HIV testing and self-reported HIV status in South African men who have sex with men: results from a community-based survey.
To investigate the characteristics of South African men who have sex with men (MSM) who (1) have been tested for HIV and (2) are HIV positive. Data were collected from 1045 MSM in community surveys using questionnaires that were administered either face-to-face, by mail or on the internet. The mean age of the men was 29.9 years. The race distribution was 35.3% black, 17.0% coloured, 5.3% Indian and 41.1% white. The proportion of MSM tested for HIV was 69.7%; having been tested was independently associated with being older, being more open about one's homosexuality and being homosexually instead of bisexually attracted; black MSM, students and MSM living in KwaZulu-Natal were less likely to have been tested. Of the 728 MSM who had been tested, 14.1% (n = 103) reported to be HIV positive (9.9% of the total sample). Being HIV positive is independently associated with two factors: men who were positive were more likely to have a lower level of education and to know other people who had HIV/AIDS; race was not independently associated with HIV status among those who had been tested. The likelihood of having been tested for HIV seems to decrease with increasing social vulnerability. Racially, the distribution of HIV among MSM seems to differ from that of the general South African population, suggesting that while intertwined with the heterosexual epidemic there is also an epidemic among South African MSM with specific dynamics. These findings suggest that in-depth research is urgently needed to address the lack of understanding of HIV testing practices and HIV prevalence in South African MSM.


Azithromycin prophylaxis and treatment of murine toxoplasmosis.
To evaluate the azithromycin effects alone and in combination with other agents in the prophylaxis and treatment of murine toxoplasmosis. A total of 280 BALB/c mice were included, and 2 x 103 Toxoplasma organisms of the RH strain Toxoplasma gondii strain ATCC50174 were given intraperitoneally to each mouse. In experiment one, 40 animals were given azithromycin 200 milligram/kilogram/daily for 3 days starting the day of inoculation, 40 mice were control. In experiment 2, the treatment was started 48 hours after inoculation and given daily for 3 days: one group received azithromycin 200 milligram/kilogram/day, the second group received pyrimethamine 25 milligram/kilogram/day, and the sulfadiazine 100 milligram/kilogram/day. The third group was control. In experiment 3, 7 groups of animals received one of the following (1) none, (2) azithromycin 200 milligram/kilogram/day, (3) pyrimethamine 25 milligram/kilogram/day and sulfadiazine 100 milligram/kilogram/day, (4) azithromycin and sulfadiazine, (5) azithromycin and pyrimethamine, (6) azithromycin with sulfadiazine and pyrimethamine, (7) sulfadiazine alone. Treatment was initiated 72 hours after inoculation for 3 days. The study was conducted at the Animal Care Facility of King Saud University, Riyadh, Kingdom of Saudi Arabia. Animals that received azithromycin simultaneously with inoculation survived, and all control animals died. All animals died in groups receiving single drug therapy. Animals treated with azithromycin and sulfadiazine showed a survival rate of 40%, sulfadiazine and pyrimethamine 40%, or azithromycin with sulfadiazine and pyrimethamine 95% (p<0.0001). Azithromycin alone was found to be effective in the prophylaxis of murine toxoplasmosis. Combination therapy was effective in the treatment of murine toxoplasmosis.


Morphological ordering in biopolymers: informational statistical thermodynamic approach.
We consider the question of the emergence of morphological ordering in an open far-from-equilibrium model of a biopolymer. We apply informational statistical thermodynamics, which was shown to be appropriate to deal with dissipative systems displaying complex behavior. The formation of nonlinear spatial ordering consisting in the emergence of static charge-density waves, producing a bioelectret-type state, is evidenced. This kind of behavior may arise in biopolymers under the influence of biochemical processes.


Association of Desmin Gene Variant rs1058261 with Cardiovascular Disease, the TAMRISK Study.
Since desmin expression is diminished in vascular smooth muscle cells during reparative processes, we wanted to study whether a common intragenic single nucleotide polymorphism at nucleotide position 828 (rs1058261) of the DES gene associates with hypertension, cerebrovascular complications, and all cardiovascular events in the Tampere adult population cardiovascular risk (TAMRISK) study. A Finnish periodic health examination cohort of 336 subjects with diagnosed hypertension and 473 controls were analyzed. Samples were genotyped for polymorphism using TaqMan techniques. Prevalence of ischemic heart diseases, incidence of cerebrovascular diseases, and transient cerebral ischemic attacks (TIAs) were obtained by self-report and the National Hospital Discharge Registry (HILMO). There was no association of any of the rs1058261 genotypes with hypertension at the age of 50. When the subjects were followed to the age of 60, after adjustment for gender and body mass index, subjects with the genotype CC had higher incidence of cerebrovascular events (cerebrovascular diseases and TIA) (4.1%) compared with the T allele (1.6%) (p = 0.046). In addition, those with CC genotype had a higher incidence of all combined cardiovascular events (12.8%) compared with subjects with the T allele (8.5%) (p = 0.028). Our findings suggest that variations in the DES gene may be involved in cardiovascular disease.


Visible light photocatalytic decomposition of 2-naphthol by anodic-biased alpha-Fe2O3 film.
Transparent alpha-Fe2O3 films with varying film thickness were formed on a SnO2 transparent conducting film-coated glass substrate by metal organic deposition. Under anodic-biased conditions, the alpha-Fe2O3 film showed a high photocatalytic activity for the decomposition of 2-NAP with visible light irradiation. The alpha-Fe2O3 is transformed to inactive hydroxide as the reaction proceeds, while the activity of alpha-Fe2O3 is almost maintained in acetonitrile.


Vaginal hysterectomy allied with Kelly-Kennedy surgery and perineal repair for the treatment of patients with a prolapsed uterus and urinary stress incontinence.
To evaluate patients with uterine prolapse, before and after surgical treatment, using urodynamic and bladder neck ultrasound. 33 postmenopausal patients with uterine prolapse were submitted to vaginal hysterectomy (Mayo-Ward technique) allied with Kelly-Kennedy surgery and perineal repair. The women were divided into three groups depending on the degree of prolapse. A urodynamic examination was performed before, after 30 days and in the third month after the operation. A bladder neck ultrasound was performed before and in the third month after the operation. In 23 women who lost urine preoperatively, 14 continued to show objective loss 90 days after the surgery. Ultrasound identified a significant elevation in the bladder neck during rest in groups I and II, but not in group III. There was a significant reduction in its mobility in all three groups. Kelly-Kennedy surgery does not have any indication, even in patients with urinary stress incontinence and a prolapsed uterus who are submitted to vaginal hysterectomy.


Lack of correlation between interferon levels induced by polyribonucleotides and their antimetastatic effect.
The inhibitory effect of poly(A)poly(U) on the pulmonary metastasis of B16-F10 melanoma was examined in comparison with that of poly(I,C)-L,C and poly(I)poly(C). The correlation between interferon (IFN) level and antimetastatic effect was also investigated. Intraperitoneal injection of poly(A)poly(U) (50 mg/kg) into C57BL/6 mice 24 h before intravenous inoculation of B16-F10 melanoma (1 X 10(5] caused a significant decrease (p less than 0.01) in the number of pulmonary nodules 14 days after tumor challenge. But poly(I,C)-L,C (1 or 0.2 mg/kg) and poly(I)poly(C) (5 mg/kg or 1 mg/kg) did not. From the kinetic study of IFN levels induced by polyribonucleotides, poly(I,C)-L,C showed the most potent IFN-inducing activity, followed by poly(I)poly(C) and poly(A)poly(U), in this order. Plasma IFN reached a peak at 6 h and still continued to be detected at 24 h after intraperitoneal injection of the polyribonucleotides. Against B16-F10 melanoma, the cytotoxicity of spleen cells stimulated by poly(A)poly(U) (50 mg/kg) was significantly (p less than 0.05) higher than that of spleen cells stimulated by poly(I)poly(C) (5 mg/kg) both at 12 and 24 h after intraperitoneal injection of those agents. The above results that there is no correlation between the IFN levels induced by polyribonucleotides and their antimetastatic effect. More extensive study of poly(A)poly(U) might give more fruitful results, which will give valuable information for future clinical trials of this lowly toxic promising agent.


René Cruchet (1875-1959), beyond encephalitis lethargica.
René Cruchet (1875-1959) was a pediatrician from Bordeaux known for his seminal description of encephalitis lethargica during World War I, at the same time as Constantin von Economo (1876-1931) in Vienna published his own description, which, unlike Cruchet's description, provided precious anatomopathological data in addition to the clinical data. Cruchet was interested in tics and dystonia and called for treatment using behavioral psychotherapy that was, above all, repressive. Cruchet was also a physiologist and an innovator in aeronautic medicine-notably, he helped pioneer the study of "aviator's disease" during World War I. Moreover, he possessed an encyclopedic knowledge, while publishing in all medical fields, writing philosophical texts as well as travel logs.


Midkine concentrations in fine-needle aspiration of benign and malignant thyroid nodules.
The primary preoperative method for distinguishing malignant from benign thyroid nodules is fine-needle aspiration (FNA) cytology, but it is frequently inconclusive. Midkine (MDK) is a heparin-binding growth factor, which is overexpressed in papillary thyroid carcinoma (PTC). We measured MDK concentrations in FNA samples from benign and malignant thyroid nodules to explore the possibility that MDK measurement might aid in the evaluation of thyroid nodules. 35 subjects underwent preoperative FNA of 45 thyroid nodules, followed by thyroidectomy, providing a histological diagnosis. FNA needle contents were first expressed for cytology, and then, the needle was washed with buffer for immunoassay. In 46 subjects without preoperative FNA samples, FNA was performed ex vivo on 62 nodules within surgically excised thyroid tissue. MDK was measured using a high-sensitivity sandwich ELISA and normalized to thyroglobulin (Tg) concentration in the sample to adjust for tissue content in the aspirate. The MDK/Tg ratio was higher in 18 PTCs than in 87 benign nodules (204 ± 106 vs 1·2 ± 0·3 ng/mg, mean ± SEM, P < 0·001). Using a threshold of 10 ng/mg, the sensitivity and specificity of the MDK/Tg ratio for diagnosis of PTC were 67% and 99%, respectively. All follicular variant PTCs had a MDK/Tg ratio <10 ng/mg. The findings indicate that, in FNA samples, the MDK/Tg ratio in PTC is greater than in benign thyroid nodules, raising the possibility that this approach might provide adjunctive diagnostic or prognostic information to complement existing approaches.


A prospective randomized study comparing division of the pedicle of modified hughes flaps at two or four weeks.
To compare the incidence of upper and lower eyelid malposition or other complications when the pedicle in modified Hughes flap repair of the lower eyelid is divided at 2 versus 4 weeks. A prospective randomized study. Data were collected on patient age and sex, horizontal tumor dimension, upper and lower eyelid position before surgery and 3 months after division of the pedicle, and any complications. Complete data from 60 patients were collected, with 32 patients in the 2-week group and 28 patients in the 4-week group. The two groups were not significantly different in terms of sex, age, or tumor dimensions. In the 2-week group, the upper eyelid was within 1 mm of its preoperative position at 3 months in 25 of 32 patients (78.1%) and in 26 of 28 (92.8%) in the 4-week group. The lower eyelid was within 1 mm of its normal position in 27 of 32 patients in the 2-week group (84.4%) versus 25 of 28 (89.3%) in the 4-week group. Statistical analysis showed no significant difference between the 2- and 4-week groups for upper and lower eyelid position at 3 months. Other complications were uncommon and evenly spread between the two groups. A modified Hughes flap pedicle may be divided at 2 weeks with no increased incidence in upper or lower eyelid malposition or other complication.


Exploration of the definition and components of food and nutrition literacy among junior secondary school students: a qualitative study.
Food and nutrition literacy (FANLit) has been proposed to promote healthy diet behaviour and is believed to decrease the prevalence of overweight, obesity and chronic disease. However, the perspective of junior secondary school students, aged 12-15 years and stakeholders towards FANLit is not well-defined. Thus, this study aims to explore the definition and components of FANLit. This qualitative study was carried out in Health region 2 including Phitsanulok, Sukhothai, Tak, Uttradit and Pethchboon. 49 participants from national and regional levels of Thailand were recruited. Data were collected by in-depth interview and focus group discussion using semi-structured questionnaire. Interview data were transcribed verbatim and analysed using thematic analysis. FANLit is defined as an individual's level of knowledge and skills (fundamental, interactive and critical) that relates to food and nutrition for appropriate selection of food and nutrient. Four themes of FANLit were identified as follows: 1) food and nutrition knowledge (Subthemes: food knowledge, food understanding, nutrition knowledge and nutrition understanding), 2) functional food and nutrition literacy (Subthemes: accessing to food and nutrition information, food selection, food preparation, daily food and nutrition planning and management), 3) interactive food and nutrition literacy (Subthemes: communication with others, sharing and discussion), and 4) critical food and nutrition literacy (Subthemes: information used in decision making, healthy food selection and effective budgeting). The results presented beneficial information regarding FANLit definition which is the initial stage to develop the assessing instrument and the intervention to improve FANlit in the adolescent group.


The molecular basis of β-lactamase production in Gram-negative bacteria from Saudi Arabia.
Resistance to β-lactams among Gram-negative bacteria is a worldwide issue. Increased prevalence of extended-spectrum β-lactamase (ESBL)-producers and the dissemination of carbapenem-resistance genes are particularly concerning. ESBL-producing strains are common in the Kingdom of Saudi Arabia, particularly among the Enterobacteriaceae, and carbapenem resistance is on the increase, especially among the non-fermenters. β-lactamase production is a major mechanism of resistance to these agents and although β-lactamase-producing strains have been documented in the Kingdom, relatively few reports characterized the molecular basis of this production. Nevertheless, available data suggest that CTX-M (CTX-M-15 in particular) is the predominant ESBL in the Enterobacteriaceae, with SHV also being prevalent in Klebsiella pneumoniae. Carbapenem resistance in the latter is mainly due to OXA-48 and NDM-1. In Pseudomonas aeruginosa, VEB-like enzymes are the most common ESBLs, and VIM is the prevalent metallo-β-lactamase. OXA-10 extended-spectrum enzymes are also frequent. PER and GES ESBLs have been reported in Acinetobacter baumannii, and oxacillinases (OXA-23 in particular) are the dominant carbapanamases in this species.


[Gamma-angiography during exercise in chronic aortic insufficiency. Development of ventricular function and regurgitation].
Twenty-three patients with chronic aortic incompetence (17 men and 6 women) aged 27 to 71 years (average 51 years) underwent sequential gamma-angiography at rest and during the different levels of exercise and recovery phase to investigate the evolution of ventricular function and regurgitant fraction and so, guide therapy. The radionuclide indices of left ventricular function (end diastolic and end systolic indexed volumes, global ejection fraction, regional wall motion) and the regurgitant fractions were calculated and compared with clinical, echocardiographic, angiographic and haemodynamic data. The changes observed on effort during gamma-angiography allowed identification of 3 groups of patients: Group I: compensated aortic incompetence with a normal left ventricular ejection fraction (0.69 +/- 0.1), a moderate regurgitant fraction (40 per cent +/- 20 per cent) and, during exercise, a stable left ventricular end diastolic volume index (less than 5 per cent variation), an end systolic volume index which decreased (average-13 per cent), an ejection fraction which increases (by more than 0.05 in 62.5 per cent of cases) and with good global and regional wall motion. Group II: intermediate cases with a left ventricular ejection fraction of 0.62 +/- 0.09 and a regurgitant fraction of 60 +/- 16 per cent. Individual variations were observed with this group which either resembled those of Group I or those of Group III.(ABSTRACT TRUNCATED AT 250 WORDS)


Triflyl-assisted reductive Pd-catalyzed Tsuji-Trost type reaction.
New (triflyl)cyclobutenes have been prepared by palladium-catalyzed hydrodetriflylation reaction using water and deuterium oxide as convenient hydrogen and deuterium sources. In addition, an investigation of the possible mechanism for this Tsuji-Trost type reaction of bis(triflyl)cyclobutenes has been facilitated by labelling studies and density functional theory (DFT) calculations.


CD8 T cells require gamma interferon to clear borna disease virus from the brain and prevent immune system-mediated neuronal damage.
Borna disease virus (BDV) frequently causes meningoencephalitis and fatal neurological disease in young but not old mice of strain MRL. Disease does not result from the virus-induced destruction of infected neurons. Rather, it is mediated by H-2(k)-restricted antiviral CD8 T cells that recognize a peptide derived from the BDV nucleoprotein N. Persistent BDV infection in mice is not spontaneously cleared. We report here that N-specific vaccination can protect wild-type MRL mice but not mutant MRL mice lacking gamma interferon (IFN-gamma) from persistent infection with BDV. Furthermore, we observed a significant degree of resistance of old MRL mice to persistent BDV infection that depended on the presence of CD8 T cells. We found that virus initially infected hippocampal neurons around 2 weeks after intracerebral infection but was eventually cleared in most wild-type MRL mice. Unexpectedly, young as well as old IFN-gamma-deficient MRL mice were completely susceptible to infection with BDV. Moreover, neurons in the CA1 region of the hippocampus were severely damaged in most diseased IFN-gamma-deficient mice but not in wild-type mice. Furthermore, large numbers of eosinophils were present in the inflamed brains of IFN-gamma-deficient mice but not in those of wild-type mice, presumably because of increased intracerebral synthesis of interleukin-13 and the chemokines CCL1 and CCL11, which can attract eosinophils. These results demonstrate that IFN-gamma plays a central role in host resistance against infection of the central nervous system with BDV and in clearance of BDV from neurons. They further indicate that IFN-gamma may function as a neuroprotective factor that can limit the loss of neurons in the course of antiviral immune responses in the brain.


Does Surgical Experience Influence Implant Survival Rate? A Systematic Review and Meta-Analysis.
The aim of this study was to assess the evidence of a correlation between the expertise of surgeons and the survival rate of dental implants. An electronic search in four databases (MEDLINE, EMBASE, SCOPUS, and the Cochrane Library) was performed for publications from their inception to May 2016 and was supplemented by manual searches. Prospective and retrospective cohorts were included if they met the following criteria: (1) the presence of an exposed group (inexperienced surgeons); and (2) the presence of a control group (experienced surgeons). Meta-analyses were performed to evaluate the effect of expertise on implant failure. Of 609 potentially eligible articles, 8 were included in the qualitative analysis and 6 in the quantitative synthesis. Two meta-analyses were performed for different definitions of experienced surgeons. In the first meta-analysis, which included four retrospective comparative studies that defined experienced professionals as specialists, the experience of the surgeon did not significantly affect the implant failure rate (P = .54), with an odds ratio (OR) of 1.24 (95% CI, 0.62-2.48). In the second meta-analysis, which included two retrospective studies that defined experienced surgeons as professionals that had placed more than 50 implants, the expertise of the surgeon did significantly affect the implant failure rates (P = .0005), with an OR of 2.18 (95% CI, 1.40-3.39). The data from the included publications suggest that surgical experience did not significantly affect implant failure when considering experience based on specialty but were significantly affected when considering experience based on the number of implants placed. Further standardized prospective studies with a control of confounding factors are needed to clarify the role of surgical expertise on implant survival rates.


[Neurological aspects of stuttering].
Stuttering is characterised by repetitions, prolongations and pausing while speaking. Researchers have looked for many explanations. However, the cause of stuttering remains unknown. In recent years, structural abnormalities in the speech-related structures of the central nervous system have been brought into focus as a cause of stuttering. Research has shown signs of a lateral hemisphere asymmetry, abnormalities in the basal ganglia, dysfunction in the supplementary motor area and/or a dysfunction in the coordination of the cerebellum. This article is a review of this part of the literature.


Weight-of-the-evidence evaluation of 2,4-D potential for interactions with the estrogen, androgen and thyroid pathways and steroidogenesis.
A comprehensive weight-of-the-evidence evaluation of 2,4-dichlorophenoxyacetic acid (2,4-D) was conducted for potential interactions with the estrogen, androgen and thyroid pathways and with steroidogenesis. This assessment was based on an extensive database of high quality in vitro, in vivo ecotoxicological and in vivo mammalian toxicological studies. Epidemiological studies were also considered. Toxicokinetic data provided the basis for determining rational cutoffs above which exposures were considered irrelevant to humans based on exceeding thresholds for saturation of renal clearance (TSRC); extensive human exposure and biomonitoring data support that these boundaries far exceed human exposures and provide ample margins of exposure. 2,4-D showed no evidence of interacting with the estrogen or androgen pathways. 2,4-D interacts with the thyroid axis in rats through displacement of thyroxine from plasma binding sites only at high doses exceeding the TSRC in mammals. 2,4-D effects on steroidogenesis parameters are likely related to high-dose specific systemic toxicity at doses exceeding the TSRC and are not likely to be endocrine mediated. No studies, including high quality studies in the published literature, predict significant endocrine-related toxicity or functional decrements in any species at environmentally relevant concentrations, or, in mammals, at doses below the TSRC that are relevant for human hazard and risk assessment. Overall, there is no basis for concern regarding potential interactions of 2,4-D with endocrine pathways or axes (estrogen, androgen, steroidogenesis or thyroid), and thus 2,4-D is unlikely to pose a threat from endocrine disruption to wildlife or humans under conditions of real-world exposures.


[Etiology--characteristics of HIV infection].
In this study the structures of the AIDS-virus are presented, furthermore the cross-reactivity of HIV-1 and HIV-2 is described as well as the known genes of both viruses. The mechanism of cell infection, its kinetics and the special role of activated T-cells and macrophages in this process are outlined. This interrelation characterized phenomenologically based on the neopterin data available is now supported by experiments at a molecular level. This should lead to therapeutical and diagnostical consequences.


Nurses' beliefs, attitudes, and opinions regarding a smoking ban in a psychiatric hospital.
This study aims to identify the beliefs, attitudes, and opinions of nursing professionals associated with tobacco smoking and its prohibition in a psychiatric hospital in Brazil. Using a cross-sectional epidemiologic study, a total of 73 nursing professionals in a smoke-free psychiatric hospital were interviewed. The Varimax Rotation and the Fisher's exact test at a 5% significance level were used to analyze the responses. Most nursing professionals reported observations of patients becoming calmer after smoking (n = 59, 80.8%) and tobacco withdrawal worsening patients' mental health symptoms, suggesting agreement among professionals that some psychiatric patients need to smoke tobacco. Most respondents stated that patients with mental health disorders have more difficulty with smoking cessation (79.4%) and are less interested in quitting smoking than those without disorders (95.9%). While one-third mentioned having used cigarettes as a reward or bribe, the majority (83.6%) was in favor of continuing the smoking ban, with more support observed from those working on a night shift and those who worked in the public psychiatric wards. Over 71% noted improvements in their health after the smoking ban. The nursing professionals were surprised by the effectiveness of the smoking ban and highlighted the improvement in the hospital environment after its implementation. As trusted healthcare professionals, nurses are essential in the fight against smoking and can contribute to awareness promotion, supporting patients during nicotine withdrawal, and decision-making processes for health policies.


Assessing cardiac function by gas exchange.
Exercise stresses the primary function of the cardiovascular system, which is the supply of O2 and removal of CO2 from the cells of the body. Even ordinary walking requires an increase in O2 consumption and CO2 production by the exercising muscles of 20 times the resting level. While pulmonary dysfunction may affect arterial blood gas tensions, the dynamics of O2 uptake and CO2 output by the lungs depend on the circulatory responses to exercise. Thus, measurement of the dynamics of O2 uptake in response to exercise has been shown to reflect cardiovascular function. Inability of the circulatory responses to meet an increased O2 requirement may be reflected in abnormalities in O2 uptake dynamics, and an early increase in CO2 output relative to O2 uptake consequent to bicarbonate buffering of lactic acid. Application of currently available technology for the continuous measurement and analysis of pulmonary gas exchange can afford the practicing or investigative cardiologist with a noninvasive and inexpensive means for assessing cardiovascular function.


N-acetylcysteine for neuropsychiatric symptoms in a woman with Williams syndrome.
Williams syndrome is a relatively rare genetic disorder caused by the hemizygous microdeletion of a region in chromosome 7q11.23. Individuals with Williams syndrome typically present with a highly social, overfriendly, and empathic personality. Comorbid medical and neuropsychiatric disorders are common. Reports of effective pharmacological treatment of associated neuropsychiatric disorders are limited. The authors describe the successful treatment of interfering anger, aggression, and hair-pulling with N-acetylcysteine in a 19-year-old woman with Williams syndrome. The neuropsychiatric symptoms emerged 1 week following an upper gastrointestinal endoscopy, for which fentanyl, midazolam, and propofol were used as anesthetics. The patient's treatment course and hypothesized mechanisms underlying the clinical presentation and symptom resolution are described.


Retrospective serological tests for determining the optimal blood concentration of voriconazole for treating fungal infection.
We investigated the optimal blood concentration of voriconazole (VRCZ) based on trough blood concentrations (C) and serological test values in patients. With regard to the regulation of VRCZ dosage (D) to maintain optimal blood concentrations, we investigated the relationship between C and D. Twenty-three patients were enrolled in the present study, and at 28 point data were analyzed retrospectively.When the beta-D-glucan or the Aspergillus antigen were decreased below the standard set values, it was evaluated as effective. The adverse events were evaluated using the Common Terminology Criteria for Adverse Events ver. 3.0. We found a significant difference (p<0.05) in the average trough blood concentration between patients in whom VRCZ was effective and those in whom VRCZ was ineffective (8.21+/-2.19 microg/ml vs. 1.01+/-0.86 microg/ml), and patients presenting with adverse events and those with no adverse events (7.64+/-2.84 microg/ml vs. 1.49+/-1.79 microg/ml). There was no significant relationship between C and D (C: D, y=0.018-2.186, r(2)=0.349).Improved efficacy and more adverse events thus occurred with higher blood concentrations. The careful regulation of the dosage must be performed while measuring blood concentration and observing for adverse events. The implementation of therapeutic drug monitoring for VRCZ is a valuable tool for achieving effective fungal infection therapy and should be aggressively investigated in future studies.


Anti-proliferative effect of isorhamnetin on HeLa cells through inducing G2/M cell cycle arrest.
As a major cancer type in females, cervical cancer has been explored in depth by researchers. HeLa is a cervical cancer cell line. Isorhamnetin is an O-methylated flavonol that is primarily extracted from sea buckthorn. In the present study, the anti-proliferative effect of isorhamnetin on HeLa cells was evaluated using a Trypan blue dye exclusion assay. Isorhamnetin inhibited the cell proliferation in a time- and dose-dependent manner. Flow cytometric analysis of the cell cycle distribution revealed that isorhamnetin inhibited the cell cycle progression of HeLa by causing G2/M phase arrest and decreasing the proportion of cells in G1 phase. In addition, western blot analysis was performed to evaluate the presence of certain cell cycle-associated proteins. It was demonstrated that isorhamnetin inhibited the protein expression of cyclin B1, cell division cycle 25C (Cdc25C) and Cdc2, but enhanced checkpoint kinase 2 (Chk2), Cdc25C and Cdc2 phosphorylation. In addition, tubulin depolymerization participated in the isorhamnetin-induced cell cycle arrest in G2/M phase. In conclusion, the present results indicated that the anti-proliferative action of isorhamnetin is associated with arrest of the cell cycle in G2/M phase, which is a consequence of activation of the ataxia telangiectasia mutated Chk2 pathway and disruption of microtubule function.


Comparing Firearm and Stabbing Injuries in the Pediatric Trauma Population Using Propensity Matching.
The objective of this study was to compare differences in mortality and nonhome discharge in pediatric patients with firearm and stab injuries, while minimizing bias. Our secondary objective was to assess the influence of insurance on these same outcomes. Patients aged 0 to 17 years included in the National Trauma Data Bank (2007-2015) with firearm and stabbing injury were matched by propensity score. Logistic regression was used to assess associations of injury type and insurance with long-term care discharge and death. The average age was 14.8 years, 19.2% were female, 48% were African American, 58.4% had an injury severity score ≤8, and assaults accounted for 73.1% of cases. Firearm injuries were associated with a higher risk of discharge to long-term care (adjusted odds ratio [aOR], 2.07) compared with propensity-matched patients who were stabbed. Similarly, we found a higher risk of mortality in those with firearm injuries compared with stabbing injuries (aOR, 1.85). Regardless of mechanism, self-pay insurance status was associated with a higher risk of mortality (aOR, 2.41). When compared with stab wound patients with commercial insurance, self-pay firearm-injured patients were found to have an increased risk of mortality (aOR, 5.25). Pediatric victims of firearm violence were more likely to die or need additional care outside the home than victims of other types of penetrating injury when accounting for confounding characteristics to minimize bias.


Circulatory changes in patients with coronary artery disease following thiamylal-succinylcholine and tracheal intubation.
Circulatory responses after thiamylal (4 mg/kg) and succinylcholine (SCh) (2 mg/kg) administration followed by direct laryngoscopy and tracheal intubation were measured in 20 patients before elective aortocoronary vein bypass graft operations. Compared with awake measurements, the mean arterial pressure (MAP) decreased 19 +/- 3 torr (mean +/- SE) and heart rate (HR) increased 9 +/- 3 bpm 1 minute after thiamylal-SCh. MAP was increased 39 +/- 4 torr and HR 20 +/- 3 bpm above awake levels in response to laryngoscopy and tracheal intubation. Blood pressure and HR returned spontaneously to near awake levels without additional anesthesia within 5 minutes of anesthetic induction. Stroke volume index was decreased significantly after tracheal intubation but cardiac index was not altered. The authors conclude that thiamylal-SCh followed by tracheal intubation is an acceptable anesthetic induction sequence for patients without evidence of left ventricular heart failure who require anesthesia for elective coronary artery revascularization.


Quality of reporting on thoracic radiotherapy technique in prospective lung cancer trials: A systematic review.
The aim of this study is to assess the quality of reporting of thoracic (T) RT technique for curative intent treatment in prospective lung cancer trials. We searched MEDLINE for eligible trials published from 1996 to 2016. We assessed the included trials' reports on whether they reported the RT dose prescription method; RT dose-planning procedures; algorithm for tissue inhomogeneity dose corrections; organs at risk dose constraints; target volume definition, simulation and/or motion management procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance as well as presence or absence of deviations in RT treatment planning and delivery adequately. We performed univariable and multivariable logistic regression to determine the factors that may influence the quality of reporting. We found 85 eligible trial reports. Target volume definition, total RT dose, and fractionation schedules were reported adequately in more than 90% of the included trials. Algorithm for tissue inhomogeneity dose corrections, simulation and verification procedures, presence or absence of deviations in RT treatment planning and delivery were reported adequately in less than 20% of the included trials. Twenty-three trials (27%) reported 7 criteria or more adequately. Both univariable and multivariable logistic regression showed that trials with RT focused research question were more likely to have adequate quality in reporting (judged as adequate reporting in 7 criteria or more) than trials with non-RT focused question (odds ratio 4.11, 95% confidence interval 1.10 to 15.43, P value = .04). There is significant variability in the quality of reporting on thoracic radiotherapy treatment in prospective lung cancer trials. Future research should focus on developing consensus guidelines to standardize the reporting of radiotherapy technique in clinical trials.


Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands.
Cancer has long been recognized to have a familial component. Elevated risks for cancers at the same site for relatives of cancer probands have been reported for both common cancers and a number of the rarer cancer sites. For a particular cancer site, however, the estimated risks to relatives have varied considerably depending on criteria for selection of probands, how cancers were determined in relatives, and overall study design. Not surprisingly, the estimated risks of other cancers in relatives of probands with cancer at a given site have been subject to even more variation. The aim of this study was to use the Utah Population Database resource to systematically study familial clustering of 28 distinct cancer site definitions among first-degree relatives (parents, siblings, and off-spring) of cancer probands. We estimated familial relative risks from the Utah Population Database by identifying all cases of cancer in these first-degree relatives. These observed values were compared with those expected based on cohort-specific internal rates calculated from 399,786 relatives of all individuals in the Utah Population Database known to have died in Utah. All sites showed an excess of cancers of the same site among relatives, with thyroid and colon cancers and lymphocytic leukemia showing the highest familial risks. When the analyses were restricted to cases with early ages at diagnosis, increased familial components for most cancer sites became evident. A significant difference in familial relative risk (FRR) between male (FRR = 4.04; 95% confidence interval [CI] = 3.13-5.07) and female (FRR = 2.24; 95% CI = 1.54-3.08) probands was found for colon cancer. Highly significant familial associations (one-sided; P < .001) were found among breast, colon, and prostate cancers and between breast and thyroid cancers. Statistically significant (one-sided, P < .01) associations were also found between tobacco-associated sites (lung, larynx, lip, and cervix). This study represents a unique comprehensive population-based study of familial cancer. The familial associations reported here will be useful in generating hypotheses about specific genetic and environmental factors that can be tested in genetic linkage and case-control studies.


[Chlamydophila pneumoniae biotype TWAR: selected details].
Chlamydophila pneumoniae biotype TWAR is classified in the Chlamydiacea family and used to be considered a cause of pneumonia. Lately it has been also proved that it can cause heart disease and diseases of the blood vessels and also take part in the pathogenesis Alzheimer and multiple sclerosis, which shows that biotype TWAR has expanded its spectrum.


Analgesia without sedatives during colonoscopies: worth considering?
Colonoscopy is a proven method for bowel cancer screening and is often experienced as a painful procedure. Today, there are two main strategies to facilitate colonoscopy. First, deep sedation results in satisfied patients but increases sedation-associated risks and raises costs for healthcare providers. Second, there is the advocacy for colonoscopies without any form of sedation. This might be an option for a special group of patients, but does not hold true for everybody. Following Moerman's hypothesis: "If pain is the crucial point, why do we need sedation?" this review shows the analgesic options for a painless procedure, increasing success rates without increasing risk of sedation. There are two agents, with the potential to be a nearly ideal analgesic agent for colonoscopy: alfentanil and nitrous oxide (N(2)O). Administration of either substance causes the patient to be comfortable yet alert and facilitates a short turnover. Advantages of these drugs include rapid onset and offset of action, analgesic and anxiolytic effects, ease of titration to desired level, rapid recovery, and an excellent safety profile.


Ascites, refractory ascites and hyponatremia in cirrhosis.
Ascites is the most common complication related to cirrhosis and is associated with increased morbidity and mortality. Ascites is a consequence of the loss of compensatory mechanisms to maintain the overall effective arterial blood volume due to worsening splanchnic arterial vasodilation as a result of clinically significant portal hypertension. In order to maintain effective arterial blood volume, vasoconstrictor and antinatriuretic pathways are activated, which increase overall sodium and fluid retention. As a result of progressive splanchnic arterial vasodilation, intestinal capillary pressure increases and results in the formation of protein-poor fluid within the abdominal cavity due to increased capillary permeability from the hepatic sinusoidal hypertension. In some patients, the fluid can translocate across diaphragmatic fenestrations into the pleural space, leading to hepatic hydrothorax. In addition, infectious complications such as spontaneous bacterial peritonitis can occur. Eventually, as the liver disease progresses related to higher portal pressures, loss of a compensatory cardiac output and further splanchnic vasodilation, kidney function becomes compromised from worsening renal vasoconstriction as well as the development of impaired solute-free water excretion and severe sodium retention. These mechanisms then translate into significant clinical complications, such as refractory ascites, hepatorenal syndrome and hyponatremia, and all are linked to increased short-term mortality. Currently, liver transplantation is the only curative option for this spectrum of clinical manifestations but ongoing research has led to further insight on alternative approaches. This review will further explore the current understanding on the pathophysiology and management of ascites as well as expand on two advanced clinical consequences of advanced liver disease, refractory ascites and hyponatremia.


Synthesis of Poly(norbornene-methylamine), a Biomimetic of Chitosan, by Ring-Opening Metathesis Polymerization (ROMP).
ROMP is an effective method for preparing functional polymers due to its having characteristics of "living" polymerization and rapid development of catalysts. In the present work, poly(norbornene-methylamine), a mimic of chitosan, was synthesized via ROMP reaction. The amino-protected product, 5-norbornene-2-(N-methyl)-phthalimide, was prepared by a reaction of 5-norbornene-2-methylamine with phthalic anhydride, which was then subjected to the ROMP reaction in the presence of Hoveyda-Grubbs 2nd catalyst to afford poly(norbornene-(N-methyl)-phthalimide). The target product, poly(norbornene-methylamine), was obtained by deprotection reaction of poly(norbornene-(N-methyl)-phthalimide). The products in each step were characterized by FTIR and ¹H-NMR, and their thermal stabilities were determined by TG analysis. The effects of molar ratio between monomer ([M]/[I]) and catalyst on the average relative molecular weight ( M n ¯ ) and molecular weight distribution of the produced polymer products were determined by gel permeation chromatography (GPC). It was found that the M n ¯ of poly(norbornene-(N-methyl)-phthalimide) was controllable and exhibited a narrow polydispersity index (PDI) (~1.10). The synthesis condition of 5-norbornene-2-(N-methyl)-phthalimide was optimized by determining the yields at different reaction temperatures and reaction times. The highest yield was obtained at a reaction temperature of 130 °C and a reaction time of 20 min. Our work provides a new strategy to synthesize polymers with controllable structures and free -NH₂ groups via ROMP.


The significance of minimal residual disease in patients with t(15;17).
Acute promyelocytic leukaemia (APL) is characterized by the t(15;17)(q22;q21) leading to the formation of PML-RARalpha and RARalpha-PML fusion genes which provide suitable targets for the assessment of minimal residual disease (MRD). Studies have focused upon detection of PML-RARalpha because, although assays for RARalpha-PML transcripts are more sensitive, they are not applicable to 25% of cases. Among patients receiving standard therapy (ATRA and anthracycline-based chemotherapy), qualitative assays using a nested reverse transcriptase-polymerase chain reaction (RT-PCR), which typically achieve sensitivities of 1 in 10(4), have been found to provide independent prognostic information suitable for directing an approach to treatment. Detection of PML-RARalpha at the end of consolidation, or subsequent recurrence of PCR positivity, heralds relapse, which may, however, be averted by additional therapy leading to improvements in survival for this "high-risk" subgroup of patients. MRD analysis has also proved of value in predicting response to autologous transplant procedures undertaken in second complete remission and in directing the need for additional therapy in the post-transplantation setting. Overall, these studies undertaken within the context of a relatively homogeneous disease entity confirm that MRD monitoring provides independent prognostic information, serving as a valuable model for improving treatment strategy in other molecularly defined subsets of acute myeloid leukaemia (AML). Nevertheless, conventional nested RT-PCR assays fail to detect residual disease in a significant proportion of patients who ultimately relapse, which may be a reflection of RNA quality and/or assay sensitivity. Therefore, it is hoped that "real-time" quantitative RT-PCR technology (RQ-PCR) which permits quantification of fusion gene transcripts in relation to endogenous control genes will be even more predictive of outcome and achieve greater standardization of MRD detection in the context of large-scale clinical trials.


Preparation time influences ankle and knee joint control during dynamic change of direction movements.
The influence of preparation time on ankle joint biomechanics during highly dynamic movements is largely unknown. The aim of this study was to evaluate the impact of limited preparation time on ankle joint loading during highly dynamic run-and-cut movements. Thirteen male basketball players performed 45°-sidestep-cutting and 180°-turning manoeuvres in reaction to light signals which appeared during the approach run. Both movements were executed under (1) an easy condition, in which the light signal appeared very early, (2) a medium condition and (3) a hard condition with very little time to prepare the movements. Maximum ankle inversion angles, moments and velocities during ground contact, as well as EMG signals of three lower extremity muscles, were analysed. In 180°-turning movements, reduced preparation time led to significantly increased maximum ankle inversion velocities. Muscular activation levels, however, did not change. Increased inversion velocities, without accompanying changes in muscular activation, may have the potential to destabilise the ankle joint when less preparation time is available. This may result in a higher injury risk during turning movements and should therefore be considered in ankle injury research and the aetiology of ankle sprains.


Outcomes of endovascular reconstruction of the inferior vena cava with self-expanding nitinol stents.
Occlusion of the inferior vena cava (IVC) often causes venous claudication, leg swelling, or skin changes. We hypothesized that the outcome of nitinol stents for endovascular reconstruction of the IVC is similar to the outcome reported for steel alloy stents. From the prospective Bern Venous Stent Registry, we investigated technical success, patency rates, and clinical outcome in consecutive patients with endovascular IVC reconstruction. During routine follow-up visits, stent patency was assessed by duplex ultrasound. Clinical outcomes were evaluated using the Bozkaya score, Villalta score, and revised Venous Clinical Severity Score. Of the 62 patients (mean age, 46 ± 18 years), 33 (53%) patients were treated for the post-thrombotic syndrome, 17 (27%) for acute thrombosis, and 12 (19%) for nonthrombotic IVC occlusion. Technical success was achieved in 61 (98%) patients, with a mean of 4.5 ± 1.9 stents (iliac kissing stents in 84%). During follow-up (mean, 21 months), 22 (36%) underwent endovascular reintervention for symptomatic stent stenosis (13 [21%] with complete stent occlusion). Primary, primary assisted, and secondary patency rates at 24 months were 57% (95% confidence interval [CI], 50%-73%), 76% (95% CI, 65%-86%), and 87% (95% CI, 80%-95%), respectively. None developed new ulcers, and all eight patients with venous ulcers at baseline had complete healing. Twenty-nine (48%) patients showed significant clinical improvement, and another 26 (43%) were free from any symptoms or signs of venous hypertension. Patients with post-thrombotic venographic changes of the femoral veins at baseline or a history of thrombosis were more likely to lose primary patency compared with patients with normal leg inflow veins and no history of thrombosis (19 [48%] vs 3 [16%]; P = .02). The clinical outcome of endovascular reconstruction of the IVC with nitinol stents was favorable. However, approximately one-third of the patients required reintervention to maintain stent patency, most likely because of the impaired venous inflow.


Adrenergic nerve fibers in the human fetal sciatic nerve.
The adrenergic innervation was studied in the human sciatic nerve at the gestational age of 16, 17, 18 and 21 weeks. Formaldehyde-induced catecholamine fluorescence, tyrosine hydroxylase (TH) and neuropeptide Y (NPY) peroxidase-antiperoxidase immunohistochemistry methods were used. At the gestational age of 16, 17 and 18 weeks no adrenergic or NPY-positive nerve fibers were seen. At 21 weeks both fluorescence microscopy and TH immunohistochemistry showed adrenergic nerve fibers around arterioles in the epiperineurium and single nerve fibers in the endoneurium not related to blood vessels. The number of adrenergic nerve fibers appeared to be higher in the sciatic than in the tibial segment of the nerve. At this age, as at earlier stages of gestation, no NPY-positive nerve fibers were seen either in the epiperineurium or in the endoneurium. The results suggest that adrenergic nerve fibers may be associated with the epiperineurial blood vessels in the human sciatic nerve, and that the innervation starts to develop between 18 and 21 weeks of gestational age.


Condensation of DNA in situ in metaphase chromosomes induced by intercalating ligands and its relationship to chromosome banding.
Interactions of certain intercalating cationic ligands with nucleic acids result in the formation of products that undergo condensation and agglomeration; this transition in solution can be monitored by light-scatter measurements. In the present study, using such intercalators as the antitumor drug mitoxantrone or fluorochromes acridine orange and quinacrine, we induced condensation of DNA in situ in Chinese hamster chromosomes. The in situ products scattered light and could be detected by darkfield- or phase-contrast microscopy. In the darkfield the complexes had a characteristic granular appearance and often generated a banding pattern on the chromosomes. In contrast, condensation of DNA in situ by the nonintercalating polyvalent cations (Co3+, spermine4+), while enhancing the chromosome's image contrast, did not produce the granular products or the banding. The condensation of free DNA, single or double stranded, natural or synthetic, the latter of various base composition and configuration, was also measured in solution. The condensation in solution and in situ was observed at similar concentrations of the respective ligands. The intercalating dye ethidium bromide, which did not condense DNA in solutions of moderate and high ionic strength, also did not generate the granular products or banding on chromosomes. The data also show that both base composition and configuration are important factors in determining the sensitivity of DNA to condensation by particular intercalating ligands. The studies suggest that the phenomenon of DNA condensation by intercalating dyes, which shows a high degree of specificity with respect to primary and secondary structures of DNA, may be associated with mechanisms of chromosome banding induced by the intercalating thiazine dyes in Giemsa staining or by quinacrine. Observation of chromosome banding based on light-scatter detection in darkfield microscopy allows the study of interactions between DNA and the ligands that neither fluoresce nor generate colored products. This principle of chromosome "counter-staining" can be explored by flow cytometry.


Screening of the prognostic targets for breast cancer based co-expression modules analysis.
The purpose of the present study was to screen the prognostic targets for breast cancer based on a co-expression modules analysis. The microarray dataset GSE73383 was downloaded from the Gene Expression Omnibus (GEO) database, including 15 breast cancer samples with good prognosis and 9 breast cancer samples with poor prognosis. The differentially expressed genes (DEGs) were identified with the limma package. The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Furthermore, the co‑expression analysis of DEGs was conducted with weighted correlation analysis. The interaction associations were analyzed with the Human Protein Reference Database and BioGRID. The protein‑protein interactions (PPI) network was constructed and visualized by Cytoscape software. A total of 491 DEGs were identified in breast cancer samples with poor prognosis compared with those with good prognosis, and they were enriched in 85 GO terms and 4 KEGG pathways. 368 DEGs were co‑expressed with others, and they were clustered into 10 modules. Module 6 was the most relevant to the clinical features, and 21 genes and 273 interaction pairs were selected out. Abnormal expression levels of required for meiotic nuclear division 5 homolog A (RMND5A) and angiopoietin‑like protein 1 (ANGPTL1) were associated with a poor prognosis. It was indicated that SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily D, member 1, SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily D, member 1, dihydropyrimidinase‑like 2, RMND5A and ANGPTL1 were potential prognostic markers in breast cancer, and the cell cycle may be involved in the regulation of breast cancer.


Comparative imaging of structure and metabolites in tumours.
A novel technique for metabolic imaging using quantitative bioluminescence and single photon imaging was used to measure the distribution of ATP and lactate in two types of human melanoma xenografts with different radiobiologically hypoxic cell fractions (MF: 45 +/- 17% and EE: 6 +/- 3%; mean +/- SD). The tumours were s.c. grown in nude mice and were used for measurement at volumes of 153-3072 mm3. For metabolic imaging the rapidly frozen tumours were serially sectioned, and each cryosection was brought into contact with a frozen bioluminescent enzyme cocktail using a specially designed glass sandwich system. After thawing section and cocktail the luminescence was started, and light was emitted from the section with an intensity that is proportional to the local metabolite concentration. The photons were imaged directly through a microscope and an imaging photon counting system. A clear-cut correlation was documented between the distribution of relatively high ATP concentrations and of viable cell regions. The data obtained showed lower ATP concentrations in the tumour centres compared to the periphery, whereas lactate was inversely distributed within the melanomas. There was a trend towards a decrease in ATP with increasing tumour size in central, but not in peripheral, parts of both melanoma types. The concentration of neither ATP nor lactate measured in corresponding tumour areas showed differences related to the melanoma type. Thus, these two metabolites did not reflect the difference in the radiosensitivity of these tumours.


Interfacial band offset engineering with barium-doping towards enhanced performance of all inorganic CsPbI2Br perovskite solar cells.
This study investigates the incorporation of Ba2+ at a low concentration into CsPbI2Br, resulting in the formation of mixed CsPb1-xBaxI2Br perovskite films. Photovoltaic devices utilizing these Ba-doped CsPbI2Br (Ba-CsPbI2Br) perovskite films achieved a higher stabilized power conversion efficiency of 14.07% compared to 11.60% for pure CsPbI2Br films. First-principles density functional theory calculations indicate that the improved device performance can be attributed to the efficient transport of conduction electrons across the interface between Ba-CsPbI2Br and the TiO2 electron transporting layer (ETL). The Ba-CsPbI2Br/TiO2 interface exhibits a type-II staggered band alignment with a smaller conduction band offset (CBO) of 0.25 eV, in contrast to the CsPbI2Br/TiO2 interface with a CBO of 0.48 eV. The reduced CBO at the Ba-CsPbI2Br/TiO2 interface diminishes the barrier for conduction electrons to transfer from the Ba-CsPbI2Br layer to the TiO2 layer, facilitating efficient charge transport.


A 17-Year-Old Girl With Acute Onset of Hemiparesis.
The presentation of acute-onset hemiparesis in a teenager can be challenging and offers a wide differential diagnosis. We discuss the approach to the patient (which should begin with thorough history taking and physical examination) and advanced imaging as directed by the patient's signs and symptoms. We report the case of an otherwise well 17-year-old girl who presented to the pediatric emergency department with a 2-day history of left-sided weakness and difficulty ambulating. Her eventual diagnosis of Balo concentric sclerosis, a rare form of multiple sclerosis, is discussed.


Superficial brachial artery crossing over the ulnar and median nerves from posterior to anterior: embryological significance.
A rare variation of the superficial brachial artery was found in the right arm of an 82-year-old male cadaver in student dissection practice. In this case, the axillary artery passed normally between the medial and lateral roots of the median nerve and then bifurcated into a large superficial brachial artery and the deep brachial artery (A. brachialis profunda). The superficial brachial artery passed medially to the ulnar nerve and then crossed over to take a lateral course to the median nerve at the midpoint of the upper arm. It finally divided into the radial and ulnar arteries at the cubital fossa. The deep brachial artery terminated as the inferior ulnar collateral artery. These findings indicate that the present variant was a well-developed medial type of the superficial brachial artery that gave off the ulnar and radial arteries. The anatomical and embryological significance of the findings are discussed.


Cardiovascular beta-adrenoceptor sensitivity of undernourished subjects.
1. Eleven normal-weight male subjects (weight/height2 (W/H2) 19.0-22.5) from a good socio-economic background and on ad lib. food intake, and eight undernourished male labourers (W/H2 16.4-18.6) on low energy intakes, were studied. 2. Comparison of cardiovascular responses to increasing single doses of the beta-agonist, isoproterenol, showed a significantly greater positive chronotropic dose response in the undernourished subjects. 3. Cardiovascular responses to head-up tilt were similar in both the normal-weight and undernourished subjects. 4. Undernourished individuals may show an increase in beta-adrenoceptor sensitivity which may be akin to a denervation type of supersensitivity as a result of a nutrition-related reduction in sympathetic activity.


Role of minimization of chemical distances between amino acids in the evolution of the genetic code.
The allocation of codons in the genetic code makes possible a moderate minimization of the chemical distances between pairs of neighboring amino acids in the code. However, the code is neither a global nor a local optimum with respect to distance minimization. These findings do not support the physicochemical postulate that distance minimization was a major factor shaping the evolution of the genetic code. They agree with the coevolution theory, which proposes that genetic code evolution was predominantly determined by the concession of codons from precursor to product amino acids in an expansion of the code to accommodate new varieties of amino acids, with distance minimization playing a subsidiary role in deciding the choice of codons to be acquired by the product amino acids from the codon domains of the precursor amino acids.


From Canadian Surgeon to Chinese Martyr: Dr. Norman Bethune and the Making of a Medical Folk Hero.
This paper reexamines the public memory of Canadian surgeon Norman Bethune. In 1938, Bethune traveled to China to serve at the communist front and to treat soldiers fighting against the invading Japanese army. Throughout China, Bethune is a household name and a communist icon. Back in Canada, however, his name does not evoke the same ubiquity. While Canadians remembered Bethune through biographies, a film, statues, and a small museum, his story in the Anglophone world is confined primarily to the telling of distant history. To explain Bethune's greater notoriety and public presence in China, this essay first turns our attention to Chinese sources that mythologized Bethune's death in 1939. The essay then revisits Chinese propaganda that established Bethune as a lasting political symbol during the Cultural Revolution in the 1960s and 1970s. These national efforts show how a volunteer surgeon such as Bethune became such an important figure in a remote foreign country. China's Communist Party turned Bethune's death into a political event to rally support for their war of resistance against Japan. Later, during the tumultuous period of the Cultural Revolution, Mao Zedong used Bethune to symbolize unwavering service and loyalty to leader and party. This essay utilizes primary materials in McGill's Osler Library and commentary from the field of memory studies to contextualize Bethune and to situate him within the broader narrative of political education that arose in China during the Cultural Revolution. A layered interpretation of Bethune - as doctor, martyr, and symbolic hero - slowly emerges. Political forces in China transformed his memory into legacy and carry this complicated figure into the present day.


Potential role for the hypothalamo-pituitary-adrenal axis in the conditioned reinforcer-induced reinstatement of extinguished cocaine seeking in rats.
We have previously reported that pretreatment with the corticosterone synthesis inhibitor ketoconazole blocks the electric foot-shock-induced reinstatement of cocaine-seeking behavior in rats, suggesting a potential role for the hypothalamo-pituitary-adrenal (HPA) axis in this animal model of relapse. This experiment was designed to investigate whether or not ketoconazole would also inhibit the reinstatement of cocaine seeking induced by the presentation of a conditioned reinforcer. The effects of the corticotropin-releasing hormone 1 (CRH1) receptor antagonist CP-154,526 were also investigated to further determine the involvement of the HPA axis in this behavior. Adult male rats were implanted with jugular catheters and trained to self-administer cocaine (0.25 mg/kg per infusion) during daily 2-h sessions. During training, cocaine delivery was paired with the presentation of a tone and the illumination of a house light. Once a stable baseline of cocaine self-administration was observed, lever pressing was extinguished to less than 20% of baseline rates. During reinstatement testing, responding by rats in the contingent group resulted in the presentation of the conditioned reinforcer (i.e., the house light and tone previously paired with self-administered cocaine). Rats in the non-contingent group were presented with the tone/house light compound stimulus once every 5 min, regardless of responding. Rats were pretreated with ketoconazole (25 mg/kg, i.p.) or CP-154,526 (20 mg/kg, i.p.) 30 min prior to testing for reinstatement with the contingent presentation of the conditioned reinforcer to determine the role for the HPA axis in this behavior. The response-contingent presentation of the conditioned reinforcer reliably reinstated extinguished cocaine-seeking behavior, while the non-contingent presentation of the same stimulus did not. Increases in plasma corticosterone were evident during cocaine self-administration as well as during extinction and reinstatement testing. However, while plasma corticosterone returned to basal levels by the end of the session during extinction, it remained elevated through the end of the session during reinstatement. Pretreatment with ketoconazole reversed the conditioned reinforcer-induced reinstatement of extinguished cocaine-seeking behavior and also attenuated the conditioned increases in plasma corticosterone observed during reinstatement. Pretreatment with CP-154,526 resulted in a similar decrease in cocaine seeking. These data suggest a potential role for the HPA axis in the ability of environmental cues to stimulate cocaine-seeking behavior.


Swallowing-related activities of respiratory and non-respiratory neurons in the nucleus of solitary tract in the rat.
Swallowing-related activity was examined in respiratory (n = 60) and non-respiratory (n = 82) neurons that were located in and around the nucleus of the solitary tract (NTS) in decerebrated, neuromuscularly blocked and artificially ventilated rats. Neurons that were orthodromically activated by electrical stimulation of the superior laryngeal nerve (SLN) were identified, and fictive swallowing was evoked by SLN stimulation. The pharyngeal phase of swallowing was monitored by hypoglossal nerve activity. Two types of non-respiratory neurons with swallowing-related bursts were identified: 'early' swallowing neurons (n = 24) fired during periods of hypoglossal bursts, and 'late' swallowing neurons (n = 8) fired after the end of hypoglossal bursts. The remaining non-respiratory neurons were either suppressed (n = 21) or showed no change in activity (n = 29) during swallowing. On the other hand, respiratory neurons with SLN inputs included 56 inspiratory and four expiratory neurons. Inspiratory neurons were classified into two major types: a group of neurons discharged simultaneously with hypoglossal bursts (type 1 neurons, n = 19), while others were silent during bursts but were active during inter-hypoglossal bursts when swallowing was provoked repetitively (type 2 neurons, n = 34). Three of the expiratory neurons fired during hypoglossal bursts. Many of the swallowing-related non-respiratory neurons and the majority of the inspiratory neurons received presumed monosynaptic inputs from the SLN. Details of the distribution and firing patterns of these NTS neurons, which have been revealed for the first time in a fictive swallowing preparation in the rat, suggest their participation in the initiation, pattern formation and mutual inhibition between swallowing and respiration.


Clinical features of patients with posterior cortex epilepsies and predictors of surgical outcome.
Posterior cortex epilepsies (PCEs) encompass a group of epilepsies originating from the occipital, parietal, or occipital border of the temporal lobe, or from any combination of these regions. When their seizures are refractory to pharmacologic treatment, these patients are usually referred for surgery. The aim of our study was to analyze clinical characteristics of all PCE patients referred for surgery from 1994 to 2003, and to search for predictors of surgical outcome. We performed a retrospective analysis of clinical and laboratory data from 81 consecutive refractory PCE patients referred for surgery. Surgical and nonsurgical groups of patients were compared, and detailed analyses of all variables of the surgical cases were performed in the search for predictors of seizure outcome. Risk factors for PCEs included gliosis (34.56%), malformations of cortical development (33.33%), tumors (8.64%), brain trauma (3.70%), Sturge-Weber disease (4.93%), vascular malformations (3.70%), family history of epilepsy (3.70%), history of CNS infections (2.46%), and low IQ (2.46%). Of the 81 patients, 44 were submitted to surgery at the time of the completion of this study. Surgical treatment was highly effective in improving seizures (p<0.001) when compared with previous pharmacologic treatment alone. Twenty-eight (65.11%) patients became seizure free after surgery versus none in the nonsurgical group. Regarding outcome predictors, patients with shorter duration of epilepsy and those without neurologic abnormalities on clinical examination had higher chances of favorable evolution. Surgical treatment is effective for the treatment of PCEs and superior to pharmacologic therapy alone. In our series, shorter duration of epilepsy and normal neurologic examination were the only independent variables that predicted better surgical outcome.


Hydrogel and Platelet-Rich Plasma Combined Treatment to Accelerate Wound Healing in a Nude Mouse Model.
Platelet-rich plasma (PRP) contains high concentrations of growth factors involved in wound healing. Hydrogel is a 3-dimensional, hydrophilic, high-molecular, reticular substance generally used as a dressing formulation to accelerate wound healing, and also used as a bio-applicable scaffold or vehicle. This study aimed to investigate the effects of PRP and hydrogel on wound healing, in combination and separately, in an animal wound model. A total of 64 wounds, with 2 wounds on the back of each nude mouse, were classified into 4 groups: a control group, a hydrogel-only group, a PRP-only group, and a combined-treatment group. All mice were assessed for changes in wound size and photographed on scheduled dates. The number of blood vessels was measured in all specimens. Immunohistochemical staining was used for the analysis of vascular endothelial growth factor (VEGF) expression. Differences in the decrease and change in wound size in the combined-treatment group were more significant than those in the single-treatment groups on days 3, 5, 7, and 10. Analysis of the number of blood vessels through histological examination showed a pattern of increase over time that occurred in all groups, but the combined-treatment group exhibited the greatest increase on days 7 and 14. Immunohistochemical staining showed that VEGF expression in the combined-treatment group exhibited its highest value on day 7. This experiment demonstrated improved wound healing using a PRP-hydrogel combined treatment compared to either treatment individually, resulting in a decrease in wound size and a shortening of the healing period.


Downregulation of miR-377 Promotes Oral Squamous Cell Carcinoma Growth and Migration by Targeting HDAC9.
microRNAs are the post-transcriptional regulators implicated in the initiation and progression of various cancer types, including oral squamous cell carcinoma (OSCC). Here, we investigated the role of miR-377 in OSCC tumorigenesis. miR-377 expression was reduced in OSCC samples and cell line (UPCI-SCC-116), and was associated with patient survival. In vitro restoration of miR-377 repressed cell growth, induced apoptosis, and reduced cell migration. We identified HDAC9 as a target of miR-377 and found miR-377 to regulate HDAC9 and its pro-apoptotic target, NR4A1/Nur77. Our findings show that miR-377 targets HDAC9 pathway in OSCC, suggesting that miR-377-HDAC9 axis may provide a novel therapeutic target for OSCC therapy.


Consequences of interspecies antennal imaginal disc transplantation on organization of olfactory glomeruli and pheromone blend discrimination.
The antennal imaginal disc was transplanted between male larvae of two different heliothine moth species, Heliothis virescens (HV) and Helicoverpa zea (HZ). Males of these species respond to distinct pheromone blends, have different peripheral and central olfactory neuron specificities, as well as distinct arrangements of antennal lobe olfactory glomeruli, in the specialized male macroglomerular complex (MGC). After pupal development and adult eclosion, unilateral (with one antennal disc left intact) and bilateral antennal transplant males were assayed in a wind tunnel to both species' pheromone blends to determine their ability to discriminate between the two signals. The postmetamorphic developmental effects of interspecific transplantation upon the primary olfactory centers in the moth brain were then examined in these same individuals. Behavioral tests showed that both types of unilateral transplant continued to exhibit upwind anemotactic flight to the normal recipient blend with occasional flights to the donor blend. In contrast, bilateral transplants preferred the HV pheromone blend regardless of the direction of transplant, with some males of each type also responding to the HZ blend. Neuroanatomic evaluation of the MGC revealed that the donor arrangement of MGC glomeruli was induced in 73% HZ donor to HV recipient transplants and 56% of the reciprocal transplant. Surprisingly, several V-Z bilateral transplant males responded to both HV and HZ pheromone blends and had two HV MGC structures. This behavioral outcome was unexpected, because responses to the HV blend are mediated by inputs that are normally antagonistic to HZ males and the normal HV antenna lacks olfactory receptor neurons capable of responding to the essential minor pheromone component of the HZ blend. These data indicate a plasticity in developmental pathways regulating the expression of peripheral olfactory receptor neurons and in the glomerular processing of species-specific olfactory information.


Synthesis and Analysis of the Structure, Diffusion and Cytotoxicity of Heterocyclic Platinum(IV) Complexes.
We have developed six dihydroxidoplatinum(IV) compounds with cytotoxic potential. Each derived from active platinum(II) species, these complexes consist of a heterocyclic ligand (HL) and ancillary ligand (AL) in the form [Pt(HL)(AL)(OH)2](2+), where HL is a methyl-functionalised variant of 1,10-phenanthroline and AL is the S,S or R,R isomer of 1,2-diaminocyclohexane. NMR characterisation and X-ray diffraction studies clearly confirmed the coordination geometry of the octahedral platinum(IV) complexes. The self-stacking of these complexes was determined using pulsed gradient stimulated echo nuclear magnetic resonance. The self-association behaviour of square planar platinum(II) complexes is largely dependent on concentration, whereas platinum(IV) complexes do not aggregate under the same conditions, possibly due to the presence of axial ligands. The cytotoxicity of the most active complex, exhibited in several cell lines, has been retained in the platinum(IV) form.


A novel nomogram and risk classification system predicting the overall survival of patients with papillary renal cell carcinoma after nephrectomy: A population-based study.
Papillary renal cell carcinoma (pRCC) is the largest histologic subtype of non-clear-cell RCC. To date, there is no reliable nomogram to predict the prognosis of patients with pRCC after nephrectomy. We aimed to first establish an effective nomogram to predict the overall survival (OS) of patients with pRCC after nephrectomy. A total of 3,528 eligible patients with pRCC after nephrectomy were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The patients were randomized into the training cohort (n = 2,472) and the validation cohort (n = 1,056) at a 7:3 ratio. In total, 122 real-world samples from our institute (titled the AHMU-pRCC cohort) were used as the external validation cohort. Univariate and subsequent multivariate Cox regression analyses were conducted to identify OS-related prognostic factors, which were further used to establish a prognostic nomogram for predicting 1-, 3-, and 5-year OS probabilities. The performance of the nomogram was evaluated by using the concordance index (C-index), receiver operating characteristic curve (ROC), calibration plot, and decision curve analysis (DCA). Multivariate Cox analysis showed that age, race, marital status, TNM stage, tumor size, and surgery were significant OS-related prognostic factors. A prognostic model consisting of these clinical parameters was developed and virtualized by a nomogram. High C-index and area under the ROC curve (AUC) values of the nomogram at 1, 3, and 5 years were found in the training, validation, and AHMU-pRCC cohorts. The calibration plot and DCA also showed that the nomogram had a satisfactory clinical application value. A risk classification system was established to risk-stratify patients with pRCC. Based on a large cohort from the public SEER database, a reliable nomogram predicting the OS of patients with pRCC after nephrectomy was constructed, which could optimize the survival assessment and clinical treatment.


What Polish hospital healthcare workers and lay persons know about counterfeit medicine products?
To report on Polish hospital health care workers' and lay persons' knowledge about counterfeit medicine products. Cross-sectional design was used. Two types of questionnaire survey about counterfeit medicine, separate for health care professionals and lay persons were completed by 201 physicians and nurses, and 450 adult Polish residents between October 2008 and January 2009. Physicians and nurses working in hospitals are more aware of counterfeit medicine than lay persons and more often notice the presence of drugs from unknown sources. Nearly 90% of physicians, 80% of nurses, and more than 40% of representatives of the lay persons had heard about the possibility of importing illegal medicine from Ukraine or China. The majority of medical workers does not know the procedure for reporting suspicious medicine and do not warn their patients against purchasing medicine from unknown sources. Increase education of nurses and physicians about counterfeit medicine particularly including the procedure of reporting suspicious medicine from unknown sources. In practice, reinforce a role of nurses and physicians in warning their patients against purchasing medicine from unknown sources and educate them about possible health hazards and life risks.


Single-chain lambda Cro repressors confirm high intrinsic dimer-DNA affinity.
The overall affinity of the bacteriophage lambda Cro repressor for its operator DNA site is limited by dimer dissociation at submicromolar concentrations. Since Cro dimer-operator complexes form at nanomolar concentrations of Cro subunits where free dimers are rare, these dimers must bind with compensating high affinities. Previous studies of the covalent dimer Cro V55C suggest little change in DNA binding affinity even though the dimeric species is quantitatively populated; this is an apparent contradiction to the expectation of high intrinsic dimer-DNA affinity. In contrast to the disulfide linkage at the center of the dimer interface in Cro V55C, polypeptide linkers that join the two subunits allow single-chain Cro repressors to bind operator DNA with picomolar affinities. A series of five single-chain Cro repressors have been expressed from fused tandem cro genes. Each contains a peptide linker of 8-16 hydrophilic residues that connects the C-terminus of one subunit to the N-terminus of the next. All bind to operator DNA with at least 100-fold higher affinity than Cro V55C. Proteins containing the longest and shortest linkers have been purified and characterized in detail. Both exhibit similar CD spectra to wild-type Cro and enhanced thermal stability. Sedimentation equilibrium experiments show that single-chain Cro repressors do not associate at concentrations up to 30 microM. The rate of dissociation of Cro-DNA complexes is almost unchanged by covalent linkage. Biophysical characterization of Cro variants such as these, where DNA binding is uncoupled from subunit assembly, is necessary for a quantitative understanding of the structural and energetic determinants of DNA recognition in this simple model system.


NMR assignments of sparsely labeled proteins using a genetic algorithm.
Sparse isotopic labeling of proteins for NMR studies using single types of amino acid (15N or 13C enriched) has several advantages. Resolution is enhanced by reducing numbers of resonances for large proteins, and isotopic labeling becomes economically feasible for glycoproteins that must be expressed in mammalian cells. However, without access to the traditional triple resonance strategies that require uniform isotopic labeling, NMR assignment of crosspeaks in heteronuclear single quantum coherence (HSQC) spectra is challenging. We present an alternative strategy which combines readily accessible NMR data with known protein domain structures. Based on the structures, chemical shifts are predicted, NOE cross-peak lists are generated, and residual dipolar couplings (RDCs) are calculated for each labeled site. Simulated data are then compared to measured values for a trial set of assignments and scored. A genetic algorithm uses the scores to search for an optimal pairing of HSQC crosspeaks with labeled sites. While none of the individual data types can give a definitive assignment for a particular site, their combination can in most cases. Four test proteins previously assigned using triple resonance methods and a sparsely labeled glycosylated protein, Robo1, previously assigned by manual analysis, are used to validate the method and develop a criterion for identifying sites assigned with high confidence.


Medicare and medicaid spending trends for immunomodulators prescribed for dermatologic conditions.
Immunomodulators are the most expensive prescription medications used in dermatology for chronic skin conditions. Each year, rising costs for immunomodulators pose significant financial burdens on patients and the healthcare system as a whole. Using the Centers for Medicare and Medicaid Services (CMS) we collected Medicare Part D (Medicare-D) and Medicaid spending data for immunomodulators with dermatologic indications or off-label use from 2012-2018. The average annual spending and average annual spending per dosage unit (AASPDU) was calculated for each of the thirteen included medications. Combined Medicare-D and Medicaid spending increased 319.9% from $2.5B in 2012 to $10.6B in 2018, with an average of $6.2B spent annually. For both Medicare-D and Medicaid, adalimumab ($1.8B, $968.8 m), etanercept ($1.4B, $467.5 m), and ustekinumab ($258.8 m, $131.0 m) had the highest overall annual spending. Additionally, ustekinumab ($16,825, $15,576), guselkumab ($10,132, $9,543), and ixekizumab ($4,895, $4,673) had the highest AASPDU for both Medicare-D and Medicaid. Medicare-D and Medicaid spending for immunomodulators has grown substantially (319.9%) from 2012-2018 and is likely to continue to rise. Given this increase in federal spending and continued emergence of new immunomodulators, it is important to learn how we can counteract the trends and reduce future expenses for patients and our healthcare system.


Development of a nomogram for predicting survival of patients with ovarian serous cystadenocarcinoma after based on SEER database.
To develop a survival time prediction model for patients with ovarian serous cystadenocarcinoma after surgery. A retrospective analysis of 5906 postoperative patients with ovarian serous cystadenocarcinoma in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015 was performed. The independent risk factors for long-term survival were analyzed with multivariate Cox proportional hazard regression model. The nomogram of 3-year and 5-year survival was developed by using R language. The receiver operator characteristic (ROC) curve and were used to test the discrimination of the model and the calibration diagram was used to evaluate the degree of calibration of the prediction model. The survival curves was conducted by the risk factors. Cox proportional hazard regression model showed that age, race, histological grade (poorly differentiated and undifferentiated), stage T (T2a, T2b, T2c, T3a, T3b and T3c), and stage M (M1) were independent factors for the prognosis of patients with ovarian serous cystadenocarcinoma after surgery. A nomogram was developed by the R language tool for predicting the 3-year and survival of patients through age, race, histological classification, stage T and stage M. The C-index was 0.688 and the areas under ROC curve of the nomogram for predicting 3-year and 5-year survival were 0.708 and 0.716, respectively. The results of the calibration indicated that the predicted values were consistent with the actual values in the prediction models. The survival time of patients with high-risk factors was shorter than that of patients with low-risk factors (<0.05). The developed nomogram in this study can be used to predict 3-year and 5-year survival of postoperative patients with ovarian serous cystadenocarcinoma, and it may be beneficial to guide clinical treatment.


Genetic Variation in the Renin-Angiotensin System and Diabetic Nephropathy in the Tunisian Population.
The aim of this study was to evaluate the association of ACE, angiotensinogen (AGT) and angiotensin II receptor type I (AGTR1) polymorphisms with diabetic nephropathy (DN) in Tunisians. The study population comprised 236 type 2 diabetic patients: with nephropathy (DN = 47) and without nephropathy (DM = 189). Genotyping of ACE-I/D-rs1799752, ACE-rs4343G>A, AGT-rs5050A>C, AGT-rs 4762C>T, AGT-rs699A>G, and AGTR1-rs5186A>C was performed by PCR-RFLP. Haplotype and statistical analysis were realized using SNP Analyzer2.0 and SPSS20, respectively. Genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for potential confounding factors (age, gender, diabetes duration, hypertension…), an increased risk for DN was associated with mutated alleles of rs4762 (OR = 10.25, p = 0.001), rs699 (OR = 22.21, p < 0.001), and rs5186 (OR = 11.25, p < 0.001). However, mutated alleles of rs1799752 seemed to be protector (OR = 0.41, p = 0.011). Adjusted ORs of DN associated with the ACE haplotype (DA) was (OR = 9.56, p = 0.047) and with the ACE-AGT haplotype (ATADAA) was (OR = 5.38, p = 0.032). This study indicates that common variants in ACE, AGT, and AGTR1 seem to play a role in genetic susceptibility to DN in Tunisian population and provides evidence for a disease haplotype: ATADAA.


Proline and glycinebetaine enhance antioxidant defense and methylglyoxal detoxification systems and reduce NaCl-induced damage in cultured tobacco cells.
Salt stress impairs reactive oxygen species (ROS) and methylglyoxal (MG) detoxification systems, and causes oxidative damage to plants. Up-regulation of the antioxidant and glyoxalase systems provides protection against NaCl-induced oxidative damage in plants. Thiol-disulfide contents, glutathione content and its associated enzyme activities involved in the antioxidant defense and glyoxalase systems, and protein carbonylation in tobacco Bright Yellow-2 cells grown in suspension culture were investigated to assess the protection offered by proline and glycinebetaine against salt stress. Salt stress increased protein carbonylation, contents of thiol, disulfide, reduced (GSH) and oxidized (GSSG) forms of glutathione, and the activity of glutathione-S-transferase and glyoxalase II enzymes, but decreased redox state of both thiol-disulfide and glutathione, and the activity of glutathione peroxidase and glyoxalase I enzymes involved in the ROS and MG detoxification systems. Exogenous application of proline or glycinebetaine resulted in a reduction of protein carbonylation, and in an increase in glutathione redox state and activity of glutathione peroxidase, glutathione-S-transferase and glyoxalase I under salt stress. Neither proline nor glycinebetaine, however, had any direct protective effect on NaCl-induced GSH-associated enzyme activities. The present study, therefore, suggests that both proline and glycinebetaine provide a protective action against NaCl-induced oxidative damage by reducing protein carbonylation, and enhancing antioxidant defense and MG detoxification systems.


The application of epiphenotyping approaches to DNA methylation array studies of the human placenta.
Background : Genome-wide DNA methylation (DNAme) profiling of the placenta with Illumina Infinium Methylation bead arrays is often used to explore the connections between in utero exposures, placental pathology, and fetal development. However, many technical and biological factors can lead to signals of DNAme variation between samples and between cohorts, and understanding and accounting for these factors is essential to ensure meaningful and replicable data analysis. Recently, "epiphenotyping" approaches have been developed whereby DNAme data can be used to impute information about phenotypic variables such as gestational age, sex, cell composition, and ancestry. These epiphenotypes offer avenues to compare phenotypic data across cohorts, and to understand how phenotypic variables relate to DNAme variability. However, the relationships between placental epiphenotyping variables and other technical and biological variables, and their application to downstream epigenome analyses, have not been well studied. Results : Using DNAme data from 204 placentas across three cohorts, we applied the PlaNET R package to estimate epiphenotypes gestational age, ancestry, and cell composition in these samples. PlaNET ancestry estimates were highly correlated with independent polymorphic ancestry informative markers, and epigenetic gestational age, on average, was estimated within 4 days of reported gestational age, underscoring the accuracy of these tools. Cell composition estimates varied both within and between cohorts, but reassuringly were robust to placental processing time. Interestingly, the ratio of cytotrophoblast to syncytiotrophoblast proportion decreased with increasing gestational age, and differed slightly by both maternal ethnicity (lower in white vs. non-white) and genetic ancestry (lower in higher probability European ancestry). The cohort of origin and cytotrophoblast proportion were the largest drivers of DNAme variation in this dataset, based on their associations with the first principal component. Conclusions : This work confirms that cohort, array (technical) batch, cell type proportion, self-reported ethnicity, genetic ancestry, and biological sex are important variables to consider in any analyses of Illumina DNAme data. Further, we demonstrate that estimating epiphenotype variables from the DNAme data itself, when possible, provides both an independent check of clinically-obtained data and can provide a robust approach to compare variables across different datasets.


Purification, pore-forming ability, and antigenic relatedness of the major outer membrane protein of Shigella dysenteriae type 1.
The major outer membrane protein (MOMP), the most abundant outer membrane protein, was purified to homogeneity from Shigella dysenteriae type 1. The purification method involved selective extraction of MOMP with sodium dodecyl sulfate in the presence of 0.4 M sodium chloride followed by size exclusion chromatography with Sephacryl S-200 HR. MOMP was found to form hydrophilic diffusion pores by incorporation into artificial liposome vesicles composed of egg yolk phosphatidylcholine and dicetylphosphate, indicating that MOMP of S. dysenteriae type 1 exhibited significant porin activity. However, the liposomes containing heat-denatured MOMP were barely active. The molecular weight of MOMP found by size exclusion chromatography was 130,000, and in sodium dodecyl sulfate-10% polyacrylamide gel it moved as an oligomer of 78,000 molecular weight. Upon boiling, fully dissociated monomers of 38,000 molecular weight were seen for S. dysenteriae type 1. However, among the four Shigella spp., the monomeric MOMP generated upon boiling ranged from 38,000 to 35,000 in molecular weight. Antibody raised in BALB/c mice immunized with MOMP of S. dysenteriae type 1 reacted strongly with purified MOMP of S. dysenteriae type 1 in an enzyme-linked immunosorbent assay (ELISA). The antibody reacted with whole-cell preparations of S. dysenteriae type 1 in an ELISA, suggesting that MOMP possessed surface components. Moreover, MOMP could be visualized on the bacterial surface by immunoelectron microscopy with anti-MOMP antibody. S. dysenteriae type 1 MOMP-specific immunoglobulin eluted from MOMP bound to a nitrocellulose membrane was found to cross-react with MOMP preparations of S. flexneri, S. boydii, and S. sonnei, indicating that MOMPs were antigenically related among Shigella species. The strong immunogenicity, surface exposure, and antigenic relatedness make MOMP of Shigella species an immunologically significant macromolecule for study.


Postthrombolytic Antiplatelet Use for Patients with Intercerebral Hemorrhage without Extensive Parenchymal Involvement Does Not Worsen Outcome.
It is unclear whether postthrombolytic antiplatelet (AP) therapy after thrombolytic-related hemorrhage without extensive parenchymal involvement (THEPI) affects the clinical outcome. This study explored whether AP administration in patients with THEPI affects short- and long-term outcomes. All of the data for this study were collected from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) registry. Patients with THEPI were assigned to either the AP (AP therapy should be commenced 24 h after intravenous thrombolysis) or AP-naïve groups. THEPI was defined according to European-Australasian Acute Stroke Study II criteria. The 90-day functional outcome, 7-day National Institutes of Health Stroke Scale (NIHSS) score, and 7-day and 90-day mortalities were compared between the AP and AP-naïve groups. Logistic regression analysis wy on the short- and long-term clinical outcomes. Of the 928 patients enrolled from those in the TIMS-China registry (n=1,440), 89 (9.6%) had nonsymptomatic intracerebral hemorrhage (ICH) within 24-36 h after thrombolysis; 33 (37%) of these patients were given AP therapy (AP group) and 56 (63%) were not (AP-naïve group). No significant differences were found for the risk of 7-day aggravated ICH (p=0.998), 7-day NIHSS score (p=0.5491), 7-day mortality [odds ratio (OR)=3.427; 95% confidence interval (95% CI)=0.344-34.160; p=0.294], 90-day mortality (OR=0.788, 95% CI=0.154-4.040, p=0.775), or modified Rankin score 5 or 6 at 90-days (OR=1.108, 95% CI=0.249-4.928, p=0.893) between the AP and AP-naïve groups after THEPI. Early administration of postthrombolytic AP therapy after THEPI does not worsen either the short- or long-term outcome. AP therapy may be a reasonable treatment option for patients with THEPI to reduce the risk of ischemic stroke recurrence.


Imaging features of central nervous system fungal infections.
Fungal infections of the central nervous system (CNS) are rare in the general population and are invariably secondary to primary focus elsewhere, usually in the lung or intestine. Except for people with longstanding diabetes, they are most frequently encountered in immunocompromised patients such as those with acquired immunodeficiency syndrome or after organ transplantation. Due to the lack of inflammatory response, neuroradiological findings are often nonspecific and are frequently mistaken for tuberculous meningitis, pyogenic abscess or brain tumor. Intracranial fungal infections are being identified more frequently due to the increased incidence of AIDS patients, better radiological investigations, more sensitive microbiological techniques and better critical care of moribund patients. Although almost any fungus may cause encephalitis, cryptococcal meningoencephalitis is most frequently seen, followed by aspergillosis and candidiasis. The biology, epidemiology and imaging features of the common fungal infections of the CNS will be reviewed. The radiographic appearance alone is often not specific, but the combination of the appropriate clinical setting along with computed tomography or magnetic resonance may help to suggest the correct diagnosis.


Finger loop inhibitors of the HCV NS5B polymerase: discovery and prospects for new HCV therapy.
The hepatitis C virus (HCV) infects millions of people wzorldwzide and currently available therapies suffer from limited efficacy and severe side effects. This review describes the discovery of a novel class of non-nucleoside HCV non-structural protein 5B (NS5B) polymerase inhibitors that inhibit the replication of viral RNA by binding to an allosteric site on the enzyme. Initial lead compounds based on a benzimidazole scaffold were optimized yielding novel indole derivatives with sub-micromolar activity in a cell-based replicon assay. X-ray crystallographic studies suggest that inhibitor binding interferes with the conformational movements of the protein that are necessary for enzyme activity. Finger loop inhibitors of HCV NS5B show potential for the development of novel anti-HCV therapeutics.


Galactomannan antigen detection in the diagnosis of invasive aspergillosis.
Invasive aspergillosis is a serious and lethal infection among immunocompromised patients, with reported mortality rates as high as 74-92%. The high mortality is related to the severe immunosuppression experienced by these patients as well as the difficulties for physicians in arriving at a timely diagnosis. Definitive diagnostic procedures (tissue biopsy for histopathology and culture) are often precluded by severe cytopenias and coagulation abnormalities. The development of minimally invasive, nonculture diagnostic methods is a major advance in the early diagnosis of invasive aspergillosis. Galactomannan is a heteropolysaccharide (mannan core and side residues of galactofuranosyl units) present in the cell wall of Aspergillus spp. The double sandwich enzyme immunoassay, which detects galactomannan in serum samples, has been available in Europe for almost a decade and in the USA since May 2003, for the diagnosis of invasive aspergillosis. However, availability of the double galactomannan enzyme immunoassay is center variable in the USA and, although its analytical performance in the diagnosis of invasive aspergillosis is well documented, its routine use in clinical practice is limited. As an adjunct in the diagnosis and management of invasive aspergillosis, incorporation of the galactomannan enzyme immunoassay into clinical trials will help to further define its role.