Location of gliomas in relation to mobile telephone use: a case-case and case-specular analysis.
The energy absorbed from the radio-frequency fields of mobile telephones depends strongly on distance from the source. The authors' objective in this study was to evaluate whether gliomas occur preferentially in the areas of the brain having the highest radio-frequency exposure. The authors used 2 approaches: In a case-case analysis, tumor locations were compared with varying exposure levels; in a case-specular analysis, a hypothetical reference location was assigned for each glioma, and the distances from the actual and specular locations to the handset were compared. The study included 888 gliomas from 7 European countries (2000-2004), with tumor midpoints defined on a 3-dimensional grid based on radiologic images. The case-case analyses were carried out using unconditional logistic regression, whereas in the case-specular analysis, conditional logistic regression was used. In the case-case analyses, tumors were located closest to the source of exposure among never-regular and contralateral users, but not statistically significantly. In the case-specular analysis, the mean distances between exposure source and location were similar for cases and speculars. These results do not suggest that gliomas in mobile phone users are preferentially located in the parts of the brain with the highest radio-frequency fields from mobile phones.


Integrating the MicroRNome into the study of lung disease.
Over the last 15 years, investigators have identified small noncoding RNAs as regulators of gene expression. One type of noncoding RNAs are termed microRNAs (miRNAs). miRNAs are evolutionary conserved, approximately 22-nucleotide single-stranded RNAs that target genes by inducing mRNA degradation or by inhibiting translation. miRNAs are implicated in many critical cellular processes, including apoptosis, proliferation, and differentiation. Furthermore, it is estimated that miRNAs may be responsible for regulating the expression of nearly one-third of the human genome. Despite the identification of greater than 500 mature miRNAs, very little is known about their biological functions and functional targets. In the last 5 years, researchers have increasingly focused on the functional relevance and role that miRNAs play in the pathogenesis of human disease. miRNAs are known to be important in solid organ and hematological malignancies, heart disease, as potential modulators of the immune response, and organ development. It is anticipated that miRNA analysis will emerge as an important complement to proteomic and genomic studies to further our understanding of disease pathogenesis. Despite the application of genomics and proteomics to the study of human lung disease, few studies have examined miRNA expression. This perspective is not meant to be an exhaustive review of miRNA biology but will provide an overview of both miRNA biogenesis and our current understanding of the role of miRNAs in lung disease as well as a perspective on the importance of integrating this analysis as a tool for identifying and understanding the biological pathways in lung-disease pathogenesis.


Special issues in injury prevention research: developing the science of program implementation.
Despite widespread application of the public health approach to injury prevention, there is an acknowledged limitation in the extent to which it facilitates translation of research evidence to injury prevention practice. In this paper we clarify the ecoepidemiological principles that underpin the public health approach to injury control in order to support explicit efforts to address the multilevel component causes and improve the evidence base on which effective program implementation depends. KEYPOINTS: If injury causation is understood in terms of the ecoepidemiological model rather than the proximal risk factor model, then quantification of the context in which the event occurs is evidently as important as quantification of the energy exchange event itself. The ecoepidemiological model of injury causation recognises barriers and facilitators to injury prevention as component causes of population burden of injury and thus delineates these factors as legitimate targets for intervention. Injury prevention programs that are designed to specifically address the factors causally related to the program's implementation, as well as the contextual factors that determine the characteristics of the energy exchange event, are more likely to be implemented and more likely to result in effective uptake of recommended energy exchange countermeasures. Interventions to reduce the burden of injury in the population should address the individual level factors that increase the risk of injury, but also the upstream factors that influence the extent to which there is widespread adoption by individuals of the recommended countermeasures.


Effects of Ca2+ on force-velocity characteristics of normal and hypertrophic smooth muscle of the rat portal vein.
Portal hypertension was induced in rats by partial ligation of the hepatic branches of the portal vein. After 5 days of hypertension the portal veins were taken out and mounted for isometric and quick-release experiments. Portal veins from sham-operated normal rats served as controls. The ligated veins had an increased cross-sectional area, indicating smooth-muscle hypertrophy. Although the absolute magnitude of active force of these veins was increased, the active force per cross-sectional area was decreased, indicating an alteration in the properties of the contractile system. No difference in the Ca2+ concentration-response relations to K+-activated intact control and hypertrophic veins was found. In chemically skinned preparations, devoid of functional plasma membranes, the hypertrophic veins had similar Ca2+ sensitivity (in the presence of I microM calmodulin) but a lower force per cross-sectional area. Force-velocity relations were determined in K+-activated intact preparations. In control veins a reduction in extracellular Ca2+ was associated with a significant reduction in both isometric force and maximal shortening velocity (Vmax). In hypertrophic veins the decreased isometric force at maximal activation was associated with a low Vmax. A comparison between hypertrophic and submaximally stimulated control vessels showed corresponding Vmax and isometric force values. We conclude that the low isometric force of hypertrophic veins is associated with a lower rate of cross-bridge turnover. This could be an effect of alterations in the activation mechanisms or in the intrinsic properties of the contractile system itself.


Pathogenesis of Atypical Hemolytic Uremic Syndrome.
Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy (TMA) defined by thrombocytopenia, microangiopathic hemolytic anemia, and renal failure. aHUS is caused by uncontrolled complement activation in the alternative pathway (AP). A variety of genetic defects in complement-related factors or acquired autoantibodies to the complement regulators have been found in 50 to 60% of all cases. Recently, however, the classification and diagnosis of aHUS are becoming more complicated. One reason for this is that some factors, which have not been regarded as complement-related factors, have been reported as predisposing factors for phenotypic aHUS. Given that genotype is highly correlated with the phenotype of aHUS, careful analysis of underlying genetic abnormalities or acquired factors is needed to predict the prognosis or to decide an optimal treatment for the disease. Another reason is that complement dysregulation in the AP have also been found in a part of other types of TMA such as transplantation-related TMA and pregnancy-related complication. Based on these findings, it is now time to redefine aHUS according to the genetic or acquired background of abnormalities.Here, we review the pathogeneses and the corresponding phenotypes of aHUS and complement-related TMAs.


Family history of psoriasis, stressful life events, and recent infectious disease are risk factors for a first episode of acute guttate psoriasis: results of a case-control study.
The association of guttate psoriasis with streptococcal pharyngitis is well accepted. The association of other risk factors is less well defined. We attempted to provide an estimate of the risk for guttate psoriasis associated with a recent infectious disease and to explore other potential risk factors, including family history of psoriasis and psychologic stress. This was a case-control study. Cases were patients with a first diagnosis ever of acute guttate psoriasis, made by a dermatologist. Controls were patients newly diagnosed as having dermatologic conditions other than psoriasis and seen in the same outpatient services as the cases. Inclusion of cases and controls was restricted to patients older than 16 years. The Holmes and Rahe Social Readjustment Rating Scale was used to assess stressful life events during the 6 months before diagnosis. A total of 73 cases (median age, 26 years) and 430 controls (median age, 28 years) were included in the analysis. A family history of psoriasis was strongly associated with guttate psoriasis, the multivariate odds ratio being 7.0 (95% confidence interval, 3.7-13.5) for subjects who reported a history of the disease in parents or siblings. Stressful life events were also associated with guttate psoriasis. The multivariate odds ratio was 1.7 (95% confidence interval, 0.8-3.6) for subjects scoring 41 to 100 and 2.6 (95% confidence interval, 1.3-5.2) for those scoring more than 100 on the Holmes and Rahe Scale. The risk increased with the reported history of any infectious disease. The analysis of specific diagnoses documented a high and significant association with acute pharyngitis, the adjusted odds ratio being 7.8 (95% confidence interval, 1.8-32.5). The study confirmed that recent pharyngeal infection is a risk factor for guttate psoriasis. It also documented the strong association between guttate psoriasis and a family history of psoriasis. Finally, the study added evidence to the belief that stressful life events may represent risk factors for the onset of psoriasis. By relying on the clinical diagnosis we possibly underestimate the association of guttate psoriasis with infection.


From ICU to hospital-wide: extending central line associated bacteraemia (CLAB) prevention.
To decrease hospital-wide central line associated bacteraemia (CLAB) by spreading the prevention programme beyond the intensive care unit (ICU) in a secondary care hospital in Auckland, New Zealand. Over 15 months, four general surgical wards, five inpatient units, and surgical theatres adopted the quality improvement initiative, and were followed for a further 15 months. The initiative included central line insertion and maintenance checklists, a central line insertion pack, training in central line care, and a dedicated database. In addition, a checklist to assess the readiness of each new area was developed; data collection and analysis processes embedded, with rapid feedback to staff and in-depth review of all CLAB events. Compliance measures improved significantly (compliance with insertion increased from a mean of 84% to 92% p=0.001; maintenance from 64% to 85%, p=0.002). The absolute numbers of CLAB fell hospital-wide from a mean of 2.3/month to 0.56/month. The rate of CLAB hospital-wide decreased from 7.04/1,000 line days to 1.37/1,000. We have demonstrated that the CLAB prevention work proven effective in the ICU can be successfully adapted and expanded to the rest of the hospital. As central lines are increasingly inserted in units outside the ICU, and maintained in general wards, this work provides some useful insights into tackling this larger problem.


The cysteine-rich domain of human proteins, neuronal chimaerin, protein kinase C and diacylglycerol kinase binds zinc. Evidence for the involvement of a zinc-dependent structure in phorbol ester binding.
Diacylglycerol (DG) and its analogue phorbol 12-myristate 13-acetate (PMA) activate the ubiquitous phospholipid/Ca2(+)-dependent protein kinase, protein kinase C (PKC), and cause it to become tightly associated with membranes. DG is produced transiently as it is rapidly metabolized by DG kinase (DGK) to phosphatidic acid. Phorbol esters such as PMA are not metabolized and induced a prolonged membrane association of PKC. Until recently, PKC was the only known phorbol ester receptor. We have shown that a novel brain-specific cDNA, neuronal chimaerin (NC), expressed in Escherichia coli, binds phorbol ester with high affinity, stereospecificity and a phospholipid requirement [Ahmed, Kozma, Monfries, Hall, Lim, Smith & Lim (1990) Biochem. J. 272, 767-773]. The proteins NC, PKC and DGK possess a cysteine-rich domain with the motif HX11/12CX2CXnCX2CX4HX2CX6/7C (where n varies between 12 and 14). The partial motif, CX2CX13CX2C, is present in a number of transcription factors including the steroid hormone receptors and the yeast protein, GAL4, in which zinc plays a structural role of co-ordinating cysteine residues and is essential for DNA binding (protein-nucleic acid interactions). The cysteine-rich domain of NC and PKC is required for phospholipid-dependent phorbol is required for phospholipid-dependent phorbol ester binding, suggesting an involvement of this domain in protein-lipid interactions. We have expressed recombinant NC, PKC and DGK glutathione S-transferase and TrpE fusion proteins in E. coli to investigate the relationship between the cysteine-rich motif, HX11/12CX2CX10-14CX2CX4HX2CX6/7C, zinc and phorbol ester binding. The cysteine-rich domain of NC, PKC and DGK bound 65Zn2+ but only NC and PKC bound [3H]phorbol 12,13-dibutyrate. When NC and PKC were subjected to treatments known to remove metal ions from GAL4 and the human glucocorticoid receptor, phorbol ester binding was inhibited. These data provide evidence for the role of a zinc-dependent structure in phorbol ester binding.


Molecular Characterization and Phylogenetic Analysis of Hoplolaimus stephanus.
Three Hoplolaimus stephanus populations were characterized morphologically, both by morphometrics and by SEM observations. These populations were used to develop a rapid and accurate molecular identification method for the species, which is useful because of the high level of morphological similarity between H. stephanus and H. galeatus. Species-specific primers for H. stephanus, amplifying a distinct fragment (260 bp) of the nuclear ribosomal internal transcribed spacer1 (ITS1), can be used in multiplex PCR along with previously developed primers for other common Hoplolaimus species. We also infer phylogenetic relationships among H. stephanus, the closely-related H. galeatus, and several other Hoplolaimus species, using sequences of the actin gene, ITS1 and LSUD.


Clinical review: blood purification for sepsis.
Sepsis is the primary cause of death in the intensive care unit. Extracorporeal blood purification therapies have been proposed for patients with sepsis in order to improve outcomes since these therapies can alter the host inflammatory response by non-selective removal of inflammatory mediators or bacterial products or both. Recent technological progress has increased the number of techniques available for blood purification and their performance. In this overview, we report on the latest advances in blood purification for sepsis and how they relate to current concepts of disease, and we review the current evidence for high-volume hemofiltration, cascade hemofiltration, hemoadsorption, coupled plasma filtration adsorption, high-adsorption hemofiltration, and high-cutoff hemofiltration/hemodialysis. Promising results have been reported with all of these blood purification therapies, showing that they are well tolerated, effective in clearing inflammatory mediators or bacterial toxins (or both) from the plasma, and efficacious for improvement of various physiologic outcomes (for example, hemodynamics and oxygenation). However, numerous questions, including the timing, duration, and frequency of these therapies in the clinical setting, remain unanswered. Large multicenter trials evaluating the ability of these therapies to improve clinical outcomes (that is, mortality or organ failure), rather than surrogate markers such as plasma mediator clearance or transient improvement in physiologic variables, are required to define the precise role of blood purification in the management of sepsis.


Metastatic disease of the femur: surgical treatment.
The senior author's 12-year consecutive series of surgery for metastatic disease of the femur was reviewed. Treatment of 97 impending pathologic fractures yielded better results than treatment of 85 completed pathologic fractures with less average blood loss (438 cc versus 636 cc), shorter hospital stay (7 days versus 11 days), greater likelihood of discharge to home as opposed to an extended care facility (79% versus 56%) and greater likelihood of resuming support-free ambulation (35% versus 12%). Internal stabilization with a reconstruction-type intramedullary nail provided satisfactory pain relief and functional preservation for most patients with impending pathologic femur fractures (69 of 97, 71%), although alternate forms of internal fixation (21 of 97, 22%) or cemented arthroplasty (seven of 97, 7%) were used successfully. Completed pathologic fractures were more likely to require some form of arthroplasty (47 of 85, 55%), although reconstruction-type nails (20 of 85, 24%), and other internal fixation techniques (18 of 85, 21%) also were used. Modular oncology-type arthroplasty systems offered a viable salvage option in both groups. In the absence of conflicting goals or contraindications, internal stabilization of impending pathologic fractures before the completion of the fracture seems to be reasonable and appropriate.


Fractionated stereotactic radiation therapy for vestibular schwannomas: Dosimetric factors predictive of hearing outcomes.
To determine dosimetric factors predictive of hearing loss in vestibular schwannoma (VS) patients treated with definitive fractionated stereotactic radiation therapy (FSRT), and to report tumor control, serviceable hearing preservation, and cranial nerve toxicities. We identified 45 patients (29 men and 16 women) with unilateral sporadic VS, who underwent definitive FSRT. All patients had serviceable hearing prior to treatment, defined as Gardner-Robertson Class 1 or 2. All patients underwent an audiogram before the start of treatment and serial audiometric assessments after treatment. The median audiometric follow-up time was 35.2 months (range, 5.0-89.7 months). Patients underwent a median of 4.5 (range, 1-9) posttreatment audiograms. The ipsilateral cochlea was contoured retrospectively, and dosimetric data were used to determine factors predictive of losing serviceable hearing. The median clinical follow-up time was 29.9 months (range, 1.5-83.6 months). At the time of the last audiometric follow-up, 62% of patients retained serviceable hearing. The actuarial 1-, 2-, and 3-year serviceable hearing preservation rates were 83%, 75%, and 51%, respectively. The estimated median time to loss of serviceable hearing was 42.2 months. On multivariate analysis, cochlear volume <0.15 mL (hazard ratio, 2.849; 95% confidence interval, 1.116-7.270; P = .029) and mean cochlear dose <4000 cGy (hazard ratio, 3.178; 95% confidence interval, 1.116-9.049; P = .030) were statistically significant variables associated with serviceable hearing preservation. The actuarial tumor control was 100%. Three of 39 patients (8%) developed hemifacial spasm after FSRT (House-Brackmann Grade 3), 2 of which completely resolved. No patients experienced deterioration in trigeminal nerve function after FSRT. Fractionated stereotactic radiation therapy can provide excellent tumor control with acceptable clinical outcomes. The mean dose to the cochlea is highly predictive of the probability of maintaining serviceable hearing after FSRT.


The nonadherence and risk factors of eradication failure by sequential therapy as first-line anti-Helicobacter pylori treatment in real-world clinical practice.
The eradication rates of sequential therapy are high in clinical trials; however, the adherence for follow-up or the patient population in a real-world setting might be different from those in trails. This study investigates the effectiveness of sequential therapy in a real-world setting and the factors that lead to treatment failure. In this retrospective study, patients receiving sequential therapy as a first-line anti-Helicobacter pylori (H. pylori) treatment in a real-world setting were reviewed. The age adjusted Charlson Comorbidity Index (age-CCI) and baseline variety of medications were reviewed to determine factors correlated with nonadherence for post-treatment testing and H. pylori eradication failure. A total of 1053 patients were reviewed. A total of 579 patients receiving sequential therapy were included in the analyses. Among them, 462 received post-treatment testing and were placed into the follow-up group. Thus, the post-treatment testing rate was 79.8%. Stroke was an independent factor of nonadherence for post-treatment testing. In the follow-up group, the eradication failure rate was 8.2%. Female sex (odds ratio [OR] 2.41 [95% CI 1.16-5.03], p = 0.02) and age-CCI ≥2 (OR 3.16 [1.05-9.48], p = 0.04) were independent factors of H. pylori eradication failure. The eradication failure rates were 14.4%, 7.8%, 7.1%, and 3.1% for the females with age-CCI ≥2, females with age-CCI <2, males with age-CCI ≥2, and males with age-CCI <2 subgroups, respectively (p = 0.027). In a real-world setting, the adherence rate of post-treatment testing for sequential therapy as a first-line anti-H. pylori treatment was found to be suboptimal. Female sex and age-CCI ≥2 were independent factors of eradication failure.


Inhibition of hematopoietic protein tyrosine phosphatase augments and prolongs ERK1/2 and p38 activation.
The hematopoietic protein tyrosine phosphatase (HePTP) is implicated in the development of blood cancers through its ability to negatively regulate the mitogen-activated protein kinases (MAPKs) ERK1/2 and p38. Small-molecule modulators of HePTP activity may become valuable in treating hematopoietic malignancies such as T cell acute lymphoblastic leukemia (T-ALL) and acute myelogenous leukemia (AML). Moreover, such compounds will further elucidate the regulation of MAPKs in hematopoietic cells. Although transient activation of MAPKs is crucial for growth and proliferation, prolonged activation of these important signaling molecules induces differentiation, cell cycle arrest, cell senescence, and apoptosis. Specific HePTP inhibitors may promote the latter and thereby may halt the growth of cancer cells. Here, we report the development of a small molecule that augments ERK1/2 and p38 activation in human T cells, specifically by inhibiting HePTP. Structure-activity relationship analysis, in silico docking studies, and mutagenesis experiments reveal how the inhibitor achieves selectivity for HePTP over related phosphatases by interacting with unique amino acid residues in the periphery of the highly conserved catalytic pocket. Importantly, we utilize this compound to show that pharmacological inhibition of HePTP not only augments but also prolongs activation of ERK1/2 and, especially, p38. Moreover, we present similar effects in leukocytes from mice intraperitoneally injected with the inhibitor at doses as low as 3 mg/kg. Our results warrant future studies with this probe compound that may establish HePTP as a new drug target for acute leukemic conditions.


Decoupling between leaf nitrogen and radiation use efficiency in vegetative and early reproductive stages in high-yielding soybean.
Ontogenic changes in soybean radiation use efficiency (RUE) have been attributed to variation in specific leaf nitrogen (SLN) based only on data collected during seed filling. We evaluated this hypothesis using data on leaf area, absorbed radiation (ARAD), aboveground dry matter (ADM), and plant nitrogen (N) concentration collected during the entire crop season from seven field experiments conducted in a stress-free environment. Each experiment included a full-N treatment that received ample N fertilizer and a zero-N treatment that relied on N fixation and soil N mineralization. We estimated RUE based on changes in ADM between sampling times and associated ARAD, accounting for changes in biomass composition. The RUE and SLN exhibited different seasonal patterns: a bell-shaped pattern with a peak around the beginning of seed filling, and a convex pattern followed by an abrupt decline during late seed filling, respectively. Changes in SLN explained the decline in RUE during seed filling but failed to predict changes in RUE in earlier stages and underestimated the maximum RUE observed during pod setting. Comparison between observed and simulated RUE using a process-based crop simulation model revealed similar discrepancies. The decoupling between RUE and SLN during early crop stages suggests that leaf N is above that needed to maximize crop growth but may play a role in storing N that can be used in later reproductive stages to meet the large seed N demand associated with high-yielding crops.


Clinical impact of suicide gene therapy in allogeneic hematopoietic stem cell transplantation.
Allogeneic hematopoietic stem cell transplantation (allo-SCT) from an HLA-matched related or unrelated donor is a curative option for patients with high-risk hematological diseases. In the absence of a matched donor, patients have been offered investigational transplantation strategies such as umbilical cord blood SCT or family haploidentical SCT. Besides the activity of the conditioning regimen, most of the antileukemic potential of allo-SCT relies on alloreactivity, promoted by donor lymphocytes reacting against patient-specific antigens, such as minor and major histocompatibility antigens, ultimately translating into cancer immunotherapy. Unfortunately, alloreactivity is also responsible for the most serious and frequent complication of allo-SCT: graft-versus-host-disease (GvHD). The risk of GvHD increases with the level of HLA disparity between host and donor, and leads to impaired quality of life and reduced survival expectancy, particularly among patients receiving transplants from HLA-mismatched donors. Gene transfer technologies are promising tools to manipulate donor T cell immunity to enforce the graft-versus-tumor effect, to promote functional immune reconstitution (graft vs. infection), and to prevent or control GvHD. To this purpose, several cell and gene transfer approaches have been investigated at the preclinical level, and are being implemented in clinical trials. Suicide gene therapy is to date the most extensive clinical application of T cell-based gene therapy. In several phase I-II clinical studies conducted worldwide this approach proved highly feasible, safe, and effective in promoting a dynamic and patient-specific modulation of alloreactivity. This review focuses on this approach.


The stepped-care approach to the treatment of hypertension in Black patients.
The Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (USA) has recommended the stepped-care approach to the treatment of hypertension. It should be modified in Black hypertensive patients on a cost-effective basis. This is based on the following reasons: (i) beta-blockers are not as effective as diuretics in the treatment of Black hypertensive patients; (ii) Black hypertensive patients probably respond better to vasodilators; and (iii) the cost of therapy on a long-term basis in developing countries should be considered, and drugs such as reserpine will continue to play a valuable role.


The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash.
Recent studies surprisingly show that dietary inorganic nitrate, abundant in vegetables, can be metabolized in vivo to form nitrite and then bioactive nitric oxide. A reduction in blood pressure was recently noted in healthy volunteers after dietary supplementation with nitrate; an effect consistent with formation of vasodilatory nitric oxide. Oral bacteria have been suggested to play a role in bioactivation of nitrate by first reducing it to the more reactive anion nitrite. In a cross-over designed study in seven healthy volunteers we examined the effects of a commercially available chlorhexidine-containing antibacterial mouthwash on salivary and plasma levels of nitrite measured after an oral intake of sodium nitrate (10mg/kg dissolved in water). In the control situation the salivary and plasma levels of nitrate and nitrite increased greatly after the nitrate load. Rinsing the mouth with the antibacterial mouthwash prior to the nitrate load had no effect on nitrate accumulation in saliva or plasma but abolished its conversion to nitrite in saliva and markedly attenuated the rise in plasma nitrite. We conclude that the acute increase in plasma nitrite seen after a nitrate load is critically dependent on nitrate reduction in the oral cavity by commensal bacteria. The removal of these bacteria with an antibacterial mouthwash will very likely attenuate the NO-dependent biological effects of dietary nitrate.


Lung cancer and internal lung doses among plutonium workers at the Rocky Flats Plant: a case-control study.
The authors conducted a nested case-control study of the association between lung cancer mortality and cumulative internal lung doses among a cohort of workers employed at the Rocky Flats Plant in Colorado from 1951 to 1989. Cases (n = 180) were individually matched with controls (n = 720) on age, sex, and birth year. Annual doses to the lung from plutonium, americium, and uranium isotopes were calculated for each worker with an internal dosimetry model. Lung cancer risk was elevated among workers with cumulative internal lung doses of more than 400 mSv in several different analytical models. The dose-response relation was not consistent at high doses. Restricting analysis to those employed for 15-25 years produced a statistically significant linear trend with dose (chi-square = 67.2, p < 0.001), suggesting a strong healthy worker survivor effect. The association between age at first internal lung dose and lung cancer mortality was statistically significant (odds ratio = 1.05, 95% confidence interval: 1.01, 1.10). No associations were found between lung cancer mortality and cumulative external penetrating radiation dose or cumulative exposures to asbestos, beryllium, hexavalent chromium, or nickel.


Leaders in cell adhesion: an interview with Richard Hynes, pioneer of cell-matrix interactions. Interview by Pamela Cowin.
On a recent visit Richard O Hynes, FRS, HHMI, Daniel K. Ludwig Professor for Cancer Research at the Koch Institute for Integrative Cancer Research, MIT, graciously agreed to be interviewed in person for the first in Cell Communication and Adhesion's series on "Leaders in Cell Adhesion". In this interview we discussed three things: 1) the early role of family, mentors, and luck on his career path; 2) his major discoveries of fibronectin, integrins and the evolution of extracellular matrix proteins; and 3) his role in, and thoughts on, current science policy. This interview reveals his characteristic calmness and infectious optimism, his spontaneous and down to earth sense of humor, and his great ability to place scientific questions in perspective. The interview, carried out on April 30(th) 2013 is reported here verbatim with only minor editing for clarity.


Quantitative nasal culture: a tool in antibiotic research.
The use of the quantitative nasal culture was investigated as a means of evaluation of new antimicrobial drugs in man. Cyclacillin was somewhat more active in vitro than penicillin G against penicillin G-resistant organisms. Cyclacillin was highly effective in suppressing staphylococci susceptible to penicillin G in nasal carriers but did not suppress staphylococci resistant to penicillin G. Although in previous studies by others cyclacillin was effective in treating mice infected with penicillin G-resistant staphylococci, in the present studies cyclacillin was not effective in suppressing nasal penicillin G-resistant staphylococci in man at doses which markedly suppressed penicillin G-sensitive organisms.


[Memory tests in healthy elderly: age factors and norms].
The study aimed to assess the strength of age effects on both standard laboratory and ecological memory tests and the psychometric qualities of these tests. Furthermore, norm data are constructed. Memory performance was assessed in a random group of older adults (mean age 62 years, range 46-89) and a group of older adults having memory complaints who applied for memory training (mean age 63 years, range 45-85). Age effects were found on almost all memory tests, whether artificial laboratory or more ecological tests were used. Age effects remained generally present after correction for educational level. Retest reliabilities of the ecological memory tests did not differ systematically from those of standard laboratory tests. However, not all tests showed satisfactory retest reliabilities, this was even true for tests often used in clinical settings. For tests with retest reliabilities above r = .65 norms corrected for age and educational level were provided. The group of older adults having memory complaints performed on average better than the random group of older adults from the population. In the first group, higher performance thresholds should be employed in assessing whether memory performance is deviant.


Outcomes of children with abdominal compartment syndrome.
Abdominal compartment syndrome (ACS) is a problem across all critical care scenarios and is associated with a high mortality. It has not been well described in pediatric populations. To describe the occurrence of ACS in a subset of critically ill pediatric patients and determine its effects on mortality and length of pediatric intensive care stay (PICU LOS). We also aimed to find predictors of mortality and development of ACS. 25 bed tertiary pediatric intensive care unit. PATIENTS less than 50 kg on mechanical ventilation and a urethral catheter. Intra-abdominal pressures (IAP) were monitored using the intra-vesical technique. ACS was defined as IAP of >12mmHg associated with new organ dysfunction or failure. Demographics, physiologic measures of organ dysfunction, PICU LOS and mortality were monitored. 14 (4.7%) of 294 eligible patients had ACS. Mortality was 50% among those with ACS versus 8.2% without (p<.001). PICU LOS stay did not differ between groups. No difference in mortality or PICU LOS was seen in primary versus secondary ACS or in patients who underwent abdominal decompression compared to those without decompression. IAP and ACS were independent predictors of mortality (odds ratio 1.53, 95% CI, 1.17 - 1.99 and 9.09, 95% CI, 1.07 - 76.84) respectively. IAP and a PRISM score of ≥17 were predictive of developing ACS. ACS is a clinical problem that increases the risk of mortality in critically ill children. IAP and PRISM scores may help identify children likely to develop ACS.


Gender specificity of resting anterior electroencephalographic asymmetry and defensiveness in the elderly.
It has been reported that defensiveness in women is associated with relative left-frontal electroencephalogram (EEG) activation, while defensiveness in men is associated with relative right-frontal EEG activation. The present study examined whether this result generalized to men and women between the ages of 58 and 70. The Marlowe-Crowne Social Desirability Scale (MCSD) and EEG testing were used to examine relationships between gender, defensiveness, and anterior asymmetry. Men (n = 18) and women (n = 54) between the ages of 58 and 70 (mean age = 64.22, standard deviation = 3.003) were recruited from Tucson and surrounding areas of Pima County, Arizona. They were selected from among participants in an integrative health sciences study of aging that took place between 1991 and 1993. Subjects were divided into high-defensive and low-defensive groups based on a median split on the MCSD. EEGs were recorded from 19 channels (standard 10-20 montage), referenced to linked ears, and digitalized on-line at 128 Hz (band pass 2-32 Hz) during consecutive 60-second eyes-open and eyes-closed baselines. Two-second epochs containing bioelectric artifacts > 50 microvolts were eliminated from analyses. Average alpha (8-13 Hz) power (microV2)) was computed by Fast Fourier Transform and natural log (ln) transformed for normalization. Asymmetry scores were computed (log[right]-log[left]) for F4-F3, Fp2-Fp1, F8-F7, C4-C3, T4-T3, T6-T5, P4-P3, and O2-O1 for aggregated eyes-open and eyes-closed baselines. R-L asymmetry scores were analyzed for the aggregate frontal lead pairs, as well as for each pair separately. Findings were similar to those previously reported in that the direction of the relationship in men and women was the same. The results differed in that we found left-frontal activation in low-defensive men, whereas the previous study found right-frontal activation in high-defensive men. Furthermore, although in the same direction, the relationship for women was nonsignificant. These differences may have been due to the age of the participants, a lax impedence criterion, or the use of the MCSD rather than the L scale of the Eysenck Personality Questionnaire, as in the earlier study. Nevertheless, the findings suggest that gender differences in the relationship between resting anterior EEG asymmetry and defensiveness may persist throughout the life span.


Advanced diffuse histiocytic lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) without maintenance therapy.
Thirty-one patients with stage III or IV diffuse histiocytic lymphoma were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) at 3- or 4-week intervals for at least six cycles or until two cycles after complete remission (CR) was achieved. At the completion of therapy, CR was documented by examination of sites known to previously contain disease. After documentation of CR, patients were followed without maintenance therapy. Fifteen patients (48%) achieved CR, four (13%) had equivocal lymphangiograms on restaging but were otherwise free of disease, two (6%) died of unrelated causes during therapy, two (6%) developed central nervous system lymphoma during therapy and despite peripheral remission eventually died of the CNS disease, and eight (26%) had either partial or no response. Twelve of the 15 patients achieving CR remain disease-free with no therapy for 9+ to 43+ months. Three patients relapsed at 3, 4, and 23 months after discontinuation of therapy. Three of the four patients with equivocal restaging lymphangiograms remain without progressive disease with no therapy for 10+ months. The projected median survival time for all patients is 41 months. The risks of long-term (maintenance) chemotherapy are considerable and include the induction of acute nonlymphoblastic leukemia. CHOP without maintenance therapy is able to induce long-term disease-free survival (and probable cure) in a significant number of patients with advanced diffuse histiocytic lymphoma.


Clinical significance of uterine scar dehiscence in women with previous cesarean delivery: prevalence and independent risk factors.
To determine the prevalence and risk factors for uterine scar dehiscence in women following cesarean delivery (CD). Our computerized database was used to identify patients with recurrent CDs in the index pregnancy (1988-2002). Women with uterine dehiscence were compared to those without dehiscence. Multiple logistic regression analysis was used to determine independent risk factors for dehiscence. Of 7,833 women with at least 1 previous CD and a CD in the index pregnancy, 81 (1.03%) had uterine scar dehiscence. This finding was associated with nonprogress of labor during the first stage, number of previous CDs, parity, preterm delivery and low Apgar scores at 5 minutes. For patients with only 1 previous CD, failure to progress during the first stage of labor and lower parity were associated with uterine scar dehiscence. The numbers of previous CDs, gravidity and placenta previa rate were significantly higher in the group with dehiscence who delivered preterm. Preterm delivery, nonprogress of labor during the first stage and number of previous CDs were found to be independent risk factors for uterine scar dehiscence. In contrast, parity had a protective effect against dehiscence.


Enhanced Detection of Sub-Retinal Pigment Epithelial Cell Layer Deposits in Human and Murine Tissue: Imaging Zinc as a Biomarker for Age-Related Macular Degeneration (An American Ophthalmological Society Thesis).
Understanding the apparent paradoxical role of zinc in the pathogenesis and prevention of age-related macular degeneration (AMD) has been limited by the lack of animal models for its detection in sub-retinal epithelial deposits (drusen), a definitive early hallmark of AMD. In-vitro studies using Zinpyr-1 showed drusen contained high levels of zinc, but the probe was not suitable for in-vivo studies. This study compares Zinpyr-1 to ZPP1, a new fluorescein-based probe for zinc, to assess the potential of ZPP1 for in-vivo detection of zinc in drusen. Flat mounts of human sub-RPE tissue using the probes were analyzed by fluorescence and confocal microscopy. Flat mounts of sub-RPE tissue from mice deficient in superoxide dismutase isoform-1 (CuZn-SOD-KO) or isoform-2 (Mn-SOD-RPE-KO) were analyzed with sub-RPE deposits confirmed by histology. Drusen are detected in greater numbers and intensity with ZPP1 compared to Zinpyr-1. Using ZPP1, drusen was detected in a sample from a 46-year old human donor without ocular history, suggesting that ZPP1 might be sensitive enough to detect drusen at an early stage. With CuZn-SOD KO mice, ZPP1 detected sub-RPE deposits at 10 months of age, whereas Zinpyr-1 required 14 months. Detection of sub-RPE deposits by ZPP1 was greatly enhanced compared to Zinpyr-1. This enhanced sensitivity will allow for more insightful analysis of zinc in AMD using human specimens and mouse models. This could result in the development of a sensitive in-vivo probe to enhance research on the role zinc in drusen formation and the early clinical diagnosis of AMD.


Retention of small charged impurities during ultrafiltration.
Ultrafiltration is used to remove small impurities from a variety of processing streams. However, the clearance of small charged impurities may be inadequate due to electrostatic exclusion by the charged ultrafiltration membranes, an effect that has been largely unappreciated. Ultrafiltration experiments were performed to evaluate the transmission of several model impurities with different electrical charge through ultrafiltration membranes having different surface charge characteristics. Highly charged impurities are strongly rejected by charged cellulose and polyethersulfone membranes even though these solutes are much smaller than the membrane pore size. These effects could be eliminated by using high ionic strength solutions to shield the electrostatic interactions. The sieving data are in good agreement with model calculations based on the partitioning of charged spheres into charged cylindrical pores. Guidelines are developed for estimating conditions needed to obtain effective removal of small charged impurities through charged ultrafiltration membranes.


Egg size and asymmetric sibling rivalry in red-winged blackbirds.
How big to make an egg is a life history decision that in birds is made coincident with a series of other similar decisions (how many eggs to have, whether to fortify them with maternally derived hormones or immune system boosters, whether to hatch the eggs synchronously or asynchronously). Though within-population variation in egg size in birds has been well studied, its adaptive significance, if any, is unclear. Here we examine within-population variation in egg size in relation to asymmetric sibling rivalry in a 17-year study of red-winged blackbirds (Agelaius phoeniceus), an altricial songbird. Egg mass showed a twofold range of variation, with roughly 80% of the variation occurring across clutches. By commencing incubation before the clutch is complete, mothers create advantaged core and disadvantaged marginal elements within their brood. Previous work on this system has shown that sibling competition is asymmetric, and that core offspring enjoy priority access to food, and as a consequence show higher growth and lower mortality than marginal offspring. Here we examine the effect of initial egg size on nestling growth and survival in relation to these competitive asymmetries. Egg mass was strongly linked to hatchling mass, and remained significantly related to the mass of both core and marginal nestlings; the effect of egg size was stronger for core offspring early in the nestling period, but the disparity between core and marginal nestlings narrowed as they approached fledging age, and slower growing marginals fell victim to brood reduction. The effect of egg mass on survival differed dramatically between core and marginal nestlings. Egg mass was significantly related to the survival of marginal but not core nestlings: below average egg mass was associated primarily with very early mortality. Asymmetric sibling competition is clearly a strong determinant of the consequences of egg size variation.


[Analysis of vitamin and mineral sufficiency in children using data of consumption with food and urinary excretion].
It has been shown that vitamin C and B2, calcium and phosphorus daily intake strongly correlated with their urinary excretion in children 5-8 years old (Moscow) from the decreased bone mineral density risk group. Hour urinary calcium, phosphorus, creatinine excretion values for adequately supplied children has been determined. Vitamin and mineral status evaluation by means of estimation of vitamins and minerals consumption and urinary level (except vitamin B2) give relatively coincided results. Difference between these methods of nutritive status assessment attains 8-25 per cent. Thus these methods are substituted for group nutritive status evaluation.


Estimating potential emerald ash borer (Coleoptera: Buprestidae) populations using ash inventory data.
Emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), a phloem-feeding pest native to Asia, was identified in June 2002 as the cause of widespread ash (Fraxinus spp.), mortality in southeastern Michigan and Windsor, Ontario, Canada. Localized populations of A. planipennis have since been found across lower Michigan and in areas of Ohio, Indiana, Illinois, Maryland, and Ontario. Officials working to contain A. planipennis and managers of forestlands near A. planipennis infestations must be able to compare alternative strategies to allocate limited funds efficiently and effectively. Empirical data from a total of 148 green ash, Fraxinus pennsylvanica Marsh., and white ash, Fraxinus americana L., trees were used to develop models to estimate surface area of the trunk and branches by using tree diameter at breast height (dbh). Data collected from 71 additional F. pennsylvanica and F. americana trees killed by A. planipennis showed that on average, 88.9 +/- 4.6 beetles developed and emerged per m2 of surface area. Models were applied to ash inventory data collected at two outlier sites to estimate potential production of A. planipennis beetles at each site. Large trees of merchantable size (dbh > or = 26 cm) accounted for roughly 6% of all ash trees at the two sites, but they could have contributed 55-65% of the total A. planipennis production at both sites. In contrast, 75- 80% of the ash trees at the outlier sites were < or =13 cm dbh, but these small trees could have contributed only < or =12% of the potential A. planipennis production at both sites. Our results, in combination with inventory data, can be used by regulatory officials and resource managers to estimate potential A. planipennis production and to compare options for reducing A. planipennis density and slowing the rate of spread for any area of interest.


Efficacy of air cleaning systems in controlling indoor radon decay products.
Field evaluations of an air filtration system and an electronic air cleaner to remove Rn decay products were performed in a single-family house located in the Northford, CT area. Field measurements included the Rn concentration, particle number concentration, and concentration and activity size distribution of Rn decay products. A semi-continuous screen diffusion battery system with six parallel sampler/detector units was used to determine the concentrations and size distributions of the Rn decay products. Indoor particles were generated by common activities such as vacuuming, washing and drying clothes, opening the outside door, and cooking. Influences on the size distributions over the size range from 0.5 nm to 500 nm of Rn decay products were investigated in the domestic environment. The effect of the air cleaners was to decrease the concentration of the decay products and to reduce the equilibrium fraction. For the filtration system in particular, the activity fractions in the smallest size range were increased. However, the overall effect of the air cleaners was to reduce the median dose. The filtration unit was found to be more effective than the electronic air cleaner.


HIV-associated lipodystrophy: a review of underlying mechanisms and therapeutic options.
Lipodystrophy (LD) is a common adverse effect of HIV treatment with highly active antiretroviral therapy, which comprises morphological and metabolic changes. The underlying mechanisms for LD are thought to be due to mitochondrial toxicity and insulin resistance, which results from derangements in levels of adipose tissue-derived proteins (adipocytokines) that are actively involved in energy homeostasis. Several management strategies for combating this syndrome are available, but they all have limitations. They include: switching from thymidine analogues to tenofovir or abacavir in lipoatrophy, or switching from protease inhibitors associated with hyperlipidaemia to a protease-sparing option; injection into the face with either biodegradable fillers such as poly-L-lactic acid and hyaluronic acid (a temporary measure requiring re-treatment) or permanent fillers such as bio-alcamid (with the risk of foreign body reaction or granuloma formation); and structured treatment interruption with the risk of loss of virological control and disease progression. There is therefore a need to explore alternative therapeutic options. Some new approaches including adipocytokines, uridine supplementation, glitazones, growth hormone (or growth hormone-releasing hormone analogues), metformin and statins (used alone or in combination) merit further investigation.


Changes in beta-lactoglobulin conformation at the oil/water interface of emulsions studied by synchrotron radiation circular dichroism spectroscopy.
The structure of proteins at interfaces is a key factor determining the stability as well as organoleptic properties of food emulsions. While it is widely believed that proteins undergo conformational changes at interfaces, the measurement of these structural changes remains a significant challenge. In this study, the conformational changes of beta-lactoglobulin (beta-Lg) upon adsorption to the interface of hexadecane oil-in-water emulsions were investigated using synchrotron radiation circular dichroism (SRCD) spectroscopy. Far-UV SRCD spectra showed that adsorption of beta-Lg to the O/W interface caused a significant increase in non-native alpha-helix structure, accompanied by a concomitant loss of beta-sheet structure. Near-UV SRCD spectra revealed that a considerable disruption of beta-Lg tertiary structure occurred upon adsorption. Moreover, heat-induced changes to the non-native beta-Lg conformation at the oil/water interface were very small compared to the dramatic loss of beta-Lg secondary structure that occurred during heating in solution, suggesting that the interface has a stabilizing effect on the structure of non-native beta-Lg. Overall, our findings provide insight into the conformational behavior of proteins at oil/water interfaces and demonstrate the applicability of SRCD spectroscopy for measuring the conformation of adsorbed proteins in optically turbid emulsions.


Locus co-occupancy, nucleosome positioning, and H3K4me1 regulate the functionality of FOXA2-, HNF4A-, and PDX1-bound loci in islets and liver.
The liver and pancreas share a common origin and coexpress several transcription factors. To gain insight into the transcriptional networks regulating the function of these tissues, we globally identify binding sites for FOXA2 in adult mouse islets and liver, PDX1 in islets, and HNF4A in liver. Because most eukaryotic transcription factors bind thousands of loci, many of which are thought to be inactive, methods that can discriminate functionally active binding events are essential for the interpretation of genome-wide transcription factor binding data. To develop such a method, we also generated genome-wide H3K4me1 and H3K4me3 localization data in these tissues. By analyzing our binding and histone methylation data in combination with comprehensive gene expression data, we show that H3K4me1 enrichment profiles discriminate transcription factor occupied loci into three classes: those that are functionally active, those that are poised for activation, and those that reflect pioneer-like transcription factor activity. Furthermore, we demonstrate that the regulated presence of H3K4me1-marked nucleosomes at transcription factor occupied promoters and enhancers controls their activity, implicating both tissue-specific transcription factor binding and nucleosome remodeling complex recruitment in determining tissue-specific gene expression. Finally, we apply these approaches to generate novel insights into how FOXA2, PDX1, and HNF4A cooperate to drive islet- and liver-specific gene expression.


Increasing the productivity of shallot planting and its impact on the agricultural market, West Java.
The main objective of this study is to increase the productivity of shallot planting and its impact on the agricultural market. This study analyzes the transmission of shallot prices at the Caringin Main Market (wholesale) level with shallot prices at the farmer (producer) level using quantitative analysis of the Asymmetric Error Correction Model (AECM). The results showed that long-term transmission with positive ECT coefficients and negative ECT showed the same and significant positive values. Positive ECT is 0.286909 and negative ECT is 0.289266, where when there is a price deviation above and below the average balance line of onion prices at the farmer level, it takes three weeks to adjust to the balance of changes in shallot prices. The onion market at the wholesale or parent market occurs asymmetric price transmission from the wholesale price level (Caringin Main Market) to production prices (at the farmer level). A significant t-value of one percent evidences this. Asymmetric price transmission can be caused by abuse of market power.


99mTc-diphosphonates bone scintigraphy for vitality evaluation in cleft palate.
Cleft of the lip, palate and alveolus are congenital oro-maxillofacial malformation with an established treatment protocol. At present, there is great interest in the alveolar bone grafting procedures that involve the use of platelet-rich-plasma (PRP), to enhance bone formation and specifically to promote bone graft healing in head and neck tissues regeneration. The aim of this retrospective case report study was to assess the condition and viability of the standard bone grafting in association with PRP (platelet rich plasma) to enhance osteogenesis and maintain osteointegration in alveolar cleft with a follow up of eight years from the surgical procedure. The viability of bone grafts was documented by means of head bone scintigraphy (99mTc-MDP). The scintigrams revealed the decreased uptake at the cleft region and the increased uptake at the adjacent alveolus of the cleft. From these findings we suggest that platelet concentrates decrease the need of further surgical intervention in cleft palate patients. In addition, scintigraphy may be useful to evaluate postoperative bone formation in the alveolar cleft.


Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis.
Malignant glioblastomas grow very rapidly and are generally resistant to either DNA-damaging drugs or gamma-irradiation. If tumor cells could be made more susceptible to cell death with treatments, this would clearly represent a significant improvement in the success of treatment. Recently, telomerase has become a focus of interest among oncologists as a target for treating cancer cells. Telomerase elongates telomeric DNA repeats (TTAGGG)n and is important in protecting and replicating DNA. The vast majority of tumor cells, indeed, express telomerase activity whereas normal somatic cells, except for a few cells, do not. Since telomerase is essential for protecting DNA, we may be able to make tumors more sensitive to treatments with DNA-damaging drugs by inhibiting telomerase activity. In this study, we used cis-diamminedichloroplatinum (cisplatin)-sensitive U87-MG cells and cisplatin-resistant U251-MG of human malignant glioblastoma cell lines. U87-MG cells did not express telomerase activity, whereas telomerase was highly detected in U251-MG cells. Interestingly, inhibition of telomerase with an antisense telomerase expression vector not only decreased telomerase activity but also increased susceptibility to cisplatin-induced apoptotic cell death in U251-MG cells. These findings suggest that treatment with antisense telomerase may represent a new chemosensitisation for tumors resistant to anticancer drugs.


Standing MRI lesions of the distal interphalangeal joint and podotrochlear apparatus occur with a high frequency in warmblood horses.
Foot pain is a common presenting complaint in Warmblood horses. The aim of this retrospective, cross-sectional study was to determine the spectrum of foot lesions detected by magnetic resonance imaging (MRI) in Warmblood horses used for dressage, jumping, and eventing. The medical records of 550 Warmblood horses with foot pain that were scanned using standing MRI were reviewed and the following data were recorded: signalment, occupation, lameness, diagnostic analgesia, imaging results, treatments, and follow-up assessments. Associations between standing MRI lesions and chronic lameness following treatment were tested. Abnormalities of the navicular bone (409 horses, 74%), distal interphalangeal joint (362 horses, 65%), and deep digital flexor (DDF) tendon (260 horses, 47%) occurred with the highest frequency. The following abnormalities were significantly associated (P < .05) with chronic lameness following conservative therapy: moderate to severe MRI lesions in the trabecular bone of the navicular bone, mild or severe erosions of the flexor surface of the navicular bone, moderate sagittal/parasagittal DDF tendinopathies, and moderate collateral sesamoidean desmopathies. Also, identification of concurrent lesions of the DDF tendon, navicular bone, navicular bursa, and distal sesamoidean impar ligament was associated with chronic lameness after conservative therapy. Development of effective treatment options for foot lesions that respond poorly to conservative therapy is necessary.


[The role for oxidative stress in neurodegenerative diseases].
A growing body of evidence suggests oxidative stress involvement in neurodegenerative diseases; however, it remains to be determined whether oxidative stress is a cause, result, or epiphenomenon of the pathological processes. This review concerns the current issue, focusing on Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS). Several studies have indicated that oxidative stress initially occurs in the disease-specific, site-restricted sources such as amyloid-beta in the cerebral cortex of AD brain, alpha-synuclein in the brain stem of PD brain, and glutamate receptor-coupled Ca2+ channel in the motor system of ALS spinal cord. Subsequent events in the neurons common to these diseases are glutamate-induced neurotoxicity and increased cytosolic Ca2+ levels, resulting in activation of Ca2+ -dependent enzymes including NADPH oxidase, cytosolic phospholipase A2, xanthine oxidase, and neuronal nitric oxide synthase (NOS). These enzymes produce reactive oxygen and nitrogen species (ROS/RNS), which oxidatively modify nucleic acid, lipid, sugar, and protein, leading to nuclear damage, mitochondrial damage, proteasome inhibition, and endoplasmic reticulum (ER) stress. Mitochondrial damage results in both ROS leakage from the electron transport system and Ca2+ release. Nuclear damage induces p53 activation, and proteasome inhibition reduces p53 degradation. The resultant increased p53 levels in the nucleus induce Bax activation and Bcl-2 inhibition, followed by a release of cytochrome c into the cytosol that truncates procaspase-9. ER stress triggers activation of caspase-12 as well as caspase-9 via the tumor necrosis factor (TNF) receptor-associated factor-2 / apoptosis-signaling kinase-1 / c-Jun N-terminal kinase pathway. Oxidative stress also stimulates astrocytes and microglia to yield and secrete cytokines such as TNFa and FasL that cause not only neuronal caspase-8 activation but also glial inflammatory response through induction of nuclear factor-kappaB-mediated, proinflammatory gene products including cytokines, chemokines, growth factors, cell adhesion molecules, and ROS/RNS-producing enzymes. The activated caspases truncate procaspase-3 to exert classical apoptosis. Moreover, oxidative DNA damage leads to the release and nuclear truncation of mitochondrial apoptosis-inducing kinase, which triggers apoptosis-like programmed cell death via cyclophilin A. These observations could indicate crucial implications for oxidative stress in several steps of the pathomechanisms of neurodegenerative diseases.


Eye-centered representation of optic flow tuning in the ventral intraparietal area.
Reference frames are important for understanding sensory processing in the cortex. Previous work showed that vestibular heading signals in the ventral intraparietal area (VIP) are represented in body-centered coordinates. In contrast, vestibular heading tuning in the medial superior temporal area (MSTd) is approximately head centered. We considered the hypothesis that visual heading signals (from optic flow) in VIP might also be transformed into a body-centered representation, unlike visual heading tuning in MSTd, which is approximately eye centered. We distinguished among eye-centered, head-centered, and body-centered spatial reference frames by systematically varying both eye and head positions while rhesus monkeys viewed optic flow stimuli depicting various headings. We found that heading tuning of VIP neurons based on optic flow generally shifted with eye position, indicating an eye-centered spatial reference frame. This is similar to the representation of visual heading signals in MSTd, but contrasts sharply with the body-centered representation of vestibular heading signals in VIP. These findings demonstrate a clear dissociation between the spatial reference frames of visual and vestibular signals in VIP, and emphasize that frames of reference for neurons in parietal cortex can depend on the type of sensory stimulation.


ALK5 and ALK1 play antagonistic roles in transforming growth factor β-induced podosome formation in aortic endothelial cells.
Transforming growth factor β (TGF-β) and related cytokines play a central role in the vascular system. In vitro, TGF-β induces aortic endothelial cells to assemble subcellular actin-rich structures specialized for matrix degradation called podosomes. To explore further this TGF-β-specific response and determine in which context podosomes form, ALK5 and ALK1 TGF-β receptor signaling pathways were investigated in bovine aortic endothelial cells. We report that TGF-β drives podosome formation through ALK5 and the downstream effectors Smad2 and Smad3. Concurrent TGF-β-induced ALK1 signaling mitigates ALK5 responses through Smad1. ALK1 signaling induced by BMP9 also antagonizes TGF-β-induced podosome formation, but this occurs through both Smad1 and Smad5. Whereas ALK1 neutralization brings ALK5 signals to full potency for TGF-β-induced podosome formation, ALK1 depletion leads to cell disturbances not compatible with podosome assembly. Thus, ALK1 possesses passive and active modalities. Altogether, our results reveal specific features of ALK1 and ALK5 signaling with potential clinical implications.


Contamination of cultures processed with the isolator lysis-centrifugation blood culture tube.
Overall contamination (on- plus off-streak) of the Isolator (Du Pont Co.) blood culture tube (23%) was greater than that of a conventional broth blood culture bottle (0.6%) or that of a biphasic blood culture bottle (1.3%). To determine the source of this contamination, Isolator cultures of blood from 59 healthy volunteers and of sterile broth from 60 vials were made. A total of 37% of the blood cultures and 22% of the broth cultures were contaminated (P = 0.06). Staphylococcus epidermidis-contaminated cultures represented 31 and 10% of the blood and broth cultures, respectively (P = 0.06). Contamination of plates processed on a bench top, in front of horizontal laminar flow, and in a biological safety cabinet with vertical laminar flow were compared. Processing plates in a biological safety cabinet resulted in a significant reduction in the number of contaminated plates (P less than 0.05). The contamination rate for 7,874 Isolator blood cultures processed in the biological safety cabinet was significantly decreased to 6.7% on-streak (9.3% on- plus off-streak). Contamination of Isolator-processed blood cultures originated from the laboratory and the patient. The former can be reduced by inoculating plates in a vertical laminar flow biological safety cabinet and by maintaining adequate quality control of media. The latter may be unavoidable.


Sex differences in longitudinal changes of episodic memory-related brain activity and cognition in cognitively unimpaired older adults with a family history of Alzheimer's disease.
Episodic memory decline is an early symptom of Alzheimer's disease (AD) - a neurodegenerative disease that has a higher prevalence rate in older females compared to older males. However, little is known about why these sex differences in prevalence rate exist. In the current longitudinal task fMRI study, we explored whether there were sex differences in the patterns of memory decline and brain activity during object-location (spatial context) encoding and retrieval in a large sample of cognitively unimpaired older adults from the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer's Disease (PREVENT-AD) program who are at heightened risk of developing AD due to having a family history (+FH) of the disease. The goal of the study was to gain insight into whether there are sex differences in the neural correlates of episodic memory decline, which may advance knowledge about sex-specific patterns in the natural progression to AD. Our results indicate that +FH females performed better than +FH males at both baseline and follow-up on neuropsychological and task fMRI measures of episodic memory. Moreover, multivariate data-driven task fMRI analysis identified generalized patterns of longitudinal decline in medial temporal lobe activity that was paralleled by longitudinal increases in lateral prefrontal cortex, caudate and midline cortical activity during successful episodic retrieval and novelty detection in +FH males, but not females. Post-hoc analyses indicated that higher education had a stronger effect on +FH females neuropsychological scores compared to +FH males. We conclude that higher educational attainment may have a greater neuroprotective effect in older +FH females compared to +FH males.


Experiences of surviving a cardiac arrest after therapeutic hypothermia treatment. An interview study.
Cardiac arrest (CA) is often associated with high mortality. In Sweden, it is reported that 13-52 per 100,000 people suffer out-of-hospital CA, and survival to one month is 2-14%. This study aimed to describe people's experiences of surviving a CA after therapeutic hypothermia treatment. A descriptive qualitative design was used. Data were collected through individual interviews with seven CA survivors. The collected data were analyzed using qualitative content analysis. The analysis resulted in six subthemes and three emerging themes. The themes were "Dealing with issues of mortality", "Living a changed life", and "Being confident with health care and family members". Surviving a CA after therapeutic hypothermia treatment means having to deal with issues of mortality, and these patients face a turning point in life. The near-death event can create regression or progression in ethos among these patients. This study implies that persons who have survived a CA need support to cope. One way to provide support might be to initially establish an individualized health care plan, including bringing up existential issues and involving family members in such conversations.


Enantioselective mercuriocyclization of gamma-hydroxy-cis-alkenes.
Asymmetric mercuriocyclization of gamma-hydroxy-(Z)-alkenes has been achieved using Hg(II) complexed with tartrate-derived 4-(2-naphthyl)bisoxazoline as chiral ligand to give rise to 2-monosubstituted tetrahydrofurans in 86-95% ee. Not only the linker connecting two oxazolines but also their 4-substituents were found crucial for high enantioselectivity. In addition, tuning the ketal protecting group of tartrate as well as adding MeOH and K(2)CO(3) worked beneficially.


Oxidant-antioxidant balance during on-pump coronary artery bypass grafting.
The aim of this study was to evaluate the changes in perioperative oxidant-antioxidant balance in ONCABG. Twenty-three patients were included in this study. Serum total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) values were assessed preoperatively, at 20 minutes after aortic clamping and at 30 minutes, 6 hours, and 48 hours after declamping (reperfusion). The patients were divided into 2 groups according to the median aortic cross clamping (XC) time: group 1 (XC time < 42 minutes) and group 2 (XC time ≥ 42 minutes). TOS and OSI values of whole patients at 30 minutes after reperfusion were higher than preoperative values (P = 0.045, P = 0.015), while perioperative TAS levels of the patients were similar to the preoperative levels (P = 0.173). XC time was correlated with TOS levels at 30 minutes after reperfusion (r = 0.43, P = 0.041). In group 2, TOS and OSI values at 30 minutes after reperfusion were higher than preoperative values (P = 0.023, P = 0.048), whereas a significant difference was not found in group 1 (P = 0.601, P = 0.327). Oxidative imbalance and increase in TOS at reperfusion in ONCABG may be associated with XC time.


Evidence for the plasma membrane localization of Al-activated malate transporter (ALMT1).
Aluminum (Al)-activated malate transporter (ALMT1) was recently identified from wheat (Triticum aestivum). Heterologous expression of ALMT1 led to higher malate exudation that is associated with enhanced Al tolerance in transgenic plants. Here, we show the first direct evidence that ALMT1 is localized in the plasma membrane of Al-tolerant wheat. Phase partitioning experiments showed that this transporter was associated with the plasma membrane fraction. ALMT1 was detected in an Al-tolerant wheat line even without Al treatments. Analysis of transient expression of ALMT1::green fluorescent protein (GFP) in onion and tobacco cells further confirmed this ALMT1 localization.


Daily heliotropic movements assist gas exchange and productive responses in DREB1A soybean plants under drought stress in the greenhouse.
Drought stress is one of the most severe environmental constraints on plant production. Under environmental pressures, complex daily heliotropic adjustments of leaflet angles in soybean can help to reduce transpiration losses by diminishing light interception (paraheliotropism), increase diurnal carbon gain in sparse canopies and reduce carbon gain in dense canopies by solar tracking (diaheliotropism). The plant materials studied were cultivar BR 16 and its genetically engineered isoline P58, ectopically overexpressing AtDREB1A, which is involved in abiotic stress responses. We aimed to follow the movements of central and lateral leaflets in vegetative stages V7-V10 and reproductive stages R4-R5, integrating the reversible morphogenetic changes into an estimate of daily plant photosynthesis using three-dimensional modeling, and to analyze the production parameters of BR 16 and P58. The patterns of daily movements of central leaflets of BR 16 in V7-V10 and R4-R5 were similar, expressing fewer diaheliotropic movements under drought stress than under non-limiting water conditions. Daily heliotropic patterns of lateral leaflets in V7-V10 and R4-R5 showed more diaheliotropic movements in drought-stressed P58 plants than in those grown under non-limiting water conditions. Leaf area in R4-R5 was generally higher in P58 than in BR 16. Drought significantly affected gas exchange and vegetative and reproductive architectural features. DREB1A could be involved in various responses to drought stress. Compared with the parental BR 16, P58 copes with drought through better compensation between diaheliotropic and paraheliotropic movements, finer tuning of water-use efficiency, a lower transpiration rate, higher leaf area and higher pod abortion to accomplish the maximum possible grain production under continued drought conditions.


Calcium requirements in humans. Report of original data and a review.
Presently submitted and previously available data indicate that the recommended calcium requirement of 800 mg/day is inadequate for a large segment of the population, particularly the elderly. With an intake of 800 mg of calcium/day, calcium balance was only slightly positive, without consideration of dermal losses or other risk factors that may play a role in calcium bioavailability and calcium retention. A calcium intake of 1000-1200 mg/day is preferable, as calcium balance increased significantly when calcium intake was increased from 800 to 1200 mg/day; there was no further improvement in calcium balance on higher calcium intakes, up to 2300 mg/day.


Guanidinylated cationic nanoparticles as robust protein antigen delivery systems and adjuvants for promoting antigen-specific immune responses in vivo.
Weak immunogenicity and transient humoral or cellular immune responses are the major limitations of modern protein vaccines. Using delivery adjuvants is a good strategy to promote their immune response in vivo. In this study, a type of guanidinylated and cationic nanoparticle adjuvant self-assembled by monomethoxy poly(ethylene glycol)-block-poly(2-(diisopropyl amino)ethyl methacrylate)-block-poly(2-(guanidyl)ethyl methacrylate) (mPEG-b-PDPA-b-PGEM, PEDG) copolymers was used as an antigen delivery carrier. PEDG nanoparticles could encapsulate the model antigen ovalbumin (OVA) by facile electrostatic absorption with a loading efficiency of approximately 200 μg of OVA per 1 mg of the polymer. Rapid OVA release within 4 hours in acidic lysosomal compartments of antigen-presenting cells was observed. PEDG nanoparticles could stimulate the maturation of mouse bone marrow-derived dendritic cells and enhance antigen uptake and presentation by 4 fold compared to free OVA. The nanoparticles also induced the activation of macrophages (RAW 264.7) to produce a high level of cytokines including TNF-α, IL-6 and IL-10. OVA-loaded PEDG nanoparticles efficiently induced a superior antigen cross-presentation effect in vitro and in vivo compared to free OVA vaccination. In vivo stimulation of mice using nanoparticle-formulated OVA robustly enhanced the antigen-specific CD8+ T cell proliferation and the secretion of antigen-specific IgG, serum IgG2a/IgG1 antibodies and cytokines (IFN-γ, IL-2). The strategy of nanoparticle delivery prolonged the antigen duration at the injection site and enhanced its migration to draining lymph nodes as indicated by fluorescence tracking. In all, the novel guanidinylated nanoparticles could act as an effective adjuvant delivery system for protein antigens to elicit both potent antigen-specific cellular immune responses, including Th1-based adaptive immunity and CD8+ T cell response, and humoral immune responses.


Predicting susceptibility of Streptococcus pneumoniae to ceftriaxone and cefotaxime by cefuroxime and ceftizoxime disk diffusion testing.
In this study, disk diffusion testing with ceftizoxime and cefuroxime was evaluated for use in predicting the susceptibility of Streptococcus pneumoniae to ceftriaxone and cefotaxime. Of the 194 isolates included in this study, 138 were susceptible, 34 were intermediate, and 22 were resistant to cefotaxime by MIC testing; 138 isolates were susceptible, 35 were intermediate, and 21 were resistant to ceftriaxone by MIC testing. A zone of inhibition around the cefuroxime disk of >/=32 mm correctly categorized 101 of 138 isolates as susceptible to cefotaxime and ceftriaxone. A zone of inhibition around the ceftizoxime disk of >/=26 mm correctly categorized 111 of 138 isolates as susceptible to cefotaxime and 114 of 138 as susceptible to ceftriaxone. We conclude that disk diffusion can separate S. pneumoniae isolates susceptible to ceftriaxone and cefotaxime from those that are not susceptible. Isolates not falling into the susceptible category by disk diffusion require additional testing to determine the MIC.


Modulation of allergy risk by breast feeding.
Breastfeeding has been suggested as a candidate for primary prevention of allergies. However, recent comprehensive and thoughtfully written systematic reviews reported mixed results and that overall there is only little evidence for breastfeeding being protective against allergic disorders. As these reviews last searched for relevant studies on 2 October 2014, the aim of our review is to shed light on the association between breastfeeding and allergic disorders (asthma, eczema, allergic rhinitis) recently published. These recent studies are varied and differ in size, settings, design, depth of data collecting, and quality of the study. Thus far, the results on the association between nonexclusive and exclusive breastfeeding with regards to asthma are mixed especially in young ages. Additionally, if eczema and allergic rhinitis are the outcomes of interest, this recent review does not provide a clearer picture. The current guidelines by WHO and European Academy of Allergy and Clinical Immunology (EAACI) on breastfeeding till 6 months and exclusively breastfeeding for 4-6 months, respectively, for the prevention of allergies are not supported by the recent study results. Nevertheless, breastfeeding should be strongly recommended for other beneficial health effects than allergy prevention.


Tibiofemoral angle and its relation to ankle sprain occurrence.
The lack of a normal joint orientation generates translational or shear forces across the joint. These forces can put abnormally high strain on the cartilage and the surrounding capsuloligamentous tissues. Ankle joint structure can affect or be affected by bony malformations of the surrounding areas, including the knee and hip. The aim of the current study is to examine the possible relationship between the tibiofemoral (TFA) angle and other factors (anthropometric characteristics, medical history, and age) on the occurrence of ankle sprains because its value provides useful information for the anatomical alignment of the lower extremity. The study sample consisted of 45 high-level athletes, evenly distributed among 3 sports (basketball, soccer, and volleyball). TFA measurements were made on radiographs. The study lasted 2 years. A logistic regression was used to determine the importance of each factor on the probability in question. A significance level of P = .1 was used. The factors contributing more to an ankle sprain were a previous injury of the same type followed by body mass index (BMI) and age. On the contrary, TFA was proven to be statistically nonsignificant. When the BMI variable was substituted with body inertia propensity, a derived variable, the TFA remained statistically nonsignificant. TFA magnitude does not seem to be a determinant factor that could increase the probability of spraining an ankle.


The expression of pre- and postcopulatory sexually selected traits reflects levels of dietary stress in guppies.
Environmental and ecological conditions can shape the evolution of life history traits in many animals. Among such factors, food or nutrition availability can play an important evolutionary role in moderating an animal's life history traits, particularly sexually selected traits. Here, we test whether diet quantity and/or composition in the form of omega-3 long chain polyunsaturated fatty acids (here termed 'n3LC') influence the expression of pre- and postcopulatory traits in the guppy (Poecilia reticulata), a livebearing poeciliid fish. We assigned males haphazardly to one of two experimental diets supplemented with n3LC, and each of these diet treatments was further divided into two diet 'quantity' treatments. Our experimental design therefore explored the main and interacting effects of two factors (n3LC content and diet quantity) on the expression of precopulatory (sexual behaviour and sexual ornamentation, including the size, number and spectral properties of colour spots) and postcopulatory (the velocity, viability, number and length of sperm) sexually selected traits. Our study revealed that diet quantity had significant effects on most of the pre- and postcopulatory traits, while n3LC manipulation had a significant effect on sperm traits and in particular on sperm viability. Our analyses also revealed interacting effects of diet quantity and n3LC levels on courtship displays, and the area of orange and iridescent colour spots in the males' colour patterns. We also confirmed that our dietary manipulations of n3LC resulted in the differential uptake of n3LC in body and testes tissues in the different n3LC groups. This study reveals the effects of diet quantity and n3LC on behavioural, ornamental and ejaculate traits in P. reticulata and underscores the likely role that diet plays in maintaining the high variability in these condition-dependent sexual traits.


Barley Mla and Rar mutants compromised in the hypersensitive cell death response against Blumeria graminis f.sp. hordei are modified in their ability to accumulate reactive oxygen intermediates at sites of fungal invasion.
The pathogenesis-related accumulation of superoxide radical anions (O2*-) and hydrogen peroxide (H2O2) was comparatively analyzed in a barley line (Hordeum vulgare L. cv Sultan-5) carrying the powdery mildew (Blumeria graminis f.sp. hordei, Speer, Bgh) resistance gene Mla12, and in susceptible mutants defective in Mla12 or in genes "required for Mla12-specified disease resistance" (Rar1 and Rar2). In-situ localization of reactive oxygen intermediates was performed both by microscopic detection of azide-insensitive nitroblue tetrazolium (NBT) reduction or diaminobenzidine (DAB) polymerization, and by an NBT-DAB double-staining procedure. The Mla12-mediated hypersensitive cell death occurred either in attacked epidermal cells or adjacent mesophyll cells of wild-type plants. Whole-cell H2O2 accumulation was detected in dying cells, while O2*- emerged in adjacent cells. Importantly, all susceptible mutants lacked these reactions. An oxalate oxidase, which is known to generate H2O2 and has been implicated in barley resistance against the powdery mildew fungus, was not differentially expressed between the wild type and all mutants. The results demonstrate that the Rar1 and Rar2 gene products, which are control elements of R-gene-mediated programmed cell death, also control accumulation of reactive oxygen intermediates but not the pathogenesis-related expression of oxalate oxidase.


Anesthesia for a patient of acromesomelic dysplasia with associated hydrocephalus, Arnold Chiari malformation and syringomyelia.
Acromesomelic dysplasias are autosomal recessive osteochondrodysplasias. Acromesomelic dysplasia Maroteaux-type (AMDM), also known as St Helena dysplasia, is of two types: The classical and the mild variety. About 50 cases of AMDM have been reported till date, most of them being the classical variety. There is scarcity of literature on anesthesia for such patients. We are reporting a case of general anesthetic management of AMDM, associated with hydrocephalus, Arnold Chiari malformation type-1 and syringomyelia. The patient was a 10-year-old short-statured boy who presented with symptomatic thoracic kyphoscoliosis, gibbus deformity and back pain. On examination, there was no neurological deficit. Radiology revealed thoracic kyphoscoliosis, mild ventriculomegaly and upper cervical syringomyelia. The patient underwent posterior fossa decompression in the prone position under general anesthesia. We will discuss the anesthetic considerations for such patients and review the pertinent literature.


Application of ionic liquid-based surfactants in the microwave-assisted extraction for the determination of four main phloroglucinols from Dryopteris fragrans.
An ionic liquid-based surfactant combined with microwave-assisted extraction method, followed by RP-HPLC-diode array detection (DAD) with a core shell column, was successfully applied in extracting and quantifying four major phloroglucinols from Dryopteris fragrans. Eight ionic liquids with different cation and anion were investigated, and 1-octyl-3-methylimidazolium bromide presented the best relative extraction efficiency for four phloroglucinols. The optimum conditions of this method were as follows: ionic liquid concentration 0.75 M, liquid/solid ratio 12:1 mL/g, extraction time 7 min, extraction temperature 50°C, and irradiation power 600 W. The quality analytical parameters of the method were obtained based on the linearity, precision, accuracy, detection, and quantification limits. The recoveries were between 96.90 and 103.5% with standard deviations not higher than 4.7%. Compared with ionic liquid-based heat reflux extraction, ultrasonic-assisted extraction, negative-pressure cavitation extraction, and conventional microwave-assisted extraction, the relative extraction efficiencies of the proposed method for four phloroglucinols increased 1.5-40.4%. The method was successfully applied for the quantification of four major phloroglucinols from D. fragrans. All these results suggest that the developed method represents an excellent alternative for the extraction and quantification of phloroglucinols in other plant materials.


Technical feasibility of embolizing aneurysms with glue (N-butyl 2-cyanoacrylate): experimental study in rabbits.
Liquid embolic agents may have potential as a therapeutic option to reconstruct a defective vessel wall. We evaluated the feasibility of transarterial glue embolization in surgically constructed carotid artery aneurysms. Reconstruction of arterial wall defects with use of glue casts was performed in 16 surgically constructed aneurysms of carotid arteries in rabbits. Via the transfemoral route, glue was injected without balloon protection through a microcatheter into the aneurysmal sac with (n = 8) and without (n = 8) a framework of coils. To identify safe and effective methods, four concentrations (28%, 33%, 40%, 50%) of glue-iodized oil mixtures were used in four aneurysms each. Immediate (n = 16) and 2-month follow-up (n = 10) postembolization angiograms were obtained to evaluate the residual aneurysmal sac and the carotid artery patency. Continuous column injection of glue was possible in all aneurysms, without fragmented migration of the injected glue cast. Catheter sticking or breakage did not occur during catheter retrieval. Glue embolization without a framework of coils (n = 8) resulted in complete obliteration of the aneurysmal sac in five aneurysms and incomplete obliteration with a small residual lumen in three. Two aneurysms resulted in carotid occlusion after catheter removal. A follow-up angiogram (n = 4) showed decreased residual lumen in two aneurysms, no change in the complete aneurysm occlusion in one, and carotid occlusion in one. Glue embolization with a coil framework (n = 8) resulted in complete obliteration of the aneurysmal sac in six aneurysms and incomplete obliteration with a small residual lumen in two. A small amount of spillage occurred in one owing to the improper position of the microcatheter caused by a difficult neck angle to the parent artery. Follow-up angiograms (n = 6) showed decreased residual lumen in one of two aneurysms and no change of the complete occlusion in five of six aneurysms. Effective glue embolization into the aneurysmal sac is technically feasible. Microcatheter position within the aneurysm, concentration of glue, and direction of the aneurysmal neck angle all must be considered. With a coil framework, glue injection was more complete, without deformity or spillage of the glue from the aneurysm.


MiR-135a regulates renal fibrosis in rats with diabetic kidney disease through the Notch pathway.
To explore the influence of micro ribonucleic acid (miR)-135a on the renal fibrosis in rats with diabetic kidney disease (DKD) through the Notch signaling pathway. A total of 30 male Wistar rats weighing 200-220 g were selected and randomly divided into Control group (n=10), diabetes mellitus (DM) group (n=10), and miR-13a inhibitor group (n=10). Streptozotocin (STZ) was intraperitoneally injected daily to establish the DM model in rats of both DM group and miR-135a group, while normal saline was given daily through intraperitoneal injection in rats of Control group. After 4 weeks, the rats in miR-135a inhibitor group were intraperitoneally injected with miR-135a inhibitor, and those in Control and DM groups were administrated with an equal amount of normal saline. Changes in the blood glucose (BG), glycated hemoglobin (GHb), serum creatinine (Scr), triglyceride (TG), and total cholesterol (TC) of rats were evaluated, and the pathological changes in the renal tissues of DM rats were observed via hematoxylin-eosin (HE) staining. Sirius red staining was performed to observe the changes in collagen fibers in the kidney of all groups of rats. The expressions of Notch and Hes1 in the renal tissues of rats in each group were detected using immunohistochemistry. Immunofluorescence assay was employed to detect the positive expression of Notch in the renal tissues of rats. The mRNA expressions of Notch and miR-135a were detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Finally, Western blotting was conducted to detect the protein expressions of Notch, Notch intracellular domain (NICD) and Hes1. Compared with Control group, rats in DM group had substantially raised levels of BG, GHb, Scr, TG, and TC (p<0.05). HE staining showed that the rats in Control group had renal tubular cells with normal morphology and well-defined structure, while those in DM group exhibited evident cavitation in the renal tubular epithelium. Sirius red staining results manifested that the red collagen fibers were evenly distributed with light staining in the glomeruli and renal tubules of rats in Control group. In contrast, the collagen fibers of the glomeruli and renal tubules of rats in DM group exhibited deep and evident red staining. Moreover, compared with DM group, rats in miR-135a inhibitor group had notably faded red staining in the glomeruli and renal tubules of rats, evenly distributed collagen and remarkably decreased fibrotic nodules. According to immunohistochemistry detection results, the protein levels of Notch and Hes1 in the renal tubulointerstitial cells and renal tubular epithelial cells of rats in DM group were markedly higher than those in Control group. Compared with those in DM group, their protein levels were remarkably lowered in miR-135a inhibitor group (p<0.05). Immunofluorescence assay results revealed that the protein level of Notch in the renal tissues of rats in DM group was considerably higher than that in Control group (p<0.05), while its protein level in miR-135a inhibitor group was significantly lower than that in DM group. According to qRT-PCR results, compared with those in Control group, mRNA expressions of Notch mRNA and miR-135a in the rat kidney tissues were substantially raised in DM group (p<0.05), and they were notably lowered in miR-13a inhibitor group compared with those in DM group (p<0.05). Finally, Western blotting results manifested that the protein levels of Notch, NIC, and Hes1 in the renal tissues of rats in DM group were considerably higher than those in Control group (p<0.05), and that their protein expression levels in miR-135a inhibitor group were markedly lower than those in DM group (p<0.05). Inhibition of miR-135a can reduce the renal fibrosis in DKD rats through the Notch pathway.


Cowpea mosaic virus: effects on host cell processes.
SUMMARY Taxonomy: Cowpea mosaic virus (CPMV) is the type member of the Comoviridae and bears a strong resemblance to animal picornaviruses, both in gene organization and in the amino acid sequence of replication proteins. Little systematic work has been done to compare isolates of the virus from different parts of the world. Physical properties: Purified preparations of virus contain three centrifugal components; empty protein shells without RNA (T) and two nucleoprotein components (M and B), containing 24% and 34% RNA, respectively. The icosahedral particles have with a diameter of 28 nm, consist of 60 copies of two coat proteins, and are heat stable. Hosts: CPMV causes one of the most commonly reported virus diseases of cowpea (Vigna unguiculata), in which it produces chlorotic spots with diffuse borders in inoculated primary leaves. Trifoliate leaves develop a bright yellow or light green mosaic of increasing severity in younger leaves. The host range is rather limited, and few hosts are known outside the Leguminosae. The virus is transmitted by various beetles with biting mouthparts. Reported in Africa, the Philippines and Iran. Is apparently absent from North and South America. Useful website: http://mmtsb.scripps.edu/viper/1cpmv.html (structure); http://image.fs.uidaho.edu/vide/descr254.htm (general information).


Spatial misalignment in time series studies of air pollution and health data.
Time series studies of environmental exposures often involve comparing daily changes in a toxicant measured at a point in space with daily changes in an aggregate measure of health. Spatial misalignment of the exposure and response variables can bias the estimation of health risk, and the magnitude of this bias depends on the spatial variation of the exposure of interest. In air pollution epidemiology, there is an increasing focus on estimating the health effects of the chemical components of particulate matter (PM). One issue that is raised by this new focus is the spatial misalignment error introduced by the lack of spatial homogeneity in many of the PM components. Current approaches to estimating short-term health risks via time series modeling do not take into account the spatial properties of the chemical components and therefore could result in biased estimation of those risks. We present a spatial-temporal statistical model for quantifying spatial misalignment error and show how adjusted health risk estimates can be obtained using a regression calibration approach and a 2-stage Bayesian model. We apply our methods to a database containing information on hospital admissions, air pollution, and weather for 20 large urban counties in the United States.


Ketamine HCl, a dissociative anesthetic for squirrel monkeys (Saimiri sciureus).
A series of 3 experiments performed in squirrel monkeys showed that ketamine HCl was satisfactory for chemical restraint at doses of less than 13 mg/kg. Doses of 25 mg/kg and above produced surgical anesthesia. When serial doses of ketamine HCl were given to squirrel monkeys at regular intervals, predictable anesthesia and recovery times were produced. Deaths occurred only at 350 mg/kg.