Broadband homodecoupled time-shared 1H-13C and 1H-15N HSQC experiments.
The concepts of pure-shift NMR and time-shared NMR are merged in a single experiment. A 13C/15N time-shared version of the real-time BIRD-based broadband homodecoupled HSQC experiment is described. This time-efficient approach affords simultaneously 1H-13C and 1H-15N pure-shift HSQC spectra in a single acquisition, while achieving substantial gains in both sensitivity and spectral resolution. We also present a related 13C/15N-F2-coupled homodecoupled version of the CLIP-HSQC experiment for the simultaneous measurement of 1JCH and 1JNH from the simplified doublets observed along the direct dimension. Finally, a novel J-resolved HSQC experiment has been designed for the simple and automated determination of both 1JCH/1JNH from a 2D J-resolved spectrum.


Does the sex of one's co-twin affect height and BMI in adulthood? A study of dizygotic adult twins from 31 cohorts.
The comparison of traits in twins from opposite-sex (OS) and same-sex (SS) dizygotic twin pairs is considered a proxy measure of prenatal hormone exposure. To examine possible prenatal hormonal influences on anthropometric traits, we compared mean height, body mass index (BMI), and the prevalence of being overweight or obese between men and women from OS and SS dizygotic twin pairs. The data were derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) database, and included 68,494 SS and 53,808 OS dizygotic twin individuals above the age of 20 years from 31 twin cohorts representing 19 countries. Zygosity was determined by questionnaires or DNA genotyping depending on the study. Multiple regression and logistic regression models adjusted for cohort, age, and birth year with the twin type as a predictor were carried out to compare height and BMI in twins from OS pairs with those from SS pairs and to calculate the adjusted odds ratios and 95% confidence intervals for being overweight or obese. OS females were, on average, 0.31 cm (95% confidence interval (CI) 0.20, 0.41) taller than SS females. OS males were also, on average, taller than SS males, but this difference was only 0.14 cm (95% CI 0.02, 0.27). Mean BMI and the prevalence of overweight or obesity did not differ between males and females from SS and OS twin pairs. The statistically significant differences between OS and SS twins for height were small and appeared to reflect our large sample size rather than meaningful differences of public health relevance. We found no evidence to support the hypothesis that prenatal hormonal exposure or postnatal socialization (i.e., having grown up with a twin of the opposite sex) has a major impact on height and BMI in adulthood.


Advanced korean industrial safety and health policy with risk assessment.
This article describes a systematic roadmap master plan for advanced industrial safety and health policy in Korea, with an emphasis on. Since Korean industries had first emergence of industrial safety and health policy in 1953, enormous efforts have been made on upgrading the relevant laws in order to reflect real situation of industrial work environment in accordance with rapid changes of Korean and global business over three decades. Nevertheless, current policy has major defects; too much techniques-based articles, diverged contents in less organization, combined enforcement and punishments and finally enforcing regulations full of commands and control. These deficiencies have make it difficult to accommodate changes of social, industrial and employment environment in customized fashion. The approach to the solution must be generic at the level of paradigm-shift rather than local modifications and enhancement. The basic idea is to establish a new system integrated with a risk assessment scheme, which encourages employers to apply to their work environment under comprehensive responsibility. The risk assessment scheme is designed to enable to inspect employers' compliances afterwards. A project comprises four yearly phases based on applying zones; initially designating and operating a specified risk zone, gradually expanding the special zones during a period of 3 years (2010-2012) and the final zone expanded to entire nation. In each phase, the intermediate version of the system is updated through a process of precise and unbiased validation in terms of its operability, feasibility and sustainability with building relevant infrastructures as needed.


Possible intermediates of Cu(phen)-catalyzed C-O cross-coupling of phenol with an aryl bromide by in situ ESI-MS and EPR studies.
The C-O coupling reaction between 2,4-dimethylphenol and 4-bromotoluene catalyzed by the CuI/K2CO3/phen system can be inhibited by the radical scavenger cumene. Complexes [Cu(i)(phen)(1-(2,4-dimethylphenoxy)-4-methylbenzene)](+) (denoted as A), {H[Cu(i)(phen)(2,4-dimethylphenoxy)]}(+) and [Cu(i)(2,4-dimethylphenoxy)2](-) (denoted as B) were observed by in situ electrospray ionization mass spectrometry (ESI-MS) analysis of the copper(i)-catalyzed C-O coupling reaction under the catalytic reaction conditions indicating that they could be intermediates in the reaction. The in situ EPR study of the reaction solution detected the Cu(ii) species with a fitted g value of 2.188. A catalytic cycle with a single electron transfer (SET) step was proposed based on these observations.


Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse reactions (SCAR) related to a variety of medications. They have a significant public health impact because of high mortality and morbidity. A multinational case-control study conducted in Europe between 1997 and 2001 evaluated the risk of medications to induce SCAR. Cases were actively detected through a hospital network covering more than 100 million inhabitants. Three hospitalized patients per case matched on age, gender, and date of interview were enrolled as controls. After validation by an expert committee blinded to exposures, 379 SCAR cases and 1,505 controls were included. Among drugs recently introduced into the market, strong associations were documented for nevirapine (relative risk (RR)>22) and lamotrigine (RR>14), and weaker associations for sertraline (RR=11 [2.7-46]), pantoprazole (RR=18 [3.9-85]), and tramadol (RR=20 [4.4-93]). Strong associations were confirmed for anti-infective sulfonamides, allopurinol, carbamazapine, phenobarbital, phenytoin, and oxicam-NSAIDs , with some changes in relative numbers of exposed cases. Thus, many cases were still related to a few "old" drugs with a known high risk. Risk was restricted to the first few weeks of drug intake. The use of such drugs as first-line therapies should be considered carefully, especially when safer alternative treatments exist. A number of widely used drugs did not show any risk for SJS and TEN.


Feedback in action within bedside teaching encounters: a video ethnographic study.
Feedback associated with teaching activities is often synonymous with reflection on action, which comprises the evaluative assessment of performance out of its original context. Feedback in action (as correction during clinical encounters) is an underexplored, complementary resource facilitating students' understanding and learning. The purpose of this study was to explore the interactional patterns and correction modalities utilised in feedback sequences between doctors and students within general practice-based bedside teaching encounters (BTEs). A qualitative video ethnographic approach was used. Participants were recorded in their natural settings to allow interactional practices to be contextually explored. We examined 12 BTEs recorded across four general practices and involving 12 patients, four general practitioners and four medical students (209 minutes and 20 seconds of data) taken from a larger corpus. Data analysis was facilitated by Transana video analysis software and informed by previous conversation analysis research in ordinary conversation, classrooms and health care settings. A range of correction strategies across a spectrum of underlying explicitness were identified. Correction strategies classified at extreme poles of this scale (high or low explicitness) were believed to be less interactionally effective. For example, those using abrupt closing of topics (high explicitness) or interactional ambiguity (low explicitness) were thought to be less effective than embedded correction strategies that enabled the student to reach the correct answer with support. We believe that educators who are explicitly taught linguistic strategies for how to manage feedback in BTEs might manage learning more effectively. For example, clinicians might maximise learning moments during BTEs by avoiding abrupt or ambiguous feedback practices. Embedded correction strategies can enhance student participation by guiding students towards the correct answer. Clinician corrections can sensitively manage student face-saving by minimising the exposure of student error to patients. Furthermore, we believe that the effective practices highlighted by our analysis might facilitate successful transformation of feedback in action into feedback for action.


Trends in human immunodeficiency virus seroincidence among street-recruited injection drug users in San Francisco, 1987-1998.
This paper reports trends in human immunodeficiency virus (HIV) incidence among street-recruited injection drug users (IDUs) in San Francisco, California, from 1987 through 1998, estimated using a sensitive/less sensitive enzyme immunoassay testing strategy. IDUs were enrolled in 23 semiannual cross-sections from three community sites. For identification of recent infections, less sensitive enzyme immunoassay testing was performed on stored specimens that had previously tested positive for HIV antibodies. Annualized incidence rates were calculated and logistic regression models were fitted for assessment of risk factors for recent HIV infection. Among 8,065 susceptible IDUs, 34 had recent infections, for an incidence rate of 1.2% (95% confidence interval: 0.7, 2.0) per person-year. This rate declined from 2.7% in 1987/1988 to approximately 1% per person-year between 1989 and 1998. Two IDU subpopulations were at highest risk for infection: persons under age 30 years (2.8% per person-year) and men who had sex with men (3.0% per person-year). Participants who reported prior HIV test-result counseling were less likely than others to become infected (adjusted odds ratio = 0.43, 95% confidence interval: 0.21, 0.87). Sensitive/less sensitive enzyme immunoassay testing is an effective tool for assessing HIV incidence. HIV incidence among street-recruited IDUs in San Francisco appears to have remained stable and moderate since the late 1980s.


Efficacy and safety profile of aliskiren: practical implications for clinicians.
Renin-angiotensin-system (RAS) is an enzymatic cascade that plays a pivotal role in the development of arterial hypertension, kidney disease and cardiovascular disease. Inhibition of the RAS with angiotensin converting enzyme (ACE) inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) has proved to be a successful strategy for the treatment of hypertension and related cardiovascular disorders. However, by reducing feedback inhibition of renin release, the effects of ACE-Is and ARBs lead to an increase in plasma renin concentration (PRC) and activity (PRA), limiting a complete inhibition of the RAS. Consequently the effects of a different pharmacological strategy that completely blocks the RAS upstream has been assessed in the last years. In this context, aliskiren is the first representative of a new class of non-peptide orally active renin inhibitor that blocks the RAS at its rate-limiting step and induces a net reduction in PRA, angiotensin II and aldosterone levels. Aliskiren effectively reduces blood pressure as a monotherapy as well in combination therapy. In addition, aliskiren has a placebo-like tolerability profile at the licensed doses of 150 mg and 300 mg. Aliskiren also exhibits additive effects on blood pressure reduction when combined with drugs that lead to a reactive increase in the PRA, such as diuretics, ACE-Is or ARBs. In previous studies, aliskiren showed beneficial effects in patients with arterial hypertension and associated clinical conditions. However, later trials indicated that the use of aliskiren should be avoided in patients with renal failure or receiving ACE-Is or ARBs. The main aim of this review is to summarize the available data on its efficacy and safety profile, highlighting clinical implications from recent trials.


Cerebrotendinous xanthomatosis without tendon xanthomas mimicking Marinesco-Sjoegren syndrome: a case report.
A 39 year old patient with cerebellar signs, juvenile cataracts, and dull normal intelligence had cerebrotendinous xanthomatosis without tendon xanthomas, diagnosed previously as Marinesco-Sjoegren syndrome. Cerebrotendinous xanthomatosis was proved by a greatly increased excretion of bile alcohols in the patient's urine. Cerebrotendinous xanthomatosis is a sterol storage disorder due to an autosomal recessive inherited defect of sterol 27-hydroxylase characterised by high cholestanol concentration in multiple tissues. If tendon xanthomas are not present, a diagnosis of cerebrotendinous xanthomatosis will often not be made, unless biochemical tests are performed. The clinical features of cerebrotendinous xanthomas strongly resembles Marinesco-Sjoegren syndrome. Marinesco-Sjoegren syndrome is a autosomal recessive disorder characterised by the triad cerebellar ataxia, congenital cataract, and mental retardation. Although a late onset after the first decade of life favours cerebrotendinous xanthomatosis as the underlying disease, a definite distinction between cerebrotendinous xanthomatosis without tendon xanthomas and Marinesco-Sjoegren syndrome based on clinical presentation may be difficult. It is considered that some patients with Marinesco-Sjoegren syndrome reported in the medical literature had cerebrotendinous xanthomatosis without tendon xanthomas. This is of crucial clinical relevance, because, by contrast with Marinesco-Sjoegren syndrome, treatment for cerebrotendinous xanthomatosis is already available.


'It terrifies me, the thought of the future': listening to the current concerns of informal carers of people with a learning disability.
The aim of this article is to report findings from a study that asked carers for their views on a wide range of topics. Issues relevant to the current concerns of carers are reported here. A mixed method triangulated design yielded both quantitative and qualitative data. A total of 647 members of a parent/carer federation were sent a questionnaire with a section on 'current concerns'. The response rate was 23 percent (151 participants). Two focus groups were held with 15 carers who had completed the questionnaire. Issues of concern to carers included access to health and social care information and services; quality and quantity of respite care; suitable educational provision; independence and quality of life (for a person with learning disability); and what would happen to the person with learning disability when the carer was no longer able to carry out their caring role.


Transferrin catabolism in mammalian species of different body sizes.
Turnover of transferrin was measured in 62 mammals from 11 species (baboon, dog, goat, guinea pig, man, mouse, pig, rabbit, rat, rhesus monkey, and sheep) using iodinelabeled transferrin of homologous and/or heterologous origin. Protein turnover was determined either from the plasma protein-bound radioactivity curves or from the slopes of total body radiation. The volume of transferrin pool, expressed as equivalent milliliters of plasma, turned over per day correlated closely with species size (r = +0.977). Using the parabolic equation, y = axb, the constants for the relationship between body weight (x) and transferrin turnover (y) were a, 22.845; and b, 0.68. However, species of comparable weights with deviating transferrin turnovers do exist within the boundaries of this relationship. From a limited number of serum transferrin estimations in all species except for rhesus, six species appeared to have transferrin concentrations in a broad middle range (2.5-3.5 mg/ml). By comparison, dog and guinea pig had markedly lower, and pig and rat had markedly higher, serum transferrin concentrations.


Alternative phenotypes and sexual selection: can dichotomous handicaps honestly signal quality?
Considerable theoretical and empirical effort has been focused on the potential of continuously variable sexual traits to honestly indicate male quality, but relatively little effort has been devoted to a similar evolutionary role for dimorphic traits. Male dimorphisms, associated with conditionally expressed alternative reproductive tactics, represent extreme phenotypic plasticity. Evidence suggests that considerable heritable variation exists in the 'liability' underlying many threshold traits; if this liability is correlated with the genetic quality of males, dimorphic traits have the potential to be reliable indicators. We investigated the genetic architecture of phenotypically plastic morph expression in the context of condition-dependent signalling theory. Male morph in the mite Sancassania berlesei is condition dependent: 'fighters' armed with thickened and sharp third pairs of legs emerge from heavier nymphs than unarmoured 'scramblers'. We selected on male morph in three replicate 'fighter' and 'scrambler' lines and recorded a significant response to selection over seven generations; this was due to a shift in the threshold reaction norm but the lines showed no correlated response in condition. This is inconsistent with models predicting a substantial genetic correlation between condition and sexual trait expression. We discuss why dimorphic sexual traits may show more condition-independent genetic variance than continuous sexual traits.


Arthrodesis of the Metacarpophalangeal and Interphalangeal Joints of the Hand: Current Concepts.
Metacarpophalangeal arthrodesis and interphalangeal arthrodesis are excellent tools in the surgeon's armamentarium to restore function of the disabled hand. Typical indications for these procedures are pain, deformity, and/or stiffness. Arthrodesis is generally considered a salvage procedure to be used when other reconstructive procedures, such as arthroplasty, are not possible or would be associated with a high rate of complication or failure. To determine the most functional position for arthrodesis in each patient, the surgeon should preoperatively evaluate the compromised joint in the context of the disease process, determine the initial cause of the joint pathology, and assess the condition of the surrounding joints. Current methods of achieving fusion of metacarpophalangeal and interphalangeal joints include options for incisions, bone preparation techniques, and surgical implants; each has advantages and associated risks.


Diversity of bat-associated Leptospira in the Peruvian Amazon inferred by bayesian phylogenetic analysis of 16S ribosomal DNA sequences.
The role of bats as potential sources of transmission to humans or as maintenance hosts of leptospires is poorly understood. We quantified the prevalence of leptospiral colonization in bats in the Peruvian Amazon in the vicinity of Iquitos, an area of high biologic diversity. Of 589 analyzed bats, culture (3 of 589) and molecular evidence (20 of 589) of leptospiral colonization was found in the kidneys, yielding an overall colonization rate of 3.4%. Infection rates differed with habitat and location, and among different bat species. Bayesian analysis was used to infer phylogenic relationships of leptospiral 16S ribosomal DNA sequences. Tree topologies were consistent with groupings based on DNA-DNA hybridization studies. A diverse group of leptospires was found in peri-Iquitos bat populations including Leptospira interrogans (5 clones), L. kirschneri (1), L. borgpetersenii (4), L. fainei (1), and two previously undescribed leptospiral species (8). Although L. kirschenri and L. interrogans have been previously isolated from bats, this report is the first to describe L. borgpetersenii and L. fainei infection of bats. A wild animal reservoir of L. fainei has not been previously described. The detection in bats of the L. interrogans serovar Icterohemorrhagiae, a leptospire typically maintained by peridomestic rats, suggests a rodent-bat infection cycle. Bats in Iquitos maintain a genetically diverse group of leptospires. These results provide a solid basis for pursuing molecular epidemiologic studies of bat-associated Leptospira, a potentially new epidemiologic reservoir of transmission of leptospirosis to humans.


Nucleation of metastable aragonite CaCO3 in seawater.
Predicting the conditions in which a compound adopts a metastable structure when it crystallizes out of solution is an unsolved and fundamental problem in materials synthesis, and one which, if understood and harnessed, could enable the rational design of synthesis pathways toward or away from metastable structures. Crystallization of metastable phases is particularly accessible via low-temperature solution-based routes, such as chimie douce and hydrothermal synthesis, but although the chemistry of the solution plays a crucial role in governing which polymorph forms, how it does so is poorly understood. Here, we demonstrate an ab initio technique to quantify thermodynamic parameters of surfaces and bulks in equilibrium with an aqueous environment, enabling the calculation of nucleation barriers of competing polymorphs as a function of solution chemistry, thereby predicting the solution conditions governing polymorph selection. We apply this approach to resolve the long-standing "calcite-aragonite problem"--the observation that calcium carbonate precipitates as the metastable aragonite polymorph in marine environments, rather than the stable phase calcite--which is of tremendous relevance to biomineralization, carbon sequestration, paleogeochemistry, and the vulnerability of marine life to ocean acidification. We identify a direct relationship between the calcite surface energy and solution Mg:Ca [corrected] ion concentrations, showing that the calcite nucleation barrier surpasses that of metastable aragonite in solutions with Mg:Ca ratios consistent with modern seawater, allowing aragonite to dominate the kinetics of nucleation. Our ability to quantify how solution parameters distinguish between polymorphs marks an important step toward the ab initio prediction of materials synthesis pathways in solution.


Incubation of fungal cultures: how long is long enough?
Fungal cultures are traditionally incubated for 4 weeks or longer to maximise the recovery of slowly growing fungi. However, the data in support of this are scarce. The objectives of this study were to determine the optimum incubation time for specimens in which moulds or yeast are suspected and to review the literature. A total of 3036 fungal cultures of 2216 dermatological and 820 non-dermatological specimens were analysed. The day on which fungal growth was first noted, was recorded. Eleven of 820 non-dermatological specimens were positive after day 14; in 10 cases, the fungus was considered clinically non-relevant and in one case, the cerebrospinal fluid of a patient receiving therapy for cryptococcosis was positive with Cryptococcus neoformans. Fourteen and three of 2216 dermatological samples showed the growth of a dermatophyte in the third week and fourth week respectively. The results indicate that for specimens sent for the detection of yeast or moulds (except dermatophytes and systemic dimorphic fungi), an incubation period of 2 weeks is sufficient, whereas for dermatophytes, a 4-week incubation period is necessary. Based on these results and previous literature, an algorithm for the incubation time of fungal cultures is proposed.


Pattern of drug use amongst antenatal patients in Benin City, Nigeria.
Drugs taken by pregnant women could have profound effect on pregnancy outcome for both the mother and fetus. In most developing country regulation of drug is poor, access is unrestricted and abuse of drugs especially antibiotics is rampant. The study was undertaken to determine the pattern and extent of drug consumption amongst pregnant women in Benin City. A cross-sectional study of 1200 pregnant patients at various gestational ages was undertaken, using a structured questionnaire to obtain details of the extent and character of drug use before or during pregnancy. Folic acid was taken by 76.08% of all the pregnant patients, while anti-malarial drugs were taken by 19.75%; 15.83% used the drugs on doctors' prescription and 3.92% without a doctor's prescription. The proportion of the mothers that consumed native herbs was 12.08%. The use of native medication was more prevalent amongst nulliparous mothers (41.82%). Native herb consumption decreased with increase in parity. Both educated and illiterate mothers consumed herbal medications. Less than 1% of the mothers smoke cigarettes. In Benin City drug use in pregnancy is characterized by a pattern of low consumption except folic acid and native herbs. This could be a major setback for any program of drug intervention, as in chemoprophylaxis for malaria in pregnancy. Much resource will be needed for patients' education for successful implementation of any planned program in the community.


Trochoidal trajectories of self-propelled Janus particles in a diverging laser beam.
We describe colloidal Janus particles with metallic and dielectric faces that swim vigorously when illuminated by defocused optical tweezers without consuming any chemical fuel. Rather than wandering randomly, these optically-activated colloidal swimmers circulate back and forth through the beam of light, tracing out sinuous rosette patterns. We propose a model for this mode of light-activated transport that accounts for the observed behavior through a combination of self-thermophoresis and optically-induced torque. In the deterministic limit, this model yields trajectories that resemble rosette curves known as hypotrochoids.


Reduced tonic inhibition in striatal output neurons from Huntington mice due to loss of astrocytic GABA release through GAT-3.
The extracellular concentration of the two main neurotransmitters glutamate and GABA is low but not negligible which enables a number of tonic actions. The effects of ambient GABA vary in a region-, cell-type, and age-dependent manner and can serve as indicators of disease-related alterations. Here we explored the tonic inhibitory actions of GABA in Huntington's disease (HD). HD is a devastating neurodegenerative disorder caused by a mutation in the huntingtin gene. Whole cell patch clamp recordings from striatal output neurons (SONs) in slices from adult wild type mice and two mouse models of HD (Z_Q175_KI homozygotes or R6/2 heterozygotes) revealed an HD-related reduction of the GABA(A) receptor-mediated tonic chloride current (I(Tonic(GABA))) along with signs of reduced GABA(B) receptor-mediated presynaptic depression of synaptic GABA release. About half of I(Tonic(GABA)) depended on tetrodotoxin-sensitive synaptic GABA release, but the remaining current was still lower in HD. Both in WT and HD, I(Tonic(GABA)) was more prominent during the first 4 h after preparing the slices, when astrocytes but not neurons exhibited a transient depolarization. All further tests were performed within 1-4 h in vitro. Experiments with SNAP5114, a blocker of the astrocytic GABA transporter GAT-3, suggest that in WT but not HD GAT-3 operated in the releasing mode. Application of a transportable substrate for glutamate transporters (D-aspartate 0.1-1 mM) restored the non-synaptic GABA release in slices from HD mice. I(Tonic(GABA)) was also rescued by applying the hyperagonist gaboxadol (0.33 μM). The results lead to the hypothesis that lesion-induced astrocyte depolarization facilitates non-synaptic release of GABA through GAT-3. However, the capacity of depolarized astrocytes to provide GABA for tonic inhibition is strongly reduced in HD.


Prevalence of diagnosed depression in South Asian and white European people with type 1 and type 2 diabetes mellitus in a UK secondary care population.
To examine the prevalence and correlates of diagnosed depression among South Asians and white Europeans with type 1 and type 2 diabetes mellitus, attending a specialist diabetes clinic in the UK. A cross-sectional study was conducted using the hospital clinic's computerised database. Medical and demographic data were extracted for 6230 people with diabetes attending the clinic between 2003 and 2005. Multiple logistic regression was used to model ethnic differences in the probability of diagnosed depression after controlling for demographic and diabetes related factors. Analyses were conducted separately for type 1 and type 2 diabetes. The unadjusted prevalence of depression in people with type 1 and type 2 diabetes was 8.0% and 9.3%, respectively. Risk factors for depression in type 1 diabetes included female gender, diabetes related complications, and comorbidities. In people with type 2 diabetes the risk factors for depression included younger age, diabetes related complications, comorbidities, insulin use and deprivation. In addition, white Europeans were significantly more likely to be diagnosed with depression compared to South Asians (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.21 to 2.08; p<0.001). Further interaction analyses revealed no evidence that the association between ethnicity and depression differed according to any of the other factors examined in this study. The findings add to the limited body of knowledge regarding ethnic differences in depression and diabetes. Among those with type 2 diabetes, white Europeans had nearly 60% higher adjusted odds of diagnosed depression compared to South Asians. Disparities may be due to differences in presentation or identification of depression between these two ethnic groups.


Safety of Medical Abortion Provided Through Telemedicine Compared With In Person.
To compare the proportion of medical abortions with a clinically significant adverse event among telemedicine and in-person patients at a clinic system in Iowa during the first 7 years of the service. We conducted a retrospective cohort study. We analyzed data on clinically significant adverse events (hospital admission, surgery, blood transfusion, emergency department treatment, and death) for all medical abortions performed by telemedicine or in person at a clinic system in Iowa between July 1, 2008, and June 30, 2015. Data on adverse events came from required reporting forms submitted to the mifepristone distributor. We calculated the prevalence of adverse events and 95% CIs comparing telemedicine with in-person patients. The analysis was designed as a noninferiority study. Assuming the prevalence of adverse events to be 0.3%, telemedicine provision was considered to be inferior to in-person provision if the prevalence were 0.6% or higher. The required sample size was 6,984 in each group (one-sided α=0.025, power 90%). To explore whether patients with adverse events presented to emergency departments and were not reported, we conducted a survey of the 119 emergency departments in Iowa, asking whether they had treated a woman with an adverse event in the prior year. During the study period, 8,765 telemedicine and 10,405 in-person medical abortions were performed. Forty-nine clinically significant adverse events were reported (no deaths or surgery; 0.18% of telemedicine patients with any adverse event [95% CI 0.11-0.29%] and 0.32% of in-person patients [95% CI 0.23-0.45%]). The difference in adverse event prevalence was 0.13% (95% CI -0.01% to 0.28%, P=.07). Forty-two emergency departments responded to the survey (35% response rate); none reported treating a woman with an adverse event after medical abortion. Adverse events are rare with medical abortion, and telemedicine provision is noninferior to in-person provision with regard to clinically significant adverse events.


Three episodes of non-arteritic posterior ischemic optic neuropathy in the same patient treated with intravenous prostaglandin E1.
Non-arteritic posterior ischemic optic neuropathy (NA-PION) is a disorder involving reduced blood flow to the retrobulbar portion of the optic nerve. This disorder usually develops acutely, and research has suggested that high-dose steroid therapy soon after the onset of visual loss can result in significant visual improvement. This treatment, however, is not universally successful. The addition of a potent vasodilator could help to restore ocular blood flow. This case report describes the use of prostaglandin E1 (PGE1), a powerful vasodilator of the microcirculation, to treat three separate episodes of NA-PION over five years in the same patient. A 68-year-old white male was first seen in June 2009 with NA-PION in the left eye, and the condition was treated with steroids and PGE1. The patient had a subsequent episode in July 2010 that was treated with steroids and PGE1 and another in May 2014 that was treated with PGE1 alone. Visual acuity improved from 4/10 to 11/10 in 2009, from 4/10 to 11/10 in 2010, and from 5/10 to 10/10 in 2014. No complications due to the use of PGE1 were noted. PGE1 should be considered as a treatment for NA-PION to immediately restore blood flow and potentially improve vision.


Reliability and Validity of the Revised Transfer Assessment Instrument.
Background: Proper transfer technique is associated with improved biomechanics and decreased pain and pathology. However, many users do not use proper technique, and appropriate assessment and training are needed to address these deficits. The transfer assessment instrument (TAI) 4.0 was designed to meet those needs and improve on past versions by removing the need for clinician training, shortening administration time, and simplifying question content. Objectives: Evaluate the psychometric properties of the TAI 4.0. Methods: A convenience sample of full-time wheelchair users was scored on multiple transfers by four raters to assess interrater, intrarater, and test-retest reliability and concurrent validity of the TAI 4.0. Each user also was scored using a visual analog scale (VAS). Results: For 44 participants, the mean TAI 4.0 and VAS across all transfers were 7.58 ± 1.12 and 7.44 ± 1.78, respectively, and scores were significantly correlated (r = 0.52-0.7). VAS scores were more strongly influenced by the flight/landing and body setup phases of the transfer. There were no significant associations between TAI 4.0 score and demographics. Intraclass correlation coefficients (ICC) ranged from 0.80 to 0.85 for interrater reliability, 0.60 to 0.76 for intrarater reliability, and 0.55 to 0.76 for test-retest reliability. The minimum detectable change (MDC) for the total score ranged from 1.02 to 1.30. Conclusion: The TAI 4.0 provides reliable and valid quantitative assessment of an individual's transfer without the need for comprehensive training, as is the case with the TAI 3.0. The tool can be completed in 3 minutes (average) in a clinical setting with only a ruler and goniometer.


Down syndrome in diverse populations.
Down syndrome is the most common cause of cognitive impairment and presents clinically with universally recognizable signs and symptoms. In this study, we focus on exam findings and digital facial analysis technology in individuals with Down syndrome in diverse populations. Photos and clinical information were collected on 65 individuals from 13 countries, 56.9% were male and the average age was 6.6 years (range 1 month to 26 years; SD = 6.6 years). Subjective findings showed that clinical features were different across ethnicities (Africans, Asians, and Latin Americans), including brachycephaly, ear anomalies, clinodactyly, sandal gap, and abundant neck skin, which were all significantly less frequent in Africans (P < 0.001, P < 0.001, P < 0.001, P < 0.05, and P < 0.05, respectively). Evaluation using a digital facial analysis technology of a larger diverse cohort of newborns to adults (n = 129 cases; n = 132 controls) was able to diagnose Down syndrome with a sensitivity of 0.961, specificity of 0.924, and accuracy of 0.943. Only the angles at medial canthus and ala of the nose were common significant findings amongst different ethnicities (Caucasians, Africans, and Asians) when compared to ethnically matched controls. The Asian group had the least number of significant digital facial biometrics at 4, compared to Caucasians at 8 and Africans at 7. In conclusion, this study displays the wide variety of findings across different geographic populations in Down syndrome and demonstrates the accuracy and promise of digital facial analysis technology in the diagnosis of Down syndrome internationally. © 2016 Wiley Periodicals, Inc.


Review of childhood pain highlights the role of negative stress.
Recurrent pain of unknown origin is a major problem in children. The aim of the present review was to examine the hypothesis of negative stress as an aetiology of recurrent pain from different aspects. Epidemiological studies, clinical experience and hormonal data give support for such a hypothesis. Negative stress as a tentative aetiology for recurrent pain is reviewed. Stress, muscular tension, the startle reaction and its tentative relation to pain is illuminated. Deviations of hormonal secretion supporting a stress aetiology are mentioned. The role of central sensitisation for recurrent pain is discussed. Possible aetiological implications of recurrent pain as a local symptom or a general disorder are presented. Brain changes due to stress are shortly reviewed. Stress and pain in the clinic are highlighted. The importance of biological, psychological and social factors, as well as genetic elements, is discussed. Stress elicits neurobiological mechanisms. They may lead to many neurophysiological deviances. Increase of muscle tension and neuromuscular excitability and enhanced startle reaction may be of importance for recurring pain. The identification of stress as a primary cause of recurrent pain can have huge implications for understanding signs and treatment in clinical practice.


Social influences on unconscious plagiarism and anti-plagiarism.
People are more likely to unconsciously plagiarise ideas from a same-sex partner than a different-sex partner, and more likely to unconsciously plagiarise if recalling alone rather than in the presence of their partner [Macrae, C. N., Bodenhausen, G. V., & Calvini, G. (1999). Contexts of cryptomnesia: May the source be with you. Social Cognition, 17, 273-297. doi: 10.1521/soco.19126.96.36.1993 ]. Two sets of experiments explore these phenomena, using extensions of the standard unconscious plagiarism paradigm. In Experiment 1A participants worked together in same- or different-sex dyads before trying to recall their own ideas or their partner's ideas. More source errors were evident for same-sex dyads (Experiment 1A), but this effect was absent when participants recalled from both sources simultaneously (Experiment 1B). In Experiment 2A, participants recalled ideas from a single source either alone or in the presence of the partner, using an extended-recall task. Partner presence did not affect the availability of ideas, but did reduce the propensity to report them as task compliant, relative to a partner-present condition. Simultaneous recall from both sources removed this social effect (Experiment 2B). Thus social influences on unconscious plagiarism are apparent, but are influenced by the salience of the alternate source at retrieval.


Chromosomal inversions associated with environmental adaptation in honeybees.
Chromosomal inversions can facilitate local adaptation in the presence of gene flow by suppressing recombination between well-adapted native haplotypes and poorly adapted migrant haplotypes. East African mountain populations of the honeybee Apis mellifera are highly divergent from neighbouring lowland populations at two extended regions in the genome, despite high similarity in the rest of the genome, suggesting that these genomic regions harbour inversions governing local adaptation. Here, we utilize a new highly contiguous assembly of the honeybee genome to characterize these regions. Using whole-genome sequencing data from 55 highland and lowland bees, we find that the highland haplotypes at both regions are present at high frequencies in three independent highland populations but extremely rare elsewhere. The boundaries of both divergent regions are characterized by regions of high homology with each other positioned in opposite orientations and contain highly repetitive, long inverted repeats with homology to transposable elements. These regions are likely to represent inversion breakpoints that participate in nonallelic homologous recombination. Using long-read data, we confirm that the lowland samples are contiguous across breakpoint regions. We do not find evidence for disruption of functional sequence by these breakpoints, which suggests that the inversions are likely maintained due to their allelic content conferring local adaptation in highland environments. Finally, we identify a third divergent genomic region, which contains highly divergent segregating haplotypes that also may contain inversion variants under selection. The results add to a growing body of evidence indicating the importance of chromosomal inversions in local adaptation.


Nitric oxide derived from L-arginine impairs cytoplasmic pH regulation by vacuolar-type H+ ATPases in peritoneal macrophages.
The ability of macrophages (Møs) to function within an acidic environment has been shown to depend on cytoplasmic pH (pHi) regulation by vacuolar-type H+ ATPases. Møs metabolize L-arginine via an oxidative pathway that generates nitric oxide, nitrate, and nitrite. Since each of these products could potentially inhibit vacuolar-type H+ ATPases, we investigated the effect of L-arginine metabolism on Mø pHi regulation in thioglycolate-elicited murine peritoneal Møs. H+ ATPase-mediated pHi recovery from an imposed cytoplasmic acid load was measured fluorometrically. When Møs were incubated with L-arginine (0.25-2.0 mM), their rate of pHi recovery declined progressively from 2 to 6 h of incubation. By contrast, the recovery rate of cells incubated in arginine-free medium remained stable over the same period. The impairment of pHi recovery was specific for L-arginine, and was blocked competitively by NG-monomethyl-L-arginine, demonstrating its dependence on L-arginine metabolism. In addition, the inhibition of pHi recovery was enhanced by lipopolysaccharide, an agent known to stimulate L-arginine metabolism by Møs. Scavenging the L-arginine metabolite nitric oxide with either ferrous sulphate or ferrous myoglobin prevented the inhibition of pHi recovery, implying that L-arginine-derived nitric oxide was the species responsible for the inhibition. This concept was supported by the finding of elevated nitrite levels in the supernatant of cells incubated in L-arginine. Furthermore, incubation of Møs with sodium nitroprusside mimicked the L-arginine-dependent inhibition of H+ ATPase activity. Treatment with the cyclic GMP analogue, 8-bromoguanosine 3':5'-cyclic monophosphate, similarly impaired Mø pHi recovery, suggesting that a nitric oxide-stimulated elevation of cyclic GMP may contribute to the L-arginine-dependent inhibition of pHi regulation.


The clinical spectrum of gouty arthritis in women.
We reviewed crystal-proved gouty arthritis in 23 women. Twenty-one (91%) developed gout after menopause onset. Tophaceous gout occurred in six (26%), polyarticular involvement in 13 (57%); 70% manifested an underlying arthropathy, usually osteoarthritis. We studied 75 men with crystal-proved gout for comparison. Women developed gout significantly later compared with men, more often were receiving diuretics before gout onset, and more frequently manifested renal insufficiency and monoarticular involvement. These differences were significant when controlled for the women's later age at onset. Significantly more men than women had alcoholism and an identifiable precipitating event for acute attacks. There were no significant differences in race, age, family history of gout, disease duration, hypertension, distribution of joint involvement, tophi, or mean serum urate concentration. Gout in women is overwhelmingly postmenopausal, apparently associated with diuretic therapy and renal insufficiency independent of the effects of age. Articular characteristics in men and women are remarkably similar.


A novel diagnosis scoring model to predict invasive pulmonary aspergillosis in the intensive care unit.
To improve the quality of invasive pulmonary aspergillosis (IPA) management for intensive care unit (ICU) patients using a practical diagnostic scoring model. This nested case-control study aimed to determine the incidence of IPA in 405 ICU patients, between July 2012 and June 2014, at 6 hospitals in Jakarta, Indonesia. Phenotypic identifications and galactomannan (GM) tests of sera and lung excreta were performed in mycology laboratory, Parasitology Department, Faculty of Medicine, Universitas Indonesia in Jakarta, Indonesia. The incidence of IPA in the ICUs was 7.7% (31 of 405 patients). A scoring model used for IPA diagnosis showed 4 variables as the most potential risk factors: lung excreta GM index (score 2), solid organ malignancy (score 2), pulmonary tuberculosis (score 2), and systemic corticosteroids (score 1). Patients were included in a high-risk group if their score was greater than 2, and in a low-risk group if their score was less than 2. This study provides a novel diagnosis scoring model to predict IPA in ICU patients. Using this model, a more rapid diagnosis and treatment of IPA may be possible. The application of the diagnosis scoring should be preceded by specified pre-requisites.


Influence of Nitrosative Stress on Fatigue During Childhood Leukemia Treatment.
The focus on a cure for childhood leukemia over the last three decades has resulted in survival rates of more than 80%. However, efforts to manage leukemia-treatment symptoms have not kept pace with new therapies. Symptom toxicity during treatment can result in complications, treatment delays, and therapy dose reductions. Compromise in therapy can negatively influence the quality of life and, even more notably, jeopardize chances for long-term survival. This study examined biologic mechanisms that influence fatigue caused by increased reactive oxidative species (ROS) or actual failure of the antioxidant defense system due to genetic variation by investigating reactive nitrosative species, a "downstream" consequence of ROS. The specific aims of this study were to characterize the trajectory of nitrosative stress during acute lymphoblastic leukemia treatment and evaluate the influence of nitrosative stress on fatigue. A repeated measures design was used to evaluate the fatigue experienced by 186 children and adolescents, 3-18 years of age, with a diagnosis of leukemia during the most intense phase of treatment. An established biomarker of nitrosative stress, protein 3-nitrotyrosine (3NT) residues in the cerebral spinal fluid, was evaluated at diagnosis, postinduction, and consolidation phases of treatment. Higher fatigue was associated with higher 3NT levels at the beginning of treatment. Two distinct groups of children experienced either consistently high or consistently low 3NT levels across the treatment trajectory, from diagnosis to 12 months postinduction. Findings from this study support continued exploration into the phenotypic biochemical mechanisms that influence a reactive response to childhood cancer treatment.


Capsaicin: a novel radio-sensitizing agent for prostate cancer.
Radio-sensitizing agents sensitize tumor cells to the lethal effects of radiotherapy (RT) allowing for use of lower doses of radiation to achieve equivalent cancer control, while minimizing adverse effects to normal tissues. Given their limited toxicity and ability to easily integrate into the diet, compounds occurring naturally in the diet make ideal potential radio-sensitizing agents. In this study, we have examined whether capsaicin, the active compound in chilli peppers, can modulate the response to RT in preclinical models of prostate cancer (PCa). The effects of RT (1-8 Gy) and/or capsaicin (1-10 µM) on colony formation rates in human PCa cells were assessed using clonogenic assays. Mechanistic studies were performed by Western Blot, immunocytochemistry, and flow cytometry. Athymic mice (n = 40) were inoculated with human LNCaP cells. Once tumors reached 100 mm(3) , animals were randomized into four groups: control, capsaicin alone (5 mg/kg/d), RT alone (6 Gy), and capsaicin and RT. Capsaicin reduced colony formation rates and radio-sensitized human PCa cells (Sensitizer enhancement ratio = 1.3) which corresponded to the suppression of NFκB, independent of TRP-V1 receptor. Cell cycle modulation occurred following RT and capsaicin treatment independently. In vivo, oral administration of capsaicin with RT resulted in a 'greater than additive' growth delay and reduction in the tumor growth rate greater than capsaicin (P < 0.001) or RT (P < 0.03) alone. Immunohistochemical analysis revealed a reduction in proliferation and NFκB expression, and increase in DNA damage. Our findings suggest that capsaicin acts as a radio-sensitzing agent for PCa through the inhibition of NFκB signalling.


Effect of speaker gaze on word learning in fragile X syndrome: a comparison with nonsyndromic autism spectrum disorder.
This study examined use of a speaker's direction of gaze during word learning by boys with fragile X syndrome (FXS), boys with nonsyndromic autism spectrum disorder (ASD), and typically developing (TD) boys. A fast-mapping task with follow-in and discrepant labeling conditions was administered. We expected that the use of speaker gaze would lead to participants selecting as the referent of the novel label the object to which they attended in follow-in trials and the object to which the examiner attended in the discrepant labeling trials. Participants were school-aged boys with FXS (n=18) or ASD (n=18) matched on age, intelligence quotient, and nonverbal cognition and younger TD boys (n=18) matched on nonverbal cognition. All groups performed above chance in both conditions, although the TD boys performed closest to the expected pattern. Boys with FXS performed better during follow-in than in discrepant label trials, whereas TD boys and boys with ASD did equally well in both trial types. The type of trial administered first influenced subsequent responding. Error patterns also distinguished the groups. The ability to utilize a speaker's gaze during word learning is not as well developed in boys with FXS or nonsyndromic ASD as in TD boys of the same developmental level.


Locomotor characteristics of the women's inaugural super league competition and the rugby league world cup.
Understanding the locomotor characteristics of competition can help rugby league (RL) coaches optimise training prescription. To date, no research exists on the locomotor characteristics of women's RL. The aim was to compare whole match and peak locomotor characteristics of women's RL competition at international (RL World Cup [WRLWC]) and domestic level (Super League [WSL]). Microtechnology data were collected from 58 players from 3-WSL clubs and 1-WRLWC team. Participants were classified into forwards (n = 30) and backs (n = 28). Partial least squares correlation analysis established which variables were important to discriminate between the level of competition (international vs. domestic) and positional group (forwards vs. backs). Linear mixed-effects models estimated the differences between standards of competition and positional group for those variables. International forwards were most likely exposed to greater peak 1-min average acceleration (standardised mean difference = 1.23 [0.42 to 2.04]) and peak 3-min average acceleration (1.13 [0.41 to 1.85]) than domestic forwards. International backs likely completed greater peak 1-min average acceleration (0.83 [0.08 to 1.58]) than domestic backs and possibly greater high-speed-distances (0.45 [-0.17 to 1.07]). Findings highlight the need for positional specific training across levels to prepare representative players for the increased match characteristics of international competition.


'Mediterranean' dietary pattern for the primary prevention of cardiovascular disease.
The Seven Countries study in the 1960s showed that populations in the Mediterranean region experienced lower cardiovascular disease (CVD) mortality probably as a result of different dietary patterns. Later observational studies have confirmed the benefits of adherence to a Mediterranean dietary pattern on CVD risk factors. Clinical trial evidence is limited, and is mostly in secondary prevention. To determine the effectiveness of a Mediterranean dietary pattern for the primary prevention of CVD. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 9 of 12, September 2012); MEDLINE (Ovid, 1946 to October week 1 2012); EMBASE (Ovid, 1980 to 2012 week 41); ISI Web of Science (1970 to 16 October 2012); Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database and Health Economics Evaluations Database (Issue 3 of 12, September 2012). We searched trial registers and reference lists of reviews and applied no language restrictions. We selected randomised controlled trials in healthy adults and adults at high risk of CVD. A Mediterranean dietary pattern was defined as comprising at least two of the following components: (1) high monounsaturated/saturated fat ratio, (2) low to moderate red wine consumption, (3) high consumption of legumes, (4) high consumption of grains and cereals, (5) high consumption of fruits and vegetables, (6) low consumption of meat and meat products and increased consumption of fish, and (7) moderate consumption of milk and dairy products. The comparison group received either no intervention or minimal intervention. Outcomes included clinical events and CVD risk factors. Two review authors independently extracted data and contacted chief investigators to request additional relevant information. We included 11 trials (15 papers) (52,044 participants randomised). Trials were heterogeneous in the participants recruited, in the number of dietary components and follow-up periods. Seven trials described the intervention as a Mediterranean diet. Clinical events were reported in only one trial (Women's Health Initiative 48,835 postmenopausal women, intervention not described as a Mediterranean diet but increased fruit and vegetable and cereal intake) where no statistically significant effects of the intervention were seen on fatal and non-fatal endpoints at eight years. Small reductions in total cholesterol (-0.16 mmol/L, 95% confidence interval (CI) -0.26 to -0.06; random-effects model) and low-density lipoprotein (LDL) cholesterol (-0.07 mmol/L, 95% CI -0.13 to -0.01) were seen with the intervention. Subgroup analyses revealed statistically significant greater reductions in total cholesterol in those trials describing the intervention as a Mediterranean diet (-0.23 mmol/L, 95% CI -0.27 to -0.2) compared with control (-0.06 mmol/L, 95% CI -0.13 to 0.01). Heterogeneity precluded meta-analyses for other outcomes. Reductions in blood pressure were seen in three of five trials reporting this outcome. None of the trials reported adverse events. The limited evidence to date suggests some favourable effects on cardiovascular risk factors. More comprehensive interventions describing themselves as the Mediterranean diet may produce more beneficial effects on lipid levels than those interventions with fewer dietary components. More trials are needed to examine the impact of heterogeneity of both participants and the intervention on outcomes.


Structural and functional characterization of plant aminoaldehyde dehydrogenase from Pisum sativum with a broad specificity for natural and synthetic aminoaldehydes.
Aminoaldehyde dehydrogenases (AMADHs, EC 184.108.40.206) belong to the large aldehyde dehydrogenase (ALDH) superfamily, namely, the ALDH9 family. They oxidize polyamine-derived omega-aminoaldehydes to the corresponding omega-amino acids. Here, we report the first X-ray structures of plant AMADHs: two isoenzymes, PsAMADH1 and PsAMADH2, from Pisum sativum in complex with beta-nicotinamide adenine dinucleotide (NAD(+)) at 2.4 and 2.15 A resolution, respectively. Both recombinant proteins are dimeric and, similarly to other ALDHs, each monomer is composed of an oligomerization domain, a coenzyme binding domain and a catalytic domain. Each subunit binds NAD(+) as a coenzyme, contains a solvent-accessible C-terminal peroxisomal targeting signal (type 1) and a cation bound in the cavity close to the NAD(+) binding site. While the NAD(+) binding mode is classical for PsAMADH2, that for PsAMADH1 is unusual among ALDHs. A glycerol molecule occupies the substrate binding site and mimics a bound substrate. Structural analysis and substrate specificity study of both isoenzymes in combination with data published previously on other ALDH9 family members show that the established categorization of such enzymes into distinct groups based on substrate specificity is no more appropriate, because many of them seem capable of oxidizing a large spectrum of aminoaldehyde substrates. PsAMADH1 and PsAMADH2 can oxidize N,N,N-trimethyl-4-aminobutyraldehyde into gamma-butyrobetaine, which is the carnitine precursor in animal cells. This activity highly suggests that in addition to their contribution to the formation of compatible osmolytes such as glycine betaine, beta-alanine betaine and gamma-aminobutyric acid, AMADHs might participate in carnitine biosynthesis in plants.


High-performance gas sensors based on a thiocyanate ion-doped organometal halide perovskite.
Thin films of a thiocyanate ion (SCN-)-doped organometal halide perovskite, CH3NH3PbI3-x(SCN)x, were used as a sensing material for developing high-performance gas sensors. The CH3NH3PbI3-x(SCN)x-based chemiresistor-type sensor can sensitively and selectively detect acetone and nitrogen dioxide (NO2) at room temperature with high sensitivities of 5.6 × 10-3 and 5.3 × 10-1 ppm-1. The limits of detection for acetone and NO2 were measured to be 20 ppm and 200 ppb. This sensor also exhibited excellent repeatability, and its environmental stability was greatly improved by doping the perovskite with SCN- ions.


Identification of vanadium dopant sites in the metal-organic framework DUT-5(Al).
Studying the structural environment of the VIV ions doped in the metal-organic framework (MOF) DUT-5(Al) ((AlIIIOH)BPDC) with electron paramagnetic resonance (EPR) reveals four different vanadium-related spectral components. The spin-Hamiltonian parameters are derived by analysis of X-, Q- and W-band powder EPR spectra. Complementary Q-band Electron Nuclear DOuble Resonance (ENDOR) experiments, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray spectroscopy (EDX), X-Ray Diffraction (XRD) and Fourier Transform InfraRed (FTIR) measurements are performed to investigate the origin of these spectral components. Two spectral components with well resolved 51V hyperfine structure are visible, one corresponding to VIV[double bond, length as m-dash]O substitution in a large (or open) pore and one to a narrow (or closed) pore variant of this MOF. Furthermore, a broad structureless Lorentzian line assigned to interacting vanadyl centers in each other's close neighborhood grows with increasing V-concentration. The last spectral component is best visible at low V-concentrations. We tentatively attribute it to (VIV[double bond, length as m-dash]O)2+ linked with DMF or dimethylamine in the pores of the MOF. Simulations using these four spectral components convincingly reproduce the experimental spectra and allow to estimate the contribution of each vanadyl species as a function of V-concentration.


Magnetic resonance imaging for in vivo assessment of three-dimensional patellar tracking.
We have developed a non-invasive measurement technique which can ultimately be used to quantify three-dimensional patellar kinematics of human subjects for a range of static positions of loaded flexion and assessed its accuracy. Knee models obtained by segmenting and reconstructing one high-resolution scan of the knee were registered to bone outlines obtained by segmenting fast, low-resolution scans of the knee in static loaded flexion. We compared patellar tracking measurements made using the new method to measurements made using Roentgen stereophotogrammetric analysis in three cadaver knee specimens loaded through a range of flexion in a test rig. The error in patellar spin and tilt measurements was less than 1.02 degrees and the error in lateral patellar shift was 0.88 mm. Sagittal plane scans provided more accurate final measurements of patellar spin and tilt, whereas axial plane scans provided more accurate measurements of lateral translation and patellar flexion. Halving the number of slices did not increase measurement error significantly, which suggests that scan times can be reduced without reducing accuracy significantly. The method is particularly useful for multiple measurements on the same subject because the high-resolution bone-models need only be created once; thus, the potential variability in coordinate axes assignment and model segmentation during subsequent measurements is removed.


Design, Synthesis, and Antimicrobial Evaluation of a Novel Bone-Targeting Bisphosphonate-Ciprofloxacin Conjugate for the Treatment of Osteomyelitis Biofilms.
Osteomyelitis is a major problem worldwide and is devastating due to the potential for limb-threatening sequelae and mortality. Osteomyelitis pathogens are bone-attached biofilms, making antibiotic delivery challenging. Here we describe a novel osteoadsorptive bisphosphonate-ciprofloxacin conjugate (BV600022), utilizing a "target and release" chemical strategy, which demonstrated a significantly enhanced therapeutic index versus ciprofloxacin for the treatment of osteomyelitis in vivo. In vitro antimicrobial susceptibility testing of the conjugate against common osteomyelitis pathogens revealed an effective bactericidal profile and sustained release of the parent antibiotic over time. Efficacy and safety were demonstrated in an animal model of periprosthetic osteomyelitis, where a single dose of 10 mg/kg (15.6 μmol/kg) conjugate reduced the bacterial load by 99% and demonstrated nearly an order of magnitude greater activity than the parent antibiotic ciprofloxacin (30 mg/kg, 90.6 μmol/kg) given in multiple doses. Conjugates incorporating a bisphosphonate and an antibiotic for bone-targeted delivery to treat osteomyelitis biofilm pathogens constitute a promising approach to providing high bone-antimicrobial potency while minimizing systemic exposure.


Comparison of insulin sensitivity tests across a range of glucose tolerance from normal to diabetes.
Adequate comparison of the relative performance of insulin sensitivity tests is not yet available. We compared the discrimination of four insulin sensitivity tests, commonly used in vivo, across a range of glucose tolerance. Normal (n = 7), impaired glucose tolerant (n = 8) and Type II (non-insulin-dependent) diabetic subjects (n = 9) had in random order two tests from the following: frequently sampled insulin-modified intravenous glucose tolerance test (FSIVGTT-MinMod); homeostasis model assessment (HOMA) and 2-h continuous infusion of glucose with model assessment (CIGMA) with immunoreactive or specific insulin; short insulin tolerance tests (ITT). The discriminatory power of tests was assessed by the ratio of the within-subject standard deviation to the underlying between-subject standard deviation (discriminant ratio - DR). The degree to which tests measured the same variable was assessed by comparing rank correlation with the maximum expected correlation given the imprecision of the tests. The unbiased lines of equivalence taking into account the precision of tests were constructed. Reciprocal fasting plasma insulin (FPI(-1)), HOMA %S and 2-h CIGMA %S, had similar DRs with ITT being less informative. The FSIVGTT-MinMod analysis was able to assess 13 out of 24 subjects and had a performance similar to ITT. Using specific rather than immunoreactive insulin for HOMA-CIGMA did not improve the DR. Reciprocal fasting plasma insulin FPI(-1), HOMA %S, 2-h CIGMA %S and S(I) FSIVGTT intercorrelated more than 90% of the expected rank correlation given the imprecision of the tests, but ITT gave only limited correlation. The HOMA-CIGMA test with immunoreactive insulin provides similar information in distinguishing insulin sensitivity between subjects with normal glucose tolerance, those with impaired glucose tolerance and those with Type II diabetes as does FSIVGTT, whereas ITT is less informative.


Differential activation and functional specialization of miR-146 and miR-155 in innate immune sensing.
Many microRNAs (miRNAs) are co-regulated during the same physiological process but the underlying cellular logic is often little understood. The conserved, immunomodulatory miRNAs miR-146 and miR-155, for instance, are co-induced in many cell types in response to microbial lipopolysaccharide (LPS) to feedback-repress LPS signalling through Toll-like receptor TLR4. Here, we report that these seemingly co-induced regulatory RNAs dramatically differ in their induction behaviour under various stimuli strengths and act non-redundantly through functional specialization; although miR-146 expression saturates at sub-inflammatory doses of LPS that do not trigger the messengers of inflammation markers, miR-155 remains tightly associated with the pro-inflammatory transcriptional programmes. Consequently, we found that both miRNAs control distinct mRNA target profiles; although miR-146 targets the messengers of LPS signal transduction components and thus downregulates cellular LPS sensitivity, miR-155 targets the mRNAs of genes pervasively involved in pro-inflammatory transcriptional programmes. Thus, miR-155 acts as a broad limiter of pro-inflammatory gene expression once the miR-146 dependent barrier to LPS triggered inflammation has been breached. Importantly, we also report alternative miR-155 activation by the sensing of bacterial peptidoglycan through cytoplasmic NOD-like receptor, NOD2. We predict that dose-dependent responses to environmental stimuli may involve functional specialization of seemingly co-induced miRNAs in other cellular circuitries as well.


Enhancing Physician's Toolkit: Integrating Storytelling in Medical Practice.
Traditional communication of medical literature using evidence-based terminologies are inadequate as the body of COVID-19 literature increases thereby requiring alternate methods of communication like podcasts, webinars, social media. A common theme in all these alternate forms of communication is the art of storytelling that allows physicians to make a connection with a patient by understanding their perspectives. Apart from few situations where story telling can be distracting in many situations where the patient's history is complex and require great listening skills and empathy.. Learning to be a good storyteller can help the physician help patients be a great change agent for them. Communicating with these patients can be done effectively using standard communication tools and using effective storytelling techniques can reinforce the patients trust in the provider and strengthen patient physician relationship. This could have a salutatory result both for the patient by increasing patient satisfaction and compliance with treatment and physician satisfaction by increasing to understand their patient's true concerns.


Loneliness and Life Satisfaction Explained by Public-Space Use and Mobility Patterns.
Previous research has shown that personal, neighborhood, and mobility characteristics could influence life satisfaction and loneliness of people and that exposure to public spaces, such as green spaces, may also affect the extent to which people feel lonely or satisfied with life. However, previous studies mainly focused on one of these effects, resulting in a lack of knowledge about the simultaneous effects of these characteristics on loneliness and life satisfaction. This study therefore aims to gain insights into how public-space use mediates the relations between personal, neighborhood, and mobility characteristics on the one hand and loneliness and life satisfaction on the other hand. Relationships were analyzed using a path analysis approach, based on a sample of 200 residents of three neighborhoods of the Dutch city 's-Hertogenbosch. The results showed that the influence of frequency of public-space use on life satisfaction and loneliness is limited. The effects of personal, neighborhood, and mobility characteristics on frequency of use of public space and on loneliness and life satisfaction were found to be significant. Age and activities of daily living (ADL) are significantly related to each other, and ADL was found to influence recreational and passive space use and loneliness and life satisfaction. Policymakers should, therefore, mainly focus on creating neighborhoods that are highly walkable and accessible, where green spaces and public-transport facilities are present, to promote physical activity among all residents.


Cohen's Conservatism and Human Enhancement.
In an intriguing essay, G. A. Cohen has defended a conservative bias in favour of existing value. In this paper, we consider whether Cohen's conservatism raises a new challenge to the use of human enhancement technologies. We develop some of Cohen's suggestive remarks into a new line of argument against human enhancement that, we believe, is in several ways superior to existing objections. However, we shall argue that on closer inspection, Cohen's conservatism fails to offer grounds for a strong sweeping objection to enhancement, and may even offer positive support for forms of enhancement that preserve valuable features of human beings. Nevertheless, we concede that Cohen's arguments may suggest some plausible and important constraints on the modality of legitimate and desirable enhancements.


Increase in diazepam binding inhibitor-like immunoreactivity (51-70) in Huntington's disease.
In Huntington's disease (HD), reduction in striatal GABA is one of the most striking abnormalities and alterations in benzodiazepine receptors, which are allosterically linked to the GABAA receptor, have also been reported. Diazepam binding inhibitor (DBI), recently isolated from rat and human brain, has been proposed as an endogenous ligand at the benzodiazepine receptor. The content of DBI-like immunoreactivity(51-70) (DBI-IR(51-70), has therefore been compared in control postmortem human brains and in HD brains (matched for age, sex and post-mortem delay), using a specific radioimmunoassay. DBI-IR(51-70) was more than 1.5-fold increased in the putamen, caudate, globus pallidus and nucleus accumbens of HD brains compared to the control group (P less than 0.001). Gel filtration chromatography showed similar elution profiles of the peptide in both control and HD extracts, thus providing no evidence for a change in the nature of the peptide itself.


'Calibrating to scale: a framework for humanitarian health organizations to anticipate, prevent, prepare for and manage climate-related health risks'.
Climate Change is adversely affecting health by increasing human vulnerability and exposure to climate-related stresses. Climate change impacts human health both directly and indirectly, through extreme weather events, changing distribution of health risks, increased risks of undernutrition, population displacement, and greater risks of injuries, disease, and death (Ebi, K., Campbell-Lendrum, D., & Wyns, A. The 1. 5 health report. WHO. 2018). This risk amplification is likely to increase the need for humanitarian support. Recent projections indicate that under a business as usual scenario of sustained greenhouse gas emissions, climate change could double the demand for humanitarian assistance by 2050 (World Health Organization. Operational Framework for building climateresilient health systems. WHO. 2015). Humanitarian assistance is currently not meeting the existing needs, therefore, any additional burden is likely to be highly challenging.Global health advocates, researchers, and policymakers are calling for urgent action on climate change, yet there is little clarity on what that action practically entails for humanitarian organizations. While some humanitarian organizations may consider themselves well designed to respond, climate change as a transversal threat requires the incorporation of a resilience approach to humanitarian action and policy responses.By bringing together authors from two historically disparate fields - climate change and health, and humanitarian assistance - this paper aims to increase the capacity of humanitarian organizations to protect health in an unstable climate by presenting an adapted framework. We adapted the WHO operational framework for climate-resilient health systems for humanitarian organizations and present concrete case studies to demonstrate how the framework can be implemented. Rather than suggest a re-design of humanitarian operations we recommend the application of a climate-lens to humanitarian activities, or what is also referred to as mainstreaming climate and health concerns into policies and programs. The framework serves as a starting point to encourage further dialogue, and to strengthen collaboration within, between, and beyond humanitarian organizations.


Myeloid Tribbles 1 induces early atherosclerosis via enhanced foam cell expansion.
Macrophages drive atherosclerotic plaque progression and rupture; hence, attenuating their atherosclerosis-inducing properties holds promise for reducing coronary heart disease (CHD). Recent studies in mouse models have demonstrated that Tribbles 1 (Trib1) regulates macrophage phenotype and shows that Trib1 deficiency increases plasma cholesterol and triglyceride levels, suggesting that reduced TRIB1 expression mediates the strong genetic association between the TRIB1 locus and increased CHD risk in man. However, we report here that myeloid-specific Trib1 (mTrib1) deficiency reduces early atheroma formation and that mTrib1 transgene expression increases atherogenesis. Mechanistically, mTrib1 increased macrophage lipid accumulation and the expression of a critical receptor (OLR1), promoting oxidized low-density lipoprotein uptake and the formation of lipid-laden foam cells. As TRIB1 and OLR1 RNA levels were also strongly correlated in human macrophages, we suggest that a conserved, TRIB1-mediated mechanism drives foam cell formation in atherosclerotic plaque and that inhibiting mTRIB1 could be used therapeutically to reduce CHD.


Mixed Model Analysis of Between-Subject Variability in Overnight Corneal Swelling and Deswelling With Silicone Hydrogel Lenses.
To model between subject variability of corneal swelling (CS) and deswelling after overnight wear of silicone hydrogel (SiHy) contact lenses. A total of 29 neophyte subjects wore 12 SiHy lenses with central transmissibility range of 31 to 211 Dk/t units on separate nights, in random order, and on one eye only. The contralateral eye served as the control. Central corneal thickness was measured using digital optical pachymetry before lens insertion, immediately after lens removal on waking, then 20, 40 minutes, 1, 2, and 3 hours later. Mixed modelling was conducted for simultaneous analysis of group and between-subject effects of CS and deswelling. The best model for overnight CS versus Dk/t was linear with a random intercept showing constant between-subject differences in CS for different Dk/t values. The best fit for corneal deswelling versus time was a curvilinear random intercept and random slope model. About 90% of the total between-subject deswelling variance in either lens or control eyes was due to the intercept variability with much less (∼10%) being due to the variability of the individual deswelling rate (slope). Subject age, sex, and ametropia were not predictors of individual corneal swelling in the swelling versus Dk/t analysis. Age, however, was a significant (inverse) predictor of the rate of corneal deswelling, only in lens-wearing eyes. A large proportion of variability in corneal swelling is because of subject-specific differences in corneal response to hypoxia. This shows that "low swellers" and "high swellers" actually do exist.


Prophylactic nasal continuous positive airway pressure for preventing morbidity and mortality in very preterm infants.
Cohort studies have suggested that nasal continuous positive airways pressure (CPAP) starting in the immediate postnatal period before the onset of respiratory disease (prophylactic CPAP) may be beneficial in reducing the need for intubation and intermittent positive pressure ventilation (IPPV) and in preventing bronchopulmonary dysplasia (BPD) in preterm or low birth weight infants. To determine if prophylactic nasal CPAP started soon after birth regardless of respiratory status in the very preterm or very low birth weight infant reduces the use of IPPV and the incidence of bronchopulmonary dysplasia (BPD) without adverse effects. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE via PubMed (1966 to 31 January 2016), EMBASE (1980 to 31 January 2016), and CINAHL (1982 to 31 January 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. All trials using random or quasi-random patient allocation of very preterm infants (under 32 weeks' gestation) or less than 1500 grams at birth were eligible. We included trials if they compared prophylactic nasal CPAP started soon after birth regardless of the respiratory status of the infant with 'standard' methods of treatment such as IPPV, oxygen therapy or supportive treatment. We excluded studies where prophylactic CPAP was compared with CPAP along with other interventions. We used the standard methods of Cochrane and its Neonatal Review Group, including independent study selection, assessment of trial quality and extraction of data by two authors. Data were analysed using risk ratio (RR) and the meta-analysis was performed using a fixed-effect model. Seven trials recruiting 3123 babies were included in the meta-analysis. Four trials recruiting 765 babies compared CPAP with supportive care and three trials (2364 infants) compared CPAP with mechanical ventilation. Apart from a lack of blinding of the intervention all studies were of low risk of bias.In the comparison of CPAP with supportive care there was a reduction in failed treatment (typical risk ratio (RR) 0.66, 95% confidence interval (CI) 0.45 to 0.98; typical risk difference (RD) -0.16, 95% CI -0.34 to 0.02; 4 studies, 765 infants, very low quality evidence). There was no reduction in bronchopulmonary dysplasia (BPD) or mortality.In trials comparing CPAP with assisted ventilation with or without surfactant, CPAP resulted in a small but clinically significant reduction in the incidence of BPD at 36 weeks, (typical RR 0.89, 95% CI 0.79 to 0.99; typical RD -0.04, 95% CI -0.08 to 0.00; 3 studies, 772 infants, moderate-quality evidence); and death or BPD (typical RR 0.89, 95% CI 0.81 to 0.97; typical RD -0.05, 95% CI -0.09 to 0.01; 3 studies, 1042 infants, moderate-quality evidence). There was also a clinically important reduction in the need for mechanical ventilation (typical RR 0.50, 95% CI 0.42 to 0.59; typical RD -0.49, 95% CI -0.59 to -0.39; 2 studies, 760 infants, moderate-quality evidence); and the use of surfactant in the CPAP group (typical RR 0.54, 95% CI 0.40 to 0.73; typical RD -0.41, 95% CI -0.54 to -0.28; 3 studies, 1744 infants, moderate-quality evidence). There is insufficient evidence to evaluate prophylactic CPAP compared to oxygen therapy and other supportive care. However when compared to mechanical ventilation prophylactic nasal CPAP in very preterm infants reduces the need for mechanical ventilation and surfactant and also reduces the incidence of BPD and death or BPD.


Intestinal pH profile in rainbow trout Oncorhynchus mykiss and microhabitat preference of the flagellate Spironucleus salmonis (Diplomonadida).
In farmed rainbow trout Oncorhynchus mykiss, the flagellate Spironucleus salmonis (Diplomonadida) is often found in the pyloric region of the intestine. While previous in vitro studies report a pH of 7.5 to 8.0 as optimal for presumed S. salmonis, no previous in vivo studies have investigated the relationship between pH and microhabitat preference. Therefore, in 698 rainbow trout (75% were 5 to 6 mo old juveniles, 10 to 20 cm total length), we recorded occurrence and density of S. salmonis, and pH, in the pyloric, anterior, middle, and posterior intestine. There were no significant differences in total length or weight between infected and uninfected fish. S. salmonis preferred the pyloric region, with occurrence and density decreasing significantly from pyloric to posterior regions. In infected fish, pH in pyloric (6.8 to 7.9, mean 7.3) and posterior regions (6.5 to 8.0, mean 7.1) was significantly lower than in anterior (6.5 to 8.5, mean 7.7) and middle (6.8 to 8.2, mean 7.7) regions; in uninfected fish, the pH profile was similar. At the individual level, 90 % of infected fish and 79% of uninfected fish showed this pH profile. In the pyloric region, pH was not significantly different among uninfected fish, and fish with light, moderate, or heavy infections. Our in vivo study suggests the optimal pH for S. salmonis is between 7.1 and 7.5, possibly close to 7.3 (the mean in pyloric region of infected fish). We conclude that while the presence of S. salmonis reflected tolerable pH, density of infection was not correlated with pH, and thus a causal relationship between microhabitat preference and pH is unlikely.


DNA determinants of structural and regulatory variation within the murine beta-glucuronidase gene complex.
The murine beta-glucuronidase (GUS) gene complex, [Gus], encompasses the GUS structural element, Gus-s, and a set of regulatory elements which serve to modulate Gus-s expression. Three common GUS haplotypes representing virtually all inbred strains of laboratory mice have been compared with respect to GUS mRNA sequence. Results of such comparisons revealed sequence variations which target the location of one of the GUS regulatory elements to sequences within Gus-s and which account for known electrophoretic and heat stability differences among GUS allozymes of the three common GUS haplotypes.


Measures of rowing performance.
Accurate measures of performance are important for assessing competitive athletes in practi~al and research settings. We present here a review of rowing performance measures, focusing on the errors in these measures and the implications for testing rowers. The yardstick for assessing error in a performance measure is the random variation (typical or standard error of measurement) in an elite athlete's competitive performance from race to race: ∼1.0% for time in 2000 m rowing events. There has been little research interest in on-water time trials for assessing rowing performance, owing to logistic difficulties and environmental perturbations in performance time with such tests. Mobile ergometry via instrumented oars or rowlocks should reduce these problems, but the associated errors have not yet been reported. Measurement of boat speed to monitor on-water training performance is common; one device based on global positioning system (GPS) technology contributes negligible extra random error (0.2%) in speed measured over 2000 m, but extra error is substantial (1-10%) with other GPS devices or with an impeller, especially over shorter distances. The problems with on-water testing have led to widespread use of the Concept II rowing ergometer. The standard error of the estimate of on-water 2000 m time predicted by 2000 m ergometer performance was 2.6% and 7.2% in two studies, reflecting different effects of skill, body mass and environment in on-water versus ergometer performance. However, well trained rowers have a typical error in performance time of only ∼0.5% between repeated 2000 m time trials on this ergometer, so such trials are suitable for tracking changes in physiological performance and factors affecting it. Many researchers have used the 2000 m ergometer performance time as a criterion to identify other predictors of rowing performance. Standard errors of the estimate vary widely between studies even for the same predictor, but the lowest errors (~1-2%) have been observed for peak power output in an incremental test, some measures of lactate threshold and measures of 30-second all-out power. Some of these measures also have typical error between repeated tests suitably low for tracking changes. Combining measures via multiple linear regression needs further investigation. In summary, measurement of boat speed, especially with a good GPS device, has adequate precision for monitoring training performance, but adjustment for environmental effects needs to be investigated. Time trials on the Concept II ergometer provide accurate estimates of a rower's physiological ability to output power, and some submaximal and brief maximal ergometer performance measures can be used frequently to monitor changes in this ability. On-water performance measured via instrumented skiffs that determine individual power output may eventually surpass measures derived from the Concept II.


Distress Tolerance Scale: A Confirmatory Factor Analysis Among Daily Cigarette Smokers.
The present investigation evaluated the factor structure of the Distress Tolerance Scale (DTS; Simons and Gaher 2005) among a sample of 173 (54.9% males) daily cigarette smokers (M=16.64 cigarettes per day, SD=7.83). Comparison of a single higher-order model and a hierarchical multidimensional model was conducted using confirmatory factor analyses (CFA). In addition, evaluation of the internal consistency and convergent and discriminant validity of the better-fitting model was completed. CFA of the DTS indicated a single second-order factor of distress tolerance, and four lower-order factors including Tolerance, Appraisal, Absorption, and Regulation; each factor demonstrated acceptable levels of internal consistency. In addition, the DTS displayed good convergent and discriminant validity with theoretically relevant smoking and affect variables. Results are discussed in terms of explicating the latent structure of distress tolerance, as measured by the DTS, within the context of smoking research.


An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer.
Early detection and efficient treatment modality of early-stage peripheral lung cancer is essential. Current nonsurgical treatments for peripheral lung cancer show critical limitations associated with various complications, requiring alternative minimally invasive therapeutics. Porphysome nanoparticle-enabled fluorescence-guided transbronchial photothermal therapy (PTT) of peripheral lung cancer was developed and demonstrated in preclinical animal models. Systemically administered porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast, as confirmed in three subtypes of orthotopic human lung cancer xenografts (A549, H460, and H520) in mice and in an orthotopic VX2 tumor in rabbits. An in-house prototype fluorescence bronchoscope demonstrated the capability of porphysomes for in vivo imaging of lung tumors in the mucosal/submucosal layers, providing real-time fluorescence guidance for transbronchial PTT. Porphysomes also enhanced the efficacy of transbronchial PTT significantly and resulted in selective and efficient tumor tissue ablation in the rabbit model. A clinically used cylindrical diffuser fiber successfully achieved tumor-specific thermal ablation, showing promising evidence for the clinical translation of this novel platform to impact upon nonsurgical treatment of early-stage peripheral lung cancer. Cancer Res; 76(19); 5870-80. ©2016 AACR.


[Shared development of printed material as a health education strategy with public school employees in Rio de Janeiro State].
This article describes the process and results of an experience with preparing a mural entitled A Day in the Life of the School Lunch Cook, conducted with public school employees in the State of Rio de Janeiro by a team of researchers and students from the Specialization Course in Workers' Health at the Center for Studies on Workers' Health of the National School of Public Health, Oswaldo Cruz Foundation, in partnership with the School Employees' Union. "Health workshops" based on participatory research were used to raise questions related to daily work by school lunch cooks and kitchen staff. Produced to share the results of workshops with other schools, the mural is highly meaningful in terms of the reality of a specific segment of public employees and is intended as food for thought. Based on the Paulo Freire popular education model, six meetings were held, following a script for the production of an educational leaflet including the selection of contents, the communications approach, and the style and format of the leaflet. The creativity in the images prepared by the school lunch employees based on actual experiences from their daily work made the workshops an enriching moment of exchange, in which the participants shared their ideas, values, beliefs, feelings, and life histories.


In-situ incubation of a coral patch for community-scale assessment of metabolic and chemical processes on a reef slope.
Anthropogenic pressures threaten the health of coral reefs globally. Some of these pressures directly affect coral functioning, while others are indirect, for example by promoting the capacity of bioeroders to dissolve coral aragonite. To assess the coral reef status, it is necessary to validate community-scale measurements of metabolic and geochemical processes in the field, by determining fluxes from enclosed coral reef patches. Here, we investigate diurnal trends of carbonate chemistry, dissolved organic carbon, oxygen, and nutrients on a 20 m deep coral reef patch offshore from the island of Saba, Dutch Caribbean by means of tent incubations. The obtained trends are related to benthic carbon fluxes by quantifying net community calcification (NCC) and net community production (NCP). The relatively strong currents and swell-induced near-bottom surge at this location caused minor seawater exchange between the incubated reef and ambient water. Employing a compensating interpretive model, the exchange is used to our advantage as it maintains reasonably ventilated conditions, which conceivably prevents metabolic arrest during incubation periods of multiple hours. No diurnal trends in carbonate chemistry were detected and all net diurnal rates of production were strongly skewed towards respiration suggesting net heterotrophy in all incubations. The NCC inferred from our incubations ranges from -0.2 to 1.4 mmol CaCO3 m-2 h-1 (-0.2 to 1.2 kg CaCO3 m-2 year-1) and NCP varies from -9 to -21.7 mmol m-2 h-1 (net respiration). When comparing to the consensus-based ReefBudget approach, the estimated NCC rate for the incubated full planar area (0.36 kg CaCO3 m-2 year-1) was lower, but still within range of the different NCC inferred from our incubations. Field trials indicate that the tent-based incubation as presented here, coupled with an appropriate interpretive model, is an effective tool to investigate, in situ, the state of coral reef patches even when located in a relatively hydrodynamic environment.


Identification of tomato phosphatidylinositol-specific phospholipase-C (PI-PLC) family members and the role of PLC4 and PLC6 in HR and disease resistance.
The perception of pathogen-derived elicitors by plants has been suggested to involve phosphatidylinositol-specific phospholipase-C (PI-PLC) signalling. Here we show that PLC isoforms are required for the hypersensitive response (HR) and disease resistance. We characterised the tomato [Solanum lycopersicum (Sl)] PLC gene family. Six Sl PLC-encoding cDNAs were isolated and their expression in response to infection with the pathogenic fungus Cladosporium fulvum was studied. We found significant regulation at the transcriptional level of the various SlPLCs, and SlPLC4 and SlPLC6 showed distinct expression patterns in C. fulvum-resistant Cf-4 tomato. We produced the encoded proteins in Escherichia coli and found that both genes encode catalytically active PI-PLCs. To test the requirement of these Sl PLCs for full Cf-4-mediated recognition of the effector Avr4, we knocked down the expression of the encoding genes by virus-induced gene silencing. Silencing of SlPLC4 impaired the Avr4/Cf-4-induced HR and resulted in increased colonisation of Cf-4 plants by C. fulvum expressing Avr4. Furthermore, expression of the gene in Nicotiana benthamiana enhanced the Avr4/Cf-4-induced HR. Silencing of SlPLC6 did not affect HR, whereas it caused increased colonisation of Cf-4 plants by the fungus. Interestingly, Sl PLC6, but not Sl PLC4, was also required for resistance to Verticillium dahliae, mediated by the transmembrane Ve1 resistance protein, and to Pseudomonas syringae, mediated by the intracellular Pto/Prf resistance protein couple. We conclude that there is a differential requirement of PLC isoforms for the plant immune response and that Sl PLC4 is specifically required for Cf-4 function, while Sl PLC6 may be a more general component of resistance protein signalling.


Enhancement of bioavailability of cefpodoxime proxetil using different polymeric microparticles.
Poorly water-soluble drugs such as cefpodoxime proxetil (400 μg/ml) offer a challenging problem in drug formulation as poor solubility is generally associated with poor dissolution characteristics and thus poor oral bioavailability. According to these characteristics, preparation of cefpodoxime proxetil microparticle has been achieved using high-speed homogenization. Polymers (methylcellulose, sodium alginate, and chitosan) were precipitated on the surface of cefpodoxime proxetil using sodium citrate and calcium chloride as salting-out agents. The pure drug and the prepared microparticles with different concentrations of polymer (0.05-1.0%) were characterized in terms of solubility, drug content, particle size, thermal behavior (differential scanning calorimeter), surface morphology (scanning electron microscopy), in vitro drug release, and stability studies. The in vivo performance was assessed by pharmacokinetic study. The dissolution studies demonstrate a marked increase in the dissolution rate in comparison with pure drug. The considerable improvement in the dissolution rate of cefpodoxime proxetil from optimized microparticle was attributed to the wetting effect of polymers, altered surface morphology, and micronization of drug particles. The optimized microparticles exhibited excellent stability on storage at accelerated condition. The in vivo studies revealed that the optimized formulations provided improved pharmacokinetic parameter in rats as compared with pure drug. The particle size of drug was drastically reduced during formulation process of microparticles.


Molecular structure of poly(methyl methacrylate) surface II: Effect of stereoregularity examined through all-atom molecular dynamics.
Utilizing all-atom molecular dynamics (MD), we have analyzed the effect of tacticity and temperature on the surface structure of poly(methyl methacrylate) (PMMA) at the polymer-vacuum interface. We quantify these effects primarily through orientation, measured as the tilt with respect to the surface normal, and the surface number densities of the α-methyl, ester-methyl, carbonyl, and backbone methylene groups. Molecular structure on the surface is a complex interplay between orientation and number densities and is challenging to capture through sum frequency generation (SFG) spectroscopy alone. Independent quantification of the number density and orientation of chemical groups through all-atom MD presents a comprehensive model of stereoregular PMMA on the surface. SFG analysis presented in part I of this joint publication measures the orientation of molecules that are in agreement with MD results. We observe the ester-methyl groups as preferentially oriented, irrespective of tacticity, followed by the α-methyl and carbonyl groups. SFG spectroscopy also points to ester-methyl being dominant on the surface. The backbone methylene groups show a very broad angular distribution, centered along the surface plane. The surface number density ratios of ester-methyl to α-methyl groups show syndiotactic PMMA having the lowest value. Isotactic PMMA has the highest ratios of ester- to α-methyl. These subtle trends in the relative angular orientation and number densities that influence the variation of surface structure with tacticity are highlighted in this article. A more planar conformation of the syndiotactic PMMA along the surface (x-y plane) can be visualized through the trajectories from all-atom MD. Results from conformation tensor calculations for chains with any of their segments contributing to the surface validate the visual observation.