Cooperative action of SLR1 and SLR2 is required for lateral root-specific cell elongation in maize.
Lateral roots play an important role in water and nutrient uptake largely by increasing the root surface area. In an effort to characterize lateral root development in maize (Zea mays), we have isolated from Mutator (Mu) transposon stocks and characterized two nonallelic monogenic recessive mutants: slr1 and slr2 (short lateral roots1 and 2), which display short lateral roots as a result of impaired root cell elongation. The defects in both mutants act specifically during early postembryonic root development, affecting only the lateral roots emerging from the embryonic primary and seminal roots but not from the postembryonic nodal roots. These mutations have no major influence on the aboveground performance of the affected plants. The double mutant slr1; slr2 displays a strikingly different phenotype than the single mutants. The defect in slr1; slr2 does not only influence lateral root specific cell elongation, but also leads to disarranged cellular patterns in the primary and seminal roots. However, the phase-specific nature of the single mutants is retained in the double mutant, indicating that the two loci cooperate in the wild type to maintain the lateral root specificity during a short time of early root development.


FMRF-amide-like substances in the leech. II. Bioactivity on the heartbeat system.
In the preceding paper (Kuhlman, J. R., C. Li, and R. L. Calabrese (1985) J. Neurosci. 5: 2301-2309) FMRF-amide-like immunoreactivity was localized to a specific set of neurons in the leech. Three types of these neurons are involved in controlling the animal's heartbeat: HE motor neurons and HA modulatory neurons which directly innervate the hearts, and the swim-initiating interneurons (cells 204) which can accelerate the heartbeat central pattern generator. Application of synthetic FMRF-amide had effects on the hearts and the heartbeat central pattern generator that mimicked the actions of the HA and cell 204 neurons. Bath application of FMRF-amide (10(-7) to 10(-6) M) to the hearts activated their myogenic rhythm and increased their beat tension, thus mimicking the effects of activity in HA cells. Bath application of lower concentrations of FMRF-amide (10(-9) to 10(-8) M) to the isolated central nervous system dramatically accelerated the central motor program for heartbeat, thus mimicking the effects of activity in cell 204. These observations suggest that an FMRF-amide-like substance may be used as a chemical signal by HA and cell 204 neurons. The role of the FMRF-amide-like substance contained in HE motor neurons remains unclear, but it may be released along with the HE cell's neuromuscular transmitter, acetylcholine.


[Chronic total coronary occlusion dis-obstruction by balloon angioplasty].
Ninety-three consecutive patients with chronic total coronary occlusion underwent an attempted mechanical des-obliteration by percutaneous coronary angioplasty with a balloon catheter. The global results were 55 p. 100 initial successes (residual stenosis less than 50 p. 100). The good prognostic factors were: 1) left coronary artery, especially left circumflex artery occlusion p less than 0.50, and 2) the proximity to the date of occlusion as assessed from the clinical history or by the occurrence of occlusion between the time of diagnostic coronary angiography and angioplasty. In cases of recent occlusion dating less than one month, the success rate was high: 69 p. 100. On the other hand, there were no successes in occlusions of over 6 months standing. The presence of myocardial infarction did not influence the results. There were few complications (7 p. 100) and these did not include any deaths or cases requiring emergency surgery. Exercise stress tests were carried out after the procedure and were negative in 28 out of 32 patients (88 p. 100). Forty-three patients successfully revascularised were followed up for 1 to 48 months (average 9 months) after angioplasty. Thirty-one patients were asymptomatic. Of the 12 symptomatic patients, 7 underwent exercise stress tests (6 positive) and all had control angiography which showed restenosis in 10 cases with 5 occlusions. Percutaneous coronary angioplasty of recent total coronary occlusions gives good initial results without major complications, and the medium term clinical results are satisfactory.


Sarpogrelate, a 5-hT2A receptor antagonist in intermittent claudication. A phase II European study.
This was a multinational, multicentre, double-blind Phase II study in Europe to evaluate the efficacy and safety of two dose regimens (200 mg bid and 200 mg tid) of sarpogrelate (MCI-9042, 5-HT2A receptor antagonist) compared to placebo in patients with stable, moderately severe intermittent claudication. Following a single-blind placebo run-in period of 6 weeks, 364 (309 male and 55 female) patients (59.2 +/- 8.4 years, mean +/- SD) were randomized to receive sarpogrelate 200 mg bid, 200 mg tid or placebo for 24 weeks with a follow-up of 8 weeks. The primary objective was the increase of absolute claudication distance (ACD) at the end of treatment (week 24) compared to placebo. Analysis of covariance (ANCOVA) was performed on the log-transformed percentage of baseline ACD: loge(ACD/baseline). A responder analysis (defined as a > or = 50% improvement in ACD) was also performed. There was a marked training/placebo effect on the ACD which persisted up to 16 weeks. At 24 weeks the primary objective did not reach statistical significance (200mg bid vs placebo, p = 0.225; 200mg tid vs placebo, p = 0.580). In the responder analysis, 200 mg bid showed a statistically significant difference vs placebo (p = 0.035). In the exploratory analysis with completers (patients completing all treadmill tests), there was a statistical difference in ACD/baseline change for 200 mg bid (p = 0.035) and in the responder analysis for 200 mg tid (p = 0.044) at 24 weeks compared to placebo. Both treatments showed a carry-over effect for ACD during the 8-week follow-up (weeks 28-32). The treatment was well tolerated and no clinically significant safety concerns were reported. In conclusion, the study results confirm that sarpogrelate is well tolerated and although the primary endpoint failed to reach statistical significance, the responder analysis showed an increased absolute walking distance, which makes a further trial warranted, including a larger population, and possibly also a longer treatment period.


Gender Minority Stress and Depressive Symptoms in Transitioned Swiss Transpersons.
Compared to the general population, transpersons are exposed to higher levels of discrimination and violence. The stigmatization of transpersons can lead to physical and psychological problems. In particular, transindividuals exhibit a higher prevalence of depression compared to the cispopulation. The gender minority stress model (GMSM) provides a comprehensive theoretical basis to interpret these biopsychosocial interactions. Using the GMSM, this study aimed to identify associations between experience of stigmatization and the mental health of transitioned transpersons using correlational analyses and multiple regression models. In total, 143 transpersons were recruited. Multivariate analyses identified three variables (i.e., unemployment, nonaffirmation of gender identity, and internalized transphobia) to explain variance of depressive symptoms. Furthermore, a mediation of the proximal factors between distal factors and depressive symptoms was found. However, the moderating effect of resilience factors was not demonstrated. The results confirmed the importance of distal and proximal minority stressors for the mental health of transpersons. At the same time, the protective influence of resilience factors seemed to be surprisingly minor. In the treatment of transpersons, practitioners should not only focus on somatic aspects, but also consider the person's previous experiences of stigmatization.


Sexuality in Adults with Differences/Disorders of Sex Development (DSD): Findings from the dsd-LIFE Study.
For various reasons, sexuality of individuals with differences/disorders of sex development (DSD) may be affected. The aim of the study was to describe sexual activity, satisfaction with sex life, satisfaction with genital function, and sexual problems in people with different DSD conditions. Data were collected from 1,040 participants in Europe. Many people with a variety of DSD conditions do not appear to be satisfied with their sex life, experience a variety of sexual problems, and are less sexually active than the general population; therefore sexuality should be explicitly addressed in the care of people with DSD.


Severe pediatric influenza in California, 2003-2005: implications for immunization recommendations.
The 2003-2004 influenza season was marked by both the emergence of a new drift "Fujian" strain of influenza A virus and prominent reports of increased influenza-related deaths in children in the absence of baseline data for comparison. In December 2003, the California Department of Health Services initiated surveillance of children who were hospitalized in California with severe influenza in an attempt to measure its impact and to identify additional preventive measures. From December 2003 to May 2005, surveillance of children who were hospitalized in PICUs or dying in the hospital with laboratory evidence of influenza was performed by hospital infection control practitioners and local public health departments using a standardized case definition and reporting form. In the 2003-2004 and 2004-2005 influenza seasons, 125 and 35 cases, respectively, of severe influenza in children were identified in California. The mean and median age of cases were 3.1 years and 1.5 years, with breakdown as follows: < 6 months, 39 (24%); 6 to 23 months, 53 (33%); 2 to 4 years, 40 (25%); 5 to 11 years, 15 (9%); and 12 to 17 years, 13 (8%). Fifty-three percent (85 of 160) had an underlying medical condition(s), including a neurologic disorder (n = 36), chronic pulmonary disease (n = 26), genetic disorder (n = 19), cardiac disease (n = 18), prematurity (n = 14), immunocompromised status (n = 12), endocrine/renal disease (n = 2), and other (n = 1). Only 16% (15 of 96) of all patients had received influenza vaccination. Thirty-seven patients had an underlying illness that met existing Advisory Committee on Immunization Practices (ACIP) or American Academy of Pediatrics (AAP) recommendations for immunization, but only 8 had been vaccinated. More than 3 times as many children were reported to be hospitalized in intensive care with influenza in California during the 2003-2004 season compared with the 2004-2005 season. Because children who are younger than 6 months remain at highest risk for severe influenza yet cannot currently be immunized, development and validation of preventive measures for them (eg, maternal immunization, breastfeeding, immunization of young infants and their close contacts) are urgently needed. ACIP's recent recommendation for influenza vaccination of children with conditions that can compromise respiratory function (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, other neuromuscular disorders) is further supported by the frequency of underlying neurologic disease in these cases of severe influenza. A significant proportion of children with severe influenza in California, including children who are aged 2 to 4 years or have underlying genetic syndromes or prematurity, would not have been routinely recommended for influenza vaccination in 2005-2006 ACIP and AAP recommendations, calling into question whether such guidelines should be expanded. Continued surveillance for severe influenza-related morbidity and mortality is important to measure the impact of influenza on children.


Brachial artery aneurysm rupture in a patient with neurofibromatosis: a case report.
Peripheral vascular manifestations of neurofibromatosis are rare but may result in fatal haemorrhaging when they rupture. Surgeons should be aware of this life-threatening condition. We report a case of 35-year-old woman with neurofibromatosis who presented with a swollen and tender mass around her right arm. Angiography revealed 2 aneurysms in the brachial artery. Surgical occlusion revealed a large amount of clotted blood within the subfascial space, and the bleeding point was identified as a pinpoint opening in the aneurysm. The brachial artery abutting the aneurysm and the surrounding soft tissues was extremely brittle and fragile, with massive oozing during dissection. The brachial artery was irreparable and was resected after ligation of the artery and surrounding soft tissues and the aneurysm. Despite an uneventful recovery, the patient died on day 4.


Fish intake during pregnancy and the risk of child asthma and allergic rhinitis - longitudinal evidence from the Danish National Birth Cohort.
Maternal fish intake during pregnancy may influence the risk of child asthma and allergic rhinitis, yet evidence is conflicting on its association with these outcomes. We examined the associations of maternal fish intake during pregnancy with child asthma and allergic rhinitis. Mothers in the Danish National Birth Cohort (n 28 936) reported their fish intake at 12 and 30 weeks of gestation. Using multivariate logistic regression, we examined the associations of fish intake with child wheeze, asthma and rhinitis assessed at several time points: ever wheeze, recurrent wheeze (>3 episodes), ever asthma and allergic rhinitis, and current asthma, assessed at 18 months (n approximately 22,000) and 7 years (n approximately 17,000) using self-report and registry data on hospitalisations and prescribed medications. Compared with consistently high fish intake during pregnancy (fish as a sandwich or hot meal > or equal to 2-3 times/week), never eating fish was associated with a higher risk of child asthma diagnosis at 18 months (OR 1·30, 95% CI 1·05, 1·63, P=0·02), and ever asthma by hospitalisation (OR 1·46, 95% CI 0·99, 2·13, P=0·05) and medication prescription (OR 1·37, 95% CI 1·10, 1·71, P=0·01). A dose-response was present for asthma at 18 months only (P for trend=0·001). We found no associations with wheeze or recurrent wheeze at 18 months or with allergic rhinitis. The results suggest that high (v. no) maternal fish intake during pregnancy is protective against both early and ever asthma in 7-year-old children.


Biocurators and biocuration: surveying the 21st century challenges.
Curated databases are an integral part of the tool set that researchers use on a daily basis for their work. For most users, however, how databases are maintained, and by whom, is rather obscure. The International Society for Biocuration (ISB) represents biocurators, software engineers, developers and researchers with an interest in biocuration. Its goals include fostering communication between biocurators, promoting and describing their work, and highlighting the added value of biocuration to the world. The ISB recently conducted a survey of biocurators to better understand their educational and scientific backgrounds, their motivations for choosing a curatorial job and their career goals. The results are reported here. From the responses received, it is evident that biocuration is performed by highly trained scientists and perceived to be a stimulating career, offering both intellectual challenges and the satisfaction of performing work essential to the modern scientific community. It is also apparent that the ISB has at least a dual role to play to facilitate biocurators' work: (i) to promote biocuration as a career within the greater scientific community; (ii) to aid the development of resources for biomedical research through promotion of nomenclature and data-sharing standards that will allow interconnection of biological databases and better exploit the pivotal contributions that biocurators are making. DATABASE URL: http://biocurator.org.


Determination of sex from the tibia of adult Turkish cadavers.
The aim of this research is to determine sex from the tibia. The tibia is an ideal bone because it resists erosive forces and keeps its anatomical shape for a long time even after being buried. Additionally, we tried to obtain a higher discrimination rate by using the biarticular breadth that was accepted as the most valid criterion in previous sex discrimination studies which were directed to the proximal part of the tibia. Right and left tibiae from 55 randomly selected adult Turkish cadavers (25 to 68 years) were measured to the nearest millimeter performed with a caliper; a total of six dimensions, one from the proximal and five from the distal ends, was measured. Canonical discriminant function test was performed to develop formulae and assess the accuracy of the technique. The results indicated that classification accuracy ranged from 89% in the right and 87% in the left for biarticular breadth. There was a minimal difference between the sides and the height of the medial malleolus. In conclusion, the distal and proximal dimensions of the tibia are highly discriminative as the sexual dimorphs in this Turkish sample. The study compares well with those on blacks and whites of North America and South Africa.


Progenitor mast cells and tryptase in Q fever.
Q fever is an infectious disease due to Coxiella burnetii. Following a primary-infection, C. burnetii may persist in some patients, leading to endocarditis and vascular infections. Mast cells (MCs), known for their role in allergic diseases, innate immunity and cardiac function, are produced by bone marrow, circulate as progenitors in the bloodstream and reach tissues for their maturation and activation. The latter may be estimated by measuring serum tryptase levels. We wondered if MC progenitors and tryptase were affected in Q fever. We showed a decrease in MC progenitor count in Q fever patients whereas serum tryptase levels were increased. Taken together, our results show alterations of MC numbers and activity in Q fever patients, suggesting that MC are involved in Q fever pathophysiology.


The Src kinase Lck facilitates assembly of HIV-1 at the plasma membrane.
HIV type 1 (HIV-1) assembly and egress are driven by the viral protein Gag and occur at the plasma membrane in T cells. Recent evidence indicates that secretory vesicles and machinery are essential components of virus packaging in both T cells and macrophages. However, the pathways and cellular mediators of Gag targeting to the plasma membrane are not well characterized. Lck, a lymphoid specific Src kinase critical for T cell activation, is found in the plasma membrane as well as various intracellular compartments and it has been suggested to influence HIV-1 replication. To investigate Lck as a potential regulator of Gag targeting, we assessed HIV-1 replication and Gag-induced virus-like particle release in the presence and absence of Lck. Release of HIV-1 and virus-like particles was reduced in the absence of Lck. This decrease in replication was not due to altered HIV-1 infection, transcription or protein translation. However, in T cells lacking Lck, HIV-1 accumulated intracellularly. In addition, expressing Lck in HeLa cells promoted HIV-1 Gag plasma membrane localization. Palmitoylation of the Lck unique domain, which is essential for directing Lck to the plasma membrane, was critical for its effect on HIV-1 replication. Furthermore, HIV-1 Gag directly interacted with the Lck unique domain in the context of infected cells. These results indicate that Lck plays a key role in targeting HIV-1 Gag to the plasma membrane in T cells.


Factors Affecting Selection of a Dialysis Modality in Elderly Patients With Chronic Kidney Disease: A Prospective Cohort Study in Korea.
We investigated factors associated with the selection of a dialysis modality for elderly patients compared to younger patients. This study included 2,514 incident dialysis patients from a Korean multicenter prospective cohort. Multivariate logistic regression analyses were performed with demographic, socioeconomic, and clinical data to analyze factors associated with the chosen dialysis modality. Differences in these factors were compared between the elderly (≥65 years) and younger (<65 years) patients. Of the enrolled patients, 1,746 (69.5%) and 768 (30.6%) selected hemodialysis (HD) and peritoneal dialysis (PD), respectively. The percentage of PD was higher in younger patients than in elderly patients (37.1 vs. 16.9%, p < 0.001). Multivariate analysis showed that planned dialysis (p < 0.001), employment status (p < 0.001), and independent economic status (p = 0.048) were independent factors for selecting PD, whereas peripheral vascular disease (p = 0.038) and tumor (p = 0.010) were factors for selecting HD in the younger group. In the elderly group, planned dialysis (p < 0.001) and congestive heart failure (CHF; p = 0.002) were associated with choosing PD; however, tumor (p = 0.006) was associated with choosing HD. A two-way ANOVA showed that planned dialysis and CHF showed a significant interaction effect with age on modality selection. As the age of patients with chronic kidney disease increased, HD was more frequently selected compared to PD. Dialysis planning and CHF interacted with age in selecting dialysis modalities in elderly patients. Elderly patients were less affected by socioeconomic status than younger patients.


Macrophage migration inhibitory factor mediates the antidepressant actions of voluntary exercise.
Voluntary exercise is known to have an antidepressant effect. However, the underlying mechanism for this antidepressant action of exercise remains unclear, and little progress has been made in identifying genes that are directly involved. We have identified macrophage migration inhibitory factor (MIF) by analyzing existing mRNA microarray data and confirmed the augmented expression of selected genes under two experimental conditions: voluntary exercise and electroconvulsive seizure. A proinflammatory cytokine, MIF is expressed in the central nervous system and involved in innate and adaptive immune responses. A recent study reported that MIF is involved in antidepressant-induced hippocampal neurogenesis, but the mechanism remains elusive. In our data, tryptophan hydroxylase 2 (Tph2) and brain-derived neurotrophic factor (Bdnf) expression were induced after MIF treatment in vitro, as well as during both exercise and electroconvulsive seizure in vivo. This increment of Tph2 was accompanied by increases in the levels of total serotonin in vitro. Moreover, the MIF receptor CD74 and the ERK1/2 pathway mediate the MIF-induced Tph2 and Bdnf gene expression as well as serotonin content. Experiments in Mif(-/-) mice revealed depression-like behaviors and a blunted antidepressant effect of exercise, as reflected by changes in Tph2 and Bdnf expression in the forced swim test. In addition, administration of recombinant MIF protein produced antidepressant-like behavior in rats in the forced swim test. Taken together, these results suggest a role of MIF in mediating the antidepressant action of exercise, probably by enhancing serotonin neurotransmission and neurotrophic factor-induced neurogenesis in the brain.


The Role of KRAS Mutation in Colorectal Cancer-Associated Thrombosis.
Venous thromboembolic events (VTE) are common in patients with colorectal cancer (CRC) and represent a significant contributor to morbidity and mortality. Risk stratification is paramount in deciding the initiation of thromboprophylaxis and is calculated using scores that include tumor location, laboratory values, patient clinical characteristics, and tumor burden. Commonly used risk scores do not include the presence of molecular aberrations as a variable. This retrospective study aims to confirm the link between KRAS-activating mutations and the development of VTE in CRC. A total of 166 patients were included in this study. They were split into two cohorts based on KRAS mutational status. We evaluated the frequency and mean time to VTE development stratified by the presence of KRAS mutations. Patients with mutant KRAS had an odds ratio (OR) of 2.758 for VTE compared to KRAS wild-type patients, with an increased risk of thrombosis being maintained in KRAS mutant patients even after adjusting for other known VTE risk factors. Taking into account the results of this study, KRAS mutation represents an independent risk factor for VTE.


The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (K(v)7) potassium channels.
Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; North American adopted name), a first-in-class antiepileptic drug (AED) that reduces neuronal excitability primarily by enhancing the activity of KCNQ2/3 (K(v)7.2/7.3) potassium channels, has recently been approved by the European Medicines Agency and the U.S. Food and Drug Administration as adjunctive therapy in adults with partial-onset seizures. Much of the RTG/EZG safety profile will be familiar to health care professionals who are experienced with the clinical use of AEDs. RTG/EZG, as a potassium channel opener, also has a pharmacologic effect on smooth muscle of the urinary bladder. Consequently, the adverse event (AE) profile of RTG/EZG includes a potential risk of effects on the urinary system. This review summarizes the urinary safety profile and any secondary renal effects of RTG/EZG using data from patients in the pivotal controlled trials and the overall phase 2/3 clinical development program. Urinary AEs were reported more frequently in patients receiving RTG/EZG compared with placebo, although most patients were able to continue with treatment. Specifically, there is an increased risk of urinary retention with RTG/EZG, with urinary hesitation representing the most frequently reported urinary retention-related AE. Potential secondary renal effects, which may be caused by an inability to empty the bladder, were evaluated. Crystals with a bilirubin-like appearance were detected in the urine of patients receiving RTG/EZG. Although investigations indicated that these crystals were not bilirubin, their composition remains undetermined. There was no causal association with urinary tract infections, and nephrolithiasis was uncommon. The reported clinical effects of RTG/EZG are consistent with its documented effects on bladder smooth muscle in preclinical studies. RTG/EZG should be used with caution in patients at risk of urinary retention.


Effect of chemical etching solutions versus air abrasion on the adhesion of self-adhesive resin cement to IPS e.max ZirCAD with and without aging.
This study evaluated the adhesion of self-adhesive resin cement to zirconia after various surface conditioning methods in non-aged and aged conditions. Zirconia (IPS e.max ZirCAD, Ivoclar Vivadent) and resin composite blocks were obtained and randomly divided into four groups according to one of the following surface conditioning methods: C: No surface treatment (Control); AS: Air abrasion (50 µm Al2O3) at low pressure (0.2 MPa) plus silane (Monobond Plus, Ivoclar Vivadent); MC: Methylene chloride for 60 min; CE: Chemical etching solution at 100°C for 60 min. Surface roughness (Ra) measurements were performed on the control and conditioned zirconia specimens using a profilometer. Each conditioned zirconia block was bonded to its corresponding resin composite block using self-adhesive resin cement (RelyX Unicem Aplicap, 3M ESPE) under a load of 300 g. Half of the groups were tested without aging; the other half were tested after x6000 thermocycling. Sticks were obtained from bonded specimens and subjected to microtensile bond strength (MTBS) testing in a universal testing machine (0.5 mm/min). Failure types were classified after debonding. Data (MPa) were analyzed using two-way ANOVA and Tukey's tests (α = 0.05). The highest mean Ra value was obtained in Group CE (0.52 µm), and the lowest in Group C (0.25 µm). Significantly lower MTBS test results were obtained in Group C, both in non-aged (17.4 ± 1.1 MPa) and aged (5.11 ± 0.5 MPa) conditions than in the other groups (34.6 ± 1.5 to 51.2 ± 1.1 MPa; 28.0 ± 0.9 to 49.5 ± 1.0 MPa in non-aged and aged conditions, respectively) (P < 0.05). Group CE presented the highest MTBS test results in both non-aged and aged conditions (51.2 ± 1.1 MPa and 49.5 ± 1 MPa, respectively) (P < 0.05). Failure types were predominantly adhesive in all groups before and after aging. After aging, less adhesive and more mixed and cohesive failures in cement were observed in Groups AS and CE than in the other groups. Chemical etching of zirconia may have potential use as a substitute for air abrasion as a surface conditioning method for zirconia.


Hyaluronan synthase 2 protects skin fibroblasts against apoptosis induced by environmental stress.
A balanced turnover of dermal fibroblasts is crucial for structural integrity and normal function of the skin. During recovery from environmental injury (such as UV exposure and physical wounding), apoptosis is an important mechanism regulating fibroblast turnover. We are interested in the role that hyaluronan (HA), an extracellular matrix molecule synthesized by HA synthase enzymes (Has), plays in regulating apoptosis in fibroblasts. We previously reported that Has1 and Has3 double knock-out (Has1/3 null) mice show accelerated wound closure and increased numbers of fibroblasts in the dermis. In the present study, we report that HA levels and Has2 mRNA expression are higher in cultured Has1/3 null primary skin fibroblasts than in wild type (WT) cells. Apoptosis induced by two different environmental stressors, UV exposure and serum starvation (SS), was reduced in the Has1/3 null cells. Hyaluronidase, added to cultures to remove extracellular HA, surprisingly had no effect upon apoptotic susceptibility to UVB or SS. However, cells treated with 4-methylumbelliferone to inhibit HA synthesis were sensitized to apoptosis induced by SS or UVB. When fibroblasts were transfected with Has2-specific siRNA that lowered Has2 mRNA and HA levels by 90%, both Has1/3 null and WT cells became significantly more sensitive to apoptosis. The exogenous addition of high molecular weight HA failed to reverse this effect. We conclude that Has1/3 null skin fibroblasts (which have higher levels of Has2 gene expression) are resistant to stress-induced apoptosis.


Influence of climate change on the water resources in an alpine region.
It is widely accepted that the global warming will impact on water resources. This study investigates the possible influence of climate change on the water resources in an alpine region. A description of the actual situation with emphasis on the water resources from the one side and on the water consuming factors, here called stressors, is given. The probable effects of climate change in the region and their influence on its water resources are then described. The main outcome is that in the analysed region the climate change will rather have positive influence on the water balance by inducing higher precipitations during the rivers' natural low flow period (winter). This outcome contradicts many common predictions, however, this due to the specifics induced by the alpine nature of the catchment.


[Mutism in children].
Mutism is absence of verbal expression with conservation of language comprehension. The origin of mutism is multifactorial and may followed from cranial trauma surgery of the posterior fossa, acquired epileptic syndromes and psychogenic origin. To refer patients who had presented mutism of diverse etiology. We analysed three children who had presented mutism originated by diverse causes. Case 1. A child with family and school problems, attention deficits and limited communication resources. Neurological examination and other auxiliary test (EEG) were normal. He presented no alteration in language or speech. We recommended the change of the school and a psychotherapeutic orientation. Case 2. A 4 year old female child who has suffered varicella 15 days earlier and presented limitations in her verbal expression despite maintain her linguistically capacity. She showed a indifferent behavior and her movements were without finality. Neurological examination was normal. The girl understood and followed instruction properly. However her verbal communication was absent. Total recuperation occurred in 72 hours. Case 3. A 12 years old child who had suffered a cranial traumatism with loss of consciousness ten days earlier. After this traumatism, he presented behavior changes, disorientation and blurred vision. Additionally he presented stereotypies and limitations in psychosocial connections. Despite his mutism, he conserved the structure and content of language. SPECT showed hypoperfusion in orbitotemporal region. Improvement was total 20 days after his traumatism. The mutism has multifactorial etiology. References were made to three cases who's mutism was related to emotional causes, post-varicella complications and posttraumatic events.


Gut hormones: emerging role in immune activation and inflammation.
Gut inflammation is characterized by mucosal recruitment of activated cells from both the innate and adaptive immune systems. In addition to immune cells, inflammation in the gut is associated with an alteration in enteric endocrine cells and various biologically active compounds produced by these cells. Although the change in enteric endocrine cells or their products is considered to be important in regulating gut physiology (motility and secretion), it is not clear whether the change plays any role in immune activation and in the regulation of gut inflammation. Due to the strategic location of enteric endocrine cells in gut mucosa, these gut hormones may play an important role in immune activation and promotion of inflammation in the gut. This review addresses the research on the interface between immune and endocrine systems in gastrointestinal (GI) pathophysiology, specifically in the context of two major products of enteric endocrine systems, namely serotonin (5-hydroxytryptamine: 5-HT) and chromogranins (Cgs), in relation to immune activation and generation of inflammation. The studies reviewed in this paper demonstrate that 5-HT activates the immune cells to produce proinflammatory mediators and by manipulating the 5-HT system it is possible to modulate gut inflammation. In the case of Cgs the scenario is more complex, as this hormone has been shown to play both proinflammatory and anti-inflammatory functions. It is also possible that interaction between 5-HT and Cgs may play a role in the modulation of immune and inflammatory responses. In addition to enhancing our understanding of immunoendocrine interaction in the gut, the data generated from the these studies may have implications in understanding the role of gut hormone in the pathogenesis of both GI and non-GI inflammatory diseases which may lead ultimately to improved therapeutic strategies in inflammatory disorders.


Pipobroman therapy of polycythemia vera.
Between 1971 and 1981, 74 patients with polycythemia vera were treated with pipobroman using a high-dose induction, low-dose maintenance regimen. Complete remission was achieved in 51 of 54 previously untreated patients (94.4%) and in 17 of 20 patients (85%) previously treated wih radioactive phosphorus (32 p) and busulfan. The earliest modifications were noted on day 16, and on the average, blood counts were normal by day 45. Thirty percent of the patients relapsed, the mean duration of the remission being 17.5 mo. Following recurrence pipobroman was consistently effective in the same doses but the mean duration of the next remissions was 10 mo. Transient leukopenia and thrombocytopenia occurred in 8% and 7% of patients, respectively, during initial phase, and anemia was noted in 3 patients. Macrocytosis was noted in 20% of patients during maintenance phase. Three cases of acute leukemia and 3 cases of osteomyelosclerosis were recorded, all occurring in patients who had previously received 32 p and/or busulfan. No hematologic malignancies were seen among patients treated with pipobroman alone; follow-up exceeded 6 yr for 20 patients and the median follow-up period was 3.6 yr. Pipobroman appears safer than other alkylating agents; it is as effective as 32 p and works more quickly. Longer follow-up will be required to evaluate the drug's oncogenic potential, which is still not known.


Effects of state-level policy changes on homicide and nonfatal shootings of law enforcement officers.
To evaluate the impact of state-level policy changes on assaults on law enforcement officers (LEOs) in the USA. Pooled time series and cross-sections with negative binomial regression were used to estimate the impact of state-level changes of right-to-carry (RTC), three-strikes and permit-to-purchase (PTP) handgun laws on fatal and non-fatal assaults of LEOs. LEO assaults were stratified by weapon type (all methods, handgun and non-handgun) and whether or not the assault was fatal. Data were collected from the Federal Bureau of Investigation's Law Enforcement Officers Killed and Assaulted database and analysed for the period 1984-2013 for fatal assaults and 1998-2013 for non-fatal assaults. RTC laws showed no association with fatal (p>0.4) or non-fatal (p>0.15) assaults on LEOs. Three-strikes laws were associated with a 33% increase in the risk of fatal assaults on LEOs. Connecticut's PTP law was not associated with fatal (p>0.16) or non-fatal (p>0.13) assaults. Missouri's repeal of its PTP legislation was marginally associated with a twofold increased risk of non-fatal handgun assaults (p=0.089). This research indicates that three-strikes laws increase the risk of fatal assaults. RTC laws are not associated with increased risk of assault. Missouri's PTP repeal may increase the risk of non-fatal handgun assaults.


Challenges to delivery of isoniazid preventive therapy in a cohort of children exposed to tuberculosis in Timor-Leste.
To evaluate the number and geographic location of children aged <5 years exposed to sputum smear-positive tuberculosis (TB) in Timor-Leste, to determine the proportion evaluated for isoniazid preventive therapy (IPT) and to review the programmatic challenges present in delivering IPT to this cohort. A total of 256 consecutive sputum smear-positive TB index cases diagnosed at Bairo Pite Clinic between August 2013 and July 2014 were interviewed about places of residence and household contacts <5 years of age in the 3 months preceding diagnosis. Attendance of these contacts for screening and the outcome of screening were recorded prospectively. The majority (225 of 256, 88%) of index cases resided in Dili, but 73 of 225 (32%) of these also had a second address outside the capital. A total of 255 contacts were identified; 172 of 255 (67%) of whom lived in Dili district and 83 of 255 (33%) of whom resided in remote districts. Only 66 of 255 (26%) contacts attended for evaluation for IPT, of whom 46 of 255 (18%) started IPT and nine of 255 (3.5%) were diagnosed with TB. Attendance was significantly less likely when the index case was not the parent of the child contact. Sputum smear-positive pulmonary TB cases frequently result in household exposure of children <5 years in Timor-Leste, and provision of IPT is suboptimal. Contacts are located in diverse and distant locations. Further studies to delineate access barriers to IPT and review programmatic models that will facilitate IPT scale up in Timor-Leste are needed.


[Non-scrotal testes; first line of management].
For non-scrotal testes a distinction can be made between retractile testes (completely descended and normally developed but sometimes situated subcutaneously in the groin area), retained testes (testes cannot be brought into the scrotum or this can only be achieved using light manual pressure) and ectopic testes (lying outside of the descent trajectory). It is estimated that 0.7-0.8% of all boys have as yet undescended testes. The first few days after the birth are the most suitable for testing and registration, as then the cremaster reflex is absent. Registration should take place in both the youth healthcare file and in the 'growth book' for the parents. Retractile testes do not require treatment. There is no consensus concerning the treatment of (possible) acquired nonscrotal testes. For undescended testes the management depends on previous testes localisations. For ectopic testes and testes that have never been scrotal, a referral for surgical treatment should be made prior to the second birthday. Orchidopexy (a better description is orchidofuniculolysis followed by orchidopexy) is only justified in the case of testes which have never descended. In the case of a clear indication, the general practitioner should make a prompt referral (before the second birthday) and in other cases assurance should be provided and an expectant policy adopted until puberty.


Knowledge, attitude, and perception of oral and maxillofacial surgery specialty amongst healthcare professionals, and the General Public from a Gulf Cooperation Council (GCC) Country.
Oral and maxillofacial surgery specialty has grown rapidly in Kuwait in recent years. However, the general public and healthcare professionals remain unaware of its expanding scope of practice. The aim of the study is to assess public and professional (dental and medical) perception of the oral and maxillofacial surgical specialty in Kuwait. This is a cross-sectional study evaluating responses of dental professionals, medical professionals, and general public in Kuwait toward the oral and maxillofacial surgical specialty using a previously validated survey instrument with 100 participants in each group. Participants were asked to choose the most appropriate specialist to treat certain procedures across 4 disciplines: reconstruction, trauma, pathology, and cosmetic. Statistical comparison was conducted between dentists and medical doctors using Fisher's exact test with a p-value of < 0.05. Disparities were noted each group's responses. Oral and maxillofacial surgery was preferred overall for most clinical scenarios in trauma (p < 0.001), pathology (p < 0.001), and reconstructive surgery (p < 0.001). Plastic surgery was preferred for cosmetic surgeries (p < 0.001). This study indicates the need to increase awareness especially towards cosmetic surgery procedures, and conduct health campaigns regarding oral and maxillofacial surgery among healthcare professionals, especially medical doctors, and the general public.


Photoreceptor differentiation in Drosophila: from immature neurons to functional photoreceptors.
How a pool of equipotent cells acquires a multitude of distinct fates is a major question in developmental biology. The study of photoreceptor (PR) cell differentiation in Drosophila has been used to address this question. PR differentiation is a process that extends over a period of 5 days: It begins in the larval eye imaginal disc when PRs are recruited and commit to particular PR fates, and it culminates in the pupal eye disc with the morphogenesis of the rhabdomeres and the initiation of rhodopsin expression. Several models for PR specification agree that the Ras and Notch signaling pathways are important for the specification of different PR subtypes (Freeman [1997] Development 124:261-270; Cooper and Bray [2000] Curr. Biol. 10:1507-1510; Tomlinson and Struhl [2001] Mol. Cell. 7:487-495). In the first part of this review, we briefly describe the different signaling pathways and transcription factors required for the specification and differentiation of the different PR subtypes in the larval eye disc. In the second part, we review the roles of several transcription factors, which are required for the terminal photoreceptor differentiation and rhodopsin expression.


EMGTools, an adaptive and versatile tool for detailed EMG analysis.
We have developed an electromyography (EMG) decomposition system called EMGTools that can extract the constituent MUAPs and firing patterns (FPs) for quantitative analysis from the EMG signal recorded at slight effort for clinical evaluation. The aim was to implement a robust system able to handle the challenges and variations in clinically recorded signals. The system extracts MUAPs recorded by concentric needle electrodes and resolves superimposed MUAPs to produce FPs. Thus, critical fixed thresholds/parameters are avoided and replaced with adaptive solutions. The decomposition algorithm consists of three stages: segmentation, clustering, and resolution of compound segments. The results are validated using three different methods, comparing mean MUAP duration with previous methods, comparing dual channel recordings, and assessing the residual signal after decomposition. The advantages and limitations of the system are discussed.


The use of optical clearing and multiphoton microscopy for investigation of three-dimensional tissue-engineered constructs.
Recent advances in three-dimensional (3D) tissue engineering have concomitantly generated a need for new methods to visualize and assess the tissue. In particular, methods for imaging intact volumes of whole tissue, rather than a single plane, are required. Herein, we describe the use of multiphoton microscopy, combined with optical clearing, to noninvasively probe decellularized lung extracellular matrix scaffolds and decellularized, tissue-engineered blood vessels. We also evaluate recellularized lung tissue scaffolds. In addition to nondestructive imaging of tissue volumes greater than 4 mm(3), the lung tissue can be visualized using three distinct signals, combined or singly, that allow for simple separation of cells and different components of the extracellular matrix. Because the 3D volumes are not reconstructions, they do not require registration algorithms to generate digital volumes, and maintenance of isotropic resolution is not required when acquiring stacks of images. Once a virtual volume of tissue is generated, structures that have innate 3D features, such as the lumens of vessels and airways, are easily animated and explored in all dimensions. In blood vessels, individual collagen fibers can be visualized at the micron scale and their alignment assessed at various depths through the tissue, potentially providing some nondestructive measure of vessel integrity and mechanics. Finally, both the lungs and vessels assayed here were optically cleared, imaged, and visualized in a matter of hours, such that the added benefits of these techniques can be achieved with little more hassle or processing time than that associated with traditional histological methods.


Systematic Review of Interventions to Increase Stool Blood Colorectal Cancer Screening in African Americans.
African Americans experience colorectal cancer (CRC) related disparities compared to other racial groups in the United States. African Americans are frequently diagnosed with CRC at a later stage, screening is underutilized, and mortality rates are highest in this group. This systematic review focused on intervention studies using stool blood CRC screening among African Americans in primary care and community settings. Given wide accessibility, low cost, and ease of dissemination of stool-based CRC screening tests, this review aims to determine effective interventions to improve participation rates. This systematic review included intervention studies published between January 1, 2000 and March 16, 2019. After reviewing an initial search of 650 studies, 11 studies were eventually included in this review. The included studies were studies conducted in community and clinical settings, using both inreach and outreach strategies to increase CRC screening. For each study, an unadjusted odds ratio (OR) for the CRC screening intervention compared to the control arm was calculated based on the data in each study to report effectiveness. The eleven studies together recruited a total of 3334 participants. The five studies using two-arm experimental designs ranged in effectiveness with ORs ranging from 1.1 to 13.0 using interventions such as mailed reminders, patient navigation, and tailored educational materials. Effective strategies to increase stool blood testing included mailed stool blood tests augmented by patient navigation, tailored educational materials, and follow-up calls or mailings to increase trust in the patient-provider relationship. More studies are needed on stool blood testing interventions to determine effectiveness in this population.


[Measles and pregnancy. Evolution and management].
Measles is a highly infectious disease. In Mexico, nevertheless the postvaccine era, continue being an endemic disease. It has been described that measles increase the maternal mortality, because pregnant women have a more severe clinical course of the disease; measles also has negative repercussion on pregnancy, increasing the frequency of premature labor. We report two pregnant women complicated with measles, both of them had a clinical course of the disease and they didn't have obstetric or neonatal complications.


Effects of hydrocortisone acetate treatment on the small intestine of the lactent marsupial Didelphis albiventris.
When hydrocortisone acetate was administered subcutaneously to the lactent Brazilian white belly opossum, it induced precocious intestinal maturation. Histological features of the small intestine were reminiscent of those seen in human protein-caloric malnutrition. There were also indications that the glucocorticoid acted as an inducer of the differentiation of Paneth, goblet and granulomucous cells within the small intestinal epithelium. In the lactent opossum the small intestine is lined by an epithelium containing cells which exhibit intense endocytic activity (Krause et al. 1977; Santiago et al. 1983; H.B. Coutinho, Beck--unpublished) verified that subcutaneous injections of hydrocortisone acetate could determine intestinal closure in lactent opossums. Krause et al. and Santiago et al. have reported that in Didelphis virginiana and Didelphis albiventris, respectively, the goblet cells and Paneth cells differentiate lately in the development of pouch opossum young. Freitas et al. (1982) mentioned that the plasma cortisol level was very low in lactent white belly opossum, but preceding weaning there was an abrupt increase of the plasma cortisol reaching levels comparable to that obtained in adult animals. These facts suggested the need for investigations to clarify if cortisol could act as an inductive agent for the differentiation of goblet cells and Paneth cells in the lactent D. albiventris.


Localization of nonspecific lipid transfer proteins correlate with programmed cell death responses during endosperm degradation in Euphorbia lagascae seedlings.
When the storage materials have been depleted, the endosperm cells undergo programmed cell death. Very little is known about how the components of the dying cells are recycled and used by the growing seedling. To learn more about endosperm degradation and nutrient recycling, we isolated soluble proteins from the endosperm of Euphorbia lagascae seedlings collected 2, 4, and 6 d after sowing. The protein extracts were subjected to two-dimensional gel electrophoresis. Proteins that increased in amount in the endosperm with time were selected for further analysis with mass spectrometry. We successfully identified 17 proteins, which became more abundant by time during germination. Among these proteins were three E. lagascae lipid transfer proteins (ElLTPs), ElLTP1, ElLTP2, and ElLTP3. Detailed expressional studies were performed on ElLTP1 and ElLTP2. ElLTP1 transcripts were detected in endosperm and cotyledons, whereas ElLTP2 transcripts were only detected in endosperm. Western blots confirmed that ElLTP1 and ElLTP2 accumulate during germination. Immunolocalization experiments showed that ElLTP1 was present in the vessels of the developing cotyledons, and also in the alloplastic space in the endosperm. ElLTP2 formed a concentration gradient in the endosperm, with higher amounts in the inner regions close to the cotyledons, and lesser amounts in the outer regions of the endosperm. On the basis of these data, we propose that ElLTP1 and ElLTP2 are involved in recycling of endosperm lipids, or that they act as protease inhibitors protecting the growing cotyledons from proteases released during programmed cell death.


Separate influences of orientation and lighting in the inverted-face effect.
Studies of the inverted-face effect typically use photos as stimuli. Inverting photos not only misorients the face but also reverses important shading and shadow cues. We decoupled the influence of spatial orientation and the direction of lighting in three experiments and found that the relation between these factors varied with the task given to observers. When the task required identification of faces (Experiments 1 and 3), the factors were additive, consistent with a strategy of mental rotation of the face prior to an interpretation of the shading cues. When faces were assigned to coarse categories (Experiments 2 and 3), these factors interacted, consistent with a more piecemeal approach to face processing. We propose that the identification of a specific individual depends on configurational information, which is preserved if the image of an inverted face is mentally rotated before the identification process is begun.


Iron deficiency alters expression of genes implicated in Alzheimer disease pathogenesis.
Neonatal brain iron deficiency occurs after insufficient maternal dietary iron intake, maternal hypertension, and maternal diabetes mellitus and results in short and long-term neurologic and behavioral deficits. Early iron deficiency affects the genomic profile of the developing hippocampus that persists despite iron repletion. The purpose of the present study was threefold: 1) quantitative PCR confirmation of our previous microarray results, demonstrating upregulation of a network of genes leading to beta-amyloid production and implicated in Alzheimer disease etiology in iron-deficient anemic rat pups at the time of hippocampal differentiation; 2) investigation of the potential contributions of iron deficiency anemia and iron treatment to this differential gene expression in the hippocampus; and 3) investigation of these genes over a developmental time course in a mouse model where iron deficiency is limited to hippocampus, is not accompanied by anemia and is not repletable. Quantitative PCR confirmed altered regulation in 6 of 7 Alzheimer-related genes (Apbb1, C1qa, Clu, App, Cst3, Fn1, Htatip) in iron-deficient rats relative to iron-sufficient controls at P15. Comparison of untreated to treated iron-deficient animals at this age suggested the strong role of iron deficiency, not treatment, in the upregulation of this gene network. The non-anemic hippocampal iron-deficient mouse demonstrated upregulation of all 7 genes in this pathway from P5 to P25. Our results suggest a role for neonatal iron deficiency in dysregulation of genes that may set the stage for long-term neurodegenerative disease and that this may occur through a histone modification mechanism.


Ontogenic aspects of cisplatin-induced nephrotoxicity in rats.
A multi-age rat model was evaluated to identify a potential age-related difference in kidney injury following administration of cisplatin (CP). Different age groups of Wistar rats (aged 3, 7, 11 and 24 weeks) were given CP intraperitoneally (6 mg/kg) and sacrificed 6 days thereafter. CP-induced nephrotoxicity caused significant decreases in body weight, creatinine clearance, urine osmolality, plasma total anti-oxidant status, cortical glutathione (GSH) concentration and superoxide dismutase activity. It increased kidney weight and plasma concentrations of creatinine and urea. It increased urinary N-acetyl-beta-D-glucosaminidase activity and protein concentration. Most of the above actions were more marked as the animals advanced in age, except for the changes in GSH, which were similar in all age groups. CP produced necrosis in renal tubules and epithelial vacuolization, the extent of which was more evident as the rats grew older. Renal CP concentration was increased with the increased age of the animal, and the cortical CP concentration in 3 week-old rats was nearly half that of 24 week-old rats. This study showed that the vulnerability profile of each age group was different, suggesting that a multi-age pediatric/geriatric animal model is appropriate to assess, more completely, age-dependent changes in drug toxicity.


Fungicidal activity of amiodarone is tightly coupled to calcium influx.
The antiarrhythmic drug amiodarone has microbicidal activity against fungi, bacteria and protozoa. In Saccharomyces cerevisiae, amiodarone triggers an immediate burst of cytosolic Ca2+, followed by cell death markers. Ca2+ transients are a common response to many forms of environmental insults and toxic compounds, including osmotic and pH shock, endoplasmic reticulum stress, and high levels of mating pheromone. Downstream signaling events involving calmodulin, calcineurin and the transcription factor Crz1 are critical in mediating cell survival in response to stress. In this study we asked whether amiodarone induced Ca2+ influx was beneficial, toxic or a bystander effect unrelated to the fungicidal effect of the drug. We show that downregulation of Ca2+ channel activity in stationary phase cells correlates with increased resistance to amiodarone. In actively growing cells, extracellular Ca2+ modulated the size and shape of the Ca2+ transient and directly influenced amiodarone toxicity. Paradoxically, protection was achieved both by removal of external Ca2+ or by adding high levels of CaCl2 (10 mM) to block the drug induced Ca2+ burst. Our results support a model in which the fungicidal activity of amiodarone is mediated by Ca2+ stress, and highlight the pathway of Ca2+ mediated cell death as a promising target for antifungal drug development.


Glucose transport by radiation-induced insulinoma and clonal pancreatic beta-cells.
Sugar uptake was measured in dispersed cells prepared from radiation-induced insulinomas transplantable in NEDH rats and in three clonal beta-cell lines maintained in continuous culture (RIN m5F, RIN 1046, HIT). Uptake of D-glucose and 3-O-methyl-D-glucose by insulinoma cells was rapid so that the intracellular concentration of D-hexoses approximated the concentration in the incubation medium by 15-30 s. L-Glucose was taken up only slowly. 3-O-methyl-D-glucose uptake by RIN m5F, RIN 1046, and HIT cells was slow; with 1 mM 3-O-methylglucose in the medium, equilibrium was attained at 20 min, but with 10 mM 3-O-methylglucose, equilibrium was not attained even at 20 min. In HIT cells incubated with D-glucose for 30 min, the intracellular concentration of glucose was less than the medium glucose concentration, indicating glucose transport is a nonequilibrium reaction in this cell line. These data indicate that radiation-induced insulinoma cells retain the capacity of normal beta-cells to transport sugar at high rates. RIN m5F, RIN 1046, and HIT cells transport sugar slowly, however, and thus differ from normal beta-cells. In RIN m5F, RIN 1046, and HIT cells, unlike in normal beta-cells, glucose transport may be the site regulating glucose metabolism.


Evidence for colorectal cancer micrometastases using reverse transcriptase-polymerase chain reaction analysis of MUC2 in lymph nodes.
Poor survival in patients following resection for early stage colorectal cancer is thought to be due in part to the presence of occult micrometastases at the time of surgery. The MUC2 mucin gene is highly expressed in the colon and associated colorectal tumors and may be a candidate marker for colorectal cancer micrometastases. We have used RT-PCR to detect expression of MUC2 mRNA transcripts in order to identify possible lymph node micrometastases in node negative (Stage I and II, or Dukes A and B) colorectal cancer patients. A total of 396 nodes (histologic stage N0) from 34 colon and nine rectal cancers were studied by RT-PCR analysis with nested primers for MUC2 (an average of 7.6 nodes per case). In the primary tumors, 42/43 (98.1%) were positive for MUC2 by RT-PCR. Evidence of the presence of MUC2 was demonstrated in nodes from 0 of 10 (0%) patients with Tis or T1, one of six (16.7%) from T2, 10 of 25 (40.0%) from T3, and one of two (50%) from T4 tumors. MUC2 RT-PCR was negative in six nodes from three patients with non-malignant colon disease and positive in histologically positive lymph nodes from six of six (100%) stage III colon cancers. In this study, using RT-PCR to detect the presence of MUC2 transcripts, we have found preliminary evidence for possible micrometastatic disease in approximately a third of histologically negative N0 colorectal cancer patients. The increased presence of MUC2 expression also correlated with more advanced T stage. We conclude that MUC2 RT-PCR may be a sensitive and specific marker for occult micrometastases. This technique has the potential to identify a group of colorectal cancer patients at risk for early cancer recurrence.


[Pirasidol treatment of depression in elderly patients with somatic diseases].
To study efficacy and tolerance of pirasidol in elderly patients with somatic diseases and depression. The study was made in 30 patients over 55 years of age with a mild or moderate depressive episode. The efficacy of a 6 week treatment with pirasidol was assessed by somatic examination, Hamilton depressive scale (17 points), General Clinical Impression Scale, 5-score subjective state scale. Pirasidol treatment led to a 36% decrease in intake of drugs. The patients took much lower doses of non-narcotic analgetics, nitroglycerine, tranquilizers, enzymatic medicines. The highest efficacy was seen in patients with exacerbation of somatic diseases which reduced faster in addition of pirasidol to somatotropic therapy. Pirasidol is well tolerated, no interaction with other drugs was found. The antidepressant pirasidol showed efficacy against depression in elderly patients with somatic pathology. It can be recommended as a drug of choice for treatment of depression in elderly patients with somatic diseases.


Validity and reliability of the Dysfunctional Behaviour Rating Instrument.
The objective of this study was to examine the reliability and validity of the Dysfunctional Behaviour Rating Instrument (DBRI) in cognitively impaired older adults living in the community. A total of 184 adults with suspected cognitive impairment received a standardized history, physical examination and work-up that included the Standardized Mini-Mental State Examination. Caregivers scored a DBRI Behaviour Problem Checklist (BPC) and Lawton Scale for each patient. The reliability of the DBRI, measured by an intraclass correlation coefficient, was 0.75. The correlation coefficient between the DBRI and the BPC total score was 0.71. The correlations between the DBRI and the cognitive, activities of daily living and self-care domain scores of the BPC were lower (0.66, 0.38 and 0.26 respectively). The DBRI is a specific, reliable and valid caregiver-reported measure of dysfunctional behaviour in cognitively impaired elderly living in the community.


Nanoparticles and Taylor Dispersion as a Linear Time-Invariant System.
The physical principles underpinning Taylor dispersion offer a high dynamic range to characterize the hydrodynamic radius of particles. While Taylor dispersion grants the ability to measure radius within nearly 5 orders of magnitude, the detection of particles is never instantaneous. It requires a finite sample volume, a finite detector area, and a finite detection time for measuring absorbance. First we show that these practical requirements bias the analysis when the self-diffusion coefficient of particles is high, which is typically the case of small nanoparticles. Second we show that the accuracy of the technique may be recovered by treating Taylor dispersion as a linear time-invariant system, which we prove by analyzing the Taylor dispersion spectra of two iron-oxide nanoparticles measured under identical experimental conditions. The consequence is that such treatment may be necessary whenever Taylor dispersion analysis is not optimized for a given size but dedicated to characterize broad groups of particles of varying size and material.


SOUND: a structured handoff tool improves patient handoffs in a pediatric emergency department.
Handoff communication is an important contributor to safety and quality in the emergency department (ED). Breakdowns in this process may lead to unsafe conditions or adverse events. The purpose of this study was to test the hypothesis that the quality of patient handoffs in the pediatric ED would improve after implementation of a structured handoff method. In this prospective, observational study, we evaluated the implementation of a structured handoff tool, SOUND, which we developed to standardize the format of handoffs. The tool contains 5 components as follows: Synthesis, Objective Data, Upcoming Tasks, Nursing Input, and Double Check. SOUND was implemented through an online module and provider education. Handoffs were observed before and after implementation of SOUND. Statistical process control was used to measure the effects of the intervention. A successful handoff was defined as one in which 4 of the 5 components were included. As a balancing measure, we calculated mean time per handoff. We observed 638 handoffs. The implementation of SOUND significantly increased the percentage of successful handoffs. Statistical process control demonstrated continued improvement over time. This improvement was associated with a modest increase in the mean time per patient discussed (52.9 vs 73.0 seconds, P < 0.01). It is feasible to standardize patient handoffs in the pediatric ED. The implementation of SOUND improved completeness of handoffs with only a modest increase in the mean time spent discussing each patient. Future study is required to determine if SOUND will prove effective in other ED settings.


Compromised Motor Dexterity Confounds Processing Speed Task Outcomes in Stroke Patients.
Most conventional measures of information processing speed require motor responses to facilitate performance. However, although not often addressed clinically, motor impairment, whether due to age or acquired brain injury, would be expected to confound the outcome measure of such tasks. The current study recruited 29 patients (20 stroke and 9 transient ischemic attack) with documented reduction in dexterity of the dominant hand, and 29 controls, to investigate the extent to which 3 commonly used processing speed measures with varying motor demands (a Visuo-Motor Reaction Time task, and the Wechsler Adult Intelligence Scale-IV Symbol Search and Coding subtests) may be measuring motor-related speed more so than cognitive speed. Analyses include correlations between indices of cognitive and motor speed obtained from two other tasks (Inspection Time and Pegboard task, respectively) with the three speed measures, followed by hierarchical regressions to determine the relative contribution of cognitive and motor speed indices toward task performance. Results revealed that speed outcomes on tasks with relatively high motor demands, such as Coding, were largely reflecting motor speed in individuals with reduced dominant hand dexterity. Thus, findings indicate the importance of employing measures with minimal motor requirements, especially when the assessment of speed is aimed at understanding cognitive rather than physical function.


Fluoroacrylate-bound fluorous-phase soluble hydrogenation catalysts
[reaction: see text] Fluoroacrylate polymer-bound hydrogenation catalysts are described. N-Acryloxysuccinimide-containing fluoroacrylate polymers were converted into phosphine ligands and subsequently into analogues of Wilkinson's catalyst by amidation of N-acryloxysuccinimide active ester residues and Rh exchange. The resulting catalysts have excellent activity and can be reused following fluorous biphasic liquid/liquid separation and extraction.


The NIH "Points to Consider" and the limits of human gene therapy.
In this essay, I examine the sources and reach of the NIH "Points to Consider." These guidelines are based on normative considerations inherited from two sets of science policy deliberations that took place in the United States during the 1970s: the discussion of research with human subjects and the recombinant DNA debate. The combined lessons of those deliberations provide six criteria by which to evaluate human gene therapy proposals. While these criteria could be used to reject proposals to attempt germ-line gene therapy or enhancement engineering today, they provide no principled basis for publicly proscribing the development of these forms of genetic intervention. Instead, they will ultimately lead us to approach the moral limits of gene therapy as a professional policy question about the goals of medicine, rather than as a social policy question about the public good.


XGef influences XRINGO/CDK1 signaling and CPEB activation during Xenopus oocyte maturation.
CPEB-mediated polyadenylation-induced translation of several developmentally important mRNAs drives Xenopus laevis oocyte meiotic progression and production of fertilizable eggs. To date, the signal transduction events that induce CPEB activation remain somewhat unclear, however, XGef has been shown to be involved in this process. P42 MAPK (ERK2) activity and XRINGO accumulation are also required for the activating phosphorylation of CPEB. We show here that XGef activity influences the early meiotic function of XRINGO/CDK1, a novel component of the progesterone signaling pathway. An XGef-specific antibody depresses XRINGO-induced GVBD, whereas XGef overexpression accelerates this process. XGef and CPEB interact with XRINGO in immature and maturing oocyte extracts and XGef, XRINGO and ERK2 interact directly in vitro. These data suggest that an XGef/XRINGO/ERK2/CPEB complex forms in ovo during early meiotic resumption. Notably, specific inhibition of XRINGO/CDK1 activity in CPEB phosphorylation-competent extracts completely blocks phosphorylation of CPEB, which suggests that XRINGO/CDK1 directly phosphorylates CPEB. Finally, overexpression of XGef (65-360), which cannot bind CPEB or ERK2, but is capable of XRINGO association, blocks XRINGO-induced meiotic progression potentially through titration of endogenous XRINGO. Combined, our results suggest that XGef is involved in XRINGO/CDK1 mediated activation of CPEB and that an XGef/XRINGO/ERK2/CPEB complex forms in ovo to facilitate this process.


Genome-wide allelotype study of primary glioblastoma multiforme.
To investigate the molecular genetic pathogenesis of primary glioblastoma multiforme (GBM) and identify which chromosomes or chromosomal regions of the entire genome may harbor tumor suppressor genes (TSGs) associated with GBM. A high-resolution allelotype study of 21 cases of primary GBM was performed by PCR-based loss of heterozygosity (LOH) analysis. Three hundred and eighty-two fluorescent dye-labeled microsatellite markers covering all 22 autosomes were applied. The mean genetic distance between two flanking markers was about 10 cM. LOH was observed on all 39 nonacrocentric autosomal arms examined in this study. The LOH frequencies of 10q, 10p, 9p, 17p and 13q were the highest (> 50%). Furthermore, high LOH frequencies were detected in the regions containing known TSGs including PTEN, DMBT1, p16, p15, p53 and RB; the LOH frequencies on 14q, 3q, 22q, 11p, 9q, 19q were also high (> 40.5%). Our study observed the following commonly deleted regions: 9p22-23, 10p12.2-14, 10q21.3, 13q12.1-14.1, 13q14.3-31, 17p11.2-12, 17p13, 3q25.2-26.2, 11p12-13, 14q13-31, 14q32.1, 14q11.1-13, 22q13.3, 4q35, 4q31.1-31.2, 6q27 and 6q21-23.3. The molecular pathogenesis of GBM is very complicated and associated with a variety of genetic abnormalities on many chromosomal arms. The most closely related chromosomal arms to the pathogenesis of GBM are 10q, 10p, 9p, 17p and 13q. Besides the well-known TSGs including PTEN, DMBT1, p16, p15, p53 and RB, multiple unknown TSGs associated with GBM may be present on the commonly deleted regions detected in the present study.


The crystal and defect structures of polar KBiNb2O7.
KBiNb2O7 was prepared from RbBiNb2O7 by a sequence of cation exchange reactions which first convert RbBiNb2O7 to LiBiNb2O7, before KBiNb2O7 is formed by a further K-for-Li cation exchange. A combination of neutron, synchrotron X-ray and electron diffraction data reveal that KBiNb2O7 adopts a polar, layered, perovskite structure (space group A11m) in which the BiNb2O7 layers are stacked in a (0, ½, z) arrangement, with the K+ cations located in half of the available 10-coordinate interlayer cation sites. The inversion symmetry of the phase is broken by a large displacement of the Bi3+ cations parallel to the y-axis. HAADF-STEM images reveal that KBiNb2O7 exhibits frequent stacking faults which convert the (0, ½, z) layer stacking to (½, 0, z) stacking and vice versa, essentially switching the x- and y-axes of the material. By fitting the complex diffraction peak shape of the SXRD data collected from KBiNb2O7 it is estimated that each layer has approximately a 9% chance of being defective - a high level which is attributed to the lack of cooperative NbO6 tilting in the material, which limits the lattice strain associated with each fault.


[Effect of disulfiram on energy metabolism (redox potential shift) coupled to paradoxical sleep episodes in rat cerebral cortex].
Disulfiram (DS) is widely used to treat patients with chronic alcoholism. DS treatment multiplies PS episodes. In this work, DS effect on the number of PS episodes and on the energy metabolism changes in the cerebral cortex (coupled to PS episodes) was investigated for the first time in rats. Polygraphic recording of the redox potential E (with platinum electrodes implanted in several cortical sites), electrocorticogram, neck electromyogram, and general motor activity were made in sleep-wake cycles. Rats received DS (100 mg/kg) with meals for two nights, after which the number of PS episodes increased almost twice during two subsequent sessions (prior to receiving DS). This was evidence of an increase in PS pressure coupled to a decrease of norepinephrine level in the brain. DS also evoked sharp decrease in the amount of the positive E shifts related to PS, which were replaced by the negative E shifts or by the two-phase E shifts (negative-positive waves). The absolute mean amplitude decreased both for the positive E shifts and the negative E shifts. These findings demonstrate prevailing glycolytic compartment as a source of fuel supporting PS and the inhibition in all brain energetic compartments. The data presented well agree with the conception that glycolysis becomes the main source for the brain activity under pathology conditions.


Smoking during pregnancy, 1990-96.
This report presents trend data for smoking during pregnancy. Data are presented for various characteristics including age of mother, race and ethnic origin, place of birth of mother, and State of residence. Descriptive tabulations were calculated using data reported on birth certificates between 1990 and 1996. The rate of smoking during pregnancy has declined each year between 1990 and 1996. In 1996 over 400,000 women reported smoking during their pregnancies (13.6 percent of all births). The rates of smoking during pregnancy for women 15-19 years of age declined between 1990 and 1994 but increased in the last two years, and now they have the highest rates of all age groups. Among race and ethnic groups, American Indian, non-Hispanic white, and Hawaiian women had the highest rates of smoking during pregnancy in 1996, while Chinese women had the lowest rates.


Goblet cell carcinoid of the appendix: laparoscopic appendectomy or right hemicolectomy?
Goblet cell carcinoids are uncommon tumours with histological features of both adenocarcinoma and carcinoid tumour. They occur predominantly in the appendix and although the malignant potential remains unclear, adenocarcinoids appear to be more aggressive than conventional carcinoids. In this case report, we present a goblet cell carcinoid with laparoscopic operative treatment in two stages. A 43-year-old female patient with constant dullness in the right lower quadrant was diagnosed with acute appendicitis and underwent laparoscopic appendectomy. Macroscopically, a diffusely inflamed appendix was found with no sign of perforation. Histopathological examination revealed a goblet cell carcinoid with characteristics of aggressive behaviour, indicating the need for laparoscopic right hemicolectomy in which, however, neither residual tumour nor metastatic lymph nodes could be found. The postoperative course was uneventful. As they may present the same clinical presentation, pathological diagnosis is required to distinguish goblet cell carcinoid from acute appendicitis. Two-stage surgery for goblet cell carcinoid is advocated in the literature, but the debate still continues as to whether the goblet cell carcinoid should be treated by appendectomy alone, as for most carcinoids, or by right hemicolectomy, as for the appendiceal adenocarcinoma.


Epidemiology of otitis media with effusion in children.
The recently accepted international classification for otitis media was applied to a study population of 898 children less than 12 years of age having otitis media with effusion persisting at least three months. Mucoid effusion was aspirated from 48% of ears, was found more often in younger than older patients, was more often bilateral, and was a more stable state during longitudinal observation than was serous otitis media or purulent otitis media (POM). Serous otitis media occurred in only 10% of ears, but was found more often than in younger patients; POM was found in only 7% of ears. Otoscopy did not distinguish among the three effusion types. Known middle-ear pathogens were cultured more often behind red and bulging tympanic membranes from these cases of chronic effusion than behind membranes lacking these characteristics. These observations provide an epidemiologic and clinical base for further investigations of these otitis media types.


Elevated arsenic exposure and efficient arsenic metabolism in indigenous women around Lake Poopó, Bolivia.
Elevated concentrations of inorganic arsenic, one of the most potent environmental toxicants and carcinogens, have been detected in well water around Lake Poopó, Bolivia. This study aimed to assess human exposure to arsenic in villages around Lake Poopó, and also to elucidate whether the metabolism and detoxification of arsenic in this population is as efficient as previously indicated in other Andean areas. We recruited 201 women from 10 villages around Lake Poopó. Arsenic exposure was determined as the sum concentration of arsenic metabolites (inorganic arsenic; monomethylarsonic acid, MMA; and dimethylarsinic acid, DMA) in urine (U-As), measured by HPLC-HG-ICP-MS. Efficiency of arsenic metabolism was assessed by the relative fractions of the urinary metabolites. The women had a wide variation in U-As (range 12-407 μg/L, median 65 μg/L) and a markedly efficient metabolism of arsenic with low %MMA (median 7.7%, range: 2.2-18%) and high %DMA (80%, range: 54-91%) in urine. In multivariable-adjusted linear regression models, ethnicity (Aymara-Quechua vs. Uru), body weight, fish consumption and tobacco smoking were associated with urinary arsenic metabolite fractions. On average, the Uru women had 2.5 lower % (percentage unit) iAs, 2.2 lower %MMA and 4.7 higher %DMA compared with the Aymara-Quechua women. Our study identified several factors that may predict these women's arsenic methylation capacity, particularly ethnicity. Further studies should focus on mechanisms underlying these differences in arsenic metabolism efficiency, and its importance for the risk of arsenic-related health effects.


The mental health of informal caregivers in Ontario: an epidemiological survey.
This study describes the mental health status, disability, physical health, and mental health service utilization of informal care-givers under the age of 65 in the province of Ontario. The study analyzed data collected in the 1991 province-wide, population-based mental health supplement to the Ontario Health Survey. Diagnoses from the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised, were generated on the basis of a structured diagnostic interview. Caregivers and noncaregivers are compared here on past-year prevalence of psychiatric disorder, physical illness, disability, and utilization of mental health services. The possible confounding effects of age, sex, employment status, and economic disadvantage are explored. Informal caregivers (n = 1219) constituted 15.0% of the sample. Caregivers had higher rates of affective (6.3% vs 4.2%) and anxiety (17.5% vs 10.9%) disorders than noncaregivers and used health services for mental health problems at nearly twice the rate. Documentation of the prevalence of caregiving and the increased prevalence of psychiatric disorders, disability, and service utilization among caregivers is of critical importance as governments continue to move toward community-based care. To accomplish this goal, the needs of caregivers must be acknowledged and met by the establishment of appropriate and readily accessible support services.


Binding characteristics of anti-Rh0(D) antibodies to Rh0(D)-positive and Du red cells.
The relation of human erythrocyte Rh0(D) to Du sites is an important unresolved question in the field of immunohematology. To compare the immunological reactivity of Rh0(D)-positive and Du erythrocytes, the binding characteristics of two anti-Rh0(D) antisera to human Rh0(D)-positive and Du ("low-grade") erythrocytes were studied. 14C-Protein A and direct antibody-labeled techniques were used to generate binding curves and to derive double-reciprocal plots. The results show that the number of antigen sites differ by a factor of 10 to 15 between the Rh0(D)-positive and Du red cells, but that the dissociation constants between anti-Rh0(D) and the Rh0(D) and Du antigens are indistinguishable when studied by the two labeling methods and two different anti-Rh0(D) antibodies. The extent of binding to 112 different Du samples showed a normal distribution and was independent of apparent phenotype. These data suggest immunologic identity of Rh0(D) and Du ("low-grade") sites and that the difference between the antigens of Rh0(D) and Du cells is quantitative only. The data are incompatible with the "missing mosaic" and gene interaction theories of mechanism.


Antioxidant and selective anticancer activities of two Euphorbia species in human acute myeloid leukemia.
In this study, two Euphorbia species (i.e. terracina and paralias) were investigated for their cytotoxic and antioxidant activities. Cytotoxicity of plant methanol and chloroform fractions was examined towards human acute myeloid leukemia (THP1) and human colon epithelial (Caco2) cancer cell lines, as well as CD 14 and IEC-6 normal cells by targeting various modulators of apoptosis or inflammation. Moreover, secondary metabolite pools (phenolic classes, alkaloids, terpenes, saponins) and antioxidant activities (DPPH, ABTS and O2- scavenging, as well as FRAP tests) were assessed in plant extracts. Both Euphorbia species appeared to be rich in phenolic compounds and terpenoids, Moreover, E. terracina polar and apolar fractions and E. paralias polar fraction were highly active against THP1 cells, with IC50 values of 2.08, 14.43 and 54.58μg/mL, respectively. However, no cytotoxicity was found against normal cells (CD14+ monocytes). The results indicate that the three fractions induce apoptosis in THP1 cell line after 6h of exposure. Furthermore, apoptosis caused by apolar fraction was related to a caspase-dependent process, whereas other death pathways seemed to be involved with the polar fractions. An enhanced production of reactive oxygen species was detected upon cell treatment with plant extracts. Interestingly, they have no effect on cytokine TNF-α secretion in THP1 and normal cells compared to untreated cells, indicating that the three fractions caused no inflammation. Euphorbia terracina and E. paralias polar fractions showed strong antioxidant activity with potent scavenging capacity against DPPH, ABTS and superoxide radicals. Moreover, these fractions displayed a very high ferric reducing power. These findings confirm the strong antioxidant capacity of Euphorbia plants and suggest a targeted anti-cancer effect with a potent anti-proliferative property of E. terracina and E. paralias extracts, which induce programmed cell death in leukemia cell lines but not in normal monocytes cells.


Assessment of the accuracy of long-range corrected functionals for describing the electronic and optical properties of silver clusters.
The absorption spectra and ionization potentials of silver clusters Ag(n) (n=4-20) are examined in the framework of density-functional theory (DFT) using several different methods of representing the exchange-correlation functional. Three different types of exchange-correlation functionals are used: those including gradient corrections to the density in the generalized gradient approximation, global hybrid functionals mixing in a portion of the Hartree-Fock exchange, and long-range-corrected (LC-) functionals. Comparison of ionization potentials calculated using DFT with those derived from experiments demonstrates that LC-functionals more accurately represent the electronic structure of the silver clusters studied. Absorption spectra are compared with both experimental spectra and those derived using higher level theoretical calculations showing that the LC-functionals appear to correctly describe the optical transitions in the gas phase, particularly when a small redshift in the experimental spectrum is accounted for due to matrix effects. It is also demonstrated that the LC-hybrid functionals significantly reduce the occurrence of spurious states in the optical absorbance spectrum while maintaining the intensity of plasmon like features of the spectra for larger silver clusters.


Oligometastatic Stomach Carcinoma From Lung Squamous Cell Carcinoma Detected by 18F-FDG PET/CT.
Metastasis from squamous cell carcinoma of the lung to the stomach is extremely rare. F-FDG PET/CT demonstrated intense F-FDG uptake in the lower lobe of the left lung, stomach, and mediastinal lymph node in a 61-year-old man. Lower lobe of the left lung resection, mediastinal lymphadenectomy, partial gastrectomy, and esophagogastric anastomosis was performed. Immunohistochemical studies revealed squamous cell lung carcinoma in the left lung and metastatic carcinoma of gastric and lymph nodes. The present case further demonstrated the value of F-FDG PET/CT in the staging of malignant disease.


Adaptive output feedback NN control of a class of discrete-time MIMO nonlinear systems with unknown control directions.
In this paper, adaptive neural network (NN) control is investigated for a class of block triangular multiinput-multioutput nonlinear discrete-time systems with each subsystem in pure-feedback form with unknown control directions. These systems are of couplings in every equation of each subsystem, and different subsystems may have different orders. To avoid the noncausal problem in the control design, the system is transformed into a predictor form by rigorous derivation. By exploring the properties of the block triangular form, implicit controls are developed for each subsystem such that the couplings of inputs and states among subsystems have been completely decoupled. The radial basis function NN is employed to approximate the unknown control. Each subsystem achieves a semiglobal uniformly ultimately bounded stability with the proposed control, and simulation results are presented to demonstrate its efficiency.


Lung health in workers exposed to reed dust.
We conducted a cross-sectional survey in a cellulose plant among 109 reed workers, exposed to reed dust and 78 unexposed office workers, to investigate respiratory health effects of reed dust exposure. Investigations included dust measurements, serum total IgE, skin prick test, pulmonary function testing and questionnaire on respiratory symptoms. Total dust level in the reed processing unit was higher than the office (9.7 and 0.02 mg/m3, respectively). Reed workers had a higher rate of current smoking (67% and 46%, respectively). After the adjustment for smoking status and age, reed dust exposure was significantly associated with wheezing, chronic cough, dyspnea, itching eyes and itching nose. Chest tightness and ODTS symptoms were only reported by reed workers (27.5% and 23.9%, respectively). After the adjustment for pack-years of smoking, percentage of predicted FEV1, FVC, FEV1/FVC and FEF25-75 in reed workers were significantly lower than office workers. Among reed workers, wheezing was associated with older age (>40 years) and ever smoking, and cross-shift decline in FVC and FEV1 with shorter duration of work. Reed dust exposure in the workplace could provoke respiratory symptoms, possibly due to an irritating effect. Health selection bias is likely, and could have underestimated the health effects of reed dust exposure.


Crocin ameliorates oxidative stress and suppresses renal damage in streptozotocin induced diabetic male rats.
Diabetes mellitus (DM) is a prevalent metabolic disorder with complications including nephropathy, neuropathy, retinopathy and peripheral vascular disease. Crocin is a water soluble carotenoid that exhibits strong antioxidant activity. I investigated the potential hypoglycemic and reno-protective effects of crocin for type 1 diabetic male rats using periodic acid-Schiff and hematoxylin staining; metalloproteinase-7 (MMP-7), phosphatase and tensin homolog (PTEN) and phospho-Akt (p-Akt) immunohistochemistry; measurement of blood glucose, malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant and total oxidant status; and oxidative stress index. I used four groups of rats: control (saline treated), diabetic (single dose of 65 mg/kg streptozotocin), crocin (treated with 50 mg/kg) and diabetic + crocin. Crocin decreased levels of MDA, SOD, oxidative stress index and glucose significantly in diabetic animals. Renal damage from DM also was decreased by crocin treatment. MMP-7 and p-Akt immunoreactivity were stronger in the diabetic group compared to other groups, but PTEN immunoreactivity was weaker. Crocin treatment returned MMP-7 and PTEN expression to near normal. The ameliorative effect of crocin is attributed to its stimulation of the antioxidant defense system and its ability to regulate the MMP-7/PTEN/Akt signaling cascade.


Inferring transcription factor complexes from ChIP-seq data.
Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) allows researchers to determine the genome-wide binding locations of individual transcription factors (TFs) at high resolution. This information can be interrogated to study various aspects of TF behaviour, including the mechanisms that control TF binding. Physical interaction between TFs comprises one important aspect of TF binding in eukaryotes, mediating tissue-specific gene expression. We have developed an algorithm, spaced motif analysis (SpaMo), which is able to infer physical interactions between the given TF and TFs bound at neighbouring sites at the DNA interface. The algorithm predicts TF interactions in half of the ChIP-seq data sets we test, with the majority of these predictions supported by direct evidence from the literature or evidence of homodimerization. High resolution motif spacing information obtained by this method can facilitate an improved understanding of individual TF complex structures. SpaMo can assist researchers in extracting maximum information relating to binding mechanisms from their TF ChIP-seq data. SpaMo is available for download and interactive use as part of the MEME Suite (http://meme.nbcr.net).


[Salem witches, flying brooms, and synthetic drugs].
As supplementary material to Health Education programs about synthetic drugs, the authors present a historical summary on LSD, stramonium and khat. "Tripis", Special K and other synthetic pills contain these substances and are being widely used by youths. The history of these main hallucinogenic active ingredients has a strong tie to the mythology of witchcraft and witches: a historically interesting time period bearing a large amount of religious intolerance. The objective of this review is to end the belief today's youth have that they are taking new substances which have no risks.


TCR-MHC docking orientation: natural selection, or thymic selection?
T cell receptors (TCR) dock on their peptide-major histocompatibility complex (pMHC) targets in a conserved orientation. Since amino acid sidechains are the foundation of specific protein-protein interactions, a simple explanation for the conserved docking orientation is that key amino acids encoded by the TCR and MHC genes have been selected and maintained through evolution in order to preserve TCR/pMHC binding. Expectations that follow from the hypothesis that TCR and MHC evolved to interact are discussed in light of the data that both support and refute them. Finally, an alternative and equally simple explanation for the driving force behind the conserved docking orientation is described.


[Erythrocyte membranes in patients with congenital cyanotic heart disease before and after obsidan therapy].
Tissue oxygen tension, peroxidation of lipids (malonic dialdehyde levels, superoxide dismutase activity), fatty acid, spectrum and phospholipid composition in the red blood cells, Na+, K(+)-ATPase were studied in 11 healthy children and 21 with cyanotic heart disease. The beta-adrenoblocker obsidan was used in the multimodality treatment of 10 patients. Unlike healthy children, the patients had decreased tissue oxygen tension, intensified lipid peroxidation, an altered lipid profile in the red blood cell membranes, their abnormal permeability, diminished intracellular ATP depot. The conventional tools of intensive care (oxygenation, cardiotropic drugs, goal-oriented fluid therapy) are low beneficial. There is evidence for the supplementation of obsidan, a beta-adrenoblocker, to a therapeutical complex for this group of patients. Clinical and metabolic evidence for the positive action of the drug on lipid peroxidation, lipid spectrum in the red blood cell membranes, their permeability and biological energy reactions.


Improvements in speech perception with an experimental nonlinear frequency compression hearing device.
The performance of an experimental frequency compression hearing device was evaluated using tests of speech understanding in quiet. The device compressed frequencies above a programmable cut-off, resulting in those parts of the input signal being shifted to lower frequencies. Below the cut-off, signals were amplified without frequency shifting. Subjects were experienced hearing aid users with moderate-to-severe sensorineural hearing loss and sloping audiograms. Their recognition of monosyllabic words was tested using the experimental device in comparison with conventional hearing aids. Of the 17 subjects, eight showed a significant score improvement (p < 0.05), whereas one subject showed a significant score decrease. Some of the improvements may have resulted from the better audibility provided in the high frequencies by the experimental device in comparison with the conventional aids. However, a subsequent study found that increasing the high-frequency gain in the conventional aids did not produce equivalent perceptual benefits.


Oxylipin biosynthesis genes positively regulate programmed cell death during compatible infections with the synergistic pair potato virus X-potato virus Y and Tomato spotted wilt virus.
One of the most severe symptoms caused by compatible plant-virus interactions is systemic necrosis, which shares common attributes with the hypersensitive response to incompatible pathogens. Although several studies have identified viral symptom determinants responsible for systemic necrosis, mechanistic models of how they contribute to necrosis in infected plants remain scarce. Here, we examined the involvement of different branches of the oxylipin biosynthesis pathway in the systemic necrosis response caused either by the synergistic interaction of Potato virus X with Potato virus Y (PVX-PVY) or by Tomato spotted wilt virus (TSWV) in Nicotiana benthamiana. Silencing either 9-lipoxygenase (LOX), 13-LOX, or α-dioxygenase-1 (α-DOX-1) attenuated the programmed cell death (PCD)-associated symptoms caused by infection with either PVX-PVY or TSWV. In contrast, silencing of the jasmonic acid perception gene, COI1 (Coronatine insensitive 1), expedited cell death during infection with compatible viruses. This correlated with an enhanced expression of oxylipin biosynthesis genes and dioxygenase activity in PVX-PVY-infected plants. Moreover, the Arabidopsis thaliana double lox1 α-dox-1 mutant became less susceptible to TSWV infection. We conclude that oxylipin metabolism is a critical component that positively regulates the process of PCD during compatible plant-virus interactions but does not play a role in restraining virus accumulation in planta.


Orientational Disorder of C60 in Li2CsC60.
The x-ray diffraction of the nonsuperconducting ternary fulleride Li(2)CsC(60) reveals at room temperature a face-centered-cubic (Fm3m) disordered structure that persists to a temperature of 13 Kelvin. The crystal structure is best modeled as containing quasispherical [radius of 3.556(4) angstroms] C(60)(3-) ions, in sharp contrast to their orientational state in superconducting face-centered-cubic K(3)C(60) (merohedral disorder) and primitive cubic Na(2)CsC(60) (orientational order). The orientational disorder of the carbon atoms on the C(60)(3-) sphere was analyzed with symmetry-adapted spherical-harmonic functions. Excess atomic density is evident in the <111> directions, indicating strong bonding Li(+)-C interactions, not encountered before in any of the superconducting alkali fullerides. The intercalate-carbon interactions and the orientational state of the fullerenes have evidently affected the superconducting pair-binding mechanism in this material.