Regulation of inducible nitric oxide synthase gene expression in vascular smooth muscle cells.
1. Formation of nitric oxide (NO) by the constitutive calcium-dependent NO synthase expressed in endothelial cells plays an important role in the control of local blood flow and vascular homeostasis. Expression of the inducible calcium-independent NO synthase (iNOS) in vascular smooth muscle cells (VSMC), on the other hand, is thought to play a potentially detrimental role in the pathogenesis of chronic inflammation or septic shock. In vascular injury, however, iNOS expression in VSMC may be beneficial as a compensatory mechanism for the lack of endothelial NO synthesis, e.g., by preventing restenosis following angioplasty or heart transplant vasculopathy. 2. Because iNOS activity does not seem to be controlled once the enzyme is expressed, regulation of NO release from iNOS-expressing cells predominantly occurs at the transcriptional and/or posttranscriptional level. 3. This review summarizes what is currently known about the regulation of expression of this enzyme in VSMC, details some of the transcription factors involved therein as well as their mode of activation, and highlights some pharmacological strategies based on these findings that may be employed for the control of iNOS expression in VSMC in the clinical arena.


Preliminary findings for the validity of the Morningness-Eveningness-Stability Scale improved (MESSi): Correlations with activity levels and personality.
Aim of the present study is an additional validation of the Morningness-Eveningness-Stability Scale improved (MESSi). We screened a total of 97 German students using the reduced Morningness-Eveningness Questionnaire (rMEQ) to identify a subsample (N = 42) of definite morning and evening types (31% males, mean age: 24.8 ± 5.8 years). The participants provided information about their sleep-wake rhythm (diary), personality traits (questionnaire) and experienced actigraphic monitoring. Correlations of the MESSi components "Morning affect subscale" (MA) (r = 0.91, p < 0.01) and "Eveningness subscale" (r = -0.87, p < 0.01) with the rMEQ showed good convergent validity. MA was also significantly negatively correlated with the acrophase and the midpoint of sleep as measured by actigraphy.


Ras signaling enhances the activity of C/EBP alpha to induce granulocytic differentiation by phosphorylation of serine 248.
The transcription factor C/EBP alpha regulates early steps of normal granulocyte differentiation since mice with a disruption of the C/EBP alpha gene do not express detectable levels of the granulocyte colony-stimulating factor receptor and produce no neutrophils. We have recently shown that C/EBP alpha function is also impaired in acute myeloid leukemias. However, how the transcriptional activity of C/EBP alpha is regulated both in myelopoiesis and leukemogenesis is not fully understood. The current study demonstrates that activated Ras enhances the ability of C/EBP alpha to transactivate the granulocyte colony-stimulating factor receptor promoter and a minimal promoter containing only C/EBP DNA binding sites. Ras signaling activates C/EBP alpha via the transactivation domain because it enhances the transactivation function of a fusion protein containing a Gal4 DNA binding domain and the C/EBP alpha transactivation domain and does not change C/EBP alpha DNA binding. Ras acts on serine 248 of the C/EBP alpha transactivation domain, because it does not enhance the transactivation function of a C/EBP alpha serine 248 to alanine point mutant. Interestingly, serine 248 of C/EBP alpha is a protein kinase C (PKC) consensus site, and a PKC inhibitor blocks the activation of C/EB alpha by Ras. Ras signaling leads to phosphorylation of C/EBP alpha in vivo. Finally, mutation of serine 248 to alanine obviates the ability of C/EBP alpha to induce granulocytic differentiation. These data suggest a model where Ras signaling enhances the activity of C/EBP alpha to induce granulocytic differentiation by phosphorylation of serine 248.


Effect of the COVID-19 pandemic on the mental health, daily and occupational activities among health professionals in Colombia: a national study.
The COVID-19 pandemic has placed an unprecedented physical and mental burden on healthcare workers who are frequently at high risk of infection, particularly in low-income countries. This study aimed to assess the prevalence and associated factors of anxiety, depression, and stress, as well as changes in daily and occupational activities among healthcare professionals due to the COVID-19 pandemic in Colombia. An observational, cross-sectional study was conducted between February and June 2021. The survey incorporated validated mental health tools such as the Generalized Anxiety Disorder-7, the Patient Health Questionnaire-9, and the Perceived Stress Scale-10. Multivariable ordinal logistic regression analysis was performed to determine the factors associated with severe mental health outcomes. Among 1345 healthcare workers the prevalence of anxiety, depression, and stress were 75.61, 59.18, and 53.09%, respectively. Anxiety (OR:1.44; 95%CI:1.16-1.8), depression (OR:1.74; 95%CI:1.27-2.37), and stress (OR:1.51; 95%CI:1.18-1.94) were more frequent in women, and individuals who expressed fear of a negative outcome (death, sequelae) (OR:2.25; 95%CI:1.60-3.25), (OR:1.49; 95%CI:1.03-2.16) and (OR:2.36; 95%CI:1.69-3.29) respectively. Age was negatively associated with anxiety (OR:0.98; 95%CI:0.98-0.99), stress (OR:0.98; 95%CI:0.97-0.99), and depression (OR:0.97; 95% CI:0.96-0.98). Reduction in consultations and surgeries (OR:1.01; 95%CI:1.0-1.01) was positively associated with anxiety. Due to the pandemic, most specialists expected to incorporate drastic long-term (> 1 year) changes in their clinical setting and daily activities. The prevalence of anxiety, depression, and stress is higher among Colombian healthcare workers compared to previous reports. Further research regarding these psychological outcomes is needed to achieve early mental health intervention strategies. Hospital Universitario Fundación Santa Fe, Ethical Committee Registration ID: CCEI-12992-2021.


Fabricating BiOI nanostructures armed catalytic strips for selective electrochemical and SERS detection of pesticide in polluted water.
We have constructed a dual mode catalytic strip equipped with 2D BiOI nanostructures and deployed for dual mode detection sensing of hazardous trichlorophenol (TCP). Synthesized BiOI nanostructures are investigated for its crystal architecture, morphology and chemical composition. The BiOI are loaded onto the catalytic strips with the assistance of gravity offered drying process. The BiOI nanostructures offers a very less charge transfer resistance indicating its superior catalytic properties upon the electrochemical impedance studies. It reflected on providing an excellent limit of detection (LOD) and linear sensing range for TCP in electrochemical mode. For SERS, a thin plasmonic Au layer is sputter coated on BiOI equipped catalytic strips (Au@BiOI) for the TCP detection. An impressive enhancement factor of 107 is obtained for SERS detection of TCP with good LOD of 10-10 M. Fabricated dual mode BiOI based strips are thoroughly examined for operational stability and performance in real time conditions. The fabricated high performance dual mode platform for the detection of hazardous pesticides appears to be a promising prospect for the on-the-spot investigation.


Acquiring multichannel analyzer spectra with a mini computer.
Spectra are produced on a multichannnel analyzer from biological samples with monochromatic fluorescent X-radiation. This mini-computer system is designed (1) to provide spectral data in a form immediately usable for computation, (2) to provide a great number of spectra stored on magnetic tape, (3) to examine the spectra in the laboratory before committing the spectra to tape and (4) facilitate the examining and manipulation of data in the laboratory. The spectra on the tape are used in high-level analyses. The mini-computer can examine parts of a spectrum, plot and print the values, identify and integrate peaks, all at the user's discretion.


Fractures of the scaphoid, capitate and triquetrum in a child: a case report.
Carpal fractures in children are rare, especially with a combination of scaphoid, capitate, and triquetrum fractures. We report one such case in a 10-year-old boy who was successfully treated with Kirschner wires.


2018 year in review: Part 2 of 4: Neonatal lung disease.
Pediatric Pulmonology publishes original research, reviews and case reports related to a wide range of children's respiratory disorders. This review (Part 2 of a 4-part series) summarizes the past year's publications in the topic area of neonatal lung diseases, in the context of selected literature from other journals relevant to the discipline.


Cardiac Surgery in Patients with Dialysis-dependent End Stage Renal Failure: Single Centre Experience.
Patients under dialysis have a high cardiovascular risk and they are at increased risk when submitted to cardiac surgery. to evaluate morbidity, early and late mortality, and predictive factors of mortality in patients under dialysis who underwent cardiac surgery. A retrospective observational study was performed including all dialysis dependent patients who underwent cardiac surgery (coronary, valvular or combined procedures) in our institution between 2007 and 2014. A population of 95 consecutive patients was obtained (no exclusions). Perioperative variables and predictors of mortality were analysed and the endpoints were early and late mortality. Propensity score matching, with a control group of patients with creatinine clearance >90mL/min, was performed by logistic regression, with a 1:1 matching. Kaplan Meier curves were performed for late mortality. Early mortality was 9.4% (EuroSCORE II 4.1%). In univariate analysis, mean time of cardiopulmonary bypass (CPB) (p=0.016) and EuroSCORE II (p=0.02) were related with early mortality. In a multivariate analysis model, combined procedures (OR 138.09; CI95% 1.82-10498.4; p=0.03) and CCS (Canadian Cardiovascular Society) 3-4 (OR 70.951; CI 95% 1.32-3810.11; p=0.037) were predictors of mortality. In multivariable analysis, CPB time >152 min was a predictor of early mortality (p=0.001). After propensity score matching, 30 day, one year and late mortality were higher in the dialysis group. Early and late mortality were significantly higher in dialysis dependent patients. Predictive factors of mortality were CPB time and EuroSCORE II in univariable analysis, and CCS 3-4 and combined procedures in multivariable analysis.


The mammography controversy: when should you screen?
ACOG's new guidelines call for more frequent breast cancer screening. The USPSTF recommends less. What's best for your patients?


Landmarks in the anatomical study of the blood supply of the skin.
The description of fasciocutaneous flaps by Pontén (1981) and the extensive, continuing studies of Cormack and Lamberty (1984) have revived interest in the anatomical study of the blood supply of the skin. It is important to know the results and conclusions of previous investigators. The purpose of this paper is to indicate some of these past achievements.


The use of patient navigation to transition detoxification patients to substance use treatment in the Alaska Interior.
Detoxification clinics manage acute intoxication and withdrawal from alcohol and other drugs. At discharge, patients are referred to treatment, yet many are readmitted to detoxification, creating a "revolving door" of discharges and admissions. This pattern disproportionately affects some groups such as Alaska Native and American Indian (AN/AI) people. The primary goals of this study are to: 1) test the effectiveness of a patient navigation intervention to increase rates of transition to alcohol treatment following detoxification, and 2) prevent readmission to detoxification within 12-months. The secondary goal is a cost-effectiveness and cost-benefit evaluation of patient navigation. This randomized controlled comparative effectiveness trial plans to recruit 440 patients (∼70% AN/AI) admitted to alcohol detoxification. We collaborated with Fairbanks Native Association (FNA) to select an appropriate intervention, control condition, and other study-related decisions. Here, we describe intervention development, study design, challenges encountered during implementation, and collaborative processes to identify solutions. Participants are equally randomized to the control (one motivational interviewing session) or intervention (one motivational interviewing session plus up to four weeks of patient navigation). The primary outcomes are successful transition to alcohol treatment within 30-days after discharge and detoxification readmission within 12-months. The secondary outcome is health-related quality of life. Patient navigation is successful in other settings and for other health conditions. It may assist in overcoming barriers to successful transition to substance use treatment and may augment interventions, such as motivational interviewing, that are less resource-intensive but may not be optimally effective by themselves. NCT03737864.


Stimulus-specific induction of an Egr-1 transgene in rat brain.
Regulated expression of Egr-1 (Zif268/NGFIA) in a variety of brain networks suggests a diversity of roles in neuronal plasticity. Here, we aimed to determine whether an egr-1 transgene would mediate transcriptional responses to different pharmacological and physiological stimuli in the brain of transgenic rats. Constitutive transgene expression was observed in the cortex, CA1 hippocampal area and pituitary, recapitulating expression of egr-1. Transgene induction was stimulus-specific. Metrazole induced widespread expression in the dentate gyrus, CA2 and CA3 areas, amygdala, and ventromedial nucleus. In contrast, induction following a light stimulus was restricted to the hypothalamic suprachiasmatic and periventricular nuclei. Our studies have provided novel insights into the differential regulation of egr-1, and facilitated approaches to the genetic manipulation of Egr-1-regulated neuronal systems.


Effect of substance P on medial forebrain bundle self-stimulation in rats following intracerebral administration.
The effect of Substance P infused intracerebrally via chronically implanted electrode-cannulae on self-stimulation induced from the same site was studied in rats. Substance P caused a significant depression of self-stimulation at 60 and 120 microgram/rat. Morphine infused into this site also caused significant depression of self-stimulation, but the doses were considerably lower than those of Substance P (5 and 10 microgram/rat). Pretreatment with naloxone, a narcotic antagonist, significantly antagonized the effects of Substance P on self-stimulation. It is proposed that Substance P modulates self-stimulation by the release of an endogenous morphine-like substance, but the possibility of a direct effect of Substance P was not ruled out.


Physical and chemical characterization of drill cuttings: A review.
Drill cuttings comprise a mixture of rocks generated during drilling activities of exploration and production of oil and gas. These residues' properties are variable, depending on several drilling parameters and drilled rock composition. Many scientific studies have been published regarding the characterization of these residues. Articles summarizing these residues' characteristics and toxicity data are poorly explored in the literature. This work reviews the principal methods used to characterize drill cuttings and data about these residues' properties. Some authors have reported the large content of Zn in drill cuttings. These cuttings can be associated with base fluids (as olefins, varying from C11 to C18), and some time crude oil (high range of TPH, unresolved complex mixtures, and PAH compounds). Acute and chronic toxicity tests have shown negative impacts of different types of fluids, the components of these fluids, and cuttings on other marine organisms.


Survival and functional recovery of primary cortical neurons exposed to actinomycin D.
Actinomycin D (ActD) is an antineoplastic antibiotic that has been commonly used for the treatment of various tumors, including Wilms' tumor, rhabdomyosarcoma, and gestational trophoblastic neoplasia. Recent studies have proposed actinomycin D (ActD) as a novel therapeutic candidate for glioblastoma. ActD significantly reduces tumor growth in recurrent glioblastoma patient-derived mouse models and increases survival by downregulating SOX2 expression. However, ActD treatment of brain tumors can lead to unnecessary exposure of surrounding neurons and normal glial cells to ActD. Cellular and molecular studies are required to estimate and minimize the neurological side effects of ActD. This study investigated the short- and long-term toxicological responses of the primary cortical neurons to ActD. We examined concentration-dependent survival of primary cortical neurons and differential susceptibilities of excitatory, inhibitory neurons, and glial cells to ActD. Distinct alterations in intracellular signaling pathways in cortical neurons were also studied when exposed to ActD. Importantly, we found that primary cortical neurons after ActD discontinuation showed active intracellular signaling pathways responding to extracellular neurotropic factors, but they had extremely poor transcription activity reversibility that was inhibited even by 30-min low-dose ActD exposure. These findings indicate the direct toxicity and extremely poor reversibility of ActD in neurons during chemotherapy for brain tumors.


Potential of Agave lechuguilla biomass for Cr(III) removal from aqueous solutions: thermodynamic studies.
Thermodynamic studies on the bioadsorption of Cr(III) onto Agave lechuguilla biomass were conduced. The experimental results at different temperatures were modeled using the Langmuir and Freundlich isotherms to obtain the characteristic parameters of each model. Both the Freundlich and Langmuir models were found to represent the bioadsorption process. The average adsorption capacities calculated from Freundlich (4.7 mg/g) and Langmuir (14.2 mg/g) isotherms showed A. lechuguilla to be an effective biomass in the removal of Cr(III) from an aqueous solution. Thermodynamic parameters (deltaG0, deltaH0 and deltaS0) determined in the temperature range from 10 to 40 degrees C along with the parameters of the Dubinin-Radushkevick equation support the idea that the binding of Cr(III) may be caused by interactions with functional groups such as carboxyl groups located on the outer surface of the cell tissue of the bioadsorbent.


Resorption controls bone anabolism driven by parathyroid hormone (PTH) receptor signaling in osteocytes.
The contribution of remodeling-based bone formation coupled to osteoclast activity versus modeling-based bone formation that occurs independently of resorption, to the anabolic effect of PTH remains unclear. We addressed this question using transgenic mice with activated PTH receptor signaling in osteocytes that exhibit increased bone mass and remodeling, recognized skeletal effects of PTH elevation. Direct inhibition of bone formation was accomplished genetically by overexpressing the Wnt antagonist Sost/sclerostin; and resorption-dependent bone formation was inhibited pharmacologically with the bisphosphonate alendronate. We found that bone formation induced by osteocytic PTH receptor signaling on the periosteal surface depends on Wnt signaling but not on resorption. In contrast, bone formation on the endocortical surface results from a combination of Wnt-driven increased osteoblast number and resorption-dependent osteoblast activity. Moreover, elevated osteoclasts and intracortical/calvarial porosity is exacerbated by overexpressing Sost and reversed by blocking resorption. Furthermore, increased cancellous bone is abolished by Wnt inhibition but further increased by blocking resorption. Thus, resorption induced by PTH receptor signaling in osteocytes is critical for full anabolism in cortical bone, but tempers bone gain in cancellous bone. Dissecting underlying mechanisms of PTH receptor signaling would allow targeting actions in different bone compartments, enhancing the therapeutic potential of the pathway.


Serum levels of vaspin and visfatin in patients with coronary artery disease-Kozani study.
The association of novel adipokines, vaspin and visfatin, with atherosclerosis is still obscure. The present study aimed to investigate the relationship of those adipokines with the existence as well as the extent of coronary artery disease (CAD), suggesting a link between adiposity and atherosclerosis. We enrolled a total of 108 patients with angiographically proven stable, asymptomatic CAD and 65 healthy controls (HC) without cardiovascular diseases. The severity of CAD was assessed using coronary angiography by the Gensini score. Clinical parameters, glycemic and lipid profile, high-sensitivity CRP (hsCRP), vaspin and visfatin levels were assayed. Serum levels of vaspin were significantly lower in subjects with CAD [0.91 (0.44-1.29) ng/ml] than healthy controls [1.42 (0.96-2.42) ng/ml] (p = 0.009). Inversely, visfatin (p = 0.016) and hsCRP (p < 0.001) levels were considerably up-regulated in CAD vs HC group. Multivariate analysis demonstrated decreased vaspin and increased visfatin levels to correlate with CAD presence, independent of other cardiovascular risk factors (p < 0.05). Standard multiple regression revealed HDL, LDL-C and vaspin to be independent determinants of Gensini score (R² = 0.189, p = 0.019). Notably, statin-free patients had even lower vaspin levels compared to statin users (p = 0.018). Decreased vaspin and increased visfatin serum levels were observed in asymptomatic patients with CAD. Low vaspin concentrations seemed to correlate with CAD severity.


Tetanus vaccine-induced human neutralizing antibodies provide full protection against neurotoxin challenge in mice.
Clostridium tetani causes life-threatening disease by producing tetanus neurotoxin (TeNT), one of the most toxic protein substances. Toxicosis can be prevented and cured by administration of anti-TeNT neutralizing antibodies. Here, we identified a series of monoclonal antibodies (mAbs) derived from memory B cells of a healthy adult immunized with the C-terminal domain of TeNT (TeNT-Hc). Thirteen mAbs bound to both tetanus toxoid (TT) and TeNT-Hc, while two mAbs recognized only TT. VH3-23 was the most frequently used germline gene in these TT-binding mAbs, and the pairwise identity values of the VH gene sequences ranged from 27% to 69%. Three of these mAbs-T3, T7, and T9-6-completely protected mice from challenge with 2× LD50 of TeNT, and two (T2 and T18) significantly prolonged the survival time. The five neutralizing mAbs recognized distinct epitopes on TT, with binding affinities ranging from 0.123 to 11.9 nM. Our study provides promising therapeutic candidates for tetanus.


Janus Kinase Inhibitor Tofacitinib Shows Potent Efficacy in a Mouse Model of Autoimmune Lymphoproliferative Syndrome (ALPS).
Autoimmune lymphoproliferative syndrome (ALPS) is a non-malignant genetic disorder of lymphocyte homeostasis with defective Fas-mediated apoptosis. Current therapies for ALPS primarily target autoimmune manifestations with non-specific immune suppressants with variable success thus highlighting the need for better therapeutics for this disorder. The spectrum of clinical manifestations of ALPS is mirrored by MRL/lpr mice that carry a loss of function mutation in the Fas gene and have proven to be a valuable model in predicting the efficacy of several therapeutics that are front-line modalities for the treatment of ALPS. We evaluated the potential efficacy of tofacitinib, an orally active, pan-JAK inhibitor currently approved for rheumatoid arthritis as a single agent modality against ALPS using MRL/lpr mice. We demonstrate that a 42-day course of tofacitinib therapy leads to a lasting reversal of lymphadenopathy and autoimmune manifestations in the treated MRL/lpr mice, Specifically, in treated mice the peripheral blood white blood cell counts were reversed to near normal levels with almost a 50 % reduction in the TCRαβ(+)CD4(-)CD8(-)T lymphocyte numbers that coincided with a parallel increase in CD8(+) T cells without a demonstrable effect on CD4(+) lymphocytes including FoxP3(+) regulatory T cells. The elevated plasma IgG and IgA levels were also drastically lowered along with a significant reduction in plasmablasts and plasmacytes in the spleen. On the basis of these results, it is likely that tofacitinib would prove to be a potent single agent therapeutic modality capable of ameliorating both offending lymphadenopathy as well as autoimmunity in ALPS patients.


Quantitative analysis of cardiac electrical restitution.
Electrical restitution (ER) of cardiac cells is an aggregate of events that rhythmically restore the initial conditions of electric signal (action potential) generation. Its analysis represents an important insight into cardiac arrhythmogenesis. The aim of this work is to theoretically substantiate and verify a novel approach allowing for the quantification of the individual ionic current components of ER. A method of analysis of the primary, initial conditions-setting restitution processes (apart from the secondary, test pulse-affected ones) is proposed. Both processes are described as sums of their measurable constituents. It is demonstrated that the optimum parameter of ER is the electric charge that is transferred through ionic channels and carriers during the test impulse. The theory was tested by using voltage-clamped canine ventricular preparations and by computer simulations. The experimental ER curve of canine ventricular muscle was constructed using action potential (AP) plateau voltage and half-repolarization time as parameters. At 30 degrees C and 0.5 Hz stimulation, the ER curve peaked, on average, after 400 ms with a 10% overshoot. Of this plateau elevation, 50% was due to 4-aminopyridine-sensitive transient outward current and 44% was due to verapamil-sensitive current. The delayed outward current antagonized the overshoot by about 6%. It was found that the initial conditions (i.e. the primary restitution processes) tend to strongly alter the plateau voltage of the premature AP. However, the final deviation is by about one order less. It is concluded that the voltage-dependent secondary processes counteract the effect of the primary processes, thereby suggesting strong negative feedback control of natural APs.


3D Printing of Diffuse Low-Grade Gliomas Involving Eloquent Cortical Areas and Subcortical Functional Pathways: Technical Note.
Surgical resection of diffuse low-grade gliomas (DLGGs) involving cortical eloquent areas and subcortical functional pathways represents a challenge in neurosurgery. Patient-specific, 3-dimensional (3D)-printed models of head and brain structures have emerged in recent years as an educational and clinical tool for patients, doctors, and surgical residents. Using multimodal high-definition magnetic resonance imaging data, which incorporates information from specific task-based functional neuroimaging and diffusion tensor imaging tractography and rapid prototyping technologies with specialized software and "in-house" 3D printing, we were able to generate 3D-printed head models that were used for preoperative patient education and consultation, surgical planning, and resident training in 2 complicated DLGG surgeries. This 3D-printed model is rapid prototyped and shows a means to model individualized, diffuse, low-level glioma in 3D space with respect to cortical eloquent areas and subcortical pathways. Survey results from 8 surgeons with different levels of expertise strongly support the use of this model for surgical planning, intraoperative surgical guidance, doctor-patient communication, and surgical training (>95% acceptance). Spatial proximity of DLGG to cortical eloquent areas and subcortical tracts can be readily assessed in patient-specific 3D printed models with high fidelity. 3D-printed multimodal models could be helpful in preoperative patient consultation, surgical planning, and resident training.


Weight Loss After Laparoscopic Sleeve Gastrectomy in Children and Adolescents.
For children and adolescents with severe obesity, metabolic and bariatric surgery including laparoscopic sleeve gastrectomy (LSG) is increasingly used to facilitate weight loss and reduce associated medical problems. Outcomes of LSG are understudied among patients under age 15 years. We sought to examine surgical complications and weight loss outcomes among children and adolescents who underwent LSG. This is a single-center retrospective cohort analysis at a high-volume metropolitan children's hospital in the northeast USA between 2011 and 2021. Weight loss was assessed at routine follow-up appointments for up to 36 months postoperatively. There were 12 patients under 13 years of age (< 13), 45 from 13 up to 15 years of age (13-14), and 57 patients aged 15 years or over (≥ 15). Among all patients, 70% were female, 41% were Hispanic, and 18% were non-Hispanic Black. There were no operative mortalities. Two patients had surgical complications requiring reoperation. Follow-up beyond 6 months occurred for 62% of patients. Weight loss was evident for each group at all time points, and there was no statistically significant difference among groups at any time point. BMI Z-score reduction at 6 months was 1.53 for the < 13 group, 0.89 for the 13-14 group, and 0.86 for the ≥ 15 group and at 36 months was 1.79, 1.50, and 1.16, respectively. These results support that LSG is a safe and effective method of achieving weight loss for young adolescents with severe obesity. Strategies to promote postoperative follow-up are needed.


Associations with myocardial infarction of six polymorphisms selected from a three-stage genome-wide association study.
Coronary heart disease, including its clinical manifestation, myocardial infarction (MI), is a common, complex disease with a substantive genetic component. State-of-the-art genetic epidemiology evaluates thousands of single nucleotide polymorphisms (SNPs) in association with disease cases and controls. In an independent but demographically similar population, this study tested 6 SNPs that were previously reported to be associated with MI. Patients hospitalized for an acute MI (n = 413) at an early age (men < 55 years, women < 65 years) were compared with age-discordant (men > or = 65 years, women > or = 70 years) control patients (n = 792) who had no MI history and no hospitalization for MI at index angiography or during longitudinal follow-up. Six SNPs were genotyped in the genes palladin, ROS1, TAS2R50, OR13G1, and ZNF627. Findings were not different from the null hypothesis, with ZNF627 (AG vs. GG: odds ratio [OR] 1.47, P = .16; AA vs. GG: OR 1.20, P = .50) and both ROS1 SNPs (GG vs AA: OR 0.72, P = .21; CC vs GG: OR 0.74, P = .24) showing potentially interesting ORs but nonsignificant probabilities. After full adjustment for all SNPs and covariables, only the ZNF627 heterozygote genotype had OR > 1.5 (P = .14). Comparison of MI cases with controls without obstructive coronary artery disease and analyses stratified by sex provided similar findings. Six SNPs previously reported to be associated with MI were not validated, suggesting that further investigation is needed to verify the applicability of those SNPs to cardiovascular medicine. These findings emphasize the high potential for false-positive results even in staged genome-wide association studies and further emphasize the need for continued refinement of cardiovascular genetic methodologies for clinical application.


On the interaction between digoxin and disopyramide.
Combined oral therapy with digoxin (0.375 mg/dl) and disopyramide (300 and 600 mg/dl) in nine subjects did not alter steady-state digoxin serum concentrations just before the daily single digoxin dose. Digoxin and creatinine clearances were not changed. After a bolus IV dose of 0.8 mg digoxin, volume of distribution (from 672 +/- 176 l to 407 +/- 153 l) and elimination t1/2 beta of digoxin were reduced significantly in five subjects after 600 mg oral disopyramide daily (from 40.2 +/- 11.7 hr to 22 +/- 7.3 hr). Total clearance and digoxin distribution t1/2 alpha did not change significantly. The clinical significance of this interaction is not clear.


Lactic acid bacteria from raw milk as potentially beneficial strains to prevent bovine mastitis.
Bovine mastitis produces a wide variety of problems in the dairy farm. The treatment of this disease is based on the use of antibiotics which are not always effective. These drugs are also responsible for the presence of residues in the milk and the increase of antibiotic-resistant strains. Probiotic products were proposed as a valid alternative to antibiotic therapies and are also useful for the prevention of infectious syndromes. With the aim of designing a probiotic product to prevent bovine mastitis, lactic acid bacteria (LAB) were isolated from foremilk samples from different dairy farms in Córdoba-Argentina. One hundred and seventeen LAB were isolated and their beneficial characteristics such as the production of inhibitory substances, surface properties and production of exopolysaccharides (EPS) were assessed. Most of them displayed low degree of hydrophobicity, autoaggregation, EPS negative phenotype and were identified as Enterococcus hirae and Pediococcus pentosaceus. Nine LAB strains inhibited three indicator bacteria. Some isolates were pre-selected and genetically identified according to the results obtained. Antibiotic resistance and virulence factors were studied for the assessment of the safety of the strains. The results obtained were compared to those reported previously from samples obtained in the North-western area of the country and some differences were found.


Combining molecular testing and the Bethesda category III:VI ratio for thyroid fine-needle aspirates: A quality-assurance metric for evaluating diagnostic performance in a cytopathology laboratory.
Molecular testing (MT) of thyroid fine-needle aspiration (FNA)-derived genetic material is commonly used to assess malignancy risk for indeterminate cases. The Bethesda System for Reporting Thyroid Cytopathology (TBS) provides limited guidance for the appropriate use of category III (atypia of undetermined significance [AUS]). The authors combined MT with cytomorphology to monitor AUS diagnoses in a cytopathology laboratory. Neoplasia-associated genetic alterations (NGAs) were determined by MT of preoperative FNA biopsies or resected malignancies and were categorized as BRAF V600E mutations, RAS-like mutations (HRAS, NRAS, or KRAS mutations or non-V600E BRAF mutations), or other mutations. Among 7382 thyroid FNA biopsies, the AUS rate was 9.3% overall and ranged from 4.3% to 24.2% among 6 cytopathologists (CPs) who evaluated >150 cases. The ratio of specimens falling into TBS category III to specimens falling into category VI (malignant) (the III:VI ratio) was 2.4 overall (range, 1.1-8.1), and the ratio of specimens falling into TBS categories III and IV (follicular neoplasm or suspicious for follicular neoplasm) combined (III+IV) to specimens falling into category VI (the [III+IV]:VI ratio) was 2.9 overall (range, 1.4-9.5). MT was performed on 588 cases from 560 patients (79% women) with a median age of 56 years (range, 8-89 years). BRAF V600E mutation was the most common (76% of cases) in TBS category VI and was rare (3%) in category III. RAS-like mutations were most common in TBS categories III (13%), IV (25%), and V (suspicious for malignancy) (17.5%). The NGA rate in AUS cases fell between 5% and 20% for 5 of 6 CPs and did not correlate with the III:VI ratio or the (III+IV):VI ratio. Lack of correlation between the NGA rate and easily calculable diagnostic ratios enables the calibration of diagnostic thresholds, even for CPs who have normal metrics. Specifically, calculation of the NGA rate and the III:VI ratio may allow individual CPs to determine whether they are overcalling or undercalling cases that other CPs might otherwise recategorize.


Communicating genetic risk information within families: a review.
This review of family communication of genetic risk information addresses questions of what the functions and influences on communication are; what, who and how family members are told about genetic risk information; what the impact for counsellee, relative and relationships are; whether there are differences by gender and condition; and what theories and methodologies are used. A systematic search strategy identified peer-reviewed journal articles published 1985-2009 using a mixture of methodologies. A Narrative Synthesis was used to extract and summarise data relevant to the research questions. This review identified 33 articles which found a consistent pattern of findings that communication about genetic risk within families is influenced by individual beliefs about the desirability of communicating genetic risk and by closeness of relationships within the family. None of the studies directly investigated the impact of communication on counsellees or their families, differences according to gender of counsellee or by condition nor alternative methods of communication with relatives. The findings mainly apply to late onset conditions such as Hereditary Breast and Ovarian Cancer. The most frequently used theory was Family Systems Theory and methods were generally qualitative. This review points to multifactorial influences on who is communicated with in families and what they are told about genetic risk information. Further research is required to investigate the impact of genetic risk information on family systems and differences between genders and conditions.


Association between angiographically assessed coronary artery disease and serum levels of prostate specific antigen.
The increased incidence of coronary artery disease (CAD) in patients with conventional cardiovascular risk factors cannot be fully explained by the known risk factors. The aim of the study was to test whether there is an association between the levels of serum total PSA with the presence of CAD and its severity. The study population consisted of 151 male patients aged < 55 years admitted at our center for elective coronary angiography. Patients having angiographic evidence of atherosclerosis (Gensini score > 6) in their epicardial coronary tree were categorized as having coronary artery disease (CAD(+) case group). Patients with Gensini score < or = 6 classified as having normal coronary arteries (CAD(-) control group). The presence and severity of CAD was determined by vessel score and Gensini score. The PSA levels were measured by the electrochemoluminescence (ECLIA) method. The mean level of serum PSA was found to be significantly higher in CAD patients than in those without CAD. In a multivariable logistic regression model, after adjusting for covariates, PSA level remained as an independent predictor for CAD occurrence (OR = 2.79; 95% CI: 1.04 - 7.49; p = 0.042). No significant correlation was found between the serum PSA level and the severity of CAD (r = 0.127, p = 0.122) or between PSA level and hsCRP level (r = 0.088, p = 0.282). It appears that PSA level is significantly associated with the presence of CAD. Further studies with larger sample size are required to confirm this result.


Bicarbonate-enhanced peroxidase activity of Cu,Zn SOD: is the distal oxidant bound or diffusible?
The Cu,Zn SOD catalyzes the bicarbonate-dependent oxidation of a wide range of substrates by H2O2. A mechanism in accord with this activity has been described. It involves the generation of a strong oxidant (Cu(I)O, Cu(II)OH, or Cu(III)) by reaction of the active site Cu with H2O2, followed by oxidation of bicarbonate to CO3-* that in turn diffuses from the active site to oxidize the various substrates in free solution. Recently, an alternative mechanism, entailing firmly bound HCO3- and CO3-*, has been proposed [J. Biol. Chem. 278 (2003) 21032-21039]. We present data supporting the diffusible CO3-* and discuss the properties of this system that can be accommodated in this way and that preclude bound intermediates.


Differences in the expression of multidrug resistance proteins in chronic rhinosinusitis according to endotype.
Chronic rhinosinusitis is a common disease of the nasal cavity and is classified into two major endotypes, which are neutrophilic and eosinophilic. Some patients with neutrophilic and eosinophilic chronic rhinosinusitis are refractory to treatment, and the mechanism of drug resistance is not completely understood. Nasal polyp samples were collected from patients with non-eosinophilic chronic rhinosinusitis (nECRS) and eosinophilic chronic rhinosinusitis (ECRS). Transcriptomic and proteomic analyses were performed simultaneously. Gene Ontology (GO) analysis was conducted to extract genes involved in drug resistance. Then, GO analysis results were validated via real-time polymerase chain reaction and immunohistochemistry analysis. The nasal polyps of patients with ECRS were enriched with 110 factors in the genes and 112 in the proteins, unlike in those of patients with nECRS. GO analysis on the combined results of both showed that the factors involved in extracellular transportation were enriched. Our analysis focused on multidrug resistance protein 1-5 (MRP1-5). Real-time polymerase chain reaction revealed that the MRP4 expression was significantly upregulated in ECRS polyps. Immunohistochemical staining showed that the MRP3 and MRP4 expressions significantly increased in nECRS and ECRS, respectively. MRP3 and MRP4 expressions were positively correlated with the number of neutrophil and eosinophil infiltrates in polyps and associated with the tendency to relapse in patients with ECRS. MRP is associated with treatment resistance and is expressed in nasal polyps. The expression pattern had different features based on chronic rhinosinusitis endotype. Therefore, drug resistance factors can be associated with therapeutic outcomes.


Developing great abstracts and posters: how to use the tools of science communication.
All nurses, clinicians and researchers are encouraged to share information on the programs they develop or the studies they conduct. This communication serves to advance the knowledge and clinical wisdom of the nursing and other health care professions. One way to do this is to submit an abstract or poster to a conference, where you can present your findings to other health care professionals. This article gives useful tips for developing successful abstracts and posters.


Physiotherapist-delivered Stress Inoculation Training for acute whiplash-associated disorders: A qualitative study of perceptions and experiences.
Formally trained and accredited physiotherapists delivered Stress Inoculation Training (SIT) integrated with guideline-based physiotherapy management to individuals with acute whiplash associated disorders (WAD) as part of a randomised controlled trial. The delivery of SIT by physiotherapists is new. To investigate physiotherapists' perspectives on delivering SIT as part of the trial and in routine practice. Qualitative descriptive. Physiotherapists (n = 11) participated in semi-structured interviews. Interviews were audio-recorded, transcribed verbatim, and analysed thematically. Findings were triangulated against an audit of physiotherapists' adherence to the SIT protocol. Three themes were identified: perceived value; capacity to deliver; and adaptation and implementation. Physiotherapists' saw value in SIT in that they perceived the program to have improved patient outcomes, enhanced their therapeutic alliance, and provided new skills to manage psychological contributors to WAD. Physiotherapists' capacity to deliver the program was facilitated through the development of confidence in their ability to deliver sessions, viewing SIT as falling within their current professional identity, and having confidence in their ability to manage mismatches in patients' expectations of care. All physiotherapists reported having used SIT to some extent in routine practice, by selectively delivering sessions and/or integrating the content with other management. Physiotherapists were able to deliver SIT as was intended (94.6% adherence). Physiotherapists' supported adding SIT to usual management of individuals with acute WAD. Education on SIT principles is recommended during pre-professional training to facilitate future implementation.


Metastatic-promoting effects of LPS: sexual dimorphism and mediation by catecholamines and prostaglandins.
Inflammation is implicated in several medical conditions that are sexually dimorphic, including depression, cardiovascular diseases, autoimmunity, and presumably cancer progression. Here we studied the effects of the proinflammatory agent, LPS, on MADB106 lung tumor retention (LTR), and sought to elucidate underlying mechanisms and sexual dimorphism. F344 male and female rats were administered with LPS (0.001-1mg/kg i.v.) simultaneously with tumor cell inoculation, and treated with a beta-blocker (nadolol, 0.2-0.3mg/kg s.c.), a COX inhibitor (indomethacin, 4mg/kg s.c.) or both drugs. To study the role of NK cells, numbers and cytotoxicity of marginating-pulmonary NK cells were studied, and selective in vivo NK-depletion was employed. Serum levels of corticosterone, IL-6, and TNF-alpha were also assessed. The findings indicated that LPS increased LTR in both sexes, but 10-fold higher doses were needed in females to reach the increase evident in males. Additionally, nadolol and indomethacin reduced the effects of LPS, more so in males. In vivo NK-depletion and ex vivo NK activity studies suggested that LPS affected LTR through both NK-independent and NK-dependent mechanisms, the latter mediated through prostaglandin release in males. Corticosterone, IL-6, and TNF-alpha responses to LPS were sexually dimorphic, but were not associated with LPS or drugs' impacts on LTR. Overall, our findings demonstrate sexual dimorphism in LPS-induced elevated susceptibility to MADB106 experimental metastasis, and in potential humoral underlying mechanisms. Further studies are needed to elucidate additional immunological and non-immunological mediators of these dimorphisms, as well as to assess their involvement in other sexually dimorphic pathologies that are associated with inflammation.


Developmental changes in thickness, contractility, and hypoxic sensitivity of newborn lamb cerebral arteries.
The present studies were conducted to examine the possibility that the increased vulnerability of the newborn brain to hypoxia may be due to age-related differences in vascular thickness and contractility. Segments of rostral choroidal (RC), posterior communicating (PC), basilar (B), and common carotid (CC) arteries were taken from 3- to 7-day-old lambs (n = 11) and adult sheep (n = 8) and studied using standard in vitro techniques. In lamb cerebral arteries, maturation was associated with significant increases in vessel thickness and tension generation. Because the increases in tension generation (77, 90, and 135% in PC, B, and RC segments) were proportionately greater than the corresponding increases in thickness (45, 75, and 34% in PC, B, and RC), force per unit area increased with maturation in the cerebral arteries. In the CC segments, the age-related increases in thickness (117%) were greater than the increases in tension generation (30%), such that average force per unit area was actually greater in the lamb than in the sheep. In response to hypoxia (PO2 less than 15 torr), all vessels exhibited significant relaxation relative to normoxic controls, although the rates and magnitudes of relaxation varied considerably. In the sheep, the carotid exhibited rapid relaxation of small magnitude (21%), whereas the cerebral arteries relaxed more slowly and more completely (56, 52, and 45% in PC, B, and RC). In contrast, the lamb carotid segments relaxed more slowly than the cerebral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)


Point prevalence survey of antimicrobial utilization in a Canadian tertiary-care teaching hospital.
Inappropriate antimicrobial use can promote antimicrobial resistance, which is associated with increased patient morbidity and mortality. Identifying the pattern of antimicrobial use can provide data from which targeted antimicrobial stewardship interventions can be made. The primary objective was to identify the prevalence of antimicrobial use at a tertiary care teaching hospital with both acute and long-term care patients. A point prevalence study was conducted on July 19th, 2012. Data on antimicrobial utilization, indication for prescribing, duration of therapy, and frequency of infectious disease or antimicrobial stewardship consultations were collected using a customized integrated stewardship database (SPIRIT) and prospective chart review. One or more antimicrobial agents were ordered in 31% and 4% of acute care and long-term care patients, respectively. Respiratory and urinary tract infections were the most common indication for antimicrobial therapy in both acute and long-term care. About 25% of surgical prophylaxis orders were prescribed for greater than 24h. This prospective point prevalence survey provided important baseline information on antimicrobial use within a large tertiary care teaching hospital and identified potential targets for future antimicrobial stewardship initiatives. A multi-center point prevalence survey should be considered to identify patterns of antimicrobial use in Canada and to establish the first steps toward international antimicrobial surveillance.


Assessment and pedagogy: a case study of two oral hygiene lecturers in South Africa.
There is evidence that most South African oral hygiene lecturers lack appropriate qualifications in the field of education. Their teaching skills are based mainly on clinical and practical experience, and this may impact on their understanding of the educational foundations of teaching, learning and assessment. To explore oral hygiene lecturers' knowledge and use of pedagogy and assessment and its alignment. A qualitative descriptive study design was used and case studies of two oral hygiene lecturers, each with qualifications in Education, were analyzed according to three themes: curriculum, pedagogy and assessment. The results showed that both participants had a good understanding of formative assessment (FA) and summative assessment (SA). They made use of FA but in neither case was the application ideal. Both used a range of teaching and assessment strategies but felt accountable to external demands of meeting outcomes. They linked their understanding of pedagogy and assessment to assist in the development of their courses and reported that this alignment had improved the quality of their programmes. This alignment by oral hygiene lecturers can influence curricular and pedagogic strategies. The professional educational development of lecturers in oral hygiene could be influential in improving the profession within the country.


[Study on chemical constituents in herbs of Anoectochilus roxburghii II].
To study the chemical constituents of Anoectochilus roxburghii. Silica gel and sephadex LH-20 column chromotography were used in the isolation from the ethanol extracts of the whole plant, the compounds were determined on the basis of various modern spectroscopic analysis and physical constants. Five compounds were isolated from the CHCl3 soluble portion, identified as p-Hydroxybenzaldehyde (I), ferulic acid (II), quercetin (III), daucosterol (IV), cirsilineol (V). All these compounds were isolated from the plant for the first time, compound V was isolated from the Orchid Family for the first time, the other compounds were isolated from this genus for the first time.


Single wall carbon nanotubes enter cells by endocytosis and not membrane penetration.
Carbon nanotubes are increasingly being tested for use in cellular applications. Determining the mode of entry is essential to control and regulate specific interactions with cells, to understand toxicological effects of nanotubes, and to develop nanotube-based cellular technologies. We investigated cellular uptake of Pluronic copolymer-stabilized, purified ~145 nm long single wall carbon nanotubes (SWCNTs) through a series of complementary cellular, cell-mimetic, and in vitro model membrane experiments. SWCNTs localized within fluorescently labeled endosomes, and confocal Raman spectroscopy showed a dramatic reduction in SWCNT uptake into cells at 4°C compared with 37°C. These data suggest energy-dependent endocytosis, as shown previously. We also examined the possibility for non-specific physical penetration of SWCNTs through the plasma membrane. Electrochemical impedance spectroscopy and Langmuir monolayer film balance measurements showed that Pluronic-stabilized SWCNTs associated with membranes but did not possess sufficient insertion energy to penetrate through the membrane. SWCNTs associated with vesicles made from plasma membranes but did not rupture the vesicles. These measurements, combined, demonstrate that Pluronic-stabilized SWCNTs only enter cells via energy-dependent endocytosis, and association of SWCNTs to membrane likely increases uptake.


Atopy--a favourable prognostic factor for survival in Hodgkin's disease.
One hundred and forty-eight patients with Hodgkin's disease (HD) were stratified into 4 groups according to atopic status. Group 1 had a personal history of atopy and Group 2 a family history of atopy. In Groups 3 and 4 there was no history of atopy but high serum IgE levels (Group 3) and normal IgE levels (Group 4). Comparison of the survival of these groups by the logrank method showed a significant trend (P = less than 0.0001) where survival was ranked Group 1 greater than 2 greater than 3 greater than 4. Known prognostic factors in HD--age, sex, stage, symptoms and histology--had to be taken into account, since their distribution differed between the atopic groups. In Group I there was more stage IA and IIA disease and less "B" symptoms, in Group 3 more nodular sclerosis histology and more "B" symptoms and in Group 4 more lymphocyte-depleted histology and a higher mean age than expected from their distribution in the combined groups. Adjustment to allow for the variation in each of the other prognostic factors and for a combination of age, symptoms and histology still showed a significant trend of survival on the basis of atopic status. The increased survival of atopic patients suggests that atopic mechanisms or the genetic basis to atopy has a protective effect in HD either directly or by interaction with treatment.


A 52-Year-Old Woman With a History of Ulcerative Colitis and New Onset Severe Dyspnea.
A 52-year-old woman was referred to the pulmonary office for evaluation of worsening dyspnea in August 2022. She had been diagnosed with asthma 22 years ago after she experienced chronic cough, sputum production, occasional wheezing, and mild exertional shortness of breath. Over the years, she was treated with different inhalers and was currently on triple inhaler therapy. A pulmonary function test in 2020 was normal. She had a history of ulcerative colitis and underwent a total colectomy in 1998. In the early 2000s, the patient also experienced episcleritis. Her other medical conditions included hyperlipidemia, gout, and gastroesophageal reflux disease.


Stereospecific morphine adsorption to phosphatidyl serine and other membranous components of brain.
In the course of investigating various membranous components for morphine binding, it was found that the major substance responsible was phosphatidyl serine. Other acidic lipids, such as phosphatidic acid and phosphoinositides bind to a considerably lesser extent, while neutral lipids, glycolipids and other phosphatides bind slightly or not at all. Total lipid extracts from a number of regions of rat brain exhibited different degrees of binding to (-)-morphine, such regions as the cerebral cortex and thalamus being the greatest. From an examination of the pH curve for binding and the effect of ionic strength, it was concluded that the binging was largely electrostatic. The method employed was the radioactive measurement of 14C-morphine adsorption to surface films of phosphatidyl serine. When the phosphatide was dispersed in a nonionic detergent near the critical micelle concentration, adsorption was maximal, attaining a value of 1 molecule of morphine adsorbed per molecule of phosphatidyl serine in the surface micelle. The relation between binding affinity and biological potency was not consistent. Morphine adsorption occurred with films prepared from a dispersion of the phosphatide and a hydrophobic protein from synaptic membranes. With the use of levorphanol and dextrorphan it could be shown that binding of morphine was stereospecific.


Does preoperative administration of metamizol (Novalgin) affect postoperative body weight and duration of recovery from ketamine-xylazine anaesthesia in mice undergoing embryo transfer: a preliminary report.
Thirty-two female mice used for embryo transfer or as controls received either metamizol or equal volumes of normal saline administered subcutaneously following induction of anaesthesia with ketamine-xylazine. Body weight was measured immediately before surgery, after 24 and after 48 h. The duration of the surgical anaesthesia was recorded and postoperative behavioural responses were measured. Comparison of the treatment groups revealed no significant differences in body weight and recovery times, nor were other signs of discomfort detected in either treatment group. It was concluded that administration of metamizol did not provide additional analgesia following embryo transfer in mice anaesthetized with ketamine-xylazine.


Oncology biomarkers: discovery, validation, and clinical use.
To discuss the discovery, validation, and clinical use of multiple types of biomarkers. Medical literature and published guidelines. Formal validation of biomarkers should include both retrospective analyses of well-characterized samples as well as a prospective clinical trial in which the biomarker is tested for its ability to predict the presence of disease or the efficacy of a cancer therapy. Biomarker development is complicated, with very few biomarker discoveries leading to clinically useful tests. Nurses should understand how a biomarker was developed, including the sensitivity and specificity before applying new biomarkers in the clinical setting.


Functional analysis of the Mn2+ requirement in the catalysis of ureohydrolases arginase and agmatinase - a historical perspective.
Ureohydrolases form a conserved family of enzymes with a strict requirement for divalent metal ions for catalytic activity. They catalyze the hydrolysis of the guanidino group and produce urea. In their active sites six highly conserved amino acid residues form a binding pocket for two catalytically essential metal ions that are needed to activate a water molecule to initiate the hydrolysis of the guanidino group in a nucleophilic attack. Focus in this review is on two members of the ureohydrolase family, the Mn2+-dependent arginase and agmatinase, which play important roles in functions related to replication and cell survival. We will focus in particular on Mn2+ binding interactions, and on how this metal ion contributes to the reaction catalyzed by these enzymes. We also include the agmatinase-like protein (ALP) because it is functionally closely related to agmatinase, also requires at least one Mn2+ ion for catalytic activity, but may possess an active site that differs significantly from all other known ureohydrolases.


Cesarean plus anoxia at birth induces hyperresponsiveness to locomotor activity by dopamine D2 agonist.
Transient global anoxia after Cesarean birth in rats may produce alterations in the subcortical DA function and related behaviors. The reports only tested the behavioral changes induced by a general DA agonist, such as amphetamine or apomorphine, in adult rats. Here we investigated the role of perinatal anoxia on the locomotion induced by a specific dopamine (DA) agonist and its relation to the DA D1-like and D2-like receptors, measured by autoradiography at two different ages, prepubertal (35 days old, P35) and postpubertal (60 days old, P60). Cesarean birth with or without (C-only) an additional period of 10 min of the anoxia was done in Sprague-Dawley rats, and the effects of the DA D1-like and D2-like agonist and their receptors were studied at P35 and P60. In addition, a third group of animals born vaginally served as the control. The quantitative autoradiography study of the DA D1-like and D2-like receptors revealed an enhancement of the DA D1-like receptor levels in the nucleus accumbens (NAcc) and dorsolateral part of the caudate-putamen in the prepubertal C-only animals. The postpubertal C-only rats showed a decrease in the levels of DA D2-like receptors in the NAcc. However, quinpirole, a DA D2 agonist (0.125 and 0.25 mg/kg, s.c.), induced a dose-dependent increase of the locomotor activity in the animals born by Cesarean with anoxia at birth at both ages. Our results suggest that Cesarean with or without anoxia at birth may mediate differently the neurodevelopmental aspects of the dopaminergic system before and after puberty.


Three-dimensional macroporous hybrid carbon aerogel with heterogeneous structure derived from MXene/cellulose aerogel for absorption-dominant electromagnetic interference shielding and excellent thermal insulation performance.
The development of electromagnetic interference (EMI) shielding materials with excellent absorption coefficient (A) is vital to completely eliminate the pollution of the ever-increasing electromagnetic waves (EMWs). In this regard, a TiC/carbon hybrid aerogel, derived from MXene/cellulose aerogel, was successfully fabricated via freeze-drying and subsequent pyrolysis process. Profiting from the open, loose three-dimensional (3D) macro pores with sheet-like morphology and high porosity, as well as the rich heterogeneous interfaces between TiC and cellulose-derived carbon, the as-prepared hybrid carbon aerogel achieves ultra-efficient EMI shielding effectiveness of 72.9 dB in conjunction with a superior A value of 0.76 and low thermal conductivity. These properties endow the as-prepared aerogel with strong absorption-dominant ultra-efficient EMI shielding and thermal insulation performance to meet the complex practical requirements. This work provides a promising strategy for achieving ultra-efficient multifunctional EMI shielding performance and superior A simultaneously.


Treatment choice in single-sided deafness and asymmetric hearing loss. A prospective, multicentre cohort study on 155 patients.
To describe the treatment choice in a cohort of subjects with single-sided deafness (SSD) and asymmetric hearing loss (AHL). To assess the reliability of the treatment trials. In this national, multicentre, prospective study, the choice of subjects was made after two consecutive trials of Contralateral Routing Of the Signal (CROS) hearing aids and a Bone Conduction Device (BCD) on a headband. Subjects could proceed with one of these two options, opt for cochlear implantation or decline all treatments. Seven tertiary university hospitals. One hundred fifty-five subjects with SSD or AHL fulfilling the candidacy criteria for cochlear implantation, with or without associated tinnitus. After the two trials, the number of subjects choosing each option was described. Repeated assessments of both generic and auditory-specific quality of life were conducted, as well as hearing assessments (speech recognition in noise and horizontal localization). CROS was chosen by 75 subjects, followed by cochlear implantation (n = 51), BCD (n = 18) and abstention (n = 11). Patients who opted for cochlear implantation had a poorer quality of life (P = .03). The improvement of quality of life indices after each trial was significantly associated with the final treatment choice (P = .008 for generic indices, P = .002 for auditory-specific indices). The follow-up showed that this improvement had been overestimated in the CROS group, with a long-term retention rate of 52.5%. More than one third of SSD/AHL subjects are unsatisfied after CROS and BCD trials. Repeated quality of life assessments help counselling the patient for his/her treatment choice.


The rate of heat storage mediates an anticipatory reduction in exercise intensity during cycling at a fixed rating of perceived exertion.
The aim of the present study was to examine the regulation of exercise intensity in hot environments when exercise is performed at a predetermined, fixed subjective rating of perceived exertion (RPE). Eight cyclists performed cycling trials at 15 degrees C (COOL), 25 degrees C (NORM) and 35 degrees C (HOT) (65% humidity throughout), during which they were instructed to cycle at a Borg rating of perceived exertion (RPE) of 16, increasing or decreasing their power output in order to maintain this RPE. Power output declined linearly in all three trials and the rate of decline was significantly higher in HOT than in NORM and COOL (2.35 +/- 0.73 W min(-1), 1.63 +/- 0.70 and 1.61 +/- 0.80 W min(-1), respectively, P < 0.05). The rate of heat storage was significantly higher in HOT for the first 4 min of the trials only, as a result of increasing skin temperatures. Thereafter, no differences in heat storage were found between conditions. We conclude that the regulation of exercise intensity is controlled by an initial afferent feedback regarding the rate of heat storage, which is used to regulate exercise intensity and hence the rate of heat storage for the remainder of the anticipated exercise bout. This regulation maintains thermal homeostasis by reducing the exercise work rate and utilizing the subjective RPE specifically to ensure that excessive heat accumulation does not occur and cellular catastrophe is avoided.


Micronucleus induction in mouse polychromatic erythrocytes by an X-ray contrast agent containing iodine.
In this article, the authors report the results of in vivo studies on bone marrow polychromatic erythrocytes (PCE) from mice treated with Urografina®292 (a mixture of sodium amidotrizoate and meglumine amidotrizoate) and with purified sodium amidotrizoate and meglumine amidotrizoate separately or in combination at the same ratio and concentration as that of the highest dose of Urografina®292 used in the experiment. The results showed that Urografina®292 significantly increased the frequencies of micronucleated polychromatic erythrocytes (MNPCEs) in both male (p=0.0082 and p=0.0062) and female (p=0.0350 and p=0.0101) mice treated with doses of 14.3 and 20.0 ml/kg body weight, respectively. When lower doses were used (5.7 and 8.6 ml/kg body weight), the treated mice did not show any significant increase in the frequencies of MNPCEs compared with the negative control group. The same result was observed for both male and female animals treated with purified sodium amidotrizoate and meglumine amidotrizoate separately or in combination. In addition, there was a significant positive correlation between the Urografina®292 doses used and the frequency of micronuclei. These results supported the hypothesis that small amounts of aryl amines present in all X-ray contrast agents containing diatrizoate and closely related triiodobenzoates were responsible for genotoxicity. The frequencies of PCEs in treated animals were determined to estimate the toxicity of Urografina®292, sodium amidotrizoate, and meglumine amidotrizoate to bone marrow, and the results indicated that they did not show any significant difference compared with the negative control group. The fact that mutagenic agents are also generally carcinogenic contributes to the concern with regard to the possible long-term risks of these agents in case of patients who are exposed to iodine-containing X-ray contrast agents during radiodiagnostic procedures.


Unusual Case of Metformin-Associated Lactic Acidosis in Patient with Type 2 Diabetes Mellitus.
BACKGROUND Metformin is recommended as the first-line therapy for type 2 diabetes mellitus, according to the American Diabetes Association. It is considered a safe medication with minimal adverse effects, with the most common being gastrointestinal. Metformin-associated lactic acidosis (MALA) is a rare but life-threatening complication. MALA usually occurs in patients with kidney dysfunction. However, it can still occur with preserved kidney function with the ingestion of a large dose of metformin. CASE REPORT A 66-year-old man with a significant medical history of type 2 diabetes mellitus presented after an intentional ingestion of a high dose of metformin (3000 mg/day). He was admitted to our hospital with symptoms of fatigue, nausea, vomiting, abdominal pain, and watery diarrhea lasting for 3 days. His initial laboratory findings were remarkable, with a serum creatinine level of 819 µmol/L. Arterial blood gas revealed severe lactic acidosis, with a pH of 6.94, HCO₃⁻- of 3 mEq/L, anion gap of 48 mmol/L, and lactate level of 15 mmol/L. Emergent continuous renal replacement therapy was done. Two days later, his condition improved considerably, and the lactic acidosis was resolved entirely. He was discharged on day 11 of hospitalization. CONCLUSIONS MALA is rare but life-threatening complication of treatment with metformin. MALA should be considered when there is evidence of metformin ingestion and renal insufficiency in patients with lactic acidosis. The curative treatment of MALA is based on hemodialysis, but the main remedy is prevention, which requires patient compliance with taking metformin as prescribed.


Modulation of dendritic release of dopamine by metabotropic glutamate receptors in rat substantia nigra.
A superfusion system was used to study the effects of metabotropic glutamate receptor (mGluR) ligands upon the release of [(3)H]dopamine ([(3)H]DA) previously taken up by rat substantia nigra (SN) slices. trans-(+/-)-1-Amino-(1S,3R)-cyclopentane dicarboxylic acid (trans-ACPD; 100 and 600 microM), a group I and II mGluR agonist, evoked the release of [(3)H]DA from nigral slices. This last effect was reduced significantly by (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)-glycine (MCCG; 300 microM), an antagonist of group II mGluR, or by the addition of tetrodotoxin (D-APV; 1 microM) to the superfusion medium. D-(-)-2-Amino-5-phosphono-valeric acid (100 microM), an N-methyl-D-aspartate receptor antagonist, or the presence of Mg(2+) (1.2mM) in the superfusion medium did not modify trans-ACPD-induced [(3)H]DA release. In addition, a group II mGluR agonist such as (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-glycine (DCG-IV; 100 microM) significantly induced the release of [(3)H]DA from nigral slices, whereas a group I mGluR agonist such as (RS)-3,5-dihydroxyphenylglycine (DHPG; 50 and 100 microM) did not modify the release of the [(3)H]-amine. Further experiments showed that the NMDA (100 microM)-evoked release of [(3)H]DA was decreased significantly by prior exposure of SN slices to trans-ACPD. Finally, partial denervation of the DA nigro-striatal pathway with 6-hydroxydopamine (6-OH-DA) increased trans-ACPD-induced release of [(3)H]DA, whereas it decreased trans-ACPD inhibitory effects on NMDA-evoked release of [(3)H]DA from nigral slices. The present results suggest that the dendritic release of DA in the SN is regulated by mGluR activation. Such nigral mGluR activation may produce opposite effects upon basal and NMDA-evoked release of DA in the SN. In addition, such mGluR-induced effects in the SN are modified in response to partial denervation of the DA nigro-striatal pathway.


Epidemiology and clinical outcomes of light-chain amyloidosis in Sweden: A nationwide population-based study.
This study evaluated data from six Swedish national registries to fill current evidence gaps on the epidemiology, clinical burden, and overall survival (OS) associated with light-chain (AL) amyloidosis. Patients newly diagnosed with AL amyloidosis were identified using six linked Swedish nationwide population-based registers. For each case, individuals from the general population were selected and matched with a maximum ratio of 1:5 based on age, sex, calendar year, and county. 846 patients newly diagnosed with AL amyloidosis and 4227 demographically matched individuals were identified. From 2011 to 2019, annual AL amyloidosis incidence increased from 10.5 to 15.1 cases per million. At baseline, patients with AL amyloidosis had a significantly higher disease burden including higher rates of cardiac and renal failure relative to the comparison group. Among patients with AL amyloidosis, 21.5% had incident heart failure and 17.1% had incident renal failure after initial diagnosis. Median OS for patients with AL amyloidosis was 56 months versus not reached in the matched general population comparison group. The incidence of newly diagnosed AL amyloidosis in Sweden increased over time with AL amyloidosis being associated with a higher risk of cardiac/renal failure and all-cause mortality compared with the general population.


Antigen-specific B cells present cartilage proteoglycan (aggrecan) to an autoreactive T cell hybridoma derived from a mouse with proteoglycan-induced arthritis.
Cartilage proteoglycan (aggrecan)-induced polyarthritis in BALB/c mice is characterized by chronic inflammation and destruction of joint tissues similar to that observed in human rheumatoid arthritis. The immunization of mice with fetal human proteoglycan (PG) elicits specific antibodies to the immunizing antigen of which a population cross-reacts with native mouse PG. This (auto)antibody production is immediately followed by an explosive proliferation of autoreactive T cells, suggesting that PG-specific B cells may participate in antigen presentation of PG to autoreactive T cells. We therefore isolated B cells from the spleens and lymph nodes of PG-immunized mice and examined their ability to present PG to a PG-specific T cell hybridoma. The antigen-specific T cell responses elicited by B cells from PG-immunized mice (both arthritic and clinically asymptomatic) were markedly higher than those of non-immune mice and keyhole limpet haemocyanin (KLH)-immunized mice, and these B cells could present low PG concentrations. Levels of B cell presentation corresponded with the serum levels of PG-specific antibodies, implying that these B cells were presenting the PG specifically via their surface immunoglobulin. This B cell-T cell interaction was strongly dependent on MHC class II/T cell receptor (TCR), LFA-1/intercellular adhesion molecule-1 (ICAM-1) and CD28/B7 interactions, as antibodies to Ia, ICAM-1 and B7-2 (but not to B7-1) markedly reduced presentation. These data indicate that PG-specific B cells may play an essential role in governing the development of PG-induced arthritis.


Synthesis of Isoxazole and 1,2,3-Triazole Isoindole Derivatives via Silver- and Copper-Catalyzed 1,3-Dipolar Cycloaddition Reaction.
The CuI- or Ag₂CO₃-catalyzed [3+2] cycloaddition of propargyl-substituted dihydroisoindolin-1-one (3) with arylnitrile oxides 1a-d (Ar = Ph, p-MeC₆H₄, p-MeOC₆H₄, p-ClC₆H₄) produces in good yields novel 3,5-disubstituted isoxazoles 4 of the ethyl-2-benzyl-3-oxo-1-((3-arylisoxazol-5yl)methyl)-2,3-dihydro-1H-isoindole-1-carboxylate type. With aryl azides 2a-d (Ar = Ph, p-MeC₆H₄, p-OMeC₆H₄, p-ClC₆H₄), a series of 1,4-disubstituted 1,2,3-triazoles 6 (ethyl-2-benzyl-3-oxo-1-((1-aryl-1H-1,2,3-triazol-4-yl)methyl)-2,3-dihydro-1H-isoindole-1-carboxylates) was obtained. The reactions proceed in a regioselective manner affording exclusively racemic adducts 4 and 6. Compared to the uncatalyzed cycloaddition, the yields are significantly improved in the presence of CuI as catalyst, without alteration of the selectivity. The regio- and stereochemistry of the cycloadducts has been corroborated by an X-ray diffraction study of 4a, and in the case of 6a by XH-correlation and HMBC spectra.


How aberrant N-glycosylation can alter protein functionality and ligand binding: An atomistic view.
Protein-assembly defects due to an enrichment of aberrant conformational protein variants are emerging as a new frontier in therapeutics design. Understanding the structural elements that rewire the conformational dynamics of proteins and pathologically perturb functionally oriented ensembles is important for inhibitor development. Chaperones are hub proteins for the assembly of multiprotein complexes and an enrichment of aberrant conformers can affect the cellular proteome, and in turn, phenotypes. Here, we integrate computational and experimental tools to investigte how N-glycosylation of specific residues in glucose-regulated protein 94 (GRP94) modulates internal dynamics and alters the conformational fitness of regions fundamental for the interaction with ATP and synthetic ligands and impacts substructures important for the recognition of interacting proteins. N-glycosylation plays an active role in modulating the energy landscape of GRP94, and we provide support for leveraging the knowledge on distinct glycosylation variants to design molecules targeting GRP94 disease-associated conformational states and assemblies.


Nationwide seroepidemiology of hepatitis B virus infection in South Korea in 2009 emphasizes the coexistence of HBsAg and anti-HBs.
Hepatitis B virus (HBV) infection is the major cause of chronic liver disease in Korea. This study investigated the seroprevalence of HBV infection with an emphasis on the coexistence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs). In all, 290,212 people undergoing health check-up examinations in 29 institutions during 2009 were recruited. The crude seroprevalences of HBsAg and anti-HBs was adjusted by age, sex, and geographic area using the 2009 estimated population of Korea. The adjusted seroprevalences of HBsAg and anti-HBs was 4.0% and 73.5%, respectively. Males showed higher HBsAg positivity and lower anti-HBs positivity than females (P<0.001). HBsAg positivity increased with age from 3.5% in people 20-29 years old to 4.8% in people 40-49 years old, followed by a decrease in people ≥ 50 years old. HBsAg positivity in Southern provinces (4.5%) including Jeju (5.9%), was significantly higher than that in Central provinces (3.6%; P<0.001). Interestingly, HBsAg and anti-HBs coexisted in 0.1% of the total subjects and in 2.9% of the HBsAg-positive group, showing distinct age distribution and higher alanine aminotransferase levels than those of the group positive for only HBsAg. In conclusion, the seroprevalence of HBsAg and anti-HBs in Korea varies significantly by age, sex and geographical location and coexisted in 2.9% of HBsAg-positive subjects. Continuous monitoring of seroepidemiology may facilitate the eventual eradication of HBV infection.


Outcome of renal transplantation from deceased donors after cardiac death: a single-center experience from a developing country.
Limited information is available in the literature about the use of organs from donation after cardiac death (DCD) renal transplantation (RTx) from a developing country. We report RTx outcome between DCD donors ≥70 years (Group 1; n = 14; mean age, 75.7 ± 5.81) and DCD donors <70 years (Group 2; n = l9; mean age, 51.7 ± 10.1) between January 1999 and January 2012. The mean age of recipients was 39.5 ± 14.7 years, 24 of whom were males. The mean donor age was 61.9 ± 14.6 years, 21 of whom were males. All recipients received single-dose thymoglobulin induction followed by immunosuppression with a steroid, a calcineurin inhibitor, and mycophenolate mofetil or azathioprine. Statistical analysis used chi-square test and unpaired Student t test. Kaplan-Meier curves were used for survival analysis. Over a mean follow-up of 3.21 ± 3.46 years, one-, five-, and ten-year, patient survival rates were 77%, 67.4%, and 67.4%, respectively, and death-censored graft survival rates were 85.7% for one, five, and ten years. Delayed graft function (DGF) was observed in 36.4% (n = 12) with 12.1% (n = 4) biopsy-proven acute rejection (BPAR). Patient survival (P = .27), graft survival (P = .20), DGF (P = .51), and BPAR (P = .74) were similar in 2 groups. A total of 27.2% (n = 9) of patients died, mainly due to infections (n = 5). Given the widespread organ shortage, outcomes of controlled DCD renal transplantation has a potential to expand the donor pool and shorten the waiting list for RTx, encouraging the use of this approach even in low-income countries.


Primary abdominal tuberculosis presenting as peritonitis in a young child-managed surgically.
Abdominal tuberculosis (TB) is the sixth commonest extra-pulmonary TB form after lymphatic, genitourinary, bone and joint, miliary and meningeal tuberculosis. We are presenting a rare case in a young female of age 7 year diagnosed as peritonitis and intestinal obstruction. Operative findings revealed dense fibrosis in interloops and perforation of the small bowel. She was put on antitubercular treatment for one year. Patient was discharged in satisfactory condition and is in follow up for 2 months.


Multiscale damage and strength of lamellar bone modeled by cohesive finite elements.
A computational multiscale model of damage mechanisms and strength of lamellar bone is presented. The analysis incorporates the hierarchical structure of bone spanning the nanoscale (mineralized collagen fibril), the sub-microscale (single lamella) and the microscale (lamellar structure) levels. Due to the presence of several constituents (collagen, hydroxyapatite minerals, and non-collagenous proteins) and the different microstructural features at each scale, various deformation and failure mechanisms occur in bone at its several levels of hierarchy. The model takes into account the dominant damage mechanisms at the above mentioned three scales and predicts the strength of bone by using a cohesive finite element method. Elastic moduli of bone at these three different scales are also obtained as part of these calculations. The obtained modeling results compare well with other theoretical and experimental data available in the literature.


Serotonin depletion prevents electrocortical synchronization following acute midbrain deactivation.
Bilateral midbrain cooling (5-15 degrees C) was performed in cats pretreated with p-chlorophenylalanine (PCPA). This was done in order to examine the possible role of 5-hydroxytryptamine (5-HT) systems in the process of electrocortical synchronization which normally accompanies midbrain reticular deactivation. Prior to treatment with PCPA, midbrain cooling always produced tonic electrocortical synchronization and behavioral unresponsiveness. Cooling following PCPA treatment on the other hand produced behavioral unresponsiveness which was not accompanied by tonic electrocortical synchronization; in that case electrocortical desynchronization persisted in spite of midbrain reticular deactivation. These results lead to the hypothesis that two distinct, tonically active, desynchronizing systems exist. During the acute blockade of the classical midbrain reticular activating system it is proposed that 5-HT systems normally operate to inhibit or otherwise prevent the expression of the second brain stem electrocortical desynchronizing mechanism. It is proposed, therefore, that 5-HT acts indirectly to produce electrocortical synchronization. In the absence of 5-HT, midbrain deactivation is not sufficient to guarantee synchronization is assured only when both desynchronizing systems are inactivated as would be the case in the acute cerveau isolé.


The relationship between metal ion levels and biogenic amine levels in epileptic mice.
The metabolism of various metal ions and biogenic amines in El mice, an inbred mutant strain susceptible to epilepsy, was investigated as a possible model for seizure mechanism. Serum Na, P, Ca, Mg, Fe and Zn levels in El mice were lower than those in ddY mice, the mother strain of El mice. Conversely, bone Ca, P, Na, Mg and Zn levels in El mice were higher than those in ddY mice. The results obtained by chemical analysis are consistent with radiographic observations. Possible mechanisms for the lower serum metal ion levels seen in El mice include a decrease in availability of these ions from bone. The dopamine (DA) level in El mouse brain was 15% lower than in ddY mice but could be raised by intraventricular administration of CaCl2. This result was supported a decreased ethanol-induced sleeping time in El as compared to ddY mice, with 'normalization' occurring after intraventricular administration of Da or CaCl2. The biogenic amine levels disorder in El mice is discussed on the basis of our pharmacological observation that biogenic amine synthesis is regulated by divalent cations via a calmodulin-dependent system. Our results suggest that the disorders of metal ion metabolism could be a mechanism for epileptic convulsions in El mice.


RNA helicase DHX33 regulates HMGB family genes in human cancer cells.
RNA helicase DHX33 has been shown to be aberrantly expressed in various human cancers, however, its role in tumorigenesis remains incompletely understood. In this report, we uncovered that a family of DNA architecture proteins, HMGBs, can be regulated by DHX33 in cancer cells but not in normal cells. Specifically, DHX33 knockdown caused the downregulation of HMGBs at the levels of both gene transcription and protein expression. Notably, in RAS driven lung tumorigenesis, nuclear HMGBs proteins can be induced via DHX33. When DHX33 was knocked out, HMGBs overexpression was debilitated. Mechanistically, DHX33 was found to bind to the promoters of HMGB family genes and regulated their transcription through demethylation on gene promoters. Our study reveals a novel mechanism for DHX33 to promote tumorigenesis and highlights its therapeutic value in human cancers.


Sorption behavior of Pb(II) onto polyvinyl chloride microplastics affects the formation and ecological functions of microbial biofilms.
Microplastics (MPs) are regarded as transport media for heavy metals in aquatic systems, whereas the effects of the heavy metal-enriched MPs on microbial biofilms are still unclear. In this study, Pb(II) sorption onto polyvinyl chloride (PVC) MPs and its effects on the formation and ecological functions of microbial biofilms were investigated. The results showed that the interaction between Pb(II) and PVC MPs was dominated by physisorption. The maximum sorption amount reached 1.25 mg/g. Afterward, microbial biofilms were exposed to the Pb(II)-enriched PVC particles. It is suggested that Pb(II)-enriched PVC exposure reduced productivities of polysaccharides and proteins in extracellular polymeric substances, which restricted the formation of microbial biofilms. Meanwhile, microbial community structure was reassembled accompanying the decline of capacities for nitrate and phosphate removal. Therefore, this study examines the ecological risk associated with the heavy metal-enriched MPs that can adversely affect microbial biofilms.


Iron-responsive element-binding protein. Phosphorylation by protein kinase C.
The iron-responsive element-binding protein (IRE-BP) is a cytosolic RNA-binding protein that functions in the maintenance of iron homeostasis by post-transcriptionally regulating transferrin receptor and ferritin synthesis. Little is known concerning how factors other than iron may modulate the activity of this central regulator of cellular iron utilization. We present evidence indicating that phosphorylation of the IRE-BP by protein kinase C (PKC) could provide a mechanism for regulation of IRE-BP function. Purified rat liver IRE-BP was phosphorylated by PKC up to 1.3 mol of phosphate/mol of protein with Ser the modified amino acid. Ser was also the phosphoacceptor in the IRE-BP in intact cells. The Km of PKC for the IRE-BP was 0.4 microM. Tryptic phosphopeptide mapping identified one major phosphopeptide plus several other peptides with lesser amounts of phosphate. Synthetic peptides of the IRE-BP containing Ser 138 (site A) and Ser 711 (site B) were phosphorylated by PKC. In HL 60 cells, addition of phorbol 12-myristate 13-acetate (PMA) stimulated IRE-BP phosphorylation within 30 min and increased high affinity IRE RNA binding activity 2-fold. After 90 min, the level of phosphorylation had increased further, and high affinity IRE RNA binding activity had increased 3-fold above the control. Incorporation of [35S]Met into immunoprecipitable IRE-BP was not altered in cells treated with PMA for 30 or 90 min. PMA also stimulated IRE-BP phosphorylation in rat fibroblasts. Taken together, our studies begin to define a novel mechanism by which hormones, growth factors, and other agents may regulate cellular iron utilization through specific phosphoregulation of the IRE-BP.


Uterine fibroid embolisation for symptomatic uterine fibroids: a survey of clinical practice in Europe.
To assess current uterine fibroid embolisation (UFE) practice in European countries and determine the clinical environment for UFE in different hospitals. In May 2009, an invitation for an online survey was sent by e-mail to all members of the Cardiovascular and Interventional Radiologic Society of Europe, representing a total number of 1,250 different candidate European treatment centres. The survey covered 21 questions concerning local UFE practice. A total of 282 respondents completed the questionnaire. Fifteen questionnaires were excluded because they were doubles from centres that had already returned a questionnaire. The response rate was 267 of 1,250 centres (21.4%). Ninety-four respondents (33%) did not perform UFE and were excluded, and six centres were excluded because demographic data were missing. The remaining 167 respondents from different UFE centres were included in the study. Twenty-six percent of the respondents were from the United Kingdom (n = 43); 16% were from Germany (n = 27); 11% were from France (n = 18); and the remaining 47% (n = 79) were from other European countries. Most centres (48%, n = 80) had 5 to 10 years experience with UFE and performed 10 to 50 procedures annually (53% [n = 88]) of respondents). Additional demographic data, as well as specific data on referral of patients, UFE techniques used, and periprocedural and postprocedural, care will be provided. Although UFE as an alternative treatment for hysterectomy or myomectomy is widespread in Europe, its impact on the management of the patient with symptomatic fibroids seems, according to the overall numbers of UFE procedures, somewhat disappointing. Multiple factors might be responsible for this observation.


The outcome of advanced or recurrent non-squamous carcinoma of the uterine cervix after platinum-based combination chemotherapy.
Data about the outcome and prognostic factors in the group of patients with non-squamous cell advanced or recurrent carcinomas of the uterine cervix are limited. We compared the outcome of patients with non-squamous with that of squamous cell carcinomas after platinum-based combination chemotherapy as first line therapy for stage IV or recurrent cervical carcinoma. A total of 200 patients with stage IV or recurrent carcinomas of the cervix received platinum-based combination chemotherapy and were included in our analysis. There were 58 patients with non-squamous and 142 patients with squamous cell carcinomas. Response to chemotherapy was 53.5% in non-squamous vs. 43.5% in squamous carcinomas. Histology was not an independent predictor of tumor response (P = 0.797). Response rates were lower in patients with relapse only in a previously irradiated area in both squamous (26.9% vs. 53.5%, P = 0.005) and non-squamous carcinomas (47.1% vs. 65%, P = 0.270). Weight loss was the only significant predictor of survival in non-squamous histology patients (P < 0.0001). There was no significant difference in median survival between squamous (11.57 months [95% CI 9.35-13.79]) and non-squamous carcinomas (19.05 months [95% CI 13.63-24.47]) (P = 0.064). After adjustment for independent prognostic factors (ECOG performance status and weight loss), differences in survival remained not significant. Our study showed a similar outcome for both squamous and non-squamous stage IV or recurrent cervical carcinomas treated with platinum-based combination chemotherapy.


Bacillus strains as human probiotics: characterization, safety, microbiome, and probiotic carrier.
Both spore and vegetative forms of Bacillus species have been used as probiotics, and they have high stability to the surrounding atmospheric conditions such as heat, gastric conditions, and moisture. The commercial Bacillus probiotic strains in use are B. cereus, B. clausii, B. coagulans, B. licheniformis, B. polyfermenticus, B. pumilus, and B. subtilis. These strains have antimicrobial, anticancer, antioxidant, and vitamin production properties. However, Bacillus probiotics can also produce toxins and biogenic amines and transfer antibiotic resistance genes; therefore, their safety is a concern. Studies on the microbiome using probiotic Bacillus strains are limited in humans. Most microbiome research has been conducted in chicken, mouse, and pig. Some Bacillus probiotics are used as fermentation starters in plant and soybean and dietary supplement of baking foods as a probiotic carrier. This review summarizes the characterization of Bacillus species as probiotics for human use and their safety, microbiome, and probiotic carrier.


Anti-PL7 antisynthetase syndrome under interferon therapy.
A 62-year-old woman with a past history of chronic hepatitis C virus infection presented an atypical predominantly painful polymyositis following a flu-like syndrome, persisting despite the withdrawal of PEG-interferon alpha-2b therapy. Clinical assessment, then immunological, electrophysiological and iconographic investigations including myositis antibodies, electromyography, pulmonary functions assessment and thoracic CT-scan found respectively "mechanic hands", arthralgia, presence of antisynthetase anti-PL7 antibody, typical myographic features of hip and shoulder girdles involvement, pulmonary fibrosis and restrictive syndrome features. A deltoid muscle biopsy revealed an unclassified myositis getting closer to anti-J0-1 and connective tissue disease associated myositis featuring: some components of polymyositis, dermatomyositis, and the following peculiar pathological aspects: noncaseous granulomatous infiltrate, endomysial microangiopathy and vascular and sarcolemic deposition of complement membrane attack complex. The diagnosis of interferon induced anti-PL7 antisynthetase syndrome with microangiopathic and granulomatous overlap myositis was retained. A treatment associating intravenous immunoglobulin and moderate tapered oral corticosteroids allowed a complete long-term resolution of myositis and a clear improvement of pulmonary involvement. This case points out the wide range of interferon alpha-associated disorders and call for a precise and detailed immunopathological analysis of myositis, instead of the usual vague classification as idiopathic polymyositis or dermatomyositis about antisynthetase syndrome.


Ablation as First-Line Therapy for Atrial Fibrillation: Not Yet for All.
Studies have established the superiority of atrial fibrillation ablation in controlling the rhythm compared with medical therapy. The procedure, however, has significant associated risks. Whether ablation therapy would improve the major outcomes of survival and stroke is not yet established. Until this information becomes available, ablation should continue to be used as a second-line option for most patient subgroups when one or more antiarrhythmic medications are ineffective.


Surgical outcomes after totally minimally invasive Ivor Lewis esophagectomy. A systematic review and meta-analysis.
A transthoracic esophagectomy is associated with high rates of morbidity. Minimally invasive esophagectomy has emerged to decrease such morbidity. The aim of this study was to accurately determine surgical outcomes after totally minimally invasive Ivor-Lewis Esophagectomy (TMIE). A systematic literature search was performed to identify original articles analyzing patients who underwent TMIE. Main outcomes included overall morbidity, major morbidity, pneumonia, arrhythmia, anastomotic leak, chyle leak, and mortality. A meta-analysis was conducted to estimate the overall weighted proportion and its 95% confidence interval (CI) for each analyzed outcome. A total of 5619 patients were included for analysis; 4781 (85.1%) underwent a laparoscopic/thoracoscopic esophagectomy and 838 (14.9%) a robotic-assisted esophagectomy. Mean age of patients was 63.5 (55-67) years and 75.8% were male. Overall morbidity and major morbidity rates were 39% (95% CI, 33%-45%) and 20% (95% CI, 13%-28%), respectively. Postoperative pneumonia and arrhythmia rates were 10% (95% CI, 8%-13%) and 12% (95% CI, 8%-17%), respectively. Anastomotic leak rate across studies was 8% (95% CI, 6%-10%). Chyle leak rate was 3% (95% CI, 2%-5%). Mortality rate was 2% (95% CI, 2%-2%). Median ICU stay and length of hospital stay were 2 (1-4) and 11.2 (7-20) days, respectively. Totally minimally invasive Ivor-Lewis esophagectomy is a challenging procedure with high morbidity rates. Strategies to enhance postoperative outcomes after this operation are still needed.


Cooling of the auditory cortex modifies neuronal activity in the inferior colliculus in rats.
There are powerful pathways descending from the auditory cortex (AC) to the inferior colliculus (IC), yet their function is not fully understood. The aim of this study is to examine the effects of a reversible cortical inactivation, achieved by cooling of the AC, on the responses of neurons in the rat IC. Extracellular single-unit or multi-unit activity was recorded in the IC of anaesthetized rats with a 16-channel multielectrode probe introduced along the IC dorso-ventral axis through the dorsal cortex (DCIC) to the central nucleus of the IC (CIC). Cooling of the AC produced an increase in spontaneous activity and magnitude of the sound-evoked response in 47% of the IC neurons. Maximal changes in the neuronal activity were observed in the DCIC and the central part of the CIC. The final segments of the sustained responses to 60 ms stimuli and the off responses were more affected than the onset segments. Inactivation of the AC resulted in a suppression of the post-excitatory inhibition and neuronal adaptation, which was reflected in a pronounced enhancement of synchronized responses to a series of fast repeated clicks. The response parameters recovered, at least partly, to the pre-cooling levels 1 h after the cooling cessation. The frequency tuning properties of the IC neurons did not show any significant changes during the cooling period. The results demonstrate that AC cooling inactivates excitatory corticofugal pathways and results in a less activated intrinsic inhibitory network in the IC.