Colorimetric, enzymatic, and liquid-chromatographic methods for serum uric acid compared.
We describe high-performance liquid chromatography in conjunction with electrochemical detection as a possible reference method for serum uric acid. Separation was effected on a column packed with "Vydac" strong anion-exchange resin, with use of a detection potential of +0.80 V vs. an Ag/AgCl reference electrode. Results were linearly related to concentration up to 1.0 g/liter, and no interferences were seen. Assay of human sera gave within-run and day-to-day coefficients of variation of 0.83% and 1.1%, respectively; analytical recoveries averaged 100%. Comparison of the new procedure (x) with the phosphotungstate and uricase methods (y) showed the following linear regression and correlation coefficients for results: y equal 0.963x + 0.219 (r = 0.995), and y = 0.991x + 0.165 (r = 0.999), respectively. As compared to these methods, the procedure we describe is more accurate, because of the selective detection system based on retention time and redox potential. Samples can be analyzed at the rate of 20/h. No deproteinization is required.


Contralateral Cavernous Sinus Thrombosis Caused by Sphenoid Sinusitis: Case Report and Literature Review.
Cavernous sinus thrombosis (CST) is a rare but life-threatening infectious disease whose diagnosis and treatment are challenging. CST can result in ocular and neurologic morbidities, as well as fatal systemic complications due to systemic thrombus. Occasionally, these clinical symptoms can be a result of contralateral sinusitis. A 75-year-old female presented with severe headache and fever. Magnetic resonance imaging revealed a multifocal filling defect in both cavernous sinuses, with heterogeneous enhancement and thrombosis of the right superior ophthalmic vein. Intravenous antibiotic was administered, and endoscopic sinus surgery was performed. The patient was discharged 40 days after admission and there were no neurologic symptoms and no evidence of sequelae during the 10-month follow-up. Symptoms of CST on the contralateral side are often missed, which delays initiation of appropriate treatment. When CST secondary to paranasal sinusitis is diagnosed, clinicians should consider contralateral as well as ipsilateral infection of the paranasal sinus. Preventing disease progression and complications through early and aggressive antibiotic administration along with sinus surgery is crucial.


Cell swelling, seizures and spreading depression: an impedance study.
The cellular processes that take place during the transition from pre-seizure state to seizure remain to be defined. In this study in awake, paralyzed rats, we used an electrical impedance measure of changes in extra-cellular intracranial volume to estimate changes in cell size in acute models of epilepsy. Animals were prepared with extradural electroencephalographic (EEG)/impedance electrodes and a venous catheter. On a subsequent day, animals were paralyzed, ventilated and treated with picrotoxin, kainic acid or fluorocitrate in doses that usually induce epileptiform discharges. We now report that increases in baseline impedance were induced by kainic acid and smaller increases by picrotoxin. We also demonstrated that epileptiform discharges were preceded by small, accelerated increases in impedance. Increases in baseline impedance were highly correlated with increases in power of non-ictal high frequency EEG activity. Seizures were accompanied by increases in impedance and all treatments induced transient, relatively large, increases in impedance often associated with unilateral reductions in low frequency EEG, likely periods of spreading depression. We conclude: cerebral cells swell in convulsant models of epilepsy, that there are pre-ictal accelerations in cell swelling, and that spreading depression-like events are frequently associated with seizures.


[N.D. Strazhesko and his role in the development of modern clinical medicine].
The article presents information on academician N.D.Strazheshko- the founder of one of key native therapeutic schools with its new, original features. In the article was shown an important contribution of the scientist to the study of significant questions related to internal medicine and his role in the development of current clinical medicine.


Photomechanochromic vs. mechanochromic fluorescence of a unichromophoric bimodal molecular solid: multicolour fluorescence patterning.
Mechanofluorochromism (MFC) of molecular solids generally results from the variation of intermolecular interactions induced by external mechanical forces. However, the use of internal photomechanical forces to perturb intermolecular interactions for multicolour fluorescence responses has yet to be demonstrated. Herein we report a unichromophoric anthracene-pentiptycene derivative (1) that displays both MFC and photomechanofluorochromism (PMFC), which lead to various fluorescence colours including red-green-blue (RGB) and near-pure white-light emission. Compound 1 crystallizes in two polymorphs, the yellow (Y) and green (G) emissive forms, in which the pairwise stacked anthracene groups undergo [4 + 4] photodimerization to form the UV (black) emissive photodimer 2 and meanwhile exert photomechanical stresses on the neighbouring molecules. While the photomechanical stresses cause an excimer-to-monomer switching that results in a blue fluorescent state for the Y form, a red-emissive "super dimer" is photomechanically produced for the G form. The recovery of the Y form demands heating, but the G form could be restored by selective photoexcitation of the super dimer. X-ray crystal structures of the Y and G forms and the photodimer 2 generated through single-crystal-to-single-crystal transformation provide a clue to the origins of polymorph-dependent PMFC. The corresponding MFC and mechano-activated vapofluorochromism (VFC) of 1 also shed light on the structure-property relationship. The ability to spatially and temporally control the fluorochromicity of 1 is demonstrated by a series of multicolour fluorescence patterning of "angelfishes".


Dispersed activation in the left temporal cortex for speech-reading in congenitally deaf people.
Does the lateral temporal cortex require acoustic exposure in order to become specialized for speech processing? Six hearing participants and six congenitally deaf participants, all with spoken English as their first langugage, were scanned using functional magnetic resonance imaging while performing a simple speech-reading task. Focal activation of the left lateral temporal cortex was significantly reduced in the deaf group compared with the hearing group. Activation within this region was present in individual deaf participants, but varied in location from person to person. Early acoustic experience may be required for regions within the left temporal cortex in order to develop into a coherent network with subareas devoted to specific speech analysis functions.


Internet-based remote health self-checker symptom data as an adjuvant to a national syndromic surveillance system.
Syndromic surveillance is an innovative surveillance tool used to support national surveillance programmes. Recent advances in the use of internet-based health data have demonstrated the potential usefulness of these health data; however, there have been limited studies comparing these innovative health data to existing established syndromic surveillance systems. We conducted a retrospective observational study to assess the usefulness of a national internet-based 'symptom checker' service for use as a syndromic surveillance system. NHS Direct online data were extracted for 1 August 2012 to 1 July 2013; a time-series analysis on the symptom categories self-reported by online users was undertaken and compared to existing telehealth syndromic data. There were 3·37 million online users of the internet-based self-checker compared to 1·43 million callers to the telephone triage health service. There was a good correlation between the online and telephone triage data for a number of syndromic indicators including cold/flu, difficulty breathing and eye problems; however, online data appeared to provide additional early warning over telephone triage health data. This assessment has illustrated some potential benefit of using internet-based symptom-checker data and provides the basis for further investigating how these data can be incorporated into national syndromic surveillance programmes.


Ligand binding to integrin alphaIIbbeta3 is dependent on a MIDAS-like domain in the beta3 subunit.
Substitution of beta3 residue Asp119, Ser121, or Ser123 results in a loss of the ligand binding function of integrin alphaIIbbeta3. Homologous residues in other integrin beta subunits are similarly critical for ligand binding function. This DXSXS motif is also present in the I domain of certain integrin alpha subunits, where it constitutes a portion of the unique metal ion-dependent adhesion site (MIDAS). In this report, we have utilized the crystal structure of the recombinant alphaM I domain to produce a three-dimensional model of the homologous region in the integrin beta3 subunit. We performed mutagenesis of candidate amino acid residues predicted from this model to be involved in cation coordination and ligand binding. We report the identification of Asp217 and Glu220 as residues essential for the ligand binding function of alphaIIbbeta3. Alanine substitution of these residues did not affect receptor expression but abolished the binding of activation-dependent (PAC1) and -independent (OPG2) ligand mimetic antibodies. In our proposed model, beta3 Asp217 is analogous to a metal-coordinating residue in the alphaM MIDAS domain, while Glu220 does not correspond to a functional MIDAS domain residue. Substitution of the highly conserved beta3 residue Thr197 corresponding to a critical MIDAS metal-coordinating Thr residue did not affect ligand binding function, suggesting that this region of beta3 adopts a structure that is very similar to but not identical to that of the MIDAS domain. These data support a functional linkage between these two sequences and further define a common feature of ligand binding to integrins.


Development of the social brain from age three to twelve years.
Human adults recruit distinct networks of brain regions to think about the bodies and minds of others. This study characterizes the development of these networks, and tests for relationships between neural development and behavioral changes in reasoning about others' minds ('theory of mind', ToM). A large sample of children (n = 122, 3-12 years), and adults (n = 33), watched a short movie while undergoing fMRI. The movie highlights the characters' bodily sensations (often pain) and mental states (beliefs, desires, emotions), and is a feasible experiment for young children. Here we report three main findings: (1) ToM and pain networks are functionally distinct by age 3 years, (2) functional specialization increases throughout childhood, and (3) functional maturity of each network is related to increasingly anti-correlated responses between the networks. Furthermore, the most studied milestone in ToM development, passing explicit false-belief tasks, does not correspond to discontinuities in the development of the social brain.


Reliability of chest wall mobility and its correlation with pulmonary function in patients with chronic obstructive pulmonary disease.
Measurements of chest wall circumference are commonly used by physical therapists in clinical practice in order to determine chest wall mobility. However, the variability in the method for measuring this has not been reported previously among patients with chronic obstructive pulmonary disease. To analyze the reliability and accuracy of chest wall mobility measurements and to investigate the association between chest wall mobility and inspiratory capacity. Twenty-six patients with chronic obstructive pulmonary disease (forced expiratory volume in the first second = 45 +/- 14% of predicted) were evaluated over 2 visits. Spirometry was performed during the first visit, to characterize the sample. At each visit, 2 independent observers made chest wall mobility measurements twice, at the levels of the axillary, xiphisternal, and abdominal regions (total of 4 measurements), using a measuring tape. Despite high variability at all levels, the main results were that (1) two measurements made on the same day by the same observer showed good reliability (intraclass correlation coefficient 0.84-0.95); (2) two independent observers making the measurements on the same day showed fair-good reliability (intraclass correlation coefficient 0.69-0.89); (3) the same observer making the measurements at different visits, at least 2 days apart, showed good reliability (intraclass correlation coefficient 0.64-0.84); (4) inspiratory capacity was not associated with axillary and xiphisternal mobility, but it was closely related to measurements taken at the abdominal level. In summary, despite high reliability of intra-observer and inter-observer measurements, both within and between visits, high variability was observed in all chest wall mobility measurements. Although there was an association between inspiratory capacity and measurements made at the abdominal level, chest wall mobility did not correlate with pulmonary function.


Value of single-voxel proton MR spectroscopy in temporal lobe epilepsy.
To study the value of different parameters derived from single-voxel proton MR spectroscopy of the mesial temporal lobes in the lateralization of the epileptogenic zone in patients with temporal lobe epilepsy. We studied 12 healthy volunteers and 21 patients with temporal lobe epilepsy refractory to medical treatment, which was clearly lateralized with electroencephalography (EEG) and MR imaging. The mesial temporal lobes were investigated with single-voxel proton MR spectroscopy using a point-resolved spectroscopic sequence with an echo time of 135 milliseconds. The normalized concentration of N-acetylaspartate (NAA), creatine (Cr), and choline-containing compounds (Cho), and the metabolite ratios NAA/Cho+Cr, NAA/Cr, Cho/Cr, and NAA/Cho were calculated from the spectra. Using these values and an asymmetry index, we assigned the patients to one of five lateralization categories. The most consistent MR spectroscopic parameter for clear lateralization was the NAA/Cho+Cr ratio, followed by the NAA ratio. But with an adequate asymmetry index, the epilepsy in 17 (81%) of 21 patients could be lateralized by EEG and MR imaging with both parameters concordantly. Symmetric bilateral abnormalities were found in four of the 21 patients with NAA/Cho+Cr and in only one of the 21 patients with NAA. With both parameters, no contradictory lateralization was found; however, this was indeed the case with the remaining ratios, NAA/Cr, Cho/Cr, and NAA/Cho, in two, three, and one of the patients, respectively. A statistically significant decrease in NAA was found on the epileptic side, but also on the contralateral side. With an adequate asymmetry index, NAA/Cho+Cr and NAA are equally sensitive in predicting the side of involvement in patients with unilateral temporal lobe epilepsy.


The use of recombinant ovine IL-1beta and TNF-alpha as natural adjuvants and their physiological effects in vivo.
In the present study we have investigated the use of recombinant ovine IL-1beta and TNF-alpha both alone and in combination, as natural adjuvants in vaccination trials in sheep. Initial experiments were conducted to investigate the physiological effects of the cytokines in vivo and determine what dose could be administered without adverse pyrogenic effects. Even at the maximum dose tested (100 microg) the only significant physiological effect was a transient increase in body temperature of approximately 2 degrees C in sheep injected with TNF-alpha. Administration of either cytokine had profound effects on the levels of circulating leucocytes for up to 5 days postinjection. The incorporation of either IL-1beta or TNF-alpha in aqueous or Al(OH)3 vaccine formulations enhanced antibody responses to a recombinant antigen from the cestode parasite Taenia ovis. The addition of IL-1beta to aqueous vaccine formulations increased antibody responses 15-20-fold and in Al(OH)3 formulations by three to six fold. TNF-alpha stimulated 1.5 to six-fold and 2.5 to seven-fold increases in antibody levels in aqueous and Al(OH)3-based formulations, respectively, in a dose-dependent manner. The addition of either cytokine to Quil A or IFA vaccines did not enhance the antibody levels elicited. When 10 microg of both IL-1beta and TNF-alpha were incorporated in the aqueous or Al(OH)3 vaccine formulations, increases of 21-fold and 25-fold, respectively, were observed in antibody levels. The adjuvant activity of IL-1beta and TNF-alpha in combination in the Al(OH)3-based vaccine resulted in antibody levels commensurate with those obtained using Quil A or IFA.


Effect of 5-hydroxytryptamine on glossopharyngeal afferent nerve activity in anesthetized rats.
Excitatory responses to 5-hydroxytryptamine (5-HT) were recorded from the whole glossopharyngeal afferent nerve in anesthetized rats, using an electrophysiological technique. Bolus intravenous injection of 5-HT (6.25-50 micrograms/kg) evoked a dose-dependent excitation of glossopharyngeal afferent nerve activity with a rapid onset and lasting a few seconds. This response was blocked by a selective 5-HT3 receptor antagonist, YM060 (10 micrograms/kg i.v.). A 5-HT3 receptor agonist, 2-methyl-5-HT (6.25-50 micrograms/kg), also produced a rapid and dose-dependent excitation of this nerve activity, and YM060 (10 micrograms/kg i.v.) caused an inhibition of this effect. In contrast, efferent glossopharyngeal nerve activity was not altered by 5-HT even at a high dose (50 micrograms/kg). These results suggest that exogenous 5-HT may elicit excitation of the glossopharyngeal afferent nerve, and that this effect might be mediated via the 5-HT3 receptors on the nerve endings.


Reliability and factorial validity of a questionnaire to assess organophosphate pesticide exposure to agricultural workers in Maule, Chile.
The aim was to evaluate the reliability and validity of a questionnaire to assess organophosphate pesticide (OP) exposure in agricultural workers. We then enrolled a random sample of 114 agricultural workers from the region of Maule, Chile (mean age = 50 years [SD = 12]). An internal consistency analysis (Cronbach's alpha> 0.70) and a Varimax rotational factorial analysis were applied. The instrument had a high reliability to predict likely occupational pesticide exposures: Cronbach's alpha = 0.95, the Kaiser-Meyer-Olkin (KMO) measure was 0.90 and the Bartell sphericity test = p < 0.001. Four factors explaining 68% of the variance were extracted. The factors identified were as follows: (1) labor conditions during application of OPs; (2) use of personal protective equipment; (3) workplace conditions related to OP exposure and (4) home conditions related to OP exposure. The questionnaire has adequate metric properties to characterize likely OP exposure of agricultural workers and to explore associated working and home conditions.


Trace fossil evidence for late ordovician animals on land.
Fossil burrows within newly recognized buried soils in the Late Ordovician Juniata Formation, near Potters Mills in central Pennsylvania, represent the oldest reported nonmarine trace fossils. They are thought to have been an original part of the soil because their greater density toward the top of the paleosols corresponds with mineralogical, microstructural, and chemical changes attributed to ancient weathering and because about half the burrows are encrusted with nodular carbonate, interpreted as caliche. Associated fossil caliche, the size distribution of the burrows, and their W-shaped backfills are evidence that the burrows may have been excavated by bilaterally symmetrical organisms that grew in well-defined growth increments and were able to withstand desiccation. Among well-known soil organisms, millipedes are burrowing animals that satisfy these requirements, but have a fossil record not quite this old. This trace fossil evidence for animals on land, together with recent palynological evidence for land plants of a bryophytic grade of evolution during Late Ordovician time, are indications of terrestrial ecosystems of slightly greater antiquity and complexity than hitherto suspected.


[Effect of pets on human health: is there a correlation?].
Is there a Relationship? Despite an increasing number of studies devoted to the health benefits of interacting with pets, the empirical evidence of such an effect still remains weak. Many reports comparing health-related variables in pet owners and non-owners do not find significant differences. Some studies find a statistical correlation between pet ownership and better health, but they do not adequately demonstrate that the better health is a result of the pet. There is experimental evidence suggesting that the presence of animals is associated with a lowering of cardiovascular responses to stressors. Accordingly, pets could be used in the therapy of stress-related diseases. Nevertheless, no consistent clinical studies testing this hypothesis have been carried out. Moreover, neither evolutionary nor learning hypothesis for the observed decrease in cardiovascular reactivity have been tested till now. Research on the benefits of pet ownership still are in its preliminary steps. Further studies are needed for the understanding of the underlying psychological mechanisms of human/animal relationship and its therapeutic possibilities.


Nivolumab-Induced Development of Pulmonary Sarcoidosis in Renal Cell Carcinoma.
A 64-year-old woman with metastatic clear cell renal carcinoma who had been on nivolumab immunotherapy for 10 months was referred for a FDG PET scan to monitor disease progress. New bilateral mediastinal and hilar FDG-avid lymphadenopathy was noted. Pathology on subsequent mediastinal nodal biopsy showed well-formed epithelioid granulomas with no evidence of malignancy consistent with sarcoidosis. This case illustrates that pulmonary sarcoidosis can be induced by immunotherapy in the treatment of renal cell carcinoma.


Examining alternative explanations of the covariation of ADHD and anxiety symptoms in children: a community study.
Attention-deficit hyperactivity disorder (ADHD) is comorbid with a range of other disorders, including anxiety disorders. The aim was to examine different explanations for the covariation of these symptom domains in children according to the framework provided by (Lilienfeld, S. O. Comorbidity between and within childhood externalizing and internalizing disorders: Reflections and directions. Journal of Abnormal Child Psychology, 2003). The covariation of ADHD symptoms and anxiety symptoms were examined over a 12-month period in a community sample of 499 children aged 8-13; 91% were retained at 12-month follow-up. Dimensional assessments were conducted using questionnaires given to children, parents and teachers, with results analyzed via structural equation modeling. Positive associations between ADHD and anxiety symptoms were linked with inattention symptoms, were particularly pronounced for girls, and were linked via temperament and behavioral problems. No support for the hypothesis that ADHD symptoms predicted the development of anxiety symptoms over time or vice versa. ADHD symptoms (particularly inattention) and anxiety symptoms are covarying phenomena that are linked with an irritable temperament and disruptive behavior.


Amelioration of biodiversity impacts of genetically modified crops: predicting transient versus long-term effects.
It has been suggested that genetically modified herbicide-tolerant crops may benefit biodiversity because spraying of crops may be delayed until later in the growing season, allowing weeds to grow during the early part of the year. This provides an enhanced resource for arthropods, and potentially benefits birds that feed on these. Thus, this technology could enhance biodiversity. Using a review of weed phenologies and a population model, we show that many weeds are unlikely to benefit because spraying is generally delayed insufficiently late in the season to allow most to set seed. The positive effects on biodiversity observed in trials lasting one or two seasons are thus likely to be transient. For one weed of particular significance (Chenopodium album, fat hen) we show that it is unlikely that the positive effects observed could be maintained by inputs of seed during other parts of the rotation. However, we find preliminary evidence that if spraying can be ceased earlier in the season, then a viable population of late-emerging weeds could be maintained. This strategy could benefit weeds in both genetically modified (GM) and non-GM crops, but would probably lead to reduced inputs in GM systems compared with conventional ones.


Physician satisfaction revisited.
Nineteen US physicians were interviewed in 1987 to identify how they defined and addressed the changes facing them. Attitudes and problem-solving approaches of physicians who remained satisfied were compared with those deemed dissatisfied. In this ten-year follow-up study, the original subjects were re-contacted and asked to describe changes in their practices, and other questions regarding their professional lives. They were rated by themselves and the authors for satisfaction. Eighteen responded and could be rearranged into three groups by ratings of satisfaction. Representative responses delineate each group and explore various aspects differentiating responses within the grouping. past satisfaction with medical practice is no predictor of current satisfaction. Only those who either embraced change or found a means of escape from the issues facing them earlier were judged satisfied. The majority describe strategies to reduce fatigue, and to maintain some control over their professional lives.


Tutorial options for clinicians undertaking postgraduate degrees online.
This article was migrated. The article was marked as recommended. Purpose: To determine clinicians' preference for types of tutorial participation and their subsequent tutorial participation and performance. Methods: Part-time online students undertaking an introductory postgraduate unit of study in clinical epidemiology were offered different tutorial options across semesters. Results: Ungraded asynchronous online discussions were poorly attended with only 118/186 (63%) posting at least once across 10 tutorials. Allocating a 1% participation mark each week and allowing students to complete tutorial tasks individually increased participation with 148/190 (78%) completing at least 8 out of 10 tutorials. Moreover, the final assignment mark distribution lost the tail of poorly performing students. In semesters when two tutorial options were offered, 192/200 (96%) chose to work alone over asynchronous online discussion and 162/190 (85%) chose to work alone over intensive face-to-face workshops. Even when students self-selected to join graded asynchronous online discussion, only 2/8 (25%) completed at least 8 out of 10 tutorials. In students who selected to attend intensive workshops, both participation and final assignment grade were better than that observed in other students. Conclusions: The majority of clinicians studying online chose to work individually. Allowing students to work alone and awarding participation marks appeared to improve both participation and knowledge attainment.


Role for brain corticotropin-releasing factor in the weight-reducing effects of chronic fenfluramine treatment in rats.
Fenfluramine is an amphetamine derivative which is used as a weight-reducing agent in the treatment of obesity. It has been postulated that fenfluramine affects brain serotonin (5HT) neurons resulting in decreased food intake and altered autonomic outflow which, in turn, increases metabolism. CRF decreases food intake and, in addition, has been demonstrated to reduce body weight in genetically obese rats through selective activation of sympathetic and inhibition of parasympathetic outflows. Because 5HT is a potent CRF secretagogue, we tested the hypothesis that the weight-reducing effects of fenfluramine administration may be mediated, in part, through altered CRF secretion. Chronic fenfluramine treatment (1-24 mg/kg sc, twice daily, 4 days) resulted in a dose-dependent decrease in hypothalamic CRF concentration at 30 min after the final drug injection and was accompanied by a significant reciprocal increase in plasma corticosterone concentration. These data suggest that the decrease in hypothalamic CRF was a consequence of increased CRF secretion. These changes in hypothalamic CRF and plasma corticosterone correlated with brain fenfluramine levels. In contrast, high dose fenfluramine treatment significantly increased hippocampus, midbrain, and spinal cord CRF concentrations whereas levels in cerebral cortex, caudate putamen, thalamus, pons/medulla, and cerebellum were unaffected. There was no effect of this fenfluramine treatment protocol on regional brain TRH or neurotensin concentrations. In keeping with the well known development of tolerance to the weight-reducing effects of fenfluramine, chronic fenfluramine treatment resulted in lesser increases in corticosterone secretion than after acute treatment. Whereas weight loss observed after chronic fenfluramine treatment was associated with stimulation of hypothalamic-pituitary-adrenocortical hormone secretion, the weight-recovery phase after cessation of drug treatment was associated with decreased levels of plasma corticosterone. These data, demonstrating fenfluramine-induced alterations in brain CRF and plasma corticosterone, suggest that CRF may represent an important endogenous transmitter which mediates the weight-reducing effects of the drug.


[Motor recovery after spinal cord injury: assessments, factors and mechanisms].
The recovery of motor functions after a spinal cord injury (SCI) can be assessed at the domain of body-functions and structures and activities. As there is no gold standard for quantifying motor functions, the recovery depends strongly on the assessment applied. After a motor complete SCI, the improvement in activities of daily life is larger as would be expected from the increase in muscle strength alone. After a motor incomplete SCI, the (prolonged) latency of the motor evoked potential remains stable, while considerable improvements in muscle strength, walking capacity and independence can be observed. Such functional recovery is based on compensational mechanisms and neuroplasticity.


Two outbreaks of diarrhoea in nurseries in Norway after farm visits, April to May 2009.
During a 2009 nationwide outbreak of sorbitolfermenting Escherichia coli O157 in Norway, the Norwegian Institute of Public Health was notified of diarrhoea outbreaks in two nurseries. A link to the nationwide outbreak was suspected and investigated, including retrospective cohort studies. Both nurseries had recently visited farms. Faecal specimens were obtained from symptomatic children as well as from the farm animals and tested for Campylobacter, Salmonella, Yersinia, Shigella and pathogenic E. coli, and isolates were further characterised. Nursery A had 12 symptomatic children, and we found the same strain of C. jejuni in faeces from children and lambs. Nursery B had nine symptomatic children, including one child with bloody diarrhoea carrying enterohaemorrhagic E. coli (EHEC) O26. EHEC O26 with a similar multiple-locus variable number tandem repeat analysis (MLVA)-profile was found in sheep. Five children had enteropathogenic E. coli (EPEC) O76. Animals were not tested for EPEC O76. We found no significant association between illness and risk factors for either nursery. The isolated pathogens differed from the one involved in the nationwide outbreak. In each nursery outbreak, the pathogens isolated from children matched those found in farm animals, implicating animal faeces as the source. Hygiene messages are important to prevent similar outbreaks.


Learning signaling network structures with sparsely distributed data.
Flow cytometric measurement of signaling protein abundances has proved particularly useful for elucidation of signaling pathway structure. The single cell nature of the data ensures a very large dataset size, providing a statistically robust dataset for structure learning. Moreover, the approach is easily scaled to many conditions in high throughput. However, the technology suffers from a dimensionality constraint: at the cutting edge, only about 12 protein species can be measured per cell, far from sufficient for most signaling pathways. Because the structure learning algorithm (in practice) requires that all variables be measured together simultaneously, this restricts structure learning to the number of variables that constitute the flow cytometer's upper dimensionality limit. To address this problem, we present here an algorithm that enables structure learning for sparsely distributed data, allowing structure learning beyond the measurement technology's upper dimensionality limit for simultaneously measurable variables. The algorithm assesses pairwise (or n-wise) dependencies, constructs "Markov neighborhoods" for each variable based on these dependencies, measures each variable in the context of its neighborhood, and performs structure learning using a constrained search.


Temporary occipital fixation in young children with severe cervical-thoracic spinal deformity.
OBJECTIVE The long-term effects of instrumentation and fusion of the occipital-cervical-thoracic spine on spinal growth in young children are poorly understood. To mitigate the effects of this surgery on the growing pediatric spine, the authors report a novel technique used in 4 children with severe cervical-thoracic instability. These patients underwent instrumentation from the occiput to the upper thoracic region for stabilization, but without bone graft at the craniovertebral junction (CVJ). Subsequent surgery was then performed to remove the occipital instrumentation, thereby allowing further growth and increased motion across the CVJ. METHODS Three very young children (15, 30, and 30 months old) underwent occipital to thoracic posterior segmental instrumentation due to cervical or upper thoracic dislocation, progressive kyphosis, and myelopathy. The fourth child (10 years old) underwent similar instrumentation for progressive cervical-thoracic scoliosis. Bone graft was placed at and distal to C-2 only. After follow-up CT scans demonstrated posterior arthrodesis without unintended fusion from the occiput to C-2, 3 patients underwent removal of the occipital instrumentation. RESULTS Follow-up cervical spine flexion/extension radiographs demonstrated partial restoration of motion at the CVJ. One patient has not had the occipital instrumentation removed yet, because only 4 months have elapsed since her operation. CONCLUSIONS Temporary fixation to the occiput provides increased biomechanical stability for spinal stabilization in young children, without permanently eliminating motion and growth at the CVJ. This technique can be considered in children who require longer instrumentation constructs for temporary stabilization, but who only need fusion in more limited areas where spinal instability exists.


Anodal tDCS over Broca's area improves fast mapping and explicit encoding of novel vocabulary.
An accumulating body of evidence suggests that transcranial direct current stimulation (tDCS) can be used to affect language processing, including word acquisition. There has been, however, no comprehensive study of effects of tDCS of the core language areas in relation to the main word-learning mechanisms. Two principal strategies have been posited as important for natural word acquisition: explicit encoding (EE) which relies on direct instructions and repetition of material, and fast mapping (FM) which operates implicitly, via context-based inference or deduction. We used anodal and cathodal tDCS of Broca's and Wernicke's areas to assess effects of stimulation site and polarity on novel word acquisition in both EE and FM regimes. 160 participants, divided into five groups, received 15 min of cathodal or anodal tDCS over one of the two areas or a sham (placebo) stimulation before learning eight novel words, presented ten times each in a short naturalistic audio-visual word-picture association session, fully counterbalanced across different learning regimes. The outcome of novel word acquisition was measured immediately after the training using a free recall task. The results showed elevated accuracy in all real stimulation groups in comparison with sham stimulation; however, this effect only reached full significance after anodal tDCS of Broca's area. Comparisons between the two learning modes indicated that Broca's anodal tDCS significantly improved both implicit and explicit acquisition of novel vocabulary in comparison with sham tDCS, without, however, any significant differences between EE and FM regimes as such. The results indicate involvement of the left inferior-frontal neocortex in the learning of novel vocabulary and suggest a possibility to promote different types of word acquisition using anodal tDCS of this area.


Helicobacter pylori pathogen regulates p14ARF tumor suppressor and autophagy in gastric epithelial cells.
Infection with Helicobacter pylori is one of the strongest risk factors for development of gastric cancer. Although these bacteria infect approximately half of the world's population, only a small fraction of infected individuals develops gastric malignancies. Interactions between host and bacterial virulence factors are complex and interrelated, making it difficult to elucidate specific processes associated with H. pylori-induced tumorigenesis. In this study, we found that H. pylori inhibits p14ARF tumor suppressor by inducing its degradation. This effect was found to be strain-specific. Downregulation of p14ARF induced by H. pylori leads to inhibition of autophagy in a p53-independent manner in infected cells. We identified TRIP12 protein as E3 ubiquitin ligase that is upregulated by H. pylori, inducing ubiquitination and subsequent degradation of p14ARF protein. Using isogenic H. pylori mutants, we found that induction of TRIP12 is mediated by bacterial virulence factor CagA. Increased expression of TRIP12 protein was found in infected gastric epithelial cells in vitro and human gastric mucosa of H. pylori-infected individuals. In conclusion, our data demonstrate a new mechanism of ARF inhibition that may affect host-bacteria interactions and facilitate tumorigenic transformation in the stomach.


Use of polytetrafluoroethylene patch for temporary wound closure after pediatric liver transplantation.
Despite numerous options for pediatric transplantation, closure of the abdominal wall after liver transplantation is occasionally difficult, resulting in increased abdominal pressure and possible vascular compromise. Since 1990, we have utilized a 2-mm thick sheet of polytetrafluoroethylene (PTFE) to overcome this situation in 21 transplants for 17 patients. The median age was 0.9 months. Ten of the 21 transplants utilized full-size grafts. The donor to recipient weight ratio was 1.7+/-1.2. Cadaveric left lateral segments were used in 8 of 21 transplants (weight ratio, 7.4+/-5.9), living donor left lateral segments were used in 3 of 21 transplants (weight ratio, 13.2+/-6.7). We were able to remove 14 of 21 patches with one additional operation, whereas 4/21 patches required two operations and 3/21 required three operations. Reoperations identified two cases of hepatic artery thrombosis not previously identified by duplex ultrasonography. There were no technical problems or adverse effects associated with the use of the PTFE patch. After patch removal, the fascia was closed with a nonabsorbable suture and the skin was allowed to close by secondary intention. There were no wound infections, portal vein thrombosis, or fluid and electrolyte abnormalities. PTFE is a safe, temporary alternative to primary wound closure in liver transplantation when the size of the graft or intestinal and graft edema does not allow conventional closure of the abdomen. Infectious, fluid/electrolyte, or ventilatory complications were not noted. The necessity of a second-look operation is useful in assessing the graft and vascular patency. The majority of patches can be removed within the first postoperative week.


Reactive Oxygen Species and NOX Enzymes Are Emerging as Key Players in Cutaneous Wound Repair.
Our understanding of the role of oxygen in cell physiology has evolved from its long-recognized importance as an essential factor in oxidative metabolism to its recognition as an important player in cell signaling. With regard to the latter, oxygen is needed for the generation of reactive oxygen species (ROS), which regulate a number of different cellular functions including differentiation, proliferation, apoptosis, migration, and contraction. Data specifically concerning the role of ROS-dependent signaling in cutaneous wound repair are very limited, especially regarding wound contraction. In this review we provide an overview of the current literature on the role of molecular and reactive oxygen in the physiology of wound repair as well as in the pathophysiology and therapy of chronic wounds, especially under ischemic and hyperglycemic conditions.


CUSUM analysis of brachial artery access for peripheral endovascular interventions.
Evaluate efficacy and safety of diagnostic and therapeutic endovascular interventions performed through transbrachial approach. Transbrachial artery catheterization has long been considered a secondary access site due to its related complication rate (7-11%). Low-profile and long-delivery endovascular systems, however, are reviving the interest in this approach. We retrospectively analysed all endovascular interventions attempted through a brachial artery access from 2003 to 2010. Two hundredth thirty seven consecutive patients (mean age 68.5 years, 89.5% male) underwent 168 transbrachial diagnostic (70.9%) and 69 therapeutic procedures (29.1%), characterised by micropuncture access (100%), 4-to-7 Fr sheath delivery systems and final digital compression (100%). CUSUM curves were created to evaluate learning effects and quality of care. All but one procedure were completed according to their scheduled intention. The overall complication rate was 5.5% (5 pseudoaneurysms (2.1%), 4 transient ischemic attack (1.7%), 3 brachial artery thromboses (1.3%) and 1 cardiac tamponade (0.4%). Surgical intervention was required in four of these patients (30.8%). No significant differences were observed according to age or sex. CUSUM curves created at a 2% theoretical risk showed two statistically significant upward inflections: one early in the series associated with diagnostic procedures (P=0.043) and another at the end of the study related to therapeutic interventions (P=0.018). Transbrachial catheterization is an effective and relatively safe access site for endovascular procedures. Its complication rate, although lower than before, still deserve it as a secondary access site. CUSUM curves let identify learning effects in diagnostic and interventional procedures.


Precocious Initiation into Smoking, Alcohol Use, and Gambling among Children with Conduct Problems.
Adolescent participation in risky and addictive behaviours, such as smoking, substance use, and gambling has the potential to lead to many serious problems. The presence of conduct problems (CPs) and early initiation into risky and addictive behaviours have been independently shown to be associated with adolescent and young adult smoking, drinking, and gambling. Nevertheless, the relation between early initiation into risky and addictive behaviours and CPs remains to be explored among pre-adolescents. Our study aims to examine the prospective relation between CPs in early primary school and pre-adolescent initiation into smoking, alcohol use, and gambling. Our study used data from participants in an ongoing prospective, longitudinal study at the Université de Sherbrooke to examine cigarette, alcohol, and gambling initiation among primary school-aged boys and girls with CPs. Children were recruited between the ages of 6 and 9 years from several low socioeconomic status public schools in diverse geographical regions of Quebec. Initiation into cigarettes, alcohol, and gambling was measured 1 year later. Children with CPs were found to be at greater risk for early initiation into smoking, alcohol, and gambling. These effects remained even once other known risk factors, such as poor parental supervision and child effortful control, were controlled for. These results suggest that CPs present in early elementary school can predict early initiation in to potentially addictive behaviours among boys and girls. Implications for targeted preventive intervention are discussed.


Correlation between white matter hyperintensity and delusional symptoms in Alzheimer's disease.
Patients with Alzheimer's disease (AD) often exhibit neuropsychiatric symptoms (NPS), particularly delusions. Previous studies have shown an association between white matter hyperintensities (WMH) and specific NPS. This study aims to explore the relationship between WMH volume and delusions in AD patients by comparing the WMH volumes of delusional and non-delusional subgroups. 80 AD patients were divided into a delusion group (n = 36) and a non-delusion group (n = 44) based on the Neuropsychiatric Inventory (NPI). The brain cortical volume and WMH volume were quantitatively calculated for all 80 patients, including total WMH volume, periventricular WMH (PVWMH) volume, deep WMH volume, as well as bilateral frontal lobe, temporal lobe, parietal lobe, and occipital lobe WMH volumes. Firstly, we compared the differences in WMH volumes between the delusion group and non-delusion group. Then, within the delusion group, we further categorized patients based on severity scores of their delusional symptoms into mild (1 point), moderate (2 points), or severe groups (3 points). We compared the WMH volumes among these three groups to investigate the role of WMH volume in delusional symptoms. There was a significant difference in left occipital lobe WMH volume between the delusion group and non-delusion group(P < 0.05). Within the delusion group itself, there were significant differences in overall WMH volume as well as PVWMH volume among patients with mild or severe levels of delusions(P < 0.05). Left occipital lobe WMH volume may be associated with the occurrence of delusional AD patients, and the total volume of whole-brain WMH and PVWMH volume may affect the degree of severity of delusional symptoms.


[Use of human liver biopsy samples as a technique for evaluation of cytochrome P-450].
Liver cytochromes-P450 are of primary importance in the metabolism of numerous drugs. Their activity is modulated by exogenous factors such as drug treatment. The parameters of human oxidase metabolism were determined "in vitro" in order to evaluate the activity of a specific monooxygenase (benzopyrene hydroxylase). Substances capable of modulating monooxygenase function were identified. This may be useful to predict drug-Cyt-P450 interaction "in vivo". The hydroxylation of benzopyrene in human microsomes prepared from human liver samples (biopsies) was used as a model to study the treatment effect on cytochrome-P450. The kinetic parameters of this reaction are stable and reproducible (Km = 1.37 +/- 0.35 microM, Vmax = 0.49 +/- 0.03 nmole 30 H-BP/min/ nmole CYT-P450). The Michaelis-Menten values are given by mean +/- standard deviation.


Human respiratory syncytial virus nonstructural protein NS2 antagonizes the activation of beta interferon transcription by interacting with RIG-I.
A wide variety of RNA viruses have been shown to produce proteins that inhibit interferon (IFN) production and signaling. For human respiratory syncytial virus (RSV), the nonstructural NS1 and NS2 proteins have been shown to block IFN signaling by causing the proteasomal degradation of STAT2. In addition, recombinant RSVs lacking either NS1 or NS2 induce more IFN production than wild-type (wt) RSV in infected cells. However, the mechanisms by which the NS proteins perform this function are unknown. In this study, we focused on defining the mechanism by which NS2 inhibits the induction of IFN transcription. We find that NS2 is required for the early inhibition of IFN transcription since the infection of cells with NS2-deletion RSV resulted in a higher level of IRF3 activation at early time points postinfection compared with that of wt or NS1-deletion RSV infection. In addition, NS2 expression inhibits IFN transcription induced by both the RIG-I and TLR3 pathways. Furthermore, we show that NS2 inhibits RIG-I-mediated IFN promoter activation by binding to the N-terminal CARD of RIG-I and inhibiting its interaction with the downstream component MAVS (IPS-1, VISA, Cardif). Thus, the RSV NS2 protein is a multifunctional IFN antagonist that targets specific components of both the IFN induction and IFN signaling pathways.


Antitumor activity and toxicity in animals of BMY-25282, a new mitomycin derivative.
BMY-25282, 7-N-(dimethylamino methylene)mitomycin C, is one of a novel series of amidino mitomycin derivatives. Some of these were discovered as intermediates in a synthetic program being conducted to find improved procedures for modifying the structure of mitomycin C (MMC). Markedly superior in vivo antitumor effects have been observed with BMY-25282 compared to MMC in initial tests against i.p.-implanted P388 leukemia and B16 melanoma. When administered i.v. to mice bearing s.c. B16 melanoma, BMY-25282 was also superior to MMC. The derivative was fully active against a line of L1210 leukemia which was partially resistant to MMC treatment but had little or no activity against a line of L1210 fully resistant to MMC. It is also 2 to 4 times more potent than MMC based on a comparison of doses required to achieve optimum antitumor effects. The superior antitumor efficacy of BMY-25282 over MMC against both i.p. and s.c. B16 melanoma was maintained when the drug was given in pluronic acid formulation. Against P-388 leukemia, however, the efficacy of the drugs was equivalent when BMY-25282 was administered in the pluronic vehicle. In an in vitro clonogenic assay involving freshly explanted human tumors, BMY-25282 was consistently more potent in cytotoxic effects than MMC. With human colorectal carcinoma samples, BMY-25282 was 13.8 times more potent than MMC. The i.v. 50% lethal dose values of BMY-25282 and MMC in C57BL/6 X DBA/2 F1 mice were 2.1 mg/kg and 8.6 mg/kg, respectively. Leukopenic effects of the drugs in mice were comparable at doses up to their respective 50% lethal dose values. Hematology studies in ferrets revealed a similar pattern of depression and recovery of lymphocytes, neutrophils, and platelets for BMY-25282 and MMC; however, with BMY-25282 there was earlier recovery of platelet counts. BMY-25282 is being further developed toward possible clinical trial.


Scan-rescan variation of measures derived from brain magnetization transfer ratio histograms obtained in healthy volunteers by use of a semi-interleaved magnetization transfer sequence.
A novel semiinterleaved gradient-echo (GE) sequence for quantitative measurement of magnetization transfer ratio (MTR) is described. With this sequence, several lines of k-space are collected for the non-MT image then several lines are collected for the MT image, thus building up the entire k-space in distinct acquisition blocks, with a good trade-off between motion-induced misregistration and degree of MT effect. The scan-rescan coefficients of variation for several MTR histogram-derived measures from 10 healthy volunteers scanned serially with this semiinterleaved sequence proved to be lower than those achieved using a conventional GE sequence. This sequence may be useful in a clinical environment to measure MTR changes over time more reliably than when acquiring the non-MT and MT images sequentially, which inevitably are affected by patient motion.


Interleukin-1alpha in the brain is induced by audiogenic seizure.
We examined the expression of the sleep-inducing cytokine interleukin-1alpha (IL-1alpha) in the brains of audiogenic seizure-susceptible mice subsequent to the induction of sound-induced seizure. Animal models of epilepsy often require lesioning or trauma that may nonspecifically alter IL-1alpha expression. To avoid this, we employed the Frings mouse strain; a model of auditory-evoked reflex epilepsy. Frings mice were exposed to a high-intensity sound stimulus to induce a tonic extension seizure, and the expression of IL-1alpha transcripts in different brain regions was measured thereafter. Compared to control animals, IL-1alpha transcripts were elevated 6 to 8 h postseizure in the hypothalamus, but not hippocampus, by a dexamethasone-sensitive pathway. Similar results were obtained from the genetically distinct DBA/2J audiogenic seizure-susceptible mouse strain. These findings demonstrate that the expression of IL-1alpha is altered following generalized seizure activity, induced by noninvasive sensory stimulation, in a brain-region-specific manner.


Estimation of the prevalence of non-insulin dependent diabetes mellitus in a rural area of Japan.
The objective of this paper is to describe a method of estimating the prevalence of non-insulin dependent diabetes mellitus (NIDDM) in a community. We first counted subjects with previously diagnosed NIDDM and those newly diagnosed by use of the 75-gram oral glucose tolerance test (OGTT). We then used the OGTT data to predict the prevalence of NIDDM at different levels of fasting plasma glucose (FPG) among the subjects who did not undergo the OGTT. Data were derived from 3,614 residents aged 20 years and older in a rural area where population-based screening for NIDDM was performed using FPG or post-prandial plasma glucose (PG). Of the 318 participants who underwent an OGTT in 1992, 35 (11.0%) were judged to have NIDDM by the 2-hour PG criterion. We applied the above-described method to the 1,179 subjects who had anFPG but failed to undergo the OGTT. The estimated prevalence of NIDDM, which included the previously diagnosed group, the newly diagnosed group and the expected group, was calculated. The estimated prevalence of diabetes in this population aged 20 years and older turned out to be 6.1% (95% CI: 5.3-6.9). As a validation study, the same method was applied to 220 subjects who did not undergo the OGTT in 1992 but did so in 1994. The actual prevalence of NIDDM among these subjects was compared to the prevalence expected from the 1992 data by our method. The actual value was within the 95% confidence interval of the expected value.


Cerebral dissecting aneurysm and intimal fibroelastic thickening of cerebral arteries. Case report.
A 19-year-old white man developed aphasia and right hemiplegia after several falls while waterskiing. Cerebral angiography displayed a ripple appearance and a "string of beads" sign along the left middle cerebral artery, with occlusion or stenosis of most of its branches. The patient died after 6 days, of transtentorial herniation due to massive left cerebral infarction. At necropsy, the infarct was found to be due to a subintimal dissecting aneurysm of the left middle cerebral artery. Multifocal areas of intimal fibroelastic thickening (IFT) were found not only at the site of dissection, but also in the other cerebral arteries, most prominent at the bifurcations of the vessels. A systematic study of cerebral arteries performed in six control cases revealed that IFT was present in a similar distribution to that seen in the patient described. However, the degree of IFT in this patient was greater than in the controls. Some individuals with excessive IFT may be more susceptible to cerebral dissecting aneurysm under a variety of stresses, especially trauma.


Striatum-Mediated Deficits in Stimulus-Response Learning and Decision-Making in OCD.
Obsessive compulsive disorder (OCD) is a prevalent psychiatric disorder characterized by obsessions and compulsions. Studies investigating symptomatology and cognitive deficits in OCD frequently implicate the striatum. The aim of this study was to explore striatum-mediated cognitive deficits in patients with OCD as they complete a stimulus-response learning task previously shown to differentially rely on the dorsal (DS) and ventral striatum (VS). We hypothesized that patients with OCD will show both impaired decision-making and learning, coupled with reduced task-relevant activity in DS and VS, respectively, compared to healthy controls. We found that patients with OCD (n = 14) exhibited decision-making deficits and learned associations slower compared to healthy age-matched controls (n = 16). Along with these behavioral deficits, OCD patients had reduced task-relevant activity in DS and VS, compared to controls. This study reveals that responses in DS and VS are altered in OCD, and sheds light on the cognitive deficits and symptoms experienced by patients with OCD.


The Relation Between Mastery, Anticipated Stigma and Depression Among Older Adults in a Primary Care Setting.
The current study evaluates the interaction between mastery, depression, and psychological barriers to care among older adults in a primary care setting, including the longitudinal effects of anticipated stigma and mastery on depressive symptoms. The sample was composed of 70 depressed older adults (age ≥ 60) who were newly recommended antidepressant treatment by their physicians. This cohort is part of a larger study examining the usefulness of the Treatment Initiation and Participation program to improve medication adherence. Anticipated stigma significantly predicted greater depression among older adults with low mastery, but not among those with high mastery. Mastery was found to moderate the relationship between anticipated stigma and depressive symptoms among older adults. Increased mastery over 28 weeks was also associated with greater reductions in depressive symptoms at follow-up, controlling for antidepressant strength and adherence. Bolstering older adults' sense of mastery in treatment could provide a source of resilience for older adults facing depression.


Detection of Treponema pallidum Sp. Pallidum DNA in Cerebrospinal Fluid (CSF) by Two PCR Techniques.
Laboratory diagnosis of neurosyphilis is complicated especially when it is asymptomatic, no single laboratory test result being appropriate to diagnose central nervous system infectivity caused by Treponema pallidum. Our objective was to evaluate two polymerase chain reaction (PCR) techniques for the detection of T. pallidum DNA in the cerebrospinal fluid (CSF) of patients with syphilis. One hundred twenty-four CSF samples from patients with reactive blood tests for syphilis were obtained. Two PCR techniques (47-PCR, polA-PCR) were used to detect T. pallidum DNA. The laboratory criteria used for the diagnosis of neurosyphilis to which the PCR techniques were compared were those recommended by the IUSTI: 2008 European guidelines on the management of syphilis. Treponema pallidum DNA was detected amplified in 37 of 124 (29.8%) and 30 of 124 (24.2%) samples with the 47-PCR and polA-PCR, respectively. Sensitivities were 75.8% and 69.7% and specificities 86.8% and 92.3%, respectively, for 47-PCR and polA-PCR techniques, respectively. The three CSF samples of patients with primary syphilis did not fulfill the criteria of neurosyphilis and DNA was only detected in one by the 47-PCR. In samples from secondary syphilis and neurosyphilis, three of nine and nine of nine respectively, results were coincident for the two PCR techniques and neurosyphilis criteria. Major discrepancies between the two PCR techniques and neurosyphilis diagnostic criteria were observed in latent syphilis. Beyond some limitations of the study, which are discussed here, both PCR techniques seem to be useful for the diagnosis of neurosyphilis, although 47-PCR presents a higher sensitivity and polA-PCR a higher specificity.


Saccadic latency is modulated by emotional content of spatially filtered face stimuli.
Models of attention and emotion assign a special status to the processing of threat. While evidence for threat-related attentional bias in highly anxious individuals is robust, effects in the normal population are mixed. An important explanation for the absence of threat-related attentional bias in nonanxious individuals may relate to the spatial frequency components of stimuli. Here we report behavioral data from two experiments examining the relationship between spatial frequency components of emotional and neutral faces and fast saccadic orienting behavior. In Experiment 1 participants had to saccade toward a single face, filtered to include mostly low, high or broad spatial frequencies (LSF, HSF or BSF), posing a fearful, happy or neutral expression presented for 20 ms in the periphery. At BSF a general emotional effect was found whereby saccadic responses were faster for fearful and happy faces relative to neutral, with no significant differences between fearful and happy faces. At LSF both fearful and happy faces had shorter saccadic latencies in comparison to neutral, demonstrating an emotional bias consistent with the BSF data. However, at LSF fearful faces resulted in significantly faster saccades than happy faces indicating that this bias was stronger for threat-related faces. There was no difference in saccadic responses between any emotions at HSF. Experiment 2 showed that the emotional bias diminished for inverted stimuli suggesting that the results were not attributable to low-level image properties. The findings suggest an overall advantage in the oculomotor system for orientation to emotional stimuli and at LSF in particular, a significantly faster localization of threat conveyed by the face stimuli in all individuals.


Observation and basis of improved blood flow to the distal latissimus dorsi muscle: a case for electrical stimulation prior to grafting.
Dynamic cardiomyoplasty, using a functional graft of the latissimus dorsi muscle, has shown promise as a treatment for selected patients with advanced heart failure. The success of this approach depends on maintaining the viability of the muscle, whose distal portion is susceptible to ischaemic damage. We investigated the effects of surgical mobilization on regional muscle blood flow and the influence of electrical stimulation of the muscle. Ten sheep were randomly assigned to two equal groups. In one group, the latissimus dorsi muscle was stimulated continuously in situ at 2 Hz for two weeks; in the other group, the muscle was not stimulated. Regional blood flows in the muscles were determined by a fluorescent microsphere technique. Serial measurements were made (a) under baseline conditions before intervention, (b) with the thoracodorsal artery occluded and (c) after interruption of the perforating collateral arteries. Surgical mobilization of the unstimulated latissimus dorsi muscles had little effect on blood flow in the proximal region, which remained at 93.1 +/- 16.9% of baseline (mean +/- SEM). The distal region was rendered significantly more ischaemic (55.8 +/- 13.5% of baseline, p < 0.002 compared to the proximal region). Electrical prestimulation abolished any significant proximodistal gradient in blood flow and improved distal muscle perfusion following mobilization (proximal vs. distal: 75.0 +/- 8.8 vs. 63.0 +/- 10.9%; p > 0.4). Distal muscle ischaemia occurred when the entire latissimus dorsi muscle was acutely elevated on the thoracodorsal pedicle alone. Electrical prestimulation of the muscle in situ improved the thoracodorsal perfusion of the distal muscle by abolishing the proximal-to-distal gradient in flow, with a substantial benefit to distal flow after mobilization. Although electrical stimulation is known to induce vascular proliferation, we argue that this effect of stimulation is brought about mainly by enhancement of the flow through anastomotic connections between proximal and distal arterial territories.


GWAS for Early-Establishment QTLs and Their Linkage to Major Phenology-Affecting Genes (Vrn, Ppd, and Eps) in Bread Wheat.
Farmers in northern and central Indian regions prefer to plant wheat early in the season to take advantage of the remaining soil moisture. By planting crops before the start of the season, it is possible to extend the time frame for spring wheat. The early-wheat-establishment experiment began in the 2017 growing season at the Borlaug Institute for South Asia (BISA) in Ludhiana, India, and, after three years of intensive study, numerous agronomic, physiological, and yield data points were gathered. This study aimed to identify wheat lines suitable for early establishment through an analysis of the agro-morphological traits and the genetic mapping of associated genes or quantitative trait loci (QTLs). Advancing the planting schedule by two-three weeks proved to be advantageous in terms of providing a longer duration for crop growth and reducing the need for irrigation. This is attributed to the presence of residual soil moisture resulting from the monsoon season. Early sowing facilitated the selection of genotypes able to withstand early elevated temperatures and a prolonged phenological period. The ideotype, which includes increased photo-growing degree days for booting and heading, as well as a longer grain-filling period, is better suited to early planting than timely planting. Senescence was delayed in combination with a slower rate of canopy temperature rise, which was an excellent trait for early-adapted ideotypes. Thus, a novel approach to wheat breeding would include a screening of genotypes for early planting and an ideotype design with consistent and appropriate features. A genome-wide association study (GWAS) revealed multiple QTLs linked to early adaptation in terms of the yield and its contributing traits. Among them, 44 novel QTLs were also found along with known loci. Furthermore, the study discovered that the phenology regulatory genes, such as Vrn and Ppd, are in the same genomic region, thereby contributing to early adaptation.


Sampling the skin transcriptome of the North Atlantic right whale.
As an initial step in defining the transcriptome of the North Atlantic right whale (Eubalaena glacialis) and developing functional genomic tools to study right whale health at the molecular physiological level, a cDNA library has been constructed from a skin biopsy. 2496 randomly selected clones (expressed sequence tags, ESTs) have been sequenced, and genes identified as important in the response to stress and immune challenges have been cloned by targeted RT-PCR from skin cDNA. The analysis of the EST collection (archived at www.marinegenomics.org and GenBank) showed a 34.79% redundancy, yielding 1578 unigenes and 27 potential microsatellite markers. 96 genes were cloned by targeted PCR; moreover, 52 of these genes are stress and immune function related. A Gene Ontology analysis of the unigene collection indicates that the skin is a rich source of expressed genes with diverse functions, suggesting an important role in multiple physiological processes including those related to immunity and stress response.


Non-specific aortoarteritis. Clinical course and long-term medical treatment.
The data on clinical course and long-term medical treatment of 215 patients with non-specific aortoarteritis are presented. Out of 180 patients who underwent antinflammatory treatment improvement was observed in 72.7%, fatal outcome occurred in 7.2%, while in the group of 35 patients who had no treatment or had irregular treatment 28.5% died. The patients were treated by steroid hormones, heparin, trentale, indocid. The treatment was long-term, sometimes up to 2 years.


CentrosomeDB: a new generation of the centrosomal proteins database for Human and Drosophila melanogaster.
We present the second generation of centrosomeDB, available online at http://centrosome.cnb.csic.es, with a significant expansion of 1357 human and drosophila centrosomal genes and their corresponding information. The centrosome of animal cells takes part in important biological processes such as the organization of the interphase microtubule cytoskeleton and the assembly of the mitotic spindle. The active research done during the past decades has produced lots of data related to centrosomal proteins. Unfortunately, the accumulated data are dispersed among diverse and heterogeneous sources of information. We believe that the availability of a repository collecting curated evidences of centrosomal proteins would constitute a key resource for the scientific community. This was our first motivation to introduce CentrosomeDB in NAR database issue in 2009, collecting a set of human centrosomal proteins that were reported in the literature and other sources. The intensive use of this resource during these years has encouraged us to present this new expanded version. Using our database, the researcher is offered the possibility to study the evolution, function and structure of the centrosome. We have compiled information from many sources, including Gene Ontology, disease-association, single nucleotide polymorphisms and associated gene expression experiments. Special interest has been paid to protein-protein interaction.


[Neuromelanin-related contrast in the substantia nigra semiquantitatively evaluated by magnetic resonance imaging at 3T: comparison between normal aging and Parkinson disease].
Fast spin-echo (FSE) T1-weighted magnetic resonance imaging (MRI) at 3T, which was optimized to detect neuromelanin-related contrast (NRC), was applied to quantitative estimation of signal alterations in the substantia nigra pars compacta (SNc) of 72 normal volunteers and 59 patients with Parkinson disease (PD). We examined relationship between NRC in SNc and clinical parameters. The NRC showed significant positive correlation with normal aging and was slightly but significantly higher in women than in men. Significant reduction in the NRC was found in PD as compared with 59 age- and sex-matched normal volunteers. The NRC in PD was negatively and significantly correlated with duration of illness and disease severity assessed by UPDRS and Hoehn & Yahr stage. Significant reduction of the NRC was demonstrated in patients with visual hallucinations as compare with patients without the symptoms. REM sleep behavior disorder also contributed reduction of NRC although it did more mildly than visual hallucination. Anosmia or hyposmia had no statistical relationship with the amount of NRC in PD. The overall visual inspection indicated that the reduction of the NRC in PD should start at the ventrolateral portion of SNc and advance medially. Additionally, we studied dementia with Lewy body disease (DLB). The NRC was reduced more significantly in DLB patients with PD symptoms than in those without them who also showed a significant reduction compared with normal controls. Quantification and distribution of the NRC obtained by 3T MRI was well correlated with pathological findings reported previously and clinical parameters in this study. Visualization and quantification of the NRC provide some parts of clinical and diagnostic information about pathologic condition of SNc.


Characterization by Deep Sequencing of Prunus virus T, a Novel Tepovirus Infecting Prunus Species.
Double-stranded RNAs purified from a cherry tree collected in Italy and a plum tree collected in Azerbaijan were submitted to deep sequencing. Contigs showing weak but significant identity with various members of the family Betaflexiviridae were reconstructed. Sequence comparisons led to the conclusion that the viral isolates identified in the analyzed Prunus plants belong to the same viral species. Their genome organization is similar to that of some members of the family Betaflexiviridae, with three overlapping open reading frames (RNA polymerase, movement protein, and capsid protein). Phylogenetic analyses of the deduced encoded proteins showed a clustering with the sole member of the genus Tepovirus, Potato virus T (PVT). Given these results, the name Prunus virus T (PrVT) is proposed for the new virus. It should be considered as a new member of the genus Tepovirus, even if the level of nucleotide identity with PVT is borderline with the genus demarcation criteria for the family Betaflexiviridae. A reverse-transcription polymerase chain reaction detection assay was developed and allowed the identification of two other PrVT isolates and an estimate of 1% prevalence in the large Prunus collection screened. Due to the mixed infection status of all hosts identified to date, it was not possible to correlate the presence of PrVT with specific symptoms.


What's up on stented valves.
Aortic valve bioprostheses are commonly implanted in the current era - also in younger patients - as they may obviate the need for anticoagulation while providing better hemodynamic performance and a more favorable quality of life. The steady increase in the use of biological valves has prompted the development of several different models of conventional stented bioprostheses. At present, there are four main types of stented aortic bioprostheses that compete in the market: the LivaNova Crown PRT (LivaNova Group, Burnaby, Canada), the St. Jude Medical Trifecta (St. Jude Medical, St. Paul, MN), the Carpentier-Edwards Perimount Magna Ease (Edwards Lifesciences, Irvine, CA), and the Medtronic Mosaic Ultra (Medtronic, Inc., Minneapolis, MN). The purpose of this review is to describe the features of these bioprosthetic valve models and to compare the data provided by the manufacturers with those derived from the available literature.


Persistent symptom relief after revascularization in patients with single-artery chronic mesenteric ischemia.
An isolated stenosis of the celiac artery (CA) or the superior mesenteric artery (SMA) is frequently detected in patients with abdominal complaints. The dilemma is whether these patients suffer from chronic mesenteric ischemia (CMI) and whether they will benefit from revascularization. We evaluated the long-term clinical success rates for single CA or SMA revascularization in patients with gastrointestinal symptoms and confirmed mucosal ischemia. This was a retrospective cohort analysis of 59 consecutive patients with gastrointestinal symptoms and a single atherosclerotic mesenteric artery stenosis who were referred to our tertiary care institution between 2006 and 2010 for standardized diagnostic workup of CMI, including measurement of mucosal ischemia with visible light spectroscopy or gastric-jejunal tonometry. Patients with multidisciplinary consensus diagnosis of CMI underwent surgical or endovascular revascularization. The primary outcome was clinical response to revascularization, defined as relief of presenting symptoms as experienced by the patient. Consensus diagnosis of CMI was obtained in 37 of 59 patients. Isolated CA stenosis was present in 30 of 37 patients (81%) and isolated SMA stenosis in seven patients. After a mean follow-up of 5.0 ± 3.0 years, 27 of 37 patients (73%) experienced sustained symptom relief after revascularization. Response was not related to lesion localization (CA, 73%; SMA, 71%; P = .919). Revascularization of the CA or SMA provides persistent symptom relief in 73% of patients diagnosed with CMI due to single atherosclerotic mesenteric artery stenosis.


Trends in instrumentation, control and automation and the consequences on urban water systems.
In recent years more and more on-line sensors have been used on different structures of urban water systems (UWS, i.e. wastewater treatment plants (WWTP), waterworks (WW), sewer systems). This development is influenced and driven by numerous trends, which will be discussed in this paper. For a better understanding, the discussion is illustrated with a factual example. The new possibilities of on-line measurement and automation technologies will also change the way as UWS will be planned, built and operated.


Mechanical assist devices for acute cardiogenic shock.
Cardiogenic shock (CS) is a state of critical end-organ hypoperfusion due to a primary cardiac disorder. For people with refractory CS despite maximal vasopressors, inotropic support and intra-aortic balloon pump, mortality approaches 100%. Mechanical assist devices provide mechanical circulatory support (MCS) which has the ability to maintain vital organ perfusion, to unload the failing ventricle thus reduce intracardiac filling pressures which reduces pulmonary congestion, myocardial wall stress and myocardial oxygen consumption. This has been hypothesised to allow time for myocardial recovery (bridge to recovery) or allow time to come to a decision as to whether the person is a candidate for a longer-term ventricular assist device (VAD) either as a bridge to heart transplantation or as a destination therapy with a long-term VAD. To assess whether mechanical assist devices improve survival in people with acute cardiogenic shock. We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid) and Web of Science Core Collection in November 2019. In addition, we searched three trials registers in August 2019. We scanned reference lists and contacted experts in the field to obtain further information. There were no language restrictions. Randomised controlled trials on people with acute CS comparing mechanical assist devices with best current intensive care management, including intra-aortic balloon pump and inotropic support. We performed data collection and analysis according to the published protocol. Primary outcomes were survival to discharge, 30 days, 1 year and secondary outcomes included, quality of life, major adverse cardiovascular events (30 days/end of follow-up), dialysis-dependent (30 days/end of follow-up), length of hospital stay and length of intensive care unit stay and major adverse events. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of a body of evidence as it relates to the studies which contribute data to the meta-analyses for the prespecified outcomes Summary statistics for the primary endpoints were risk ratios (RR), hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). The search identified five studies from 4534 original citations reviewed. Two studies included acute CS of all causes randomised to treatment using TandemHeart percutaneous VAD and three studies included people with CS secondary to acute myocardial infarction who were randomised to Impella CP or best medical management. Meta-analysis was performed only to assess the 30-day survival as there were insufficient data to perform any further meta-analyses. The results from the five studies with 162 participants showed mechanical assist devices may have little or no effect on 30-day survival (RR of 1.01 95% CI 0.76 to 1.35) but the evidence is very uncertain. Complications such as sepsis, thromboembolic phenomena, bleeding and major adverse cardiovascular events were not infrequent in both the MAD and control group across the studies, but these could not be pooled due to inconsistencies in adverse event definitions and reporting. We identified four randomised control trials assessing mechanical assist devices in acute CS that are currently ongoing. There is no evidence from this review of a benefit from MCS in improving survival for people with acute CS. Further use of the technology, risk stratification and optimising the use protocols have been highlighted as potential reasons for lack of benefit and are being addressed in the current ongoing clinical trials.


[Tympanostomy tubes and water].
An in vitro study was conducted to set the necessary pressure in fluids that could break resistance and cross the opening of a tympanostomy tube. A water column model was created and graduated in centimeters from base to top. We adapted three sorts of tympanostomy tubes. In each model, fluids were tested (tap water, seawater, river water, soapy water and eardrops). The column was filled with fluid until a threshold was reached, flowing through the tube opening. The threshold was registered and represented the pressure in cmH2O. The results show that pressure is necessary so that a fluid can cross the opening of a ventilation tube. In spite of limitations of our in vitro study, the literature suggests that no ear protection is needed during shower, since there is neither direct flow of water nor pressure in the ear. Bathing with soapy water is potentially dangerous due to the reduction in surface tension. The direct relation of pressure and surface tension through the opening of tympanostomy tubes indicates the need to decrease pressure when diving and to avoid strong head movements in the water.


High-Resolution Computed Tomography and Pulmonary Function Findings of Occupational Arsenic Exposure in Workers.
The number of studies where non-malignant pulmonary diseases are evaluated after occupational arsenic exposure is very few. To investigate the effects of occupational arsenic exposure on the lung by high-resolution computed tomography and pulmonary function tests. Retrospective cross-sectional study. In this study, 256 workers with suspected respiratory occupational arsenic exposure were included, with an average age of 32.9±7.8 years and an average of 3.5±2.7 working years. Hair and urinary arsenic levels were analysed. High-resolution computed tomography and pulmonary function tests were done. In workers with occupational arsenic exposure, high-resolution computed tomography showed 18.8% pulmonary involvement. In pulmonary involvement, pulmonary nodule was the most frequently seen lesion (64.5%). The other findings of pulmonary involvement were 18.8% diffuse interstitial lung disease, 12.5% bronchiectasis, and 27.1% bullae-emphysema. The mean age of patients with pulmonary involvement was higher and as they smoked more. The pulmonary involvement was 5.2 times higher in patients with skin lesions because of arsenic. Diffusing capacity of lung for carbon monoxide was significantly lower in patients with pulmonary involvement. Besides lung cancer, chronic occupational inhalation of arsenic exposure may cause non-malignant pulmonary findings such as bronchiectasis, pulmonary nodules and diffuse interstitial lung disease. So, in order to detect pulmonary involvement in the early stages, workers who experience occupational arsenic exposure should be followed by diffusion test and high-resolution computed tomography.


Enol-enamine tautomerism in crystals of 1,3-bis(pyridin-2-yl) propan-2-one: a combined crystallographic and quantum-chemical investigation of the effect of packing on tautomerization processes.
The enolpyridine, OH-ketoenamime, NH equilibrium in crystals of 1,3-bis(pyridin-2-yl)propan-2-one was studied using temperature-dependent single-crystal X-ray diffraction. The relative population of the different tautomers was found to be sensitive to the temperature in the range of 100-300 K, illustrating the small thermodynamic difference between these two tautomers. This energy resemblance is partially attributed to the molecular packing in the crystal, where the molecules are arranged in the form of dimers. Ab initio electronic energy calculations (HF/6-31G** and MP2/6-31G**) reveal the effect of dimerization in the crystal on the electronic energy levels. Several tautomeric states were identified in the dimer of 1,3-bis(pyridin-2-yl)propan-2-one. A model is proposed in which four of these dimer states are populated in the crystal at ambient temperatures. The crystallographic data were treated according to this four-state dimer model, suggesting that the free energy of the OH-NH dimers is higher than that of the OH-OH dimers by 120 +/- 10 cal mol(-1) and that the NH-NH dimers are yet higher in free energy by 50 +/- 10 cal mol(-1).


Anterior and posterior corneal changes after crosslinking for keratoconus.
To evaluate anterior and posterior changes in corneal topography and tomography after corneal crosslinking (CXL) in eyes with progressive keratoconus. Scheimpflug analyses (Pentacam, Oculus) of 20 eyes with keratoconus performed before and after corneal CXL were included into retrospective analysis. Mean follow-up was 2 years. Changes in topographic, tomographic, and pachymetric values were statistically analyzed applying analysis of variance. Further, the distance and direction between the anterior maximum keratometry (K(max)) and the apex as well as the distance and direction between the thinnest point in corneal thickness (TPCT) and the corneal apex before and after CXL were studied. Two years after CXL, a statistically significant reduction of the keratometry at the flat meridian (-0.8 D, p < 0.05), the steep meridian (-0.5 D, p < 0.05), the "index of surface variance" (-5.3, p < 0.05), and the "index of highest decentration" (-0.05, p < 0.05) could be demonstrated. While the elevation of the front surface at the apex decreased (-1.5 μm, p < 0.05), the back elevation at the apex (+2 μm, p < 0.05) increased. Although not reaching statistical significance, the maximum front and back elevation demonstrated the same trend; while maximum front elevation data remained stable (-0.3 μm, p = 0.961), maximum back elevation data increased (+6.7 μm, p = 0.122). The corneal thickness at the apex (-22.0 μm, p < 0.001) and the TPCT (-20.0 μm, p < 0.001) decreased, leading to an increase of the corneal thickness progression from the corneal apex to the periphery. The position of K(max) and TPCT remained stable. Corneal topography proved to be useful in the follow-up for CXL because of significant changes in the keratometry. Increasing posterior elevation values, despite a stabilized anterior corneal surface, might be a sign of ongoing ectatic changes in the posterior corneal surface.


Intermediate and low abundant protein analysis of vitamin D deficient obese and non-obese subjects by MALDI-profiling.
Obesity is a pathological condition caused by genetic and environmental factors, including vitamin D deficiency, which increases the risk of developing cardiovascular disorders and diabetes. This case-control study was designed to verify whether serum profiles could be identified differentiating obese and non-obese Saudis characterized by vitamin D deficiency and pathological levels of triglycerides, high-density lipoprotein cholesterol and high total cholesterol levels. The serum protein profiles of 64 vitamin D deficient (serum 25(OH)D < 50nmol/L) individuals with metabolic syndrome and with (n = 31; BMI ≥ 30) or without (n = 33; BMI < 30) obesity were analyzed by a quantitative label-free mass spectrometry approach (MALDI-profiling), combined with different serum immunodepletion strategies (Human7 and Human14 immuno-chromatographies), to analyze the intermediate- and low-abundant protein components. The analysis of intermediate-abundant proteins (Human7) in obese vs. non-obese subjects identified 14 changed peaks (p < 0.05) in the m/z range 1500-35000. Furthermore, the Human14 depletion provided new profiles related to obesity (121 changed peaks). Among changed peaks, 11 were identified in the m/z range 1500-4000 Da by high-resolution tandem mass spectrometry, belonging to apolipoprotein CIII, apolipoprotein B100, alpha-1-antichymotrypsin and complement C3. Data herein show that distinct protein profiles identify specific peptides belonging to lipid metabolism and inflammation processes that are associated with obesity and vitamin D deficiency.


Gender differences in depression among the very old.
The aim of this study was to investigate factors associated with depression among men and women aged 85 and over. A population-based study was undertaken in northern Sweden. Out of 527 eligible participants, aged 85, 90 or > or = 95, 363 were evaluated for depression. Data were collected from structured interviews, assessments and medical charts and from relatives and caregivers. Depression was screened for using the Geriatric Depression Scale-15 and further assessed using the Montgomerysberg Depression Rating Scale (MADRS). A higher proportion of women were diagnosed with depression (33% vs. 18.6%, p = 0.006). In both men and women experienced loneliness (OR 3.4 vs. 7.0) and not going outside independently (OR 2.6 vs. 26.0) were associated with depression in the final regression model. Depression among men was also independently associated with loss of a child/children during the preceeding ten years (OR 30.0). Depression was more common among women than among men. Experienced loneliness and not going outside independently seem to be closely related to depression in both men and women. Loss of a child seems to be the most important factor among men.


New and improved molecular sexing methods for museum bird specimens.
We present two new avian molecular sexing techniques for nonpasserine and passerine birds (Neognathae), which are more suitable for use with museum specimens than earlier methods. The technique for nonpasserines is based on a new primer (M5) which, in combination with the existing P8 primer, targets a smaller amplicon in the CHD1 sex-linked gene than previously. Primers targeting ATP5A1, an avian sex-linked gene not previously used for sex identification, were developed for passerines. Comprehensive testing across species demonstrated that both primer pairs sex a range of different species within their respective taxonomic groups. Rigorous evaluation of each method within species showed that these permitted sexing of specimens dating from the 1850s. For corn bunting museum specimens, the ATP5A1 method sexed 98% of 63 samples (1857-1966). The M5/P8 CHD1 method was similarly successful, sexing 90% of 384 moorhen specimens from six different museum collections (1855-2001). In contrast, the original P2/P8 CHD1 sexing method only identified the sex of less than half of 111 museum moorhen samples. In addition to dried skin samples, these methods may be useful for other types of material that yield degraded or damaged DNA, and are hence potential new sexing tools for avian conservation genetics, population management and wildlife forensics.


Violence against female sex workers in Cameroon: accounts of violence, harm reduction, and potential solutions.
Female sex workers (FSWs) in Cameroon, and West Africa generally, suffer a disproportionate burden of HIV. Although violence against FSWs has been documented extensively in other parts of the world, data on violence from West African countries are lacking. The aim of this study was to qualitatively document violence and harm reduction strategies from the perspective of FSWs in Cameroon as well as to understand how experiences of violence may increase FSWs' HIV risk. FSWs from 7 major cities in Cameroon (Douala, Yaounde, Bamenda, Bertoua, Nagoundere, Kribi, and Bafoussam) were purposively recruited. Data from 31 in-depth interviews and 7 focus groups (n = 70; with some overlapping participants from in-depth interviews) conducted with these FSWs in 6 of these 7 cities (excluding Kribi) were analyzed using a grounded theory approach. Transcripts revealed 3 primary themes related to violence: (1) sources and types of violence, including sexual, physical, and financial violence perpetrated by clients and police, (2) harm reduction strategies, including screening clients and safe work locations, receipt of payment before sexual act, and formation of an informal security network, and (3) recommendations on structural changes to reduce violence that emphasized sex work decriminalization and increased police accountability. As in other parts of the world, violence against FSWs is pervasive in Cameroon. Interventions targeting violence and HIV must address the forms of violence cited locally by FSWs and can build on FSWs' existing strengths and harm reduction strategies. Structural changes are needed to ensure access to justice for this population.


Mechanisms underlying cortical resonant states: implications for levodopa-induced dyskinesia.
A common observation in recordings of neuronal activity from the cerebral cortex is that populations of neurons show patterns of synchronized oscillatory activity. However, it has been suggested that neuronal synchronization can, in certain pathological conditions, become excessive and possibly have a pathogenic role. In particular, aberrant oscillatory activation patterns have been implicated in conditions involving cortical dysfunction. We here review the mechanisms thought to be involved in the generation of cortical oscillations and discuss their relevance in relation to a recent finding indicating that high-frequency oscillations in the cerebral cortex have an important role in the generation of levodopa-induced dyskinesia. On the basis of these insights, it is suggested that the identification of physiological changes associated with symptoms of disease is a particularly important first step toward a more rapid development of novel treatment strategies.


Effect of maternal age on foetal chromosomal defects: an investigation based on non-invasive prenatal testing.
This study aimed to evaluate the value of non-invasive prenatal testing (NIPT) in the prenatal screening of foetal aneuploidy-associated diseases at different gestational ages. Briefly, cell-free foetal DNAs were extracted from plasma first, followed by DNA sequencing and bioinformatics analyses for chromosome aneuploidy (T21, T18, and T13), sex chromosome aneuploidy (SCA), and microdeletion/microduplication. Subsequently, the positive results were subject to karyotype analyses. The pregnant women included in this study were divided into six groups, and the results, such as chromosome diagnoses, and clinical phenotypes, were collected for data analyses. According to the results of the data analysis, the positivity rates of foetal chromosomal abnormalities in pregnant women under 20, 20-24, 25-29, 30-34, 35-39, and >40 years old were 0%, 0.17%, 0.25%, 0.27%, 0.60%, and 1.66%, respectively. The positive predictive value (PPV) in the 20-24 years group was 41.67%, that in the 25-29 years group was 62.5%, that in the 30-34 years group was 66.67%, that in the 35-39 years group was 90.74%, and that in the >40 years group was 90.32%. Overall, NIPT detection in elderly pregnant women has excellent clinical application value in reducing the incidence of either birth defects or abortion caused by invasive chromosome examination.


Histidine-rich glycoprotein protects from systemic Candida infection.
Fungi, such as Candida spp., are commonly found on the skin and at mucosal surfaces. Yet, they rarely cause invasive infections in immunocompetent individuals, an observation reflecting the ability of our innate immune system to control potentially invasive microbes found at biological boundaries. Antimicrobial proteins and peptides are becoming increasingly recognized as important effectors of innate immunity. This is illustrated further by the present investigation, demonstrating a novel antifungal role of histidine-rich glycoprotein (HRG), an abundant and multimodular plasma protein. HRG bound to Candida cells, and induced breaks in the cell walls of the organisms. Correspondingly, HRG preferentially lysed ergosterol-containing liposomes but not cholesterol-containing ones, indicating a specificity for fungal versus other types of eukaryotic membranes. Both antifungal and membrane-rupturing activities of HRG were enhanced at low pH, and mapped to the histidine-rich region of the protein. Ex vivo, HRG-containing plasma as well as fibrin clots exerted antifungal effects. In vivo, Hrg(-/-) mice were susceptible to infection by C. albicans, in contrast to wild-type mice, which were highly resistant to infection. The results demonstrate a key and previously unknown antifungal role of HRG in innate immunity.


Perforator-Based Interposition Flaps Perform Better Than Full-Thickness Grafts for the Release of Burn Scar Contractures: A Multicenter Randomized Controlled Trial.
Burn scar contractures remain a significant problem for the severely burned patient. Reconstructive surgery is often indicated to improve function and quality of life. Skin grafts (preferably full-thickness grafts) are frequently used to cover the defect that remains after scar release. Local flaps are also used for this purpose and provide healthy skin subcutaneous tissue. The vascularization and versatility of local flaps can be further improved by enclosing a perforator at the base of the flap. Until now, no randomized controlled trial has been performed to determine which technique has the best effectiveness in burn scar contracture releasing procedures. A multicenter randomized controlled trial was performed to compare the effectiveness of perforator-based interposition flaps to full-thickness skin grafts for the treatment of burn scar contractures. The primary outcome parameter was change in the surface area of the flap or full-thickness skin graft. Secondary outcome parameters were width, elasticity, color, Patient and Observer Scar Assessment Scale score, and range of motion. Measurements were performed after 3 and 12 months. The mean surface area between flaps (n = 16) and full-thickness skin grafts (n = 14) differed statistically significantly at 3 months (123 percent versus 87 percent; p < 0.001) and 12 months (142 percent versus 92 percent; p < 0.001). In terms of the secondary outcome parameters (specifically, the Patient and Observer Scar Assessment Scale observer score and color), interposition flaps showed superior results compared with full-thickness skin grafts. Perforator-based interposition flaps result in a more effective scar contracture release than full-thickness skin grafts and should therefore be preferred over full-thickness skin grafts when possible. Therapeutic, I.