Role of public-private partnerships in achieving UNAIDS HIV treatment targets.
Despite progress towards achieving UNAIDS 90-90-90 goals, barriers persist in laboratory systems in sub-Saharan Africa (SSA) restricting scale up of early infant diagnosis (EID) and viral load (VL) test monitoring of patients on antiretroviral therapy. If these facilities and system challenges persist, they may undermine recorded gains and appropriate management of patients. The aim of this review is to identify Public Private Partnerships (PPP) in SSA that have resolved systemic barriers within the VL and EID treatment cascade and demonstrated impact in the scale up of VL and EID. We queried five HIV and TB laboratory databases from 2007 to 2017 for studies related to laboratory system strengthening and PPP. We identified, screened and included PPPs that demonstrated evidence in alleviating known system level barriers to scale up national VL and EID testing programs. PPPs that improved associated systems from the point of viral load test request to the use of the test result for patient management were deemed eligible. We identified six PPPs collaborations with multiple activities in select countries that are contributing to address challenges to scale up national viral load programs. One of the six PPPs reached 14.5 million patients in remote communities and transported up to 400,000 specimens in a year. Another PPP enabled an unprecedented 94% of specimens to reach national laboratory through improved sample referral network and enabled a cost savings of 62%. Also PPPs reduced cost of reagents and enabled 300,000 tested infants to be enrolled in care as well as reduced turnaround time of reporting results by 50%. Our review identified the benefits, enabling factors, and associated challenges for public and private sectors to engage in PPPs. PPP contributions to laboratory systems strengthening are a model and present opportunities that can be leveraged to strengthen systems to achieve the UNAIDS 90-90-90 treatment targets for HIV/AIDS. Despite growing emphasis on engaging the private sector as a critical partner to address global disease burden, PPPs that specifically strengthen laboratories, the cornerstone of public health programs, remain largely untapped.


Metallic nanoparticle shape and size effects on aluminum oxide-induced enhancement of exciton-plasmon coupling and quantum dot emission.
We investigate the shape and size effects of gold metallic nanoparticles on the enhancement of exciton-plasmon coupling and emission of semiconductor quantum dots induced via the simultaneous impact of metal-oxide and plasmonic effects. This enhancement occurs when metallic nanoparticle arrays are separated from the quantum dots by a layered thin film consisting of a high index dielectric material (silicon) and aluminum oxide. Our results show that adding the aluminum oxide layer can increase the degree of polarization of quantum dot emission induced by metallic nanorods by nearly two times, when these nanorods have large aspect ratios. We show when the aspect ratio of these nanorods is reduced to half, the aluminum oxide loses its impact, leading to no improvement in the degree of polarization. These results suggest that a silicon/aluminum oxide layer can significantly enhance exciton-plasmon coupling when quantum dots are in the vicinity of metallic nanoantennas with high aspect ratios.


[The elderly patient with urge incontinence or urge-stress incontinence - efficacy and cardiac safety of propiverine].
The efficacy of propiverine in elderly patients suffering from urge incontinence or urge-stress incontinence was intended to be investigated. Especially in elderly patients a cardiac influence of propiverine is possible due to its dual mode of action. That is why besides the efficacy especially the cardiac safety was intended to be investigated. Ninety-eight patients (21 male, 77 female; 67.7 +/- 6.3 years of age) suffering from urgency, urge incontinence or mixed urge-stress incontinence were included in the double-blind, multicentre, placebo-controlled, randomized study. After a two-week placebo run-in period, the patients received propiverine (15 mg t. i. d.) or placebo (t. i. d.) for four weeks. Before (U 1, U 2) and during the treatment period (U 3, U 4), standard ECG's and 24 h long-term ECG's were recorded. Propiverine caused a significant reduction in the micturition frequency (U 2 : 8.7 +/- 4.2, U 4 : 6.5 +/- 3.2 ml; p < 0.01) reflected in a significant increase in the average micturition volume (U 2 : 163.5 +/- 65.9, U 4 : 216.3 +/- 101.5 ml; p < 0.01) and a significant reduction in the episodes of incontinence (- 54 %; p < or = 0.05). These findings were confirmed by the overall assessment after four weeks in which approximately 90 % of patients under propiverine were either free from urge incontinence and urge symptoms or improved. The efficacy parameters demonstrated a better efficacy for urge incontinence than for mixed urge-stress incontinence. Resting and ambulatory electrocardiograms evidenced no significant changes. Neither QTc interval nor other cardiac parameters were relevantly altered. The frequency of cardiac events (Lown classes IV a/b) was fortuitous, revealing no difference between placebo and propiverine. The incidence of adverse events was very low (2 % dryness of the mouth under propiverine) and confirmed by the findings from the quality of life questionnaires. A favourable benefit-risk ratio in the treatment of elderly patients suffering from urgency, urge incontinence or combined urge-stress incontinence is therefore proven for propiverine. Cardiac arrhythmia were not induced.


[Fundamental Studies on Improvement of Count Rate Performance of Scintillation Detectors].
The purpose of this article is to introduce fundamental studies on improvement of count rate performance of scintillation detectors which Dr. Eiichi Tanaka dedicated himself to carrying out. He proposed a new technique based on the combination of pulse shortening and selective integration in which the integration period is not fixed but shortened by the arrival of the following pulse. Theoretical analysis of the degradation of the statistical component of resolution is made for the proposed system with delay line pulse shortening, and the factor of resolution loss is formulated as a function of the input pulse rate. A new method is also presented for determining the statistical component of resolution separately from the non-statistical system resolution. Preliminary experiments with a NaI (Tl) detector had been carried out, the results of which are consistent with the theoretical prediction. The related works are also introduced.


Preterm birth and exercise capacity: what do we currently know?
The long-term cardiopulmonary outcomes following preterm birth during the surfactant era remain unclear. Respiratory symptoms, particularly exertional symptoms, are common in preterm children. Therefore, cardiopulmonary exercise testing may provide insights into the pathophysiology driving exertional respiratory symptoms in those born preterm. This review aims to outline the current knowledge of cardiopulmonary exercise testing in the assessment of children born preterm in the surfactant era. This study is a narrative literature review. Published manuscripts concerning the assessment of pulmonary outcomes using cardiopulmonary exercise testing in preterm children (aged <18 years) were reviewed. Search terms related to preterm birth, bronchopulmonary dysplasia, and exercise were entered into electronic databases, including Medline, PubMed, and Google Scholar. Reference lists from included studies were scanned for additional manuscripts. Preterm children have disrupted lung development with significant structural and functional lung disease and increased respiratory symptoms. The association between these (resting) assessments of respiratory health and exercise capacity is unclear; however, expiratory flow limitation and an altered ventilatory response (rapid, shallow breathing) are seen during exercise. Due to the heterogeneity of participants, treatments, and exercise protocols, the effect of the aforementioned limitations on exercise capacity in children born preterm is conflicting and poorly understood. Risk factors for reduced exercise capacity in those born preterm remain poorly understood; however, utilizing cardiopulmonary exercise testing to its full potential, the pathophysiology of exercise limitation in survivors of preterm birth will enhance our understanding of the role exercise may play. The role of exercise interventions in mitigating the risk of chronic disease and premature death following preterm birth has yet to be fully realized and should be a focus of future robust randomized controlled trials.


Impact of anesthetic agents on cerebrovascular physiology in children.
The role of the pediatric neuroanesthetist is to provide comprehensive care to children with neurologic pathologies. The cerebral physiology is influenced by the developmental stage of the child. The understanding of the effects of anesthetic agents on the physiology of cerebral vasculature in the pediatric population has significantly increased in the past decade allowing a more rationale decision making in anesthesia management. Although no single anesthetic technique can be recommended, sound knowledge of the principles of cerebral physiology and anesthetic neuropharmacology will facilitate the care of pediatric neurosurgical patients.


Dynamics after a sweep through a quantum critical point.
The coherent quantum evolution of a one-dimensional many-particle system after slowly sweeping the Hamiltonian through a critical point is studied using a generalized quantum Ising model containing both integrable and nonintegrable regimes. It is known from previous work that universal power laws of the sweep rate appear in such quantities as the mean number of excitations created by the sweep. Several other phenomena are found that are not reflected by such averages: there are two different scaling behaviors of the entanglement entropy and a relaxation that is power law in time rather than exponential. The final state of evolution after the quench is not characterized by any effective temperature, and the Loschmidt echo converges algebraically for long times, with cusplike singularities in the integrable case that are dynamically broadened by nonintegrable perturbations.


Relationship between free-running period and minimum tolerable light pulse interval of skeleton photoperiods in field mice Mus booduga.
The entrainment of the circadian rhythm of locomotor activity was studied in the field mouse Mus booduga in order to examine the relationship between the free-running period (tau) and minimum tolerable light pulse interval of the skeleton photoperiods. The animals were entrained under three different light/dark (LD) schedules, each out of phase with the other. They were then subjected to various skeleton photoperiods created by two repeated light pulses (LPs) interrupting darkness. Animals that selected the shorter interval between the LPs as their "subjective night" had significantly shorter tau (23.13 +/- 0.38 h) as compared to those that selected the longer dark interval as subjective night (tau = 23.87 +/- 0.18 h). When the longer dark interval was 12 h, animals selecting that interval as their subjective night included both long-tau and short-tau individuals. When both intervals of darkness were of equal duration, no difference in the selection of subjective night was seen between short and long-tau animals. When the "dusk" LP for the animals that selected the longer dark interval as subjective night was advanced by 2 h to create a new skeleton photoperiod, the number of transient cycles appearing before steady-state entrainment was found to depend on the duration of the photoperiods. When the night defined by the two LPs was reduced below 6h, a dramatic "phase jump" in the activity rhythm was observed, and the initial phase relationship was restored after a relaxation in the night duration. We observed considerable interindividual variation in the "minimum tolerable light pulse interval of skeleton photoperiods," which we suggest may be due to the observed variation in tau among individuals.


Sequence programmed DNA three-way junctions for templated assembly of fluorescent silver nanoclusters.
Fluorescent silver nanoclusters (AgNCs) templated by DNA are promising label free fluorophores with excellent photostability and tunable optical properties. Most of the reported DNA-nanocluster fluorescent tags comprise of programmed strands for the cluster formation either on the edges as overhangs or as loops on the duplex strands. Herein, we report a design strategy for sequence programmed, DNA three-way junctions (DNA-3WJ), comprising of unhybridized cytosine nucleobases in the 3WJ-center, capable of binding to silver ions and stabilizing the AgNCs. The formation of AgNCs in these DNA-3WJs were confirmed by various spectroscopic and microscopic techniques. 3WJ20-C12 comprising of 12 cytosine bases in the center of the DNA-3WJ, form fluorescent nanoclusters with an emission maximum around 630 nm and 12% fluorescence quantum yield. Control DNA-3WJs with six cytosine bases in the center (3WJ20-C6) and ones without cytosine bases (3WJ20) failed to form fluorescent AgNCs confirming the requirement of central, unhybridized cytosine bases for the stabilization of the nanoclusters. Further, the duplex arms of DNA-3WJs were shown to influence the fluorescent properties of AgNCs by varying the size and stability of the cytosine-loop structure of DNA-3WJs. Metal ion interaction studies shows the selectivity of the 3WJ20-C12/AgNCs towards Hg2+ with sensitivity in the nanomolar range.


Time to give up on a single explanation for autism.
We argue that there will be no single (genetic or cognitive) cause for the diverse symptoms defining autism. We present recent evidence of behavioral fractionation of social impairment, communication difficulties and rigid and repetitive behaviors. Twin data suggest largely nonoverlapping genes acting on each of these traits. At the cognitive level, too, attempts at a single explanation for the symptoms of autism have failed. Implications for research and treatment are discussed.


Making use of qualitative research.
Many have discussed the importance of using research in practice. To understand this issue, we examined what authors of qualitative research in oncology said about the uses of their research findings. Analysis ofthe authors' implications sections was conducted with 42 articles published between 1995 and 2001 and indexed in either Medline or CINAHL The two categories from this analysis were implications for future research and communication. The categories and related subcategories are illustrated with selected quotes from some of the articles. Findings confirm the importance of language in health and illness.


A case of intussusceptions at two parts of the ileum caused by an ileus tube.
An 87-year-old woman was admitted to our hospital for paralytic ileus, and she was treated using an ileus tube. Although her symptoms improved, abdominal fullness developed again on day 3 after ileus tube insertion. Abdominal computed tomography indicated intussusceptions at the ileum and the terminal part of the ileum;therefore, an emergency surgery was performed. During the surgery, antegrade intussusceptions were found in the ileum 60cm from the ileocecal valve and the terminal part of the ileum into the ascending colon. The intussusception of the anal side was resolved by manual reduction, but the oral side needed a partial resection of small bowel because of the presence of necrosis. There were no lesions, such as tumors, at the intussusceptions sites. Therefore, the two intussusceptions were thought to be caused by the ileus tube. We diagnosed a rare case of intussusceptions in the two parts of the ileum as a complication of the placement of an ileus tube.


Capabilities of an optical direct push probe for 2D-subsurface imaging.
Characterization of hydrological conditions at polluted sites is critical for understanding of contaminant distribution and transport. Standard techniques for site characterization, such as soil coring together with well installation for piezometric measurements and water sampling, allow only some insights into subsurface properties and processes. To obtain additional data, direct-push techniques are often used in soils and unconsolidated formations. The various available techniques provide high resolution information on cm to mm scale. Recently, the Optical Imaging Profiler (OIP) was developed for detection of fluorescent contaminants. Here, we have investigated the applicability of the OIP for groundwater tracing using fluorophores. Our laboratory experiments show that it is possible to qualitatively trace various fluorophores meaning that light emitted by the fluorophores can be detected by a standard digital camera sensor. The measured fluorescence depends on the number of fluorophore molecules present in the pore space adjacent to the OIP and decreases with smaller pore size as well as fluorophore concentration. In a field trial, an injected eosin Y solution could be very clearly detected after the injection within a radius of 0.5 m around the injection point. When the OIP is equipped with a second light source emitting visible light, images of the soil texture and color can be captured. Sediment color can act as a proxy for various soil properties. Tests at a second field site, indicate that detected variation in soil color depend on water saturation and redox processes. Hence, the OIP is a flexible, cost effective and multifunctional tool for characterization of contaminated sites.


4/6-Herto-arm and 4/6-mikto-arm star-shaped block polymeric drug-loaded micelles and their pH-responsive controlled release properties: a dissipative particle dynamics simulation.
Star-shaped polymers have received significant attention and have been widely developed for prospective applications in drug delivery owing to their topological structure and unique physiochemical characteristics. The anticancer drug doxorubicin (DOX) was used as a model drug, and four/six-arm star-shaped block polymeric micelles were employed as the carriers. The dissipative particle dynamics (DPD) method was adopted to simulate the formation of micelles, the effects of the hydrophobic/hydrophilic block ratio on the micellar structure and drug-loading performance, the effect of the drug loading content on the micellar morphology, and the effect of the pH-sensitive block ratio on the drug release properties. Under neutral conditions (pH = 7.4), increasing the hydrophobic block ratio reduces the stability of the micelle structure but could improve its drug loading performance. Increasing the pH-sensitive block (DEAEMA) ratio is beneficial to the drug loading performance of the mikto-arm star-shaped polymeric micelles and is detrimental to the drug loading performance of the herto-arm star-shaped polymeric micelles. After comparing the structural changes, radial distribution function (RDF) and mean square displacement (MSD) of the polymeric micelles with different pH-sensitive block ratios under weakly acidic conditions (pH = 5.0), the drug release properties of the drug-loaded micelles were systematically analysed. The results showed that the higher the proportion of the pH-sensitive block in the polymeric micelles, the better their pH-response performance, and the looser the structure of the micelles during the release process. A too high or too low ratio of pH-sensitive blocks in the polymeric micelles was detrimental to drug release performance. This study could provide theoretical support for the structural design and development of novel functional block polymers.


[Long-term survival after palliative embolization of kidneys affected by tumors].
Based on their own experience and data in the literature, the authors recommend to use also in future palliative embolization of the kidney as part of comprehensive treatment of patients with inoperable tumours of the kidney. They describe their experience with a group of 20 patients. In one female patient after palliative embolization an unusually favourable effect was observed with macroscopic disappearance of the tumour and affection of the pleura, associated with prolonged survival.


Peritonsillar Abscess at a Dedicated Otolaryngology Emergency Department.
Aim Peritonsillar abscess (PTA) is the most common suppurative complication of acute tonsillitis. It requires urgent specialist treatment due to the risk of progression to airway compromise. We aimed to review referral pathways to a dedicated otolaryngology emergency department (ORL-ED), identify causative organisms and discuss COVID-19 implications. Methods A retrospective review of patients presenting to the ORL-ED between January 2018 and December 2019 was undertaken. Data extracted included demographics, referral source, treatment, microbiology results and length of stay. Statistical analysis of seasonal variation of presentation and causative organisms employed Chi-Square and Fisher's Exact Test, respectively. Results There were 53 PTA presentations. 51 were admitted accounting for 44.3% (51/115) of ED admissions. The median patient age was 31 years (IQR 20-40yrs). GP referral accounted for 48/53 (90.6%). There was no statistically significant seasonality (χ2=5.94, p=0.11) in presentation. Microbiology samples were available for 44 patients. Streptococcus was identified in 19/44 (43.2%) patients. 85% (45/53) of patients received Co-amoxiclav. Discussion PTA is a perennial condition with diverse causative organisms. Antibiotic choice should reflect this. The majority of patients are referred from primary care, emphasising the role of the GP in initial diagnosis and the importance of clinical education in this regard.


Filovirus Disease Outbreaks: A Chronological Overview.
Filoviruses cause outbreaks which lead to high fatality in humans and non-human primates, thus tagging them as major threats to public health and species conservation. In this review, we give account of index cases responsible for filovirus disease outbreaks that have occurred over the past 52 years in a chronological fashion, by describing the circumstances that led to the outbreaks, and how each of the outbreaks broke out. Since the discovery of Marburg virus and Ebola virus in 1967 and 1976, respectively, more than 40 filovirus disease outbreaks have been reported; majority of which have occurred in Africa. The chronological presentation of this review is to provide a concise overview of filovirus disease outbreaks since the discovery of the viruses, and highlight the patterns in the occurrence of the outbreaks. This review will help researchers to better appreciate the need for surveillance, especially in areas where there have been no filovirus disease outbreaks. We conclude by summarizing some recommendations that have been proposed by health and policy decision makers over the years.


Identification of hub genes for glaucoma: a study based on bioinformatics analysis and experimental verification.
To explore hub genes for glaucoma based on bioinformatics analysis and an experimental model verification. In the Gene Expression Omnibus (GEO) database, the GSE25812 and GSE26299 datasets were selected to analyze differentially expressed genes (DEGs) by the GEO2R tool. Through bioinformatics analysis, 9 hub genes were identified. Receiver operating characteristic (ROC) curves and principal component analysis (PCA) were performed to verify whether the hub gene can distinguish glaucoma from normal eyes. The mouse model of glaucoma was constructed, and the real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) assay was performed to detect the expression levels of hub genes in glaucoma. There were 128 overlapping DEGs in the GSE25812 and GSE26299 datasets, mainly involved in intracellular signalling, cell adhesion molecules and the Ras signalling pathway. A total of 9 hub genes were screened out, including GNAL, BGN, ETS2, FCGP4, MAPK10, MMP15, STAT1, TSPAN8, and VCAM1. The area under the curve (AUC) values of 9 hub genes were greater than 0.8. The PC1 axle could provide a 70.5% interpretation rate to distinguish glaucoma from normal eyes. In the ocular tissues of glaucoma in the mice model, the expression of BGN, ETS2, FCGR4, STAT1, TSPAN8, and VCAM1 was increased, while the expression of GNAL, MAPK10, and MMP15 was decreased. Nine hub genes in glaucoma are identified, which may provide new biomarkers and therapeutic targets for glaucoma.


Quantifying Caregiver Movement when Measuring Infant Movement across a Full Day: A Case Report.
There is interest in using wearable sensors to measure infant movement patterns and physical activity, however, this approach is confounded by caregiver motion. The purpose of this study is to estimate the extent that caregiver motion confounds wearable sensor data in full-day studies of infant leg movements. We used wearable sensors to measure leg movements of a four-month-old infant across 8.5 hours, during which the infant was handled by the caregiver in a typical manner. A researcher mimicked the actions of the caregiver with a doll. We calculated 7744 left and 7107 right leg movements for the infant and 1013 left and 1115 right "leg movements" for the doll. In this case, approximately 15% of infant leg movements can be attributed to background motion of the caregiver. This case report is the first step toward removing caregiver-produced background motion from the infant wearable sensor signal. We have estimated the size of the effect and described the activities that were related to noise in the signal. Future research can characterize the noise in detail and systematically explore different methods to remove it.


Synthesis of fused 1-aminoindole polycycles by a sequence of palladium-catalyzed N–H and C(sp2)–H arylations.
An efficient Pd-catalyzed selective intramolecular arylation of functionalized N,N′-substituted 1-aminoindoles has been reported. In all cases, the reactions take place rapidly in DMA and efficiently proceed in the presence of a Pd(OAc)2/Dpephos catalytic system, furnishing the fused indolo[2,1-a]phthalazines in high yields. Additionally, the one-pot double C–H arylation at positions C-2 and C-3 of N,N′-substituted 1-aminoindoles is effective and leads to unknown complex scaffolds of biological interest.


Reduced binocular depth inversion in patients with alcoholism.
Binocular depth inversion represents an illusion of visual perception, serving to invert the perception of implausible hollow objects, e.g. a hollow face into a normal face. Such inversion occurs frequently, especially when objects with a higher degree of familiarity (e.g. photographs of faces) are displayed. Cognitive factors are assumed to override the binocular disparity cues of stereopsis. The hypothesis was tested that during mild and moderate alcohol withdrawal, and severe and mild alcohol intoxication, the central nervous system is unable to correct implausible perceptual hypotheses. Measurements of binocular depth inversion in perception of three-dimensional objects were performed in 10 patients with severe alcohol intoxication, in 10 subjects with mild alcohol intoxication, in nine patients with moderate alcohol withdrawal treated with carbamazepine, in 10 patients with moderate alcohol withdrawal without any pharmacological treatment, in 11 patients with mild alcohol withdrawal and in 10 healthy volunteers. The binocular depth inversion scores were highly elevated in the severely intoxicated patients group and in the group with moderate withdrawal symptoms without carbamazepine treatment, in comparison to the healthy volunteers. The data demonstrate a strong impairment of binocular depth inversion in moderate alcohol withdrawal and during severe alcohol intoxication. This supports the view that these states may be accompanied by a disorganization of the interaction between sensory input and top-down component. The effects of carbamazepine are discussed.


An ab initio study of tunneling splittings in the water dimer.
Tunneling splittings in the water dimer have been determined by the semiclassical WKB method, based on pathways characterized at the computational level of second-order Møller-Plesset (MP2) theory with basis sets of aug-cc-pVTZ quality. This calculation takes into account all three acceptor tunneling, donor-acceptor interchange, and bifurcation tunneling rearrangements of the water dimer. The tunneling splittings were evaluated as 7.73 cm(-1) (large splitting) and 0.42 cm(-1) (small splitting), which are in good agreement with the corresponding experimental values of 11.18 cm(-1) and 0.70 cm(-1), respectively.


Production of Odd-Carbon Dicarboxylic Acids in Escherichia coli Using an Engineered Biotin-Fatty Acid Biosynthetic Pathway.
Dicarboxylic acids are commodity chemicals used in the production of plastics, polyesters, nylons, fragrances, and medications. Bio-based routes to dicarboxylic acids are gaining attention due to environmental concerns about petroleum-based production of these compounds. Some industrial applications require dicarboxylic acids with specific carbon chain lengths, including odd-carbon species. Biosynthetic pathways involving cytochrome P450-catalyzed oxidation of fatty acids in yeast and bacteria have been reported, but these systems produce almost exclusively even-carbon species. Here we report a novel pathway to odd-carbon dicarboxylic acids directly from glucose in Escherichia coli by employing an engineered pathway combining enzymes from biotin and fatty acid synthesis. Optimization of the pathway will lead to industrial strains for the production of valuable odd-carbon diacids.


Implication of the nucleus accumbens shell, but not core, in the acute and sensitizing effects of cocaine in rats.
Expression of cocaine-evoked motor behaviors appears to be dependent on dopamine neurotransmission particularly in the target area of the mesolimbic system, i.e. the nucleus accumbens (NAc). To test potential anatomical component of the locomotor effects of cocaine and expression of its behavioral sensitization, male Wistar rats were implanted with bilateral cannulae aimed at the two subregions of the NAc (the shell or the core) and then intracranially injected with cocaine (locomotor activity) or injected with cocaine given either systemically or intracranially following the repeated (5 days) systemic drug administration (sensitization). Sensitization was measured at early (5-day) and late (21-day) withdrawal periods. Acute administration of intra-NAc shell cocaine (6.73-50 microg/side) in a dose-dependent manner increased locomotor activity in rats; significant hyperactivation was observed after 25 and 50 microg/side of cocaine. Intra-NAc core injection of cocaine (12.5-50 microg/side) did not change rats' locomotor activity. After 5- or 21-day withdrawal, behavioral sensitization (ca. 2 times higher locomotor activity than that after acute drug administration) was observed when cocaine was injected either systemically (10 mg/kg) or intra-NAc shell (12.5-25 microg/side) in animals repeatedly treated with cocaine (10 mg/kg). No difference was observed in the response to the challenge with intra-NAc core cocaine (12.5-25 micorg/side) in rats treated repeatedly with cocaine at either withdrawal period. The above findings show the differential regulation of motor responses to cocaine within the subregions of the NAc. They also indicate a preferential effect for the NAc shell in expression of the acute and sensitizing effects of cocaine in rats.


The next generation of literature analysis: integration of genomic analysis into text mining.
Text-mining systems are indispensable tools to reduce the increasing flux of information in scientific literature to topics pertinent to a particular interest in focus. Most of the scientific literature is published as unstructured free text, complicating the development of data processing tools, which rely on structured information. To overcome the problems of free text analysis, structured, hand-curated information derived from literature is integrated in text-mining systems to improve precision and recall. In this paper several text-mining approaches are reviewed and the next step in development of text-mining systems, which is based on a concept of multiple lines of evidence, is described: results from literature analysis are combined with evidence from experiments and genome analysis to improve the accuracy of results and to generate additional knowledge beyond what is known solely from literature.


Marker encoded fringe projection profilometry for efficient 3D model acquisition.
This paper presents a novel marker encoded fringe projection profilometry (FPP) scheme for efficient 3-dimensional (3D) model acquisition. Traditional FPP schemes can introduce large errors to the reconstructed 3D model when the target object has an abruptly changing height profile. For the proposed scheme, markers are encoded in the projected fringe pattern to resolve the ambiguities in the fringe images due to that problem. Using the analytic complex wavelet transform, the marker cue information can be extracted from the fringe image, and is used to restore the order of the fringes. A series of simulations and experiments have been carried out to verify the proposed scheme. They show that the proposed method can greatly improve the accuracy over the traditional FPP schemes when reconstructing the 3D model of objects with abruptly changing height profile. Since the scheme works directly in our recently proposed complex wavelet FPP framework, it enjoys the same properties that it can be used in real time applications for color objects.


Evaluation of Shoulder Muscle Improvement in Patients Following Free Latissimus Dorsi Muscle Pedicle Flap Transfer.
Aim: This study aimed to evaluate the clinical outcomes, shoulder muscle strength, and donor site morbidity following the free latissimus dorsi (LD) muscle pedicle flap transfer. Materials: Patients with free LD muscle pedicle flap reconstructions and with asymptomatic shoulders (affected and contralateral side) were included. The follow-up duration was 12 months. The combined shoulder range of motion (ROM), Constant-Murley shoulder (CMS), and quick disabilities of the arm, shoulder, and hand (QuickDASH) scores were measured preoperatively and at 1 year postoperatively. The ratio of the isokinetic muscle strength and total work was measured with an isokinetic dynamometer (Cybex 350®) both preoperatively and at sixth month postoperatively. Results: Twenty patients with a mean age of 37.06 ± 9.74 years and a mean body mass index of 23.49 ± 8.6 kg/m2 were included. The difference in shoulder ROM and CMS and increase in QuickDASH were not significant at the first postoperative year. The peak torque and total work performed decreased by 13%-16% for the adductor and extensor functions at the six month postoperatively, and these differences were significant. Although the adductor peak torque was significantly lower in the postoperative test of the operated side, no significant difference was found between the operated and unaffected shoulder peak torque values. Moreover, no significant difference was noted between the operated and unaffected shoulders in all isokinetic tests pre- and postoperatively. Conclusion: The free LD muscle pedicle flap harvest did not decrease function and ROM at the first postoperative year. The muscle strength and total work of shoulders after the LD muscle transfer returned to the preoperative condition at the sixth month, except adductor and extensor muscle strengths. However, adductor and extensor muscle strengths of the operated shoulders were not significantly different postoperatively.


Direct reconstruction of two ultrashort pulses based on non-interferometric frequency-resolved optical gating.
We describe a non-interferometric ultrashort-pulse measurement technique based on frequency-resolved optical gating (FROG) with which pulses can be reconstructed directly, i.e. non-iteratively. Two different FROG spectrograms are measured, which represent the only information required to reconstruct the amplitudes and phases of two independent input pulses. The direct reconstruction method is demonstrated with a single-shot FROG setup used to obtain the spectrograms generated from two synchronized input pulses. To demonstrate and determine the reconstruction quality for complex pulses, a programmable pulse shaper is used to modify the pulses sourced from a Kerr-lens mode-locked Ti:sapphire oscillator.


Altered cerebral blood flow velocity features in fibromyalgia patients in resting-state conditions.
The aim of this study is to characterize in resting-state conditions the cerebral blood flow velocity (CBFV) signals of fibromyalgia patients. The anterior and middle cerebral arteries of both hemispheres from 15 women with fibromyalgia and 15 healthy women were monitored using Transcranial Doppler (TCD) during a 5-minute eyes-closed resting period. Several signal processing methods based on time, information theory, frequency and time-frequency analyses were used in order to extract different features to characterize the CBFV signals in the different vessels. Main results indicated that, in comparison with control subjects, fibromyalgia patients showed a higher complexity of the envelope CBFV and a different distribution of the power spectral density. In addition, it has been observed that complexity and spectral features show correlations with clinical pain parameters and emotional factors. The characterization features were used in a lineal model to discriminate between fibromyalgia patients and healthy controls, providing a high accuracy. These findings indicate that CBFV signals, specifically their complexity and spectral characteristics, contain information that may be relevant for the assessment of fibromyalgia patients in resting-state conditions.


Single-stage anterior debridement and fibular allograft implantation followed by posterior instrumentation for complicated infectious spondylitis: report of 20 cases and review of the literature.
Complicated infectious spondylitis is an infrequent infection with severe spinal destruction, and is indicated for combined anterior and posterior surgeries. Staged debridement and subsequent reconstruction is advocated in the literature. The purpose of this study is to evaluate the feasibility and clinical outcome of patients who underwent single-stage combined anterior debridement and fibular allograft implantation followed by supplemental posterior fixation for complicated infectious spondylitis. We retrospectively reviewed the medical records of 20 patients who underwent single-stage combined anterior and posterior surgeries for complicated infectious spondylitis from January 2005 to December 2010. Complicated infectious spondylitis was defined as at least 1 vertebral osteomyelitis with pathological fracture or severe bony destruction and adjacent discitis, based on imaging studies. The severity of the neurological status was evaluated using the Frankel scale. The clinical outcomes were assessed by careful physical examination and regular serological tests to determine the visual analog scale (VAS) score and Macnab criteria. Correction of the sagittal Cobb angle on radiography was also compared before and after surgery. The Wilcoxon signed-rank test was used to analyze patient surgical prognosis and radiological findings. All patients with complicated infectious spondylitis were successfully treated by single-stage combined anterior and posterior surgeries. No patients experienced neurologic deterioration. The average VAS score was 7.8 before surgery and significantly decreased to 2.1 at discharge. Three patients had excellent outcomes and 17 had good outcomes, based on Macnab criteria. The average length of the allograft for reconstruction was 64.0 mm. Kyphotic deformity improved in all patients, with an average correction angle of 13.4°. There was no implant breakage or allograft dislodgement during at least 36 months of follow-up. Single-stage anterior debridement and fibular allograft implantation followed by posterior pedicle screw instrumentation provide immediate stability, satisfactory alignment, and successful infection control. Fibular allograft implantation seems to be a good alternative for anterior reconstruction; it can proceed to bony incorporation and avoids donor site morbidity.


Renal failure in childhood.
Renal failure in infants and children requires prompt and thorough diagnostic evaluation for reversible causes and careful medical management. Congenital malformations of the renal parenchyma and urinary drainage system must be excluded in any child, even the adolescent. The management of these patients requires close cooperation with the (pediatric) urologist. These children are at highest risk for the development of complications, such as growth failure, osteodystrophy, and urinary tract infections. Prolonged progressive renal insufficiency in this group must be anticipated. In contrast, acquired renal insults may result in acute, reversible renal failure. Awareness of the hemodynamic or nephrotoxic insults that can result in ARF, and appropriate diagnostic and therapeutic maneuvers, may minimize morbidity and mortality. CRF presents the physician with long-term and complex challenge of medical management. Dietary and drug therapy can be remarkably effective in reducing the complications of CRF. Rehabilitation with successful renal transplantation is an attainable goal for most uremic children.


Excess fluoride interferes with chloride-channel-dependent endocytosis in ameloblasts.
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF). Both CF and dental fluorosis result in protein retention in mature enamel. We hypothesized that excess fluoride might cause protein retention by interfering with CFTR function, resulting in abnormal expression of proteases and pathological endocytosis. Millimolar concentrations of fluoride reduced uptake of Emdogain, an enamel matrix derivative, in ameloblast-like PABSo-E cells, while stimulating an acidic intracellular environment at the same time. When CFTR function was inhibited by either an siRNA or a chloride channel inhibitor, CFTRinh-172, fluoride's effect on Emdogain uptake was partially blocked. Treatment of cells with CFTR siRNA down-regulated expression of proteases MMP20 and KLK4 and increased intracellular pH. We conclude that excess fluoride inhibits endocytic activity of ameloblasts through the CFTR chloride channel or other chloride channels. The intracellular pH might be the key mechanism by which abnormal proteolytic activity and defective endocytosis cause the residual protein observed in enamel of patients with CF and dental fluorosis.


Clinical nurse leader and clinical nurse specialist role delineation in the acute care setting.
More than 90 members of the American Association of Colleges of Nursing and 190 practice sites have partnered to develop the clinical nurse leader (CNL) role. The partnership has created synergy between education and practice and nurtured innovation and diffusion of learning on a national basis. In this ongoing department, the editor, Jolene Tornabeni, MA, RN, FAAN, FACHE, showcases a variety of nurse leaders who discuss their new patient care delivery models in preparation for the CNL role and CNLs who highlight partnerships with their clinical colleagues to improve patient care. In this article, the authors explore differences and similarities between the CNL and the clinical nurse specialist roles, describing the working strategies between a CNL and clinical nurse specialist, and role delineations that have resulted from their cooperation, collaboration, and planning.


Individualized Strategies for Intraoperative Localization of Non-palpable Pulmonary Nodules in a Hybrid Operating Room.
Background: Precise preoperative localization of small pulmonary nodules is a key prerequisite to their successful excision. With the advent of hybrid operating rooms (HORs), a patient-tailored approach encompassing simultaneous localization and removal of small pulmonary nodules has become feasible. In this study, we describe our individualized image-guided video assisted thoracoscopic surgery (iVATS) strategies implemented within a HOR environment. Specifically, localization was performed through different marking approaches (single- vs. double-marker) and access routes [percutaneous technique with Dyna-computed tomography (DynaCT) imaging vs. electromagnetic navigation bronchoscopy (ENB)]. Methods: Between April 2017 and November 2018, a total of 159 consecutive patients (harboring 174 pulmonary nodules) were treated with iVATS. The marking approach and access route were individually tailored according to lesion localization and its distance from the pleural surface. The efficacy and safety of our iVATS technique were determined through a retrospective review of clinical charts. Results: All of the localization procedures were performed in a HOR by a single team of thoracic surgeons. The mean tumor size on preoperative CT was 8.28 mm (95% confidence interval [CI]: 7.6-8.96 mm), whereas their mean distance from the pleural surface was 9.44 mm (95% CI: 8.11-10.77 mm). Of the 174 tumors, 150 were localized through a percutaneous DynaCT-guided approach (single-marker: 139, dual-marker: 11), whereas localization in the remaining 24 was accomplished via the ENB-guided approach (single-marker: 4; dual-marker: 20). The mean localization time was 17.78 min (95% CI:16.17-19.39 min). The overall localization success rate was 95.9%. We failed to localize a total of seven nodules either because of technical complications (pneumothorax, n = 3; microcoil dislodgement; n = 1) or machine failure (n = 3). No operative deaths were observed, and the mean length of postoperative stay was 3.65 days (95% CI: 3.19-4.11 days). Conclusions: The use of tailored marking approaches and access routes allowed us to individualize the iVATS procedure for small pulmonary nodules, ultimately promoting a more patient-centered workflow.


Testosterone differentially modulates gonadotropin subunit messenger ribonucleic acid responses to gonadotropin-releasing hormone pulse amplitude.
Testosterone (T) inhibits GnRH secretion and can also modulate the effects of GnRH on gonadotropin synthesis and secretion. To assess the effect of T on GnRH stimulation of alpha, LH beta, and FSH beta mRNA expression, we replaced T at three levels to reproduce low (1.5 +/- 0.5 ng/ml), medium (3.5 +/- 0.3 ng/ml), and high (6.2 +/- 0.6 ng/ml) physiological plasma concentrations. Additionally, as peripheral conversion to dihydrotestosterone (DHT) or estradiol (E2) may mediate T action, the effects of GnRH pulses in the presence of DHT and E2 were also studied. Male rats were castrated, and steroids were replaced via implants containing either T (three doses) or DHT or E2 (two doses each). GnRH pulses (10-250 ng/pulse) were administered iv at 30-min intervals for 48 h. Pituitary subunit mRNA concentrations, gonadotropin content, and LH and FSH secretion were determined. The patterns of alpha, LH beta, and FSH beta mRNA responses to increasing GnRH pulse amplitude were similar at all concentrations of plasma T. Alpha mRNA concentrations were increased 2- to 4-fold by GnRH pulses. At the same plasma T concentration, all doses of GnRH produced similar increases in alpha mRNA, but the response tended to be lower at the higher (6.2 ng/ml) levels of T. LH beta mRNA showed a clear dependence on GnRH pulse amplitude, with the maximum responses (2- to 3-fold) occurring after 10- to 25-ng GnRH pulses. At the higher (3.5 and 6.2 ng/ml) T concentrations, the dose-response curve was shifted to the left. The lowest GnRH pulse dose (10 ng) produced maximum responses, and LH beta mRNA increments in response to the higher GnRH doses were suppressed. FSH beta mRNA concentrations were increased by T in saline-pulsed controls. FSH beta mRNA responses were similar (2- to 3-fold) after all GnRH doses and at all concentrations of T. Increasing GnRH pulse doses reduced the pituitary content of both LH and FSH at all levels of T. Acute LH secretion was maximal after 10- and 25-ng pulses of GnRH when plasma T was low, but increased progressively with GnRH dose at the highest plasma T concentrations. Plasma FSH did not show any differential responsiveness to GnRH pulse dose or to increasing plasma T. Thus, LH synthesis and secretion are affected more than those of FSH by changing plasma concentrations of T. T may modulate posttranslational events in LH secretion. The higher GnRH doses effected LH release without increasing LH beta mRNA in the presence of higher physiological concentrations of T.(ABSTRACT TRUNCATED AT 400 WORDS)


Restrictive eating is associated with emotion regulation difficulties in a non-clinical sample.
The relationship between emotion regulation difficulties and restrictive eating has not been established in non-clinical samples. In this study, undergraduates (n = 98) provided information regarding general and specific emotion regulation difficulties on the Difficulties in Emotion Regulation Scale (DERS) and whether they had engaged in recent restrictive eating. Generalized linear models were used to determine if individuals endorsing versus denying recent restrictive eating differed on emotion regulation problems. Results indicated that individuals endorsing restrictive eating had elevated DERS Total (p < .001), Goals (p = .001), Impulse (p < .001), and Strategies (p < .001) scores. Results remained primarily unchanged after controlling for the related construct of dietary restraint. Findings indicate that endorsement of restrictive eating among non-clinical individuals is uniquely associated with emotion regulation deficits, especially those reflecting emotional under-control. Interventions targeting emotion regulation may enhance prevention and treatment of restrictive eating across severity.


Central vasopressin V1-receptors mediate indomethacin-induced antipyresis in rats.
Central microinjection or infusion of an arginine vasopressin (AVP) V1-receptor antagonist within the brain of the conscious, unrestrained, and febrile rat inhibited or abolished the antipyretic effects of peripherally administered indomethacin (Indo). The degree of Indo-induced antipyresis was determined by 2-h thermal indexes (degree C.h) calculated from the time of Indo injection. Microinjection of saline or V1-receptor antagonist within the ventral septal area (VSA) of the rat brain immediately followed by intraperitoneal Indo evoked antipyretic responses of -1.63 +/- 0.17 and -0.24 +/- 0.09 degrees C.h, respectively (P less than 0.01). Infusion of the VSA with saline or V1-receptor antagonist before and after Indo resulted in thermal indexes of -1.35 +/- 0.16 and 0.13 +/- 0.30 degree C.h, respectively (P less than 0.01). Central microinjection of a V2-receptor antagonist did not significantly effect Indo-induced antipyresis compared with paired saline controls. Neither saline nor the V1-receptor antagonist affected nonfebrile body temperature when microinjected into the VSA. These data indicate the importance of AVP V1-receptors within the VSA in mediating the potent fever-reducing properties of the antipyretic drug Indo. Furthermore, these data call into question whether prostaglandin synthesis inhibition is a sufficient explanation of drug-induced antipyresis.


Commentary: Serving the nation, serving the people: echoes of war in the early NHS.
It is something of a cliché to speak of Britain as having been transformed by the traumas of World War II and by its aftermath. From the advent of the 'cradle to grave' Welfare State to the end of (formal) empire, the effects of total war were enduring. Typically, they have been explored in relation to demographic, socioeconomic, technological and geopolitical trends and events. Yet as the articles in this volume observe across a variety of examples, World War II affected individuals, groups and communities in ways both intimate and immediate. For them, its effects were directly embodied That is, they were experienced physically and emotionally-in physical and mental wounds, in ruptured domesticities and new opportunities and in the wholesale disruption and re-formation of communities displaced by bombing and reconstruction. So it is, perhaps, unsurprising that Britain's post-war National Health Service, as the state institution charged with managing the bodies and behaviour of the British people, was itself permeated by a 'wartime spirit' long after the cessation of international hostilities.


Pulmonary and testicular angiotensin-converting isoenzymes.
A variant of angiotensin-converting enzyme occurs in (male) germinal cells. This testicular isozyme is catalytically similar to the widespread pulmonary-type isozyme, but contains a shorter polypeptide chain and does not appear until puberty. The two proteins differ at their NH2- and COOH-termini, but share many tryptic peptides. All antigenic determinants of the testicular form are represented in the pulmonary molecule whereas the latter contains determinants unrelated to catalysis which are lacking in the testicular species. The data indicate that the testicular isozyme corresponds closely to an internal part of the pulmonary polypeptide which includes its active site. The structural and developmental differences between the two polypeptides are pretranslationally determined since they are demonstrable in a cell-free system programmed by the appropriate mRNAs. Characterization of the molecular mechanisms responsible for the relationship of these isozymes may yield useful information regarding cell-specific protein expression.


Behavioral characterization of blocking the ErbB signaling during adolescent and adulthood in reward-liking (preference) and reward-related learning.
Adolescence is a critical period in brain development. During this critical period the seeking for hedonic activities is increased, and their activity signals are stronger than the regulatory signals of judgment and reasoning. We recently reported that alteration of ErbB signaling during this period led to elevated striatal dopamine levels and reduced preference for sweetness without affecting locomotor activity and exploratory behavior. In the current study, we extend our findings and explore whether inhibition of the ErbB pathway during adolescence or adulthood also affects alcohol preference (hedonic "liking"), avoidance learning, and motivational reward "wanting". We demonstrated that chronic administration of the pan-ErbB kinase inhibitor JNJ28871063 (JNJ) to adolescent mice, but not to adult mice, reduced alcohol preference compared with the saline-injected group, without affecting avoidance learning as measured by increasing concentrations of quinine in the bitter avoidance test. Adolescent JNJ-treated mice continue to demonstrate less alcohol preference in adulthood compared with their saline-injected controls. In addition, adolescent JNJ-treated mice and their saline-injected controls did not differ in the time they spent in the food-condition chamber, and in their preference for social odor. In contrast to adolescent JNJ- treated mice, blocking the pathway during adulthood alter the preference to natural reward. These data support our initial findings that interruption of the ErbB pathway during adolescence emerges in a reduced hedonic capacity that persists into adulthood, without disturbing avoidance and reward learning. In addition, this paper provides a further behavioral role of the ErbB signaling pathway in the reward system, and suggests a different time period for the involvement of the pathway in the "liking" and the "wanting" components of the system.


Letter to the editor: Stability of Random Forest importance measures.
The goal of this article (letter to the editor) is to emphasize the value of exploring ranking stability when using the importance measures, mean decrease accuracy (MDA) and mean decrease Gini (MDG), provided by Random Forest. We illustrate with a real and a simulated example that ranks based on the MDA are unstable to small perturbations of the dataset and ranks based on the MDG provide more robust results.


Well-positioned nucleosomes punctuate polycistronic pol II transcription units and flank silent VSG gene arrays in Trypanosoma brucei.
The compaction of DNA in chromatin in eukaryotes allowed the expansion of genome size and coincided with significant evolutionary diversification. However, chromatin generally represses DNA function, and mechanisms coevolved to regulate chromatin structure and its impact on DNA. This included the selection of specific nucleosome positions to modulate accessibility to the DNA molecule. Trypanosoma brucei, a member of the Excavates supergroup, falls in an ancient evolutionary branch of eukaryotes and provides valuable insight into the organization of chromatin in early genomes. We have mapped nucleosome positions in T. brucei and identified important differences compared to other eukaryotes: The RNA polymerase II initiation regions in T. brucei do not exhibit pronounced nucleosome depletion, and show little evidence for defined -1 and +1 nucleosomes. In contrast, a well-positioned nucleosome is present directly on the splice acceptor sites within the polycistronic transcription units. The RNA polyadenylation sites were depleted of nucleosomes, with a single well-positioned nucleosome present immediately downstream of the predicted sites. The regions flanking the silent variant surface glycoprotein (VSG) gene cassettes showed extensive arrays of well-positioned nucleosomes, which may repress cryptic transcription initiation. The silent VSG genes themselves exhibited a less regular nucleosomal pattern in both bloodstream and procyclic form trypanosomes. The DNA replication origins, when present within silent VSG gene cassettes, displayed a defined nucleosomal organization compared with replication origins in other chromosomal core regions. Our results indicate that some organizational features of chromatin are evolutionarily ancient, and may already have been present in the last eukaryotic common ancestor.


Scaling and root planing, systemic metronidazole and professional plaque removal in the treatment of chronic periodontitis in a Brazilian population. I. clinical results.
The current investigation evaluated the clinical effects of scaling and root planing (SRP) alone or in combination with systemic metronidazole and/or repeated professional removal of supragingival plaque in subjects with chronic periodontitis. Fourty-four adult subjects (mean age: 45+/-6 years) with periodontitis were randomly assigned to four treatment groups; a control (C, n=10) that received SRP and placebo and three test groups treated as follows: Test 1 (T1) (n=12) received SRP and metronidazole (400 mg t.i.d., M) for 10 days; Test 2 (T2) (n=12) received SRP, weekly professional supragingival plaque removal for three months (professional cleaning (PC)) and placebo; and Test 3 (T3) (n=10) received SRP, M and PC. Pocket depth (PD), attachment level (AL), bleeding on probing (BOP) and presence of visible plaque and suppuration were measured at six sites per tooth at baseline and at 90 days post-therapy. Significance of differences over time was determined using the Wilcoxon test, and among groups using ancova. A reduction in full-mouth mean clinical parameters was observed at 90 days after all therapies. Sites with baseline PD<4 mm showed an increase in mean PD in the control group and in mean AL in all treatment groups. Sites with baseline PD of 4-6 mm in subjects who received PC as part of therapy (T2, T3) showed a marked reduction in PD, AL and in the % of sites with BOP. Subjects who received metronidazole (T1 and T3) showed the best clinical response at sites with an initial PD of >6 mm. The major clinical benefit occurred when the combination of SRP, M and PC was used. Group T3 showed the least attachment loss in initially shallow pockets. This group also exhibited the greatest reduction in the % of sites with BOP and suppuration as well as in mean PD and AL at sites with baseline PD>4 mm. The data suggest a significant clinical benefit in combining SRP, systemic metronidazole and weekly professional supragingival plaque removal for the treatment of chronic periodontitis.


Prospective cross-validation of three methods of predicting failing pregnancies of unknown location.
We compared the performance of each of three tests for predicting pregnancy failure in the pregnancy of unknown (PUL) population. In a prospective observational study, we compared the performance of three models for the prediction of pregnancy failure in women with a PUL: (i) logistic-regression model incorporating vaginal bleeding, endometrial thickness (ET), initial serum progesterone and hCG levels; (ii) serum progesterone at 0 h; and (3) the hCG ratio. A total of 5942 consecutive pregnant women attending the Early Pregnancy Unit were scanned and 439 (7.4%) were classified as PULs. Of these women, 420 had complete data for serum hCG at 0 and 48 h, the hCG ratio, serum progesterone at 0 h, vaginal bleeding and ET. The final outcomes were 219 (52.1%) failing PULs, 167 (39.8%) intra-uterine pregnancies and 34 (8.1%) ectopic pregnancies. For the prediction of pregnancy failure in the PUL population, the area under the receiver operating characteristic (ROC) curve (AUC) for the logistic-regression model was 0.907 (Standard error (SE) 0.015), the AUC for serum progesterone was 0.952 (SE 0.010) and the AUC for the hCG ratio was 0.980 (SE 0.004). This improved performance of the hCG ratio was significant when compared with that of initial serum progesterone (P = 0.0076) and the logistic-regression model (P < 0.0001). Using the hCG ratio cut-offs of < 0.87 and <or=0.79, the serum progesterone cut-off of < 20 nmol l(-1) and the logistic-regression cut-off of >70% for the prediction of failing PUL, sensitivities were 86.3 and 82.2% (S), 87.2% (NS) and 78.1% (S), specificities were 97.0 and 98.0% (NS), 89.6% (S) and 88.6% (S), positive-likelihood ratios were 28.91, 41.30, 8.34 and 6.82 and negative-likelihood ratios were 0.14, 0.18, 0.14 and 0.25, respectively. The hCG ratio seems to be an optimal test for the prediction of pregnancy failure in a PUL population. The hCG ratio cut-off of 0.79 is recommended on the basis of minimizing risk to those PULs discharged at 48 h. Most importantly, when the hCG ratio is below a particular cut-off, these women can be discharged at 48 h without intervention and need for further follow-up.


A clinical study on the effect of Rishyagandha (Withania coagulans) in the management of Prameha (Type II Diabetes Mellitus).
The study was conducted with an objective of evaluating the role of Rishyagandha (Withania coagulans) powder in clinically diagnosed cases of Prameha. 53 Registered cases were divided into 3 groups; Group A (Rishyagandha fruits powder), Group B (Oral Hypoglycaemic Agent i.e. OHA), and Group C (Rishyagandha fruits powder and OHA both). Statistically significant improvement was observed in objective and subjective parameters in all 3 groups after completion of the course of treatment. Based on the results, it has been concluded that, Rishyagandha fruits powder is an effective therapeutic regimen in the management of uncomplicated cases of Prameha.


Unmeasured Confounding in Observational Studies with Multiple Treatment Arms: Comparing Emergency Department Mortality of Severe Trauma Patients by Trauma Center Level.
Comparing emergency department mortality across different levels of trauma care (nontrauma centers, level I and II centers) is important in evaluating regionalized care. Patient population characteristics differ across different levels of trauma care and it is essential to adjust for baseline covariates to make valid comparisons. Propensity score matching has been established as a more robust method to infer causal relationship in observational studies than conventional regression adjustment. We designed and implemented a three group matching methodology. First, we conducted optimal pair matching between the treatment group (nontrauma centers) and the first control group (level I trauma centers); second, we conducted optimal pair matching between the nontrauma centers and the second control group (level II trauma centers); the final step was to link the two sets of matched pairs by the common treatment subjects to form matched triplets. We then implemented a sensitivity analysis with three treatment arms, Lu's imputation based method, to assess the impact due to potential unmeasured confounding. The results showed that if the most severe adult trauma patients treated in nontrauma centers were to be treated in level I or II trauma centers, the odds of emergency department death would be reduced dramatically (odds ratio [OR] = 0.61 and 0.49). There was no difference between being treated in level I or II trauma centers. The sensitivity analysis revealed that the positive association between being treated at level I or II trauma centers and the reduced odds of mortality would remain present even in the presence of strong unmeasured confounding.


A comparison of public health care utilization by gay men and intravenous drug users with AIDS in San Francisco.
A group of gay-identified men (n = 81) and intravenous drug users (n = 88) diagnosed with AIDS in San Francisco were surveyed regarding their use and satisfaction with their health care services. The interview contained a mix of qualitative and quantitative questions. The two groups of AIDS patients were not statistically different in terms of age or self-reported level of health during the previous 3 months, although the gay men had been diagnosed with AIDS somewhat longer (20 months) than the group of intravenous drug users (15 months). Analysis of the quantitative data revealed that intravenous drug users receive more medical care for HIV disease than did gay men and were equally satisfied with the care that they did receive. Analysis of the qualitative data showed that considerable agreement exists between the perceptions of both gay men and intravenous drug users of the health care system.


Long-Term Testosterone Administration on Insulin Sensitivity in Older Men With Low or Low-Normal Testosterone Levels.
Serum testosterone levels and insulin sensitivity both decrease with age. Severe testosterone deficiency is associated with the development of insulin resistance. However, the effects of long-term testosterone administration on insulin sensitivity in older men with low or low-normal testosterone levels remain unknown. The Testosterone Effects on Atherosclerosis in Aging Men Trial was a placebo-controlled, randomized, double-blind trial. The participants were 308 community-dwelling men, ≥60 years old, with total testosterone 100 to 400 ng/dL or free testosterone <50 pg/mL. A subset of 134 nondiabetic men (mean age, 66.7 ± 5.1 years) underwent an octreotide insulin suppression test at baseline and at 3 and 36 months after randomization to measure insulin sensitivity. Insulin sensitivity was estimated as the steady-state plasma glucose (SSPG) concentration at equilibrium during octreotide and insulin administration. Secondary outcomes included total lean mass (TLM) and total fat mass (TFM) by dual energy x-ray absorptiometry. There was a significant (P = 0.003) increase in SSPG in the placebo group, whereas no change was seen in testosterone-treated subjects from baseline to 36 months; however, the between-group differences in change in SSPG over 3 years were not statistically significant (+15.3 ± 6.9 mg/dL in the placebo group vs +6.2 ± 6.4 mg/dL in the testosterone group; mixed-model effect, P = 0.17). Changes in SSPG with testosterone treatment were not associated with changes in serum total or free testosterone concentrations. Changes in TFM but not TLM were associated with increases in SSPG. Stratification by age or baseline total testosterone level did not show significant intervention effects. Testosterone administration for 36 months in older men with low or low-normal testosterone levels did not improve insulin sensitivity.


Mechanical properties of the passive pharynx in Vietnamese pot-bellied pigs. I. Statics.
The static mechanical properties of the passive pharynx were investigated in Vietnamese pot-bellied pigs by using an isolated upper airway preparation. During general anesthesia and neuromuscular blockade, cross-sectional area (A) of the pharynx was measured while airway pressure (Paw) was held at various pressures in the absence of airflow. The static A-Paw relationship was measured during application of 0, 1, and 2 cm of caudal tracheal displacement. Relative to humans, closing pressures (Pclose) of the pig pharynx were very low (-15 to -35 cmH(2)O). Tracheal displacement significantly decreased compliance of the hypopharynx (from 0.074 +/- 0.02 cm(2)/cmH(2)O with no displacement to 0.052 +/- 0.01 cm(2)/cmH(2)O with 2 cm of displacement) and decreased Pclose of the oropharynx (from -18.2 +/- 9.9 cmH(2)O to -24.1 +/- 10.5 and -28.7 +/- 12.3 cmH(2)O with 1 and 2 cm of displacement, respectively). Tracheal displacement did not affect A of the pharyngeal segments. In conclusion, tracheal displacement decreased collapsibility of the passive pharynx. The pharynx of the pot-bellied pig is structurally more resistant to collapse than the human pharynx.


Copying of RNA Sequences without Pre-Activation.
Template-directed incorporation of nucleotides at the terminus of a growing complementary strand is the basis of replication. For RNA, this process can occur in the absence of enzymes, if the ribonucleotides are first converted to an active species with a leaving group. Thus far, the activation required a separate chemical step, complicating prebiotically plausible scenarios. Here we show that a combination of a carbodiimide and an organocatalyst induces near-quantitative incorporation of any of the four ribonucleotides. Upon in situ activation, adenosine monophosphate was found to also form oligomers in aqueous solution. So, both de novo strand formation and sequence-specific copying can occur without an artificial synthetic step.


A kinetic study on the isomerization of hop alpha-acids.
In this article, a detailed study on hop alpha-acid isomerization kinetics is presented. Because of the complex wort matrix and interfering interactions occurring during real wort boiling (i.e., trub formation and alpha-acids/iso-alpha-acids complexation), this investigation on alpha-acid isomerization kinetics was performed in aqueous buffer solution as a function of time (0-90 min) and heating temperature (80-100 degrees C). Rate constants and activation energies for the formation of individual iso-alpha-acids were determined. It was found that iso-alpha-acid formation follows first-order kinetics and Arrhenius behavior. Differences in activation energies for the formation of trans- and cis-isomers were noticed, the activation energy for the formation of trans-iso-alpha-acids being approximately 9 kJmol (-1) lower.


Synergistic Effects of C/α-MoC and Ag for Efficient Oxygen Reduction Reaction.
It remains challenging to prepare highly active and stable catalysts from earth-abundant elements for the oxygen reduction reaction (ORR). Herein we report a facile method to synthesize cost-effective heterogeneous C/α-MoC/Ag electrocatalysts. Rotating disc electrode (RDE) experiments revealed that the obtained C/α-MoC/Ag exhibited much superior catalytic performance for ORR than that of C/Ag, C/α-MoC, or even the conventional Pt/C. First-principles calculations indicated that the enhanced activity could be attributed to the efficient synergistic effects between Ag and α-MoC/C by which the energy barrier for O2 dissociation has been substantially reduced. Furthermore, Li-air and Al-air cells were assembled to demonstrate the unprecedented electrochemical performance of C/α-MoC/Ag nanocomposites surpassing the Pt/C. Thus experimental results and theoretical calculations together showed that the heterogeneous C/α-MoC/Ag nanocomposites are a promising alternative to platinum for applications in industrial metal-air batteries.


Leisure as a resource for successful aging by older adults with chronic health conditions.
Drawing on the model of Selective Optimization with Compensation (SOC) (Baltes & Baltes, 1990), the purpose of this article is to examine leisure-related goals of older adults with chronic conditions and the strategies they use to not only successfully manage their chronic health conditions but live well with them. Semi-structured in-person interviews were conducted with 18 community-dwelling older adults (nine males, nine females, ages 58-87 years) with a variety of chronic conditions. Inductive and deductive within and cross-case thematic analyses resulted in descriptions of changes and continuity in participants' leisure participation following the onset of their chronic condition and construction of four themes: drawing on existing resources for continued involvement, setting leisure-based goals, using strategies to get more out of life, and more than managing: living a life of meaning. Implications for promoting successful aging are discussed, specifically the benefits of incorporating information and skill-building to help older adults recognize that leisure can be a resource for healthy aging and self-managing their chronic health condition.


Complete heart block in a patient with Wegener's granulomatosis in remission--a case report.
Wegener's granulomatosis is a systemic inflammatory disorder of unknown cause that usually affects the upper and lower respiratory tracts as well as the kidney. Cardiac involvement is rare, although electrocardiographic abnormalities, coronary artery vasculitis, cardiac arrhythmias, and myocardial infarction have been reported in the literature. A 27-year-old female patient with Wegener's granulomatosis in remission is described in whom complete heart block developed in the 13th month of treatment with cyclophosphamide. A temporary pacing was applied and pulse methylprednisolone and cyclophosphamide were commenced. On the ninth day of treatment, normal sinus rhythm was achieved. In conclusion, cardiac rhythm abnormalities should always be kept in mind both in the diagnosis and follow-up of Wegener's granulomatosis.


A case of refractory chronic respiratory tract infection due to Pseudomonas aeruginosa successfully controlled by combination of clarithromycin and azithromycin.
The prognosis of patients with chronic respiratory tract infections, especially diffuse panbronchiolitis, is remarkably improved by long-term administration of low-dose macrolides. However, in some cases, patients are refractory to macrolide treatment and show a low or no response; therefore, new treatment strategies are required. Here we present a patient refractory to either single low-dose clarithromycin or azithromycin but responded remarkably to the combination usage of both macrolides.


Endoscopic surgery in Senegal. Benefits, costs and limits.
Evaluating the introduction of endoscopic surgery in Senegal may be useful for assessing the role of this technology in developing countries. The endoscopic surgery performed at the Hospital Principal and the Hospital Le Dantec, Dakar, from January 1995 to December 2000 was evaluated retrospectively. Operative time, postoperative stay, patients, and hospital costs were compared in samples of 100 patients treated endoscopically and 80 patients treated with open techniques. Altogether, 826 endoscopic procedures were performed (11.6% of elective surgical activity). Of these, thoracoscopic (34%) and laparoscopic (14%) vagotomy, cholecystectomy (21%), fundoplication (12%), and diagnostic laparoscopy (11%) were selected for comparisons. Operative time proved to be reduced by endoscopic surgery except for laparoscopic fundoplication (+40 min). After endoscopic surgery, postoperative hospitalization was 3.7 days shorter, and patient fees were consequently reduced. In 6 years, 87% of the hospital investment (36,000 Euro) was recovered. Developing countries can benefit from endoscopic surgery. First-world countries might supply staff training.


Induced pluripotent stem cell: A headway in reprogramming with promising approach in regenerative biology.
Since the embryonic stem cells have knocked the doorsteps, they have proved themselves in the field of science, research, and medicines, but the hovered restrictions confine their application in human welfare. Alternate approaches used to reprogram the cells to the pluripotent state were not up to par, but the innovation of induced pluripotent stem cells (iPSCs) paved a new hope for the researchers. Soon after the discovery, iPSCs technology is undergoing renaissance day by day, i.e., from the use of genetic material to recombinant proteins and now only chemicals are employed to convert somatic cells to iPSCs. Thus, this technique is moving straightforward and productive at an astonishing pace. Here, we provide a brief introduction to iPSCs, the mechanism and methods for their generation, their prevailing and prospective applications and the future opportunities that can be expected from them.


Lack of close relationship between three strains of human rhinoviruses as determined by their RNA sequences.
The possible genomic homologies between three serotypes of human rhinoviruses (HRV 1A, HRV 2, and HRV 14) were investigated. First we confirmed that these viruses were unrelated by the criterion of the absence of common antigenic determinants on the surfaces of the native virions, as detected by cross-neutralization of complementfixation. RNA-RNA hybridization was then examined with purified, highly radioactive, double-stranded, replicative-form RNA and excess single-stranded virion RNA. Single-stranded RNA showed 100% homology with the minus strand from the replicative-form RNA of the same type of virus. HRV 1A, HRV 2, and HRV 14 showed low intertypic homologies; these were not significantly greater than those found between the rhinoviruses and polivirus, which were used as a negative control. The immunological relationship and the RNA homology between HRV 1A and HRV 1B were also examined by the above techniques. It was confirmed that HRV 1A and HRV 1B share some surface determinants and it was also found that HRV 1B RNA shares 70% homology with HRV 1A RNA.


Identification and characterization of GCP16, a novel acylated Golgi protein that interacts with GCP170.
GCP170, a member of the golgin family associated with the cytoplasmic face of the Golgi membrane, was found to have a Golgi localization signal at the NH2-terminal region (positions 137-237). Using this domain as bait in the yeast two-hybrid screening system, we identified a novel protein that interacted with GCP170. The 2.0-kilobase mRNA encoding a 137-amino acid protein of 16 kDa designated GCP16 was ubiquitously expressed. Immunofluorescence microscopy showed that GCP16 was co-localized with GCP170 and giantin in the Golgi region. Despite the absence of a hydrophobic domain sufficient for participating in membrane localization, GCP16 was found to be tightly associated with membranes like an integral membrane protein. Labeling experiments with [3H]palmitic acid and mutational analysis demonstrated that GCP16 was acylated at Cys69 and Cys72, accounting for its tight association with the membrane. A mutant without potential acylation sites (C69A/C72A) was no longer localized to the Golgi, indicating that the acylation is prerequisite for the Golgi localization of GCP16. Although the mutant GCP16, even when overexpressed, had no effect on protein transport, overexpression of the wild type GCP16 caused an inhibitory effect on protein transport from the Golgi to the cell surface. Taken together, these results indicate that GCP16 is the acylated membrane protein, associated with GCP170, and possibly involved in vesicular transport from the Golgi to the cell surface.


[Isolation and characterization of 27 polymorphic microsatellite markers in Armillaria luteo-virens ( Physalacriaceae)].
[OBJECTIVE] The objectives of this study were to use Roche 454 GS FLX system to develop SSR markers for Armillaria luteo-virens. These datasets will be valuable for detecting genetic diversity and population structure of this species. [METHODS] We collected Armillaria luteo-virens samples from Yushu in Qinghai province, China. Total RNA was isolated by using the TRIzol reagent, after that we constructed cDNA library and performed one quarter plate of the whole run 454 pyrosequencing. We selected 98 primer pairs randomly from the 321 SSRs to evaluate their application and the polymorphism across 66 individuals (Armillaria luteo-virens) representing 3 wild populations. [RESULTS] Roche 454 sequencing yielded 197,121 reads with a total nucleotide size of 88,585,965bp. 27 of 98 SSRs loci were polymorphic. Numbers of alleles (Na) ranged from 2 to 8. Expected heterozygosity (HE) ranged from less than 0. 001 to 0. 810 at locus ALV65, while observed heterozygosity (Ho) from 0 at loci AIV64 and AIV92 to 0. 900 at loci ALV8. We found no evidence of linkage disequiliburium, however 10 of 27 SSR markers showed significant deviation from Hardy-weinberg equilibrium. [CONCLUSION] These remaining 17 pairs of Armillaria luteo-virens SSR markers will be valuable for future research on detecting population structure and conservation of this species.


Gastric foreign body: a comb.
The ingestion of a foreign body is a common occurrence. Psychiatric patients and prisoners may swallow objects on purpose. Occasionally emergent exploratory laparotomy may be indicated if the diagnosis is uncertain, and emergent removal of the foreign body may be needed to prevent substantial risk of serious complications including perforation, fistula, or gastrointestinal bleeding.


The effect of rate responsive pacing in patients with angina pectoris on the extent of ischemia on 201-thallium exercise scintigraphy.
In patients with coronary artery disease (CAD), rate responsive pacing is considered to be contraindicated because an increase in heart rate may increase oxygen demand. Although previous studies have shown no subjective increase in ischemia during rate responsive pacing, data from objective assessment have not been documented. The goal of this study was to determine if there was an increase in ischemia on 201-Thallium (201 Tl) exercise scintigraphy in this mode of pacing in patients with CAD and angina. Eighteen consecutive patients with chronic atrial fibrillation and symptomatic bradyarrhythmias with a pacemaker for more than 6 months participated in the study. In VVI and VVIR modes a symptom-limited exercise 201 Tl scintigram was performed in a single blind randomized crossover fashion. Exercise duration, anginal attacks, use of nitroglycerine (NTG) tablets, blood pressure, and analysis of the scintigrams were assessed during each pacing mode. Fifteen men and three women were included (age 65.9 +/- 4.9 years, LVEF 0.44 +/- 0.07). Four were in Class III angina pectoris, and 14 in class II. The mean exercise duration increased 28% in the VVIR group without an increase in anginal attacks per week or the use of NTG tablets. On scintigrams, no differences were seen between the two groups. One patient was withdrawn from the study because of an increase in angina pectoris (AP) attacks during VVIR pacing. Rate responsive pacing is safe and effective in patients with CAD without an increase in subjective and objective signs of ischemia.


Multiple Sclerosis: Immunopathology and Treatment Update.
The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumb, ocrelizumab, alentuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS.


Microglial immunophenotype in dementia with Alzheimer's pathology.
Genetic risk factors for Alzheimer's disease imply that inflammation plays a causal role in development of the disease. Experimental studies suggest that microglia, as the brain macrophages, have diverse functions, with their main role in health being to survey the brain parenchyma through highly motile processes. Using the Medical Research Council Cognitive Function and Ageing Studies resources, we have immunophenotyped microglia to investigate their role in dementia with Alzheimer's pathology. Cerebral cortex obtained at post-mortem from 299 participants was analysed by immunohistochemistry for cluster of differentiation (CD)68 (phagocytosis), human leukocyte antigen (HLA)-DR (antigen-presenting function), ionized calcium-binding adaptor molecule (Iba1) (microglial motility), macrophage scavenger receptor (MSR)-A (plaque-related phagocytosis) and CD64 (immunoglobulin Fcγ receptor I). The presence of dementia was associated positively with CD68 (P < 0.001), MSR-A (P = 0.010) and CD64 (P = 0.007) and negatively with Iba1 (P < 0.001). Among participants without dementia, the cognitive function according to the Mini-Mental State Examination was associated positively with Iba1 (P < 0.001) and negatively with CD68 (P = 0.033), and in participants with dementia and Alzheimer's pathology, positively with all microglial markers except Iba1. Overall, in participants without dementia, the relationship with Alzheimer's pathology was negative or not significant, and positive in participants with dementia and Alzheimer's pathology. Apolipoprotein E (APOE) ε2 allele was associated with expression of Iba1 (P = 0.001) and MSR-A (P < 0.001) and APOE ε4 with CD68, HLA-DR and CD64 (P < 0.001). Our findings raise the possibility that in dementia with Alzheimer's pathology, microglia lose motility (Iba-1) necessary to support neurons. Conversely, other microglial proteins (CD68, MSR-A), the role of which is clearance of damaged cellular material, are positively associated with Alzheimer's pathology and impaired cognitive function. In addition, our data imply that microglia may respond differently to Aβ and tau in participants with and without dementia so that the microglial activity could potentially influence the likelihood of developing dementia, as supported by genetic studies, highlighting the complexity and diversity of microglial responses.


Analytical approximations for spiral waves.
We propose a non-perturbative attempt to solve the kinematic equations for spiral waves in excitable media. From the eikonal equation for the wave front we derive an implicit analytical relation between rotation frequency Ω and core radius R(0). For free, rigidly rotating spiral waves our analytical prediction is in good agreement with numerical solutions of the linear eikonal equation not only for very large but also for intermediate and small values of the core radius. An equivalent Ω(R(+)) dependence improves the result by Keener and Tyson for spiral waves pinned to a circular defect of radius R(+) with Neumann boundaries at the periphery. Simultaneously, analytical approximations for the shape of free and pinned spirals are given. We discuss the reasons why the ansatz fails to correctly describe the dependence of the rotation frequency on the excitability of the medium.


Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus.
Gangliosides serve as receptors for internalization and infection by members of the polyomavirus family. Specificity is determined by recognition of carbohydrate moieties on the ganglioside by the major viral capsid protein VP1. For the mouse polyomavirus (MuPyV), gangliosides with terminal sialic acids in specific linkages are essential. Although many biochemical and cell culture experiments have implicated gangliosides as MuPyV receptions, the role of gangliosides in the MuPyV-infected mouse has not been investigated. Here we report results of studies using ganglioside-deficient mice and derived cell lines. Knockout mice lacking complex gangliosides were completely resistant to the cytolytic and pathogenic effects of the virus. Embryo fibroblasts from these mice were likewise resistant to infection, and supplementation with specific gangliosides restored infectibility. Although lacking receptors for viral infection, cells from ganglioside-deficient mice retained the ability to respond to the virus. Ganglioside-deficient fibroblasts responded rapidly to virus exposure with a transient induction of c-fos as an early manifestation of a mitogenic response. Additionally, splenocytes from ganglioside-deficient mice responded to MuPyV by secretion of IL-12, previously recognized as a key mediator of the innate immune response. Thus, while gangliosides are essential for infection in the animal, gangliosides are not required for mitogenic responses and innate immune responses to the virus.


Submicroscopic Plasmodium falciparum infections before and after sulfadoxine-pyrimethamine and artesunate association treatment in Dienga, Southeastern Gabon.
It has been shown that Plasmodium falciparum submicroscopic infections (SMI) can contribute to malaria-associated anemia as well as to cerebral malaria. Polymerase chain reaction (PCR) assays are usually used as an alternative to microscopy in detecting subpatently infected individuals. The main objective of this study was to investigate the occurrence of SMI before and after a suppressive antimalarial treatment in the population of the village of Dienga in Gabon. Nested PCR was used to detect SMI and to determine genotypes. The prevalence rates of SMI were 13.67% (38/278) at day 0 and 8.99% (25/278) at day 14 after sulfadoxine-pyrimethamine-artesunate treatment. Genotype analysis of two polymorphic regions of the merozoite surface protein (MSP)-1 block 2, MSP-2 and a dimorphic region of the erythrocyte binding antigen (EBA-175) revealed that as many as 88% (22/25) of SMI detected after treatment were completely new alleles, indicating either previously sequestered parasites or newly acquired infections. These results demonstrate the usefulness of sulfadoxine-pyrimethamine-artesunate association treatment in the population of Dienga and confirmed early parasite genotype change after a suppressive antimalarial treatment in endemic areas.


Decreased transcriptional corepressor p107 is associated with exercise-induced mitochondrial biogenesis in human skeletal muscle.
Increased mitochondrial content is a hallmark of exercise-induced skeletal muscle remodeling. For this process, considerable evidence underscores the involvement of transcriptional coactivators in mediating mitochondrial biogenesis. However, our knowledge regarding the role of transcriptional corepressors is lacking. In this study, we assessed the association of the transcriptional corepressor Rb family proteins, Rb and p107, with endurance exercise-induced mitochondrial adaptation in human skeletal muscle. We showed that p107, but not Rb, protein levels decrease by 3 weeks of high-intensity interval training. This is associated with significant inverse association between p107 and exercise-induced improved mitochondrial oxidative phosphorylation. Indeed, p107 showed significant reciprocal correlations with the protein contents of representative markers of mitochondrial electron transport chain complexes. These findings in human skeletal muscle suggest that attenuated transcriptional repression through p107 may be a novel mechanism by which exercise stimulates mitochondrial biogenesis following exercise.


Risk stratifying the acute coronary syndrome patient: a focus on treatable risk.
Providing the optimal treatment for patients who present to the emergency room with chest pains or suspected acute coronary syndrome (ACS) remains a dilemma for many practitioners due to subjectivity, delayed diagnoses, and widely variable mechanisms with similar clinical presentations. In treating patients with chest pain but no obvious electrocardiogram changes, practitioners frequently utilize the American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines. The guidelines group possible ACS patients together as unstable angina/non-ST-segment elevation myocardial infarction (NSTEMI) and recommend that treatment be based on level of risk. The challenge for practitioners is discriminating between "risk" and "treatable risk." Evaluation of troponin levels can help identify patients with possible ACS who are at high risk of death and MI, and guide early decision making. Available data indicate that in the troponin-negative patient, routine interventions such as unfractionated heparin, glycoprotein IIb/IIIa receptor antagonists, and invasive approaches have no benefit in terms of reducing death and MI. Although the ACC/AHA Guidelines combine patients with unstable angina and NSTEMI, it is essential to evaluate troponin status in order to optimize patient outcomes and safety in the treatment of suspected ACS.


Comparison and Refinement of Integrated Pest Management Tactics for Halyomorpha halys (Hemiptera: Pentatomidae) Management in Apple Orchards.
Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) has been managed primarily with broad-spectrum insecticides in orchard systems. Recently, IPM techniques have been developed specifically for managing H. halys in apple orchards to reduce insecticide inputs and take advantage of its perimeter-driven behavior. In 2015 and 2016, we compared these IPM tactics to one another and an untreated control to measure differences in overall crop protection and insecticide inputs. Tactics included trap-based threshold-triggered spray applications, perimeter-based attract-and-kill (AK) trees treated every 7- and 14-d, and perimeter spray applications applied every 7- and 14-d. All plots were monitored with baited black pyramid traps deployed in plot interiors. In both years, mean number of H. halys captured in untreated control plot traps was significantly greater than plots managed using IPM tactics. In 2015, significantly more insecticide applications were made in 7- and 14-d perimeter and AK plots compared with trap-based threshold plots. There was no significant difference in the percentage of injured fruit in plot interiors among IPM tactics; all were significantly lower than the control. In 2016, significantly more insecticide applications were made in 7-d perimeter spray and AK plots compared with all other treatments. Significantly less injury was detected in plot interiors for 7- and 14-d perimeter and trap-based threshold plots compared with the control and 7- and 14-d AK plots. Although all IPM tactics reduced H. halys injury in apples using a trap-based treatment threshold required fewer insecticide inputs and only during brief periods of the season, while all others required season-long maintenance.


Enhancement of indoleamine 2,3-dioxygenase activity in cancer patients receiving interferon-beta Ser.
Degradation of tryptophan to kynurenine, catalyzed by indoleamine 2,3-dioxygenase (IDO), has been shown previously to be augmented in human peripheral blood mononuclear cells (PBMCs) treated in vitro with interferons-alpha, -beta, and -gamma (IFNs), and in human epithelial cells treated with IFN-gamma. To determine whether administration of IFN in vivo also induced IDO activity, tryptophan degradation by PBMCs purified from patients was measured. PBMCs, obtained prior to and 24 h after i.v. bolus injection of 90 X 10(6) units or 180 X 10(6) units of IFN-beta Ser, were cultivated in medium containing [3H]tryptophan. After 48 h incubation, culture supernatants were harvested, and the amount of tryptophan degraded was measured by fractionation with high-performance liquid chromatography and quantification of radioactivity in resultant fractions. Significantly enhanced IDO activity was observed after IFN-beta Ser treatment, with a mean paired increase of 43% of maximum inducible activity. Thus, measurement of in vivo induction of IDO activity may be a useful indicator in optimizing therapeutic use of IFNs in neoplastic, infectious, and other clinical disorders.


Accurate internal-external rotation measurement in total knee prostheses: A magnetic solution.
In this work we tackled the problem of accurate measurement of internal-external (IE) rotations in the prosthetic knee. We presented a magnetic measurement system to be implanted in the knee prostheses in order to measure IE without soft tissue artifacts. The measurement system consisted of a permanent magnet attached under the tibial plate of the prosthesis and a combination of magnetic sensors in the polyethylene insert. Two different sensor configurations were designed, and five different angle estimators for measurement of IE angles were defined and tested based on several static and dynamic measurements toward a stereophotogrammetry motion capture system. Also a noise analysis was done to see which estimators are less sensitive to measurement noise. One-sensor configuration provided lower power budget with dynamic RMS error of 0.49° and a noise range of ±0.53°. Two-sensor configuration doubles the power consumption but provided slightly lower dynamic RMS error (0.37°) and a noise range of ±0.42°, and offers the possibility of having redundancy in case of damaged sensor.


Let-7 underlies metformin-induced inhibition of hepatic glucose production.
SignificanceA clear mechanistic understanding of metformin's antidiabetic effects is lacking. This is because suprapharmacological concentrations of metformin have been used in most studies. Using mouse models and human primary hepatocytes, we show that metformin, at clinically relevant doses, suppresses hepatic glucose production by activating a conserved regulatory pathway encompassing let-7, TET3, and a fetal isoform of hepatocyte nuclear factor 4 alpha (HNF4α). We demonstrate that metformin no longer has potent antidiabetic actions in a liver-specific let-7 loss-of-function mouse model and that hepatic delivery of let-7 ameliorates hyperglycemia and improves glucose homeostasis. Our results thus reveal an important role of the hepatic let-7/TET3/HNF4α axis in mediating the therapeutic effects of metformin and suggest that targeting this axis may be a potential therapeutic for diabetes.