Psychometric properties of the French and English short form of the Protective Behavioural Strategies for Marijuana Scale in Canadian university students.
The Protective Behavioural Strategies for Marijuana (PBSM-17) scale serves to identify and measure strategies employed by young adults before, during or after cannabis use. After the adaptation and translation of the PBSM-17 into French, a methodological study was conducted to evaluate the psychometric properties of this French version (FV) and of the original English version (EV) in a sample of bilingual Canadian university students. A total of 211 cannabis users (mean age=22.1 years) completed a sociodemographic questionnaire, a question on frequency of cannabis use (four categories: 1-3 times a month, once a week, more than once a week, everyday) and both versions (FV and EV) of the PBSM-17. Both versions had similar internal reliability (α=0.91; α=0.88). The one-factor solution explained 36.46% of the variance for the FV and 42.26% for the EV. As hypothesised, greater use of protective behavioural strategies was related to lower frequency of cannabis use. One-way ANOVA test results revealed a statistically significant difference in use of strategies by frequency of cannabis use for both the FV (F(3, 207)=27.38, p<0.001) and EV (F(3, 207)=29.32, p<0.001). Post hoc comparisons showed that everyday users employed fewer strategies on average than lower-frequency users. The FV and EV of the PBSM-17 demonstrated satisfactory psychometric properties. The proposed FV of the PBSM-17 is a reliable instrument that could be used for research and clinical purposes. Protective behavioural strategies can serve as indicator of lower-risk cannabis use and could be targeted in prevention interventions.


Interprofessional jargon: how is it exclusionary? Cultural determinants of language use in health care practice.
Language can impact significantly on the ways in which health care professionals relate and provide clinical services, as well as the way in which patients conceptualize their role in the healthcare encounter. The aim of this project was to explore the barriers and challenges to developing a collaborative approach in health care. A hermeneutic research approach was used with a convenience sample of international key informants representing 6 disciplines. A total of 10 individual, semi-structured interviews were conducted. Findings emphasized the need to be more inclusive by avoiding the use of exclusionary jargon so that all members of the health care team, including patients and families, can adopt a collaborative practice orientation.


Segmental determination in Drosophila central nervous system.
We have analyzed the control of two segment-specific features in the central nervous system of Drosophila larvae. One of them is present only in the thoracic ganglia of the larva, where it represents the anlage of the adult leg neuromeres; the other is found in the first abdominal, as well as in the thoracic, ganglia. We show that mutations within the bithorax complex have parallel but independent effects on these neural structures and on the larval epidermis. We also show that the central nervous system is very sensitive to mild perturbations of the bithorax complex, and in particular to haploinsufficiency.


Maximum ultrafiltration rates during peritoneal dialysis in rats.
It has been suggested that filtration pressure equilibrium could occur in peritoneal capillaries during peritoneal dialysis with very hypertonic exchanges. Rats were exposed to peritoneal dialysis solutions using 16 ml instillations, 30 minute cycles, and dextrose concentrations from 1.4 to 20 g%. There was a plateau in ultrafiltration per exchange at mean osmotic gradients above 360 mOsm/kg H2O near 12.5 ml/ex (0.42 ml/min). The findings are also compatible with filtration pressure equilibrium predictions at an effective capillary plasma flow of 0.84 ml/min and a filtration fraction near 50%. Studies with cardiovascular drugs (norepinephrine i.v., nitroprusside i.p., and dobutamine i.v.) showed no effects on the maximum ultrafiltration rates. This might indicate that flow is rather fixed because of known microcirculatory effects of solutions themselves.


Platelet rich plasma and plasma rich in growth factors for split-thickness skin graft donor site treatment in the burn patient setting: A randomized clinical trial.
Management of donor site morbidity in the setting of split thickness skin graft (STSG) is of crucial importance with no superior wound dressing described to date and the growing need of decreasing epithelializing time. The purpose of the study was to compare the standard of care using a hydrocolloid dressing to platelet rich plasma (PRP) and plasma rich in growth factors (PRGF) in order to determine its therapeutic potential in this setting. A randomized clinical trial was conducted in which each patient served as its own control. PRGF was obtained by means of freeze-thaw out of the PRP from the subject of the study. Patients from the study had three donor sites and each donor site received either to PRP, PRGF or the standard of care, hydrocolloid. The main variable was time to epithelialization, and secondary variables subject to study were pain, quality of the scar, complications and cost. 20 patients were recruited with a total number of 60 donor sites to study. On the 8th post-operative day 55% and 45% of the sites treated with PRP and PRGF, respectively, complete epithelialization was observed as compared to 20% of the sites treated with hydrocolloid, statistical significance was achieved between the latter two (p = 0.036). The areas treated with PRP and PRGF received inferior values on the visual analog scale on post-op day 5 and 8 compared to hydrocolloid. Values on wound healing metrics were lower in the PRP when compared to hydrocolloid. No adverse effects were recorded. Donor site of STSG treated with PRP in the setting of the burn patient decreased time to epithelialization. In our study a better pain control and in scar quality was observed in both, the PRP and PRGF group.


Eighty percent of cancer is related to the environment.
Five reasons lead us to believe that much of cancer is environmentally related: 1. Beginning with the work of Yamagiwa and Ichikawa in 1915, cancer has been produced in the laboratory under the control of man. 2. The trends of cancer incidence (and mortality) have been sharply up in some cases (lung), and sharply down in others (stomach, uterine cervix). 3. There are large differences in cancer among different parts of the world, and within the United States. 4. Migrants from one part of the world to another take on the rates of the part of the world to which they migrate. 5. Removal of known causes from the environment has been followed by reduced cancer incidence. Environmental causes of cancer lie in both personal environment: cigarette smoking, use of alcohol, sexual habits, perhaps diet; and in the impersonal environment: industrial and occupational pollutants, water and air contaminants, pesticides, flame retardants, diet additives, drugs. A joint effort by persons and by governments can reduce the incidence of cancer.


Fibrinolysis Shutdown and Hypofibrinolysis Are Not Synonymous Terms: The Clinical Significance of Differentiating Low Fibrinolytic States.
Low fibrinolytic activity has been associated with pathologic thrombosis and multiple-organ failure. Low fibrinolytic activity has two commonly associated terms, hypofibrinolysis and fibrinolysis shutdown. Hypofibrinolysis is a chronic state of lack of ability to generate an appropriate fibrinolytic response when anticipated. Fibrinolysis shutdown is the shutdown of fibrinolysis after systemic activation of the fibrinolytic system. There has been interchanging of these terms to describe critically ill patients in multiple settings. This is problematic in understanding the pathophysiology of disease processes related to these conditions. There is also a lack of research on the cellular mediators of these processes. The purpose of this article is to review the on and off mechanisms of fibrinolysis in the context of low fibrinolytic states to define the importance in differentiating hypofibrinolysis from fibrinolysis shutdown. In many clinical scenarios, the etiology of a low fibrinolytic state cannot be determined due to ambiguity if a preceding fibrinolytic activation event occurred. In this scenario, the term "low fibrinolytic activity" or "fibrinolysis resistance" is a more appropriate descriptor, rather than using assumptive of hypofibrinolysis and fibrinolysis shutdown, particularly in the acute setting of infection, injury, and surgery.


Chromoendoscopy is a valuable tool for screening of high-risk patients with head and neck cancer for early detection of esophageal cancer.
The incidence of esophageal cancer is markedly increased in patients with head and neck cancer, and the presence of esophageal cancer is associated with reduced survival rates. We investigated whether the results of screening for esophageal cancer in patients with head and neck cancer using chromoendoscopy would change the treatment of such patients. 87 patients with head and neck cancer and known alcohol or nicotine abuse were screened for esophageal cancer. The patients underwent esophagogastroduodenoscopy and staining of the esophagus with 2% Lugol's solution. Biopsies were taken from unstained areas for histopathological assessment. Esophageal cancer was newly diagnosed in 10 patients (11.5%), including 2 with carcinoma in situ. There were dysplastic changes in 6 patients (7%) and an unknown Barrett esophagus in 4 patients (5%). In 36 patients (41%) unstained areas were associated with esophagitis. While unstained areas could not be detected in 17 patients, the histology was normal in 14 patients with unstained areas. In all the patients with newly detected invasive esophageal cancer, the treatment had to be changed from a curative neoadjuvant approach to palliative treatment. In 2 patients with carcinoma in situ mucosectomy was performed. In the cases with dysplastic areas and newly detected Barrett epithelium a careful follow-up regime was arranged. The staging of patients with head and neck cancer, and the risk factors for esophageal cancer should include chromoendoscopy of the esophagus as a standard procedure. Extended staging provides critical additional information, which helps to more safely distinguish future candidates for curative and palliative treatment.


The influence of isotope and prostate volume on urinary morbidity after prostate brachytherapy.
To evaluate the influence of isotope and prostate size on International Prostate Symptom Score (IPSS) normalization, catheter dependency, and the need for surgical intervention secondary to bladder outlet obstruction after prostate brachytherapy. Between January 1998 and June 2003, 976 consecutive patients underwent brachytherapy for clinical stage T1b-T3a (2002 American Joint Committee on Cancer) prostate cancer. Seven hundred eighty-nine (80.8%) were implanted with 103Pd and 187 (19.2%) with 125I. The median follow-up was 41.2 months. Patients were stratified into size cohorts < or = 25 cm3, 25.1-35 cm3, 35.1-45 cm3, and >45 cm3. Four hundred eighteen patients (42.8%) received androgen deprivation therapy (ADT). Four hundred eighty-six patients (49.7%) received supplemental external-beam radiation therapy (XRT). In all patients, an alpha blocker was initiated before implantation and continued at least until the IPSS returned to baseline. IPSS resolution was defined as a return to within one point of baseline. The median number of IPSS determinations per patient was 21. Clinical, treatment, and dosimetric parameters evaluated included patient age, pretreatment PSA, Gleason score, clinical T stage, percent positive biopsies, preimplant IPSS, ultrasound volume, planning volume, isotope, V(100/150/200), D(90), urethral dose (average and maximum), supplemental XRT, ADT, and the duration of ADT (< or = 6 months vs. >6 months). Catheter dependency and the need for postsurgical intervention were also evaluated. For both isotopes and all prostate size cohorts, IPSS peaked 1 month after implantation and returned to baseline at a mean of 1.9 months. Stratification of prostate size cohorts by isotope demonstrated no significant differences in prolonged catheter dependency (> or = 5 days), IPSS resolution, or postimplant surgical intervention. In Cox regression analysis, IPSS normalization was best predicted by preimplant IPSS, XRT, and any need for a catheter after brachytherapy. Catheter dependency correlated with prostate size and ADT, whereas the need for surgical intervention was most closely related to any catheter dependency, maximum urethral dose, ADT, and maximum IPSS increase. Regardless of prostate size, isotope did not impact IPSS resolution, catheter dependency, or the need for postbrachytherapy surgical intervention. Although prostate size did predict for short-term (<5 days) catheter dependency, it did not influence IPSS resolution or the need for surgical intervention.


Monensin residues in the production of Minas Frescal cheese: Stability, effects on fermentation, fate and physicochemical characteristics of the cheese.
Considering the widespread use of the antibiotic monensin (MON) in the Brazilian livestock and the possibility of residues in milk, this paper aimed to study the stability and fate of this drug during the production of Brazilian Minas Frescal cheese, its effects on milk fermentation and on the physicochemical characteristics of this product. For that, samples of raw milk were fortified with MON at three different nominal concentrations (1.0, 2.0 and 8.0 μg/kg), passed through heat treatment and used to produce Minas Frescal cheese. Pasteurization efficiency was certified by alkaline phosphatase and peroxidase enzyme tests and cheese samples were evaluated for pH, moisture and total protein and fat content. MON residues were determined by LC-MS/MS in the following steps: raw milk, heat-treated milk, whey and cheese. No significant degradation of MON due to heat treatment was observed, suggesting that the drug is resistant to high temperatures. Moreover, the residue levels quantified in cheese and whey demonstrated a concentration of this antibiotic in the curd by about 5-fold, with a small amount of MON being lost during draining. There were no significant differences (p > 0.05) considering the physicochemical parameters evaluated in cheese samples. Fermentation was also not affected by the presence of the drug. The results showed that residues of MON in milk are stable during cheese production and may be concentrated in the final product, as well as indicate the need to establish a MON safe residue level for this food commodity.


Metastatic neuroendocrine carcinoma of right adrenal gland successfully treated with laparoscopic adrenalectomy after multimodal therapy.
We report a case of laparoscopic adrenalectomy in a salvage setting after multiple chemotherapies for neuroendocrine carcinoma. A 49-year-old man was diagnosed with unknown primary carcinoma with single brain metastasis, and right supraclavicular and mediastinal lymph node metastases. After stereotactic radiotherapy of the brain metastasis and systemic chemotherapy, lymphadanectomy was performed. The pathologic diagnosis was neuroendocrine carcinoma. At 11 months after surgery, computed tomography revealed right adrenal metastasis. Local radiotherapy initially resulted in complete remission. However, adrenal recurrence was noted 10 months later. Laparoscopic adrenalectomy was performed with curative intent. The patient is currently alive without recurrence at 20 months after the operation. Adrenalectomy can become a treatment option if other metastases are well-controlled with systemic therapy. Surgical elimination of oligometastases can offer long-term disease control in selected patients as part of a multimodal approach.


Epidemiology and prevalence of lean nonalcoholic fatty liver disease and associated cirrhosis, hepatocellular carcinoma, and cardiovascular outcomes in the United States: a population-based study and review of literature.
Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and metabolic syndrome conditions. However, a subset of NAFLD patients express a normal or low body mass index (lean NAFLD [L-NAFLD]). Our aim is to compare the prevalence of L-NAFLD to the obesity-associated NAFLD in the United States by assessing prevalence, potential risk factors, liver-related complications, and coronary artery disease outcomes. A multicenter database (Explorys Inc.) of >70 million patients across the United States was screened. A cohort of patients with "nonalcoholic fatty liver" between 1999 and 2021 was identified. Two sub-cohorts of NAFLD patients were identified: those with a body mass index (BMI) < 25 kg/m2 (L-NAFLD) and those with a BMI > 30 kg/m2 (obesity-associated NAFLD). We excluded patients with age <18 and those who have viral hepatitis, hemochromatosis, Wilson's disease, biliary cirrhosis, alcoholic liver disease, cystic fibrosis, alpha-1-antitrypsin deficiency, and autoimmune hepatitis. Multivariate analysis was performed to adjust for confounders. 68 892 260 individuals were screened. NAFLD prevalence was four per 100 000, and L-NAFLD prevalence was 0.6 per 100 000. Compared with those without, patients with L-NAFLD tended to be older (OR 2.16), females (OR 1.28), and smokers (OR 4.67) and of Asian race (OR 2.12). L-NAFLD patients were more likely to have acute coronary syndromes (OR 30.00) and metabolic syndrome (OR 2.31) despite the normal/low BMI. Esophageal varices and hepatocellular carcinoma risks were high in both cirrhosis patients. This is the largest study to assess L-NAFLD prevalence in the United States. L-NAFLD are at a significantly higher risk for acute coronary syndromes, esophageal varices, and hepatocellular carcinoma.


Facial expression in patients with bipolar disorder and schizophrenia in response to emotional stimuli: a partially shared cognitive and social deficit of the two disorders.
It has recently been highlighted that patients affected by schizophrenia (SCZ) and those affected by bipolar disorder (BD) undergo gradual chronic worsening of cognitive and social functioning. The objective of the current study was to evaluate and compare (using the Facial Action Coding System [FACS]) the way by which patients with the two disorders experience and display emotions in relation to specific emotional stimuli. Forty-five individuals participated in the study: 15 SCZ patients, 15 BD patients, and 15 healthy controls. All participants watched emotion-eliciting video clips while their facial activity was videotaped. The congruent/incongruent feeling of emotions and the facial expression in reaction to emotions were evaluated. SCZ and BD patients presented similar incongruent emotive feelings and facial expressions (significantly worse than healthy participants); SCZ patients expressed the emotion of disgust significantly less appropriately than BD patients. BD and SCZ patients seem to present a similar relevant impairment in both experiencing and displaying emotions; this impairment may be seen as a behavioral indicator of the deficit of social cognition present in both the disorders. As the disgust emotion is mainly elaborated in the insular cortex, the incongruent expression of disgust of SCZ patients can be interpreted as a further evidence of a functional deficit of the insular cortex in this disease. Specific remediation training could be used to improve emotion and social cognition in SCZ and BD patients.


Dose-dependent kinetics of ethotoin in man.
1. A gas-chromatographic assay for the anticonvulsant drug ethotoin in plasma has been used to establish a kinetic basis for therapy in eight newly diagnosed epileptic patients. 2. Only a small fraction of ethotoin was excreted unchanged. Elimination curves were only rectilinear below a plasma concentration of 8 mg/l. During constant medication plasma concentrations tended to decrease in the first week. Steady-state plasma levels varied considerably between individuals. For all patients the plasma concentration/dose ratio increased with increasing dose. 3. Most of the results point to dose-dependent elimination kinetics in the therapeutic range and parallel what is known for phenytoin. Control of therapy by measurement of plasma levels of ethotoin is accordingly advocated.


Synthesis of novel 2-nitroimidazole-tethered tricyclic quinolines, bearing a second heteroatom, and their in vitro evaluation as hypoxia-selective cytotoxins and radiosensitizers.
Two novel nitroimidazole-based bioreductive compounds, 10-[3-(2-nitroimidazolyl)-propylamino]-3,4-dihydro-1H-thiopyrano[4,3-b]quinoline hydrochloride (8a) and 10-[3-(2-nitroimidazolyl)propylamino]-2-methyl-1,2,3,4-tetrahydro-benzo[b]-1,6-naphthyridine hydrochloride (8b) have been synthesized and evaluated in V79 cells as hypoxia-selective cytotoxins and radiosensitizers that target DNA through weak intercalation. Both compounds were relatively good radiosensitizers (C(1.6) values of 40.0+/-0.8 and 59.0+/-0.4 microM for 8a and 8b, respectively) but neither of the compounds was superior to 2 which does not carry a second heteroatom in the DNA-intercalating chromophore.


Surface modification of sepiolite with quaternary amines.
This study was aimed at elucidating the mechanism of adsorption of quaternary amines, stearyldimethylbenzylammoniumchloride (SDBAC), as monomers and as micelles, distearyldimethylammoniumchloride (DDAC) and hexadecyltrimethylammoniumchloride (HTAC), on the surface of sepiolite. The adsorption capacity for these surfactants onto sepiolite, calculated by fitting the experimental data to the Langmuir-Freundlich equation, were 324% (SDBAC), 278% (DDAC), and 258% (HTAC) of the cation exchange capacity of sepiolite. The Mg(2+) ions released during the exchange process were higher than the CEC value of sepiolite because of the simultaneous dissolution of the present minerals. The water adsorption decreased with the increasing surfactant loading up to 250 mmol/kg of sepiolite, which can be ascribed to an intensification of the hydrophobic properties. With loadings above 250 mmol/kg, the water adsorption increases. Simple kinetic analysis of SDBAC adsorption was performed. The properties and the type of bonding between the surfactants and sepiolite were investigated by DT, TG, and DTG analysis. During the gradual heating in oxidizing atmosphere, the adsorbed organic material is oxidized giving rise to significant exothermic peaks. The exothermic peak temperatures in the range 200-500 degrees C depended on the surfactant loadings and provided evidence of the formation of multilayers on the sepiolite surface.


Phase I trial of ICRF-159 in combination with 1.3 bis-(2-chloroethyl)-1-nitrosourea (MeCCNU).
Both ICRF-159 and methyl-CCNU are agents with antitumor activity against gastrointestinal carcinoma; hence the exploration of this combination for possible synergism. Results of the study involving 19 patients show that bone marrow toxicity is the limiting factor for this combination of drugs. Moreover, a dose of 130 mg/mg of MeCCNU with 800 mg/m2/day of ICRF is well tolerated.


Aflatoxin B1-specific cytochrome P-450 isozyme (P-450-AFB) inducible by 3-methylcholanthrene in golden hamsters.
Hepatic microsomes of polychlorinated biphenyl (PCB)-treated Syrian Golden hamsters possessed a higher potency toward aflatoxin B1 activation, based on the Ames test, than other animal species. This activity was induced in hamsters preferentially by treatment with 3-methylcholanthrene rather than phenobarbital. The contribution of an isozyme of cytochrome P-450 (P-450-AFB) to the activity of hamster livers for aflatoxin B1 was studied. P-450-AFB, purified from 3-methylcholanthrene-treated hamster livers, was shown to possess the highest activation of aflatoxin B1 in the Ames test. The quantification of this isozyme by a fluorometric sandwich enzyme-linked immunosorbent assay (ELISA) demonstrated that P-450-AFB was induced mainly in Syrian Golden hamsters but not in Chinese hamsters, or in other species. This isozyme constitutes approximately 40% of the total cytochrome P-450 of the hepatic microsomes from 3-methylcholanthrene-treated Golden hamsters but only 1% in the microsomes of phenobarbital-treated hamsters. Thus, we conclude that the high activity of Golden hamster livers towards aflatoxin B1 activation was due presumably to this distinct and unique cytochrome P-450 isozyme which was induced mainly by 3-methylcholanthrene in Golden hamsters.


Interposition spiral saphenous vein graft bypass in bilateral simultaneous radical neck dissection.
We advocate the use of the spiral saphenous vein bypass of the IJV when bilateral radical neck dissections are performed with the sacrifice of both IJV. The technique we have described herein is uniformly successful in this setting and associated with only 30 minutes to one hour of increased operative time. This bypass will decrease the postoperative facial edema and associated complications and allow the patient to go on to radiation and chemotherapy in an expeditious and safe manner.


[The effect of linoleyl hydroxamic acid on lipid peroxidation processes and on the enzymatic activity of the antioxidant system in rats under hypoxia].
It was studied the effect of new blocker of lipoxygenase way of arachidontic acid metabolism--linoleyl-hydroxamic acid--on the status of lipid peroxidation and antioxidant system in blood, heart, liver, lung and brain in rats under acute hypoxic hypoxia. It was shows that preliminary introduction of this substance lead to increase of antioxidant enzymes activity--superoxide dismutase and ceruloplasmine, and to decrease of lipid peroxidation level during hypoxia in blood, heart, liver and lung (without brain).


cAMP-dependent differential regulation of extracellular matrix (ECM) gene expression in cultured rat Schwann cells.
cAMP-dependent regulation of the steady-state mRNA levels for the ECM components, laminin A, B1 and B2 chains, collagen types I, III and IV were examined by Northern blot analysis in cultured rat Schwann cells. ECM mRNAs of laminin B1 chain and collagen types I and IV were expressed at high levels in the control Schwann cells, while laminin B2 chain and collagen type III mRNA levels were low, and laminin A chain mRNA was not detectable. When Schwann cells were treated with forskolin or cAMP derivatives, the gene expression for the ECM molecules constituting the Schwann cell basement membrane, laminin B1 and B2 chains, and collagen type IV, was enhanced in time- and dose-dependent manners for exogenously administered forskolin or cAMP derivatives, while the mRNA levels for the ECM molecules, which are not the major components of the basement membrane, fibrillary collagen types I and III were significantly suppressed. This cAMP-dependent differential regulation of Schwann cell ECM gene expression may be related to the role of each ECM molecule in the peripheral nerve development and regeneration.


Memory deficits, postconcussive complaints, and posttraumatic stress disorder in a volunteer sample of veterans.
To better understand how memory impairment is related to postconcussive complaints and to posttraumatic stress disorder (PTSD) and whether these relationships remain after controlling for premorbid cognitive ability. We examined memory impairment, premorbid cognitive ability, postconcussive complaints, and symptoms of PTSD in 205 veterans, 135 of who gave a self-reported history of concussion and exposure to a traumatic life event. We limited our sample to those who gave good effort on cognitive testing according to a symptom validity measure. Although memory impairment was not associated with a history of concussion, it was associated with severity of postconcussive complaints. That association was no longer significant after controlling for premorbid IQ. A similar analysis yielded slightly different findings for PTSD. Memory impairment was associated with PTSD diagnosis, although it was not associated with severity of PTSD symptoms after controlling for premorbid ability. These data are consistent with multifactorial models of the etiology of postconcussion disorder and PTSD such as the "burden of adversity hypothesis" described by Brenner, Vanderploeg, and Terrio (2009). In such models, symptom severity and course of recovery are determined not only by trauma severity but (also) premorbid risk factors and postonset complications. (PsycINFO Database Record (c) 2013 APA, all rights reserved).


Naturally occurring antibodies for the group B streptococcal surface immunogenic protein (Sip) in pregnant women and newborn babies.
Sip is a surface-exposed protein of GBS, which causes severe neonatal disease. Because Sip elicits a protective immune response in mice, we assessed whether pregnant women and newborns have Sip antibodies. Sera were collected from 644 pregnant women and 176 of their healthy newborns, and 10 newborns with GBS disease and their mothers. Using ELISA, most (99%) women and newborns (97%) had serum Sip antibodies, as did most newborns followed through 6 months. This suggests that naturally occurring Sip antibodies cross the placenta and persist into infancy, which underscores the need to study Sip further as a potential vaccine candidate.


Lipophagy-mediated cholesterol synthesis inhibition is required for the survival of hepatocellular carcinoma under glutamine deprivation.
Glutamine is critical for tumor progression, and restriction of its availability is emerging as a potential therapeutic strategy. The metabolic plasticity of tumor cells helps them adapting to glutamine restriction. However, the role of cholesterol metabolism in this process is relatively unexplored. Here, we reported that glutamine deprivation inhibited cholesterol synthesis in hepatocellular carcinoma (HCC). Reactivation of cholesterol synthesis enhanced glutamine-deprivation-induced cell death of HCC cells, which is partially duo to augmented NADPH depletion and lipid peroxidation. Mechanistically, glutamine deprivation induced lipophagy to transport cholesterol from lipid droplets (LDs) to endoplasmic reticulum (ER), leading to inhibit SREBF2 maturation and cholesterol synthesis, and maintain redox balance for survival. Glutamine deprivation decreased mTORC1 activity to induce lipophagy. Importantly, administration of U18666A, CQ, or shTSC2 viruses further augmented GPNA-induced inhibition of xenograft tumor growth. Clinical data supported that glutamine utilization positively correlated with cholesterol synthesis, which is associated with poor prognosis of HCC patients. Collectively, our study revealed that cholesterol synthesis inhibition is required for the survival of HCC under glutamine-restricted tumor microenvironment.


DNA methylation of IL-4 gene and the association with childhood trauma in panic disorder.
Increasing evidence suggests that aberrations in the immune-inflammatory pathways contribute to the pathophysiology of panic disorder (PD). We aimed to investigate whether an aberrant DNA methylation of the inflammation-related genes in the development of PD, including CCL3, CRP, CSF2, CXCL8, IFNG, IL12B, IL1A, IL-4, IL-6, TNF. Then, the effect of childhood trauma(CT) on methylation levels of inflammation-related genes and the severity of PD was also investigated. We compared the methylation levels of the inflammation-related genes between 113 patients with PD and 130 matched healthy controls using MethylTarget approach. In addition, the Hamilton Anxiety Rating Scale (HAMA), Panic Disorder Severity Scale (PDSS) and Childhood Trauma Questionnaire-28 item Short Form (CTQ-28) were respectively assessed to all subjects. The result found that the methylation levels of IL-4 gene was significantly higher in PD patients than controls. ROC results found that the IL-4 gene had a sensitivity of 52.3% and a specificity of 74.6%. The methylation levels of IL-4 gene was significantly positively related to the severity of panic and anxiety. Finally, the hypermethylation of CSF2, CXCL8 and IL-4 genes was significantly associated with higher CT.


Quantitative trait loci influence renal disease progression in a mouse model of Alport syndrome.
Alport syndrome is a human hereditary glomerulonephritis which results in end-stage renal failure (ESRF) in most cases. It is caused by mutations in any one of the collagen alpha3(IV), alpha4(IV), or alpha5(IV) chain genes (COL4A3-COL4A5). Patients carrying identical mutations can exhibit very different disease courses, suggesting that other genes or the environment influence disease progression. We previously generated a knockout mouse model of Alport syndrome by mutating Col4a3. Here, we show that genetic background strongly influences the timing of onset of disease and rate of progression to ESRF in these mice. On the 129X1/SvJ background, Col4a3 -/- mice reached ESRF at approximately 66 days of age, while on the C57BL/6J background, the mean age at ESRF was 194 days of age. This suggests the existence of modifier genes that influence disease progression. A detailed histopathological analysis revealed that glomerular basement membrane lesions typical of Alport syndrome were significantly more frequent in homozygotes on the 129X1/SvJ background than on the C57BL/6J background as early as two weeks of age, suggesting that modifier genes act by influencing glomerular basement membrane structure. Additional data indicated that differential physiological responses to basement membrane splitting also underlie the differences in disease progression. We attempted to map the modifier genes as quantitative trait loci (QTLs) using age at ESRF as the quantitative trait. Genome scans were performed on mice at the two extremes in a cohort of mutant F1 x C57BL/6J backcross mice. Analysis with Map Manager QT revealed QTLs linked to markers on chromosomes 9 and 16. A more detailed understanding of how these QTLs act could lead to new approaches for therapy in diverse renal diseases.


Effect of Nicorandil, Diltiazem, or Isosorbide Mononitrate for Oral Antispastic Therapy After Coronary Artery Bypass Grafting Using Radial Artery Grafts-A Pilot Randomized Controlled Trial (ASRAB-Pilot): Rationale and Study Protocol.
The current evidence for chronic oral antispastic medication use after coronary artery bypass grafting using radial artery grafts (RA-CABG) is controversial. Calcium channel blockers, such as diltiazem, are the most commonly used antispastic medications after RA-CABG; other options include nitrates and nicorandil, but to date no sufficiently powered randomized controlled trials have been conducted to compare their efficacy. This is a single-center, open-label, parallel three-arm, pilot randomized controlled trial. Patients without contraindications to any study medications and who successfully underwent RA-CABG surgery will be consecutively screened. Eligible patients will be randomized in a ratio of 1:1:1 (a total of 150 patients, 50 per arm) to receive nicorandil 5 mg orally thrice daily, diltiazem 180 mg orally once daily, or isosorbide mononitrate 50 mg orally once daily for 24 weeks. The primary outcomes are RA graft failure at week 1 and week 24. The secondary outcomes include major adverse cardiovascular event (MACE, a composite of all-cause death, myocardial infarction, stroke, and unplanned revascularization) and angina recurrence. The safety outcomes include hypotension occurrence, withdrawal of renin angiotensin aldosterone system inhibitors, serious adverse events, and other concerned adverse events within 24 weeks. This pilot trial will compare the preliminary effects of nicorandil, diltiazem, and isosorbide mononitrate on angiographic and clinical outcomes in patients who have undergone RA-CABG. Recruitment began in June 2020, and the estimated primary completion date is early 2023. Results of this study will provide much needed information for design of large confirmatory trials on the effectiveness of oral antispastic medications after RA-CABG.


A qualitative study of men's behavioural changes during weight loss maintenance.
This study aims to understand the behaviour changes men who attended a weight loss programme engage in during weight maintenance. Understanding the needs of men in the context of weight loss maintenance is important, as they are underrepresented in this body of literature. Given its focus on personal experience, this study adopted a qualitative design. Semi-structured interviews supported by participant-generated photo-elicitation techniques to explore the behavioural changes 12 men engaged in 6 months after attending a men-only weight loss programme. Data analysis was undertaken through thematic analysis and Gleeson's polytextual thematic analysis. This study suggests that the key behaviours men engaged in to maintain weight loss can be classified into four categories: (1) 'Small' changes, (2) Informed decisions, (3) Monitoring of behaviours, and (4) Dealing with ambivalence. This study makes an original contribution to knowledge and can have important implications for practice in the area of men's health, particularly with regard to the long-term impact of weight loss interventions.


Substance P: a carotid body peptide.
Immunofluorescent studies have shown that substance P or substance P-like material is present in the cat carotid body, being located in some of the glomus cells and also in nerve axons. About 20% of the glomus cells were substance P positive. Substance P may be stored in glomus cells containing monoamine(s), but further studies are needed to investigate this aspect and also to determine what role, if any, substance P plays in the process of chemoreception.


Proteolytic analysis of Trichoderma reesei in celluase-inducing condition reveals a role for trichodermapepsin (TrAsP) in cellulase production.
Filamentous fungi produce a variety of proteases with significant biotechnological potential and show diverse substrate specificities. Proteolytic analysis of the industrial enzyme producer Trichoderma reesei has been sparse. Therefore, we determined the substrate specificity of T. reesei secretome and its main protease Trichodermapepsin (TrAsP) up to P1 position using FRETS-25Xaa-libraries. The role of TrAsP was analyzed using T. reesei QM9414 and the deletant QM∆trasp in Avicel. We observed higher activities of CMCase, Avicelase, and Xylanase in QM∆trasp compared to that of QM9414. Saccharification rate of cellulosic biomass also increased when using secretome of QM∆trasp but the effect was not significant due to the absence of difference in BGL activity compared to QM9414. Higher TrAsP was produced when monosaccharides were used as a carbon source compared to cellulase inducers such as Avicel and α-sophorose. These results elucidate the relationship between TrAsP and cellulase production in T. reesei and suggest a physiological role for TrAsP.


The Genetics of Multiple Sclerosis: From 0 to 200 in 50 Years.
Multiple sclerosis (MS) is a common autoimmune disease that targets myelin in the central nervous system (CNS). Multiple genome-wide association studies (GWAS) over the past 10 years have uncovered more than 200 loci that independently contribute to disease pathogenesis. As with many other complex diseases, risk of developing MS is driven by multiple common variants whose biological effects are not immediately clear. Here, we present a historical perspective on the progress made in MS genetics and discuss current work geared towards creating a more complete model that accurately represents the genetic landscape of MS susceptibility. Such a model necessarily includes a better understanding of the individual contributions of each common variant to the cellular phenotypes, and interactions with other genes and with the environment. Future genetic studies in MS will likely focus on the role of rare variants and endophenotypes.


Pyoderma gangrenosum with necrotizing sclerokeratitis after cataract surgery.
A 78-year-old man who had had uneventful extracapsular cataract extraction in the left eye 3 months earlier developed pyoderma gangrenosum (PG)-associated peripheral ulcerative keratitis (PUK) after suture removal. The patient had a 13-year history of PG associated with monoclonal immunoglobulin-A gammopathy. He presented with extensive, painful PUK at the incision site, with a descemetocele and a high risk for perforation. Fibrin glue tissue adhesive was used to stabilize the corneal ulcer as an adjunct to topical and systemic treatment. The patient had been treated with tapering doses of prednisone and cyclophosphamide (50 mg/day). High-dose human intravenous immunoglobulin (0.4 mg/kg/d for 4 days) was administered. The ulcer healed 1 month later with a loss of visual acuity. To our knowledge, this is the first reported case of PG-associated sclerokeratitis following cataract surgery. Early recognition of this rare ocular localization of PG is important to institute the appropriate therapy.


TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations.
TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90-100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.


Rational design of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors: predicting enzyme conformational change and metabolism.
From metabolic considerations and prediction of an inhibitor-induced conformational change, novel adenosine deaminase (ADA) inhibitors with improved activities and oral bioavailability have been developed on the basis of our originally designed non-nucleoside ADA inhibitors. They demonstrated in vivo efficacy in models of inflammation and lymphoma. Furthermore, X-ray crystal structure analysis has revealed a novel induced fit to ADA.


Recombination reaction of rhodopsin in situ studied by photoconversion of "indicator yellow".
We measured the kinetics of recombination of 11-cis-retinal with opsin in intact frog rod outer segment (ROS). The rhodopsin in ROS was bleached and allowed to decay to "indicator yellow," a photoproduct where all-trans-retinal is partly free, and partly bound to non-specific amino groups of disk membranes. By briefly illuminating the "indicator yellow" by an intense 465 or 380-nm flash, we then photoconverted all-trans-retinal to (mostly) the 11-cis- form thus introducing into ROS a certain amount of cis-chromophore. The recombination of cis-retinal with opsin and the formation of rhodopsin were followed by fast single-cell microspectrophotometry. Regeneration proceeded with a time constant of approximately 3.5 min; up to 27% of bleached visual pigment was restored. The regenerated pigment consisted of 91% rhodopsin (11-cis-chromophore) and 9% of presumably isorhodopsin (9-cis-chromophore). The recombination of 11-cis-retinal with opsin inside the ROS proceeds substantially faster than rhodopsin regeneration in the intact eye and, hence, is not the rate-limiting step in the visual cycle.


Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation of the MAK16 gene and analysis of an adjacent gene essential for growth at low temperatures.
MAK16 is an essential gene on chromosome I defined by the thermosensitive lethal mak16-1 mutation. MAK16 is also necessary for M double-stranded RNA replication at the permissive temperature for cell growth. As part of an effort to clone all the DNA from chromosome I, plasmids that complemented both the temperature-sensitive growth defect, and the M1 replication defects of mak16-1 strains were isolated from a plasmid YCp50: Saccharomyces cerevisiae recombinant DNA library. The two plasmids analysed contained overlapping inserts that hybridized proportionally to strains carrying different dosages of chromosome I. Furthermore, integration of a fragment of one of these clones occurred at a site linked to ade 1, confirming that this clone was derived from the appropriate region of chromosome I. An open reading frame adjacent to MAK16 potentially coding for a 468 amino acid protein was defined by sequence analysis. 185 amino acids of this open reading frame were replaced with a 1.2 kb fragment carrying the S. cerevisiae URA3 gene by a one-step gene disruption. The resulting strains grew at a rate indistinguishable from the wild type at 20 degrees C, 30 degrees C, or 37 degrees C, but could not grow at 8 degrees C. The deleted region is thus essential only at 8 degrees C, and we name this gene LTE1 (low temperature essential).


A robotic assistant for stereotactic neurosurgery on small animals.
This work presents the development and performance analysis of a robotic system for stereotactic neurosurgery on small animals. The system is dedicated to the precise placement of probes in the small animal brain, thus providing an improved framework for brain research. Based on an analysis of small animal stereotaxy, the mechanical design of the robotic system is presented. Details of the structure and mechanical components and a kinematic description are outlined. The calibration process of the system for arbitrary probes is described. To analyse the mechanical positioning accuracy of the system, a testbed is presented. Positioning performance results show that the system features a mean mechanical positioning accuracy of 32 microm and a mean positioning repeatability of 11 microm. The system meets the requirements of targeting small functional areas within the brain of small animals and thus offers a new tool for small animal brain research.


Myocardial hypertrophy of the left ventricle during familial arterial hypertension.
In patients with familial arterial hypertension and their relatives preclinical signs of myocardial hypertrophy were observed before the formation of stably increased blood pressure. We evaluated echocardiographic sings of left ventricular myocardial hypertrophy in normotensive relatives of patients with arterial hypertension.


The Ethiopian telecom industry: gaps and recommendations towards meaningful connectivity and a thriving digital ecosystem.
Ethiopia, the second-most populous country in Africa with 110 million inhabitants, has one of the oldest public telecommunication operators established in 1894. Despite its age, Ethiopian telecommunication remains one of the least developed in the world. According to ITU, in 2019, mobile-cellular subscription (per 100 people) was 39 % and 20 % Internet penetration. As of June 2018, the international transmission speed per Internet user was two kbits/s. Different studies widely acknowledge that no modern economy can be developed short of telecommunication services. It is no wonder that Ethiopia is depicted as one of the weakest economies in the world. This paper identifies the causes for extraordinarily poor telecommunications service in Ethiopia and offers recommendations for near-term improvement. The approach considered includes existing work surveys and document examination, and to this end, the work has relied primarily on secondary data sources. Inexperienced and ineffectual regulatory oversight, absence of facilities-based competition, inadequate interconnection with the neighboring nation's networks, and inability to localize outbound traffics are identified as factors affecting the Ethiopian telecom industry performance. Full liberalization with an effective regulatory body and hosting a sizeable Internet Exchange Points (IXPs) are recommended for better connectivity and a thriving digital ecosystem in Ethiopia.


Botulinum toxin versus pneumatic dilatation in the treatment of achalasia: a randomised trial.
Intrasphincteric injection of botulinum toxin is a new treatment option for achalasia. To compare the immediate and long term efficacy of botulinum toxin with that of pneumatic dilatation. Symptomatic patients with achalasia were randomised to botulinum toxin (22 patients, median age 57 years) or pneumatic dilatation (20 patients, median age 56 years). Symptom scores were assessed initially, and at one, three, six, nine, and 12 months after treatment. Objective assessment included oesophageal manometry initially and at one month, and barium oesophagram initially and at one, six, and 12 months post-treatment. Pneumatic dilatation resulted in a significantly (p=0.02) higher cumulative remission rate. At 12 months, 14/20 (70%) pneumatic dilatation and 7/22 (32%) botulinum toxin treated patients were in symptomatic remission (p=0.017). Failure rates were similar initially, but failure over time was significantly (p=0.01) higher after botulinum toxin (50%) than pneumatic dilatation (7%). Pneumatic dilatation resulted in significant (p<0.001) reduction in symptom scores, and lower oesophageal sphincter pressure, oesophageal barium column height, and oesophageal diameter. Botulinum toxin produced significant reduction in symptom scores (p<0.001), but no reduction in objective parameters. At one year pneumatic dilatation is more effective than botulinum toxin. Symptom improvement parallels objective oesophageal measurements after pneumatic dilatation but not after botulinum toxin treatment for achalasia.


Intrapartum fetal pulse oximetry in the presence of fetal cardiac arrhythmia.
We report our experience with a reflectance pulse oximeter in intrapartum monitoring of a fetus with atrial flutter and heart block. During labor fetal arterial oxygen saturation ranged between 50% and 85%. Spontaneous vaginal delivery occurred with good maternal and neonatal outcome.


Analysis of urinary tract infections in patients undergoing prostatectomy.
Analysis is presented of 260 patients on whom in the years 1974--1976 an operation for adenoma removal was performed. 115 patients (44.2%) had a permanently placed catheter or were repeatedly catheterized before operation, and 145 (55.8%) were able to urinate without any need for catheterization. In the group of preoperatively catheterized patients infection of the urinary system was demonstrated in 84 cases, which amounts to 75%. Among patients not catheterized before operation, infection already existed in 29 cases (20%). Operation by Millin's method was carried out in 181 patients; non-infected urine was postoperatively found in 40 cases, which amounts to 22.3%. 79 patients were operated on by the transvesical method; in this group non-infected urine was found in four cases, i.e. 5.1%. Calculated x2 indicated a significant connection between the investigated items, consisting in a much more frequent occurrence of urinary system infection in patients operated on by the transvesical method. The duration of catheter reposition in the urinary bladder after prostatectomy considerably influences the number of postoperative infections of the urinary system.


Systemic treatment with pulsed electromagnetic fields do not affect bone microarchitecture in osteoporotic rats.
Pulsed electromagnetic fields (PEMF) are currently used in the treatment of spinal fusions and non-unions. There are indications that PEMF might also be effective in the treatment of osteoporosis. In this study we examined whether whole-body PEMF treatment affects the bone microarchitecture in an osteoporotic rat model. Twenty-week-old female rats were ovariectomised (n=20). Four different PEMF treatment protocols based on previous experimental studies and based on clinically used PEMF signals were examined (2 h/day, 5 days/week). A control group did not receive PEMF. At zero, three and six weeks cancellous and cortical bone architectural changes at the proximal tibia were evaluated using in vivo microCT scanning. PEMF treatment did not induce any changes in cancellous or cortical bone compared to untreated controls. Although previous studies have shown strong effects of PEMF in osteoporosis we were unable to demonstrate this in any of the treatment protocols. Using in vivo microCT scanning we were able to identify small bone changes in time. Subtle differences in the experimental set-up might explain the differences in study outcomes in the literature. Since PEMF treatment is safe, future experimental studies on the effect of PEMF on bone can better be performed directly on humans, eliminating the potential translation issues between animals and humans. In this study we found no support for the use of PEMF in the treatment of osteoporosis.


Levels of selected metals in ambient air PM10 in an urban site of Zaragoza (Spain).
An assessment of the air quality of Zaragoza (Spain) was performed by determining the trace element content in airborne PM10 in a sampling campaign from July 2001 to July 2002. Samples were collected in a heavy traffic area with a high volume air sampler provided with a PM10 cutoff inlet. The levels of 16 elements (Al, Ba, Ca, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, Sr, V, and Zn) were quantified after collecting the PM10 on Teflon-coated glass fiber filters (GFF). Regarding the PM10, 32% exceedance of the proposed PM10 daily limit was obtained, some of them corresponding to summer and autumn periods. The limit values of toxic trace elements from US-EPA, WHO, and EC were not exceeded, considering Zaragoza as a moderately polluted city under the current air quality guidelines. The contribution of anthropogenic sources to atmospheric elemental levels was reflected by the high values of enrichment factors for Zn, Pb, and Cu compared to the average crustal composition. Statistical analyses also determined the contribution of different sources to the PM10, finding that vehicle traffic and anthropogenic emissions related to combustion and industrial processes were the main pollutant sources as well as natural sources associated with transport of dust from Africa for specific dates. Regarding the influence of meteorological conditions on PM10 and trace elements concentrations, it was found that calm weather conditions with low wind speed favor the PM10 collection and the pollution for trace elements, suggesting the influence of local sources.


Lectin binding patterns of alveolar epithelium and subepithelial seromucous glands of the bronchi in sepsis and controls--an approach to characterize the non-specific immunological response of the human lung to sepsis.
A delayed or deficient immunological protection as well as an overstimulation of the mucosal immune system may act as possible additional promoters of sepsis-induced lung injury in patients suffering from a severe septic condition. Lectin-binding patterns in pulmonary tissue samples obtained at autopsy from septic patients and control individuals were studied using 11 carbohydrate-specific lectins (Con A, UEA, GSA I, GSA II, MPA, PNA, Jac, WGA, MAA, LPA, and SNA). There were no differences in the secretory product of serous parts of bronchial glands detectable in the two study groups, whereas lectin binding patterns of alveolar epithelium and mucous parts of subepithelial seromucous glands were different in sepsis cases when compared to controls. Apart from differences in binding sites for alpha-mannose, N-acetyl-neuraminic acid and alpha-(2-6)-galactose (as detected by different expression for Con A, MAA and SNA) in the two study groups, the main finding was that no binding sites for alpha-N-acetyl-galactosamine (as investigated by MPA immunoreactivity) could be detected on alveolar epithelial cells and mucous parts of subepithelial seromucous glands in sepsis cases in contrast to the presence of such binding sites in the control cases. We hypothesize that the finding of an altered secretory product of alveolar epithelial cells and bronchial glands in sepsis may be a result of specific carbohydrate deprivation or consumption, respectively, possibly due to direct bacterial effects or pathogenetic events in response to bacterial toxins during the complex cascade of the host's systemic inflammatory response in sepsis. The altered type of mucus glycoprotein physiologically secreted by alveolar epithelium and mucous parts of subepithelial seromucous glands of the bronchi with subsequent loss of a considerable proportion of protection of the mucosal barrier in sepsis may play an important additional role in the development of sepsis-induced lung injury.


[Formation of a heterotopic hemopoiesis focus from the administration of a cryptococcal heteropolysaccharide to bone marrow donors and recipients].
The effect of Cryptococcus luteolus (strain 228) heteropolysaccharide on heterotopic bone marrow organ formation was studied. Heteropolysaccharide (Hp) injections were initiated on the next day after bone marrow transplantation and were performed weekly for 30 days. This resulted in the increase in both the cellularity and the weight of the ossicle. The injections performed twice weekly produced the decrease of cellularity while ossicle weight did not change. Higher dose of Hp produced no changes in heterotopic bone marrow organ. Hp injections to donor mice did not result in any changes in heterotopic organ in bone marrow recipients. Thus, this kind of Hp was capable both of stimulating and inhibiting heterotopic bone marrow organ formation in relation to the dose and scheme of administration.


Glycation of plasma lipoprotein lipid membrane and screening for lipid glycation inhibitor.
We recently reported that phosphatidylethanolamine (PE)-linked Amadori product (Amadori-PE) increased abnormally in diabetic plasma. However, the glycation mechanism of human plasma low-density lipoprotein (LDL) is still unclear. Moreover, lipid glycation inhibitors have yet to be discovered. In this study, we compared the glycation kinetics of LDL lipid and LDL protein in vitro and screened lipid glycation inhibitors. LDL-PE was converted to Amadori-PE followed by LDL protein (apoB) glycation. Pyridoxal 5'-phosphate could easily react with PE before the glucose-PE reaction, and the PE-pyridoxal 5'-phosphate adduct was detected in human red blood cells. Pyridoxal 5'-phosphate can be used in diabetes prevention.


The dermaseptin superfamily: a gene-based combinatorial library of antimicrobial peptides.
Skin secretions of hylid frogs show amazing levels of interspecific and intraspecific diversity and are comprised of a cocktail of genetically-related, but markedly diverse antimicrobial peptides that are grouped into a superfamily, termed the dermaseptins, comprising several families: dermaseptins (sensu stricto), phylloseptins, plasticins, dermatoxins, phylloxins, hyposins, caerins, and aureins. Dermaseptin gene superfamily evolution is characterized by repeated gene duplications and focal hypermutations of the mature peptide coding sequence, followed by positive (diversifying) selection. We review here molecular mechanisms leading to these vast combinatorial peptide libraries, and structural and functional properties of antimicrobial peptides of the dermaseptin and plasticin families, as well as those of dermaseptin S9, an amyloidogenic peptide with antimicrobial and chemoattractant activities.


Antibiotic Stewardship in Urology.
An increase in antibiotic resistance and a decrease in the production of new antimicrobials have created a difficult problem for our health care system. We review issues associated with antibiotic stewardship, which refers to organized processes aimed at measuring and optimizing the use of antimicrobials to decrease toxicity and resistance and improve outcomes. Urologists are in a unique position to implement these programs given that the genitourinary tract is a common source of infection. In this article we discuss particularly relevant infectious problems in urology and highlight the need for antibiotic stewardship in our field.


A tale of two methods: combining near-infrared spectroscopy with MRI for studies of brain oxygenation and metabolism.
Combining magnetic resonance imaging (MRI) with near-infrared spectroscopy (NIRS) leads to excellent synergies which can improve the interpretation of either method and can provide novel data with respect to measuring brain oxygenation and metabolism. MRI has good spatial resolution, can detect a range of physiological parameters and is sensitive to changes in deoxyhemoglobin content. NIRS has lower spatial resolution, but can detect, and with specific technologies, quantify, deoxyhemoglobin, oxyhemoglobin, total hemoglobin and cytochrome oxidase. This paper reviews the application of both methods, as a multimodal technology, for assessing changes in brain oxygenation that may occur with changes in functional activation state or metabolic rate. Examples of hypoxia and ischemia are shown. Data support the concept of reduced metabolic rate resulting from hypoxia/ischemia and that metabolic rate in brain is not close to oxygen limitation during normoxia. We show that multimodal MRI and NIRS can provide novel information for studies of brain metabolism.


Acrylamide-induced damage to postsynaptic plasticity is CYP2E1 dependent in an SH-SY5Y co-culture system.
Acrylamide (ACR), a neurotoxic substance, is characterized by a range of industrial and population exposures. The effects of ACR on synapses have been examined, but the regulation and molecular mechanism of key proteins related to ACR and its metabolite glycidamide (GA) have not been elucidated. In this study, we constructed two co-culture systems to mimic neurons that do not express and overexpress CYP2E1. In these co-cultures, we observed the effects and relative influence of ACR and GA on cell survival as well as synaptic structural and functional plasticity. Next, we investigated the relationship between ACR-induced nerve damage and key proteins in the postsynaptic membrane. After ACR exposure, cell death and synaptic damage were significantly worse in CYP2E1-overexpressing co-culture systems, suggesting that ACR-induced neurotoxicity may be related to metabolic efficiency (including CYP2E1 activity). Moreover, with increasing doses of ACR, the key postsynaptic membrane proteins PSD-95 expression was reduced and CaMKII and NMDAR-2B phosphorylation was increased. ACR exposure also triggered a rapid dose- and time-dependent increase in intracellular Ca2+, whose changes can affect the expression of the above-mentioned key proteins. In summary, we clarified the relationship between ACR exposure, neuronal damage and postsynaptic plasticity and proposed an ACR-CYP2E1-GA: Ca2+-PSD-95-NMDAR-Ca2+-CaMKII effect chain. This information will further improve the development of an alternative pathway strategy for investigating the risk posed by ACR.


Electron count and electronic structure of bare icosahedral Au32 and Au33 ionic nanoclusters and ligated derivatives. Stable models with intermediate superatomic shell fillings.
DFT calculations were carried out on bare Au32 and Au33 nanoclusters with various charges, in order to analyze their stability with respect to different cluster electron numbers. Results indicate that in addition to the neutral Au32 hollow species, significant HOMO-LUMO gaps are computed for [Au32]8+ (hollow) and [Au32]4+ (two-shell structure). Species with smaller HOMO-LUMO gaps can reach stability upon "passivation" by a ligand shell, as experimentally exemplified. Icosahedral frameworks of Ih or lower symmetry are favored for the cationic nanoclusters whereas different structures are computed for the anionic ones.


Resveratrol treatment modulates several antioxidant and anti-inflammatory genes expression and ameliorated oxidative stress mediated fibrosis in the kidneys of high-fat diet-fed rats.
Resveratrol is a polyphenolic compound that possesses strong antioxidant and anti-inflammatory activities. This study evaluated the effects of resveratrol on oxidative stress, fibrosis and multiple genes regulation in the kidneys of high fat (HF) diet-fed rats. Wistar rats were fed with HF diet for eight weeks. These rats were also treated with resveratrol for eight weeks. Finally, kidney tissue samples were isolated from all sacrificed rats. The histological changes, creatinine and uric acid levels, oxidative stress parameters such as malondialdehyde (MDA), nitric oxide, and advanced oxidation protein product (AOPP) levels were analyzed. The antioxidant enzymes such as catalase, superoxide dismutase (SOD) activities and reduced glutathione (GSH) levels; gene expression of inflammatory and fibrosis-related genes namely, inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), transforming growth factor beta1 (TGF-β1), and collagen-1 were assessed. Moreover, gene expression of oxidative stress-related genes such as nuclear factor erythroid 2-related factor 2 (Nrf-2), SOD, catalase, and glutathione reductase, were also assessed. HF diet-fed rats showed increased creatinine and uric acid levels in plasma which were lowered by resveratrol treatment. The study findings also revealed that resveratrol counterbalanced the oxidative stress and prevented the expression of the inflammatory genes; restored the catalase and SOD activities followed by the up-regulation of antioxidant genes expression in the kidneys of HF diet-fed rats. HF diet caused the Nrf-2 down-regulation followed by the decreased expression of HO-1 and HO-2 genes, which was restored by resveratrol treatment. Moreover, the histological assessment showed lipotoxicity and increased fibrosis in the kidneys of HF diet-fed rats. Resveratrol prevented the kidney fibrosis probably by limiting oxidative stress, inflammation, and down-regulating TGF-β1 mediated signaling pathway. In conclusion, resveratrol treatment showed beneficial effects in preventing oxidative stress and fibrosis in the kidneys of HF diet-fed rats probably by modulating the gene expression of oxidative stress and inflammation related factors and enzymes.


High-dose chemotherapy with autologous marrow transplantation for malignant melanoma. Case reports and literature review.
Present-day therapy for disseminated malignant melanoma is unsatisfactory; chemotherapy offers a small fraction of patients a short-lived palliative effect. Evidence exists to suggest more responses to chemotherapy could occur if dosages of chemotherapeutic agents were increased. The dosages of many chemotherapeutic agents used for melanoma are limited by myelotoxicity of the drugs. Autologous bone marrow transplantation offers a means to escalate chemotherapeutic dosages by shortening the period of life-threatening marrow toxicity to a survivable length of time. A review of 103 cases of melanoma treated with high-dose chemotherapy and autologous marrow rescue plus two cases reported here revealed that 48% of patients responded to therapy and 34% of those were complete responses. The exact role this technic will play in management of disseminated malignant melanoma requires further study.


Illness perceptions are associated with higher health care use in survivors of endometrial cancer-a study from the population-based PROFILES registry.
According to the Common Sense Model of self-regulation, cancer survivors construct perceptions of their illness as a (mal)adaptive mechanism. These perceptions might impact on health care use. We aimed to explore the association between illness perceptions and health care use in stage I-II endometrial cancer (EC) survivors, and whether these associations differed by time since diagnosis. A survey was conducted in 2008 by the population-based PROFILES registry among EC survivors diagnosed between 1999 and 2007. Survivors (n = 742, 77% response) completed the Brief Illness Perception Questionnaire (BIPQ) and questions on health care use in the past 12 months. Clinical data were accessed from the Netherlands Cancer Registry. Multiple logistic regression was used to evaluate the relationship between illness perceptions and health care use. Between 15 and 22% of the survivors had negative illness perceptions. Survivors with more negative perceptions on consequences, timeline, treatment control, identity, cognitive representation, concern, emotion, and emotional representation were more likely to make ≥ 1 visit to their family physician/general practitioner in relation to their cancer when compared with survivors with more positive illness perceptions. More negative perceptions on consequences, timeline, identity, and concern were associated with ≥ 2 general or cancer-related visits to the medical specialists. The association between negative illness perceptions and health care use was more prominent among long-term (>5 years post-diagnosis) EC survivors. Negative illness perceptions among EC survivors were associated with higher health care use. For individuals with maladaptive illness perceptions, visits to their health care provider may reduce worry about their illness. Future research might address the effects of intervening in maladaptive illness perceptions on use of health care in this category of survivors.


The R7 subfamily of RGS proteins assists tachyphylaxis and acute tolerance at mu-opioid receptors.
Members of the R7 subfamily of regulators of G-protein signaling (RGS) proteins (RGS6, RGS7, RGS9-2, and RGS11) are found in the mouse CNS. The expression of these proteins was effectively reduced in different neural structures by blocking their mRNA with antisense oligodeoxynucleotides (ODNs). This was achieved without noticeable changes in the binding characteristics of labeled beta-endorphin to opioid receptors. Knockdown of R7 proteins enhanced the potency of antinociception promoted by morphine and [D-Ala(2), N-MePhe(4), Gly-ol(5)]-enkephalin (DAMGO)-both agonists at mu-opioid receptors. The duration of morphine analgesia was greatly increased in RGS9-2 and in RGS11 knockdown mice. The impairment of R7 proteins brought about different changes in the analgesic activity of selective delta agonists. Knockdown of RGS11 reduced [D-Ala(2)]deltorphin II analgesic effects. Those of RGS6 and RGS9-2 proteins caused [D-Ala(2)]deltorphin II to produce a smoothened time-course curve-the peak effect blunted and analgesia extended during the declining phase. RGS9-2 impairment also promoted a similar pattern of change for [D-Pen(2,5)]-enkephalin (DPDPE). RGS7-deficient mice showed an increased response to both [D-Ala(2)]deltorphin II and DPDPE analgesic effects. A single intracerebroventricular (i.c.v.) ED(80) analgesic dose of morphine gave rise to acute tolerance in control mice, but did not promote tolerance in RGS6, RGS7, RGS9-2, or RGS11 knockdown animals. Thus, R7 proteins play a critical role in agonist tachyphylaxis and acute tolerance at mu-opioid receptors, and show differences in their modulation of delta-opioid receptors.


Mutants of the two-component regulatory protein FixJ of Rhizobium meliloti that have increased activity at the nifA promoter.
FixL and FixJ belong to a two-component regulatory system in Rhizobium meliloti that induces the expression of numerous nitrogen-fixation genes during symbiosis with alfalfa. FixJ is a positive activator required for transcription of the regulatory genes nifA and fixK, while FixL is an oxygen-binding hemoprotein capable of regulating the phosphorylation status of both itself and FixJ, in response to oxygen availability. In this study, we isolated four FixJ mutants that display increased activity at the nifA promoter (PnifA) in Escherichia coli. All four mutants possess amino acid changes in a domain of FixJ that is conserved in other response regulator proteins, and all exhibit increased activity at PnifA in R. meliloti that is dependent on the presence of FixL. One of the mutant proteins, while less efficient at accepting phosphate from a truncated derivative of FixL (FixL*), nevertheless has a phosphorylated form that is more stable than the phosphorylated form of wild-type (wt) FixJ and is more resistant to the phosphatase activity of FixL*. The wt FixJ-phosphate was found to have a half-life of approximately 4 h, which makes it an unusually long-lived response regulator protein. The exceptional stability of wt FixJ-phosphate and the altered phosphorylation properties observed for the mutant are discussed in relation to signal transduction in the FixLJ system.


[Treatment of unstable pelvic girdle fractures with Wagner external fixation].
Two cases of unstable pelvic ring fractures were stabilized by external fixation with a Wagner apparatus. This enabled a pain-free mobilization treatment to be started immediately afterwards, and, already 6 weeks later, a painless mobilization with a walking frame was achieved.


[Comparative sensitivity of surviving sections of hippocampus to corticosteroids and angiotensin II].
Sensitivity of CA3 field neurones to hydrocortisone hemisuccinate, sodium dexamethasone-21-phosphate and angiotensin II was studied in experiments on surviving sections of the mouse hippocampus. High sensitivity of the neurones of surviving sections of the hippocampus to the steroid hormones (hydrocortisone and dexamethasone) and virtually complete absence of responses to angiotensin II were demonstrated.


Effect of moisture and nitrogen levels on the decomposition of wheat straw in soil.
Two per cent of wheat straw was mixed with samples of a slightly degraded chernozem soil, and its decomposition was studied at 10, 20, and 30 per cent moisture content of the soil with the addition of 160, 240, and 400 ppm of NH4 + -N. The overall decomposition, measured as CO2 production, and total carbon loss from the soil at 28 degrees C was enhanced by the added nitrogen at all levels of moisture in proportion to the quantity added. Maximum mineralization of the straw carbon was observed at 30 per cent moisture content but there was no significant difference between the amount of carbon mineralized at 20 and 30 per cent moisture levels. No stabilization of the substrate took place in the soil except at 240 and 400 ppm of applied nitrogen at 30 per cent moisture level towards the end of the incubation period. More straw carbon was mineralized when the soil samples were subjected to daily measurements of CO2 evolved than when CO2 measurements were made at intervals over the same period of incubation.


Mucin-producing carcinoid ("composite tumor") of upper third of esophagus: a variant of carcinoid tumor.
An unusual upper esophageal polypoid tumor was found to be predominantly a carcinoid tumor and in part a mucin-producing adenocarcinoma. A review of literature showed this to be a unique tumor in this location.


Partially failing ALT flap salvaged using its own distal run-off vessel.
This case report presents salvage of a partially failing anterolateral thigh flap. A 37-year-old male, a victim of head and neck squamous cell carcinoma, received tumor ablation and a chimeric anterolateral thigh skin and vastus lateralis muscle flap reconstruction. Before ligation of pedicle, both skin and muscle portions had robust blood supply; however, only the vastus lateralis muscular component remained revascularized rather than the skin paddle with some underlying muscle 30 minutes after patent microanastomosis with recipient vessel. The skin paddle flap was then salvaged by perfusion from a new anastomosis between the distal run-off of the pedicle artery and the perforator artery of this skin flap. From this experience, we recommend to preserve longer distal run-off of the pedicle in chimeric anterolateral thigh flap harvest for necessary "self-revascularization" in similar cases.


Ultra-long metal nanowire arrays on solid substrate with strong bonding.
Ultra-long metal nanowire arrays with large circular area up to 25 mm in diameter were obtained by direct electrodeposition on metalized Si and glass substrates via a template-based method. Nanowires with uniform length up to 30 μm were obtained. Combining this deposition process with lithography technology, micrometre-sized patterned metal nanowire array pads were successfully fabricated on a glass substrate. Good adhesion between the patterned nanowire array pads and the substrate was confirmed using scanning acoustic microscopy characterization. A pull-off tensile test showed strong bonding between the nanowires and the substrate. Conducting atomic force microscopy (C-AFM) measurements showed that approximately 95% of the nanowires were electrically connected with the substrate, demonstrating its viability to use as high-density interconnect.


prevalence and causes of blindness and low vision revisited after 5 years of eye care in Timor-Leste.
To estimate the 2010 prevalence and causes of blindness and low vision among Timor-Leste adults aged ≥40 years, and compare these to the results of a survey conducted 5 years previously. A population-based cross-sectional survey used multistage cluster random sampling proportionate to size to identify 50 clusters of 45 people each. Cause of vision loss was determined for each eye with presenting visual acuity worse than 6/18. A participation rate of 89.5% (n = 2014) was achieved. The gender-age-domicile adjusted prevalence was 7.7% (95% confidence interval [CI] 6.5, 8.8) for 6/60, and 3.6% (95% CI 2.7, 4.4) for 3/60 blindness (better eye presenting vision worse than 6/60 and 3/60, respectively) among Timorese aged ≥40 years. Cataract caused most blindness (69.3% at 6/60). The population prevalence of low vision (better eye presenting vision of 6/60 or better, but worse than 6/18) was 13.6% (95%CI 12.1, 15.1), most caused by uncorrected refractive error (57.4%) or cataract (39.5%). The prevalence and causes of blindness were unchanged compared with 5 years earlier, but low vision was less common. Unusually for a developing country, Timor-Leste has initiated a cycle of evidence-based eye care in which, although with limitations, population data are periodically available for monitoring and planning.


The role of leaf resin in the interaction between Eriodictyon californicum (Hydrophyllaceae) and its herbivore, Trirhabda diducta (Chrysomelidae).
The chaparral shrub Eriodictyon californicum secretes a phenolic leaf resin composed of flavonoid aglycones. We used leaves with artificially altered resin contents to test the effects of resin on the feeding, growth, and oviposition of the specialist herbivore Trirhabda diducta. In addition, we compared Trirhabda feeding and growth on young foliage with that on foliage from the preceding year. Our results show that the Eriodictyon leaf resin affects Trirhabda larvae and adults similarly, having no significant effect on growth rates or on nutrient utilization at up to 5X the resin levels normally encountered by larvae in the field. Both Trirhabda larvae and adults respond to high resin concentrations by increasing their consumption rates, with concomitant decreases in digestibility and the efficiency of conversion of ingested food to biomass. Low-resin foliage is preferred by larvae for feeding and by adults for oviposition. Larvae feeding on leaves of the current season have higher growth efficiencies, consumption, and growth compared to larvae feeding on leaves from the preceding year.


Electron microscopy of secondary structure in partially denatured precursor and mature Escherichia coli 16 S and 23 S rRNA.
The secondary structure of 16 S and 23 s rRNA sequences in 30 S preribosomal RNA of Escherichia coli was analyzed by electron microscopy after partial denaturation and compared to mature 16 S and 23 S rRNA examined under the same conditions. The sequences in the pre-rRNA notably lack the specific loops that dominate the 5'-terminal regions of mature 16 S and 23 S rRNA. In other respects, the sizes and locations of loops in the 23 S rRNA sequence are qualitatively very similar in mature and pre-rRNA. Eleven of 12 loops outside of the 5'-terminal domain correspond, with the most frequent features in the 3'-half of the molecule. In contrast, the sizes and locations of loops in the 16 S rRNA sequence differ between precursor and mature forms. In the pre-rRNA, instead of the 370-nucleotide 5'-terminal loop of mature rRNA, some 1000-nucleotide terminal loops are observed. The pre-rRNA also shows a frequent 610-nucleotide central loop and a large 1240-nucleotide loop not seen in the mature rRNA. Also, in the 3'-region of the sequence, the largest loops in pre-rRNA are 120 nucleotides shorter than in mature rRNA. We suggest that the structure of pre-rRNA may promote some alternate conformational features, and that these could be important during ribosome formation or function.


Neuroprotection of Intermedin Against Cerebral Ischemia/Reperfusion Injury Through Cerebral Microcirculation Improvement and Apoptosis Inhibition.
Ischemic stroke is the primary cause of disability and mortality worldwide. Ischemia/reperfusion (I/R)-induced microcirculatory dysfunction and organ injury generally occur after ischemic stroke. Several studies have shown that intermedin (IMD) has a regulating function on cerebral microcirculation and blood-brain barrier via relaxing cerebral vessels and improving the local blood supply after cerebral ischemia. However, a unified conclusion has not been reached, and the underlying mechanism remains unclear. To observe and analyze the changes of cerebral microcirculation perfusion of cerebral IRI by IMD post-treatment in the rats and further explore the mechanism underlying the beneficial effect of IMD on cerebral IRI. Thirty-nine rats were divided into three groups: sham, I/R, and I/R + IMD groups. After IMD ischemia post-treatment, the rat cerebral infarction rate and the degree of neurological deficit were evaluated by TTC staining and neurological function score; the changes in the amount of cerebral microcirculation implantation on the injured side of the rats were observed by laser Doppler; the pathological changes and cell ultrastructure of rat cortex and hippocampus were observed by HE staining and transmission electron microscopy; the neuron apoptosis in the rat cortex and hippocampus was detected by TUNEL staining and immunohistochemical staining. Impaired neurological function, abnormal cortical/hippocampal neuron morphology, and the proportion of cerebral infarction were significantly improved in the IMD group compared with the I/R group, which suggested a possible neuroprotective role of IMD. IMD treatment also increased the average perfusion of cerebral surface microcirculation in rats by astonished 42.7 times. Finally, IMD administration decreased the caspase-3- and Bax-positive cell numbers and apoptotic cell ratio. IMD has a significant protective effect on neuronal damage caused by cerebral I/R in rats by improving cerebral microcirculation and inhibiting apoptosis.


Parkinson's disease and the Stroop color word test: processing speed and interference algorithms.
Processing speed alters the traditional Stroop calculations of interference. Consequently, alternative algorithms for calculating Stroop interference have been introduced to control for processing speed, and have done so in a multiple sclerosis sample. This study examined how these processing speed correction algorithms change interference scores for individuals with idiopathic Parkinson's disease (PD, n = 58) and non-PD peers (n = 68). Linear regressions controlling for demographics predicted group (PD vs. non-PD) differences for Jensen's, Golden's, relative, ratio, and residualized interference scores. To examine convergent and divergent validity, interference scores were correlated with standardized measures of processing speed and executive function. PD-non-PD differences were found for Jensen's interference score, but not Golden's score, or the relative, ratio, and residualized interference scores. Jensen's score correlated significantly with standardized processing speed but not executive function measures. Relative, ratio, and residualized scores correlated with executive function but not processing speed measures. Golden's score did not correlate with any other standardized measures. The relative, ratio, and residualized scores were comparable for measuring Stroop interference in processing speed-impaired populations. Overall, the ratio interference score may be the most useful calculation method to control for processing speed in this population.


Surgical palliation or primary transplantation for aortic valve atresia.
The study objective was to describe the surgical pathway progression through adolescence of an inception cohort of neonates with aortic valve atresia managed initially with surgical palliation or primary transplantation, comparing survival and self-reported health-related quality of life. From 1994 to 2000, 565 neonates with aortic atresia were admitted to 26 Congenital Heart Surgeons' Society hospitals and followed annually for vital status. Initial management included surgical palliation (n = 453) and primary cardiac transplantation (n = 68). PedsQL health-related quality of life questionnaires were sent cross-sectionally to a subgroup of 198 patients alive at previous follow-up, with 80 responses. Risk of death was initially high for both treatment strategies. However, compared with initial surgical palliation, survival with primary transplantation, including wait-list mortality, was greater and persisted long-term (65% vs 40% at 15 years; P = .002). Survival after secondary transplantation (48% at 9 years) was lower than after primary transplantation (74%). Health-related quality of life total score was lower overall than that of the general adolescent population (71 ± 16 vs 84 ± 13; P = .0001; normal = 100), but similar to that of adolescents with chronic diseases. It was similar in the surgical palliation and primary transplantation groups (70 ± 16 vs 75 ± 15; P = .3). Patients who received surgical palliation reported more symptoms (76 ± 15 vs 63 ± 18; P = .02). Patients receiving primary heart transplantation for aortic atresia in 1994 to 2000 experienced better survival, fewer symptoms, and equivalent quality of life compared with those undergoing initial surgical palliation. Notwithstanding the limited availability of neonatal and infant donor hearts, primary transplantation may be considered for those neonates with risk factors predictive of exceptionally poor survival after surgical palliation.


Pro-oxidative activity of nitroxides in their reactions with glutathione.
Nitroxides are unreactive towards glutathione in vitro. Interaction of nitroxides with peroxynitrite does not lead to a significant loss of their electron paramagnetic resonance (EPR) signal. However, addition of peroxynitrite to a solution containing glutathione and nitroxides induces an irreversible disappearance of EPR signal of nitroxides and augmentation of glutathione oxidation which is a pro-oxidant effect of these compounds. Nitroxide loss leading to the formation of amine derivatives is initiated by products of glutathione oxidation by peroxynitrite. The pro-oxidant action of nitroxides at micromolar concentrations may be important in view of the proposed use of these compounds as antioxidants.


Dual-signal ratiometric electrochemical immunosensor constructed with snowflake-like FeSe2-AuNPs and PAA-ZIF@TB for sensitive detection of CYFRA21-1.
In this study, a ratiometric electrochemical immunosensor has been developed to detect the cytokeratin 19 fragment 21-1 (CYFRA21-1) biomarker in a highly sensitive manner through a dual-signal output model. As one of signal indicators, snowflake-like FeSe2 loaded with AuNPs (FeSe2-AuNPs) as sensing substrate with good conductivity and large active sites provides a differential pulse voltammetry (DPV) signal at +0.4 V. Another signal indicator, toluidine blue (TB) with the water-solubility property is an excellent redox probe that can generate DPV signal at -0.3 V. To solve the water-solubility problem, the TB is absorbed with polyacrylic acid (PAA) functionalized ZIF-67 (PAA-ZIF-67), which retains the properties of ZIF-67 that are large specific surface area and strong adsorption properties. The ratio of signals, stemmed from PAA-ZIF@TB and FeSe2-AuNPs (IPAA-ZIF@TB/IFeSe2-AuNPs), increases with the CYFRA21-1 concentration. Under optimal experimental conditions, CYFRA21-1 was detected in a wide dynamic range from 0.1 pg/mL to 100 ng/mL, with a lower limit of detection of 0.02 pg/mL. Looking ahead, this ratio based strategy provides prospective clinical applications for detecting other biomarkers.


Epicardial fat volume is associated with preexisting atrioventricular conduction abnormalities and increased pacemaker implantation rate in patients undergoing transcatheter aortic valve implantation.
Epicardial fat tissue (EFT) is a highly metabolically active fat depot surrounding the heart and coronary arteries that is related to early atherosclerosis and adverse cardiac events. We aimed to investigate the relationship between the amount of EFT and preexisting cardiac conduction abnormalities (CCAs) and the need for new postinterventional pacemaker in patients with severe aortic stenosis planned for transcatheter aortic valve implantation (TAVI). A total of 560 consecutive patients (54% female) scheduled for TAVI were included in this retrospective study. EFT volume was measured via a fully automated artificial intelligence software (QFAT) using computed tomography (CT) performed before TAVI. Baseline CCAs [first-degree atrioventricular (AV) block, right bundle branch block (RBBB), and left bundle branch block (LBBB)] were diagnosed according to 12-lead ECG before TAVI. Aortic valve calcification was determined by the Agatston score assessed in the pre-TAVI CT. The median EFT volume was 129.5 ml [IQR 94-170]. Baseline first-degree AV block was present in 17%, RBBB in 10.4%, and LBBB in 10.2% of the overall cohort. In adjusted logistic regression analysis, higher EFT volume was associated with first-degree AV block (OR 1.006 [95% CI 1.002-1.010]; p = 0.006) and the need for new pacemaker implantation after TAVI (OR 1.005 [95% CI 1.0-1.01]; p = 0.035) but not with the presence of RBBB or LBBB. EFT volume did not correlate with the Agatston score of the aortic valve. Greater EFT volume is associated independently with preexisting first-degree AV block and new pacemaker implantation in patients undergoing TAVI. It may play a causative role in degenerative processes and the susceptibility of the AV conduction system.


Addressing Antibiotic Abuse in China: An Experimental Audit Study.
China has high rates of antibiotic abuse and antibiotic resistance but the causes are still a matter for debate. Strong physician financial incentives to prescribe are likely to be an important cause. However, patient demand (or physician beliefs about patient demand) is often cited and may also play a role. We use an audit study to examine the effect of removing financial incentives, and to try to separate out the effects of patient demand. We implement a number of different experimental treatments designed to try to rule out other possible explanations for our findings. Together, our results suggest that financial incentives are the main driver of antibiotic abuse in China, at least in the young and healthy population we draw on in our study.


Sex-specific associations of cardiovascular risk factors and coronary plaque composition for hemodynamically significant coronary artery stenosis: a coronary computed tomography angiography study.
It has been reported that there are sex differences in plaque composition and hemodynamically significant stenosis. This study aimed to explore the impact of sex on cardiovascular risk factors for specific plaque compositions and hemodynamically significant stenosis. Data regarding demographics and cardiovascular risk factors were collected. Hemodynamically significant stenosis was identified by a computed tomography-derived fractional flow reserve of ≤ 0.8. Associations among cardiovascular risk factors, plaque composition, and hemodynamically significant stenosis were assessed using a multivariate binary logistic regression analysis across sexes. The discriminating capacity of diverse plaque components for hemodynamically significant stenosis was assessed by area under the receiver-operating characteristics curve with 95% confidence intervals. A total of 1164 patients (489 men and 675 women) were included. For men, hyperlipidemia and cigarette smoking were risk factors for each plaque component (all P < 0.05), and diabetes mellitus also predicted fibrotic components (P < 0.05). For women, risk factors for each plaque component were hypertension and diabetes mellitus (all P < 0.01). Nonetheless, hyperlipidemia (P < 0.05) was a specific risk factor for non-calcified components. Calcified components combined with fibrotic components showed superior discrimination of hemodynamically significant stenosis in men and calcified components alone in women (all P < 0.01). Hypertension (P < 0.01) was a risk factor for hemodynamically significant stenosis in women. In contrast, diabetes, hyperlipidemia, and cigarette smoking were risk factors for hemodynamically significant stenosis in men (all P < 0.05). In men, hemodynamically significant stenosis was predicted by a combination of calcified and fibrotic components with multiple risk factors. In women, hemodynamically significant stenosis was predicted by calcified components caused by a single risk factor. It might be a key point to improve prognosis by more precise risk management between men and women, which needs to be proved by further prospective trials.


Impact of maternal-fetal surgery for myelomeningocele on the progression of ventriculomegaly in utero.
Intrauterine myelomeningocele (MMC) repair decreases hindbrain herniation and the need for postnatal ventriculoperitoneal shunting. We examined the impact of intrauterine repair on the progression of ventriculomegaly in utero. Fetuses with MMC were identified through computerized databases from June 1988 to April 2003. A retrospective cohort design was used to evaluate the impact of intrauterine repair on ventricular progression with a multivariate linear regression model that included baseline ventricle measurement, gestational age, level of lesion, and gender. Fourteen fetuses with intrauterine repair and 39 fetuses with postnatal repair were identified. The natural history of progression of ventricular diameter increased in a linear fashion throughout gestation (0.57 mm/week). After adjusting for confounding variables, no transient or sustained difference was observed in the rate progression of ventriculomegaly between intrauterine and postnatal repair (0.27 +/- 0.35 mm/week; P=.45). Intrauterine MMC repair does not impact the progression of ventriculomegaly.


Regulation of glucose transporter-4 intervention with S. saman leaves extract in streptozotocin-induced diabetic rats.
Diabetes mellitus is the leading disorder and affects more than millions of people worldwide. Nowadays, the usage of herbal drugs is said to control adiposity and hyperglycemia. The current research investigated the anti-adiposity and antidiabetic activity of S. saman leaf extract and bioactive compounds. Therefore, the results lower the sugar absorption into the blood and reveal the extract's antidiabetic properties. STZ-induced diabetic rats, Samanea saman methanolic extract show improvement in the parameters like fasting blood glucose levels, body weight, other biochemical parameters supported by the histopathological analysis, and an increase in serum levels in the experimental groups. The antioxidant plays a vital role by increasing SOD and catalase activity levels and decreasing lipid peroxidation levels. The methanolic extract protects the tissue from oxidation stress, which is responsible for the glycemic properties. According to the findings, diabetic-treated rats had overnight blood glucose levels lower and near standard biochemical markers. Histopathology of the liver, pancreas, kidneys, and adipose tissues supported the pharmacological observations. Further, we screened and documented S. saman extract used for in vitro and in vivo methods. In terms of effectiveness, the crude extracts exhibit 0.8-fold GLUT4 down-regulation. Consequently, this result contributes to clinical trials and develops antidiabetic therapy as a substitute for synthetic pharmaceuticals.


[Preparation of a uncoordinated-5 homolog B monoclonal antibody and its effect on melanoma cell migration in vitro].
To prepare and characterize the monoclonal antibody (mAb) against uncoordinated-5 homolog B (UNC5B) and analyze its effect on the migration of melanoma cells. UNC5B gene fragment was cloned into the prokaryotic expression vector pET-32a. The recombinant UNC5B protein was expressed in E.coli BL21 (DE3) and purified by affinity chromatography. BALB/c mice were immunized with the recombinant protein and the hybridoma cell clones stably secreting UNC5B antibody were screened by traditional hybridoma technique. ELISA, Western blotting and flow cytometry were used to characterize the specificity of the antibodies. In addition, the effect of the mAb on melanoma cell migration was analyzed by wound healing assay. The recombinant UNC5B protein was expressed and purified. One high-titer antibody 2C9 was obtained. ELISA, Western blotting and flow cytometry all demonstrated that 2C9 antibody specifically recognized the UNC5B protein. Wound healing assay indicated that the UNC5B mAb could promote melanoma cell migration at the presence of netrin-1. A UNC5B-specific monoclonal antibody was prepared and proved to have the ability of promoting melanoma cell migration at the presence of netrin-1.