Perturbations in immune responses induced by concurrent subchronic exposure to arsenic and endosulfan.
The metalloid arsenic and the chlorinated insecticide endosulfan are common environmental contaminants. Humans, animals, and birds are exposed to these chemicals through water and food. Although health effects due to either arsenic or endosulfan exposure are documented, the toxicological impact of co-exposure to these environmental pollutants is unpredictable and unknown. The present study was undertaken to assess whether concurrent exposure to arsenic and endosulfan induces significant alterations in immunological functions. Day-old chicks were exposed to 3.7 ppm of arsenic via drinking water and to 30 ppm of endosulfan-mixed feed either individually or concurrently for up to 60 days. All the chicks were vaccinated with Ranikhet disease virus (F-strain; RD-F) on days 1 and 30. During the course of study and at term, parameters of cellular and humoral immunity were determined. None of the treatments altered the absolute body weight or body weight gain, except arsenic significantly reduced weight gain on day 60. Absolute, but not the relative, weights of spleen, thymus and bursa of Fabricius were significantly reduced in all the treatment groups. The metalloid and insecticide combination significantly depressed the ability of peripheral blood and splenic lymphocytes to proliferate in response to antigen RD-F and mitogen Con A. The delayed type hypersensitivity response to 2,4-dinitro-1-chlorobenzene or to PHA-P was also significantly decreased. Nitric oxide production by RD-F or lipopolysaccharide-stimulated peripheral blood and splenic mononuclear cells was significantly suppressed following concurrent exposure to arsenic and endosulfan. Furthermore, the combined exposure also decreased the antibody response to RD-F. The suppression of cellular and humoral immune responses was also evident following administration of individual compounds, and it was not exacerbated following concurrent exposure. To our knowledge, this is the first report describing the suppression of immune responses following exposure to arsenic alone or in combination with endosulfan at environmentally realistic concentrations in avian species. Therefore, immunotoxicological effects induced by concurrent exposure to arsenic and chlorinated pesticides should be considered when assessing the risk to human and animal health.


Hydroxyethylene isosteres introduced in type II collagen fragments substantially alter the structure and dynamics of class II MHC A(q)/glycopeptide complexes.
Class II major histocompatibility complex (MHC) proteins are involved in initiation of immune responses to foreign antigens via presentation of peptides to receptors of CD4(+) T-cells. An analogous presentation of self-peptides may lead to autoimmune diseases, such as rheumatoid arthritis (RA). The glycopeptide fragment CII259-273, derived from type II collagen, is presented by A(q) MHCII molecules in the mouse and has a key role in development of collagen induced arthritis (CIA), a validated model for RA. We have introduced hydroxyethylene amide bond isosteres at the Ala(261)-Gly(262) position of CII259-273. Biological evaluation showed that A(q) binding and T cell recognition were dramatically reduced for the modified glycopeptides, although static models predicted similar binding modes as the native type II collagen fragment. Molecular dynamics (MD) simulations demonstrated that introduction of the hydroxyethylene isosteres disturbed the entire hydrogen bond network between the glycopeptides and A(q). As a consequence the hydroxyethylene isosteric glycopeptides were prone to dissociation from A(q) and unfolding of the β1-helix. Thus, the isostere induced adjustment of the hydrogen bond network altered the structure and dynamics of A(q)/glycopeptide complexes leading to the loss of A(q) affinity and subsequent T cell response.


Structural and regulatory genes required to make the gas dimethyl sulfide in bacteria.
Dimethyl sulfide (DMS) is a key compound in global sulfur and carbon cycles. DMS oxidation products cause cloud nucleation and may affect weather and climate. DMS is generated largely by bacterial catabolism of dimethylsulfoniopropionate (DMSP), a secondary metabolite made by marine algae. We demonstrate that the bacterial gene dddD is required for this process and that its transcription is induced by the DMSP substrate. Cloned dddD from the marine bacterium Marinomonas and from two bacterial strains that associate with higher plants, the N(2)-fixing symbiont Rhizobium NGR234 and the root-colonizing Burkholderia cepacia AMMD, conferred to Escherichia coli the ability to make DMS from DMSP. The inferred enzymatic mechanism for DMS liberation involves an initial step in which DMSP is modified by addition of acyl coenzyme A, rather than the immediate release of DMS by a DMSP lyase, the previously suggested mechanism.


Clinical signs of early osteoarthritis: reproducibility and relation to x ray changes in 541 women in the general population.
The definition and classification of early clinically apparent osteoarthritis both in clinical situations and in epidemiological surveys remains a problem. Few data exist on the between-observer reproducibility of simple clinical methods of detecting hand and knee osteoarthritis in the population and their sensitivity and specificity as compared with radiography. Two observers first studied the reproducibility of a number of clinical signs in 41 middle aged women. Good rates of agreement were found for most of the clinical signs tested (kappa = 0.54-1.0). The more reproducible signs were then tested on a population of 541 women, aged 45-65, drawn from general practice, screening centres, and patients previously attending hospital for non-rheumatic problems. The major clinical signs used had a high specificity (87-99%) and lower sensitivity (20-49%) when compared with radiographs graded on the Kellgren and Lawrence scale (2+ = positive). When analysis was restricted to symptomatic radiographic osteoarthritis, levels of sensitivity were increased and specificity was lowered. These data show that certain physical signs of osteoarthritis are reproducible and may be used to identify clinical disease. They are not a substitute for radiographs, however, if radiographic change is regarded as the 'gold standard' of diagnosis. As the clinical signs tested seemed specific for osteoarthritis they may be of value in screening populations for clinical disease.


Amino acid receptor-mediated transmission at primary afferent synapses in rat spinal cord.
Intracellular recording techniques have been used to provide information on the identity of excitatory transmitters released at synapses formed between dorsal root ganglion (DRG) and spinal cord neurones in two in vitro preparations. Explants of embryonic rat DRG were added to dissociated cultures of embryonic dorsal horn neurones and synaptic potentials recorded intracellularly from dorsal horn neurones after DRG explant stimulation. More than 80% of dorsal horn neurones received at least one fast, DRG-evoked, monosynaptic input. In the presence of high divalent cation concentrations (5 mmol l-1 Ca2+, 3 mmol l-1 Mg2+) the acidic amino acid receptor agonists, L-glutamate, kainate (KA) and quisqualate (QUIS) excited all dorsal horn neurones which received a monosynaptic DRG neurone input, whereas L-aspartate and N-methyl-D-aspartate (NMDA) had little or no action. 2-Amino-5-phosphonovalerate (APV), a selective NMDA receptor antagonist, was relatively ineffective at antagonizing DRG-evoked synaptic potentials and L-glutamate-evoked responses. In contrast, kynurenate was found to be a potent antagonist of amino acid-evoked responses and of synaptic transmission at all DRG-dorsal horn synapses examined. The blockade of synaptic transmission by kynurenate appeared to result from a postsynaptic action on dorsal horn neurones. Intracellular recordings from motoneurones in new-born rat spinal cord were used to study the sensitivity of the Ia excitatory postsynaptic potential (EPSP) to antagonists of excitatory amino acids. Superfusion of the spinal cord with APV did not inhibit the Ia EPSP but did suppress later, polysynaptic components of the afferent-evoked response. Kynurenate was a potent and selective inhibitor of the Ia EPSP, acting via a postsynaptic mechanism. These findings indicate that L-glutamate, or a glutamate-like compound, but not L-aspartate, is likely to be the predominant excitatory transmitter that mediates fast excitatory postsynaptic potentials at primary afferent synapses with both dorsal horn neurones and motoneurones.


Factors Associated with Positive SARS-CoV-2 Test Results in Outpatient Health Facilities and Emergency Departments Among Children and Adolescents Aged <18 Years - Mississippi, September-November 2020.
As of December 14, 2020, children and adolescents aged <18 years have accounted for 10.2% of coronavirus disease 2019 (COVID-19) cases reported in the United States.* Mitigation strategies to prevent infection with SARS-CoV-2, the virus that causes COVID-19, among persons of all ages, are important for pandemic control. Characterization of risk factors for SARS-CoV-2 infection among children and adolescents can inform efforts by parents, school and program administrators, and public health officials to reduce SARS-CoV-2 transmission. To assess school, community, and close contact exposures associated with pediatric COVID-19, a case-control study was conducted to compare exposures reported by parents or guardians of children and adolescents aged <18 years with SARS-CoV-2 infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing (case-patients) with exposures reported among those who received negative SARS-CoV-2 RT-PCR test results (control participants). Among 397 children and adolescents investigated, in-person school or child care attendance ≤14 days before the SARS-CoV-2 test was reported for 62% of case-patients and 68% of control participants and was not associated with a positive SARS-CoV-2 test result (adjusted odds ratio [aOR] = 0.8, 95% confidence interval [CI] = 0.5-1.3). Among 236 children aged ≥2 years who attended child care or school during the 2 weeks before SARS-CoV-2 testing, parents of 64% of case-patients and 76% of control participants reported that their child and all staff members wore masks inside the facility (aOR = 0.4, 95% CI = 0.2-0.8). In the 2 weeks preceding SARS-CoV-2 testing, case-patients were more likely to have had close contact with a person with known COVID-19 (aOR = 3.2, 95% CI = 2.0-5.0), have attended gatherings† with persons outside their household, including social functions (aOR = 2.4, 95% CI = 1.1-5.5) or activities with other children (aOR = 3.3, 95% CI = 1.3-8.4), or have had visitors in the home (aOR = 1.9, 95% CI = 1.2-2.9) than were control participants. Close contacts with persons with COVID-19 and gatherings contribute to SARS-CoV-2 infections in children and adolescents. Consistent use of masks, social distancing, isolation of infected persons, and quarantine of those who are exposed to the virus continue to be important to prevent COVID-19 spread.


Cost-effectiveness analysis in the courts: recent trends and future prospects.
This article provides an initial look at how managed care organizations (MCOs) might incorporate cost-effectiveness analysis (CEA) into their decision-making process and how the courts might respond. Because so few medical liability cases directly involve CEA, we must look at other areas of the law to assess potential MCO liability for applying CEA. In general negligence cases, courts rely on a risk-benefit test to determine customary practice. Likewise, in product liability cases, courts use a risk-utility calculus to determine liability for product design defects. And in challenges to government regulation, courts examine how agencies use CEA to set regulatory policy. The results have been mixed. In product liability cases, CEA has led to some punitive damage awards against automobile manufacturers. But courts have integrated it in negligence cases without generating juror antipathy, and generally defer to agency expertise in how to incorporate CEA. The article discusses the implications of these cases for MCO use of CEA and outlines various options for setting the standard of care in the managed care era.


Multi-Sensor Based State Prediction for Personal Mobility Vehicles.
This paper presents a study on multi-modal human emotional state detection while riding a powered wheelchair (PMV; Personal Mobility Vehicle) in an indoor labyrinth-like environment. The study reports findings on the habituation of human stress response during self-driving. In addition, the effects of "loss of controllability", change in the role of the driver to a passenger, are investigated via an autonomous driving modality. The multi-modal emotional state detector sensing framework consists of four sensing devices: electroencephalograph (EEG), heart inter-beat interval (IBI), galvanic skin response (GSR) and stressor level lever (in the case of autonomous riding). Physiological emotional state measurement characteristics are organized by time-scale, in terms of capturing slower changes (long-term) and quicker changes from moment-to-moment. Experimental results with fifteen participants regarding subjective emotional state reports and commercial software measurements validated the proposed emotional state detector. Short-term GSR and heart signal characterizations captured moment-to-moment emotional state during autonomous riding (Spearman correlation; ρ = 0.6, p < 0.001). Short-term GSR and EEG characterizations reliably captured moment-to-moment emotional state during self-driving (Classification accuracy; 69.7). Finally, long-term GSR and heart characterizations were confirmed to reliably capture slow changes during autonomous riding and also of emotional state during participant resting state. The purpose of this study and the exploration of various algorithms and sensors in a structured framework is to provide a comprehensive background for multi-modal emotional state prediction experiments and/or applications. Additional discussion regarding the feasibility and utility of the possibilities of these concepts are given.


Overexpression of the riboflavin biosynthetic pathway in Pichia pastoris.
High cell density cultures of Pichia pastoris grown on methanol tend to develop yellow colored supernatants, attributed to the release of free flavins. The potential of P. pastoris for flavin overproduction is therefore given, but not pronounced when the yeast is grown on glucose. The aim of this study is to characterize the relative regulatory impact of each riboflavin synthesis gene. Deeper insight into pathway control and the potential of deregulation is established by overexpression of the single genes as well as a combined deregulation of up to all six riboflavin synthesis genes. Overexpression of the first gene of the riboflavin biosynthetic pathway (RIB1) is already sufficient to obtain yellow colonies and the accumulation of riboflavin in the supernatant of shake flask cultures growing on glucose. Sequential deregulation of all the genes, by exchange of their native promoter with the strong and constitutive glyceraldehyde-3-phosphate dehydrogenase promoter (PGAP) increases the riboflavin accumulation significantly. The regulation of the pathway is distributed over more than one gene. High cell density cultivations of a P. pastoris strain overexpressing all six RIB genes allow the accumulation of 175 mg/L riboflavin in the supernatant. The basis for rational engineering of riboflavin production in P. pastoris has thus been established.


Ethnic differences and determinants of diabetes and central obesity among South Asians of Pakistan.
To study the within ethnic subgroup variations in diabetes and central obesity among South Asians. Data from 9442 individuals age > or = 15 years from the National Health Survey of Pakistan (NHSP) (1990-1994) were analysed. Diabetes was defined as non-fasting blood glucose > or = 7.8 mmol/l, or known history of diabetes. Central obesity was measured at the waist circumference. Distinct ethnic subgroups Muhajir, Punjabi, Sindhi, Pashtun, and Baluchi were defined by mother tongue. The age-standardized prevalence of diabetes varied among ethnic subgroups (P = 0.002), being highest among the Muhajirs (men 5.7%, women 7.9%), then Punjabis (men 4.6%, women 7.2%), Sindhis (men 5.1%, women 4.8%), Pashtuns (men 3.0%, women 3.8%), and lowest among the Baluchis (men 2.9%, women 2.6%). While diabetes was more prevalent in urban vs. rural dwellers [odds ratio (OR) 1.50, 95% confidence interval (CI) 1.24, 1.82], this difference was no longer significant after adjusting for central obesity (OR 1.15, 95% CI 0.95, 1.42). However, the ethnic differences persisted after adjusting for major sociodemographic risk factors (unadjusted OR for Pashtun vs. Punjabi 0.59, 95% CI 0.42, 0.84, adjusted OR 0.54, 95% CI 0.37, 0.78). Ethnic variation was also observed in central obesity, which varied with gender, and did not necessarily track with ethnic differences in diabetes. Unmeasured environmental or genetic factors account for ethnic variations in diabetes and central obesity, and deserve further study.


Identification of novel protein functions and signaling mechanisms by genetics and quantitative phosphoproteomics in Caenorhabditis elegans.
Stable isotope labeling by amino acids combined with mass spectrometry is a widely used methodology for measuring relative changes in protein and phosphorylation levels at a global level. We have applied this method to the model organism Caenorhabditis elegans in combination with RNAi-mediated gene knockdown by feeding the nematode on pre-labeled lysine auxotroph Escherichia coli. In this chapter, we describe in details the generation of the E. coli strain, incorporation of heavy isotope-labeled lysine in C. elegans, and the procedure for a comprehensive global phosphoproteomic experiment.


A US postmarketing evaluation of the frequency and safety of live attenuated influenza vaccine use in nonrecommended children younger than 5 years: 2009-2010 season.
The 2007 US approval for use of Ann Arbor strain live attenuated influenza vaccine (LAIV) in children aged 24 through 59 months included precautions against use in (1) children <24 months and children aged 24 through 59 months with (2) asthma, (3) recurrent wheezing, and (4) altered immunocompetence. Results from the third season (2009-2010) of a 3-year study postmarketing commitment to monitor LAIV vaccination rates and frequency of hospitalizations or emergency department visits within 42 days after LAIV are reported here. As in the first 2 seasons, LAIV usage in cohorts 1, 2, and 4 were low relative to those in LAIV-recommended populations. The only numerically increased risk observed was for respiratory events in children aged <24 months administered LAIV, compared to those administered trivalent inactivated influenza vaccine (TIV). The number of children vaccinated with LAIV was small and precluded precise quantification of rare event.


Central nervous system germ cell tumors: controversies in diagnosis and treatment.
The variability and complexity of central nervous system germ cell tumors have led to controversy in both diagnosis and management. If a germ cell tumor is suspected, the measurement of cerebrospinal fluid and serum alpha-fetoprotein and beta-human chorionic gonadotropin is essential. A histologic specimen is not necessary if the patient has elevated levels; however, if the tumor markers are negative, a biopsy is needed to confirm the diagnosis of a germinoma. Germinomas are extremely radiosensitive, enabling 5-year survival rates that exceed 90%. Treatment has traditionally included focal and craniospinal axis irradiation; however, multiple ongoing studies are being conducted to examine the efficacy of reduction or elimination of radiation therapy with the addition of chemotherapy. Nongerminomatous germ cell tumors, on the other hand, are relatively radioresistant with a poorer outcome. The combination of chemotherapy and irradiation is associated with overall survival rates of up to 60%. This article provides a review of the controversies in diagnosis and treatment of central nervous system germ cell tumors.


Long-term effects of chronic nicotine exposure on brain nicotinic receptors.
Chronic nicotine exposure results in long-term homeostatic regulation of nicotinic acetylcholine receptors (nAChRs) that play a key role in the adaptative cellular processes leading to addiction. However, the relative contribution of the different nAChR subunits in this process is unclear. Using genetically modified mice and pharmacological manipulations, we provide behavioral, electrophysiological, and pharmacological evidence for a long-term mechanism by which chronic nicotine triggers opposing processes differentially mediated by beta2*- vs. alpha7*nAChRs. These data offer previously undescribed insights into the understanding of nicotine addiction and the treatment of several human pathologies by nicotine-like agents chronically acting on beta2*- or alpha7*nAChRs.


Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase.
Mitochondria were isolated from skin fibroblast cultures derived from healthy individuals (controls) and from a group patients with complex I (NADH-CoQ reductase) deficiency of the mitochondrial respiratory chain. The complex I deficient patients included those with fatal infantile lactic acidosis (FILA), cardiomyopathy with cataracts (CC), hepatopathy with tubulopathy (HT), Leigh's disease (LD), cataracts and developmental delay (CD), and lactic acidemia in the neonatal period followed by mild symptoms (MS). Production of superoxide radicals, on addition of NADH, were measured using the luminometric probe lucigenin with isolated fibroblast mitochondrial membranes. Superoxide production rates were highest with CD and decreased in the order CD >> MS > LD > control > HT > FILA = CC. The quantity of Mn-superoxide dismutase (MnSOD), as measured by ELISA techniques, however, was highest in CC and FILA and lowest in CD. Plots of MnSOD quantity versus superoxide production showed an inverse relationship for most conditions with complex I deficiency. We hypothesize that oxygen radical production is increased when complex I activity is compromised. However, the observed superoxide production rates are modulated by the variant induction of MnSOD which decreases the rates, sometimes below those seen in control fibroblast mitochondria. In turn, we show that the variant induction of MnSOD is most likely a function of the change in the redox state of the cell experienced rather than a result of the complex I defect per se.


An ethnographic study exploring factors that minimize lunch waste in Tokyo elementary schools.
To explore factors that minimize lunch waste in Tokyo elementary schools and to consider how such factors can be modified and applied in US schools. Focused ethnographic study using interviews, observation, participant observation and document review. Data were analysed using thematic analysis. Tokyo, Japan. Five school dietitians participated in the study. Data collection methods included in-depth interviews, observation of nutrition education lessons, participant observation of school lunchtime and review of relevant school documents (e.g. lunch menus, food waste records). Five themes emerged from the analysis: (i) reinforcement of social norms to eat without waste; (ii) menu planning to increase exposure to unfamiliar and/or disliked foods; (iii) integration of food and nutrition education into the school curriculum; (iv) teacher lunchtime practices related to portion sizes, distributing leftover food and time management; and (v) engagement of students in reducing school lunch waste. Practical and tangible applications to US schools include measuring and reporting lunch waste to influence social norms, teaching students about the importance of reducing food waste, offering flexible school lunch portion sizes and providing students with meaningful opportunities to contribute to solving the problem of school lunch waste. Japan offers a model for minimizing school lunch waste through a holistic approach that includes factors that operate at and interact across multiple levels of society. Modifying and applying such an approach in US schools is worth considering given the urgent need to address food waste in order to support healthy diets and sustainable food systems.


Surgical versus non-surgical interventions for treating patellar dislocation.
Patellar dislocation occurs when the patella disengages completely from the trochlear (femoral) groove. Following reduction of the dislocation, conservative rehabilitation with physiotherapy may be used. Since recurrence of dislocation is common, some surgeons have advocated surgical intervention in addition to rehabilitation. The purpose of this review was to assess the clinical and radiological outcomes of surgical, compared with non-surgical, interventions for treating people with primary or recurrent patellar dislocation. We searched the Cochrane Bone, Joint and Muscle Trauma Group's Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, AMED, CINAHL, ZETOC, Physiotherapy Evidence Database (PEDro), and a variety of other literature databases and trial registries. Corresponding authors were contacted to identify additional studies. Date searched: August 2010. Eligible for inclusion were randomised and quasi-randomised controlled clinical trials evaluating surgical versus non-surgical interventions for treating lateral patellar dislocation. Two reviewers independently examined titles and abstracts of each identified study to assess study eligibility, extract data and assess risk of bias. Primary outcomes assessed were the frequency of recurrent dislocation, and validated patient-rated knee or physical function scores. When appropriate, data were pooled. Risk ratios were calculated for dichotomous outcomes, and mean differences for continuous outcomes. Five studies (339 participants) were included. All studies had methodological shortcomings, especially the two quasi-randomised trials that presented a high risk for selection bias. Follow-up was a minimum of two years in two studies and between five and seven years in three studies. There was no significant difference between surgical and non-surgical management of primary (first-time) patellar dislocation in the risk of recurrent dislocation (47/182 versus 53/157; risk ratio 0.81, 95% confidence interval 0.56 to 1.17; 5 trials), Kujala patellofemoral disorder scores (mean difference 3.13, 95% confidence interval -7.34 to 13.59; 5 trials) nor the requirement for subsequent surgery (risk ratio 1.09, 95% CI 0.72 to 1.65; 3 trials). Adverse events were reported by one trial, citing four major complications that occurred in the surgical group. No randomised controlled trials have assessed populations with recurrent patellar dislocation. There is insufficient high quality evidence to confirm any significant difference in outcome between surgical or non-surgical initial management of people following primary patellar dislocation, and none examining this comparison in people with recurrent patellar dislocation. Adequately powered randomised, multi-centre controlled trials, conducted and reported to contemporary standards are recommended.


A general measles vaccination campaign in urban Guinea-Bissau: Comparing child mortality among participants and non-participants.
Measles vaccination campaigns targeting children aged 9-59months are conducted every three years in Guinea-Bissau. Studies have demonstrated beneficial non-specific effects of measles vaccine. We compared mortality one year after the December 2012 measles vaccination campaign in Bissau city for children who received campaign measles vaccine with children who did not receive campaign measles vaccine. Field workers from Bandim Health Project registered all children living in the Bandim Health Project's study area who received measles vaccination at the campaign posts. Children not seen during the campaign were visited at home and campaign participation status was assessed. We compared mortality rates of participants vs. non-participants in Cox regression models. 5633 children aged 9-59months (85%) received campaign measles vaccination and 1006 (15%) did not. During the subsequent year 16 children died. Adjusted for background factors, the hazard ratio (HR) comparing measles vaccinated versus unvaccinated was 0.28 (95% CI: 0.10-0.77). The benefit was larger for girls (HR: 0.17 (0.05-0.59)) and for children who had received routine measles vaccine before the campaign (HR: 0.15 (0.04-0.63)). We found indications of strong beneficial non-specific effects of receiving measles vaccine during the 2012 campaign, especially for girls and children with previous routine measles vaccination. Measles vaccination campaigns may be an effective way of improving child survival.


The Impact of Conservation Management on the Community Composition of Multiple Organism Groups in Eutrophic Interconnected Man-Made Ponds.
Ponds throughout the world are subjected to a variety of management measures for purposes of biodiversity conservation. Current conservation efforts typically comprise a combination of multiple measures that directly and indirectly impact a wide range of organism groups. Knowledge of the relative impact of individual measures on different taxonomic groups is important for the development of effective conservation programs. We conducted a field study of 28 man-made ponds, representing four management types differing in the frequency of periodic pond drainage and the intensity of fish stock management. We disentangled the relative importance of direct and indirect effects of pond management measures on the community composition of phytoplankton, zooplankton, aquatic macro-invertebrates, submerged and emergent vascular plants. With the exception of phytoplankton, pond management had strong effects on the community composition of all investigated biota. Whether management affected communities directly or indirectly through its impact on fish communities or local environmental conditions in the pond varied between organism groups. Overall, the impact of pond drainage regime and fish community characteristics on the community composition of target organism groups were more important than local environmental conditions. The majority of taxa were negatively associated with fish density, whereas multiple emergent plant species and several taxa of aquatic macro-invertebrates were positively affected by increased drainage frequency. The effects of fish community and drainage tended to be largely independent. The present study indicates that pond drainage is an important element for biodiversity conservation in eutrophicated shallow and interconnected man-made ponds.


Financing Long-Term Services And Supports: Options Reflect Trade-Offs For Older Americans And Federal Spending.
About half of older Americans will need a high level of assistance with routine activities for a prolonged period of time. This help is commonly referred to as long-term services and supports (LTSS). Under current policies, these individuals will fund roughly half of their paid care out of pocket. Partly as a result of high costs and uncertainty, relatively few people purchase private long-term care insurance or save sufficiently to fully finance LTSS; many will eventually turn to Medicaid for help. To show how policy changes could expand insurance's role in financing these needs, we modeled several new insurance options. Specifically, we looked at a front-end-only benefit that provides coverage relatively early in the period of disability but caps benefits, a back-end benefit with no lifetime limit, and a combined comprehensive benefit. We modeled mandatory and voluntary versions of each option, and subsidized and unsubsidized versions of each voluntary option. We identified important differences among the alternatives, highlighting relevant trade-offs that policy makers can consider in evaluating proposals. If the primary goal is to significantly increase insurance coverage, the mandatory options would be more successful than the voluntary versions. If the major aim is to reduce Medicaid costs, the comprehensive and back-end mandatory options would be most beneficial.


Associations of presbyopia with vision-targeted health-related quality of life.
To evaluate the associations of presbyopia and its correction, particularly monovision optical correction, with vision-targeted health-related quality of life. The National Eye Institute Refractive Error Quality of Life (NEI-RQL) Instrument was prospectively self-administered by subjects from 6 medical centers in the following age and correction categories: subjects with emmetropia younger than 45 years (n = 75), subjects with emmetropia aged 45 years or older (n = 38), and subjects with ametropia aged 45 years or older without monovision (n = 486) or corrected with monovision (n = 38). Differences in the 13 NEI-RQL Instrument subscale scores among subjects in the 4 groups were examined. The age of 45 years or older was used as a surrogate for presbyopia. A comparison of older (age > or =45 years) vs younger (age <45 years) persons with emmetropia suggests that presbyopia was associated with reduced scores in 7 of 13 subscales (P<.05). In those aged 45 years or older, correction of presbyopia with monovision was associated with statistically significantly better scores on 3 subscales (expectations, dependence on correction, and appearance) compared with single-vision correction. One subscale (dependence on correction) showed worsening scores with increasing age without adjustment for need or type of correction. Older persons with monovision correction had significantly worse scores than younger subjects with emmetropia on all subscales except suboptimal correction and appearance. Presbyopia is associated with worse vision-targeted health-related quality of life compared with younger subjects with emmetropia. Monovision correction of presbyopia is related to some improvements in health-related quality of life, but it is still worse than that for younger subjects with emmetropia in several areas.


Contribution of Arab researchers to ophthalmology: a bibliometric and comparative analysis.
Through history, Arabs and Muslims have made valuable contribution to medicine and science. The main objective of this study was to assess the contribution of Arab researchers to ophthalmology using bibliometric indicators. Published articles in "Ophthalmology" authored by Arab researchers were screened and analyzed using ISI Web of Science database. Worldwide research productivity in ophthalmology was 216,921 documents while that from Arab countries; Israel, Turkey and Iran were 2083, 2932, 3027 and 859 documents respectively. Those from Arab countries were published in 85 peer-reviewed ophthalmology related journals with 280 (13.44%) documents published in Journal Francais d Ophtalmologie. Among Arab countries, Kingdom of Saudi Arabia had the highest (828 (39.75%)) research output followed by Egypt (461 (22.13%)) and Tunisia 210 (10.08). Countries with highest collaboration with researchers in Arab world in ophthalmology research were USA; (397; 19.06%) followed by England (92; 4.42%) and Spain (91; 4.37%). The most research productive organization in Arab countries was King Khalid Eye Specialist Hospital (396; 19.01%). Ophthalmology articles authored or co-authored by an Arab researcher had a total citation f 21098 with an average citation of 10.13 per document and an h-index of 51. In conclusion, the present data show promising increase but relatively low ophthalmology research productivity from Arab countries. Wide variation in research productivity do exists. Compared with other non-Arab countries in the Middle East, Arab countries showed lesser ophthalmology research activity than Israel and Turkey but higher than that in Iran.


Asymptomatic children with multiple endocrine neoplasia type 1 mutations may harbor nonfunctioning pancreatic neuroendocrine tumors.
Multiple endocrine neoplasia type 1 (MEN1) is characterized by the occurrence of parathyroid, pituitary, and pancreatic tumors. MEN1, an autosomal dominant disorder, has a high degree of penetrance, such that more than 95% of patients develop clinical manifestations by the fifth decade, although this is lower at approximately 50% by age 20 yr. However, the lower penetrance in the younger group, which is based on detecting hormone-secreting tumors, may be an underestimate because patients may have nonfunctioning tumors and be asymptomatic. The aim of the study was to evaluate the occurrence of nonfunctioning pancreatic neuroendocrine tumors in asymptomatic children with MEN1. Twelve asymptomatic Northern European children, aged 6 to 16 yr, who were known to have MEN1 mutations were studied. Two asymptomatic children, who were aged 12 and 14 yr, had normal plasma fasting gastrointestinal hormones and were found to have nonfunctioning pancreatic neuroendocrine tumors that were more than 2 cm in size. Surgery and immunostaining revealed that the tumors did not have significant expression of gastrointestinal hormones but did contain chromogranin A and synaptophysin, features consistent with those of nonfunctioning pancreatic neuroendocrine tumors. The tumors had a loss of menin expression. The 14 yr old also had primary hyperparathyroidism and a microprolactinoma, and the 12 yr old had a nonfunctioning pituitary microadenoma. Three other children had primary hyperparathyroidism and a microprolactinoma. Nonfunctioning pancreatic neuroendocrine tumors may occur in asymptomatic children with MEN1 mutations, and screening for such enteropancreatic tumors in MEN1 children should be considered earlier than the age of 20 yr, as is currently recommended by the international guidelines.


Small but powerful: top predator local extinction affects ecosystem structure and function in an intermittent stream.
Top predator loss is a major global problem, with a current trend in biodiversity loss towards high trophic levels that modifies most ecosystems worldwide. Most research in this area is focused on large-bodied predators, despite the high extinction risk of small-bodied freshwater fish that often act as apex consumers. Consequently, it remains unknown if intermittent streams are affected by the consequences of top-predators' extirpations. The aim of our research was to determine how this global problem affects intermittent streams and, in particular, if the loss of a small-bodied top predator (1) leads to a 'mesopredator release', affects primary consumers and changes whole community structures, and (2) triggers a cascade effect modifying the ecosystem function. To address these questions, we studied the top-down effects of a small endangered fish species, Barbus meridionalis (the Mediterranean barbel), conducting an enclosure/exclosure mesocosm experiment in an intermittent stream where B. meridionalis became locally extinct following a wildfire. We found that top predator absence led to 'mesopredator release', and also to 'prey release' despite intraguild predation, which contrasts with traditional food web theory. In addition, B. meridionalis extirpation changed whole macroinvertebrate community composition and increased total macroinvertebrate density. Regarding ecosystem function, periphyton primary production decreased in apex consumer absence. In this study, the apex consumer was functionally irreplaceable; its local extinction led to the loss of an important functional role that resulted in major changes to the ecosystem's structure and function. This study evidences that intermittent streams can be affected by the consequences of apex consumers' extinctions, and that the loss of small-bodied top predators can lead to large ecosystem changes. We recommend the reintroduction of small-bodied apex consumers to systems where they have been extirpated, to restore ecosystem structure and function.


Heterogeneity in signaled active avoidance learning: substantive and methodological relevance of diversity in instrumental defensive responses to threat cues.
Individuals exposed to traumatic stressors follow divergent patterns including resilience and chronic stress. However, researchers utilizing animal models that examine learned or instrumental threat responses thought to have translational relevance for Posttraumatic Stress Disorder (PTSD) and resilience typically use central tendency statistics that assume population homogeneity. This approach potentially overlooks fundamental differences that can explain human diversity in response to traumatic stressors. The current study tests this assumption by identifying and replicating common heterogeneous patterns of response to signaled active avoidance (AA) training. In this paradigm, rats are trained to prevent an aversive outcome (shock) by performing a learned instrumental behavior (shuttling between chambers) during the presentation of a conditioned threat cue (tone). We test the hypothesis that heterogeneous trajectories of threat avoidance provide more accurate model fit compared to a single mean trajectory in two separate studies. Study 1 conducted 3 days of signaled AA training (n = 81 animals) and study 2 conducted 5 days of training (n = 186 animals). We found that four trajectories in both samples provided the strongest model fit. Identified populations included animals that acquired and retained avoidance behavior on the first day (Rapid Avoiders: 22 and 25%); those who never successfully acquired avoidance (Non-Avoiders; 20 and 16%); a modal class who acquired avoidance over 3 days (Modal Avoiders; 37 and 50%); and a population who demonstrated a slow pattern of avoidance, failed to fully acquire avoidance in study 1 and did acquire avoidance on days 4 and 5 in study 2 (Slow Avoiders; 22.0 and 9%). With the exception of the Slow Avoiders in Study 1, populations that acquired demonstrated rapid step-like increases leading to asymptotic levels of avoidance. These findings indicate that avoidance responses are heterogeneous in a way that may be informative for understanding both resilience and PTSD as well as the nature of instrumental behavior acquisition. Characterizing heterogeneous populations based on their response to threat cues would increase the accuracy and translatability of such models and potentially lead to new discoveries that explain diversity in instrumental defensive responses.


The Man I Once Knew: Grief and Inflammation in Female Partners of Veterans With Traumatic Brain Injury.
Grief, although traditionally conceptualized as a bereavement-related reaction, is also experienced by significant others in response to the profound cognitive and personality changes associated with a traumatic brain injury (TBI) in a loved one. Grief associated with the death of a loved one is related to increases in proinflammatory cytokines, yet it is not clear whether this is the case for grief experienced by individuals caring for a significant other with TBI. The purpose of this cross-sectional, exploratory study was to examine grief and its association with a proinflammatory cytokine, tumor necrosis factor α (TNF-α), in wives/partners caring for veterans with TBI. Participants completed written measures of grief, perceived stress, and depressive symptoms and provided morning saliva samples for TNF-α analysis. Participants reported levels of grief comparable to those reported in studies evaluating individuals grieving the death of a loved one. Path analysis revealed that grief was not associated with TNF-α; however, participants reporting high levels of blame/anger, a subscale of the grief scale, had higher levels of TNF-α. In addition, both grief and blame/anger were related to increased perceived stress and depressive symptoms; however, path analysis demonstrated that perceived stress and depressive symptoms did not mediate the influence of blame/anger on TNF-α. These findings suggest that blame/anger associated with grief may be related to the elevations in TNF-α exhibited by individuals caring for a loved one with TBI.


Psychosis Risk: What Is It and How Should We Talk About It?
Schizophrenia and other psychosis spectrum disorders do not develop de novo but emerge from prodromal stages that are named and operationalized differently depending on the research group or consortium and its theoretical orientation. As a result, a complex lexicon now exists for characterizing individuals' risk of subclinical symptoms converting to psychosis. Researchers aim to develop instruments and methods to identify people at risk of psychosis, better understand their risks, and offer preventative treatments to arrest conversion to psychosis; ethical and policy questions loom large with each of these projects. In this paper, we canvass the lexical complexities of the at-risk status for psychosis and then consider ethical and policy challenges that researchers and clinicians face in disclosing, preventing, and treating psychosis risk.


RNA polymerase errors cause splicing defects and can be regulated by differential expression of RNA polymerase subunits.
Errors during transcription may play an important role in determining cellular phenotypes: the RNA polymerase error rate is >4 orders of magnitude higher than that of DNA polymerase and errors are amplified >1000-fold due to translation. However, current methods to measure RNA polymerase fidelity are low-throughout, technically challenging, and organism specific. Here I show that changes in RNA polymerase fidelity can be measured using standard RNA sequencing protocols. I find that RNA polymerase is error-prone, and these errors can result in splicing defects. Furthermore, I find that differential expression of RNA polymerase subunits causes changes in RNA polymerase fidelity, and that coding sequences may have evolved to minimize the effect of these errors. These results suggest that errors caused by RNA polymerase may be a major source of stochastic variability at the level of single cells.


Type 1 diabetes self-management behaviors among emerging adults: Racial/ethnic differences.
Emerging adulthood is a vulnerable period for poor blood glucose control and self-management behaviors (SMBs) among individuals with type 1 diabetes. Racial/ethnic minority young adults have poorer glycemic outcomes than non-Hispanic whites; however, little is known about possible racial/ethnic differences in frequency of SMBs among emerging adults (EAs). To examine racial/ethnic differences in SMBs and to determine associations between SMBs and blood glucose control. A sample of EAs (ages 18-25 years; N = 3456) from the type 1 diabetes exchange registry was used to conduct multivariate analyses to examine (a) racial/ethnic differences in SMBs and (b) associations between SMBs and blood glucose control for each racial/ethnic group. Compared to non-Hispanic whites, African Americans and Hispanics less frequently took an insulin bolus for snacks, less frequently checked blood glucose with a meter, and were more likely to not use insulin to carbohydrate ratios. African Americans also less frequently checked blood glucose prior to mealtime boluses and more frequently missed insulin doses. SMBs that were associated with blood glucose control across groups were frequency of checking blood glucose at mealtime, missing an insulin dose, and checking blood glucose with a meter. Promoting two SMBs: checking blood glucose and taking insulin doses as needed among African American EAs may be important to address racial disparities in glycemic outcomes. Future research should evaluate possible social and contextual mechanisms contributing to low engagement in these behaviors among African Americans to inform strategies to address racial differences in glycemic outcomes.


Multistate resistive switching in silver nanoparticle films.
Resistive switching devices have garnered significant consideration for their potential use in nanoelectronics and non-volatile memory applications. Here we investigate the nonlinear current-voltage behavior and resistive switching properties of composite nanoparticle films comprising a large collective of metal-insulator-metal junctions. Silver nanoparticles prepared via the polyol process and coated with an insulating polymer layer of tetraethylene glycol were deposited onto silicon oxide substrates. Activation required a forming step achieved through application of a bias voltage. Once activated, the nanoparticle films exhibited controllable resistive switching between multiple discrete low resistance states that depended on operational parameters including the applied bias voltage, temperature and sweep frequency. The films' resistance switching behavior is shown here to be the result of nanofilament formation due to formative electromigration effects. Because of their tunable and distinct resistance states, scalability and ease of fabrication, nanoparticle films have a potential place in memory technology as resistive random access memory cells.


Pure alexia as a disconnection syndrome: new diffusion imaging evidence for an old concept.
Functional neuroimaging and studies of brain-damaged patients made it possible to delineate the main components of the cerebral system for word reading. However, the anatomical connections subtending the flow of information within this network are still poorly defined. Here we study the connectivity of the Visual Word Form Area (VWFA), a pivotal component of the reading network achieving the invariant identification of letter strings, and reproducibly located in the left lateral occipitotemporal sulcus. Diffusion images and functional imaging data were gathered in a patient who developed pure alexia following a small surgical lesion in the vicinity of his VWFA. We had a unique opportunity to compare images obtained before, early after, and late after surgery. Analysis of diffusion images with white matter tractography and voxel-based morphometry showed that the VWFA was mainly linked to the occipital cortex through the inferior longitudinal fasciculus (ILF), and to perisylvian language areas (supramarginal gyrus) through the arcuate fasciculus. After surgery, we observed the progressive and selective degeneration of the ILF, while the VWFA was anatomically intact. This allowed us to establish the critical causal role of this fiber tract in normal reading, and to show that its disruption is one pathophysiological mechanism of pure alexia, thus clarifying a long-standing debate on the role of disconnection in neurocognitive disorders.


Cytokine regulation of the epidermal barrier.
Studies published in recent years have highlighted the role of epidermal barrier defects in both atopic skin disease and the development of broader allergic manifestations. While genetic determinants of barrier function are important, it is clear that local acquired effects are also involved in disease pathogenesis. In this review, we aimed to summarize the known influences of cytokines abundantly expressed during atopic skin disease on components of epidermal barrier integrity and function.


Implementing patient safety initiatives in rural hospitals.
Implementation of patient safety initiatives can be costly in time and energy. Because of small volumes and limited resources, rural hospitals often are not included in nationally driven patient safety initiatives. This article describes the Tennessee Rural Hospital Patient Safety Demonstration project, whose goal was to strengthen capacity for patient safety initiatives in 8 small Tennessee rural hospitals using a multi-organizational collaborative model. The demonstration identified and facilitated implementation of 3 patient safety interventions: the Agency for Healthcare Research and Quality (AHRQ) patient safety culture survey, use of personal digital assistants (PDAs), and sharing of emergency room protocols. The experience suggested that a collaborative model between rural hospitals, a payer, a hospital association, a quality improvement organization, and academic institutions can effectively support patient safety activities in rural hospitals. Successful implementation of the 3 patient safety interventions depended on leadership provided by nursing and patient safety/quality managers and open, trusting communications within the hospitals.


Identification of novel aspartic proteases from Strongyloides ratti and characterisation of their evolutionary relationships, stage-specific expression and molecular structure.
Aspartic proteases are known to play an important role in the biology of nematode parasitism. This role is best characterised in blood-feeding nematodes, where they digest haemoglobin, but they are also likely to play important roles in the biology of nematode parasites that do not feed on blood. In the present work, we investigate the evolution and expression of aspartic proteases in Strongyloides ratti, which permits a unique comparison between parasitic and free-living adult forms within its life-cycle. We identified eight transcribed aspartic protease sequences and a further two genomic sequences and compared these to homologues in Caenorhabditis elegans and other nematode species. Phylogenetic analysis demonstrated a complex pattern of gene evolution, such that some S. ratti sequences had a one-to-one correspondence with orthologues of C. elegans but that lineage-specific expansions have occurred for other aspartic proteases in these two nematodes. These gene duplication events may have contributed to the adaptation of the two species to their different lifestyles. Among the set of S. ratti aspartic proteases were two closely-related isoforms that showed differential expression during different life stages: ASP-2A is highly expressed in parasitic females while ASP-2B is predominantly found in free-living adults. Molecular modelling of the ASP-2 isoforms reveals that their substrate specificities are likely to be very similar, but that ASP-2B is more electrostatically negative over its entire molecular surface than ASP-2A. This characteristic may be related to different pH values of the environments in which these two isoforms operate. We have demonstrated that S. ratti provides a powerful model to explore the genetic adaptations associated with parasitic versus free-living life-styles. We have discovered gene duplication of aspartic protease genes in Strongyloides and identified a pair of paralogues differentially expressed in either the parasitic or the free-living phase of the nematode life-cycle, consistent with an adaptive role for aspartic proteases in the evolution of nematode parasitism.


Raised extracellular potassium attenuates the sympathetic modulation of sino-atrial node pacemaking in the isolated guinea-pig atria.
Intense exercise or myocardial ischaemia can significantly increase both the concentration of extracellular potassium ([K(+)](o)) and cardiac sympathetic nerve activity. Since changes in [K(+)](o) modulate membrane currents involved in sino-atrial node pacemaking, in particular the voltage-sensitive hyperpolarization-activated current (I(f)), we investigated whether raised [K(+)](o) (from 4 mM to 8 or 12 mM) could directly affect the heart rate response to cardiac sympathetic nerve stimulation (SNS). In the isolated guinea-pig atrial-right stellate ganglion preparation, raised [K(+)](o) significantly decreased the maximum diastolic potential, amplitude and maximum rate of rise of the upstroke of sino-atrial node pacemaker action potentials in 8 and 12 mM [K(+)](o) (P < 0.05). At 12 mM [K(+)](o) these effects were associated with significant decreases in baseline heart rate (4 mM [K(+)](o) = 187 +/- 5 beats min(-1) (bpm); 12 mM = 144 +/- 11 bpm; P < 0.05) and the heart rate response to SNS (1, 3 and 5 Hz; P < 0.05). A 10 % increase in the baseline heart rate with sympathetic activation (3 Hz) was associated with a significant enhancement of the slope of the pacemaker diastolic depolarization at 4 mM [K(+)](o) (increased by 16 +/- 6 %; n = 7; P < 0.05), but not with raised [K(+)](o). When the I(f) current was blocked with 2 mM caesium (n = 8), 12 mM [K(+)](o) had no effect on baseline heart rate and the heart rate response to 3 Hz SNS. The heart rate response to bath-applied noradrenaline (0.01-100 microM) was significantly attenuated by 12 mM [K(+)](o) (at 4 mM [K(+)](o,) EC(50) = -6.31 +/- 0.18; at 12 mM [K(+)](o,) EC(50) = -5.80 +/- 0.10; n = 6, ANOVA, P < 0.05). In conclusion, extreme physiological levels of [K(+)](o) attenuate the positive chronotropic response to cardiac sympathetic activation due to decreased activation of the I(f) current. This is consistent with raised [K(+)](o) protecting the myocardium from potentially adverse effects of excessive noradrenaline. Experimental Physiology (2001) 86.1, 19-25.


Toward a typology of technology users: how older people experience technology's potential for active aging.
This paper outlines an emerging typology of older users of information and communication technology (ICT) to facilitate active aging. Through inductive data analysis from focus groups, iterative workshops, and personal interviews, we suggest three types of technology users. These types are "the Excluded," "the Entertained," and "the Networker." Clearly, ICT offers several benefits to those who are enthusiastic and frequent users, exemplified as the Entertained and the Networker. Hence, our findings support the notion of technology as a tool to maintain or increase an older person's engagement and activity level. Conversely, for those reluctant, uninterested, or incapable of using ICT, such potentials are limited and imply fewer opportunities for participation in activities.


Oral Bioavailability and Plasma Disposition of Pefloxacin in Healthy Broiler Chickens.
The pharmacokinetics of pefloxacin after single 10 mg/kg BW intravenous (IV) and oral doses were studied in healthy broiler chickens. For 24 h, serial blood samples were obtained after IV and oral administration. Concentrations of pefloxacin and its major metabolite N-demethyl pefloxacin (norfloxacin) were measured by use of high-performance liquid chromatography. The plasma concentrations-time data were found to fit a two-compartment open model. For pefloxacin, the elimination half-life (t½β) was 8.44 ± 0.48 and 13.18 ± 0.82 h after IV and oral administration, respectively. After single oral dose, pefloxacin was rapidly absorbed with an absorption half-life (t½a) and TMAX of 0.87 ± 0.07 and 2.01 ± 0.12 h, respectively. Maximum plasma concentration (CMAX) was 4.02 ± 0.31 µg/mL. Oral bioavailability of pefloxacin was found to be 70 ± 2%. Pefloxacin was converted to N-demethyl pefloxacin (norfloxacin). This metabolite represented 5% of the parent drug plasma concentrations. The maximal plasma concentration (CMAX) of N-demethyl pefloxacin (norfloxacin) was calculated as 0.19 ± 0.01 mg/mL. The t½β of N-demethyl pefloxacin after oral pefloxacin administration was 10.93 ± 0.80 h. The results indicate that an oral dose of 10 mg pefloxacin/kg BW, every 24 h, should be effective in treatment of the most systemic infections in poultry.


Does raised intraocular pressure begin in utero?
To determine whether fetal and infant growth, as assessed by weight at birth and weight at 1 year, are related to intraocular pressure. 717 men and women born in Hertfordshire between 1920 and 1930, for whom records of birth weight and weight at 1 year were available, were examined. Visual fields were assessed using the Takagi central 25 degrees 75 point static threshold screening program. Tonometry was performed using the Perkin's tonometer. The disc was assessed by direct ophthalmoscopy through dilated pupils. A significant inverse relation was found between systolic blood pressure and birth weight. However, no association was found between birth weight or weight at 1 year and intraocular pressure, cup/disc ratio, or visual field defects. There was no evidence to support fetal or infant growth as being important factors for the subsequent development of raised intraocular pressure.


MicroRNA-29a inhibits cell migration and invasion by targeting Roundabout 1 in breast cancer cells.
Epithelial ovarian cancer (EOC) remains a major gynecological problem, with a poor 5-year-survival rate due to distant metastases. The identification of microRNAs (miRNAs) may provide a novel avenue for diagnostic and treatment regimens for EOC. Several miRNAs have been reported to be involved in the progression of EOC, among which miRNA (miR)-137 has been observed to be downregulated in the ovarian tissues of patients with EOC. However, the functions of miR-137 in EOC cell apoptosis, migration and invasion remain to be elucidated. In the present study, the expression of miR-137 was measured in clinical ovarian cancer specimens and cell lines using reverse transcription-quantitative polymerase chain reaction. The role of miR-137 in the growth and survival of the SKOV3 human ovarian cancer cell line was determined using several in vitro approaches and in nude mouse models. The results demonstrated that the expression of miR-137 was downregulated in the ovarian cancer specimens and cell lines. It was also observed that enforced expression of miR-137 in the EOC cell lines decreased cell proliferation, clonogenicity, migration and invasion, and induced G1 arrest and cell apoptosis in vitro. Notably, the enforced expression of miR-137 suppressed tumor growth in the nude mice models. These findings suggested that miR-137 may act as a tumor suppressor and be used as a potential therapeutic agent for the treatment of EOC.


Translocation of DNA through Ultrathin Nanoslits.
2D nanoslit devices, where two crystals with atomically flat surfaces are separated by only a few nanometers, have attracted considerable attention because their tunable control over the confinement allows for the discovery of unusual transport behavior of gas, water, and ions. Here, the passage of double-stranded DNA molecules is studied through nanoslits fabricated from exfoliated 2D materials, such as graphene or hexagonal boron nitride, and the DNA polymer behavior is examined in this tight confinement. Two types of events are observed in the ionic current: long current blockades that signal DNA translocation and short spikes where DNA enters the slits but withdraws. DNA translocation events exhibit three distinct phases in their current-blockade traces-loading, translation, and exit. Coarse-grained molecular dynamics simulation allows the different polymer configurations of these phases to be identified. DNA molecules, including folds and knots in their polymer structure, are observed to slide through the slits with near-uniform velocity without noticeable frictional interactions of DNA with the confining graphene surfaces. It is anticipated that this new class of 2D-nanoslit devices will provide unique ways to study polymer physics and enable lab-on-a-chip biotechnology.


High excitation transfer efficiency from energy relay dyes in dye-sensitized solar cells.
The energy relay dye, 4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCM), was used with a near-infrared sensitizing dye, TT1, to increase the overall power conversion efficiency of a dye-sensitized solar cell (DSC) from 3.5% to 4.5%. The unattached DCM dyes exhibit an average excitation transfer efficiency (ETE) of 96% inside TT1-covered, mesostructured TiO(2) films. Further performance increases were limited by the solubility of DCM in an acetonitrile based electrolyte. This demonstration shows that energy relay dyes can be efficiently implemented in optimized dye-sensitized solar cells, but also highlights the need to design highly soluble energy relay dyes with high molar extinction coefficients.


Gastrointestinal Polyposis in Cowden Syndrome.
To further characterize the gastrointestinal manifestations of Cowden syndrome in clinically well-annotated patients to improve the diagnosis of this syndrome. The gastrointestinal manifestations of Cowden Syndrome, an important heritable and multiorgan cancer syndrome, are not well defined. Proper diagnosis is essential for effective cancer surveillance and prevention in these patients. Cowden patients with gastrointestinal polyps were selected for medical record and pathologic slide review. Of 19 total patients, genetic testing revealed pathogenic PTEN mutations in 12. Pan-colonic (11-patients, 58%) and pan-gastrointestinal (8-patients, 42%) polyp distributions were common. Inflammatory (juvenile) polyps were the most common of the hamartomatous polyp (18 patients, 95%), along with expansive lymphoid follicle polyps (12 patients, 63%), ganglioneuromatous polyps (10 patients, 53%), and intramucosal lipomas (5 patients, 26%). The findings of 2 or more hamartomatous polyp types per patient emerged as a newly described and highly prevalent (79%) feature of Cowden syndrome. Ganglioneuromatous polyps, rare in the general population, and intramucosal lipomas, which may be unique to Cowden syndrome, should both prompt further evaluation. Colonic adenomas and adenocarcinomas were common; 10 patients (53%) had single and 3 (16%) had ≥3 adenomas, whereas 2 (11%) had colonic adenocarcinoma, strengthening the emerging association of colorectal cancer with Cowden syndrome. The clinical phenotypes and gastrointestinal manifestations in Cowden syndrome are quite variable but this series adds the following new considerations for this syndromic diagnosis: multiple gastrointestinal hamartomas, especially 2 or more hamartoma types, and any intramucosal lipomas or ganglioneuromas. These features should warrant consideration of Cowden syndrome.


Comparative height measurements of dip-pen nanolithography-produced lipid membrane stacks with atomic force, fluorescence, and surface-enhanced ellipsometric contrast microscopy.
Dip-pen nanolithography (DPN) with phospholipids has been shown to be a powerful tool for the generation of biologically active surface patterns, but screening of the obtained lithographic structures is still a bottleneck in the quality control of the prepared samples. Here we performed a comparative study with atomic force microscopy (AFM), fluorescence microscopy (FM), and surface-enhanced ellipsometric contrast (SEEC) microscopy of phospholipid membrane stacks consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) with high admixing of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[6-[(2,4-dinitrophenyl)amino]hexanoyl] (DNP Cap PE) produced by DPN. We present a structural model of membrane stacking based on the combined information gained from the three microscopic techniques. Domains of phase-separated DNP Cap PE can be detected at high DNP Cap PE admixing that are not present at medium or low admixings. While the optical methods allow for a high-throughput screening of lithographic structures (compared to AFM), it was found that, when relying on FM alone, artifacts due to phase-separation phenomena can be introduced in the case of thin membrane stacks.


Hip, Knee, and Ankle Functional Demand During Habitual and Fast-Pace Walking in Younger and Older Women.
This study compared functional demand (FD) between older and younger women walking at habitual and fast speed and determined strength thresholds necessary to maintain FD below 80%. FD was calculated by expressing walking flexion and extension joint torques of the ankle, knee, and hip as a percentage of maximal strength. Young women had an average FD of 65% across joint actions and speeds, whereas older women had FD of 90%. In older women, the greatest FD occurred in the hip musculature. The hip, knee, and ankle extensor strengths required to maintain FD below 80% were 1.66, 1.86, and 0.57 Nm/kg, and flexor strengths were 1.24, 0.49, and 0.69 Nm/kg, respectively. Older women have limited functional reserve to increase gait speed and rely heavily on available hip strength during walking. This study identifies strength targets for the hip, knee, and ankle that will assist in maintaining FD of older women at a sustainable level.


The effect of miswak extract on plaque pH. An in vivo study.
The aim of this study was to document changes in plaque pH when an acidic challenge was followed by rinsing with miswak extract (Salvadora persica), and to evaluate the effect of miswak rinse on parotid gland secretion rate. Plaque pH was measured in 3-day-old plaque using the microtouch electrode. Rinsing with miswak extract, compared with water rinsing, resulted in protracted elevation of plaque pH (>6.0). The difference in plaque pH between miswak extract and water rinse was statistically significant at 30 min (p < 0.001). Rinsing with miswak extract stimulated parotid gland secretion (p < 0.01). In conclusion, miswak extract raised the plaque pH, suggesting a potential role in caries prevention.


Common infection-related conditions and risk of lymphoid malignancies in older individuals.
Chronic antigenic stimulation may initiate non-Hodgkin (NHL) and Hodgkin lymphoma (HL) development. Antecedent, infection-related conditions have been associated, but evidence by lymphoproliferative subtype is limited. From the US SEER-Medicare database, 44,191 NHL, 1832 HL and 200,000 population-based controls, frequency-matched to all SEER cancer cases, were selected. Logistic regression models, adjusted for potential confounders, compared infection-related conditions in controls with HL and NHL patients and by the NHL subtypes diffuse large B-cell, T-cell, follicular and marginal zone lymphoma (MZL). Stratification by race was undertaken. Respiratory tract infections were broadly associated with NHL, particularly MZL. Skin infections were associated with a 15-28% increased risk of NHL and with most NHL subtypes, particularly cellulitis with T-cell lymphoma (OR 1.36, 95%CI 1.24-1.49). Only herpes zoster remained associated with HL following Bonferroni correction (OR 1.55, 95% CI 1.28-1.87). Gastrointestinal and urinary tract infections were not strongly associated with NHL or HL. In stratified analyses by race, sinusitis, pharyngitis, bronchitis and cellulitis showed stronger associations with total NHL in blacks than whites (P<0.001). Infections may contribute to the aetiologic pathway and/or be markers of underlying immune modulation. Precise elucidation of these mechanisms may provide important clues for understanding how immune disturbance contributes to lymphoma.


N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo.
N,N-dimethyltryptamine (DMT) is a component of the ayahuasca brew traditionally used for ritual and therapeutic purposes across several South American countries. Here, we have examined, in vitro and vivo, the potential neurogenic effect of DMT. Our results demonstrate that DMT administration activates the main adult neurogenic niche, the subgranular zone of the dentate gyrus of the hippocampus, promoting newly generated neurons in the granular zone. Moreover, these mice performed better, compared to control non-treated animals, in memory tests, which suggest a functional relevance for the DMT-induced new production of neurons in the hippocampus. Interestingly, the neurogenic effect of DMT appears to involve signaling via sigma-1 receptor (S1R) activation since S1R antagonist blocked the neurogenic effect. Taken together, our results demonstrate that DMT treatment activates the subgranular neurogenic niche regulating the proliferation of neural stem cells, the migration of neuroblasts, and promoting the generation of new neurons in the hippocampus, therefore enhancing adult neurogenesis and improving spatial learning and memory tasks.


Lack of association between the ITPA 94C>A polymorphism and adverse effects from azathioprine.
A 94C>A missense mutation in the ITPA gene which encodes inosine triphosphate pyrophosphatase has been associated with adverse effects from azathioprine, specifically flu-like symptoms, pancreatitis and rash. We hypothesized that this association may also be present in a larger, population-based group of inflammatory bowel disease patients intolerant of thiopurine drugs. We performed genotyping for this polymorphism and TPMT*2 and TPMT*3 in 73 such patients and 74 patients with inflammatory bowel disease who have tolerated azathioprine. We could not demonstrate a significant association between the ITPA94C>A genotype and any adverse effects (Odds ratio (OR) 1.015, 95% confidence interval (CI) 0.360-2.867, P = 0.593), flu-like symptoms (OR 1.547, 95%CI 0.368-6.496, P = 0.398), rash (no ITPA 94C>A polymorphism identified) or pancreatitis (no ITPA 94C>A polymorphism identified). We found no significant association between the ITPA 94C>A polymorphism and adverse effects to thiopurine drugs.


Predictors of longer-term development of expressive language in two independent longitudinal cohorts of language-delayed preschoolers with Autism Spectrum Disorder.
Studies estimate that 30% of individuals with autism are minimally verbal. Understanding what factors predict longer-term expressive development in children with language delays is critical to inform identification and treatment of those at-risk for persistent language impairments. The present study examined predictors of expressive language development in language-delayed preschoolers followed through later school-age and young adulthood. Children using single words or less on the Autism Diagnostic Observation Schedule (ADOS) at approximately 3 years old were drawn from the Early Diagnosis (EDX) and Pathways in ASD longitudinal cohorts. Age-3 predictors of Age-19 ADOS language level were identified using Classification and Regression Trees (CART) in the EDX sample. Linear mixed models examined the effects of CART-identified predictors on Vineland expressive communication (VExp) trajectories from Age-3 to Age-19. The same linear mixed models were examined in the Pathways sample, identifying predictors of VExp from ages 3 to 10.5 years. Significantly delayed fine motor skills (T-score < 20) was the strongest CART predictor of Age-19 language. In the linear mixed models, time, Age-3 fine motor skills and initiation of joint attention (IJA) predicted VExp trajectories in the EDX sample, even when controlling for Age-3 visual receptive abilities. In the Pathways sample, time and Age-3 fine motor skills were significant predictors of VExp trajectories; IJA and cognitive skills were not significant predictors. Marked deficits in fine motor skills may be a salient proxy marker for identifying language-delayed children with ASD who are at risk for persistent language impairments. This finding adds to the literature demonstrating a relation between motor and language development in ASD. Investigating individual skill areas (e.g., fine motor and nonverbal problem-solving skills), rather than broader indices of developmental level (e.g., nonverbal IQ) may provide important cues to understanding longer-term language outcomes that can be targeted in early intervention.


SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder.
N-linked glycosylation is the most frequent modification of secreted and membrane-bound proteins in eukaryotic cells, disruption of which is the basis of the congenital disorders of glycosylation (CDGs). We describe a new type of CDG caused by mutations in the steroid 5alpha-reductase type 3 (SRD5A3) gene. Patients have mental retardation and ophthalmologic and cerebellar defects. We found that SRD5A3 is necessary for the reduction of the alpha-isoprene unit of polyprenols to form dolichols, required for synthesis of dolichol-linked monosaccharides, and the oligosaccharide precursor used for N-glycosylation. The presence of residual dolichol in cells depleted for this enzyme suggests the existence of an unexpected alternative pathway for dolichol de novo biosynthesis. Our results thus suggest that SRD5A3 is likely to be the long-sought polyprenol reductase and reveal the genetic basis of one of the earliest steps in protein N-linked glycosylation.


Terminalia arjuna in coronary artery disease: ethnopharmacology, pre-clinical, clinical & safety evaluation.
Terminalia arjuna (Roxb.) Wight & Arn. is one of the most popular and beneficial medicinal plants in indigenous system of medicine for the treatment of cardiovascular diseases. This comprehensive review provides latest updates on traditional use, phytochemistry, pharmacological and toxicological data, clinical efficacy and safety of Terminalia arjuna as well as outlined strategies for future research and development to scientifically validate the therapeutic potential of this plant. Information about Terminalia arjuna was collected via a systematic electronic and library search of various indexed and non-indexed journals, some local books and varied articles published on ethnopharmacology, phytochemistry and traditional uses. Various pre-clinical (2000-2014) and clinical studies (1990-2014) have also been considered regarding efficacy and safety profile of Terminalia arjuna. Evidence from various in vitro, in vivo and clinical trials reveal the pleiotropic effects of Terminalia arjuna such as anti-atherogenic, hypotensive, inotropic, anti-inflammatory, anti-thrombotic and antioxidant actions for treatment of various cardiovascular disorders. It is clearly documented that this plant has a good safety profile when used in conjunction with other conventional drugs. However, there is a paucity of data regarding the exact molecular mechanism of its action, appropriate form of drug administration, whether whole crude drug or aqueous or alcoholic extract should be used, toxicological studies and its interaction with other drugs. In conclusion, this review highlights the importance as well as pleiotropic actions and functional aspects of Terminalia arjuna especially in cardiovascular diseases. Though, various pharmacological studies and clinical trials support its benefit in the CVD as per traditional use, new clinical trials using more rigorous state of the art technology and in a larger population setup are warranted to assess the traditional putative efficacy of Terminalia arjuna.


Rare variants in the GABAA receptor subunit ε identified in patients with a wide spectrum of epileptic phenotypes.
Epilepsy belongs to a group of chronic and highly heterogeneous brain disorders. Many types of epilepsy and epileptic syndromes are caused by genetic factors. The neural amino acid y-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the mammalian central nervous system. It regulates activity of channel pores by binding to transmembrane GABA-receptors (GABRs). The GABRs are heteropentamers assembled from different receptor subunits (α1-6, β1-3, γ1-3, δ, ε, θ, π, and ρ1-3). Several epileptic disorders are caused by mutations in genes encoding single GABRs. We applied trio- and single-whole exome sequencing to search for genetic sequence variants associated with a wide range of epileptic phenotypes accompanied by intellectual disability and/or global developmental delay in the investigated patients. We identified four hemizygous sequence variants in the GABAA receptor subunit ε gene (GABRE), including one nonsense (NM_004961.3: c.399C>A, p.Tyr133*), two missense variants (NM_004961.3: c.664G>A, p.Glu222Lys; NM_004961.3: c.1045G>A, p.Val349Ile), and one variant affecting the translation initiation codon (NM_004961.3: c.1A>G, p.Met1?) in four unrelated families. Our clinical and molecular genetic findings suggest that GABRE is a likely candidate gene for epilepsy. Nevertheless, functional studies are necessary to better understand pathogenicity of the GABRE-mutations and their associations with epileptic phenotypes.


Methylenetetrahydrofolate reductase enzyme polymorphisms as maternal risk for Down syndrome among Turkish women.
Advanced maternal age is the only fully accepted risk factor for trisomy 21, while most children with Down syndrome (DS) are born to younger mothers (<35 years). The relationship between chromosomal nondisjunction leading to aneuploidy and folate metabolism has drawn attention in the recent years. In this study, we examined the two polymorphisms in genes encoding the folate metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR), namely, 677C > T and 1298A > C. The prevalence of these variant genotypes in mothers of DS children (case mothers) (n = 152) was compared with controls (n = 91). Frequencies of MTHFR 677C > T genotypes (CC, CT, and TT) and also combination of heterozygous and homozygous variant genotypes (CT or TT) (P = 0.28) demonstrated no difference between the case and control groups. Genotype frequencies of MTHFR 1298A > C (AA, AC, and CC) were similar among the case and control mothers. Variant genotypes of MTHFR 1298A > C (AC or CC) were also insignificant when compared between the two groups. This is yet the largest case-control study conducted for MTHFR 677C > T and also the first to investigate a possible relation with MTHFR 1298A > C. The data presented in this study fail to support the relationship between MTHFR 677C > T and 1298A > C polymorphisms and risk of having a child with DS.


Changing the culture of hand hygiene compliance using a bundle that includes a violation letter.
Hand hygiene is the best method of preventing transmission of infections in health care, but compliance is usually suboptimal. In one hospital, compliance with hand hygiene was improved and sustained using a multifaceted bundle approach. A unique aspect of the bundle was the creation of a violation letter that was sent to and enforced by managers of noncompliant personnel. The letter appeared to be the major factor in raising the hand hygiene compliance rate from 34% to >90% in a 2-year period.


Interleukin-18 induces EMMPRIN expression in primary cardiomyocytes via JNK/Sp1 signaling and MMP-9 in part via EMMPRIN and through AP-1 and NF-kappaB activation.
IL-18 and the extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN) stimulate the expression of proinflammatory cytokines and MMPs and are elevated in myocardial hypertrophy, remodeling, and failure. Here, we report several novel findings in primary cardiomyocytes treated with IL-18. First, IL-18 activated multiple transcription factors, including NF-κB (p50 and p65), activator protein (AP)-1 (cFos, cJun, and JunD), GATA, CCAAT/enhancer-binding protein, myocyte-specific enhancer-binding factor, interferon regulatory factor-1, p53, and specific protein (Sp)-1. Second, IL-18 induced EMMPRIN expression via myeloid differentiation primary response gene 88/IL-1 receptor-associated kinase/TNF receptor-associated factor-6/JNK-dependent Sp1 activation. Third, IL-18 induced a number of MMP genes, particularly MMP-9, at a rapid rate as well as tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-3 at a slower rate. Finally, the IL-18 induction of MMP-9 was mediated in part via EMMPRIN and through JNK- and ERK-dependent AP-1 activation and p38 MAPK-dependent NF-κB activation. These results suggest that the elevated expression of IL-18 during myocardial injury and inflammation may favor EMMPRIN and MMP induction and extracellular matrix degradation. Therefore, targeting IL-18 or its signaling pathways may be of potential therapeutic benefit in adverse remodeling.


Differences in cell division rates drive the evolution of terminal differentiation in microbes.
Multicellular differentiated organisms are composed of cells that begin by developing from a single pluripotent germ cell. In many organisms, a proportion of cells differentiate into specialized somatic cells. Whether these cells lose their pluripotency or are able to reverse their differentiated state has important consequences. Reversibly differentiated cells can potentially regenerate parts of an organism and allow reproduction through fragmentation. In many organisms, however, somatic differentiation is terminal, thereby restricting the developmental paths to reproduction. The reason why terminal differentiation is a common developmental strategy remains unexplored. To understand the conditions that affect the evolution of terminal versus reversible differentiation, we developed a computational model inspired by differentiating cyanobacteria. We simulated the evolution of a population of two cell types -nitrogen fixing or photosynthetic- that exchange resources. The traits that control differentiation rates between cell types are allowed to evolve in the model. Although the topology of cell interactions and differentiation costs play a role in the evolution of terminal and reversible differentiation, the most important factor is the difference in division rates between cell types. Faster dividing cells always evolve to become the germ line. Our results explain why most multicellular differentiated cyanobacteria have terminally differentiated cells, while some have reversibly differentiated cells. We further observed that symbioses involving two cooperating lineages can evolve under conditions where aggregate size, connectivity, and differentiation costs are high. This may explain why plants engage in symbiotic interactions with diazotrophic bacteria.


Endoscopic management of anastomotic leakage after gastrectomy for gastric cancer: how efficacious is it?
Anastomotic leak is a dreadful complication with a high mortality rate. The authors aimed to evaluate the efficacy of endoscopic closure of anastomotic dehiscence after gastrectomy in patients with gastric cancer. The authors retrospectively reviewed 33 patients with anastomotic leakage who had underdone endoscopic treatment among 5249 patients with gastric cancer who underwent radical total or subtotal gastrectomy. Methods of endoscopic closure included clipping with or without detachable snare, fibrosealant, Histoacryl® or stent insertion. Results of endoscopic treatment were categorized as complete, partial closure and failure. The size of the tissue defect was the only factor that had statistically significant differences among the cases with complete closure, partial closure and failure (p = 0.005). For tissue defects smaller than 2 cm in size, complete closure was achieved in 19 (73.1%), partial closure in 5 patients (19.2%) and 2 failed (7.6%). For those larger than 2 cm in size, one (14.3%) was completely closed, four (57.1%) were partially closed and two (28.6%) failed. Endoscopic treatment for anastomotic dehiscence smaller than 2 cm in size had excellent success rate in this study.


Mesenchymal stem/progenitor cells promote the reconstitution of exogenous hematopoietic stem cells in Fancg-/- mice in vivo.
Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow failure and complex congenital anomalies. Although mutations in FA genes result in a characteristic phenotype in the hematopoietic stem/progenitor cells (HSPCs), little is known about the consequences of a nonfunctional FA pathway in other stem/progenitor cell compartments. Given the intense functional interactions between HSPCs and the mesenchymal microenvironment, we investigated the FA pathway on the cellular functions of murine mesenchymal stem/progenitor cells (MSPCs) and their interactions with HSPCs in vitro and in vivo. Here, we show that loss of the murine homologue of FANCG (Fancg) results in a defect in MSPC proliferation and in their ability to support the adhesion and engraftment of murine syngeneic HSPCs in vitro or in vivo. Transplantation of wild-type (WT) but not Fancg(-/-) MSPCs into the tibiae of Fancg(-/-) recipient mice enhances the HSPC engraftment kinetics, the BM cellularity, and the number of progenitors per tibia of WT HSPCs injected into lethally irradiated Fancg(-/-) recipients. Collectively, these data show that FA proteins are required in the BM microenvironment to maintain normal hematopoiesis and provide genetic and quantitative evidence that adoptive transfer of WT MSPCs enhances hematopoietic stem cell engraftment.


Vitamin-D-deficient rickets in Manitoba, 1972-84.
Vitamin-D-deficient rickets still exists in children in Manitoba and adjacent areas. Between 1972 and 1984, 48 cases were documented at Winnipeg Children's Hospital. The patients ranged in age from 1 to 49 months; 40 were Canadian natives (38 Indians and 2 Inuit), most of whom lived in the Island Lake area of northern Manitoba. Of the 48, 16 had clinical signs of rickets, 12 had tetany due to hypocalcemia and 38 had radiologic evidence of rickets. Hypocalcemia was found in 27, and hypophosphatemia in 19; hyperaminoaciduria was found in 7 of 20. All 48 had elevated serum alkaline phosphatase levels. In addition to rickets, 16 patients aged 12 months or more had evidence of malnutrition. Climate and lifestyle in northern areas of the Canadian midwest result in little or no biosynthesis of vitamin D by solar radiation; therefore, adequate dietary vitamin D intake is essential to prevent deficiency. The diets of pregnant women and infants in these areas are deficient in vitamin D. The authors recommend vitamin D supplements for all pregnant women and infants in areas of risk to eradicate this preventable disease.


Review article: Common emergency department presenting complaints of prisoners: A systematic review.
Prisoners are a particularly vulnerable minority group whose healthcare needs and management differ substantially from the general population. The overall burden of disease of prisoners is well documented; however, little is known regarding the aetiology and frequency of prisoners' acute medical complaints requiring an ED visit. Objectives of the review were to identify, review and appraise existing literature regarding prisoners' presentations to EDs. We performed systematic electronic searches in MEDLINE, EMBASE, PsycINFO, PubMed, Cochrane, and Web of Science using MeSH terms and keywords. Two reviewers abstracted data and conducted quality appraisal using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Nine articles met the predefined inclusion criteria. Apart from two European studies in the past 5 years, there is a scarcity of literature primarily addressing the common presenting complaints to EDs by prisoners. Existing studies demonstrated that prisoners have a disproportionately high burden of traumatic, infectious and psychiatric disease requiring emergency treatment. With the increasing number of emergency presentations made by prisoners each year, it is vital that further research is undertaken to identify trends of these acute medical complaints in order to ensure optimal therapeutic outcomes for prisoners.


Home health care nurses as a new channel for smoking cessation treatment: outcomes from project CARES (Community-nurse Assisted Research and Education on Smoking).
Clinical guidelines for smoking cessation may not be sufficient for helping some subgroups of smokers quit. Incorporating smoking cessation into home-based medical care can proactively reach high-risk smokers who may not have access to (or spontaneously seek) smoking cessation. Home health care nurses (N = 98) were randomly assigned to deliver either Motivational Enhancement (ME; Motivational Interviewing + Carbon Monoxide Feedback) or Standard Care (AHCPR Guidelines for smoking cessation) to their patients. Seventy percent of patients were eligible and willing to participate (N = 273; 54% female, mean age = 57 years, 83% Caucasian, 41% < high school education). The study was conducted in Providence, RI, USA from 1998 to 2003. Biochemically verified continuous abstinence rates at the 12-month follow-up were 4.2% (SC) and 8.7% (ME) for intent to treat analyses, and 5.2% (SC) and 11.8% (ME) using all available cases (P > 0.05). ME reported more quit attempts and significantly greater reductions in the number of cigarettes smoked per day at all follow-ups through 12 months of post-treatment (all P values < 0.05). Use of an existing public health channel such as home health care to reach smokers who vary in their motivation to quit could have the potential for large public health impact.


The influence of dietary supplementation with urea on resilience and resistance to infection with Haemonchus contortus.
Previous research has indicated that supplementing an apparently adequate diet with additional protein improves both host resistance and resilience in lambs infected with Haemonchus contortus. The present study tested the influence of supplementation with non-protein nitrogen (urea). Helminth-naive Hampshire Down lambs were given an apparently adequate basal diet or a diet supplemented with urea. The lambs were then infected with Haemonchus contortus for 10 weeks. Supplementation with urea had no discernible effect on resistance to infection; faecal egg counts, worm burdens, worm lengths and mean number of eggs per adult female worm did not differ between the 2 groups. However, lambs on the supplemented diet showed better resilience; they had greater packed red cell volumes, higher plasma albumin concentrations and increased liveweight gain compared to lambs on the basal diet. The loss of appetite following infection was less in lambs fed the urea-supplemented diet. The observed effect of urea supplementation was seemingly due to greater food consumption as well as the better diet.


Effects of exposing chicken eggs to a cell phone in "call" position over the entire incubation period.
The aim of the present study was to assess the effects of exposing fertile chicken eggs to a cell phone repeatedly calling a ten-digit number at 3-min intervals over the entire period of incubation. A pre-experiment was performed first to adjust incubation conditions in an experimental chamber devoid of metallic content and without automatic turning until the overall performance of hatchability was reproducible in the absence of the cell phone. The experimental period consisted of a series of 4 incubations referred to as "replicates". For each replicate, one batch of 60 eggs was exposed to the immediate environment (<or= 25 cm) of a cell phone in the "call" position (exposed group), while another batch of 60 eggs, 1.5m away from the exposed group and also in the incubation chamber, was exposed to a similar cell phone in the "off" position (sham group). For each replicate, 2 other groups each of 60 eggs were also incubated, one in a standard mini-incubator ("Control I" group) and the second in a standard medium size incubator ("Control II" group). Temperature, relative humidity and electromagnetic fields in the experimental chamber were permanently monitored over the entire experiment. A significantly higher percentage of embryo mortality was observed in the "exposed" compared to the "sham" group in 2 of the 4 replicates (p< .05). In comparison with control groups, additional embryo mortality in the exposed group occurred mainly between Days 9 and 12 of incubation but a causal relationship between the intensity of the electric field and embryo mortality could not be established.


Large intestine obstruction complicated with perforation: a rare manifestation of Schistosoma mansoni infection.
The authors report a case of a 25 year old Brazilian man with a history of crampy abdominal pain in the left iliac fossa for 2 weeks, abdominal distention, mucous diarrhea and anorexia. The patient presented signs of hemodynamic instability and a hard mass palpated in the left iliac fossa presented peritoneal irritation. At laparotomy, fecal peritonitis and a punched-out perforation of the midsigmoid colon were found. A left hemicolectomy was performed with terminal colostomy. Specimen examination revealed a thickened rectosigmoid wall, narrow lumen and multiple mucosal polyps. Microscopically, chronic granulomatous colitis with Schistosoma mansoni eggs confirmed the etiology. To the authors' knowledge, this is the first case of obstruction complicated with perforation due to mansoni schistosomiasis reported in the literature.


Comparison of the collagen VI content within the islet-exocrine interface of the head, body, and tail regions of the human pancreas.
Efficient islet isolation depends on the use of collagenase to digest the extracellular matrix within the islet-exocrine interface, the molecular structure of which is poorly understood. Recently it has been reported that transplantable yields of islets can be isolated from the tail segment of the pancreas alone. This study aimed to quantify and compare the amount of collagenase-resistant collagen VI within the islet-exocrine interface of the head, body, and tail of the human pancreas. Human adult pancreata (n = 5) were retrieved from heart-beating donors (age range, 40-62 years; cold ischemia times <10 hours). Tissue blocks from the head, body, and tail region of each pancreas were fixed in formalin and processed for immuno-labelling of collagen VI, which was quantified in the islet-exocrine interface using a Zeiss KS-400 image analysis system. Data were expressed as area of collagen at the interface relative to the islet area. Statistical analysis was done using paired t test. The mean islet areas in the head, body, and tail regions were not significantly different. Collagen VI was uniformly present within the islet-exocrine interface of all regions of the pancreas and was 0.326 +/- 0.064, 0.324 +/- 0.060, and 0.334 +/- 0.052 microm(2)/islet area (P = .441) in the head, body, and tail, respectively. The content of collagen VI within the islet-exocrine interface was uniform throughout all parts of the adult pancreas. Targeting this collagen subtype with novel collagenase blends may result in consistently improved islet yields and enable a wider number of available donor pancreata to be used.