Near-Field Energy Transfer into Silicon Inversely Proportional to Distance Using Quasi-2D Colloidal Quantum Well Donors.
Silicon is the most prevalent material system for light-harvesting applications; however, its inherent indirect bandgap and consequent weak absorption limits its potential in optoelectronics. This paper proposes to address this limitation by combining the sensitization of silicon with extraordinarily large absorption cross sections of quasi-2D colloidal quantum well nanoplatelets (NPLs) and to demonstrate excitation transfer from these NPLs to bulk silicon. Here, the distance dependency, d, of the resulting Förster resonant energy transfer from the NPL monolayer into a silicon substrate is systematically studied by tuning the thickness of a spacer layer (of Al2 O3 ) in between them (varied from 1 to 50 nm in thickness). A slowly varying distance dependence of d-1 with 25% efficiency at a donor-acceptor distance of 20 nm is observed. These results are corroborated with full electromagnetic solutions, which show that the inverse distance relationship emanates from the delocalized electric field intensity across both the NPL layer and the silicon because of the excitation of strong in-plane dipoles in the NPL monolayer. These findings pave the way for using colloidal NPLs as strong light-harvesting donors in combination with crystalline silicon as an acceptor medium for application in photovoltaic devices and other optoelectronic platforms.


Isolated perivesicular hematoma after military parachuting.
Isolated perivesicular hematomas are uncommonly described and not an injury typically reported in the literature after parachuting or skydiving. Herein, we described a series of three patients with isolated perivesicular hematomas sustained after military parachuting. All three patients were managed nonoperatively after a somewhat prolonged hospital course. Despite the lack of orthopedic injuries, all required physical therapy consultation and required an assisting device to aide with ambulation at the time of discharge. For all three individuals, follow-up imaging months after the injury demonstrated a continued presence of the hematoma. Clinically, the patients continued to have ambulatory and urological difficulties for several months after their injury. This injury pattern is uncommonly reported in the literature. An appropriate index of suspicion must be maintained or there may be a delay in diagnosis. Management of these injuries requires coordinated care between the trauma service, urology, and physical therapy.


Barriers to human papillomavirus vaccination among US adolescents: a systematic review of the literature.
Since licensure of the human papillomavirus (HPV) vaccine in 2006, HPV vaccine coverage among US adolescents has increased but remains low compared with other recommended vaccines. To systematically review the literature on barriers to HPV vaccination among US adolescents to inform future efforts to increase HPV vaccine coverage. We searched PubMed and previous review articles to identify original research articles describing barriers to HPV vaccine initiation and completion among US adolescents. Only articles reporting data collected in 2009 or later were included. Findings from 55 relevant articles were summarized by target populations: health care professionals, parents, underserved and disadvantaged populations, and males. Health care professionals cited financial concerns and parental attitudes and concerns as barriers to providing the HPV vaccine to patients. Parents often reported needing more information before vaccinating their children. Concerns about the vaccine's effect on sexual behavior, low perceived risk of HPV infection, social influences, irregular preventive care, and vaccine cost were also identified as potential barriers among parents. Some parents of sons reported not vaccinating their sons because of the perceived lack of direct benefit. Parents consistently cited health care professional recommendations as one of the most important factors in their decision to vaccinate their children. Continued efforts are needed to ensure that health care professionals and parents understand the importance of vaccinating adolescents before they become sexually active. Health care professionals may benefit from guidance on communicating HPV recommendations to patients and parents. Further efforts are also needed to reduce missed opportunities for HPV vaccination when adolescents interface with the health care system. Efforts to increase uptake should take into account the specific needs of subgroups within the population. Efforts that address system-level barriers to vaccination may help to increase overall HPV vaccine uptake.


Association of sperm source with miscarriage and take-home baby after ICSI in cryptozoospermia: a meta-analysis of testicular and ejaculated sperm.
Miscarriage and take-home baby are the most important issues to patients with cryptozoospermia in receiving intracytoplasmic sperm injection (ICSI). The ICSI usually use ejaculated or testicular sperm. Unfortunately, no synthesized evidence reported miscarriage and take-home baby rate between the two sperm sources. This study aimed to compare the miscarriage and take-home baby rate of ICSI using testicular and ejaculated sperm in patient with cryptozoospermia. We conducted meta-analyses that were based on data from Cochrane library, Ovid, PubMed, ScienceDirect, Scopus, and Web of Science. The pooled analyses used risk ratio (RR) in random-effects model. Sensitivity analyses by subgrouping were completed to explore the associations between mean age and outcome. This study identified 331 potential citations and included four cohort studies for qualitative and quantitative synthesis. The four studies involved 331 patients with 479 ICSI cycles. The results showed no significant difference in miscarriage between testicular sperm group and ejaculated sperm group (RR = 1.06, 95% CI 0.48-2.35, p = 0.88). Yet, take-home babies per embryo transfer in testicular sperm group (53/226, 23.45%) was more than ejaculated sperm group (59/429, 13.75%) (RR = 1.72, 95% CI 1.21-2.44, p = 0.002). Similar results can be found in take-home babies per ICSI cycle (RR = 1.77, 95% CI 1.28-2.44, p = 0.0005), especially in younger couple (RR = 1.93, 95% CI 1.11-3.34, p = 0.02). No small study bias was detected in the analyses. This study found that testicular sperm has more advantage for ICSI in patients with cryptozoospermia, especially in younger couple. These findings may help guide us when deciding the optimal method of sperm harvest for men with cryptozoospermia. Comparing to ejaculated sperm, testicular sperm showed benefits for take-home baby rate, but not for miscarriage in patients with cryptozoospermia.


Consumer/patient encounters with prescription drug monitoring programs: evidence from a Medicaid population.
Prescription drug monitoring programs issue reports about a patient's controlled substance prescription history upon request to physicians, law enforcement officials, and pharmacists. The dual purposes of these programs are to reduce the abuse and diversion of controlled substances while not preventing access to these medications for legitimate medical need. The purpose of this study was to examine the experiences of Medicaid patients with Kentucky's Prescription Drug Monitoring Program (PDMP). A random sample of Medicaid patients was surveyed in 2010; respondents were matched with patient retrospective claims data from 6 months prior to the survey's administration. Kentucky Medicaid patients from across the state. A combination of patient surveys and Medicaid claims data was used to test the relationship between patient characteristics and patient-reported interactions with physicians regarding their PDMP reports and whether they experienced difficulty obtaining or filling a prescription for a controlled substance due to a PDMP report. Most Medicaid patients are unaffected by the PDMP; however, patients diagnosed with chronic non-cancer pain conditions and patients reporting a Hispanic ethnicity are significantly more likely to have a physician discuss their PDMP report with them. Patients diagnosed with chronic non-cancer pain conditions are also significantly more likely to report difficulty obtaining a prescription for a controlled substance than patients that have not been diagnosed with chronic non-cancer pain conditions. Patients living in rural areas are significantly less likely than patients in urban areas to report difficulty obtaining a prescription for a controlled substance. The utilization of controlled substance prescriptions by respondents was not measured or monitored. The Medicaid population examined in this study may not be representative of the population as a whole. These results suggest that more attention to the consumer/patient perspective is warranted in maintaining a balanced approach to decreasing drug abuse and diversion while not limiting access to controlled substances in cases of legitimate medical need.


The disease-modifying effect of dehydroepiandrosterone in different stages of experimentally induced osteoarthritis: a histomorphometric study.
Osteoarthritis (OA) is likely to become an increasing burden in the coming decades. Various agents have been developed to slow the progression of OA, and are collectively known as 'disease-modifying drugs', however, there is still little reliable evidence that such agents will be successful. Dehydroepiandrosterone (DHEA), a sex hormone precursor, has been recently proven as protective agent against OA, but the exact mechanism is still unkown. In the current study, the effects of weekly intra-articular injections of DHEA in preventing the progression of existing cartilage degeneration in an OA rabbit model were evaluated. The aim of the current study is to demonstrate the feature of its disease-modifying efficacy during OA progression. Thirty male New Zealand white rabbits were used in this study. An anterior cruciate ligament transection (ACLT) model was used to create a progressive OA model in twenty rabbits. The animals were treated with DHEA or a placebo and were necropsied at 9 and 16 weeks. Ten rabbits receiving sham operations served as controls. The articular cartilage of the medial femoral condyle (MFC), lateral femoral condyle (LFC), medial tibial plateau (MTP) and lateral tibial plateau (LTP) was evaluated macroscopically and histologically. In the joints of the sham-operated rabbits, few histological changes were detected on the articular surfaces of the femoral condyles and tibial plateaus. ACLT obviously induced erosive changes on the cartilage surfaces. Compared to the placebo group, the macroscopic and Mankin score analyses demonstrated that the DHEA treatment markedly reduced the cartilage lesions and delayed cartilage degeneration in the four regions of the knee at 9 weeks after operation (macroscopic score: MFC P = 0.013; LFC P = 0.048; MTP P = 0.045; LTP P = 0.02, Mankin score: MFC P = 0.012; LFC P = 0.034; MTP P = 0.016; LTP P = 0.002). At 16 weeks, DHEA demonstrated chondroprotective effects on the lateral compartment of the knee compared to the placebo group, whereas the cartilage degeneration at the medial compartment of the knee did not differ among the groups (macroscopic score: LFC P = 0.046; LTP = 0.034, Mankin score: LFC P = 0.005; LTP P = 0.002). The disease-modifying efficacy of DHEA aganist OA is time-specific and site-dependent. DHEA could be used as a disease-modifying strategy to limit the progression of OA, especially in the middle stage.


Investigations of the potential influence of environmental contaminants on the thymus and spleen of harbor porpoises (Phocoena phocoena).
Harbor porpoises from the German North and Baltic Seas exhibit a higher incidence of bacterial infections compared to whales from less polluted arctic waters. The potential adverse effect of environmental contaminants such as polychlorinated biphenyls (PCBs) and heavy metals on the immune system and the health status of marine mammals is still discussed controversially. The aim of the present study was to investigate the possible influence of PCB, polybrominated diphenyl ether (PBDE), toxaphene, (p,p'-dichlorodiphenyl)trichlorethane (DDT), and (p,p'-dichlorodiphenyl)dichlorethene (DDE) on the immune system of harbor porpoises. Lymphoid organs are influenced by a variety of factors, and therefore special emphasis was given to separating the confounding effect of age, health status, nutritional state, geographical location, and sex from the effect of contaminant levels upon thymus and spleen. Contaminant analysis and detailed pathological examinations were conducted on 61 by-caught and stranded whales from the North and Baltic Seas and Icelandic and Norwegian waters. Stranded harbor porpoises were more severely diseased than by-caught animals. Thymic atrophy and splenic depletion were significantly correlated to increased PCB and PBDE levels. However, lymphoid depletion was also associated with emaciation and an impaired health status. The present report supports the hypothesis of a contaminant-induced immunosuppression, possibly contributing to disease susceptibility in harbor porpoises. However, further studies are needed to determine if lymphoid depletion is primarily contaminant-induced or secondary to disease and emaciation in this cetacean species.


Retrospective review of relapse after systemic cyclosporine in children with atopic dermatitis.
Cyclosporine is a systemic therapy used for control of severe atopic dermatitis (AD) in children. Although traditionally recommended at a dose of 5 mg/kg/day for 6 months, a longer duration of treatment may be necessary to bring a child with active and severe disease into remission. There are few data on the short- and long-term effectiveness of longer courses of therapy. This was a retrospective chart review of children treated with cyclosporine at a Canadian hospital-affiliated clinic between 2000 and 2013. Fifteen patients with adequate follow-up were identified. Twelve (80%) were male and the mean age at initiation of cyclosporine was 11.2 ± 3.4 years. The mean duration of cyclosporine therapy was 10.9 ± 2.7 months (range 7-15 months) at a starting dose of 2.8 ± 0.6 mg/kg/day. Of 12 patients (80%) who responded to cyclosporine, 5 patients (42%) had relapsed at a follow-up of 22.7 ± 15.0 months. The duration of therapy was longer in patients who did not relapse (17.7 ± 10.7 months) than in those who did (10.2 ± 2.7 months) (p = 0.06). Adverse events led to discontinuation in three patients (20%) and included infection-related complications in two patients and reversible renal toxicity in one. These results suggest that a longer duration of low-dose cyclosporine may help decrease the risk of relapse in patients with severe AD who are resistant to topical therapies.


Freeze gelated porous membranes for periodontal tissue regeneration.
Guided tissue regeneration (GTR) membranes have been used for the management of destructive forms of periodontal disease as a means of aiding regeneration of lost supporting tissues, including the alveolar bone, cementum, gingiva and periodontal ligaments (PDL). Currently available GTR membranes are either non-biodegradable, requiring a second surgery for removal, or biodegradable. The mechanical and biofunctional limitations of currently available membranes result in a limited and unpredictable treatment outcome in terms of periodontal tissue regeneration. In this study, porous membranes of chitosan (CH) were fabricated with or without hydroxyapatite (HA) using the simple technique of freeze gelation (FG) via two different solvents systems, acetic acid (ACa) or ascorbic acid (ASa). The aim was to prepare porous membranes to be used for GTR to improve periodontal regeneration. FG membranes were characterized for ultra-structural morphology, physiochemical properties, water uptake, degradation, mechanical properties, and biocompatibility with mature and progenitor osteogenic cells. Fourier transform infrared (FTIR) spectroscopy confirmed the presence of hydroxyapatite and its interaction with chitosan. μCT analysis showed membranes had 85-77% porosity. Mechanical properties and degradation rate were affected by solvent type and the presence of hydroxyapatite. Culture of human osteosarcoma cells (MG63) and human embryonic stem cell-derived mesenchymal progenitors (hES-MPs) showed that all membranes supported cell proliferation and long term matrix deposition was supported by HA incorporated membranes. These CH and HA composite membranes show their potential use for GTR applications in periodontal lesions and in addition FG membranes could be further tuned to achieve characteristics desirable of a GTR membrane for periodontal regeneration.


Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE).
Worldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS. The Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial is a large international blinded randomized controlled trial of dabigatran vs placebo in patients who suffered MINS. We used a partial factorial design to also determine the effect of omeprazole vs placebo in reducing upper gastrointestinal bleeding and complications. Both study drugs were initiated in eligible patients within 35 days of suffering MINS and continued for a maximum of 2 years. The primary outcome is a composite of major vascular complications for the dabigatran trial and a composite of upper gastrointestinal complications for the omeprazole trial. We present the rationale and design of the trial and baseline characteristics of enrolled patients. The trial randomized 1754 patients between January 2013 and July 2017. Patients' mean age was 69.9 years, 51.1% were male, 14.3% had a history of peripheral artery disease, 6.6% had a history of stroke or transient ischemic attack, 12.9% had a previous myocardial infarction, and 26.0% had diabetes. The diagnosis of MINS was on the basis of an isolated ischemic troponin elevation in 80.4% of participants. MANAGE is the first randomized controlled trial to evaluate a potential treatment of patients who suffered MINS.


Willingness to pay for health insurance: an analysis of the potential market for new low-cost health insurance products in Namibia.
This study analyzes the willingness to pay for health insurance and hence the potential market for new low-cost health insurance product in Namibia, using the double bounded contingent valuation (DBCV) method. The findings suggest that 87 percent of the uninsured respondents are willing to join the proposed health insurance scheme and on average are willing to insure 3.2 individuals (around 90 percent of the average family size). On average respondents are willing to pay NAD 48 per capita per month and respondents in the poorest income quintile are willing to pay up to 11.4 percent of their income. This implies that private voluntary health insurance schemes, in addition to the potential for protecting the poor against the negative financial shock of illness, may be able to serve as a reliable income flow for health care providers in this setting.


Universal Design as a Technical Norm and Juridical Term - A Factor of Development or Recession?
Universal design was introduced as an ideological and technical concept in Norway in 1996 and was introduced in the first law in 2003. Since then universal design has replaced accessibility for people with disabilities in national policies, laws, regulations, standards, projects and everyday language. Accessibility is now used to characterize solutions made more exclusively for people with disabilities or when a high, general quality is not required. Few countries have made this extensive use of the concept of universal design and the concept has faced several challenges from lawmakers, architects, economists, user organizations, entrepreneurs and debaters. This paper reflects on some aspects of more than 20 years of extensive use of the concept of universal design and try to answer the question: Is universal design an academic invention with little extra positive impact compared to accessibility for people with disability, or does the concept defend its supposed role as a step towards a society with equal opportunities for all?


Reassessment of major products of N2 fixation by bacteroids from soybean root nodules.
NH3/ was the principal product from soybean bacteroids, prepared by various procedures, when assayed in solution in a flow chamber under N2 fixation conditions. In addition, small quantities of alanine were produced (reaching 20% of NH3/ under some conditions). Some 15N was assimilated by bacteroids purified from soybean root nodules on Percoll density gradients and shaken with 15N2 and 0.008 atm O2. Under these conditions, accounted for 93% of the (15)N fixed into the soluble fraction. This fraction contained no measurable [15N]alanine. Neither these bacteroids nor those prepared by the previously used differential centrifugation method, when incubated with exogenous alanine under non-N2-fixing conditions, gave rise to NH3 from alanine. Therefore, contamination of bacteroid preparations with enzymes of plant cytosolic origin and capable of producing NH3 from alanine cannot explain the failure to detect [15N]alanine [as reported elsewhere: Waters, J. K., Hughes, B. L., II, Purcell, L. C., Gerhardt, K. O., Mawhinney, T. P. & Emerich, D. W. (1998). Proc Natl Acad Sci USA 95, 12038-12042]. Cell-free extracts of the bacteroids as used in the 15N experiments contained alanine dehydrogenase and were able to produce alanine from pyruvate and. Other experiments with alanine dehydrogenase in extracts of cultured rhizobia and bacteroids are reported and discussed in relation to the 15N experiments. Possible reasons for the differences between laboratories regarding the role of alanine are discussed. It is concluded that NH3 is the principal soluble product of N2 fixation by suspensions of soybean bacteroids ex planta and that should continue to be considered the principal product of N2 fixation which is assimilated in vivo in soybean nodules.


Clinical psychopharmacology of AD/HD: implications for animal models.
A working knowledge of the clinical psychopharmacology of the psychostimulants in AD/HD is essential to the development of valid animal models of the disorder. The clinical pharmacokinetics and pharmacodynamics of D-amphetamine (D-AMP) and methylphenidate (MPH) have been well-studied. The plasma half-life of these compounds in children is approximately 5 h, with an onset of therapeutic action within a half-hour, and peak action at 1-3 h. The effective dose range for D-AMP in children is 0.2-0.5 mg/kg, and for MPH 0.3-1.0 mg/kg. In humans, psychostimulants bring about reductions in activity level and impulsivity, and improvement in attention span. Enhancement of executive processes mediated in the pre-frontal cortex in humans (especially tolerance for delay) is believed to mediate these therapeutic effects. There are no long-term remedial effects of the drug on behavior-i.e. symptoms return when the drugs are withdrawn. When used in the therapeutic dose range, there is no evidence of the development of significant tolerance or sensitization. These and other clinical findings to be discussed must guide and constrain the development of animal models of stimulant drug effects in AD/HD.


The Category Cued Recall test in very mild Alzheimer's disease: discriminative validity and correlation with semantic memory functions.
Episodic memory tests that measure cued recall may be particularly effective in the diagnosis of early Alzheimer's disease (AD) because they examine both episodic and semantic memory functions. The Category Cued Recall (CCR) test provides superordinate semantic cues at encoding and retrieval, and high discriminative validity has been claimed for this test. The aim of this study was to investigate the discriminative validity for this test when compared with the 10-word memory list from Alzheimer's Disease Assessment Scale (ADAS-cog) that measures free recall. The clinical diagnosis of AD was taken as the standard. It was also investigated whether the two episodic memory tests correlated with measures of semantic memory. The tests were administered to 35 patients with very mild AD (Mini Mental State Examination score >22) and 28 control subjects. Both tests had high sensitivity (>88%) with high specificity (>89%). One out of the five semantic memory tests was significantly correlated to performances on CCR, whereas delayed recall on the ADAS-cog memory test was significantly correlated to two semantic tests. In conclusion, the discriminative validity of the CCR test and the ADAS-cog memory test was equivalent in very mild AD. This may be because CCR did not tap more semantic processes, which are impaired in the earliest phases of AD, than a test of free recall.


The management of conditioned nutritional requirements in heart failure.
Patients suffering from congestive heart failure exhibit impaired myocardial energy production, myocyte calcium overload and increased oxidative stress. Nutritional factors known to be important for myocardial energy production, calcium homeostasis and the reduction of oxidative stress, such as thiamine, riboflavin, pyridoxine, L-carnitine, coenzyme Q10, creatine and taurine are reduced in this patient population. Furthermore, deficiencies of taurine, carnitine, and thiamine are established primary causes of dilated cardiomyopathy. Studies in animals and limited trials in humans have shown that dietary replacement of some of these compounds in heart failure can significantly restore depleted levels and may result in improvement in myocardial structure and function as well as exercise capacity. Larger scale studies examining micronutrient depletion in heart failure patients, and the benefits of dietary replacement need to be performed. At the present time, it is our belief that these conditioned nutritional requirements, if unsatisfied, contribute to myocyte dysfunction and loss; thus, restoration of nutritional deficiencies should be part of the overall therapeutic strategy for patients with congestive heart failure.


Probing the coupling between proton and electron transfer in photosystem II core complexes containing a 3-fluorotyrosine.
The catalytic cycle of numerous enzymes involves the coupling between proton transfer and electron transfer. Yet, the understanding of this coordinated transfer in biological systems remains limited, likely because its characterization relies on the controlled but experimentally challenging modifications of the free energy changes associated with either the electron or proton transfer. We have performed such a study here in Photosystem II. The driving force for electron transfer from Tyr(Z) to P(680)(*+) has been decreased by approximately 80 meV by mutating the axial ligand of P(680), and that for proton transfer upon oxidation of Tyr(Z) by substituting a 3-fluorotyrosine (3F-Tyr(Z)) for Tyr(Z). In Mn-depleted Photosystem II, the dependence upon pH of the oxidation rates of Tyr(Z) and 3F-Tyr(Z) were found to be similar. However, in the pH range where the phenolic hydroxyl of Tyr(Z) is involved in a H-bond with a proton acceptor, the activation energy of the oxidation of 3F-Tyr(Z) is decreased by 110 meV, a value which correlates with the in vitro finding of a 90 meV stabilization energy to the phenolate form of 3F-Tyr when compared to Tyr (Seyedsayamdost et al. J. Am. Chem. Soc. 2006, 128,1569-1579). Thus, when the phenol of Y(Z) acts as a H-bond donor, its oxidation by P(680)(*+) is controlled by its prior deprotonation. This contrasts with the situation prevailing at lower pH, where the proton acceptor is protonated and therefore unavailable, in which the oxidation-induced proton transfer from the phenolic hydroxyl of Tyr(Z) has been proposed to occur concertedly with the electron transfer to P(680)(*+). This suggests a switch between a concerted proton/electron transfer at pHs < 7.5 to a sequential one at pHs > 7.5 and illustrates the roles of the H-bond and of the likely salt-bridge existing between the phenolate and the nearby proton acceptor in determining the coupling between proton and electron transfer.


Predictive value of dobutamine stress echocardiography for coronary artery disease detection in liver transplant candidates.
Patients with obstructive coronary artery disease (CAD) undergoing orthotopic liver transplantation (OLT) are at increased risk of poor outcomes. The accuracy of dobutamine stress echocardiography (DSE) to detect obstructive CAD is not well established in this population. We retrospectively identified patients with end-stage liver disease who underwent both DSE and coronary angiography as part of risk stratification prior to OLT. One hundred and five patients had both DSE and angiography, of whom 14 had known CAD and 27 failed to reach target heart rate during DSE. Among the remaining 64 patients (45 men; average age 61 +/- 8 years) DSE had a low sensitivity (13%), high specificity (85%), low positive predictive value (PPV) (22%) and intermediate negative predictive value (NPV) (75%) for obstructive CAD. DSE as a screening test for obstructive CAD in OLT candidates has a poor sensitivity. The frequent chronotropic incompetence and low sensitivity in patients who achieve target heart rate, even in those with multiple cardiovascular disease risk factors, suggest that alternative or additional methods of risk stratification are necessary.


A longitudinal study of Salmonella infection in different types of turkey flocks in Great Britain.
Salmonella is, after Campylobacter, the most reported zoonotic pathogen in the EU. Poultry are a common source of infection to humans, and turkey flocks are commonly colonized with the organism. We investigated the prevalence and risk factors of Salmonella infection in 179 houses in 60 holdings representative of turkey meat and breeder production in Great Britain. From each holding, up to four houses were chosen, and two consecutive flocks per house were sampled/tested for Salmonella to investigate the persistence, elimination and introduction of Salmonella in consecutive crops. At the first sampling, the overall flock-level Salmonella prevalence was 32.8% and 8.9% for meat and breeding flocks respectively. There was a higher prevalence of Salmonella in flocks in the rearing stage than in the fattening and breeding stages. At the first sampling, the flock-level prevalence of Salmonella was 26.8% (95% CI: 20.7-33.7%), while the prevalence level in the subsequent flock was 20.5% (95% CI: 13.6-29.7%). No houses were positive for any of the EU-regulated serovars. The most commonly encountered serovars were S. Kottbus and S. Kedougou. Carry-over of infection was observed in 44.8% of the positive houses, and introduction of new infection occurred in 8.4% of houses. Data from the questionnaires and auditing of all holdings and houses were combined and used to calculate adjusted farm- and house-adjusted risk factors. Significant risk factors were feed from a source other than a national compounder (OR = 2.4), feeder type other than pan feeders (OR = 2.4) and hygiene practices other than terminal cleaning and disinfection using power-washing with sanitizer and anteroom with boot change (OR = 2.8). The study discusses the main challenges currently faced by the industry to control Salmonella in turkey production.


Role of speciation in organotin toxicity to the yeast Candida maltosa.
Assessment of organometal pollution requires an understanding of the various processes that influence the bioavailability and toxicity of the contaminant. Organotins may exist as both cationic species and neutral hydroxides in aqueous solution, with the formation of chloride species in the presence of Cl-. Although these species have different chemical properties, there is very little information on the influence of speciation on organotin and microbial cell interactions. Tributyltin (TBT) and triphenyltin (TPT) interactions with the yeast Candida maltosa were investigated between pH 3.5 and 7.5 and in up to 0.5 M NaCl at pH 5.5. Toxicity increased with both pH and NaCl concentration and the mechanisms of interaction depended on the species present in solution. TBT and TPT interacted by different mechanisms, as evidenced by action on membrane fluidity. Furthermore, there was a strong correlation between toxicity and overall octanol-water distribution ratio (D(OW)) of organotin compounds. Triorganotin cations are less toxic than triorganotin hydroxides, which are in turn less toxic than triorganotin chlorides. These findings underline the importance of speciation effects on organotin interactions in the environment.


Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice.
Mast cell degranulation is important in the pathogenesis of anaphylaxis and allergic disorders. Many animal venoms contain components that can induce mast cell degranulation, and this has been thought to contribute to the pathology and mortality caused by envenomation. However, we recently reported evidence that mast cells can enhance the resistance of mice to the venoms of certain snakes and that mouse mast cell-derived carboxypeptidase A3 (CPA3) can contribute to this effect. Here, we investigated whether mast cells can enhance resistance to the venom of the Gila monster, a toxic component of that venom (helodermin), and the structurally similar mammalian peptide, vasoactive intestinal polypeptide (VIP). Using 2 types of mast cell-deficient mice, as well as mice selectively lacking CPA3 activity or the chymase mouse mast cell protease-4 (MCPT4), we found that mast cells and MCPT4, which can degrade helodermin, can enhance host resistance to the toxicity of Gila monster venom. Mast cells and MCPT4 also can limit the toxicity associated with high concentrations of VIP and can reduce the morbidity and mortality induced by venoms from 2 species of scorpions. Our findings support the notion that mast cells can enhance innate defense by degradation of diverse animal toxins and that release of MCPT4, in addition to CPA3, can contribute to this mast cell function.


The impact of oligofructose on stimulation of gut hormones, appetite regulation and adiposity.
To investigate the effect of nutrient stimulation of gut hormones by oligofructose supplementation on appetite, energy intake (EI), body weight (BW) and adiposity in overweight and obese volunteers. In a parallel, single-blind and placebo-controlled study, 22 healthy overweight and obese volunteers were randomly allocated to receive 30 g day(-1) oligofructose or cellulose for 6 weeks following a 2-week run-in. Subjective appetite and side effect scores, breath hydrogen, serum short chain fatty acids (SCFAs), plasma gut hormones, glucose and insulin concentrations, EI, BW and adiposity were quantified at baseline and post-supplementation. Oligofructose increased breath hydrogen (P < 0.0001), late acetate concentrations (P = 0.024), tended to increase total area under the curve (tAUC)420 mins peptide YY (PYY) (P = 0.056) and reduced tAUC450 mins hunger (P = 0.034) and motivation to eat (P = 0.013) when compared with cellulose. However, there was no significant difference between the groups in other parameters although within group analyses showed an increase in glucagon-like peptide 1 (GLP-1) (P = 0.006) in the cellulose group and a decrease in EI during ad libitum meal in both groups. Oligofructose increased plasma PYY concentrations and suppressed appetite, while cellulose increased GLP-1 concentrations. EI decreased in both groups. However, these positive effects did not translate into changes in BW or adiposity.


Can inflammatory mediators affect fibrinolysis in the pleural space?
The pleural space in patients with empyema and complicated parapneumonic effusions is a stage for intensive activity representing mobilization of various host responses. Release of inflammatory mediators accompanied by influx of leucocytes as well as alternations of the fibrinolytic cascade are some of the characteristic events occurring in the pleural space during infection. The possible relationship between these two systems is the subject of the article by Alemán and co-workers in this issue of Clinical Science, and is discussed in this comment.


Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis.
Cerebral venous sinus thrombosis (CVST) is a disease with potentially serious consequences. The clinical presentation and outcomes of these patients have not been described in Oman. We sought to describe the clinical characteristics and outcomes of patients with CVST. We conducted a retrospective study in two tertiary care centers in Oman, which included all Omani adults with radiologically confirmed CVST. We recorded and analyzed patients' demographic, clinical, and outcome data. Fifty-four patients had radiologically confirmed CVST. The commonest presenting feature was headache (85.0%), followed by focal motor deficits (48.0%) and seizures (27.0%). In this cohort, 24.0% were pregnant or postpartum, 11.0% had an inherited thrombophilia, 11.0% were on hormonal therapy, and 11.0% had systemic lupus erythematous; 38.9% of patients had multiple sinus thrombosis while 35.2% had sigmoid and transverse sinus thrombosis. Antiphospholipid antibody syndrome and infection accounted for 7.0% and 13.0% of causes, respectively, while cancer accounted for 2.0%. No cause was identified in 33.0% of cases. Only 1.9% of patients died, while 29.6% had a residual neurological deficit at hospital discharge. Age was a predictor for residual neurological deficit (p = 0.003). Pregnancy and postpartum were the most common predisposing factors for CVST in our cohort. Although the mortality rate is low, the risk of residual neurological deficit remains high. We recommend a prospective study for better characterization and outcome assessment.


Value of combined intravenous renal arteriography and pyelography in the diagnosis of renovascular hypertension.
1. The technique of combined intravenous renal arteriography and pyelography is described and results in 848 hypertensive patients are reported. 2. The procedure was tolerated better than Seldinger arteriography and the diagnostic accuracy for renal artery stenosis was 95%. 3. The prevalence of renovascular disease was 7%. 4. Cost-effectiveness calculations favour combined intravenous arteriography and pyelography rather than the usual approach based on assessment of the indications for Seldinger arteriography from clinical and urographic signs.


The benefits of adding a brief measure of simple reaction time to the assessment of executive function skills in early childhood.
Early childhood represents a period of rapid cognitive developmental change in executive function (EF) skills along with a variety of related cognitive processes, including processing speed. This leads to interpretational challenges in that children's performance on EF tasks reflects more than EF skills per se. We tested whether the inclusion of a brief measure of simple reaction time (SRT) during EF assessments could help to partially address this challenge. Data were drawn from a cross-sectional convenience sample of 830 preschool-aged children. Individual differences in SRT were significantly associated with performance on all tasks (R2s = .09-.26); slower performance on the SRT task was associated with poorer performance on each EF task. Age-related differences in individual EF tasks were reduced by approximately one half after accounting for age-related differences in SRT, and EF task scores were less coherent (i.e., less strongly intercorrelated with each other) after the removal of SRT. Age-related differences in EF were smaller (Cohen ds = 1.36 vs. 0.78), and poverty-related differences in EF were larger (Cohen ds = 0.30 vs. 0.46) after accounting for SRT-related variation. Finally, consistent with previous studies, SRT-related differences in fluid reasoning were mediated by EF skills. Results are discussed with respect to using a brief measure of SRT to partially address the problem of measurement impurity at the level of individual EF tasks.


Role of CPS1 in Cell Growth, Metabolism and Prognosis in LKB1-Inactivated Lung Adenocarcinoma.
Liver kinase B1 ( LKB1 ) is a tumor suppressor in lung adenocarcinoma (LADC). We investigated the proteomic profiles of 45 LADC cell lines with and without LKB1 inactivation. Carbamoyl phosphate synthetase 1 (CPS1), the first rate-limiting mitochondrial enzyme in the urea cycle, was distinctively overexpressed in LKB1-inactivated LADC cell lines. We therefore assessed the role of CPS1 and its clinical relevance in LKB1-inactivated LADC. Mass spectrometric profiling of proteome and metabolome and function of CPS1 were analyzed in LADC cell lines. CPS1 and LKB1 expression in tumors from 305 LADC and 160 lung squamous cell carcinoma patients was evaluated by immunohistochemistry. Kaplan-Meier and Cox regression analyses were applied to assess the association between overall survival and CPS1 and LKB1 expression. All statistical tests were two-sided. CPS1 knockdown reduced cell growth, decreased metabolite levels associated with nucleic acid biosynthesis pathway, and contributed an additive effect when combined with gemcitabine, pemetrexed, or CHK1 inhibitor AZD7762. Tissue microarray analysis revealed that CPS1 was expressed in 65.7% of LKB1-negative LADC, and only 5.0% of LKB1-positive LADC. CPS1 expression showed statistically significant association with poor overall survival in LADC (hazard ratio = 3.03, 95% confidence interval = 1.74 to 5.25, P < .001). Our findings suggest functional relevance of CPS1 in LKB1-inactivated LADC and association with worse outcome of LADC. CPS1 is a promising therapeutic target in combination with other chemotherapy agents, as well as a prognostic biomarker, enabling a personalized approach to treatment of LADC.


African-American adolescents residing in high-risk urban environments do use condoms: correlates and predictors of condom use among adolescents in public housing developments.
African-American adolescents living in high-risk inner-city environments have been disproportionately affected by the epidemics of human immunodeficiency virus (HIV) and other sexually transmitted diseases. Understanding the factors that influence the use of condoms by adolescents is critical for developing effective behavioral interventions. The present study examined the demographic, psychosocial, and behavioral correlates of condom use among African-American adolescents residing in public housing developments in an HIV epicenter (San Francisco) and prospectively evaluated the stability of these significant cross-sectional variables to predict consistent condom use. A prospective study. Two public housing developments in San Francisco. African-American adolescents and young adults between 12 and 21 years of age were recruited though street outreach and completed a theoretically derived research interview assessing HIV-related knowledge, attitudes, and behaviors. After a 6-month period, adolescents completed a follow-up interview similar to the baseline measure. Among adolescents reporting sexual activity in the 6 months before completing the baseline interview (n = 116), logistic regression analysis evaluated the influence of demographic, psychosocial, and behavioral factors on consistent condom use. Adolescents who had high assertive self-efficacy to demand condom use (adjusted odds ratio [OR], 11), perceived peer norms as supporting condom use (OR, 4.2), had greater impulse control (OR, 3.7), were male (OR, 4.7), and were younger (OR, 2.9) were more likely to report consistent condom use. Frequency of sexual intercourse was inversely related to condom use; adolescents with higher numbers of sexual episodes were less likely to use condoms consistently. Prospective analyses identified the baseline level of condom use as the best predictor of condom use at the 6-month follow-up. Adolescents who were consistent condom users at baseline were 7.4 times as likely to be consistent condom users during the follow-up period. Of those adolescents changing their frequency of condom use during the follow-up interval, significantly more engaged in risky behavior; 33.3% changed from consistent to inconsistent condom use, whereas 20.6% changed from inconsistent to consistent use (OR, 1.6). The findings suggest that HIV prevention programs need to be implemented early, before high-risk behaviors are established and may be more difficult to modify.


Definitive radiotherapy with image-guided adaptive brachytherapy for primary vaginal cancer.
Primary vaginal cancer is a rare cancer and clinical evidence to support recommendations on its optimal management is insufficient. Because primary vaginal cancer resembles cervical cancer in many aspects, treatment strategies are mainly adopted from evidence in locally advanced cervical cancer. To date, the organ-sparing treatment of choice is definitive radiotherapy, consisting of external beam radiotherapy and brachytherapy, combined with concurrent chemotherapy. Brachytherapy is an important component of the treatment and its steep dose gradient enables the delivery of high doses of radiation to the primary tumour, while simultaneously sparing the surrounding organs at risk. The introduction of volumetric CT or MRI image-guided adaptive brachytherapy in cervical cancer has led to better pelvic control and survival, with decreased morbidity, than brachytherapy based on x-ray radiographs. MRI-based image-guided adaptive brachytherapy with superior soft-tissue contrast has also been adopted sporadically for primary vaginal cancer. This therapy has had promising results and is considered to be the state-of-the-art treatment for primary vaginal cancer in standard practice.


Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: a randomized controlled trial.
Microbial-derived uremic toxins, p-cresyl sulfate (PCS), indoxyl sulfate (IS) and indole 3-acetic acid (IAA), have been associated with the burden of chronic kidney disease (CKD). Prebiotics have emerged as an alternative to modulate the gut environment and to attenuate toxin production. This trial aims to investigate the effect of a prebiotic fructooligosaccharide (FOS) on uremic toxins of non-dialysis-dependent CKD (NDD-CKD) patients. A double-blind, placebo-controlled, randomized trial was conducted for 3 months. In all, 50 nondiabetic NDD-CKD patients [estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2], aged 18-80 years, were allocated to prebiotic (FOS, 12 g/day) or placebo (maltodextrin, 12 g/day) groups. Primary outcomes were changes in serum (total and free) and urinary (total) PCS. Secondary outcomes included changes in IS, IAA, serum markers of intestinal permeability (zonulin), gut-trophic factors (epidermal growth factor and glucagon-like peptide-2), eGFR, inflammation (high sensitive c-reactive protein and interleukin-6), homeostatic model assessment-insulin resistance, lipid profile and gastrointestinal symptoms. From 50 participants (54% men, 57.3 ± 14.6 years and eGFR 21.4 ± 7.6 mL/min/1.73 m2), 46 completed the follow-up. No changes in dietary intake or gastrointestinal symptoms were observed. There was a trend in the difference of serum total ΔPCS (treatment effect adjusted for baseline levels: -12.4 mg/L; 95% confidence interval (-5.6 to 0.9 mg/L; P = 0.07) and serum-free Δ%PCS [intervention -8.6 (-41.5 to 13.9%) versus placebo 3.5 (-28.8 to 85.5%); P = 0.07] between the groups. The trend in the difference of serum total ΔPCS was independent of eGFR and dietary protein:fiber ratio intake. No difference was found in urinary PCS. Aside from the decreased high-density lipoprotein cholesterol in the intervention, no differences were observed in the change of IS, IAA or other secondary outcome between the groups. Our result suggests the potential of FOS in reducing serum total and free PCS in nondiabetic NDD-CKD patients.


Design framework for mechanically tunable soft biomaterial composites enhanced by modified horseshoe lattice structures.
Soft biomaterials have a wide range of applications in many areas. However, one material can only cover a specific range of mechanical performance such as the elastic modulus and stretchability. In order to improve the mechanical performance of soft biomaterials, lattice structures are embedded to reinforce the biomaterials. In this paper, rectangular and triangular lattice structures formed by modified horseshoe microstructures are used because their mechanical properties are tunable and can be tailored precisely to match the desired properties by adjusting four geometrical parameters, the length L, radius R, width w and arc angle θ0. A theoretical design framework for the modified horseshoe lattice structures is developed to predict the dependence of the mechanical behaviors on geometrical parameters. Both experiments and finite element simulations on lattice structures are conducted to validate the theoretical models. Results show that a wide range of design space for the elastic modulus (a few kPa to hundreds of MPa), stretchability (strain up to 180%) and Poisson ratio (ranging from -0.5 to 1.2) can be achieved. Experiments on lattice-hydrogel composites are also conducted to verify the reinforcement effect of lattice structures on the hydrogel. This work provides a theoretical method to predict the mechanical behaviors of the lattice structures and aid the rational design of reinforced biomaterials, which has applications in tissue engineering, drug delivery and intraocular lenses.


Social inequality and alcohol consumption-abuse in Bahia, Brazil-- interactions of gender, ethnicity and social class.
This paper reports findings on Alcohol Consumption-Abuse (ACAb) in Bahia, Brazil, a research setting characterized by racial/ethnic and socioeconomic diversity. A household survey was conducted with a sample of 2,302 adults. ACAb was defined as daily intake of more than two units of beverage, with drunkenness, or weekly binge drinking plus episodes of drunkenness, or any use of alcoholic beverages with frequent drunkenness, with failed attempts to stop drinking. The rate of 12-month prevalence was 7%, with an overall male: female ratio of 6:1. A positive association of ACAb prevalence with education and social class was found. Male gender and higher socio-economic status were associated with increased odds of ACAb. No relationship was found between ethnicity and ACAb. Stratified analysis yielded consistent gender effects, throughout all strata of independent variables. A strong interaction of gender (male) and social class (upper class) was found for Mulattos and Morenos (maximum Prevalence rate=9.04). Interaction patterns found defy simple generalizations based on class, ethnicity, and gender considered alone.


TNFα regulates cortisol metabolism in vivo in patients with inflammatory arthritis.
To determine the relationship between inflammation and glucocorticoid metabolism in vivo, in a clinical study of patients with inflammatory arthritis treated with anti-TNFα therapy. Urine samples were collected from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) as part of a multicentre study assessing responses to infliximab and etanercept. Systemic measures of glucocorticoid metabolism were assessed by gas chromatography/mass spectrometry at weeks 0 (baseline), 4 and 12 after anti-TNFα therapy. Clinical data including DAS28 and C-reactive protein were also collected. Systemic measures of 11β-HSD1 activity in patients with inflammatory arthritis decreased significantly following anti-TNFα therapy in patients with RA and PsA. Additionally, the activity of the glucocorticoid inactivating enzyme 5α-reductase appeared to increase significantly. This study demonstrates, for the first time, that the increased 11β-HSD1 activity seen in patients with inflammatory arthritis is mediated through TNFα. Furthermore, the changes in related glucocorticoid metabolising enzymes suggest that there is a coordinated change in glucocorticoid metabolism which promotes higher tissue glucocorticoid levels.


AIDS-associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa.
AIDS-associated Kaposi's sarcoma is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. In western countries, the introduction of combination antiretroviral therapy (cART) and new chemotherapeutic agents has resulted in decreased incidence and improved prognosis of AIDS-associated Kaposi's sarcoma. In African cohorts, however, mortality remains high. In this study, we describe disease characteristics and risk factors for mortality in a public sector HIV programme in South Africa. We analysed data from an observational cohort study of HIV-infected adults with AIDS-associated Kaposi's sarcoma, enrolled between May 2001 and January 2007 in three primary care clinics. Paper records from primary care and tertiary hospital oncology clinics were reviewed to determine the site of Kaposi's sarcoma lesions, immune reconstitution inflammatory syndrome stage, and treatment. Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Cox regression was used to model associations with mortality. Of 6292 patients, 215 (3.4%) had AIDS-associated Kaposi's sarcoma. Lesions were most commonly oral (65%) and on the lower extremities (56%). One quarter of patients did not receive cART. The mortality and lost-to-follow-up rates were, respectively, 25 (95% CI 19-32) and eight (95% CI 5-13) per 100 person years for patients who received cART, and 70 (95% CI 42-117) and 119 (80-176) per 100 person years for patients who did not receive cART. Advanced T stage (adjusted HR, AHR = 5.3, p < 0.001), advanced S stage (AHR = 5.1, p = 0.008), and absence of chemotherapy (AHR = 2.4, p = 0.012) were associated with mortality. Patients with AIDS-associated Kaposi's sarcoma presented with advanced disease and high rates of mortality and loss to follow up. Risk factors for mortality included advanced Kaposi's sarcoma disease and lack of chemotherapy use. Contributing factors to the high mortality for patients with AIDS-associated Kaposi's sarcoma likely included late diagnosis of HIV disease, late accessibility to cART, and sub-optimal treatment of advanced Kaposi's sarcoma. These findings confirm the importance of early access to both cART and chemotherapy for patients with AIDS-associated Kaposi's sarcoma. Early diagnosis and improved treatment protocols in resource-poor settings are essential.


Simultaneous determination of amphetamines and amphetamine-derived designer drugs in human urine by GC-MS.
The purpose of this study is to evaluate the gas chromatographicmass spectrometric method (GC-MS) for assay of stimulants of amphetamine type: amphetamine (AMP), methamphetamine (MAMP), ephedrine (EPH), norephedrine (NOREPH), and the amphetamine-derived designer drugs 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), 3,4-methylenedioxy-N-ethylamphetamine (MDEA) and N-methyl-benzodioxolylbutanamine (MBDB) in urine. These drugs are often encountered in forensic and clinical toxicological analysis. GC-MS method after mixed-mode solid-phase extraction (SPE) and derivatization with heptafluorobutyric anhydride (HFBA) is presented for quick and reliable screening as well as identification and quantification of amphetamines and amphetamine derived designer drugs in urine. The measurement of calibration dependence allowed to determine the extent of linearity in the concentration range from 10 to 2,000 ng/ml for all amphetamines except AMP and for all amphetamine-derived designer drugs with correlation coefficients exceeding 0.98. Detection limits were established at 5 ng/ml and quantification limits at 10 ng/ml for all analytes, except AMP. LOD for AMP was established at 20 ng/ml and LOQ at 50 ng/ml. Extraction efficiency for all analytes at concentration levels 50 and 500 ng/ml (n=6) was established in the range 60-99%. Repeatability was measured at concentration levels 50 and 500 ng/ml (n=6), relative standard deviations (RSDs) were under 10% for all analytes. The GC-MS method after mix-mode solid-phase extraction and derivatization with heptafluorobutyric anhydride is presented for screening followed by identification and quantification of AMP, MAMP, EPH, NOREPH, MDA, MDMA, MDEA, and MBDB. The applicability of the GC-MS method was proven by analyzing authentic urine samples.


Future ozone-related acute excess mortality under climate and population change scenarios in China: A modeling study.
Climate change is likely to further worsen ozone pollution in already heavily polluted areas, leading to increased ozone-related health burdens. However, little evidence exists in China, the world's largest greenhouse gas emitter and most populated country. As China is embracing an aging population with changing population size and falling age-standardized mortality rates, the potential impact of population change on ozone-related health burdens is unclear. Moreover, little is known about the seasonal variation of ozone-related health burdens under climate change. We aimed to assess near-term (mid-21st century) future annual and seasonal excess mortality from short-term exposure to ambient ozone in 104 Chinese cities under 2 climate and emission change scenarios and 6 population change scenarios. We collected historical ambient ozone observations, population change projections, and baseline mortality rates in 104 cities across China during April 27, 2013, to October 31, 2015 (2013-2015), which included approximately 13% of the total population of mainland China. Using historical ozone monitoring data, we performed bias correction and spatially downscaled future ozone projections at a coarse spatial resolution (2.0° × 2.5°) for the period April 27, 2053, to October 31, 2055 (2053-2055), from a global chemistry-climate model to a fine spatial resolution (0.25° × 0.25°) under 2 Intergovernmental Panel on Climate Change Representative Concentration Pathways (RCPs): RCP4.5, a moderate global warming and emission scenario where global warming is between 1.5°C and 2.0°C, and RCP8.5, a high global warming and emission scenario where global warming exceeds 2.0°C. We then estimated the future annual and seasonal ozone-related acute excess mortality attributable to both climate and population changes using cause-specific, age-group-specific, and season-specific concentration-response functions (CRFs). We used Monte Carlo simulations to obtain empirical confidence intervals (eCIs), quantifying the uncertainty in CRFs and the variability across ensemble members (i.e., 3 predictions of future climate and air quality from slightly different starting conditions) of the global model. Estimates of future changes in annual ozone-related mortality are sensitive to the choice of global warming and emission scenario, decreasing under RCP4.5 (-24.0%) due to declining ozone precursor emissions but increasing under RCP8.5 (10.7%) due to warming climate in 2053-2055 relative to 2013-2015. Higher ambient ozone occurs under the high global warming and emission scenario (RCP8.5), leading to an excess 1,476 (95% eCI: 898 to 2,977) non-accidental deaths per year in 2053-2055 relative to 2013-2015. Future ozone-related acute excess mortality from cardiovascular diseases was 5-8 times greater than that from respiratory diseases. Ozone concentrations increase by 15.1 parts per billion (10-9) in colder months (November to April), contributing to a net yearly increase of 22.3% (95% eCI: 7.7% to 35.4%) in ozone-related mortality under RCP8.5. An aging population, with the proportion of the population aged 65 years and above increased from 8% in 2010 to 24%-33% in 2050, will substantially amplify future ozone-related mortality, leading to a net increase of 23,838 to 78,560 deaths (110% to 363%). Our analysis was mainly limited by using a single global chemistry-climate model and the statistical downscaling approach to project ozone changes under climate change. Our analysis shows increased future ozone-related acute excess mortality under the high global warming and emission scenario RCP8.5 for an aging population in China. Comparison with the lower global warming and emission scenario RCP4.5 suggests that climate change mitigation measures are needed to prevent a rising health burden from exposure to ambient ozone pollution in China.


Visual destabilisation of posture in normal subjects.
A new and simple method of assessing reliance on vision for postural control was evaluated in 41 normal subjects. Left-right reversal of peripheral vision induced by a head-mounted mirror device caused an initial dramatic instability in approximately half the subjects, when standing on foam to reduce the value of proprioception. Lateral reversal of central vision by means of a prism device evoked similar responses. Sensitivity to vision reversal was significantly correlated with motion sickness susceptibility. Despite some rapid habituation (partially retained over several weeks) sway remained as great as with eye closure in the anterior-posterior as well as lateral direction, indicating complete suppression of the visual input. Balancing with vision reversal caused a selective decrement in performance of a visuo-spatial memory task, suggesting that coping with misleading visual input may place continuous demands on cortical spatial processing.


Spatial distribution of mammography adherence in a Swiss urban population and its association with socioeconomic status.
Local physical and social environment has a defining influence on individual behavior and health-related outcomes. However, it remains undetermined if its impact is independent of individual socioeconomic status. In this study, we evaluated the spatial distribution of mammography adherence in the state of Geneva (Switzerland) using individual-level data and assessed its independence from socioeconomic status (SES). Georeferenced individual-level data from the population-based cross-sectional Bus Santé study (n = 5002) were used to calculate local indicators of spatial association (LISA) and investigate the spatial dependence of mammography adherence. Spatial clusters are reported without adjustment; adjusted for neighborhood income and individual educational attainment; and demographic factors (age and Swiss nationality). The association between adjusted clusters and the proximity to the nearest screening center was also evaluated. Mammography adherence was not randomly distributed throughout Geneva with clusters geographically coinciding with known SES distributions. After adjustment for SES indicators, clusters were reduced to 56.2% of their original size (n = 1033). Adjustment for age and nationality further reduced the number of individuals exhibiting spatially dependent behavior (36.5% of the initial size). The identified SES-independent hot spots and cold spots of mammography adherence were not explained by proximity to the nearest screening center. SES and demographic factors play an important role in shaping the spatial distribution of mammography adherence. However, the spatial clusters persisted after confounder adjustment indicating that additional neighborhood-level determinants could influence mammography adherence and be the object of targeted public health interventions.


Fast and slow synaptic potentials produced in a mammalian sympathetic ganglion by colon distension.
Radial distension of the large intestine produced a slow depolarization in a population of neurons in the inferior mesenteric ganglion of the guinea pig. The slow potentials often occurred simultaneously with cholinergic fast potentials [( excitatory postsynaptic potentials (EPSPs]) yet persisted in the presence of nicotinic and muscarinic cholinergic antagonists when all fast EPSPs were absent. The amplitude of the distension-induced noncholinergic slow depolarization increased with increasing distension pressure. For distensions of 1-min duration at pressures of 10-20 cm of water, the mean depolarization amplitude was 3.4 mV. The slow depolarization was associated with an increase in membrane resistance, and prolonged periods of colon distension resulted in a tachyphylaxis of the depolarization. Desensitization of ganglion cells to the peptide substance P attenuated the distension-induced slow potential by an average of 49% +/- 17%. Thus, two colonic mechanosensory afferent pathways converge on principal ganglion cells in the inferior mesenteric ganglion: one was previously described to be mediated by acetylcholine, and the other is described here, whose transmitter remains to be determined but which preliminary evidence suggests is mediated in part by substance P. The noncholinergic afferent pathway may enhance the intestinal inhibitory reflex mediated by cholinergic mechanosensory afferent input to the abdominal prevertebral sympathetic ganglia.


Interpersonal violence as a major contributor towards the skewed burden of trauma in KwaZulu-Natal, South Africa.
Trauma is one of the foremost causes of death worldwide, but there is a paucity of data on demographics and injury patterns in developing countries. To quantify and describe the major trauma burden at a regional hospital in KwaZulu-Natal (KZN), South Africa (SA), over a 5-year period. Ngwelezane Hospital is a large regional hospital in northern KZN. A database is maintained of all major trauma patients admitted to the Emergency Department (ED) resuscitation unit. Statistical analysis was performed to quantify the burden of trauma and analyse trends in these data. Over a 5-year period, 3 735 major trauma patients were admitted to the ED resuscitation unit. Analysis showed a male predominance, with a mean patient age of 28.6 years. An average of 62 patients per month were admitted, the rate peaking over the holiday seasons. Trauma secondary to interpersonal violence (IPV) predominated. A disproportionately high level of pedestrian-motor vehicle collisions (PMVCs) in relation to total road traffic collisions was noted. Blunt force trauma secondary to motor vehicle collisions was the leading cause of death, while blunt force trauma secondary to PMVC s carried the highest mortality rate. This study highlights the high incidences of both IPV and PMVCs typical of trauma in an SA setting. The demographics and injury patterns noted may be used to drive public health interventions to address this burden of trauma.


Solution structure of Pi4, a short four-disulfide-bridged scorpion toxin specific of potassium channels.
Pi4 is a short toxin found at very low abundance in the venom of Pandinus imperator scorpions. It is a potent blocker of K(+) channels. Like the other members of the alpha-KTX6 subfamily to which it belongs, it is cross-linked by four disulfide bonds. The synthetic analog (sPi4) and the natural toxin (nPi4) have been obtained by solid-phase synthesis or from scorpion venom, respectively. Analysis of two-dimensional (1)H NMR spectra of nPi4 and sPi4 indicates that both peptides have the same structure. Moreover, electrophysiological recordings of the blocking of Shaker B K(+) channels by sPi4 (K(D) = 8.5 nM) indicate that sPi4 has the same blocking activity of nPi4 (K(D) = 8.0 nM), previously described. The disulfide bonds have been independently determined by NMR and structure calculations, and by Edman-degradation/mass-spectrometry identification of peptides obtained by proteolysis of nPi4. Both approaches indicate that the pairing of the half-cystines is (6)C-(27)C, (12)C-(32)C, (16)C-(34)C, and (22)C-(37)C. The structure of the toxin has been determined by using 705 constraints derived from NMR data on sPi4. The structure, which is well defined, shows the characteristic alpha/beta scaffold of scorpion toxins. It is compared to the structure of the other alpha-KTX6 subfamily members and, in particular, to the structure of maurotoxin, which shows a different pattern of disulfide bridges despite its high degree of sequence identity (76%) with Pi4. The structure of Pi4 and the high amounts of synthetic peptide available, will enable the detailed analysis of the interaction of Pi4 with K(+) channels.


Doublecortin as a marker of adult neuroplasticity in the canary song control nucleus HVC.
It is established that in songbirds the size of several brain song control nuclei varies seasonally, based on changes in cell size, dendritic branching and, in nucleus HVC, the incorporation of newborn neurons. In the developing and adult mammalian brain, the protein doublecortin (DCX) is expressed in postmitotic neurons and, as a part of the microtubule machinery, required for neuronal migration. We recently showed that in adult canaries, DCX-immunoreactive (ir) cells are present throughout the telencephalon, but the link between DCX and the active neurogenesis observed in songbirds remained uncertain. We demonstrate here that DCX labels recently born cells in the canary telencephalon and that, in parallel with changes in HVC volume, the number of DCX-ir cells is increased specifically in the HVC of testosterone-treated males compared with castrates, and in castrated testosterone-treated males paired with a female as compared with males paired with another male. The numbers of elongated DCX-ir cells (presumptive migrating neurons) and round multipolar DCX-ir cells (differentiating neurons) were also affected by the sex of the subjects and their photoperiodic condition (photosensitive vs photostimulated vs photorefractory). Thus, in canaries the endocrine state, as well as the social or photoperiodic condition independently of variation in steroid hormone action, affects the number of cells expressing a protein involved in neuronal migration specifically in brain areas that incorporate new neurons in the telencephalon. The DCX gene may be one of the targets by which testosterone and social stimuli induce seasonal changes in the volume of song nuclei.


Childhood idiopathic steroid resistant nephrotic syndrome in Southwestern Nigeria.
Clinical charts of 23 Nigerian children diagnosed with idiopathic steroid resistant nephrotic syndrome (iSRNS) between January 2001 and December 2007 were retrospectively reviewed to determine their clinicopathologic characteristics and outcome. iSRNS (54.8%) was primary in 19 patients (83%) and secondary in four (17%). The mean age at diagnosis was 8.3 ± 3.5 years (2.1-13 years). Histopathology revealed membranoproliferative glomerulonephritis (MPGN) in 43.5%, focal and segmental glomerulosclerosis (FSGS) in 39.1% and mesangial proliferative glomerulonephritis in 8.7% of the patients while minimal change disease (MCD) and membranous nephropathy accounted for 4.35% each. Routine treatment protocol comprised pulse intravenous (i.v.) cylophosphamide infusion and i.v. dexamethasone lisinopril or spironolactone. Cumulative Complete Remission (CR) rate was 57.12%. The overall median time to CR from start of steroid sparing agents in 12/21 treated patients was 4.5 weeks. CR was better achieved in MPGN than FSGS (P = 0.0186). Five patients had eight relapses with the overall median relapse-free duration being four months. Cumulative renal survival at 36 months was 41.8%. The median follow-up duration was eight months. Our study revealed that there was a high prevalence of iSRNS and preponderance of non-MCD lesions, with MPGN and FSGS being the major morphologic lesions. The outcome with steroid and cyclophosphamide-based treatment for iSRNS was further enhanced with addition of either lisinopril or spironolactone.


Effect of two dietary fibers on satiety and glycemic parameters: a randomized, double-blind, placebo-controlled, exploratory study.
Dietary carbohydrates may affect metabolic and physiologic parameters. The present study evaluated whether a combination of two dietary fibers, oligofructose (OFS) and pectin (P), altered satiety and glycemic parameters. The primary objective of this study was to determine whether dietary supplementation for 3 weeks with OFS + P would produce a greater reduction in energy intake of an ad libitum test meal compared to control. This was a single center, randomized, double-blind, placebo-controlled, parallel group study in overweight and obese, otherwise healthy, subjects (N = 96). There were two OFS + P treatment groups: high-dose (30 g/d), low-dose (15 g/d), and a control group (maltodextrin 15 g/d). Energy intake, appetite measures based on Satiety Labeled Intensity Magnitude (SLIM) scale, fasting and post-prandial glucose, and insulin levels and body weight were measured at baseline and at the end of 3 weeks. Adverse events and gastrointestinal tolerability of the treatments were also assessed. An analysis of covariance (ANCOVA) performed on the primary endpoint change from baseline in energy intake, showed no statistically significant difference in energy intake among the three treatment groups (p = 0.5387). The LS mean changes (SE) in energy intake from baseline to week 3 were -58.3 (42.4) kilocalories (kcal) for the high dose group, -74.2 (43.6) kcal for the low dose group, and -9.0 (42.9) kcal for the control group. For the pairwise comparisons of OFS + P doses and control, confidence intervals were constructed around the difference in LS mean changes. All study products were generally well tolerated. There was a directional benefit in ad libitum energy intake for both OFS + P doses compared to control, with a greater reduction in kilocalories in the low dose comparison, but the reductions were not significant. Further studies are warranted. GSK Clinical Study Register # W7781293.


Effect of local matrix crystal variations in matrix-assisted ionization techniques for mass spectrometry.
Intense intact molecular ion signals have been obtained from phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, and phosphatidyiinositol using matrix-enhanced secondary ion mass spectrometry (ME-SIMS). It was found that the high-mass (m/z >500) regions of the ME-SIMS spectra closely resembled those obtained using matrix-assisted laser desorption/ionization (MALDI). Using high spatial resolution SIMS, a detailed investigation of dried-droplet samples was performed. Based on the detected Na+ and 2,5-DHB matrix signal intensities, different crystal types were distinguished, in addition to different sizes of crystals. Spatially mapping the pseudomolecular and fragment ions of the phospholipids revealed that the nature of the pseudomolecular ions formed, as well as the ratio of intact molecular to fragment ion, was dependent on the type and surface composition of the crystal. The observed chemical bias effects due to crystal heterogeneity and the resulting variation in desorption/ionization efficiency will complicate the interpretation of data obtained from matrix-assisted mass spectrometric (imaging) techniques and is an important factor in the "hot spot" phenomenon frequently encountered in MALDI experiments. In this respect, imaging SIMS was found to be a versatile tool to investigate the effects of the local physicochemical conditions on the detected molecular species.


Air pollution and development in Africa: impacts on health, the economy, and human capital.
Africa is undergoing both an environmental and an epidemiological transition. Household air pollution is the predominant form of air pollution, but it is declining, whereas ambient air pollution is increasing. We aimed to quantify how air pollution is affecting health, human capital, and the economy across Africa, with a particular focus on Ethiopia, Ghana, and Rwanda. Data on household and ambient air pollution were from WHO Global Health Observatory, and data on morbidity and mortality were from the 2019 Global Burden of Disease Study. We estimated economic output lost due to air pollution-related disease by country, with use of labour income per worker, adjusted by the probability that a person (of a given age) was working. Losses were expressed in 2019 international dollars and as a proportion of gross domestic product (GDP). We also quantified the contribution of particulate matter (PM)2·5 pollution to intelligence quotient (IQ) loss in children younger than 10 years, with use of an exposure-response coefficient based on previously published data. Air pollution was responsible for 1·1 million deaths across Africa in 2019. Household air pollution accounted for 697 000 deaths and ambient air pollution for 394 000. Ambient air pollution-related deaths increased from 361 000 in 2015, to 383 000 in 2019, with the greatest increases in the most highly developed countries. The majority of deaths due to ambient air pollution are caused by non-communicable diseases. The loss in economic output in 2019 due to air pollution-related morbidity and mortality was $3·02 billion in Ethiopia (1·16% of GDP), $1·63 billion in Ghana (0·95% of GDP), and $349 million in Rwanda (1·19% of GDP). PM2·5 pollution was estimated to be responsible for 1·96 billion lost IQ points in African children in 2019. Ambient air pollution is increasing across Africa. In the absence of deliberate intervention, it will increase morbidity and mortality, diminish economic productivity, impair human capital formation, and undercut development. Because most African countries are still early in development, they have opportunities to transition rapidly to wind and solar energy, avoiding a reliance on fossil fuel-based economies and minimising pollution. UN Environment Programme.


Metformin-pioglitazone and metformin-rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndrome.
Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin. The combination of metformin with thiazolidinediones is less well studied. The aim of the present study was to assess the differential effect, and tolerability, of metformin combined with pioglitazone or rosiglitazone on glucose, coagulation and fibrinolysis parameters in patients with type 2 diabetes mellitus and metabolic syndrome. This 12-month, multicentre, double-blind, randomized, controlled, parallel-group trial was conducted at three study sites in Italy. We assessed patients with type 2 diabetes mellitus (duration >or=6 months) and with metabolic syndrome. All patients were required to have poor glycaemic control with diet, or experienced adverse effects with diet and metformin, administered up to the maximum tolerated dose. Patients were randomized to receive either pioglitazone or rosiglitazone self-administered for 12 months. We assessed body mass index (BMI), glycaemic control [glycosylated haemoglobin (HbA(1c)), fasting and postprandial plasma glucose and insulin levels (FPG, PPG, FPI, and PPI respectively), homeostasis model assessment (HOMA) index], lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG)], lipoprotein (a) [Lp(a)] and homocysteine (HCT) at baseline and at 3, 6, 9 and 12 months of treatment. No BMI change was observed at 3, 6, 9 and 12 months in either group. Significant HbA(1c) decreases were observed at 9 and 12 months in both groups. After 9 and 12 months, mean FPG and PPG levels decreased in both groups. Decreases in FPI and PPI were observed at 9 and 12 months compared with the baseline in both groups. Furthermore, in both groups, the HOMA index improved but only at 12 months. Significant TC, LDL-C, HDL-C, TG improvement was present in the pioglitazone group at 12 months compared with the baseline values, and these variations were significantly different between groups. No TC, LDL-C, TG improvement was present in the rosiglitazone group after 12 months. Significant Lp(a) and HCT improvement was present in the pioglitazone group at 12 months compared with the baseline values, and Lp(a) change was significant compared with the rosiglitazone group. Significant HCT decrease was observed in the rosiglitazone group at the end of the study. In our type 2 diabetic patients, both drugs were safe and effective for glycaemic control and improving HCT plasma levels. However, long-term treatment with metformin plus pioglitazone significantly reduced Lp(a) plasma levels, whereas metformin + rosiglitazone did not. For patients with type 2 diabetes mellitus and metabolic syndrome, combined treatment with metformin and rosiglitazone or pioglitazone is safe and effective, However, the pioglitazone combination also reduced the plasma Lp(a) levels whereas the rosiglitazone combination did not.


Dynamic independence of pulsed antiphased modes.
We analyze theoretically a case of antiphase dynamics in the self-pulsing regime involving two orthogonal polarizations in intracavity second-harmonic generation. We show that, for this model, antiphase dynamics may lead to a nonreciprocal independence of the two polarizations as a result of partial overlap between the pulses. In the case in which two modes oscillate with one polarization and a single mode oscillates with orthogonal polarization, we find that the two modes can display chaos while the orthogonal mode remains periodic, despite coupling among all the modes.


Plasmodium vivax Malaria in Cambodia.
The Cambodian National Strategic Plan for Elimination of Malaria aims to move step by step toward elimination of malaria across Cambodia with an initial focus on Plasmodium falciparum malaria before achieving elimination of all forms of malaria, including Plasmodium vivax in 2025. The emergence of artemisinin-resistant P. falciparum in western Cambodia over the last decade has drawn global attention to support the ultimate goal of P. falciparum elimination, whereas the control of P. vivax lags much behind, making the 2025 target gradually less achievable unless greater attention is given to P. vivax elimination in the country. The following review presents in detail the past and current situation regarding P. vivax malaria, activities of the National Malaria Control Program, and interventional measures applied. Constraints and obstacles that can jeopardize our efforts to eliminate this parasite species are discussed.


Oligomeric properties of alpha-dendrotoxin-sensitive potassium ion channels purified from bovine brain.
Neuronal acceptors for alpha-dendrotoxin (alpha-DTX) have recently been purified from mammalian brain and shown to consist of two classes of subunit, a larger (approximately 78,000 M(r)) protein (alpha) whose N-terminal sequence is identical to that of a cloned, alpha-DTX-sensitive K+ channel, and a novel M(r) 39,000 (beta) polypeptide of unknown function. However, little information is available regarding the oligomeric composition of these native molecules. By sedimentation analysis of alpha-DTX acceptors isolated from bovine cortex, two species have been identified. A minority of these oligomers contain only the larger protein, while the vast majority possess both subunits. Based on accurate determination of the molecular weights of these two forms it is proposed that alpha-DTX-sensitive K+ channels exist as alpha 4 beta 4 complexes because this combination gives the best fit to the experimental data.


Commentary: Evaluating faculty productivity in research: an interesting approach, but questions remain.
Academic institutions must have strategies for evaluating research productivity by faculty. Such strategies are useful in guiding resource allocations for the research enterprise, for decisions on faculty promotions, and for broader institutional planning, including program development. Commonly, decisions about research space utilization, and funding to support the space, are considered within the purview of the institutional administration. Peer review, in manuscript and grant submissions and the promotions process, is more commonly used to evaluate the impact of faculty research. The article by Iyengar et al in this issue of Academic Medicine takes an interesting approach to evaluate research productivity of individual faculty by integrating benchmarks for research funding and publication impact. The strategy of using these benchmarks to partition faculty into quadrants to guide faculty development activities is clever and useful. Less clear are the philosophy and long-term utility of the approach. The applicability to the stated goal of promoting multidisciplinary and interdisciplinary translational research is not obvious, nor is it apparent that faculty will continue to view decisions as transparent and fair over the longer term. Nevertheless, the authors' article is a welcome contribution at a time when many institutions are struggling with issues of evaluating faculty investigators and allocating resources for research.


Integrating sorghum whole genome sequence information with a compendium of sorghum QTL studies reveals uneven distribution of QTL and of gene-rich regions with significant implications for crop improvement.
A comprehensive analysis was conducted using 48 sorghum QTL studies published from 1995 to 2010 to make information from historical sorghum QTL experiments available in a form that could be more readily used by sorghum researchers and plant breeders. In total, 771 QTL relating to 161 unique traits from 44 studies were projected onto a sorghum consensus map. Confidence intervals (CI) of QTL were estimated so that valid comparisons could be made between studies. The method accounted for the number of lines used and the phenotypic variation explained by individual QTL from each study. In addition, estimated centimorgan (cM) locations were calculated for the predicted sorghum gene models identified in Phytozome (JGI GeneModels SBI v1.4) and compared with QTL distribution genome-wide, both on genetic linkage (cM) and physical (base-pair/bp) map scales. QTL and genes were distributed unevenly across the genome. Heterochromatic enrichment for QTL was observed, with approximately 22% of QTL either entirely or partially located in the heterochromatic regions. Heterochromatic gene enrichment was also observed based on their predicted cM locations on the sorghum consensus map, due to suppressed recombination in heterochromatic regions, in contrast to the euchromatic gene enrichment observed on the physical, sequence-based map. The finding of high gene density in recombination-poor regions, coupled with the association with increased QTL density, has implications for the development of more efficient breeding systems in sorghum to better exploit heterosis. The projected QTL information described, combined with the physical locations of sorghum sequence-based markers and predicted gene models, provides sorghum researchers with a useful resource for more detailed analysis of traits and development of efficient marker-assisted breeding strategies.


Central venous-to-arterial carbon dioxide gradient as a marker of occult tissue hypoperfusion after major surgery.
The central venous-arterial carbon dioxide tension gradient ('CO₂gap') has been shown to correlate with cardiac output and tissue perfusion in septic shock. Compared to central venous oxygen saturation (SCVO2), the CO₂gap is less susceptible to the effect of hyperoxia and may be particularly useful as an adjunctive haemodynamic target in the perioperative period. This study investigated whether a high CO₂gap was associated with an increased systemic oxygen extraction (O2ER >0.3) or occult tissue hypoperfusion in 201 patients in the immediate postoperative period. The median CO₂gap of all patients was 8 mmHg (IQR 6 to 9), and a large CO₂gap was very common (> 6mmHg in 139 patients [69%], 95% CI 63 to 75; >5 mmHg in 170 patients [85%], 95% CI 79 to 89). A CO₂ gap >5 mmHg had a higher sensitivity (93%) and negative predictive value (74%) than a CO₂gap >6 mmHg in excluding occult tissue hypoperfusion. Of the four variables that were predictive of an increased O₂ER in the multivariate analysis-CO₂gap, arterial pH, haemoglobin and arterial lactate concentrations-the CO₂gap (odds ratio 4.41 per mmHg increment, 95% CI 1.7 to 11.2, P=0.002) was most important and explained about 34% of the variability in the risk of occult tissue hypoperfusion. In conclusion, a normal CO₂ gap (<5 mmHg) had a high sensitivity and negative predictive value in excluding inadequate systemic oxygen delivery and may be useful as an adjunct to other haemodynamic targets in avoiding occult tissue hypoperfusion in the perioperative setting when high inspired oxygen concentrations are used.


Diversity, distribution and sources of bacteria in residential kitchens.
Bacteria readily colonize kitchen surfaces, and the exchange of microbes between humans and the kitchen environment can impact human health. However, we have a limited understanding of the overall diversity of these communities, how they differ across surfaces and sources of bacteria to kitchen surfaces. Here we used high-throughput sequencing of the 16S rRNA gene to explore biogeographical patterns of bacteria across > 80 surfaces within the kitchens of each of four households. In total, 34 bacterial and two archaeal phyla were identified, with most sequences belonging to the Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. Genera known to contain common food-borne pathogens were low in abundance but broadly distributed throughout the kitchens, with different taxa exhibiting distinct distribution patterns. The most diverse communities were associated with infrequently cleaned surfaces such as fans above stoves, refrigerator/freezer door seals and floors. In contrast, the least diverse communities were observed in and around sinks, which were dominated by biofilm-forming Gram-negative lineages. Community composition was influenced by conditions on individual surfaces, usage patterns and dispersal from source environments. Human skin was the primary source of bacteria across all kitchen surfaces, with contributions from food and faucet water dominating in a few specific locations. This study demonstrates that diverse bacterial communities are widely distributed in residential kitchens and that the composition of these communities is often predictable. These results also illustrate the ease with which human- and food-associated bacteria can be transferred in residential settings to kitchen surfaces.


Retinopathy and retinal function in insulin-dependent diabetes mellitus.
Sixty-six insulin-dependent diabetic patients with normal visual acuity were studied (132 eyes). The mean age was 27.7 years with a mean duration of diabetes mellitus of 8.7 years. Their mean electro-oculogram ratio, Arden grating and Munsell-Farnsworth scores were markedly abnormal (p much less than 0.00001). Background retinopathy was present in 53 eyes (40.2%), abnormal Arden grating scores (greater than 82) in 70 eyes (53%), abnormal Farnsworth-Munsell 100-hue score (greater than 100) in 88 eyes (56.7%), and 29 eyes (22%) had an electro-oculogram ratio less than 160. These abnormalities of retinal function did not correlate with retinopathy and were not secondary to it. Smoking caused a significant deterioration in contrast sensitivity.


A systematic review on the effectiveness of physical and rehabilitation interventions for chronic non-specific low back pain.
Low back pain (LBP) is a common and disabling disorder in western society. The management of LBP comprises a range of different intervention strategies including surgery, drug therapy, and non-medical interventions. The objective of the present study is to determine the effectiveness of physical and rehabilitation interventions (i.e. exercise therapy, back school, transcutaneous electrical nerve stimulation (TENS), low level laser therapy, education, massage, behavioural treatment, traction, multidisciplinary treatment, lumbar supports, and heat/cold therapy) for chronic LBP. The primary search was conducted in MEDLINE, EMBASE, CINAHL, CENTRAL, and PEDro up to 22 December 2008. Existing Cochrane reviews for the individual interventions were screened for studies fulfilling the inclusion criteria. The search strategy outlined by the Cochrane Back Review Groups (CBRG) was followed. The following were included for selection criteria: (1) randomized controlled trials, (2) adult (≥ 18 years) population with chronic (≥ 12 weeks) non-specific LBP, and (3) evaluation of at least one of the main clinically relevant outcome measures (pain, functional status, perceived recovery, or return to work). Two reviewers independently selected studies and extracted data on study characteristics, risk of bias, and outcomes at short, intermediate, and long-term follow-up. The GRADE approach was used to determine the quality of evidence. In total 83 randomized controlled trials met the inclusion criteria: exercise therapy (n = 37), back school (n = 5), TENS (n = 6), low level laser therapy (n = 3), behavioural treatment (n = 21), patient education (n = 1), traction (n = 1), and multidisciplinary treatment (n = 6). Compared to usual care, exercise therapy improved post-treatment pain intensity and disability, and long-term function. Behavioural treatment was found to be effective in reducing pain intensity at short-term follow-up compared to no treatment/waiting list controls. Finally, multidisciplinary treatment was found to reduce pain intensity and disability at short-term follow-up compared to no treatment/waiting list controls. Overall, the level of evidence was low. Evidence from randomized controlled trials demonstrates that there is low quality evidence for the effectiveness of exercise therapy compared to usual care, there is low evidence for the effectiveness of behavioural therapy compared to no treatment and there is moderate evidence for the effectiveness of a multidisciplinary treatment compared to no treatment and other active treatments at reducing pain at short-term in the treatment of chronic low back pain. Based on the heterogeneity of the populations, interventions, and comparison groups, we conclude that there are insufficient data to draw firm conclusion on the clinical effect of back schools, low-level laser therapy, patient education, massage, traction, superficial heat/cold, and lumbar supports for chronic LBP.


The membrane estrogen receptor GPR30 mediates cadmium-induced proliferation of breast cancer cells.
Cadmium (Cd) is a nonessential metal that is dispersed throughout the environment. It is an endocrine-disrupting element which mimics estrogen, binds to estrogen receptor alpha (ERalpha), and promotes cell proliferation in breast cancer cells. We have previously published that Cd promotes activation of the extracellular regulated kinases, erk-1 and -2 in both ER-positive and ER-negative human breast cancer cells, suggesting that this estrogen-like effect of Cd is not associated with the ER. Here, we have investigated whether the newly appreciated transmembrane estrogen receptor, G-protein coupled receptor 30 (GPR30), may be involved in Cd-induced cell proliferation. Towards this end, we compared the effects of Cd in ER-negative human SKBR3 breast cancer cells in which endogenous GPR30 signaling was selectively inhibited using a GPR30 interfering mutant. We found that Cd concentrations from 50 to 500 nM induced a proliferative response in control vector-transfected SKBR3 cells but not in SKBR3 cells stably expressing interfering mutant. Similarly, intracellular cAMP levels increased about 2.4-fold in the vector transfectants but not in cells in which GPR30 was inactivated within 2.5 min after treatment with 500 nM Cd. Furthermore, Cd treatment rapidly activated (within 2.5 min) raf-1, mitogen-activated protein kinase kinase, mek-1, extracellular signal regulated kinases, erk-1/2, ribosomal S6 kinase, rsk, and E-26 like protein kinase, elk, about 4-fold in vector transfectants. In contrast, the activation of these signaling molecules in SKBR3 cells expressing the GPR30 mutant was only about 1.4-fold. These results demonstrate that Cd-induced breast cancer cell proliferation occurs through GPR30-mediated activation in a manner that is similar to that achieved by estrogen in these cells.


Long-term disability in neuromyelitis optica spectrum disorder with a history of myelitis is associated with age at onset, delay in diagnosis/preventive treatment, MRI lesion length and presence of symptomatic brain lesions.
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system (CNS) that preferentially targets the spinal cord and optic nerves. Increasing disability is accrued with each inflammatory attack. Disability has been shown to be an independent predictor of poor quality of life in those with NMOSD. Factors associated with increasing disability need further systematic investigation. We performed a multi-center retrospective chart analysis of aquaporin-4 (AQP4) seropositive NMOSD patients with a history of myelitis seen at five large referral centers for patients with NMOSD worldwide for whom thorough records including relapse history and corresponding imaging were available. Potential contributors to long-term disability were extracted including demographics, radiographic findings, and clinical characteristics. Multivariable regression modeling was conducted to determine correlates of disability in patients with NMOSD, as measured by the Expanded Disability Status Scale (EDSS). One hundred eighty-two AQP4 seropositive patients (88% female) were included in this analysis. Multiple regression modeling revealed that older age at disease onset, delay in diagnosis/preventive treatment, length of longest acute myelitis lesion and presence of symptomatic brain/brainstem lesions were associated with increased disability when holding other variables constant. While age at onset is a factor that cannot be controlled in NMOSD, we can reduce the delay in diagnosis/preventive treatment and reduce future relapses in the brain/brainstem and spinal cord. Delay in diagnosis/preventive treatment and imaging variables that contributed to increased disability support the need for improved measures for early, accurate diagnosis and management of NMOSD, and aggressive treatment of acute relapses.