Modification and application of an in vitro assay to examine inositol phosphate degradation in the digestive tract of poultry.
An in vitro assay was modified to study the disappearance of inositol hexakisphosphate (InsP6 ) and the formation of lower inositol phosphate (InsP) isomers in the poultry digestive tract, and three experiments investigated the influence of diets with different ingredients and additives. Using the poultry diet as a matrix, the assay simulated the conditions (e.g. pH, temperature, proteolytic enzymes, water content, and retention time) of the crop, stomach, and small intestine, and extraction and analysis of InsP isomers were immediately conducted. The assay produced highly reproducible results with coefficients of variation ≤10% for an InsP isomer concentration ≥0.4 µmol g-1 DM (n = 3), and it was sensitive to the factors that varied in the three experiments. The described assay is a suitable tool that can be used to screen feed enzymes and to investigate the effects of supplements in the absence of endogenous phytases. The ease of handling and high reproducibility of the assay indicated that the assay is a rapid and feasible method that can be used to examine the degradation pathway of phytate in feed under gastrointestinal conditions. © 2017 Society of Chemical Industry.


Genomic analysis in nephrology--towards systems biology and systematic medicine?
With the advent of transcriptome profiling techniques, an enormous amount of data has been generated in the field of molecular nephrology. We will review analysis tools and challenges for genomic approaches and present their application in gene-expression studies on kidney biopsies. The findings in this rapidly evolving field may ultimately complement histopathological analysis, the current diagnostic and prognostic gold standard. Altogether, genomics may bring nephrology one-step closer to a systematic understanding of biological processes involved in renal disease.


Patterned growth and field-emission properties of AlN nanocones.
Patterned growth of AlN nanocones on a Ni-coated Si substrate is demonstrated through the reaction between AlCl(3) and NH(3) at 700 degrees C with Mo grid as a mask. The AlN nanocones are selectively deposited in the hollow region of the mask with diameters of approximately 10 nm at the tips and 50-60 nm at the roots. The field-emission (FE) performance is effectively enhanced by the patterned growth mainly because of the decreased screening effect, and both turn-on and threshold fields are dramatically decreased, less than half of the corresponding ones for the unpatterned product with similar sizes. The results indicate that patterned growth is an efficient and reproducible way to enhance the FE performance of AlN nanocones, which could be applied to optimize the FE properties of other nanoscale field emitters.


Chronic effects of superimposed electromyostimulation during cycling on aerobic and anaerobic capacity.
To examine if chronic endurance training by means of simultaneously applied, superimposed electromyostimulation (EMS) can be used to improve performance and physiological core parameters compared to the traditional cycling. Twenty-one male subjects (VO2peak 55.2 ± 5.1 ml min- 1 kg- 1) were assigned to either a cycling (C) or cycling with superimposed EMS (C + E) group. Before and after the 4-week training period, including 14 sessions of moderate cycling [60 min at 60% peak power output (PPO)], participants performed a 20-min time-trial, a step test to exhaustion, a 30-s isokinetic sprint test, and maximum force- and power-tests. Markers of muscle damage and metabolic condition were assessed during the training period. Step test results revealed increases in PPO, VO2peak, lactate threshold 1, and the anaerobic threshold for both groups (p < 0.05). Mean power output (MPO) obtained from time-trial was improved in C and C + E (p < 0.05). Isokinetic sprint test revealed increased PPO in both groups, whereas MPO was only changed in C (p < 0.05). Strength parameters were unaffected. Although metabolic stimuli and markers of muscle damage were higher in C + E compared to C, improvements of endurance performance and capacity were not significantly different between C and C + E. Despite a higher metabolic, respiratory, and muscular demand, chronic additional superimposed EMS during cycling does not result in superior improvements in endurance and strength performance compared to the traditional cycling.


[Ocular findings in former premature infants at the age of 11 to 14 years].
Functional disturbances as well as morphologic changes can be various in regressed retinopathy of prematurity (ROP). To investigate the incidence and the degree of such changes, we examined prematurely born infants in the age of 11 to 14 years. Of the 142 prematures (birthweight < or = 2000 g), who were cared for in their first weeks of life in the University Children's Hospital at the Klinikum Mannheim in 1977 to 1979, 48 could be reexamined. Of 48 infants (mean birth weight 1808 +/- 211 g, gestational age 34.6 +/- 3.1 weeks) six (12.5%; birth weight 1742 +/- 218 g, gestational age 32.2 +/- 2.5) had had acute ROP (stage 2 or 3). When reexamined in school age 10 (21%) of the children had physical deficits. Eight (17%) visited a school for handicapped children. Eight (17%) children had a squint. In 13 out of 96 (14%) eyes visual acuity was reduced to 0.8 or less. Thirteen eyes (14%) were emmetropic, 67 (70%) hyperopic, 16 (17%) myopic and 15 (16%) astigmatic. The intraocular pressure was normal in all eyes (15 +/- 4 mm Hg). The anterior segments did not show findings caused by ROP. The fundus findings in the 12 eyes, in which the diagnosis of acute ROP was established in the first weeks of life, showed in 5 (42%) eyes a slightly reduced angle kappa between the vascular arcades and avascular retina in the temporal fundus periphery in all of the 12 (100%) eyes. In 1 (8%) eye the retinal periphery showed extensive scarring after cryotherapy because of acute ROP. None of the eyes which had had acute ROP showed macular ectopia or retinal folds (amotio falciformis). In 16 of the 84 (19%) eyes, which did not have a history of acute ROP, minor changes of the retinal periphery, the peripheral retinal vessels and the pigment epithelium were present, which were caused by prematurity. Prematurely born infants examined in school age, who were comparatively mature preterms at birth (mean birth weight 1800 g; mean gestational age 34.6 weeks), did not show a higher risk of refractive errors, i.e. myopia. However, they were at higher risk having squint. The functional disturbances found in the prematurely born infants in this study were not caused by morphologic changes due to ROP.


Delivery room hospice.
Advances in perinatal science over the past five decades have reduced the practical 'threshold of viability' by approximately one week every 10 years such that survivors are expected as early as 22 weeks. Ethical standards regarding treatment of this periviable patient population remain enigmatic. We review limitations in the current ethical rationale for caring for these infants in the delivery room and introduce an alternative utilising a delivery room hospice care approach involving the administration of opioids.


Predestinative role acidic cerebrospinal fluid on the destiny of central channel in spinal cord following subarachnoid hemorrhage: an experimental study.
Acidosis is the most dangerous complication in subarachnoid hemorrhage (SAH). This study aimed to investigate the effect of acidic cerebrospinal fluid on central canal structures after SAH. Twenty-eight hybrid rabbits were studied. Blood and cerebrospinal fluid pH values were recorded before/during/after the experimental procedures. The structures related to the central canals at the level of C5 of the cervical spinal cord were then examined histopathologically. The relationship between pH values of ependymal cells and degenerated epithelial cell densities was statistically analyzed. Mean blood pH values and degenerated ependymal cell density (n/mm2) were as follows: 7.351 ± 0.033/23 ± 7 in control, 7.322 ± 0.059/78 ± 13 in SHAM, and 7.261 ± 0.048/254 ± 62 in study animals. Gross examinations revealed swelling, edema, pia-arachnoid adhesions, ventral canal dilatation, arachnoiditis, central canal hemorrhage, occlusions, and dilatation in the spinal cord. Cerebrospinal fluid acidosis-induced central channel pathologies should be considered an important complication of SAH following SAH.


Biosynthesis of the wall acidic polysaccharide in Bacillus cereus AHU 1356.
Biosynthetic studies on an acidic polysaccharide, comprising galactose, rhamnose, N-acetylglucosamine and sn-glycerol 1-phosphate, were carried out with a membrane system obtained from Bacillus cereus AHU 1356. Incubation of the membranes with UDP-[14C]Gal, TDP-[14C]Rha and UDP-[14C]GlcNAc resulted in the formation of four or more labeled-sugar-linked lipids and a labeled polysaccharide. Data on structural analysis of the sugar moieties released from the glycolipids, together with results of enzymatic conversion of [14C]galactose-linked lipid and [14C]Rha-Gal-linked lipid to higher-oligosaccharide-linked lipids and polysaccharide, led to the conclusion that the acidic polysaccharide is probably synthesized through the following pathway: (sequence in text) The glycerophosphate residues seem to be derived from phosphatidylglycerol.


The Role of Chemokines and Chemokine Receptors in Diabetic Nephropathy.
Kidney function decline is one of the complications of diabetes mellitus and may be indicated as diabetic nephropathy (DN). DN is a chronic inflammatory disease featuring proteinuria and a decreasing glomerular filtration rate. Despite several therapeutic options being currently available, DN is still the major cause of end-stage renal disease. Accordingly, widespread innovation is needed to improve outcomes in patients with DN. Chemokines and their receptors are critically involved in the inflammatory progression in the development of DN. Although recent studies have shown multiple pathways related to the chemokine system, the specific and direct effects of chemokines and their receptors remain unclear. In this review, we provide an overview of the potential role and mechanism of chemokine systems in DN proposed in recent years. Chemokine system-related mechanisms may provide potential therapeutic targets in DN.


The use of transcutaneous electrical nerve stimulation (TENS) in a major cancer center for the treatment of severe cancer-related pain and associated disability.
Cancer pain is difficult to treat, often requiring a multimodal approach. While medication management remains the mainstay for the treatment of cancer pain, medications are often associated with undesired side effects. Transcutaneous electrical nerve stimulation (TENS) provides a potential adjunctive method for treating cancer pain with minimal side effects. Few studies have been performed evaluating the efficacy of TENS on cancer pain. We sought to examine the usefulness of TENS on all cancer patients and to specifically look at the use of TENS as a goal-directed therapy to improve functionality. Retrospective cohort study. Since 2008, patients with chronic cancer pain and on multimodal pain regimens were trialed with TENS. Those patients who showed an improvement in pain symptoms or severity were educated about and provided with a TENS unit for use at home. Pain symptoms and scores were monitored with the visual analog scale (VAS), the numerical rating pain (NRP) scale, and Short-Form McGill Questionnaire at the start of TENS treatment and at 2 months follow-up. TENS proved beneficial in 69.7% of patients over the course of 2 months. In TENS responsive patients, VAS scores decreased by 9.8 on a 0-100 mm scale (P < 0.001), and NRP scores decreased by 0.8 on a 1-10 scale (P < 0.001). Lack of placebo and lack of blinding of physician and patient. TENS provides a beneficial adjunct for the treatment of cancer pain, especially when utilized as a goal-directed therapy.


Interactive effects of water, light and heat stress on photosynthesis in Fremont cottonwood.
Fremont cottonwood seedlings are vulnerable to water stress from rapid water-table decline during river recession in spring. Water stress is usually cited as the reason for reduced establishment, but interactions of water stress with microclimate extremes are more likely the causes of mortality. We assessed photosynthetic responses of Fremont cottonwood seedlings to water, light and heat stresses, which commonly co-occur in habitats where seedlings establish. Under moderate temperature and light conditions, water stress did not affect photosynthetic function. However, stomatal closure during water stress predisposed Fremont cottonwood leaves to light and heat stress, resulting in greatly reduced photosynthesis beginning at 31 °C versus at 41 °C for well-watered plants. Ontogenetic shifts in leaf orientation from horizontal to vertical, which occur as seedlings mature, reduce heat and light stress, especially during water stress. When compared with naturally occurring microclimate extremes, seedling stress responses suggest that reduced assimilation and photoprotection are common for Fremont cottonwood seedlings on exposed point bars where they establish. These reductions in photosynthesis likely have negative impacts on growth and may predispose young (<90-day-old) seedlings to early mortality during rapid water-table declines. Interactions with heat and light stress are more important in these effects than water stress alone.


Mechanisms of cadmium-induced proximal tubule injury: new insights with implications for biomonitoring and therapeutic interventions.
Cadmium is an important industrial agent and environmental pollutant that is a major cause of kidney disease. With chronic exposure, cadmium accumulates in the epithelial cells of the proximal tubule, resulting in a generalized reabsorptive dysfunction characterized by polyuria and low-molecular-weight proteinuria. The traditional view has been that as cadmium accumulates in proximal tubule cells, it produces a variety of relatively nonspecific toxic effects that result in the death of renal epithelial cells through necrotic or apoptotic mechanisms. However, a growing volume of evidence suggests that rather than merely being a consequence of cell death, the early stages of cadmium-induced proximal tubule injury may involve much more specific changes in cell-cell adhesion, cellular signaling pathways, and autophagic responses that occur well before the onset of necrosis or apoptosis. In this commentary, we summarize these recent findings, and we offer our own perspectives as to how they relate to the toxic actions of cadmium in the kidney. In addition, we highlight recent findings, suggesting that it may be possible to detect the early stages of cadmium toxicity through the use of improved biomarkers. Finally, some of the therapeutic implications of these findings will be considered. Because cadmium is, in many respects, a model cumulative nephrotoxicant, these insights may have broader implications regarding the general mechanisms through which a variety of drugs and toxic chemicals damage the kidney.


Role of the leader peptide of maltose-binding protein in two steps of the export process.
During the process of export of maltose-binding protein to the periplasm of Escherichia coli, the leader peptide is involved in at least two steps. The presence of the leader portion of maltose-binding protein was shown to be necessary to mediate initial binding of the precursor to the membrane. However, the presence of a mutationally altered leader which does not sustain export in vivo was sufficient to allow this interaction. Thus, the defect in export which is manifested in vivo by this mutational substitution occurs at a step that follows membrane association, most likely the translocation step. Translocation occurs at discrete sites that are not uniformly distributed over the cytoplasmic membrane. A large proportion of the membrane involved in translocation has a higher density than that of bulk cytoplasmic membrane.


[A case of tuberculous pyothorax after an interval of four years of finishing with the first treatment for pulmonary tuberculosis].
We reported a case of tuberculous pyothorax which developed at four years after finishing with the first treatment for pulmonary tuberculosis. A 50-year-old female was admitted to our hospital with right chest pain. Tuberculous pyothorax was diagnosed by means of polymerase chain reaction (PCR method) of pleural effusion and of histological findings of the pleural section. She was cured by operation, pleural drainage and anti-tuberculous drugs. The bone scincigram of 99mTc revealed accumulation in the right 9th rib, tuberculous empyema might have been a secondary development from osteomyelitis.


Prevention of alcohol-related deaths in middle-aged heavy drinkers.
Alcohol as a cause of death in middle-aged patients is well-known from clinical studies. A similarly important correlation in the general population of urban middle-aged men is highly underestimated. Health screening investigations have shown that mortality related to alcohol is five times more common in nonparticipants than in participants. From the mid-70s, the Malmoe Screening and Intervention Study (MSIS) commenced screening investigations including a large number of residents of Malmoe. One goal was to find intervention programs for individuals in an early development of problem drinking, thereby preventing development of serious complications of endstage alcoholism. Herein, we report on the mortality of heavy drinkers (drinking more than 40 g alcohol/day) who were randomized to an intervention or control procedure and whose median survival was 13 years postentry into the MSIS. Health-screened men, aged 45-49 years at the initial screening examination and displaying serum gamma-glutamyltransferase (GT) in the top decentile of the GT distribution, were included. A total of 978 out of 11,257 participants met this criteria. A randomized intervention and control study was performed for four years and consisted of men (n = 667) who were born between 1927-1937 and who had two consecutive high GT values within 3 weeks along with heavy alcohol consumption. Half the individuals were informed of the test results and invited for further assessment by a senior physician (n = 365). The principles for brief intervention (DiClemente et al.,1991; Miller and Sanchez, 1993; National Institute of Alcohol Abuse and Alcoholism, 1999) were applied. The other half of the men (n = 302) were left with the information that they had a high GT value and were followed up with laboratory checkups every 2nd year. Mortality was followed up until 1991 and information on deaths was obtained from hospital and police records, necropsy reports, and death certificates. Long-term follow-up of mortality for 10-16 years (median, 13 years) showed that 124 of the 978 men had died (12.7%). Autopsy was performed in 96.5% of the cases. In 59 men (48%), death was alcohol-related. In the intervention group (n = 365), 38 (10.4%) men were dead and in the control group (n = 302), 42 (13.9%) men had died. There was a statistically significant difference (p = 0.026), with advantage for treatment. Less alcohol-related deaths and deaths occurring later during follow-up were found in the intervention group compared with the control group. The difference between the groups in total mortality, coronary heart disease, and cancer death was not statistically significant. These findings support previous results from the MSIS study indicating that long-term intervention in urban males with alcohol-induced GT increases may be beneficial in terms of survival.


Heavy metals in bamboo shoots from Southeastern China and risk assessment.
Bamboo shoot is an indispensable vegetable in Southeastern China, so a survey of heavy metals in bamboo shoots is a relevant topic of interest. The present study sought to analyse the content of seven heavy metals (As, Cd, Cr, Cu, Mn, Pb and Zn) in six bamboo shoot species from Southeastern China. Percentages of 3.8% (Cd) and 8.9% (Pb) of the samples exceeded the maximum limits as established by the Chinese legislation. Further health risk assessment exhibited that the Cd intake contribution of these samples could not be negligible. The hazard index (HI) at average exposure was less than one. The average HI values in moso bamboo shoot were significantly higher than those of other bamboo shoot species. Overall, the results indicated that the intake of bamboo shoots is safe for consumers in Southeastern China.


[The evaluation of the efficacy of Alflutop in the complex treatment of patients with chronic lower back pain (the observational study ZEITNOT)].
To analyze the effect of Alflutop on neuroinflammation in patients with chronic lower back pain (CBP). Forty-one patients with a verified CBP diagnosis were enrolled in the study. Alflutop was used for treating CBP, 1 ml once/day, for 20 days. Treatment efficacy was monitored using the Visual Analogue Scale (VAS), DN4 test; the Roland-Morris questionnaire; the index of pain activity in the lumbar spine; and the level of tumor necrosis factor-α (TNF-α) in blood plasma. There were three visits in total: screening (visit 0), treatment start (visit 1, 0-3 days after screening) and visit 2 (3 months later (±7 days) from the start of treatment). Before the start of therapy, in some patients (group 1, n=14 (34.1%) the TNF-α concentration in the blood plasma was below the detectable level (less than 4.0 pg/ml), while in group 2 (n=27 (659%)), the expression of TNF-α in peripheral blood was observed at the level of 6.3 [4.9; 7.4] pg/ml. Patients in group 2 significantly (p<0.05) differed from patients in group 1 by the greater number of CBP exacerbations over the last year as well as by the results of testing on DN4 (higher values) and SBI (greater discomfort). In group 2, a significant relationship was found between the TNF-α level in blood plasma and the number of exacerbations as well as between the TNF-α level and the number of DN4 points. At visit 2, patients in group 2 had a significant (p<0.05) decrease in pain intensity according to VAS, an improvement in the quality of life according to the Roland-Morris questionnaire, a decrease in the severity of the neuropathic component of pain according to DN4 test as well as subjective condition improvement associated with the activity of pain in the lumbar spine. A significant relationship was found between the level of TNF-α and the number of DN4 points after treatment and the period of active observation. In the majority of CBP patients, the high relapse rate and neuropathic nature of pain may be associated with persistent neuroinflammation due to TNF-α synthesis. Alflutop inhibits the TNF-α expression substantially, which significantly correlates with a decrease in the neuropathic pain syndrome component according to the DN4 questionnaire. The use of Alflutop can be considered as an effective method of treating patients with CBP, which has an impact on the process of neuroinflammation as one of the leading causes of changes in the pain nature and its chronicity.


Androgen Excess Induced Mitochondrial Abnormality in Ovarian Granulosa Cells in a Rat Model of Polycystic Ovary Syndrome.
Androgen excess could profoundly lead to follicular dysplasia or atresia, and finally result in polycystic ovary syndrome (PCOS); however, the exact mechanism remains to be fully elucidated. PCOS model rats were induced by dehydroepiandrosterone, and their fertility was assessed. The ovarian granulosa cells (GCs) from matured follicles of PCOS model rats were collected and identified by immunofluorescence. The mitochondrial ultrastructure was observed by transmission electron microscope and the mitochondrial function was determined by detecting the adenosine triphosphate (ATP) content and mtDNA copy number. Besides, the expressions of respiratory chain complexes and ATP synthases in relation to mitochondrial function were analyzed. The PCOS model rats were successfully induced, and their reproductive outcomes were obviously adverse. The GCs layer of the ovarian was apparently cut down and the mitochondrial ultrastructure of ovarian GCs was distinctly destroyed. The ATP content and mtDNA copy number of ovarian GCs in PCOS model rats were greatly reduced, and the expressions of NDUFB8 and ATP5j were significantly down-regulated without obvious deletion of mtDNA 4834-bp. Androgen excess could damage mitochondrial ultrastructure and function of GCs in rat ovary by down-regulating expression of NDUFB8 and ATP5j in PCOS.


The use of a sensitive equilibrium dialysis method for the measurement of free testosterone levels in healthy, cycling women and in human immunodeficiency virus-infected women.
Measurements of total and free testosterone levels in women have lacked precision and accuracy because of limited assay sensitivity. The paucity of normative data on total and free testosterone levels in healthy women has confounded interpretation of androgen levels in women with human immunodeficiency virus (HIV) infection and other disease states. Therefore, the objectives of this study were to develop sensitive assays for the measurement of the low total and free testosterone levels in women to define the range for these hormones during the normal menstrual cycle and assess the total and free testosterone levels in HIV-infected women. By using a larger volume of serum, increasing the incubation time, and reducing the antibody concentration, the sensitivity of the total testosterone assay was increased to 0.008 nmol/L, and that of the free testosterone assay was increased to 2 pmol/L. The mean percent free testosterone was 1.0 +/- 0.1% of the total testosterone. Serum total and free testosterone levels in the follicular and luteal phases were not significantly different, but both demonstrated a modest preovulatory increase, 3 days before the LH peak. Serum total [0.50 +/- 0.32 (14.60 +/- 9.22) vs. 1.2 +/- 0.7 nmol/L (34.3 +/- 21.0 ng/dL); P < 0.0001] and free testosterone levels (5.56 +/- 2.70 (1.58 +/- 0.80) vs. 12.8 +/- 5.5 pmol/L (3.4 +/- 1.7 pg/mL); P < 0.0001) were significantly lower in HIV-infected women (n = 37) than in healthy women (n = 34). Serum total and free testosterone levels were also significantly lower in HIV-infected women who were menstruating normally. There were no significant differences in serum total and free testosterone levels between those who had lost weight and those who had not. Testosterone levels correlated inversely with plasma HIV ribonucleic acid copy number. Serum FSH, but not LH, levels were significantly higher in HIV-infected women than in controls. Using assays with sufficient sensitivity, we defined the range for total and free testosterone levels during the normal menstrual cycle. Serum total and free testosterone levels are lower in HIV-infected women and correlate inversely with plasma HIV ribonucleic acid levels. The hypothesis that androgen deficiency contributes to wasting in HIV-infected women remains to be tested.


Feasibility of bidimensional speckle-tracking echocardiography for strain analysis in consecutive patients in daily clinical practice.
We aimed to analyze the feasibility of two-dimensional speckle-tracking echocardiography (2DSTE) in evaluating myocardial strain in consecutive, nonselected patients in daily clinical practice. Strain analysis using 2DSTE was attempted in 59 consecutive patients: 24 patients with severe aortic stenosis, 28 patients with dilated cardiomyopathy, and 7 healthy controls. The analysis was done by four expert echocardiographers and one cardiology resident. It was possible to obtain reliable data for radial strain in 175 of 354 segments (49%), circumferential strain in 192 of 354 segments (54%), and longitudinal strain in 319 of 354 segments (90%). Experienced echocardiographers felt assessment of radial and circumferential strain was appropriate in more segments than did the cardiology resident (57% and 58% vs. 23% and 40%, respectively, P < 0.01). Longitudinal strain analysis with 2DSTE is feasible in most segments, but the radial and circumferential strain evaluation was only feasible in approximately half of the patients.


Does atazanavir cause lipodystrophy?
Atazanavir is a once-a-day non-pepsidic inhibitor of HIV protease which is licensed for use in the UK and the USA. One of its major advantages is that it does not produce lipid abnormalities in patients who receive it. This feature has been widely interpreted as implying that in the future there will be no abnormalities associated with fat redistribution when the drug is administered. This article explores that view.


Tetrahedral chalcogenide clusters and open frameworks.
By integrating porosity with electrical or optical properties, microporous chalcogenides may have unique applications. Here we review recent advances and discuss concepts in the synthesis and crystal structure of tetrahedral clusters and their frameworks. These chalcogenides can be viewed as trivalent metal chalcogenides doped with tetra-, di-, or monovalent metal cations. Low-valent cations help to increase the cluster size, while high-valent cations have the opposite effect.


Chemoprofile and functional diversity of fungal and bacterial endophytes and role of ecofactors - A review.
Endophytes represent a hidden world within plants. Almost all plants that are studied harbor one or more endophytes, which help their host to survive against pathogens and changing adverse environmental conditions. Fungal and bacterial endophytes with distinct ecological niches show important biological activities and ecological functions. Their unique physiological and biochemical characteristics lead to the production of niche specific secondary metabolites that may have pharmacological potential. Identification of specific secondary metabolites in adverse environment can also help us in understanding mechanisms of host tolerance against stress condition such as biological invasions, salt, drought, temperature. These metabolites include micro as well as macromolecules, which they produce through least studied yet surprising mechanisms like xenohormesis, toxin-antitoxin system, quorum sensing. Therefore, future studies should focus on unfolding all the underlying molecular mechanisms as well as the impact of physical and biochemical environment of a specific host over endophytic function and metabolite elicitation. Need of the hour is to reshape the focus of research over endophytes and scientifically drive their ecological role toward prospective pharmacological as well as eco-friendly biological applications. This may help to manage these endophytes especially from untapped ecoregions as a useful undying biological tool to meet the present challenges as well as lay a strong and logical basis for any impending challenges.


The Association between Liver Enzymes and Mortality Stratified by Non-Alcoholic Fatty Liver Disease: An Analysis of NHANES III.
Associations between liver enzymes or De Ritis ratio (DRR; aspartate aminotransferase (AST)/alanine aminotransferase (ALT)) and mortality stratified by non-alcoholic fatty liver disease (NAFLD), which have rarely been analyzed in previous studies, were investigated using the National Health and Nutrition Examination Survey (NHANES) III (1988-1994). Participants without risk factors for liver diseases other than NAFLD were linked with National Death Index records through 2019 (n = 11,385) and divided into two cohorts with or without NAFLD, based on ultrasound examination. Liver enzyme concentrations were categorized into sex-specific deciles and subsequently grouped (AST and ALT: 1-3, 4-9, 10; gamma glutamyltransferase (GGT): 1-8, 9-10). DRR was categorized into tertiles. Cox proportional hazards regression models adjusted for confounders were fitted to estimate associations with mortality. Compared with low levels, high GGT and DRR in participants with and without NAFLD had significantly higher hazard ratios for all-cause mortality. Compared with intermediate concentrations, low ALT showed higher all-cause mortality in participants with and without NAFLD, whereas low AST had higher HR in participants without NAFLD and high AST in those with NAFLD. Mortality was associated with liver enzymes or DRR in participants both with and without NAFLD, indicating that the relationship is not mediated solely by hepatocellular damage.


Supplementing monosodium glutamate to partial enteral nutrition slows gastric emptying in preterm pigs(1-3).
Emerging evidence suggests that free glutamate may play a functional role in modulating gastroduodenal motor function. We hypothesized that supplementing monosodium glutamate (MSG) to partial enteral nutrition stimulates gastric emptying in preterm pigs. Ten-day-old preterm, parenterally fed pigs received partial enteral nutrition (25%) as milk-based formula supplemented with MSG at 0, 1.7, 3.0, and 4.3 times the basal protein-bound glutamate intake (468 mg·kg(-1)·d(-1)) from d 4 to 8 of life (n = 5-8). Whole-body respiratory calorimetry and (13)C-octanoic acid breath tests were performed on d 4, 6, and 8. Body weight gain, stomach and intestinal weights, and arterial plasma glutamate and glutamine concentrations were not different among the MSG groups. Arterial plasma glutamate concentrations were significantly higher at birth than after 8 d of partial enteral nutrition. Also at d 8, the significant portal-arterial concentration difference in plasma glutamate was substantial (∼500 μmol/L) among all treatment groups, suggesting that there was substantial net intestinal glutamate absorption in preterm pigs. MSG supplementation dose-dependently increased gastric emptying time and decreased breath (13)CO2 enrichments, (13)CO2 production, percentage of (13)CO2 recovery/h, and cumulative percentage recovery of (13)C-octanoic acid. Circulating glucagon-like peptide-2 (GLP-2) concentration was significantly increased by MSG but was not associated with an increase in intestinal mucosal growth. In contrast to our hypothesis, our results suggest that adding MSG to partial enteral nutrition slows the gastric emptying rate, which may be associated with an inhibitory effect of increased circulating GLP-2.


Acyclovir reduces the duration of fever in patients with infectious mononucleosis-like illness.
Acyclovir is known for its antiviral activity against some pathogenic viruses such as the Epstein-Barr virus (EBV) that causes infectious mononucleosis (IM) and IM-like illness. Therefore, we empirically administered acyclovir to patients with suspected EBV-IM and IM like-illness, upon their admission to our hospital. We admitted 25 patients, who were hospitalized for fever and lymphadenopathy, to the Tohoku University Hospital Infectious Disease Ward. As part of treatment, 8 of these patients were given acyclovir (750 mg/day) with their consent and were assigned to the acyclovir group; the remaining 17 patients were assigned to the control group. The mean age of acyclovir patients (all men) was 42±5.2 years, and that of control patients (13 men and 4 women) was 31±3.0 years. The cause of illness was confirmed as EBV-IM in 6 patients (1, acyclovir; 5, control), and remained unknown for the other 19 IM-like illness patients (7, acyclovir; 12, control). A shorter duration of hospitalization and fever was observed in the acyclovir compared to that in the control patients (hospitalization duration: 16±3.7 vs. 27±7.7 days, P=0.36; fever duration: 4.5±1.8 vs. 18±6.5 days, P=0.04). Additionally, serum amyloid A (SAA) levels were lower in acyclovir than that in control patients (98±37 vs. 505±204 µg/mL, P=0.02). Therefore, we propose that acyclovir is a potential therapeutic agent for both EBV-IM and IM like-illnesses. Future studies should further examine its mechanism of action.


Generation of Chlamydomonas strains that efficiently express nuclear transgenes.
The unicellular green alga Chlamydomonas reinhardtii is both an invaluable model organism for plant biology and an attractive biotechnological production system. Despite the availability of efficient methods for introduction of foreign genes into the nuclear genome of the alga, transgene expression levels are usually very poor. This is a serious limitation that has severely hampered both post-genomics research in Chlamydomonas and use of the alga in molecular farming. Here we report a solution to this problem. We have designed a genetic screen that facilitates isolation of algal strains that efficiently express introduced transgenes. The levels of accumulation of foreign protein in our expression strains are almost uniformly high in all transgenic clones and are little influenced by position effects. The possibility of expressing transgenes to high levels will greatly facilitate post-genomics research in Chlamydomonas, and will also boost exploitation of the alga as an inexpensive production host for biopharmaceuticals and other valuable compounds.


Sequential MR imaging of denervated and reinnervated skeletal muscle as correlated to functional outcome.
To prospectively assess the short inversion time inversion-recovery (STIR) magnetic resonance (MR) signal intensity changes of denervated and reinnervated skeletal muscle over time in clinical patients. This study was approved by the institutional review board, and informed consent was obtained from all patients. Twenty-three patients with complete traumatic transection of the median or ulnar nerve in the forearm were prospectively followed for 12 months after surgical nerve repair. STIR MR images of selected intrinsic hand muscles were obtained 1, 3, 6, 9, and 12 months after nerve repair, and signal intensities of denervated and reinnervated muscles were measured semiquantitatively. After 12 months, hand function was assessed. Signal intensity ratios were correlated to functional outcome with analysis of variance. Of the 23 patients, 10 had good function recovery, while 13 had poor recovery. For the group with good function recovery, mean signal intensity ratios of 1.267 ± 0.060 (standard deviation), 1.357 ± 0.116, 1.297 ± 0.111, 1.205 ± 0.096, and 1.086 ± 0.104 were found at 1-, 3-, 6-, 9-, and 12-month follow-up, respectively. In the group with poor recovery, mean signal intensity ratios of 1.299 ± 0.056, 1.377 ± 0.094, 1.419 ± 0.117, 1.398 ± 0.111, and 1.342 ± 0.095 were found at 1-, 3-, 6-, 9-, and 12-month follow-up, respectively. Comparison of the group with poor function recovery and the group with good function recovery showed significant differences at 6-, 9-, and 12-month follow-up (P = .035, P = .001, and P < .001, respectively), with normalizing signal intensities in the group with good function recovery and sustained high signal intensity in the group with poor function recovery. STIR MR imaging can be used to differentiate between denervated and reinnervated muscles for at least 12 months after nerve transection.


Cognitive enhancing effects of pazopanib in D‑galactose/ovariectomized Alzheimer's rat model: insights into the role of RIPK1/RIPK3/MLKL necroptosis signaling pathway.
Necroptosis, a programmed form of necrotic cell death carried out by receptor-interacting serine/threonine protein kinase 1 (RIPK1) and RIPK3, has been found to be implicated in the pathogenesis of Alzheimer's disease (AD). An FDA-approved anti-cancer drug, pazopanib, is reported to possess potent inhibitory effect against necroptosis via interfering with RIPK1. So far, there are no existing data on the influence of pazopanib on necroptotic pathway in AD. Thus, this study was designed to explore the impact of pazopanib on cognitive impairment provoked by ovariectomy (OVX) together with D-galactose (D-Gal) administration in rats and to scrutinize the putative signaling pathways underlying pazopanib-induced effects. Animals were allocated into four groups; the first and second groups were exposed to sham operation and administered normal saline and pazopanib (5 mg/kg/day, i.p.), respectively, for 6 weeks, while the third and fourth groups underwent OVX then were injected with D-Gal (150 mg/kg/day, i.p.); concomitantly with pazopanib in the fourth group for 6 weeks. Pazopanib ameliorated cognitive deficits as manifested by improved performance in the Morris water maze besides reversing the histological abnormalities. Pazopanib produced a significant decline in p-Tau and amyloid beta (Aβ) plaques. The neuroprotective effect of pazopanib was revealed by hampering neuroinflammation, mitigating neuronal death and suppressing RIPK1/RIPK3/MLKL necroptosis signaling pathway. Accordingly, hindering neuroinflammation and the necroptotic RIPK1/RIPK3/MLKL pathway could contribute to the neuroprotective effect of pazopanib in D-Gal/OVX rat model. Therefore, this study reveals pazopanib as a valuable therapeutic agent in AD that warrants future inspection to provide further data regarding its neuroprotective effect.


Modulation of inner junction proteins contributes to axoneme differentiation.
Cilia build distinct subdomains with variable axonemal structures to perform diverse functions in cell motility and signaling. In sensory cilia across species, an axoneme differentiates longitudinally into a middle segment with nine microtubule (MT) doublets and a distal segment with nine MT singlets that extends from the A tubules of the doublets. Here, we study axoneme differentiation in Caenorhabditis elegans by analyzing the flagellar inner junction protein FAP20 and PCRG1 that connect A and B tubules in Chlamydomonas. The nematode CFAP-20 is restricted to the middle segment with doublets, and its loss disconnects A and B tubules. However, PCRG-1 is absent from most sensory cilia, and its deletion does not disrupt cilia. Ectopic introduction of PCRG-1 into cilia generated abnormal MT doublets in the distal segment and reduced intraflagellar transport and animal sensation. Thus, the absence of an inner junction protein prevents B-tubule extension, which contributes to axoneme differentiation and ciliary function.


Unified interpretation of liver stiffness measurement by M and XL probes in non-alcoholic fatty liver disease.
The latest model of vibration-controlled transient elastography (VCTE) automatically selects M or XL probe according to patients' body built. We aim to test the application of a unified interpretation of VCTE results with probes appropriate for the body mass index (BMI) and hypothesise that this approach is not affected by hepatic steatosis. We prospectively recruited 496 patients with non-alcoholic fatty liver disease who underwent VCTE by both M and XL probes within 1 week before liver biopsy. 391 (78.8%) and 433 (87.3%) patients had reliable liver stiffness measurement (LSM) (10 successful acquisitions and IQR:median ratio ≤0.30) by M and XL probes, respectively (p<0.001). The area under the receiver operating characteristic curves was similar between the two probes (0.75-0.88 for F2-4, 0.83-0.91 for F4). When used in the same patient, LSM by XL probe was lower than that by M probe (mean difference 2.3 kPa). In contrast, patients with BMI ≥30 kg/m2 had higher LSM regardless of the probe used. When M and XL probes were used in patients with BMI <30 and ≥30 kg/m2, respectively, they yielded nearly identical median LSM at each fibrosis stage and similar diagnostic performance. Severe steatosis did not increase LSM or the rate of false-positive diagnosis by XL probe. High BMI but not severe steatosis increases LSM. The same LSM cut-offs can be used without further adjustment for steatosis when M and XL probes are used according to the appropriate BMI.


Protein kinase C ϵ stabilizes β-catenin and regulates its subcellular localization in podocytes.
Kidney disease has been linked to dysregulated signaling via PKC in kidney cells such as podocytes. PKCα is a conventional isoform of PKC and a well-known binding partner of β-catenin, which promotes its degradation. β-Catenin is the main effector of the canonical Wnt pathway and is critical in cell adhesion. However, whether other PKC isoforms interact with β-catenin has not been studied systematically. Here we demonstrate that PKCϵ-deficient mice, which develop proteinuria and glomerulosclerosis, display lower β-catenin expression compared with PKC wild-type mice, consistent with an altered phenotype of podocytes in culture. Remarkably, β-catenin showed a reversed subcellular localization pattern: Although β-catenin exhibited a perinuclear pattern in undifferentiated wild-type cells, it predominantly localized to the nucleus in PKCϵ knockout cells. Phorbol 12-myristate 13-acetate stimulation of both cell types revealed that PKCϵ positively regulates β-catenin expression and stabilization in a glycogen synthase kinase 3β-independent manner. Further, β-catenin overexpression in PKCϵ-deficient podocytes could restore the wild-type phenotype, similar to rescue with a PKCϵ construct. This effect was mediated by up-regulation of P-cadherin and the β-catenin downstream target fascin1. Zebrafish studies indicated three PKCϵ-specific phosphorylation sites in β-catenin that are required for full β-catenin function. Co-immunoprecipitation and pulldown assays confirmed PKCϵ and β-catenin as binding partners and revealed that ablation of the three PKCϵ phosphorylation sites weakens their interaction. In summary, we identified a novel pathway for regulation of β-catenin levels and define PKCϵ as an important β-catenin interaction partner and signaling opponent of other PKC isoforms in podocytes.


Exposure of motor vehicle examiners to carbon monoxide: a historical prospective mortality study.
The National Institute for Occupational Safety and Health (NIOSH) investigated the health effects of chronic exposure to low concentrations of carbon monoxide by conducting a historical prospective cohort study of mortality patterns among 1,558 white male motor vehicle examiners who were employed in New Jersey for a minimum of 6 months between 1944 and 1973. Industrial hygiene surveys indicated that the examiners were exposed to carbon monoxide at a time-weighted average (TWA) of 10-24 ppm; the exposure level recommended by NIOSH is 35 ppm TWA. A modified life table technique was used to calculate cause-specific expected deaths for the cohort adjusted for age and calendar time periods. The expected deaths were compared to the number of observed deaths through August 1973. The cohort demonstrated a slight overall increase in cardiovascular disease deaths (124 observed vs. 118.4 expected), but a more pronounced excess was observed within the first 10 yr. following employment (28 observed vs. 20.9 expected). A statistically significant excess of cancer mortality was found for motor vehicle examiners after 30 yr latency (13 observed vs. 6.9 expected, P < 0.5); this excess, however, was not confined to any particular organ site. The number of deaths due to accidents was significantly lower than expected (8 observed vs. 19.6 expected, P < .01).


The gracilis myofasciocutaneous flap: vascular anatomy and clinical application.
Unreliable skin perfusion has been reported frequently in the gracilis myocutaneous flap, resulting in moderately high partial flap necrosis. We modified the traditional myocutaneous operative technique by including all available regional fascia and created a myofasciocutaneous flap with increased skin viability. In addition, we defined the arterial anatomy of the flap that contributes to enhanced flap survival. In a cadaver study, blue latex was injected into the external iliac arteries of 11 cadaveric legs and the gracilis myofasciocutaneous flap dissected. Selective ink injection of the pedicle and perforating vessels also was performed in 8 legs. Two additional legs were injected with a barium-latex mixture, cut into 2-cm-thick transverse sections, and radiographed. Dissections demonstrated arterial connections between the pedicle vessel (medial femoral circumflex artery) and fasciocutaneous perforating vessels from the superficial femoral artery. Perforating vessels contribute to an axially oriented fascial network that supplies the overlying skin. Selective ink injections demonstrated the individual primary cutaneous vascular territories for each perforator. Radiographs of 2-cm-thick transverse sections confirmed the presence of arterial connections between the pedicle and the superficial femoral artery perforators. Twelve patients, previously pelvically irradiated, then underwent harvest of 18 large, longitudinally oriented (8-cm-wide, up to 30-cm-long) gracilis myofasciocutaneous flaps. All fascia beneath the skin paddle was taken in continuity with the deep fascia surrounding the gracilis muscle to minimize disturbance of any connecting vasculature held within the fascia. Patients were followed for an average of 12.1 months (range 3 to 31 months). Minor complications related to the flaps occurred in 6 of 12 patients (50 percent), i.e., seromas, mild wound infections, and a partial dehiscence; however, vascularity was excellent with no partial or complete flap necrosis. All wounds healed completely.


Implementation of a Research Information Management System in a Pediatric Hospital.
Faculty publications have been collected in universities, health, and medical institutions for many years, and Cincinnati Children's is no exception. Since 1949, a yearly list of faculty publications was manually compiled using multiple data sources and disseminated by the Edward L. Pratt Research Library. Products to centralize faculty publication collection and analysis with bibliometric tools are growing in popularity. This article will review the collaborative decision to choose a Research Information Management System and the implementation process including successes, challenges, and future opportunities.


Intra-operative digital angiography as a control of the in situ saphenous vein by-pass grafts.
Forty-two patients undergoing in situ saphenous vein by-pass grafting procedures, in two patients bilaterally, were examined intra-operatively with digital subtraction angiography. In 19 (43%) of the examinations the graft and the anastomoses appeared adequate. In 8 cases (18%) significant abnormalities were found, including stenoses (11%), deficient anastomoses (5%) and graft kinking (2%). Remaining arteriovenous fistulas were found in 17 patients (39%). In most cases immediate correction was possible avoiding later re-operation. At follow up 11 of the 44 grafts were occluded, 10 of these during the first five months and of these five during the first week.


Improved glycemic control with use of oral hypoglycemic therapy with or without insulin.
To determine whether combination oral hypoglycemic therapy in insulin-using patients with non-insulin-dependent diabetes mellitus (NIDDM) can improve glycemic control for a prolonged period. We expanded and extended an earlier study to include 130 patients with NIDDM for 10 to 30 years who had been using twice-daily mixed insulin for less than 10 years. Reduction and eventual elimination of the insulin therapy and substitution of metformin and a sulfonylurea were attempted. At follow-up visits, patients were weighed, random plasma glucose levels were determined, and glycosylated hemoglobin values were obtained. Of 130 C-peptide-positive patients with NIDDM receiving twice-daily mixed insulin, 100 were successfully transferred to combination oral hypoglycemic therapy with glyburide originally and later glimepiride and metformin--a primary failure rate of 23.1%. Secondary failure occurred in 20 patients after a mean duration of 6.4 months. Two patients with successful conversion to oral combination therapy resumed insulin treatment because of cost. Of the patients with primary failures, 6 had gastrointestinal side effects, 10 were successfully managed on combination oral therapy plus evening mixed insulin, and 14 ultimately received twice-daily insulin and metformin. Of the secondary failures, 13 were controlled on combination oral therapy plus evening insulin and 7 on twice-daily insulin in conjunction with metformin. No difference was found in the original C-peptide levels among these three groups. Glycosylated hemoglobin levels were significantly less on combined oral hypoglycemic therapy (9.8% versus 8.3%; P = 0.0001), on combination oral therapy plus evening insulin (11.2% versus 9.7%; P = 0.001), and on return to twice-daily mixed insulin with metformin (11.0% versus 9.9%; P = 0.04). Those eight patients who resumed twice-daily insulin therapy alone, however, had a nonsignificant increase in glycosylated hemoglobin (9.3% versus 9.9%). Improvement in glycosylated hemoglobin level in insulin-using patients with NIDDM can be obtained with combination oral therapy alone, combination oral therapy with once-daily evening insulin, or twice-daily mixed insulin with metformin in comparison with twice-daily insulin alone.


Conjunctival provocation test for the diagnosis of ocular hypersensitivity to chlorobutanol.
Conjunctival provocation test (CPT) is a useful tool for the determination of the reagent in patients with allergic conjunctivitis. Our aim is to present an unusual reaction of ocular hypersensitivity to chlorobutanol by using this technique. This case describes a 56-year-old woman who presented intense ocular pruritus and conjunctival hyperemia with each instillation of Colircusi Fluotest (Alcon, El Masnou, Spain). Skin tests and CPTs were considered. Skin tests were all negative. CPTs were performed with commercially available ophthalmic products that were selected for their compositions. Chlorobutanol was presumed as the reagent through elimination. Positive CPT with purified chlorobutanol confirmed this hypothesis. CPT performed with commercially available products can be a useful, accessible, and inexpensive technique to orient the diagnosis of suspected ocular hypersensitivity to a pharmacologic component. To our knowledge, this is the first report of ocular hypersensitivity to chlorobutanol.


Coracoacromial ligament division.
The object of this paper is to report on the findings of a retrospective study of 40 patients with 41 shoulders with persistent painful arc syndrome secondary to a chronic coracoacromial ligament inflammation who underwent simple coracoacromial ligament division at the Toronto East General and Orthopaedic Hospital between January 1973 and June 1979. Initial therapy was always nonoperative. Surgical intervention was reserved for patients who did not respond to conservative management and who had a painful arc with tenderness of the coracoacromial ligament. The aim of the coracoacromial ligament division was to relieve impingement by releasing the coracoacromial arch. Patients were carefully examined to rule out associated neck pathology, rotator cuff problems, and lesions of the acromioclavicular joint. Any patients with significantly large osteophytes under the anterior acromion were excluded. Forty patients (41 shoulders) were questioned and examined in followup. There were 29 males and 11 females. The ages ranged from 21 to 72 years (average 43.5 years). In 21 shoulders (51%), there was a history of trauma as the initiating factor. The follow-up ranged from 8 to 76 months (average 36.3 months). According to a described rating system, the results were satisfactory to excellent in 39 of 41 shoulders (95%) and unsatisfactory in two of 41 shoulders (5%). The back to work time ranged from 1 to 16 weeks (average 5.7 weeks).(ABSTRACT TRUNCATED AT 250 WORDS)


Successful treatment of recalcitrant nonunions with combined magnetic field stimulation.
Nonunions and delayed unions have been classically defined by Bassett as an arrest of the fracture healing process at an intermediary stage of repair, at which time the fracture gap is bridged by fibrocartilage. It is estimated that approximately 10-20 % of long bone fractures in the United States will result in delayed unions when compared to the average rate of healing for the location and type of fracture. Many of these will go on to a nonunion if biological or biomechanical factors are not optimized to enhance healing. Additional commorbities such as smoking, ethanol abuse, malnutrition, malabsorption and altered neurologic conditions can contribute to delayed unions or nonunions. Even despite appropriate and aggressive early management of long bone fractures, a certain percentage still lack progression of healing and go on to nonunion. Classical surgical management of nonunions includes obtaininjg fracture stabilization with ORIF techniques and bone grafting, with reported clinical successes ranging from 50-80%. Those that fail to achieve union despite classical management are indeed recalcitrant nonunions.


Effects of delta-9-tetrahydrocannabinol on mouse spleens.
A study was undertaken to ascertain the effects of delta-9-Tetrahydrocannabinol on the plaque forming cell response of mice immunized with sheep erythrocytes. It was found that a marked suppression of plaque forming cells occurred concomitant with a general loss of spleen cellularity following administration of delta-9-THC. These results suggest rather marked effects of this drug on antibody synthesis.


A case of severe verapamil overdose.
We report here on a 73-year-old woman who ingested 3.6 g (40 mg x 90 tablets) of verapamil in a suicide attempt. On arrival, the patient was awake and well oriented. Two and a half hours after ingestion, she lost consciousness, as her heart rate and blood pressure began to decrease. Cardiac monitoring showed atrioventricular dissociation. Although she suffered from extreme hypotension, an echocardiogram revealed that the wall motion of the heart was almost normal, and cardiac output measured with a Swan-Ganz catheter was well preserved. The plasma verapamil concentration in this patient was 1499 ng/ml 4 h after ingestion. Hyperglycemia and hypokalemia, laboratory data revealed, continued for 18 h after admission. The patient was successfully resuscitated with intravenous saline, dopamine, and norepinephrine. Besides reporting on this case, we also report on a treatment for severe verapamil overdose.


Potential therapeutic value of drugs inhibiting semicarbazide-sensitive amine oxidase: vascular cytoprotection in diabetes mellitus.
Semicarbazide-sensitive amine oxidase (SSAO) is a copper-containing enzyme found in large amounts in blood plasma and in vascular smooth muscle. The catalytic activity of this enzyme is elevated in diabetes mellitus and some substrates, such as aminoacetone and methylamine also occur in increased amounts in this disease. After deamination by SSAO highly angiotoxic products are formed, methylglyoxal and formaldehyde, respectively. Moreover, hydrogen peroxide is also formed as a side-product. These products arising from SSAO-catalysed reactions may partially explain late-diabetic damages in the kidneys, eyes and peripheral nerves, as well as other cardiovascular disorders. It is therefore proposed that inhibition of SSAO may decrease the formation of these cytotoxic products and therefore prevent or slow the development of late-diabetic complications.


Soy and other legumes: 'Bean' around a long time but are they the 'superfoods' of the millennium and what are the safety issues for their constituent phytoestrogens?
The recognition that legumes and, in particular, soybeans provide not only an excellent source of vegetable protein but also contain appreciable amounts of a number of phytoprotectants has increased general awareness of their potential nutritional and health properties. Since the discovery that soybeans are one of the richest dietary sources of bioavailable phytoestrogens, this legume has been elevated to the forefront of clinical nutritional research. These natural 'selective oestrogen receptor modulators' have been shown to be bioactive. The recent approval by the Food and Drug Administration in the United States for a health claim for soy protein reducing risk for heart disease by its effects on lowering cholesterol levels has led to the increased awareness of the health benefits of soy protein. However, the presence of high levels of phytoestrogens in soybeans has also led to concerns over the potential safety of soy foods. This review will focus on the cardioprotective benefits of legumes and discuss the hypothetical concerns regarding the constituent phytoestrogens.


Safety of a proteoliposome from Neisseria meningitides as adjuvant for a house dust mite allergy vaccine.
The proteoliposome (PL) of Neisseria meningitidis serogroup B has been reported as a safe and potent vaccine adjuvant, inducing a TH1-skewed response. The present study describes a pre-clinical safety evaluation of an allergy therapeutic vaccine candidate based on purified allergens from Dermatophagoides siboney house dust mite and PL as adjuvant, both components adsorbed onto aluminum hydroxide gel. Two separate studies of acute toxicity evaluation were performed in mice and rabbits, and two repeat-dose studies were conducted in non-sensitized and allergen-sensitized Balb/c mice, respectively. The study in sensitized mice intends to model a therapeutic setting. Aerosolized allergen challenge was used in both settings to model natural respiratory exposure. In the therapeutic setting, mice were administered with three doses containing 2 μg allergen at weekly intervals [subcutaneous route] and subsequently challenged with aerosolized allergen for 6 consecutive days. Parameters of general toxicity effects were assessed via measures of behavior, body weight, food and water consumption, and macroscopic evaluation of organs. Histological examination of organs and the injection site was performed. Potential immunotoxicity effects at the systemic level were assessed by blood eosinophil counting and serum allergen specific IgE by ELISA The vaccine did not produce general or functional toxic effects of significance, at a dose up to 100 μg allergen per kg body weight. An expected local reaction at the injection site was observed, which could be attributed mostly to the immunological effect of aluminum hydroxide. The models implemented here suggest an acceptable safety profile of this vaccine for testing in clinical trials of allergy immunotherapy.


Circumcision and HIV transmission.
To review the recent literature on male circumcision and its effect on HIV acquisition. The report from the randomized clinical trial of male circumcision in South Africa demonstrating a 60% protective effect in preventing HIV acquisition provided the first clinical trial evidence of efficacy of male circumcision in protecting men against HIV infection. This protective effect was consistent with both ecological and epidemiologic studies which also show a protective effect of 50-70% in men at high risk for HIV infection. Biological studies also demonstrate an increased number of HIV receptor cells in the mucosa of foreskin providing additional evidence of HIV susceptibility in the uncircumcised male. Male circumcision may also have a beneficial effect in preventing HIV acquisition in women and lowering selected sexually transmitted infections in both sexes. The results of two ongoing randomized clinical trials of male circumcision in Kenya and Uganda are awaited with interest, however male circumcision should be carefully considered as a potential public health tool in preventing HIV acquisition. If other trials confirm the results of the South African trial, implementation of this surgical procedure will need to be carefully scaled up and integrated into other prevention programs with emphasis on surgical training, aseptic techniques, acceptability, availability and cultural considerations.


[Effects of habitat fragmentation on nesting site selection of red-crowned crane].
During April and May of 1985, 1995 and 1998, red-crowned crane's nesting and variation of breeding population quantities in Shuangtaihekou National Natural Reserve in Liaoning, and also the habitat fragmentation there were investigated. Associated with previous data of the reserve, red-crowned crane's nesting habitat had been seriously fragmentated into 91 patches from one integrated reed wetland. The area of the smallest patch was 0.37 km2, and the minimum distance of two nests was 304 m. Compared with records of previous data, the minimum area of nesting habitat reduced by 0.72 km2. However, the breeding population quantities of red-crowned crane had maintained at about 30 pairs for a long period. The red-crowned crane adapted to the changed environment by the ecological adaptation strategy of reducing area of nesting habitat.


An Unusual Case of Caecal Volvulus due to Appendicitis, Successfully Managed by Caecopexy.
Caecal volvulus is a rare cause of intestinal obstruction. Caecal volvulus precipitated by acute appendicitis is even rarer. We report an unusual case of caecal volvulus with acute appendicitis as a cause. A 55-year female presented in surgical emergency with 3 days history of abdominal pain, distension and absolute constipation; and 2 days history of vomiting. Her past surgical history was significant for hysterectomy 5 years back. On examination, abdomen was distended and bowel sounds exaggerated. X-ray abdomen erect showed a single large air fluid level in the right hemiabdomen. A preoperative diagnosis of intestinal obstruction due to adhesions was made and patient prepared for exploratory laparotomy. On exploration, a huge caecum was lying in the midline and was twisted around a band arising from the appendix and attached deep into the pelvis. The appendix was densely inflammed. The volvulus was de-twisted in a counter clockwise manner. Viability of the caecum was confirmed and appendectomy was done. Caecopexy was performed and abdomen was closed. Postoperative recovery of the patient was uneventful and she was safely discharged on 5th postoperative day.


Electron Dynamics in Open Quantum Systems: The Driven Liouville-von Neumann Methodology within Time-Dependent Density Functional Theory.
A first-principles approach to describe electron dynamics in open quantum systems driven far from equilibrium via external time-dependent stimuli is introduced. Within this approach, the driven Liouville-von Neumann methodology is used to impose open boundary conditions on finite model systems whose dynamics is described using time-dependent density functional theory. As a proof of concept, the developed methodology is applied to simple spin-compensated model systems, including a hydrogen chain and a graphitic molecular junction. Good agreement between steady-state total currents obtained via direct propagation and those obtained from the self-consistent solution of the corresponding Sylvester equation indicates the validity of the implementation. The capability of the new computational approach to analyze, from first principles, non-equilibrium dynamics of open quantum systems in terms of temporally and spatially resolved current densities is demonstrated. Future extensions of the approach toward the description of dynamical magnetization and decoherence effects are briefly discussed.


Simulating a patient's fall as a means to improve routine communication: Joint training for nursing and fifth-year medical students.
Physicians and nursing staff interact as a team on a daily basis in hospital settings. However, both educational paths offer few opportunities to establish contact with the other professional group. Neither professional group can practice its later role with the other group in a "safe" learning environment. Routine interprofessional collaboration is described as being in need of great improvement and carries with it the potential for conflict. To improve interprofessional communication and task management, a simulation-based emergency training session for nursing students and fifth-year medical students was developed at the KRH Klinikum Nordstadt in Hanover, Germany. As a pilot project, the course was held twice in the form of a one-day session with ten nursing and four medical students. Using the example of a patient's fall, course participants were able to observe and actively treat multiple simulated patients. Following each simulation the trainer conducted a comprehensive debriefing. The course was then evaluated using a questionnaire. The evaluation of the team training showed a high level of acceptance among the two participating professional groups. On a scale of 1 (hardly applicable) to 5 (strongly applicable), the course was given a 4 by both professional groups for its relevance to daily work. In the open-ended written responses praise was specifically given for the opportunity to learn how to switch perspectives as a result of the simulation exercises. A common emergency on the hospital ward offers a good opportunity to establish and practice interprofessional team skills. With the knowledge gained about communication and the ability to change viewpoints, participants are able to improve their team skills. Participants demonstrated a high degree of acceptance for the training program.


Three-Dimensional Superlocalization Imaging of Gliding Mycoplasma mobile by Extraordinary Light Transmission through Arrayed Nanoholes.
In this paper, we describe super-resolved sampling of live bacteria based on extraordinary optical transmission (EOT) of light. EOT is produced by surface plasmon confinement and coupling with nanostructures. Bacterial fluorescence is excited by the localized fields for subdiffraction-limited sampling. The concept was applied to elucidating bacterial dynamics of gliding Mycoplasma mobile (M. mobile). The results analyzed with multiple M. mobile bacteria show individual characters and reveal that M. mobile undergoes a significant axial variation at 94 nm. The sampling error of the method is estimated to be much smaller than 1/10 of the diffraction limit both in the lateral and depth axis. The method provides a powerful tool for investigation of biomolecular dynamics at subwavelength precision.


Disruption of myofibroblastic Notch signaling attenuates liver fibrosis by modulating fibrosis progression and regression.
The phenotypic transformation of hepatic myofibroblasts (MFs) is involved in the whole process of the progression and regression of liver fibrosis. Notch signaling has been demonstrated to modulate the fibrosis. In this study, we found that Notch signaling in MFs was overactivated and suppressed with the progression and regression of hepatic fibrosis respectively, by detecting Notch signaling readouts in MFs. Moreover, we inactivated Notch signaling specifically in MFs with Sm22αCreER-RBPjflox/flox mice (RBPjMF-KO), and identified that MFs-specific down-regulation of Notch signaling significantly alleviated CCl4-induced liver fibrosis during the progression and regression. During the progression of liver fibrosis, MFs-specific blockade of Notch signaling inhibited the activation of HSCs to MFs and increases the expression of MMPs to reduce the deposition of ECM. During the regression of fibrosis, blocking Notch signaling in MFs increased the expression of HGF to promote proliferation in hepatocytes and up-regulated the expression of pro-apoptotic factors, Ngfr and Septin4, to induce apoptosis of MFs, thereby accelerating the reversal of fibrosis. Collectively, the MFs-specific disruption of Notch signaling attenuates liver fibrosis by modulating fibrosis progression and regression, which suggests a promising therapeutic strategy for liver fibrosis.


Frequency and source of prescription eyewear insurance coverage in Ontario: a repeated population-based cross-sectional study using survey data.
Insurance coverage may reduce cost barriers to obtain vision correction. Our aim was to determine the frequency and source of prescription eyewear insurance to understand how Canadians finance optical correction. We conducted a repeated population-based cross-sectional study using 2003, 2005 and 2013-2014 Canadian Community Health Survey data from respondents aged 12 years or older from Ontario, Canada. In this group, the cost of prescription eyewear is not covered by the government unless one is registered with a social assistance program or belongs to a specific population. We determined the frequency and source of insurance coverage for prescription eyewear in proportions. We used survey weights provided by Statistics Canada in all analyses to account for sample selection, a complex survey, and adjustments for seasonal effect, poststratification, nonresponse and calibration. We compared unadjusted proportions and adjusted prevalence ratios (PRs) of having insurance. Insurance covered all or part of the costs of prescription eyewear for 62% of Ontarians in all 3 survey years. Of those insured, 84.1%-86.0% had employer-sponsored coverage, 9.0%-10.3% had government-sponsored coverage, and 5.7%-6.8% had private plans. Employer-sponsored coverage remained constant for those in households with postsecondary graduation but decreased significantly for those in households with less than secondary school graduation, from 67.0% (95% confidence interval [CI] 63.2%-70.8%) (n = 175 000) in 2005 to 54.6% (95% CI 50.1%-59.2%) (n = 123 500) in 2013-2014. Government-sponsored coverage increased significantly for those in households with less than secondary school graduation, from 29.2% (95% CI 25.5%-32.9%) (n = 76 400) in 2005 to 41.7% (95% CI 37.2%-46.1%) (n = 93 900) in 2013-2014. In 2013-2014, Ontarians in households with less than secondary school graduation were less likely than those with secondary school graduation to report employer-sponsored coverage (adjusted PR 0.79, 95% CI 0.75-0.84) but were more likely to have government-sponsored coverage (adjusted PR 1.27, 95% CI 1.06-1.53). Sixty-two percent of Ontarians had prescription eyewear insurance in 2003, 2005 and 2013-2014; the largest source of insurance was employers, primarily covering those with higher education levels, whereas government-sponsored insurance increased significantly among those with lower education levels. Further research is needed to elucidate barriers to obtaining prescription eyewear and the degree to which affordability impairs access to vision correction.


A theoretical analysis of cellulase product inhibition: effect of cellulase binding constant, enzyme/substrate ratio, and beta-glucosidase activity on the inhibition pattern.
Theoretical analysis of cellulase product inhibition (by cellobiose and glucose) has been performed in terms of the mathematical model for enzymatic cellulose hydrolysis. The analysis showed that even in those cases when consideration of multienzyme cellulase system as one enzyme (cellulase) or two enzymes (cellulase and beta-glucosidase) is valid, double-reciprocal plots, usually used in a product inhibition study, may be nonlinear, and different inhibition patterns (noncompetitive, competitive, or mixed type) may be observed. Inhibition pattern depends on the cellulase binding constant, enzyme concentration, maximum adsorption of the enzyme (cellulose surface area accessible to the enzyme), the range in which substrate concentration is varied, and beta-glucosidase activity. A limitation of cellulase adsorption by cellulose surface area that may occur at high enzyme/substrate ratio is the main reason for nonlinearity of double-reciprocal plots. Also, the results of calculations showed that material balance by substrate, which is usually neglected by researchers studying cellulase product inhibition, must be taken into account in kinetic analysis even in those cases when the enzyme concentration is rather low.


A view on beta cell transplantation in diabetes.
Organ donors also offer a source of insulin-producing tissue that might be used for the treatment of diabetes. Clinical protocols for transplantation of this tissue aim for the prevention of chronic diabetes complications without introducing new serious side effects. Pancreas and islet cell transplantation are discussed in this perspective. The future of islet cell implants looks favorable but depends on finding ways to induce immune tolerance to the donor beta cells. Clinical trials can take advantage of relevant progress in animal models. In a limited study, recipient treatment with antilymphocyte antibodies and culture of donor cell preparations appeared useful to induce a state of operational immune tolerance in type 1 diabetic patients, as indirectly judged by graft survival and by analysis of auto- and alloreactivities in recipients. Use of cultured beta cell preparations also allows donor cell recruitment from suboptimal donor organs and increases the degree of standardization and quality control of islet cell grafts. The future of these grafts will depend on the development of techniques for the neogenesis of beta cells.


Bootstrap quantification of estimation uncertainties in network degree distributions.
We propose a new method of nonparametric bootstrap to quantify estimation uncertainties in functions of network degree distribution in large ultra sparse networks. Both network degree distribution and network order are assumed to be unknown. The key idea is based on adaptation of the "blocking" argument, developed for bootstrapping of time series and re-tiling of spatial data, to random networks. We first sample a set of multiple ego networks of varying orders that form a patch, or a network block analogue, and then resample the data within patches. To select an optimal patch size, we develop a new computationally efficient and data-driven cross-validation algorithm. The proposed fast patchwork bootstrap (FPB) methodology further extends the ideas for a case of network mean degree, to inference on a degree distribution. In addition, the FPB is substantially less computationally expensive, requires less information on a graph, and is free from nuisance parameters. In our simulation study, we show that the new bootstrap method outperforms competing approaches by providing sharper and better-calibrated confidence intervals for functions of a network degree distribution than other available approaches, including the cases of networks in an ultra sparse regime. We illustrate the FPB in application to collaboration networks in statistics and computer science and to Wikipedia networks.


Estrogen reduces proliferation and agonist-induced calcium increase in coronary artery smooth muscle cells.
Epidemiological evidence and estrogen replacement studies suggest that estrogen has a protective effect on the cardiovascular system against coronary artery disease. Vascular smooth muscle (VSM) cell replication has been shown to play a causative role in the pathogenesis of atherosclerosis. Therefore, in this study, we investigated the effect of chronic treatment of cultured guinea pig coronary artery VSM cells with physiological concentrations of 17beta-estradiol (E2) on thymidine incorporation, cell proliferation, and bradykinin-stimulated cytosolic calcium concentration ([Ca2+]i). Bradykinin at physiological concentrations causes contraction of endothelium-denuded guinea pig coronary artery rings in a concentration-dependent manner. VSM cells were first treated with low doses of E2 (10 pg/ml) for 1-2 days followed by treatment for 4-6 days with 50 pg/ml of E2, a concentration similar to that found in pregnancy. Using these protocols, we consistently observed the presence of E2-receptor mRNA in VSM cells by a ribonuclease protection assay. Fetal calf serum-stimulated [3H]thymidine incorporation was significantly reduced (P < 0.05) in E2-treated cells compared with untreated control cells. Similarly, E2 treatment significantly inhibited fetal calf serum-stimulated VSM cell proliferation compared with untreated control cells (P < 0.05). We also tested the hypothesis that E2 treatment attenuates agonist-stimulated [Ca2+]i in VSM cells because acute E2 treatment has been shown to produce relaxation of precontracted isolated coronary artery preparations. E2 treatment of VSM cells resulted in a significant decrease in bradykinin-stimulated [Ca2+]i compared with untreated cells (P < 0.05). In conclusion, our data demonstrate that estrogen at physiological concentrations directly regulates coronary VSM cell function.


Hericium erinaceus, in combination with natural flavonoid/alkaloid and B3/B8 vitamins, can improve inflammatory burden in Inflammatory bowel diseases tissue: an ex vivo study.
Hericium erinaceus, berberine, and quercetin are effective in experimental colitis. It is unknown whether they can ameliorate inflammatory bowel diseases in humans. This ex vivo study aimed to evaluate the anti-inflammatory potential of a nutraceutical compound of HBQ-Complex® (H. erinaceus, berberine, and quercetin), biotin, and niacin in inflammatory bowel disease patients. Tissue specimens were obtained either from Normal-Appearing Mucosa (NAM) or from Inflamed Mucosa (IM) in 20 patients with inflammatory bowel disease. mRNA and protein expression of COX-2, IL-10, and TNF-α were determined in NAM and IM biopsy samples (T0). IM samples were then incubated in HBQ-Complex® (with the addition of niacin and biotin), and COX-2, IL-10, and TNF-α tissue levels were evaluated at 120 minutes (T1) and 180 minutes (T2). Incubation with this compound resulted in a progressive decrease in gene and protein COX-2 and TNF-α expression at T1/T2 in the IM. IL-10 showed an opposite trend, with a progressive increase of mRNA and protein expression over the same time window. HBQ-Complex® (with the addition of niacin and biotin) decreased the expression of proinflammatory cytokines at the mRNA and protein levels in IBD tissue. On the contrary, mRNA and protein expression of the anti-inflammatory cytokine IL-10 showed a progressive increase.


Dextroamphetamine and individual susceptibility to reinforcement in verbal operant conditioning.
The present investigation was designed to study the relationships between extraversion, d-amphetamine and modes of reinforcement in verbal operant conditioning. A factorial design involving two levels of extraversion (extraverts and introverts), two reinforcement conditions ('good' and 'electric shock') and three treatments (placebo and two doses, 7.5 and 12.5 mg, of d-amphetamine) with repeated measures on the last factor was used. Sixty postgraduate female students were individually subjected to Taffel's verbal conditioning procedure. The study supported the following conclusions: (1) under the placebo condition, the extraverted subjects condition better with the rewarding reinforcer while the introverted subjects condition better with the punishing reinforcer; (2) under the influence of d-amphetamine, the extraverted subjects condition better with the punishing reinforcer while the conditioning scores of introverted subjects decrease with the punishing reinforcer but are not influenced with the rewarding reinforcer.


Root surface temperature variation during mechanical removal of root canal filling material. An in vitro study.
The aim of this study was to analyze in vitro temperature changes on the outer surface of the dental root during mechanical filling removal procedures. Thirty recently extracted single-rooted lower premolars were cut transversally at 16 mm from the apex in order to standardize sample length. Endodontic treatment was performed on them. The filling material was subsequently removed using Gates Glidden (G1, G2, G3); Peeso (P1, P2, P3) and PostecPlus FRC (FRC) reamers while temperatures were measured on the outer surface using a digital device with thermocouple at 0, 2, 4, 6, 8, 10 and 15 seconds. Temperatures were compared using repeated measures ANOVA followed by pairwise comparison with Tukey's test. All reamers caused significant temperature variation between different times (p<0.05). Pairwise comparisons indicated that temperature increased with time for all reamers (p<0.05). Significant differences in temperature were found between different reamers after 0, 2, 4, 6, 8,10 and 15 seconds (p<0.05). Temperature at the root surface increased considerably. Values higher than 50°C were recorded, the greatest increase from baseline being 16°C. Accordingly, if the procedure were begun at 37°C (physiological temperature), the temperature in the surrounding tissues - cementum, periodontium and bone - would rise to 53°C. An increase in 10°C above body temperature at the root surface may cause lesions in surrounding tissues. While removing filling material, it is essential to cool, control action time and use instruments in perfect condition, all of which may contribute to reducing the heat generated and transmitted to the outer root surface.


Endovaginal sonographic appearance of benign ovarian masses.
This article illustrates the different appearances of benign ovarian and paraovarian masses at endovaginal sonography. A retrospective study was performed of the records for 118 patients with 140 surgically proved benign adnexal masses, including dermoid cysts (n = 27), endometriomas (n = 40), epithelial inclusion cysts (n = 14), serous cystadenomas (n = 11), mucinous cystadenomas (n = 14), fibromas (n = 11), cystadenofibromas (n = 12), paratubal cysts (n = 5), hydrosalpinges (n = 3), and tubo-ovarian abscesses (n = 3). Preoperative diagnosis was made in 96% of the dermoid cysts on the basis of a hyperechoic attenuating component or multiple small horizontal interfaces and in 100% of uncomplicated fibromas on the basis of a hypoechoic attenuating mass. There was an overlap among the endovaginal sonographic appearances of the other condition.


The usefulness of diagnostic tests on pericardial fluid.
To determine the physical, chemical, and cellular characteristics of pericardial fluid in various disease states and to assess their diagnostic accuracies. A metropolitan university hospital. Consecutive case series. One hundred seventy-five hospital patients, aged 1 month to 87 years, who had undergone pericardiocentesis (n = 165) or control subjects who had undergone open heart surgery (n = 10) between 1984 and 1996. The appearance of pericardial fluid and results of chemistry tests, cell counts, cytologic studies, Gram's stain, and microbial cultures were obtained by chart review. The etiology of each pericardial fluid sample was determined using prospective diagnostic criteria. Exudates differed from transudates by higher leukocyte counts and ratios of fluid to serum lactate dehydrogenase levels. Fluid glucose levels were significantly less in exudates. Sensitivity for detecting exudates was high for specific gravity > 1.015 (90%), fluid total protein > 3.0 g/dL (97%), fluid to serum protein ratio > 0.5 (96%), fluid lactate dehydrogenase ratio > 0.6 (94%), and fluid to serum glucose ratio < 1.0 (85%). None of these indicators were specific. Fluid total protein and specific gravity were moderately correlated (r = 0.56). Fluid cytologic study had a sensitivity of 92% and specificity of 100% for malignant effusion. No other test was diagnostic for a specific etiology. Among infection-associated effusions, culture-positive fluid had more neutrophils, higher lactate dehydrogenase levels, and lower ratios of fluid to serum glucose than culture-negative (parainfective) fluid. Evaluation of pericardial fluid might be limited to cell count, glucose, protein, and lactate dehydrogenase determinations plus bacterial culture and cytology. While not used routinely, other tests that may be highly specific for particular diseases should be ordered only to confirm a high clinical suspicion.


Concrete, abstract, formal, and systematic operations as observed in a "Piagetian" balance-beam task series.
We performed a Rasch analysis of cross-sectional developmental data gathered from children and adults who were presented with a task series derived from Inhelder's and Piaget's balance beam. The partial credit model situates both participants and items along a single hierarchically ordered dimension. As the Model of Hierarchical Complexity predicted, order of hierarchical complexity accurately predicted item difficulty, with notable exceptions at the formal and systematic levels. Gappiness between items was examined using the saltus model. A two level saltus model, which examined the gap between the concrete/abstract and formal/systematic items, was a better predictor of performance than the Rasch analysis (chi square = 71.91, df = 4, p < .01).


Microbeam resonant x-ray scattering from bromine-substituted bent-core liquid crystals.
We studied the local layer structure in the B2 phase of bromine-substituted bent-core liquid crystals in the cell geometry using microbeam resonant x-ray scattering. In the homochiral state of B2 phase, the 3/2 order satellite peak was observed only when the incident x-ray energy is at the K absorption edge of bromine. This result clearly indicates that the B2 homochiral domain forms two-layer superlattice in adjacent layers, the same as in the rodlike Sm-C(A) phase. The work reports on microbeam resonant x-ray scattering experiment from the local layer of the bent-core liquid crystal in the device geometry. Moreover, we can say that bromine is also useful for the analysis of the superstructure of soft materials using resonant x-ray scattering.


Do selective COX-2 inhibitors increase the risk of cerebrovascular events? A meta-analysis of randomized controlled trials.
To evaluate the risk of cerebrovascular events (CVEs) associated with selective cyclooxygenase-2 inhibitors (coxibs). Systematic review and meta-analysis of randomized controlled trials (RCTs). A fixed-effect model was used to estimate the odds ratios (ORs) for risk of CVE associated with coxibs compared against placebo, non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and other coxibs. Forty trials (88 116 patients) were included in the meta-analysis. The overall pooled OR for CVE for any coxib against placebo was 1.03 (95% CI: 0.71, 1.50). Comparing individual coxibs against placebo, we found that celecoxib, rofecoxib, etoricoxib and lumiracoxib were associated with higher CVE risks and valdecoxib was associated with a lower CVE risk, although there were no significant differences detected. There was also no significant difference in risk of CVE when comparing coxibs against any non-selective NSAIDs; the corresponding pooled OR was 0.86 (95% CI: 0.64, 1.16). On the basis of a detailed analysis of available RCTs, there does not appear to be any significant difference in risk of CVEs associated with coxibs when compared against placebo or non-selective NSAIDs. It is likely that the increased risk of thrombotic vascular events associated with coxibs is largely attributable to an increased risk of myocardial infarction, rather than CVEs.


[10 Years of Experience in Living Donation for Liver Transplantation in Pediatric Patients - A Single Centre Study].
Living donor liver transplantation poses new issues related to the performance of a major surgery on a healthy person - the living donor. Thus, it requires precise logistics to ensure positive outcome for both the donor and the recipient, outweighing the risks associated with donation and transplantation. For this purpose, we developed an original three phase protocol for evaluation of candidate donors with set of mandatory assays. This paper aims to analyze the outcomes of this protocol. 89 candidates have been examined for the performance of 23 living donor liver transplantations. The procedure was successfully completed by 25 candidates (28.1%), including two cases of procedure suspension due to occurrence of a suitable deceased donor. The majority of exclusions occurred in the third phase, generally due to anatomical variations: arterial (17%), portal (9.68%), venous (18.15%) and biliary (18.15%), and for several reasons simultaneously (6.7%). NO exclusions occurred due to inadequate potential graft or residual volume. All living donors underwent left lateral resection and the measured volumes were enough for both the recipients and the donors. No significant complications occurred in the donors (Clavien 1: 21%, Clavien II: 4%), with no need of transfusion, reoperation or re-hospitalization. The laboratory parameters were restored to normal values within the 10th postoperative day as the average hospital stay was 14.7 days. All donors were discharged with normal laboratory, instrumental and physical parameters. No abnormalities were observed at long-term follow-up. No primary graft dysfunction was observed. The large proportion of declined candidates requires strict adherence to the precise sequence of the evaluation protocol. The main reasons for decline are anatomical variation. Los level of complicatons was registered, with short postoperative stay, normal laboratory results at discharge and normal physiological parameters at long-term follow-up. The concept of donor advocate was introduced for the first time in Bulgaria. His task is to defend the interests of the candidate donor and to provide assistance in making an informed decision.


Prognostic correlative values of the late-infancy MRI pattern in term infants with perinatal asphyxia.
The aim of this study was to define the risk ratios of the late-infancy magnetic resonance imaging pattern for long-term outcome in term infants with perinatal asphyxia. We evaluated 65 term infants with perinatal asphyxia and performed magnetic resonance imaging examinations between 4-12 months of age. Magnetic resonance imaging scans were classified as follows: (1) periventricular leukomalacia in 21 (32%) infants, (2) marked cortical atrophy in 17 (26%) infants, (3) multicystic encephalomalacia in 10 (15%) infants, (4) deep gray matter involvement in 8 (12%) infants, (5) focal cortical involvement in 6 (9%) infants, (6) myelination delay in 3 (5%) infants. The overall outcome was favorable in 19 (29%) of 65 infants. Infants with diffuse cortical involvement (multicystic encephalomalacia and marked cortical atrophy) are four times (odds ratio: 4.4 and 4.1 respectively) more likely to attain the unfavorable outcome than the infants with other patterns of magnetic resonance imaging. Infants with focal cortical involvement had relatively favorable outcome in 60% of the cases. In conclusion, it appears that the overall outcome of infants with perinatal asphyxia correlated well with the magnetic resonance imaging patterns obtained between 4 and 12 months of age.


Morphological studies on clinical isolates of Aspergillus fumigatus.
Morphological variation was examined in 19 strains of Aspergillus fumigatus Fres. isolated from the sputum of five patients with aspergilloma. For each patient a series of variant strains was obtained which exhibited gross differences in growth rate, colour and texture of the colony. On microscopical examination, some of the strains were found to produce markedly abnormal fruiting heads which were uncharacteristic for the species. Scanning electron microscopy revealed that the variant produced conidia of anomalous size, shape and surface-sculpturing. The significance of the isolation of morphological variants of A. fumigatus in sputum and their selection in vivo are discussed.


Purification of a HeLa cell nuclear protein that binds selectively to DNA irradiated with ultra-violet light.
Ultraviolet (UV) light induces a variety of lesions in DNA of which the pyrimidine dimer represents the major species. Pyrimidine dimers exist as both a cyclobutane type and a 6-4' (pyrimidine-2'-one) photoproduct. We have purified a protein of M(r) approximately 125,000 from HeLa cell nuclei which binds efficiently to double-stranded DNA irradiated with UV light but not to undamaged DNA. This protein was designated UVBP1 (UV damage binding protein 1). UVBP1 did not recognise DNA damaged by cisplatin. Using oligonucleotides with a single dipyrimidine site for induction of UV photoproducts, binding of UVBP1 to a TC-containing substrate was shown to be more efficient than to substrates containing a TT, a CT or a CC pair. This binding specificity implies selective recognition of the 6-4' photoproduct. Further evidence for this was provided by the finding that hot alkali treatment of the substrate (which selectively hydrolyses 6-4' photoproducts) abrogated binding of UVBP1, whereas incubation with DNA photolyase to remove cyclobutane dimers did not. No detectable DNA helicase, ATPase or exonuclease activity was associated with the purified protein. We suggest that UVBP1 may be involved in the lesion recognition step of DNA excision repair and could contribute to the preferential repair of 6-4' photoproducts from the DNA of UV-irradiated mammalian cells.


Antihypertensive effect of patulitrin and other constituents from Tagetes patula L. (French marigold) in acute L-NAME induced hypertensive rats.
The work is aimed to evaluate the blood pressure reducing effect of constituents from methanol extract and associated constituents of Tagetes patula flowers in normotensive and L-NAME induced hypertensive rats. The HPLC analysis of methanol extract of Tagetes patula flowers (JFM) resulted in the quantitative identification and percent comparison of four phenolic constituents, protocatechuic acid (PA), methyl protocatechuate (MPA), patulitrin (TRIN) and patuletin (PAT). All the extracts, fractions and compounds examined showed significant blood pressure lowering activity. Patulitrin (TRIN) which has emerged as the major constituent (15.33%) of T. patula flowers showed significant 30% and 68% fall in blood pressure in normotensive and L-NAME induced hypertensive rats respectively. The patuletin (PAT), which is an aglycone of TRIN displayed high percentage (84%) of antihypertensive activity. Further, comprehensive and advanced studies on these constituents may result in preparation of an effective blood pressure lowering medicine with active precious rare flavonoids, patuletin and patulitrin.


Pharmacophoric requirements for cannabinoid side chains: multiple bond and C1'-substituted delta 8-tetrahydrocannabinols.
Accumulated evidence indicates that within the cannabinoid structure the aliphatic side chain plays a pivotal role in determining cannabimimetic activity. We describe the synthesis and affinities for the CB1 and CB2 receptors of a series of novel delta 8-THC analogues in which the side-chain pharmacophores are conformationally more defined than in the parent molecule. No analogue has the side-chain pharmacophore in a fully restricted conformation. However, our design serves to narrow down the scope of options for conformational requirements at the receptor active sites. All the analogues tested showed nanomolar or subnanomolar affinities for the receptors; 2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-1-hydroxy-6H- dibenzo[b,d]pyranyl)-2-hexyl-1,3-dithiolane was found to possess very high affinity for both cannabinoid receptors (CB1, Ki = 0.32 nM; CB2, Ki = 0.52 nM).