Cyclothiazide unmasks an AMPA-evoked release of arachidonic acid from cultured striatal neurones.
The joint, but not independent, activation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and metabotropic glutamate receptors induces liberation of arachidonic acid from cultured mouse striatal neurones. We examined whether blocking AMPA receptor desensitisation with cyclothiazide would modify this response. Cyclothiazide strongly potentiated the combined AMPA/(1 S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD)-evoked release of arachidonic acid (EC50 of approximately 7 microM) but did not modulate the basal, ACPD, or NMDA response. The enhanced liberation of arachidonic acid, observed in the presence of cyclothiazide, was due to the appearance of a genuine AMPA response that was independent of an associative activation of metabotropic receptors. The potentiated and nonpotentiated AMPA responses were inhibited by both competitive [2,3-di-hydroxy-6-nitro-7-sulphamoylbenzo (f) quinoxaline] and 2,3-benzodiazepine noncompetitive (GYKI 53655 and GYKI 52466) receptor antagonists. Cyclothiazide was equally effective at potentiating the AMPA response in either the presence or absence of glucose, suggesting that the increased glutamate-evoked arachidonic acid release observed in these cells under conditions of glucose deprivation is not due to reduced AMPA receptor desensitisation. The enhanced liberation of arachidonic acid measured in the presence of cyclothiazide appeared to result from a large (fourfold) elevation of the AMPA-induced increase in intracellular calcium level. Therefore, an AMPA-evoked mobilisation of arachidonic acid could potentially contribute to non-NMDA receptor-mediated neurotoxicity, which has been observed in neuronal cells in the presence of cyclothiazide.


Studies on the control of bovine ostertagiasis using a morantel sustained release bolus.
The efficacy of a morantel sustained release bolus to control ostertagiasis in grazing calves was assessed. Administration of the bolus into the rumen of calves immediately before turnout on to spring pasture in May substantially reduced the level of pasture contamination with infective larvae later in the season. Compared with controls there was a 71 per cent reduction in worm burdens acquired over the entire grazing season with a mean improvement in weight gain of 24 kg. When administration was delayed until midsummer (July) a good anthelmintic effect was obtained but there was little reduction in pasture contamination levels. Worm burdens acquired over the grazing season were reduced by only 48 per cent with a mean weight gain advantage of only 9 kg compared with controls. The control obtained against Dictyocaulus viviparus by both treatments was not absolute, failing to prevent the development of mild parasitic bronchitis.


Nutritional supplement products: Does the label information influence purchasing decisions for the physically active?
The increase in sales of nutritional supplement globally can be attributed, in part, to aggressive marketing by manufacturers, rather than because the nutritional supplements have become more effective. Furthermore, the accuracy of the labelling often goes unchallenged. Therefore, any effects of the supplement, may be due to contaminants or adulterants in these products not reflected on the label. A self-administered questionnaire was used to determine how consumers of nutritional supplements acquired information to assist their decision-making processes, when purchasing a product. The study was approved by the University of Cape Town, Faculty of Health Sciences Human Research Ethics Committee. The questionnaire consisted of seven, closed and open-ended questions. The participants were asked to respond to the questions according to a defined list of statements. A total of 259 participants completed and returned questionnaires. The data and processing of the returned questionnaires was captured using Windows-based Microsoft® Office Excel 2003 SP 1 (Excel © 1985-2003 Microsoft Corporation). Statistica Version 10 (copyright © Stat Soft, Inc. 1984-2011) was used to calculate the descriptive statistics. The main finding of the study was that nearly 70% of the respondents who purchased supplements were strongly influenced by container label information that stipulated that the nutritional supplement product is free of banned substances. The second finding was that just over 50% of the respondents attached importance to the quality of the nutritional supplement product information on the container label. The third finding was that about 40% of the respondents were strongly influenced by the ingredients on the labels when they purchased nutritional supplements. This study, (i) identifies short-comings in current labelling information practices, (ii) provides opportunities to improve label and non-label information and communication, and, (iii) presents the case for quality assurance laboratory "screening testing" of declared and undeclared contaminants and/or adulterants, that could have negative consequences to the consumer.


TCA cycle-mediated generation of ROS is a key mediator for HeR-MRSA survival under β-lactam antibiotic exposure.
Methicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug resistant pathogen responsible for several difficult-to-treat infections in humans. Clinical Hetero-resistant (HeR) MRSA strains, mostly associated with persistent infections, are composed of mixed cell populations that contain organisms with low levels of resistance (hetero-resistant HeR) and those that display high levels of drug resistance (homo-resistant HoR). However, the full understanding of β-lactam-mediated HeR/HoR selection remains to be completed. In previous studies we demonstrated that acquisition of the HoR phenotype during exposure to β-lactam antibiotics depended on two key elements: (1) activation of the SOS response, a conserved regulatory network in bacteria that is induced in response to DNA damage, resulting in increased mutation rates, and (2) adaptive metabolic changes redirecting HeR-MRSA metabolism to the tricarboxylic acid (TCA) cycle in order to increase the energy supply for cell-wall synthesis. In the present work, we identified that both main mechanistic components are associated through TCA cycle-mediated reactive oxygen species (ROS) production, which temporally affects DNA integrity and triggers activation of the SOS response resulting in enhanced mutagenesis. The present work brings new insights into a role of ROS generation on the development of resistance to β-lactam antibiotics in a model of natural occurrence, emphasizing the cytoprotective role in HeR-MRSA survival mechanism.


Separation of mononuclear leukocytes and polymorphonuclear leukocytes from equine blood.
The present study describes a two step technique for the separation of mononuclear leukocytes or mononuclear and polymorphonuclear leukocytes from whole equine blood. First, the leukocyte rich plasma was obtained by sedimentation of erythrocytes in the undiluted blood. Subsequently, separation of the different populations of white blood cells was performed by centrifugation with different gradients overlaid with the leukocyte rich plasma. The optimal separation of the mononuclear cells was obtained by the centrifugation of the leukocyte rich plasma overlaying the gradient containing 24 parts of 9.5% ficoll and ten parts of 34% isopaque. The mononuclear leukocytes (95% lymphocytes and 5% monocytes) formed a monolayer band at the plasma-ficoll-isopaque interface and other blood cells migrated to the bottom of the tube. For the separation of mononuclear and granular leukocytes from the blood, the gradient containing 24 parts of 10% ficoll and ten parts of 34% isopaque was used. The separated monuclear leukocytes responded to stimulation with phytohemagglutin and viability of both mononuclear and polymorphonuclear leukocytes was not affected by ficoll-isopaque separation.


Olive oil prevents the adverse effects of dietary conjugated linoleic acid on chick hatchability and egg quality.
Dietary conjugated linoleic acid (CLA) decreases yolk 18:1(n-9), induces chick embryonic mortality and alters egg quality. A study was conducted to determine whether olive oil would prevent these adverse effects of CLA. Hens (15 per treatment) were fed diets containing 0.5 g corn oil/100 g (CO), 0.5 g CLA/100 g (CLA), 0.5 g corn oil plus 10 g olive oil/100 g (CO + OO) or 0.5 g CLA plus 10 g olive oil/100 g (CLA + OO). After 74 d of feeding, hens were placed on CO for 10 d. Hens were artificially inseminated weekly. For hatchability studies, fertile eggs were collected daily, stored at 15 degrees C for 24 h and then incubated. After 6 d of feeding, embryonic mortality rates were 15, 100, 8 and 16% in the CO, CLA, CO + OO and CLA + OO groups, respectively. When CLA-fed hens were fed the CO diet, hatchability improved to that of the CO group within 7 d. For fatty acid analysis, three eggs were obtained at the 7 d of feeding. Relative CLA levels of yolk from CO-, CLA-, CO + OO- and CLA + OO-fed hens were 0.11 +/- 0.01, 1.91 +/- 0.16, 0.08 +/- 0.04 and 0.69 +/- 0.07 g/100 g fatty acids, respectively. The ratios of 16:0/16:1(n-7) and 18:0/18:1(n-9) of yolk from CLA-fed hens were approximately 1- and approximately 1.5-fold greater, respectively, compared with those fed CO. OO prevented CLA-induced increases in 16:0 and 18:0 and the decrease in 18:1(n-9) in yolk. Fertile eggs were stored at 4 degrees C for 2 or 10 wk and analyzed for pH or mineral levels. Dietary CLA caused abnormal pH changes of albumen and yolk when eggs were stored at 4 degrees C. The pH of yolk and albumen from CO-fed hens after 10 wk of storage was 6.12 +/- 0.12 and 9.06 +/- 0.03, respectively, versus 7.89 +/- 0.25 and 8.32 +/- 0.16, respectively, in eggs from CLA-fed hens. OO prevented CLA-induced abnormal changes in the pH of albumen and yolks. Eggs from CLA-fed hens had greater iron, calcium and zinc concentrations and lower magnesium, sodium and chloride concentrations in albumen relative to those from hens fed CO. OO prevented CLA-induced mineral exchange between yolk and albumen, presumably by reducing the yolk saturated fatty acids, which are believed to disrupt the vitelline membrane during cold storage. This study suggests that the adverse effects of CLA may be due to the increased level of saturated fatty acids. However, because the addition of olive oil also lowered egg CLA content, the direct role of egg CLA on egg hatchability and quality cannot be ruled out.


Isozyme phenotypes of polyoma virus tumors in mice.
Isozyme profiles for 32 enzyme systems were studied in tumors induced by two strains of polyoma virus (2PTA and LID1), in two conventional mouse strains (C3H/BiDa and NIH), and in athymic (nude) mice of two genetic backgrounds (C3H/Hes nu/nu and NIH nu/nu). Tumors studied were: primary and transplant passages of salivary gland tumors (127); primary thymic epithelial tumors (12); primary subcutaneous sarcomas (6); primary hair follicle tumors (5); primary and transplant passages of mammary tumors (18); primary ameloblastomas (3); and primary renal medullary sarcomas (3). Regardless of mouse strain or virus strain, the isozyme arrays were highly constant and unique for each tumor histotype with the exception of salivary and mammary tumors, which shared a single profile differing from that of each of the other histotype-associated profiles. Other tumor types could be distinguished from each other and from the salivary-mammary tumor pair by as few as five isozymes: glycerol-3-phosphate dehydrogenase; glyceraldehydephosphate dehydrogenase; lactate dehydrogenase; sorbitol dehydrogenase; and alkaline phosphatase. Twelve nonpolyoma mammary tumors and their passages from mouse mammary tumor virus-expressed C3H/Hes nu/+ mice were analyzed for the same enzymes; variations in activity and isozyme profiles were found for ten enzyme systems. Three spontaneous salivary myoepitheliomas in BALB/c mice were also analyzed; two different lactate dehydrogenase profiles were observed, and all three tumors lacked the placental alkaline phosphatase present in polyoma virus-induced salivary tumors. Uniformity of isozyme phenotype may be characteristic of DNA virus transformation of cells in a particular differentiative state. This uniformity does not appear to occur in mouse mammary tumor virus-associated tumors, spontaneous tumors, and, according to the literature, chemically induced tumors.


What's for dinner this time?: DNA authentication of "wild mushrooms" in food products sold in the USA.
Mushrooms have been consumed by humans for thousands of years, and while some have gastronomic and nutritional value, it has long been recognized that only select species of mushrooms are suitable for consumption. Adverse health effects of consuming poisonous mushrooms range from mild illness to death. Many valuable edible mushrooms are either impractical or unable to be grown commercially, requiring them to be harvested from the wild. In the U.S., products containing these wild-collected mushrooms are often sold with the nonspecific and undefined label "wild mushrooms," although in some cases particular species are listed in the ingredients. However, the ambiguity of the definition of "wild mushrooms" in foods makes it impossible to know which species are involved or whether they are truly wild-collected or cultivated varieties. As a consequence, any individual adverse reactions to consuming the mushrooms in these products cannot be traced to the source due to the minimal regulations around the harvest and sale of wild mushrooms. For this study, we set out to shed light on what species of fungi are being sold as "wild mushrooms" using DNA metabarcoding to identify fungal contents of various food products acquired from locally sourced grocers and a large online retail site. Twenty-eight species of mushroom were identified across 16 food products, ranging from commonly cultivated species to wild species not represented in global DNA databases. Our results demonstrate that "wild mushroom" ingredients often consist entirely or in part of cultivated species such as the ubiquitous white and brown "button" mushrooms and portabella (Agaricus bisporus), oyster (Pleurotus spp.) and shiitake (Lentinula edodes). In other cases truly wild mushrooms were detected but they were not always consistent with the species on the label. More alarmingly, a few products with large distribution potential contained species whose edibility is at best dubious, and at worst potentially toxic.


The basic data for residents aged 16 years or older who received a comprehensive health check examinations in 2011-2012 as a part of the Fukushima Health Management Survey after the great East Japan earthquake.
To assist in the long-term health management of residents and evaluate health impacts after the Tokyo Electric Power Company's Fukushima Daiichi Nuclear Power Plant accident in Fukushima Prefecture, the Fukushima prefectural government decided to conduct the Fukushima Health Management Survey. This report describes the results for residents aged 16 years or older who received the health check examinations and evaluates the data obtained from 2011 and 2012. The target group consisted of residents aged 16 years or older who had lived in the evacuation zone. The health check examinations were performed on receipt of an application for a health check examination from any of the residents. The examinations, including measurements of height, weight, abdominal circumference/body mass index (BMI), blood pressure, biochemical laboratory findings, and peripheral blood findings, were performed as required. 1) A total of 56,399 (30.9%) and 47,009 (25.4%) residents aged 16 years or older received health checks in 2011 and 2012, respectively. 2) In both years, a number of male and female residents in the 16-39 year age group were found to suffer obesity, hyperlipidemia, hyperuricemia, or liver dysfunction, and the prevalence of obesity and hyperlipidemia among residents increased with age. Furthermore, the proportion of residents with hypertension, glucose metabolic abnormalities or renal dysfunction was higher in those aged 40 years or older. 3) The frequencies of obesity, hypertension and hyperlipidemia among residents in 2012 were lower than those in 2011. However, the prevalence of liver dysfunction, hyperuricemia, glucose metabolic abnormalities and renal dysfunction among residents was higher in 2012 than in 2011. These results suggested the number of residents who had lived in the evacuation zone with obesity, hyperlipidemia, hyperuricemia, liver dysfunction, hypertension, glucose metabolic abnormalities, or renal dysfunction increased with age in all age groups. Therefore, we think that it is necessary to continue with health check examinations for these residents in order to ameliorate lifestyle-related disease.


[Efficacy of mexidol in the combination with thrombolytic therapy in patients with ischemic stroke].
Comparative efficiency of ethylmethylhydroxypyridine succinate (Mexidol) in combination with thrombolytic therapy in patients with ischemic stroke was studied in 116 patients. All patients divided into 2 groups: group (46 patients) received thrombolysis with mexidol and group (70 patients) received thrombolysis with standard therapy. These results showed that the synergy this one therapy leads to significantly faster normalize acute indicators, which correlated with the degree of reduction the neurological deficiency. Thus, the results showed that the synergistic therapy creates the conditions not only for the restoration of neurological status, but also to prevent secondary brain damage.


Sterile Product Packaging and Delivery Systems.
Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology.


Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death.
An intronic expansion of GGGGCC repeats within the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). Ataxin-2 with intermediate length of polyglutamine expansions (Ataxin-2 Q30x) is a genetic modifier of the disease. Here, we found that C9ORF72 forms a complex with the WDR41 and SMCR8 proteins to act as a GDP/GTP exchange factor for RAB8a and RAB39b and to thereby control autophagic flux. Depletion of C9orf72 in neurons partly impairs autophagy and leads to accumulation of aggregates of TDP-43 and P62 proteins, which are histopathological hallmarks of ALS-FTD SMCR8 is phosphorylated by TBK1 and depletion of TBK1 can be rescued by phosphomimetic mutants of SMCR8 or by constitutively active RAB39b, suggesting that TBK1, SMCR8, C9ORF72, and RAB39b belong to a common pathway regulating autophagy. While depletion of C9ORF72 only has a partial deleterious effect on neuron survival, it synergizes with Ataxin-2 Q30x toxicity to induce motor neuron dysfunction and neuronal cell death. These results indicate that partial loss of function of C9ORF72 is not deleterious by itself but synergizes with Ataxin-2 toxicity, suggesting a double-hit pathological mechanism in ALS-FTD.


The radiologic diagnosis of autopsy-proven ventilator-associated pneumonia.
An abnormal chest roentgenogram is essential for the diagnosis of ventilator-associated pneumonia. The diagnostic accuracy of various roentgenographic signs of pneumonia has not been assessed previously in the portable anteroposterior roentgenograms obtained in ventilated patients. Seven roentgenographic signs (air bronchograms, alveolar infiltrates, silhouette sign, cavities, fissure abutment, atelectasis, and asymmetric infiltrates superimposed on diffuse bilateral infiltrates) were evaluated for their accuracy in predicting pneumonia alone, in combination with other signs, or in combination with clinical parameters. The last roentgenogram prior to autopsy of 69 ventilated patients was interpreted by three reviewers and the above signs were correlated with autopsy evidence of pneumonia. Pneumonia was present in 24 (35 percent) of the 69 autopsies. No roentgenographic sign had a diagnostic efficiency of greater than 68 percent. By stepwise logistic regression, the presence of air bronchograms was the only roentgenographic sign that correlated with pneumonia in the total group, correctly predicting 64 percent of pneumonias. In patients without adult respiratory distress syndrome (ARDS), the presence of air bronchograms or alveolar infiltrates correlated with pneumonia, while in patients with ARDS, no roentgenographic sign and only the clinical parameter of purulent sputum correlated with pneumonia. Only a minority (7/22) of worsening alveolar infiltrates in all groups were due to pneumonia and were often confused with ARDS. Alveolar hemorrhage occurred with a surprising frequency (38 percent of autopsies), including 13/45 (29 percent) patients without pneumonia. Alveolar hemorrhage was associated with 29 percent of multiple air bronchograms and 30 percent of bilateral alveolar infiltrates in patients without pneumonia. We conclude that in intubated patients with diffuse bilateral roentgenographic infiltrates, no roentgenographic sign correlates well with pneumonia. No clinical parameter added to the accuracy of either an alveolar infiltrate or an air bronchogram in patients without diffuse infiltrates. Pulmonary hemorrhage and/or infarction are frequent autopsy findings in intubated patients and may be confused radiologically with pneumonia.


The national colonoscopy audit: a nationwide assessment of the quality and safety of colonoscopy in the UK.
To perform a comprehensive audit of all colonoscopy undertaken in the UK over a 2-week period. Multi-centre survey. All adult (≥16 years of age) colonoscopies that took place in participating National Health Service hospitals between 28 February 2011 and 11 March 2011 were included. Data on 20,085 colonoscopies and 2681 colonoscopists were collected from 302 units. A validation exercise indicated that data were collected on over 94% of all procedures performed nationally. The unadjusted caecal intubation rate (CIR) was 92.3%. When adjusted for impassable strictures and poor bowel preparation the CIR was 95.8%. The polyp detection rate was 32.1%. The polyp detection rate for larger polyps (≥10 mm diameter) was 11.7%. 92.3% of resected polyps were retrieved. 90.2% of procedures achieved acceptable levels of patient comfort. A total of eight perforations and 52 significant haemorrhages were reported. Eight patients underwent surgery as a consequence of a complication. This is the first national audit of colonoscopy that has successfully captured the majority of adult colonoscopies performed across an entire nation during a defined time period. The data confirm that there has been a significant improvement in the performance of colonoscopy in the UK since the last study reported seven years ago (CIR 76.9%) and that performance is above the required national standards.


Second nationwide survey of bilirubin encephalopathy in preterm infants in Japan.
To determine the clinical features of bilirubin encephalopathy in preterm infants (pBE) in Japan. We performed a retrospective, nationwide questionnaire-based survey. The initial survey determined the number of children with pBE who were born after 2000. Using a structured questionnaire, the second survey clarified the clinical manifestations and characteristics of children with pBE, including demographic data, neurological symptoms, and MRI and auditory brainstem response (ABR) findings. The initial survey identified 41 pBE infants from 18 institutions. After exclusion of patients included in previous studies, clinical information was collected from 30 patients (21 boys and 9 girls) during the secondary survey. The median gestational age was 26 weeks and the median birthweight was 846 g. Chronic lung disease and symptomatic patent ductus arteriosus were common neonatal complications. Head control was observed in 63% and functional gait in 17% of patients. Purposeful hand use was seen in 57% and verbal communication in 50% of patients. MRI showed T2 hyperintensities in the globus pallidus of 29 of 30 patients. ABR abnormalities were present in 11 of 15 patients. None of the variables were significantly different between the 2017 and 2021 surveys. The pBE infants had severely impaired gross motor function and relatively preserved manual function and verbal communication. MRI and ABR findings aid in the diagnosis of pBE.


Isolation and partial characterization of Hsp90 from Candida albicans.
Hsp90 is a stress-induced protein involved in many cellular processes including the regulation of signal transduction and steroid hormone response pathways in higher eukaryotic cells. Candida albicans hsp90 has a mass of 82 -Da and has previously been implicated as a virulence factor. A 47-kDa C-terminal fragment of Candida hsp90 is a target for an immune response to C. albicans infections. A C. albicans hsp90 specific polyclonal antibody was developed against a synthetic peptide containing a previously defined epitope of the 47-kDa fragment. This antibody was used to investigate the cellular localization and induction of hsp90 in the fungus. By means of cell surface protein extraction, hsp90 is shown to be localized on the cell surface as well as in the cytoplasm. On the cell surface, it appears only as an 82-kDa protein. In the cytoplasm, anti-hsp90 detected the 82-kDa protein as well as 72-kDa and 47-kDa bands on SDS-PAGE gels. The cytoplasmic protein bands were heat inducible and appeared to be estrogen induced as well, suggesting that C. albicans modulates hsp90 expression in response to environmental changes. Since the 82-kDa protein is also found on the surface of the cells, hsp90 may be directly involved in sensing environmental changes. It may also be important for recognition of its host or elements of the host immune system and antibody responses to the molecule and may therefore be useful for diagnostic or prognostic evaluation.


Depressive symptoms and perceived burdens related to being a student: Survey in three European countries.
Despite a high prevalence of depressive symptoms among university students, few studies have examined how this mental health problem is associated with perceived stress and perceived burdens related to being a student. We conducted a cross-sectional study of 2,103 first year students from one western (Germany), one central (Poland), and one south-eastern European country (Bulgaria). The self-administered questionnaires included the modified Beck Depression Inventory and Cohen's Perceived Stress Scale. A 13 item scale measured perceived burdens related to being a student with four subscales: "Course work", "Relationships", "Isolation", and "Future". Depressive symptoms were highly prevalent in all three countries (M-BDI >/=35: 34% in Poland, 39% in Bulgaria, and 23% in Germany). Students felt more burdened by course work and bad job prospects ("Future") than by relationship problems or by feelings of isolation. The perceived burdens subscales "Future", "Relationship" and "Isolation" remained associated with depressive symptoms after adjusting for perceived stress, which displayed a strong association with depressive symptoms. The association between perceived stress and depressive symptoms differed by gender. These findings were similar in all three countries. Perceived burdens related to studying are positively associated with higher depression scores among students, not only by mediation through perceived stress but also directly. While the strong association between perceived stress and depressive symptoms suggests the need for interventions that improve stress management, perceived burdens should also be addressed.


Local endogenous opiate activity in dog myocardium: receptor blockade with naloxone.
The participation of endogenous opiates in myocardial performance and coronary blood flow was investigated. Heart rate, left ventricular contractile force (LVCF), left coronary blood flow (LCBF), and left ventricular oxygen extraction were monitored in anesthetized dogs before and after intracoronary opiate receptor blockade with naloxone. LVCF consistently increased in a dose-dependent fashion following intracoronary naloxone. The increasing LVCF was accompanied by significant increases in LCBF and myocardial oxygen consumption, without changes in heart rate. Rapid onset of responses suggested the presence of endogenous opiates operating locally within the myocardium. Similar effects did not follow right atrial injection of naloxone, ruling out a systemic mechanism. Furthermore, naloxone injected into the isolated left anterior descending artery selectively increased contractile force in that perfusion territory while the adjacent untreated circumflex territory showed no change. The administration of dynorphin into the coronaries produced a depression of LVCF qualitatively consistent with these effects. The effect of dynorphin was subsequently reversed with naloxone. These results support the concept that endogenous opiates participate in the regulation of myocardial function through local mechanisms at the myocardial level.


Investigating human responses to political and environmental change through paleodiet and paleomobility.
Bioarchaeological approaches are well suited for examining past responses to political and environmental changes. In the Andes, we hypothesized that political and environmental changes around AD 1100 resulted in behavioral changes, visible as shifts in paleodiet and paleomobility, among individuals in the San Pedro de Atacama oases and Loa River Valley. To investigate this hypothesis, we generated carbon and oxygen isotope data from cemeteries dating to the early Middle Horizon (Larache, Quitor-5, Solor-3), late Middle Horizon (Casa Parroquial, Coyo Oriental, Coyo-3, Solcor-Plaza, Solcor-3, Tchecar), and Late Intermediate Period (Caspana, Quitor-6 Tardío, Toconce, Yaye-1, Yaye-2, Yaye-3, Yaye-4). Carbon isotope data demonstrate a greater range of carbon sources during the late Middle Horizon compared with the Late Intermediate Period; while most individuals consumed largely C3 sources, some late Middle Horizon individuals consumed more C4 sources. Oxygen isotope data demonstrate greater diversity in drinking water sources during the late Middle Horizon compared with the Late Intermediate Period. Water samples were analyzed to provide baseline data on oxygen isotope variability within the Atacama Desert, and demonstrated that oxygen isotope values are indistinguishable in the San Pedro and Loa Rivers. However, oxygen isotope values in water sources in the high-altitude altiplano and coast are distinct from those in the San Pedro and Loa Rivers. In conclusion, instead of utilizing a wider variety of resources after environmental and political changes, individuals exhibited a wider range of paleodietary and paleomobility strategies during the Middle Horizon, a period of environmental and political stability.


Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases.
The intimate relationship between mediators of the ubiquitin (Ub)-signaling system and human diseases has sparked profound interest in how Ub influences cell death and survival. While the consequence of Ub attachment is intensely studied, little is known with regards to the effects of other Ub-like proteins (UBLs), and deconjugating enzymes that remove the Ub or UBL adduct. Systematic in vivo RNAi analysis identified three NEDD8-specific isopeptidases that, when knocked down, suppress apoptosis. Consistent with the notion that attachment of NEDD8 prevents cell death, genetic ablation of deneddylase 1 (DEN1) suppresses apoptosis. Unexpectedly, we find that Drosophila and human inhibitor of apoptosis (IAP) proteins can function as E3 ligases of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Finally, we demonstrate that DEN1 reverses this effect by removing the NEDD8 modification. Altogether, our findings indicate that IAPs not only modulate cellular processes via ubiquitylation but also through attachment of NEDD8, thereby extending the complexity of IAP-mediated signaling.


Looking good or doing good? Motivations for organisational citizenship behaviour in Turkish versus South Korean collectivists.
The purpose of this article is to explore potential motivations to perform organisational citizenship behaviour (OCB) in collectivistic Turkish and South Korean societies. Although collectivism has been proposed as a predictor of OCB, previous research has not fully explored the possibility that collectivistic individuals' OCB may result from their self-oriented motives (i.e. social desirability concerns) or their future-oriented motives (i.e. long-term orientation concerns). We predicted that OCB stems from social desirability concerns among Turkish collectivists, meaning it is used for maintaining a positive image within the organisation. However, for South Korean collectivists, we predicted that OCB stems from their long-term orientation concerns, meaning it is used to make the organisation better. The results were in line with our predictions, and the findings are discussed in terms of their implications for firms in collectivistic societies.


Prevalence of coeliac disease in children and adolescents with type 1 diabetes mellitus in a clinic based population.
Although the association between type 1 diabetes mellitus (T1DM) and coeliac disease is well known, the presenting features and clinical characteristics of the two diseases when they coexist are less well documented. All patients with T1DM attending a paediatric diabetes clinic in London, UK, were screened for coeliac disease by serological testing for coeliac antibodies (antiendomysial and either/both tissue transglutaminase and antigliadin). Antibody positive patients were reviewed and their presenting symptoms, tissue biopsy result and coexisting morbidities investigated. Glycaemic control, growth and the effect of a gluten-free diet on these variables were also evaluated. Of the 113 patients with T1DM, 7 (6.2%) tested antibody positive. Jejunal biopsy confirmed coeliac disease in 5 of the 7 (4.4%) patients. Coeliac disease presented atypically or silently in the majority of cases with an unpredictable interval between diagnosis of diabetes and coeliac disease presentation. Coeliac disease did not appear to affect growth. Mean glycated haemoglobin (HbA1c) levels were not significantly raised in subjects (9.87%) compared with matched controls without coeliac disease (9.08%) (p = 0.249). Analyses of the effect of a gluten-free diet on growth and HbA1c were limited. Of the seven subjects, two suffered other autoimmune diseases. Coeliac disease presents atypically and unexpectedly in children and adolescents with T1DM. This, along with the strong association between the two diseases, supports the regular screening of coeliac disease among these patients. The value of a gluten-free diet cannot be commented on from this study alone although other studies show it reduces the risk of complications.


Pharmacokinetic and pharmacodynamic analysis comparing diverse effects of detomidine, medetomidine, and dexmedetomidine in the horse: a population analysis.
The present study characterizes the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of the α2-adrenergic receptor agonists detomidine (DET), medetomidine (MED) and dexmedetomidine (DEX) in parallel groups of horses from in vivo data after single bolus doses. Head height (HH), heart rate (HR), and blood glucose concentrations were measured over 6 h. Compartmental PK and minimal physiologically based PK (mPBPK) models were applied and incorporated into basic and extended indirect response models (IRM). Population PK/PD analysis was conducted using the Monolix software implementing the stochastic approximation expectation maximization algorithm. Marked reductions in HH and HR were found. The drug concentrations required to obtain inhibition at half-maximal effect (IC50 ) were approximately four times larger for DET than MED and DEX for both HH and HR. These effects were not gender dependent. Medetomidine had a greater influence on the increase in glucose concentration than DEX. The developed models demonstrate the use of mechanistic and mPBPK/PD models for the analysis of clinically obtainable in vivo data.


Management of hepatitis B virus in HIV-positive patients.
High rates of coinfection with human immunodeficiency virus-1 (HIV) and the hepatitis B virus (HBV) are commonly found in at risk populations due to their shared parenteral route of transmission. Although the increasingly widespread use of highly active antiretroviral therapy (HAART) has prolonged survival for those with HIV, it has also increased the potential for morbidity and mortality from other diseases and opportunistic infections. Liver-related illness is a leading cause of morbidity and mortality in those infected with HIV and HBV is responsible for a vast proportion of this, especially in regions of high HBV prevalence. HIV/HBV coinfected patients may exhibit atypical serological markers of HBV infection, hindering appropriate diagnosis. They may experience faster progression to cirrhosis, decompensation, and hepatocellular carcinoma than HBV-monoinfected patients. Rates of response to vaccine against HBV are abrogated in those with HIV, facilitating the spread of the virus. Treatment of HBV must be monitored for resistance, although newer agents appear to have less risk of resistance development. Moreover, treatment of HIV with antivirals must be monitored closely for liver toxicity. Because liver damage with HBV occurs via the immune response to the virus, liver damage is possible with HAART-mediated immune reconstitution. Although liver transplant is not commonly undertaken in HIV-positive patients, centers undertaking transplantation report improved survival and low rates of HBV recurrence.


Impact of the presence of medical equipment in images on viewers' perceptions of the trustworthiness of an individual on-screen.
It is now common practice for doctors to consult patients by means other than face-to-face, often appearing before the patient on a computer screen. Also, many websites are using depictions of health professionals to increase the credibility of their services. Being trustworthy is an essential attribute for successful ehealth services. Little is known about which depicted accessories make a health professional appear more trustworthy. To estimate the odds of an individual on-screen being rated trustworthy when viewed in a static image holding or wearing specific items of medical equipment. We surveyed consecutive people attending community pharmacies to collect prescriptions in Western Australia. Respondents were presented with a series of 10 photographs, generated at random, of a man with varying numbers and combinations of medical equipment: stethoscope, reflex hammer, surgical scrubs, otoscope, and pen. They were then invited to rate the man as honest, trustworthy, honorable, moral, ethical, or genuine, or a combination of these, on the Source Credibility Scale. A total of 168 of 250 people gave informed consent, for a participation rate of 67.2%. There were 102 female and 66 male respondents. Of the 168 respondents, 96 (57%) were born in Australia and 102 (60.7%) were attending medical practices with more than one general practitioner. The mean age of respondents was 47 (SD 16) years (range 26-92 years). When only 1 item was present in an image, the stethoscope was associated with the highest odds for the person being considered honest (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.6-4.3), trustworthy (OR 2.3, 95% CI 1.4-3.8), honorable (OR 2.7, 95% CI 1.6-4.5), moral (OR 2.4 95% CI 1.4-4.1), ethical (OR 2.6, 95% CI 1.5-4.6), and genuine (OR 1.8, 95% CI 1.0-3.1). The presence of a stethoscope increased the odds of the person being rated in a positive light in all photographs in which it was included. When an individual is portrayed in a static image, concurrent presentation of 3 or more items of medical equipment, and especially a stethoscope, is likely to exert a positive influence on the viewers' perceptions of the qualities of the person depicted.


Use of annexin-V to demonstrate the role of phosphatidylserine exposure in the maintenance of haemostatic balance by endothelial cells.
Annexin-V (PAP-I, lipocortin-V) acts as a potent anticoagulant in vitro by binding to negatively charged phospholipids with higher affinity than vitamin K-dependent proteins, with a Kd in the 10(-10) M range. The purpose of the present study was to use annexin-V as a probe to assess the catalytic potential of phospholipids in pro- and anti-coagulant reactions in purified systems and at the surface of endothelial cells in culture after stimulation. Procoagulant tissue factor and anticoagulant thrombomodulin activities were compared by using specific two-stage amidolytic assays performed with purified proteins. Procoagulant activity was estimated by the generation of Factor Xa by the Factor VII(a)-tissue factor complex. Anticoagulant activity was estimated by the generation of activated protein C by either the thrombin-thrombomodulin complex or Factor Xa. Annexin-V induced a decrease of 70% of thrombomodulin activity when thrombomodulin (5.4-214 nM) was reconstituted into phosphatidylcholine/phosphatidylserine (1:1, mol/mol) vesicles at 37.5 or 75 microM-phospholipid concentration, the apparent Ki being 0.5 microM at 75 microM-lipid. The saturating concentration of annexin-V was dependent on phospholipid concentration, but was independent of the phospholipid/thrombomodulin ratio. By contrast, when thrombomodulin was not reconstituted in vesicles, annexin-V had no effect. At 2 microM, annexin-V totally inhibited the generation of activated protein C by Factor Xa in the presence of 75 microM-lipid, the saturating inhibitory concentration being dependent on phospholipid concentration. At 0.1 microM, annexin-V totally inhibited tissue-factor activity present in crude brain thromboplastin. In the absence of stimulation, human endothelial cells in culture expressed significant thrombomodulin activity and no detectable tissue-factor activity. Basal thrombomodulin activity was only slightly inhibited (less than 15%) by 0.5 microM-annexin-V. Phorbol myristate acetate (PMA) induced the expression of tissue-factor activity and decreased thrombomodulin activity at the endothelial-cell surface. Annexin-V, at a concentration of 16 microM, caused an 80% decrease of tissue-factor activity induced by PMA at 10 ng/ml, whereas it inhibited thrombomodulin activity by only 15% on the same stimulated cells. Our results confirm that annexin-V inhibits, in vitro, procoagulant tissue-factor activity and anticoagulant activities (activation of protein C by the thrombin-thrombomodulin complex and by Factor Xa), through phospholipid-dependent mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)


Factors influencing reversion from virus infection in sweetpotato.
Viruses limit sweetpotato (Ipomoea batatas) production worldwide. Many sweetpotato landraces in East Africa are, however, largely virus-free. Moreover, some plants infected by the prevalent Sweet potato feathery mottle virus (SPFMV) may be able to revert to virus-free status. In this study, we analysed reversion from SPFMV, Sweet potato virus C, Sweet potato mild mottle virus, Sweet potato chlorotic stunt virus (SPCSV) and Sweet potato leaf curl Uganda virus using the indicator plant I. setosa and PCR/reverse-transcriptase PCR. We also investigated environmental factors (temperature and soil nutrients) that may influence reversion from virus infection. We tested reversion in the East African cultivars New Kawogo, NASPOT 1 and NASPOT 11, and the United States cultivars Resisto and Beauregard. Reverted plants were asymptomatic and virus was undetectable in assayed parts of the plant. After graft inoculation, only the East African cultivars mostly reverted at a high rate and from most viruses though cultivar Beauregard fully reverted following sap inoculation with Sweet potato virus C. None of the tested cultivars fully reverted from single or double infections involving SPCSV, and reversion was only observed in co-infections involving potyviruses. Root sprouts derived from SPFMV-reverted plants were also virus free. Reversion generally increased with increasing temperature and by improved soil nutrition. Overall, these results indicate variation in reversion by cultivar and that the natural ability of sweetpotato plants to revert from viruses is malleable, which has implications for both breeding and virus control.


Regulation of innate CD8+ T-cell activation mediated by cytokines.
Virus-specific CD8(+) T cells develop the ability to function in an "innate" capacity by responding to a remarkable array of cytokines in a TCR-independent manner. Although several cytokines such as IL-12 and IL-18 have been identified as key regulators of CD8(+) T-cell activation, the role of other cytokines and the ways in which they interact with each other remain unclear. Here, we have used an unbiased, systematic approach to examine the effects of 1,849 cytokine combinations on virus-specific CD8(+) T-cell activation. This study identifies several unexpected cytokine combinations that synergize to induce antigen-independent IFNγ production and CD69 up-regulation by CD8(+) T cells in addition to cytokines that exhibit differential regulatory functions, with the ability to either enhance or inhibit T-cell IFNγ production, depending on which cytokine partner is present. These findings underscore the complexity of cytokine interactions while also providing insight into the multifaceted regulatory network controlling virus-specific CD8(+) T-cell functions.


[Molecular bases for the development of variants of idiopathic fibrosing alveolitis].
The purpose of the study was to examine the specific features of morphological manifestations and molecular mechanisms of controlling the processes of proliferation, apoptosis, cell differentiation, neoangiogenesis, and fibrosis, which result in lung tissue rearrangement in different types of idiopathic fibrosing alveolitis (IFA). Open and transbronchial biopsy specimens obtained from 103 patients with IFA and intact lung tissue biopsy specimens taken from those clinically diagnosed as having sarcoidosis as a control group were examined. The serial paraffin sections immunohistochemically revealed the following antigens: cytokeratins 5, 6, 7, 8, 19 (Uni-Heidelberg, DAKO), MMP 1, MMP 2, MMP 7, and TIMP 4, Apo-protein (Novocastra), Ki67, PCNA, PDGF, EGFR, CD34, SMA (smooth muscle actin), FGFb (LabVision). Biotin-conjugated antibodies to murine and rabbit immunoglobulins (Dako LSAB + KIT, PEROXIDASE) were used as secondary antibodies. The nuclei were stained with hematoxylin. Positive and negative control tests were carried out. The results of immunohistochemical tests were estimated in percentage of cells showing positive reactions (Ki67, PCNA), as well as those of a semiquantitative analysis in scores and statistical analyses (Mann-Whitney U-test, Fisher's test, and Spearman's rank correlation coefficient) were employed. OIP was ascertained to differ from other IFA in higher values of the cytokines under study, as well as in the predominant rearrangement of the lung interstice and dysregeratory epithelial changes at the site of respiratory bronchiolar transformation. At the same time there was an intensive proliferation of the epithelium and stromal cells (high expression of PCNA, PDGF by hyperplastic alveolocytes, alveolar macrophages, fibroblasts and myofibroblasts), and neogenesis (the high density of newly formed vessels with endothelial expression of CD34). Elevated alveolocytic apoptosis (from Apo-protein expression) was also observed. Cell proliferation and neoangiogenesis was attained by high MMPs expression. The practical value of the study is that the expression of the study markers may serve as a criterion for differential diagnosis and determination of prognosis in different types of IFA.


Behavioral effects of benzylideneoxymorphone (BOM), a low efficacy µ opioid receptor agonist and a δ opioid receptor antagonist.
Opioids remain the drugs of choice for treating moderate to severe pain, although adverse effects often limit use. Drugs acting concomitantly as agonists at μ opioid receptors and antagonists at δ opioid receptors produce antinociceptive effects with a reduced profile of adverse effects; one such drug, benzylideneoxymorphone (BOM), might further limit adverse effects because it appears to have lower pharmacological efficacy than other μ opioid receptor agonists. The current study compared the acute behavioral effects of BOM with the effects of other μ opioid receptor agonists. Discriminative stimulus and rate-decreasing effects were studied in 1 group of 7 rats discriminating 3.2 mg/kg morphine while responding under a fixed-ratio 10 schedule of food presentation. Antinociceptive effects were determined in a second group of 8 rats using a warm water tail withdrawal procedure. Reinforcing effects were evaluated in a third group of 12 rats with a history of remifentanil self-administration. BOM produced morphine-lever responding and both discriminative stimulus and rate-decreasing effects were antagonized by naltrexone. BOM did not markedly increase tail-withdrawal latencies from water maintained at 50 °C and did not substantially attenuate the antinociceptive effects of morphine. BOM was not self-administered and did not change remifentanil self-administration. Some effects of BOM (e.g., discriminative stimulus effects) appear to be mediated by μ opioid receptors; however, BOM is not self-administered by rats, suggesting that it might have limited abuse liability and a reduced profile of adverse effects compared with currently prescribed opioids.


Water-drinking Test and Pharmacologic Mydriasis as Provocative Tests in Primary Angle Closure Suspects.
To compare the water-drinking test (WDT) and pharmacologic mydriasis as provocative tests in patients with primary angle closure suspect (PACS). This observational non-randomized comparative study evaluated changes in intraocular pressure (IOP) in 21 patients with PACS who underwent pharmacologic mydriasis and compared it with IOP changes in 26 patients given the WDT. Ocular biometric and anterior chamber parameters were also assessed. Tests were repeated on the same patient two weeks after performing laser peripheral iridotomy (LPI). The mean age ± standard deviation was 60 ± 7 and 57 ± 9 years in the mydriasis and WDT groups, respectively (P = 0.201). Before LPI, both provocative tests were associated with a significant increase in IOP (mydriasis: 15.1 ± 3.1 to 16.6 ± 3.5 mmHg, P = 0.025; WDT: 16.2 ± 2.8 to 18.5 ± 3.3 mmHg, P < 0.001). However, the IOP changes were not statistically different between groups (P = 0.102). After LPI, only the WDT group showed a continued significant IOP elevation after the test (mydriasis: 16.4 ± 3.3 to 16.7 ± 3.5 mmHg, P = 0.569; WDT: 14.9 ± 3.0 to 17.8 ± 4.1 mmHg, P < 0.001). The post-test IOP change was significantly greater in the WDT than in the mydriasis group (3.0 versus 0.3 mmHg, respectively; P = 0.002). Step-wise multiple regression analysis verified the type of provocative test as the only independent factor affecting the post-test IOP change after LPI (regression coefficient: 2.664; P = 0.002). Pharmacologic mydriasis and the WDT had similar IOP elevation before LPI, but after LPI, IOP elevation was much greater in the WDT group.


Dosimetric characteristics of the DRAXIMAGE model LS-1 1-125 interstitial brachytherapy source design: a Monte Carlo investigation.
(Received 5 June 2001; accepted for publication 26 December 2001; published 19 March 2002) We have used Monte Carlo photon transport simulations to evaluate dosimetric characteristics of a new 125I seed, the DRAXIMAGE BrachySeed (model LS-1) source for interstitial brachytherapy and to calculate the dosimetric parameters recommended by the AAPM Task Group 43 (TG-43). To eliminate thick end welds, preformed closed-ended Ti shells are welded together near the transverse plane. The radioactivity is localized near the seed ends in order to maximize isotropy at typical prescription distances. Transmission radiography reveals that its internal components can move by as much as 200 microm under the influence of gravitational forces affecting the dose-rate constant and relative dose distribution by as much as 5% and 10%, respectively. However, the clinical dose distribution can be well represented by a weighted average of dose distributions corresponding to three different orientation-dependent internal geometry configurations. This average dose distribution agrees closely (within 1% at 1 cm) with that derived from the geometry specified by the vendor model (seed components uniformly spaced), from which the recommended relative dosimetry parameters were derived. An average dose-rate constant of 0.935 cGy h(-1) U(-1) is recommended for clinical application and values of 0.919, 0.963, and 0.920 for vertical orientation, horizontal orientation, and the vendor specified geometries, respectively. The NIST wide-angle free-air chamber realization of the air-kerma strength primary standard, SKN99, was explicitly simulated. We show that the output of Ag characteristic x rays is about half that of the model 6711 source resulting in a relative dose distribution between that of the model 6711 source and pure 125I x-ray emitters. Finally, it is demonstrated that the TG-43 point-source formalism more accurately estimates solid-angle weighted dose at small distances if one uses a radial dose function data prepared using a point-source, rather than line-source, geometry factor.


Update on Biology of Cutaneous T-Cell Lymphoma.
Cutaneous T cell lymphomas (CTCL) comprise of a heterogeneous group of non-Hodgkin lymphomas derived from skin-homing T cells. Variation in clinical presentation and lack of definitive molecular markers make diagnosis especially challenging. The biology of CTCL remains elusive and clear links between genetic aberrations and epigenetic modifications that would result in clonal T cell expansion have not yet been identified. Nevertheless, in recent years, next generation sequencing (NGS) has enabled a much deeper understanding of the genomic landscape of CTCL by uncovering aberrant genetic pathways and epigenetic dysregulations. Additionally, single cell profiling is rapidly advancing our understanding of patients-specific tumor landscape and its interaction with the surrounding microenvironment. These studies have paved the road for future investigations that will explore the functional relevance of genetic alterations in the progression of disease. The ultimate goal of elucidating the pathogenesis of CTCL is to establish effective therapeutic targets with more durable clinical response and treat relapsing and refractory CTCL.


Effectiveness of service linkages in primary mental health care: a narrative review part 1.
With the move to community care and increased involvement of generalist health care providers in mental health, the need for health service partnerships has been emphasised in mental health policy. Within existing health system structures the active strategies that facilitate effective partnership linkages are not clear. The objective of this study was to examine the evidence from peer reviewed literature regarding the effectiveness of service linkages in primary mental health care. A narrative and thematic review of English language papers published between 1998 and 2009. Studies of analytic, descriptive and qualitative designs from Australia, New Zealand, UK, Europe, USA and Canada were included. Data were extracted to examine what service linkages have been used in studies of collaboration in primary mental health care. Findings from the randomised trials were tabulated to show the proportion that demonstrated clinical, service delivery and economic benefits. A review of 119 studies found ten linkage types. Most studies used a combination of linkage types and so the 42 RCTs were grouped into four broad linkage categories for meaningful descriptive analysis of outcomes. Studies that used multiple linkage strategies from the suite of "direct collaborative activities" plus "agreed guidelines" plus "communication systems" showed positive clinical (81%), service (78%) and economic (75%) outcomes. Most evidence of effectiveness came from studies of depression. Long term benefits were attributed to medication concordance and the use of case managers with a professional background who received expert supervision. There were fewer randomised trials related to collaborative care of people with psychosis and there were almost none related to collaboration with the wider human service sectors. Because of the variability of study types we did not exclude on quality or attempt to weight findings according to power or effect size. There is strong evidence to support collaborative primary mental health care for people with depression when linkages involve "direct collaborative activity", plus "agreed guidelines" and "communication systems".


The influence of handling technique on the strength of phosphate-bonded investments.
This study examined the influence of six handling techniques on the strength of four phosphate-bonded investment (PBI) materials. The size and distribution of pores produced by the handling techniques were investigated and their effect on room temperature strength determined. Specimens were tested for strength using four point bend at a cross-head speed of 1 mm min-1. The fracture surface of randomly selected specimens was viewed through a light microscope to determine the pore size. A three-parameter Weibull distribution was used to describe strength giving values of Weibull modulus and characteristic strength. The handling technique that produced the smallest pore size resulted in the highest strength. Significant differences in strength (90% confidence level) were found between most handling techniques. The reduction of pore size by mechanical spatulation and setting under pressure was found to be the most effective method of increasing the strength of PBI. Previous studies have related handling technique to the inclusion of air bubbles in dental investments but have not reported any consequent effect on strength. PBI materials are used in production of a range of dental appliances with a variety of different material forming processes and are required to withstand the loads applied without fracture or distortion to ensure accuracy of fit of these prostheses. The use of a handling technique that reduces pore size can significantly increase the strength of PBIs, thereby decreasing the possibility of die fracture or degradation.


Studies on thermal destruction of Escherichia coli in milk and milk products.
Escherichia coli (ATCC no. 9637) was shown to have mean D values (slope of destruction rate curve) of 28.2, 5.1, 1.3, 0.00195, 0.00100, 0.00055, 0.00029, and 0.00016 min in milk at temperatures of 125, 130, 135, 168, 170, 172, 174, and 176 F, respectively. The mean D values for this organism in chocolate milk were 32.2, 10.4, 2.6, 0.00265, 0.00133, 0.00069, 0.00035, and 0.00028 min at respective temperatures of 125, 130, 135, 168, 170, 172, 174, and 176 F. Mean D values of 34.4, 10.0, 3.5, 0.00093, 0.00080, 0.00068, 0.00043, and 0.00036 min were found in cream for respective temperatures of 125, 130, 135, 168, 170, 172, 174, and 176 F. In ice cream mix the organism was found to have mean D values of 39.3, 15.2, 5.1, 0.00147, 0.00120, 0.00078, 0.00070, and 0.00053 min for temperatures of 125, 130, 135, 170, 172, 174, 176, and 178 F, respectively. The slopes of the thermal death time curves were found to be 10.2, 10.2, 10.0, and 10.3 F for this organism in milk, chocolate milk, 40% fat cream, and ice cream mix, respectively.


Vitamin D receptor agonists, cancer and the immune system: an intricate relationship.
Vitamin D receptor (VDR) agonists can inhibit cell growth, promote apoptosis, and induce differentiation of many cell types, in addition to inhibiting metastasis and angiogenesis, all desirable properties for a drug to control cancer. However, from an immunological perspective, the immunomodulatory properties of VDR agonists are apparently just opposite to the main aims of cancer immunotherapy: boosting the immune response and breaking tumor-related tolerance. While it may be possible to identify VDR agonists with enhanced anti-proliferative/pro-differentiative and reduced immunomodulatory activities as anti-cancer agents, a complementary approach could rely on identifying clinical indications where their systemic immunomodulatory properties could be minimized. Superficial bladder cancer, where treatments are usually administered by vesical instillation, may represent such an indication. We have observed a strong synergism in vitro between calcitriol and doxorubicin or epirubicin in the inhibition of bladder cancer cell proliferation. Thus, calcitriol and doxorubicin or epirubicin in combination may have clinical value in the management of superficial bladder cancer.


Rescue percutaneous coronary intervention after failed thrombolysis: results from the Acute Coronary Syndrome Israel Surveys (ACSIS).
The benefit of rescue percutaneous coronary intervention (PCI) in acute myocardial infarction patients, who fail to show signs of reperfusion after full dose thrombolysis, is still an unresolved issue. To assess the outcomes of patients who underwent rescue PCI after full-dose thrombolytic therapy and compare them to patients treated only with thrombolysis in the Acute Coronary Syndrome Israel Surveys (ACSIS). ACSIS is a biannual survey on acute myocardial infarction performed in all 26 intensive cardiac care units in Israel during a two-month period. 2,018 patients were admitted with acute myocardial infarction during the two-month period in the 2000 and 2002 surveys, and 796 of them were treated with thrombolytic therapy. Rescue PCI was performed in 99 patients who failed to show signs of reperfusion. The control group consisted of patients with unsuccessful thrombolysis and no further intervention. Patients who underwent rescue PCI had a numerically higher incidence of anterior wall myocardial infarction, diabetes, higher Killip class on admission and cardiogenic shock. Furthermore, almost half of these patients had reduced left ventricular function (P = 0.03). During hospitalization, there was a significantly higher prevalence of recurrent ischemic events and major bleeding complications in patients who underwent rescue PCI. In-hospital, 30-day and one-year mortality rates were similar between the two groups. By multivariate analyses, Killip class 3-4 (OR: 2.62, CI = 0.95-6.58, P = 0.05) and streptokinase treatment (OR: 0.623, CI = 0.4-0.97, P = 0.05) were independent predictors of rescue PCI. Rescue angioplasty was associated with 15% risk-reduction (CI = 0.45-1.97, P = 0.05) in 30-day mortality and recurrent emergent hospitalization. Patients who underwent rescue PCI had similar short- and long-term mortality rates compared to patients treated with thrombolysis alone, despite differences in baseline characteristics. Rescue angioplasty was associated with a 15% risk reduction in mortality at 30-days, at the cost of higher rate of recurrent ischemic events and bleeding complications. Therefore, rescue angioplasty may be an equalizer in severely ill patients who receive thrombolytic therapy and fail to show signs of reperfusion.


Isolation of the yeast regulatory gene GAL4 and analysis of its dosage effects on the galactose/melibiose regulon.
GAL4 is a classically defined positive regulatory gene controlling the five inducible structural genes of galactose/melibiose utilization in yeast. The positive regulatory function of the GAL4 gene product in turn is controlled by the product of another gene, the negative regulator GAL80. We have cloned a 3.1-kilobase fragment containing GAL4 by homologous complementation using the multicopy chimeric vector YEp24 and demonstrated that multiple copies of GAL4 in yeast have pronounced dosage effects on the expression of the structural genes. Yeast transformed with GAL4-bearing plasmid become constitutive for expression of the galactose/melibiose genes, even in normally repressing (glucose) medium. Multiple copies of the GAL4 plasmid also increase expression of the structural genes in inducing (galactose) medium and can partially overcome the effects of a dominant super-repressor mutant, GAL80S. Using an internal deletion in GAL4, we have demonstrated that these dosage effects are due to overproduction of GAL4 positive regulatory product rather than an effect of the flanking sequences titrating out a negative regulator. These results point to the importance of competitive interplay between the positive and negative regulatory proteins in the control of this system. We have also used the dosage effect of GAL4 plasmid in combination with different GAL4 and GAL80 alleles to create new phenotypes. We interpret these phenotypes as indicating that (i) the repressing effects of glucose, at least in part, are mediated by the product of the negative regulatory gene, GAL80, and (ii) the GAL80 protein may have specific interactions with the control regions of the structural genes.


Impaired coronary blood flow in nonculprit arteries in the setting of acute myocardial infarction. The TIMI Study Group. Thrombolysis in myocardial infarction.
While attention has focused on coronary blood flow in the culprit artery in acute myocardia infarction (MI), flow in the nonculprit artery has not been studied widely, in part because it has been assumed to be normal. We hypothesized that slower flow in culprit arteries, larger territories infarcted and hemodynamic perturbations may be associated with slow flow in nonculprit arteries. The number of frames for dye to first reach distal landmarks (corrected TIMI [Thrombolysis in Acute Myocardial Infarction] frame count [CTFC]) were counted in 1,817 nonculprit arteries from the TIMI 4, 10A, 10B and 14 thrombolytic trials. Nonculprit artery flow was slowed to 30.9 +/- 15.0 frames at 90 min after thrombolytic administration, which is 45% slower than normal flow in the absence of acute MI (21 +/- 3.1, p < 0.0001). Patients with TIMI grade 3 flow in the culprit artery had faster nonculprit artery CTFCs than those patients with TIMI grades 0, 1 or 2 flow (29.1 +/- 13.7, n = 1,050 vs. 33.3 +/- 16.1, n = 752, p < 0.0001). The nonculprit artery CTFC improved between 60 and 90 min (3.3 +/- 17.9 frames, n = 432, p = 0.0001), and improvements were related to improved culprit artery flow (p = 0.0005). Correlates of slower nonculprit artery flow included a pulsatile flow pattern (i.e., systolic flow reversal) in the nonculprit artery (p < 0.0001) and in the culprit artery (p = 0.01), a left anterior descending artery culprit artery location (p < 0.0001), a decreased systolic blood pressure (p = 0.01), a decreased ventriculographic cardiac output (p = 0.02), a decreased double product (p = 0.0002), a greater percent diameter stenosis of the nonculprit artery (p = 0.01) and a greater percent of the culprit artery bed lying distal to the stenosis (p = 0.04). Adjunctive percutaneous transluminal coronary angioplasty (PTCA) of the culprit artery restored a culprit artery CTFC (30.4 +/- 22.2) that was similar to that in the nonculprit artery at 90 min (30.2 +/- 13.5), but both were slower than normal CTFCs (21 +/- 3.1, p < 0.0005 for both). If flow in the nonculprit artery was abnormal (CTFC > or = 28 frames) then the CTFC after PTCA in the culprit artery was 17% slower (p = 0.01). Patients who died had slower global CTFCs (mean CTFC for the three arteries) than patients who survived (46.8 +/- 21.3, n = 47 vs. 39.4 +/- 16.7, n = 1,055, p = 0.02). Acute MI slows flow globally, and slower global flow is associated with adverse outcomes. Relief of the culprit artery stenosis by PTCA restored culprit artery flow to that in the nonculprit artery, but both were 45% slower than normal flow.


Facile synthesis of hyaluronic acid-modified Fe3O4/Au composite nanoparticles for targeted dual mode MR/CT imaging of tumors.
A facile co-precipitation approach for synthesizing hyaluronic acid (HA)-modified Fe3O4/Au composite nanoparticles (CNPs) for targeted dual mode tumor magnetic resonance (MR) and computed tomography (CT) imaging is reported. In this work, polyethyleneimine (PEI) was employed as a stabilizer to form gold NPs (PEI-Au NPs). In the presence of the PEI-Au NPs, controlled co-precipitation of Fe(ii) and Fe(iii) salts was performed, leading to the formation of the Fe3O4/Au-PEI CNPs, which were further modified with hyaluronic acid (HA). We show that the formed Fe3O4/Au-PEI-HA CNPs are colloidally stable, hemocompatible and cytocompatible in a given concentration range, and have a high affinity to target CD44 receptor-overexpressing cancer cells. Due to the presence of Fe3O4 and Au components, the formed Fe3O4/Au-PEI-HA CNPs display a high r2 relaxivity (264.16 mM-1 s-1) and good X-ray attenuation property, rendering them with an ability to be used as a nanoprobe for targeted dual mode MR/CT imaging of CD44 receptor-overexpressing cancer cells in vitro and a xenografted tumor model in vivo. The Fe3O4/Au-PEI-HA CNPs developed via this facile approach may hold great promise to be used as a unique platform for precision imaging of CD44 receptor-overexpressing tumors.


Microsomal epoxide hydrolase polymorphisms.
Microsomal epoxide hydrolase plays a dual role in the activation and detoxification of carcinogenic compounds. Two polymorphic sites have been described in exons 3 and 4 of the microsomal epoxide hydrolase gene that change tyrosine residue 113 to histidine (Tyr113His) and histidine 139 to arginine (His139Arg), respectively. The exon 3 polymorphism reduces enzyme activity by approximately 50%, whereas the exon 4 polymorphism causes a 25% increase in activity. In the present study, the distribution of these polymorphisms in a Turkish population including 625 unrelated healthy individuals was examined using a PCR-RFLP method. The observed genotype frequencies of microsomal epoxide hydrolase exon 3 were 54, 38 and 8% for Tyr113Tyr, Tyr113His and His113His, respectively. Exon 4 genotype frequencies were found to be 69, 29 and 2% for His139His, His139Arg and Arg139Arg, respectively.


Evidence for a Mesothelial Origin of Body Cavity Effusion Lymphomas.
Primary effusion lymphoma (PEL) is a Kaposi's sarcoma herpes virus (KSHV)-induced lymphoma that typically arises in body cavities of HIV-infected patients. PEL cells are often co-infected with Epstein-Barr virus (EBV). "PEL-like" lymphoma is a KSHV-unrelated lymphoma that arises in body cavities of HIV-negative patients. "PEL-like" lymphoma is sometimes EBV positive. The derivation of PEL/"PEL-like" cells is unclear. Mesothelial cells were cultured from body cavity effusions of 23 patients. Cell proliferation, cytokine secretion, marker phenotypes, KSHV/EBV infection, and clonality were evaluated by standard methods. Gene expression was measured by quantitative polymerase chain reaction and immunoblotting. A mouse model of PEL (3 mice/group) was used to evaluate tumorigenicity. We found that the mesothelia derived from six effusions of HIV-infected patients with PEL or other KSHV-associated diseases contained rare KSHV + or EBV + mesothelial cells. After extended culture (16-17 weeks), some mesothelial cells underwent a trans-differentiation process, generating lymphoid-type CD45 + /B220 + , CD5 + , CD27 + , CD43 + , CD11c + , and CD3 - cells resembling "B1-cells," most commonly found in mouse body cavities. These "B1-like" cells were short lived. However, long-term KSHV + EBV - and EBV + KSHV - clonal cell lines emerged from mesothelial cultures from two patients that were clonally distinct from the monoclonal or polyclonal B-cell populations found in the patients' original effusions. Mesothelial-to-lymphoid transformation is a newly identified in vitro process that generates "B1-like" cells and is associated with the emergence of long-lived KSHV or EBV-infected cell lines in KSHV-infected patients. These results identify mesothelial cultures as a source of PEL cells and lymphoid cells in humans.


Design of the Lanthanum hexaboride based plasma source for the large plasma device at UCLA.
The Large Plasma Device (LAPD) at UCLA (University of California, Los Angeles) produces an 18 m long, magnetized, quiescent, and uniform plasma at a high repetition rate to enable studies of fundamental plasma physics. Here, we report on a major upgrade to the LAPD plasma source that allows for more robust operation and significant expansion of achievable plasma parameters. The original plasma source made use of a heated barium oxide (BaO) coated nickel sheet as an electron emitter. This source had a number of drawbacks, including a limited range of plasma density (≲4.0 × 1012 cm-3), a limited discharge duration (∼10 ms), and susceptibility to poisoning following oxygen exposure. The new plasma source utilizes a 38 cm diameter lanthanum hexaboride (LaB6) cathode, which has a significantly higher emissivity, allowing for a much larger discharge power density, and is robust to exposure to air. Peak plasma density of up to 3.0 × 1013 cm-33 in helium gas has been achieved. The typical operating pressure is ∼10-5 Torr, while dynamic pressure can be achieved through the gas-puffing technique. Discharges as long as 70 ms have been produced, enabling a variety of long-time-scale studies of processes, such as turbulent particle transport. The new source has been in continuous operation for 14 months, having survived air leaks, power outages that led to rapid temperature changes on the cathode and heater, and planned machine openings. We describe the design, construction, and initial operation of this novel new large-area LaB6 plasma source.


Airway inflammation and illness severity in response to experimental rhinovirus infection in asthma.
The nature of bronchial mucosal inflammation and its physiologic and clinical significance in rhinovirus-induced asthma exacerbations is unclear. We investigated bronchial mucosal inflammatory response and its association with physiologic and clinical outcomes in an experimental model of rhinovirus-induced asthma exacerbations. We used immunohistochemistry methods to detect phenotypes of inflammatory cells infiltrating the bronchial mucosa before and after experimental rhinovirus infection in 10 subjects with asthma and 15 normal subjects. Compared with baseline, rhinovirus infection significantly increased the number of epithelial (P = .005) and subepithelial (P = .017) neutrophils in subjects with asthma only and subepithelial CD68+ macrophages in both subjects with asthma (P = .009) and normal subjects (P = .018) but more so in those with asthma (P = .021). Numbers of CD45+, CD68+, and CD20+ cells; neutrophils; and eosinophils at day 4 postinfection were positively associated with virus load (r = 0.50-0.72, P = .016-0.03). At acute infection in subjects with asthma, CD4+ cells correlated with chest symptom scores (r = 0.69, P = .029), the fall in the 10% fall in FEV1 (PC10) correlated with neutrophils (r = -0.89, P = .029), the PC10 correlated inversely with CD4+ (r = -0.67, P = .023) and CD8+ cells (r = -0.65, P = .03), the 20% fall in FEV1 was inversely associated with CD20+ cells (r = -0.65, P = .03), and higher epithelial CD8+ cell counts were significantly associated with a greater maximum fall in FEV1 (r = -0.72, P = .03), whereas higher subepithelial mast cell counts were significantly associated with a lower maximum percent fall in peak expiratory flow (r = 0.8, P = .024). In subjects with asthma, rhinovirus infection induces bronchial mucosal neutrophilia and more severe monocyte/macrophage infiltration than in normal subjects. Airway neutrophils, eosinophils, and T and B lymphocytes during infection are related to virus load and physiologic and clinical severity, whereas mast cells are related to greater lung function.


[Epidemiologic and etiologic study of acute respiratory infections in children under 5 years of age].
This study also included epidemiologic data to determine the risk factors for the enhancement of these infections. The coagglutination technique for the rapid diagnosis of streptococcus was tried. Five hundred and thirty one samples of pharingeal swabs were obtained from children with ARI. 74% were younger than one year old. Brochopneumonias constituted 66.39% of the cases. In total 357 agents were isolated 35% corresponding to bacteria in pure culture, 23.3% to mixed infections and 11.6% only viruses. The bacteria were: Haemphilus influenza (12.4%), Streptococcus pneumoniae (11%), Staphylococcus aureus (9%), and Klebsiella pneumoniae (6.3%), Mycoplasma pneumoniae was identified in 5 children and M. hominis in 3. Adenoviruses were isolated in 98 patients, parainfluenza in 19, respiratory syncytial virus in 4, influenza in 1 and picornavirus in 2. Predominating socioeconomic factors were: overcrowding, deficient schooling and low income of parents which favor malnutrition. The more frequent agents were constitutes by bacteria. Viruses were a less cause of infection. It was confirmed that babies under 12 months are more susceptible to bacterial pneumonia and prompt treatment with antimicrobial agents lowered the lethality. Low socioeconomic level is a possible predisposing factor for respiratory diseases.


Neuroendocrine tumours within a Meckel's diverticulum.
A Meckel's diverticulum is a common anomaly of the gastrointestinal tract. Although the majority of patients do not have any symptoms, malignancies can develop inside these diverticula, with neuroendocrine tumours being the most common. Diverticulectomy is the best option for complicated diverticula but prophylactic resection of asymptomatic diverticula in adults remains controversial. We present a case series of three patients with a neuroendocrine tumour found in a Meckel's diverticulum. Given the number of asymptomatic diverticula not resected, it seems likely that incidental neuroendocrine tumours are more prevalent than thought previously. With the minimally invasive techniques now available and the low complication rate for incidental diverticulectomy, we believe that the benefits of resection of this high risk area for cancer outweigh the risks of surgery.


Evaluation of transesophageal Doppler detection of air embolism in dogs.
The authors assessed the use of a cylindrical sensor which transceives (transmits and receives) ultrasound in a 360 degree arc mounted on a standard esophageal stethoscope catheter to detect air embolism in dogs. They used electronic circuitry developed specifically to provide a continuous analog recording of high frequency Doppler energy as well as an audible signal. They found that the esophageal Doppler sensor was easy to position. In 25 of 30 dogs, the system distinguished Doppler sounds of venous air emboli that were present either in the superior vena cava, right atrium, right ventricle, or pulmonary artery from normal cardiovascular sounds. In the remaining five animals, Doppler heart and air emboli sounds were initially of poor quality, but improved with aspiration of air from the esophagus. In another five dogs, arterial air emboli produced by left ventricular injections also were detected. The esophageal sensor was sensitive to both venous and arterial air emboli ranging from 0.05--0.2 ml of air, and the authors consistently detected repeated intravenous injections of air throughout a 5-h time period. Optimal position of the sensor for detection of venous air emboli was at the level of the superior vena cava above its junction with the right atrium. Optimal position to detect arterial air emboli introduced via a left ventricular catheter was at the level of the aortic arch. Tissue analysis of the esophagus revealed no morphologic damage due to the sensor or transmitted energy.


Highly luminescent N-doped carbon dots as a fluorescence detecting platform for Fe3+ in solutions and living cells.
Iron (Fe3+) is one of the most essential elements in the human body; deficiency or overdose of Fe3+ may have adverse effects on human health and immunity. Hence, it is essential to establish a sensitive and selective method for ion detection. In this study, novel green fluorescent N-doped carbon dots (N-CDs) were prepared with caffeic acid as the carbon source via a simple hydrothermal method. The solution of the as-prepared N-CDs exhibits 21.5% quantum yield, good salt stability, excellent water solubility, low cytotoxicity and good photobleaching resistance. The N-CDs can be used as a fluorescent probe for the detection of Fe3+ ions in aqueous solutions and bioimaging in living cells.


Recovery and decision-making involvement in people with severe mental illness from six countries: a prospective observational study.
Clinical decision-making is the vehicle of health care provision, and level of involvement predicts implementation and satisfaction. The aim of this study was to investigate the impact of decision-making experience on recovery. Data derived from an observational cohort study "Clinical decision making and outcome in routine care for people with severe mental illness" (CEDAR). Adults (aged 18-60) meeting standardised criteria for severe mental illness were recruited from caseloads of outpatient and community mental health services in six European countries. After consenting, they were assessed using standardised measures of decision-making, clinical outcome and stage of recovery at baseline and 1 year later. Latent class analysis was used to identify course of recovery, and proportional odds models to investigate predictors of recovery stage and change. Participants (n = 581) clustered into three stages of recovery at baseline: Moratorium (N = 115; 19.8%), Awareness/Preparation (N = 145; 25.0%) and Rebuilding/Growth (N = 321; 55.2%). Higher stage was cross-sectionally associated with being male, married, living alone or with parents, and having better patient-rated therapeutic alliance and fewer symptoms. The model accounted for 40% of the variance in stage of recovery. An increased chance of worse outcome (change over 1 year to lower stage of recovery) was found for patients with active involvement compared with either shared (OR = 1.84, 95% CI 1.15-2.94) or passive (OR = 1.71, 95% CI = 1.00-2.95) involvement. Overall, both process (therapeutic relationship) and outcome (symptomatology) are cross-sectionally associated with stage of recovery. Patient-rated decision-making involvement and change in stage of recovery are associated. Joint consideration of decision practise within the recovery process between patient and clinician is supposed to be a useful strategy to improve clinical practice (ISRCTN registry: ISRCTN75841675. Retrospectively registered 15 September 2010).


GLR-1, a non-NMDA glutamate receptor homolog, is critical for long-term memory in Caenorhabditis elegans.
Long-term memory for habituation to tap in Caenorhabditis elegans depends on glr-1, a homolog of mammalian non-NMDA glutamate receptors; mutations in glr-1 blocked long-term memory formation. Green fluorescent protein (GFP) constructs were used to visualize glr-1 expression in the interneurons of the mechanosensory circuit and synaptobrevin in the tap sensory neurons of trained and untrained worms. Trained animals had less GLR-1::GFP expression than untrained animals; there was no difference in the vesicle marker synaptobrevin. Heat shock during training blocked both the behavioral expression of long-term memory and the change in GLR-1::GFP expression. Thus, long-term memory in C. elegans is dependent on glr-1 and likely involves changes in the expression or localization of glutamate receptors.


Anticipatory prescribing in community end-of-life care.
Our work aims to critically review the use of anticipatory medicines in our inner-city hospice community population and whether our current practices are fit for purpose. Retrospective audit of community palliative care patients at the end-of-life prescribed anticipatory medicines within a 3-month period. Anticipatory charts and case notes reviewed. Intervention included updating local guidelines, local teaching for medical and non-medical prescribers and sharing results nationally. Eighteen months later, reaudit was performed assessing impact. In total, 76 patients included. 75/76 (99%) were prescribed an analgesic, antiemetic, antisecretory and anxiolytic. 49/76 (64%) were administered 'as required' medications at home. Haloperidol was the favoured antiemetic (88%), costing our hospice ~£2000/month. Case note review highlighted prescribing and administration issues. Reaudit showed a reduction in prescriptions of antisecretory (by 57%) and antiemetic (by 50%), with a wider range of antiemetics (levomepromazine 47%, haloperidol 35%, cyclizine 14%, metoclopramide 3%) indicating individualised prescribing. Those without an antiemetic prescribed did not later require one dispensing. Our work challenges the orthodoxy that an analgesic, antiemetic, antisecretory and anxiolytic medication must always be included for effective anticipatory prescribing. Antiemetics may not be universally required and individualised prescribing was cost-effective and safe at a local level. Further work evaluating the impacts of altered practice on patients, caregivers, professionals and in other community settings is required.


Partial recovery from cortical blindness following carbon monoxide intoxication.
Patients with carbon monoxide (CO) intoxication may show neurological signs such as headache, seizures, extrapyramidal findings, and coma. However, cortical blindness is rare in these cases. This study describes a woman exhibiting confusion and axial rigidity after CO intoxication. Ten days after intoxication, her pupils were isonormocoric and reactive to light. A fundoscopic examination was normal, but visual acuity was light-perception in both eyes. There were diffuse EEG slow waves. Magnetic resonance imaging (MRI) demonstrated bilateral hyperintensity in the basal ganglia. The P100 latencies of visual evoked potentials (VEP) were increased and dispersed. One year later, the patient's visual acuity was almost normal and VEPs showed mild dispersion in P100 latencies. The authors found this case of interest because cortical blindness due to CO intoxication is only rarely seen with a relatively good outcome.


Allergic reaction to topical eyedrops.
To examine recently published papers dealing with drug-induced allergic reactions. As allergy is only one possible mechanism, this review was extended to all reports or studies describing allergic, inflammatory or toxic effects related to eyedrops since 2004. These studies were first classified into clinical reports or surveys, experimental works and biological studies showing drug-induced effects on the ocular surface or eyelids. Studies aimed at determining the role of preservatives or comparing preservative-free and preserved eyedrops were further analysed separately. Reports on allergic or toxic reactions of eyedrops are published repeatedly. The reports raising the most important issues are those concerning antiglaucoma drugs. They consistently describe inflammatory reactions at the conjunctival level, with strong evidence that preservative is a major source of toxicity for the ocular surface.


Kinetic investigation of thermal and photoinduced homolysis of alkylated verdazyls.
The on-demand generation of stable organic radicals from the precursors can be considered as an essential challenge for the plethora of applications in various fields of science. In this contribution, we prepared a range of N-(methyl)benzyl derivatives of 6-oxoverdazyl via atom transfer radical addition from moderate to high yields and studied their thermal- and photo-initiated homolysis. The kinetics of homolysis was measured, and the dissociating rate constant kd, activation energy Ea and frequency factor A were estimated. Variation of the substituent at the C3-position of the verdazyl ring was successfully applied for fine-tuning the homolysis rate: the value of kd was higher for alkylverdazyls with electron-withdrawing groups, e.g., the para nitro group afforded a 6-fold increase in kd. In contrast to thermal homolysis, the rate of photoinduced decomposition depends on both the extinction coefficient and the value of activation energy. Thus, nitro-containing alkylated verdazyls show the highest homolysis rate in both types of initiations. The achieved results afford a novel opportunity in the controlled generation of verdazyls and further application of these compounds in medicine and chemical industry.


[Polymorphism of the renin-angiotensin system and renal failure].
The renin-angiotenin-aldosterone system (RAAS) is not only involved in cardiovascular disease but also in renal pathophysiology and progression of renal disease. Several polymorphisms of genes coding for components of the RAAS have been identified. The I/D polymorphism of the ACE gene, a variant of the angiotensiogen gen, the M235T polymorphism, and the variant A1166 C polymorphism of the angiotensin II type 1 receptor gene are the most important. Several studies have suggested a potential role for I/D polymorphism of the ACE gen in the progression of renal diseases and in the cardiovascular death rate of patients with renal failure. Data on RAAS polymorphisms as determinants of the prevalence of renal diseases and the response to renoprotective therapies are conflicting. Given the polygenic nature of renal and cardiovascular disease and the growing number of candidate genes, large prospective and collaborative studies are required to assess the effect of RAAS polymorphisms on the progression of renal disease and on the response to renoprotective therapies.


A mobile school-based HCT service - is it youth friendly?
Despite an increase in HIV Counselling and Testing (HCT), few young people have been tested. It has been suggested that they do not test because formal health services (where HCT is provided) are often not youth friendly. The World Health Organisation describes a youth-friendly health service (YFHS) as one which is accessible, equitable, acceptable, appropriate, and effective. A mobile school-based model has been implemented by a non-governmental organisation in Cape Town in an attempt to make HCT more youth friendly and accessible to young people. The objective of this study was to explore whether this mobile school-based HCT service is youth friendly. The study was descriptive, using three qualitative data collection methods: observation of the HCT site at two secondary schools; interviews with six service providers; and direct observation of 21 HCT counselling sessions. The mobile school-based HCT service fulfilled some of the criteria for being a YFHS. The service was equitable in that all students, irrespective of race, gender, age, or socio-economic status, were free to use the service. It was accessible in terms of location and cost, but students were not well informed to make decisions about using the service. The service was acceptable in that confidentiality was guaranteed and the service providers were friendly and non-judgemental, but it was not considered acceptable in that there was limited privacy. The service was appropriate in that HCT is recommended as an intervention for decreasing the transmission of HIV, based on evidence and expert opinion; however, in this case, HCT was provided as a stand-alone service rather than part of a full package of services. Moreover, studies have suggested that young people want to know their HIV status. The service was ineffective in that it identified students who are HIV positive; however, these students were not assisted to access care. Providing HCT in the school setting may make HCT more accessible for students, but it needs to be provided in an equitable, accessible, acceptable, and effective way.


A unique coincidence of a 17q12 deletion and duplication in a Czech family led to a refined genotype-phenotype correlation.
Chromosomal band 17q12 is a gene-rich region flanked by segmental duplications, making the region prone to deletions and duplications via the non-allelic homologous recombination mechanism. While deletions cause a well-described disorder with a specific phenotype called renal cysts and diabetes mellitus, the phenotype caused by reciprocal duplications is less specific, primarily because of variable expressivity, and incomplete penetrance. We present an unusual family with four children carrying the 17q12 microduplication inherited from their clinically healthy mother, who was a carrier of both the duplication and, interestingly, also of an atypical deletion of the 17q12 region. The duplication was inherited from her diabetic father and the deletion from her diabetic mother who also suffered from a renal disorder. Clinical manifestations in the family were variable, but all children showed some degree of a neurodevelopmental disorder, such as epilepsy, intellectual disability, delayed speech development, or attention deficit disorder. The simultaneous occurrence of a deletion and duplication in the same chromosomal region in one family is very rare, and to our knowledge, individuals carrying both a deletion and a duplication of this region have never been described.


A highly selective and sensitive red-emitting fluorescent probe for visualization of endogenous peroxynitrite in living cells and zebrafish.
Peroxynitrite (ONOO-) has been proven to participate in various physiological and pathological processes, and may also be a contributing factor in many diseases. In view of this, there is a need to develop detection tools for unambiguously tracking a small amount of endogenous ONOO- to reveal its exact mechanisms. In this paper, a colorimetric and red-emitting fluorescent probe Red-PN, based on a rhodamine-type fluorophore and hydrazide reactive site is described. The probe Red-PN possesses the advantages of rapid response (within 5 s), visual color change (from colorless to pink), preeminent sensitivity (detection limit = 4.3 nM) and selectivity. Because of these outstanding performances, it was possible to accurately detect endogenous ONOO-. It was encouraging that the probe Red-PN could be used effectively for tracking the relatively low levels of endogenous and exogenous ONOO- in living cells and zebrafish. Thus, it is envisioned that the probe Red-PN would have promising prospects in applications for imaging ONOO- in a variety of biological settings.


Effects of decentralization on the functionality of health facility governing committees in lower and middle-income countries: a systematic literature review.
Health facility governing committees (HFGCs) were established by lower and middle-income countries (LMICs) to facilitate community participation at the primary facility level to improve health system performance. However, empirical evidence on their effects under decentralization reform on the functionality of HFGCs is scant and inconclusive. This article reviews the effects of decentralization on the functionality of HFGCs in LMICs. A systematic literature review was conducted using various search engines to obtain a total number of 24 relevant articles from 14 countries published between 2000 and 2020. Inclusion criteria include studies must be on community health committees, carried out under decentralization, HFGCs operating at the individual facility, effects of HFGCs on health performance or health outcomes and peer-reviewed empirical studies conducted in LMICs. The study has found varied functionality of HFGCs under a decentralization context. The study has found many HFGCs to have very low functionality, while a few HFGCs in other LMICs countries are performing very well. The context and decentralization type, members' awareness of their roles, membership allowance and availability of resource to the facility in which HFGCs operate to produce the desired outcomes play a significant role in facilitating/limiting them to effectively carry out the devolved duties and responsibilities. Fiscal decentralization has largely been seen as important in making health committees more autonomous, even though it does not guarantee the performance of HFGCs.


Intravenous iron in chronic kidney disease: haemoglobin change shortly after treatment of patients neither on dialysis nor on erythropoietin.
Anaemia is a common in chronic kidney disease. Although erythropoietin and iron supplementation are established treatments, knowledge on the use of IV iron alone in patients not on dialysis or erythropoietin is incomplete. The responses of 82 patients referred to the renal anaemia service with haemoglobin of 11.5 g/dl or less were assessed 1 week after completing four once weekly doses of 200 mg of venofer. No patients were on dialysis or erythropoietin. The haemoglobin rise 1 week after treatment was 0.53 g/dl. Ferritin levels improved from 110.8 to 410.2 ng/l and transferrin saturation from 17.7 to 27.3%. Ferritin levels remained below our target range (200-500 ng/l) in 7.7% while 25.6% had levels above this. Ferritin levels remained less than 800 ng/l in nearly all patients. Intravenous iron is cost effective and should be considered for use in patients with renal anaemia. Patients with CKD stage 5 appeared to respond less well.


Liquid biopsy for lung cancers: an update on recent developments.
Liquid biopsy in lung cancer is evolving as an important added tool for screening, early detection, monitoring, and even prognostication of lung cancer. Guidelines and expert recommendations for its use in practice are available and there are specific scenarios in which liquid biopsy is actively being adopted. Several biomarkers, from which important tumor genomic information is obtained, are currently the subject of ongoing investigation. In this review, we summarize the available data on each specific biomarker and provide an overview on how they play a role in current clinical practice.