Verbal Fluency Test in Children with Neurodevelopmental Disorders.
Background The verbal fluency task is a widely used psychometric test to account for cognitive functions, particularly, verbal and executive functions. Being an easy and fast test to administer, it is a good neuropsychological tool in low technology environments. Our objective was to analyze the performance in verbal fluency of Spanish-speaking children with neurodevelopmental disorders. Methods We performed a retrospective cross-sectional study to analyze the performance of children who had undergone a verbal fluency test in a neuropsychological assessment. Results We included 115 participants. There were 41 (35.65%) participants with low intellectual performance (LIP), 63 (54.78%) with attention deficit hyperactive disorder (ADHD), and 11(9.57%) participants with dyslexia. Participants with LIP showed lower phonological and semantic fluency scores than participants with ADHD, and a lower performance in semantic fluency than the dyslexia group. The probability of having LIP was 6.12 times greater when somebody had a scale score lower than 7 in the phonological task and it was 7.9 times greater when the scale score was lower than 7 in the semantic task. Conclusion There was a direct relationship between Full Scale Intelligence Quotient and verbal fluency test performance, the latter being a brief and effective neuropsychological test that can reveal deficit not only in executive functions and verbal abilities but also detect LIP.


Rights and health care--beyond equity and efficiency.
Economic analysis in general has difficulty accommodating the concept of rights. The economic analysis of health care in particular proposes triage as the model of a rational delivery system, with no place for traditional ethical limits and obligations. Familiar arguments based on resource constraints do not prove that rights cannot reasonably be recognized. Nor are rights in general and rights in medical care in particular adequately respected by attending to considerations of just distribution or equity. Rights in medical care are different from rights to medical care, and must be respected in any decent, advanced society. That such rights may be overridden in emergencies does not mean that respect for rights is not a constraint upon the pursuit of equity and efficiency.


In vitro activity of tigecycline against gram-positive and gram-negative pathogens as evaluated by broth microdilution and Etest.
The current surveillance establishes the activity profile of tigecycline against recent clinical U.S. isolates of target pathogens. Findings from a distributed surveillance that utilized Etest yielded a tigecycline activity profile that varied from that observed in a separate centralized broth microdilution (BMD) surveillance (D. C. Draghi et al., Poster D-0701, 46th Intersci. Conf. Antimicrob. Agents Chemother., San Francisco, CA). Differences were noted among Acinetobacter spp. and Serratia marcescens and, to a lesser extent, with Streptococcus pyogenes. To address whether these differences were due to discordance in testing methodology or to variations among the analyzed populations, isolates from the current surveillance were concurrently tested by BMD and Etest. In all, 1,800 Staphylococcus aureus, 259 S. pyogenes, 226 Streptococcus pneumoniae, 93 Enterococcus faecalis, 1,356 Enterobacteriaceae, and 227 Acinetobacter baumannii strains were evaluated. Tigecycline had potent activity by BMD, with >99.6% susceptibility (%S) observed for all pathogens with interpretive criteria, excluding Enterobacter cloacae (98.3% S) and E. faecalis (86.0% S), and MIC(90)s ranged from 0.03 mug/ml (S. pyogenes/S. pneumoniae) to 1 mug/ml (Enterobacteriaceae/A. baumannii). Similar profiles were observed by Etest, with the exception of A. baumannii, although for most evaluated pathogens Etest MICs trended one doubling-dilution higher than BMD MICs. Major or very major errors were infrequent, and a high degree of essential agreement was observed, excluding A. baumannii, S. marcescens, and S. pneumoniae, for which >/=4-fold differences in MICs were observed for 29, 27.1, and 34% of the isolates, respectively. Further analysis regarding the suitability of the tigecycline Etest for testing S. marcescens, Acinetobacter spp., and S. pneumoniae is warranted.


Testing for vitamin D and other trends in the clinical management of osteoporosis.
This descriptive paper identifies some salient trends in the Australian management of osteoporosis. Changes in pharmaceutical consumption and medical utilisation are analysed. The total national consumption of four pharmaceuticals is estimated. From 2001 to 2011, the consumption of bisphosphonates and vitamin D increased. After 2006, the management rate for osteoporosis decreased. During the first decade of the millennia, the total cost of vitamin D tests has increased significantly within many health care jurisdictions worldwide. Australia reports a 100-fold increase. Legitimately, concerns regarding the economic effectiveness of this test exist. The purpose of this paper is to identify what other salient clinical trends could affect the efficacy of this test when treating osteoporosis. Longitudinal data from two Australian datasets are analysed. The first are data obtained from Medicare Australia, which report pharmaceutical consumption. The second are data obtained from a national survey of general practitioners. The management of osteoporosis has been characterised by a movement away from single to combination formularies. The consumption of calcium carbonate has declined, and the use of bisphosphonates has increased. While the gross consumption of risedronate increased steadily over the decade (8.4 to 186.5 kg), the consumption of alendronate declined after 2007. The consumption of vitamin D (over-the-counter and prescription) has increased from 0.58 to 2.8 kg over the decade. While prescription vitamin D comprised just 10% of the total, its consumption has undergone a 20-fold increase since 2006. Importantly, we can also report that the management of osteoporosis by Australia's general practitioners increased steadily until 2007-2008, before declining by 36%. Further research is required to determine possible casual relationships that may exist between these data. Until a formal economic evaluation of vitamin D testing in this clinical setting is completed, no conclusions regarding its economic effectiveness should be drawn.


Selective release of lysosomal hydrolases from phagocytic cells by cytochalasin B.
1. Cytochalasin B (10mug/ml) enhances the release of rabbit polymorphonuclear leucocyte lysosomal acid hydrolases induced by retinol (vitamin A alcohol). 2. This effect is seen at doses of the vitamin that cause selective release of acid hydrolases and those causing more general enzyme release indicated by the loss of lactate dehydrogenase. 3. Cytochalasin B (2-50mug/ml) has no effect on the release of sedimentable acid hydrolases of intact granules obtained from disrupted polymorphonuclear leucocytes. 4. Cytochalasin B (2-10mug/ml) causes a time- and dose-dependent release of mouse peritoneal macrophage acid hydrolases. 5. This effect is selective at all doses of cytochalasin B used, since no release of lactate dehydrogenase, malate dehydrogenase and leucine 2-naphthylamidase was detected. 6. Treatment with cytochalasin B at doses of up to 10mug/ml for as long as 72h did not significantly change the total activities of any of the enzymes measured. 7. The lack of toxicity of cytochalasin B was shown by dye-exclusion tests and its failure to release radioactive colloidal gold stored in secondary lysosomes.


Nuclear Factor-κB-inducing Kinase Is Expressed in Synovial Endothelial Cells in Patients with Early Arthritis and Correlates with Markers of Inflammation: A Prospective Cohort Study.
The nuclear factor-κB (NF-κB) family of transcription factors is strongly involved in synovial inflammation. We have previously shown that NF-κB-inducing kinase (NIK) is a key regulator of inflammation-induced angiogenesis in rheumatoid arthritis (RA) synovial tissue (ST). Here, we investigated synovial NIK expression in patients with early arthritis and in autoantibody-positive individuals at risk of developing RA. ST biopsies were obtained by arthroscopy from 154 patients with early arthritis (duration < 1 yr) with various diagnoses and 54 IgM rheumatoid factor-positive and/or anticitrullinated protein antibodies-positive individuals without evidence of arthritis. ST was stained for NIK and endothelial cell (EC) markers. Additionally, measures of disease activity were collected and contrast-enhanced magnetic resonance imaging (MRI) was performed in a subset of these patients. In patients with early arthritis, NIK was predominantly expressed in EC of small blood vessels. Further, NIK expression correlated with erythrocyte sedimentation rate (r 0.184, p = 0.024), C-reactive protein (r 0.194, p = 0.017), joint swelling (r 0.297, p < 0.001), synovial immune cell markers (lining r 0.585, p < 0.001; sublining macrophages r 0.728, p < 0.001; T cells r 0.733, p < 0.001; and B cells r 0.264, p = 0.040), MRI effusion (r 0.665, p < 0.001), MRI synovitis (r 0.632, p < 0.001), and MRI total score (r 0.569, p < 0.001). In 18.5% of autoantibody-positive individuals, ST NIK(+)EC were present, but this was not predictive of the development of arthritis. NIK(+)EC are present in the earliest phase of synovial inflammation and may be indicative of high angiogenic activity in the inflamed ST. Therefore, NIK(+)EC may play an important role in the persistence of synovitis. Collectively, our data underscore the importance of angiogenesis in synovial inflammation and identify NIK as a potential therapeutic target in arthritis.


Alternative development in Polystoma gallieni (Platyhelminthes, Monogenea) and life cycle evolution.
Considering the addition of intermediate transmission steps during life cycle evolution, developmental plasticity, canalization forces and inherited parental effect must be invoked to explain new host colonization. Unfortunately, there is a lack of experimental procedures and relevant models to explore the adaptive value of alternative developmental phenotypes during life cycle evolution. However, within the monogeneans that are characterized by a direct life cycle, an extension of the transmission strategy of amphibian parasites has been reported within species of Polystoma and Metapolystoma (Polyopisthocotylea; Polystomatidae). In this study, we tested whether the infection success of Polystoma gallieni within tadpoles of its specific host, the Stripeless Tree Frog Hyla meridionalis, differs depending on the parental origin of the oncomiracidium. An increase in the infection success of the parasitic larvae when exposed to the same experimental conditions as their parents was expected as an adaptive pattern of non-genetic inherited information. Twice as many parasites were actually recorded from tadpoles infected with oncomiracidia hatching from eggs of the bladder parental phenotype (1.63 ± 0.82 parasites per host) than from tadpoles infected with oncomiracidia hatching from eggs of the branchial parental phenotype (0.83 ± 0.64 parasites per host). Because in natural environments the alternation of the two phenotypes is likely to occur due to the ecology of its host, the differential infection success within young tadpoles could have an adaptive value that favors the parasite transmission over time.


Optimal microRNA Sequencing Depth to Predict Cancer Patient Survival with Random Forest and Cox Models.
(1) Background: tumor profiling enables patient survival prediction. The two essential parameters to be calibrated when designing a study based on tumor profiles from a cohort are the sequencing depth of RNA-seq technology and the number of patients. This calibration is carried out under cost constraints, and a compromise has to be found. In the context of survival data, the goal of this work is to benchmark the impact of the number of patients and of the sequencing depth of miRNA-seq and mRNA-seq on the predictive capabilities for both the Cox model with elastic net penalty and random survival forest. (2) Results: we first show that the Cox model and random survival forest provide comparable prediction capabilities, with significant differences for some cancers. Second, we demonstrate that miRNA and/or mRNA data improve prediction over clinical data alone. mRNA-seq data leads to slightly better prediction than miRNA-seq, with the notable exception of lung adenocarcinoma for which the tumor miRNA profile shows higher predictive power. Third, we demonstrate that the sequencing depth of RNA-seq data can be reduced for most of the investigated cancers without degrading the prediction abilities, allowing the creation of independent validation sets at a lower cost. Finally, we show that the number of patients in the training dataset can be reduced for the Cox model and random survival forest, allowing the use of different models on different patient subgroups.


Hormonal regulation of retinoic acid-binding proteins in the mammary gland.
A cytosolic retinoic acid-binding (RAB) protein that sediments specifically as a 2S component on sucrose density gradients was detected in the mammary glands of virgin, pregnant and lactating rats. Mammary cytosol from pregnant rats contained significantly higher concentrations of cytosolic RAB protein than did cytosol from either virgin or lactating rats. The glands of pregnant animals exhibited increased concentration of cytosolic RAB protein during the first 5 days of pregnancy, and a steady decline was observed thereafter. The concentration of cytosolic RAB protein dropped to the value observed during lactation on the day 20 of pregnancy. Moreover, throughout lactation, low concentrations of cytosolic RAB protein were maintained. Daily treatment of virgin and lactating animals with 5 micrograms of oestradiol-17 beta for 1 week increased cytosolic RAB protein to concentrations comparable with those seen in pregnant rats. Progesterone, however, did not affect the mammary cytosolic RAB protein content of virgin rats. These results suggest hormonal involvement in the regulation of cytosolic RAB protein concentration of mammary gland during differentiation.


Enhanced enzymatic activity of Candida species responsible for oral candidiasis in renal transplant recipients.
Renal transplant recipients (RTRs) are regarded to be predisposed to oral candidiasis. This study was undertaken to evaluate the activity of hydrolytic enzymes in strains causing oral candidiasis in RTR. A total of 123 Candida albicans and 10 Candida krusei strains were isolated from 200 RTRs (39 RTRs suffered from symptomatic candidiasis, the remaining patients had no clinical symptoms of infection). All fungi were identified based on routine mycological procedures. Because of a small number of non-albicans strains, only C. albicans isolates were compared for enzymatic activity. The activity of 19 hydrolytic enzymes was assessed by API ZYM(®) test. The usage of mycophenolate mofetil was connected with higher ratio of clinically apparent oral candidiasis compared to immunosuppressive regimens without this drug (74.4% vs. 46.8%, respectively, P < 0.01). Candida albicans from RTRs showed higher enzymatic activity compared with strains from immunocompetent patients. Only two enzymes were found to be more active in C. albicans causing symptomatic candidiasis in RTRs (cystine arylamidase: P = 0.001, and α-fucosidase: P = 0.01) compared with saprophytic strains. Atrophic candidiasis showed higher activity of esterase lipase (C8) and α-mannosidase compared with the pseudomembraneous type. We suggest that the enhanced enzymatic activity is responsible for higher invasiveness of Candida residing in the oral cavity of RTRs.


Does Length of Extended Resection Beyond Transition Zone Change Clinical Outcome for Hirschsprung Pull-Through?
A proximal resection margin greater than 5 cm from the intra-operative histologically determined transition zone has been deemed necessary to minimize the risk of transition zone pull-through. This extended resection may require the sacrifice of vascular supply and even further bowel resection. The impact of extended proximal resection margin on post-operative complications and functional outcomes is unclear. A retrospective chart review of patients who underwent primary pull-through for Hirschsprung disease at a single institution between January 2008 and December 2022 was performed. An adequate proximal margin was defined by a circumferential normally ganglionated ring and absence of hypertrophic nerves. The extended margin was defined as the total length of proximal colon with normal ganglion cells and without hypertrophic nerves. Fecal incontinence severity was assessed with the Pediatric Fecal Incontinence Severity Score (PFISS). Eighty seven patients met criteria for inclusion. Median age at primary pull-through was 17 days (IQR 10-92 days), 55% (n = 48) of patients had an extended proximal margin (EPM) ≤ 5 cm, and 45% (n = 39) had an EPM > 5 cm. An EPM ≤5 cm was not associated with increased rates of Hirschsprung associated enterocolitis (≤5 cm 43%, >5 cm 39%, P = 0.701), diversion post pull-through (≤5 cm 10%, >5 cm 5%, P = 0.367) or reoperation for transition zone pull-through (≤5 cm 3%, >5 cm 0%, P = 0.112). EPM ≤5 cm had more frequent involuntary daytime bowel movements (P = 0.041) and more frequent voluntary bowel movements (P = 0.035). There were no differences in other measures of fecal incontinence severity. Shorter proximal extended margins beyond the adequate ganglionated margin do not significantly impact post-operative complication rates and have an unclear effect on fecal incontinence. Case Control. Level III.


Use of hospitalists and office-based primary care physicians' productivity.
Growth in the care of hospitalized patients by hospitalists has the potential to increase the productivity of office-based primary care physicians (PCPs) by allowing them to focus on outpatient practice. Our aim was to examine the association between utilization of hospitalists and the productivity of office-based PCPs. The cross-sectional study was conducted using the 2008 Health Tracking Physician Survey Restricted Use File linked to the Area Resource File. We analyzed a total of 1,158 office-based PCPs representing a weighted total of 97,355 physicians. Utilization of hospitalists was defined as the percentage of a PCP's hospitalized patients treated by a hospitalist. The measures of PCPs' productivity were: (1) number of hospital visits per week, (2) number of office and outpatient clinic visits per week, and (3) direct patient care time per visit. We found that the use of hospitalists was significantly associated with a decreased number of hospital visits. The use of hospitalists was also associated with an increased number of office visits, but this was only significant for high users. Physicians who used hospitalists for more than three-quarters of their hospitalized patients had an extra 8.8 office visits per week on average (p = 0.05), which was equivalent to a 10 % increase in productivity over the predicted mean of 87 visits for physicians who did not use hospitalists. We did not find any significant differences in direct patient care time per visit. Our study demonstrates that the increase in productivity for the one-third of PCPs who use hospitalists extensively may not be sufficient to offset the current loss of PCP workforce. However, our findings provide cautious optimism that if more PCPs effectively and efficiently used hospitalists, this could help mitigate a PCP shortage and improve access to primary care services.


Phylogenetics Identifies Two Eumetazoan TRPM Clades and an Eighth TRP Family, TRP Soromelastatin (TRPS).
Transient receptor potential melastatins (TRPMs) are most well known as cold and menthol sensors, but are in fact broadly critical for life, from ion homeostasis to reproduction. Yet, the evolutionary relationship between TRPM channels remains largely unresolved, particularly with respect to the placement of several highly divergent members. To characterize the evolution of TRPM and like channels, we performed a large-scale phylogenetic analysis of >1,300 TRPM-like sequences from 14 phyla (Annelida, Arthropoda, Brachiopoda, Chordata, Cnidaria, Echinodermata, Hemichordata, Mollusca, Nematoda, Nemertea, Phoronida, Priapulida, Tardigrada, and Xenacoelomorpha), including sequences from a variety of recently sequenced genomes that fill what would otherwise be substantial taxonomic gaps. These findings suggest: 1) the previously recognized TRPM family is in fact two distinct families, including canonical TRPM channels and an eighth major previously undescribed family of animal TRP channel, TRP soromelastatin; 2) two TRPM clades predate the last bilaterian-cnidarian ancestor; and 3) the vertebrate-centric trend of categorizing TRPM channels as 1-8 is inappropriate for most phyla, including other chordates.


A two-part, double-blind, placebo-controlled trial of exogenous melatonin in REM sleep behaviour disorder.
Rapid eye movement (REM) sleep behaviour disorder (RBD) has been suggested to predict the development of neurodegenerative disorders. Patients with RBD are acting out dream behaviour associated with loss of normal muscle atonia of REM sleep. The aim of the present study was to confirm that exogenous melatonin improves RBD. Eight consecutively recruited males (mean age 54 years) with a polysomnographically (PSG) confirmed diagnosis of RBD were included in a two-part, randomized, double-blind, placebo-controlled cross-over study. Patients received placebo and 3 mg of melatonin daily in a cross-over design, administered between 22:00 h and 23:00 h over a period of 4 weeks. PSG recordings were performed in all patients at baseline, at the end of Part I of the trial and at the end of Part II of the trial. Compared to baseline, melatonin significantly reduced the number of 30-s REM sleep epochs without muscle atonia (39% versus 27%; P = 0.012), and led to a significant improvement in clinical global impression (CGI: 6.1 versus 4.6; P = 0.024). Interestingly, the number of REM sleep epochs without muscle atonia remained lower in patients who took placebo during Part II after having received melatonin in Part I (-16% compared to baseline; P = 0.043). In contrast, patients who took placebo during Part I showed improvements in REM sleep muscle atonia only during Part II (i.e. during melatonin treatment). The data suggest that melatonin might be a second useful agent besides clonazepam in the treatment of RBD.


Early postnatal additional high-dose oral vitamin A supplementation versus placebo for 28 days for preventing bronchopulmonary dysplasia or death in extremely low birth weight infants.
Prematurity and the associated risk for bronchopulmonary dysplasia (BPD) remain a significant threat to extremely low birth weight (ELBW) infants. Vitamin A has been considered a therapeutic alternative in reducing the rate of BPD and mortality. To investigate whether early postnatal, additional high-dose oral vitamin A supplementation for 28 days is more efficient in reducing BPD or death in ELBW infants than placebo treatment. This is a multicenter, double-blind RCT comparing postnatal high-dose oral vitamin A supplementation (5,000 IU vitamin A/kg/day vs. placebo) for 28 days in ELBW neonates requiring mechanical ventilation, noninvasive ventilatory support or supplemental oxygen at 24 h of age. The primary end point is the proportion of children who died before 36 weeks' gestational age or developed moderate or severe BPD. BPD is defined as the need for supplemental oxygen to maintain SaO2 of ≥92% at rest at 36 weeks' postmenstrual age (PMA). Clinical secondary end points include the following: BPD (including mild form), intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, total number of days of mechanical ventilation and oxygen supplementation, and safety and tolerability of high-dose vitamin A supplementation. The results of the NeoVitaA trial will provide robust data with regard to the efficacy of high-dose oral vitamin A supplementation in reducing the incidence of BPD or death at 36 weeks' PMA in ELBW infants.


Hormone-induced filopodium formation and movement of pigment, carotenoid droplets, into newly formed filopodia.
Treatment of cultured goldfish xanthophores by hormone (ACTH) or c-AMP induces not only pigment dispersion, but subsequent outgrowth of processes, and pigment translocation into these processes. These latter effects are shown to proceed as follows: First the edge of the cytoplasmic lamellae takes on a scalloped contour with numerous protrusions. These presumably serve as nucleation centers where short microfilament bundles are assembled. Later, the microfilament bundles elongate ("grow"), often resulting in an extension of the protrusions to become filopodia while the proximal end of the microfilaments penetrates into the thicker portion of the cellular process which now houses the pigment, i.e., the carotenoid droplets. Carotenoid droplets appear to migrate along the microfilament bundles, or cytoplasmic channels associated with them, into the filopodia. Finally, some of the filopodia become broader, thicker and laden with carotenoid droplets and are then recognized by light microscopy as pigmented cellular processes. The microfilaments have been shown to be actin filaments by their thickness, the size of their subunits, and decoration by heavy meromyosin. Evidence is presented which suggests that the growth of these actin filaments may come about by recruitment from short F-actin strands found in random orientation in adjacent areas.


Stimulation of human eosinophil and neutrophil polymorphonuclear leukocyte chemotaxis and random migration by 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid.
A human platelet lipoxygenase-generated product of arachidonic acid, identified by thin-layer chromatographic and mass spectrometric properties as 12-L-hydroxy-5,8,10,14-eicosatertraenoic acid (HETE), was selectively chemotactic in vitro for human polymorphonuclear leukocytes (PMN), as compared to mononuclear leukocytes, with a preference for eosinophils. Preincubation of PMN with partially-purified HETE at peak chemotactic concentrations of 8-24 mug/ml reduced their random and chemotactic migration and stimulated the activity of their hexose monophosphate shunt; minimally chemotactic concentrations of 0.03-1 mug/ml enhanced PMN random migration without influencing other functions. HETE may thus be capable of preferentially attracting eosinophils to foci of tissue reaction associated with platelet activation.


Terahertz continuous wave system using phase shift interferometry for measuring the thickness of sub-100-μm-thick samples without frequency sweep.
A terahertz continuous wave system is demonstrated for thickness measurement using Gouy phase shift interferometry without frequency sweep. One arm of the interferometer utilizes a collimated wave as a reference, and the other arm applies a focused beam for sample investigation. When the optical path difference (OPD) of the arms is zero, a destructive interference pattern is produced. Interference signal intensity changes induced by the OPD changes can be easily predicted by calculations. By minimizing the difference between the measured and the calculated signal against the OPD, the thicknesses of sub-100-μm-thick samples are determined at 625 GHz.


HIV-1 transcriptional regulation in the central nervous system and implications for HIV cure research.
Human immunodeficiency virus type-1 (HIV-1) invades the central nervous system (CNS) during acute infection which can result in HIV-associated neurocognitive disorders in up to 50% of patients, even in the presence of combination antiretroviral therapy (cART). Within the CNS, productive HIV-1 infection occurs in the perivascular macrophages and microglia. Astrocytes also become infected, although their infection is restricted and does not give rise to new viral particles. The major barrier to the elimination of HIV-1 is the establishment of viral reservoirs in different anatomical sites throughout the body and viral persistence during long-term treatment with cART. While the predominant viral reservoir is believed to be resting CD4(+) T cells in the blood, other anatomical compartments including the CNS, gut-associated lymphoid tissue, bone marrow, and genital tract can also harbour persistently infected cellular reservoirs of HIV-1. Viral latency is predominantly responsible for HIV-1 persistence and is most likely governed at the transcriptional level. Current clinical trials are testing transcriptional activators, in the background of cART, in an attempt to purge these viral reservoirs and reverse viral latency. These strategies aim to activate viral transcription in cells constituting the viral reservoir, so they can be recognised and cleared by the immune system, while new rounds of infection are blocked by co-administration of cART. The CNS has several unique characteristics that may result in differences in viral transcription and in the way latency is established. These include CNS-specific cell types, different transcription factors, altered immune surveillance, and reduced antiretroviral drug bioavailability. A comprehensive understanding of viral transcription and latency in the CNS is required in order to determine treatment outcomes when using transcriptional activators within the CNS.


Legislative aspects of hazardous waste management.
In the fall of 1976 Congress enacted the Resource Conservation and Recovery Act, commonly referred to as RCRA. The objective of the statute is to create an orderly system for the generation, handling and disposal of hazardous waste by means of a comprehensive tracking and record keeping mechanism. RCRA does not regulate directly by statute so much as it delegates rule making authority to the U.S. Environmental Protection Agency. Pursuant to its mandate to develop regulations in accordance with the broad criteria of RCRA, EPA has published extensive regulations. These regulations address hazardous waste generation, transportation, treatment, storage and handling and its final disposal. The statute also offers remedies available to both EPA and the public at large to ensure enforcement of the provisions of RCRA and the EPA regulations. Additionally, it sets guidelines for states to implement their own hazardous waste management programs. This article is intended to introduce this complicated statutory/regulatory package to scientists and health professionals. It outlines the provisions of RCRA and the EPA regulations, abbreviates early judicial decisions interpreting these provisions and sets forth a brief description of various state approaches to hazardous waste management.


Rab40C is a novel Varp-binding protein that promotes proteasomal degradation of Varp in melanocytes.
Varp (VPS9-ankyrin repeat protein) was originally identified as an activator of small GTPase Rab21 through its VPS9 domain, but it has subsequently been shown to function as a Rab32/38 effector through its first ANKR1 domain. Although these functions of Varp are important for melanogenesis, Varp contains a second ANKR2 domain, whose function remained completely unknown. Here we identified Rab40C, an atypical Rab containing a SOCS box that recruits a ubiquitin ligase complex, as a novel ANKR2-binding protein and investigated its involvement in melanogenic enzyme trafficking in melanocytes. The results showed that overexpression of Rab40C in melanocytes caused a dramatic reduction in melanogenic enzyme Tyrp1 signals by promoting proteasomal degradation of Varp in a SOCS-box-dependent manner and that knockdown of Rab40C in melanocytes caused an increase in the amount of Varp. Intriguingly, Rab40C knockdown also caused a dramatic reduction in Tyrp1 signals, the same as Varp overexpression did. These findings indicated that Rab40C is a previously unexpected regulator of Tyrp1 trafficking in melanocytes through controlling the proteasomal degradation of Varp.


Utility of the Visceral Adiposity Index and Hypertriglyceridemic Waist Phenotype for Predicting Incident Hypertension.
The aim of this study was to assess the utility of the visceral adiposity index (VAI) and the hypertriglyceridemic waist (HTGW) phenotype as possible hypertension (HTN) predictors in a high-risk population without diabetes and HTN. Incident HTN over a 7-year follow-up was assessed among 1,375 first-degree non-diabetic and non-hypertensive relatives of consecutive patients with type 2 diabetes who were 30 to 70 years of age. HTN was defined as a blood pressure reading ≥140/90 mm Hg or the use of antihypertensive medications. We examined the incidence of HTN across VAI quintiles and four groups defined according to baseline fasting serum triglyceride (TG) levels and waist circumference (WC). The VAI and the HTGW phenotype at baseline were related to an increased risk for HTN. In comparison with the lowest VAI quintile, the highest VAI quintile showed a significant associated with HTN in an age- and gender-adjusted model (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.07 to 2.55). Those with HTGW were 2.3 times (OR, 2.27; 95% CI, 1.54 to 3.35) more likely to develop HTN than those with a normal WC and normal TG levels. Greater VAI values weakly predicted HTN, whereas the HTGW phenotype was a stronger predictor of incident HTN in an Iranian high-risk population.


Effect of early nutrition on deaths due to severe traumatic brain injury.
Traumatic brain injury (TBI) remains a serious public health crisis requiring continuous improvement in pre-hospital and inhospital care. This condition results in a hypermetabolic state that increases systemic and cerebral energy requirements, but achieving adequate nutrition to meet this demand has not been a priority in reducing death due to TBI. The effect of timing and quantity of nutrition on death within the first 2 weeks of injury was analyzed in a large prospective database of adult patients with severe TBI in New York State. The study is based on 797 patients with severe TBI (Glasgow Coma Scale [GCS] score < 9) treated at 22 trauma centers enrolled in a New York State quality improvement program between 2000 and 2006. The inhospital section of the prospectively collected database includes information on age, initial GCS score, weight and height, results of CT scanning, and daily parameters such as pupillary status, arterial hypotension, GCS score, and number of calories fed per day. Patients who were not fed within 5 and 7 days after TBI had a 2- and 4-fold increased likelihood of death, respectively. The amount of nutrition in the first 5 days was related to death; every 10-kcal/kg decrease in caloric intake was associated with a 30-40% increase in mortality rates. This held up even after controlling for factors known to affect mortality, including arterial hypotension, age, pupillary status, initial GCS score, and CT scan findings. Nutrition is a significant predictor of death due to TBI. Together with prevention of arterial hypotension, hypoxia, and intracranial hypertension it is one of the few therapeutic interventions that can directly affect TBI outcome.


[Usefulness of 99mTc-DTPA renography and diuretic renography in predicting successful stone discharge following outpatient ESWL in patients with a single ureteral stone].
We analyzed the 99mTc-DTPA renogram with and without diuresis to predict the possibility of stone discharge on the outpatient basis by renogram patterns. Between October, 1993 and December, 1995, 99mTc-DTPA renography was performed in 79 patients with a single ureteral stone. The 99mTc-DTPA renogram pattern was classified into the three types of normal function, obstruction and lower function patterns and the complete stone discharge rate was 93, 63 and 25%, respectively. In addition, diuretic renography using Furosemide was performed in patients with an obstruction pattern and the three renogram patterns of return to the normal curve, a diuretic response and no response were obtained; the complete stone discharge rate was 44, 65.3 and 93%, respectively. From this study, patients with a single ureteral stone with a normal pattern on the regular DTPA renogram and patients with no response pattern on the diuretic renogram, even if in such patients an obstructive pattern was seen on the regular DTPA renogram, seem to be a good candidate for obtaining a high rate of a stone discharge with extracorporeal shock wave lithotripsy (ESWL) treatment in the outpatients basis.


Empirical evaluation of data transformations and ranking statistics for microarray analysis.
There are many options in handling microarray data that can affect study conclusions, sometimes drastically. Working with a two-color platform, this study uses ten spike-in microarray experiments to evaluate the relative effectiveness of some of these options for the experimental goal of detecting differential expression. We consider two data transformations, background subtraction and intensity normalization, as well as six different statistics for detecting differentially expressed genes. Findings support the use of an intensity-based normalization procedure and also indicate that local background subtraction can be detrimental for effectively detecting differential expression. We also verify that robust statistics outperform t-statistics in identifying differentially expressed genes when there are few replicates. Finally, we find that choice of image analysis software can also substantially influence experimental conclusions.


Bioprospecting of xylanase producing fungal strains: Multilocus phylogenetic analysis and enzyme activity profiling.
The study aims to explore potential xylanase-producing indigenous fungi isolated from soil and vegetable wastes containing plant degraded matter, reporting multilocus phylogenetic analysis and xylanase enzyme activity from selective strains. Four potential xylanolytic fungi were identified through distinct primary and secondary screening of 294 isolates obtained from the samples. Morphological characterization and multigene analysis (ITS rDNA, 18S rDNA, LSU rDNA, β-tubulin, and actin gene) confirmed them as Aspergillus sp. AUMS56, Aspergillus tubingensis AUMS60 and AUMS64, and Aspergillus fumigatus AUKEMS24; achieving crude xylanase activities (through submerged fermentation using corn cobs) of 18.9, 32.29, 30.68, and 15.82 U ml-1 , respectively. AUMS60 and AUMS64 (forming lineage with A. tubingensis and Aspergillus niger in the same phylogroup with 100% Bayesian posterior probability support) secreted single xylanase (Xyn60; 36 kDa) and multiple xylanases (Xyn64A and Xyn64B; 33.4 and 19.8 kDa) respectively, having pH optima of 6.0 and exhibiting maximal activity at 60°C. These enzymes were highly stable at 40°C (120 h) and retained more than 70% activity at 50°C and at pH 5-6 (upon 72 h incubation). Our analysis suggested these enzymes to be endoxylanases demonstrating substrate hydrolysis within 15 min of reaction and maximum efficiency of xylanases from AUMS60 and AUMS64 achieving 51.1% (13 h) and 52.2% (24 h) saccharification, respectively. They also showed enhanced catalytic activity with various cations. Based on our investigation on xylan hydrolysis, we believe that these xylanases may find significant industrial applications as they have a real potential of working as a bio-catalytic cocktail (patent file number: IN E1/38213/2020-DEL) for the enhanced saccharification of lignocelluloses.


Contribution of chronic conditions to disability in men and women in France.
Women report more disability than men perhaps due to gender differences in the prevalence of diseases and/or in their disabling impact. We compare the contribution of chronic diseases to disability in men and women in France, using a disability survey conducted in both private households and institutions, and we also examine the effect of excluding the institutionalized population. Data comprised 17 549 individuals age 50+, who participated in the 2008-09 French Disability Health Survey including people living in institutions. Disability was defined by limitations in activities people usually do due to health problems (global activity limitation indicator). Additive regression models were fitted separately by gender to estimate the contribution of conditions to disability taking into account multi-morbidity. Musculoskeletal diseases caused most disability for both men (10.1%, CI: 8.1-12.0) and women (16.0%, CI 13.6-18.2). The second contributor for men was heart diseases (5.7%, CI: 4.5-6.9%), and for women anxiety-depression (4.0, CI 3.1-5.0%) closely followed by heart diseases (3.8%, CI 2.9-4.7%). Women's higher contribution of musculoskeletal diseases reflected their higher prevalence and disabling impact; women's higher contribution of anxiety-depression and lower contributions of heart diseases reflected gender differences in prevalence. Excluding the institutionalized population did not change the overall conclusions. The largest contributors to the higher disability of women than men are moderately disabling conditions with a high prevalence. Whereas traditional disabling conditions such as musculoskeletal diseases are more prevalent and disabling in women, fatal diseases such as cardiovascular disease are also important contributors in women and men.


Directions in healthcare research: pointers from retailing and services marketing.
Although the importance of the environment in relation to healing processes has been well established, empirical evidence for environmental effects on patient well-being and behavior is sparse. In addition, few attempts have been made to integrate insights from related fields of research such as retailing and services marketing with findings from healthcare studies. In this paper, relevant findings and insights from these domains are discussed. What insights and findings from retailing and services marketing are (potentially) of interest to the healthcare context, and how should one interpret and follow up on these results in healthcare environments? Research in retailing and services marketing indicates that physical environmental factors (i.e., music and scent) and social environmental factors (i.e., crowded conditions) may affect consumer satisfaction and well-being. In addition, environmental effects have been shown to vary with contextual factors (e.g., the type of environment) and consumer needs (e.g., the extent to which consumers value social contact or stimulation in a specific setting). Although the evidence base for environmental factors in health environments is steadily growing, few attempts have been made to integrate findings from both domains. The findings presented indicate that environmental variables such as music and scent can contribute to patient well-being and overall satisfaction. In addition, findings suggest that these variables may be used to counteract the negative effects resulting from crowded conditions in different healthcare units. Taking into account recent developments in the healthcare industry, the importance of creating memorable and pleasant patient experiences is likely to grow in the years to come. Hence, the finding that subtle and relatively inexpensive manipulations may affect patient well-being in profound ways should inspire follow-up research aimed at unraveling the specifics of environmental influences in health environments.


Clinical efficacy of gene-modified stem cells in adenosine deaminase-deficient immunodeficiency.
Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation. Subjects were followed from 33 to 84 months at the time of data analysis. Safety of the procedure was assessed by recording the number of adverse events. Efficacy was assessed by measuring engraftment of gene-modified hematopoietic stem/progenitor cells, ADA gene expression, and immune reconstitution. With the exception of the oldest subject (15 years old at enrollment), all subjects remained off ERT with normalized peripheral blood mononuclear cell (PBMC) ADA activity, improved lymphocyte numbers, and normal proliferative responses to mitogens. Three of nine subjects were able to discontinue intravenous immunoglobulin replacement therapy. The MND-ADA vector was persistently detected in PBMCs (vector copy number [VCN] = 0.1-2.6) and granulocytes (VCN = 0.01-0.3) through the most recent visits at the time of this writing. No patient has developed a leukoproliferative disorder or other vector-related clinical complication since transplant. These results demonstrate clinical therapeutic efficacy from gene therapy for ADA-deficient SCID, with an excellent clinical safety profile. ClinicalTrials.gov NCT00794508. Food and Drug Administration Office of Orphan Product Development award, RO1 FD003005; NHLBI awards, PO1 HL73104 and Z01 HG000122; UCLA Clinical and Translational Science Institute awards, UL1RR033176 and UL1TR000124.


The levels of caspase-cleaved cytokeratin 18 are elevated in serum from patients with lung cancer and helpful to predict the survival.
Caspase-cleaved cytokeratin 18 fragments (M30 antigen) can be detected in the circulation of patients with carcinoma and are believed to reflect cell death of tumors of epithelial origin. M30 antigens cleaved at Asp396 are detected using an epitope-specific antibody (M30 antibody). We here measured the levels of such fragments in patients with lung cancer (n=60), patients with benign lung disease (n=22) and healthy control subjects (n=32). A statistically significant difference was observed between these groups (p<0.001; Kruskal-Wallis). Basal M30 antigen levels were evaluated with regard to their predictive power of survival. The best cut-off value for M30 antigen level for the prediction of death was 43.8 U/L. Patients with basal M30 antigen levels higher than 43.8 U/L had significantly shorter median survival than those with lower basal M30 antigen levels (p=0.013; hazard ratio: 3.9) (95% CI=1.3-11.4). To determine whether cytotoxic therapy increases serum M30 antigen in lung cancer patients, we monitored the levels of M30 antigen in 18 lung cancer patients before chemotherapy and after 24 and 48 h. An approximately four-fold increase in M30 antigen levels was observed at 48 h (p<0.001). These results suggest as a first time that serum M30 antigen might be used as a novel biomarker for prediction of survival as well as for monitoring the efficiency of chemotherapy in lung cancer patients.


Positive selection on a bacterial oncoprotein associated with gastric cancer.
Helicobacter pylori is a vertically inherited gut commensal that is carcinogenic if it possesses the cag pathogenicity island (cag PaI); infection with H.pylori is the major risk factor for gastric cancer, the second leading cause of death from cancer worldwide (WHO). The cag PaI locus encodes the cagA gene, whose protein product is injected into stomach epithelial cells via a Type IV secretion system, also encoded by the cag PaI. Once there, the cagA protein binds to various cellular proteins, resulting in dysregulation of cell division and carcinogenesis. For this reason, cagA may be described as an oncoprotein. A clear understanding of the mechanism of action of cagA and its benefit to the bacteria is lacking. Here, we reveal that the cagA gene displays strong signatures of positive selection in bacteria isolated from amerindian populations, using the Ka/Ks ratio. Weaker signatures are also detected in the gene from bacteria isolated from asian populations, using the Ka/Ks ratio and the more sensitive branches-sites model of the PAML package. When the cagA gene isolated from amerindian populations was examined in more detail it was found that the region under positive selection contains the EPIYA domains, which are known to modulate the carcinogenicity of the gene. This means that the carcinogenicity modulating region of the gene is undergoing adaptation. The results are discussed in relation to the high incidences of stomach cancer in some latin american and asian populations. Positive selection on cagA indicates antagonistic coevolution between host and bacteria, which appears paradoxical given that cagA is detrimental to the human host upon which the bacteria depends. This suggests several non-exclusive possibilities; that gastric cancer has not been a major selective pressure on human populations, that cagA has an undetermined benefit to the human host, or that horizontal transmission of H.pylori between hosts has been more important in the evolution of H.pylori than previously recognized, reducing the selective pressure to lower the pathogenicity of the bacteria. The different patterns of adaptation of the gene in different human populations indicates that there are population specific differences in the human gut environment - due either to differences in host genetics or diet and other lifestyle features.


Analysis of the essential and excision repair functions of the RAD3 gene of Saccharomyces cerevisiae by mutagenesis.
The RAD3 gene of Saccharomyces cerevisiae, which is involved in excision repair of DNA and is essential for cell viability, was mutagenized by site-specific and random mutagenesis. Site-specific mutagenesis was targeted to two regions near the 5' and 3' ends of the coding region, selected on the basis of amino acid sequence homology with known nucleotide binding and with known specific DNA-binding proteins, respectively. Two mutations in the putative nucleotide-binding region and one in the putative DNA-binding region inactivate the excision repair function of the gene, but not the essential function. A gene encoding two tandem mutations in the putative DNA-binding region is defective in both excision repair and essential functions of RAD3. Seven plasmids were isolated following random mutagenesis with hydroxylamine. Mutations in six of these plasmids were identified by gap repair of mutant plasmids from the chromosome of strains with previously mapped rad3 mutations, followed by DNA sequencing. Three of these contain missense mutations which inactivate only the excision repair function. The other three carry nonsense mutations which inactivate both the excision repair and essential functions. Collectively our results indicate that the RAD3 excision repair function is more sensitive to inactivation than is the essential function. Overexpression of wild-type Rad3 protein and a number of rad3 mutant proteins did not affect the UV resistance of wild-type yeast cells. However, overexpression of Rad3-2 protein rendered wild-type cells partially UV sensitive, indicating that excess Rad3-2 protein is dominant to the wild-type form. These and other results suggest that Rad3-2 protein retains its affinity for damaged DNA or other substrates, but is not catalytically active in excision repair.


Melting and crystallization of sugars in high-solids systems.
Crystalline structures of sugars, particularly that of sucrose, depend on crystallization conditions and the presence of impurities. Sugar crystals show melting that often occurs at low temperatures with time- and temperature-dependent characteristics. Melting at low temperatures can be accounted for by the presence of impurties and defects. Sugar crystals also contain noncrystalline regions that may undergo decomposition and subsequent dissolution at the decomposition interface and acceleration of decomposition reactions. Such processes with melting establish a supersaturated condition for the remaining crystals, leading to a time-dependent melting point depression and subsequent melting of the remaining crystals. Decomposition of sugars, as well as dissolution and melting of sugar crystals, are separate phenomena, although they are commonly found to coincide. Decomposition of sugars requires the presence and mobility of molecules for reactions outside the crystal lattice; that is, the molecular mobility of amorphous or melted regions is a prerequisite for decomposition, whereas melting of sugar crystals occurs as a separate thermodynamic process with no chemical change of the molecules.


Metal-free cAMP-dependent protein kinase can catalyze phosphoryl transfer.
X-ray structures of several ternary product complexes of the catalytic subunit of cAMP-dependent protein kinase (PKAc) have been determined with no bound metal ions and with Na(+) or K(+) coordinated at two metal-binding sites. The metal-free PKAc and the enzyme with alkali metals were able to facilitate the phosphoryl transfer reaction. In all studied complexes, the ATP and the substrate peptide (SP20) were modified into the products ADP and the phosphorylated peptide. The products of the phosphotransfer reaction were also found when ATP-γS, a nonhydrolyzable ATP analogue, reacted with SP20 in the PKAc active site containing no metals. Single turnover enzyme kinetics measurements utilizing (32)P-labeled ATP confirmed the phosphotransferase activity of the enzyme in the absence of metal ions and in the presence of alkali metals. In addition, the structure of the apo-PKAc binary complex with SP20 suggests that the sequence of binding events may become ordered in a metal-free environment, with SP20 binding first to prime the enzyme for subsequent ATP binding. Comparison of these structures reveals conformational and hydrogen bonding changes that might be important for the mechanism of catalysis.


Characterization of Prenylated C-terminal Peptides Using a Thiopropyl-based Capture Technique and LC-MS/MS.
Posttranslational modifications play a critical and diverse role in regulating cellular activities. Despite their fundamentally important role in cellular function, there has been no report to date of an effective generalized approach to the targeting, extraction, and characterization of the critical c-terminal regions of natively prenylated proteins. Various chemical modification and metabolic labeling strategies in cell culture have been reported. However, their applicability is limited to cell culture systems and does not allow for analysis of tissue samples. The chemical characteristics (hydrophobicity, low abundance, highly basic charge) of many of the c-terminal regions of prenylated proteins have impaired the use of standard proteomic workflows. In this context, we sought a direct approach to the problem in order to examine these proteins in tissue without the use of labeling. Here we demonstrate that prenylated proteins can be captured on chromatographic resins functionalized with mixed disulfide functions. Protease treatment of resin-bound proteins using chymotryptic digestion revealed peptides from many known prenylated proteins. Exposure of the protease-treated resin to reducing agents and hydro organic mixtures released c-terminal peptides with intact prenyl groups along with other enzymatic modifications expected in this protein family. Database and search parameters were selected to allow for c-terminal modifications unique to these molecules such as CAAX box processing and c-terminal methylation. In summary, we present a direct approach to enrich and obtain information at a molecular level of detail about prenylation of proteins from tissue and cell extracts using high-performance LC-MS without the need for metabolic labeling and derivatization.


Magnetic resonance imaging after 'diffuse' nonmissile head injury. A neurobehavioral study.
The diagnosis of diffuse brain injury is considered when computed tomography provides no evidence of an intracranial mass lesion in acute nonmissile head injury. Magnetic resonance imaging (MRI) of a young woman who had sustained severe diffuse brain injury five years earlier disclosed multifocal lesions involving the frontal, temporal, parietal, and occipital lobes. We report the results of serial neurobehavioral assessment for clinical correlation with the brain lesions visualized by MRI. Pending confirmation of our findings in a series of patients studied by MRI during the acute and chronic stages of recovery from head injury, we postulate that the presence and type of neurobehavioral sequelae of diffuse brain injury are related to the intrahemispheric loci of predominantly white matter lesions and degeneration.


B7RP-1-ICOS interactions are required for optimal infection-induced expansion of CD4+ Th1 and Th2 responses.
Although initial reports linked the costimulatory molecule ICOS preferentially with the development of Th2 cells, there is evidence that it is not required for protective type 2 immunity to helminths and that it contributes to Th1 and Th2 responses to other parasites. To address the role of ICOS in the development of infection-induced polarized Th cells, ICOS(-/-) mice were infected with Trichuris muris or Toxoplasma gondii. Wild-type mice challenged with T. muris developed Th2 responses and expelled these helminths by day 18 postinfection, whereas ICOS(-/-) mice failed to clear worms and produced reduced levels of type 2 cytokines. However, by day 35 postinfection, ICOS(-/-) mice were able to mount an effective Th2 response and worms were expelled. This delay in protective immunity was associated with a defect in infection-induced increases in the number of activated and proliferating CD4+ T cells. Similarly, following challenge with T. gondii ICOS was required for optimal proliferation by CD4+ T cells. However, the reduced number of activated CD4+ T cells and associated defect in the production of IFN-gamma did not result in increased susceptibility to T. gondii, but rather resulted in decreased CNS pathology during the chronic phase of this infection. Taken together, these data are consistent with a model in which ICOS is not involved in dictating polarity of the Th response but rather regulates the expansion of these subsets.


Needlestick and sharps injuries: practice update.
Member states of the European Union have until May 112013 to implement the Council Directive 2010/32/EU Implementing the Framework Agreement on Prevention from Sharps Injuries in the Hospital and Healthcare Sector. The aim of this legislation is to achieve a safe working environment and prevent injuries to healthcare professionals caused by all medical sharps, including needlesticks. This article examines the issues surrounding needlestick and sharps injuries, including risk assessment and prevention, information provision, raising awareness, use of safety devices, training and reporting procedures.


Development of Environment-Friendly Insecticides Based on Enantioselectivity: Bifenthrin as a Case.
Chiral insecticides significantly contribute to the environmental pollutions recently. As the development of industry and agriculture, increasing number of chiral insecticides are to be introduced into the market. However, their enantioselective toxicology to ecosystem still remains uncertain. In this review, we embarked on a structured search of bibliographic databases for peer-reviewed articles regarding the enantioselective effects of bifenthrin, a typical chiral insecticide, on both target and non-target species. With this enantioselective property of chiral insecticides, they often exhibit adverse effects on non-target species enantioselectively. Specifically, the enantioselective effects of bifenthrin on target and non-target organisms were discussed. In target species, R-bifenthrin exerts more significant activities in deinsectization, compared with S-bifenthrin. On the other hand, Sbifenthrin is more toxic to non-target species than R-bifenthrin, which suggests that the application of sole enantiomer is more efficient and environment-friendly than that of racemate. This review confirms the choice of environment-friendly insecticides from the perspective of the enantioselectivity of chiral insecticides. To make insecticides more efficient to target species and less toxic to non-target species, further research should be done to investigated the potential effects of targetactive enantiomers on non-target organisms as well as the enantioselective fate of enantiomers in multiple environmental matrix.


p53 controls low DNA damage-dependent premeiotic checkpoint and facilitates DNA repair during spermatogenesis.
Previously, it was implicated that p53 plays a role in spermatogenesis. Here we report that p53 knockout mice exhibit significantly less mature motile spermatozoa than their p53(+/+) counterparts. To better understand the role of p53 in spermatogenesis, we analyzed the response of spermatogenic cells to DNA insult during prophase. It was found that although low-level gamma-irradiation activated a p53-dependent premeiotic delay, higher levels of gamma-irradiation induced a p53-independent apoptosis during meiosis. Furthermore, p53 knockout mice exhibited reduced in vivo levels of unscheduled DNA synthesis, indicative of compromised DNA repair. Thus, p53 provides another level of stringency in addition to other spermatogenic "quality control" mechanisms.


Prognostic implications of normal (<0.10 ng/ml) and borderline (0.10 to 1.49 ng/ml) troponin elevation levels in critically ill patients without acute coronary syndrome.
Borderline increase of troponin I (cTnI) is associated with higher rates of cardiovascular events compared with normal levels in the setting of acute coronary syndrome (ACS), but the significance of borderline cTnI levels in patients without chest pain may differ. The aim of this study was to determine the prognostic implications of intermediate serum cTnI levels in patients without ACS in the intensive care unit (ICU). This was a 12-month retrospective study of 240 patients without ACS in the ICU with normal (<0.1 ng/ml) or intermediate (0.1 to 1.49 ng/ml) cTnI levels. End points included in-hospital mortality, lengths of ICU and hospital stays, and rates of postdischarge readmission and mortality. Overall in-hospital mortality was 13%, with 5% in the normal cTnI group and 28% in the intermediate cTnI group. By multivariate analysis, intermediate cTnI was independently associated with in-hospital mortality (p = 0.004) and length of ICU stay (p = 0.028). The only other independent risk factor for inpatient mortality was a standardized ICU prognostic measurement (Simplified Acute Physiology Score II score). Intermediate cTnI had no prognostic implications regarding length of hospital stay, readmission rate, or postdischarge mortality at 6 months. In conclusion, an intermediate level of cTnI in patients without ACS in the ICU is an independent prognostic marker predicting in-hospital mortality and length of ICU stay. Patients with intermediate cTnI levels who survive to discharge have equivalent out-of-hospital courses for up to 6 months compared with patients with normal cTnI levels.


Persistence of bcr-able gene expression following bone marrow transplantation for chronic myelogenous leukemia in chronic phase.
The bcr-abl RNA transcript is the molecular counterpart of the Philadelphia chromosome and is detectable by an extremely sensitive polymerase chain reaction assay in most patients with chronic myelogenous leukemia. To determine the effectiveness of ablative radiochemotherapy and bone marrow transplantation in eradicating molecular evidence of the malignant clone, we assayed for bcr-abl RNA expression in specimens from 19 patients with CML in chronic phase (CP) who have survived for at least one year post-BMT. We correlated these results with the patients' remission status based on cytogenetic analysis and BM morphology, and with evidence of mixed hematopoietic chimerism by analysis of RBC antigen and DNA restriction fragment length polymorphism patterns. Thirteen of the 19 patients had detectable bcr-abl RNA at some time following BMT. Twelve of these patients have remained in remission by morphologic and karyotypic criteria from 16.6 to 63.7 months following BMT. One of these 13 patients relapsed both by cytogenetic and clinical criteria at 28.1 months after BMT. Six of these 13 patients are still positive at the time of their most recent analysis. Only two patients have evidence for mixed chimerism of normal hematopoietic elements by either RBC antigen or DNA RFLP patterns. These results suggest that, in some patients transplanted for CML in CP, small numbers of residual leukemic cells may persist or reappear transiently without leading to clinical relapse. The definition of complete remission in CML may need to be revised in light of the enhanced ability to detect minimal residual disease by PCR technology.


Feeding and Bleeding: The Institutional Banalization of Risk to Healthy Volunteers in Phase I Pharmaceutical Clinical Trials.
Phase I clinical trials are the first stage of testing new pharmaceuticals in humans. The majority of these studies are conducted under controlled, inpatient conditions using healthy volunteers who are paid for their participation. This article draws on an ethnographic study of six phase I clinics in the United States, including 268 semistructured interviews with research staff and healthy volunteers. In it, I argue that an institutional banalization of risk structures the perceptions of research staff and healthy volunteers participating in the studies. For research staff, there are three mechanisms by which risk becomes banal: a perceived homogeneity of studies, Fordist work regimes, and data-centric discourse. For healthy volunteers, repeat study participation contributes to the institutional banalization of risk both through the process of desensitization to risk and the formation of trust in the clinics. I argue that the institutional banalization of risk also renders invisible ethical concerns about exploitation of underprivileged groups in pharmaceutical research.


How do osteoporosis patients perceive their illness and treatment? Implications for clinical practice.
Non-adherence inhibits successful treatment of osteoporosis. This study used a theoretical framework to explore osteoporosis patients' cognitive and emotional representations of their illness and medication, using both interviews and drawing. We recorded some misconceptions patients have about their condition and medication which could act as barriers to treatment adherence. Despite the high efficacy of current treatments in reducing fracture risk, poor adherence is still a problem in osteoporosis. This qualitative study aims to inform the development of a psychological intervention to increase adherence through the investigation of osteoporosis patients' perceptions of their illness and medication. The self-regulation model (Leventhal) provided the framework for the study. Participants were 14 female outpatients from a London teaching hospital who suffer with osteoporosis or osteopenia. Data were collected using both semi-structured interviews and drawings. Drawings were used to elicit participants' visual representations (imagery) of their condition. We found that patients held illness and medication beliefs that were not in accord with current scientific evidence. Interviews revealed that participants had good knowledge of what osteoporosis is, but they had low understanding of the role of medication in reducing fracture risk, various concerns about the side effects of medication, poor understanding of the causes of osteoporosis and uncertainty about how it can be controlled. Additionally, drawings elicited more information about the perceived effects of osteoporosis and emotional reactions to the condition. Osteoporosis sufferers need a better understanding of their fracture risk and what they can do to control their condition. Concerns about medication need to be addressed in order to improve adherence, particularly in relation to the management of side effects. Since drawings of osteoporosis were found to arouse emotions, it is concluded that risk communication in osteoporosis could benefit from using visual images.


Post-combat invincibility: violent combat experiences are associated with increased risk-taking propensity following deployment.
Combat exposure is associated with increased rates of mental health problems such as post-traumatic stress disorder, depression, and anxiety when Soldiers return home. Another important health consequence of combat exposure involves the potential for increased risk-taking propensity and unsafe behavior among returning service members. Survey responses regarding 37 different combat experiences were collected from 1252 US Army Soldiers immediately upon return home from combat deployment during Operation Iraqi Freedom. A second survey that included the Evaluation of Risks Scale (EVAR) and questions about recent risky behavior was administered to these same Soldiers 3 months after the initial post-deployment survey. Combat experiences were reduced to seven factors using principal components analysis and used to predict post-deployment risk-propensity scores. Although effect sizes were small, specific combat experiences, including greater exposure to violent combat, killing another person, and contact with high levels of human trauma, were predictive of greater risk-taking propensity after homecoming. Greater exposure to these combat experiences was also predictive of actual risk-related behaviors in the preceding month, including more frequent and greater quantities of alcohol use and increased verbal and physical aggression toward others. Exposure to violent combat, human trauma, and having direct responsibility for taking the life of another person may alter an individual's perceived threshold of invincibility and slightly increase the propensity to engage in risky behavior upon returning home after wartime deployment. Findings highlight the importance of education and counseling for returning service members to mitigate the public health consequences of elevated risk-propensity associated with combat exposure.


Field note use in family medicine residency training: learning needs revealed or avoided?
Field notes (FNs) are used in Family Medicine residency programs to foster reflective learning and facilitate formative assessment. Residents assess their strengths and weaknesses and develop action plans for further improvement. This study explored the use of FNs in the University of Manitoba's Family Medicine residency program 5 years after their implementation. This multi-method study examined 520 FNs from 16 recent graduates from the University of Manitoba Family Medicine residency program. Quantitative analysis (frequencies and means) enabled descriptions and comparisons between training sites. Four themes emerged from inductive content analysis highlighting common ideas reflected upon. Residents displayed cyclical variation in the FN generation over 2 years. Eight of the 99 Priority Topics (addressing complex psychosocial issues) were not captured in this data set. The domains of Care of First Nations, Inuit, and Metis; Care of the Vulnerable and Underserved; and Behavioural Medicine and the CanMEDS-FM roles of FM - Procedural Skill, Leader/Manager, and Professional were less frequently reflected upon. Four themes (Patient-Centered Care, Patient Safety, Achieving Balance, and Confidence) were identified from qualitative analysis of residents' narrative notes. Vygotsky's Sociocultural Theory of Cognitive Development was proposed as a lens through which to examine factors influencing resident learning. Residents' discomfort with certain topics may lead to avoidance in reflecting upon certain competencies in FNs, impacting skill acquisition. Further research should explore factors influencing residents' perceptions FNs and how to best assist residents in becoming competent, confident practitioners.


Signal transmission, conversion and multiplication by polar molecules confined in nanochannels.
The mechanism of signal transmission, conversion and multiplication at molecular level has been of great interest lately, due to its wide applications in nanoscience and nanotechnology. The interferences between authentic signals and thermal noises at the nanoscale make it difficult for molecular signal transduction. Here we review some of our recent progress on the signal transduction mediated by water and other polar molecules confined in nanochannels, such as Y-shaped carbon nanotubes. We also explore possible future directions in this emerging field. These studies on molecular signal conduction might have significance in future designs and applications of nanoscale electronic devices, and might also provide useful insights for a better understanding of signal conduction in both physical and biological systems.


[Change of immunologic reactivity of the animal body under the effect of various antiblastic agents during primary immune response].
Tests staged with mice and rats demonstrated 5-fluorouracil, fluorafur, methotrexate, cyclophosphane and vinblastine capable of inhibiting to a different degree the primary immune response and the factors of nonspecific immunity. Methotrexate displays the highest activity and specificity of the immunodepressive effect. By using different doses of the drug in immunizing the animals with sheep erythrocytes and vi-antigens the factors of both specific and non-specific immunity were inhibited in all cases. With their single introduction 5-fluorouracil and fluorofur can stimulate the synthesis of humoral antibodies and have no effect on the immune response. With their multiple administration the immunological reactivity of the organism becomes depressed. The extent of changes involving non-specific factors doses not depend upon the pattern and schedule of the drug administration. Cyclophosphane and vinblastin inhibit the immune response when they are introduced 24 hours after immunization. Vinblastin had the faculty of bringing down the activity of the nonspecific immunity, whereas under the effect of cyclophosphane it did not change, except for the complement.


Essential health services delivery in South Africa during COVID-19: Community and healthcare worker perspectives.
Between May 2020 and February 2022, South Africa's health system bore strain as it battled mitigating the coronavirus pandemic. The country's pandemic response was scrutinized. This period also brought into focus pre-existing shortcomings in the healthcare system and its governing bodies. Contextually, there is a paucity in literature on the experiences of healthcare providers and users. This study aimed to contribute information on COVID-19, with the intention of providing guidance on preparing for future infectious disease outbreaks. Cross sectional exploratory qualitative methodology was employed using semi-structured interviews and focus group discussions with community members (CM) and healthcare workers (HCW) from two South African study sites: (a) rural Bushbuckridge (run by Agincourt Health and Socio-Demographic Surveillance Site) and (b), Regions D and F in Johannesburg Metropole. After interviewing 42 CMs and 43 HCWs, it emerged that mandated process changes while minimizing COVID-19 exposure, necessitated healthcare personnel focusing on critical care treatment at the expense of less acute ones. COVID-19 isolation protocols, extensive absenteeism and HCWs with advanced skills being perceived as more adept to treat COVID-19 patients contributed to HCWs experiencing higher workloads. Fears regarding contracting and transmitting COVID-19, suffering financial losses, and not being able to provide adequate advice to patients were recurrent themes. Dissemination of relevant information among healthcare facility personnel and communities suffered due to breakdowns in communication. Concessions and novel strategies to avail medication to patients had to be created. Since providence was lacking, government needs to formulate health intervention strategies that embrace health literacy, alternate methods of chronic medication dispensation, improved communication across health care platforms and the use of telehealth, to circumvent the threats of possible further infectious disease outbreaks.


Behavior of beef-heart cytochrome c oxidase in reconstituted proteovesicles. A systemtic evaluation of the influence of phospholipid polar headgroup and fatty-acyl side chains.
1. Phospholipid-depleted cytochrome c oxidase is incorporated in vesicles, built up of phospholipids of known polar headgroup and fatty-acyl side chains. 2. Maximal reactivation is obtained only when the fatty-acyl side chains provide a fluid environment. 3. Fluid zwitterionic phospholipids are found to be more efficient reactivators than fluid anionic ones. 4. Irrespective of the polar headgroup type, two narrow ranges of activation energies for the enzymatic reaction are calculated from the Arrhenius plots: 81--92 kJ/mol in solid and 51--61 kJ/mol in fluid conditions. 5. Cytochrome c oxidase is also incorporated in a series of vesicles, each built up of an equimolar amount of two phospholipids which differ in their polar headgroup type and/or their fatty-acyl side chain characteristics. From the localization of the enzyme activity profiles, obtained with these mixtures, tentative deductions are made about the preference of cytochrome c oxidase for different phospholipid molecules.


Seasonal variation in sudden death in the Negev desert region of Israel.
Previous studies have documented an increased incidence of cardiac mortality and sudden death during winter months. To evaluate seasonal variation in sudden death in a hot climate such as the desert region of southern Israel. We analyzed the files of 243 consecutive patients treated for out-of-hospital sudden death by the Beer Sheva Mobile Intensive Care Unit during 1989-90. Daily, monthly and seasonal incidence of sudden death was correlated with meteorological data, including temperature, heat stress, relative humidity and barometric pressure. The seasonal distribution of sudden death was 23% in spring, 21% in summer, 25% in autumn and 31% in winter (not significant). In patients with known heart disease there were more episodes of sudden death in cold weather (< 15.4 degrees C) than hot (> 34.2 degrees C) (16 vs. 3, P < 0.05). Resuscitation was less successful in cold compared with hot weather (28 vs. 11, P < 0.05). Of patients older than 65 years, 11 sustained sudden death when heat stress was below 12.4 degrees C compared to 2 patients when heat stress was above 27.5 degrees C (P = 0.05). Despite the warm desert climate, there were more cases of sudden death in older patients and in those with known heart disease during the winter season and on particularly cold days.


Cholesterol decreases secretion of the secreted form of amyloid precursor protein by interfering with glycosylation in the protein secretory pathway.
Cerebral deposits of beta-amyloid (betaA) are a major feature in Alzheimer's disease. betaA is derived from amyloid precursor protein (APP). APP is subject to N- and O-glycosylation and undergoes a series of proteolytic cleavages that lead to the release of betaA or of a non-amyloidogenic secreted form of APP (APPs). We used primary neuronal and glial cultures to investigate how cholesterol affects the production and secretion of APPs. Exposure to cholesterol for 2 h did not change the neuronal release of APPs; after 6 h APPs release was slightly lower, whereas 24 h of exposure decreased APPs in the medium by approx. 60%. The time courses were similar in astrocytes and microglia preparations. To verify whether the effect of cholesterol was a consequence of membrane rigidification we tested the activity of ganglioside GM1 and prion protein fragment PrP 106-126, which affect membrane fluidity similarly to cholesterol, on APPs secretion. Neither altered the production of APPs. APP mRNA and the total amount of APP in the cells were slightly decreased by cholesterol after 2 and 24 h respectively. Immunoblot analysis of APP associated with neuronal cells and astrocytes indicated that cholesterol progressively decreased the glycosylated forms of the protein; a similar tendency was noted in cells treated with brefeldin A and monensin, two substances that interfere with protein glycosylation. The cell-surface biotinylation method showed that in cholesterol-treated cells APP reached the plasma membrane. Our results indicate that cholesterol decreases the secretion of APPs by interfering with APP maturation and inhibiting glycosylation of the protein; although APP is inserted in the membrane it is not cleaved by alpha-secretase.


Multicenter, double-blind, randomized, intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for Breast MR imaging (DETECT Trial).
To intraindividually compare 0.1 mmol/kg doses of gadobenate dimeglumine and gadopentetate dimeglumine for contrast material-enhanced breast magnetic resonance (MR) imaging by using a prospective, multicenter double-blind, randomized protocol. Institutional review board approval and patient informed consent were obtained. One hundred sixty-two women (mean age, 52.8 years ± 12.3 [standard deviation]) enrolled at 17 sites in Europe and China between July 2007 and May 2009 underwent at least one breast MR imaging examination at 1.5 T by using three-dimensional spoiled gradient-echo sequences. Of these, 151 women received both contrast agents in randomized order in otherwise identical examinations separated by more than 2 but less than 7 days. Images, acquired at 2-minute or shorter intervals after contrast agent injection, were evaluated independently by three blinded radiologists unaffiliated with enrollment centers. Histopathologic confirmation was available for all malignant lesions (n = 144), while benign lesions were confirmed either by using histopathologic examination (n = 52) or by at least 12-month diagnostic follow-up (n = 20) with mammography and/or ultrasonography. Determinations of malignant lesion detection rates and diagnostic performance (sensitivity, specificity, accuracy, positive predictive value [PPV], and negative predictive value [NPV]) were performed and compared (McNemar and Wald tests). A full safety assessment was performed. Significant superiority for gadobenate dimeglumine was noted by readers 1, 2, and 3 for malignant lesion detection rate (91.7%, 93.1%, 94.4% vs 79.9%, 80.6%, 83.3%, respectively; P ≤ .0003). Readers 1, 2, and 3 reported significantly superior diagnostic performance (sensitivity, specificity, and accuracy) for breast cancer detection with gadobenate dimeglumine (91.1%, 94.5%, 95.2% vs 81.2%, 82.6%, 84.6%; 99.0%, 98.2%, 96.9% vs 97.8%, 96.9%, 93.8%; 98.2%, 97.8%, 96.7% vs 96.1%, 95.4%, 92.8%, respectively; P ≤ .0094) and significantly superior PPV (91.1%, 85.2%, 77.2% vs 80.7%, 75.5%, 60.9%, respectively; P ≤ .0002) and NPV (99.0%, 99.4%, 99.4% vs 97.8%, 98.0%, 98.1%, respectively; P ≤ .0003). No safety concerns were noted with either agent. Gadobenate dimeglumine is superior to gadopentetate dimeglumine for breast cancer diagnosis. © RSNA, 2010 Clinical trial registration no. NCT00486473 (http://www.clinicaltrials.gov/). http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100968/-/DC1.


Polarizing effect of aligned nanoparticles in terahertz frequency region.
We report the polarizing behavior of aligned Ni nanoparticles (NPs) having average diameter of 165±15 nm in ~210 μm thick polyvinyl alcohol (PVA) matrix in the frequency range of 0.2-1.6 THz. The NPs have been prepared via a wet chemical route and then aligned in PVA film by using an external magnetic field. When the polarization of THz electric field is parallel to the NPs alignment direction, a strong THz absorption is observed whereas a minimum THz absorption is noticed for the corresponding perpendicular configuration. Degree of polarization is calculated to be 0.9±0.08. Considering the good polarizing performance, ease of preparation, durability, and low maintenance, this aligned NP system is a perfect candidate to emerge as a potential THz polarizer.


Steps length error detector algorithm in phase-shifting interferometry using Radon transform as a profile measurement.
Phase-shifting is one of the most useful methods of phase recovery in digital interferometry in the estimation of small displacements, but miscalibration errors of the phase shifters are very common. In practice, the main problem associated with such errors is related to the response of the phase shifter devices, since they are dependent on mechanical and/or electrical parts. In this work, a novel technique to detect and measure calibration errors in phase-shifting interferometry, when an unexpected phase shift arises, is proposed. The described method uses the Radon transform, first as an automatic-calibrating technique, and then as a profile measuring procedure when analyzing a specific zone of an interferogram. After, once maximum and minimum value parameters have been registered, these can be used to measure calibration errors. Synthetic and real interferograms are included in the testing, which has thrown good approximations for both cases, notwithstanding the interferogram fringe distribution or its phase-shifting steps. Tests have shown that this algorithm is able to measure the deviations of the steps in phase-shifting interferometry. The developed algorithm can also be used as an alternative in the calibration of phase shifter devices.


Effects of hypothalamic neuropeptides on extracellular signal-regulated kinase (ERK1 and ERK2) cascade in human tumoral pituitary cells.
The G protein-coupled receptor (GPCR) activation has been demonstrated to affect the ERK1/2 cascade in different cell lines. We investigated the effects of hypothalamic neuropeptides acting via GPCR on this pathway in GH-secreting (GH-oma) and nonsecreting (NFPA) pituitary adenomas. GHRH increased ERK1/2 activity (236 +/- 80%) in both gsp- and gsp+ GH-omas, this effect being almost completely abolished by protein kinase C (PKC) blockade. Both GnRH and pituitary adenylate-activating peptide caused a similar PKC-dependent activation of ERK1/2 in most NFPA. Increasing cAMP by forskolin caused a protein kinase A-dependent increase of ERK activity (287 +/- 37%) in GH-omas and had no effect in NFPA. ERK cascade blockade in GH-omas did not affect basal and GHRH-stimulated GH release, whereas it totally prevented the 3-fold increase in cyclin D1 protein expression induced by GHRH. In conclusion, this study demonstrated that in pituitary adenomas the activation of GPCR by neurohormones caused a PKC-dependent activation of ERK1/2 cascade that, at least in GH-omas, resulted to be involved in cyclin D1 induction by GHRH. Moreover, a stimulatory effect of the protein kinase A-dependent pathway on ERK1/2 cascade occurred selectively in GH-omas, probably contributing to the mitogenic potential of the cAMP pathway in this cell type.


Clinical efficacy of flossing versus use of antimicrobial rinses.
Dental floss is only used by a small part of the population on a daily basis. Therefore, an easy, applicable alternative is needed. This alternative could be a mouthrinse with antimicrobial activity for daily use. The aim of the present study was to evaluate the efficacy of two mouthrinses in reducing interdental plaque and gingivitis compared to dental floss. A total of 156 healthy volunteers were randomly assigned to the following groups: 1) toothbrushing and rinsing (0.06% chlorhexidine and 0.025% fluoride); 2) toothbrushing and rinsing (0.1% cetylpyridiniumchloride and 0.025% fluoride); 3) toothbrushing and flossing; and 4) toothbrushing only (N = 39 subjects in each group). At baseline, the modified proximal plaque index (MPPI) and papillary bleeding index (PBI) were recorded. Thereafter, subjects had to brush in the usual manner during 8 weeks. Additionally, test groups had to rinse once a day (groups 1 and 2: 30 seconds) or to floss (group 3). Eight weeks after baseline, indices were recorded again and improvements were calculated. Analysis of variance (ANOVA) and the Bonferroni test served for statistical analysis. After 8 weeks, reductions for all indices were found in all groups (P <0.05). With respect to the MPPI, mouthrinse groups performed better than the control and floss groups: 1) 0.73; 2) 0.82; 3) 0.40; and 4) 0.32 (P <0.05). The PBI showed no statistically significant difference between groups: 1) 0.46; 2); 0.50; 3); 0.42; and 4) 0.37. The results suggest that, in combination with toothbrushing, daily use of the tested mouthrinses may result in a higher interproximal plaque reduction than daily flossing.


Can car air filters be useful as a sampling medium for air pollution monitoring purposes?
Urban air quality and real human exposure to chemical environmental stressors is an issue of high scientific and political interest. In an effort to find innovative and inexpensive means for air quality monitoring, the ability of car engine air filters (CAFs) to act as efficient samplers collecting street level air, to which people are exposed to, was tested. In particular, in the case of taxis, air filters are replaced after regular distances, the itineraries are almost exclusively urban, cruising mode is similar and, thus, knowledge of the air flow can provide with an integrated city air sample. The present pilot study focused on polycyclic aromatic hydrocarbons (PAHs), the most important category of organic pollutants associated with traffic emissions. Concentrations of ΣPAHs in CAFs ranged between 650 and 2900 μg CAF(-1), with benzo[b]fluoranthene, benzo[k]fluoranthene and indeno[123-cd]pyrene being the most abundant PAHs. Benzo[a]pyrene (BaP) ranged between 110 and 250 μg CAF(-1), accounting regularly for 5-15% of the total carcinogenic PAHs. The CAF PAH loads were used to derive road-level atmospheric PAH concentrations from a standard formula relating to the CAF air flow. Important parameters/assumptions for these estimates are the cruising speed and the exposure duration of each CAF. Based on information obtained from the garage experts, an average 'sampled air volume' of 48,750 m(3) per CAF was estimated, with uncertainty in this calculation estimated to be about a factor of 4 between the two extreme scenarios. Based on this air volume, ΣPAHs ranged between 13 and 56 ng m(-3) and BaP between 2.1 and 5.0 ng m(-3), suggesting that in-traffic BaP concentrations can be many times higher than the limit values set by the UK (0.25 ng m(-3)) and the European Union (1.0 ng m(-3)), or from active sampling stations normally cited on building roof tops or far from city centres. Notwithstanding the limitations of this approach, the very low cost, the continuous availability of very high amounts of "sample", and the "retroactivity" render it very useful and complementary to existing passive sampling techniques. This approach yields estimated air concentrations that reflect the pollutant concentrations to which taxi drivers, pedestrians, cyclists and road-related professionals are exposed.


Plant-derived measles virus hemagglutinin protein induces neutralizing antibodies in mice.
Measles remains a significant problem in both the developed and developing world, and new measles vaccination strategies need to be developed. This paper examines the strategy of utilizing transgenic plants expressing a measles antigen for the development of an oral sub-unit measles vaccine. A 1.8 kb fragment encompassing the coding region of the measles virus hemagglutinin (H) protein was cloned into a plant expression cassette. Three different expression constructs were tested: pBinH (H gene alone), pBinH/KDEL (addition of a C-terminal endoplasmic reticulum-retention sequence SEKDEL) and pBinSP/H/KDEL (further addition of an authentic N-terminal plant signal peptide). The highest levels of recombinant H protein production were observed in plants transformed with pBinH/KDEL. Mice inoculated intraperitoneally with transgenic plant derived recombinant H protein produced serum anti-H protein antibodies that neutralized the measles virus (MV) in vitro. Mice gavaged with transgenic tobacco leaf extracts also developed serum H protein-specific antibodies with neutralizing activity against MV in vitro. These results indicate that the plant-derived measles H protein is immunogenic when administered orally and that, with further development, oral vaccination utilizing transgenic plants may become a viable approach to measles vaccine development.


Effect of erythritol on microbial ecology of in vitro gingivitis biofilms.
Gingivitis is one of the most common oral infections in humans. While sugar alcohols such as erythritol are suggested to have caries-preventive properties, it may also have beneficial effects in prevention of gingivitis by preventing maturation of oral biofilms. The aim of this study was to assess the effect of erythritol on the microbial ecology and the gingivitis phenotype of oral microcosms. Biofilms were inoculated with stimulated saliva from 20 healthy donors and grown in a gingivitis model in the continuous presence of 0 (control group), 5, and 10% erythritol. After 9 days of growth, biofilm formation, protease activity (gingivitis phenotype), and microbial profile analyses were performed. Biofilm growth was significantly reduced in the presence of erythritol, and this effect was dose dependent. Protease activity and the Shannon diversity index of the microbial profiles of the biofilms were significantly lower when erythritol was present. Microbial profile analysis revealed that presence of erythritol induced a compositional shift from periodontitis- and gingivitis-related taxa toward early colonizers. The results of this study suggest that erythritol suppresses maturation of the biofilms toward unhealthy composition. The gingivitis phenotype was suppressed and biofilm formation was reduced in the presence of erythritol. Therefore, it is concluded that erythritol may contribute to a healthy oral ecosystem in vitro.


[Septicemia. Etiology, epidemiology, clinical aspects and prognosis in 446 patients].
Between 1979 and 1982 446 patients with clinically and bacteriologically established septicaemia were ascertained in a prospective study in a university hospital complex with 1200 beds. This corresponded to an incidence of 8,4 cases of septicaemia in 1000 admissions. In 47.1% of patients the infection had been acquired as out-patient, 52.9% were hospital-acquired. 53.1% of patients were more than 60 years of age, 71.3% had predisposing underlying diseases or risk factors. Main signs of infection were increased temperatures of more than 38.5 degrees C (77.8%), anaemia and leukocytosis. The fairly equal distribution of gram-positive (207) and gram-negative (200) organisms was remarkable. The most frequently isolated bacterial species were E. coli (25.3%), Staph. aureus (21.8%), streptococci (11.1%), Staph. epidermidis (8.4%), enterococci (8.2%), and Klebsiellae (6.5%). 29.1% of patients succumbed. Nosocomial disease, liver cirrhosis, underlying malignant diseases, infections with Staph. aureus, enterococci, pneumococci, Pseudomonas aeruginosa and polymicrobial aetiology had an unfavourable prognostic influence. Thus, frequency and mortality of septicaemic diseases remain of unchanged considerable relevance in medical and surgical units. At present, aetiology and treatment will again have to consider gram-negative organisms to an increased extent.


Evaluation of clinical spasticity assessment in cerebral palsy using inertial sensors.
Spasticity is clinically assessed using goniometry to measure the joint angle of the catch (AOC) during fast passive muscle stretch. The precision and accuracy of the goniometric AOC measurements are questionable, because of the inevitable joint repositioning after occurrence of the catch. This study aims to evaluate the use of goniometry in estimating the AOC in spasticity assessment of the medial hamstrings, soleus and gastrocnemius in twenty children with Cerebral palsy (CP), using inertial sensors (IS) as reference system. The IS were initially validated with an optoelectronic system to measure 3d-orientation and proved to be accurate within 1 degree. To evaluate the precision and accuracy of the goniometry, the joint angle measured with the goniometer after repositioning was compared to the joint angle measured simultaneously with the IS, and to the true AOC, detected and measured with the IS during the fast muscle stretch. Results showed that goniometry is an imprecise method to measure the true AOC in spasticity assessment. The error is mainly due to joint repositioning after the fast muscle stretch. For spasticity assessment, it is advised to apply inertial sensors when a precise measurement of the angle of catch is required.


HLA-Gm/kappam interaction in sarcoidosis. Suggestions for a complex genetic structure.
The aetiology of sarcoidosis is still unknown. Environmental exposures are believed to interact with genetic factors in determining the pattern of sarcoidosis presentation, progression and prognosis. The frequency of serological polymorphism of immunoglobulin G heavy chain (Gm) and kappa light chain (kappam) markers in 107 patients with biopsy-proven sarcoidosis and in 227 controls, and their interactions with histocompatibility leukocyte antigen (HLA) class I, II, and III markers, were studied. A "protective" effect of the Gm(3 5*) phenotype in the sarcoid group versus controls (p-value for number of specificities tested (p(c))=0.05, odds ratio 0.15) and a reduced frequency of Gm(3 23 5*) in patients with advanced chest radiographic stage (Chi-squared (two degrees of freedom)(chi2(2df) 17.61, p(c)=0.0058) were observed. With reference to epistatic interactions, the combination Gm(3 23 5*)/BfS had a "protective" effect towards stage II (chi2(2dt) 13.86, p(c)=0.043). Finally, correspondence analysis defined two clusters: HLA-DR4, C4BQ0, Gm(1, 3, 17 23 5*, 21, 28) and BfF associated with stage II, and HLA-DR3, C4AQ0, kappam(1) and Gm(3 23 5*) associated with stage I. These data further support the hypothesis that sarcoidosis results from an interplay of environmental factors and genes, each contributing to the susceptibility/resistance to and/or the clinical heterogeneity of the disease. In addition, these data provide the first evidence of an interaction between immunoglobulin G heavy chain/kappa light chain markers and histocompatibility leukocyte antigen class III genes in a disease.