In vitro and in vivo efficacy of miramistin against drug-resistant fungi.
Miramistin is a topical antiseptic with broad antimicrobial activity that was developed in the Soviet Union during the Cold War. To investigate the antifungal activity of miramistin against clinically relevant drug-resistant fungi. The in vitro activity of miramistin was determined following Clinical and Laboratory Standards Institute (CLSI) guidelines. Mammalian cell toxicity was tested using a McCoy cell line and topical and systemic tolerability, and in vivo efficacy was tested using Galleria mellonella models. The minimal inhibitory concentration (MIC) range against fungi was 1.56-25 mg l-1 (GM 3.13 mg l-1 ). In the G. mellonella model, miramistin provided potent survival benefits for Candida albicans and Aspergillus fumigatus infection. Miramistin was tolerated by McCoy cell lines at concentrations up to 1000 mg l-1 and was systemically safe in G. mellonella at 2000 mg kg-1. Topical administration at 32 000 mg l-1 was well tolerated with no adverse effects. These findings support further investigation of miramistin and suggest its possible use for treatment of superficial fungal infections.


An inducible and reversible mouse genetic rescue system.
Inducible and reversible regulation of gene expression is a powerful approach for uncovering gene function. We have established a general method to efficiently produce reversible and inducible gene knockout and rescue in mice. In this system, which we named iKO, the target gene can be turned on and off at will by treating the mice with doxycycline. This method combines two genetically modified mouse lines: a) a KO line with a tetracycline-dependent transactivator replacing the endogenous target gene, and b) a line with a tetracycline-inducible cDNA of the target gene inserted into a tightly regulated (TIGRE) genomic locus, which provides for low basal expression and high inducibility. Such a locus occurs infrequently in the genome and we have developed a method to easily introduce genes into the TIGRE site of mouse embryonic stem (ES) cells by recombinase-mediated insertion. Both KO and TIGRE lines have been engineered for high-throughput, large-scale and cost-effective production of iKO mice. As a proof of concept, we have created iKO mice in the apolipoprotein E (ApoE) gene, which allows for sensitive and quantitative phenotypic analyses. The results demonstrated reversible switching of ApoE transcription, plasma cholesterol levels, and atherosclerosis progression and regression. The iKO system shows stringent regulation and is a versatile genetic system that can easily incorporate other techniques and adapt to a wide range of applications.


The gut microbiome in intestinal fibrosis: environmental protector or provocateur?
In individuals with inflammatory bowel diseases, intestinal fibrosis is a serious clinical complication with no specific therapies. Patients develop bowel fistulae and strictures that usually require surgery and often reoccur. The main driver of gut fibrogenesis is believed to be chronic inflammation, which leads to mesenchymal cell recruitment and activation. Recent findings suggest that the environment--in particular, the microbiome--plays a critical role in this process.


Pharmacology down under in 2000.
In December the pharmacologists and toxicologists of Australia and New Zealand get together for their annual scientific meeting, which is made up of pre-meeting workshops followed by invited lectures, symposia and free communications. This year, one of the pre-meeting workshops was on "Animal Models for the Development of Molecular Pharmaceuticals." Symposia included "Models and New Therapies for Traumatic Brain Injury" and "New Targets for Rheumatoid Arthritis." Novel medicines being developed in Australia revealed at the meeting included potassium channel blockers, C5a receptor agonists and antagonists, brain-derived neurotrophic factor mimetics and AM-36.


Adverse reactions to topical ocular anesthetics.
The purpose of this article is to clarify some of the misunderstanding about adverse reactions to topical ocular anesthetics. Discussion will include: types of adverse reactions that are theoretically and practically possible; advice on handling the reactions that can occur; and precautions for minimizing their occurrence.


The molecular logic of Notch signaling--a structural and biochemical perspective.
The Notch signaling pathway constitutes an ancient and conserved mechanism for cell-cell communication in metazoan organisms, and has a central role both in development and in adult tissue homeostasis. Here, we summarize structural and biochemical advances that contribute new insights into three central facets of canonical Notch signal transduction: (1) ligand recognition, (2) autoinhibition and the switch from protease resistance to protease sensitivity, and (3) the mechanism of nuclear-complex assembly and the induction of target-gene transcription. These advances set the stage for future mechanistic studies investigating ligand-dependent activation of Notch receptors, and serve as a foundation for the development of mechanism-based inhibitors of signaling in the treatment of cancer and other diseases.


Phylogenetic patterns and conservation among North American members of the genus Agalinis (Orobanchaceae).
North American Agalinis Raf. species represent a taxonomically challenging group and there have been extensive historical revisions at the species, section, and subsection levels of classification. The genus contains many rare species, including the federally listed endangered species Agalinis acuta. In addition to evaluating the degree to which historical classifications at the section and subsection levels are supported by molecular data sampled from 79 individuals representing 29 Agalinis species, we assessed the monophyly of 27 species by sampling multiple individuals representing different populations of those species. Twenty-one of these species are of conservation concern in at least some part of their range. Phylogenetic relationships estimated using maximum likelihood analyses of seven chloroplast DNA loci (aligned length = 11,076 base pairs (bp) and the nuclear ribosomal DNA ITS (internal transcribed spacer) locus (733 bp); indicated no support for the historically recognized sections except for Section Erectae. Our results suggest that North American members of the genus comprise six major lineages, however we were not able to resolve branching order among many of these lineages. Monophyly of 24 of the 29 sampled species was supported based on significant branch lengths of and high bootstrap support for subtending branches. However, there was no statistical support for the monophyly of A. acuta with respect to Agalinis tenella and Agalinis decemloba. Although most species were supported, deeper relationships among many species remain ambiguous. The North American Agalinis species sampled form a well supported, monophyletic group within the family Orobanchaceae relative to the outgroups sampled. Most hypotheses regarding section- and subsection-level relationships based on morphology were not supported and taxonomic revisions are warranted. Lack of support for monophyly of Agalinis acuta leaves the important question regarding its taxonomic status unanswered. Lack of resolution is potentially due to incomplete lineage sorting of ancestral polymorphisms among recently diverged species; however the gene regions examined did distinguish among almost all other species in the genus. Due to the important policy implications of this finding we are further evaluating the evolutionary distinctiveness of A. acuta using morphological data and loci with higher mutation rates.


Blood-brain barrier permeability during the development of experimental bacterial meningitis in the rat.
In an attempt to examine whether routes of bacterial entry into the central nervous system have any bearing on subsequent changes in blood-brain barrier permeability, we examined cerebrospinal fluid (CSF) penetration of circulating 125I-albumin in two different models of experimental meningitis due to K1 Escherichia coli, type III group B streptococcus, or Haemophilus influenzae type b in infant rats: hematogenous meningitis subsequent to subcutaneous inoculation of bacteria vs meningitis induced by direct inoculation of bacteria into the CSF via the cisterna magna. In the model of hematogenous meningitis, the mean CSF penetration was significantly greater in animals with H. influenzae type b meningitis than in those with meningitis due to K1 E. coli or type III group B streptococcus. In contrast, the mean CSF penetration was significantly enhanced in all animals with meningitis induced by intracisternal inoculation regardless of infecting pathogens. Tumor necrosis factor activity in CSF appeared to correlate with the functional penetration of circulating albumin across the blood-brain barrier in both models of experimental meningitis. These findings suggest that the alterations of blood-brain barrier permeability during development of experimental meningitis may vary for different models of inducing meningitis and that the mechanisms responsible for these different permeability changes may be multifactorial.


Survey and audit of diabetes care in general practice in south London.
A survey was made of the diabetic care given by general practitioners in six family practitioner committee areas. Replies were received from 388 practices, representing 1034 principals (effective response rate 69%), serving over two million patients. Fourteen per cent of practices offered mini-clinic facilities for their diabetic patients, although a much greater proportion professed to give either full or shared care to patients in ordinary surgery time. One quarter of practices kept a diabetes register, but fewer had a system of recall for patients to ensure anticipatory care. The barriers which general practitioners most often perceived in the provision of adequate care for diabetics were: lack of time, absence of a recall system and deficiency in their own clinical skills. Seventy seven of the doctors responding to the initial questionnaire participated in an audit of the level of supervision provided for 378 of their diabetic patients. Better levels of supervision of non-insulin dependent diabetics were shown in those practices where diabetes registers were kept, and where special arrangements were made for caring for diabetes. The levels of care provided by those doctors setting aside specific clinic times were not demonstrably superior to those who did not. The findings suggest that provision of support services, particularly expertise in dietetics, would help to increase general practitioners' confidence and enable more of them to improve their care of diabetic patients.


Computed cranial tomography in acoustic tumor diagnosis.
With the development of computed cranial tomography (CCT), many physicians have come to rely on this technique as their sole means of excluding a diagnosis of acoustic neurinoma. In our series of 237 patients with acoustic tumors, 29% of tumors were not detected by CCT. New thin-section scanners improve this detection rate. Tumors within the internal auditory canal, however, will not be detected without special techniques. We recommend that contrast studies of the posterior fossa be employed to exclude definitely the diagnosis of acoustic tumor when one is suspected.


The complete chloroplast genome of Kolkwitzia amabilis (Caprifoliaceae), an endangered horticultural plant in China.
The complete chloroplast genome of Kolkwitzia amabilis (Caprifoliaceae) is first presented in the current study. The cp genome of K. amabilis was 156 875 bp in length and composed of two short inverted repeat (IRa and IRb) regions of 23 946 bp which were separated by a small single copy (SSC) region of 18 846 bp and a large single copy (LSC) region of 90 137 bp. The genome encoded 130 genes contained 81 coding genes, 39 tRNA genes, and 8 rRNA genes. The overall AT content of K. amabilis is 61.6% and the corresponding values of the SSC, LSC and IR regions are 66.8%, 64.1%, and 57.3%, respectively. The phylogenetic analysis based on the maximum parsimony tree revealed that K. amabilis was closely related to Lonicera japonica.


Experimental pediatric arterial ischemic stroke model reveals sex-specific estrogen signaling.
Pediatric stroke, birth to 18 years, is a significant cause of long-term disability in the United States; however, there is currently little experimental data on the pathophysiology of childhood stroke owing to lack of animal models. We developed a novel mouse model of experimental childhood-onset arterial ischemic stroke to characterize the sex-specific response of the adolescent brain to cerebral ischemia and assess the neuroprotective effect of estrogen at this developmental stage. Postnatal day 20 to 25 mice were subjected to 90 minutes experimental stroke via the intraluminal filament middle cerebral artery occlusion model and ischemic damage assessed 22 hours after reperfusion. Real-time quantitative real-time polymerase chain reaction was performed 22 hours after middle cerebral artery occlusion to determine the effects of ischemia and estrogen treatment on the proapoptotic gene Bax. Ischemic injury did not differ between male and female juvenile (postnatal day 20-25) mice after middle cerebral artery occlusion. However, estrogen reduced ischemic injury in female mice, whereas having no effect in juvenile males. No differences in estrogen receptor expression were observed on postnatal day between 20 males and females. In contrast, estrogen minimized the ischemia-induced increase in the proapoptotic gene Bax in female mice, whereas having no effect on Bax induction in the male brain. Focal ischemia has fundamentally different effects in the juvenile brain compared with the adult, as evidenced by the lack of sex difference in ischemic injury in the murine postnatal day 20 to 25 middle cerebral artery occlusion model and the sexually dimorphic response to estrogen neuroprotection.


The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4.
The integrated stress response (ISR) is activated in response to diverse stress stimuli to maintain homeostasis in neurons. Central to this process is the phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). Here, we report a critical role for ISR in regulating the mammalian circadian clock. The eIF2α kinase GCN2 rhythmically phosphorylates eIF2α in the suprachiasmatic circadian clock. Increased eIF2α phosphorylation shortens the circadian period in both fibroblasts and mice, whereas reduced eIF2α phosphorylation lengthens the circadian period and impairs circadian rhythmicity in animals. Mechanistically, phosphorylation of eIF2α promotes mRNA translation of Atf4. ATF4 binding motifs are identified in multiple clock genes, including Per2, Per3, Cry1, Cry2, and Clock. ATF4 binds to the TTGCAGCA motif in the Per2 promoter and activates its transcription. Together, these results demonstrate a significant role for ISR in circadian physiology and provide a potential link between dysregulated ISR and circadian dysfunction in brain diseases.


[GBA mutations and Parkinson's disease].
Parkinson's disease (PD) is a common neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra and the intraneuronal Lewy bodies in this area. Genetic mutations in PD pathogenesis have been explored and better understood in recent years. GBA variants are now considered to be the single largest risk factor for PD. Gaucher disease (GD) is a lysosomal storage disorder disease and an inherited deficiency of lysosomal glucocerebrosidase (GCase) arising from mutations in the gene GBA. A group of patients with GD exhibit parkinsonian symptoms, meanwhile, GBA mutations are more frequently observed in patients with PD. These lines of evidence suggest a close relationship between GBA mutations and PD. GBA mutations are associated with an earlier onset age and a distinct cognitive decline in PD. GCase loss-of-function caused by GBA mutations interferes with the degradation of α-synuclein, and α-synuclein pathology in turn inhibits normal GCase function in PD, which forms a vicious cycle. However, the exact mechanisms for this bidirectional pathogenic loop have not to be fully elucidated. In this review, we summarize the current understandings on the potential link between GBA mutations and PD pathogenesis, which may show novel insights into PD etiology and therapeutics.


Evaluation of the ACRRM national radiology program for Australian rural and remote medical practitioners.
In 2000, the Australian College of Rural and Remote Medicine (ACRRM) developed a national radiology quality assurance (QA) and continuing medical education (CME) program for rural and remote non-specialist Australian doctors. The program commenced on 1 January 2001. It required rural doctors to obtain 30 radiology QA/CME points over a 4 year period. At least 15-20 of these points had to be obtained by one of two mandatory options of the program, either: (1) film interpretation, report and review clinical audit activity; or (2) a radiology clinical attachment. Doctors submitted their completed film review forms and clinical attachment logbooks to the program manager as confirmation of their educational activity to receive their professional development points. Data from film review forms and clinical attachment logbooks were de-identified and entered into two Microsoft EXCEL spreadsheets. The data were categorised and analysed in EXCEL. From 1 January 2001 to September 2004, 823 rural and remote doctors enrolled in the ACRRM radiology program. This included 281 locums who enrolled in the short-term locum option of the program and 563 doctors who enrolled in the full program. In September 2004, 419 doctors had completed a radiology film review with a radiologist and 41 doctors completed a radiology clinical attachment in 31 different public and private radiology practices. One hundred and ninety-five doctors completed the short-term locum activity. Ninety-two different specialist radiologists participated in the program and assisted rural and remote doctors to enhance their radiology knowledge, confidence and skills. This article describes results from the two mandatory activities. The evaluation of the ACRRM radiology program after its first 3 years and 9 months shows there are a large number of rural and remote Australian doctors undertaking professional development and quality assurance activities in radiology.


Abstraction and the (Misnamed) Language Familiarity Effect.
Talkers are recognized more accurately if they are speaking the listeners' native language rather than an unfamiliar language. This "language familiarity effect" has been shown not to depend upon comprehension and must instead involve language sound patterns. We further examine the level of sound-pattern processing involved, by comparing talker recognition in foreign languages versus two varieties of English, by (a) English speakers of one variety, (b) English speakers of the other variety, and (c) non-native listeners (more familiar with one of the varieties). All listener groups performed better with native than foreign speech, but no effect of language variety appeared: Native listeners discriminated talkers equally well in each, with the native variety never outdoing the other variety, and non-native listeners discriminated talkers equally poorly in each, irrespective of the variety's familiarity. The results suggest that this talker recognition effect rests not on simple familiarity, but on an abstract level of phonological processing.


Modeling of cryopreservation pathway operation at an aquatic biomedical stock center for zebrafish.
Aquatic biomedical model organisms play a substantial role in advancing our understanding of human health, however, comparably little work has been directed towards developing dependable, high-throughput storage programs for valuable genetic resources. The Zebrafish International Resource Center (ZIRC) has developed a standardized cryopreservation pathway and stored thousands of genetic lines in their repository for use by the biomedical research community. This has yet to be replicated in other facilities, and an overall repository-level pathway has never been analyzed for aquatic species. To encourage repository development for other biomedical models and to improve the ZIRC storage process and system, this study used discrete-event simulation modeling to systematically analyze the cryopreservation pathway for efficiency, and to identify improvements. The models reflected "real-world" working conditions and were used to simulate key outputs, such as production capacity over time (throughput) and steps in the process that limit production (bottlenecks). With these models, recommendations were identified to eliminate waiting times and increase efficiency. These included following proper husbandry protocols because male quality significantly affected production time, and the use of part-time operators to assist with steps that had longer Waiting Times (i.e., time samples spent in a queue) to increase production capacity. Simulation process modeling is a powerful tool that can improve the operations of existing repositories. It can also support repository development at other biomedical stock centers, and at other facilities devoted to aquatic species such as research, conservation, and aquaculture production hatcheries.


First radiation hybrid map of the river buffalo X chromosome (BBUX) and comparison with BTAX.
We report the first radiation hybrid map of the river buffalo X chromosome generated from a recently constructed river buffalo (Bubalus bubalis) whole-genome radiation hybrid panel (BBURH(5000)). This map contains a total of 33 cattle-derived markers, including 10 genes, four ESTs and 19 microsatellites. The markers are distributed in two linkage groups: LG1 contains eight markers spanning 125.6 cR, and LG2 contains 25 markers spanning 366.3 cR. LG1 contains six markers in common with bovine sequence assembly build 3.1. With the exception of BMS2152, the order of these markers on our BBUX map is shuffled when compared to the cow X chromosome (Bos taurus; BTAX). From LG2, two markers (AMELX and BL22) map to a more distal portion of BTAX compared to BBUX. In addition, two pairs of LG2 markers exhibit inversions compared to BTAX (ILSTS017 and ATRX; XBM38 and PPEF1). Alternatively, when compared to the most recent bovine RH map (Bov-Gen 3000rads), BL1098 and BMS2227 from LG1 as well as PLS3 and BMS1820 from LG2 showed inverted positions on the BBUX map. These discrepancies in buffalo and cattle maps may reflect evolutionary divergence of the chromosomes or mapping errors in one of the two species. Although the set of mapped markers does not cover the entire X chromosome, this map is a starting point for the construction of a high-resolution map, which is necessary for characterization of small rearrangements that might have occurred between the Bubalus bubalis and Bos taurus X chromosomes.


Double-stranded RNA bending by AU-tract sequences.
Sequence-dependent structural deformations of the DNA double helix (dsDNA) have been extensively studied, where adenine tracts (A-tracts) provide a striking example for global bending in the molecule. However, in contrast to dsDNA, sequence-dependent structural features of dsRNA have received little attention. In this work, we demonstrate that the nucleotide sequence can induce a bend in a canonical Watson-Crick base-paired dsRNA helix. Using all-atom molecular dynamics simulations, we identified a sequence motif consisting of alternating adenines and uracils, or AU-tracts, that strongly bend the RNA double-helix. This finding was experimentally validated using atomic force microscopy imaging of dsRNA molecules designed to display macroscopic curvature via repetitions of phased AU-tract motifs. At the atomic level, this novel phenomenon originates from a localized compression of the dsRNA major groove and a large propeller twist at the position of the AU-tract. Moreover, the magnitude of the bending can be modulated by changing the length of the AU-tract. Altogether, our results demonstrate the possibility of modifying the dsRNA curvature by means of its nucleotide sequence, which may be exploited in the emerging field of RNA nanotechnology and might also constitute a natural mechanism for proteins to achieve recognition of specific dsRNA sequences.


Brain extract induces synaptic characteristics in the basal lamina of cultured myotubes.
The basal lamina (BL) that occupies the synaptic cleft of the skeletal neuromuscular junction is antigenically distinct from extrasynaptic muscle fiber BL, rich in acetylcholinesterase (AChE), and bears projections that form junctional folds in the postsynaptic membrane. We report here that these synapse-specific features of BL are all present at low levels in embryonic rat myotubes cultured without nerve, and that their levels are markedly increased by addition of a soluble extract from adult rat brain. Light and electron microscopic methods show that: (1) antibodies which bind preferentially to synaptic BL in vivo stain small, discrete patches of the myotube's BL; (2) AChE accumulates in patches on the myotube surface; and (3) myotube BL and membrane form invaginations that resemble junctional folds. Patches of BL that bear synaptic antigens, AChE, or folds usually overlie clusters of acetylcholine receptors in the plasma membrane. Myotubes treated with a brain extract bear 5 to 20 times more junctional folds and patches rich in acetylcholine receptors, synaptic BL antigens, and AChE than control myotubes. Together with a previous demonstration that electrical and/or contractile activity can modulate the amount and composition of myotube BL (Sanes, J.R., and J.C. Lawrence, Jr. (1983) Dev. Biol. 97: 123-136), these results suggest that nerves could regulate differentiation of muscle fiber BL by a combination of activity-dependent and -independent mechanisms.


Integrating Worksite Smoking Cessation Services Into the Construction Sector: Opportunities and Challenges.
Background. Smoking prevalence among Hispanic/Latino construction workers in the United States is very high (31%). Aims. To investigate tobacco use profiles in these minority workers and explore their management's views about implementing sustainable worksite smoking cessation services. Methods. Analysis of baseline data from a smoking cessation trial among Hispanic/Latino construction workers (n = 134; adult men ≥18 years), and semistructured, 45-minute interviews with 24 key personnel at six construction companies in south Florida were conducted. Interviews were recorded, transcribed, and analyzed thematically. Results. Overall, 43.3% of workers were Cuban, and 81.3% had low acculturation level. Nicotine dependence levels were "high" in 61.8% of workers. Half of the workers had a successful quit attempt but only 9.9% received advice from a physician to quit smoking, 16.7% used medication to quit, and 79.2% did not receive assistance. Participants in the interviews stated that nothing was provided to help smokers quit smoking and considered distributing self-help materials with free medications as the most appropriate service. Challenges to integrating the service were time restriction and cost. Recommendations for implementing the service were local/state government mandate. Discussion. Tailoring tobacco treatment to Hispanic/Latino construction workers' job circumstances and culture is essential to support their cessation efforts. Integrating worksite tobacco treatment services into other available health promotion programs (e.g., safety) and enforcing smoke-free legislation in the construction sector can facilitate its adoption. Conclusion. Involving key stakeholders and mandating the service by the State and local government are necessary to integrate sustainable worksite smoking cessation services in the construction sector.


The importance of nurse caring behaviors as perceived by Swedish hospital patients and nursing staff.
The present study identified patient (n = 81) and nursing staff (n = 105) perceptions of the most and least important nurse caring behaviors. Using a Swedish version of the CARE-Q instrument, patients ranked as most important competent clinical know-how, while the nursing staff ranked expressive/affective behaviors as most important to make patients feel cared for. The results show significant differences (p less than 0.05) between the two groups in the rating of 29 of the instrument's 50 specific behaviors and in five out of six subscales combining individual items. Thus, patient perceptions of important nurse caring behaviors differ from staff perceptions. These results are similar to those from other studies of hospitalized patients' perceptions of caring. The staff's results are in accordance with studies of professional nurses' perceptions of caring. The findings support conclusions by other authors.


Agglomeration of titanium dioxide nanoparticles increases toxicological responses in vitro and in vivo.
The terms agglomerates and aggregates are frequently used in the regulatory definition(s) of nanomaterials (NMs) and hence attract attention in view of their potential influence on health effects. However, the influence of nanoparticle (NP) agglomeration and aggregation on toxicity is poorly understood although it is strongly believed that smaller the size of the NPs greater the toxicity. A toxicologically relevant definition of NMs is therefore not yet available, which affects not only the risk assessment process but also hinders the regulation of nano-products. In this study, we assessed the influence of NP agglomeration on their toxicity/biological responses in vitro and in vivo. We tested two TiO2 NPs with different primary sizes (17 and 117 nm) and prepared ad-hoc suspensions composed of small or large agglomerates with similar dispersion medium composition. For in vitro testing, human bronchial epithelial (HBE), colon epithelial (Caco2) and monocytic (THP-1) cell lines were exposed to these suspensions for 24 h and endpoints such as cytotoxicity, total glutathione, epithelial barrier integrity, inflammatory mediators and DNA damage were measured. Large agglomerates of 17 nm TiO2 induced stronger responses than small agglomerates for glutathione depletion, IL-8 and IL-1β increase, and DNA damage in THP-1, while no effect of agglomeration was observed with 117 nm TiO2. In vivo, C57BL/6JRj mice were exposed via oropharyngeal aspiration or oral gavage to TiO2 suspensions and, after 3 days, biological parameters including cytotoxicity, inflammatory cell recruitment, DNA damage and biopersistence were measured. Mainly, we observed that large agglomerates of 117 nm TiO2 induced higher pulmonary responses in aspirated mice and blood DNA damage in gavaged mice compared to small agglomerates. Agglomeration of TiO2 NPs influences their toxicity/biological responses and, large agglomerates do not appear less active than small agglomerates. This study provides a deeper insight on the toxicological relevance of NP agglomerates and contributes to the establishment of a toxicologically relevant definition for NMs.


Breaking barriers to rehabilitation: the role of behavior change theories in overcoming the challenge of exercise-related behavior change.
Promoting exercise-related behavior change in rehabilitation is a challenge. The lack of integration between rehabilitation program prescriptions, behavior change interventions, and behavioral change theories is profound. Using behavior change theories properly is crucial for better adherence and promoting positive outcomes. Therefore, it is essential to bring theories that support the understanding of exercise-related behavioral change to the attention of rehabilitation practitioners. This masterclass article aims to provide the theoretical background of theories and strategies for exercise behavior change within the physical therapy context based on acknowledged behavioral change theoretical models. This is a narrative review that examines six behavior theories; five of them well-established, and a new (and promising) theory that has exhibited the most favorable outcomes in rehabilitation settings. The development process for this masterclass included conversations between authors, reviewing behavior theories, summarizing and discussing the theories' concepts and strategies for physical therapy. The included theories were self-determination theory, social-cognitive theory, the transtheoretical model, the theory of planned behavior, the health belief model, and the unifying theory of physical activity. Each theory offers a unique perspective on exercise behavior change within rehabilitation, exploring constructs such as motivation, self-efficacy, stages of change, behavioral intention, perceived threat, and the core elements of physical activity expression. These theoretical models provide a foundation for understanding and developing strategies for promoting exercise behavior change in rehabilitation. Knowing and using these theories is important for respecting the patient's individuality.


Responses to elevated carbon dioxide in artificial tropical ecosystems.
Carbon, nutrient, and water balance as well as key plant and soil processes were simultaneously monitored for humid tropical plant communities treated with CO(2)-enriched atmospheres. Despite vigorous growth, no significant differences in stand biomass (of both the understory and overstory), leaf area index, nitrogen or water consumption, or leaf stomatal behavior were detected between ambient and elevated CO(2) treatments. Major responses under elevated CO(2) included massive starch accumulation in the tops of canopies, increased fine-root production, and a doubling of CO(2) evolution from the soil. Stimulated rhizosphere activity was accompanied by increased loss of soil carbon and increased mineral nutrient leaching. This study points at the inadequacy of scaling-up from physiological baselines to ecosystems without accounting for interactions among components, and it emphasizes the urgent need for whole-system experimental approaches in global-change research.


Dislocation arthropathy of the shoulder.
Seventy-four shoulders in seventy patients with a history of single or multiple dislocations of the shoulder demonstrated radiographic evidence of glenohumeral arthropathy. In every patient radiographs of the contralateral shoulder failed to reveal any abnormality (except, of course, in patients with bilateral dislocation). There were sixty-two anterior and eleven posterior dislocations, and one multidirectional dislocation. Shoulders with a posterior dislocation had a much higher incidence of moderate and severe arthrosis than those that had an anterior dislocation. This seemed to be related to delay in diagnosis. The number of recurrent dislocations or the presence of defects of either the glenoid rim or the humeral head, or both, was not related to the severity of the arthrosis. Operations in which internal fixation devices intruded on joint cartilage frequently resulted in moderate to severe arthrosis. Ten of the fifteen shoulders with severe arthrosis and six of the fourteen with moderate arthrosis had had no operation for the dislocation. Six of these sixteen shoulders had had a posterior dislocation for which reduction had been delayed.


Synesthesia in twins: incomplete concordance in monozygotes suggests extragenic factors.
Colored-sequence synesthesia (CSS) is a neurological condition in which sequential stimuli such as letters, numbers, or days of the week trigger simultaneous, involuntary color perception. Although the condition appears to run in families and several studies have sought a genetic link, the genetic contribution to synesthesia remains unclear. We conducted the first comparative twin study of CSS and found that CSS has a pairwise concordance of 73.9% in monozygotic twins, and a pairwise concordance of 36.4% in dizygotic twins. In line with previous studies, our results suggest a heritable element of synesthesia. However, consonant with the findings of previous single-pair case studies, our large sample size verifies that synesthesia is not completely conferred by genetics; if it were, monozygotic twins should have 100% concordance. These findings implicate a genetic mechanism of CSS that may work differently than previously thought: collectively, our data suggest that synesthesia is a heritable condition with incomplete penetrance that is substantially influenced by epigenetic and environmental factors.


Oxygen diffusion in perovskite: implications for electrical conductivity in the lower mantle.
Experimental determination of oxygen self-diffusion in CaTiO(3) perovskite, a structural analog of (Mg,Fe)SiO(3) perovskite, confirms a theoretical relation between diffusion constants and anion porosity. Oxygen diffusion rates in (Mg,Fe)SiO(3) perovskite calculated with this relation increase by about eight orders of magnitude through the lower mantle. Electrical conductivity values calculated from these diffusion rates are consistent with inferred conductivity values for the lower mantle. This result suggests that the dominant conductivity mechanism in the deep mantle is ionic.


Spectroscopic and electrochemical characterization of a Pr4+ imidophosphorane complex and the redox chemistry of Nd3+ and Dy3+ complexes.
The molecular tetravalent oxidation state for praseodymium is observed in solution via oxidation of the anionic trivalent precursor [K][Pr3+(NP(1,2-bis-tBu-diamidoethane)(NEt2))4] (1-Pr(NP*)) with AgI at -35 °C. The Pr4+ complex is characterized in solution via cyclic voltammetry, UV-vis-NIR electronic absorption spectroscopy, and EPR spectroscopy. Electrochemical analyses of [K][Ln3+(NP(1,2-bis-tBu-diamidoethane)(NEt2))4] (Ln = Nd and Dy) by cyclic voltammetry are reported and, in conjunction with theoretical modeling of electronic structure and oxidation potential, are indicative of principal ligand oxidations in contrast to the metal-centered oxidation observed for 1-Pr(NP*). The identification of a tetravalent praseodymium complex in in situ UV-vis and EPR experiments is further validated by theoretical modeling of the redox chemistry and the UV-vis spectrum. The latter study was performed by extended multistate pair-density functional theory (XMS-PDFT) and implicates a multiconfigurational ground state for the tetravalent praseodymium complex.


German family study on hereditary breast-ovarian cancer.
An estimated 5% to 10% of all breast and ovarian cancers are attributed to dominant susceptibility genes. Two such genes, BRCA1 and BRCA2, were recently identified. The involvement of these genes was studied in 43 German breast only and breast-ovarian cancer families. All families contained three or more cases of breast or ovarian cancer, with at least two diagnosed under the age of 60 years. Multipoint linkage analysis gave a maximum lod score of 2.13 at the BRCA1 locus under the assumption of genetic heterogeneity, with an estimated 50% of families being linked. Among the 33 breast only cancer and 10 breast-ovarian cancer families, the estimated proportions of linked families were 35% and 75%, respectively. Sixteen families with at least four cases of female breast cancer diagnosed under the age of 60 years, or male breast cancer diagnosed at any age, were analysed for linkage to BRCA2. Positive lod scores at BRCA2 were obtained in six families.


Medical students` perceptions of supporting pharmacology learning in English by key information prepared in Arabic.
We explored medical students` perceptions of supporting pharmacology self-learning in English by focused materials prepared in Arabic. This study targeted third-year medical students at the Arabian Gulf University in Bahrain (n= 183). During the endocrine and metabolism subunit, which is taught in English, slides containing focused information in Arabic preceded detailed English ones. At the end of the subunit, students` perceptions were explored by a questionnaire and focus group discussions. Most participants reported that this intervention made pharmacology learning easier, improved confidence in drug selection, knowledge of adverse drug reactions, detection of response to medications and occurrence of adverse reactions. Most respondents thought that this intervention would help them during the clinical phase of their study and in communicating drug therapy to patients in Arabic. Supporting pharmacology learning in a foreign language with instructional materials prepared in a native language improved students self-reported learning and satisfaction.


Reserve or Resident Progenitors in Cartilage? Comparative Analysis of Chondrocytes versus Chondroprogenitors and Their Role in Cartilage Repair.
Introduction Articular cartilage is made up of hyaline tissue embodying chondrocytes, which arise from mesenchymal stromal cells (MSCs) and specialized extracellular matrix. Despite possessing resident progenitors in and around the joint primed for chondrogenesis, cartilage has limited intrinsic capacity of repair and cell turnover. Advances in isolation, culture, and characterization of these progenitors have raised the possibility for their use in cell-based cartilage repair. Chondroprogenitors (CPCs) have been classified as MSCs and have been postulated to play a vital role in injury response and are identified by their colony forming ability, proliferative potential, telomere dynamics, multipotency, and expression of stem cell markers. The combined presence of CPCs and chondrocytes within the same tissue compartments and the ability of chondrocytes to dedifferentiate and acquire stemness during culture expansion has obscured our ability to define and provide clear-cut differences between these 2 cell populations. Objective This review aims to evaluate and summarize the available literature on CPCs in terms of their origin, growth kinetics, molecular characteristics, and differential and therapeutic potential with emphasis on their difference from daughter chondrocytes. Design For this systematic review, a comprehensive electronic search was performed on PubMed and Google Scholar using relevant terms such as chondrocytes, chondroprogenitors, and surface marker expression. Results and Conclusion Our comparative analysis shows that there is an ill-defined distinction between CPCs and chondrocytes with respect to their cell surface expression (MSC markers and CPC-specific markers) and differentiation potential. Accumulating evidence indicates that the 2 subpopulations may be distinguished based on their growth kinetics and chondrogenic marker.


High seroprevalence of pathogenic Yersinia spp. in sheep and goats across nine government farms in the Pakistani Punjab.
Seroprevalence of Y. enterocolitica and Y. pseudotuberculosis infections in animals and humans is not established in Pakistan. There are only a few reports on the prevalence of pathogenic Yersinia spp. and infections in small ruminants, however, the role of sheep and goats in the transmission of pathogenic Yersinia remains unclear. A primary survey investigated the presence of anti-Yersinia antibodies among a small population of ruminants detected by recombinant antigen targets in nine government farms dispersed throughout the Punjab province of Pakistan. Antibodies specific for Y. enterocolitica were detected in 7/9 sheep flocks and in 4/4 goat flocks. Antibodies specific for Y. pseudotuberculosis were detected in 4/9 sheep flocks. Two sheep flocks revealed the presence of both Y. enterocolitica and Y. pseudotuberculosis specific antibodies. Due to the high number of the population involved in raising small ruminants the risk to veterinary and public health must be rapidly determined.


Consent and participation: ethical issues in the treatment of children in out-of-home care.
Mental health service (MHS) providers confront questions of informed consent for evaluation and treatment of children in state custody who are placed in residential or foster care programs, where legal responsibility is shared between state and parent. There are ethical issues encountered by MHS providers who work with this growing population of children in placement. Matters of informed consent and access to information about treatment influence relationships with the parents, legal guardians, Child Protective Service workers, and the child. These specific concerns are addressed: informed consent, the right to be informed, and the rights of parents or foster carers to participate in a child's treatment. Recommendations for resolving dilemmas faced by MHS providers are discussed.


Channel waveguide lasers in Nd:LGS crystals.
Optical channel waveguides have been produced in Nd:LGS laser crystals by using ultrafast laser inscription with a depressed cladding configuration. The cross sectional shape of the cladding waveguides is circular, surrounded by low refractive index tracks, which makes the channel waveguides as three-dimensional tubular structures. Under optical pump of 810 nm light, continuous-wave waveguide lasers at 1068 nm have been achieved at room temperature, with minimum lasing threshold of 54 mW, a maximum slope efficiency of 24% and a maximum output power of 16 mW.


Physical activity behaviour: an overview of current and emergent theoretical practices.
Physical activity research has been dominated by traditional cognitive rationale paradigms utilized within other domains. Though this approach to physical activity behavior has greatly enhanced our understanding of the key determinants, it has done little to eradicate the health problems we currently face. In order to achieve lasting change though, multilevel interventions may prove effective. Ecological perspectives have been proposed as an effective approach in combating current physical inactivity levels. Nevertheless, this approach is in its infancy and much has still to be learned. The aim of this paper is to provide an overview of the main behavioral models used within the physical activity domain while proposing the need for further models that will embrace the principles presented by ecological and complexity theories.


Relationship of structural to functional impairment during alveolar-capillary membrane development.
Bronchopulmonary dysplasia is a chronic lung disease of extreme preterm infants and results in impaired gas exchange. Although bronchopulmonary dysplasia is characterized histologically by alveolar-capillary simplification in animal models, it is clinically defined by impaired gas diffusion. With the use of a developmentally relevant model, we correlated alveolar-capillary structural simplification with reduced functional gas exchange as measured by the diffusing factor for carbon monoxide (DFCO). Neonatal mouse pups were exposed to >90% hyperoxia or room air during postnatal days 0 to 7, and then all pups were returned to room air from days 7 to 56. At day 56, DFCO was measured as the ratio of carbon monoxide uptake to neon dilution, and lungs were fixed for histologic assessment of alveolar-capillary development. Neonatal hyperoxia exposure inhibited alveolar-capillary septal development as evidenced by significantly increased mean linear intercept, increased airspace-to-septal ratio, decreased nodal density, and decreased pulmonary microvasculature. Importantly, alveolar-capillary structural deficits in hyperoxia-exposed pups were accompanied by a significant 28% decrease in DFCO (0.555 versus 0.400; P < 0.0001). In addition, DFCO was highly and significantly correlated with structural measures of reduced alveolar-capillary growth. Simplification of alveolar-capillary structure is highly correlated with impaired gas exchange function. Current mechanistic and therapeutic animal models of inhibited alveolar development may benefit from application of DFCO as an alternative physiologic indicator of alveolar-capillary development.


Lyme disease surveillance in England and Wales, 1986 1998.
Improved surveillance indicates that Lyme borreliosis, an emerging zoonosis in the United Kingdom, has increased from 0.06/100,000 during 1986-1992 to 0.32/100,000 since 1996. Case reports peaked in the third quarter of each year. Several high-incidence localities were identified. Erythema migrans was reported in 41% of patients; arthritis in 4%; musculoskeletal symptoms in 18%; and neuroborreliosis in 15%.


Musculoskeletal disorders, psychosocial stress and associated factors among home-based migrant care workers.
Prevalence of musculoskeletal disorders (MSDs) and psychological stress in home-based female migrant care workers (MCWs) remain unknown. To 1) investigate the prevalence of MSDs and psychological stress and associations between subjective questionnaires on MSDs/psychological stress and biomedical examinations, and 2) identify the risk factors related to MSDs and psychological stress. This study recruited 85 MCWs. Data was collected using questionnaires, urine analysis and X-ray examinations. Correlations between subjective questionnaires and biomedical examinations were investigated. Multivariable logistic regression analyses were used to explore risk factors. The prevalence of MSDs and psychological stress were 70.6% and 37.6%, respectively. MSDs were commonly reported over the neck, lower back, shoulders, and upper back. There was a moderate correlation between MSDs and abnormal X-ray findings. Risk factors associated with MSDs included higher education level, frequent transferring and bedside care activities, lacking caregiver training in Taiwan, inadequate sleep, and drinking tea or coffee. Risk factors associated with psychological stress included inadequate salary, lacking caregiver training in Taiwan, and insufficient knowledge of body mechanics techniques. MSDs and psychological stress were common among home-based female MCWs. Educational level, frequent transferring and bedside care activities, and lack of caregiver training in Taiwan, were the most dominant risk factors.


Why do shear bond tests pull out dentin?
It is widely accepted that a dentin shear bond test which pulls out dentin must mean that the adhesive strength is superior to the cohesive strength of the dentin. Using numerical modeling techniques, Van Noort et al. (1988, 1989) and DeHoff et al. (1995) alerted the scientific community that there were massive stress concentrations in the familiar dentin bond test. It is not inconceivable that these localized high tensile stresses could initiate cracks which diverge monolithically into dentin, leaving the interface unchallenged. To test this hypothesis, we developed a failure accumulation simulation program which determined localized failure interactively "on the fly" with a finite element solver, and also included brittle behavior, adhesive and cohesive failure, stochastic response, and dynamic remeshing. All of the familiar dentin bond variables were included in the simulation. A parallel experimental dentin bond test validation was run, and the fractography was examined in the scanning electron microscope for mode of failure. The simulation confirmed the tensile monolithic fracture hypothesis. It is also confirmed that dentin pull-out was partly due to the biomechanics of the test and did not necessarily mean superior adhesive strength or even that the cohesive strength of the dentin was reduced. There is clear need for a new technology for the evaluation of biological interfaces, and the present work has shown the vital role of numerical modeling in the interpretation of such experimental procedures.


The soma and neurites of primary afferent neurons in the guinea-pig intestine respond differentially to deformation.
1. Intrinsic primary afferent neurons in the small intestine are exposed to distortion of their processes and of their cell bodies. Recordings of mechanosensitivity have previously been made from these neurons using intracellular microelectrodes, but this form of recording has not permitted detection of generator potentials from the processes, or of responses to cell body distortion. 2. We have developed a technique to record from enteric neurons in situ using patch electrodes. The mechanical stability of the patch recordings has allowed recording in cell-attached and whole cell configuration during imposed movement of the neurons. 3. Pressing with a fine probe initiated generator potentials (14 +/- 9 mV) from circumscribed regions of the neuron processes within the same myenteric ganglion, at distances from 100 to 500 microm from the cell body that was patched. Generator potentials persisted when synaptic transmission was blocked with high Mg2+, low Ca2+ solution. 4. Soma distortion, by pressing down with the whole cell recording electrode, inhibited action potential firing. Consistent with this, moderate intra-electrode pressure (10 mbar; 1 kPa) increased the opening probability of large-conductance (BK) potassium channels, recorded in cell-attached mode, but suction was not effective. In outside-out patches, suction, but not pressure, increased channel opening probability. Mechanosensitive BK channels have not been identified on other neurons. 5. The BK channels had conductances of 195 +/- 25 pS. Open probability was increased by depolarization, with a half-maximum activation at a patch potential of 20 mV and a slope factor of 10 mV. Channel activity was blocked by charybdotoxin (20 nM). 6. Stretch that increased membrane area under the electrode by 15 % was sufficient to double open probability. Similar changes in membrane area occur when the intestine changes diameter and wall tension under physiological conditions. Thus, the intestinal intrinsic primary afferent neurons are detectors of neurite distortion and of compression of the soma, these stimuli having opposite effects on neuron excitability.


Effect of early or late resynchronization based on different methods of pregnancy diagnosis on reproductive performance of dairy cows.
The aim of this study was to compare the reproductive performance of dairy cows subjected to early (ER) or late (LR) resynchronization programs after nonpregnancy diagnoses based on either pregnancy-associated glycoproteins (PAG) ELISA or transrectal palpation, respectively. In addition, the accuracy of the PAG ELISA for early pregnancy diagnosis was assessed. Lactating Holstein cows were subjected to a Presynch-Ovsynch protocol with timed artificial insemination (AI) performed between 61 and 74 DIM. On the day of the first postpartum AI, 1,093 cows were blocked by parity and assigned randomly to treatments; however, because of attrition, 452 ER and 520 LR cows were considered for the statistical analyses. After the first postpartum AI, cows were observed daily for signs of estrus and inseminated on the same day of detected estrus. Cows from ER that were not reinseminated in estrus received the first GnRH injection of the Ovsynch protocol for resynchronization 2d before pregnancy diagnosis. On d 28 after the previous AI (d 27 to 34), pregnancy status was determined by PAG ELISA, and nonpregnant cows continued on the Ovsynch protocol for reinsemination. Pregnant cows had pregnancy status reconfirmed on d 46 after AI (d 35 to 52) by transrectal palpation, and those that lost the pregnancies were resynchronized. Cows assigned to LR had pregnancy diagnosed by transrectal palpation on d 46 after AI (d 35 to 52) and nonpregnant cows were resynchronized with the Ovsynch protocol. Blood was sampled on d 28 after AI (d 27 to 34) from cows in both treatments that had not been reinseminated on estrus and again on d 46 after AI (d 35 to 52) for assessment of PAG ELISA to determine the accuracy of the test. Cows were subjected to treatments for 72d after the first insemination. Pregnancy per AI (P/AI) at first postpartum timed AI did not differ between treatments and averaged 28.9%. The proportion of nonpregnant cows that were resynchronized and received timed AI was greater for ER than for LR (30.0 vs. 7.6%). Cows in ER had a shorter interval between inseminations when inseminated following spontaneous estrus (21.7±1.1 vs. 27.8±0.8d) or after timed AI (35.3±1.2 vs. 55.2±1.4d). Nevertheless, the ER did not affect the rate of pregnancy (adjusted hazard ratio=1.23; 95% confidence interval=0.94 to 1.61) or the median days postpartum to pregnancy (ER=132 vs. LR=140). A total of 2,129 PAG ELISA were evaluated. Overall, sensitivity, specificity, and positive and negative predictive values averaged 95.1, 89.0, 90.1, and 94.5%, respectively, and the accuracy was 92.1%. In conclusion, PAG ELISA for early diagnosis of pregnancy had acceptable accuracy, but early resynchronization after nonpregnancy diagnosis with PAG ELISA did not improve the rate of pregnancy or reduce days open in dairy cows continuously observed for estrus.


Integrated Care Delivery for HIV Prevention and Treatment in Adolescent Girls and Young Women in Zambia: Protocol for a Cluster-Randomized Controlled Trial.
Among countries in sub-Saharan Africa, Zambia has one of the highest incidences of HIV. Adolescent girls and young women (AGYW) are a particularly affected group because of their social and economic vulnerability. The goal of this study is to test a multilevel package of interventions at the community and health system levels in Zambia in order to connect AGYW with a source of regular care, which will in turn allow for sustainable, successful implementation of regular HIV testing and adherence to antiretroviral treatment. We will adapt prior tools to create the SHIELD (Support for HIV Integrated Education, Linkages to Care, and Destigmatization) intervention to educate and empower Zambian AGYW of 10-24 years of age and their families and to create community-based youth clubs to foster peer support. We will also develop integrated wellness care clinics to offer a youth-friendly environment that provides tailored clinical services. We will perform formative research, including focus groups and in-depth interviews, among AGYW, caregivers, and stakeholders to help inform the development and tailoring of the interventions. A cluster-randomized controlled trial will be implemented in Lusaka, with six clinic catchment areas randomized into three groups: zones with integrated wellness care clinics and SHIELD intervention, zones with only SHIELD intervention, and control zones with no intervention. We will assess HIV testing among the HIV-negative or unknown (HIV-/u) cohort, and retention in care along with viral load suppression will be evaluated in the HIV-positive (HIV+) cohort. We will use in-depth interviews and surveys to collect staff and stakeholder feedback after the trial. Cost-effectiveness of the interventions and return-on-investment impacts will be quantified using a microsimulation model. Interim results are expected in 2021, and the final results are expected in 2022. If this multilevel intervention is successful in establishing a comprehensive care continuum for HIV-affected AGYW, the Zambian Ministry of Health may advocate for expansion to additional settings to support national scale-up. This integrated service delivery model can also be a platform to implement additional preventive services, so HIV-/u and HIV+ AGYW can receive comprehensive, integrated services. ClinicalTrials.gov NCT03995953; https://clinicaltrials.gov/ct2/show/NCT03995953. PRR1-10.2196/15314.


Dynamic carbon flux network of a diverse marine microbial community.
The functioning of microbial ecosystems has important consequences from global climate to human health, but quantitative mechanistic understanding remains elusive. The components of microbial ecosystems can now be observed at high resolution, but interactions still have to be inferred e.g., a time-series may show a bloom of bacteria X followed by virus Y suggesting they interact. Existing inference approaches are mostly empirical, like correlation networks, which are not mechanistically constrained and do not provide quantitative mass fluxes, and thus have limited utility. We developed an inference method, where a mechanistic model with hundreds of species and thousands of parameters is calibrated to time series data. The large scale, nonlinearity and feedbacks pose a challenging optimization problem, which is overcome using a novel procedure that mimics natural speciation or diversification e.g., stepwise increase of bacteria species. The method allows for curation using species-level information from e.g., physiological experiments or genome sequences. The product is a mass-balancing, mechanistically-constrained, quantitative representation of the ecosystem. We apply the method to characterize phytoplankton-heterotrophic bacteria interactions via dissolved organic matter in a marine system. The resulting model predicts quantitative fluxes for each interaction and time point (e.g., 0.16 µmolC/L/d of chrysolaminarin to Polaribacter on April 16, 2009). At the system level, the flux network shows a strong correlation between the abundance of bacteria species and their carbon flux during blooms, with copiotrophs being relatively more important than oligotrophs. However, oligotrophs, like SAR11, are unexpectedly high carbon processors for weeks into blooms, due to their higher biomass. The fraction of exudates (vs. grazing/death products) in the DOM pool decreases during blooms, and they are preferentially consumed by oligotrophs. In addition, functional similarity of phytoplankton i.e., what they produce, decouples their association with heterotrophs. The methodology is applicable to other microbial ecosystems, like human microbiome or wastewater treatment plants.


Structural Insights of Electrical Aging in PZT Thin Films as Revealed by In Situ Biasing X-ray Diffraction.
Electrical aging in lead zirconate titanate (PbZrxTi1-xO3) thin films has been intensively studied from a macroscopic perspective. However, structural origins and consequences of such degradation are less documented. In this study, we have used synchrotron radiation to evaluate the behavior of ferroelectric domains by X-ray diffraction (XRD). The sample was loaded with an AC triangular bias waveform between ±10 V with a number of cycle varying from one up to 108. At each step of the aging procedure, XRD spectra had been collected in situ during the application of an electric field on a capacitor. The fine analysis of the (200) pseudo-cubic peak structure allows to separate the evolution of the volume of a/c tetragonal and rhombohedral domains along the electrical biasing. Throughout the aging, both intrinsic and extrinsic responses of tetra and rhombohedral domains are altered, the behavior depending on the observed phase. This methodology opens up new perspectives in the comprehension of the aging effect in ferroelectric thin film.


Polymorphism in transmembrane region of MICA gene and cholelithiasis.
To study the significance of polymorphism of MHC class I chain-related gene A (MICA) gene in patients with cholelithiasis. Subjects included 170 unrelated adults (83 males) with cholelithiasis and 245 randomly selected unrelated adults (130 males) as controls. DNA was extracted from peripheral leukocytes and analyzed for polymorphism of 5 alleles (A4, A5, A5.1, A6 and A9) of the MICA gene. There was no significant difference in phenotype, allele, and genotype frequencies of any of the 5 alleles between cholelithiasis patients and controls. This study demonstrates that MICA alleles studied bear no relation to cholelithiasis.


Characteristics of electron transport chain and affecting factors for thiosulfate-driven perchlorate reduction.
The mechanism for perchlorate reduction was investigated using thiosulfate-driven (T-driven) perchlorate reduction bacteria. The influences of various environmental conditions on perchlorate reduction, including pH, temperature and electron acceptors were examined. The maximum perchlorate removal rate was observed at pH 7.5 and 40 °C. Perchlorate reduction was delayed due to the coexistence of perchlorate-chlorate and perchlorate-nitrate. The mechanism of the T-driven perchlorate reduction electron transport chain (ETC) was also investigated by utilizing different inhibitors. The results were as follows: firstly, the NADH dehydrogenase was not involved in the ETC; secondly, the FAD dehydrogenase and quinone loop participated in the ETC; and thirdly, cytochrome oxidase was the main pathway in the ETC. Meanwhile, microbial consortium structure analysis indicated that Sulfurovum which can oxidize sulfur compounds coupled to the reduction of nitrate or perchlorate was the primary bacterium in the T-driven and sulfur-driven consortium. This study generates a better understanding of the mechanism of T-driven perchlorate reduction.


Polymerase and hydrolase activities of Bacillus subtilis levansucrase can be separately modulated by site-directed mutagenesis.
The levansucrase (sucrose:2,6-beta-D-fructan 6-beta-D-fructosyltransferase, EC 18.104.22.168) structural gene from a Bacillus subtilis mutant strain displaying a low polymerase activity was sequenced. Only one missense mutation changing Arg331 to His was responsible for this modified catalytic property. From this allele we created new mutations by directed mutagenesis, which modified the charge and polarity of site 331. Examination of the kinetics of the purified levansucrase variants revealed that transfructosylation activities are affected differently by the substitution chosen. His331----Arg completely restored the properties of the wild-type enzyme. The most striking feature of the other variants, namely Lys331, Ser331 and Leu331, was that they lost the ability of the wild-type enzyme to synthesize levan from sucrose alone. They were only capable of catalysing the first step of levan chain elongation, which is the formation of the trisaccharide ketose. The variant His331----Lys presented a higher kcat. for sucrose hydrolysis than the wild-type, and only this hydrolase activity was preserved in a solvent/water mixture in which the wild-type acted as a true polymerase. The two other substitutions reduced the efficiency of transfructosylation activities of the enzyme via the decrease of the rate of fructosyl-enzyme intermediate formation. For all variants, the sucrose affinity was slightly affected. This strong modulation of the enzyme specificities from a single amino acid substitution led us to postulate the hypothesis that bacterial levansucrases and plant fructosyltransferases involved in fructan synthesis may possess a common ancestral form.


Using the method of triads in the validation of a food frequency questionnaire to assess the consumption of fatty acids in adults.
It is of great value to develop valid instruments to estimate food consumption; for this purpose, the triads method has been applied in validation studies of dietary intake to evaluate the correlation between three measurements [food frequency questionnaire (FFQ), reference method and biomarker]. The main aim of the present study was to validate a FFQ for Brazilian adults by means of the method of triads by estimating the ingestion of total fatty acids based on the level of saturation. The present study enrolled 152 Brazilian adults of both sexes, who were residents in the city of Viçosa, Brazil. The ingestion of total saturated, monounsaturated, polyunsaturated, trans, linoleic and linolenic fatty acids was assessed by means of a FFQ, two food records, and biomarkers, which were detected by gas chromatography. The validation coefficients were calculated using the method of triads and concordance was determined by Kappa statistics. The FFQ was considered an adequate dietary method, because, based on the validation coefficients, it estimates the intake of total fat (0.84), as well as linolenic (0.90) and linoleic acids (0.31). A high concordance rate was confirmed for all nutrients assessed by the FFQ and food records. Regarding the biomarkers, linolenic acid and linoleic acid presented greater concordance. According to the validation coefficients, the FFQ precisely estimated total fat, linolenic acid and linoleic acid contents.


Selection against late emergence and small offspring in Atlantic salmon (Salmo salar).
Timing of breeding and offspring size are maternal traits that may influence offspring competitive ability, dispersal, foraging, and vulnerability to predation and climatic conditions. To quantify the extent to which these maternal traits may ultimately affect an organism's fitness, we undertook laboratory and field experiments with Atlantic salmon (Salmo salar). To control for confounding effects caused by correlated traits, manipulations of the timing of fertilization combined with intraclutch comparisons were used. In the wild, a total of 1462 juveniles were marked at emergence from gravel nests. Recapture rates suggest that up to 83.5% mortality occurred during the first four months after emergence from the gravel nests, with the majority (67.5%) occurring during the initial period ending 17 days after median emergence. Moreover, the mortality was selective during this initial period, resulting in a significant phenotypic shift toward an earlier date of and an increased length at emergence. However, no significant selection differentials were detected thereafter, indicating that the critical episode of selection had occurred at emergence. Furthermore, standardized selection gradients indicated that selection was more intense on date of than on body size at emergence. Timing of emergence had additional consequences in terms of juvenile body size. Late-emerging juveniles were smaller than early-emerging ones at subsequent samplings, both in the wild and in parallel experiments conducted in seminatural stream channels, and this may affect success at subsequent size-selective episodes, such as winter mortality and reproduction. Finally, our findings also suggest that egg size had fitness consequences independent of the effects of emergence time that directly affected body size at emergence and, in turn, survival and size at later life stages. The causality of the maternal effects observed in the present study supports the hypothesis that selection on juvenile traits may play an important role in the evolution of maternal traits in natural populations.


How well is acute pain in children managed? A snapshot in one English hospital.
This study set out to obtain a picture of pediatric pain management practices in one English hospital. Data were collected on two wards. Nonparticipant observation combined with a chart audit was used to collect data about actual practices. Questionnaires were used to collect information from parents and young people. Observational data showed that practices conformed to current guidelines in some but not all areas. When prescribed, the dosage of analgesic drugs complied with the hospital's guidelines, and drugs were usually administered as prescribed. There was some involvement of parents in decision making but this was usually initiated by them rather than the nurses. Pain assessment tools were not always used nor was a pain history routinely taken. Documentation about pain management was limited and there was little evidence of nonpharmacologic methods of pain relief being used. Parents and young people felt that their pain management was of an acceptable level or very good. This was despite the fact that 58% of children experienced severe pain and 24% moderate pain. The results provide a snapshot of pain management in one English hospital. As in other studies, pain management practices do not adhere to current guidelines in all areas, and children appear to be experiencing moderate to severe pain. Despite this, parents and children indicated that they were happy with the quality of pain management. There is a need to explore this further and to identify strategies that support the implementation of guidelines in practice.


[State of coagulation hemostasis and fibrinolysis processes in dynamics of rapidly progressing forms of botulinal intoxication].
Phase disturbances of coagulation blood potential were revealed in experiments on white rats in dynamics of rapidly progressing form of botulinic intoxication, intoxication being caused by intraperitoneal injection of type C toxin. In preclinical period of intoxication activation of procoagulant and anticoagulant parts of hemostasis system, as well as fibrinolysis system, was noted. Similar shifts were revealed in the developmental period of generalized pareses of skeletal musculature. Only in the terminal stage of intoxication insufficiency of mechanism in formation of prothrombinase activity developed by simultaneous activation of anticoagulant mechanism and fibrinolysis system.


Stereotactic microdebrider in deep lateral orbital decompression for patients with thyroid eye disease.
Stereotactic navigation systems have been used in neurosurgery and otolaryngology with great success. The current investigation illustrates the novel use of a microdebrider with built-in stereotactic guidance in a series of thyroid orbitopathy patients who underwent deep lateral orbital wall decompression surgery. A noncomparative, interventional, retrospective case series of patients who underwent deep lateral deep orbital wall decompression from 2006 to 2013 was conducted in accordance with Institutional Review Board policy and the Declaration of Helsinki. Patient demographics, indications for surgery, pre-, intra-, and postoperative findings along with complications were recorded. One hundred eight deep lateral orbital decompression surgeries were performed in 69 patients using the Straightshot M4 Microdebrider with built-in stereotactic guidance (Medtronics). Seventy-eight cases were in women and 30 cases were in men. The average age was 50.4 years (SD = 11.9 years). Indications for surgery included proptosis, exposure keratopathy, or compressive optic neuropathy. No patient experienced intraoperative complications. Specifically, cerebrospinal fluid leak, visual loss, infection, or unanticipated inflammation were not encountered. The average postoperative follow-up time was 5.35 months. Mean reduction in proptosis was 3.72 mm (SD = 2.1). Visual acuity improved in 32.4% (35/108) of cases. This surgical instrument combines a single handpiece locator, microdebrider, irrigator, retractor, and suction device into one. It enhances anatomical localization during orbital decompression and, with an integrated tissue guard, may decrease the risk of injury to orbital soft tissues. Stereotactic navigation enhances the surgeon's ability to determine the maximal limits of decompression in real time by confirming depth of bone removal and may potentially increase surgeons' confidence in orbital decompression surgery.


Microarray analysis of virulence gene profiles in Salmonella serovars from food/food animal environment.
Rapid, accurate and inexpensive analysis of the disease-causing potential of foodborne pathogens is an important consideration in food safety and biodefense, particularly in developing countries. The objective of this study is to demonstrate the use of a robust and inexpensive microarray platform to assay the virulence gene profiles in Salmonella from food and/or the food animal environment, and then use ArrayTrack™ for data analysis. The spotted array consisted of 69 selected Salmonella-specific virulence gene probes (65bp each). These probes were printed on poly-L-lysine-coated slides. Genomic DNA was digested with Sau3AI, labeled with Cy3 dye, hybridized to the gene probes, and the images were captured and analyzed by GenePix 4000B and ArrayTrack™, a free software developed by Food and Drug Administration (FDA) researchers. Nearly 58% of the virulence-associated genes tested were present in all Salmonella strains tested. In general, genes belonging to inv, pip, prg, sic, sip, spa or ttr families were detected in more than 90% of the isolates, while the iacP, avrA, invH, rhuM, sirA, sopB, sopE or sugR genes were detected in 40 to 80% of the isolates. The gene variability was independent of the Salmonella serotype. This hybridization array presents an accurate and cost-effective method for evaluating the disease-causing potential of Salmonella in outbreak investigations by targeting a selective set of Salmonella-associated virulence genes.


Developing an information systems strategy for nursing.
With the rapidly changing health care environment and information technology advances, organizations need to engage in strategic, planned change in order to allocate limited resources, achieve the organization's goals, and fulfill its mission [1]. One of the most important aspects of the organization's planned strategies for change concerns the information systems. The involvement of the nursing department in this process is critical. This poster presentation will communicate how nurses can develop an information systems strategic plan that will enable them to play an active role as contributors and vital participants in the strategic and business planning processes for information systems. This information systems strategy for nursing will: a) provide direction and purpose, b) guide nursing in identifying the kinds of information technology needed, c) assist in timely implementation of a system that supports nursing, and d) identify desired outcomes and benefits of an information system. The nursing information systems plan must be built on, and support, the organization's mission and business plan and integrate into the over-all information systems plans [2]. Components of the nursing strategic plan include the nursing mission statement and vision, an assessment of the current environment to identify supporting technology needed to achieve the nursing vision, expectations/anticipated outcomes, environmental considerations, and special staffing/expertise considerations. The nursing vision and mission statement is an articulation of the overall direction and purpose of the nursing organization. An assessment of the nursing organization, problem areas, opportunities for growth, the physical environment, existing systems, communications requirements, and resources is carried out to help identify areas where new technologies and automated methods of managing information could be applied. Special staffing and expertise not currently available in the organization, but necessary to the successful implementation of the plan, should be identified, and plans for filling those needs should be included in the planning and prioritization process. Based on the mission and assessment findings, goals or anticipated outcomes are developed. These goals must be realistic, financially feasible, and logistically achievable; they should also provide direction for action and decision-making [3]. Measurable objectives and detailed action plans can then be developed from these goals when implementation of this aspect of the strategic plan is begun. It is especially important, even at a strategic planning level, to consider change management techniques, including specific steps to involve individuals who will be affected by the change and to ensure open communication throughout the process. Efforts to collaborate with all affected departments and to offer input and educational opportunities to the various members of the health care team should be included in the strategic plan. A business plan describing the mission, goals, and objectives for a specific system implementation is the final step in the strategic planning process. The business plan includes expected outcomes and cost justification and may be done in cooperation with other departments (in the organization) that will be involved with this system. The business plan is used to communicate the information system's needs to the administration and governing board of the organization. With a good information systems strategy, nursing will be prepared to make more timely and better informed decisions related to applying information technology within the nursing department. The end results of this planning should be evident in the improved utilization of information technology to support the nursing vision and mission.


Stiffness-Controlled Hydrogels for 3D Cell Culture Models.
Nanofibrillated cellulose (NFC) hydrogel is a versatile biomaterial suitable, for example, for three-dimensional (3D) cell spheroid culturing, drug delivery, and wound treatment. By freeze-drying NFC hydrogel, highly porous NFC structures can be manufactured. We freeze-dried NFC hydrogel and subsequently reconstituted the samples into a variety of concentrations of NFC fibers, which resulted in different stiffness of the material, i.e., different mechanical cues. After the successful freeze-drying and reconstitution, we showed that freeze-dried NFC hydrogel can be used for one-step 3D cell spheroid culturing of primary mesenchymal stem/stromal cells, prostate cancer cells (PC3), and hepatocellular carcinoma cells (HepG2). No difference was observed in the viability or morphology between the 3D cell spheroids cultured in the freeze-dried and reconstituted NFC hydrogel and fresh NFC hydrogel. Furthermore, the 3D cultured spheroids showed stable metabolic activity and nearly 100% viability. Finally, we applied a convolutional neural network (CNN)-based automatic nuclei segmentation approach to automatically segment individual cells of 3D cultured PC3 and HepG2 spheroids. These results provide an application to culture 3D cell spheroids more readily with the NFC hydrogel and a step towards automatization of 3D cell culturing and analysis.


Uptake, accumulation and elimination of polystyrene microspheres in tadpoles of Xenopus tropicalis.
Microplastic is an emerging contaminant affecting freshwater and marine ecosystem across the globe. In the present study, the filter feeding tadpoles of Xenopus tropicalis were exposed to polystyrene microspheres (1 and 10 μm) for 48 h. Microspheres were observed in gills and digestive tract of tadpoles within 1 h after exposure as well as in feces 6 h after exposure. The accumulation of microspheres in the tadpoles were concentration dependent (Univariate ANOVA, p < 0.001), but no time dependent accumulation of microspheres was observed in tadpoles 48 h after exposure (Univariate ANOVA, p > 0.05). After the exposed tadpoles were transferred to clean water, the number of microspheres in the tadpoles decreased dramatically after 1 d and continued to decrease gradually afterwards. The absorbed polystyrene particles in unfed tadpoles was significantly higher than those in the fed tadpoles at 12 and 24 h after exposure. After transfer to clean water, the fed tadpoles showed a significant decrease in the amount of absorbed polystyrene particles, while the unfed tadpoles showed no significant change in the amount of absorbed polystyrene particles. Our results suggested that microspheres were likely to be ingested and egested relatively fast by tadpoles. Our results indicated that aquatic vertebrate organisms might ingest more microplastics if the abundance of microplastics continues to increase while the available food becomes less.


The potential of amifostine: from cytoprotectant to therapeutic agent.
Amifostine is an inorganic thiophosphate cytoprotective agent known chemically as ethanethiol, 2-[(3-aminopropyl)amino]dihydrogen phosphate. It is a pro-drug of free thiol that may act as a scavenger of free radicals generated in tissues exposed to cytotoxic drugs, and binds to reactive metabolites of such drugs. Amifostine was originally developed as a radioprotective agent in a classified nuclear warfare project. Following declassification of the project it was evaluated as a cytoprotective agent against toxicity of the alkylating drugs and cisplatin. In fact, pretreatment with amifostine was well tolerated and reduced the cumulative hematologic, renal and neurological toxicity associated with cisplatin, cyclophosphamide and vinblastine therapy of advanced and metastatic solid tumors. The objective of this review is to focus the importance of amifostine as a myeloprotective and cytoprotective drug during treatment with chemotherapeutics, presenting the most recent results, and to discuss the application of amifostine in the therapy of myelodysplastic syndromes. The material analyzed in this study includes data published or under publication by the authors as full papers or clinical protocols. Articles and abstracts published in Journals covered by Medline constitute the other source of information. Amifostine, formerly known as WR-2721, is an organic thiophosphate that was developed to protect normal tissues selectively against the toxicities of chemotherapy and radiation. Amifostine is a pro-drug that is dephosphorylated at the tissue site to its active metabolite by alkaline phosphatase. Differences in the alkaline phosphatase concentrations of normal versus tumor tissues can result in greater conversion of amifostine in normal tissues. Once inside the cell the free thiol provides an alternative target to DNA and RNA for the reactive molecules of alkylating or platinum agents and acts as a potent scavenger of the oxygen free radicals induced by ionizing radiation and some chemotherapies. Preclinical animal studies demonstrated that the administration of amifostine protected against a variety of chemotherapy-related toxicities including cisplatin-induced nephrotoxicity, cisplatin-induced neurotoxicity, cyclophosphamide- and bleomycin-induced pulmonary toxicity, and the cytotoxicities (including cardiotoxicity) induced by doxorubicin and related chemotherapeutic agents. Amifostine was shown to protect a variety of animal species from lethal doses of radiation. Studies in tumor-bearing animals demonstrated that the administration of amifostine results in cytoprotection without loss of antitumor activity. Multiple phase I studies were carried out with amifostine in combination with chemotherapy for various neoplasms. Appropriate doses of amifostine resulted to be 740-910 mg/m(2) in a single dose regimen, and 340 mg/m(2) in a multiple dose regimen. Amifostine afforded not only hematologic protection, but also other organ protection from cytotoxic agents such as nephrotoxicity, mucositis and peripheral neuropathy from cisplatin. Many studies have been performed to investigate cytoprotective efficacy of amifostine. In brief, amifostine gives hematologic protection from cyclophosphamide, carboplatin, mitomycin C, fotemustine and radiotherapy; renal and peripheral nerve protection from cisplatin; mucosa, skin, and salivary gland from radiotherapy. In phase I/II studies these properties have been confirmed, together with a generally good tolerability of the drug, hypotension being the most common side effect. It has been observed that amifostine possibly enhances the anti-tumor effect of carboplatin, nitrogen mustard, melphalan, and cisplatin combined with 5-FU or vinblastine. For all these characteristics, amifostine is at present broadly used as supportive treatment during chemotherapy, in lymphomas and solid tumors, and its spec


Role of Human Action in the Spread of Honey Bee (Hymenoptera: Apidae) Pathogens.
The increased annual losses in European honey bee (Apis mellifera) colonies in North America and some other countries is usually attributed to a range of factors including pathogens, poor nutrition, and insecticides. In this essay, I will argue that the global trade in honey bees and migratory beekeeping practices within countries has enabled pathogens to spread quickly. Beekeepers' management strategies have also contributed to the spread of pathogens as well as the development of resistance to miticides and antibiotics, and exacerbated by hobby beekeepers. The opportunities for arresting honey bee declines rest as strongly with individual beekeepers as they do with the dynamics of disease.


[Exposure to external pain in the treatment of bronchial asthma].
Immediate results of treatment of 55 patients with bronchial asthma of different severity by a method of the exposure to external pain are described. The method is shown to be efficient in bronchial asthma of any genesis, its use to be promising for overcoming any drug (even hormonal) dependence.


Assessment of a new trauma workflow concept implementing a sliding CT scanner in the trauma room: the effect on workup times.
We developed a new shockroom resuscitation setting that includes a moveable, multislice computed tomography (CT) scanner capable of scanning patients during the initial trauma resuscitation phase without (multiple) patient transfers that previously were necessary. This enables us to perform a complete diagnostic trauma workup, without leaving the shockroom. In this study, we assess the effect of the new Trauma Workflow Concept on the initial diagnostic workup times in the trauma room. Data of 100 consecutive trauma patients were collected prospectively (2005 cohort) and compared with 100 consecutive trauma patients seen in our previous trauma resuscitation setting (2003 cohort). For all patients, time management was evaluated using video registration and complemented with electronic imaging times. Patients with and without CT scanning were compared with the effect of CT scanning on complete workup time, defined as time from admission to the trauma room to time of completion of diagnostic workup. Patient demographics, including appliance of CT imaging were similar. Complete diagnostic workup for patients who underwent CT imaging took an average of 79 minutes (standard deviation +/- 29 minutes) in the 2005 cohort and 105 minutes (standard deviation +/- 48 minutes) in the 2003 cohort. Complete diagnostic workup without CT imaging took 56 minutes and 53 minutes for the 2005 and 2003 cohorts, respectively. There was no difference found for nonscanned patients, whereas there was a significant difference between 2005 and 2003 for scanned patients (p < 0.01). Our new trauma workflow concept with a sliding CT scanner was significantly faster for completing the initial diagnostic workup, especially when CT imaging was required.


Molecular epidemiology of Streptococcus pneumoniae with decreased susceptibility to penicillin in a Paris children's hospital.
Among pneumococci with decreased susceptibility or pneumococci resistant to penicillin (PRP) isolated at Armand-Trousseau children's hospital, those expressing capsular serotypes 23F, 9V, and 14 were the most frequently isolated. We compared 53 clinical isolates (14 type 9V, 26 type 23F, and 13 type 14) by analysis of chromosomal macrorestriction patterns and DNA restriction patterns of the penicillin-binding protein (PBP) genes pbp 2b, pbp 2x, and pbp 1a. All 9V isolates originated from the same clone. Five 23F clones were distinguished, the largest of which comprised 20 isolates. The main type 14 clone comprised nine isolates; three other type 14 strains were closely related to the 9V clone, probably by horizontal transfer of capsular biosynthesis genes. Most 23F and type 14 isolates shared the same PBP gene restriction patterns as the 9V clone, suggesting horizontal transfer of altered PBP genes.


Not your "typical island woman": anorexia nervosa is reported only in subcultures in Curaçao.
Anorexia nervosa (AN), once thought to be a problem of wealthier, Western countries has now been documented in survey studies and case reports across geographic and economic groups; however, few epidemiological studies including interview have been done on these populations. We report on a comprehensive study on Curaçao, a Caribbean island in economic transition, where the majority of the population is of predominantly black African origin. As part of an epidemiological study on the island of Curaçao indigenous cases of AN were identified. Participants were interviewed and asked to complete standardized measures of eating behaviors and cultural attitudes. In addition, matched controls completed the same measures and were seen in a focus group to assess their knowledge of eating disorders and perceived current and future challenges to young Curaçao women. Six of the nine indigenous cases of AN were successfully traced; all were of mixed race. No cases of anorexia were found among the majority black population. The women with AN were from the high-education and high-income sectors of the society and the majority had spent time overseas. The women with a history of anorexia reported higher levels of perfectionism and anxiety than the matched controls. All of the women reported challenges to maintaining an active professional and personal life and viewed themselves as different from the norm. Women who presented with AN evidenced vulnerability to a triple threat to identity formation: (1) they were of mixed race, aspiring to fit into the mobile elite (and mostly white) subgroup while distancing themselves from the black majority; (2) they had the means for education and travel that left them caught between modern and traditional constructs of femininity; and (3) they had lived overseas, and therefore struggled upon reentry with the frustrations of what was possible within the island culture. The race, class and overseas exposures of the women with anorexia were anything but typical on the island. Cases of anorexia in other developing countries may similarly be limited to specific subgroups, which require specialized treatment and planning efforts.


Promoting physical activity in patients with colon adenomas: a randomized pilot intervention trial.
Physical activity decreases risk of colon polyps and colon cancer and might reduce risk of colon cancer recurrence. Focusing on recent calls for translation of epidemiologic evidence into clinical care, our pilot study delivered an evidence-based physical activity intervention in adults with polyps, who are thus at elevated risk of developing colon cancer. The objective was to evaluate change in physical activity, measured by steps per day and minutes of moderate/vigorous physical activity. Sixteen adults with adenomas detected and removed at screening colonoscopy were recruited to a 12-week physical activity intervention. Participants were randomized to receive a standard (30 minutes/day) or high (60 minutes/day) walking program. Physical activity was measured via blinded pedometer and accelerometer at baseline and follow-up. Intervention messages focused on self-monitoring using pedometers and overcoming barriers to engaging in physical activity. Participants in both arms significantly increased objectively measured minutes of moderate/vigorous physical activity over the course of the intervention. Both arms exceeded the intervention goal, but there was not a significant difference between arms at follow-up. Results were similar for pedometer measured physical activity, with a significant overall increase in steps/day from baseline to follow-up, but no between arm difference in change. Simple interventions of minimal contact time focusing on walking can significantly increase physical activity in individuals at increased risk of developing colon cancer. ClinicalTrials.gov NCT01476631.


Neurosteroid paradoxical enhancement of paired-pulse inhibition through paired-pulse facilitation of inhibitory circuits in dentate granule cells.
Neurosteroids are produced in the brain independently of peripheral endocrine glands to act locally in the nervous system. They exert potent promnesic effects and play significant roles in mental health-related disorders. In part, neurosteroids act by affecting ligand-gated ion channels and metabotropic receptors through rapid non-genomic processes. We have previously demonstrated that neurosteroids also affect synaptic transmission presynaptically in the CA1 region of the hippocampus. Here we describe the effects of the most abundant neurosteroid in the rodent brain, pregnenolone sulfate (PregS), on signal processing in the dentate subfield of the hippocampus. We show that PregS acts presynaptically at low concentrations (300 nM) to enhance paired-pulse facilitation (PPF) in perforant pathway terminals on dentate granule cells. Similar effects were found with two steroid sulfatase inhibitors demonstrating a potential contribution of endogenous steroids to dentate synaptic plasticity. This enhanced presynaptic facilitation paradoxically increases paired-pulse inhibition (PPI) at short interpulse intervals. Based on these data, a model of dentate gyrus circuit interactions is proposed for the presynaptic action of PregS on the filtering dynamics of the dentate subfield at frequencies similar to those of the endogenous signals from the entorhinal cortex. These modeling studies are consistent with experimental measurements demonstrating positive modulation by PregS at low frequencies and negative modulation at high frequencies. These studies show an important role for the presynaptic action of neurosteroids in modulating input signals to the hippocampus.


Atherosclerosis and myocardial disease in relation to physical activity of occupation.
This study supports the data of other authors in finding that the proportional mortality of sudden heart death and coronary heart disease is greater in men aged 40-59 years with sedentary occupations than in those with strenuous occupations. Clear evidence was found of an association between the extent of raised coronary lesions (mainly fibrous plaque and calcified lesions in the left anterior descending coronary artery and complicated lesions in each artery) and inactivity of occupation. The evidence for a similar association with the prevalence of coronary stenosis, myocardial lesions, and the extent of raised lesions of the aorta was suggestive but less clear. There was no evidence of an association between the physical activity of occupation and the extent of calcified lesions in the aorta or coronary arteries. Prevalence and extent of atherosclerotic and myocardial lesions were compared in each of 6 cause of death groups, between those who had been in strenuous, medium, and sedentary occupations.