Complement component C3 binds to activated normal platelets without preceding proteolytic activation and promotes binding to complement receptor 1.
It has been reported that complement is activated on the surface of activated platelets, despite the presence of multiple regulators of complement activation. To reinvestigate the mechanisms by which activated platelets bind to complement components, the presence of complement proteins on the surfaces of nonactivated and thrombin receptor-activating peptide-activated platelets was analyzed by flow cytometry and Western blot analyses. C1q, C4, C3, and C9 were found to bind to thrombin receptor-activating peptide-activated platelets in lepirudin-anticoagulated platelet-rich plasma (PRP) and whole blood. However, inhibiting complement activation at the C1q or C3 level did not block the binding of C3 to activated platelets. Diluting PRP and chelating divalent cations also had no effect, further indicating that the deposition of complement components was independent of complement activation. Furthermore, washed, activated platelets bound added C1q and C3 to the same extent as platelets in PRP. The use of mAbs against different forms of C3 demonstrated that the bound C3 consisted of C3(H(2)O). Furthermore, exogenously added soluble complement receptor 1 was shown to bind to this form of platelet-bound C3. These observations indicate that there is no complement activation on the surface of platelets under physiological conditions. This situation is in direct contrast to a number of pathological conditions in which regulators of complement activation are lacking and thrombocytopenia and thrombotic disease are the ultimate result. However, the generation of C3(H(2)O) represents nonproteolytic activation of C3 and after factor I cleavage may act as a ligand for receptor binding.


Disease manifestations of Helicobacter pylori infection in Arctic Canada: using epidemiology to address community concerns.
Helicobacter pylori infection, linked to gastric cancer, is responsible for a large worldwide disease burden. H pylori prevalence and gastric cancer rates are elevated among indigenous Arctic communities, but implementation of prevention strategies is hampered by insufficient information. Some communities in northern Canada have advocated for H pylori prevention research. As a first step, community-driven research was undertaken to describe the H pylori-associated disease burden in concerned communities. Participants in this cross-sectional study completed a clinical interview and gastroscopy with gastric biopsies taken for histopathological examination in February 2008. Study procedures were carried out at the health centre in Aklavik, Northwest Territories, Canada (population ∼600). All residents of Aklavik were invited to complete a clinical interview and gastroscopy; 194 (58% female participants; 91% Aboriginal; age range 10-80 years) completed gastroscopy and had gastric biopsies taken. This analysis estimates the prevalence of gastric abnormalities detected by endoscopy and histopathology, and associations of demographic and clinical variables with H pylori prevalence. Among 194 participants with evaluable gastric biopsies, 66% were H pylori-positive on histology. Among H pylori-positive participants, prevalence was 94% for acute gastritis, 100% for chronic gastritis, 21% for gastric atrophy and 11% for intestinal metaplasia of the gastric mucosa, while chronic inflammation severity was mild in 9%, moderate in 47% and severe in 43%. In a multivariable model, H pylori prevalence was inversely associated with previous gastroscopy, previous H pylori therapy and aspirin use, and was positively associated with alcohol consumption. In this population, H pylori-associated gastric histopathology shows a pattern compatible with elevated risk of gastric cancer. These findings demonstrate that local concern about health risks from H pylori is warranted and provide an example of how epidemiological research can address health priorities identified by communities.


Probing Photocurrent Nonuniformities in the Subcells of Monolithic Perovskite/Silicon Tandem Solar Cells.
Perovskite/silicon tandem solar cells with high power conversion efficiencies have the potential to become a commercially viable photovoltaic option in the near future. However, device design and optimization is challenging because conventional characterization methods do not give clear feedback on the localized chemical and physical factors that limit performance within individual subcells, especially when stability and degradation is a concern. In this study, we use light beam induced current (LBIC) to probe photocurrent collection nonuniformities in the individual subcells of perovskite/silicon tandems. The choices of lasers and light biasing conditions allow efficiency-limiting effects relating to processing defects, optical interference within the individual cells, and the evolution of water-induced device degradation to be spatially resolved. The results reveal several types of microscopic defects and demonstrate that eliminating these and managing the optical properties within the multilayer structures will be important for future optimization of perovskite/silicon tandem solar cells.


Anthocyanins double the shelf life of tomatoes by delaying overripening and reducing susceptibility to gray mold.
Shelf life is an important quality trait for many fruit, including tomatoes. We report that enrichment of anthocyanin, a natural pigment, in tomatoes can significantly extend shelf life. Processes late in ripening are suppressed by anthocyanin accumulation, and susceptibility to Botrytis cinerea, one of the most important postharvest pathogens, is reduced in purple tomato fruit. We show that reduced susceptibility to B. cinerea is dependent specifically on the accumulation of anthocyanins, which alter the spreading of the ROS burst during infection. The increased antioxidant capacity of purple fruit likely slows the processes of overripening. Enhancing the levels of natural antioxidants in tomato provides a novel strategy for extending shelf life by genetic engineering or conventional breeding.


A Qualitative Study of Community-Based HIV/AIDS Prevention Interventions, Programs, and Projects for Rural and Remote Regions in Canada: Implementation Challenges and Lessons Learned.
Fifteen percent to 20% of the Canadian and American populations live outside urban areas, and despite growing regional HIV/AIDS-related health disparities, there is little published research specific to rural or remote (rural/remote) HIV/AIDS prevention programming. To document implementation challenges, lessons learned, and evaluation approaches of promising and proven HIV/AIDS prevention programs and interventions developed and delivered by organizations with rural/remote catchment areas in Canada to provide a foundation for information sharing among agencies. Qualitative study design, using a community-based participatory research approach. We screened Canadian community-based organizations with an HIV/AIDS prevention mandate to determine whether they offered services for rural/remote populations and invited organizational representatives to participate in semistructured telephone interviews. Interviews were audio-recorded and transcribed. Content analysis was used to identify categories in the interview data. Canada, provinces (all except Prince Edward Island), and territories (all except Nunavut). Twenty-four community-based organizations. Screening calls were completed with 74 organizations, of which 39 met study criteria. Twenty-four (62%) interviews were conducted. Populations most frequently served were Indigenous peoples (n = 13 organizations) and people who use drugs (n = 8 organizations) (categories not mutually exclusive). Key lessons learned included the importance of involving potential communities served in program development; prioritizing community allies/partnerships; building relationships; local relevancy and appropriateness; assessing community awareness or readiness; program flexibility/adaptability; and addressing stigma. Evaluation activities were varied and used for funder reporting and organizational learning. Rural/remote HIV/AIDS programs across Canada expressed similar challenges and lessons learned, suggesting that there is potential for knowledge exchange, and development of a community of practice. Top-down planning and evaluation models may fail to capture program achievements in rural/remote contexts. The long-term engagement practices that render rural/remote programs promising do not always conform to planning and implementation requirements of limited funding.


Friends in low places: The impact of locations and companions on 21st birthday drinking.
The present research examined how various locations and companions were associated with hazardous drinking during 21st birthday celebrations. The sample included 912 college students (57% female) who completed an online survey to examine 21st birthday drinking. Locations included bars, friends' houses, restaurants, outdoor barbecues, homes, parents' homes, and Fraternity/Sorority houses. Companions included friends, family members, casual acquaintances, roommates, significant others, Fraternity/Sorority members, and none (alone). Participants consumed an average of 7.6 drinks and reached an average eBAC of .15 during their 21st birthday celebrations. Locations accounted for 20%/18% of the variance in number of drinks and eBAC, respectively, whereas companions accounted for 23%/20% of the variance. Drinking with romantic partners was associated with less drinking, whereas drinking with Fraternity/Sorority members was associated with more drinking. Stepwise regressions combining locations and companions suggested that, overall, celebrating in a bar setting and with Fraternity and Sorority members were the strongest variables associated with drinking. With the exception of a bar setting, companions were the most important contextual factors associated with 21st birthday drinking.


Synthetic lipid membrane channels formed by designed DNA nanostructures.
We created nanometer-scale transmembrane channels in lipid bilayers by means of self-assembled DNA-based nanostructures. Scaffolded DNA origami was used to create a stem that penetrated and spanned a lipid membrane, as well as a barrel-shaped cap that adhered to the membrane, in part via 26 cholesterol moieties. In single-channel electrophysiological measurements, we found similarities to the response of natural ion channels, such as conductances on the order of 1 nanosiemens and channel gating. More pronounced gating was seen for mutations in which a single DNA strand of the stem protruded into the channel. Single-molecule translocation experiments show that the synthetic channels can be used to discriminate single DNA molecules.


A Mitochondrial Polymorphism Alters Immune Cell Metabolism and Protects Mice from Skin Inflammation.
Several genetic variants in the mitochondrial genome (mtDNA), including ancient polymorphisms, are associated with chronic inflammatory conditions, but investigating the functional consequences of such mtDNA polymorphisms in humans is challenging due to the influence of many other polymorphisms in both mtDNA and the nuclear genome (nDNA). Here, using the conplastic mouse strain B6-mtFVB, we show that in mice, a maternally inherited natural mutation (m.7778G > T) in the mitochondrially encoded gene ATP synthase 8 (mt-Atp8) of complex V impacts on the cellular metabolic profile and effector functions of CD4+ T cells and induces mild changes in oxidative phosphorylation (OXPHOS) complex activities. These changes culminated in significantly lower disease susceptibility in two models of inflammatory skin disease. Our findings provide experimental evidence that a natural variation in mtDNA influences chronic inflammatory conditions through alterations in cellular metabolism and the systemic metabolic profile without causing major dysfunction in the OXPHOS system.


Phylogeography of the spring and fall waves of the H1N1/09 pandemic influenza virus in the United States.
Spatial variation in the epidemiological patterns of successive waves of pandemic influenza virus in humans has been documented throughout the 20th century but never understood at a molecular level. However, the unprecedented intensity of sampling and whole-genome sequencing of the H1N1/09 pandemic virus now makes such an approach possible. To determine whether the spring and fall waves of the H1N1/09 influenza pandemic were associated with different epidemiological patterns, we undertook a large-scale phylogeographic analysis of viruses sampled from three localities in the United States. Analysis of genomic and epidemiological data reveals distinct spatial heterogeneities associated with the first pandemic wave, March to July 2009, in Houston, TX, Milwaukee, WI, and New York State. In Houston, no specific H1N1/09 viral lineage dominated during the spring of 2009, a period when little epidemiological activity was observed in Texas. In contrast, major pandemic outbreaks occurred at this time in Milwaukee and New York State, each dominated by a different viral lineage and resulting from strong founder effects. During the second pandemic wave, beginning in August 2009, all three U.S. localities were dominated by a single viral lineage, that which had been dominant in New York during wave 1. Hence, during this second phase of the pandemic, extensive viral migration and mixing diffused the spatially defined population structure that had characterized wave 1, amplifying the one viral lineage that had dominated early on in one of the world's largest international travel centers.


Emergence of La Crosse virus from endemic foci. Fluorescent antibody studies of overwintered Aedes triseriatus.
The frequency and distribution of La Crosse (LAC) virus overwintering in Aedes triseriatus diapause eggs were studied during 1974 by following 64 tree-hole oviposition sites in four enzootic hardwood forest areas. A direct fluorescent antibody technique, adapted for detection of LAC virus in individual mosquitoes, proved to be a rapid, reliable and economical tool for ascertaining true field infection rates. Virus was found in larvae from each of the four study areas before the seasonal emergence of adults and detected in 10 (0.6%) of 1,698 individually processed adults reared from collected larvae. In one of these study areas, all 12 located tree-holes were enclosed with screen before the seasonal emergence of adults, to ensure that all collected from these sites originated from overwintered eggs. Of 1,280 Aedes triseriatus processed from this area throughout the season, 16 (1.2%) contained virus. Isolates were found in overwintered Aedes triseriatus throughout the summer months, demonstrating the role of these tree-hole sites as foci for both overwintering and continuing summer season source of LAC virus in these forested areas.


Antisense acid invertase (TIV1) gene alters soluble sugar composition and size in transgenic tomato fruit.
Invertase (beta-fructosidase, EC 22.214.171.124) hydrolyzes sucrose to hexose sugars and thus plays a fundamental role in the energy requirements for plant growth and maintenance. Transgenic plants with altered extracellular acid invertase have highly disturbed growth habits. We investigated the role of intracellular soluble acid invertase in plant and fruit development. Transgenic tomato (Lycopersicon esculentum Mill.) plants expressing a constitutive antisense invertase transgene grew identically to wild-type plants. Several lines of transgenic fruit expressing a constitutive antisense invertase gene had increased sucrose and decreased hexose sugar concentrations. Each transgenic line with fruit that had increased sucrose concentrations also had greatly reduced levels of acid invertase in ripe fruit. Sucrose-accumulating fruit were approximately 30% smaller than control fruit, and this differential growth correlated with high rates of sugar accumulation during the last stage of development. These data suggest that soluble acid invertase controls sugar composition in tomato fruit and that this change in composition contributes to alterations in fruit size. In addition, sucrose-accumulating fruit have elevated rates of ethylene evolution relative to control fruit, perhaps as a result of the smaller fruit size of the sucrose-accumulating transgenic lines.


Repeated thermal therapy up-regulates endothelial nitric oxide synthase and augments angiogenesis in a mouse model of hindlimb ischemia.
Nitric oxide (NO), constitutively produced by endothelial NO synthase (eNOS), plays roles in angiogenesis. Having reported that thermal therapy up-regulated the expression of arterial eNOS in hamsters, we investigated whether this therapy increased angiogenesis in mice with hindlimb ischemia. Unilateral hindlimb ischemia was induced in apolipoprotein E-deficient mice, which were divided into control and thermal therapy groups. The latter mice were placed in a far-infrared dry sauna at 41 degrees C for 15 min and then at 34 degrees C for 20 min once daily for 5 weeks. Laser Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls (0.79+/-0.04 vs 0.54+/-0.08, p<0.001). Significantly greater capillary density was seen in thermal therapy group (757+/-123 /mm2 vs 416+/-20 /mm2, p<0.01). Western blotting showed thermal therapy markedly increased hindlimb eNOS expression. To study possible involvement of eNOS in thermally induced angiogenesis, thermal therapy was given to mice with hindlimb ischemia with or without N(G)-nitro-L-arginine methyl ester (L-NAME) administration for 5 weeks. L-NAME treatment eliminated angiogenesis induced using thermal therapy. Thermal therapy did not increase angiogenesis in eNOS-deficient mice. Angiogenesis was induced via eNOS using thermal therapy in mice with hindlimb ischemia.


Six views of embodied cognition.
The emerging viewpoint of embodied cognition holds that cognitive processes are deeply rooted in the body's interactions with the world. This position actually houses a number of distinct claims, some of which are more controversial than others. This paper distinguishes and evaluates the following six claims: (1) cognition is situated; (2) cognition is time-pressured; (3) we off-load cognitive work onto the environment; (4) the environment is part of the cognitive system; (5) cognition is for action; (6) off-line cognition is body based. Of these, the first three and the fifth appear to be at least partially true, and their usefulness is best evaluated in terms of the range of their applicability. The fourth claim, I argue, is deeply problematic. The sixth claim has received the least attention in the literature on embodied cognition, but it may in fact be the best documented and most powerful of the six claims.


Role of aromatase in sex-specific cerebrovascular endothelial function in mice.
Stroke risk and outcome are strongly modified by estrogen. In addition to ovaries, estrogen is produced locally in peripheral tissue by the enzyme aromatase, and extragonadal synthesis becomes the major source of estrogen after menopause. Aromatase gene deletion in female mice exacerbates ischemic brain damage after stroke. However, it is not clear which cell type is responsible for this effect, since aromatase is expressed in multiple cell types, including cerebrovascular endothelium. We tested the hypothesis that cerebrovascular aromatase contributes to sex differences in cerebrovascular endothelial function. Cerebrocortical microvascular responses to the endothelium-dependent vasodilator ACh were compared between male and female wild-type (WT) and aromatase knockout (ArKO) mice by measuring laser-Doppler perfusion in vivo through a closed cranial window. Additional studies were performed in WT mice treated with the aromatase inhibitor fadrozole or vehicle. WT female mice had significantly greater responses to ACh compared with WT males (P < 0.001), which was associated with higher aromatase expression in female compared with male cerebral vessels (P < 0.05). ACh responses were significantly lower in ArKO compared with WT females (P < 0.05) and in WT females treated with fadrozole versus vehicle (P < 0.001). Conversely, ACh responses were significantly higher in ArKO versus WT males (P < 0.05). Levels of phosphorylated endothelial nitric oxide synthase (eNOS) were lower in ArKO versus WT female brains, but were not altered by aromatase deletion in males. We conclude that cerebrovascular endothelial aromatase plays an important and sexually dimorphic role in cerebrovascular function and that aromatase inhibitors in clinical use may have cardiovascular consequences in both males and females.


Antibiotic prophylaxis with amoxicillin to prevent infective endocarditis in periodontitis patients reconsidered: a narrative review.
To discuss first, the adequacy of the antibiotic prophylaxis regimen currently recommended for the prevention of infective endocarditis in periodontitis patients, and second, preventive measures to decrease the rate of bacteraemia after periodontal treatment. A bibliographic literature search identifying clinical trials between January 1990 and January 2021, focusing on microorganisms in bacteraemia after periodontal treatment and bacteria in infective endocarditis, was performed. Two reviewers independently identified and screened the literature by systematically searching in Medline/Premedline, EMBASE and Cochrane Library. Two hundred and seventy articles were identified, of which twenty-three met the inclusion criteria. Bacteraemia rates after periodontal treatment ranged from 10-94% in the investigated patients. Mainly oral pathogens related to infective endocarditis, such as viridans group streptococci (up to 70%) and HACEK group pathogens (e.g., Aggregatibacter actinomycetemcomitans), were detected. But typical oral and periodontopathogenic species, such as Porphyromonas spp. (P.s gingivalis) (up to 50%), Actinomyces spp. (up to 30%) and Fusobacterium spp. (up to 30%), which do not usually cause infective endocarditis, were also found. Infective endocarditis episodes that might have been in association with a dental treatment were mainly caused by viridans group streptococci. Prophylactic measures like rinse application of chlorhexidine, povidone-iodine or essential oils, diode laser or systemic antibiotic prescription were described as decreasing the bacteraemia rate after periodontal interventions to 5-70%. The currently recommended systemic antibiotic prophylaxis with amoxicillin before periodontal treatment in high-risk cardiovascular patients still covers the most common oral bacteria causing infective endocarditis, namely viridans group streptococci, and therefore seems adequate in this context. Since bacteraemia, not infective endocarditis, is the endpoint in most studies, the causality between bacteraemia after periodontal treatments and infective endocarditis remains difficult to elucidate. Until more evidence is available regarding this, adherence to current guidelines for antibiotic prophylaxis in patients at high risk for infective endocarditis undergoing periodontal treatment remains recommended.


Limbic encephalitis: Clinical spectrum and long-term outcome from a developing country perspective.
Limbic encephalitis (LE) is characterized by rapidly progressive short-term memory loss, psychiatric symptoms and seizures. We describe the clinical spectrum, underlying etiology and long-term follow-up of patients with LE from India. This prospective study included patients during the period of January 2009 and December 2011 with the clinical features consistent with LE with one or more of the following: (1) Magnetic resonance imaging (MRI) evidence of temporal lobe involvement; (2) cerebrospinal fluid inflammatory abnormalities, or (3) detection of antineuronal antibodies. Patients with metastasis, infection, metabolic and nutritional deficits, stroke, were excluded. There were 16 patients (9 females), mean age of presentation was 36.6 years (range 15-69 years). The mean duration of symptoms before presentation was 11 months (range 5 days-2 years). The most common symptom at presentation was short-term memory impairment in 7 patients followed by seizures in 5 and behavioral changes in three. Nine patients had seizures, 11 had change in behavior, language involvement in eight, cerebellar features in 3 and autonomic dysfunction in two. Four patients had associated malignancy, 3 of four presented with neurological symptoms and on investigations found to be have malignancy. Antineuronal antibody testing was done in 6 of 12 non paraneoplastic and two paraneoplastic patients, one positive for N-methyl-D-aspartate and one for anti-Hu antibody. MRI brain showed typical fluid attenuated inversion recovery or T2 bilateral temporal lobe hyperintensities in 50% of patients. At a mean follow-up of 21 months (3-36 months), 10 patients improved, 4 patients remained same and two patients expired. Early recognition of LE is important based upon clinical, MRI data in the absence of antineuronal surface antibody screen in developing nations. Early institution of immunotherapy will help in improvement in outcome of these patients in long-term.


Protective effect of hydrogen rich saline solution on experimental ovarian ischemia reperfusion model in rats.
The present study aimed to investigate the effects of hydrogen rich saline solution (HRSS) in a rat model of ovarian ischemia-reperfusion injury. Thirty-six female Wistar-albino rats were grouped randomly, into six groups of six rats. The groups were classified as: sham (S), hydrogen (H), torsion (T), torsion/detorsion (TD), hydrogen-torsion (HT), and hydrogen-torsion/detorsion (HTD). Bilateral adnexal torsion was performed for 3h in all torsion groups. HRSS was given 5ml/kg in hydrogen groups intraperitoneally. Malondialdehyde (MDA) and glutathione-S-transferase (GST) levels were measured in both the plasma and tissue samples. Tissue sections were evaluated histopathologically, and the apoptotic index was detected by TUNEL assay. The results were analyzed by Kruskal-Wallis and Pearson chi-square tests using computer software, SPSS Version 20.0 for Windows. The MDA levels were higher and GST levels were lower in the torsion and detorsion groups when compared to other groups, but the differences were insignificant (P>0.05). The MDA levels were lower and GST levels were higher in the HT and HTD groups compared with the T and TD groups (P>0.05). Follicular injury, edema, vascular congestion, loss of cohesion and apoptotic index were higher in the torsion groups but decreased in the groups that received HRSS. According to histopathological and biochemical examinations, HRSS is effective in attenuating ischemia-reperfusion induced ovary injury.


The meanings of place and space in forensic psychiatric care - A qualitative study reflecting patients' point of view.
The outcome of care for patients sentenced to forensic psychiatric care is of importance not only for the patient but also for society, in preventing new crimes. In recent years, a person-centered perspective is influencing the care, recognizing the design of the physical environment as a therapeutic resource. To capture the complexity of patients' experience of the physical environment, a qualitative approach is needed. The aim of this study was to investigate the meanings of the patient room as a place and space in forensic psychiatric in-patient care from the patients' perspective. An explorative qualitative design was chosen, data were collected by photovoice; a combination of photographs, taken by the patients, followed by interviews. Eleven (N = 11) patients were interviewed. The interviews were analysed by a thematic analysis method. Four themes emerged from the data revealing the meanings of the patient room as a place and space: (i) striving towards normality; (ii) being anchored and protected; (iii) being at-home and homeness; and (iv) being in communion and meaningfulness. The findings show that the physical environment has a say in patients' basic needs and a role in maintaining normality. Substandard reveals a lack of respect and dignity towards this patient group. Involving patients in the design process of new facilities can be a way to make progress.


Endurance exercise increases the SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1alpha protein expressions in rat skeletal muscle.
Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is considered to play a pivotal role in the exercise-induced metabolic adaptation of skeletal muscle. Although the oxidized form of nicotinamide adenine dinucloetide (NAD(+))-dependent histone deacetylase SIRT1 has been shown to mediate PGC-1alpha-induced metabolic adaptation, the effect of endurance exercise on the SIRT1 protein remains to be elucidated. The purposes of this study were (1) to investigate the distribution of SIRT1 and PGC-1alpha proteins in skeletal muscle and (2) to examine the effects of acute endurance exercise and low- or high-intensity exercise training on SIRT1 and PGC-1alpha protein expressions and on the metabolic components in rat skeletal muscle. Both the SIRT1 and PGC-1alpha proteins preferentially accumulate in red oxidative muscles. Acute endurance exercise on a motor-driven treadmill (20 m/min, 18.5% incline, 45 minutes) increases the PGC-1alpha protein expression at 18 hours after exercise and the SIRT1 protein expression at 2 hours after exercise in the soleus muscle. In the training experiment, the rats were divided into control, low-intensity (20 m/min, 18.5% incline, 90 min/d), and high-intensity (30 m/min, 18.5% incline, 60 min/d) training groups. After 14 days of training, the SIRT1 and PGC-1alpha proteins, hexokinase activity, mitochondrial proteins and enzyme activities, and glucose transporter 4 protein in the soleus muscle were increased by both trainings. In the plantaris muscle, SIRT1, hexokinase activity, mitochondrial proteins and enzyme activities, and glucose transporter 4 were increased by high-intensity training whereas the PGC-1alpha was not. These results suggest that endurance exercise increases the skeletal muscle SIRT1 protein content. In addition, the findings also raise the possibility that the SIRT1 protein expression may play a potentially important role in such adaptations, whereas an increase in the PGC-1alpha protein expression is not necessary for such adaptations.


Creating Political Will for Action on Health Equity: Practical Lessons for Public Health Policy Actors.
Despite growing evidence on the social determinants of health and health equity, political action has not been commensurate. Little is known about how political will operates to enact pro-equity policies or not. This paper examines how political will for pro-health equity policies is created through analysis of public policy in multiple sectors. Eight case studies were undertaken of Australian policies where action was either taken or proposed on health equity or where the policy seemed contrary to such action. Telephone or face-to-face interviews were conducted with 192 state and non-state participants. Analysis of the cases was done through thematic analysis and triangulated with document analysis. Our case studies covered: trade agreements, primary healthcare (PHC), work conditions, digital access, urban planning, social welfare and Indigenous health. The extent of political will for pro-equity policies depended on the strength of path dependency, electoral concerns, political philosophy, the strength of economic and biomedical framings, whether elite interests were threatened and the success or otherwise of civil society lobbying. Public health policy actors may create political will through: determining how path dependency that exacerbates health inequities can be broken, working with sympathetic political forces committed to fairness; framing policy options in a way that makes them more likely to be adopted, outlining factors to consider in challenging the interests of elites, and considering the extent to which civil society will work in favour of equitable policies. A shift in norms is required to stress equity and the right to health.


Retrobulbar ocular blood flow changes measured by colour Doppler imaging after intra-arterial chemotherapy in retinoblastoma.
To evaluate the effects of intra-arterial chemotherapy on retrobulbar blood flow parameters in patients with retinoblastoma. 20 eyes of 10 patients with unilateral retinoblastoma that were treated with intra-arterial chemotherapy were evaluated using colour Doppler imaging. The peak systolic and end-diastolic velocities of the ophthalmic, central retinal and posterior ciliary arteries were determined. The pulsatility and resistance indices were calculated automatically. The treated eye was compared with the untreated (control) eye and with itself before and after intra-arterial chemotherapy. When comparing the retinoblastoma-containing eyes with the contralateral normal eyes, the peak systolic and end-diastolic velocities of the central retinal artery were significantly higher in the tumorous eyes than in the normal eyes before intra-arterial chemotherapy. Moreover, the peak systolic and end-diastolic velocities in the posterior ciliary and central retinal arteries were significantly decreased after intra-arterial chemotherapy in the tumorous eyes (p<0.05). There were no statistically significant differences in the other parameters. Our results suggest that intra-arterial chemotherapy has a measurable effect on the retrobulbar blood flow, which can cause a decrease in the peak systolic and end-diastolic velocities in the posterior ciliary and central retinal arteries.


Caffeinated Energy Drinks Improve High-Speed Running in Elite Field Hockey Players.
The aim of this investigation was to determine the efficacy of a caffeine-containing energy drink to improve physical performance of elite field hockey players during a game. On 2 days separated by a week, 13 elite field hockey players (age and body mass = 23.2 ± 3.9 years and 76.1 ± 6.1 kg) ingested 3 mg of caffeine per kg of body mass in the form of an energy drink or the same drink without caffeine (placebo drink). After 60 min for caffeine absorption, participants played a simulated field hockey game (2 × 25 min). Individual running pace and instantaneous speed during the game were assessed using GPS devices. The total number of accelerations and decelerations was determined by accelerometry. Compared with the placebo drink, the caffeinated energy drink did not modify the total distance covered during the game (6,035 ± 451 m and 6,055 ± 499 m, respectively; p = .87), average heart rate (155 ± 13 beats per min and 158 ± 18 beats per min, respectively; p = .46), or the number of accelerations and decelerations (697 ± 285 and 618 ± 221, respectively; p = .15). However, the caffeinated energy drink reduced the distance covered at moderate-intensity running (793 ± 135 and 712 ± 116, respectively; p = .03) and increased the distance covered at high-intensity running (303 ± 67 m and 358 ± 117 m; p = .05) and sprinting (85 ± 41 m and 117 ± 55 m, respectively; p = .02). Elite field hockey players can benefit from ingesting caffeinated energy drinks because they increase the running distance covered at high-intensity running and sprinting. Increased running distance at high speed might represent a meaningful advantage for field hockey performance.


A membrane protease is targeted to the relict plastid of toxoplasma via an internal signal sequence.
The apicoplast is a secondary plastid found in Toxoplasma gondii, Plasmodium species and many other apicomplexan parasites. Although the apicoplast is essential to parasite survival, little is known about the protein constituents of the four membranes surrounding the organelle. Luminal proteins are directed to the endoplasmic reticulum (ER) by an N-terminal signal sequence and from there to the apicoplast by a transit peptide domain. We have identified a membrane-associated AAA protease in T. gondii, FtsH1. Although the protein lacks a canonical bipartite-targeting sequence, epitope-tagged FtsH1 colocalizes with the recently identified apicoplast membrane marker APT1 and immunoelectron microscopy confirms the residence of FtsH1 on plastid membranes. Trafficking appears to occur via the ER because deletion mutants lacking the peptidase domain are retained in the ER. When extended to include the peptidase domain, the protein trafficks properly. The transmembrane domain is required for localization of the full-length protein to the apicoplast and a truncation mutant to the ER. Thus, at least two distinct regions of FtsH1 are required for proper trafficking, but they differ from those of luminal proteins and would not be detected by the algorithms currently used to identify apicoplast proteins.


3-D Isotropic MR Imaging for Planning Bone Reconstruction in Patients With Femoroacetabular Impingement.
Femoroacetabular impingement (FAI) is commonly seen in young or middle-aged patients. Early detection and correction of FAI-related bony deformities or pelvic realignment are essential to prevent the development or progression of hip osteoarthritis. Computed tomography (CT) and magnetic resonance (MR) imaging are the reference standards for the evaluation of bony anatomy and treatable internal derangement findings of the hip, respectively. Surgeons prefer CT imaging for preoperative bone delineation because of its 3-D isotropic capabilities and excellent multiplanar reconstructions. Three-Tesla (3T) MR scans enable high-resolution 3-D MR reconstructions for bone depiction similar to 3-D CT reconstructions and have the potential to eliminate the need for duplicate (CT and MR) scanning. This technical report illustrates the feasibility of such an approach and compares bone rendering obtained using isotropic data from 3-D MR with 3-D CT in the same patient.


Exposure to Tomographic Scans and Cancer Risks.
Worldwide use of computed tomography (CT) scans has increased. However, the ionizing radiation from CT scans may increase the risk of cancer. This study examined the association between medical radiation from CT scans and the risk of thyroid cancer, lymphoma, and non-Hodgkin lymphoma (NHL) in adults. We conducted a nested case-control study in a cohort constructed from a population-based universal health insurance dataset in Taiwan in 2000-2013. In total, 22 853 thyroid cancer, 13 040 leukemia, and 20 157 NHL cases with their matched controls were included. Median follow-up times were 9.29-9.90 years for the three case-control groups. Medical radiation from CT scans was identified through physician order codes in medical insurance data from the index date to 3 years before a cancer diagnosis. Conditional logistic regression modeling was used for the overall and subsets of the population defined by sex and age groups to estimate the odds ratio (OR) and 95% confidence interval (CI) of the cancer risk associated with medical radiation. Exposure to medical radiation from CT scans was associated with elevated risk of thyroid cancer (OR = 2.55, 95% CI = 2.36 to 2.75) and leukemia (OR = 1.55, 95% CI = 1.42 to 1.68). The elevated risk of thyroid cancer and leukemia in association with medical CT was stronger in women than in men. No statistically significant association between the risk of cancer and CT scans was observed in overall patients with NHL (OR = 1.05, 95% CI = 0.98 to 1.12); however, increased risks were found in patients aged 45 years or younger. A clear dose-response relationship was observed in patients 45 years or younger for all three cancers. CT scans may be associated with an increased risk of thyroid cancer and leukemia in adults and in those diagnosed with NHL at a younger age.


Diode laser spectrometer for monitoring up to five atmospheric trace gases in unattended operation.
An automated diode laser spectrometer for recording concentrations of trace gases is described. It has been tested for unattended operation in the laboratory and at an atmospheric surveillance station for several months. The sensitivities reached are, e.g., 50 ppt for NO(2) and 300 ppt for NO. In an optical path length of 100 m the lowest extinction measured in unattended operation is ~1.5 x 10(-5) for a measuring time of ~60 s. Recordings of trace gases are shown for urban and rural atmospheric conditions.


The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma.
The Ocular Hypertension Treatment Study (OHTS) has shown that topical ocular hypotensive medication is effective in delaying or preventing the onset of primary open-angle glaucoma (POAG) in individuals with elevated intraocular pressure (ocular hypertension) and no evidence of glaucomatous damage. To describe baseline demographic and clinical factors that predict which participants in the OHTS developed POAG. Baseline demographic and clinical data were collected prior to randomization except for corneal thickness measurements, which were performed during follow-up. Proportional hazards models were used to identify factors that predicted which participants in the OHTS developed POAG. In univariate analyses, baseline factors that predicted the development of POAG included older age, race (African American), sex (male), larger vertical cup-disc ratio, larger horizontal cup-disc ratio, higher intraocular pressure, greater Humphrey visual field pattern standard deviation, heart disease, and thinner central corneal measurement. In multivariate analyses, baseline factors that predicted the development of POAG included older age, larger vertical or horizontal cup-disc ratio, higher intraocular pressure, greater pattern standard deviation, and thinner central corneal measurement. Baseline age, vertical and horizontal cup-disc ratio, pattern standard deviation, and intraocular pressure were good predictors for the onset of POAG in the OHTS. Central corneal thickness was found to be a powerful predictor for the development of POAG.


Population, behavioural and environmental drivers of malaria prevalence in the Democratic Republic of Congo.
Malaria is highly endemic in the Democratic Republic of Congo (DRC), but the limits and intensity of transmission within the country are unknown. It is important to discern these patterns as well as the drivers which may underlie them in order for effective prevention measures to be carried out. By applying high-throughput PCR analyses on leftover dried blood spots from the 2007 Demographic and Health Survey (DHS) for the DRC, prevalence estimates were generated and ecological drivers of malaria were explored using spatial statistical analyses and multilevel modelling. Of the 7,746 respondents, 2268 (29.3%) were parasitaemic; prevalence ranged from 0-82% within geographically-defined survey clusters. Regional variation in these rates was mapped using the inverse-distance weighting spatial interpolation technique. Males were more likely to be parasitaemic than older people or females (p < 0.0001), while wealthier people were at a lower risk (p < 0.001). Increased community use of bed nets (p = 0.001) and community wealth (p < 0.05) were protective against malaria at the community level but not at the individual level. Paradoxically, the number of battle events since 1994 surrounding one's community was negatively associated with malaria risk (p < 0.0001). This research demonstrates the feasibility of using population-based behavioural and molecular surveillance in conjunction with DHS data and geographic methods to study endemic infectious diseases. This study provides the most accurate population-based estimates to date of where illness from malaria occurs in the DRC and what factors contribute to the estimated spatial patterns. This study suggests that spatial information and analyses can enable the DRC government to focus its control efforts against malaria.


Seasonal erosion and restoration of Mars' northern polar dunes.
Despite radically different environmental conditions, terrestrial and martian dunes bear a strong resemblance, indicating that the basic processes of saltation and grainfall (sand avalanching down the dune slipface) operate on both worlds. Here, we show that martian dunes are subject to an additional modification process not found on Earth: springtime sublimation of Mars' CO(2) seasonal polar caps. Numerous dunes in Mars' north polar region have experienced morphological changes within a Mars year, detected in images acquired by the High-Resolution Imaging Science Experiment on the Mars Reconnaissance Orbiter. Dunes show new alcoves, gullies, and dune apron extension. This is followed by remobilization of the fresh deposits by the wind, forming ripples and erasing gullies. The widespread nature of these rapid changes, and the pristine appearance of most dunes in the area, implicates active sand transport in the vast polar erg in Mars' current climate.


What is the experience of national quality campaigns? Views from the field.
To identify key characteristics of a national quality campaign that participants viewed as effective, to understand mechanisms by which the campaign influenced hospital practices, and to elucidate contextual factors that modified the perceived influence of the campaign on hospital improvements. In-depth interviews, hospital surveys, and Health Quality Alliance data. We conducted a qualitative study using in-depth interviews with clinical and administrative staff (N = 99) at hospitals reporting strong influence (n = 6) as well as hospitals reporting limited influence (n = 6) of the Door-to-Balloon (D2B) Alliance, a national quality campaign to improve heart attack care. We analyzed these qualitative data as well as changes in hospital use of recommended strategies reported through a hospital survey and changes in treatment times using Health Quality Alliance data. In-depth, open-ended interviews; hospital survey. Key characteristics of the national quality campaign viewed as enhancing its effectiveness were as follows: credibility of the recommendations, perceived simplicity of the recommendations, alignment with hospitals' strategic goals, practical implementation tools, and breadth of the network of peer hospitals in the D2B Alliance. Perceived mechanisms of the campaign's influence included raising awareness and influencing goals, fostering strategy adoption, and influencing aspects of organizational culture. Modifying contextual factors included perceptions about current performance and internal championship for the recommended changes. The impact of national quality campaigns may depend on both campaign design features and on the internal environment of participating hospitals.


Fabrication of spherical mitigation pit on KH2PO4 crystal by micro-milling and modeling of its induced light intensification.
Micro-machining is the most promising method for KH(2)PO(4) crystal to mitigate the surface damage growth in high power laser system. In this work, spherical mitigation pit is fabricated by micro-milling with an efficient machining procedure. The light intensification caused by rear surface features before and after mitigation is numerically modeled based on the finite-difference time-domain method. The results indicate that the occurrence of total internal reflections should be responsible for the largest light intensification inside the crystal. For spherical pits after mitigation, the light intensification can be greatly alleviated by preventing the occurrence of total internal reflections. The light intensification caused by spherical mitigation pit is strongly dependent on the width-depth ratio and it is suggested that the width-depth ratio of spherical mitigation pit must be devised to be larger than 5.0 to achieve the minimal light intensification for the mitigation of surface damage growth. Laser damage tests for KH(2)PO(4) crystal validate that the laser damage resistance of initially damaged surface can be retrieved to near the level of ideal surface by replacing initial damage site with predesigned mitigation pit.


Generation of 103 fs mode-locked pulses by a gain linewidth-variable Nd,Y:CaF2 disordered crystal.
We have demonstrated a diode-pumped passively mode-locked femtosecond Nd,Y:CaF2 disordered crystal laser for the first time to our knowledge. By choosing appropriate Y-doping concentration, a broad fluorescence linewidth of 31 nm has been obtained from the gain linewidth-variable Nd,Y:CaF2 crystal. With the Nd,Y:CaF2 disordered crystal as gain medium, the mode-locked laser generated pulses with pulse duration as short as 103 fs, average output power of 89 mW, and repetition rate of 100 MHz. To our best knowledge, this is the shortest pulse generated from Nd-doped crystal lasers so far. The research results show that the Nd,Y:CaF2 disordered crystal will be a potential alternative as gain medium of repetitive chirped pulse amplification for high-peak-power lasers.


Phase conjugation of low-power optical beans using liquid-crystal light valves.
A real-time hologram generated in the liquid-crystal layer of a leaky-mirror silicon light valve is read by the same low-intensity beams used to record it. For a particular geometry, one of the diffracted beams propagating away from the device is the optical phase conjugate of one of the original beams, thus permitting correction of path-propagation aberrations. Experimental results show correction of tilt, focusing error, and random phase aberrations.


Transtrochanteric rotational osteotomy for nontraumatic osteonecrosis of the femoral head in young adults.
Transtrochanteric rotational osteotomy (TRO) is a controversial procedure with reported inconsistent results. We reviewed 50 patients (60 hips) who underwent this procedure for extensive osteonecrosis of the femoral head, focusing on varization to determine its effectiveness as a head-preserving procedure in young adults. The mean age of the patients was 28 years (range, 18-46 years). Using the Ficat-Arlet classification, 40 hips had Stage II and 20 hips had Stage III involvement. According to the classification system of Shimizu et al., the extent of the lesions were Grade C in 54 hips and Grade B in six hips; the location of the lesions were Grade c in 56 hips and Grade b in four hips. Minimum followup was 18 months (mean, 84 months; range, 18-156 months). The mean preoperative Harris hip score was 44.7 points (range, 32-62 points) which improved to an average postoperative score of 80.1 points (range, 44-100 points) at the latest followup. Forty-four hips showed no radiographic evidence of progression of collapse. Ten hips showed progressive collapse, seven hips showed progressive varus deformity, three hips had stress fractures of the femoral neck, and one hip had infection. We believe TRO with varization is worth attempting for extensive osteonecrosis of the femoral head in young adults, although failures and complications are not uncommon. Level IV, case series. See the Guidelines for Authors for a complete description of levels of evidence.


Continuing uncertainty about the value of percutaneous revascularization in atherosclerotic renovascular disease: a meta-analysis of randomized trials.
To study the effect of revascularization on blood pressure (BP) and serum creatinine (SCr) in patients with atherosclerotic renovascular disease (ARVD). Three randomized studies comparing balloon angioplasty (plus medication if necessary) with medical therapy alone in patients with ARVD were identified. In one study, patients were stratified and analysed according to whether they had unilateral or bilateral disease. Therefore, four sets of results were available for inclusion in a meta-analysis comparing BP and SCr at 6 months and changes from baseline. The three trials recruited 210 patients. There was no clear benefit for angioplasty when comparing BP at 6 months. Relative to the medical therapy group, the mean (95% CI) systolic/diastolic BP was 2.9 mmHg (-9.1, 3.4)/0.35 mmHg (-3.6, 2.9) lower in the angioplasty group (P=0.4/0.8). There was, however, some suggestion of benefit for angioplasty when changes in BP were compared. There was a greater reduction in the systolic/diastolic BP in the angioplasty group, with a difference of 6.3 mmHg (-11.7, -0.8)/3.3 mmHg (-6.2, -0.4) in the mean change (P=0.02/0.03). There was some suggestion of benefit for angioplasty in terms of changes in SCr, although this was not significant (P=0.06). The reported trials have been too small to determine reliably the role of angioplasty in ARVD. Although the combined results of three previous trials exclude the possibility of a large improvement in renal function or hypertension after angioplasty, a moderate but clinically worthwhile benefit cannot be ruled out. Further large-scale randomized evidence is needed.


Heart Rate, Stress, and Occupational Noise Exposure among Electronic Waste Recycling Workers.
Electronic waste (e-waste) is a growing occupational and environmental health issue around the globe. E-waste recycling is a green industry of emerging importance, especially in low-and middle-income countries where much of this recycling work is performed, and where many people's livelihoods depend on this work. The occupational health hazards of e-waste recycling have not been adequately explored. We performed a cross-sectional study of noise exposures, heart rate, and perceived stress among e-waste recycling workers at a large e-waste site in Accra, Ghana. We interviewed 57 workers and continuously monitored their individual noise exposures and heart rates for up to 24 h. More than 40% of workers had noise exposures that exceeded recommended occupational (85 dBA) and community (70 dBA) noise exposure limits, and self-reported hearing difficulties were common. Workers also had moderate to high levels of perceived stress as measured via Cohen's Perceived Stress Scale, and reported a variety of symptoms that could indicate cardiovascular disease. Noise exposures were moderately and significantly correlated with heart rate (Spearman's ρ 0.46, p < 0.001). A mixed effects linear regression model indicated that a 1 dB increase in noise exposure was associated with a 0.17 increase in heart rate (p-value = 0.01) even after controlling for work activities, age, smoking, perceived stress, and unfavorable physical working conditions. These findings suggest that occupational and non-occupational noise exposure is associated with elevations in average heart rate, which may in turn predict potential cardiovascular damage.


Comparative analysis of the Cancer Council of Victoria and the online Commonwealth Scientific and Industrial Research Organisation FFQ.
FFQ are commonly used to examine the association between diet and disease. They are the most practical method for usual dietary data collection as they are relatively inexpensive and easy to administer. In Australia, the Cancer Council of Victoria FFQ (CCVFFQ) version 2 and the online Commonwealth Scientific and Industrial Research Organisation FFQ (CSIROFFQ) are used. The aim of our study was to establish the level of agreement between nutrient intakes captured using the online CSIROFFQ and the paper-based CCVFFQ. The CCVFFQ and the online CSIROFFQ were completed by 136 healthy participants. FFQ responses were analysed to give g per d intake of a range of nutrients. Agreement between twenty-six nutrient intakes common to both FFQ was measured by a variety of methods. Nutrient intake levels that were significantly correlated between the two FFQ were carbohydrates, total fat, Na and MUFA. When assessing ranking of nutrients into quintiles, on average, 56 % of the participants (for all nutrients) were classified into the same or adjacent quintiles in both FFQ, with the highest percentage agreement for sugar. On average, 21 % of participants were grossly misclassified by three or four quintiles, with the highest percentage misclassification for fibre and Fe. Quintile agreement was similar to that reported by other studies, and we concluded that both FFQ are suitable tools for dividing participants' nutrient intake levels into high- and low-consumption groups. Use of either FFQ was not appropriate for obtaining accurate estimates of absolute nutrient intakes.


Detection of an Unknown Trypanosoma DNA in a Phlebotomus stantoni (Diptera: Psychodidae) Collected From Southern Thailand and Records of New Sand Flies With Reinstatement of Sergentomyia hivernus Raynal & Gaschen, 1935 (Diptera: Psychodidae).
Although female sand flies are best known as the vectors of Leishmania parasites and viruses, several previous reports have demonstrated that these insects can also act as vectors for the trypanosomes of bats, lizards, and snakes. In this report, we created an inventory of Phlebotomine sand flies from southern Thailand. A novel trypanosome was found in a specimen of Phlebotomus stantoni, and two sand fly species newly recorded in the country, Sergentomyia khawi and Sergentomyia hivernus, were described. PCR primer pairs specific for the internal transcribed spacer 1 (ITS1) and the small subunit ribosomal DNA (SSU rDNA) gene of trypanosomatids were used to demonstrate the presence of the parasite in the sand fly. In addition, the Cytochrome b (CytB) gene was used to identify the sand fly species. Among the 45 samples of the sand fly that were collected, seven samples were Ph. stantoni sand flies and a single sample was positive for Trypanosoma sp. through PCR analysis. This study represents the first detection of Trypanosoma sp. in a sand fly from Thailand. The ITS1 and SSU rDNA sequences indicated that this specimen is suspected to be a novel Trypanosoma species. Further studies of this suspected new Trypanosoma species, including its vertebrate hosts and pathogenic potential, are therefore necessary.


Adrenal insufficiency.
A 44-year-old woman reported several weeks of fatigue, somnolence, pain in the large joints, nausea, and decreased appetite. She had also noted an unintentional 11-kg weight loss over a period of 6 months. She had a remote history of amenorrhea, but she was presently menstruating regularly. She was taking no medications, with the exception of acetaminophen as needed for knee pain. The diagnosis of adrenal insufficiency (AI) was considered. Serum cortisol level after adrenocorticotropin hormone (ACTH) stimulation was abnormal. Because her plasma ACTH level was not increased, a diagnosis of secondary AI (due to deficiency in ACTH) was made. Magnetic resonance imaging of the brain performed to exclude the presence of a sellar or suprasellar mass showed reduction in size of the pituitary gland and an increased cerebrospinal fluid content within the sella, consistent with a partially empty sella. The patient's symptoms improved rapidly with hydrocortisone therapy but during follow-up, the dose of hydrocortisone was found to be excessive. Important differences exist between primary and secondary AI, and the diagnosis of secondary AI may be challenging. The therapy of AI should be carefully tailored to the requirements of the individual patient.


Postinfectious glomerulonephritis in the elderly.
Postinfectious glomerulonephritis (PIGN) is primarily a childhood disease that occurs after an upper respiratory tract infection or impetigo; its occurrence in older patients is not well characterized. Here, we report 109 cases of PIGN in patients ≥65 years old diagnosed by renal biopsy. The male to female ratio was 2.8:1. An immunocompromised background was present in 61%, most commonly diabetes or malignancy. The most common site of infection was skin, followed by pneumonia and urinary tract infection. The most common causative agent was staphylococcus (46%) followed by streptococcus (16%) and unusual gram-negative organisms. Hypocomplementemia was present in 72%. The mean peak serum creatinine was 5.1 mg/dl, and 46% of patients required acute dialysis. The most common light microscopic patterns were diffuse (53%), focal (28%), and mesangial (13%) proliferative glomerulonephritis. IgA-dominant PIGN occurred in 17%. Of the 72 patients with ≥3 months of follow-up (mean, 29 months), 22% achieved complete recovery, 44% had persistent renal dysfunction, and 33% progressed to ESRD. The presence of diabetes, higher creatinine at biopsy, dialysis at presentation, the presence of diabetic glomerulosclerosis, and greater tubular atrophy and interstitial fibrosis predicted ESRD. In summary, the epidemiology of PIGN is shifting as the population ages. Older men and patients with diabetes or malignancy are particularly at risk, and the sites of infection and causative organisms differ from the typical childhood disease. Prognosis for these older patients is poor, with fewer than 25% recovering full renal function.


Opioid misuse and perceived smoking-pain relationships among HIV+ individuals with pain: Exploring negative affect responses to pain.
Persons living with HIV/AIDS (PLWHA) report high rates of clinically significant pain that is associated with several negative outcomes, including higher CD4 T-cell count, poor medication adherence, and substance use and misuse. Importantly, PLWHA also report elevated rates of both opioid and tobacco use, and these elevated rates have often been associated with increased pain experience. Although research suggests that negative affective responses to pain may be uniquely associated with substance misuse among individuals in the general population, little work has examined these relations among PLWHA. The current study examined negative emotions in response to pain as a predictor of current opioid misuse, future opioid misuse, and perceived smoking-pain relationships among 66 (Mage = 51.26, SD = 8.00, 60.6% male) HIV+ adults with co-occurring pain. Results indicated that negative emotions in response to pain uniquely predicted each of the substance use outcomes, with clinically significant effect sizes that may be characterized as medium in magnitude. Overall, these findings suggest that negative affective responses to pain may play a role in prescription opioid misuse and smoking among PLWHA. These findings may inform the development of tailored interventions for PLWHA smokers who are prescribed opioid pain medications.


Treatment for LMCA ostial stenosis using a bifurcation technique with a retrograde approach.
A 69-year-old man who underwent coronary artery bypass surgery in February 2008. The surgery included grafting of the left internal thoracic artery (LITA) to the diagonal branch (D1) and a saphenous vein graft (SVG) to the left circumflex artery (LCX) due to ostial stenosis of the left main coronary artery (LMCA). The patient presented with recurring effort chest pain 18 months later. Coronary CT revealed that the LITA-D1 graft was patent, the SVG-LCX graft was occluded, and there was severe ostial stenosis of the LMCA. Coronary angiography was performed in August 2009, but a 5-Fr diagnostic catheter could not be engaged due to the severe ostial stenosis. Percutaneous coronary intervention (PCI) was performed 5 days later with an attempt to cross the lesion with a guidewire using a retrograde approach through the LITA-D1 graft. However, the guidewire could not be crossed using a conventional technique due to the extreme angulation of the LITA-D1 anastomosis. Therefore, we attempted to use a reversed guidewire technique. After crossing the LMCA ostial lesion the retrograde wire was snared through antegradely for insertion of the guiding catheter via the right brachial artery. We were able to engage the guiding catheter in the left coronary artery and implant the stent successfully using the antegrade approach.


Risk assessment model for development of advanced age-related macular degeneration.
To design a risk assessment model for development of advanced age-related macular degeneration (AMD) incorporating phenotypic, demographic, environmental, and genetic risk factors. We evaluated longitudinal data from 2846 participants in the Age-Related Eye Disease Study. At baseline, these individuals had all levels of AMD, ranging from none to unilateral advanced AMD (neovascular or geographic atrophy). Follow-up averaged 9.3 years. We performed a Cox proportional hazards analysis with demographic, environmental, phenotypic, and genetic covariates and constructed a risk assessment model for development of advanced AMD. Performance of the model was evaluated using the C statistic and the Brier score and externally validated in participants in the Complications of Age-Related Macular Degeneration Prevention Trial. The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. The model did well on performance measures, with very good discrimination (C statistic = 0.872) and excellent calibration and overall performance (Brier score at 5 years = 0.08). Successful external validation was performed, and a risk assessment tool was designed for use with or without the genetic component. We constructed a risk assessment model for development of advanced AMD. The model performed well on measures of discrimination, calibration, and overall performance and was successfully externally validated. This risk assessment tool is available for online use.


Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion.
Head trauma and concussion in football players have recently received considerable media attention. Postmortem evidence suggests that accrual of damage to the brain may occur with repeated blows to the head, even when the individual blows fail to produce clinical symptoms. There is an urgent need for improved detection and characterization of head trauma to reduce future injury risk and promote development of new therapies. In this study we examined neurological performance and health in the presence of head collision events in high school football players, using longitudinal measures of collision events (the HIT(™) System), neurocognitive testing (ImPACT(™)), and functional magnetic resonance imaging MRI (fMRI). Longitudinal assessment (including baseline) was conducted in 11 young men (ages 15-19 years) participating on the varsity and junior varsity football teams at a single high school. We expected and observed subjects in two previously described categories: (1) no clinically-diagnosed concussion and no changes in neurological behavior, and (2) clinically-diagnosed concussion with changes in neurological behavior. Additionally, we observed players in a previously undiscovered third category, who exhibited no clinically-observed symptoms associated with concussion, but who demonstrated measurable neurocognitive (primarily visual working memory) and neurophysiological (altered activation in the dorsolateral prefrontal cortex [DLPFC]) impairments. This new category was associated with significantly higher numbers of head collision events to the top-front of the head, directly above the DLPFC. The discovery of this new category suggests that more players are suffering neurological injury than are currently being detected using traditional concussion-assessment tools. These individuals are unlikely to undergo clinical evaluation, and thus may continue to participate in football-related activities, even when changes in brain physiology (and potential brain damage) are present, which will increase the risk of future neurological injury.


Psychological trauma symptom improvement in veterans using emotional freedom techniques: a randomized controlled trial.
This study examined the effect of Emotional Freedom Techniques (EFT), a brief exposure therapy combining cognitive and somatic elements, on posttraumatic stress disorder (PTSD) and psychological distress symptoms in veterans receiving mental health services. Veterans meeting the clinical criteria for PTSD were randomized to EFT (n = 30) or standard of care wait list (SOC/WL; n = 29). The EFT intervention consisted of 6-hour-long EFT coaching sessions concurrent with standard care. The SOC/WL and EFT groups were compared before and after the intervention (at 1 month for the SOC/WL group and after six sessions for the EFT group). The EFT subjects had significantly reduced psychological distress (p < 0.0012) and PTSD symptom levels (p < 0.0001) after the test. In addition, 90% of the EFT group no longer met PTSD clinical criteria, compared with 4% in the SOC/WL group. After the wait period, the SOC/WL subjects received EFT. In a within-subjects longitudinal analysis, 60% no longer met the PTSD clinical criteria after three sessions. This increased to 86% after six sessions for the 49 subjects who ultimately received EFT and remained at 86% at 3 months and at 80% at 6 months. The results are consistent with that of other published reports showing EFT's efficacy in treating PTSD and comorbid symptoms and its long-term effects.


The Congenital Heart Disease Genetic Network Study: Cohort description.
The Pediatric Cardiac Genomics Consortium (PCGC) designed the Congenital Heart Disease Genetic Network Study to provide phenotype and genotype data for a large congenital heart defects (CHDs) cohort. This article describes the PCGC cohort, overall and by major types of CHDs (e.g., conotruncal defects) and subtypes of conotrucal heart defects (e.g., tetralogy of Fallot) and left ventricular outflow tract obstructions (e.g., hypoplastic left heart syndrome). Cases with CHDs were recruited through ten sites, 2010-2014. Information on cases (N = 9,727) and their parents was collected through interviews and medical record abstraction. Four case characteristics, eleven parental characteristics, and thirteen parent-reported neurodevelopment outcomes were summarized using counts and frequencies and compared across CHD types and subtypes. Eleven percent of cases had a genetic diagnosis. Among cases without a genetic diagnosis, the majority had conotruncal heart defects (40%) or left ventricular outflow tract obstruction (21%). Across CHD types, there were significant differences (p<0.05) in the distribution of all four case characteristics (e.g., sex), four parental characteristics (e.g., maternal pregestational diabetes), and five neurodevelopmental outcomes (e.g., learning disabilities). Several characteristics (e.g., sex) were also significantly different across CHD subtypes. The PCGC cohort is one of the largest CHD cohorts available for the study of genetic determinants of risk and outcomes. The majority of cases do not have a genetic diagnosis. This description of the PCGC cohort, including differences across CHD types and subtypes, provides a reference work for investigators who are interested in collaborating with or using publically available resources from the PCGC.


Bridging the Gap Between Fluid Biomarkers for Alzheimer's Disease, Model Systems, and Patients.
Alzheimer's disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of two proteins in fibrillar form: amyloid-β (Aβ) and tau. Despite decades of intensive research, we cannot yet pinpoint the exact cause of the disease or unequivocally determine the exact mechanism(s) underlying its progression. This confounds early diagnosis and treatment of the disease. Cerebrospinal fluid (CSF) biomarkers, which can reveal ongoing biochemical changes in the brain, can help monitor developing AD pathology prior to clinical diagnosis. Here we review preclinical and clinical investigations of commonly used biomarkers in animals and patients with AD, which can bridge translation from model systems into the clinic. The core AD biomarkers have been found to translate well across species, whereas biomarkers of neuroinflammation translate to a lesser extent. Nevertheless, there is no absolute equivalence between biomarkers in human AD patients and those examined in preclinical models in terms of revealing key pathological hallmarks of the disease. In this review, we provide an overview of current but also novel AD biomarkers and how they relate to key constituents of the pathological cascade, highlighting confounding factors and pitfalls in interpretation, and also provide recommendations for standardized procedures during sample collection to enhance the translational validity of preclinical AD models.


DNA synthesis-dependent relief of repression of transcription from the adenovirus type 2 IVa(2) promoter by a cellular protein.
The promoter of the human adenovirus type 2 IVa(2) gene, which becomes active only during the late phase of infection, is built largely from sequences spanning, and downstream of, the sites of initiation of transcription. These sequences comprise an initiator, an intragenic sequence necessary for efficient transcription from the promoter by RNA polymerase II, and an intragenic binding site for a cellular repressor of IVa(2) transcription. The properties of the latter protein, which is termed IVa(2)-RF, suggested that it might account for the viral DNA synthesis-dependent activation of IVa(2) transcription during the adenoviral productive cycle. Here we report the results of experiments to assess the contributions of DNA template concentration and IVa(2)-RF binding to the activity of the IVa(2) promoter using a transient expression system. When a IVa(2)-EGFP reporter gene was introduced into HeLa cells, in which IVa(2)-RF was identified, no EFGP synthesis could be detected. In contrast, in IVa(2)-RF-containing cells in which the plasmid carrying the chimeric gene replicated, synthesis of both the EGFP protein and the IVa(2)-EGFP mRNA was readily detected. A vector mutation that blocked plasmid replication reduced IVa(2) promoter activity to undetectable levels. In contrast, a IVa(2) promoter substitution that impaired binding of IVa(2)-RF increased IVa(2) promoter activity under all conditions examined. Furthermore, introduction of DNA containing the IV-RF binding site with the chimeric reporter genes resulted in increased transcription from the IVa(2) promoter in the absence of plasmid replication. These properties are consistent with the hypothesis that the relative concentration of the IVa(2) promoter and of the cellular repressor that binds to it governs transcription from this adenoviral promoter.


Late Stone Age human remains from Ishango (Democratic Republic of Congo): New insights on Late Pleistocene modern human diversity in Africa.
Although questions of modern human origins and dispersal are subject to intense research within and outside Africa, the processes of modern human diversification during the Late Pleistocene are most often discussed within the context of recent human genetic data. This situation is due largely to the dearth of human fossil remains dating to the final Pleistocene in Africa and their almost total absence from West and Central Africa, thus limiting our perception of modern human diversification within Africa before the Holocene. Here, we present a morphometric comparative analysis of the earliest Late Pleistocene modern human remains from the Central African site of Ishango in the Democratic Republic of Congo. The early Late Stone Age layer (eLSA) of this site, dated to the Last Glacial Maximum (25-20 Ky), contains more than one hundred fragmentary human remains. The exceptional associated archaeological context suggests these remains derived from a community of hunter-fisher-gatherers exhibiting complex social and cognitive behaviors including substantial reliance on aquatic resources, development of fishing technology, possible mathematical notations and repetitive use of space, likely on a seasonal basis. Comparisons with large samples of Late Pleistocene and early Holocene modern human fossils from Africa and Eurasia show that the Ishango human remains exhibit distinctive characteristics and a higher phenotypic diversity in contrast to recent African populations. In many aspects, as is true for the inner ear conformation, these eLSA human remains have more affinities with Middle to early Late Pleistocene fossils worldwide than with extant local African populations. In addition, cross-sectional geometric properties of the long bones are consistent with archaeological evidence suggesting reduced terrestrial mobility resulting from greater investment in and use of aquatic resources. Our results on the Ishango human remains provide insights into past African modern human diversity and adaptation that are consistent with genetic theories about the deep sub-structure of Late Pleistocene African populations and their complex evolutionary history of isolation and diversification.


Tamponade caused by cardiac lipomatous hypertrophy.
Cardiac lipomatous hypertrophy is an unusual disorder that typically affects the interatrial septum. We report a case in which large subpericardial deposits of fat were initially mistaken for a pericardial effusion and the subsequent clinical picture resembled tamponade. The patient improved following a pericardiectomy.


Synaptic consolidation: from synapses to behavioral modeling.
Synaptic plasticity, a key process for memory formation, manifests itself across different time scales ranging from a few seconds for plasticity induction up to hours or even years for consolidation and memory retention. We developed a three-layered model of synaptic consolidation that accounts for data across a large range of experimental conditions. Consolidation occurs in the model through the interaction of the synaptic efficacy with a scaffolding variable by a read-write process mediated by a tagging-related variable. Plasticity-inducing stimuli modify the efficacy, but the state of tag and scaffold can only change if a write protection mechanism is overcome. Our model makes a link from depotentiation protocols in vitro to behavioral results regarding the influence of novelty on inhibitory avoidance memory in rats.


Effect of Tocilizumab on Fatigue and Bone Mineral Density in Patients with Rheumatoid Arthritis.
Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients. To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data. Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported.


The financial burden and distress of patients with cancer: Understanding and stepping-up action on the financial toxicity of cancer treatment.
"Financial toxicity" has now become a familiar term used in the discussion of cancer drugs, and it is gaining traction in the literature given the high price of newer classes of therapies. However, as a phenomenon in the contemporary treatment and care of people with cancer, financial toxicity is not fully understood, with the discussion on mitigation mainly geared toward interventions at the health system level. Although important, health policy prescriptions take time before their intended results manifest, if they are implemented at all. They require corresponding strategies at the individual patient level. In this review, the authors discuss the nature of financial toxicity, defined as the objective financial burden and subjective financial distress of patients with cancer, as a result of treatments using innovative drugs and concomitant health services. They discuss coping with financial toxicity by patients and how maladaptive coping leads to poor health and nonhealth outcomes. They cover management strategies for oncologists, including having the difficult and urgent conversation about the cost and value of cancer treatment, availability of and access to resources, and assessment of financial toxicity as part of supportive care in the provision of comprehensive cancer care. CA Cancer J Clin 2018;68:153-165. © 2018 American Cancer Society.


Clinical effect of peripherally inserted central catheters based on modified seldinger technique under guidance of vascular ultrasound.
To observe and analyze the application effect of ultrasound-guided modified Seldinger technique (MST) in Peripherally Inserted Central Catheter (PICC) catheterization. Two hundred patients treated with PICC catheterization from January 2013 to December 2015 were selected and randomly divided into two groups, namely, observation group and control group. The observation group adopted ultrasound-guided MST for catheterization while the control group applied traditional puncture technique for catheterization. Then efficacy of catheterization, success rate of catheterization and incidence rates of complications were compared between two groups. Various indicators of catheterization effects of the observation group were better than those of the control group, and the differences were statistically significant (P<0.05); one-time success rate of puncture and catheterization of the observation group was both higher than the control group (P<0.05);. Moreover, the incidence of puncture points bleeding, phlebitis and thrombus were all lower than those of the control group (P<0.05). Implementing PICC catheterization based on ultrasound-guided modified Seldinger puncture technique can increase success rate of puncture, improve the effect of catheterization, lower incidence rate of adverse effects of catheterization and improve satisfaction and comfort level of patients.


Virulence and viremia characteristics of 1992 epizootic subtype IC Venezuelan equine encephalitis viruses and closely related enzootic subtype ID strains.
Following a 19-year hiatus, Venezuelan equine encephalitis (VEE) reemerged in western Venezuela in December 1992. This outbreak is important in understanding VEE emergence because phylogenetic studies imply that sympatric, enzootic, subtype ID VEE viruses mutated to generate the epizootic/epidemic. Although the 1992-1993 strains belong to subtype IC, a serotype implicated in extensive outbreaks during the 1960s and in 1995, relatively small numbers of human and equine cases occurred in 1992-1993. We, therefore, evaluated the pathogenicity of these Venezuelan enzootic ID and epizootic IC viruses to determine 1) if they exhibit phenotypes like those described previously for more distantly related enzootic and epizootic strains, and 2) if the 1992-1993 outbreak was limited by the inability of these IC viruses to exploit equines as amplification hosts. All strains were virulent in mice and guinea pigs, but were benign for cotton rats, natural hosts of enzootic viruses. However, only the IC strains produced equine disease, with mean peak viremias of 10(5) suckling mouse 50% lethal doses per mL serum, and some titers exceeding 10(7). These viremias approximate those observed previously with VEE strains isolated during more extensive epizootics, suggesting that efficient equine amplification did not limit the scope and duration of the 1992-1993 outbreak. Enzootic ID virus infection protected all horses from challenge with epizootic strain P676, supporting the hypothesis that epizootics bypass regions of enzootic transmission due to natural immunization of equines by enzootic VEE viruses.


DNA commission of the International society for forensic genetics: Assessing the value of forensic biological evidence - Guidelines highlighting the importance of propositions: Part I: evaluation of DNA profiling comparisons given (sub-) source propositions.
The interpretation of evidence continues to be one of the biggest challenges facing the forensic community. This is the first of two papers intended to provide advice on difficult aspects of evaluation and in particular on the formulation of propositions. The scientist has a dual role: investigator (crime-focused), where often there is no suspect available and a database search may be required; evaluator (suspect-focused), where the strength of evidence is assessed in the context of the case. In investigative mode, generally the aim is to produce leads regarding the source of the DNA. Sub-source level propositions will be adequate to help identify potential suspects who can be further investigated by the authorities. Once in evaluative mode, given the defence version of events of the person of interest, it may become necessary to consider alternatives that go beyond the source of the DNA (i.e., to consider activity level propositions). In the evaluation phase, it is crucial that formulation of propositions allows the assessment of all the results that will help with the issue at hand. Propositions should therefore be precise (indication of the number of contributors, information on the relevant population etc.), be about causes, not effects (e.g. a 'matching' DNA profile) and to avoid bias, must not be findings-led. This means that ideally, propositions should be decided based on the case information and before the results of the comparisons are known. This paper primarily reflects upon what has been coined as "sub-source level propositions". These are restricted to the evaluation of the DNA profiles themselves, and help answer the issue regarding the source of the DNA. It is to be emphasised that likelihood ratios given sub-source level propositions cannot be carried over to a different level - for example, activity level propositions, where the DNA evidence is put into the context of the alleged activities. This would be highly misleading and could give rise to miscarriages of justice; this will be discussed in a second paper. The value of forensic results depends not only on propositions, but also on the type of results (e.g. allelic designations, peak heights, replicates) and upon the model used: it is therefore important to discuss these aspects. Finally, since communication is key to help understanding by courts, we will explore how to convey the value of the results and explain the importance of avoiding the practice of transposing the conditional.


Between No Help and Coercion: Toward Referral to Involuntary Psychiatric Admission. A Qualitative Interview Study of Stakeholders' Perspectives.
Objective: Paths toward referral to involuntary psychiatric admission mainly unfold in the contexts where people live their everyday lives. Modern health services are organized such that primary health care services are often those who provide long-term follow-up for people with severe mental illness and who serve as gatekeepers to involuntary admissions at the secondary care level. However, most efforts to reduce involuntary admissions have been directed toward the secondary health care level; interventions at the primary care level are sparse. To adapt effective measures for this care level, a better understanding is needed of the contextual characteristics surrounding individuals' paths ending in referrals for involuntary admission. This study aims to explore what characterizes such paths, based on the personal experiences of multiple stakeholders. Method: One hundred and three participants from five Norwegian municipalities participated in individual interviews or focus groups. They included professionals from the primary and secondary care levels and people with lived experience of severe mental illness and/or involuntary admission and carers. Data was subject to constant comparison in inductive analysis inspired by grounded theory. Results: Four main categories emerged from the analysis: deterioration and deprivation, difficult to get help, insufficient adaptation of services provided, and when things get acute. Combined, these illustrate typical characteristics of paths toward referral for involuntary psychiatric admission. Conclusion: The results demonstrate the complexity of individuals' paths toward referral to involuntary psychiatric admission and underline the importance of comprehensive and individualized approaches to reduce involuntary admissions. Furthermore, the findings indicate a gap in current practice between the policies to reduce involuntary admissions and the provision of, access to, and adaptation of less restrictive services for adults with severe mental illness at risk of involuntary admissions. To address this gap, further research is needed on effective measures and interventions at the primary care level.


Food Insecurity, Safety Nets, and Coping Strategies during the COVID-19 Pandemic: Multi-Country Evidence from Sub-Saharan Africa.
The COVID-19 pandemic has affected food security across the world. As governments respond in different ways both with regards to containing the pandemic and addressing food insecurity, in parallel detailed datasets are being collected and analysed. To date, literature addressing food insecurity during the pandemic, using these datasets, has tended to focus on individual countries. By contrast, this paper provides the first detailed multi-country cross-sectional snapshot of the social dimensions of food insecurity during the COVID-19 pandemic across nine African countries (Chad, Djibouti, Ethiopia, Kenya, Malawi, Mali, Nigeria, South Africa, and Uganda). Econometric analysis reveals that female-headed households, the poor, and the less-formally educated, appear to suffer more in terms of food insecurity during this global pandemic. Importantly, our findings show that the negative consequences of the pandemic are disproportionately higher for lower-income households and those who had to borrow to make ends meet rather than relying on savings; impacts are country-specific; and there is considerable spatial heterogeneity within country food insecurity, suggesting that tailored policies will be required. These nine countries employ both food and cash safety nets, with the evidence suggesting that, at least when these data were collected, cash safety nets have been slightly more effective at reducing food insecurity. Our results provide a baseline that can be used by governments to help design and implement tailored policies to address food insecurity. Our findings can also be used as lessons to reshape policies to tackle the heterogeneous impacts of climate change.


The dental remains from the Early Upper Paleolithic of Manot Cave, Israel.
This study presents the dental remains discovered at Manot Cave (MC), Western Galilee, Israel. The cave contains evidence for human occupation during the Early Upper Paleolithic period (46-33 ka) mainly of Early Ahmarian (∼46-42 ka) and Levantine Aurignacian (∼38-34 ka) cultural levels. Six teeth (three deciduous and three permanent) were found at the site, of which four could be thoroughly analyzed. The morphology of the teeth was qualitatively described and analyzed using traditional and geometric morphometric methods. A large comparative sample was used in order to assess the morphological affiliation of the Manot specimens with other Homo groups. The results provided equivocal signals: the upper first premolar (MC-9 P3) is probably modern human; the upper deciduous second molar (MC-10 dm2) and the upper second permanent molar (MC-8 M2) might be modern humans; the lower second deciduous molar (MC-7 dm2) might be Neanderthal. Owing to the small sample size and the almost total lack of distinctive characteristics, our outcome could not supply conclusive evidence to address the question of whether Manot Aurignacian population came from Europe or descended from the local Ahmarian population.


Medical education about alcohol: review of its role and effectiveness.
Many reports have described inadequate responses by doctors to problems associated with alcohol misuse. Low levels of medical knowledge and inappropriate attitudes continue to be documented in the alcohol area. However, in recent years, greater emphasis has been placed on the need to improve doctors' skills in relation to alcohol problem detection and intervention. Experiential teaching approaches have been recommended and strategies which incorporate feedback methods offer considerable promise. In the United Kingdom and Canada, there has been no centrally funded approach to improve alcohol medical education. In contrast, federally funded initiatives in the United States of America and Australia have been associated with impressive increases in alcohol-related teaching hours and elective opportunities. Despite the substantial effort invested in achieving these curriculum gains, there is a dearth of research demonstrating impacts on medical behaviours or evaluating the cost-effectiveness of different educational strategies. Evidence from trials in smoking cessation training indicate that well-designed programmes can alter doctor behaviours in relation to substance abuse. If the alcohol medical education field is to progress, there is an urgent need for the development and evaluation of programmes which are better designed and are more informed by theory.


Reactive nitrogen intermediates and outcome in severe adult malaria.
The role of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the pathophysiology of severe falciparum malaria remains unclear. We conducted a retrospective case-control study of Vietnamese adults with severe malaria to determine the relationship between outcome and admission plasma reactive nitrogen intermediates (RNI), the stable metabolites of NO. The study was designed to take into account the potential confounders of recent dietary nitrogen intake and renal function. Seventy-six patients who died from severe malaria were matched for age and sex with 76 survivors from a prospectively studied series of 560 patients. Median untransformed unadjusted plasma RNI levels were slightly higher in fatal cases (45 mumol/L, range 0-482) than in survivors (24.1 mumol/L, range 1.4-466) (P = 0.031, Wilcoxon signed-rank). There was a significant positive correlation between RNI levels and plasma creatinine (Spearman's rho = 0.35, P < 0.0001), and the addition of plasma creatinine as a covariate in a multivariate analysis abolished the trend towards higher RNI levels in fatal cases (P for the coefficient for RNI = 0.96). There was no association between RNI levels and either depth of coma on admission or time to regain consciousness. These findings do not support a pivotal role for systemic generation of NO in the pathogenesis of severe malaria in general, or cerebral malaria in particular.


Novel integrated paired emitter-detector diode (PEDD) as a miniaturized photometric detector in HPLC.
A novel low power, low cost, highly sensitive, miniaturized light emitting diode (LED) based flow detector has been used as optical detector for the detection of sample components in high performance liquid chromatography (HPLC). This colorimetric detector employs two LEDs, one operating in normal mode as a light source and the other is reverse biased to work as a light detector. Instead of measuring the photocurrent directly, a simple timer circuit is used to measure the time taken for the photocurrent generated by the emitter LED (lambda(max) 500 nm) to discharge the detector LED (lambda(max) 621 nm) from 5 V (logic 1) to 1.7 V (logic 0) to give digital output directly without using an A/D converter. Employing a post-column reagent method, a Nucleosil 100-7 column (functionalized with iminodiacetic acid (IDA) groups) was used to separate a mixture of transition metal complexes, manganese(II) and cobalt(II) in 4-(2-pyridylazo)-resorcinol (PAR). All optical measurements were taken by using both the in-built HPLC variable wavelength detector and the proposed paired-emitter-detector-diode (PEDD) optical detector configured in-line for data comparison. The concentration range investigated using the PEDD was found to give a linear response to the Mn(II) and Co(II) PAR complexes. The effects of flow rate and emitter LED light source intensity were investigated. Under optimised conditions the PEDD detector offered a linear range of 0.9-100 microM and LOD of 0.09 microM for Mn-PAR complex. A linear range of 0.2-100 microM and LOD of 0.09 microM for Co-PAR complex was achieved.


An apple oligogalactan enhances the growth inhibitory effect of 5-fluorouracil on colorectal cancer.
Treatment of colorectal cancer (CRC) remains a clinical challenge, since current therapies are associated with obvious side effects and high expenses. These limitations highlight an urgent need for developing novel and safe treatment strategies. It is suggested that combinatorial strategies could be more effective and much safer than monotherapy in cancer treatment. In our previous study, an apple oligogalactan (AOG) has been found to show beneficial effect on treating CRC. This study tried to investigate whether AOG could enhance the growth inhibitory effect of 5-FU in human CRC cells (HT-29 and SW-620), a mouse model of colitis associated colorectal cancer and a murine model of xenograft tumor. The IC50 values of 5-FU were 26.70±0.21μM in HT-29 cells and 26.71±2.06μM in SW-620 cells. Pretreatment with 0.05 or 0.1mM AOG down-regulated IC50 values of 5-FU to 22.44±1.01 or 18.67±1.16μM in HT-29 and 21.21±1.49 or 17.99±1.42μM in SW-620 cells. AOG enhanced 5-FU-induced cell apoptosis and S phase arrest. The combination not only protected ICR mice against intestinal toxicities and carcinogenesis induced by 1,2-dimethylhydrazine and dextran sodium sulfate, but also decreased the xenograft tumor size, triggered apoptosis and inhibited proliferation of tumor cells in nude mice. The mechanisms of AOG on enhancing the growth inhibitory effect of 5-FU may be through the influence of TLR-4/NF-κB pathway. Taken together, the combinatorial therapy using AOG and 5-FU is a promising strategy for the treatment of colorectal cancer.