Partner Support for Family Planning and Modern Contraceptive Use in Luanda, Angola.
Husband's/partner's support for family planning may influence a women's modern contraceptive use. Socio-demographic factors, couple communication about family planning, and fertility preferences are known to play a role in contraceptive use. We conducted logistic regression analysis to investigate the relationship between perceived husband's/partner's approval and husband's/partner's encouragement of modern contraceptive use, adjusting for socio-demographic factors and recent couple communication about family planning. We also examined mediating roles potentially played by perceived contraceptive accessibility and contraceptive self-efficacy (using index created by principal component analysis). Perceived husband's/partner's approval was associated with triple the odds of women's modern contraceptive use and remained significantly associated with 1.6 times the odds, after controlling for contraceptive accessibility and contraceptive self-efficacy. Husband's/partner's encouragement, while initially significantly associated with contraceptive use, became non-significant after adjustments for socio-demographic factors and couple communication. Perceived husband's/partner's approval, separate from a woman's sense of self-efficacy and perceived accessibility of contraceptives, appears strongly and positively associated with current modern contraceptive use. Increased couple communication may help women identify their husband's/partner's approval. Difference between the meaning of approval and encouragement should be explored. Interventions involving information education and communication campaigns geared to men and promoting male involvement in family planning could increase contraceptive prevalence.


Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study.
The etiology of autism is unknown. A strong genetic component has been detected but non-genetic factors may also be involved in the etiology. We used data from the Danish Psychiatric Central Register and the Danish Civil Registration System to study some risk factors of autism, including place of birth, parental place of birth, parental age, family history of psychiatric disorders, and paternal identity. A total of 943,664 children younger than ten years were followed from 1994 to 2001; of those, 818 children developed autism. The highest risks of autism were found in siblings of children with autism, or Asperger's syndrome and other pervasive developmental disorders (PDDs), with relative risks of 22 and 13, respectively. The relative risk of autism in the child was about twice as high if the mother had been diagnosed with a psychiatric disorder. The risk of autism was associated with increasing degree of urbanisation of the child's place of birth and with increasing paternal, but not maternal, age. An increased relative risk of 1.4 was found if the mother was born outside Europe, and in children of parents who were born in different countries. The highest risk of autism was found in families with a history of autism, or Asperger's syndrome and other PDDs in siblings, supporting the commonly accepted knowledge that genetic factors are involved in the etiology of autism.


Evaluation of a rapid point-of-care test for the detection of gonococcal infection among female sex workers in Benin.
To assess the validity of the PATH (Seattle, Washington, USA) GC-Check rapid test, a point-of-care immunochromatographic strip test, in the detection of gonococcal infection among female sex workers (FSWs) in Benin. Women consulting consecutively at two FSW-dedicated clinics in Cotonou and Porto Novo (Benin) were recruited over three, 1-month periods between October 2003 and July 2004. After written informed consent, participants were administered a short interview and underwent a speculum examination where two cervical swabs were collected (in a subset of women, a vaginal swab was also collected). One cervical swab and the vaginal swab were immediately tested with the rapid test. The other cervical swab was frozen at -20 degrees C for at most four weeks and then transported to Québec (Canada), where it was tested with the Roche Amplicor CT/NG PCR assay. Samples positive for gonococcal infection were confirmed using a 16SrRNA PCR assay. 1084 FSWs (median age 29 years) participated in the study, of whom 50 (4.6%) had a confirmed gonococcal infection. The sensitivity, specificity, positive and negative predictive values of the rapid test on cervical samples were 70.0% (95% confidence interval (CI) 55.4% to 82.1%), 97.2% (95% CI 96.0% to 98.1%), 54.7% and 98.5%, respectively. The sensitivity of the rapid test on vaginal swabs among 759 women (37 positives for gonococcal infection) was significantly lower than with the cervical swab (54.1%, p = 0.008), whereas the specificity was comparable (98.2%, p = 0.13). The PATH GC-Check test may be as efficient as a gold standard polymerase chain reaction (PCR) test for treating gonococcal infection when taking into account the proportion of women who do not return for their test results. In clinics serving populations with moderate prevalence of this infection, it could significantly reduce over-treatment compared to the syndromic approach.


Cerebrovascular function in patients with chronic obstructive pulmonary disease: the impact of exercise training.
This study examined cerebral blood flow (CBF) and its regulation before and after a short-term periodized aerobic exercise training intervention in patients with chronic obstructive pulmonary disease (COPD). Twenty-eight patients with COPD (forced expiratory volume in 1 s/forced vital capacity < 0.7 and <lower limit of normal) and 24 healthy control subjects participated in the study. Extracranial CBF (duplex ultrasound), middle cerebral artery velocity (MCAv; transcranial Doppler), cerebrovascular reactivity to hypocapnia and hypercapnia, and dynamic cerebral autoregulation (transfer function analysis) were quantified. These tests were repeated in both patients with COPD ( n = 23) and control subjects ( n = 20) after 8 wk of periodized upper and lower body aerobic exercise training (3 sessions/wk). At baseline, global extracranial CBF was comparable between the COPD and control groups (791 ± 290 vs. 658 ± 143 ml/min, P = 0.25); however, MCAv was lower in patients with COPD compared with control subjects (46 ± 9 vs. 53 ± 10 cm/s, P = 0.05). Although there were no group differences in dynamic cerebral autoregulation or the MCAv response to hypercapnia, patients with COPD had a lower MCAv response to hypocapnia compared with control subjects (-1.1 ± 1.5 vs. -1.6 ± 1.3 cm·s-1·mmHg-1, P = 0.02). After aerobic training, absolute peak O2 consumption increased in both groups, with a greater improvement in control subjects (1.7 ± 0.4 vs. 4.1 ± 0.2 ml·kg-1·min-1, respectively, P = 0.001). Despite these improvements in peak O2 consumption, there were no significant alterations in CBF or any measures of cerebrovascular function after exercise training in either group. In conclusion, patients with COPD have a blunted cerebrovascular response to hypocapnia, and 8 wk of aerobic exercise training did not alter cerebrovascular function despite significant improvements in cardiorespiratory fitness. NEW & NOTEWORTHY No study to date has investigated whether exercise training can alter resting cerebral blood flow (CBF) regulation in patients with chronic obstructive pulmonary disease (COPD). This study is the first to assess CBF regulation at rest, before, and after aerobic exercise training in patients with COPD and healthy control subjects. This study demonstrated that while exercise training improved aerobic fitness, it had little effect on CBF regulation in patients with COPD or control subjects.


Differential effects of 1 alpha,25-dihydroxycholecalciferol and 24R,25-dihydroxycholecalciferol on the proliferation and the differentiated phenotype of rabbit costal chondrocytes in culture.
1 alpha,25-Dihydroxycholecalciferol [1,25-(OH)2D3] stimulated the proliferation and DNA synthesis of rabbit costal growth cartilage cells in the logarithmic growth phase in culture. The stimulatory effects of 1,25-(OH)2D3 were observable at a concentration of 10(-10) M and maximal at a concentration of 10(-8) M. On the other hand, 1,25-(OH)2D3 inhibited their expression of the cartilage phenotype, as judged morphologically, histochemically, and biochemically by a decrease in glycosaminoglycan (GAG) synthesis. The inhibition of GAG synthesis was also dose dependent and observable at a concentration of 10(-10) M. 1,25-(OH)2D3 also stimulated the proliferation of resting cartilage cells and inhibited their GAG synthesis, but its effects on these cells were less than those on growth cartilage cells, suggesting that 1,25-(OH)2D3 acts more specifically on growth cartilage cells than on resting cartilage cells. 1,25-(OH)2D3 had no effect on either DNA synthesis or GAG synthesis of growth cartilage cells in confluent cultures. 24R,25-Dihydroxycholecalciferol [24,25-(OH)2D3] had no effect on proliferation, DNA synthesis, or GAG synthesis of growth cartilage cells in the logarithmic growth phase. However, 24,25-(OH)2D3 had no effect on DNA synthesis of these cells in confluent cultures, but stimulated their expression of the cartilage phenotype. The stimulatory effect was dose dependent and maximal at 10(-7) M. Since chondrocytes express their differentiated phenotype as they become confluent in culture, these results suggest that 1,25-(OH)2D3 stimulates the growth of rapidly proliferating chondrocytes with a poorly differentiated phenotype and suppresses their expression of the cartilage phenotype, while 24,25-(OH)2D3 stimulates expression of the differentiated phenotype of highly differentiated chondrocytes.


Nurses' use of non-pharmacological methods in children's postoperative pain management: educational intervention study.
This paper is a report of study of the impact of an educational intervention in pain management on nurses' self-reported use of non-pharmacological methods for children's postoperative pain relief and their perceptions of barriers that limited their use of these methods. Non-pharmacological methods have been shown to be effective in relieving pain; however, many barriers, including lack of knowledge, limit nurses' use of these methods. Pain education is a promising strategy for changing nursing practice, but only a few authors have examined the effectiveness of educational interventions for nurses to help relieve children's postoperative pain. A quasi-experimental one-group pre- and post-test design was used. Questionnaire surveys were conducted with a convenience sample of 108 Registered Nurses in two public hospitals in Singapore in 2008. Statistically significant increases were found in nurses' self-reported use of imagery, positive reinforcement, thermal regulation, massage and positioning in the postintervention survey. Before the intervention, these methods were less frequently used compared to other methods. Heavy workload/lack of time and the child's inability to cooperate were the most commonly reported barriers at pre- and post-test. The educational intervention had a positive effect on nurses' use of several non-pharmacological methods. Regular dissemination of updated information to nurses on these pain management methods is recommended to maintain the positive changes. Nevertheless, education alone was not sufficient to optimize nurses' use of these methods, as various barriers limited their practice.


The muscle chloride channel ClC-1 is not directly regulated by intracellular ATP.
ClC-1 belongs to the gene family of CLC Cl(-) channels and Cl(-)/H(+) antiporters. It is the major skeletal muscle chloride channel and is mutated in dominant and recessive myotonia. In addition to the membrane-embedded part, all mammalian CLC proteins possess a large cytoplasmic C-terminal domain that bears two so-called CBS (from cystathionine-beta-synthase) domains. Several studies indicate that these domains might be involved in nucleotide binding and regulation. In particular, Bennetts et al. (J. Biol. Chem. 2005. 280:32452-32458) reported that the voltage dependence of hClC-1 expressed in HEK cells is regulated by intracellular ATP and other nucleotides. Moreover, very recently, Bennetts et al. (J. Biol. Chem. 2007. 282:32780-32791) and Tseng et al. (J. Gen. Physiol. 2007. 130:217-221) reported that the ATP effect was enhanced by intracellular acidification. Here, we show that in striking contrast with these findings, human ClC-1, expressed in Xenopus oocytes and studied with the inside-out configuration of the patch-clamp technique, is completely insensitive to intracellular ATP at concentrations up to 10 mM, at neutral pH (pH 7.3) as well as at slightly acidic pH (pH 6.2). These results have implications for a general understanding of nucleotide regulation of CLC proteins and for the physiological role of ClC-1 in muscle excitation.


RGG: a general GUI Framework for R scripts.
R is the leading open source statistics software with a vast number of biostatistical and bioinformatical analysis packages. To exploit the advantages of R, extensive scripting/programming skills are required. We have developed a software tool called R GUI Generator (RGG) which enables the easy generation of Graphical User Interfaces (GUIs) for the programming language R by adding a few Extensible Markup Language (XML) - tags. RGG consists of an XML-based GUI definition language and a Java-based GUI engine. GUIs are generated in runtime from defined GUI tags that are embedded into the R script. User-GUI input is returned to the R code and replaces the XML-tags. RGG files can be developed using any text editor. The current version of RGG is available as a stand-alone software (RGGRunner) and as a plug-in for JGR. RGG is a general GUI framework for R that has the potential to introduce R statistics (R packages, built-in functions and scripts) to users with limited programming skills and helps to bridge the gap between R developers and GUI-dependent users. RGG aims to abstract the GUI development from individual GUI toolkits by using an XML-based GUI definition language. Thus RGG can be easily integrated in any software. The RGG project further includes the development of a web-based repository for RGG-GUIs. RGG is an open source project licensed under the Lesser General Public License (LGPL) and can be downloaded freely at (http://rgg.r-forge.r-project.org).


Cocaine self-administration selectively decreases noradrenergic regulation of metabotropic glutamate receptor-mediated inhibition in dopamine neurons.
Stimulant drugs of abuse have several effects on neural activity, including altering the excitability of dopamine neurons via the noradrenergic and glutamatergic systems. Thus, an interaction between noradrenergic and glutamatergic systems may play a role in drug-seeking behavior. Although many of the direct pharmacological effects of psychostimulants on dopamine neuron physiology are well established, the neurophysiological bases of drug-seeking behavior have yet to be fully elucidated. The present study measured short-term (3 d) and long-term (14 d) access to cocaine, by self-administration or passive exposure, and the regulation of metabotropic glutamate receptor (mGluR)-mediated inhibition of dopamine cells in rat midbrain slices. The results indicated that alpha-adrenoreceptor modulation of the mGluR-mediated inhibition is selectively reduced in animals that self-administered cocaine for 3 d. This effect was not observed in slices from either yoked cocaine animals, which were given cocaine in an amount and pattern equal to that used for the self-administering animals, or saline control animals. However, after 14 d of cocaine, alpha-adrenoreceptor regulation of the mGluR-mediated inhibition was equally reduced in both self-administering and yoked cocaine animals relative to saline controls. The results suggest that alpha-adrenoreceptor regulation of the mGluR-mediated inhibition is an adaptive cellular mechanism involved in early cocaine self-administration that is distinct from a direct pharmacological effect of cocaine on dopamine neurons. The noradrenergic system could therefore serve to alter the reward value of stimuli that have significant effects on dopamine neuron firing pattern through mGluRs.


Media distortion of the public's perception of recidivism and psychiatric rehabilitation.
The public's perception about the success or failure of psychiatric rehabilitation is frequently dependent upon information received through the news media. The primary objective of this report is to present an example of how the news media can distort public perceptions of treatment outcome. Verbatim quotations were presented from a television news series that alleged criminal recidivism by nine patients purportedly treated for various paraphilias at a large, community-based sexual disorders clinic. Brief case vignettes about each of the nine were then reviewed. This allowed for comparisons between what the media had alleged and what had actually occurred. Two of the nine cases were relatively minor instances of recidivism involving no genital contact, although the media presentation had either failed to report this or had suggested otherwise. A third case of alleged recidivism involved a patient who was evaluated but never actually treated by the clinic in the community. A fourth patient had refused recommended clinic treatment upon prison release, and a fifth patient had been discharged from treatment at the clinic because of noncompliance years before recidivating. Other cases presented contained additional misleading information. None of the nine cases was reported by the media in the context of a balanced approach that included treatment successes. Clinic staff were constrained from responding publicly to correct certain misinformation because of patient-psychiatrist privilege. Inaccurate media presentations about psychiatric rehabilitation that ignore treatment successes and focus only on alleged failures do a disservice to patients, mental health workers, and society at large.


Divergent genetic selection for residual feed intake impacts mitochondria reactive oxygen species production in pigs.
The objective of this study was to determine the extent to which genetic selection for residual feed intake (RFI) impacts electron leakage and reactive oxygen species (ROS) production in mitochondria from muscle and liver tissue. Understanding how genetic selection for RFI impacts animal physiology and growth efficiency is of the utmost importance as the world population increases. Production efficiency is tied directly to energy use. Mitochondria were used in this study because they produce 90% of the ATP in the body and use a large majority of dietary energy. Mitochondria were isolated from both muscle and liver tissue from pigs genetically selected for RFI (n = 8 per RFI line; 34 ± 4 kg). A 2,7-dichlorofluorscein diacetate assay was used to detect differences in hydrogen peroxide production between the more efficient low RFI line and the less efficient high RFI line. Our hypothesis was that greater efficiency would be linked to less ROS production from the mitochondria. There was less ROS production in mitochondria from the white portion of the semitendinosus in the low RFI line compared with the high RFI line, when both NADH and Flavin Adenine Dinucleotide (FADH2) energy substrates were used (glutamate and succinate, respectively). Additionally, mitochondria from the red portion of the semitendinosus in the low RFI line had less ROS production when succinate was used as an energy substrate (P < 0.05). A positive correlation was observed between RFI and ROS in mitochondria from the LM. These data indicate genetic selection for RFI may influence mitochondrial ROS production and efficiency of pork production.


Broad Hepatitis C Treatment Scenarios Return Substantial Health Gains, But Capacity Is A Concern.
Treatment of hepatitis C virus, the most common chronic viral infection in the United States, has historically suffered from challenges including serious side effects, low efficacy, and ongoing transmission and reinfection. Recent innovations have produced breakthrough therapies that are effective in more than 90 percent of patients. These treatments could dramatically reduce the virus's prevalence but are costly. To quantify the benefit of these treatments to society, including the value of reduced transmission, we estimated the effects of several hepatitis C treatment strategies on cost and population health. Treating patients at all disease stages could generate $610-$1,221 billion in additional quality-adjusted life-years, plus an additional $139 billion in saved medical expenditures over fifty years, and minimize the disease burden, but up-front treatment costs would exceed $150 billion. An intermediate scenario--treating 5 percent of the infected population annually, regardless of patients' disease stages--would also return substantial benefits and would be much more affordable under current financing schemes.


4D CT lung ventilation images are affected by the 4D CT sorting method.
Four-dimensional (4D) computed tomography (CT) ventilation imaging is a novel promising technique for lung functional imaging. The current standard 4D CT technique using phase-based sorting frequently results in artifacts, which may deteriorate the accuracy of ventilation imaging. The purpose of this study was to quantify the variability of 4D CT ventilation imaging due to 4D CT sorting. 4D CT image sets from nine lung cancer patients were each sorted by the phase-based method and anatomic similarity-based method, designed to reduce artifacts, with corresponding ventilation images created for each method. Artifacts in the resulting 4D CT images were quantified with the artifact score which was defined based on the difference between the normalized cross correlation for CT slices within a CT data segment and that for CT slices bordering the interface between adjacent CT data segments. The ventilation variation was quantified using voxel-based Spearman rank correlation coefficients for all lung voxels, and Dice similarity coefficients (DSC) for the spatial overlap of low-functional lung volumes. Furthermore, the correlations with matching single-photon emission CT (SPECT) ventilation images (assumed ground truth) were evaluated for three patients to investigate which sorting method provides higher physiologic accuracy. Anatomic similarity-based sorting reduced 4D CT artifacts compared to phase-based sorting (artifact score, 0.45 ± 0.14 vs 0.58 ± 0.24, p = 0.10 at peak-exhale; 0.63 ± 0.19 vs 0.71 ± 0.31, p = 0.25 at peak-inhale). The voxel-based correlation between the two ventilation images was 0.69 ± 0.26 on average, ranging from 0.03 to 0.85. The DSC was 0.71 ± 0.13 on average. Anatomic similarity-based sorting yielded significantly fewer lung voxels with paradoxical negative ventilation values than phase-based sorting (5.0 ± 2.6% vs 9.7 ± 8.4%, p = 0.05), and improved the correlation with SPECT ventilation regionally. The variability of 4D CT ventilation imaging due to 4D CT sorting was moderate overall and substantial in some cases, suggesting that 4D CT artifacts are an important source of variations in 4D CT ventilation imaging. Reduction of 4D CT artifacts provided more physiologically convincing and accurate ventilation estimates. Further studies are needed to confirm this result.


Contribution of polysynaptic pathways in the mediation and plasticity of Aplysia gill and siphon withdrawal reflex: evidence for differential modulation.
The gill and siphon withdrawal (GSW) reflex of Aplysia is centrally mediated by a monosynaptic and a polysynaptic pathway between sensory and motor neurons. The first objective of this article was to evaluate quantitatively the relative importance of these two components in the mediation of the GSW reflex. We have used an artificial sea water (ASW) solution containing a high concentration of divalent cations to raise the action potential threshold of the interneurons without affecting the monosynaptic component of the reflex (2:1 ASW). Compound EPSPs induced in gill or siphon motor neurons by direct stimulation of the siphon nerve or by tactile stimulation of the siphon skin were reduced by more than 75% in 2:1 ASW. These results indicate that interneurons intercalated between sensory and motor neurons are responsible for a considerable proportion of the afferent input to the motor neurons of the reflex. The second objective of this article was to compare the modulation of the monosynaptic and polysynaptic pathways. We have evaluated their respective contribution in sensitization of the GSW reflex by testing the effects of two neuromodulators of the reflex, 5-HT and small cardioactive peptide B (SCPB). We found that these two neuromodulators have a differential action on the two components of the GSW neuronal network. The polysynaptic pathway was more facilitated than the monosynaptic pathway by the neuropeptide SCPB. By contrast, 5-HT displayed an opposite selectivity. These results suggest that the polysynaptic component of the neuronal network underlying the GSW reflex is very important for its mediation. The data also indicate that the monosynaptic and polysynaptic components of the reflex can be differentially modulated. The diversity of modulatory actions at various sites of the GSW network should be relevant for learning-associated modifications in the intact animal.


NGF causes TrkA to specifically attract microtubules to lipid rafts.
Membrane protein sorting is mediated by interactions between proteins and lipids. One mechanism that contributes to sorting involves patches of lipids, termed lipid rafts, which are different from their surroundings in lipid and protein composition. Although the nerve growth factor (NGF) receptors, TrkA and p75(NTR) collaborate with each other at the plasma membrane to bind NGF, these two receptors are endocytosed separately and activate different cellular responses. We hypothesized that receptor localization in membrane rafts may play a role in endocytic sorting. TrkA and p75(NTR) both reside in detergent-resistant membranes (DRMs), yet they responded differently to a variety of conditions. The ganglioside, GM1, caused increased association of NGF, TrkA, and microtubules with DRMs, but a decrease in p75(NTR). When microtubules were induced to polymerize and attach to DRMs by in vitro reactions, TrkA, but not p75(NTR), was bound to microtubules in DRMs and in a detergent-resistant endosomal fraction. NGF enhanced the interaction between TrkA and microtubules in DRMs, yet tyrosine phosphorylated TrkA was entirely absent in DRMs under conditions where activated TrkA was detected in detergent-sensitive membranes and endosomes. These data indicate that TrkA and p75(NTR) partition into membrane rafts by different mechanisms, and that the fraction of TrkA that associates with DRMs is internalized but does not directly form signaling endosomes. Rather, by attracting microtubules to lipid rafts, TrkA may mediate other processes such as axon guidance.


Evolution and allometry of calcaneal elongation in living and extinct primates.
Specialized acrobatic leaping has been recognized as a key adaptive trait tied to the origin and subsequent radiation of euprimates based on its observed frequency in extant primates and inferred frequency in extinct early euprimates. Hypothesized skeletal correlates include elongated tarsal elements, which would be expected to aid leaping by allowing for increased rates and durations of propulsive acceleration at takeoff. Alternatively, authors of a recent study argued that pronounced distal calcaneal elongation of euprimates (compared to other mammalian taxa) was related primarily to specialized pedal grasping. Testing for correlations between calcaneal elongation and leaping versus grasping is complicated by body size differences and associated allometric affects. We re-assess allometric constraints on, and the functional significance of, calcaneal elongation using phylogenetic comparative methods, and present an evolutionary hypothesis for the evolution of calcaneal elongation in primates using a Bayesian approach to ancestral state reconstruction (ASR). Results show that among all primates, logged ratios of distal calcaneal length to total calcaneal length are inversely correlated with logged body mass proxies derived from the area of the calcaneal facet for the cuboid. Results from phylogenetic ANOVA on residuals from this allometric line suggest that deviations are explained by degree of leaping specialization in prosimians, but not anthropoids. Results from ASR suggest that non-allometric increases in calcaneal elongation began in the primate stem lineage and continued independently in haplorhines and strepsirrhines. Anthropoid and lorisid lineages show stasis and decreasing elongation, respectively. Initial increases in calcaneal elongation in primate evolution may be related to either development of hallucal-grasping or a combination of grasping and more specialized leaping behaviors. As has been previously suggested, subsequent increases in calcaneal elongation are likely adaptations for more effective acrobatic leaping, highlighting the importance of this behavior in early euprimate evolution.


Identity-driven differences in stakeholder concerns about hunting wolves.
Whereas past wolf management in the United States was restricted to recovery, managers must now contend with publicly contentious post-recovery issues including regulated hunting seasons. Understanding stakeholder concerns associated with hunting can inform stakeholder engagement, communication, and policy development and evaluation. Social identity theory (SIT) has been used to understand how groups interact, why they conflict, and how collaboration may be achieved. Applying SIT to stakeholder conflicts about wolf hunting may help delineate groups according to their concern about, support for or opposition to the policy choice of hunting wolves. Our objective was to assess concerns about hunting as a tool to resolve conflict in Michigan, using SIT as a framework. We used a mixed-modal sampling approach (e.g., paper, Internet) with wolf hunting-related public meeting participants in March 2013. Survey questions focused on 12 concerns previously identified as associated with hunting as a management tool to resolve conflict. Respondents (n = 666) cared greatly about wolves but were divided over hunting wolves. Wolf conflicts, use of science in policy decisions, and maintaining a wolf population were the highest ranked concerns. Principle components analysis reduced concerns into three factors that explained 50.7% of total variance; concerns crystallized over justifications for hunting. General linear models revealed a lack of geographic influence on care, fear and support for hunting related to wolves. These findings challenge assumptions about regional differences and suggest a strong role for social identity in driving dichotomized public perceptions in wildlife management.


Regulation of primate angiotensin II receptors during altered sodium intake.
In the rat, angiotensin II receptors of the adrenal glomerulosa and smooth muscle undergo reciprocal regulatory changes that parallel the changes in target cell sensitivity to angiotensin II during altered sodium intake. In primates, the relative importance of angiotensin II receptor regulation during sodium-induced changes in angiotensin II sensitivity is not clear. To evaluate the role of angiotensin II receptor regulation in the primate, we analyzed the changes in angiotensin II receptors of adrenal and bladder membrane-rich particles after 4 to 6 days of high or low sodium intake in the monkey (Macaca fascicularis). Consistent with the decreased pressor response to angiotensin II, smooth muscle angiotensin II receptors were fewer in sodium-restricted monkeys (93 +/- 17 fmol/mg) than in sodium-loaded monkeys (171 +/- 6 fmol/mg). However, in contrast to the rat, changes in zona glomerulosa angiotensin II receptors in monkey adrenal were similar to those in smooth muscle, decreasing with sodium restriction and increasing with sodium loading (344 +/- 64 and 660 +/- 68 fmol/mg, respectively). There was no change in angiotensin II receptor affinity in either smooth muscle or adrenal particles during altered sodium intake. Concomitant with the decrease in adrenal angiotensin II receptors, 18-hydroxylase activity was increased twofold in adrenal mitochondria from sodium-restricted monkeys (74 +/- 8 fmol/mg/min) compared with sodium-loaded animals (28 +/- 11 fmol/mg/min). The increased sensitivity of the primate adrenal to angiotensin II despite a fall in angiotensin II receptors indicates that full activation of steroidogenesis by angiotensin II can be maintained with partial receptor occupancy.(ABSTRACT TRUNCATED AT 250 WORDS)


Healthcare personnel attire in non-operating-room settings.
Healthcare personnel (HCP) attire is an aspect of the medical profession steeped in culture and tradition. The role of attire in cross-transmission remains poorly established, and until more definitive information exists priority should be placed on evidence-based measures to prevent healthcare-associated infections (HAIs). This article aims to provide general guidance to the medical community regarding HCP attire outside the operating room. In addition to the initial guidance statement, the article has 3 major components: (1) a review and interpretation of the medical literature regarding (a) perceptions of HCP attire (from both HCP and patients) and (b) evidence for contamination of attire and its potential contribution to cross-transmission; (2) a review of hospital policies related to HCP attire, as submitted by members of the Society for Healthcare Epidemiology of America (SHEA) Guidelines Committee; and (3) a survey of SHEA and SHEA Research Network members that assessed both institutional HCP attire policies and perceptions of HCP attire in the cross-transmission of pathogens. Recommendations for HCP attire should attempt to balance professional appearance, comfort, and practicality with the potential role of apparel in the cross-transmission of pathogens. Although the optimal choice of HCP attire for inpatient care remains undefined, we provide recommendations on the use of white coats, neckties, footwear, the bare-below-the-elbows strategy, and laundering. Institutions considering these optional measures should introduce them with a well-organized communication and education effort directed at both HCP and patients. Appropriately designed studies are needed to better define the relationship between HCP attire and HAIs.


Determining the level of evidence for the effectiveness of spinal manipulation in upper limb pain: A systematic review and meta-analysis.
The use of spinal manipulation (SM) for upper limb pain has been advocated based on the concept of regional interdependence. However, its evidence has not been established. To determine the level of evidence for the effectiveness of SM in patients with upper limb pain as part of the concept of regional interdependence. MeSH and Key words representing two broad subject areas: SM and upper limb disorders were used to conduct an electronic search in sixteen electronic databases. Randomized controlled trials and/or controlled clinical trials investigating the effects of SM in patients with upper limb pain were included. Studies including pain in the neck or scapular region and those using spinal mobilization were excluded. Meta-analysis was conducted to examine the effects of SM on upper limb pain. The overall quality of evidence was assessed using the GRADE system. Out of 3307 studies, six trials met inclusion criteria for this review. Of these, three studies were included in meta-analysis. Meta-analysis results suggested there were no statistical differences between SM and other interventions in the effects on reducing upper limb pain. The overall quality of evidence was very low. The number of studies regarding the current topic is limited. There is very low quality evidence that SM is not better nor inferior than other interventions in the management of upper limb pain.


A statistical model to detect asymptomatic infectious individuals with an application in the Phytophthora alni-induced alder decline.
In some diseases-in particular, tree root infection-stages of infection and inoculum production level and timing are not readily observable because of uncertainty or time lags in symptom appearance. Here, we pose a criterion, based on relative hazard of disease symptoms, to discriminate between healthy and asymptomatic infected individuals. We design a statistical procedure to estimate the criterion for a 6-year survey of alder decline along a northeastern French river. Individual tree symptom hazard was modeled with Cox's regression model, taking estimation of local infection pressure as a risk factor. From an inoculum production experiment, we thereafter assessed the inoculum production level of target trees, including symptomatic and asymptomatic trees ranked according to their symptoms hazard. Using receiver operating characteristic methods, we first evaluated the criterion performance and determined the discrimination threshold to sort out asymptomatic individuals into healthy and infected. Then, we highlighted the fact that the infected asymptomatic trees were among the major inoculum producers whereas severely declining and dead trees were found to be poor inoculum sources.


Efficient Cancer Detection Using Multiple Neural Networks.
The inspection of live excised tissue specimens to ascertain malignancy is a challenging task in dermatopathology and generally in histopathology. We introduce a portable desktop prototype device that provides highly accurate neural network classification of malignant and benign tissue. The handheld device collects 47 impedance data samples from 1 Hz to 32 MHz via tetrapolar blackened platinum electrodes. The data analysis was implemented with six different backpropagation neural networks (BNN). A data set consisting of 180 malignant and 180 benign breast tissue data files in an approved IRB study at the Aurora Medical Center, Milwaukee, WI, USA, were utilized as a neural network input. The BNN structure consisted of a multi-tiered consensus approach autonomously selecting four of six neural networks to determine a malignant or benign classification. The BNN analysis was then compared with the histology results with consistent sensitivity of 100% and a specificity of 100%. This implementation successfully relied solely on statistical variation between the benign and malignant impedance data and intricate neural network configuration. This device and BNN implementation provides a novel approach that could be a valuable tool to augment current medical practice assessment of the health of breast, squamous, and basal cell carcinoma and other excised tissue without requisite tissue specimen expertise. It has the potential to provide clinical management personnel with a fast non-invasive accurate assessment of biopsied or sectioned excised tissue in various clinical settings.


How to fulfill residents' training needs and public service missions in outpatient general internal medicine? An observational pilot study.
QUESTION UNDER STUDY/PRINCIPLES: Ambulatory care is a mandatory component of post-graduate training in general internal medicine. Academic outpatient clinics face challenges in training residents in terms of exposure to sufficient patient case-mix, diversity of clinical activities and continuity of care while fulfilling their mission to provide care to vulnerable populations. We report the development and evaluation of a new postgraduate curriculum in ambulatory care in Geneva, Switzerland, designed to overcome such challenges. The content of learning activities was adapted to core competencies and learning objectives. In the new 2-year curriculum, residents had their working week divided into 2½ days of continuity clinic over two years, and 2½ days of 6 to 12 months rotations (e.g., walk-in clinics). Team work was consolidated through the creation of subunits including an attending physician, 1-2 senior residents during one year and 6- to 8 residents, who met in bi-monthly meetings with other health professionals. In both local and national surveys, residents and senior residents expressed an overall global satisfaction with the new curriculum. Nursing and administrative staff were less satisfied, because of reduced residents' time in each unit. Interprofessional meetings were highly appreciated for both patient care and team building. Management of residents' absences became more complex. The new curriculum met its goals in gaining residents' satisfaction and in reinforcing interprofessional collaboration although management of human resources became more complex. It also gave insights into challenges to be addressed when disseminating a new curriculum, such as strong leadership, educational expertise and management skills and tools.


Resuscitation and transfusion management in trauma patients: emerging concepts.
Severe trauma is associated with hemorrhage, coagulopathy and transfusion of blood and blood products, all associated with considerable mortality and morbidity. The aim of this review is to focus on resuscitation, transfusion strategies and the management of bleeding in trauma as well as to emphasize on why coagulation has to be monitored closely and to discuss the rationale of modern and future transfusion strategies. Coagulopathy and uncontrolled bleeding remain leading causes of death in trauma, lead to blood transfusions and increased mortality as it has been recently shown that blood transfusion per se results in an adverse outcome. In the last years, damage control resuscitation, a combination of permissive hypotension, hemostatic resuscitation and damage control surgery, has been introduced to treat severely traumatized patients in hemorrhagic shock. Goals of treatment in trauma patients remain avoiding metabolic acidosis, hypothermia, treating coagulopathy and stabilizing the patient as soon as possible. The place of colloids and crystalloids in trauma resuscitation as well as the role of massive transfusion protocols with a certain FFP : RBC ratio and even platelets have to be reevaluated. Close monitoring of bleeding and coagulation in trauma patients allows goal-directed transfusions and thereby optimizes the patient's coagulation, reduces the exposure to blood products, reduces costs and may improve clinical outcome.


The deployment of intersensory selective attention: a high-density electrical mapping study of the effects of theanine.
: Ingestion of the nonproteinic amino acid theanine (5-N-ethylglutamine) has been shown to increase oscillatory brain activity in the so-called alpha band (8-14 Hz) during resting electroencephalographic recordings in humans. Independently, alpha band activity has been shown to be a key component in selective attentional processes. Here, we set out to assess whether theanine would cause modulation of anticipatory alpha activity during selective attentional deployments to stimuli in different sensory modalities, a paradigm in which robust alpha attention effects have previously been established. : Electrophysiological data from 168 scalp electrode channels were recorded while participants performed a standard intersensory attentional cuing task. : As in previous studies, significantly greater alpha band activity was measured over parieto-occipital scalp for attentional deployments to the auditory modality than to the visual modality. Theanine ingestion resulted in a substantial overall decrease in background alpha levels relative to placebo while subjects were actively performing this demanding attention task. Despite this decrease in background alpha activity, attention-related alpha effects were significantly greater for the theanine condition. : This increase of attention-related anticipatory alpha over the right parieto-occipital scalp suggests that theanine may have a specific effect on the brain's attention circuitry. We conclude that theanine has clear psychoactive properties, and that it represents a potentially interesting, naturally occurring compound for further study, as it relates to the brain's attentional system.


Efficient CD28 signalling leads to increases in the kinase activities of the TEC family tyrosine kinase EMT/ITK/TSK and the SRC family tyrosine kinase LCK.
Optimal T cell activation requires crosslinking of the T cell receptor (TCR) concurrently with an accessory receptor, most efficiently CD28. Crosslinking of CD28 leads to increased interleukin 2 (IL2) production, inhibition of anergy and prevention of programmed cell death. Crosslinking of CD28 leads to rapid increases in tyrosine phosphorylation of specific intracellular substrates including CD28 itself. Since CD28 does not encode an intrinsic tyrosine kinase domain, CD28 must activate an intracellular tyrosine kinase(s). Indeed, crosslinking of CD28 increases the activity of the intracellular tyrosine kinases EMT/ITK and LCK. The phosphatidylinositol 3-kinase (PI3K) and GRB2 binding site in CD28 is dispensable for optimal IL2 production in Jurkat T cells. We demonstrate herein that murine Y170 (equivalent to human Y173) in CD28 is also dispensable for activation of the SRC family tyrosine kinase LCK and the TEC family tyrosine kinase EMT/ITK. In contrast, the distal three tyrosines in CD28 are required for optimal IL2 production as well as for optimal activation of the LCK and EMT/ITK tyrosine kinases. The distal three tyrosines of CD28, however, are not required for recruitment of PI3K to CD28. Furthermore, PI3K is recruited to CD28 in JCaM1 cells which lack LCK and in which EMT/ITK is not activated by ligation of CD28. Thus optimal activation of LCK or EMT/ITK is not obligatory for recruitment of PI3K to CD28 and thus is also not required for tyrosine phosphorylation of the YMNM motif in CD28. Taken together the data indicate that the distal three tyrosines in CD28 are integral to the activation of LCK and EMT/ITK and for subsequent IL2 production.


Annual and Perennial Alleyway Cover Crops Vary in Their Effects on Pratylenchus penetrans in Pacific Northwest Red Raspberry (Rubus idaeus).
Cover crops can provide many benefits to agroecosystems, such as lessening soil erosion and increasing water infiltration. However, cover crop use is not common in established red raspberry (Rubus idaeus) fields in the Pacific Northwest. Raspberry growers are concerned about resource competition between the cover crop and raspberry crop, as well as increasing population densities of the plant-parasitic nematode Pratylenchus penetrans, which has a wide host range and has been shown to reduce raspberry plant vigor and yield. A 2-yr study was conducted in an established 'Meeker' raspberry field in northwest Washington to evaluate the effects of nine alleyway cover crops, mowed weed cover, and the industry standard of bare cultivated soil on P. penetrans population dynamics, raspberry yield, and fruit quality. The host status for P. penetrans of cover crops included in the field experiment, as well as Brassica juncea 'Pacific Gold' and Sinapis alba 'Ida Gold', was also evaluated in greenhouse experiments. In the field experiment, P. penetrans population densities did not increase in alleyway cover crop roots over time or in alleyway soil surrounding cover crop roots (means range from 0 to 116 P. penetrans/100 g of soil) compared with the bare cultivated control (means range from 2 to 55 P. penetrans/100 g of soil). Pratylenchus penetrans populations did not increase over time in raspberry grown adjacent to alleyways with cover crops (means range from 1,081 to 6,120 P. penetrans/g of root) compared with those grown adjacent to bare cultivated soil alleyways (means range from 2,391 to 5,536 P. penetrans/g of root). Raspberry grown adjacent to bare cultivated soil did not have significantly higher yield or fruit quality than raspberry grown adjacent to cover crops in either year of the experiment. In the greenhouse assays, 'Norwest 553' wheat and a perennial ryegrass mix were poor hosts for P. penetrans, whereas 'Nora' and 'TAM 606' oat and 'Pacific Gold' and 'Ida Gold' mustard were good hosts. These results support the idea that the potential benefits of alleyway cover crops outweigh the potential risk of increasing P. penetrans population densities and do not compromise raspberry yield or fruit quality.


Learning reward frequency over reward probability: A tale of two learning rules.
Learning about the expected value of choice alternatives associated with reward is critical for adaptive behavior. Although human choice preferences are affected by the presentation frequency of reward-related alternatives, this may not be captured by some dominant models of value learning, such as the delta rule. In this study, we examined whether reward learning is driven more by learning the probability of reward provided by each option, or how frequently each option has been rewarded, and assess how well models based on average reward (e.g. the delta model) and models based on cumulative reward (e.g. the decay model) can account for choice preferences. In a binary-outcome choice task, participants selected between pairs of options that had reward probabilities of 0.65 (A) versus 0.35 (B) or 0.75 (C) versus 0.25 (D). Crucially, during training there were twice the number of AB trials as CD trials, such that option A was associated with higher cumulative reward, while option C gave higher average reward. Participants then decided between novel combinations of options (e.g., AC). Most participants preferred option A over C, a result predicted by the Decay model, but not the Delta model. We also compared the Delta and Decay models to both more simplified as well as more complex models that assumed additional mechanisms, such as representation of uncertainty. Overall, models that assume learning about cumulative reward provided the best account of the data.


Proteome-Wide Effect of 17-β-Estradiol and Lipoxin A4 in an Endometriotic Epithelial Cell Line.
Endometriosis affects approximately 10% of women of reproductive age. This chronic, gynecological inflammatory disease results in a decreased quality of life for patients, with the main symptoms including chronic pelvic pain and infertility. The steroid hormone 17-β Estradiol (E2) plays a key role in the pathology. Our previous studies showed that the anti-inflammatory lipid Lipoxin A4 (LXA4) acts as an estrogen receptor-alpha agonist in endometrial epithelial cells, inhibiting certain E2-mediated effects. LXA4 also prevents the progression of endometriosis in a mouse model via anti-proliferative mechanisms and by impacting mediators downstream of ER signaling. The aim of the present study was therefore to examine global proteomic changes evoked by E2 and LXA4 in endometriotic epithelial cells. E2 impacted a greater number of proteins in endometriotic epithelial cells than LXA4. Interestingly, the combination of E2 and LXA4 resulted in a reduced number of regulated proteins, with LXA4 mediating a suppressive effect on E2-mediated signaling. These proteins are involved in diverse pathways of relevance to endometriosis pathology and metabolism, including mRNA translation, growth, proliferation, proteolysis, and immune responses. In summary, this study sheds light on novel pathways involved in endometriosis pathology and further understanding of signaling pathways activated by estrogenic molecules in endometriotic epithelial cells.


Transfusion outcomes in patients undergoing coronary artery bypass grafting treated with prasugrel or clopidogrel: TRITON-TIMI 38 retrospective data analysis.
Coronary artery bypass grafting-related bleeding and associated transfusion is a concern with dual antiplatelet therapy in patients with acute coronary syndromes. The objective of the present study was to characterize a potential risk-adjusted difference in transfusion requirements between prasugrel and clopidogrel cohorts. The data from 422 patients undergoing isolated coronary artery bypass grafting from the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 were analyzed retrospectively. We found no difference in baseline transfusion risk scores between cohorts. As predicted, the number of units of red blood cells transfused perioperatively correlated with the transfusion risk score (P < .0001). Overall, the 12-hour chest tube drainage volumes and platelet transfusion rates in the prasugrel cohort were significantly greater. However, no statistically significant differences were found in the number of red blood cell transfusions, total hemostatic components transfused, or total blood donor exposure. A significantly greater number of platelet units were transfused postoperatively in the prasugrel patients who underwent surgery within 5 days or less after withdrawal of drug. In an analysis adjusted for the predicted risk of mortality, total donor exposure was not associated with increased mortality. The use of prasugrel compared with clopidogrel was associated with greater 12-hour chest tube drainage volumes and platelet transfusion rates but without any significant differences in red blood cell transfusions, total hemostatic components transfused, or total blood donor exposure.


A ranking index for quality assessment of forensic DNA profiles forensic DNA profiles.
Assessment of DNA profile quality is vital in forensic DNA analysis, both in order to determine the evidentiary value of DNA results and to compare the performance of different DNA analysis protocols. Generally the quality assessment is performed through manual examination of the DNA profiles based on empirical knowledge, or by comparing the intensities (allelic peak heights) of the capillary electrophoresis electropherograms. We recently developed a ranking index for unbiased and quantitative quality assessment of forensic DNA profiles, the forensic DNA profile index (FI) (Hedman et al. Improved forensic DNA analysis through the use of alternative DNA polymerases and statistical modeling of DNA profiles, Biotechniques 47 (2009) 951-958). FI uses electropherogram data to combine the intensities of the allelic peaks with the balances within and between loci, using Principal Components Analysis. Here we present the construction of FI. We explain the mathematical and statistical methodologies used and present details about the applied data reduction method. Thereby we show how to adapt the ranking index for any Short Tandem Repeat-based forensic DNA typing system through validation against a manual grading scale and calibration against a specific set of DNA profiles. The developed tool provides unbiased quality assessment of forensic DNA profiles. It can be applied for any DNA profiling system based on Short Tandem Repeat markers. Apart from crime related DNA analysis, FI can therefore be used as a quality tool in paternal or familial testing as well as in disaster victim identification.


Systematic analysis of a novel human renal glomerulus-enriched gene expression dataset.
Glomerular diseases account for the majority of cases with chronic renal failure. Several genes have been identified with key relevance for glomerular function. Quite a few of these genes show a specific or preferential mRNA expression in the renal glomerulus. To identify additional candidate genes involved in glomerular function in humans we generated a human renal glomerulus-enriched gene expression dataset (REGGED) by comparing gene expression profiles from human glomeruli and tubulointerstitium obtained from six transplant living donors using Affymetrix HG-U133A arrays. This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus. Genes with 'a priori' known prominent glomerular expression served for validation and were all found in the novel dataset (e.g. CDKN1, DAG1, DDN, EHD3, MYH9, NES, NPHS1, NPHS2, PDPN, PLA2R1, PLCE1, PODXL, PTPRO, SYNPO, TCF21, TJP1, WT1). The mRNA expression of several novel glomerulus-enriched genes in REGGED was validated by qRT-PCR. Gene ontology and pathway analysis identified biological processes previously not reported to be of relevance in glomeruli of healthy human adult kidneys including among others axon guidance. This finding was further validated by assessing the expression of the axon guidance molecules neuritin (NRN1) and roundabout receptor ROBO1 and -2. In diabetic nephropathy, a prevalent glomerulopathy, differential regulation of glomerular ROBO2 mRNA was found.In summary, novel transcripts with predominant expression in the human glomerulus could be identified using a comparative strategy on microdissected nephrons. A systematic analysis of this glomerulus-specific gene expression dataset allows the detection of target molecules and biological processes involved in glomerular biology and renal disease.


Striatal dopaminergic functioning in patients with sporadic and hereditary spastic paraplegias with parkinsonism.
Sporadic spastic paraplegia (SSP) and hereditary spastic paraplegia (HSP) belong to a clinical and genetically heterogeneous group of disorders characterized by progressive spasticity and weakness in the lower extremities. The symptoms are associated with pyramidal tract dysfunction and degeneration of the corticospinal tracts. Parkinsonism is uncommon in SSP/HSP patients. However, both disorders are associated with damage to the nigrostriatal dopaminergic system. In the present study, the clinical features of patients with SSP/HSP were investigated, and nigrostriatal dopaminergic binding potential was assessed using dopamine transporter (DAT) single-photon emission computer tomography (SPECT). Nine patients with spastic paraplegia participated in the present study. The subjects underwent DAT SPECT using the agent [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato (3-)-N2,N20,S2,S20]oxo-[IR-(exo-exo)])-[(99)mTc]technetium ([(99)mTc]TRODAT-1). The [(99)mTc]TRODAT-1 SPECT images of five patients appeared normal, whereas the images of four patients revealed reduced striatal ligand uptake. Among the four patients with reduced uptake, two had parkinsonism, and one exhibited periodic limb movements and restless leg syndrome. Our DAT SPECT imaging study shows that reduced DAT density may be observed in patients with parkinsonism. The results of the present study offer an explanation for the spectrum of spastic paraplegia symptoms and the progression of the disorder.


Roles of DNA polymerases in replication, repair, and recombination in eukaryotes.
The functioning of the eukaryotic genome depends on efficient and accurate DNA replication and repair. The process of replication is complicated by the ongoing decomposition of DNA and damage of the genome by endogenous and exogenous factors. DNA damage can alter base coding potential resulting in mutations, or block DNA replication, which can lead to double-strand breaks (DSB) and to subsequent chromosome loss. Replication is coordinated with DNA repair systems that operate in cells to remove or tolerate DNA lesions. DNA polymerases can serve as sensors in the cell cycle checkpoint pathways that delay cell division until damaged DNA is repaired and replication is completed. Eukaryotic DNA template-dependent DNA polymerases have different properties adapted to perform an amazingly wide spectrum of DNA transactions. In this review, we discuss the structure, the mechanism, and the evolutionary relationships of DNA polymerases and their possible functions in the replication of intact and damaged chromosomes, DNA damage repair, and recombination.


The benefits of breakfast cereal consumption: a systematic review of the evidence base.
There have been no comprehensive reviews of the relation of breakfast cereal consumption to nutrition and health. This systematic review of all articles on breakfast cereals to October 2013 in the Scopus and Medline databases identified 232 articles with outcomes related to nutrient intake, weight, diabetes, cardiovascular disease, hypertension, digestive health, dental and mental health, and cognition. Sufficient evidence was available to develop 21 summary evidence statements, ranked from A (can be trusted to guide practice) to D (weak and must be applied with caution). Breakfast cereal consumption is associated with diets higher in vitamins and minerals and lower in fat (grade B) but is not associated with increased intakes of total energy or sodium (grade C) or risk of dental caries (grade B). Most studies on the nutritional impact are cross-sectional, with very few intervention studies, so breakfast cereal consumption may be a marker of an overall healthy lifestyle. Oat-, barley-, or psyllium-based cereals can help lower cholesterol concentrations (grade A), and high-fiber, wheat-based cereals can improve bowel function (grade A). Regular breakfast cereal consumption is associated with a lower body mass index and less risk of being overweight or obese (grade B). Presweetened breakfast cereals do not increase the risk of overweight and obesity in children (grade C). Whole-grain or high-fiber breakfast cereals are associated with a lower risk of diabetes (grade B) and cardiovascular disease (grade C). There is emerging evidence of associations with feelings of greater well-being and a lower risk of hypertension (grade D), but more research is required.


Non-Vitamin K Antagonist Oral Anticoagulant Dosing in Patients With Atrial Fibrillation and Renal Dysfunction.
Dose reduction of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in patients with atrial fibrillation (AF) with renal impairment. Failure to reduce the dose in patients with severe kidney disease may increase bleeding risk, whereas dose reductions without a firm indication may decrease the effectiveness of stroke prevention. The goal of this study was to investigate NOAC dosing patterns and associated outcomes, i.e., stroke (ischemic stroke and systemic embolism) and major bleeding in patients treated in routine clinical practice. Using a large U.S. administrative database, 14,865 patients with AF were identified who initiated apixaban, dabigatran, or rivaroxaban between October 1, 2010, and September 30, 2015. We examined use of a standard dose in patients with a renal indication for dose reduction (potential overdosing) and use of a reduced dose when the renal indication is not present (potential underdosing). Cox proportional hazards regression was performed in propensity score-matched cohorts to investigate the outcomes. Among the 1,473 patients with a renal indication for dose reduction, 43.0% were potentially overdosed, which was associated with a higher risk of major bleeding (hazard ratio: 2.19; 95% confidence interval: 1.07 to 4.46) but no statistically significant difference in stroke (3 NOACs pooled). Among the 13,392 patients with no renal indication for dose reduction, 13.3% were potentially underdosed. This underdosing was associated with a higher risk of stroke (hazard ratio: 4.87; 95% confidence interval: 1.30 to 18.26) but no statistically significant difference in major bleeding in apixaban-treated patients. There were no statistically significant relationships in dabigatran- or rivaroxaban-treated patients without a renal indication. In routine clinical practice, prescribed NOAC doses are often inconsistent with drug labeling. These prescribing patterns may be associated with worse safety with no benefit in effectiveness in patients with severe kidney disease and worse effectiveness with no benefit in safety in apixaban-treated patients with normal or mildly impaired renal function.


Venlafaxine in the treatment of atypical facial pain: a randomized controlled trial.
To study in a randomized placebo-controlled design the efficacy of the antidepressant venlafaxine, a serotonin and a weak noradrenaline reuptake inhibitor, in the treatment of atypical facial pain (AFP). The study was a randomized, double-blind, crossover comparison of venlafaxine and a placebo. It consisted of 2 treatment periods, each of 4 weeks' duration, separated by a 2-week washout period. Thirty patients suffering from chronic pain who had been diagnosed with AFP after a thorough clinical examination were recruited. Pain intensity and pain relief were registered at 6 visits. Anxiety, depression, and adverse effects were recorded. Venous blood samples were collected at the end of each treatment period for the determination of serum levels of venlafaxine and its metabolites. Twenty patients completed the trial. Eight patients discontinued because of adverse effects and 2 patients were excluded because of noncompliance. Two patients completed the trial but were excluded from the analysis because they experienced no pain at the baseline visit. There was no significant difference in pain intensity reduction between the maximum tolerated dose of venlafaxine (75 mg in most cases) and the placebo. Pain relief was significantly greater with venlafaxine than with the placebo treatment. Significantly more escape medication was consumed during the placebo period compared with the venlafaxine period. No significant correlation was found between the serum concentration of the drug and the response to treatment. Anxiety and depression scores did not differ between venlafaxine and placebo treatment. Adverse effects were equally common during both treatments. Venlafaxine was only modestly effective in the treatment of AFP.


The U2 RNA analogue of Trypanosoma brucei gambiense: implications for a splicing mechanism in trypanosomes.
We have isolated the gene coding for the U2 analogue in trypanosomes. The 148 nucleotide long U2 RNA is capped and transcribed from a single copy gene. The 5' half of the molecule is highly homologous to mammalian U2 RNA, while the 3' half does not show any significant sequence homology with the mammalian counterpart. Nevertheless, the trypanosome U2 RNA can be folded into a secondary structure resembling the one proposed for U2 RNA. The presence of a U2 analogue and most likely other U RNAs in trypanosomes suggests that splicing is involved at some point in the maturation of mRNA. Possible interactions of the U2 RNA with the spliced leader RNA are considered.


Effect of Temperature on Thekopsora minima Urediniospores and Uredinia.
Thekopsora minima is a heteroecious rust, with spermogonia and aecia occurring on the needles of hemlock (Tsuga spp.) and uredinia, telia, and basidia occurring on the leaves of ericaceous genera, including species of Rhododendron. The effect of temperature was determined for urediniospore germination, germ tube growth, and infection efficiency on Rhododendron 'White Lights'. Percent germination and germ tube growth were assessed at 10, 15, 20, 25, and 30°C after 3 h of incubation on 1.5% water agar in the dark. Polynomial regression analyses revealed a significant effect of temperature on both germination (P < 0.001, R2adj = 0.936) and germ tube growth (P < 0.001, R2adj = 0.933), with predicted optimum temperatures of 21.5 and 22.0°C, respectively. Germination and germ tube growth were reduced greatly at 30°C and below 15°C. Temperature also was found to have a significant effect on infection efficiency, as measured by incubation period (P < 0.001, R2adj = 0.808) and uredinia produced (P < 0.001, R2adj = 0.866). On excised leaf disks of Rhododendron 'White Lights' maintained under a 14-h photoperiod, the shortest mean incubation periods of 10.7 and 10.0 days were at 20 and 25°C, respectively, with a predicted optimum of 23°C. The mean incubation period at 15 and 30°C was approximately 4 and 3 days longer, respectively, than at the predicted optimum temperature. The number of uredinia produced was similar at 15, 20, and 25°C, but was reduced sixfold at 30°C. The predicted optimum temperature for uredinial production was 19.5°C, with a 5% variation in uredinia production between 17.5 and 22°C.


Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo.
Elevated vascular endothelial growth factor (VEGF) levels are required for ocular and tumor angiogenesis in animal models. Ischemic hypoxia is strongly correlated with increased VEGF expression in these systems and is considered a physiologically relevant stimulus. Because ischemic hypoxia is often followed by reperfusion and reactive oxygen intermediate (ROI) generation, we examined the potential role of ROI in the control of VEGF gene expression. Human retinal pigment epithelial cells exposed to superoxide or hydrogen peroxide rapidly increased VEGF mRNA levels. Superoxide-associated mRNA increases were dose dependent, blocked by antioxidants, and associated with elevated VEGF protein levels in conditioned media. Increases in VEGF mRNA levels were also observed in cultured human melanoma and rat glioblastoma cells with superoxide or hydrogen peroxide. Cycloheximide prevented the ROI-associated increases in VEGF mRNA. Transcriptional inhibition with actinomycin D revealed an inducible increase in VEGF mRNA half-life, but nuclear run-on experiments showed no increase in VEGF transcriptional rate. Reoxygenation of human retinal pigment epithelial cells in vitro and ocular reperfusion in vivo increased retinal VEGF mRNA levels. Antioxidants prevented the reperfusion-associated VEGF mRNA increases in retina. We conclude that ROIs increase VEGF gene expression in vitro and during the reperfusion of ischemic retina in vivo. The ROI-associated increases are mediated largely through increases in VEGF mRNA stability.


Obesity and obstructive sleep apnea in patients with keratoconus in a Turkish population.
The aim of this study was to compare the frequency of occurrence of obesity and high risk of developing obstructive sleep apnea (OSA) in a keratoconus population with that of a control group. This prospective, case-controlled multicenter study was performed on patients with keratoconus and age- and gender-matched control subjects. One hundred forty-six patients were included in each group, and the Berlin Questionnaire was used for classifying patients as having a high risk or low risk of developing OSA. The patients' demographic and clinical characteristics were compared with the Mann-Whitney U test for continuous variables and with the χ test for categorical variables. The keratoconus (85 male/61 female) and control (79 male/67 female) groups' median ages were 25 (8-65) and 24 (9-60) years, respectively. Of the 146 patients in each group, 11 (7.5%) patients were determined to be at a high risk of developing OSA in the keratoconus group, and 8 (5.5%) patients were determined to be at a high risk of developing OSA in the control group. There was no significant difference between the groups (P = 0.477). The keratoconus and control groups' median body mass index values were found to be within normal ranges of 23.2 and 23.4, respectively. In this study, the mean body mass index value of the keratoconus group was determined to be within normal limits. In a Turkish population, the ratio of a high risk of developing OSA was not found to be significantly different between the keratoconus and control groups.


Novelty and Convergence in Adaptation to Whole Genome Duplication.
Whole genome duplication (WGD) can promote adaptation but is disruptive to conserved processes, especially meiosis. Studies in Arabidopsis arenosa revealed a coordinated evolutionary response to WGD involving interacting proteins controlling meiotic crossovers, which are minimized in an autotetraploid (within-species polyploid) to avoid missegregation. Here, we test whether this surprising flexibility of a conserved essential process, meiosis, is recapitulated in an independent WGD system, Cardamine amara, 17 My diverged from A. arenosa. We assess meiotic stability and perform population-based scans for positive selection, contrasting the genomic response to WGD in C. amara with that of A. arenosa. We found in C. amara the strongest selection signals at genes with predicted functions thought important to adaptation to WGD: meiosis, chromosome remodeling, cell cycle, and ion transport. However, genomic responses to WGD in the two species differ: minimal ortholog-level convergence emerged, with none of the meiosis genes found in A. arenosa exhibiting strong signal in C. amara. This is consistent with our observations of lower meiotic stability and occasional clonal spreading in diploid C. amara, suggesting that nascent C. amara autotetraploid lineages were preadapted by their diploid lifestyle to survive while enduring reduced meiotic fidelity. However, in contrast to a lack of ortholog convergence, we see process-level and network convergence in DNA management, chromosome organization, stress signaling, and ion homeostasis processes. This gives the first insight into the salient adaptations required to meet the challenges of a WGD state and shows that autopolyploids can utilize multiple evolutionary trajectories to adapt to WGD.


Vagal control of pacemaker periodicity and intranodal conduction in the rabbit sinoatrial node.
Effects of brief vagal bursting on pacemaker periodicity and intranodal conduction were studied by recording transmembrane potentials in isolated rabbit sinoatrial preparations. Postganglionic vagal terminals were activated by applying brief (50- to 150-msec) trains of pulses (duration, 100 mu sec; frequency, 200 Hz) to the endocardial surface of the node. Sympathetic effects were prevented by superfusion with Tyrode's solution containing propranolol (1 microgram/ml). Vagal trains applied singly every 10 seconds produced brief hyperpolarizations in "true" pacemaker and transitional cells, and induced phasic changes in periodicity and conduction. These changes were out of phase with each other, and were dependent on the magnitude and duration of the vagal train, as well as on its position within the pacemaker period. When similar trains were applied repetitively at cycle lengths (200-1200 msec) that were independent of the pacemaker period, complex patterns of vagus-sinoatrial node interactions resulted. Hence, depending on the vagal stimulus cycle length, the sinoatrial pacemaker was forced to beat at stable and predictable harmonic (i.e., 1:1, 1:2, 2:1, etc.), subharmonic (3:2, 4:3, etc.), or more complex entrainment ratios. At some of these ratios, arrhythmic sinus patterns coexisted with intranodal conduction disturbances, including first- and second-degree block, Wenckebach phenomena, or combinations thereof. At other entrainment ratios, arrhythmias occurred in the absence of conduction changes. At still other ratios, conduction disturbances developed in the presence of apparently undisturbed sinus rhythm. These results provide insight into the mechanism of the dynamic vagal control of sinoatrial periodicity and conduction, and may have clinical implications as well.


Tetrazepam: a benzodiazepine which dissociates sedation from other benzodiazepine activities. II. In vitro and in vivo interactions with benzodiazepine binding sites.
Tetrazepam is a 1,4-benzodiazepine (BZD) derivative which, in rodents, appears to have very little sedative and ataxic effects. In an attempt to identify the molecular mechanisms underlying this particular pharmacological profile we examined the interaction of tetrazepam with BZD binding sites. Tetrazepam interacted competitively with "central" and "peripheral" BZD binding sites and exhibited comparable affinities for both sites. Tetrazepam was approximately one-seventh as potent as diazepam at the central receptor and as potent as diazepam at the peripheral binding site. Tetrazepam did not distinguish type I from type II central BZD receptors, as evidenced by comparable affinities for the cerebellar and hippocampal receptors. In vitro autoradiographic studies showed that tetrazepam displaced [3H]flunitrazepam from rat brain membranes without any clear regional specificity. Like all BZD receptor agonists, tetrazepam exhibited a gamma-aminobutyric acid shift, a photoaffinity shift and potentiated the binding of 35S-t-butyl-bicyclophosphorothionate to rat brain membranes. However, the latter effect was observed at relatively high concentrations of tetrazepam. In vivo, tetrazepam displaced specifically bound [3H]flunitrazepam from mouse brain (ID50, 37 mg/kg p.o. vs 3.5 mg/kg p.o. for diazepam) and from mouse kidney (ID50, 38 mg/kg p.o. vs. 21 mg/kg p.o. for diazepam). It is concluded that tetrazepam is a BZD receptor agonist; the molecular mechanisms which underly the low sedative potential of the drug cannot at present be explained by a particular interaction with either central or peripheral BZD binding sites, but may be related to the drug's relatively weak effect on 35S-t-butyl-bicyclophosphorothionate binding.


Examining the "liberal media" claim: journalists' views on politics, economic and social policy (including health care), and media coverage.
The conservative critique of the news media rests on two general propositions: journalists hold views that are to the left of the public, and journalists frame news content in a way that accentuates these left perspectives. Previous research has revealed persuasive evidence against the latter claim, but the validity of the former claim has often been taken for granted. This research project examined the supposed left orientation of media personnel by surveying Washington-based journalists who cover national politics and/or economic policy at U.S. outlets. The findings include: (1) On select issues from corporate power and trade to Social Security and Medicare to health care and taxes, journalists are actually more conservative than the general public. (2) Journalists are mostly centrist in their political orientation. (3) The minority of journalists who do not identify with the "center" are more likely to identify with the "right" when it comes to economic issues and to identify with the "left" when it comes to social issues. (4) Journalists report that "business-oriented news outlets" and "major daily newspapers" provide the highest quality coverage of economic policy issues, while "broadcast network TV news" and "cable news services" provide the worst.


Neuroprotective Effects of Cyclosporine in a Porcine Pre-Clinical Trial of Focal Traumatic Brain Injury.
Mitochondrial dysfunction is thought to be a hallmark of traumatic brain injury (TBI) and plays a pivotal role in the resulting cellular injury. Cyclophilin D-mediated activation of the mitochondrial permeability transition pore has been suggested to contribute to this secondary injury cascade. Cyclosporine possesses neuroprotective properties that have been attributed to the desensitization of mitochondrial permeability transition pore activation. In vivo animal experiments have demonstrated neuroprotective effects of cyclosporine in more than 20 independent experimental studies in a multitude of different experimental models. However, the majority of these studies have been carried out in rodents. The aim of the present study was to evaluate the efficacy of a novel and cremophor/kolliphor EL-free lipid emulsion formulation of cyclosporine in a translational large animal model of TBI. A mild-to-moderate focal contusion injury was induced in piglets using a controlled cortical impact device. After initial step-wise analyses of pharmacokinetics and comparing with exposure of cyclosporine in clinical TBI trials, a 5-day dosing regimen with continuous intravenous cyclosporine infusion (20 mg/kg/day) was evaluated in a randomized and blinded placebo-controlled setting. Cyclosporine reduced the volume of parenchymal injury by 35%, as well as improved markers of neuronal injury, as measured with magnetic resonance spectroscopic imaging. Further, a consistent trend toward positive improvements in brain metabolism and mitochondrial function was observed in the pericontusional tissue. In this study, we have demonstrated efficacy using a novel cyclosporine formulation in clinically relevant and translatable outcome metrics in a large animal model of focal TBI.


A brief questionnaire measure of multidimensional schizotypy predicts interview-rated symptoms and impairment.
The present study employed structured diagnostic interviews to assess the construct validity of the brief version of the Multidimensional Schizotypy Scale (MSS-B), which was developed to assess positive, negative, and disorganized dimensions of schizotypy. It was hypothesized that the MSS-B subscales would be associated with differential patterns of symptoms and impairment, comparable to findings for the full-length MSS. A total of 177 young adults completed structured diagnostic interviews assessing symptoms and impairment. As hypothesized, MSS-B positive schizotypy was significantly associated with interview ratings of positive (psychotic-like) symptoms, as well as schizotypal and paranoid personality disorder traits. MSS-B negative schizotypy was associated with interview ratings of negative symptoms, as well as schizoid, paranoid, and schizotypal traits. Furthermore, negative schizotypy predicted Cluster A personality disorder diagnoses. MSS-B disorganized schizotypy was associated with interview ratings of disorganized symptoms. All three schizotypy dimensions were associated with impaired functioning. This was the first study to evaluate the validity of the MSS-B using interview measures, and the pattern of findings for each MSS-B subscale was closely comparable to the findings for the full-length MSS. Contrary to our hypothesis, cannabis use was largely unassociated with psychotic-like symptoms and did not moderate the expression of the schizotypy dimensions. The MSS-B has good psychometric properties, high concordance with the full-length MSS, and good construct validity. Thus, it appears to be a promising brief alternative to traditional schizotypy measures.


Biomimetic enterobactin analogue mediates iron-uptake and cargo transport into E. coli and P. aeruginosa.
The design, synthesis and biological evaluation of the artificial enterobactin analogue EntKL and several fluorophore-conjugates thereof are described. EntKL provides an attachment point for cargos such as fluorophores or antimicrobial payloads. Corresponding conjugates are recognized by outer membrane siderophore receptors of Gram-negative pathogens and retain the natural hydrolyzability of the tris-lactone backbone. Initial density-functional theory (DFT) calculations of the free energies of solvation (ΔG(sol)) and relaxed Fe-O force constants of the corresponding [Fe-EntKL]3- complexes indicated a similar iron binding constant compared to natural enterobactin (Ent). The synthesis of EntKL was achieved via an iterative assembly based on a 3-hydroxylysine building block over 14 steps with an overall yield of 3%. A series of growth recovery assays under iron-limiting conditions with Escherichia coli and Pseudomonas aeruginosa mutant strains that are defective in natural siderophore synthesis revealed a potent concentration-dependent growth promoting effect of EntKL similar to natural Ent. Additionally, four cargo-conjugates differing in molecular size were able to restore growth of E. coli indicating an uptake into the cytosol. P. aeruginosa displayed a stronger uptake promiscuity as six different cargo-conjugates were found to restore growth under iron-limiting conditions. Imaging studies utilizing BODIPYFL-conjugates, demonstrated the ability of EntKL to overcome the Gram-negative outer membrane permeability barrier and thus deliver molecular cargos via the bacterial iron transport machinery of E. coli and P. aeruginosa.


Patient-specific dosimetry using pretherapy [¹²⁴I]m-iodobenzylguanidine ([¹²⁴I]mIBG) dynamic PET/CT imaging before [¹³¹I]mIBG targeted radionuclide therapy for neuroblastoma.
Iodine-131-m-iodobenzylguanidine ([(131)I]mIBG)-targeted radionuclide therapy (TRT) is a standard treatment for recurrent or refractory neuroblastoma with response rates of 30-40 %. The aim of this study is to demonstrate patient-specific dosimetry using quantitative [(124)I]mIBG positron emission tomography/X-ray computed tomography (PET/CT) imaging with a GEometry ANd Tracking 4 (Geant4)-based Monte Carlo method for better treatment planning. A Monte Carlo dosimetry method was developed using the Geant4 toolkit with voxelized anatomical geometry and source distribution as input. The presegmented hybrid computational human phantoms developed by the University of Florida and the National Cancer Institute (UF/NCI) were used as a surrogate to characterize the anatomy of a given patient. S values for I-131 were estimated by the phantoms coupled with Geant4 and compared with those estimated by OLINDA|EXM and MCNPX for the newborn model. To obtain patient-specific biodistribution of [(131)I]mIBG, a 10-year-old girl with relapsed neuroblastoma was imaged with [(124)I]mIBG PET/CT at four time points prior to the planned [(131)I]mIBG TRT. The organ- and tumor-absorbed doses of the clinical case were estimated with the Geant4 method using the modified UF/NCI 10-year-old phantom with tumors and the patient-specific residence time. For the newborn model, the Geant4 S values were consistent with the MCNPX S values. The S value ratio of the Geant4 method to OLINDA|EXM ranged from 0.08 to 6.5 of all major organs. The [(131)I]mIBG residence time quantified from the pretherapy [(124)I]mIBG PET/CT imaging of the 10-year-old patient was mostly comparable to those previously reported. Organ-absorbed dose for the salivary glands was 98.0 Gy, heart wall 36.5 Gy, and liver 34.3 Gy, while tumor-absorbed dose ranged from 143.9 to 1,641.3 Gy in different sites. Patient-specific dosimetry for [(131)I]mIBG TRT was accomplished using pretherapy [(124)I]mIBG PET/CT imaging and a Geant4-based Monte Carlo dosimetry method. The Geant4 method with quantitative pretherapy imaging can provide dose estimates to normal organs and tumors with more realistic simulation geometry, and thus may improve treatment planning for [(131)I]mIBG TRT.


Frontal Tasks and Behavior in Rigid or Tremor-Dominant Parkinson Disease.
Parkinson disease (PD) is not an unambiguous entity, and there is a general consensus for the statement that an akinetic-rigid dominant type of presentation has a worse prognosis, in the follow-up. The aim of our study was to examine the differences in frontal tasks and behavior, in 2 PD naive groups: the rigid and the tremor-dominant types of presentation, according to motor scores. Our study has showed some important differences in frontal tasks and in behavior, performing more apathy, aggressiveness, and irritability in the rigid type, and more depression and anxiety in the tremor-dominant type. The former group causes the caregiver more distress and has a very rapid disease progression. It can be argued that rigid type PD presentation needs specific dedicated cares and more strong clinical attention.


Survival, Growth, and Localization of Epiphytic Fitness Mutants of Pseudomonas syringae on Leaves.
Among 82 epiphytic fitness mutants of a Pseudomonas syringae pv. syringae strain that were characterized in a previous study, 4 mutants were particularly intolerant of the stresses associated with dry leaf surfaces. These four mutants each exhibited distinctive behaviors when inoculated onto and into plant leaves. For example, while none showed measurable growth on dry potato leaf surfaces, they grew to different population sizes in the intercellular spaces of bean leaves and on dry bean leaf surfaces, and one mutant appeared incapable of growth in both environments although it grew well on moist bean leaves. The presence of the parental strain did not influence the survival of the mutants immediately following exposure of leaves to dry, high-light incubation conditions, suggesting that the reduced survival of the mutants did not result from an inability to produce extracellular factors in planta. On moist bean leaves that were colonized by either a mutant or the wild type, the proportion of the total epiphytic population that was located in sites protected from a surface sterilant was smaller for the mutants than for the wild type, indicating that the mutants were reduced in their ability to locate, multiply in, and/or survive in such protected sites. This reduced ability was only one of possibly several factors contributing to the reduced epiphytic fitness of each mutant. Their reduced fitness was not specific to the host plant bean, since they also exhibited reduced fitness on the nonhost plant potato; the functions altered in these strains are thus of interest for their contribution to the general fitness of bacterial epiphytes.


Tissue response to collagen containing polypropylene meshes in an ovine vaginal repair model.
Pelvic Organ Prolapse (POP) is the herniation of pelvic organs into the vagina. Despite broad acceptance of mesh use in POP surgical repair, the complication rate is unacceptable. We hypothesized that collagen-containing polypropylene (PP) mesh types could modulate mesh-tissue integration and reduce long-term inflammation, thereby reducing mesh-associated complications. This study compared the long-term tissue response to an unmodified PP mesh and two collagen containing meshes in an ovine model which has similar pelvic anatomy and vaginal size to human. Three commercially available macroporous PP meshes, uncoated PP mesh (Avaulta Solo) (PP), the same textile PP mesh layered with a sheet of cross-linked porcine acellular matrix (Avaulta Plus) (PP-ACM) and a different yet also macroporous PP (Sofradim) mesh coated with solubilized atelocollagen (Ugytex) (PP-sCOL) were implanted in the ovine vagina and tissue explanted after 60 and 180days. The macrophage phenotype and response to implanted meshes, and vascularity were quantified by immunostaining and morphometry. We quantified changes in extracellular matrix composition biochemically and collagen organisation and percentage area around the interface of the mesh implants by Sirius Red birefringence and morphometry. PP-ACM induced a more sustained inflammatory response, indicated by similar CD45(+) leukocytes but reduced CD163(+) M2 macrophages at 60days (P<0.05). PP-sCOL increased Von Willebrand Factor (vWF)-immunoreactive vessel profiles after 60days. At the micro-molecular level, collagen birefringence quantification revealed significantly fewer mature collagen fibrils (red, thick fibrils) at the mesh-tissue interface than control tissue for all mesh types (P<0.001) but still significantly greater than the proportion of immature (green thin fibrils) at 60days (P<0.05). The proportion of mature collagen fibrils increased with time around the mesh filaments, particularly those containing collagen. The total collagen percent area at the mesh interface was greatest around the PP-ACM mesh at 60days (P<0.05). By 180days the total mature and immature collagen fibres at the interface of the mesh filaments resembled that of native tissue. In particular, these results suggest that both meshes containing collagen evoke different types of tissue responses at different times during the healing response yet both ultimately lead to physiological tissue formation approaching that of normal tissue. Pelvic organ prolapse (POP) is the descent of the pelvic organs to the vagina. POP affects more than 25% of all women and the lifetime risk of undergoing POP surgery is 19%. Although synthetic polypropylene (PP) meshes have improved the outcome of the surgical treatment for POP, there was an unacceptable rate of adverse events including mesh exposure and contracture. It is hypothesized that coating the PP meshes with collagen would provide a protective effect by preventing severe mesh adhesions to the wound, resulting in a better controlled initial inflammatory response, and diminished risk of exposure. In this study we assessed the effect of two collagen-containing PP meshes on the long-term vaginal tissue response using new techniques to quantify these tissue responses.


Integration and reimbursement of complementary and alternative medicine by managed care and insurance providers: 2000 update and cohort analysis.
To assess the status of managed care and insurance coverage of complementary and alternative medicine (CAM) and the integration of such services into managed care. A literature review and information search were conducted to determine which new insurers had special policies for CAM from 1999 to 2000. Telephone interviews were conducted with a sample of 6 new managed care organizations (MCOs) or insurers identified in 2000 and a nonrepresentative cohort of 4 of the original 18 MCOs and insurers who responded both to the original survey in 1997 and again in 1998 to determine trends. This study constitutes the results of the third year of an ongoing annual survey. For the year 2000, a total of 14 new companies were identified as offering some CAM coverage. Survey results were analyzed for 6 of these who responded to the current survey as well as the results of the cohort mentioned above. Most of the insurers interviewed offer some coverage for the following: nutrition counseling, biofeedback psychotherapy, acupuncture, preventive medicine, chiropractic, osteopathy, and physical therapy. All new companies indicated that market demand was a primary motivator for covering CAM. Factors determining whether insurers would offer coverage for additional therapies included potential cost-effectiveness, consumer interest, and demonstrable clinical efficacy. Among the most common obstacles listed for incorporating CAM into mainstream healthcare were lack of research on clinical or cost-effectiveness, economics, ignorance about CAM, provider competition, and lack of standards of practice. Consumer demand for CAM is motivating more MCOs and insurance companies to assess the clinical and cost benefits of incorporating CAM. Outcomes studies for both conventional and CAM therapies are needed to help create a healthcare system based on treatments that work, whether they are conventional, complementary, alternative, or integrative medicine.


Computational tools in the discovery of new G-quadruplex ligands with potential anticancer activity.
Guanine-rich sequences found at telomeres and oncogenes have the capacity to form G-quadruplex (G4) structures. It has been found a relationship between the ability to stabilizing G4 structures and anticancer activity. Guanine quadruplexes stabilization and its implication in cancer phenomena is a therapeutic target relatively recent. Computer-aided drug design has been a very useful tool for the search of new candidates. In last years, methodologies have improved with the development of the computational sciences. The hardware is also enhanced, new techniques are explored. NMR and X-ray information about different targets are discovered continually. The continuous augmentation of new powerful and comprehensive software's with this purpose is other significant factor that contributes to the discovering of new compounds. Nevertheless computer-aided drug design has not been vastly employed in the design of new compound with G4 stabilization activity. All things considered, this review will be focused on the influence of computational techniques on speeding up the discovery of new G4 ligands.


Adaptive membership functions for handwritten character recognition by Voronoi-based image zoning.
In the field of handwritten character recognition, image zoning is a widespread technique for feature extraction since it is rightly considered to be able to cope with handwritten pattern variability. As a matter of fact, the problem of zoning design has attracted many researchers who have proposed several image-zoning topologies, according to static and dynamic strategies. Unfortunately, little attention has been paid so far to the role of feature-zone membership functions that define the way in which a feature influences different zones of the zoning method. The result is that the membership functions defined to date follow nonadaptive, global approaches that are unable to model local information on feature distributions. In this paper, a new class of zone-based membership functions with adaptive capabilities is introduced and its effectiveness is shown. The basic idea is to select, for each zone of the zoning method, the membership function best suited to exploit the characteristics of the feature distribution of that zone. In addition, a genetic algorithm is proposed to determine-in a unique process-the most favorable membership functions along with the optimal zoning topology, described by Voronoi tessellation. The experimental tests show the superiority of the new technique with respect to traditional zoning methods.


Linkage on chromosome 3 of autoimmune diabetes and defective Fc receptor for IgG in NOD mice.
A congenic, non-obese diabetic (NOD) mouse strain that contains a segment of chromosome 3 from the diabetes-resistant mouse strain B6.PL-Thy-1a was less susceptible to diabetes than NOD mice. A fully penetrant immunological defect also mapped to this segment, which encodes the high-affinity Fc receptor for immunoglobulin G (IgG), Fc gamma RI. The NOD Fcgr1 allele, which results in a deletion of the cytoplasmic tail, caused a 73 percent reduction in the turnover of cell surface receptor-antibody complexes. The development of congenic strains and the characterization of Mendelian traits that are specific to the disease phenotype demonstrate the feasibility of dissecting the pathophysiology of complex, non-Mendelian diseases.