Repeated amphetamine administration outside the home cage enhances drug-induced Fos expression in rat nucleus accumbens.
Induction of the immediate early gene protein product Fos has been used extensively to assess neural activation in the striatum after repeated amphetamine administration to rats in their home cages. However, this technique has not been used to examine striatal activation after repeated administration outside the home cage, an environment where repeated drug administration produces more robust psychomotor sensitization. We determined the dose-response relationship for amphetamine-induced psychomotor activity and Fos expression in nucleus accumbens and caudate-putamen 1 week after repeated administration of amphetamine or saline in locomotor activity chambers. Repeated administration of amphetamine enhanced amphetamine-induced locomotor activity and stereotypy and Fos expression in nucleus accumbens, but not in caudate-putamen. In comparison, levels of Fos expression induced by 1mg/kg amphetamine were not altered in nucleus accumbens or caudate-putamen by repeated amphetamine administration in the home cage. Double-labeling of Fos protein and enkephalin mRNA indicates that Fos is expressed in approximately equal numbers of enkephalin-negative and enkephalin-positive neurons in nucleus accumbens and caudate-putamen following injections outside the home cage. Furthermore, repeated amphetamine administration increased drug-induced Fos expression in enkephalin-positive, but not enkephalin-negative, neurons in nucleus accumbens. We conclude that repeated amphetamine administration outside the home cage recruits the activation of enkephalin-containing nucleus accumbens neurons during sensitized amphetamine-induced psychomotor activity.


The thalamic reticular nucleus is activated by cortical spreading depression in freely moving rats: prevention by acute valproate administration.
This study investigated the effect of repetitive cortical spreading depression (CSD) on behaviour and the anatomical and physiological patterns of cellular activation of cortical and subcortical areas in awake, moving rats. Rat behaviours in response to repetitive CSD events evoked by the application of KCl were quantified with electrophysiological recording. Immunohistochemistry was used to quantify anatomical regions of cellular activation. The effects of acute valproic acid administration on the behavioural parameters and cellular activation were evaluated. CSD significantly decreased locomotor activity and induced freezing in awake, moving rats, and stimulated c-Fos expression in the cortex, trigeminal nucleus caudalis (TNC), and amygdala. CSD also resulted in a prominent increase in c-Fos expression in the ipsilateral thalamic reticular nucleus (TRN) visual sector. Electrophysiological recordings revealed propagation of CSD into the TRN. Valproic acid pretreatment decreased the duration of CSD-induced freezing episodes and reversed the CSD-induced reduction in locomotor activity. Acute valproic acid administration also significantly blocked CSD-induced c-Fos expression in the TNC and TRN. These findings show that CSD events cause consistent behavioural responses and activate specific brain regions in awake, freely moving rats. Selective activation of TRN by CSD and the suppression of this activation by valproic acid suggest that this brain region may play an important role in migraine pathogenesis and may represent a novel target for migraine therapy.


Being 'rational' and being 'human': How National Health Service rationing decisions are constructed as rational by resource allocation panels.
The English National Health Service Constitution states that patients have the right to expect all decisions about access to medicines and treatments to be made 'rationally'. Rationality in health care can be framed as instrumental, institutional or practical. In this article, we present a case example from an ethnographic study of the work of 'Individual Funding Request' panels to explore how rationality is enacted and accounted for in deliberations about the rationing of health care in the National Health Service. Our rhetorical analysis highlights how an embodied, practical rationality emerges as a significant aspect of rationality in practice, but at the same time has a problematic status in formal accounts of decision-making. We suggest that being both 'human' and 'rational' is a 'delicate balance' and creates a dilemma for Individual Funding Request panels. Aristotle's notion of phronesis provides a useful lens for theorising our observation of panel deliberations, and we argue for greater attention to the value of narrative ethics in helping us understand the challenges faced by resource allocators.


Evaluation of a Portable Collision Warning Device for Patients With Peripheral Vision Loss in an Obstacle Course.
A pocket-sized collision warning device equipped with a video camera was developed to predict impending collisions based on time to collision rather than proximity. A study was conducted in a high-density obstacle course to evaluate the effect of the device on collision avoidance in people with peripheral field loss (PFL). The 41-meter-long loop-shaped obstacle course consisted of 46 stationary obstacles from floor to head level and oncoming pedestrians. Twenty-five patients with tunnel vision (n = 13) or hemianopia (n = 12) completed four consecutive loops with and without the device, while not using any other habitual mobility aid. Walking direction and device usage order were counterbalanced. Number of collisions and preferred percentage of walking speed (PPWS) were compared within subjects. Collisions were reduced significantly by approximately 37% (P < 0.001) with the device (floor-level obstacles were excluded because the device was not designed for them). No patient had more collisions when using the device. Although the PPWS were also reduced with the device from 52% to 49% (P = 0.053), this did not account for the lower number of collisions, as the changes in collisions and PPWS were not correlated (P = 0.516). The device may help patients with a wide range of PFL avoid collisions with high-level obstacles while barely affecting their walking speed.


(13)C NMR assignments of regenerated cellulose from solid-state 2D NMR spectroscopy.
From the assignment of the solid-state (13)C NMR signals in the C4 region, distinct types of crystalline cellulose, cellulose at crystalline surfaces, and disordered cellulose can be identified and quantified. For regenerated cellulose, complete (13)C assignments of the other carbon regions have not previously been attainable, due to signal overlap. In this study, two-dimensional (2D) NMR correlation methods were used to resolve and assign (13)C signals for all carbon atoms in regenerated cellulose. (13)C-enriched bacterial nanocellulose was biosynthesized, dissolved, and coagulated as highly crystalline cellulose II. Specifically, four distinct (13)C signals were observed corresponding to conformationally different anhydroglucose units: two signals assigned to crystalline moieties and two signals assigned to non-crystalline species. The C1, C4 and C6 regions for cellulose II were fully examined by global spectral deconvolution, which yielded qualitative trends of the relative populations of the different cellulose moieties, as a function of wetting and drying treatments.


Mechanisms of mitochondrial toxicity of the kinase inhibitors ponatinib, regorafenib and sorafenib in human hepatic HepG2 cells.
Previous studies have shown that certain kinase inhibitors are mitochondrial toxicants. In the current investigation, we determined the mechanisms of mitochondrial impairment by the kinase inhibitors ponatinib, regorafenib, and sorafenib in more detail. In HepG2 cells cultured in galactose and exposed for 24 h, all three kinase inhibitors investigated depleted the cellular ATP pools at lower concentrations than cytotoxicity occurred, compatible with mitochondrial toxicity. The kinase inhibitors impaired the activity of different complexes of the respiratory chain in HepG2 cells exposed to the toxicants for 24 h and in isolated mouse liver mitochondria exposed acutely. As a consequence, they increased mitochondrial production of ROS in HepG2 cells in a time- and concentration-dependent fashion and decreased the mitochondrial membrane potential concentration-dependently. In HepG2 cells exposed for 24 h, they induced mitochondrial fragmentation, lysosome content and mitophagy as well as mitochondrial release of cytochrome c, leading to apoptosis and/or necrosis. In conclusion, the kinase inhibitors ponatinib, regorafenib, and sorafenib impaired the function of the respiratory chain, which was associated with increased ROS production and a drop in the mitochondrial membrane potential. Despite activation of defense measures such as mitochondrial fission and mitophagy, some cells were liquidated concentration-dependently by apoptosis or necrosis. Mitochondrial dysfunction may represent a toxicological mechanism of hepatotoxicity associated with certain kinase inhibitors.


Real-time fluorescence loop mediated isothermal amplification for the diagnosis of malaria.
Molecular diagnostic methods can complement existing tools to improve the diagnosis of malaria. However, they require good laboratory infrastructure thereby restricting their use to reference laboratories and research studies. Therefore, adopting molecular tools for routine use in malaria endemic countries will require simpler molecular platforms. The recently developed loop-mediated isothermal amplification (LAMP) method is relatively simple and can be improved for better use in endemic countries. In this study, we attempted to improve this method for malaria diagnosis by using a simple and portable device capable of performing both the amplification and detection (by fluorescence) of LAMP in one platform. We refer to this as the RealAmp method. Published genus-specific primers were used to test the utility of this method. DNA derived from different species of malaria parasites was used for the initial characterization. Clinical samples of P. falciparum were used to determine the sensitivity and specificity of this system compared to microscopy and a nested PCR method. Additionally, directly boiled parasite preparations were compared with a conventional DNA isolation method. The RealAmp method was found to be simple and allowed real-time detection of DNA amplification. The time to amplification varied but was generally less than 60 minutes. All human-infecting Plasmodium species were detected. The sensitivity and specificity of RealAmp in detecting P. falciparum was 96.7% and 91.7% respectively, compared to microscopy and 98.9% and 100% respectively, compared to a standard nested PCR method. In addition, this method consistently detected P. falciparum from directly boiled blood samples. This RealAmp method has great potential as a field usable molecular tool for diagnosis of malaria. This tool can provide an alternative to conventional PCR based diagnostic methods for field use in clinical and operational programs.


Deletion of Adseverin in Osteoclasts Affects Cell Structure But Not Bone Metabolism.
Adseverin is an actin-severing/capping protein that may contribute to osteoclast differentiation in vitro but its role in bone remodeling of healthy animals is not defined. We analyzed bone and osteoclast structure in adseverin conditional null mice at alveolar and long bone sites. In wild-type and adseverin null mice, as measured by dual-energy X-ray absorptiometry, there were no differences of bone mineral content or bone mineral density, indicating no change of bone metabolism. In tibiae, TRAcP+ osteoclasts were formed in comparable numbers in adseverin null and wild-type mice. Ultrastructural analysis showed normal and similar abundance of ruffled borders, sealing zones, and mitochondria, and with no difference of osteoclast nuclear numbers. In contrast, analyses of long bone showed that in the absence of adseverin osteoclasts were smaller (120 ± 13 vs. 274 ± 19 µm2; p < 0.05), as were nuclear size and the surface area of cytoplasm. The nuclei of adseverin null osteoclasts exhibited more heterochromatin (31 ± 3%) than wild-type cells (8 ± 1%), suggesting that adseverin affects cell differentiation. The data indicate that in healthy, developing tissues, adseverin contributes to the regulation of osteoclast structure but not to bone metabolism in vivo.


Distinguishing mechanisms underlying EMT tristability.
The Epithelial-Mesenchymal Transition (EMT) endows epithelial-looking cells with enhanced migratory ability during embryonic development and tissue repair. EMT can also be co-opted by cancer cells to acquire metastatic potential and drug-resistance. Recent research has argued that epithelial (E) cells can undergo either a partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype that typically displays collective migration, or a complete EMT to adopt a mesenchymal (M) phenotype that shows individual migration. The core EMT regulatory network - miR-34/SNAIL/miR-200/ZEB1 - has been identified by various studies, but how this network regulates the transitions among the E, E/M, and M phenotypes remains controversial. Two major mathematical models - ternary chimera switch (TCS) and cascading bistable switches (CBS) - that both focus on the miR-34/SNAIL/miR-200/ZEB1 network, have been proposed to elucidate the EMT dynamics, but a detailed analysis of how well either or both of these two models can capture recent experimental observations about EMT dynamics remains to be done. Here, via an integrated experimental and theoretical approach, we first show that both these two models can be used to understand the two-step transition of EMT - E→E/M→M, the different responses of SNAIL and ZEB1 to exogenous TGF-β and the irreversibility of complete EMT. Next, we present new experimental results that tend to discriminate between these two models. We show that ZEB1 is present at intermediate levels in the hybrid E/M H1975 cells, and that in HMLE cells, overexpression of SNAIL is not sufficient to initiate EMT in the absence of ZEB1 and FOXC2. These experimental results argue in favor of the TCS model proposing that miR-200/ZEB1 behaves as a three-way decision-making switch enabling transitions among the E, hybrid E/M and M phenotypes.


Evolutionary Convergence of Pathway-Specific Enzyme Expression Stoichiometry.
Coexpression of proteins in response to pathway-inducing signals is the founding paradigm of gene regulation. However, it remains unexplored whether the relative abundance of co-regulated proteins requires precise tuning. Here, we present large-scale analyses of protein stoichiometry and corresponding regulatory strategies for 21 pathways and 67-224 operons in divergent bacteria separated by 0.6-2 billion years. Using end-enriched RNA-sequencing (Rend-seq) with single-nucleotide resolution, we found that many bacterial gene clusters encoding conserved pathways have undergone massive divergence in transcript abundance and architectures via remodeling of internal promoters and terminators. Remarkably, these evolutionary changes are compensated post-transcriptionally to maintain preferred stoichiometry of protein synthesis rates. Even more strikingly, in eukaryotic budding yeast, functionally analogous proteins that arose independently from bacterial counterparts also evolved to convergent in-pathway expression. The broad requirement for exact protein stoichiometries despite regulatory divergence provides an unexpected principle for building biological pathways both in nature and for synthetic activities.


Adapting narrative exposure therapy for Chinese earthquake survivors: a pilot randomised controlled feasibility study.
Narrative exposure therapy (NET) is a brief, manualised treatment for Posttraumatic Stress Disorder (PTSD). It has been shown to have therapeutic benefits for a wide range of individuals and settings. This study, following our previous work applying the original NET in earthquake survivors, aimed to revise NET to be adaptable for treating PTSD after a natural disaster. A randomised waiting-list controlled study was conducted with 30 adult participants with PTSD who were randomly allocated to NET (n = 10), revised NET (NET-R; n = 10) or a waiting list condition (WL; n = 10). Participants in NET and NET-R received treatment immediately; those in the WL condition received NET-R treatment after a waiting period. All groups were assessed on PTSD, general distress, anxiety, depression, social support, coping and posttraumatic change before and after treatment and three-month follow-up. Compared with WL, both NET and NET-R groups showed significant reductions in PTSD and related symptoms. Significant increases were found in posttraumatic growth, active coping and perceived social support. The WL group showed similar improvements after treatment. Further reductions on PTSD symptoms were found at three months, showing that NET-R is as effective as the original NET in treating post-earthquake traumatic symptoms in adult Chinese earthquake survivors. NET-R is a feasible and cost-effective intervention for Chinese earthquake survivors. Further studies are needed to replicate these findings in other survivor populations, and with larger samples and over longer periods. This study highlighted the value of oral narrative approach, which is well-accepted and useful in the context of single natural disaster and lower- income area. Chinese Clinical Trial Registry: ChiCTR-TRC-12002931.


Efficacy and tolerability of topical sertaconazole versus topical terbinafine in localized dermatophytosis: A randomized, observer-blind, parallel group study.
Epidermal dermatophyte infections most commonly manifest as tinea corporis or tinea cruris. Topical azole antifungals are commonly used in their treatment but literature suggests that most require twice-daily application and provide lower cure rates than the allylamine antifungal terbinafine. We conducted a head-to-head comparison of the effectiveness of the once-daily topical azole, sertaconazole, with terbinafine in these infections. We conducted a randomized, observer-blind, parallel group study (Clinical Trial Registry India [CTRI]/2014/09/005029) with adult patients of either sex presenting with localized lesions. The clinical diagnosis was confirmed by potassium hydroxide smear microscopy of skin scrapings. After baseline assessment of erythema, scaling, and pruritus, patients applied either of the two study drugs once daily for 2 weeks. If clinical cure was not seen at 2 weeks, but improvement was noted, application was continued for further 2 weeks. Patients deemed to be clinical failure at 2 weeks were switched to oral antifungals. Overall 88 patients on sertaconazole and 91 on terbinafine were analyzed. At 2 weeks, the clinical cure rates were comparable at 77.27% (95% confidence interval [CI]: 68.52%-86.03%) for sertaconazole and 73.63% (95% CI 64.57%-82.68%) for terbinafine (P = 0.606). Fourteen patients in either group improved and on further treatment showed complete healing by another 2 weeks. The final cure rate at 4 weeks was also comparable at 93.18% (95% CI 88.75%-97.62%) and 89.01% (95% CI 82.59%-95.44%), respectively (P = 0.914). At 2 weeks, 6 (6.82%) sertaconazole and 10 (10.99%) terbinafine recipients were considered as "clinical failure." Tolerability of both preparations was excellent. Despite the limitations of an observer-blind study without microbiological support, the results suggest that once-daily topical sertaconazole is as effective as terbinafine in localized tinea infections.


Vaginal laceration during barium enema with extraperitoneal extravasation: Case report and literature review.
Unrecognized vaginal intubation during the barium enema procedure with subsequent balloon inflation and contrast instillation is a potentially fatal complication of an otherwise common and routine procedure. We describe a patient who, while undergoing a routine barium enema, had misplacement of the enema catheter into the vagina, subsequent rupture of the superior/lateral vagina upon inflation of the catheter retention balloon, and injection of barium contrast into the retroperitoneum. The patient was admitted for surgical repair of the vaginal laceration and monitoring for chemical peritonitis; and was managed without exploratory laparotomy. We review the existing literature, summarize 18 reported cases from worldwide literature, detail potential complications and propose management and prevention strategies based on the mechanism of injury.


Pseudophakic corneal edema. An 11-year study of its development, incidence, and treatment.
This paper studies the appearance and development of pseudophakic corneal edema (PCE) in a series of 840 patients referred for keratoplasty for corneal edema. There were no cases of PCE in 100 eyes with corneal edema studied between 1960 and 1970. In 200 cases of corneal edema studied between 1978 and 1980, there were 30 eyes with PCE (15%). The disease has gradually increased to 56% of all cases of corneal edema seen in 1986. A tendency of PCE to decrease has been noted in the last 2 years. The high incidence of PCE in recent years, which is the main reason for keratoplasty today, seems to be related to the use of closed loop anterior chamber lenses. Fuchs' dystrophy, which formed the bulk of cases of corneal edema, may be present in many cases of PCE. results of keratoplasty with intraocular lens (IOL) removal or exchange provided better than 80% good results in a group of 230 cases followed from 1 to 7 years with visual improvement better than 20/100 in over 50% of cases. The removal of an intraocular lens causing progressive visual symptoms is advised even at the risk of causing corneal edema.


Professional Caregivers' Perceptions on how Persons with Mild Dementia Might Experience the Usage of a Digital Photo Diary.
Cognitive impairments influence the possibility of persons with dementia to remember daily events and maintain a sense of self. In order to address these problems a digital photo diary was developed to capture information about events in daily life. The device consisted of a wearable digital camera, smart phone with Global Positioning System (GPS) and a home memory station with computer for uploading the photographs and touch screen. The aim of this study was to describe professional caregiver's perceptions on how persons with mild dementia might experience the usage of this digital photo diary from both a situation when wearing the camera and a situation when viewing the uploaded photos, through a questionnaire with 408 respondents. In order to catch the professional caregivers' perceptions a questionnaire with the semantic differential technique was used and the main question was "How do you think Hilda (the fictive person in the questionnaire) feels when she is using the digital photo diary?". The factor analysis revealed three factors; Sense of autonomy, Sense of self-esteem and Sense of trust. An interesting conclusion that can be drawn is that professional caregivers had an overall positive view of the usage of digital photo diary as supporting autonomy for persons with mild dementia. The meaningfulness of each situation when wearing the camera and viewing the uploaded pictures to be used in two different situations and a part of an integrated assistive device has to be considered separately. Individual needs and desires of the person who is living with dementia and the context of each individual has to be reflected on and taken into account before implementing assistive digital devices as a tool in care.


Neuroimaging in childhood arterial ischaemic stroke: evaluation of imaging modalities and aetiologies.
The aim of this study was to describe neuroimaging patterns associated with arterial ischaemic stroke (AIS) in childhood and to differentiate them according to stroke aetiology. Clinical and neuroimaging (acute and follow-up) findings were analysed prospectively in 79 children (48 males, 31 females) aged 2 months to 15 years 8 months (median 5 y 3 mo) at the time of stroke by the Swiss Neuropaediatric Stroke Registry from 2000 to 2006. Stroke was confirmed in the acute period in 36 out of 41 children who underwent computed tomography, in 53 of 57 who underwent T2-weighted magnetic resonance imaging (MRI) and in all 48 children who underwent diffusion-weighted MRI. AIS occurred in the anterior cerebral artery (ACA) in 63 participants and in all cases was associated with lesions of the middle cerebral artery (MCA). The lesion was cortical-subcortical in 30 out of 63 children, cortical in 25 out of 63, and subcortical in 8 of 63 children. Among participants with AIS in the posterior circulation territory, the stroke was cortical-subcortical in 8 out of 16, cortical in 5 of 16, and thalamic in 3 out of 16 children. AIS mainly involves the anterior circulation territory, with both the ACA and the MCA being affected. The classification of Ganesan is an appropriate population-based classification for our Swiss cohort, but the neuroimaging pattern alone is insufficient to determine the aetiology of stroke in a paediatric population. The results show a poor correlation between lesion pattern and aetiology.


Response to the BMP gradient requires highly combinatorial inputs from multiple patterning systems in the Drosophila embryo.
Pattern formation in the developing embryo relies on key regulatory molecules, many of which are distributed in concentration gradients. For example, a gradient of BMP specifies cell fates along the dorsoventral axis in species ranging from flies to mammals. In Drosophila, a gradient of the BMP molecule Dpp gives rise to nested domains of target gene expression in the dorsal region of the embryo; however, the mechanisms underlying the differential response are not well understood, partly owing to an insufficient number of well-studied targets. Here we analyze how the Dpp gradient regulates expression of pannier (pnr), a candidate low-level Dpp target gene. We predicted that the pnr enhancer would contain high-affinity binding sites for the Dpp effector Smad transcription factors, which would be occupied in the presence of low-level Dpp. Unexpectedly, the affinity of Smad sites in the pnr enhancer was similar to those in the Race enhancer, a high-level Dpp target gene, suggesting that the affinity threshold mechanism plays a minimal role in the regulation of pnr. Our results indicate that a mechanism involving a conserved bipartite motif that is predicted to bind a homeodomain factor in addition to Smads and the Brinker repressor, establishes the pnr expression domain. Furthermore, the pnr enhancer has a highly complex structure that integrates cues not only from the dorsoventral axis, but also from the anteroposterior and terminal patterning systems in the blastoderm embryo.


Amyloid fibrils prepared using an acetylated and methyl amidated peptide model of the α-Synuclein NAC 71-82 amino acid stretch contain an additional cross-β structure also found in prion proteins.
The 71-82 fragment of the non-amyloid-β component (NAC) region of the Parkinson's disease (PD) and dementia with Lewy bodies (DLB) related protein α-Synuclein, has been reported to be important during protein misfolding. Although reports have demonstrated the importance of this fragment for the aggregation properties of the full-length protein, its exact role in pre-fibrillar oligomerisation, fibrillar growth and morphology has not yet been fully elucidated. Here, we provide evidence that fibrils prepared from an acetylated and methyl amidated peptide of the NAC 71-82 amino acid stretch of α-Synuclein are amyloid and contain, in addition to the cross-β structure detected in the full-length protein fibrils, a cross-β structure previously observed in prion proteins. These results shed light on the aggregation propensity of the NAC 71-82 amino acid stretch of the full-length protein but also the roles of the N- and C-terminal domains of α-Synuclein in balancing this aggregation propensity. The results also suggest that early aggregated forms of the capped NAC 71-82 peptide generated structures were stabilised by an anti-parallel and twisted β-sheet motif. Due to its expected toxicity, this β-sheet motif may be a promising molecular target for the development of therapeutic strategies for PD and DLB.


Neoliberal austerity and corporate crime: the collapse of the Maxima supermarket in Riga, Latvia.
The roof collapse of the Maxima supermarket in Riga, Latvia on November 21, 2013 left 54 dead. This analysis identifies the disaster as a "safety crime." Neoliberal deregulatory measures, intensified by the global economic and financial crisis and a programme of radical austerity, together with corporate and state disregard of public safety and well-being, combined to produce the disaster. The wider context and underlying causes of catastrophic safety failure exemplify the inherently contradictory character of the neoliberal "Baltic model" of austerity, recently much in vogue with international policymakers in both Europe and the United States. The authors conclude that the current renewed drive by the European Commission towards reducing regulation for business, especially in the aftermath of the crisis, further justifies longstanding anti-regulatory preferences of neoliberal domestic elites, with the result that the costs of disregard for public safety are externalized onto the general populace.


The interplay between clathrin-coated vesicles and cell signalling.
Internalization of cargo proteins and lipids at the cell surface occurs in both a constitutive and signal-regulated manner through clathrin-mediated and other endocytic pathways. Clathrin-coated vesicle formation is a principal uptake route in response to signalling events. Protein-lipid and protein-protein interactions control both the targeting of signalling molecules and their binding partners to membrane compartments and the assembly of clathrin coats. An emerging aspect of membrane trafficking research is now addressing how signalling cascades and vesicle coat assembly and subsequently disassembly are integrated.


[Steroids in the critical care children with septic shock and other conditions].
Steroids are indicated in paediatric intensive care as anti-inflammatory drugs or for substitutive treatment. During septic shock, the incidence of adrenal insufficiency (AI) varies between 18 à 52%, depending on the relative or absolute nature of the AI. Contrary to adults, for whom long courses of low doses of corticosteroids were shown to reduce mortality and increased shock reversibility, particularly in those with a negative synacthene test, no study provided sufficient evidence to show a benefit of steroids in terms of outcome in children with septic shock. In neonates, AI occurs frequently after cardiac surgery and the administration of steroids can improve haemodynamic condition. The recommended dose of hydrocortisone during septic shock or after cardiac surgery is 30 to 100 mg/m(2)/d. Dexamethasone is efficient to reduce postextubation stridor in children and neonate and the rate of reintubations in neonate. During croup, oral or parenteral steroids reduce clinical symptoms. Dexamethasone also reduces the incidence of severe chronic lung disease and the duration of tracheal intubation in premature infants. However the high incidence of side effects, particularly on the central nervous system, makes steroids currently not recommended for bronchopulmonary dysplasia. At last, steroids are indicated for severe asthma and for bacterial meningitis. In this latter indication, dexamethasone was shown to improve neurological outcome, indeed mortality in Haemophilus influenzae and Streptococcus pneumoniae meningitis.


Solution structure of the tandem acyl carrier protein domains from a polyunsaturated fatty acid synthase reveals beads-on-a-string configuration.
The polyunsaturated fatty acid (PUFA) synthases from deep-sea bacteria invariably contain multiple acyl carrier protein (ACP) domains in tandem. This conserved tandem arrangement has been implicated in both amplification of fatty acid production (additive effect) and in structural stabilization of the multidomain protein (synergistic effect). While the more accepted model is one in which domains act independently, recent reports suggest that ACP domains may form higher oligomers. Elucidating the three-dimensional structure of tandem arrangements may therefore give important insights into the functional relevance of these structures, and hence guide bioengineering strategies. In an effort to elucidate the three-dimensional structure of tandem repeats from deep-sea anaerobic bacteria, we have expressed and purified a fragment consisting of five tandem ACP domains from the PUFA synthase from Photobacterium profundum. Analysis of the tandem ACP fragment by analytical gel filtration chromatography showed a retention time suggestive of a multimeric protein. However, small angle X-ray scattering (SAXS) revealed that the multi-ACP fragment is an elongated monomer which does not form a globular unit. Stokes radii calculated from atomic monomeric SAXS models were comparable to those measured by analytical gel filtration chromatography, showing that in the gel filtration experiment, the molecular weight was overestimated due to the elongated protein shape. Thermal denaturation monitored by circular dichroism showed that unfolding of the tandem construct was not cooperative, and that the tandem arrangement did not stabilize the protein. Taken together, these data are consistent with an elongated beads-on-a-string arrangement of the tandem ACP domains in PUFA synthases, and speak against synergistic biocatalytic effects promoted by quaternary structuring. Thus, it is possible to envision bioengineering strategies which simply involve the artificial linking of multiple ACP domains for increasing the yield of fatty acids in bacterial cultures.


The metazoan ATAC and SAGA coactivator HAT complexes regulate different sets of inducible target genes.
Histone acetyl transferases (HATs) play a crucial role in eukaryotes by regulating chromatin architecture and locus-specific transcription. The GCN5 HAT was identified as a subunit of the SAGA (Spt-Ada-Gcn5-Acetyltransferase) multiprotein complex. Vertebrate cells express a second HAT, PCAF, that is 73% identical to GCN5. Here, we report the characterization of the mammalian ATAC (Ada-Two-A-Containing) complexes containing either GCN5 or PCAF in a mutually exclusive manner. In vitro ATAC complexes acetylate lysine 14 of histone H3. Moreover, ATAC- or SAGA-specific knock-down experiments suggest that both ATAC and SAGA are involved in the acetylation of histone H3K9 and K14 residues. Despite their catalytic similarities, SAGA and ATAC execute their coactivator functions on distinct sets of inducible target genes. Interestingly, ATAC strongly influences the global phosphorylation level of histone H3S10, suggesting that in mammalian cells a cross-talk exists linking ATAC function to H3S10 phosphorylation.


Immunological properties of antivenins. II. Univalent Naja haje antivenin.
A purified Naja haje antivenin was tested against Egyptian N. haje and N. nigricollis venoms, Indian N. naja venom, Iranian N. naja oxiana, Vipera lebetina, and V. persica venoms, and Echis carinatus venom from both Iran and Egypt. The different elapid venoms, with the exception of that of N. naja oxiana, showed a considerable number of identical and similar precipitin components by immunodiffusion and immunoelectrophoresis. On the other hand, only a few identical and partially identical lines were detected when this antiserum was tested against the viper venoms. Cross neutralization tests in mice showed variable degrees of protection by the antiserum against the different venoms studied; there was no direct correlation with the immunodiffusion results.


'We both just wanted to be normal parents': a qualitative study of the experience of maternity care for women with learning disability.
More women with learning disability (LD) are becoming mothers. Women with LD have rights to equal access to maternity care that meets their needs, however, many have poor pregnancy and birth outcomes compared to other women in the UK. Research is limited in this area. The aim of the study was to explore the lived experiences of pregnancy, childbirth, prenatal and postnatal care and services received by this group of women in the UK, including their expressed information and support needs relating to maternity care. A qualitative study in which data were generated using in-depth semistructured interviews with learning disabled women who were pregnant or had given birth within the last 3 years in the UK; data were analysed using interpretative phenomenological analysis. 9 women with varying levels of cognitive impairment took part. 4 super-ordinate themes were identified: 'I hate being treated differently', 'I find it harder to understand than other people', 'We've had to prove ourselves' and 'Make sure you've got very good support around you'. Subthemes included: 'Negative attitudes and denial of choice', 'Understanding of normal care', 'Written information' and 'Being judged by professionals'. With support from family and services, learning disabled women can become confident and successful parents. Maternity services should make reasonable adjustments when providing care to this group, including adapting to their individual communication and learning needs: allowing sufficient time in appointments, offering clear explanations of each aspect of care and sensitive support for autonomy and fully informed choice. Mothers who will be subject to a social care assessment of their parenting skills need clear information about the process, their choices and the level of skill they must demonstrate, as well as access to sufficient antenatal and postnatal support to give them the best possible chance of passing the assessment.


A dual perspective on the microwave-assisted synthesis of HCN polymers towards the chemical evolution and design of functional materials.
In this paper, the first study on NH4CN polymerization induced by microwave radiation is described, where a singular kinetic behaviour, especially when this reaction is conducted in the absence of air, is found. As a result, a complex conjugated N-heterocyclic polymer system is obtained, whose properties are very different, and even improved according to morphological features, characterized by their X-ray diffraction patterns and scanning electron microscopy analysis, with respect to those produced under conventional thermal treatment. In addition, a wide variety of relevant bioorganics have been identified, such as amino acids, nucleobases, co-factors, etc., from the synthetized NH4CN polymers. These particular families of polymers are of high interest in the fields of astrobiology and prebiotic chemistry and, more recently, in the development of smart multifunctional materials. From an astrobiological perspective, microwave-driven syntheses may simulate hydrothermal environments, which are considered ideal niches for increasing organic molecular complexity, and eventually as scenarios for an origin of life. From an industrial point of view and for potential applications, a microwave irradiation process leads to a notable decrease in the reaction times, and tune the properties of these new series macromolecular systems. The characteristics found for these materials encourage the development of further systematic research on this alternative HCN polymerization.


Polycyclic aromatic hydrocarbons in residential dust and risk of childhood acute lymphoblastic leukemia.
Several polycyclic aromatic hydrocarbons (PAHs) are known or probable human carcinogens. We evaluated the relationship between PAH exposure and risk of childhood acute lymphoblastic leukemia (ALL) using concentrations in residential dust as an exposure indicator. We conducted a population-based case-control study (251 ALL cases, 306 birth-certificate controls) in Northern and Central California from 2001 to 2007. We collected residential dust using a high volume small surface sampler (HVS3) (n=185 cases, 212 controls) or by sampling from participants' household vacuum cleaners (n=66 cases, 94 controls). We evaluated log-transformed concentrations of 9 individual PAHs, the summed PAHs, and the summed PAHs weighted by their carcinogenic potency (the toxic equivalence). We calculated odds ratios (ORs) and 95% confidence intervals (CI) using logistic regression adjusting for demographic characteristics and duration between diagnosis/reference date and dust collection. Among participants with HVS3 dust, risk of ALL was not associated with increasing concentration of any PAHs based on OR perln(ng/g). Among participants with vacuum dust, we observed positive associations between ALL risk and increasing concentrations of benzo[a]pyrene (OR perln[ng/g]=1.42, 95% CI=0.95, 2.12), dibenzo[a,h]anthracene (OR=1.98, 95% CI=1.11, 3.55), benzo[k]fluoranthene (OR=1.71, 95% CI=0.91, 3.22), indeno[1,2,3-cd]pyrene (OR=1.81, 95% CI=1.04, 3.16), and the toxic equivalence (OR=2.35, 95% CI=1.18, 4.69). The increased ALL risk among participants with vacuum dust suggests that PAH exposure may increase the risk of childhood ALL; however, reasons for the different results based on HVS3 dust samples deserve further study.


Painful parotid hypertrophy with bulimia: a report of medical management.
In eating disorders, such as bulimia nervosa, body image disturbance often extends beyond the realm of weight and shape into the dermatologic spectrum. While commonly associated conditions due to binging and self-induced vomiting include cutaneous entities (e.g., Russell's sign, acne, alopecia and hypertrichosis) and oral pathologies (e.g., enamel erosion, caries and mild parotid hypertrophy), a rare but troubling manifestation is disfiguring parotid enlargement (sialoadenomegaly). This article presents a case of painful sialoadenomegaly associated with hyperamylasemia in a bulimic patient successfully managed with pilocarpine.


Role of osteoplastic frontal sinus obliteration in the era of endoscopic sinus surgery.
Objective. Determining the indications for osteoplastic frontal sinus obliteration (OFSO) for the treatment of inflammatory frontal sinus disease. Study Design. Retrospective case series from a single tertiary care facility. Methods. Thirty-four patients who underwent OFSO for chronic frontal sinusitis (n = 23) and frontal sinus mucocele (n = 11) comprised our study group. Data reviewed included demographics, history of prior frontal sinus operation(s), imaging, diagnosis, and operative complications. Results. The age range was 19 to 76 years. Seventy percent of patients with chronic frontal sinusitis underwent OFSO as a salvage surgery after previous frontal sinus surgery failures, while 30% underwent OFSO as a primary surgery. For those in whom OFSO was a salvage procedure, the failed surgeries were endoscopic approaches to the frontal sinus (69%), Lynch procedure (12%), and OFSO outside this study period (19%). For patients with frontal sinus mucocele, 72% had OFSO as a first-line surgery. Within the total study population, 15% of patients presented for OFSO with history of prior obliteration, with a range of 3 to 30 years between representations. Conclusions. Osteoplastic frontal sinus obliteration remains a key surgical treatment for chronic inflammatory frontal sinus disease both as a salvage procedure and first-line surgical therapy.


Reversal of chloroquine resistance in murine malaria parasites by prostaglandin derivatives.
An oligomeric ester of prostaglandin B2 (OC-5186) was found to reverse chloroquine resistance in the murine malarial parasite Plasmodium berghei. When mice were infected with either chloroquine-sensitive or -resistant P. berghei on day 0 (by intraperitoneal injection of 1 x 10(6) parasitized erythrocytes), they died before day 23. When treated with 15 mg/kg/day of chloroquine for the first four days of infection, all mice infected with the sensitive-strain survived, while all those infected with the resistant strain died before day 23. When OC-5186 (3-12 mg/kg/day) was administered in combination with chloroquine for the first four days, 60% of the animals infected with the resistant strain survived. The differences in the survival rate between the group treated with chloroquine only and the group treated with a combination of drugs (chloroquine plus 3-12 mg/kg/day of OC-5186) were significant. There was also a significant inhibition of parasitemia in the group treated with the combination of drugs. The combinations of chloroquine and a monomer ester of prostaglandin B2 (OC-5181) had some antimalarial activity, but the differences between the chloroquine-treated group and the combination treatment group were not significant in terms of both the parasitemia and the survival rate. Another oligomeric ester of prostaglandin E1 (MR-356) as well as unesterified monomer prostaglandins (PGA2 and PGB2) were ineffective by themselves and in combination with chloroquine.


Brain-computer interface design for asynchronous control applications: improvements to the LF-ASD asynchronous brain switch.
The low-frequency asynchronous switch design (LF-ASD) was introduced as a direct brain-computer interface (BCI) technology for asynchronous control applications. The LF-ASD operates as an asynchronous brain switch (ABS) which is activated only when a user intends control and maintains an inactive state output when the user is not meaning to control the device (i.e., they may be idle, thinking about a problem, or performing some other action). Results from LF-ASD evaluations have shown promise, although the reported error rates are too high for most practical applications. This paper presents the evaluation of four new LF-ASD designs with data collected from individuals with high-level spinal cord injuries and able-bodied subjects. These new designs incorporated electroencephalographic energy normalization and feature space dimensionality reduction. The error characteristics of the new ABS designs were significantly better than the LF-ASD design with true positive rate increases of approximately 33% for false positive rates in the range of 1%-2%. The results demonstrate that the dimensionality of the LF-ASD feature space can be reduced without performance degradation. The results also confirm previous findings that spinal cord-injured subjects can operate ABS designs to the same ability as able-bodied subjects.


Physiological and Biochemical Analyses Shed Light on the Response of Sargassum vulgare to Ocean Acidification at Different Time Scales.
Studies regarding macroalgal responses to ocean acidification (OA) are mostly limited to short-term experiments in controlled conditions, which hamper the possibility to scale up the observations to long-term effects in the natural environment. To gain a broader perspective, we utilized volcanic CO2 vents as a "natural laboratory" to study OA effects on Sargassum vulgare at different time scales. We measured photosynthetic rates, oxidative stress levels, antioxidant contents, antioxidant enzyme activities, and activities of oxidative metabolic enzymes in S. vulgare growing at a natural acidified site (pH 6.7) compared to samples from a site with current pH (pH 8.2), used as a control one. These variables were also tested in plants transplanted from the control to the acidified site and vice-versa. After short-term exposure, photosynthetic rates and energy metabolism were increased in S. vulgare together with oxidative damage. However, in natural populations under long-term conditions photosynthetic rates were similar, the activity of oxidative metabolic enzymes was maintained, and no sign of oxidative damages was observed. The differences in the response of the macroalga indicate that the natural population at the acidified site is adapted to live at the lowered pH. The results suggest that this macroalga can adopt biochemical and physiological strategies to grow in future acidified oceans.


Acute lung injury after mechanical circulatory support implantation in patients on extracorporeal life support: an unrecognized problem.
We observed early acute lung injury (ALI) after a switch from veno-arterial extracorporeal life support (VA-ECLS) to long-term mechanical circulatory support (MCS). The aim of our study was to analyse the frequency, impact on mortality and characteristics of patients presenting ALI after MCS implantation in the bridge-to-bridge (BTB) strategy. We retrospectively analysed data from 55 consecutive cardiogenic shock patients who underwent a BTB strategy between January 2004 and March 2012 in our centre. ALI was defined as severe acute respiratory failure (PaO2/FiO2 <200) with or without need for iterative VA-ECLS or veno-venous (VV)-exracorporeal membrane oxygenation (ECMO) occurring within 48 h of MCS implantation. ALI was observed in 15 of 55 (27%) patients. Eleven patients required VV-ECMO or VA-ECLS and 4 were treated medically. The median (interquartile range) duration of support under a long-term device was 47.5 (168.8) days. Mortality while on long-term support was significantly higher in patients who developed ALI (13 of 15, 87%) than in those who did not (21 of 40, 53%; P = 0.03). Hazard ratio for death while on support in patients who developed ALI when compared with those who did not was 3.390 (95% confidence interval, 1.636-7.026, P = 0.001). Univariate risk factors for postimplant ALI included: signs of pulmonary oedema while under extracorporeal life support (ECLS) during the week preceding long-term device implantation; mechanical ventilation, the incomplete recovery of renal and hepatic functions and the number of red blood cell units transfused at the time of long-term device implantation, and use of pulsatile, biventricular support. Implantation of a long-term MCS device in patients on ECLS can result in severe ALI, which is associated with ominous outcomes. Various preimplant risk factors for ALI have been identified and might allow devising strategies to prevent this complication.


Computerized versus motivational interviewing alcohol interventions: impact on discrepancy, motivation, and drinking.
The authors conducted two randomized clinical trials with ethnically diverse samples of college student drinkers in order to determine (a) the relative efficacy of two popular computerized interventions versus a more comprehensive motivational interview approach (BASICS) and (b) the mechanisms of change associated with these interventions. In Study 1, heavy drinking participants recruited from a student health center (N = 74, 59% women, 23% African American) were randomly assigned to receive BASICS or the Alcohol 101 CD-ROM program. BASICS was associated with greater post-session motivation to change and self-ideal and normative discrepancy relative to Alcohol 101, but there were no group differences in the primary drinking outcomes at 1-month follow-up. Pre to post session increases in motivation predicted lower follow-up drinking across both conditions. In Study 2, heavy drinking freshman recruited from a core university course (N = 133, 50% women, 30% African American) were randomly assigned to BASICS, a web-based feedback program (e-CHUG), or assessment-only. BASICS was associated with greater post-session self-ideal discrepancy than e-CHUG, but there were no differences in motivation or normative discrepancy. There was a significant treatment effect on typical weekly and heavy drinking, with participants in BASICS reporting significantly lower follow-up drinking relative to assessment only participants. In Study 2, change in the motivation or discrepancy did not predict drinking outcomes. Across both studies, African American students assigned to BASICS reported medium effect size reductions in drinking whereas African American students assigned to Alcohol 101, e-CHUG, or assessment did not reduce their drinking.


Resistance exercise, muscle loading/unloading and the control of muscle mass.
Muscle mass is determined by the difference between the rate of protein synthesis and degradation. If synthesis is greater than degradation, muscle mass will increase (hypertrophy) and when the reverse is true muscle mass will decrease (atrophy). Following resistance exercise/increased loading there is a transient increase in protein synthesis within muscle. This change in protein synthesis correlates with an increase in the activity of protein kinase B/Akt and mTOR (mammalian target of rapamycin). mTOR increases protein synthesis by increasing translation initiation and by inducing ribosomal biogenesis. By contrast, unloading or inactivity results in a decrease in protein synthesis and a significant increase in muscle protein breakdown. The decrease in synthesis is due in part to the inactivation of mTOR and therefore a decrease in translation initiation, but also to a decrease in the rate of translation elongation. The increase in degradation is the result of a co-ordinated response of the calpains, lysosomal proteases and the ATP-dependent ubiquitin-proteosome. Caspase 3 and the calpains act upstream of the ubiquitin-proteosome system to assist in the complete breakdown of the myofibrillar proteins. Two muscle specific E3 ubiquitin ligases, MuRF1 and MAFbx/atrogen-1, have been identified as key regulators of muscle atrophy. In this chapter, these pathways and how the balance between anabolism and catabolism is affected by loading and unloading will be discussed.


Proximal promoter elements of the human zeta-globin gene confer embryonic-specific expression on a linked reporter gene in transgenic mice.
We have investigated the transcriptional regulation of the human embryonic zeta-globin gene promoter. First, we examined the effect that deletion of sequences 5' to zeta-globin's CCAAT box have on zeta-promoter activity in erythroid cell lines. Deletions of sequences between -116 and -556 (cap = 0) had little effect while further deletion to -84 reduced zeta-promoter activity by only 2-3-fold in both transiently and stably transfected erythroid cells. Constructs containing 67, 84 and 556 bp of zeta-globin 5' flanking region linked to a beta-galactosidase reporter gene (lacZ) and hypersensitive site -40 (HS-40) of the human alpha-globin gene cluster were then employed for the generation of transgenic mice. LacZ expression from all constructs, including a 67 bp zeta-globin promoter, was erythroid-specific and most active between 8.5 and 10.5 days post-fertilisation. By 16.5 days gestation, lacZ expression dropped 40-100-fold. These results suggest that embryonic-specific activation of the human zeta-globin promoter is conferred by a 67 bp zeta-promoter fragment containing only a CCAAT and TATA box.


Iridium containing honeycomb Delafossites by topotactic cation exchange.
We report the structure and magnetic properties of two new iridium-based honeycomb Delafossite compounds, Cu3NaIr2O6 and Cu3LiIr2O6, formed by a topotactic cation exchange reaction. The starting materials Na2IrO3 and Li2IrO3, which are based on layers of IrO6 octahedra in a honeycomb lattice separated by layers of alkali ions, are transformed to the title compounds by a topotactic exchange reaction through heating with CuCl below 450 °C; higher temperature reactions cause decomposition. The new compounds display dramatically different magnetic behavior from their parent compounds - Cu3NaIr2O6 has a ferromagnetic like magnetic transition at 10 K, while Cu3LiIr2O6 retains the antiferromagnetic transition temperature of its parent compound but displays significantly stronger dominance of antiferromagnetic coupling between spins. These results reveal that a surprising difference in the magnetic interactions between the magnetic Ir ions has been induced by a change in the non-magnetic interlayer species. A combination of neutron and X-ray powder diffraction is used for the structure refinement of Cu3NaIr2O6 and both compounds are compared to their parent materials.


Ambient odor of orange in a dental office reduces anxiety and improves mood in female patients.
Essential oils have been used as remedies for a long time in different cultures across the world. However, scientific proof of such application is scarce. We included 72 patients between the ages of 22 and 57 while waiting for dental treatment in our study. The participants were assigned to either a control group (14 men, 23 women) or to an odor group (18 men and 17 women). Ambient odor of orange was diffused in the waiting room through an electrical dispenser in the odor group whereas in the control group no odor was in the air. We assessed by means of self-report demographic and cognitive variables, trait and state anxiety, and current pain, mood, alertness, and calmness. In this study, we report that exposure to ambient odor of orange has a relaxant effect. Specifically, compared to the controls, women who were exposed to orange odor had a lower level of state anxiety, a more positive mood, and a higher level of calmness. Our data support the previous notion of sedative properties of the natural essential oil of orange (Citrus sinensis).


Simultaneous interfacial rheology and microstructure measurement of densely aggregated particle laden interfaces using a modified double wall ring interfacial rheometer.
The study of particle laden interfaces has increased significantly due to the increasing industrial use of particle stabilized foams and Pickering emulsions, whose bulk rheology and stability are highly dependent on particle laden interface's interfacial rheology, which is a function of interfacial microstructure. To understand the physical mechanisms that dictate interfacial rheology of particle laden interfaces requires correlating rheology to microstructure. To achieve this goal, a double wall ring interfacial rheometer has been modified to allow real time, simultaneous interfacial visualization and shear rheology measurements. The development of this tool is outlined, and its ability to provide novel and unique measurements is demonstrated on a sample system. This tool has been used to examine the role of microstructure on the steady shear rheology of densely packed, aggregated particle laden interfaces at three surface concentrations. Through examination of the rheology and analysis of interfacial microstructure response to shear, a transition from shear thinning due to aggregated cluster breakup to yielding at a slip plane within the interface has been identified. Interestingly, it is found that aggregated interfaces transition to yielding well before they reached a jammed state. Furthermore, these systems undergo significant shear induced order when densely packed. These results indicate that the mechanics of these interfaces are not simply jammed or unjammed and that the interfacial rheology relationship with microstructure can give us significant insight into understanding how to engineer particle laden interfaces in the future. By examining both rheology and microstructure, the mechanisms that dictate observed rheology are now understood and can be used to predict and control the rheology of the interface.


Oral Human Papillomavirus Infection in Men Who Have Sex with Men: A Systematic Review and Meta-Analysis.
The epidemiology of oral human papillomavirus (HPV) infection in men who have sex with men (MSM) differs from anogenital HPV infection. The impact of HPV vaccination has, to date, largely focussed on anogenital outcomes. Vaccination of MSM in the UK has been recommended and, if implemented, baseline estimates of oral HPV prevalence will be useful. We searched Medline, Embase and psycINFO databases for studies reporting prevalence, incidence, and clearance of oral HPV infection in MSM. We performed a random-effects meta-analysis and meta-regression on prevalence estimates and summarised within-study risk factors for oral HPV DNA detection and incidence/clearance rates. We also performed a meta-analysis of the effect of MSM on oral HPV prevalence compared to heterosexual men. 26 publications were identified. The pooled prevalence of oral HPV16 from twelve estimates was 3.0% (95%CI 0.5-5.5) in HIV-negative and 4.7% (95%CI 2.1-7.3) in HIV-positive MSM. Median age of study participants explained 38% of heterogeneity (p<0.01) in HPV prevalence estimates (pooled = 17% and 29% in HIV-negative and HIV-positive, respectively; 22 estimates). Nine studies compared MSM to heterosexual men and found no difference in oral HPV prevalence (pooled OR 1.07 (95%CI 0.65-1.74)). The clearance rate was higher than incidence within studies. Type-specific concordance between oral and anogenital sites was rare. There was substantial heterogeneity between estimates of oral HPV prevalence in MSM populations that was partly explained by HIV status and median age.


Prospective study of electrical impedance scanning for identifying young women at risk for breast cancer.
One way to improve the cost-benefit ratio for breast cancer screening in younger women is to identify those at high-risk of breast cancer and manage them in an optimal manner. The purpose of this study is to evaluate the sensitivity and specificity of Electrical Impedance Scanning (EIS) for identifying young women who are at risk for having breast cancer and should be followed with directed imaging technologies. A prospective, observational, two-arm, multi-site clinical trial was performed on women aged 30-45 years. The 'Sensitivity Arm' included Clinical Breast Examinations (CBE) and EIS (T-Scan 2000ED) on 189 women prior to scheduled breast biopsy. The 'Specificity Arm' included 1361 asymptomatic women visiting clinics for routine annual well-woman examination. Sensitivity and specificity were determined. Relative probability for a woman with a positive EIS examination was computed and compared with other approaches commonly used to define 'high-risk' in this population. Fifty of 189 women in the Sensitivity arm had verified cancers, 19 of whom had positive EIS examination resulting in sensitivity of 38% (19/50). Of the 1361 women in the Specificity arm, 67 had positive EIS examination resulting in a specificity of 95% (1294/1361). The relative probability of a woman with a positive EIS examination was 7.68, which compares favorably with other established risk identifiers (e.g. two first-degree relatives with breast cancer or atypical ductal hyperplasia). EIS may have an important role as a screening tool for identifying young women that should be followed more closely with advanced imaging technologies for early detection of breast cancer.


Cannabis withdrawal syndrome: An important diagnostic consideration in adolescents presenting with disordered eating.
Although previously thought to have no withdrawal symptoms, there is now convergent evidence for a cannabis withdrawal syndrome (CWS), criteria for its diagnosis, and evidence of its impact in the adolescent population. Cannabis withdrawal syndrome represents an important and under-recognized consideration in adolescents with disordered eating. We describe three clinical cases of adolescents presenting to an eating disorders program with primary complaints of gastrointestinal symptoms, food avoidance, and associated weight loss. They did not meet the criteria for an eating disorder, but did fulfill the DSM-5 criteria for CWS. This report emphasizes the importance of considering the impact of heavy cannabis use in adolescents presenting with gastrointestinal complaints, and eating disorder symptoms, including weight loss.


The expression of the miR-25/93/106b family of micro-RNAs in the adipose tissue of women with polycystic ovary syndrome.
In adipose tissue (AT) micro-RNA-93 (miR-93) is significantly overexpressed in polycystic ovary syndrome (PCOS) women and non-PCOS women with insulin resistance (IR). Overexpressed miR-93 directly inhibits glucose transporter isoform 4, impairing both glucose metabolism and insulin sensitivity. The mechanisms behind increased miR-93 expression are unclear. Our objective was to determine whether miR-93 expression is concordant with its host gene, MCM7, which contains the miR-25/93/106b gene cluster. AT was excised from 16 women with PCOS (eight with and eight without IR) and 15 non-PCOS (nine with and six without IR). Expression of MCM7 and miR-25/93/106b was measured in AT and 3T3-L1 cells. MCM7 expression was lower in both non-PCOS/IR and PCOS women and tended to be lowest in women with PCOS and IR. Overall, the expression of MCM7 in human AT was negatively associated with miR-93 expression and with increased subject IR. Additionally, miR-25 and miR-106b expression is uncoupled from the MCM7 host gene and are positively correlated with IR, although no PCOS-specific difference was observed. MCM7 expression appears to be negatively correlated with increasing fasting glucose. In 3T3-L1 adipocytes, increasing glucose had no effect on miR-93 or miR-25, although it reduced MCM7 and increased miR-106b expression in a dose-dependent fashion. In turn, in 3T3-L1 adipocytes, increasing insulin had no effect on either MCM7 or miR-25/93/106b expression. Our data suggest that the expression of MCM7 and miR-93/25 is PCOS and IR related, whereas that of miR-106b is related to IR only. In 3T3-L1 adipocytes, neither hyperglycemia nor hyperinsulinemia altered the expression of miR-93 or miR-25, although increasing glucose levels down-regulated MCM7 and paradoxically increased that of miR-106b expression. The expression of the miR-25/93/106b family may be regulated through mechanisms distinct from its host gene, MCM7. Finally, our studies suggest potential epigenetic mechanisms for both IR and PCOS.


Demographic characteristics of patients undergoing aortic valve replacement for stenosis: relation to valve morphology.
To determine the relative importance of the different causes of isolated aortic valve stenosis in a surgical series, and to relate these to patient characteristics including the rate of insertion of bypass grafts for coronary artery disease. Survey of the clinical and pathological data on patients undergoing aortic valve replacement for isolated stenosis. Tertiary care cardiothoracic surgical unit. 465 adult patients undergoing aortic valve replacement representing a consecutive series in one surgical unit. Retrospective review of patients records and classification of cause of aortic stenosis based on pathological examination of excised valve cusps. 63.7% patients had calcific bicuspid valves, 26.9% tricuspid calcific valves, and 5.4% rheumatic, 2.6% mixed pathology and 1.5% unicommissural valves. The ratio of males to females for bicuspid valves was 1.85:1 and for tricuspid calcific valves 0.76:1. The mean age of patients with bicuspid valves was 64.9 years compared with 73.4 years for those with tricuspid valves. Some 22.3% of patients with bicuspid valves and 44.8% of those with tricuspid valves had sufficient coronary artery disease to necessitate insertion of coronary bypass grafts. The differential rate of insertion of coronary bypass grafts was independent of age. Bicuspid calcified aortic valves are the predominant cause of isolated aortic valve stenosis followed by tricuspid calcified aortic valves. The sex and age distribution of bicuspid and tricuspid calcific aortic valve stenosis is different. The higher rate of insertion of vascular grafts in tricuspid calcific aortic valves may indicate that risk factors for atherosclerosis enhance cusp calcification in these patients.


The effects of daily exercise on susceptibility to sudden cardiac death.
The purpose of this study was to investigate the effects of daily exercise on susceptibility to sudden cardiac death. A 2 min coronary occlusion was initiated during the last minute of an exercise stress test and continued for 1 min after cessation of exercise in chronically instrumented dogs with a healed anterior wall myocardial infarction. Thirteen dogs developed ventricular fibrillation (VF; susceptible), while five did not (resistant). Before the exercise plus ischemia test, the baroreflex was evaluated with a bolus injection of phenylephrine (10 micrograms/kg). The changes in heart rate caused by a 30 mm Hg increase in systolic arterial pressure as well as the slopes of either heart rate or RR interval plotted against systolic arterial pressure were significantly lower in dogs that developed VR (resistant, -49.6 +/- 7.8; susceptible, -15.3 +/- 6.4 beats/min; p less than .001). Four resistant and eight susceptible animals were then placed on a 6 week daily exercise program, while eight susceptible dogs had an equal period of rest. At the end of the 6 week period the exercise plus ischemia test was repeated; no susceptible animal that performed daily exercise developed VF, and all but one of the rested animals did. Daily exercise improved baroreflex control of heart rate in the susceptible group but not in the resistant group. Rest did not alter baroreflex function (change in heart rate after 30 mm Hg increase in systolic arterial pressure: after 6 weeks of exercise, resistant -43.3 +/- 18.9 beats/min, susceptible -60.8 +/- 16.6 beats/min; after 6 weeks of rest, susceptible 27.4 +/- 11.0 beats/min). We conclude that daily exercise prevents VF induced by acute myocardial ischemia in a subpopulation of dogs that were previously identified as susceptible to sudden cardiac death. Exercise also altered the autonomic control of the heart, possibly decreasing sympathetic and/or increasing parasympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)


Neurosyphilis Masquerading as Stroke in an 84-year-old.
The case of an 84 years old woman with uncharacteristic neurologic and cognitive symptoms, suspected of ischemic stroke is presented. Following an extensive assessment in the departments of neurology and internal medicine, the unusual aetiology of stroke was identified as meningovascular neurosyphilis. The patient fully recovered after antibiotic therapy. To our knowledge, this the eldest patient with tertiary neurosyphilis reported in the literature.


Ventilatory efficiency and aerobic capacity in people with multiple sclerosis: A randomized study.
To assess ventilatory efficiency and aerobic capacity in people with multiple sclerosis and whether treadmill walking or progressive strength training has an effect on these parameters in this population. In all, 24 adults with multiple sclerosis with an Expanded Disability Status Scale score of ≤6 completed a cardiopulmonary exercise test before and after 8 weeks of exercise. They were randomized to treadmill walking of low-to-moderate intensity (50%-70% of peak heart rate) or progressive strength training (six repetitions × two at 80% of one repetition maximum). Both groups exercised for 30 min three times per week. Primary outcome measure was ventilatory efficiency measured as the minute ventilation/carbon dioxide production (VE/VCO2) ratio and oxygen uptake efficiency slope. Secondary outcome was aerobic capacity, measured as peak oxygen uptake (VO2peak). Despite low aerobic capacity, ventilatory efficiency was found to be within normal range. After 8 weeks of exercise, no significant between-group differences emerged in (1) VE/VCO2 ratio (26 ± 2.2 to 26 ± 2.0, 29 ± 2.0 to 28 ± 2.3, p = 0.66), (2) oxygen uptake efficiency slope (2697 ± 442 to 2701 ± 577, 2473 ± 800 to 2481 ± 896, p = 0.71), or (3) VO2peak in mL/kg/min (28 ± 4.4 to 30 ± 4.3, 29 ± 6.7 to 29 ± 6.4, p = 0.38) in treadmill walking and progressive strength training, respectively. There were no significant within-group differences either. No adverse events occurred during cardiopulmonary exercise test or exercise training. In people with mild-to-moderate multiple sclerosis, 8 weeks of treadmill walking of low-to-moderate intensity or progressive strength training did not have any effect on ventilatory efficiency or aerobic capacity. Although aerobic capacity was lower than reference values, ventilatory efficiency was not reduced.


Functional brain architecture is associated with the rate of tau accumulation in Alzheimer's disease.
In Alzheimer's diseases (AD), tau pathology is strongly associated with cognitive decline. Preclinical evidence suggests that tau spreads across connected neurons in an activity-dependent manner. Supporting this, cross-sectional AD studies show that tau deposition patterns resemble functional brain networks. However, whether higher functional connectivity is associated with higher rates of tau accumulation is unclear. Here, we combine resting-state fMRI with longitudinal tau-PET in two independent samples including 53 (ADNI) and 41 (BioFINDER) amyloid-biomarker defined AD subjects and 28 (ADNI) vs. 16 (BioFINDER) amyloid-negative healthy controls. In both samples, AD subjects show faster tau accumulation than controls. Second, in AD, higher fMRI-assessed connectivity between 400 regions of interest (ROIs) is associated with correlated tau-PET accumulation in corresponding ROIs. Third, we show that a model including baseline connectivity and tau-PET is associated with future tau-PET accumulation. Together, connectivity is associated with tau spread in AD, supporting the view of transneuronal tau propagation.


Comparing competitive fitness of West Nile virus strains in avian and mosquito hosts.
Enzootic transmission of West Nile virus (WNV; Flaviviridae, Flavivirus) involves various species of birds and ornithophilic mosquitoes. Single nucleotide substitutions in the WNV genome may impact viral fitness necessary for WNV adaptation and evolution as previously shown for the WN02 genotype. In an effort to study phenotypic change, we developed an in vivo fitness competition model in two biologically relevant hosts for WNV. The House Finch (HOFI; Haemorhous mexicanus) and Culex tarsalis mosquitoes represent moderately susceptible hosts for WNV, are highly abundant in Western North America and frequently are infected with WNV in nature. Herein, we inoculated HOFIs and Cx. tarsalis competitively (dually) and singly with infectious-clone derived viruses of the founding California isolate COAV997-2003 (COAV997-IC), the founding North American isolate NY99 (NY99-IC), and a 2004 field isolate from California (CA-04), and compared the replicative capacities (fitness) of these viruses to a genetically marked virus of COAV997 (COAV997-5nt) by measuring RNA copy numbers. COAV997 and COAV997-5nt exhibited neutral fitness in HOFIs and Cx. tarsalis, and the temperature-sensitive phenotype of COAV997 did not affect replication in HOFIs as none of the infected birds became febrile. The NY99 and CA-04 isolates demonstrated elevated fitness in HOFIs compared to COAV997-5nt, whereas all viruses replicated to similar titers and RNA copies in Cx. tarsalis, and the only fitness differences were related to infection rates. Our data demonstrated that competitive replication allows for the sensitive comparison of fitness differences among two genetically closely related viruses using relevant hosts of WNV while eliminating host-to-host differences. In conclusion, our approach may be helpful in understanding the extent of phenotypic change in fitness associated with genetic changes in WNV.


Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia.
Myelodysplastic syndromes and chronic myelomonocytic leukemia (CMML) are characterized by mutations in genes encoding epigenetic modifiers and aberrant DNA methylation. DNA methyltransferase inhibitors (DMTis) are used to treat these disorders, but response is highly variable, with few means to predict which patients will benefit. Here, we examined baseline differences in mutations, DNA methylation, and gene expression in 40 CMML patients who were responsive or resistant to decitabine (DAC) in order to develop a molecular means of predicting response at diagnosis. While somatic mutations did not differentiate responders from nonresponders, we identified 167 differentially methylated regions (DMRs) of DNA at baseline that distinguished responders from nonresponders using next-generation sequencing. These DMRs were primarily localized to nonpromoter regions and overlapped with distal regulatory enhancers. Using the methylation profiles, we developed an epigenetic classifier that accurately predicted DAC response at the time of diagnosis. Transcriptional analysis revealed differences in gene expression at diagnosis between responders and nonresponders. In responders, the upregulated genes included those that are associated with the cell cycle, potentially contributing to effective DAC incorporation. Treatment with CXCL4 and CXCL7, which were overexpressed in nonresponders, blocked DAC effects in isolated normal CD34+ and primary CMML cells, suggesting that their upregulation contributes to primary DAC resistance.


The development and validation of the core competencies scale (CCS) for the college and university students.
This article describes the development and validation of the Core Competencies Scale (CCS) using Bok's (2006) competency framework for undergraduate education. The framework included: communication, critical thinking, character development, citizenship, diversity, global understanding, widening of interest, and career and vocational development. The sample comprised 70 college and university students. Results of analysis using Rasch rating scale modelling showed that there was strong empirical evidence on the validity of the measures in contents, structure, interpretation, generalizability, and response options of the CCS scale. The implication of having developed Rasch-based valid and dependable measures in this study for gauging the value added of college and university education to their students is that the feedback generated from CCS will enable evidence-based decision and policy making to be implemented and strategized. Further, program effectiveness can be measured and thus accountability on the achievement of the program objectives.


White tail disease of the giant freshwater prawn Macrobrachium rosenbergii in Thailand.
White tail disease (WTD) of the freshwater prawn Macrobrachium rosenbergii has recently been the cause of high mortalities in Thai prawn farms. The causative agents of this disease in other countries are M. rosenbergii nodavirus (MrNV) and extra small virus (XSV), which are usually detected using reverse transcriptase-polymerase chain reaction (RT-PCR) protocols. Using RT-PCR, most Thai post-larvae (PL) samples showing gross signs of WTD tested positive for MrNV but only a few were positive for XSV. In contrast, all tested brooder samples were positive for both MrNV and XSV. The possibility that brooders infected with MrNV and XSV could transmit the viruses to larvae and PL should be examined. Cloning, sequencing and comparison of deduced amino acid sequences of RT-PCR amplicons of WTD samples from Thailand with those of MrNV and XSV previously reported from the French West Indies and China revealed that the MrNV were closely related but not identical while those from XSV were identical. This is the first report of MrNV and XSV from Thailand.


Psychological Distress and Revictimization Risk in Youth Victims of Sexual Abuse.
Psychological distress, including depression and anxiety, has been associated with increased risk for sexual revictimization in youth who have experienced child sexual abuse. The present study utilized assessment information from treatment seeking youth with histories of sexual abuse to explore specific risk indicators for revictimization-risk taking, social problems, maladaptive cognitions, and posttraumatic stress-that may be indicated by self-reported distress. The relationship between initial levels of distress and change in symptoms over a 12-week course of treatment was also explored. Participants were 101 youth referred to a child-focused therapeutic group for victims of sexual abuse, 65 youth referred to an adolescent-focused group, and their non-offending caregivers. Results revealed that when combined into a distress score, depression and anxiety were associated with delinquent behaviors, interpersonal difficulties, maladaptive cognitions, and posttraumatic stress symptoms for child and adolescent group participants at presentation to treatment. Children exhibited improvement on measures of interpersonal difficulties, maladaptive cognitions, and self-reported posttraumatic stress disorder (PTSD) symptoms. Adolescents exhibited less change over time, with significant improvement on self-reported social problems and PTSD only. Higher psychological distress was associated with less improvement in regard to negative expectations of abuse impact for child group participants. The findings suggest that distress indicates the presence of specific revictimization risk indicators, helping to identify targetable symptoms for intervention. Therefore, screening for psychological distress after discovery of sexual abuse may help detect youth at higher risk for revictimization and guide treatment.


Drug binding to the inactivated state is necessary but not sufficient for high-affinity binding to human ether-à-go-go-related gene channels.
Drug block of the human ether-à-go-go-related gene K(+) channel (hERG) is the most common cause of acquired long QT syndrome, a disorder of cardiac repolarization that may result in ventricular tachycardia and sudden cardiac death. We investigated the open versus inactivated state dependence of drug block by using hERG mutants N588K and N588E, which shift the voltage dependence of inactivation compared with wild-type but in which the mutated residue is remote from the drug-binding pocket in the channel pore. Four high-affinity drugs (cisapride, dofetilide, terfenadine, and astemizole) demonstrated lower affinity for the inactivation-deficient N588K mutant hERG channel compared with N588E and wild-type hERG. Three of four low-affinity drugs (erythromycin, perhexiline, and quinidine) demonstrated no preference for N588E over N588K channels, whereas dl-sotalol was an example of a low-affinity state-dependent blocker. All five state-dependent blockers showed an even lower affinity for S620T mutant hERG (no inactivation) compared with N588K mutant hERG (greatly reduced inactivation). Computer modeling indicates that the reduced affinity for S620T compared with N588K and wild-type channels can be explained by the relative kinetics of drug block and unblock compared with the kinetics of inactivation and recovery from inactivation. We were also able to calculate, for the first time, the relative affinities for the inactivated versus the open state, which for the drugs tested here ranged from 4- to 70-fold. Our results show that preferential binding to the inactivated state is necessary but not sufficient for high-affinity binding to hERG channels.


Disruption of vitellogenin gene function in adult honeybees by intra-abdominal injection of double-stranded RNA.
The ability to manipulate the genetic networks underlying the physiological and behavioural repertoires of the adult honeybee worker (Apis mellifera) is likely to deepen our understanding of issues such as learning and memory generation, ageing, and the regulatory anatomy of social systems in proximate as well as evolutionary terms. Here we assess two methods for probing gene function by RNA interference (RNAi) in adult honeybees. The vitellogenin gene was chosen as target because its expression is unlikely to have a phenotypic effect until the adult stage in bees. This allowed us to introduce dsRNA in preblastoderm eggs without affecting gene function during development. Of workers reared from eggs injected with dsRNA derived from a 504 bp stretch of the vitellogenin coding sequence, 15% had strongly reduced levels of vitellogenin mRNA. When dsRNA was introduced by intra-abdominal injection in newly emerged bees, almost all individuals (96%) showed the mutant phenotype. An RNA-fragment with an apparent size similar to the template dsRNA was still present in this group after 15 days. Injection of dsRNA in eggs at the preblastoderm stage seems to allow disruption of gene function in all developmental stages. To dissect gene function in the adult stage, the intra-abdominal injection technique seems superior to egg injection as it gives a much higher penetrance, it is much simpler, and it makes it possible to address genes that are also expressed in the embryonic, larval or pupal stages.


Gain-Sparsity and Symmetry-Forced Rigidity in the Plane.
We consider planar bar-and-joint frameworks with discrete point group symmetry in which the joint positions are as generic as possible subject to the symmetry constraint. We provide combinatorial characterizations for symmetry-forced rigidity of such structures with rotation symmetry or dihedral symmetry of order 2k with odd k, unifying and extending previous work on this subject. We also explore the matroidal background of our results and show that the matroids induced by the row independence of the orbit matrices of the symmetric frameworks are isomorphic to gain sparsity matroids defined on the quotient graph of the framework, whose edges are labeled by elements of the corresponding symmetry group. The proofs are based on new Henneberg type inductive constructions of the gain graphs that correspond to the bases of the matroids in question, which can also be seen as symmetry preserving graph operations in the original graph.


Maxillomandibular Advancement for OSA: A 25-year perspective
The aim of this study was to evaluate the result of maxillomandibular advancement (MMA) for the treatment of obstructive sleep apnea (OSA) by a single surgeon. Patients that underwent MMA for the treatment of OSA over a 25-year period were included in the study. Patients who initially presented for revision MMA surgery were excluded. Demographics (e.g., age, gender, pre- and post-MMA body mass index [BMI]), pre- and post-MMA cephalometrics (e.g., sella-nasion-point A angle [SNA], sella-nasion-point B angle [SNB], posterior airway space base of tongue [PAS]) and pre- and post-MMA sleep study metrics (e.g., respiratory disturbance index [RDI], lowest desaturation [SpO2-nadir], oxygen desaturation index [ODI], total sleep time [TST], % TST Stage N3 sleep, % TST rapid eye movement [REM] sleep) were abstracted. MMA surgical success was defined as a ≥ 50% reduction in RDI (or ODI) and post-MMA RDI (or ODI) < 20 events/hour. MMA surgical cure was defined as a post-MMA RDI (or ODI) < 5 events/hour. A total of 1010 patients underwent MMA for the treatment of OSA. The mean age was 39.6 ± 14.3 years, and the majority were male (77%). Nine hundred forty-one patients with complete pre- and postoperative PSG data were analyzed. The mean ODI and RDI improved from 32.6 ± 27.4 to 7.7 ± 15.5 and 39.1 ± 24.2 to 13.6 ± 14.6 events per hour, respectively. The overall surgical success and surgical cure based on ODI was 79.4% and 71.9%, respectively. The overall surgical success and surgical cure based on RDI was 73.1% and 20.7%, respectively. Stratified by preoperative RDI showed older age, greater BMI were associated with greater preoperative RDI. Bivariate predictors of greater RDI reduction include younger age, female gender, lower preoperative BMI, higher preoperative RDI, greater BMI reduction postoperatively and greater change in SNA and PAS. Bivariate predictors of surgical cure based on RDI (RDI < 5) include younger age, female gender, lower preoperative RDI, and greater change in SNA and PAS. Bivariate predictor of RDI success (RDI < 20) include younger age, female gender, lower preoperative BMI, lower preoperative RDI, greater BMI reduction, greater increase in SNA, SNB and PAS postoperatively. Comparison of the first 500 patients and the later 510 patients demonstrate patients undergoing MMA have become younger, having lower RDI while achieving a better surgical outcome. Linear multivariate associations of greater percentage RDI reduction include younger age, greater percent change of SNA, greater preoperative SNA, lower preoperative BMI and higher preoperative RDI. MMA is an effective treatment to improve OSA, but the result can vary. Patient selection based on favorable prognostic factors and maximizing the advancement distance can improve outcomes.


Neural Correlates of Drug-Related Attentional Bias in Heroin Dependence.
The attention of drug-dependent persons tends to be captured by stimuli associated with drug consumption. This involuntary cognitive process is considered as attentional bias (AB). AB has been hypothesized to have causal effects on drug abuse and drug relapse, but its underlying neural mechanisms are still unclear. This study investigated the neural basis of AB in abstinent heroin addicts (AHAs), combining event-related potential (ERP) analysis and source localization techniques. Electroencephalography data were collected in 21 abstinent heroin addicts and 24 age- and gender-matched healthy controls (HCs) during a dot-probe task. In the task, a pair of drug-related image and neutral image was presented randomly in left and right side of the cross fixation, followed by a dot probe replacing one of the images. Behaviorally, AHAs had shorter reaction times (RTs) for the congruent condition compared to the incongruent condition, whereas this was not the case in the HCs. This finding demonstrated the presence of AB towards drug cues in AHAs. Furthermore, the image-evoked ERPs in AHAs had significant shorter P1 latency compared to HCs, as well as larger N1, N2, and P2 amplitude, suggesting that drug-related stimuli might capture attention early and overall require more attentional resources in AHAs. The target-related P3 had significantly shorter latency and lower amplitude in the congruent than incongruent condition in AHAs compared to HCs. Moreover, source localization of ERP components revealed increased activity for AHAs as compared to HCs in the dorsal posterior cingulate cortex (dPCC), superior parietal lobule and inferior frontal gyrus (IFG) for image-elicited responses, and decreased activity in the occipital and the medial parietal lobes for target-elicited responses. Overall, the results of our study confirmed that AHAs may exhibit AB in drug-related contexts, and suggested that the bias might be related to an abnormal neural activity, both in early and late attention processing stages.


Lung Abscess Remains a Life-Threatening Condition in Pediatrics - A Case Report.
Pulmonary abscess or lung abscess is a lung infection which destroys the lung parenchyma leading to cavitations and central necrosis in localised areas formed by thick-walled purulent material. It can be primary or secondary. Lung abscesses can occur at any age, but it seems that paediatric pulmonary abscess morbidity is lower than in adults. We present the case of a one year and 5-month-old male child admitted to our clinic for fever, loss of appetite and an overall altered general status. Laboratory tests revealed elevated inflammatory biomarkers, leukocytosis with neutrophilia, anaemia, thrombocytosis, low serum iron concentration and increased lactate dehydrogenase level. Despite wide-spectrum antibiotic therapy, the patient's progress remained poor after seven days of treatment and a CT scan established the diagnosis of a large lung abscess. Despite changing the antibiotic therapy, surgical intervention was eventually needed. There was a slow but steady improvment and eventually, the patient was discharged after approximately five weeks.


Effects of saddle height, pedaling cadence, and workload on joint kinetics and kinematics during cycling.
It is not clear how noncyclists control joint power and kinematics in different mechanical setups (saddle height, workload, and pedaling cadence). Joint mechanical work contribution and kinematics analysis could improve our comprehension of the coordinative pattern of noncyclists and provide evidence for bicycle setup to prevent injury. To compare joint mechanical work distribution and kinematics at different saddle heights, workloads, and pedaling cadences. Quantitative experimental research based on repeated measures. Research laboratory. 9 healthy male participants 22 to 36 years old without competitive cycling experience. Cycling on an ergometer in the following setups: 3 saddle heights (reference, 100% of trochanteric height; high, +3 cm; and low, -3 cm), 2 pedaling cadences (40 and 70 rpm), and 3 workloads (0, 5, and 10 N of braking force). Joint kinematics, joint mechanical work, and mechanical work contribution of the joints. There was an increased contribution of the ankle joint (P=.04) to the total mechanical work with increasing saddle height (from low to high) and pedaling cadence (from 40 to 70 rpm, P<.01). Knee work contribution increased when saddle height was changed from high to low (P<.01). Ankle-, knee-, and hip-joint kinematics were affected by saddle height changes (P<.01). At the high saddle position it could be inferred that the ankle joint compensated for the reduced knee-joint work contribution, which was probably effective for minimizing soft-tissue damage in the knee joint (eg, anterior cruciate ligament and patellofemoral cartilage). The increase in ankle work contribution and changes in joint kinematics associated with changes in pedaling cadence have been suggested to indicate poor pedaling-movement skill.


Clinical significance of variations in the interconnections between flexor digitorum longus and flexor hallucis longus in the region of the knot of Henry.
Tendon transfer of the flexor digitorum longus tendon (FDLT) or the flexor hallucis longus tendon (FHLT) into the tibialis posterior tendon is carried out in patients with tibialis posterior dysfunction. FDLT and FHLT are connected in the region of the knot of Henry. The present study has investigated the anatomical variations of this tendinous interconnection. The results could be used to determine which of the two tendons should be transected proximal to the region of the knot of Henry in the surgical treatment of tibialis posterior dysfunction. In over two-thirds of cadaver specimens investigated, tension applied solely to FHLT resulted in flexion of all digits and the hallux. On the basis of these results, we propose that identification of the tendon to be transected should be decided at the time of surgery depending on the anatomical pattern. Based on the evidence provided by 16 cadaveric dissections, transection of FDLT proximal to the region of the knot of Henry for the repair of tibialis posterior dysfunction would result in retention of function of the hallux and lesser digits in the majority of cases.


Evaluation of combined LED-fluorescence microscopy and bleach sedimentation for diagnosis of tuberculosis at peripheral health service level.
Sputum microscopy is the only diagnostic for tuberculosis (TB) available at peripheral levels of health service in resource-poor countries. Its sensitivity is reduced in high HIV-prevalence settings. Sodium hypochlorite (NaOCl) specimen sedimentation prior microscopy and light-emitting diode (LED)-fluorescence microscopy (FM) can individually improve performance of microscopy. This study aimed to evaluate the performance of combined LED-FM and NaOCl sputum sedimentation for TB detection at peripheral level of health services. A prospective study was conducted in an urban health clinic in Nairobi, Kenya. Three sputum specimens were collected over 2 days from consecutive TB suspects. Smears were prepared and stained with auramine O and Ziehl-Neelsen (ZN) methods. Bleach (3.5%) was added to the remaining specimen before overnight sedimentation at room temperature. Auramine O staining was performed on smears of sediment. A 4(th) specimen was collected for TB culture. Auramine smears were read under the same microscope as used for ZN smears, but equipped with the LED FluoLED™ fluorescence illuminator. 497 patients were included, and 1394 specimens collected. The yield of positive specimen was significantly increased after NaOCl sedimentation (24.9%) compared to direct LED-FM (20.6%) and direct ZN (20.3%). In detecting smear-positive patients, sensitivity was 78.5% for LED-FM after NaOCl sedimentation compared to 73.2% and 72.0% for direct LED-FM (P = 0.06) and direct ZN (P = 0.06), respectively. Specificity was 87.8% for LED-FM after NaOCl sedimentation compared to 96.7% and 95.9% for direct LED-FM (P<0.01) and direct ZN (P<0.01), respectively. Inter-reading agreement (kappa = 0.7) and technicians' acceptability were good. NaOCl sedimentation did not improve the performance of LED-FM in the diagnosis of pulmonary TB at peripheral health service level.


Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.
To reassess the role of plasmapheresis in the treatment of neurologic disorders. We evaluated the available evidence based on a structured literature review for relevant articles from 1995 through September 2009. In addition, due to revision of the definitions of classification of evidence since the publication of the previous American Academy of Neurology assessment in 1996, the evidence cited in that manuscript was reviewed and reclassified. Plasmapheresis is established as effective and should be offered in severe acute inflammatory demyelinating polyneuropathy (AIDP)/Guillain-Barré syndrome (GBS) and in the short-term management of chronic inflammatory demyelinating polyneuropathy (Class I studies, Level A). Plasmapheresis is established as ineffective and should not be offered for chronic or secondary progressive multiple sclerosis (MS) (Class I studies, Level A). Plasmapheresis is probably effective and should be considered for mild AIDP/GBS, as second-line treatment of steroid-resistant exacerbations in relapsing forms of MS, and for neuropathy associated with immunoglobulin A or immunoglobulin G gammopathy, based on at least one Class I or 2 Class II studies (Level B). Plasmapheresis is probably not effective and should not be considered for neuropathy associated with immunoglobulin M gammopathy, based on one Class I study (Level B). Plasmapheresis is possibly effective and may be considered for acute fulminant demyelinating CNS disease (Level C). There is insufficient evidence to support or refute the use of plasmapheresis for myasthenia gravis, pediatric autoimmune neuropsychiatric disorders associated with streptococcus infection, and Sydenham chorea (Class III evidence, Level U).