Association of adipocyte genes with ASP expression: a microarray analysis of subcutaneous and omental adipose tissue in morbidly obese subjects.
Prevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP) and Triglyceride (TG) (LAT) vs High ASP and TG (HAT). Subcutaneous (SC) and omental (OM) adipose tissues (n = 21) were analysed by microarray, and biologic pathways in lipid metabolism and inflammation were specifically examined. LAT and HAT groups were matched in age, obesity, insulin, and glucose, and had similar expression of insulin-related genes (InsR, IRS-1). ASP related genes tended to be increased in the HAT group and were correlated (factor B, adipsin, complement C3, p < 0.01 each). Differences between LAT and HAT group were almost exclusively in SC tissue, with little difference in OM tissue. Increased C5L2 (p < 0.01), an ASP receptor, in HAT suggests a compensatory ASP pathway, associated with increased TG storage. HAT adipose tissue demonstrated increased lipid related genes for storage (CD36, DGAT1, DGAT2, SCD1, FASN, and LPL), lipolysis (HSL, CES1, perilipin), fatty acid binding proteins (FABP1, FABP3) and adipocyte differentiation markers (CEBPalpha, CEBPbeta, PPARgamma). By contrast, oxidation related genes were decreased (AMPK, UCP1, CPT1, FABP7). HAT subjects had increased anti-inflammatory genes TGFB1, TIMP1, TIMP3, and TIMP4 while proinflammatory PIG7 and MMP2 were also significantly increased; all genes, p < 0.025. Taken together, the profile of C5L2 receptor, ASP gene expression and metabolic factors in adipose tissue from morbidly obese HAT subjects suggests a compensatory response associated with the increased plasma ASP and TG.


Structure of bacteriorhodopsin at 1.55 A resolution.
Th?e atomic structure of the light-driven ion pump bacteriorhodopsin and the surrounding lipid matrix was determined by X-ray diffraction of crystals grown in cubic lipid phase. In the extracellular region, an extensive three-dimensional hydrogen-bonded network of protein residues and seven water molecules leads from the buried retinal Schiff base and the proton acceptor Asp85 to the membrane surface. Near Lys216 where the retinal binds, transmembrane helix G contains a pi-bulge that causes a non-proline? kink. The bulge is stabilized by hydrogen-bonding of the main-chain carbonyl groups of Ala215 and Lys216 with two buried water molecules located between the Schiff base and the proton donor Asp96 in the cytoplasmic region. The results indicate extensive involvement of bound water molecules in both the structure and the function of this seven-helical membrane protein. A bilayer of 18 tightly bound lipid chains forms an annulus around the protein in the crystal. Contacts between the trimers in the membrane plane are mediated almost exclusively by lipids.


Scientific hazards of human reproductive 'cloning'.
The scientific and clinical professional societies and associations covering the remit of Human Fertility are unanimously opposed to human reproductive 'cloning'. This article describes the main scientific objections to human reproductive 'cloning'. Data collected from numerous studies in a range of animal species indicate a high incidence of fetal defects, a stillbirth rate typically of more than 90% and a lack of adequate information on postnatal development. These concerns are exacerbated by misconceptions about the current ability to screen preimplantation embryos for 'cloning-induced' defects. Scientists and clinicians are sometimes treated with mistrust in the eyes of the public and media over such issues, perhaps because scientific information is not as well communicated as it might be. The duty of reproductive specialists is to convey the limits of their knowledge on this issue to the public and policymakers.


Effectiveness of Fipronil as a Systemic Control Agent Against Xenopsylla cheopis (Siphonaptera: Pulicidae) in Madagascar.
Fipronil was evaluated as a systemic control agent for the rat flea Xenopsylla cheopis (Rothschild), the main vector of Yersinia pestis (Yersin), the causative agent of plague, in Madagascar. The effectiveness of fipronil as a systemic control agent against X. cheopis was assessed by determining the toxicity values of the "Lethal Dose 50" (LD50). Two techniques were used to evaluate the systemic action of the insecticide on the vector: 1) an artificial feeding device filled with blood-fipronil mixture from which X. cheopis was fed and 2) rodent hosts, Rattus norvegicus (Berkenhout) and Rattus rattus (L.), which fed on fipronil-treated bait. As a standardized control method, the susceptibility of X. cheopis to fipronil was evaluated by exposure to impregnated paper within World Health Organization (WHO) insecticide test protocol to compare its effect to the systemic activity of the studied insecticide. Results showed that when administered in a systemic way, fipronil appears to be more effective: the toxicity level was evaluated to be ninefold higher compared with the WHO test. Compared with other methods, which require indiscriminate dusting of rodent burrows and human dwellings, fipronil applied in a systemic way enables the direct targeting of the plague vector. Thus, this method appears to be a superior alternative to fipronil-dusting for the control of the main plague vector in Madagascar. However, subsequent tests in the field are necessary to confirm the suitability of fipronil administration in a systemic way on large scales.


Integration of Digital Tools Into Community Mental Health Care Settings That Serve Young People: Focus Group Study.
Digital mental health tools have substantial potential to be easily integrated into people's lives and fundamentally impact public health. Such tools can extend the reach and maximize the impact of mental health interventions. Before implementing digital tools in new settings, it is critical to understand what is important to organizations and individuals who will implement and use these tools. Given that young people are highly familiar with technology and many mental health concerns emerge in childhood and adolescence, it is especially crucial to understand how digital tools can be integrated into settings that serve young people. This study aims to learn about considerations and perspectives of community behavioral health care providers on incorporating digital tools into their clinical care for children and adolescents. Data were analyzed from 5 focus groups conducted with clinicians (n=37) who work with young people at a large community service organization in the United States. This organization provides care to more than 27,000 people annually, most of whom are of low socioeconomic status. The transcripts were coded using thematic analysis. Clinicians first provided insight into the digital tools they were currently using in their treatment sessions with young people, such as web-based videos and mood-tracking apps. They explained that their main goals in using these tools were to help young people build skills, facilitate learning, and monitor symptoms. Benefits were expressed, such as engagement of adolescents in treatment, along with potential challenges (eg, accessibility and limited content) and developmental considerations (eg, digital devices getting taken away as punishment). Clinicians discussed their desire for a centralized digital platform that securely connects the clinician, young person, and caregivers. Finally, they offered several considerations for integrating digital tools into mental health care, such as setting up expectations with clients and the importance of human support. Young people have unique considerations related to complex accessibility patterns and technology expectations that may not be observed when adults are the intended users of mental health technologies. Therefore, these findings provide critical insights to inform the development of future tools, specifically regarding connectivity, conditional restraints (eg, devices taken away as punishment and school restrictions), expectations of users from different generations, and the blended nature in which digital tools can support young people.


Effect of Brugia malayi infections on endothelial cells: a morphological study.
Athymic mice (C3H/HeN) parasitized by Brugia malayi develop gross lymphatic dilations at the chronic stage of infection. The hyperplastic endothelial cells and low fluid pressure of the lymphatics, characteristic of these infections, suggest that abnormal changes in these cells may play an important role in the dilation. We studied the lymphatic and vascular endothelium of parasitized mice for morphological changes by scanning and/or transmission electron microscopy. The lymphatic endothelium of dilated lymphatics was perturbed, scalloped, bulbous and highly indented. Numerous mononuclear and giant cells were closely apposed to the endothelial wall. Endothelial cells of both the lymphatics and the adjacent venules revealed no focal cytoplasmic lesions. Growth factor-dependent cell proliferation was significantly suppressed in vitro in endothelial cell cultures containing adult female worms, male worms or microfilariae. The actin cytoskeletal network appeared intact in these cells, and no gross changes in distribution were evident. Although the lymphatic walls were highly tortuous, our examination revealed no significant alterations in their morphology. Perivascular infiltration of activated mast cells, lymphocytes and monocytes/macrophages indicated polarization of inflammatory cells into the lymphatic tissue. It is possible that these inflammatory cells might induce temporal functional changes in the lymphatics of infected athymic mice.


Nicotine delivery to rats via lung alveolar region-targeted aerosol technology produces blood pharmacokinetics resembling human smoking.
Nicotine is a heavily used addictive drug acquired through smoking tobacco. Nicotine in cigarette smoke is deposited and absorbed in the lungs, which results in a rapidly peaked slowly declining arterial concentration. This pattern plays an important role in initiation of nicotine addiction. A method and device were developed for delivering nicotine to rodents with lung alveolar region-targeted aerosol technology. The dose of delivery can be controlled by the nicotine aerosol concentration and duration of exposure. Our data showed that, in the breathing zone of the nose-only exposure chamber, the aerosol droplet size distribution was within the respirable diameter range. Rats were exposed to nicotine aerosol for 2 min. The arterial blood nicotine concentration reached 43.2 ± 15.7 ng/ml (mean ± SD) within 1-4 min and declined over the next 20 min, closely resembling the magnitude and early pharmacokinetics of a human smoking a cigarette. The acute inhalation toxicity of nicotine: LC50 = 2.3mg/L was determined; it was affected by pH, suggesting that acidification decreases nicotine absorption and/or bioavailability. A noninvasive method and toolkit were developed for delivering nicotine to rodents that enable rapid delivery of a controllable amount of nicotine into the systemic circulation and brain-inducing dose-dependent pharmacological effects, even a lethal dose. Aerosol inhalation can produce nicotine kinetics in both arterial and venous blood resembling human smoking. This method can be applied to studies of the effects of chronic intermittent nicotine exposure, nicotine addiction, toxicology, tobacco-related diseases, teratogenicity, and for discovery of pharmacological therapeutics.


Hematopoietic but not endothelial cell MyD88 contributes to host defense during gram-negative pneumonia derived sepsis.
Klebsiella pneumoniae is an important cause of sepsis. The common Toll-like receptor adapter myeloid differentiation primary response gene (MyD)88 is crucial for host defense against Klebsiella. Here we investigated the role of MyD88 in myeloid and endothelial cells during Klebsiella pneumosepsis. Mice deficient for MyD88 in myeloid (LysM-Myd88(-/-)) and myeloid plus endothelial (Tie2-Myd88(-/-)) cells showed enhanced lethality and bacterial growth. Tie2-Myd88(-/-) mice reconstituted with control bone marrow, representing mice with a selective MyD88 deficiency in endothelial cells, showed an unremarkable antibacterial defense. Myeloid or endothelial cell MyD88 deficiency did not impact on lung pathology or distant organ injury during late stage sepsis, while LysM-Myd88(-/-) mice demonstrated a strongly attenuated inflammatory response in the airways early after infection. These data suggest that myeloid but not endothelial MyD88 is important for host defense during gram-negative pneumonia derived sepsis.


[Delay in the diagnosis of malignant tumors (breast, larynx, bladder)].
Cancer is the second leading cause of mortality in developed countries. Irrespective of its malignant degree, certain histological types and locations, there is a number of authors who hold the view that a delay in diagnosis can be one of the factors leading to a fatal outcome of the disease. In this study an assessment was made of diagnostic delay in three locations (breast, bladder, and larynx) in which the disease usually begins with evident alarm symptoms. The natural history of disease, from the first symptom to hospital admission and clinical diagnosis, was reconstructed by means of a questionnaire administered to patients from May, first, 1989, to April, 30th, 1990. It is concluded that patient's responsibility is great for the diagnostic delay of breast malignant tumors, whereas such a responsibility can be attributed to the Health Maintenance System for the other two types of cancer, bladder and larynx.


Proto-oncogene expression in dermal naevi and melanomas.
Overexpression of proto-oncogenes (c-onc) may be involved in the initiation and progression of human neoplasia. We investigated the mRNA expression of the proto-oncogenes c-myc, c-fos, c-neu (erb B-2) and Ha-ras in 12 cutaneous melanocytic lesions (four dermal naevi, seven melanomas; one cutaneous metastatis of melanoma) and in normal skin (five cases) by Northern blot analysis; mRNA expression levels were quantified by densitometry of the specific bands. The expression of c-myc mRNA was higher in naevi than in melanomas, whereas c-fos mRNA expression was significantly higher in melanomas than in naevi. No significant differences were detected in the c-neu and Ha-ras mRNA levels in naevi and melanomas. The expression of c-neu mRNA was higher in normal skin than in the melanocytic lesions examined. Our results suggest that enhanced c-myc and c-fos expression may play an important role in the growth of melanocytic naevi and melanomas. The overexpression of c-fos may be involved in the progression of a particular subset of melanoma. Activation of Ha-ras and the c-neu gene, as determined by mRNA overexpression, does not seem to play a significant role in the progression of cutaneous pigmented lesions. Expression of c-neu may have an important function in the proliferation and/or differentiation of normal cells of the epidermis.


Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus.
A T-->G transversion at nt 8993 in mitochondrial DNA of MTATP6 (encoding ATPase 6 of complex V of the respiratory chain) causes impaired mitochondrial ATP synthesis in two related mitochondrial disorders: neuropathy, ataxia and retinitis pigmentosa and maternally inherited Leigh syndrome. To overcome the biochemical defect, we expressed wildtype ATPase 6 protein allotopically from nucleus-transfected constructs encoding an amino-terminal mitochondrial targeting signal appended to a recoded ATPase 6 gene (made compatible with the universal genetic code) that also contained a carboxy-terminal FLAG epitope tag. After transfection of human cells, the precursor polypeptide was expressed, imported into and processed within mitochondria, and incorporated into complex V. Allotopic expression of stably transfected constructs in cytoplasmic hybrids (cybrids) homoplasmic with respect to the 8993T-->G mutation showed a significantly improved recovery after growth in selective medium as well as a significant increase in ATP synthesis. This is the first successful demonstration of allotopic expression of an mtDNA-encoded polypeptide in mammalian cells and could form the basis of a genetic approach to treat a number of human mitochondrial disorders.


Summary and findings of the EPA and CDC symposium on air pollution exposure and health.
The U.S. Environmental Protection Agency (EPA) and the U.S. Centers for Disease Control (CDC) co-organized a symposium on "Air Pollution Exposure and Health" at Research Triangle Park, North Carolina on September 19-20, 2006. The symposium brought together health and environmental scientists to discuss the state of the science and the cross-jurisdictional and methodological challenges in conducting air pollution epidemiology, environmental public health tracking and accountability research. The symposium was held over 2 days and consisted of technical presentations and breakout group discussions on each of the three principal themes of this meeting: (1) monitoring and exposure modeling information, (2) health effects data and (3) linkage of air quality and health data for research, tracking and accountability. This paper summarizes the symposium presentations and the conclusions and recommendations developed during the meeting. The accompanying two papers, which appear in this issue of the Journal, provide more in-depth discussion of issues pertinent to obtaining and analyzing air pollution exposure and health information. The symposium succeeded in identifying areas where there are critical gaps of knowledge in existing air pollution exposure and health information and in discovering institutional or programmatic barriers, which impede accessing and linking disparate data sets. Several suggestions and recommendations emerged from this meeting, directed toward (1) improving the utility of air monitoring data for exposure quantification, (2) improving access to and the quality of health data, (3) studying emerging air quality and health issues, (4) exploring improved or novel methods for linking data and (5) developing partnerships, building capacity and facilitating interdisciplinary communication. The meeting was successful in promoting an interdisciplinary dialogue around these issues and in formulating strategies to support these recommended activities. Finally, this symposium subsequently led to strengthening and initiating new partnerships or interactions between the EPA, CDC, States, academia and the research community at large.


Life-cycle energy and CO2 analysis of stormwater treatment devices.
Environmental impacts associated with the construction, maintenance, and disposal of low-impact stormwater management devices are one aspect that should be considered during decision-making and life-cycle assessment (LCA) is a suitable method for quantifying such impacts. This paper reports a pilot study that employs LCA to compare life-cycle energy requirements and CO2 emissions of two stormwater devices in New Zealand. The two devices are a raingarden servicing an urban feeder road, and a sand filter that could have been installed in its stead. With an assumed life-time of 50 years, the life-cycle energy requirements of the built raingarden were almost 20% less than for the sand filter, while the CO2 emissions were 30% less. Our analysis shows that given the difference between the infiltration rates used in the raingarden design (0.3 m/day) and measured during monitoring (3 m/day) there was potential to make significantly greater life-time savings using a smaller design for the raingarden that would have also met the treatment efficiency expectations. The analysis highlights the significant contribution of transportation-of both materials and staff-and ongoing maintenance to a treatment device's life-cycle energy and CO2 profiles.


Bacteriology and drug sensitivity of chronic suppurative otitis media at a central hospital in Zimbabwe.
A retrospective study was done on 173 cases of chronic suppurative otitis media at Harare Central Hospital. Using conventional pus swabs from the discharging ears only aerobic organisms were isolated in 155 cases. These were, in order of frequency, Staphylococcus aureus, Pseudomonas aeruginosa, Lactose fermenting, Coliforms and Proteus. There were no anaerobes reported, unlike in other studies. Mixed infections were present in 48 percent of the cases. Penicillin G, Ampicillin, Tetracycline Sulphamethoxazole and trimethoprin which are commonly used when culture and sensitivity results are not available, were found to be less useful. Gentamyoin, Chloramphenical, Clindamyoin and erythromycin were more useful. More research needs to be done on the role of topical drugs in chronic suppurative otitis media.


Ploidy is an important determinant of fluoroquinolone persister survival.
Genetic mutants have demonstrated the importance of homologous recombination (HR) to fluoroquinolone (FQ) persistence, which suggests that single-cell chromosome (Chr) abundance might be a phenotypic variable of importance to persisters. Here, we sorted stationary-phase E. coli based on ploidy and subjected the subpopulations to tolerance assays. Subpopulations sorted to contain diploid cells harbored up to ∼40-fold more FQ persisters than those sorted to contain monoploid cells. This association was observed with distinct FQs, in independent environmental conditions, and with more than one strain of E. coli (MG1655; uropathogenic CFT073) but was abolished in HR-deficient strains (ΔrecA and ΔrecB). It was observed that the persister level of monoploid subpopulations exceeded those of ΔrecA and ΔrecB by 10-fold or more, and subsequent high-purity sorting confirmed that observation. Those data suggested the existence of distinct FQ persister subtypes: those that are and are not proficient with HR. Time-lapse microscopy revealed significant differences in initial size and growth dynamics during the post-antibiotic recovery period for persisters from monoploid- and diploid-enriched subpopulations. In addition, non-persisters in monoploid-enriched subpopulations elongated minimally following FQ treatment, resembling previous observations of HR-deficient strains, whereas non-persisters in diploid-enriched subpopulations on average filamented extensively. Together, these results identify a phenotypic variable with a significant impact on FQ persistence, establish the existence of more than one type of persister to the same antibiotic in an isogenic culture, and reveal roles for RecA and RecB in FQ persistence, even in the absence of homologous chromosomes.


Substrate specificity to maintain cellular ATP along the mouse nephron.
To evaluate substrate utilization along the mouse nephron, cellular ATP content was measured under various conditions by the luciferin-luciferase technique. Individual micro-dissected nephron segments were incubated in a modified Hanks' solution (pH 7.4) with or without each of the following substrates: D-glucose, DL-lactate, beta-hydroxybutyrate (HBA), and L-glutamine. ATP production from glucose was minimal in the early proximal tubule (S1), but was substantial in the late proximal tubule (S3). Glutamine and lactate were the preferred substrates in proximal tubules. In contrast, ATP production from glutamine was less than that from the other substrates in distal nephron segments, including medullary and cortical thick ascending limbs of Henle's loop (MTAL and CTAL), distal tubule including the connecting tubule (DT), and cortical and medullary collecting tubules (CCT and MCT). Lactate and HBA were preferred substrates for ATP maintenance in CTAL, MTAL, and DT. Glucose was the best substrate in CCT. In addition, the specific contribution of anaerobic metabolism to maintaining cellular ATP was low in MTAL and CTAL. On the other hand, the glycolytic capacity of CCT and MCT was high. The above results demonstrate the substrate requirements for maintaining cellular ATP content within specific nephron segments.


Polarization of rheumatoid macrophages is regulated by the CDKN2B-AS1/ MIR497/TXNIP axis.
The polarization of macrophages plays a critical role in the pathophysiology of rheumatoid arthritis. The macrophages can have pro-inflammatory M1 polarization and various types of alternative anti-inflammatory M2 polarization. Our preliminary results showed that the CDKN2B-AS1/MIR497/TXNIP axis might regulate macrophages of rheumatoid arthritis patients. Therefore, we hypothesized that this axis regulated the polarization of rheumatoid macrophages. Flow cytometry was used to determine the surface polarization markers in M1 or M2 macrophages from healthy donors and rheumatoid arthritis patients. The QPCR and Western Blotting were used to compare the expression of the CDKN2B-AS1/MIR497/TXNIP axis in these macrophages. We Knocked down and overexpressed the axis in the macrophage cell line MD to test its roles in macrophage polarization. Compared to cells from healthy donors, cells from rheumatoid arthritis patients expressed higher levels of CD40 and CD80 and lower levels of CD16, CD163, CD206, and CD200R after polarization, they also expressed higher CDKN2B-AS1, lower MIR497, and higher TXNIP. In macrophages from healthy donors, there was no correlation among CDKN2B-AS1, MIR497, and TXNIP. But in macrophages from patients, there were significant correlations. The CDKN2B-AS1 knockdown, MIR497 mimics suppressed the M1 polarization but promoted the M2 polarization in MD cells, while the MIR497 knockdown and the TXNIP overexpression did the opposite. This study demonstrated that elevated CDKN2B-AS1 in macrophages promotes the M1 polarization and inhibited the M2 polarization of macrophages by the CDKN2B-AS1/ MIR497/TXNIP axis.


Generating ROC curves for artificial neural networks.
Receiver operating characteristic (ROC) analysis is an established method of measuring diagnostic performance in medical imaging studies. Traditionally, artificial neural networks (ANN's) have been applied as a classifier to find one "best" detection rate. Recently researchers have begun to report ROC curve results for ANN classifiers. The current standard method of generating ROC curves for an ANN is to vary the output node threshold for classification. In this work, we propose a different technique for generating ROC curves for a two-class ANN classifier. We show that this new technique generates better ROC curves in the sense of having greater area under the ROC curve (AUC), and in the sense of being composed of a better distribution of operating points.


Effect of occlusion effect by bone-conducted sound on monosyllable articulation.
Bone conduction (BC) technology allows us to hear sounds without having anything blocking our ears and enables hearing even when wearing earplugs. However, optimizing this technology presents challenges, particularly in relation to the occlusion effect (OE), a phenomenon that takes place when the ear canal is occluded, causing low-frequency sounds to seem louder than their original intensity. While some facial regions exhibit greater OE than conventional areas, the impact of OE on speech perception in different facial regions has not been thoroughly investigated. This study explores the relationship between OE and speech perception in various facial regions to inform the functionality of BC technology. We conducted a quantitative analysis of monosyllable articulation in the mastoid process, condylar process, nasal bone, and infraorbital region using both female and male voices to assess OE's impact on speech perception. Our findings reveal that OE improves articulation, facilitating voice communication; however, the extent of articulation enhancement varies depending on the stimulus location and phoneme. By examining OE's role in speech perception, this research report contributes to the development and use of more effective BC technology applications.


Decompression alone versus decompression and instrumented fusion for the treatment of isthmic spondylolisthesis: a randomized controlled trial.
The most advocated surgical technique to treat symptoms of isthmic spondylolisthesis is decompression with instrumented fusion. A less-invasive classical approach has also been reported, which consists of decompression only. In this study the authors compared the clinical outcomes of decompression only with those of decompression with instrumented fusion in patients with isthmic spondylolisthesis. Eighty-four patients with lumbar radiculopathy or neurogenic claudication secondary to low-grade isthmic spondylolisthesis were randomly assigned to decompression only (n = 43) or decompression with instrumented fusion (n = 41). Primary outcome parameters were scores on the Roland Disability Questionnaire (RDQ), separate visual analog scales (VASs) for back pain and leg pain, and patient report of perceived recovery at 12-week and 2-year follow-ups. The proportion of reoperations was scored as a secondary outcome measure. Repeated measures ANOVA according to the intention-to-treat principle was performed. Decompression alone did not show superiority in terms of disability scores at 12-week follow-up (p = 0.32, 95% CI -4.02 to 1.34), nor in any other outcome measure. At 2-year follow-up, RDQ disability scores improved more in the fusion group (10.3, 95% CI 3.9-8.2, vs 6.0, 95% CI 8.2-12.4; p = 0.006, 95% CI -7.3 to -1.3). Likewise, back pain decreased more in the fusion group (difference: -18.3 mm, CI -32.1 to -4.4, p = 0.01) on a 100-mm VAS scale, and a higher proportion of patients perceived recovery as showing "good results" (44% vs 74%, p = 0.01). Cumulative probabilities for reoperation were 47% in the decompression and 13% in the fusion group (p < 0.001) at the 2-year follow-up. In patients with isthmic spondylolisthesis, decompression with instrumented fusion resulted in comparable short-term results, significantly better long-term outcomes, and fewer reoperations than decompression alone. Decompression with instrumented fusion is a superior surgical technique that should in general be offered as a first treatment option for isthmic spondylolisthesis, but not for degenerative spondylolisthesis, which has a different etiology.


Plague reservoir species throughout the world.
Plague has been known since ancient times as a re-emerging infectious disease, causing considerable socioeconomic burden in regional hotspots. To better understand the epidemiological cycle of the causative agent of the plague, its potential occurrence, and possible future dispersion, one must carefully consider the taxonomy, distribution, and ecological requirements of reservoir-species in relation either to natural or human-driven changes (e.g. climate change or urbanization). In recent years, the depth of knowledge on species taxonomy and species composition in different landscapes has undergone a dramatic expansion, driven by modern taxonomic methods such as synthetic surveys that take into consideration morphology, genetics, and the ecological setting of captured animals to establish their species identities. Here, we consider the recent taxonomic changes of the rodent species in known plague reservoirs and detail their distribution across the world, with a particular focus on those rodents considered to be keystone host species. A complete checklist of all known plague-infectable vertebrates living in plague foci is provided as a Supporting Information table.


Repeated batch production of L-phenylalanine from phenylpyruvate and NH(4)Cl by immobilized cells of Nocardia opaca under hydrogen high pressure.
Among various microbial cells examined under screening conditions, Nocardia opaca showed the highest activity for production of phenylalanine from phenylpyruvate. Here NH(4)Cl as well as amino acids were used as an amino donor for phenylalanine production. The phenylalanine production rate increased with increasing hydrogen pressure. The specific activity of phenylalanine dehydrogenase was increased by culturing N. opaca cells in nutrient broth containing 0.3% phenylalanine. As a result, the phenylalanine production rate increased from 0.69 to 4.4 mumol/min g dry cells. Immobilized cells were activated in nutrient broth containing ZnCl(2) before phenylalanine production. Phenylalanine dehydrogenase activity and cell number in the gel increased with increasing incubation time, and the maximum phenylalanine dehydrogenase activity was obtained at 36 h incubation. Then, phenylalanine was produced from phenylpyruvate, NH(4)Cl, and 100 atm H(2) with the activated immobilized cells. The rate of phenylalanine production was 0.24 mumol/min cm(3) gel. The conversion of phenylpyruvate to phenylalanine was 82%. Immobilized cells retained 76% of the initial phenylalanine production rate after 10 h reactions were repeated 11 times with two intervening reactivations.


Spatiotemporal patterns of gene expression during fetal monkey brain development.
Human DNA microarrays are used to study the spatiotemporal patterns of gene expression during the course of fetal monkey brain development. The 444 most dynamically expressed genes in four major brain areas are reported at five different fetal ages. The spatiotemporal profiles of gene expression show both regional specificity as well as waves of gene expression across the developing brain. These patterns of expression are used to identify statistically significant clusters of co-regulated genes. This study demonstrates for the first time in the primate the relevance, timing, and spatial locations of expression for many developmental genes identified in other animals and provides clues to the functions of many unknowns. Two different microarray platforms are used to provide high-throughput cross validation of the most important gene expression changes. These results may lead to new understanding of brain development and new strategies for treating and repairing disorders of brain function.


Boosting forward-time population genetic simulators through genotype compression.
Forward-time population genetic simulations play a central role in deriving and testing evolutionary hypotheses. Such simulations may be data-intensive, depending on the settings to the various parameters controlling them. In particular, for certain settings, the data footprint may quickly exceed the memory of a single compute node. We develop a novel and general method for addressing the memory issue inherent in forward-time simulations by compressing and decompressing, in real-time, active and ancestral genotypes, while carefully accounting for the time overhead. We propose a general graph data structure for compressing the genotype space explored during a simulation run, along with efficient algorithms for constructing and updating compressed genotypes which support both mutation and recombination. We tested the performance of our method in very large-scale simulations. Results show that our method not only scales well, but that it also overcomes memory issues that would cripple existing tools. As evolutionary analyses are being increasingly performed on genomes, pathways, and networks, particularly in the era of systems biology, scaling population genetic simulators to handle large-scale simulations is crucial. We believe our method offers a significant step in that direction. Further, the techniques we provide are generic and can be integrated with existing population genetic simulators to boost their performance in terms of memory usage.


Incidence of type 1 and type 2 diabetes before and during the COVID-19 pandemic in Germany: analysis of routine data from 2015 to 2021.
To date, there is no data available depicting the trend of the incidence of type 1 and type 2 diabetes across all age groups for the COVID-19 pandemic years in Germany. Based on anonymized routine data from nine million persons covered by statutory health insurance, newly diagnosed diabetes cases (ICD diagnosis E10.- to E14.-) in inpatient or (confirmed in two quarters) outpatient setting were estimated for 2015 to 2021, differentiating between type 1 and type 2 diabetes. The data were linked to the German Index of Socioeconomic Deprivation. The results are age-standardised (population as of 31 Dec. 2021). Between 2015 and 2021, the incidence of type 1 diabetes increased from 9.5 to 11.6 per 100,000 persons (from 7,007 to 8,699 new cases per year). In contrast, the incidence of type 2 diabetes tended to decline between 2015 and 2019. It continued to drop initially in 2020 during the pandemic, and then rose to 740 per 100,000 persons in 2021 (556,318 new cases per year). The diabetes type-specific seasonal pattern of previous years has changed during the pandemic years. The incidence of both type 1 and type 2 diabetes was observed to be higher in regions of high socioeconomic deprivation as compared to regions characterised by low socioeconomic deprivation. The increase in the incidence of type 1 and type 2 diabetes in 2021 may possibly be related to the COVID-19 pandemic. The high incidence and the differences by regional socioeconomic deprivation indicate that there is a need for targeted prevention strategies.


Matrix metalloproteinases MMP-2, -9 and tissue inhibitors TIMP-1, -2 expression and secretion by primary human osteoblast cells in response to titanium, zirconia, and alumina ceramics.
Osteogenic properties of bone cells are a key parameter governing osseointegration of implant devices. In this context, osteoblasts have a central role via extracellular matrix synthesis and remodeling that they regulate through different protease activity. In this study, we have analyzed the expression of two matrix metalloproteinases (MMPs): MMP-2 (72 kDa) and MMP-9 (92 kDa) and their specific tissue inhibitors TIMP-1 and TIMP-2 in primary human osteoblastic cells. The effect of titanium, zirconia, and alumina ceramics on the synthesis of these proteases was assessed using reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and zymographic analysis. Our results showed that osteoblasts express MMP-2 and -9 mRNA. Furthermore, MMP-2 mRNA expression was decreased by titanium and increased by alumina whereas zirconia did not have any significant effect. Conversely, MMP-9 mRNA expression was stimulated by titanium but decreased with zirconia, whereas alumina induced no significant changes. Zymographic analysis has evidenced pro-MMP-2 gelatinolytic activity in all cell populations with time-dependent increase profile; pro-MMP-9, however, was not detected. Enzyme-linked immunosorbent assay data confirmed the production of MMP-2 and very low levels of MMP-9. In addition, TIMP-1 was secreted in 24-h-cultured cells and increased to maximal level at 48-72 h whereas TIMP-2 levels were very low. The interactions between human osteoblasts and the studied biomaterials altered both MMP-2, -9 and TIMP-1expression indicating that biomaterials may influence osseointegration and bone remodeling.


A TTX-resistant propagating calcium action potential.
The cross-commissural (CC) cell in the supraesophageal ganglion of the giant barnacle, Balanus nubilus, was stimulated intrasomatically and antidromically in normal saline and 3 X 10(-7) M tetrodotoxin (TTX) saline. The action potential in normal saline contained both sodium and calcium components, each independently capable of propagation. Evidence that the action potential in TTX saline was calcium dependent included: the amplitude of the spike in TTX saline increased monotonically with increasing calcium; it was blocked by the calcium channel blockers La, Ni, Cd and Co; and equimolar substitution of Ba or Sr for Ca in TTX saline supported regenerative activity. Evidence that the calcium component could propagate alone included: the distance over which the calcium action potential traveled exceeded the space constant of the axon; the biphasic nature of the extracellularly recorded action potential, which propagated to the axon in the nerve root, indicated inward regenerative current was occurring on the axon; electrotonically spread potentials were clearly distinguishable from active regenerative potentials. In addition, optical experiments using the calcium indicator dye arsenazo III (28) showed that the relative magnitude of the calcium signal was not diminished along the axon in TTX saline compared with normal saline. The critical external calcium concentration necessary to support the propagating action potential in TTX saline was estimated to be between 1.25 and 5 mM. To our knowledge, this is the first direct observation of a neuron with sodium and calcium channels of apparently normal kinetics where the calcium component alone can propagate in the absence of an outward current blocker. Our results suggest that there is a greater density of calcium channels on the CC axon than on the axons of other neurons.


Exploring the burden of emergency care: predictors of stress-health outcomes in emergency nurses.
This paper is a report of a study that examines (1) whether emergency nurses differ from a general hospital nursing comparison group in terms of job and organizational characteristics and (2) to what extent these characteristics predict job satisfaction, turnover intention, work engagement, fatigue and psychosomatic distress in emergency nurses. The work environment and job characteristics of nurses are important predictors of stress-health outcomes. Emergency nurses are particularly exposed to stressful events and unpredictable work conditions. This cross-sectional study (N = 254) was carried out in 15 emergency departments of Belgian general hospitals in 2007-2008 by means of the Leiden Quality of Work Questionnaire for Nurses, the Checklist Individual Strength, the Utrecht Work Engagement Scale and the Brief Symptom Inventory. Emergency nurses report more time pressure and physical demands, lower decision authority, less adequate work procedures and less reward than a general hospital nursing population. They report, however, more opportunity for skill discretion and better social support by colleagues. Work-time demands appear to be important determinants of psychosomatic complaints and fatigue in emergency nurses. Apart from personal characteristics, decision authority, skill discretion, adequate work procedures, perceived reward and social support by supervisors prove to be strong determinants of job satisfaction, work engagement and lower turnover intention in emergency nurses. Emergency departments should be screened regularly on job and organizational characteristics to identify determinants of stress-health outcomes that can be the target of preventive interventions.


A New Injury Prevention Target: Summer Hair Braids.
Scald injuries caused by hair braiding have become increasingly common in our pediatric burn center's African-American population. This injury mechanism has received little attention in the medical literature. To guide prevention, the present study aims to characterize this novel mechanism of injury and identify patterns underlying its frequency. A retrospective cohort analysis was performed on all cases of scald injury due to hair braiding in African-American girls treated at our burn center from 2000 to 2016. Data were gathered from the patient's medical records to determine demographics, details of the injury, and treatment rendered. Patterns of injury frequency were identified and statistically analyzed. Thirty-four patients suffered scald injuries associated with hair braiding. The mean patient age was 8.4 years (SD ± 5 years). The majority of injuries (90%) occurred in the home. The frequency of injuries significantly increased starting in the year 2012, rising from less than 3% to more than 10% of evaluated injuries in African-American girls (P = .0015). Injuries were significantly more frequent in summer months. Injuries resulted in considerable usage of medical resources, including ambulance transport, hospital admission, clinic visits, prolonged wound care, and surgery. Complications developed in 41% of injured children; the most frequent complication was scarring. Pediatric scald injuries caused by braiding practices are morbid, have recently become increasingly frequent, tend to occur in the summer, and may be related to a new do-it-yourself style trend among African-American girls.


Understanding gene functions and disease mechanisms: Phenotyping pipelines in the German Mouse Clinic.
Since decades, model organisms have provided an important approach for understanding the mechanistic basis of human diseases. The German Mouse Clinic (GMC) was the first phenotyping facility that established a collaboration-based platform for phenotype characterization of mouse lines. In order to address individual projects by a tailor-made phenotyping strategy, the GMC advanced in developing a series of pipelines with tests for the analysis of specific disease areas. For a general broad analysis, there is a screening pipeline that covers the key parameters for the most relevant disease areas. For hypothesis-driven phenotypic analyses, there are thirteen additional pipelines with focus on neurological and behavioral disorders, metabolic dysfunction, respiratory system malfunctions, immune-system disorders and imaging techniques. In this article, we give an overview of the pipelines and describe the scientific rationale behind the different test combinations.


Sex disparities in overall burden of disease among HIV-infected individuals in the Veterans Affairs healthcare system.
Whether sex disparities exist in overall burden of disease among human immunodeficiency virus (HIV)-infected individuals in the Veterans Affairs healthcare system (VA) is unknown. To determine whether sex differences exist in overall burden of disease after 1 year of combined antiretroviral therapy (ART) among HIV-infected individuals in VA. Retrospective cohort study. Among patients in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC), all ART-naïve HIV-infected Veterans who received VA-based HIV care between 1996 and 2009. Overall burden of disease was measured using the VACS Index, an index that incorporates HIV (e.g. CD4 cell count) and non-HIV biomarkers (e.g. hemoglobin) and is highly predictive of all-cause mortality. Possible scores range from 0 to 164, although scores typically range from 0 to 50 for 80 % of patients in VACS-VC. A higher score indicates greater burden of disease (each additional five points indicates approximately 20 % increased 5-year mortality risk). ART adherence was measured using pharmacy data. Complete data were available for 227 women and 8,073 men. At ART initiation, compared with men, women were younger and more likely to be Black, less likely to have liver dysfunction, but more likely to have lower hemoglobin levels. Median VACS Index scores changed from ART initiation to 1 year after ART initiation: women's scores went from 41 to 28 for women (13 point improvement) and men's from 42 to 27 for men (15 point improvement). In multivariable regression, women had 3.6 point worse scores than men after 1 year on ART (p = 0.002); this difference decreased to 3.2 points after adjusting for adherence (p = 0.004). In VA, compared to men, women experienced less improvement in overall burden of disease after 1 year of HIV treatment. Further study is needed to elucidate the modifiable factors that may explain this disparity.


Dissociable electrophysiological correlates of semantic access of motor and non-motor concepts.
The notion of semantic embodiment posits that concepts are represented in the same neural sensorimotor systems that were involved in their acquisition. However, evidence in support of embodied semantics - in particular the hypothesised contribution of motor and premotor cortex to the representation of action concepts - is varied. Here, we tested the hypothesis that, consistent with semantic embodiment, sensorimotor cortices will rapidly become active while healthy participants access the meaning of visually-presented motor and non-motor action verbs. Event-related potentials revealed early differential processing of motor and non-motor verbs (164-203 ms) within distinct regions of cortex likely reflecting rapid cortical activation of differentially distributed semantic representations. However, we found no evidence for a specific role of sensorimotor cortices in supporting these representations. Moreover, we observed a later modulation of the alpha band (8-12 Hz) from 555-785 ms over central electrodes, with estimated generators within the left superior parietal lobule, which may reflect post-lexical activation of the object-directed features of the motor action concepts. In conclusion, we find no evidence for a specific role of sensorimotor cortices when healthy participants judge the meaning of visually-presented action verbs. However, the relative contribution of sensorimotor cortices to action comprehension may vary as a function of task goals.


Effect and safety of topical application of tranexamic acid to reduce perioperative blood loss in elderly patients with intertrochanteric fracture undergoing PFNA.
The specific method and dose of tranexamic acid (TXA) topically applied for intertrochanteric fractures have not been well established. The aim of this study is to investigate the efficacy and safety of TXA topically administered via our protocol for perioperative bleeding management in elderly patients with intertrochanteric fractures who underwent proximal femoral nail anti-rotation (PFNA).A retrospective comparative analysis was performed. The TXA group was composed of 82 patients with topical use of TXA, and the control group was composed of 82 patients without TXA use during the PFNA procedure. Intraoperative, total and hidden amounts of blood loss, drainage volumes, postoperative blood transfusion volumes and complications were compared between the 2 groups.The intraoperative, total and hidden amounts of blood loss and the drainage volumes were significantly lower in the TXA group than in the control group (P = .012, P < .01, P < .01, P = .014, respectively). The volume and rate of blood transfusion in the TXA group were significantly lower than those in the control group (P < .01). There were no significant differences in complications between the 2 groups (P > .05).Topical application of TXA offers an effective and safe option for reducing perioperative blood loss and transfusion in elderly patients with intertrochanteric fractures undergoing PFNA.


ATA box transcription mutation in beta-thalassemia.
DNA sequence analysis of a cloned beta-globin gene from a Chinese patient with beta-thalassemia revealed a single nucleotide substitution (A leads to G) within the ATA box homology and 28 base pairs upstream from the cap site. The patient was homozygous for this particular allele based on restriction mapping at nine different polymorphic sites in the beta-globin gene cluster. Upon transient expression in HeLa cells this gene directed the production of 3-5-fold less beta-globin mRNA than the normal beta-gene. In RNA isolated from the patient's erythroid cells beta-RNA was 10-fold less abundant relative to alpha-RNA than normal, indicating close approximation of the heterologous cell expression results and the in vivo state. These findings support the validity of such transient expression assays for analysis of phenotypes associated with naturally occurring mutant genes and establish the functional significance of nucleotide substitutions at position -28 for human beta-globin gene transcription.


Comparison of amplification enzymes for Hepatitis C Virus quasispecies analysis.
Hepatitis C virus (HCV) circulates as quasispecies (QS), whose evolution is associated with pathogenesis. Previous studies have suggested that the use of thermostable polymerases without proofreading function may contribute to inaccurate assessment of HCV QS. In this report, we compared non-proofreading (Taq) with proofreading (Advantage High Fidelity-2; HF-2) polymerases in the sensitivity, robustness, and HCV QS diversity and complexity in the second envelope glycoprotein gene hypervariable region 1 (E2-HVR1) on baseline specimens from 20 patients in the HALT-C trial and in a small cohort of 12 HCV/HIV co-infected patients. QS diversity and complexity were quantified using heteroduplex mobility assays (HMA). The sensitivities of both enzymes were comparable at 50 IU/ml, although HF-2 was more robust and slightly more sensitive than Taq. Both enzymes generated QS diversity and complexity scores that were correlated (r = 0.68; p < 0.0001, and r = 0.47; p < 0.01; Spearman's rank correlation). QS diversity was similar for both Taq and HF-2 enzymes, although there was a trend for higher diversity in samples amplified by Taq (p = 0.126). Taq amplified samples yielded complexity scores that were significantly higher than HF-2 samples (p = 0.033). HALT-C patients who were HCV positive or negative following 20 weeks of pegylated IFN plus ribavirin therapy had similar QS diversity scores for Taq and HF-2 samples, and there was a trend for higher complexity scores from Taq as compared with HF-2 samples. Among patients with HCV and HIV co-infection, HAART increased HCV QS diversity and complexity as compared with patients not receiving therapy, suggesting that immune reconstitution drives HCV QS evolution. However, diversity and complexity scores were similar for both HF-2 and Taq amplified specimens. The data suggest that while Taq may overestimate HCV QS complexity, its use does not significantly affect results in cohort-based studies of HCV QS analyzed by HMA. However, the use of proofreading enzymes such as HF-2 is recommended for more accurate characterization of HCV QS in vivo.


Polymer film formulations for the preparation of enteric pharmaceutical capsules.
Standard pharmaceutical capsules are designed to dissolve in the acidic environment of the stomach releasing the encapsulated contents for absorption. When release is required further along the gastrointestinal tract capsules can be coated with acid insoluble polymers to enable passage through the stomach and dissolution in the intestine. This paper describes formulations that have the potential to be used to produce two-piece hard capsules for post-gastric delivery without the requirement of an exterior coat. The formulation uses three polysaccharides: sodium alginate, hypromellose and gellan gum to provide acid insolubility and the ability to form capsules using standard industrial equipment. The rheological profile, on cooling, of the base material, water content and thickness of the films were shown to be comparable with those of commercial capsules. The capsules remained intact for 2 h in 100 mm HCl at pH 1.2, and within 5 min of being removed from the acid and submerged in phosphate-buffered saline at pH 6.8 were ruptured. Selected formulations from this study have potential for use as delayed release capsules.


A Delphi survey based construction and validation of test for oropharyngeal dysphagia in Indian neonates.
SLPs have a crucial need to depend on comprehensive clinical swallowing assessments to determine the presence of dysphagia in neonates. A comprehensive clinical swallowing assessment that is ethnoculturally sensitive may help to identify the presence and severity of swallowing problems in neonates. The study aimed to construct and validate the contents of a test for oropharyngeal dysphagia in Indian neonates (TOD-IN). The test for oropharyngeal dysphagia in Indian neonates (TOD-IN) was developed using the Delphi process. Five expert panelists served as participants; two rounds of electronic questionnaire-based survey was carried out to develop and validate the contents of TOD-IN. Round one rendered descriptive data that was analyzed quantitatively and qualitatively. At the end of round one, panelists unequivocally agreed on the need for research to develop a validated assessment tool for dysphagia in Indian neonates. The second round dealt with establishing the face and content validity of the final version of TOD-IN. A unanimous consensus was obtained regarding the format, scoring system, and the construct of the final version of the tool. Practicing clinicians in India are met with several challenges such as resource constraints, limited infrastructure, increasing caseload, and a lack of trained workforce. We believe that inexperienced clinicians will benefit from the structured guidance provided by TOD-IN in a restrained resource context where prioritization of patients is the key. Further studies investigating the psychometric properties of TOD-IN are in progress.


The role of endothelium in vascular response of diabetic rats.
The responses of aortas to various vasoactive agents were compared in streptozotocin-induced diabetic male rats and age-matched normal controls. There was a shift of the dose-response curve of norepinephrine (NE) to the right from streptozotocin-induced diabetic rats of 8 weeks duration as compared that of to normal rats. The median effective concentration (EC50) of NE in diabetic aortas to NE was significantly increased from 10(-7.5) M to 10(-7.2) M, while the maximum response of diabetic aortas to NE was not different from that of normal controls. In addition, the EC50 and maximum contractile response to KCl were also not different between the two groups. Meanwhile, the contractions induced by angiotensins I and II, were also significantly attenuated in diabetic aortas. The endothelium-dependent relaxation produced by carbachol in aortic rings which is precontracted with NE was significantly lower in diabetic preparations than that in age-matched control animals. The EC50 of carbachol in diabetic and normal aortas to carbachol were 2.8 x 10(-6) M vs 1.2 x 10(-6) M respectively. These results suggest that deterioration of endothelium might exist in diabetic rats.


[Incidence variation in malignancies associated or not with AIDS at an outpatient care center, 1997-2005].
In Argentina there are no published data on the incidence of AIDS (ARM) and non-AIDS related malignancies (non-ARM) in the HIV positive population. Our aim was to establish the incidence of these malignancies at an ambulatory care center between 1997 and 2005. We describe 103 cases of malignancies, 73 out of them were ARM and 30 were non-ARM. There were no differences in terms of age, gender and proportion of patients on highly active antiretroviral treatment (HAART). Among those patients with ARM, simultaneous diagnosis of malignancy and HIV infection was more frequently seen (p <0.001) and the proportion of patients with AIDS was higher (p = 0.015). Among those patients with non-ARM the mean duration of HIV infection and HAART was higher (p = 0.038 and 0.002 respectively); also was higher the mean CD4 count nadir (p = 0.009), and CD4 count at the time of malignancy diagnosis (p <0.001). The incidence of ARM was 18 cases/1000 patients-year in 1997 and dropped to 3.1 cases/1000 patients-year in 2005 (p = 0.001). The incidence of non-ARM was always lower than ARM, and similar in each year. In conclusion, ARM were more frequent than non-ARM, but their incidence dropped significantly because of massive use of HAART, while non-ARM remained stable. The high proportion of simultaneous diagnosis of ARM and HIV infection should enable much earlier HIV diagnosis.


Outpatient cataract surgery by ophthalmology residents in a county hospital.
As more people come to depend on public hospitals for health care, fewer inpatient beds are available for elective ocular surgery. At our county hospital, ophthalmology residents with faculty supervision have successfully performed cataract surgery on an outpatient basis. The postoperative outcomes of these outpatients are similar to those of a corresponding inpatient population. Outpatient cataract surgery can preserve the quality of patient care while providing potential advantages.


Levels of imperviousness in the schizophrenic's family.
That the schizophrenic is "out of contact with reality," and hence impervious to it, has been recognized from the time that the term "schizophreniz" was coined. That the members of the schizophrenic's family are also "impervious" (Lidz et al., 1958), and hence also "out of contact with reality," has only comparatively recently been recognized (Bateson et al., 1956; Wynne et al., 1958; Laing and Esterson, 1964). Imperviousness is here defined as an individual's inability (or unwillingness) to consciously grasp. become aware of, register, and acknowledge another person's interpersonal perception despite the fact that this perception has been clearly stated or presented to him.-1 This paper will focus on the levels of imperviousness that are characteristically established within the parent-child sub-system in the schizophrenix's family. This is not meant to deny the presence of imperviousness in the other subsystems within the family - i.e., between husband and wife or between the children themselves - for they, too, exist and are significant. However, to simplify matters, only imperviousness in the parent-child sub-system will be focused on here.


Distribution of RGS4 mRNA in mouse brain shown by in situ hybridization.
RGS proteins (regulators of G protein signaling) are a newly identified group of proteins that negatively regulate G proteins. Some, including RGS4, have been shown to act as GTPase-activating proteins for several members of the Gi alpha subunits and the Gq alpha subunit. However, the signaling pathways of G protein-coupled receptors regulated by RGS4 are not well understood. We isolated the mouse RGS4 cDNA to investigate the roles of RGS4 protein in mouse brain. Expression of mouse RGS4 in yeast stimulated adaptation to mating pheromone, suggesting that it negatively regulates that G protein-mediated signaling pathway. Northern blot analysis of various mouse tissues revealed that RGS4 is expressed at high levels in brain, moderately low levels in heart, and very low levels in lung, liver, and skeletal muscle. In situ hybridization of mouse brain showed RGS4 mRNA mainly in the cerebral cortex, hippocampus, anterior olfactory nucleus, piriform cortex, olfactory tubercle, caudate-putamen, nucleus accumbens, islands of Calleja, substantia nigra, amygdala, the granular layer of cerebellum, middle cerebellar peduncle, and perifacial zone. These results suggest that RGS4 is expressed in various types of cells in the brain and may regulate multiple G protein-mediated signaling pathways.


Mechanisms and Management of Asthma Exacerbations.
Acute asthma remains an important medical emergency, the most frequent cause of acute admissions in children and a major source of morbidity for adults with asthma. In all ages with asthma, the presence of exacerbations is an important defining characteristic of asthma severity. In this review, we assess the epidemiology of acute asthma, the triggers of acute exacerbations, and the mechanisms that underlie these exacerbations. We also assess current treatments that prevent exacerbations, with an emphasis on the role of type 2 airway inflammation in the context of acute exacerbations and the novel treatments that effectively target this. Finally we review current management strategies of the exacerbations themselves.


Imaging features and progression of hyperostosis cranialis interna.
HCI is a unique autosomal-dominant sclerosing bone dysplasia affecting the skull base and the calvaria, characterized by cranial nerve deficits due to stenosis of neuroforamina, whereby the mandible is affected to a lesser extent. The aim of this study is to describe the specific radiologic characteristics and course of the disorder. CT scans of affected individuals within 1 family were analyzed and compared with scans of their unaffected family members and with an age- and sex-matched control group. Linear measurements were performed of the inner table, the medulla, and the outer table of different skull locations, and attenuation (density) measurements of the same regions were recorded. Neuroforamina widths were recorded as well. There was significant thickening of the skull in the frontal, parietal, temporal, and occipital regions, which was mainly due to thickening of the inner table of the skull. The attenuation of the deposited hyperostotic bone was lower than normal cortical bone. HCI is the only genetic bone dysplasia known that is confined to the craniofacial area. The hyperostotic bone is less attenuated than normal cortical bone. The observed radiologic abnormalities explain the possible impairment of the olfactory, optic, trigeminal, facial, and vestibulocochlear nerves.


Factors influencing long-term treatment response to botulinum toxin injection for spasmodic dysphonia.
The purpose of this study was to evaluate the outcomes of long-term botulinum toxin type A (BoNTA) treatment for adductor spasmodic dysphonia (AdSD) and to determine the factors predictive of treatment response by investigating dose stability and average intervals. Retrospective cohort study. Academic tertiary medical centre. A total of 470 patients with adductor spasmodic dysphonia, who received electromyography-guided BoNTA injections over 12 years, were retrospectively enrolled in this study. The patients' demographic data, baseline voice dynamics and treatment profiles (dose, frequency and intervals) were evaluated. Factors correlating with the dose adjustment ratio (number of increasing dosing/total number of BoNTA toxin injections) and changes in intervals between injections were statistically analysed. A total of 122 patients, who received ≥ 4 injections and whose average treatment interval was < 240 days, were finally evaluated. Of them, 115 (94.3%) were female and seven (5.7%) were male, and the mean age at initial treatment was 34.89 ± 13.07 and 41.14 ± 12.71 years, respectively. On average, patients received 18.00 ± 13.33 injections (1.67 ± 0.60 U/injection) to alternating unilateral vocal folds. The treatment period was 65.07 ± 43.28 months and the mean interval between injections was 4.16 ± 1.28 months. The mean dose adjustment ratio among patients who received ≥ 4 injections was 0.15 ± 0.13, and dose changes occurred 4.36 times/patient. The patients' age and gender significantly affected the treatment response, where younger or female patients showed greater dosing variability and shorter intervals between injections. However, the baseline voice dynamics (voice handicap index, fundamental frequency, jitter, shimmer, noise-to-harmonic ratio, maximum phonation time and degree of voice breaks) did not predict the dose adjustment ratio or interval changes. In addition, patients with fluctuating doses showed lower age and higher VHI subscale scores, and patients with short-treatment interval (< 100 days) showed higher SDF0. Almost all patients received stable low doses of BoNTA over time, irrespective of the baseline results. Patients' age, gender and VHI scores were correlated with poor treatment responses, such as frequent dose changes and shorter intervals between injections.


Current management of newly diagnosed acute promyelocytic leukemia.
The management of acute promyelocytic leukemia (APL) has considerably evolved during the past two decades. The advent of all-trans retinoic acid (ATRA) and its inclusion in combinatorial regimens with anthracycline chemotherapy has provided cure rates exceeding 80%; however, this widely adopted approach also conveys significant toxicity including severe myelosuppression and rare occurrence of secondary leukemias. More recently, the advent of arsenic trioxide (ATO) and its use in association with ATRA with or without chemotherapy has further improved patient outcome by allowing to minimize the intensity of chemotherapy, thus reducing serious toxicity while maintaining high anti-leukemic efficacy. The advantage of ATRA-ATO over ATRA chemotherapy has been recently demonstrated in two large randomized trials and this option has now become the new standard of care in low-risk (i.e. non-hyperleukocytic) patients. In light of its rarity, abrupt onset and high risk of early death and due to specific treatment requirements, APL remains a challenging condition that needs to be managed in highly experienced centers. We review here the results of large clinical studies conducted in newly diagnosed APL as well as the recommendations for appropriate diagnosis, prevention and management of the main complications associated with modern treatment of the disease.


Dorsal striatal D2-like receptor availability covaries with sensitivity to positive reinforcement during discrimination learning.
Deviations in reward sensitivity and behavioral flexibility, particularly in the ability to change or stop behaviors in response to changing environmental contingencies, are important phenotypic dimensions of several neuropsychiatric disorders. Neuroimaging evidence suggests that variation in dopamine signaling through dopamine D(2)-like receptors may influence these phenotypes, as well as associated psychiatric conditions, but the specific neurocognitive mechanisms through which this influence is exerted are unknown. To address this question, we examined the relationship between behavioral sensitivity to reinforcement during discrimination learning and D(2)-like receptor availability in vervet monkeys. Monkeys were assessed for their ability to acquire, retain, and reverse three-choice, visual-discrimination problems, and once behavioral performance had stabilized, they received positron emission tomography (PET) scans. D(2)-like receptor availability in dorsal aspects of the striatum was not related to individual differences in the ability to acquire or retain visual discriminations but did relate to the number of trials required to reach criterion in the reversal phase of the task. D(2)-like receptor availability was also strongly correlated with behavioral sensitivity to positive, but not negative, feedback during learning. These results go beyond electrophysiological findings by demonstrating the involvement of a striatal dopaminergic marker in individual differences in feedback sensitivity and behavioral flexibility, providing insight into the neural mechanisms that are affected in neuropsychiatric disorders that feature these deficits.


Understanding the physical and chemical nature of the warfarin drug binding site in human serum albumin: experimental and theoretical studies.
Human serum albumin (HSA) is one of the major carrier proteins in the body and constitutes approximately half of the protein found in blood plasma. It plays an important role in lipid metabolism, and its ability to reversibly bind a large variety of pharmaceutical compounds makes it a crucial determinant of drug pharmacokinetics and pharmacodynamics. This review deals with one of the protein's major binding sites "Sudlow I" which includes a binding pocket for the drug warfarin (WAR). The binding nature of this important site can be characterized by measuring the spectroscopic changes when a ligand is bound. Using several drugs, including WAR, and other drug-like molecules as ligands, the results emphasize the nature of Sudlow I as a flexible binding site, capable of binding a variety of ligands by adapting its binding pockets. The high affinity of the WAR pocket for binding versatile molecular structures stems from the flexibility of the amino acids forming the pocket. The binding site is shown to have an ionization ability which is important to consider when using drugs that are known to bind in Sudlow I. Several studies point to the important role of water molecules trapped inside the binding site in molecular recognition and ligand binding. Water inside the protein's cavity is crucial in maintaining the balance between the hydrophobic and hydrophilic nature of the binding site. Upon the unfolding and refolding of HSA, more water molecules are trapped inside the binding site which cause some swelling that prevents a full recovery from the denatured state. Better understanding of the mechanism of binding in macromolecules such as HSA and other proteins can be achieved by combining experimental and theoretical studies which produce significant synergies in studying complex biochemical phenomena.


Genetic heterogeneity in acute intermittent porphyria: characterisation and frequency of porphobilinogen deaminase mutations in Finland.
The occurrence of different porphobilinogen deaminase mutant types in 68 patients with acute intermittent porphyria from 33 unrelated families in Finland was studied with biochemical and immunological techniques. In this fairly homogenous population four different porphobilinogen deaminase mutant types were identified and their frequencies determined. Most (about 80%) of the mutations were cross reacting immunological material (CRIM) negative, including a large kindred with normal erythrocyte porphobilinogen deaminase activities. The remainder of the families had CRIM positive mutations, including an unusual type (type 2) that had an immunoreactive, non-catalytic porphobilinogen deaminase level considerably greater than the maximal theoretical ratio of CRIM to activity of 2.0 for a single mutant allele. Correlations of the amount of residual porphobilinogen deaminase activity and the occurrence of acute clinical manifestations in each mutant type suggested that CRIM positive type 2 patients may have fewer acute symptoms.


Increased tumor vascularization is associated with the amount of immune competent PD-1 positive cells in testicular germ cell tumors.
Testicular germ cell cancer in a metastatic state is curable with a cisplatin-based first line chemotherapy. However, 10-15% of these patients are resistant to first line chemotherapy and are thus left with only palliative options. Immunotherapies and inhibition of angiogenesis used in multiple types of cancer; however, the molecular context of angiogenesis and immune checkpoints in the development and progression of testicular cancers is still unknown. Therefore, the present study performed tissue micro array based analysis of 84 patients with immunohistochemistry of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) of testicular cancer and corresponding normal appearing testis tissue, matching the results with clinical data. The results demonstrated that PD-L1 was significantly upregulated in testicular tumors and that PD-1 positive cells significantly infiltrated the testicular tumor when compared with normal testicular tissue. VEGFR2 was significantly upregulated in testicular cancer. It was indicated that PD-1 expressing cytotoxic cells may require pathologic tumor vessels to pass the blood-testis-barrier in order to migrate into the tumor. Notably, when matching the clinical data for PD-1, PD-L1 and VEGFR2 there were no differences in expression in the different International Germ Cell Cancer Collaborative Group stages of non-seminoma. These data suggested that the anti-PD-1/PD-L1 immunotherapy and the anti-angiogenic therapy, sequentially or in combination, may be a promising option in the treatment of testicular cancer.


Specific plasma membrane receptors for reovirus on rat pituitary cells in culture.
Specific cellular and host tropism is a characteristic property of many viruses mediated by the interaction of viral attachment proteins with components of the plasma membrane of the cell. We have studied the binding of virus to cells quantitatively by using type 3 reovirus labeled with 125I and GH4C1 pituitary cells in culture. Binding was rapid at both 4 degrees and 15 degrees C and was stable over a 9-h period. Unlabeled virus inhibited binding of the labeled virus in a dose-dependent manner. Scatchard analysis revealed 4,200 viral binding sites/cell with an apparent affinity of 1.2 X 10(-11) M. Also, binding of type 3 reovirus was inhibited by antibodies directed against the viral hemagglutinin and partially inhibited by type 2 reovirus, but was unaffected by type 1 reovirus or a variety of other ligands that bind to receptors on GH4C1 cells. These data indicate that reovirus binds to a high affinity, specific receptor on target cells, which may control its tropism and ultimate disease expression.


A unifying framework for metapopulation dynamics.
Many biologically important processes, such as genetic differentiation, the spread of disease, and population stability, are affected by the (natural or enforced) subdivision of populations into networks of smaller, partly isolated, subunits. Such "metapopulations" can have extremely complex dynamics. We present a new general model that uses only two functions to capture, at the metapopulation scale, the main behavior of metapopulations. We show how complex, structured metapopulation models can be translated into our generalized framework. The metapopulation dynamics arising from some important biological processes are illustrated: the rescue effect, the Allee effect, and what we term the "antirescue effect." The antirescue effect captures instances where high migration rates are deleterious to population persistence, a phenomenon that has been largely ignored in metapopulation conservation theory. Management regimes that ignore a significant antirescue effect will be inadequate and may actually increase extinction risk. Further, consequences of territoriality and conspecific attraction on metapopulation-level dynamics are investigated. The new, simplified framework can incorporate knowledge from epidemiology, genetics, and population biology in a phenomenological way. It opens up new possibilities to identify and analyze the factors that are important for the evolution and persistence of the many spatially subdivided species.


Adsorption of a single molecule of a diarylethene photochromic dye on Cu(111).
On the route to single (large) molecule unimolecular chemistry, the adsorption of a photochromic dithienylethene dye on Cu(111) at a submonolayer level has been studied by Ultra High Vacuum-Scanning Tunneling Microscopy at Low Temperature. This technique has shown that the observed adsorbed molecule's shape is compatible with an helical conformation but has also revealed a surrounding electronic corrugation due to the perturbed surface states. Careful examination of the standing wave pattern indicated that only a part of the molecule is indeed interacting with the metallic substrate. Geometric considerations were used to infer that the bridging ethene moiety could be responsible for the electronic scattering. Scanning Tunneling Spectroscopy has shown a substantial amount of charge transfer from the surface to the adsorbate. The hypothesis that this precise double bond is a reactive locus toward charge transfer processes is confirmed by the electrochemical results: this double bond is indeed reduced upon coulometric reduction on glassy carbon. Furthermore, the use of a copper cathode strongly facilitates the reduction since a +0.6 V shift was recorded.


Phenotypic changes in colonial morphology of Neisseria gonorrhoeae.
Phenotypic changes in the colonial morphology of four opacity variants of Neisseria gonorrhoeae strain F62 occurred upon growth in the presence of 14 mM pyruvate. Each of the naturally occurring opacity variants, a transparent, an opaque, and two deeply opaque, became more opaque; in addition, colonies of the opaque variants became rougher. Pyruvate did not appear to have a direct function in these colonial changes. Its effects were due to the ability of pyruvate to retard the oxidation of cysteine that was added to the medium in a defined supplement. Sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS-PAGE) of outer membranes showed that the opacity-associated proteins of the naturally occurring variants were not affected by growth in the presence of pyruvate; therefore, the induced opacity changes appear to have another basis. However, other proteins were affected. SDS-PAGE of the outer membranes, as well as of cell fractions composed predominantly of cytosol and of cytoplasmic membranes, revealed quantitative differences in the protein profiles after growth in the presence of pyruvate of each variant.


COPA syndrome caused by a novel p.Arg227Cys COPA gene variant.
COPA syndrome is a recently described and rare monogenic autosomal dominant disease caused by heterozygous missense mutations in the Coatomer Protein Subunit alpha (COPA) gene that encodes the alpha subunit of coat protein complex I (COPI). Its main clinical manifestations are inflammatory lung disease, arthritis, and renal disease. The development of inflammation in COPA syndrome maybe due to abnormal autophagic response and abnormal activation of type I interferon pathway. To date, 59 cases of COPA have been reported worldwide. In this case, Trio-whole exome sequencing was employed in the proband and her parents to identify the underlying genetic cause. COPA variant were detected and the clinical presentation of the patient was described. Herein, we report a case of a 5-year-old girl with COPA syndrome who presented with symptoms of arthritis combined with Anti-neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis (AAV), and progressive renal decline with minimal pulmonary involvement. Trio-whole exome sequencing was performed which revealed a novel heterozygous likely pathogenic variation in the COPA gene (c.679C>T,p.Arg227Cys), which was maternally inherited. Her mother was a heterozygote, but she had no phenotypic manifestations. No other mutations associated with the clinical phenotype were identified. The present identification and characterization of a novel mutation expands the genotypic spectra of the COPA syndrome and provide reference data to guide future clinical diagnosis and treatment of COPA syndrome.


Therapeutic effect of lincomycin and spectinomycin water medication on swine dysentery.
The therapeutic effects of various water medications on swine dysentery were determined in 223 pigs under controlled conditions. Carrier pigs were mixed with test animals until the disease was established. Lincomycin (22 mg/liter), spectinomycin (44 mg/liter) alone and lincomycin and spectinomycin in combination (66 mg/liter) and sodium arsanilate (161 mg/liter) in drinking water for seven days were the drugs evaluated. Negative and positive controls were also included. The experiment was terminated 41 to 43 days after initial medication. Mortality, mean value for stool consistency, incidence of dysenteric days and gross lesions of swine dysentery were the parameters measured for each treatment group.The lincomycin-spectinomycin water medication was effective for the treatment of swine dysentery. Pigs treated with lincomycin-spectinomycin had a higher survival rate, a lower incidence of dysenteric days and fewer gross lesions of swine dysentery than pigs treated with sodium arsanilate, lincomycin or spectinomycin alone or the infected controls (P < 0.05).


Ultrasonographic features of intestinal adenocarcinoma in five cats.
Adenocarcinoma, followed by lymphosarcoma, are the most common feline intestinal neoplasms. Clinicopathological, survey radiographic, and ultrasonographic findings of five cats with intestinal adenocarcinoma are reported. An abdominal mass was palpable in all five cats, but the mass could be localized to bowel in only two cats. Radiographically an abdominal mass was detected in only one cat. Ultrasonographically there was a segmental intestinal mural mass in all five cats. The mass was characterized by circumferential bowel wall thickening with transmural loss of normal sonographic wall layers. In one cat, the circumferential symmetric hypoechoic bowel wall thickening was similar to that reported for segmental lymphoma. In the other four cats, the sonographic features of the thickened bowel wall were varied, being mixed echogenicity and asymmetric in 3 cats and mixed echogenicity and symmetric in one. The results of the present report suggest that sonographic observation of mixed echogenicity segmental intestinal wall thickening in the cat represents adenocarcinoma rather than lymphosarcoma, although other infiltrative diseases should be considered.


Beyond missing heritability: prediction of complex traits.
Despite rapid advances in genomic technology, our ability to account for phenotypic variation using genetic information remains limited for many traits. This has unfortunately resulted in limited application of genetic data towards preventive and personalized medicine, one of the primary impetuses of genome-wide association studies. Recently, a large proportion of the "missing heritability" for human height was statistically explained by modeling thousands of single nucleotide polymorphisms concurrently. However, it is currently unclear how gains in explained genetic variance will translate to the prediction of yet-to-be observed phenotypes. Using data from the Framingham Heart Study, we explore the genomic prediction of human height in training and validation samples while varying the statistical approach used, the number of SNPs included in the model, the validation scheme, and the number of subjects used to train the model. In our training datasets, we are able to explain a large proportion of the variation in height (h(2) up to 0.83, R(2) up to 0.96). However, the proportion of variance accounted for in validation samples is much smaller (ranging from 0.15 to 0.36 depending on the degree of familial information used in the training dataset). While such R(2) values vastly exceed what has been previously reported using a reduced number of pre-selected markers (<0.10), given the heritability of the trait (∼ 0.80), substantial room for improvement remains.


Exposure to hypoxia rapidly induces mitochondrial channel activity within a living synapse.
One of the earliest effects of hypoxia on neuronal function is to produce a run-down of synaptic transmission, and more prolonged hypoxia results in neuronal death. An increase in the permeability of the outer mitochondrial membrane, controlled by BCL-2 family proteins, occurs in response to stimuli that trigger cell death. By patch clamping mitochondrial membranes inside the presynaptic terminal of a squid giant synapse, we have now found that several minutes of hypoxia trigger the opening of large multiconductance channels. The channel activity is induced concurrently with the attenuation of synaptic responses that occurs under hypoxic conditions. Hypoxia-induced channels are inhibited by NADH, an agent that inhibits large conductance channels produced by a pro-apoptotic fragment of BCL-xL in these synaptic mitochondria. The appearance of hypoxia-induced channels was also prevented by the caspase/cysteine protease inhibitor benzyloxycarbonyl-VAD-fluoromethyl ketone (Z-VAD-fmk), which inhibits proteolysis of BCL-xL during hypoxia. Both NADH and Z-VAD-fmk reduced significantly the rate of decline of synaptic responses during hypoxia. Our results indicate that an increase in outer mitochondrial channel activity is a very early event in the response of neurons to hypoxia and suggest that this increase in activity may contribute to the decline in synaptic function during hypoxia.


Transient global amnesia.
Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of anterograde amnesia (the inability to encode new memories), accompanied by repetitive questioning, sometimes with a retrograde component, lasting up to 24 hours, without compromise of other neurologic functions. Herein, we review current knowledge on the epidemiology, pathophysiology, clinical diagnosis, and prognosis of TGA. For this review, we conducted a literature search of PubMed, with no date limitations, using the following search terms (or combinations of them): transient global amnesia, etiology, pathophysiology, venous hypertension, migraine, magnetic resonance imaging, computed tomography, electroencephalography, prognosis, and outcome. We also reviewed the bibliography cited in the retrieved articles. Transient global amnesia is a clinical diagnosis, and recognition of its characteristic features can avoid unnecessary testing. Several pathophysiologic mechanisms have been proposed (venous insufficiency, arterial ischemia, and migrainous or epileptic phenomena), but none of them has been proved to consistently explain cases of TGA. Brain imaging may be considered and electroencephalography is recommended when episodes are brief and recurrent, but otherwise no investigations are necessary in most cases. Data on long-term prognosis are limited, but available information suggests that the relapse rate is low, the risk of stroke and seizures is not considerably increased, and cognitive outcome is generally good.


Diurnal responses of mammals to acute exposure to a hyperdynamic environment.
Acute exposure to hyperdynamic environments elicits significant depressions in core temperature in both diurnal squirrel monkeys and nocturnal rats. This study describes time of day variations in core temperature responses in squirrel monkeys and rats exposed for 70 min to a hyperdynamic environment (2 g) produced via centrifugation. Experiments were performed during the middle of the light or dark phase. After a 70-min control period, squirrel monkey resting core temperature was 38.6 +/- 0.2 (SE) and 36.8 +/- 0.2 degrees C during the day and night, respectively. At the end of a 7-min exposure to 2 g, squirrel monkey core temperature decreased 1.3 +/- 0.2 degree C during the day but remained a constant 36.8 +/- 0.4 degrees C at night. Core temperature of rats exposed to an identical 70-min 2 g profile decreased 1.5 +/- 0.4 degree C from a resting 37.1 +/- 0.6 degrees C during the day and 2.3 +/- 0.2 degrees C from a resting 37.8 +/- 0.3 degrees C at night. Thus, in both species, there were clear day-night differences in response to hyperdynamic environments, with the greatest fall in core temperature occurring during the animal's active period.


Is ictal recording mandatory in temporal lobe epilepsy? Not when the interictal electroencephalogram and hippocampal atrophy coincide.
To investigate the concordance between scalp electroencephalogram (EEG) lateralization and side of hippocampal atrophy in patients with temporal lobe epilepsy (TLE). We studied 184 consecutive patients with TLE without lesions other than those compatible with mesial temporal sclerosis. In this study, we studied specifically hippocampal atrophy and the results of scalp EEG investigation. Patients were classified according to the localization of interictal epileptiform discharges as unilateral, bilateral asymmetric, and bilateral symmetric. The EEG seizure onsets were also classified separately as unilateral, bilateral asymmetric, and bilateral symmetric. The hippocampal atrophy was determined by volumetric measurements using high-resolution magnetic resonance imaging (MRIVol). Only 3% of patients had discordance between the ictal and interictal EEG lateralizations; however, none of these had unilateral interictal EEG abnormalities. Interictal EEGs were considered unilateral in 62.0% of patients, bilateral asymmetric in 31.5%, and bilateral symmetric in 6.5%. Ictal EEGs were considered unilateral in 63.5% of patients, bilateral asymmetric in 30.0%, and bilateral symmetric in 6.5%. The MRIVol showed unilateral hippocampal atrophy in 60.9% of patients, bilateral asymmetric hippocampal atrophy in 19.0%, symmetric hippocampal atrophy in 3.8%, and normal volumes in 16.3%. There was a significant concordance between MRIVol lateralization and both interictal and ictal EEG lateralization (P<.001). All patients with unilateral hippocampal atrophy had concordant interictal and ictal EEG lateralization. Six (18.2%) of the 33 patients with bilateral asymmetric hippocampal atrophy had MRI lateralization discordant with EEG lateralization. We found a strong concordance between EEG and MRIVol lateralization in patients with TLE. Unilateral hippocampal atrophy predicted ipsilateral interictal epileptiform abnormalities and ipsilateral seizure onsets with no false lateralization. Previous studies in addition to the present series support that a concordant outpatient EEG evaluation in patients with TLE and unilateral hippocampal atrophy would obviate the need for inpatient EEG monitoring.


Evidence for a protective role for adiponectin in osteoarthritis.
Obesity has been associated with an increased risk of osteoarthritis (OA). However, the mechanism by which obesity contributes to OA remains uncertain. Adiponectin, an adipocyte-derived hormone, has shown anti-diabetic and anti-atherogenic properties. In the present study, we aimed to investigate the potential role of adiponectin in OA disease. We demonstrated that adiponectin was present in OA synovial fluid (SF) and its expression level was almost 100-fold decrease compared with that in OA plasma. FPLC and ELISA studies revealed the distribution and abundance of the adiponectin complexes in plasma and SF from patients with OA. The percentage of high molecular weight (HMW) per total adiponectin in OA SF was lower than in OA plasma, while that of the hexamer form was similar and the trimer form was higher. The expression levels of adiponectin receptors AdipoR1 and AdipoR2 were examined in human OA tissues by RT-PCR. AdipoR1 was abundantly expressed in cartilage, bone and synovial tissues, whereas AdipoR2 was rarely detected. Finally, the effects of adiponectin on primary chondrocyte functions were studied by using antibody-based protein array and RT-PCR. The patterns of mRNA expression and protein production strongly indicate that adiponectin is involved in the modulation of cartilage destruction in chondrocytes by up-regulating TIMP-2 and down-regulating IL-1beta-induced MMP-13. Together these findings clearly indicate that the adiponectin may act as a protective role in the progression of OA, and this also provide new thinking on the relationship between obesity and OA.


Sliding of a 43S ribosomal complex from the recognized AUG codon triggered by a delay in eIF2-bound GTP hydrolysis.
During eukaryotic translation initiation, 43S ribosomal complex scans mRNA leader unless an AUG codon in an appropriate context is found. Establishing the stable codon-anticodon base-pairing traps the ribosome on the initiator codon and triggers structural rearrangements, which lead to Pi release from the eIF2-bound GTP. It is generally accepted that AUG recognition by the scanning 43S complex sets the final point in the process of start codon selection, while latter stages do not contribute to this process. Here we use translation reconstitution approach and kinetic toe-printing assay to show that after the 48S complex is formed on an AUG codon, in case GTP hydrolysis is impaired, the ribosomal subunit is capable to resume scanning and slides downstream to the next AUG. In contrast to leaky scanning, this sliding is not limited to AUGs in poor nucleotide contexts and occurs after a relatively long pause at the recognized AUG. Thus, recognition of an AUG per se does not inevitably lead to this codon being selected for initiation of protein synthesis. Instead, it is eIF5-induced GTP hydrolysis and Pi release that irreversibly trap the 48S complex, and this complex is further stabilized by eIF5B and 60S joining.


Proteomic analysis of effects on natural herb additive containing immunoglobulin Yolksac (IgY) in pigs.
Thirty male pigs were infected orally with E. coli and Salmonella typhimurium, and divided into a control group and two additive groups to determine the effect of an additive mixture on the changes in protein expression. The pigs were given a food supplemented with a natural herbal additive containing immunoglobulin yolksac (IgY) at concentrations of 0.5% or 1%. On the 1st day and after eight weeks of feeding, the body weight gain, food intake and serum GOT/GPT levels were examined. The GOT/GPT levels on the 1st day were similar in the three groups. However, after eight weeks of feeding, the GOT level was significantly lower in the additive treatment groups (0.5% and 1.0%). In addition, the changes in the spleen proteome as a response to the herbal additive were examined using two-dimensional polyacrylamide gel electrophoresis. A total of 31 differentially expressed protein spots were identified by comparing the protein profiles of the control and additive treated porcine spleens. Finally, 19 proteins were detected by MALDI-TOF/MS. Overall, the proteins detected are involved in a range of biological process, such as metabolic processes, biological processes, transport, carbohydrate metabolic processes, generation of precursors and energy. In conclusion, these results support of the hypothesis that a natural herbal additive containing IgY can affect the immune regulation system and reduce the stress of microbial infections.


Microplastic inputs to the Mediterranean Sea during wet and dry seasons: The case of two Lebanese coastal outlets.
Few studies have highlighted the impact of urbanization and meteorological events on the quantity of microplastics (MPs) discharged into the sea through rivers. To evaluate this issue in the Mediterranean Basin, surface water samples were collected from two more or less urbanized Lebanese Rivers: the Nahr Ibrahim (S1) and the Nahr Antelias (S2), during dry and wet periods. A significant higher abundance of 14.02 ± 9.8 particles/L was reported in the most industrialized river S2 compared to 1.73 ± 1.38 particles/L at S1. A correlation was found between particle contamination and the season at each site. Our results indicate that the MP concentrations were highest on the first sampling day of the wet season and tended to decrease progressively with increasing cumulative precipitation. Some polymers were identified only during one season. Meteorological events should be taken more specifically into account in order to define the influx of plastic pollution into coastal waters more accurately.