta4/Drosophila norpA, respectively. A phylogenetic analysis of the PLC family and the protein kinase C (PKC) family, together with that of the G protein alpha subunit (Galpha) family, revealed that the origin of the set of genes G(alpha)q, PLC, PKC involved in the inositol phospholipid signaling pathway is very old, going back to dates before the parazoan-eumetazoan split, the earliest branching among extant animal phyla.


Community-level evolutionary processes: Linking community genetics with replicator-interactor theory.
Understanding community-level selection using Lewontin's criteria requires both community-level inheritance and community-level heritability, and in the discipline of community and ecosystem genetics, these are often conflated. While there are existing studies that show the possibility of both, these studies impose community-level inheritance as a product of the experimental design. For this reason, these experiments provide only weak support for the existence of community-level selection in nature. By contrast, treating communities as interactors (in line with Hull's replicator-interactor framework or Dawkins's idea of the "extended phenotype") provides a more plausible and empirically supportable model for the role of ecological communities in the evolutionary process.


SALL1 enforces microglia-specific DNA binding and function of SMADs to establish microglia identity.
Spalt-like transcription factor 1 (SALL1) is a critical regulator of organogenesis and microglia identity. Here we demonstrate that disruption of a conserved microglia-specific super-enhancer interacting with the Sall1 promoter results in complete and specific loss of Sall1 expression in microglia. By determining the genomic binding sites of SALL1 and leveraging Sall1 enhancer knockout mice, we provide evidence for functional interactions between SALL1 and SMAD4 required for microglia-specific gene expression. SMAD4 binds directly to the Sall1 super-enhancer and is required for Sall1 expression, consistent with an evolutionarily conserved requirement of the TGFβ and SMAD homologs Dpp and Mad for cell-specific expression of Spalt in the Drosophila wing. Unexpectedly, SALL1 in turn promotes binding and function of SMAD4 at microglia-specific enhancers while simultaneously suppressing binding of SMAD4 to enhancers of genes that become inappropriately activated in enhancer knockout microglia, thereby enforcing microglia-specific functions of the TGFβ-SMAD signaling axis.


Remediation of wastewater containing 4-nitrophenol using ionic liquid stabilized nanoparticles: Synthesis, characterizations and applications.
In the present study, an ionic liquid (IL) based on 1-butyl-3- (trimethoxysilylpropyl) -imidazolium tetrafluoroborate (IL) was prepared using metathesis and anion exchange reactions and used to stabilize silver (AgNPs) nanoparticles. The IL-stabilized silver nanoparticles AgNPs@[BMSI]BF4 were produced in an aqueous solution with NaBH4 as a reducing agent. TGA, FTIR, XRD, BET, FSEM, TEM/HRTEM, XPS, and UV-Vis spectra were used to analyze AgNPs@[BMSI]BF4 and were used for the catalytic reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the presence of NaBH4. AgNPs@[BMSI]BF4 showed excellent catalytic properties for the reduction of 4-NP to 4-AP and showed 100% conversion of 4-NP to 4-AP within 6 min and the rate constant (k) was found to be 8.33 × 10-3 s-1. The reusability results indicated that 97.8% of 4-NP was converted to 4-AP with highly stable rate constants over six consecutive cycles. The activity factor (AF) and the turn-over frequency (TOF) at room temperature were 3.33 s-1 gm-1 and 0.166 s-1, respectively. This study extends a new approach to the production of stable catalysts for the growing needs in wastewater treatment.


Exposure of Cultured Astrocytes to Menadione Triggers Rapid Radical Formation, Glutathione Oxidation and Mrp1-Mediated Export of Glutathione Disulfide.
Menadione (2-methyl-1,4-naphthoquinone) is a synthetic derivative of vitamin K that allows rapid redox cycling in cells and thereby generates reactive oxygen species (ROS). To test for the consequences of a treatment of brain astrocytes with menadione, we incubated primary astrocyte cultures with this compound. Incubation with menadione in concentrations of up to 30 µM did not affect cell viability. In contrast, exposure of astrocytes to 100 µM menadione caused a time-dependent impairment of cellular metabolism and cell functions as demonstrated by impaired glycolytic lactate production and strong increases in the activity of extracellular lactate dehydrogenase and in the number of propidium iodide-positive cells within 4 h of incubation. In addition, already 5 min after exposure of astrocytes to menadione a concentration-dependent increase in the number of ROS-positive cells as well as a concentration-dependent and transient accumulation of cellular glutathione disulfide (GSSG) were observed. The rapid intracellular GSSG accumulation was followed by an export of GSSG that was prevented in the presence of MK571, an inhibitor of the multidrug resistance protein 1 (Mrp1). Menadione-induced glutathione (GSH) oxidation and ROS formation were found accelerated after glucose-deprivation, while the presence of dicoumarol, an inhibitor of the menadione-reducing enzyme NQO1, did not affect the menadione-dependent GSSG accumulation. Our study demonstrates that menadione rapidly depletes cultured astrocytes of GSH via ROS-induced oxidation to GSSG that is subsequently exported via Mrp1.


Local recurrence in patients with rectal cancer diagnosed between 1988 and 1992: a population-based study in the west Netherlands.
We carried out a population-based study of local recurrence rates in curatively resected patients with rectal cancer, diagnosed between 1988 and 1992. The first objective was to make an inventory of the overall local recurrence rate after non-standardized conventional surgery, inter-institutional recurrence rate variability, and correlations between patient- and tumour-related factors and recurrence rate. A second objective was to investigate the compliance to guidelines for post-operative radiotherapy. Data were obtained from the Comprehensive Cancer Centre West. The study comprised 1105 patients from 12 hospitals. Of these patients, 437 were ineligible because of missing medical records, no carcinoma, incorrect registration, no laparotomy, non-curative resection, or loss to follow-up. The overall local recurrence rate was 22.5% with a range of 9-36% between the hospitals. These differences were not significant. Dukes' Astler-Coller stage, tumour location, and residual tumour were significant independent prognostic factors for the risk of local recurrence. Indications for post-operative radiotherapy were Dukes' Astler-Coller B2 and C tumours, positive surgical margins, and tumour spill. Compliance to the guidelines for radiotherapy was only 50%. However, no significant difference in recurrence rate was found between patients treated according to the guidelines and those not treated according to the guidelines. This study shows a large variability in local recurrence rate between the participating hospitals and confirms that the risk of recurrence in primary rectal cancer is dependent on Dukes' Astler-Coller stage, tumour location and residual tumour. Furthermore, this study contributes to the discussion about the feasibility of guidelines for post-operative radiotherapy.


Sustainability in transformation of maternal mortality by interaction based approach in Dairi, Indonesia.
Health and mortality problems are closely related to the maternal mortality rate (MMR). Efforts to reduce MMR have been carried out by many countries, including the Indonesian government. This research was conducted using two approaches, namely quantitative and qualitative or mixed methods and 149 respondents and 26 informants, to reduce MMR in Dairi Regency. This study was also carried out to determine the dominant variable that affects mother's behavior in an effort to reduce MMR in accordance with the existing theory. Mother's intention to contribute to the reduction of MMR in this study was influenced by the good factor directly or indirectly. This is indicated by the score p<0.005. The study also shows that it is very important for the health workers to be able to communicate well with individuals and communities. The present study will help to reduce maternal fatalities, and will help to build systems and processes that will allow control the behaviour of the pregnant women and determine the cause of death as well as its contributing factors.


Diaminopropionate ammonia-lyase from Salmonella typhimurium. Purification and characterization of the crystalline enzyme, and sequence determination of the pyridoxal 5'-phosphate binding peptide.
We have found a wide occurrence of alpha,beta-diaminopropionate ammonia-lyase in bacteria and actinomycetes. Considerable amounts of this enzyme were found in Salmonella typhimurium. The enzyme was purified and crystallized from S. typhimurium (IFO 12529). The relative molecular mass of the native enzyme, estimated by the ultracentrifugal equilibrium method, is 89,000 Da, and the enzyme consists of two subunits identical in molecular mass. The enzyme exhibits absorption maxima at 278 and 413 nm and contains 2 mol of pyridoxal 5'-phosphate(pyridoxal-P)/mol of enzyme. The enzyme catalyzes the alpha,beta-elimination reaction of both L- and D-alpha,beta-diaminopropionate, the most suitable substrates, to form pyruvate and ammonia. The L- and D-isomers of serine were also degraded, though slowly. After the internal Schiff base with pyridoxal-P had been reduced with sodium borohydride, followed by trypsin or lysyl endopeptidase digestion of the enzyme, we determined the sequence of about 20 amino acid residues around the lysine residue which binds pyridoxal-P. No homology was found in either the amino acid sequence of the pyridoxal-P binding peptide or the amino-terminal amino acid sequence between the enzyme and other pyridoxal-P-dependent enzymes.


Nitric oxide, caveolae, and vascular pathology.
Endothelial nitric oxide synthase (eNOS) is an enzyme that plays a critical role in normal cardiovascular function. Caveolae are structures within the surface membrane of cells in which many signaling and second messenger pathways, including nitric oxide, are regulated. Many interventions in cardiovascular disease act, in part, either by changing factors that directly influence eNOS, or by changing a complex set of proteins that act indirectly on caveolae, to alter eNOS activity. In this review, we will focus on the regulation of eNOS activity by circulating factors which are altered in cardiovascular disease and the effects of pharmacological interventions that act partially through effects on eNOS.


Canine osteosarcoma: amputation and chemoimmunotherapy.
Canine osteosarcoma is a highly metastatic cancer commonly seen in large breed dogs. At the time of diagnosis, approximately 90% to 95% of the dogs have established micrometastases. Dogs undergoing amputation alone have a median survival time of 3 to 4 months. Amputation followed by cisplatin chemotherapy increases median survival times to 9 to 11 months. When dogs are treated with amputation and cisplatin, followed by immunotherapy (with liposome-encapsulated muramyl tripeptide phosphatidylethanolamine), median survival times increase to 14.4 months, the longest reported median survival time for dogs with osteosarcoma treated by amputation and any form of adjuvant therapy.


Characterization of calcium phosphate powders originating from Phyllacanthus imperialis and Trochidae Infundibulum concavus marine shells.
The study reports the preparation and characterization of powders consisting of the different phases of calcium phosphates that were obtained from the naturally derived raw materials of sea-shell origins reacted with H3PO4. Species of sea origin, such as corals and nacres, attracted a special interest in bone tissue engineering area. Nacre shells are built up of calcium carbonate in aragonite form crystallized in an organic matrix. In this work two natural marine origin materials (shells of echinoderm Sputnik sea urchin - Phyllacanthus imperialis and Trochidae Infundibulum concavus mollusk) were involved in the developing powders of calcium phosphate based biomaterials (as raw materials for bone-scaffolds) by hotplate and ultrasound methods. Thermal analyses of the as-prepared materials were made for an assessment of the thermal behavior and heat treatment temperatures. Samples from both sea shells each of them prepared by the above mentioned methods were subjected to thermal treatments at 450 °C and 850 °C in order to evaluate the crystalline transformations of the calcium phosphate structures in the heating process. By X-ray diffraction analyses various calcium phosphate phases were identified. In Sputnik sea urchins originated samples were found predominantly brushite and calcite as a small secondary phase, while in Trochidae I. concavus samples mainly monetite and HA phases were identified. Thermal treatment at 850 °C resulted flat-plate whitlockite crystals - β-MgTCP [(Ca, Mg)3 (PO4)2] for both samples regardless the preparation method (ultrasound or hotplate) or the targeted Ca/P molar ratio according with XRD patterns. Scanning electron microscopy and Fourier transformed infrared spectroscopy were involved more in the characterization of these materials and the good correlations of the results of these methods were made.


Neonatal capsaicin treatment prevents insulin-stress-induced adrenal catecholamine secretion in vivo: possible involvement of sensory nerves containing substance P.
We have investigated the effects of neonatal capsaicin treatment on stress-induced catecholamine release from adult rats in vivo. Catecholamines released into the inferior vena cava following insulin injection were separated by HPLC and measured by electrochemical detection. Neonatal capsaicin treatment depleted the substance P levels in the splanchnic nerve of adult rats by 70% and prevented the insulin-induced hypoglycaemia from evoking release of adrenaline. The results of this study provide the first evidence in vivo for the neuromodulatory role of sensory nerves containing substance P in the secretion of catecholamines from the adrenal medulla.


Iron nanoparticles decorated multi-wall carbon nanotubes modified carbon paste electrode as an electrochemical sensor for the simultaneous determination of uric acid in the presence of ascorbic acid, dopamine and L-tyrosine.
Iron nanoparticles decorated multi-wall carbon nanotubes modified carbon paste electrode (Fe-MWCNTs/MCPE) was prepared by bulk-modification method. The electrochemical impedance spectroscopy (EIS) suggests least charge transfer resistance at the modified electrode. The electrochemical behavior of UA was studied in 0.1M phosphate buffer solution (PBS) of pH3.0 using cyclic voltammetry (CV) while differential pulse voltammetry (DPV) was used for quantification. The spectroelectrochemial study of oxidation of UA at Fe-MWCNTs/MCPE showed a decrease in the absorbance of two peaks with time, which are ascribed to π to π(⁎) and n to π(⁎) transitions. Under optimum condition, the DPV response offered two linear dynamic ranges for UA in the concentration range 7.0×10(-8)M-1.0×10(-6)M and 2.0×10(-6)M-1.0×10(-5)M with detection limit (4.80±0.35)×10(-8)M (S/N=3). The practical analytical application of this sensor was successfully evaluated by determination of spiked UA in clinical samples, such as human blood serum and urine with good percentage recovery. The proposed electrochemical sensor offers a simple, reliable, rapid, reproducible and cost effective analysis of a quaternary mixture of biomolecules containing AA, DA, UA and Tyr which was free from mutual interferences.


Choice of antibiotic for group B streptococcus in women in labour based on antibiotic sensitivity testing.
To determine whether pregnant women testing positive for Group B Streptococcus (GBS) are receiving appropriate antibiotic prophylaxis in labour based on sensitivity testing. We performed a retrospective chart review of all women who delivered at our institution from January 1 to December 31, 2008. We identified all GBS-positive women, and then abstracted data regarding demographic characteristics, method of GBS detection (recto-vaginal or urine culture), prevalence, and antibiotic use. The main outcome measure was the proportion of GBS-positive women who were managed appropriately. During the study period 628 (22%) of 2878 women were identified as having GBS-positive cultures. Sensitivity testing was available for 481 of the recto-vaginal cultures. All were sensitive to penicillin. The rates of resistance for recto-vaginal culture were 22% for erythromycin, 19% for clindamycin, and 18% for both. Four hundred eighty-one women (93%) were treated with penicillin, 30 (6%) with clindamycin, three with cefazolin, and two with vancomycin. One hundred nine women (17%) who were GBS-positive did not receive antibiotics. Forty-four women (9%) did not receive appropriate antibiotic prophylaxis based on sensitivity testing. Most GBS-positive women at our institution received an appropriate antibiotic during labour based on sensitivity testing. Our population reflects the Canadian GBS-positivity rate, which is similar to those observed in published studies from other populations. Future work should focus on developing strategies that re-emphasize GBS testing and treatment guidelines for prenatal care providers and on systems to ensure GBS-positive women are given the appropriate antibiotics during labour.


Validation of the alcohol use item banks from the Patient-Reported Outcomes Measurement Information System (PROMIS).
The Patient-Reported Outcomes Measurement Information System (PROMIS) includes five item banks for alcohol use. There are limited data, however, regarding their validity (e.g., convergent validity, responsiveness to change). To provide such data, we conducted a prospective study with 225 outpatients being treated for substance abuse. Assessments were completed shortly after intake and at 1-month and 3-month follow-ups. The alcohol item banks were administered as computerized adaptive tests (CATs). Fourteen CATs and one six-item short form were also administered from eight other PROMIS domains to generate a comprehensive health status profile. After modeling treatment outcome for the sample as a whole, correlates of outcome from the PROMIS health status profile were examined. For convergent validity, the largest correlation emerged between the PROMIS alcohol use score and the Alcohol Use Disorders Identification Test (r=.79 at intake). Regarding treatment outcome, there were modest changes across the target problem of alcohol use and other domains of the PROMIS health status profile. However, significant heterogeneity was found in initial severity of drinking and in rates of change for both abstinence and severity of drinking during follow-up. This heterogeneity was associated with demographic (e.g., gender) and health-profile (e.g., emotional support, social participation) variables. The results demonstrated the validity of PROMIS CATs, which require only 4-6 items in each domain. This efficiency makes it feasible to use a comprehensive health status profile within the substance use treatment setting, providing important prognostic information regarding abstinence and severity of drinking.


Overexpression of programmed death ligand 1 in dendritic cells inhibits allogeneic lymphocyte activation in mice.
Co-stimulatory molecules are pivotal for T cell activation. It is increasingly recognized that programmed death ligand 1 (PD-L1) is a novel co-stimulatory molecule, which raises the question as to whether PD-L1 regulates T cell responses. This study aimed to investigate the inhibitory effects of PD-L1 on T cell activation. We constructed a transgenic vector containing the complete PD-L1 gene, which interacts with the inhibitory receptor PD-1 in T cell-mediated immune activation. Donor dendritic cells (DCs) derived from C57BL/6 mice were transfected with PD-L1 and mixed with allogeneic, recipient T cells from BALB/c mice. The T cell activation was determined by the MTT assay and T cell proliferation was determined using carboxyfluoroscein succinimidyl ester (CFSE)-labeling following in vitro mixed leukocyte reactions. The expression of PD-L1 protein in PD-L1-transfected DCs was 47.97% ± 1.06%, compared with 4.66% ± 0.76% and 5.30% ± 0.60% in blank and negative controls, respectively (P < 0.05). PD-L1 protein was effectively expressed in DCs. Furthermore, in DCs stably transfected with PD-L1, T cell activation was significantly suppressed and T cell proliferation rate was decreased by 35% compared with untransfected DCs (P < 0.05). PD-L1 delivers an immunoinhibitory signal, suppressing T cell activation. Overexpression of PD-L1 signaling induces tolerance, which presents a promising immunotherapeutic approach for long-term graft acceptance.