Children and toxic substances: confronting a major public health challenge.
Despite early warnings of lead toxicity, until recently this metal was added to a variety of consumer and industrial products. Today, thousands of children in the United States, and probably tens of thousands more worldwide, are suffering the consequences of exposure to lead. The lead story looms as major public policy failure that will eventually cost billions of dollars to remedy. Little is known about the toxicological properties of the more than 70,000 chemicals in commerce. Consequently, it seems likely that other "leads" are finding their way into our food, water, and air. Inadequate testing of chemicals to which the public is exposed presents a serious public health risk, particularly to children whose nervous systems are still developing. The Federal government should expand toxicological testing programs for existing and new chemicals, requiring increased developmental toxicological, particularly neurotoxicological, testing of chemicals to which the public is significantly exposed. In keeping with the concept of full-cost pricing, the costs of these tests should be incurred by the manufacturer, not the government, and should be considered a routine cost of product development.


The discovery of ubiquitin-dependent proteolysis.
In early 1980, Irwin A. Rose, Avram Hershko, and Aaron Ciechanover published two papers in PNAS that reported the astounding observation that energy-dependent intracellular proteolysis was far more complicated than the previously accepted models of lysosomal proteolysis or the action of ATP-dependent proteases such as bacterial lon. In fact, it has turned out to be even more complicated than they could have suspected. The general model of covalently attaching a small protein as a targeting signal has proved to be every bit as important to eukaryotic cells as the better understood modifications such as phosphorylation or acetylation. The key player in this modification, a small protein called ubiquitin (APF-1 in these papers), is the founding member of a large family of proteins containing the beta-grasp fold and is used as a posttranslational targeting signal to modify the structure, function, and/or localization of other proteins. The story of this discovery is a textbook example of the confluence of intellectual curiosity, unselfish collaboration, chance, luck, and preparation.


Anthropometric, biochemical and clinical parameters in climacteric yoga practitioners.
This study aimed to evaluate anthropometric, biochemical and clinical parameters in climacteric yoga practitioners. This study investigated 108 climacteric women. We recruited 28 women between 40 and 65 years old who started yoga practices in premenopause and had already practiced for at least 5 years. As controls, we selected 30 physical activity (PA) practitioners who had practiced for at least 5 years and 50 sedentary women in the same age range. We conduced anthropometric, biochemical and blood pressure measurements. The yoga group had significantly lower fasting blood glucose than the PA practitioners and sedentary women. Yoga practitioners also had lower weight, body mass index, waist circumference, body fat percentage and waist-to-height ratio; higher levels of high-density lipoprotein cholesterol; lower levels of triglycerides, insulin, Homeostasis Model Assessment of Insulin Resistance, uric acid, apolipoprotein B and high-sensitivity C-reactive protein; and lower frequency of metabolic syndrome, lipid accumulation product, visceral adiposity index and systolic blood pressure than the sedentary women. Yoga practitioners had lower glucose serum concentrations than the PA practitioners and sedentary women. Overall, the yoga group also had better anthropometric, biochemical and clinical variables than the other groups. Although further investigation is required, yoga practice in premenopause seems to be beneficial for women when they reach menopause.


Mechanisms underlying the differential control of blood flow in the renal medulla and cortex.
There is much evidence that the medullary circulation plays a key role in regulating renal salt and water handling and, accordingly, the long-term level of arterial pressure. It has also recently become clear that various regulatory factors can affect medullary blood flow (MBF) differently from cortical blood flow (CBF). It appears likely that the influence of hormonal and neural factors on the control of arterial pressure is mediated partly through their impact on MBF. In this review, we focus on the mechanisms underlying the differential control of MBF and CBF, particularly the relative insensitivity of MBF to vasoconstrictors such as angiotensin II, endothelin-1 and the sympathetic nerves. The vascular architecture of the kidney appears to be arranged in a way that protects the renal medulla from ischaemic insults, with juxtamedullary arterioles, the source of MBF, having larger calibre than their counterparts in other kidney regions. Indeed, recent studies using vascular casting methodology suggest that juxtamedullary glomerular arterioles are not the chief regulators of MBF, which is consistent with the idea that outer medullary descending vasa recta play a key role in MBF control. Release of vasoactive paracrine factors such as nitric oxide and various eicosanoids from the vascular endothelium, and probably also from the tubular epithelium, appear to differentially modulate responses of MBF and CBF to hormonal and neural factors. The prevailing intrarenal hormonal milieu and existing haemodynamic conditions also appear to strongly modulate these responses, indicating that multiple control systems interact to regulate regional kidney blood flow at an integrative level.


Adverse event reporting: lessons learned from 4 years of Florida office data.
Patient safety regulations and medical error reporting systems have been at the forefront of current health care legislature. In 2000, Florida mandated that all physicians report, to a central collecting agency, all adverse events occurring in an office setting. To analyze the scope and incidence of adverse events and deaths resulting from office surgical procedures in Florida from 2000 to 2004. We reviewed all reported adverse incidents (the death of a patient, serious injury, and subsequent hospital transfer) occurring in an office setting from March 1, 2000, through March 1, 2004, from the Florida Agency for Health Care Administration. We determined physician board certification status, hospital privileges, and office accreditation via telephone follow-up and Internet searches. Of 286 reported office adverse events, 77 occurred in association with an office surgical procedure (19 deaths and 58 hospital transfers). There were seven complications and five deaths associated with the use of intravenous sedation or general anesthesia. There were no adverse events associated with the use of dilute local (tumescent) anesthesia. Liposuction and/or abdominoplasty under general anesthesia or intravenous sedation were the most common surgical procedures associated with a death or complication. Fifty-three percent of offices reporting an adverse incident were accredited by the Joint Commission on Accreditation of Healthcare Organizations, American Association for Accreditation of Ambulatory Surgical Facilities, or American Association for Ambulatory Health Care. Ninety-four percent of the involved physicians were board certified, and 97% had hospital privileges. Forty-two percent of the reported deaths were delayed by several hours to weeks after uneventful discharge or after hospital transfer. Requiring physician board certification, physician hospital privileges, or office accreditation is not likely to reduce office adverse events. Restrictions on dilute local (tumescent) anesthesia for liposuction would not reduce adverse events and could increase adverse events if patients are shifted to riskier approaches. State and/or national legislation establishing adverse event reporting systems should be supported and should require the reporting of delayed deaths.


Effect of parathyroidectomy on T cell functions in patients with primary hyperparathyroidism.
The notion that parathyroid hormone (PTH) can serve as an immunomodulator was examined. T cell function tests were performed in 3 patients with primary hyperparathyroidism before and 1 month after parathyroidectomy (PTX). Three normal volunteers, age and sex matched, were used as controls. One patient with lipoma of the neck was also examined before and after surgical removal of the lesion. In the primary hyperparathyroidism patients the total T cells were lower, the suppressors were higher and the helper to suppressor ratio was significantly lower than in control subjects. The lectin-stimulated lymphocyte transformation was significantly inhibited. All these abnormalities were restored to normal after PTX. Depressed lymphocyte activity was found also in the patient with lipoma. However, no change occurred after surgery. These results support the assumption that excess blood levels of PTH may have an immunosuppressive effect.


[Clinical relevance of immunoscintigraphy with 99mTc-labelled anti-CEA antigen-binding fragments in the follow-up of patients with colorectal carcinoma. Assessment of surgical resectability with a combination of conventional imaging methods].
Conventional imaging modalities (e.g. ultrasound, computed tomography [CT] and magnetic resonance [MRI]) are used in the routine follow-up of patients with colorectal carcinoma. But they have only limited diagnostic reliability. This study was undertaken to evaluate immunoscintigraphy (IS) with 99mTc-labelled anti-CEA antigen-binding fragments (CEA-Scan) alone or combined with conventional imaging methods. 22 patients, operated on for colorectal carcinoma and suspected of having a recurrence, underwent scintigraphy with CEA-scan and whole-body single-photon emission computed tomography (SPECT). All results were compared with those by computed tomography (CT) and, in 19 of the patients, with histological findings (surgical specimen or biopsy). The potential influence of the scintigraphic results on surgical management was analysed retrospectively with respect to the preoperative estimate of tumour resectability. Lesion-based sensitivity of IS was 94%, diagnostic accuracy 92%, both being unrelated to the CEA-serum level. When CT and IS were concordant regarding resectability, this estimate was correct in all instances. But in case of discordance the results of IS were verified operatively in 88% of cases. In no patient was there measurable immune reaction with formation of human-mouse-antibodies (HAMA). These results indicate that IS together with SPECT can achieve reliable and sensitive localisation of tumour lesions. CEA-Scan does not, contrary to other murine antibodies, cause the formation of HAMA. The combination of IS with conventional imaging techniques can improve noninvasively the estimate of surgical resectability.


Impact of E-Schooling on Digital Eye Strain in Coronavirus Disease Era: A Survey of 654 Students.
To assess digital eye strain (DES) among schoolchildren during lockdown. An online questionnaire-based, cross-sectional study was conducted. A validated, self-administered, electronic questionnaire was circulated among students of 5-18 years of age. The duration of data collection was from May 18, 2020 to May 24, 2020. Rasch-based Computer-Vision Symptom Scale was deployed to measure the DES. A total of 654 students (mean age: 12.02 ± 3.9 years) completed the survey. The average per day digital device exposure was 5.2 ± 2.2 h. A total of 507 (92.8%) children reported experiencing at least one asthenopic/dry eye symptom (AS/DS). The most prevalent symptoms were eye redness (69.1%) and heaviness of eyelids (79.7%). Significant positive correlation was reported between age and per day duration of digital device exposure (Pearson correlation 0.25; P < 0.001). Computer vision syndrome (CVS) score for spectacle users was significantly higher (P < 0.001). CVS score was found to correlate significantly with age and duration of digital device exposure (P < 0.001). Most of the students surveyed, experienced at least one symptom of DS or AS, indicating a need to educate them about the possible deleterious effects and help them adapt to the currently evolving education system.


The Reliability and Validity of the "Activity and Participation" Component in the Brief ICF Core Set for Chronic Obstructive Pulmonary Diseases Based on Rasch Analysis.
To analyze the reliability and validity of the "activity and participation" component of the brief international classification of functioning, disability and health (ICF) core set for chronic obstructive pulmonary disease (COPD) using a Multi-faceted Rasch model. A total of 103 patients with COPD were selected by two raters to evaluate their ability levels in the four categories of the "activity and participation" component of brief ICF core set for COPD. The Multi-faceted Rasch model was used for data analysis. The analysis software used FACETS (Minifac) 3.67.0. The "activity and participation" of brief ICF core set for COPD had a high internal consistency (separation index of 5.08, reliability of 0.96, P <0.05) and good inter-rater reliability (mean-square fit statistic range was 0.97-1.04, the separation index was 0.00, the reliability was 0.00, P >0.05), the construct validity was good (mean-square fit statistic range was 0.79-1.36), and the consistency of each category measurement was high (the separation index was 1.70, the reliability was 0.74). The "activity and participation" of brief ICF core set for COPD has good reliability and validity, which can be used to test the daily activities of patients with COPD.


Pulse Proteolysis and Precipitation for Target Identification.
In recent years, phenotypic screening has assumed a leading role in drug discovery efforts. However, development of new drugs from bioactive compounds obtained in screening campaigns requires identification of the cellular targets responsible for their biological activities. A new energetics-based method for target identification is presented: pulse proteolysis and precipitation for target identification (PePTID). In this method, proteins incubated with or without a ligand and submitted to a brief proteolytic pulse are directly analyzed and compared using a label-free semiquantitative mass spectrometry strategy, dispensing the SDS-PAGE readout and greatly improving the throughput. As a proof-of-concept, we applied the PePTID method to identify ATP-binding proteins in Mycobacterium smegmatis, a model system for Mycobacterium tuberculosis, the etiological agent of tuberculosis.


Bulimia from a gynecological view: hormonal changes.
Gynecological problems are one of the most frequent somatic complications of eating disorders. The purpose of the present study was to assess the role of improper eating habits in the aetiology of menstrual disturbances, anovulation and hormonal related changes. Bulimia nervosa is the focus of attention since amenorrhea is considered a diagnostic criterium in anorexia nervosa. Subjects of the BITE (Bulimia Investigation Test, Edinburgh) test who were infertile were studied (n = 58) In the studied population there were 6 cases of clinical and 8 cases of subclinical bulimia nervosa. Symptoms and severity subscales of the BITE test significantly correlated with body mass index (p = 0.003). All 14 patients suffering from clinical and subclinical bulimia nervosa had pathologically low FSH and LH hormone levels. In those with clinical bulimia nervosa (n = 6) we diagnosed 4 cases of multicystic ovary (MCO) and in the eating disorder not otherwise specified (EDNOS) group (n = 22) there were 2 cases of MCO and 5 cases of polycystic ovary syndrome (PCOS). The results suggest that unsatisfactory nutrition (binges and "crash diet") in bulimia nervosa results in hormonal dysfunction, menstrual disturbances and infertility. The authors question the necessity for immediately estrogen replacement: they consider the reversibility of the hormonal status by early treatment of eating disorders is more appropriate. Excessive use of hormonal contraceptives in therapy has to be questioned.


Association between LGALS2 3279C>T and coronary artery disease: A case-control study and a meta-analysis.
Coronary artery disease (CAD) has become the main cause of mortality worldwide. Lectin galactoside-binding soluble-2 (LGALS2) is involved in the cytokine lymphotoxin-α (LTA) cascade that may influence the progress of CAD. The aim of the present study was to assess the association between the LGALS2 3279C>T (rs7291467) polymorphism and CAD. A total of 562 cases and 572 controls were recruited to examine the association. A systematic meta-analysis was performed to evaluate the contribution of LGALS2 3279C>T polymorphism to the risk of CAD among 12,093 cases and 11,020 controls. There was no significant association found in the present case-control study. However, the meta-analysis showed that LGALS2 3279C>T played a protective role in CAD [P=0.008, odds ratio (OR), 0.90; 95% confidence interval (95% CI), 0.82-0.97] and particularly in the Asian population (P=0.006; OR, 0.82; 95% CI, 0.71-0.94). The present case-control study did not find a significant association between LGALS2 3279C>T and CAD in the Eastern Han Chinese population. However, the meta-analysis indicated that LGALS2 3279C>T played a protective role in CAD, suggesting an ethnic difference in the association of the locus with CAD.


Structure-switching aptamer sensors for the specific detection of piperaquine and mefloquine.
Tracking antimalarial drug use and efficacy is essential for monitoring the current spread of antimalarial drug resistance. However, available methods for determining tablet quality and patient drug use are often inaccessible, requiring well-equipped laboratories capable of performing liquid chromatography-mass spectrometry (LC-MS). Here, we report the development of aptamer-based fluorescent sensors for the rapid, specific detection of the antimalarial compounds piperaquine and mefloquine-two slow-clearing partner drugs in current first-line artemisinin-based combination therapies (ACTs). Highly selective DNA aptamers were identified that bind piperaquine and mefloquine with dissociation constants (K d's) measured in the low nanomolar range via two independent methods. The aptamers were isolated from a library of single-stranded DNA molecules using a capture-systematic evolution of ligands by exponential enrichment (SELEX) technique and then adapted into structure-switching aptamer fluorescent sensors. Sensor performance was optimized for the detection of drug from human serum and crushed tablets, resulting in two sensing platforms. The patient sample platform was validated against an LC-MS standard drug detection method in samples from healthy volunteers and patients with malaria. This assay provides a rapid and inexpensive method for tracking antimalarial drug use and quality for the containment and study of parasite resistance, a major priority for malaria elimination campaigns. This sensor platform allows for flexibility of sample matrix and can be easily adapted to detect other small-molecule drugs.


Structure of the normal rat larynx.
Recent studies have shown the rat larynx to be an important organ in the evaluation of irritancy of inhaled materials. Serial sections and scanning electron microscope observations have clarified its basic structure. In particular the cartilage pattern and the distribution of the epithelia lining the lumen have been determined. There are 2 specialised epithelia--stratified squamous (found in areas subject to wear) and ciliated pseudostratified columnar (which produces and transports mucus). Aways intervening between these is an unspecialised epithelium, the non-ciliated columnar. The marked variation in type of epithelium over a short distance within the larynx emphasises the need to take sections in the same plane when comparing different specimens.


Clinical Utility of Ultra-Widefield Imaging with the Optos Optomap Compared with Indirect Ophthalmoscopy in the Setting of Non-Traumatic Rhegmatogenous Retinal Detachment.
To evaluate the clinical utility of ultra-widefield imaging as an adjunctive tool in the diagnosis, management, and follow-up of eyes with non-traumatic rhegmatogenous retinal detachment. Retrospective chart review of patients with a rhegmatogenous retinal detachment who received ultra-widefield imaging with the Optos® Optomap® P200Tx. Comparisons were made between UWF imaging and indirect ophthalmoscopy for features of detachments, including extent of detachment, holes, retinopexy, and related pathology. Thirty-six eyes of 34 patients were included. Preoperatively, ultra-widefield imaging more precisely documented the extent of retinal detachments in the superior, inferior, and nasal quadrants in 13.9% of cases. Ultra-widefield imaging failed to detect retinal holes in the superior and inferior quadrants in 11.1% and 19.4% of cases, respectively. In postoperative imaging, UWF photos did not detect retinopexy which was ophthalmoscopy-visible both superiorly and inferiorly in 19.4% of cases. The mean differences in clock hours of the detachments as documented on the clinical exam compared to ultra-widefield imaging in the superior, inferior, temporal, and nasal quadrants were -0.18 ± 0.84, 0.41 ± 1.16, 0.08 ± 1.08, and -0.13 ± 2.25 hours, respectively. Ultra-widefield imaging is a useful adjunct for documentation of rhegmatogenous retinal detachments and their postoperative repair. However, detection of retinal holes, tears, and postoperative scarring is poor, especially in the inferior and superior periphery.


Dietary Pattern, Nutrition-Related Knowledge and Attitudes of Working Women in Western Province, Sri Lanka.
Healthy eating behaviour of women is critical not only for their health but also for their children's health and well-being. The present study examined the dietary pattern, nutrition-related knowledge, and attitudes of working women in Western Province, Sri Lanka. In addition, this study identified the factors associated with dietary diversity score (DDS). A cross-sectional study was conducted among 300 working women, aged 20-60 years, in Western Province, Sri Lanka. The data on socio-demography, dietary patterns, and nutrition-related knowledge and attitudes were collected. Overall, 38% of the women were overweight and 13% were obese. The median frequency of intake of chicken, fish, eggs, milk and milk products, green leafy vegetables, and fruits were 2, 5, 2, 9, 5, and 10 respectively, per week. A large majority of the women (70%) had tea/coffee with sugar and snacks (60%) at least four times a week. Only a third of the women met the minimum DDS, while more than half of the women had good nutrition-related knowledge and attitudes. Women with good nutrition-related knowledge were more frequent consumers of roots/tubers, shellfish, vegetables, fruit, fruit juice, nuts and oils, and fast food. Women with good nutrition-related attitudes had a significantly lower frequency of consumption of soya meat, while having a higher frequency of consumption of fast food. Multiple regression analysis showed that age and household income were significantly independently related to DDS, while attitudes were negatively associated. While there was a trend, the association of nutrition-related knowledge with DDS was not statistically significant (p = 0.057). The overall F ratio (8.46) was highly significant (p = 0.001) and the adjusted R2 was 0.093. The results demonstrate that a significant proportion of working women have good basic nutrition-related knowledge and attitudes, while two-thirds of them do not meet the minimum DDS. Furthermore, age, family income, and knowledge were positively associated with DDS, while attitudes were negatively associated. Before designing any intervention, further research is needed using a qualitative approach to understand how nutrition knowledge and eating behaviour are related in this population group.


The importance of perinatal autopsy. Review of the literature and series of cases.
Perinatal autopsy remains the gold-standard procedure used to establish the fetal, neonatal or infant abnormalities. Progressively, perinatal pathology has become a specialized field with important roles of audit for fetal prenatal diagnostic tools, in parents counseling regarding future pregnancies, in scientific research, for epidemiology of congenital abnormalities and teaching. The differences between prenatal ultrasound and autopsy reports represent a strong argument for the autopsy examination following termination of pregnancy. The reasons for such discrepancies are related to the ultrasonographic or pathological examination conditions, the type of the anomalies, the expertise and availability of the operators. Several facts led to an undesirable increase of refusals from parents to consent to a conventional invasive autopsy: the centralization of pathology services, the poor counseling provided by non-experts in fetal medicine and the clinicians' over-appreciation of the importance of the ultrasound diagnostic investigation. Although non-invasive alternatives have been tested with promising results, conventional autopsy remains the gold standard technique for the prenatal diagnosis audit. We report and analyze several cases of prenatally diagnosed malformed fetuses with different particularities that underline the necessity of perinatal autopsy. We discuss the antenatal findings and management and post-mortem autopsies in the respective pregnancies.


In vitro studies on the antifungal effect of PUVA.
The effect of PUVA therapy upon 12 dermatophyte strains, 3 of Candida albicans, and 4 of mould fungi was evaluated by the agar dilution method on Sabouraud agar. 8-MOP, 30 microgram/ml medium plus UVA, 4 Joule/cm2 proved to be fungicidal dose to all the strains studied, with the exception of three of the mould fungi. For dematophytes and Candida albicans the MIC was between 1 and 3 microgram, 8-MOP plus UVA, 4 J; and 3 microgram when the UVA dose was reduced to 1--2 J. For mould fungi it was higher. The MFC varied within the range 2 to 30 microgram, when the UVA dose was fixed at 4 J. It reached 16 J when the dose of 8-MOP was kept at 4 microgram. The wide range in the MFC of the dermatophytes could be due to resistant colonies. 8-MOP alone had a distinctly inhibitory effect upon dermatophytes, but not upon Candida albicans or mould fungi.


Effect of nanoparticles of silver on redox status and the accumulation of Ag in chicken tissues.
The aim of the study was to verify the hypothesis that there are doses of silver nanoparticles (Ag-NPs) that improve antioxidant defence in chickens without compromising their growth performance and health. The results of our study suggest that, irrespective of the concentration, the administration of Ag-NPs (5 nm) at a dose not exceeding 54 mg/bird has no negative effect on the growth performance of chickens. The administration of Ag-NPs (5 nm) in the amount of 2.87 to 63.74 mg/bird does not cause silver to accumulate in the breast muscle. The ingestion of 2.87 mg/bird was found to result in the accumulation of this element in the wall of the small intestine and in the liver, and a further increase in the dose increases the accumulation of Ag in these tissues. Accumulation of Ag in the heart of the chickens was not observed until the dose reached 22.5 mg/bird. Our research has shown that the application of Ag-NPs (5 nm), especially at doses greater than the 'no observable adverse effect level' (NOAEL) of 9.47 mg/bird, can induce oxidative reactions in the blood, small intestinal wall, liver and breast muscle of chickens. © 2018 Society of Chemical Industry.


[Choroidal granuloma in sarcoidosis. Discussion apropos of 2 cases].
Specific granuloma of the choroid is an exceptional localization of sarcoidosis. It is characterized by overlying neurosensory retinal detachment without anterior uveitis. Other more frequent findings can be revealed by fundus examination in sarcoidosis. Choroidal granuloma is often part of a systemic sarcoidosis. Most often, systemic corticosteroid therapy provides a prompt improvement of the lesion. The diagnosis relies on clinical and paraclinical informations which are reviewed in this survey on recent cases.


Contribution of anthocyanin fraction to the antioxidant properties of wine.
The wine is a beverage with an important antioxidant efficiency which is attributed to their bioactives compounds, especially polyphenols. The anthocyanins are the main phenolic compounds of red wine and its consumption has been partially related with the "French Paradox". The aim of the present work was to evaluate the contribution of the anthocyanins to the antioxidant properties of red wines. So, total antioxidant capacity (TAC), hydroxyl and superoxide scavenger activity and lipid peroxidation of 80 Spanish red wines and their anthocyanins fractions have been assessed for ABTS, DPPH, DMPD, and FRAP methods, hydroxyl radical (HRSA), superoxide radical scavenger activity (SRSA) and ABAP-lipid peroxidation (ABAP-LP). The results showed that free anthocyanins fraction are main responsible of the total antioxidant capacity of red wines correlated with electron transference processes. In similar way, free anthocyanins are the maximum responsible of HRSA scavenger activity of red wines, contributing less extensively to their SRSA capacity or to their protective action on lipid peroxidation. Furthermore, simple anthocyanins exert a low action in TAC process involved with proton transference. Glycosilated and methoxylic anthocyanins as malvidin-3-glucoside, seem to be the type of anthocyanins with higher participation on the antioxidant effect of red wine.


Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse.
This study was conducted in order to test the concept that oxidative damage is associated with aging and may be a factor in the modulation of life span in response to variations in caloric intake. Mice fed a diet that was 40% lower in calories (DR) than the ad libitum fed (AL) animals exhibited a 43% extension in average life span and a 61% prolongation in mortality rate doubling time. A comparison of AL and DR mice at 9, 17 and 23 months of age indicated that the protein carbonyl content in the brain, heart and kidney increased with age and was significantly greater in the AL than DR group in each organ at each of the three ages. Mitochondrial state 4 or resting respiratory rate increased with age in the AL, but not the DR group, and was also relatively higher in the former. The rates of mitochondrial superoxide and hydrogen peroxide generation increased with age and were higher in the AL than DR mice in all the three organs at each age. In contrast, there was no clear-cut overall pattern of age-related or dietary-related changes in antioxidant defenses provided by superoxide dismutase, catalase and glutathione peroxidase. Results suggest that mechanisms of aging and life span shortening by enhanced caloric intake are associated with oxidative damage arising from corresponding changes in mitochondrial oxidant production. Protein carbonyl content, and mitochondrial O2.- and H2O2 generation may act as indices of aging.


Percutaneous closure of atrial septal defects: immediate and mid-term results.
The incidence of percutaneous closure of secundum atrial septal defects (ASD) and patent foramen ovale (PFO), which has become an established therapy, is constantly increasing. In this study, which is the first in the Greek literature, we present the immediate and mid-term results from this intervention in our center. From April 2004 to April 2008, 103 patients underwent percutaneous closure of an ASD or PFO using Amplatzer closure devices. Thirty were male, the mean age was 37 +/- 15.5 years, and the mean follow-up period 21.7 +/- 14.8 months. The procedure was successful in 102 of the above patients; 69 (mean age 36.3 years +/- 17.1, 81% female) underwent secundum ASD closure, while 33 patients (mean age 39.1 +/- 10.5 years, 16 female and 17 male) underwent percutaneous closure of a PFO due to cryptogenic stroke. There were no major complications during the procedure (death, device embolization or need for immediate cardiac surgery). There were minor complications in 8 (7.7%) patients (bleeding at the puncture site, transient ST elevation in the inferior leads, multiple atrial and ventricular ectopics). The transient ST elevation in the inferior leads appeared in 5 patients (5%) and was probably due to air embolization. This transient complication completely resolved within 3 minutes. During the follow-up period, no patient had a major complication (cardiac rupture, device embolization, thrombus formation, thromboembolism or infective endocarditis). Most importantly, in the patients who underwent PFO closure there were no recurrences of cryptogenic stroke during the follow-up period (24.3 +/- 14.5 months). This study shows that using Amplatzer closure devices for atrial septal communications is both safe and effective, with sustained results over a maximum follow-up period of four years. Appropriate patient selection, as well as accurate device sizing fitting the dimensions of the defect, are important factors for the success and the safety of the method.


3-Methyl pyruvate enhances radiosensitivity through increasing mitochondria-derived reactive oxygen species in tumor cell lines.
Considerable interest has recently been focused on the special characteristics of cancer metabolism, and several drugs designed to modulate cancer metabolism have been tested as potential anticancer agents. To date, however, very few studies have been conducted to investigate the combined effects of anticancer drugs and radiotherapy. In this study, to evaluate the role of mitochondria-derived reactive oxygen species (ROS) in the radiation-induced cell death of tumor cells, we have examined the effect of 3-methyl pyruvate (MP). MP is a membrane-permeable pyruvate derivative that is capable of activating mitochondrial energy metabolism in human lung carcinoma A549 cells and murine squamous carcinoma SCCVII cells. Pretreatment with MP significantly enhanced radiation-induced cell death in both cell lines, and also led to increases in the mitochondrial membrane potential, intracellular adenosine triphosphate content, and mitochondria-derived ROS production following the exposure of the cells to X-rays. In A549 cells, MP-induced radiosensitization was completely abolished by vitamin C. In contrast, it was partially abolished in SCCVII cells. These results therefore suggest that the treatment of the cells with MP induced radiosensitization via the production of excess mitochondria-derived ROS in tumor cells.


The influence of exercise on growth hormone and testosterone in prepubertal and early-pubertal boys.
The purpose of this study was two fold a) to determine the levels of hormonal parameters which are related to growth and sexual maturation (T, SHBG, FAI, GH) in 66 pre-pubertal and early-pubertal boys (11-13 years old) who systematically engage in individual and team sports activities of endurance, strength, speed and skill, respectively, and b) to investigate the effect of two different forms of exercise namely aerobic (AG) and weight training (WG) on androgen levels in 19 sedentary pre-pubertal boys. The control groups (CG) consisted of boys of the same age who attended only the school physical education programmes. The individuals included in the study participated voluntarily after their parents had been informed and had given their written consent. Hormonal concentrations were determined using radioimmunoassay and immunoradiometric assays. No differences were observed among the various athletes' groups as regards Tanner stages, height and weight. The mean T and FAI values of the control group did not differ from those of the corresponding athletes group. Significant differences were observed among the groups regarding BMI, % body fat, T, SHBG, FAI and GH (p<0.05). T and FAI values in the WG group were significantly higher than the corresponding concentrations: a) in the AG group by 338 and 609%, p<0.05 and b) in the control group CG by 91 and 96%, p<0.05, respectively. The hormonal differences detected among the various groups of athletes must be attributed as much to the type of physical exercise and to developmental factors as to the selection criteria used for the different athletic talents. The importance of the specificity of training stimulus in the hormonal adaptations of pre-pubertal sedentary subjects was demonstrated.


A large cystic tumor with bile duct communication originating around the hepatic hilum.
Biliary cystic tumors are rare neoplasms occurring in the liver and less frequently in the extrahepatic biliary system. Recently, biliary cystic tumors in the liver are thought to be divided into a biliary mucinous cystic neoplasm and intraductal papillary neoplasm of the bile duct. We report a case of a large cystic tumor originating around the hepatic hilum which had luminal communication with the bile duct. A 74 year-old-woman underwent abdominal ultrasonography for a routine checkup. It revealed a large cystic tumor in the liver. CT scan and MRI showed a multilocular cystic tumor about 12 cm in diameter with a mural nodule occupying the medial and anterior segment of the liver. Intraoperative cholangiography showed a communication between the cystic tumor and the bile duct. Central bisegmentectomy of the liver and extrahepatic bile duct resection was performed. A papillary tumor existed in the common hepatic duct and was connected with the cystic tumor in the liver. The tumor was mostly composed of noninvasive papillary adenocarcinoma with adenoma components, and was associated with focal microinvasion of adenocarcinoma. Ovarian-like stroma was not observed. This lesion was diagnosed as a cystic variant of intraductal papillary neoplasm of the bile duct. The patient is alive with no recurrence for 18 months since the surgery.


[Analysis of allelic drop-out at short tandem repeat loci].
To explore the cause for allelic drop-out at short tandem repeat (STR) loci upon paternity testing with a PowerPlex® 16 kit. A total of 10 642 DNA confirmed paternity testing cases (18 314 parent/child allelic transfers) were analyzed with the PowerPlex® 16 kit. Samples suspected for having allelic drop-out were verified with an Identifiler™ kit and/or locus-specific singleplex amplification systems. PCR products of null alleles were separated and directly sequenced. Eight cases of allelic drop-out were found. The overall rate of null allele in the PowerPlex® 16 system was 0.437 × 10(-3). DNA sequencing has confirmed single base variations within the binding region of published primers, in which 4 cases involved the D18S51 locus (2 cases with G>A transitions at 79 bp upstream of the repeats, 1 case with G>T transversion at 162 bp downstream of the repeats and 1 case with G>C transversion at 74 bp upstream of the repeats), 2 cases involved the D21S11 locus (1 case with C>A transversion at 17 bp upstream of the repeats and 1 case with A>G transition at 12 bp upstream of the repeats). One case involved the FGA locus (1 case with G>A transition at 142 bp downstream of the repeats) and 1 case involved TPOX locus (1 case with G>A transition at 198 bp downstream of the repeats). Base variation in the primer binding region may cause failed PCR and result in null allele reports. Alternative primer sets should be used to verify the suspected allelic drop-out. Attention should be paid to this during paternity testing and data exchange for personal identification.


Kinetics of reciprocal pro-urokinase/plasminogen activation--stimulation by a template formed by the urokinase receptor bound to poly(D-lysine).
The two zymogens, plasminogen and pro-urokinase plasminogen activator (pro-uPA), constitute a system of reciprocal activation, since plasmin, generated by uPA-catalysed plasminogen activation, can activate pro-uPA to uPA. Two such zymogens, when mixed, will undergo autocatalytic, reciprocal activation resulting in generation of proteolytic activity. As an example of reciprocal zymogen activation, the plasminogen/pro-uPA system was analysed in terms of a kinetic model which describes the progression in activated enzymes. This model gave a detailed description of the progress curves in plasmin and uPA. It accounted for the effects of varying the concentration of the zymogens, and also for the effects of plasmin substrates and inhibitors in the reaction mixture. The model assumes non-significant zymogen activity. It did not, however, exclude that a very low initial proteolytic activity, accounting for maximally 0.01% of that obtained when pro-uPA is fully activated, could be attributed to a genuine pro-uPA activity. Binding of the uPA receptor (uPAR) to pro-uPA/uPA might affect separate steps of the reciprocal activation reaction, or it might induce a significant pro-uPA activity. To distinguish between these possibilities the effect of a recombinant soluble (residues 1-277) form of uPAR, uPAR-(1-277)-peptide, on reciprocal pro-uPA/plasminogen activation was studied. uPAR-(1-277)-peptide attenuated reciprocal zymogen activation, and the results suggested that this was due to a decreased accessibility of the pro-uPA/uPAR-(1-277)-peptide complex to activation by plasmin. The uPAR-(1-277)-peptide in the presence of poly(D-lysine) caused a 20-fold enhancement of reciprocal zymogen activation. Kinetic analysis of separate activation steps revealed that this was due to a threefold stimulation of plasminogen activation by uPA/uPAR-(1-277)-peptide combined with a sixfold stimulation of plasmin's activation of pro-uPA/uPAR-(1-277)-peptide. The results suggested that poly(D-lysine) provided a template for a catalytically favourable interaction between plasminogen/plasmin and the uPAR-(1-277)-peptide complex with pro-uPA/uPA. There was no indication of a significant uPAR-(1-277)-peptide-induced enhancement of pro-uPA activity.


Vademecum-based approach to multi-scale topological material design.
The work deals on computational design of structural materials by resorting to computational homogenization and topological optimization techniques. The goal is then to minimize the structural (macro-scale) compliance by appropriately designing the material distribution (microstructure) at a lower scale (micro-scale), which, in turn, rules the mechanical properties of the material. The specific features of the proposed approach are: (1) The cost function to be optimized (structural stiffness) is defined at the macro-scale, whereas the design variables defining the micro-structural topology lie on the low scale. Therefore a coupled, two-scale (macro/micro), optimization problem is solved unlike the classical, single-scale, topological optimization problems. (2) To overcome the exorbitant computational cost stemming from the multiplicative character of the aforementioned multiscale approach, a specific strategy, based on the consultation of a discrete material catalog of micro-scale optimized topologies (Computational Vademecum) is used. The Computational Vademecum is computed in an offline process, which is performed only once for every constitutive-material, and it can be subsequently consulted as many times as desired in the online design process. This results into a large diminution of the resulting computational costs, which make affordable the proposed methodology for multiscale computational material design. Some representative examples assess the performance of the considered approach.


Duplication of (12)(pter-q13.3) combined with deletion of (22)(pter-q11.2) in a patient with features of both chromosome aberrations.
We report a patient with multiple dysmorphic signs and congenital malformations, representing a combination of clinical features of duplication (12p) and deletion (22)(q11.2) syndromes. The girl had overgrowth at birth, showed abnormal cranio-facial findings, cleft uvula, a complex conotruncal heart defect, a polycystic right kidney, and an umbilical hernia. She died at the age of 6 months of cardio-respiratory failure. Cytogenetic examination demonstrated a derivative chromosome 12 replacing one of the two chromosomes 22. The paternal karyotype was normal 46,XY while the mother's karyotype was 46,XX,rcp(12;22)(q13.2;q11.2). According to the published data, all patients with deletion 22q11.2 combined with other unbalanced chromosomal aberration have a more severe clinical expression than those with interstitial deletions.


Exome sequencing analysis: a guide to disease variant detection.
Whole exome sequencing presents a powerful tool to study rare genetic disorders. The most challenging part of using exome sequencing for the purpose of disease-causing variant detection is analyzing, interpreting, and filtering the large number of detected variants. In this chapter we provide a comprehensive description of the various steps required for such an analysis. We address strategies in selecting samples to sequence, and technical considerations involved in exome sequencing. We then discuss how to identify variants, and methods for first annotating detected variants using characteristics such as allele frequency, location in the genome, and predicted severity, and then classifying and prioritizing the detected variants based on those annotations. Finally, we review possible gene annotations that may help to establish a relationship between genes carrying high-priority variants and the phenotype in question, in order to identify the most likely causative mutations.


Dispersed synthesis of uniform Fe3O4 magnetic nanoparticles via in situ decomposition of iron precursor along cotton fibre for Sudan dyes analysis in food samples.
Fe3O4 magnetic nanoparticles, with a negative charge surface, are known to have efficient adsorbent properties, but they tend to be agglomerated into larger aggregates or flocs, which can cause loss of specific area. The addition of cotton fibre, as a stabiliser in preparation of the Fe3O4 nanoparticles, is able to efficiently reduce particle aggregation, and thus, effective particle size, resulting in much greater specific surface area and adsorption sites. Fe3O4 nanoparticles synthesis was accomplished by in situ high-temperature decomposition of the precursor ferric ion in the presence of cotton fibre and ethylene glycol solvent. The morphology of Fe3O4 nanoparticles was characterised by field emission scanning electron microscopy and X-ray diffraction, which confirmed that the magnetic nanoparticles are highly dispersed. These Fe3O4 nanoparticles were used for clean-up and pre-concentration of Sudan dyes in chilli and hot red sauces, prior to their determination by capillary liquid chromatography diode array detection. A comparative study of analyte pre-concentration was conducted with magnetic nanoparticles prepared with and without cotton fibre showing that both solid phases adsorb the analytes, but higher recoveries were obtained when using cotton fibre which therefore was selected for extraction of Sudan dyes.


Human Genes Encoding Transcription Factors and Chromatin-Modifying Proteins Have Low Levels of Promoter Polymorphism: A Study of 1000 Genomes Project Data.
The expression level of each gene is controlled by its regulatory regions, which determine the precise regulation in a tissue-specific manner, according to the developmental stage of the body and the necessity of a response to external stimuli. Nucleotide substitutions in regulatory gene regions may modify the affinity of transcription factors to their specific DNA binding sites, affecting the transcription rates of genes. In our previous research, we found that genes controlling the sensory perception of smell and genes involved in antigen processing and presentation were overrepresented significantly among genes with high SNP contents in their promoter regions. The goal of our study was to reveal functional features of human genes containing extremely small numbers of SNPs in promoter regions. Two functional groups were found to be overrepresented among genes whose promoters did not contain SNPs: (1) genes involved in gene-specific transcription and (2) genes controlling chromatin organization. We revealed that the 5'-regulatory regions of genes encoding transcription factors and chromatin-modifying proteins were characterized by reduced genetic variability. One important exception from this rule refers to genes encoding transcription factors with zinc-coordinating DNA-binding domains (DBDs), which underwent extensive expansion in vertebrates, particularly, in primate evolution. Hence, we obtained new evidence for evolutionary forces shaping variability in 5'-regulatory regions of genes.


Relationship of family life events, maternal depression, and child-rearing problems.
The relationship between maternal reports of child-rearing problems, family life events, and maternal depressive symptoms was studied in a birth cohort of children in New Zealand. Rates of child-rearing problems showed a steady increase with both increasing levels of family life events and maternal depressive symptoms. Log-linear modeling of the results suggested that the apparent correlation between family life events and reports of child-rearing problems was mediated by the effects of maternal depression so that women subject to large numbers of adverse life events suffered increased rates of depression and in turn reported higher rates of problem behavior in their children. There was no significant correlation between family life events and reports of child-rearing problems when the effects of maternal depressive symptoms were taken into account. The findings tend to suggest that the previously reported association between family life events and child-rearing problems arises because life events provoke depressive symptoms in women and in turn this alters the way in which they perceive or evaluate their children's behavior.


[Reliability of DNA measurement after simultaneous staining of DNA and RNA by acridine-orange for flow-cytophotometry (author's transl)].
The reliability of DNA cell content measurement by flow cytophotometry was assessed after simultaneous staining of DNA and RNA by acridine-orange. The methods of staining allowing the lowest CV were determined. The specificity of this staining for DNA appeared satisfactory. When the distribution in the various phases of the cell cycle was computerized, a good correlation was found for the S phase with the 3H-thymidine labeling index. The interest of this method for prognosis and monitoring of acute leukemia is underlined.


Energetic N,N,N',N'-tetraaminopiperazinium salts.
The formation of terraminopiperazinium salts using water as solvent provides a green, straightforward approach to highly energetic salts that exhibit good thermal stabilities and moderate densities. The N,N,N',N'-tetraaminopiperazinium cation was selected for this study because of its high nitrogen-nitrogen bond content and its hign positive near or formation. Theoretical and empirical calculations on energetic salts based on this nitrogen-rich cation reveal them to have high positive molar enthalpies of formation, as high as 1034.0 kJ mol(-1), supporting the application of these new salts as potential energetic materials.


Efficient green electrophosphorescence with Al cathode using an effective electron-injecting polymer as the host.
Efficient green phosphorescent polymer light-emitting diodes (PLED) based on aluminum (Al) cathode were demonstrated. The device composed of neutral aminoalkyl substituted polyfluorene, poly[(9,9-bis(3'-(N,N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)] (PFN) as the host and an Ir complex, fac-tris(2-(4-tert-butyl)-phenylpyridine)iridium (Ir(Bu-PPy)(3)), as the dopant. High luminous efficiency of 35.7 cd/A and a luminance of more than 10 000 cd/m(2) were obtained. The device performance was comparable to those of the devices from (Ir(Bu-PPy)(3)), doped into PVK as the host with a low work-function metal as cathode (such as barium and calcium). We found out that the high-performance was due to the effective electron injection from PFN/Al bilayer cathode, improved charge balance as well as significant reduction of back-transfer of excitons from Ir complex to the low-lying PFN triplet level in the PVK/PFN interface.


Expression of HSP70 and Its Relation with Other Cytokines in Human Middle Ear Effusion.
While other cytokines are known to be associated with otitis media with effusion (OME), the involvement of heat shock protein 70 (HSP70) in middle ear effusion (MEE) is unknown. This study was undertaken to investigate the possibility of there being a HSP70 expression in human MEE and to determine its potential role as a cytokine in OME. The levels of HSP70, tumor necrosis factor-alpha and interleukin-1beta were measured by enzyme-linked immunosorbent assay in the effusion of different groups of OME patient following collection of the MEE using our new collection system. The clinical characteristics of the OME patients and the MEE status were analyzed. HSP70 was expressed in all the types of MEE. The mucous and seromucous effusions showed higher HSP70 levels than that of the serous effusion. The HSP70 level was correlated with the levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta in the effusions. The positive correlations between HSP70, TNF-alpha and IL-1beta were statistically significant (P<0.05). The highly elevated level of HSP70 in the seromucous and mucous effusions implicates this protein in the chronicity of OME.


[Correlation of anthropometric parameters and blood-pressure in elderly people].
The elderly represent a growing segment of populations in developed and also in developing countries. Anthropological measurements offer a cheap and easy way method for assessment of health and nutritional status and in prediction for mortality. Anthropological parameters and their relation to blood pressure were studied in elderlies. Two hundred-thirteen elderly people (83 men over 65 y and 110 women over 60 y) were involved. The weight, height, waist- and hip circumferences were measured and waist: hip ratio, and body mass index (BMI) were calculated. Blood pressure was measured by the use of sphygmomanometer. Hypertension was diagnosed when systolic blood pressure was >/= 140 and/or diastolic >/= 90 mmHg. The SPSS 10 version for Windows was used for statistical analysis. According to the BMI, 72% of men and 65% women were considered overweight or obese. According to waist circumference 51% of men and 83% of women belonged to the high risk group. Under 80 y the mean blood pressure was in the pathological range both in the case of men and women. That could be considered as a sign of the insufficient efficiency of treatment or bad compliance. By 60% of this elderly population hypertension was registered. 75% of people, considered overweight or obese according to BMI, showed hypertension. According to the waist circumference, in 73% of people in the high risk group hypertension was detected versus 6% of persons in the non-risk group. This relation could not be observed in women. The prevalence of obesity and overweight is higher in the elderly group than in the younger adult population. Decrease in body mass may be suggested only by cautious nutritional intervention, control of systolic blood pressure should be more regular and prudent.


Connexins and Integrins in Exosomes.
Connexins and integrins, the two structurally and functionally distinct families of transmembrane proteins, have been shown to be inter-connected by various modes of cross-talk in cells, such as direct physical coupling via lateral contact, indirect physical coupling via actin and actin-binding proteins, and functional coupling via signaling cascades. This connexin-integrin cross-talk exemplifies a biologically important collaboration between channels and adhesion receptors in cells. Exosomes are biological lipid-bilayer nanoparticles secreted from virtually all cells via endosomal pathways into the extracellular space, thereby mediating intercellular communications across a broad range of health and diseases, including cancer progression and metastasis, infection and inflammation, and metabolic deregulation. Connexins and integrins are embedded in the exosomal membranes and have emerged as critical regulators of intercellular communication. This concise review article will explain and discuss recent progress in better understanding the roles of connexins, integrins, and their cross-talk in cells and exosomes.


[Anti-edema effects of some H1-receptor antagonists].
Experiments carried out with mice of CFLP strain have shown that antihistaminics (chloropyramine, cyproheptadine and dimethindene maleate) significantly inhibit the extents of ear oedema induced by croton oil, dithranol or capsaicin. In rats of Wistar strain, oedema was induced in the hind paw by the subplantar injection of carrageenin, and simultaneously by the application of croton oil to the inner surface on the ear. Preliminary antihistamine treatment inhibited the development of both types of oedema, to statistically significant extent.


Power calculator for instrumental variable analysis in pharmacoepidemiology.
Instrumental variable analysis, for example with physicians' prescribing preferences as an instrument for medications issued in primary care, is an increasingly popular method in the field of pharmacoepidemiology. Existing power calculators for studies using instrumental variable analysis, such as Mendelian randomization power calculators, do not allow for the structure of research questions in this field. This is because the analysis in pharmacoepidemiology will typically have stronger instruments and detect larger causal effects than in other fields. Consequently, there is a need for dedicated power calculators for pharmacoepidemiological research. The formula for calculating the power of a study using instrumental variable analysis in the context of pharmacoepidemiology is derived before being validated by a simulation study. The formula is applicable for studies using a single binary instrument to analyse the causal effect of a binary exposure on a continuous outcome. An online calculator, as well as packages in both R and Stata, are provided for the implementation of the formula by others. The statistical power of instrumental variable analysis in pharmacoepidemiological studies to detect a clinically meaningful treatment effect is an important consideration. Research questions in this field have distinct structures that must be accounted for when calculating power. The formula presented differs from existing instrumental variable power formulae due to its parametrization, which is designed specifically for ease of use by pharmacoepidemiologists.


Accelerating sensory recovery after sciatic nerve crush: non-selective versus melanocortin MC4 receptor-selective peptides.
Melanocortin receptor ligands accelerate functional recovery after peripheral nerve crush. It is not known which mechanism is involved or via which melanocortin receptor this effect occurs, albeit indirect evidence favours the melanocortin MC4 receptor. To test whether the melanocortin MC4 receptor is involved in the effects of melanocortins on functional recovery, we used melanocortin compounds that distinguish the melanocortin MC4 receptor from the melanocortin MC1, MC3 and MC5 receptors on basis of selectivity and agonist/antagonist profile. Activation and binding studies indicated that the previously described peptides JK1 (Ac-Nle-Gly-Lys-D-Phe-Arg-Trp-Gly-NH2) and [D-Tyr4]melanotan-II ([D-Tyr4]MTII. Ac-Nle-c[Asp-His-D-Tyr-Arg-Trp-Lys]NH2) are selective for the rat melanocortin MC4 receptor as compared to the rat melanocortin MC3 and MC5 receptors, but are also potent on the melanocortin MC1 receptor. Both peptides did not accelerate sensory recovery in rats with a sciatic nerve crush, whereas the non-selective melanocortin agonist melanotan-II (MTII, Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]NH2) was effective. The melanocortin MC3/MC4 receptor antagonist SHU9119 (Ac-Nle-c[Asp-His-D-Nal(2)-Arg-Trp-Lys]NH2) also enhanced sensory recovery. This effect was probably not due to interaction with the melanocortin MC4 receptor, since JK46 (Ac-Gly-Lys-His-D-Nal(2)-Arg-Trp-Gly-NH2), a selective melanocortin MC4 receptor antagonist, was ineffective. Taken together, these data suggest that melanocortins do not accelerate sensory recovery via interaction with the melanocortin MC4 receptor. From the known melanocortin receptors, only the involvement of the melanocortin MC5 receptor in acceleration of recovery could not be excluded.


Antimicrobial Resistance and Molecular Investigation of H2S-Negative Salmonella enterica subsp. enterica serovar Choleraesuis Isolates in China.
Salmonella enterica subsp. enterica serovar Choleraesuis is a highly invasive pathogen of swine that frequently causes serious outbreaks, in particular in Asia, and can also cause severe invasive disease in humans. In this study, 21 S. Choleraesuis isolates, detected from 21 patients with diarrhea in China between 2010 and 2011, were found to include 19 H2S-negative S. Choleraesuis isolates and two H2S-positive isolates. This is the first report of H2S-negative S. Choleraesuis isolated from humans. The majority of H2S-negative isolates exhibited high resistance to ampicillin, chloramphenicol, gentamicin, tetracycline, ticarcillin, and trimethoprim-sulfamethoxazole, but only six isolates were resistant to norfloxacin. In contrast, all of the isolates were sensitive to cephalosporins. Fifteen isolates were found to be multidrug resistant. In norfloxacin-resistant isolates, we detected mutations in the gyrA and parC genes and identified two new mutations in the parC gene. Pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and clustered regularly interspaced short palindromic repeat (CRISPR) analysis were employed to investigate the genetic relatedness of H2S-negative and H2S-positive S. Choleraesuis isolates. PFGE revealed two groups, with all 19 H2S-negative S. Choleraesuis isolates belonging to Group I and H2S-positive isolates belonging to Group II. By MLST analysis, the H2S-negative isolates were all found to belong to ST68 and H2S-positive isolates belong to ST145. By CRISPR analysis, no significant differences in CRISPR 1 were detected; however, one H2S-negative isolate was found to contain three new spacers in CRISPR 2. All 19 H2S-negative isolates also possessed a frame-shift mutation at position 760 of phsA gene compared with H2S-positive isolates, which may be responsible for the H2S-negative phenotype. Moreover, the 19 H2S-negative isolates have similar PFGE patterns and same mutation site in the phsA gene, these results indicated that these H2S-negative isolates may have been prevalent in China. These findings suggested that surveillance should be increased of H2S-negative S. Choleraesuis in China.


Variation in intramembrane components of Trypanosoma brucei from intact and x-irradiated rats: a freeze-cleave study.
Additional information on host interactions with trypanosomatid membranes was obtained from studies of a monomorphic strain of Trypanosoma brucei harvested at peak parasitemia from intact and lethally irradiated rats. Pellets of trypanosomes were fixed briefly in glutaraldehyde and processed for thin section electron microscopy or freeze-cleave replicas. Observations of sectioned material facilitated orientation and comparison of details seen in replicas. Fracture faces of cell body and flagellar membranes as well as 3-dimensional views of the nuclear membrane were studied. Cell body membranes of 80% of the organisms from intact rats contained random arrays of intramembranous particles (IMP). Aggregated clusters of particles appeared on the fracture faces of 20% of the trypanosomes. Some of these membranes had nonrandomly distributed particles aligned in distinct rows on the outer fracture face of both cell body and flagellum. Many inner face fractures of the cell body membranes had a particle arrangement similar to the longitudinal alignment of cytoskeletal microtubules. No aggregated particle distribution was seen in membranes of trypanosomes harvested from lethally irradiated rats. Replicas of trypanosome pellets also had plasmanemes as a series of attached, empty, coated membrane vesicles. These structures were found in close association with, as well as widely separated from the parasites. The shedding of these vesicles and the variation of particles in cell body membranes are discussed in light of antibody-induced architectural and antigenic changes in surface properties of trypanosomatids. The convex face of the inner membrane of the nucleus also is covered with randomly arrayed particles. More IMP were observed on the inner than on the outer nuclear membranes. Images of nuclear pores were also seen. The importance of these structures in drug and developmental studies of trypanosomes is discussed. On fracture faces of the flagellar membrane there were miniature maculae adherentes, unique to the inner fracture face and occurring only at regions of membrane apposition between cell body and flagellum. Each cluster of particles exposed by the freeze-cleave method corresponds to an electron-dense plaque seen in thin section images. However, because of a unique fracture pattern, these plaques were not revealed on the apposing body membranes, as illustrated in thin sectioned organisms.


Identification of Potential Pharmacoperones Capable of Rescuing the Functionality of Misfolded Vasopressin 2 Receptor Involved in Nephrogenic Diabetes Insipidus.
Pharmacoperones correct the folding of otherwise misfolded protein mutants, restoring function (i.e., providing "rescue") by correcting their trafficking. Currently, most pharmacoperones possess intrinsic antagonist activity because they were identified using methods initially aimed at discovering such functions. Here, we describe an ultra-high-throughput homogeneous cell-based assay with a cAMP detection system, a method specifically designed to identify pharmacoperones of the vasopressin type 2 receptor (V2R), a GPCR that, when mutated, is associated with nephrogenic diabetes insipidus. Previously developed methods to identify compounds capable of altering cellular trafficking of V2R were modified and used to screen a 645,000 compound collection by measuring the ability of library compounds to rescue a mutant hV2R [L83Q], using a cell-based luminescent detection system. The campaign initially identified 3734 positive modulators of cAMP. The confirmation and counterscreen identified only 147 of the active compounds with an EC50 of ≤5 µM. Of these, 83 were reconfirmed as active through independently obtained pure samples and were also inactive in a relevant counterscreen. Active and tractable compounds within this set can be categorized into three predominant structural clusters, described here, in the first report detailing the results of a large-scale pharmacoperone high-throughput screening campaign.


Evaluation of the Cepheid Xpert C. difficile/Epi and meridian bioscience illumigene C. difficile assays for detecting Clostridium difficile ribotype 033 strains.
Clostridium difficile PCR ribotype 033 (RT033) is found in the gastrointestinal tracts of production animals and, occasionally, humans. The illumigene C. difficile assay (Meridian Bioscience, Inc.) failed to detect any of 52 C. difficile RT033 isolates, while all strains signaled positive for the binary toxin genes but were reported as negative for C. difficile by the Xpert C. difficile/Epi assay (Cepheid).


Suspected fatal venous air embolism during anaesthesia in a Pomeranian dog with pulmonary calcification.
Death occurred in a 1.25 kg, 9-month-old female Pomeranian dog undergoing anaesthesia for surgical repair of partially healed fractures of the radius and ulna. Following sedation, anaesthesia was induced using thiopentone and maintained with halothane in oxygen. An acute decrease in the dog's end-tidal carbon dioxide (EtCO2) measurements was noted approximately 50 min after induction, immediately following delivery of a 5-ml bolus of lactated Ringer's solution (LRS) administered to flush a small (0.06 ml) volume of fentanyl via a pre-placed intravenous (I/V) catheter. Venous air embolism (VAE) was suspected and the dog died despite interventive therapy. On post-mortem examination, several air bubbles were noted when the right ventricle was opened under water. Histologically, the kidneys appeared abnormal with immature glomeruli, and the lungs appeared diffusely mineralised. The origin of the air was probably small bubbles and microbubbles that may have been present in the extension set and 20 ml syringe used for the administration of fentanyl and I/V fluids to the dog. Renal dysplasia and diffuse pulmonary calcification, with VAE as the probable cause of death. In this case of VAE-associated anaesthetic death, it is further speculated that underlying pulmonary disease, in the form of pulmonary calcification, may have contributed to an increased sensitivity to the adverse effects of VAE.


Intercostal Cryoablation During Video-Assisted Lung Resection Can Decrease Postoperative Opioid Use.
Pain requiring opioid use remains an issue even with minimally invasive thoracic surgery. The objective of this study was to investigate the effectiveness of intercostal nerve cryoablation (CRYO) for pain control in adult patients undergoing pulmonary resection. A retrospective analysis of patients undergoing pulmonary resection by uniportal video-assisted thoracic (uVATS) approach was undertaken. Patients treated with our usual pain regimen (STANDARD) were compared with those who additionally received CRYO. STANDARD includes intercostal bupivacaine, patient-controlled analgesia (24 h), ketorolac (48 to 72 h), and tramadol. Intraoperative CRYO was performed on 5 intercostal levels. The primary aim was to compare pain scores (range, 0 to 10) and morphine equivalent dosages (MED). Secondary outcomes included length of stay, chest tube duration, presence of an air leak, and adverse events. A p value <0.05 was considered significant. There were 49 patients (34 female, 15 male). The median age was 74 (37 to 90) years. Procedures included lobectomy (n = 32), segmentectomy (n = 7), and wedge resections (n = 10). There were 23 (46.9%) CRYO and 26 (53.1%) STANDARD patients. Baseline characteristics were similar. Mean length of stay (2.9 vs 3.5 days), chest tube duration (2.2 vs 1.8 days), and adverse events (9 of 23 vs 7 of 26) were similar. There were no complications attributable to CRYO. Pain scores were not significantly different on postoperative days (POD) 1 to 4. MED was significantly reduced after CRYO on POD 1 (5 vs 47.24), POD 2 (10.93 vs 25.04), POD 3 (8.13 vs 21.7), and POD 4 (7.08 vs 19.17). CRYO can be performed safely during pulmonary resection and can decrease in-hospital opioid use. The results from this retrospective study will need to be validated in future prospective studies.


Polypharmacy and enteral nutrition in patients with complex chronic diseases
Oral medications are often administered through enteral feeding tubes in patients with complex chronic diseases. It is important to consider possible interactions between drugs and enteral nutrition that might lead to unsuccessful treatment or tube occlusion. These patients become subjects for higher risk of problems and errors such as drug incompatibility with enteral nutrition and inappropriate dosage form selection. It is possible to minimize the risk of tube occlusion and incompatibilities problems by recognizing potential medication errors, selecting the most appropriate drug and dosage form and using appropriate administration techniques. In this context, high-alert medications for patients with chronic diseases deserve special attention. Furthermore, risk exposure should be considered among healthcare professionals and patient caregivers handling hazardous drugs. Therefore, main incompatibility problems between drugs and enteral nutrition have been reviewed, including general recommendations for administration of oral medications through enteral feeding tubes and safe handling of hazardous drugs. Specific recommendations for administration of high-alert medications for patients with chronic diseases are also included.


An outline of inherited disorders of the thyroid hormone generating system.
To date, various genetic defects impairing the biosynthesis of thyroid hormone have been identified. These congenital heterogeneous disorders result from mutations of genes involved in many steps of thyroid hormone synthesis, storage, secretion, delivery, or utilization. In contrast to thyroid dyshormonogenesis, the elucidation of the underlying etiology of most cases of thyroid dysgenesis is much less understood. It is suggested that genetic factors might play a role in some cases of thyroid dysgenesis and the best candidate genes involved are those encoding transcription factors known to play a role in the embryonic development of the thyroid gland. Moreover, discordance for thyroid dysgenesis is the rule for monozygotic twins as recently reported and this may result from epigenetic phenomena, early somatic mutations, or postzygotic events. In the final part of this review the molecular defects involved in proteins that transport thyroid hormone in the circulation are described: thyroxine-binding globulin (TBG), transtiretin and albumin, that may be associated with altered thyroid function tests and other pathologic conditions such as amyloidotic polyneuropathy.


Safety of mineralocorticoid receptor antagonists in patients receiving hemodialysis.
To evaluate the literature supporting the safe use of mineralocorticoid antagonists (MRAs) in patients with end-stage renal disease who are receiving hemodialysis. A review of the literature was performed using MEDLINE (1950 through week 2 of February 2012) using the key words and MeSH terms mineralocorticoid antagonists, aldosterone antagonists, spironolactone, or eplerenone combined with dialysis, renal disease, or kidney disease. Studies eligible for inclusion evaluated the impact of MRAs on serum potassium levels in patients with end-stage renal disease receiving hemodialysis. Data related to the patient populations and outcomes of interest were extracted from each publication. Ten studies were included in this review (spironolactone, 9; eplerenone, 1) and reported on the impact of MRAs on potassium levels in this population. In aggregate, the studies, with spironolactone doses ranging from 25 mg 3 times/week after dialysis to 300 mg/day and eplerenone doses of 25 mg twice daily, have shown little increases in serum potassium, particularly with the lower doses. The overall incidence of severe hyperkalemia was low. The literature base is limited by significant methodologic weaknesses of the studies, including low patient numbers, short follow-up periods, and lack of a blinded control group. The current literature suggests that MRAs may be used safely in patients with end-stage renal disease receiving hemodialysis, although additional large controlled trials are needed before definitive treatment recommendations can be made.


Using Ecological Momentary Assessment to Identify Mechanisms of Change: An Application From a Pharmacotherapy Trial With Adolescent Cannabis Users.
The present study used youth's in vivo reports of subjective responses to cannabis while smoking in their natural environments to identify real-world mechanisms of topiramate treatment for cannabis misuse. Participants were 40 cannabis users (≥ twice weekly in past 30 days), ages 15-24 years (47.5% female), with at least one cannabis use episode during the final 3 weeks of a 6-week, randomized clinical trial. Youth reported subjective "high" while smoking, stimulation, sedation, stress, craving, and grams of marijuana used in the natural environment via wireless electronic devices. Bayesian multilevel structural equation modeling (MSEM) evaluated mediation via indirect effect tests. Significant within (daily) and between (person) variability and distinctive within and between effects supported the MSEM approach. Subjective high while smoking was significantly reduced for youth in the topiramate condition, relative to placebo, and the indirect effect of reduced subjective high on total grams of cannabis smoked that day was significant. Indirect effects through other subjective responses were not significant. The results of this initial study suggest that altering subjective responses to smoking, specifically subjective high, may be a key target for developing adjunctive pharmacotherapies for cannabis misuse. More generally, this work provides an example for applying ecological momentary assessment and analytic techniques to evaluate mechanisms of behavior change in longitudinal data.


Serum metalloproteinases 2 and 9 as predictors of gait status, pressure ulcer and mortality after hip fracture.
The aim of this study is to evaluate the serum activity of metalloproteinases (MMPs) -2 and -9 as predictors of pressure ulcer (PU), gait status and mortality 6 months after hip fracture. Eighty-seven patients over the age of 65 admitted to the orthopedic unit from January to December 2010 with hip fracture were prospectively evaluated. Upon admission, patient demographic information, including age, gender and concomitant diseases, was recorded. Blood samples were taken for analysis of MMP -2 and -9 activity by gel zymography and for biochemical examination within the first 72 hours of the patient's admission, after clinical stabilization. The fracture pattern (neck, trochanteric or subtrochanteric), time from admission to surgery, surgery duration and length of hospital stay were also recorded. Two patients were excluded due to the presence of pathological fractures (related to cancer), and three patients were excluded due to the presence of PU before admission. Eighty-two patients, with a mean age of 80.4 ± 7.3 years, were included in the analysis. Among these patients, 75.6% were female, 59.8% had PU, and 13.4% died 6 months after hip fracture. All patients underwent hip fracture repair. In a univariate analysis, there were no differences in serum MMP activity between hip fracture patients with or without PU. In addition, the multiple logistic regression analysis models, which were adjusted by age, gender, length of hospital stay and C-reactive protein, showed that the pro-MMP-9 complexed with neutrophil gelatinase-associated lipocalin form (130 kDa) was associated with gait status recovery 6 months after hip fracture. In conclusion, serum pro-MMP-9 is a predictor of gait status recovery 6 months after hip fracture.


Atypical serum cholinesterase in the Netherlands.
Pseudocholinesterase was examined in 322 samples from unrelated, healthy blood donors. In 14 cases heterozygosity was found, i.e. the frequency of the allele for atypical cholinesterase amounts to 0.022. A comparison is made with other European populations.


Mitochondrial Retroprocessing Promoted Functional Transfers of rpl5 to the Nucleus in Grasses.
Functional gene transfers from the mitochondrion to the nucleus are ongoing in angiosperms and have occurred repeatedly for all 15 ribosomal protein genes, but it is not clear why some of these genes are transferred more often than others nor what the balance is between DNA- and RNA-mediated transfers. Although direct insertion of mitochondrial DNA into the nucleus occurs frequently in angiosperms, case studies of functional mitochondrial gene transfer have implicated an RNA-mediated mechanism that eliminates introns and RNA editing sites, which would otherwise impede proper expression of mitochondrial genes in the nucleus. To elucidate the mechanisms that facilitate functional gene transfers and the evolutionary dynamics of the coexisting nuclear and mitochondrial gene copies that are established during these transfers, we have analyzed rpl5 genes from 90 grasses (Poaceae) and related monocots. Multiple lines of evidence indicate that rpl5 has been functionally transferred to the nucleus at least three separate times in the grass family and that at least seven species have intact and transcribed (but not necessarily functional) copies in both the mitochondrion and nucleus. In two grasses, likely functional nuclear copies of rpl5 have been subject to recent gene conversion events via secondarily transferred mitochondrial copies in what we believe are the first described cases of mitochondrial-to-nuclear gene conversion. We show that rpl5 underwent a retroprocessing event within the mitochondrial genome early in the evolution of the grass family, which we argue predisposed the gene towards successful, DNA-mediated functional transfer by generating a "pre-edited" sequence.


Spin-orbit coupling and electron spin resonance theory for carbon nanotubes.
A theoretical description of electron spin resonance (ESR) in 1D interacting metals is given, with primary emphasis on carbon nanotubes. The spin-orbit coupling is derived, and the resulting ESR spectrum is analyzed using a low-energy field theory. Drastic differences in the ESR spectra of single-wall and multiwall nanotubes are found. For single-wall tubes, the predicted double peak spectrum is linked to spin-charge separation. For multiwall tubes, a single narrow asymmetric peak is expected.


Complications associated with the prophylactic use of methylprednisolone during surgical stabilization after spinal cord injury.
The authors attempted to determine if there is a significant relationship between the incidence of medical complications and the prophylactic use of methylprednisolone (MP) during spine surgery in patients with acute spinal cord injury (SCI) who had already received MP on hospital admission (typically in the setting of an Emergency Room/Trauma Center). The authors studied 73 patients with acute SCI who were admitted to the hospital for at least 7 days postinjury. All patients 1) received a 24-hour regimen of MP in the acute period of hospitalization; and 2) underwent surgery to stabilize the spine and/or decompress the spinal cord. Patients were separated into two groups on the basis of whether they received additional MP therapy during spine surgery. A chart review was conducted retrospectively to determine the incidence of complications up to 6 weeks postinjury. Muscle strength and American Spinal Injury Association grades were determined prospectively throughout the follow-up period. In patients who received two courses of MP following acute SCI (one at initial hospitalization and one during surgery), a significantly increased probability of complications was demonstrated compared with those who received no MP therapy during surgery. This was particularly evident when the incidences of serious complications were compared. Prophylactic use of MP as a neuroprotective agent during spine surgery in patients with acute SCI should be avoided in those in whom MP was administered on admission to the hospital.


Bioinformatics Analyses of the Role of Vascular Endothelial Growth Factor in Patients with Non-Small Cell Lung Cancer.
This study was aimed to identify the expression pattern of vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC) and to explore its potential correlation with the progression of NSCLC. Gene expression profile GSE39345 was downloaded from the Gene Expression Omnibus database. Twenty healthy controls and 32 NSCLC samples before chemotherapy were analyzed to identify the differentially expressed genes (DEGs). Then pathway enrichment analysis of the DEGs was performed and protein-protein interaction networks were constructed. Particularly, VEGF genes and the VEGF signaling pathway were analyzed. The sub-network was constructed followed by functional enrichment analysis. Total 1666 up-regulated and 1542 down-regulated DEGs were identified. The down-regulated DEGs were mainly enriched in the pathways associated with cancer. VEGFA and VEGFB were found to be the initiating factor of VEGF signaling pathway. In addition, in the epidermal growth factor receptor (EGFR), VEGFA and VEGFB associated sub-network, kinase insert domain receptor (KDR), fibronectin 1 (FN1), transforming growth factor beta induced (TGFBI) and proliferating cell nuclear antigen (PCNA) were found to interact with at least two of the three hub genes. The DEGs in this sub-network were mainly enriched in Gene Ontology terms related to cell proliferation. EGFR, KDR, FN1, TGFBI and PCNA may interact with VEGFA to play important roles in NSCLC tumorigenesis. These genes and corresponding proteins may have the potential to be used as the targets for either diagnosis or treatment of patients with NSCLC.


Crystal structure of P450cin in a complex with its substrate, 1,8-cineole, a close structural homologue to D-camphor, the substrate for P450cam.
Cytochrome P450cin catalyzes the monooxygenation of 1,8-cineole, which is structurally very similar to d-camphor, the substrate for the most thoroughly investigated cytochrome P450, cytochrome P450cam. Both 1,8-cineole and d-camphor are C(10) monoterpenes containing a single oxygen atom with very similar molecular volumes. The cytochrome P450cin-substrate complex crystal structure has been solved to 1.7 A resolution and compared with that of cytochrome P450cam. Despite the similarity in substrates, the active site of cytochrome P450cin is substantially different from that of cytochrome P450cam in that the B' helix, essential for substrate binding in many cytochrome P450s including cytochrome P450cam, is replaced by an ordered loop that results in substantial changes in active site topography. In addition, cytochrome P450cin does not have the conserved threonine, Thr252 in cytochrome P450cam, which is generally considered as an integral part of the proton shuttle machinery required for oxygen activation. Instead, the analogous residue in cytochrome P450cin is Asn242, which provides the only direct protein H-bonding interaction with the substrate. Cytochrome P450cin uses a flavodoxin-like redox partner to reduce the heme iron rather than the more traditional ferredoxin-like Fe(2)S(2) redox partner used by cytochrome P450cam and many other bacterial P450s. It thus might be expected that the redox partner docking site of cytochrome P450cin would resemble that of cytochrome P450BM3, which also uses a flavodoxin-like redox partner. Nevertheless, the putative docking site topography more closely resembles cytochrome P450cam than cytochrome P450BM3.


Antibiotic dispensing practice in community pharmacies: A simulated client study.
Dispensing antibiotics without a prescription, although forbidden by Sri Lankan law since 1986, is a common practice throughout the country. This study attempted to quantify this practice for the first time. To evaluate the response of community pharmacy staff to an antibiotic product request without a prescription and to explore possible factors influencing such practice. A cross-sectional simulated client study was conducted from Jan to Sept 2017. A total of 242 community pharmacies were visited by trained simulated clients (SCs) and they requested for one of four antibiotics (erythromycin tablets, amoxicillin syrup, metronidazole tablets, or ciprofloxacin tablets) without a prescription. Data on the interaction between the pharmacy staff and SC was recorded using a data collection sheet immediately after each visit. Nearly 50% of pharmacies had a pharmacist on duty during the visit. Attending pharmacy staff asked for a prescription for the requested antibiotic in 47% of the instances. Only 16 (7%) pharmacy staff recommended the SC to see a doctor. Overall, 61% of pharmacies dispensed antibiotics without a prescription. The highest dispensed antibiotic was ciprofloxacin (44/63 requests; 70%) and the least was amoxicillin (32/62; 52%). Patient history was obtained in only a few instances and none of the pharmacies dispensed alternative over the counter medicines. The availability of a pharmacist reduced the risk of dispensing an antibiotic without a prescription (Adj. OR = 0.54, 95% CI: 0.30-0.95; P = 0.033), however, it did not have any impact on patient history taking. Dispensing antibiotics without a prescription is a common practice in Sri Lankan community pharmacies. In most instances, pharmacy staff neither inquired about patient history nor requested the patient to obtain the advice of a doctor. Presence of a pharmacist may reduce dispensing antibiotics without prescription, but may not have an effect on interactions with clients requesting antibiotics.


Oxidative decomposition of propylene carbonate in lithium ion batteries: a DFT study.
This paper reports an in-depth mechanistic study on the oxidative decomposition of propylene carbonate in the presence of lithium salts (LiClO4, LiBF4, LiPF6, and LiAsF6) with the aid of density functional theory calculations at the B3LYP/6-311++G(d,p) level of theory. The solvent effect is accounted for by using the implicit solvation model with density method. Moreover, the rate constants for the decompositions of propylene carbonate have been investigated by using transition-state theory. The shortening of the original carbonyl C-O bond and a lengthening of the adjacent ethereal C-O bonds of propylene carbonate, which occurs as a result of oxidation, leads to the formation of acetone radical and CO2 as a primary oxidative decomposition product. The termination of the primary radical generates polycarbonate, acetone, diketone, 2-(ethan-1-ylium-1-yl)-4-methyl-1,3-dioxolan-4-ylium, and CO2. The thermodynamic and kinetic data show that the major oxidative decomposition products of propylene carbonate are independent of the type of lithium salt. However, the decomposition rate constants of propylene carbonate are highly affected by the lithium salt type. On the basis of the rate constant calculations using transition-state theory, the order of gas volume generation is: [PC-ClO4](-) > [PC-BF4](-) > [PC-AsF6](-) > [PC-PF6](-).


Combined indocyanine green and medical glue enables stable and precise position in animal studies: promising for fluorescence-guided pulmonary ground glass nodule resection.
Accurate preoperative localization of pulmonary nodules is crucial for surgical treatment. The use of indocyanine green (ICG) for localization is prone to thoracic contamination and spread, resulting in the eventual failure of localization. By using medical glue combined with ICG, we can accurately and permanently locate various tissues in animal study, which can provide evidences for clinical translations. A series of medical glue and ICG volume ratios of 2:3, 3:3, 4:3, 6:3, and 9:3 were mixed and injected immediately into subcutaneous tissues of BALB/c nude mice; either medical glue or ICG was injected singly in the control group. Fluorescence intensity over time and boundary sharpness were investigated to determine the optimal ratio. Then, fluorescence guided resection of tissue was performed ex vivo on the pig intestine utilizing optimal ratio. Further, localization agents with the optimal ratio were injected into the organs of living mice, and fluorescence imaging for accurate positioning was performed 24 hours later. The localization agents with a volume ratio of 4:3 showed the best boundary sharpness and the strongest photostability. With the guidance of fluorescence navigation, the marked tissues were accurately separated and removed from the surrounding tissue both on mice and on pig intestines. In the organs of living mice, the localization agents (ratio 4:3) realized accurate positioning of marked tissues. Additionally, the medical glue limited the diffusion of ICG, promising to enable more stable and precise positioning of the nodules during surgery. The combination of ICG and medical glue presents a superior approach when compared to the individual use of either ICG or medical glue. This technique offers enhanced precision and durability and sealed the wound, thereby mitigating the risk of pneumothorax following puncture procedures. This innovative technique optimizes the properties of medical adhesive to augment tissue density while harnessing the real-time fluorescent endoscopic marking capabilities of ICG during surgical interventions. By employing this innovative technique, it holds significant promise for augmenting the accuracy of pulmonary nodule localization in thoracoscopic surgery within future clinical applications.


H1N1: can a pandemic cycle be broken?
The influenza virus that caused the 2009 H1N1 swine-origin flu pandemic is antigenically similar to the one that caused the devastating 1918 pandemic. Over time, the human population became susceptible to a modified version of the 1918 pandemic H1N1 virus that had been archived in swine. Now, two papers, one in this issue of Science Translational Medicine and one in Science, shed mechanistic light on how glycosylation gave rise to seasonal human flu viruses that are immunologically distinct from their 1918 pandemic precursor and the 2009 pandemic strain. These findings suggest strategies to anticipate and prevent future pandemics.


The protective and pathogenic role of Th17 cell plasticity and function in the tumor microenvironment.
At the turn of the century, researchers discovered a unique subtype of T helper cells that secretes IL-17 and defined it as Th17. The latest study found that Th17 cells play both positive and negative definitive roles in the regulation of antitumor immune responses. Although the function of Th17 in the tumor microenvironment remains poorly understood, more and more studies have shown that this paradoxical dual role is closely related to the plasticity of Th17 cells in recent decades. Further understanding of the characteristics of Th17 cells in the tumor microenvironment could yield novel and useful therapeutic approaches to treat cancer. In this review, we further present the high plasticity of Th17 cells and the function of Th17-producing IL-17 in tumor immunity.


[Analysis of deletional damage in SMN1, SMN2, and NAIP genes in patients with spinal muscular atrophy in the northwestern region of Russia].
Polymerase chain reaction with subsequent SSCP (single-strand DNA conformational polymorphism) and restriction (BselI restriction endonuclease) analyses were used to type the DNA samples of affected individuals and their relatives from 23 Russian families with high risk of spinal muscular atrophy (SMA) residing in the northwestern region of Russia. Deletions of exon 7 of the SMN gene were found in 96% of the individuals examined. The frequency of homozygous deletion of exons 7 and 8 of the SMN1 gene was 65%. The frequency of homozygous isolated deletion of the SMN1 gene exon 7 among the SMA patients was 4.3%. Homozygous deletion of exon 5 of the NAIP gene was found in 22% of SMA patients. In SMA patients, a total of seven deletion types involving the SMN1, NAIP, and SMN2 genes were detected. Deletion of exons 7 and 8 of the SMN1 gene was the most common mutation associated with SMA in patients from the northwestern Russia.


Pain management in pigs undergoing experimental surgery; a literature review (2012-4).
Failure to provide effective analgesia to animals in noxious studies contravenes the obligation to refine animal experimentation and, by increasing 'noise' in physiological data sets, may decrease the scientific validity of results. Pig models of surgical conditions are becoming increasingly important and used for translational work. This review aimed to determine the extent to which the recent biomedical literature describes pain assessment and alleviation in pigs recovering from experimental surgery. Three databases (Medline, Web of Knowledge, and Google Scholar) were searched to find relevant studies published from January 2012 to March 2014. Information on pain assessment and peri- and postoperative analgesia was extracted. The review identified 233 papers meeting selection criteria. Most articles (193/233, 83%) described use of drugs with analgesic properties, but only 87/233 (37%) described postoperative analgesia. No article provided justification for the analgesic chosen, despite the lack of guidelines for analgesia in porcine surgical models and the lack of formal studies on this subject. Postoperative pain assessment was reported in only 23/233 (10%) articles. It was found that the reporting of postoperative pain management in the studies was remarkably low, reflecting either under-reporting or under-use. Analgesic description, when given, was frequently too limited to enable reproducibility. Development of a pain-scoring system in pigs, together with the mandatory description of pain management in submitted articles, would contribute to improved laboratory pig welfare.


[Study of expression of cytokine genes in the process of cultivation of healthy donor leukocytes].
Study of expression of cytokine genes in the process of cultivation of healthy donor leukocytes. RNA isolated before, after 3 and 24 hours of cultivation of leukocytes of 15 healthy donors aged 19 - 32 years was the object of the study. Study of the expression of genes of 8 cytokines by the level of their mRNA was performed by using polymerase chain reactionwith reverse transcription. In healthy donors among with individual differences, general regularities were traced: higher levels of IFNalpha and anti-inflammatory cytokine gene expression, as well as predominantly low expression of pro-inflammatory cytokines. In most of the cases in the process of cultivation of leukocytes isolated from blood donors the highest level of gene expression of pro-inflammatory cytokines is noted after 3 hours of cultivation, and expression of genes of anti-inflammatory cytokines remains constant for 24 hours of cultivation.


Synthesis and purification of two SP (6-11) analogues with enhanced selectivity for the NK-1 receptor.
Two hexapeptide analogues of Substance P (6-11) have been synthesized. Replacement of Gly9 by proline provides a peptide with tenfold enhanced selectivity for the NK-1 receptor. The corresponding proline-containing glycopeptide incorporating a beta-D-glucopyranosyl residue linked to the side-chain of Glu6 was 100 times more selective than Substance P for the same receptor.