Primary malignant lymphoma of the uterus and broad ligament: a case report and review of literature.
Primary malignant lymphoma of the uterus and broad ligament is rare. Here, we present a rare case of primary diffuse large B-cell lymphoma (DLBCL) of uterus and broad ligament in a 63-year-old female. The patient presenting with lower abdominal distention was referred to our hospital. Subsequent abdominal and pelvic ultrasound revealed the presence of a large mass, which was highly suspected as subserosal uterine leiomyoma. A large tumor was found with unclear boundary with right posterior wall, broad ligament and bilateral adnexa during surgery. Her uterus and the tumor of a broad ligament and bilateral adnexa were all excised as a result. Postoperative pathological examination showed DLBCL in uterus and broad ligament. Further examinations excluded metastatic diseases, which supported the diagnosis of primary DLBCL of the uterus and broad ligament. The patient received six cycles of R-CHOP (21 days) regimen. During the 8 months follow-up, no evidence of disease recurrence was identified. As the prevalence of primary extranodal lymphoma is increasing, the details of this rare case may highlight the importance and facilitate treatment of similar diseases. A summary focusing on the presentation and prognosis as well as a review of current management is also discussed.


Lower Critical Solution Temperature Tuning and Swelling Behaviours of NVCL-Based Hydrogels for Potential 4D Printing Applications.
The phase transitions of poly (N-vinyl caprolactam) (PNVCL) hydrogels are currently under investigation as possible materials for biomedical applications thanks to their thermosensitive properties. This study aims to use the photopolymerisation process to simulate the 4D printing process. NVCL-based polymers with different thermal properties and swellability were prepared to explore the possibility of synthetic hydrogels being used for 4D printing. In this contribution, the thermal behaviours of novel photopolymerised NVCL-based hydrogels were analysed. The lower critical solution temperature (LCST) of the physically crosslinked gels was detected using differential scanning calorimetry (DSC), ultraviolet (UV) spectroscopy, and cloud point measurement. The chemical structure of the xerogels was characterised by means of Fourier transform infrared spectroscopy (FTIR). Pulsatile swelling studies indicated that the hydrogels had thermo-reversible properties. As a result, the effect of varying the macromolecular monomer concentration was apparent. The phase transition temperature is increased when different concentrations of hydrophilic monomers are incorporated. The transition temperature of the hydrogels may allow for excellent flexibility in tailoring transition for specific applications, while the swelling and deswelling behaviour of the gels is strongly temperature- and monomer feed ratio-dependent.


2,3-Butanediol production using soy-based nitrogen source and fermentation process evaluation by a novel isolate of Bacillus licheniformis BL1.
2,3-Butanediol (2,3-BDO) has varied applications in chemical, pharmaceutical, & food industry. Microorganisms belonging to Klebsiella, Enterobacter & Serratia genera are well-known producers of 2,3-BDO. However, they have limited usage in industrial-scale owing to their pathogenic nature. A nonpathogenic soil isolate identified as Bacillus licheniformis (BL1) was thus investigated for 2,3-BDO production. Soy flakes, soy flour, defatted soy, and soybean meal-based hydrolysates replaced yeast extract and peptone as nitrogen sources. Defatted soy flakes and soybean meal hydrolysate led to an equivalent 2,3-BDO yield and productivity as compared to that of Yeast Extract and peptone. The pH and oxygen variation influenced the proportion of various products of the mixed acid-butanediol pathway. Further, the batch mode fermentation with soy hydrolysate and optimized process parameter resulted in 2,3-BDO titer, yield and productivity of 11.06 g/L, 0.43 g/g and 0.48 g/L h respectively. Glucose concentration above 5% was inhibitory and led to reduction in the specific growth rate of BL1 in batch cultivation. Intermittent glucose feeding in fed-batch mode overcame this substrate limitation resulting in increased titers (49.8 g/L) and productivity (0.62 g/L h). Modified medium containing soy hydrolysate as nitrogen source with fermentation process optimization resulted in 67% decrease in medium cost for 2,3-BDO production.


Examining University Men's Psychobiological and Behavioral Response-Recovery Profile From a Social-Evaluative Body Image Threat.
Negative body image, which often results from social-evaluative body image threats, is common in young men and related to many harmful outcomes. Using social self-preservation theory (SSPT), the present study investigated the psychobiological (i.e., shame and cortisol) and behavioral (e.g., submission) response-recovery profile to a social-evaluative body image threat in university men. Participants (N = 69; Mage = 20.80 years, SD = 1.84) were randomly assigned to a high-threat (n = 34) or low-threat condition (n = 35). Men in the high-threat condition reported greater post-threat body shame, had greater post-threat cortisol levels, and exhibited more shame-relevant behaviors than men in the low-threat condition. There were no significant differences between conditions for body shame or cortisol at the final post-threat time point (after resting for 30 min). These findings are consistent with SSPT and suggest that men respond to, and recover from, body image threats relatively efficiently.


Penicillin resistance is not extrapolable to amoxicillin resistance in Streptococcus pneumoniae isolated from middle ear fluid in children with acute otitis media.
We evaluated the in vitro antibacterial activity of amoxicillin against penicillin-susceptible and -nonsusceptible Streptococcus pneumoniae strains isolated from children with acute otitis media (AOM). Children more than 3 months of age with AOM who were seen in the Dr Sótero del Rio and Luis Calvo Mackenna Hospitals in Santiago, Chile, between July 1998 and December 2002 were subjected to tympanic puncture for middle ear fluid culture. The penicillin and amoxicillin susceptibilities of the S pneumoniae isolates were determined by epsilometer test (E test). A bacterial pathogen was isolated in 432 of 543 children (80%) as follows: S pneumoniae, 40%; Haemophilus influenzae, 29%; Moraxella catarrhalis, 7%; and Streptococcus pyogenes, 4%. Penicillin-susceptible S pneumoniae strains were less common than amoxicillin-susceptible strains (60% versus 95%; odds ratio [OR], 0.08; 95% confidence interval [CI], 0.04 to 0.18). Both intermediate- and high-resistance strains were more common for penicillin (22% versus 4.5%; OR, 5.6; 95% CI, 2.5 to 12.7) than for amoxicillin (18% versus 0.5%; OR, 41.3; 95% CI, 6.0 to 821). Penicillin resistance is not extrapolable to amoxicillin among S pneumoniae strains isolated from middle ear fluid of children with AOM. Our results support the recommendation to evaluate the minimal inhibitory concentrations of penicillin-nonsusceptible S pneumoniae for amoxicillin and to continue use of this antimicrobial as a first-line antimicrobial choice for children with AOM.


Assessing readiness for childhood obesity prevention in German municipalities: application of the community readiness model.
The World Health Organization has identified childhood obesity as one of the most serious public health problems of the 21st century. Understanding a municipality's readiness to address it is crucial to achieve successful interventions. However, the preparedness of German municipalities to address childhood obesity has not yet been investigated. This study is the first in Germany to apply the community readiness model (CRM) in this context. The purpose was to determine readiness of five municipalities for childhood obesity prevention and to identify factors that influence their readiness. Therefore, 27 semi-structured key informant interviews were conducted. First, the interviews were analysed following the CRM protocol to categorize the municipalities into a readiness level between one and nine. In a second step, a content analysis was carried out for an in-depth interpretation of the readiness scores. The municipalities achieved an average readiness of 3.84, corresponding to the 'Vague Awareness' stage. A lack of prioritization and leadership support, insufficient low-threshold efforts, a lack of knowledge and problem awareness as well as a lack of structures and resources were identified as factors that can determine municipal readiness to prevent childhood obesity. This study not only extends the application of the CRM to childhood obesity in German municipalities but also offers practical implications for professionals in assessing readiness.


Factors influencing dressing performance after stroke.
Sixty consecutive patients with a diagnosis of stroke were assessed using the Nottingham stroke dressing assessment as well as a series of physical and cognitive assessments. Generally the items of clothing worn on the lower half of the body were significantly correlated with the physical assessments and the items of clothing worn on the upper half were significantly correlated with the cognitive assessments. These results support other studies which suggest that motor recovery and perceptual abilities are important determinants of dressing ability.


Ligand-Functionalized Poly(ethylene glycol) Particles for Tumor Targeting and Intracellular Uptake.
Drug carriers typically require both stealth and targeting properties to minimize nonspecific interactions with healthy cells and increase specific interaction with diseased cells. Herein, the assembly of targeted poly(ethylene glycol) (PEG) particles functionalized with cyclic peptides containing Arg-Gly-Asp (RGD) (ligand) using a mesoporous silica templating method is reported. The influence of PEG molecular weight, ligand-to-PEG molecule ratio, and particle size on cancer cell targeting to balance stealth and targeting of the engineered PEG particles is investigated. RGD-functionalized PEG particles (PEG-RGD particles) efficiently target U-87 MG cancer cells under static and flow conditions in vitro, whereas PEG and cyclic peptides containing Arg-Asp-Gly (RDG)-functionalized PEG (PEG-RDG) particles display negligible interaction with the same cells. Increasing the ligand-to-PEG molecule ratio improves cell targeting. In addition, the targeted PEG-RGD particles improve cell uptake via receptor-mediated endocytosis, which is desirable for intracellular drug delivery. The PEG-RGD particles show improved tumor targeting (14% ID g-1) when compared with the PEG (3% ID g-1) and PEG-RDG (7% ID g-1) particles in vivo, although the PEG-RGD particles show comparatively higher spleen and liver accumulation. The targeted PEG particles represent a platform for developing particles aimed at balancing nonspecific and specific interactions in biological systems.


Durability of bonds and clinical success of adhesive restorations.
Resin-dentin bond strength durability testing has been extensively used to evaluate the effectiveness of adhesive systems and the applicability of new strategies to improve that property. Clinical effectiveness is determined by the survival rates of restorations placed in non-carious cervical lesions (NCCL). While there is evidence that the bond strength data generated in laboratory studies somehow correlates with the clinical outcome of NCCL restorations, it is questionable whether the knowledge of bonding mechanisms obtained from laboratory testing can be used to justify clinical performance of resin-dentin bonds. There are significant morphological and structural differences between the bonding substrate used in in vitro testing versus the substrate encountered in NCCL. These differences qualify NCCL as a hostile substrate for bonding, yielding bond strengths that are usually lower than those obtained in normal dentin. However, clinical survival time of NCCL restorations often surpass the durability of normal dentin tested in the laboratory. Likewise, clinical reports on the long-term survival rates of posterior composite restorations defy the relatively rapid rate of degradation of adhesive interfaces reported in laboratory studies. This article critically analyzes how the effectiveness of adhesive systems is currently measured, to identify gaps in knowledge where new research could be encouraged. The morphological and chemical analysis of bonded interfaces of resin composite restorations in teeth that had been in clinical service for many years, but were extracted for periodontal reasons, could be a useful tool to observe the ultrastructural characteristics of restorations that are regarded as clinically acceptable. This could help determine how much degradation is acceptable for clinical success.


A zebrafish model of Ifih1-driven Aicardi-Goutières syndrome reproduces the interferon signature and the exacerbated inflammation of patients.
Type I interferonopathies are a heterogenic group of rare diseases associated with an increase in type I interferon (IFN). The main challenge for the study of Type I interferonopathies is the lack of a well-founded animal model to better characterize the phenotype as well as to perform fast and large drug screenings to offer the best treatment options. In this study, we report the development of a transgenic zebrafish model of Type I interferonopathy overexpressing ifih1 carrying the mutation p.Arg742His (Tg(ifih1_mut)), corresponding to the human mutation p.Arg779His. RNA sequence analysis from Tg(ifih1_mut) larvae revealed a systemic inflammation and IFN signature upon a suboptimal poly I:C induction compared with wild-type larvae, confirming the phenotype observed in patients suffering from Type I interferonopathies. More interestingly, the phenotype was manifested in the zebrafish inflammation and Type I IFN reporters nfkb:eGFP and isg15:eGFP, respectively, making this zebrafish model suitable for future high-throughput chemical screening (HTS). Using the unique advantages of the zebrafish model for gene editing, we have generated Tg(ifih1_mut) knocked down for mavs and ikbke, which completely abrogated the Poly I:C induction and activation of the GFP of the reporters. Finally, we used an FDA-approved drug, Baricitinib (Jak1/Jak2 inhibitor), which was able to reduce the inflammation and the ISG expression. Our results demonstrate the potential of this model to further understand AGS pathological mechanisms and to identify novel therapeutic drugs by HTS.


A palette of fluorophores that are differentially accumulated by wild-type and mutant strains of Escherichia coli: surrogate ligands for profiling bacterial membrane transporters.
Our previous work demonstrated that two commonly used fluorescent dyes that were accumulated by wild-type Escherichia coli MG1655 were differentially transported in single-gene knockout strains, and also that they might be used as surrogates in flow cytometric transporter assays. We summarize the desirable properties of such stains, and here survey 143 candidate dyes. We eventually triage them (on the basis of signal, accumulation levels and cost) to a palette of 39 commercially available and affordable fluorophores that are accumulated significantly by wild-type cells of the 'Keio' strain BW25113, as measured flow cytometrically. Cheminformatic analyses indicate both their similarities and their (much more considerable) structural differences. We describe the effects of pH and of the efflux pump inhibitor chlorpromazine on the accumulation of the dyes. Even the 'wild-type' MG1655 and BW25113 strains can differ significantly in their ability to take up such dyes. We illustrate the highly differential uptake of our dyes into strains with particular lesions in, or overexpressed levels of, three particular transporters or transporter components (yhjV, yihN and tolC). The relatively small collection of dyes described offers a rapid, inexpensive, convenient and informative approach to the assessment of microbial physiology and phenotyping of membrane transporter function.


Raised carbohydrate antigen 19-9 levels detect recurrences and impacts overall and disease-free survival in radically resected gallbladder cancer: A simple surveillance marker?
There are no established markers which can be used for surveillance after curative resection in gallbladder carcinoma (GBC). Though carbohydrate antigen 19-9 (CA 19-9) has low specificity as a diagnostic marker, its role as a surveillance marker has not been explored. The aim of this study is to evaluate the predictive ability of CA 19-9 as a surveillance marker to detect recurrences on follow-up. A retrospective analysis of a prospectively maintained database of radically resected GBC who were either on observation or completed adjuvant therapy (chemotherapy or chemoradiation) were followed up 3 monthly with CA 19-9 and ultrasound (US) abdomen for the first 2 years and 6 monthly CA 19-9 and US for further 3 years. Patients with raised CA 19-9 and a recurrent lesion on US abdomen were confirmed with contrast-enhanced computed tomography (CECT) abdomen and fine-needle aspiration cytology (FNAC) of recurrent lesion to establish the diagnosis of recurrence. The performance of CA 19-9 levels (20 and more units/mL) for prediction of recurrence and its impact on survival was estimated. Out of sixty patients on follow-up, 40% recurred: loco-regional (16.7%) and distant metastases (23.4%). The sensitivity, specificity, positive predictive value, and negative predictive value of CA 19-9 in detecting recurrence were 79.1%, 97.2%, 95%, and 87.5%, respectively. The median disease-free survival was 56 months versus 15 months (P = 0.008, hazard ratio [HR]: 7.4 [1.3-40]) and the median overall survival was not reached versus 20 months (P = 0.000, HR: 10.7 [confidence interval 4.2-27.3]) for CA 19-9 levels less than and more than 20 ng/mL. Based on the high positive and negative predictive value in our dataset, CA 19-9 can be used as a surveillance biomarker for follow-up of radically resected GBC. Raised levels of >20 ng/mL should be correlated with imaging findings and any suspicious lesion should be confirmed for recurrence by FNAC and CECT abdomen. Levels >20 ng/mL should be taken as a threshold for suspecting recurrence.


Ductal carcinoma in situ arising in mammary hamartoma.
Hamartoma of the breast is an uncommon lesion. Although it can possess characteristic radiological features, the pathological appearance is not distinctive. Hamartoma is generally considered benign, but four cases have been reported with ductal and lobular carcinoma arising in hamartomas. This report describes further cases of hamartoma from which ductal carcinoma in situ arose, with one showing early invasion. In both cases, the tumours were within the hamartomas and were adequately excised during lumpectomies of the hamartomas, and the patients were well afterwards. This report emphasises the importance of adequate sampling of mammary hamartoma.


[Small cell neuroendocrine carcinoma of the urinary bladder: a case report].
A 60-year-old male was referred to our hospital with a complaint of asymptomatic gross hematuria. Cystoscopic examination revealed a non-papillary broad-based tumor on the posterior wall of the urinary bladder. Computed tomography revealed no evidence of metastases. Transurethral resection of bladder tumor (TUR-BT) was performed and muscle invasion was detected by histological examination of the specimen. Total cystectomy and ileal conduit formation were performed at the preoperative diagnosis of T2-3N0M0. Hematoxylin-eosin staining of the specimen revealed small cancer cells with hyperchromatic nucleus and scanty cytoplasm growing in the muscle layer of the urinary bladder and in the left obturator lymph nodes. Immunohistochemistry for neurospecific enolase showed diffuse staining in the cytoplasm of cancer cells, and ultrastructural study showed dense core granules. From these findings, the patient was diagnosed with small cell neuroendocrine carcinoma of the urinary bladder at the stage of pT3bpN1M0. Three courses of adjuvant chemotherapies with cis-platinum (CDDP) and etoposide were administered. The patient is still alive with no evidence of any recurrence at 22 months after the operation. This case suggests that treatment with combined total cystectomy and adjuvant CDDP and etoposide chemotherapies is effective against neuroendocrine carcinoma of the urinary bladder with regional lymph node metastases.


Community-based intervention to increase HIV testing and case detection in people aged 16-32 years in Tanzania, Zimbabwe, and Thailand (NIMH Project Accept, HPTN 043): a randomised study.
In developing countries, most people infected with HIV do not know their infection status. We aimed to assess whether HIV testing could be increased by combination of community mobilisation, mobile community-based voluntary counselling and testing (VCT), and support after testing. Project Accept is underway in ten communities in Tanzania, eight in Zimbabwe, and 14 in Thailand. Communities at each site were paired according to similar demographic and environmental characteristics, and one community from each pair was randomly assigned to receive standard clinic-based VCT (SVCT), and the other community was assigned to receive community-based VCT (CBVCT) plus access to SVCT. Randomisation and assignment of communities to intervention groups was done by the statistics centre by computer; no one was masked to treatment assignment because the interventions were community based. Intervention was provided for about 3 years (2006-09). The primary endpoint of HIV incidence is pending completion of assessments after the intervention. In this interim analysis, we examined the secondary endpoint of uptake in HIV testing, differences in characteristics of clients receiving their first HIV test, and repeat testing. Analyses were limited to clients aged 16-32 years. This study is registered with ClinicalTrials.gov, number NCT00203749. The proportion of clients receiving their first HIV test during the study was higher in CBVCT communities than in SVCT communities in Tanzania (2341 [37%] of 6250 vs 579 [9%] of 6733), Zimbabwe (5437 [51%] of 10,700 vs 602 [5%] of 12,150), and Thailand (7802 [69%] of 11,290 vs 2319 [23%] 10,033). The mean difference in the proportion of clients receiving HIV testing between CBVCT and SVCT communities was 40·2% (95% CI 15·8-64·7; p=0·019) across three community pairs (one per country). HIV prevalence was higher in SVCT communities than in CBVCT communities, but CBVCT detected almost four times more HIV cases than did SVCT across the three study sites (952 vs 264; p=0·003). Repeat HIV testing in CBVCT communities increased in all sites to reach 28% of all those testing for HIV by the end of the intervention period. CBVCT should be considered as a viable intervention to increase detection of HIV infection, especially in regions with restricted access to clinic-based VCT and support services after testing. US National Institute of Mental Health, HIV Prevention Trials Network (via US National Institute of Allergy and Infectious Diseases), and US National Institutes of Health.


BRAF mutations in non-small cell lung cancer: has finally Janus opened the door?
B-Raf mutations occur in about 1-2% of non-small cell lung cancers (NSCLC). These mutations generate a permanent activation of the mitogen activated protein kinase (MAPK) pathway, which promotes tumor growth and proliferation. In the present review, we discuss B-Raf mutation epidemiology, diagnostic methods to detect B-Raf mutations, the role of B-Raf as a driver mutation and a potential therapeutic target in NSCLC. The results of clinical trials involving B-Raf or MAPK pathway inhibitors for the treatment of NSCLC are also discussed. Clinical trials evaluating B-Raf inhibitors in BRAF mutated NSCLC patients have shown promising results, and larger prospective studies are warranted to validate these findings. Enrollment of these patients in clinical trials is an interesting strategy to offer a potentially more effective and less toxic targeted therapy.


Human liver-specific very-long-chain acyl-coenzyme A synthetase: cDNA cloning and characterization of a second enzymatically active protein.
Activation of fatty acids, catalyzed by acyl-coenzyme A (acyl-CoA) synthetases, is required for their subsequent metabolism. Peroxisomes and microsomes contain very-long-chain acyl-CoA synthetases (VLCSs) capable of activating fatty acids with a chain length of 22 or more carbons. Decreased peroxisomal VLCS activity is, in part, responsible for the biochemical pathology in X-linked adrenoleukodystrophy (X-ALD), illustrating the importance of VLCSs in cellular fatty acid homeostasis. We previously cloned two human genes encoding proteins homologous to rat peroxisomal VLCS; one (hVLCS) is the human ortholog to the rat VLCS gene and another (hVLCS-H1) encodes a related heart-specific protein. Here, we report the cloning of a third gene (hVLCS-H2) and characterization of its protein product. The hVLCS-H2 gene is located on human chromosome 19 and encodes a 690-amino-acid protein. The amino acid sequence of hVLCS-H2 is 44-45% identical and 67-69% similar to those of both hVLCS and hVLCS-H1. COS-1 cells transiently overexpressing hVLCS-H2 activated the very-long-chain fatty acid lignocerate (C24:0) at a rate >1.5-fold higher than that of nontransfected cells (P < 0.002). The hVLCS-H2-dependent activation of long- and branched-chain fatty acids following transient transfection was less striking. However, hVLCS-H2-dependent acyl-CoA synthetase activity with long- and very-long-chain fatty acid substrates was detected in COS-1 cells stably expressing hVLCS-H2. For all substrates tested (C18:0, C20:0, C24:0, C26:0), the hVLCS-H2 catalyzed activity was significantly increased (P < 0.01 to P < 0.0001). By both Northern analysis and reverse transcription polymerase chain reaction, hVLCS-H2 is expressed primarily in liver. Indirect immunofluorescence of COS-1 cells or human hepatoma-derived HepG2 cells expressing epitope-tagged hVLCS-H2 revealed that the protein was associated with the endoplasmic reticulum but not with peroxisomes. Thus, the primary role of hVLCS-H2 is likely to be in fatty acid elongation or complex lipid synthesis rather than in degradation.


Toward Objective Evaluation of Working Memory in Visualizations: A Case Study Using Pupillometry and a Dual-Task Paradigm.
Cognitive science has established widely used and validated procedures for evaluating working memory in numerous applied domains, but surprisingly few studies have employed these methodologies to assess claims about the impacts of visualizations on working memory. The lack of information visualization research that uses validated procedures for measuring working memory may be due, in part, to the absence of cross-domain methodological guidance tailored explicitly to the unique needs of visualization research. This paper presents a set of clear, practical, and empirically validated methods for evaluating working memory during visualization tasks and provides readers with guidance in selecting an appropriate working memory evaluation paradigm. As a case study, we illustrate multiple methods for evaluating working memory in a visual-spatial aggregation task with geospatial data. The results show that the use of dual-task experimental designs (simultaneous performance of several tasks compared to single-task performance) and pupil dilation can reveal working memory demands associated with task difficulty and dual-tasking. In a dual-task experimental design, measures of task completion times and pupillometry revealed the working memory demands associated with both task difficulty and dual-tasking. Pupillometry demonstrated that participants' pupils were significantly larger when they were completing a more difficult task and when multitasking. We propose that researchers interested in the relative differences in working memory between visualizations should consider a converging methods approach, where physiological measures and behavioral measures of working memory are employed to generate a rich evaluation of visualization effort.


Protective effect of montelukast on paraquat-induced lung toxicity in rats.
In the current study, the possible protective effect of montelukast (Mont, 50 mg/kg, p.o given 2, 24, and 48 h after paraquat injection) against acute paraquat toxicity (PQ, 25 mg/kg i.p.) in rats was evaluated. The effects of treatment on selected oxidative stress parameters in lung tissues as well as certain inflammatory markers in serum were evaluated. The obtained results revealed that Mont can ameliorate the biochemical alterations in the lung tissues which were induced by PQ in rats. This was evidenced by the significant reduction in lung tissues lipid peroxidation, protein carbonyl content and DNA fragmentation, as well as by normalization of glutathione and myeloperoxidase activities. Moreover, the elevated levels of serum TNF-alpha, and LDH induced by paraquat were reversed in Mont-treated rats. Meanwhile, lung paraquat concentration was significantly reduced after Mont treatment compared with PQ alone group. Additionally, a higher survival percentage was observed in rats treated with Mont (80%) compared with the PQ alone group (30%) during 7 days observation. The results indicate that Mont protects lung tissue by balancing oxidant?antioxidant status, inhibiting neutrophil infiltration, and by regulating the generation of inflammatory mediators. In conclusion, the obtained results emphasize the beneficial effect of Mont in ameliorating the toxicity signs of paraquat in rats. The current study greatly recommends the usage of Mont in management of paraquat toxicity.


Treatment-related and patient-related expectations of patients with musculoskeletal disorders: a systematic review of published measurement tools.
Many of the various types of treatments that are used in the rehabilitation of patients with musculoskeletal disorders (MSD) require active involvement of the patient. Patient expectations, for instance with regard to treatment, such as physical therapy, could be important prognostic factors. Behavioral interventions to modify those expectations might improve treatment outcome and prevent chronicity. To facilitate this field of research, valid and reliable measurement instruments to assess patient expectations are needed. The aim of this systematic overview was to identify all the relevant published measurement instruments and to describe their clinimetric properties. A systematic search of the relevant databases was performed, and all relevant articles were included. Two independent reviewers included the relevant articles and assessed the clinimetric properties. A total of 24 measurement instruments were eligible for inclusion in the review. For most types of MSD, there was only one instrument available. Construct validity, assessed with factor analysis, was tested in two-thirds of the instruments. Other forms of construct validity (eg, convergent validity and divergent validity) were only tested in 10 of the 24 instruments. Reproducibility was only tested in 5 instruments, but the test methods were seldom satisfactory, hampering the interpretation of these results. In summary, many instruments have been developed for the treatment of many types of MSD, but the data regarding the validity or reliability of many of the instruments included in this review are scarce. Therefore, in the first place, we strongly recommend that further research is to be carried out to assess the validity and reliability of these instruments. Secondly, it is necessary to assess the instrument's ability to detect change to be able to evaluate the effectiveness of interventions that focus on self-efficacy and outcome expectations.


Polyphenol identification based on systematic and robust high-resolution accurate mass spectrometry fragmentation.
High-mass resolution multi-stage mass spectrometry (MS(n)) fragmentation was tested for differentiation and identification of metabolites, using a series of 121 polyphenolic molecules. The MS(n) fragmentation approach is based on the systematic breakdown of compounds, forming a so-called spectral tree. A chip-based nanoelectrospray ionization source was used combined with an ion-trap, providing reproducible fragmentation, and accurate mass read-out in an Orbitrap Fourier transform (FT) MS enabling rapid assignment of elemental formulas to the molecular ions and all fragment ions derived thereof. The used protocol resulted in reproducible MS(n) fragmentation trees up to MS(5). Obtained results were stable over a 5 month time period, a concentration change of 100-fold, and small changes in normalized collision energy, which is key to metabolite annotation and helpful in structure and substructure elucidation. Differences in the hydroxylation and methoxylation patterns of polyphenolic core structures were found to be reflected by the differential fragmentation of the entire molecule, while variation in a glycosylation site displayed reproducible differences in the relative intensities of fragments originating from the same aglycone fragment ion. Accurate MS(n)-based spectral tree data are therefore a powerful tool to distinguish metabolites with similar elemental formula, thereby assisting compound identification in complex biological samples such as crude plant extracts.


Tuberculosis infection control practice and associated factors among health care workers in Ethiopia: Systematic review and meta-analysis.
The poor practice of tuberculosis infection control may increase the risk of transmission of tuberculosis in healthcare settings. Thus, this study aimed to determine the pooled magnitude of good tuberculosis infection control practice and associated factors among healthcare workers in Ethiopia. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist guideline was followed for this review and meta-analysis. The electronic databases (Pub Med, Cochrane Library, Google scholar and grey literatures) were searched to retrieve articles by using keywords. The Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument was used to assess the quality of studies. Heterogeneity was assessed using the I2 statistic. The meta-analysis with a 95% confidence interval using STATA 17 software was computed to present the pooled practice and odds ratio of the determinant factors. Publication bias was assessed visually by inspecting the funnel plot asymmetry and using statistical tests using the eggers and begs test. Seven studies were included in this meta-analysis, with a total of 3256 health workers. The overall pooled magnitude of good tuberculosis infection control practice was 46.44% (95% CI: 34.21%, 58.67%). In subgroup analysis, the highest practice was in Addis Ababa 51.40% (95% CI: 47.40, 55.40%) and the lowest prevalence of tuberculosis infection control practice was in Amhara region 40.24% (95% CI: 15.46, 65.02%). Working in TB clinics (AOR; 7.42, 95% CI: 3.89, 14.13) and good TB related knowledge (AOR; 4.40, 95% CI: 1.76, 10.97) were the significant predictors of good TB infection control practice. Only less than half of the health care workers had good practice of TB infection control. Working in TB clinics and having good TB related knowledge were statistically significant predictors of TB infection control practice. Periodic shifting of health care workers to work in TB clinics and an emphasis on TB infection control related skill based training was recommended to increase the TB infection control practice.


Real-time, once-daily monitoring of symptoms and FEV in cystic fibrosis patients--a feasibility study using a novel device.
We investigated feasibility and value of a real-time electronic monitoring system adapted for early detection of cystic fibrosis (CF) pulmonary exacerbations (P Exs). This was a 6-month prospective study. Patients recorded once daily their symptom score and spirometry using an electronic diary. The data were sent daily to the research team in real time. P Ex was considered to be present when change in symptoms and lung function values met a preset criteria. Number of P Exs during the study was compared with a parallel period of the previous and of the following years. Only 19 patients (37.2%) completed recording that could be evaluated. A total of 53 P Exs were identified, 26 (49.0%) of which needed intravenous (IV) antibiotics. The number of total P Exs in the study year did not differ from the previous or the following year, but the number of courses of oral antibiotics was greater than those given during the previous year. Remote daily monitoring of symptoms and spirometry had a poor uptake among CF patients. For those who completed the study, this method early detected P Exs that were treated with oral antibiotics that might otherwise required IV antibiotics.


Investigating the role of protein kinase-G in the antidepressant-like response of sildenafil in combination with muscarinic acetylcholine receptor antagonism.
The cGMP/PK-G pathway plays a crucial role in neuroprotection and neurotrophin support, and is possibly involved in antidepressant action. Recently we reported on a novel antidepressant-like response following simultaneous administration of sildenafil (phosphodiesterase 5 (PDE5) inhibitor, thereby increasing cGMP levels), and atropine (muscarinic acetylcholine receptor antagonist) in the rat forced swim test (FST). However, it is unclear whether the antidepressant-like activity of sildenafil+atropine is mediated via the activation of PK-G, an important down-stream effector for cGMP, and whether this may target known pathways in antidepressant action. We investigated whether the antidepressant-like response of sildenafil+/-atropine could be reversed by Rp-8-Br-PET-cGMP, a PK-G inhibitor, and also whether a combination of 8-Br-cGMP (PK-G activator)+/-atropine would likewise be active in the FST, and whether this combination could be attenuated by a PK-G inhibitor. 8-Br-cGMP alone, but not sildenafil alone, reduced immobility and selectively increased swimming in the FST. The antidepressant-like action of sildenafil was only evident following co-administration of atropine, and selectively increased climbing behaviour. Importantly, PK-G inhibition prevented the antidepressant-like effects of both 8-Br-cGMP and the sildenafil/atropine combination. These results confirm cholinergic-cGMP-PK-G interactions in the antidepressant-like effects of sildenafil, putatively acting via noradrenergic mechanisms, whereas direct PK-G activation induces antidepressant-like effects that are associated with enhancement of serotonergic neurotransmission.


2013 NCHS Urban-Rural Classification Scheme for Counties.
This report details development of the 2013 National Center for Health Statistics' (NCHS) Urban-Rural Classification Scheme for Counties (update of the 2006 NCHS scheme) and applies it to health measures to demonstrate urban-rural health differences. The methodology used to construct the 2013 NCHS scheme was the same as that used for the 2006 NCHS scheme, but 2010 census-based data were used rather than 2000 census-based data. All U.S. counties and county-equivalent entities are assigned to one of six levels (four metropolitan and two nonmetropolitan) based on: 1) their February 2013 Office of Management and Budget designation as metropolitan, micropolitan, or noncore; 2) for metropolitan counties, the population size of the metropolitan statistical area (MSA) to which they belong; and 3) for counties in MSAs of 1 million or more, the location of principal city populations within the MSA. The 2013 and 2006 NCHS schemes were applied to data from the National Vital Statistics System (NVSS) and National Health Interview Survey (NHIS) to illustrate differences in selected health measures by urbanization level and to assess the magnitude of differences between estimates from the two schemes. County urban-rural assignments under the 2013 NCHS scheme are very similar to those under the 2006 NCHS scheme. Application of the updated scheme to NVSS and NHIS data demonstrated the continued usefulness of the six categories for assessing and monitoring health differences among communities across the full urbanization spectrum. Residents of large central and large fringe metro counties differed substantially on many health measures, illustrating the importance of continuing to separate these counties. Residents of large fringe metro counties generally fared better than residents of less urban counties. Estimates obtained from the 2013 and 2006 schemes were similar.


Recent mechanistic and synthetic developments in the chemistry of transition-metal vinylidene complexes.
Transition-metal vinylidene complexes are intermediates in a number of synthetically important transformations of alkynes. Underpinning these applications is the ability of various electron-rich transition-metal complexes to effectively facilitate the conversion of alkynes into their vinylidene tautomers. Recent experimental and theoretical studies have provided considerable insight into the mechanisms by which this process occurs and they are detailed herein. In particular, it has been demonstrated that different substituents on both the metal and the alkyne may have profound effects on both the kinetic and thermodynamic profiles of the alkyne/vinylidene tautomerisation. An important finding is that internal alkynes may be employed to prepare disubstituted vinylidene complexes under easily accessible conditions. This discovery brings to light a new facet of the potential synthetic applications of transition metal vinylidene complexes.


Pedobacter suwonensis sp. nov., isolated from the rhizosphere of Chinese cabbage (Brassica campestris).
A mesophilic bacterium, strain 15-52(T), was isolated from the rhizosphere of Chinese cabbage (Brassica campestris). On the basis of phenotypic and genotypic characteristics, the bacterium was identified as representing a novel species belonging to the genus Pedobacter. The strain is non-flagellated, non-spore-forming and grows at temperatures in the range 1-37 degrees C. Physiological tests of the strain showed the presence of oxidase, catalase, protease (gelatin and casein hydrolysis), beta-glucosidase and beta-galactosidase activities. The highest levels of 16S rRNA gene sequence similarity were found with respect to Pedobacter roseus CL-GP80(T) (97.3 %) and Pedobacter sandarakinus DS-27(T) (97.2 %). A phylogenetic analysis based on 16S rRNA gene sequence data indicated that strain 15-52(T) is a member of the genus Pedobacter. DNA-DNA hybridization analysis revealed low levels of relatedness (<42.3 %) between the isolate and two phylogenetically related type strains, P. roseus KCCM 42272(T) and P. sandarakinus KCTC 12559(T). The DNA G+C content is 44.2 mol% and the predominant fatty acids are iso-C(15 : 0) (35.4 %), iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c (27.8 %) and iso-C(17 : 0) 3-OH (15.8 %). On the basis of these data, strain 15-52(T) represents a novel species of the genus Pedobacter, for which the name Pedobacter suwonensis sp. nov. is proposed. The type strain is 15-52(T) (=KACC 11317(T)=DSM 18130(T)).


The effect of latanoprost and brimonidine on rabbit subconjunctival fibroblasts.
Subconjunctival fibroblasts play a critical role in scarring and treatment failure in fistulizing surgery for glaucoma. The proliferation of subconjunctival fibroblasts appears to be modulated by topical glaucoma medications. This study was conducted to evaluate the effects of latanoprost and brimonidine on subconjunctival fibroblast proliferation in rabbit eyes. Twelve pigmented Dutch-belted rabbits were divided into treatment groups of four: latanoprost 0.005%, brimonidine 0.2%, or balanced saline solution (BSS) each were administered to one treatment group, both eyes of each rabbit, twice a day, 6 days a week for 10 weeks. The eyes were then enucleated along with the conjunctiva, fixed, processed, and evaluated by light microscopy and immunohistochemistry using anti-proliferating cell nuclear antigen (PCNA) and anti-muscle-specific actin antibody (HHF-35). Fibroblast cell counts were performed at magnification x40. In all groups, few inflammatory cells were seen in the subconjunctival space under light microscopy. PCNA staining revealed a statistically significant increase in the mean number of labeled fibroblasts in the group receiving brimonidine compared with the control (BSS) group. The group receiving latanoprost also had a significantly higher mean number of labeled fibroblasts than the groups receiving brimonidine or BSS. Only a few fibroblasts stained positively with the anti HHF antibody. Eyes treated with latanoprost, however, had significantly higher numbers of positively labeled cells than eyes treated with brimonidine or BSS. When applied to rabbit eyes, latanoprost and brimonidine appear to increase the number of positively labeled proliferating subconjunctival fibroblasts.


Uncovering Divergence in Gene Expression Regulation in the Adaptation of Yeast to Nitrogen Scarcity.
Saccharomyces cerevisiae rewires its transcriptional output to survive stressful environments, such as nitrogen scarcity under fermentative conditions. Although divergence in nitrogen metabolism among natural yeast populations has been reported, the impact of regulatory genetic variants modulating gene expression and nitrogen consumption remains to be investigated. Here, we employed an F1 hybrid from two contrasting S. cerevisiae strains, providing a controlled genetic environment to map cis factors involved in the divergence of gene expression regulation in response to nitrogen scarcity. We used a dual approach to obtain genome-wide allele-specific profiles of chromatin accessibility, transcription factor binding, and gene expression through ATAC-seq (assay for transposase accessible chromatin) and RNA-seq (transcriptome sequencing). We observed large variability in allele-specific expression and accessibility between the two genetic backgrounds, with a third of these differences specific to a deficient nitrogen environment. Furthermore, we discovered events of allelic bias in gene expression correlating with allelic bias in transcription factor binding solely under nitrogen scarcity, where the majority of these transcription factors orchestrates the nitrogen catabolite repression regulatory pathway and demonstrates a cis × environment-specific response. Our approach allowed us to find cis variants modulating gene expression, chromatin accessibility, and allelic differences in transcription factor binding in response to low nitrogen culture conditions. IMPORTANCE Historically, coding variants were prioritized when searching for causal mechanisms driving adaptation of natural populations to stressful environments. However, the recent focus on noncoding variants demonstrated their ubiquitous role in adaptation. Here, we performed genome-wide regulatory variation profiles between two divergent yeast strains when facing nitrogen nutritional stress. The open chromatin availability of several regulatory regions changes in response to nitrogen scarcity. Importantly, we describe regulatory events that deviate between strains. Our results demonstrate a widespread variation in gene expression regulation between naturally occurring populations in response to stressful environments.


Design and Evaluation of Hydrophobic Ion Paired Insulin Loaded Self Micro-Emulsifying Drug Delivery System for Oral Delivery.
Despite several novel and innovative approaches, clinical translation of oral insulin delivery into commercially viable treatment is still challenging due to its poor absorption and rapid degradation in GIT. Thus, an insulin-SDS hydrophobic ion pair loaded self-microemulsifying drug delivery system (SMEDDS) was formulated to exploit the hypoglycemic effects of orally delivered insulin. Insulin was initially hydrophobically ion paired with sodium dodecyl sulphate (SDS) to enhance its lipophilicity. The successful complexation of Insulin-SDS was confirmed by FTIR and surface morphology was evaluated using SEM. Stability of insulin after its release from HIP complex was evaluated using SDS PAGE. Subsequently, Ins-SDS loaded SMEDDS was optimized using two factorial designs. In vitro stability of insulin entrapped in optimized SMEDDS against proteolytic degradation was also assessed. Further, antidiabetic activity of optimized Ins-SDS loaded SMEDDS was evaluated in diabetic rats. Insulin complexed with SDS at 6:1 (SDS/insulin) molar ratio with almost five-fold increased lipophilicity. The SMEDDS was optimized at 10% Labraphil M2125 CS, 70% Cremophore EL, and 20% Transcutol HP with better proteolytic stability and oral antidiabetic activity. An Ins-SDS loaded SMEDDS was successfully optimized. Compared with insulin and Ins-SDS complex, the optimized SMEDDS displayed considerable resistance to GI enzymes. Thus, the SMEDDS showed potential for effective delivery of macromolecular drugs with improved oral bioavailability.


Electrosynthesis of Quasi-Epitaxial Crystals on Liquid Metals.
Electrosynthesis of single-crystalline metallic and intermetallic particles with a preferred orientation onto liquid metal electrodes has been performed. Liquid gallium electrodes immersed in aqueous alkaline electrolytes without any molecular additive or external solid seeding substrates were used to electroreduce separately Pb2+, Bi3+, Pd2+, and Mn2+. The crystallinity, composition, and orientation of the electrodeposition products were characterized by using scanning electron microscopy, transmission electron microscopy, selected area electron diffraction, grazing incidence X-ray diffraction, and energy-dispersive X-ray spectroscopy. Electrodeposition of Pb and Bi results in the incipient formation of two-dimensional (2D) nuclei that subsequently direct the growth of Pb and Bi single crystals along the most close-packed [111] and [0001] directions, respectively. The absence of any intervening surface oxides and a low electroreduction flux are necessary to avoid polycrystalline dendrite formation. Under comparable conditions, the electrodeposition of Pd and Mn results in single-crystalline intermetallic particles at the interface. Each crystal exhibits a preferred orientation consistent with the unique atomic packing of the near-surface region of the liquid Ga. The presented study suggests a new concept in electrodeposition processes where the liquid metal structure imparts quasi-epitaxial growth in a system in which the electrode material specifically has no crystallinity or long-range order. This study is thus the first demonstration of highly oriented electrodeposition at a liquid/liquid interface under ambient conditions, highlighting the unique solvation environment of liquid metal interfaces for forming thin metallic and intermetallic films.


Late language development in a child unable to recognize or produce speech sounds.
A boy with severe quadriplegia who neither recognized nor uttered speech sounds acquired language. Until the age of 6 years he was considered to be of severely subnormal intelligence. At age 6 years 9 months he was introduced to a manual sign system. Subsequently he was able to read, write, converse, and produce imaginative stories. Attention and memory were unimpaired and affective and social responsiveness developed appropriately. The case history demonstrates the selective effects of brain lesions that, despite extensive damage, may spare functional systems necessary for cognitive and linguistic development. It highlights the difficulty in diagnosing and evaluating the intellectual and affective potential of a multihandicapped child without functional hearing or speech and emphasizes the importance of sign language as a communication channel and prerequisite for the acquisition of reading and writing skills.


Synthesis, characterization, and computational study of the trans-IO2F5(2-) anion.
The combination of CH(3)CN solutions of [N(CH(3))(4)][F] and a mixture of cis- and trans-[N(CH(3))(4)][IO(2)F(4)] produces the novel trans-IO(2)F(5)(2)(-) anion. Under the given conditions, only the trans-IO(2)F(4)(-) anion acts as a fluoride ion acceptor, thus allowing the separation of isomerically pure, soluble cis-IO(2)F(4)(-) from insoluble trans-IO(2)F(5)(2)(-). The trans-IO(2)F(5)(2)(-) and cis-IO(2)F(4)(-) anions were characterized by infrared and Raman spectroscopy and theoretical calculations at the LDFT and HF levels of theory. The trans-IO(2)F(5)(2)(-) anion has a pentagonal-bipyramidal geometry with the two oxygen atoms occupying the axial positions. It represents the first example of a heptacoordinated main group AO(2)X(5) species and completes the series of pentagonal-bipyramidal iodine fluoride and oxide fluoride species. The geometries of the pentagonal-bipyramidal series IO(2)F(5)(2)(-), IOF(5)(2)(-), IF(5)(2)(-), IOF(6)(-), IF(6)(-), and IF(7) and the corresponding octahedral series IO(2)F(4)(-), IOF(4)(-), IF(4)(-), IOF(5), IF(5), and IF(6)(+) were calculated by identical methods. It is shown how the ionic charge, the oxidation state of the iodine atom, the coordination number, and the replacement of fluorine ligands by either an oxygen ligand or a free valence electron pair influence the stuctures and bonding of these species.


In vitro assays of cellular immunity in progressive coccidioidomycosis: evaluation of suppression with parasitic-phase antigen.
Patients with progressive coccidioidomycosis commonly have depressed cell-mediated immune responses to coccidioidal antigens. We studied in vitro lymphocyte transformation in response to spherulin, as extract of the parasitic phase of Coccidioides immitis, and the nonspecific mitogen phytohemagglutinin in patients with progressive disseminated coccidioidomycosis who were anergic to spherulin and in healthy skin test-positive and skin test-negative control subjects. Lymphocyte responses to phytohemagglutinin were indistinguishable for all three groups. When assayed in pooled blood group AB serum, lymphocyte responses to spherulin were identical for patients and skin test-positive control subjects; however, the patients' responses to spherulin were depressed in autologous serum. Prolonged incubation of cells in vitro did not restore the hyporesponsiveness. Serial studies of the patients revealed a trend toward restoration of the lymphocyte response during therapy. Preliminary experiments suggest that, although there were no intrinsic cell defects in these patients with coccidioidomycosis, there may be specificity of patient cells to be suppressed by serum. A prospective study of the incidence of depression of lymphocyte responsiveness in autologous serum revealed that this occurs in a minority of patients with negative spherulin skin tests, is rare in patients with positive skin tests, and appears to be associated with clinical deterioration.


Effect of trans-10, cis-12 conjugated linoleic acid on performance, adipose depot weights, and liver weight in early-lactation dairy cows.
In feeding practice, conjugated linoleic acid (CLA) supplements are used to decrease milk fat excretion in early-lactation dairy cows to save energy to counteract the physiological negative energy balance. The present study was conducted to examine the effects of CLA on energy metabolism, changes in liver weight, and the weight of different adipose depots during early lactation. Primiparous lactating German Holstein cows (n=25) were divided into 5 groups and each group contained 5 animals. The experiment started 21 d prepartum and continued until 105 d in milk (DIM). Cows were slaughtered at 1, 42, and 105 DIM. The experiment was divided into a prepartum period (21 d prepartum until calving), period 1 (1 until 42 DIM), and period 2 (>42 until 105 DIM). In the prepartum period, all animals were housed together and fed the same diet with no CLA supplementation. At 1 DIM, an initial group, with no CLA supplementation, was slaughtered. The 20 remaining cows were assigned to 2 diets. One group received 100g/d of a control fat supplement (CON; n=10) and the other group 100g/d of a CLA supplement (CLA; n=10) from 1 DIM until slaughter. Five cows of each feeding group were slaughtered after 42 DIM and the remaining animals after 105 DIM. The CLA supplement contained approximately 10% each of trans-10, cis-12 CLA and cis-9, trans-11 CLA. During the slaughter process the empty body weight was recorded and the omental, mesenteric, retroperitoneal, and s.c. adipose depots, as well as the liver, were dissected and weighed. The CLA treatment decreased milk fat content in period 1 (14.1%). In period 2, milk fat content (25.4%) and yield (17.1%) were lower in the CLA group. No effect of CLA on milk yield was observed. The net energy intake, milk energy output, and the calculated energy balance remained unchanged by CLA supplementation. No effect of CLA on the weights of liver, omental, mesenteric, or s.c. adipose depots was observed when related to empty body weight. Liver weight increased with DIM, whereas the retroperitoneal adipose depot weight decreased at the same time. Compared with the initial group, the retroperitoneal adipose depot weight for control animals slaughtered after 42 DIM was decreased (47.7%); however, for the CLA group slaughtered after 42 DIM, a trend to a lower retroperitoneal adipose depot weight (34.0%) was observed. This suggests a CLA-induced deceleration of mobilization of the retroperitoneal adipose depot during the first 42 DIM.


Encounter with venus: an update.
This report is an introduction to the accompanying collection of early results from the Pioneer Venus orbiter and multiprobe missions, which encountered Venus on 4 December and 9 December 1978, respectively. Initial results for the multiprobe mission and for the first 30 days of the orbiter mission were reported in the 23 February issue of Science. Additional mission features and updated mission parameters based on refined tracking data and trajectory computations are presented here. New scientific results for both missions are given in the subsequent reports which cover the first 130 days (or orbits) of the nominal 243-day orbiter mission.


Vitamin E-loaded dialyzer resets PBMC-operated cytokine network in dialysis patients.
In hemodialysis patients the activity of stimulated Th1 lymphocytes is depressed, while Th2 cells are constitutively primed. Such phenomena may depend on monocyte activation and altered release of interleukin (IL)-12 and IL-18, which regulate Th cell differentiation. Reactive oxygen species (ROS) activate monocytes; therefore, a hemodialyzer with antioxidant activity would contrast ROS, prevent monocyte activation, reset IL-12 and IL-18 release, and restore Th1/Th2 balance. Ten patients on regular dialysis treatment (RDT) with cellulosic membrane (CM) were shifted to vitamin E-coated dialyzer (VE). During treatment with CM and after 3, 6, and 12 months of treatment with VE, peripheral blood mononuclear cells (PBMC) and purified CD4+ cells were isolated, and cultured, resting, mitogen-stimulated, and interferon gamma (IFNgamma), IL-4, IL-10, IL-12, and IL-18 release was measured. Vitamin E and A plasma levels and the effects of a single dialysis session on peripheral blood NO levels were assayed. The constitutive release of IL-4 and IL-10 by CD4+ cells was abated significantly by treatment with VE (nadir -77.8% and -55.3%, respectively, at 12 months). INFgamma release by mitogen-stimulated CD4+ recovered with VE (zenith +501% at 12 months). PBMC constitutive production of IL-12 and IL-18 was significantly reduced by VE (nadir at 12 months -64.7% and -51.3%, respectively). VE increased plasma levels of vitamins E and A. NO plasma levels fell after a single dialysis treatment with VE (-17%, P < 0.05) in contrast with CU (+27.1%, P < 0.05). The network of cytokines released by monocytes and Th cells is reset toward normality by treatment with vitamin E-coated dialyzer.


Design of polymeric core-shell carriers for combination therapies.
Particle engineering for co-delivery of drugs has the potential to combine multiple drugs with different pharmaceutical mechanisms within the same carrier, increasing the therapeutic efficiency while improving patient compliance. This work proposes a novel approach for producing polymer-polymer core-shell microparticles by multi-step processing of emulsion and spray drying. The particle core was obtained by an oil-in-water emulsion of poly(ε-caprolactone) (PCL) loaded with curcumin (CM), followed by the resuspension in poly(vinyl alcohol) (PVA) containing ciprofloxacin (CPx) forming the shell layer by spray-drying. The obtained core-shell particles showed an average size of 3.8 ± 1.2 μm, which is a suitable size for inhalation therapies. The spatial distribution of the drugs was studied using synchrotron-based macro attenuated total reflection Fourier transform infrared (macro ATR-FTIR) microspectroscopy to map the chemical distribution of the components within the particles and supported the presence of CM and CPx in the core and shell layers, respectively. The formation of the core-shell structure was further supported by the differences in the release profile of CM from these particles, when compared to the release profile observed for the single particle structure (PCL-CM). Both empty and drug-loaded carriers (up to 100 μg.mL-1) showed no cytotoxic effects on A549 cells while exhibiting the antibacterial activity of CPx against Gram-positive and Gram-negative bacteria. These polymer core-shell microparticles provide a promising route for the combination and sequential drug release therapies, with the potential to be used in inhalation therapies.


Prolonged time between donor brain death and organ retrieval results in an increased risk of mortality in cardiac transplant recipients.
In cardiac transplantation longer ischemic times relate to poorer outcomes. However, brain death also promotes donor organ injury. The aim of this study was to ascertain if there was an association between longer time periods between donor brain death and organ retrieval with recipient mortality. This retrospective single centre study included 157 cardiac transplants performed between February 1999 and 2009. The time between the second brain stem death test and the cross-clamp time at organ retrieval was noted in hours. This was compared with survival time in years. Cox regression analysis was performed. The following variables were included: donor and recipient sex, age and cytomegalovirus status; donor smoking history; ischemic time and number of rejection episodes. Of the 157 transplants, 37 recipients have died. The mean follow-up was 4.1 years. The mean time between brain stem death test and cross-clamp time was 13.2±3.96 hours. Considering the above variables, the most significant finding is: increased time between brain stem death test and organ retrieval cross-clamp time, predicted a greater recipient mortality [hazard ratio (HR)=1.15; 95% confidence interval (CI)=1.06-1.24; P<0.001]. Longer delays between donor brain death and cross-clamp time are associated with a higher-risk of mortality in cardiac transplant recipients.


Lifestyle and Metabolic Syndrome: Contribution of the Endocannabinoidome.
Lifestyle is a well-known environmental factor that plays a major role in facilitating the development of metabolic syndrome or eventually exacerbating its consequences. Various lifestyle factors, especially changes in dietary habits, extreme temperatures, unusual light-dark cycles, substance abuse, and other stressful factors, are also established modifiers of the endocannabinoid system and its extended version, the endocannabinoidome. The endocannabinoidome is a complex lipid signaling system composed of a plethora (>100) of fatty acid-derived mediators and their receptors and anabolic and catabolic enzymes (>50 proteins) which are deeply involved in the control of energy metabolism and its pathological deviations. A strong link between the endocannabinoidome and another major player in metabolism and dysmetabolism, the gut microbiome, is also emerging. Here, we review several examples of how lifestyle modifications (westernized diets, lack or presence of certain nutritional factors, physical exercise, and the use of cannabis) can modulate the propensity to develop metabolic syndrome by modifying the crosstalk between the endocannabinoidome and the gut microbiome and, hence, how lifestyle interventions can provide new therapies against cardiometabolic risk by ensuring correct functioning of both these systems.


Piroxicam pharmacokinetics: recent clinical results relating kinetics and plasma levels to age, sex, and adverse effects.
A large body of data is available regarding the relationship between demographic factors, particularly age, sex, and disease state, and the pharmacokinetics of piroxicam. Of additional interest is the relationship between piroxicam pharmacokinetics (particularly steady-state plasma levels) and adverse effects. Studies with piroxicam that are reviewed herein include studies on kinetics in renal impairment, single-dose studies, multiple-dose studies, and therapeutic drug monitoring studies. Although results were not always consistent, some studies suggested that plasma levels of piroxicam tend to be increased in elderly female patients. However, the increases were small and did not correlate with adverse events. These data suggest that there is no correlation between piroxicam plasma concentrations and adverse events.


Detection of mutations in EGFR in circulating lung-cancer cells.
The use of tyrosine kinase inhibitors to target the epidermal growth factor receptor gene (EGFR) in patients with non-small-cell lung cancer is effective but limited by the emergence of drug-resistance mutations. Molecular characterization of circulating tumor cells may provide a strategy for noninvasive serial monitoring of tumor genotypes during treatment. We captured highly purified circulating tumor cells from the blood of patients with non-small-cell lung cancer using a microfluidic device containing microposts coated with antibodies against epithelial cells. We performed EGFR mutational analysis on DNA recovered from circulating tumor cells using allele-specific polymerase-chain-reaction amplification and compared the results with those from concurrently isolated free plasma DNA and from the original tumor-biopsy specimens. We isolated circulating tumor cells from 27 patients with metastatic non-small-cell lung cancer (median number, 74 cells per milliliter). We identified the expected EGFR activating mutation in circulating tumor cells from 11 of 12 patients (92%) and in matched free plasma DNA from 4 of 12 patients (33%) (P=0.009). We detected the T790M mutation, which confers drug resistance, in circulating tumor cells collected from patients with EGFR mutations who had received tyrosine kinase inhibitors. When T790M was detectable in pretreatment tumor-biopsy specimens, the presence of the mutation correlated with reduced progression-free survival (7.7 months vs. 16.5 months, P<0.001). Serial analysis of circulating tumor cells showed that a reduction in the number of captured cells was associated with a radiographic tumor response; an increase in the number of cells was associated with tumor progression, with the emergence of additional EGFR mutations in some cases. Molecular analysis of circulating tumor cells from the blood of patients with lung cancer offers the possibility of monitoring changes in epithelial tumor genotypes during the course of treatment.


Truncated prelamin A expression in HGPS-like patients: a transcriptional study.
Premature aging syndromes are rare genetic disorders mimicking clinical and molecular features of aging. A recently identified group of premature aging syndromes is linked to mutation of the LMNA gene encoding lamins A and C, and is associated with nuclear deformation and dysfunction. Hutchinson-Gilford progeria syndrome (HGPS) was the first premature aging syndrome linked to LMNA mutation and its molecular bases have been deeply investigated. It is due to a recurrent de novo mutation leading to aberrant splicing and the production of a truncated and toxic nuclear lamin A precursor (prelamin AΔ50), also called progerin. In this work and based on the literature data, we propose to distinguish two main groups of premature aging laminopathies: (1) HGPS and HGP-like syndromes, which share clinical features due to hampered processing and intranuclear toxic accumulation of prelamin A isoforms; and (2) APS (atypical progeria syndromes), due to dominant or recessive missense mutations affecting lamins A and C. Among HGPS-like patients, several deleted prelamin A transcripts (prelamin AΔ50, AΔ35 and AΔ90) have been described. The purpose of this work was to characterize those transcripts in eight patients affected with HGP-like rare syndromes. When fibroblasts were available, the relationships between the presence and ratios of these transcripts and other parameters were studied, aiming to increase our understanding of genotype-phenotype relationships in HGPS-like patients. Altogether our results evidence that progerin accumulation is the major pathogenetic mechanism responsible for HGP-like syndromes due to mutations near the donor splice site of exon 11.


Exogenous clustered neuropilin 1 enhances vasculogenesis and angiogenesis.
Neuropilin 1 (NP-1) is a receptor for vascular endothelial growth factor (VEGF) 165 (VEGF165) and acts as a coreceptor that enhances VEGF165 function through tyrosine kinase VEGF receptor 2 (VEGFR-2). Transgenic overexpression of np-1 results in an excess of capillaries and blood vessels and a malformed heart. Thus, NP-1 may have a key role in vascular development. However, how NP-1 regulates vascular development is not well understood. This study demonstrates how NP-1 can regulate vasculogenesis and angiogenesis in vitro and in vivo. In homozygous np-1 mutant (np-1(-/-)) murine embryos, vascular sprouting was impaired in the central nervous system and pericardium. Para-aortic splanchnopleural mesoderm (P-Sp) explants from np-1(-/-) mice also had vascular defects in vitro. A monomer of soluble NP-1 (NP-1 tagged with Flag epitope) inhibited vascular development in cultured wild-type P-Sp explants by sequestering VEGF165. In contrast, a dimer of soluble NP-1 (NP-1 fused with the Fc part of human IgG) enhanced vascular development in cultured wild-type P-Sp explants. Moreover, the NP-1-Fc rescued the defective vascular development in cultured np-1(-/-) P-Sp explants. A low dose of VEGF alone did not promote phosphorylation of VEGFR-2 on endothelial cells from np-1(-/-) embryos, but simultaneous addition of a low dose of VEGF and NP-1-Fc phosphorylated VEGFR-2 significantly. Moreover, NP-1-Fc rescued the defective vascularity of np-1(-/-) embryos in vivo. These results suggest that a dimer form of soluble NP-1 delivers VEGF165 to VEGFR-2-positive endothelial cells and promotes angiogenesis.


A National Survey on the Use of Immersive Simulation for Interprofessional Education in Physical Therapist Education Programs.
There is growing recognition that collaborative practice among healthcare professionals is associated with improved patient outcomes and enhanced team functioning, but development of collaborative practitioners requires interprofessional education (IPE). Immersive simulation, a clinically relevant experience that deeply engages the learner in realistic clinical environments, is used increasingly for IPE. The purpose of this study was to assess the use of immersive simulation as a strategy for IPE in physical therapist (PT) education programs. During fall 2014 and spring 2015, we contacted all 214 Commission on Accreditation in Physical Therapy Education accredited PT education programs in the United States and invited a faculty member to participate in our online survey. One hundred fourteen PT programs responded (53% response rate). Eighty responding programs (70%) identified themselves as users of immersive simulation, and 45 programs (39%) used simulation for IPE. Of these 45 programs, more than 90% included Interprofessional Education Collaborative competency learning objectives of roles/responsibilities, interprofessional communication, and teams/teamwork and 51% reported learning objectives for values/ethics for interprofessional practice. Interprofessional simulations with PT students commonly included nursing (91%). In programs using immersive simulation for IPE, 91% included debriefing and 51% included debriefing by interprofessional teams. Eighty accredited PT programs (70%) that responded to the survey use immersive simulation, and 45 programs (39%) use simulation for IPE. Most programs conduct simulations consistent with recognized best practice, including debriefing and Interprofessional Education Collaborative competency learning objectives for promoting interprofessional collaborative practice. We anticipate an increase in the use of immersive simulation for IPE as an educational strategy to comply with the revised Commission on Accreditation in Physical Therapy Education accreditation standards related to interprofessional collaborative practice that will become effective on January 1, 2018.


Na(+)-K(+)-ATPase and Ca(2+) clearance proteins in smooth muscle: a functional unit.
The Na(+)-K(+)-ATPase (NKA) can affect intracellular Ca(2+) concentration regulation via coupling to the Na(+)-Ca(2+) exchanger and may be important in myogenic tone. We previously reported that in mice carrying a transgene for the NKA alpha(2)-isoform in smooth muscle (alpha(2sm+)), the alpha(2)-isoform protein as well as the alpha(1)-isoform (not contained in the transgene) increased to similar degrees (2-7-fold). Aortas from alpha(2sm+) mice relaxed faster from a KCl-induced contraction, hypothesized to be related to more rapid Ca(2+) clearance. To elucidate the mechanisms underlying this faster relaxation, we therefore measured the expression and distribution of proteins involved in Ca(2+) clearance. Na(+)-Ca(2+) exchanger, sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), and plasma membrane Ca(2+)-ATPase (PMCA) proteins were all elevated up to approximately fivefold, whereas actin, myosin light chain, and calponin proteins were not changed in smooth muscle from alpha(2sm+) mice. Interestingly, the corresponding Ca(2+) clearance mRNA levels were unchanged. Immunocytochemical data indicate that the Ca(2+) clearance proteins are distributed similarly in wild-type and alpha(2sm+) aorta cells. In studies measuring relaxation half-times from a KCl-induced contraction in the presence of pharmacological inhibitors of SERCA and PMCA, we estimated that together these proteins were responsible for approximately 60-70% of relaxation in aorta. Moreover, the percent contribution of SERCA and PMCA to relaxation rates in alpha(2sm+) aorta was not significantly different from that in wild-type aorta. The coordinate expressions of NKA and Ca(2+) clearance proteins without change in the relative contributions of each individual protein to smooth muscle function suggest that NKA may be but one component of a larger functional Ca(2+) clearance system.


Application of oocyte cryopreservation technology in TALEN-mediated mouse genome editing.
Reproductive engineering techniques, such as in vitro fertilization (IVF) and cryopreservation of embryos or spermatozoa, are essential for preservation, reproduction, and transportation of genetically engineered mice. However, it has not yet been elucidated whether these techniques can be applied for the generation of genome-edited mice using engineered nucleases such as transcription activator-like effector nucleases (TALENs). Here, we demonstrate the usefulness of frozen oocytes fertilized in vitro using frozen sperm for TALEN-mediated genome editing in mice. We examined side-by-side comparisons concerning sperm (fresh vs. frozen), fertilization method (mating vs. IVF), and fertilized oocytes (fresh vs. frozen) for the source of oocytes used for TALEN injection; we found that fertilized oocytes created under all tested conditions were applicable for TALEN-mediated mutagenesis. In addition, we investigated whether the ages in weeks of parental female mice can affect the efficiency of gene modification, by comparing 5-week-old and 8-12-week-old mice as the source of oocytes used for TALEN injection. The genome editing efficiency of an endogenous gene was consistently 95-100% when either 5-week-old or 8-12-week-old mice were used with or without freezing the oocytes. Thus, our report describes the availability of freeze-thawed oocytes and oocytes from female mice at various weeks of age for TALEN-mediated genome editing, thus boosting the convenience of such innovative gene targeting strategies.


Atrial fibrillation as a nonpsychiatric predictor of delirium after cardiac surgery: a pilot study.
Preoperative atrial fibrillation (AF) increases the risk of cardiac surgery and the occurrence of postoperative complications, including arrhythmias, low-output syndrome, delirium, and death. The aim was to evaluate its direct influence on prognosis of patients subjected to cardiac surgery. This is a pilot study of the CODACS trial (COnsciousness Disorders After Cardiac Surgery). Two hundred sixty patients admitted for open-heart surgery were prospectively included in the study. Preoperative AF was diagnosed on the basis of multiple electrocardiographic examinations and confirmed by 24-h Holter monitoring. Diagnosis of delirium following surgical intervention was based on DSM-IV criteria. Preoperative AF was diagnosed in 23 patients (8.8%): in 15 patients in the nondelirious group (7%) and 8 (27.0%) in the delirious group. Preoperative AF was an independent predictor of postoperative delirium (p<0.001), increasing its risk of occurrence over sevenfold (OR=7.2). AF also increased the risk of such postoperative complications as supraventricular arrhythmia (AF: 78.3% vs. non-AF: 22.8%, p<0.001), stroke (8.7% vs. 1.3%, p<0.001), and low-output syndrome (21.7% vs. 17.3%, p=0.033) and worsened prognosis, significantly increasing the risk of death (8.7% vs. 0.8%, p<0.001). Preoperative AF was an independent risk factor of postoperative delirium (OR=7.2). It was also associated with significantly worse postoperative outcome (supraventricular arrhythmia, stroke, low-output syndrome, and risk of death). These results and data from available studies suggest that preoperative AF should be considered as an important predictor of postoperative outcome. This problem should be the subject of future research to establish beneficial treatment options.


The technique of percutaneous renal biopsy. How to minimize risk while ensuring adequate tissue sampling.
Percutaneous renal biopsy is useful in diagnosing a variety of kidney disorders, as well as certain systemic diseases with renal and/or nonrenal manifestations. The procedure is performed while the kidney is viewed by continuous ultrasonographic imaging. The kidney is first located with a spinal needle and the area is anesthetized. The biopsy needle is then inserted and advanced toward the capsule. When the capsule is pierced, the trochar is advanced into the renal cortex. The sheath is lowered, encompassing the cutting edge and the core biopsy sample. Complications, although rare, may include the creation of an arteriovenous malformation and laceration of the kidney or other intra-abdominal organ; close monitoring after the procedure is therefore required.


Motivating Latino caregivers of children with asthma to quit smoking: a randomized trial.
Secondhand smoke exposure is associated with asthma onset and exacerbation. Latino children have higher rates of asthma morbidity than other groups. The current study compared the effectiveness of a newly developed smoking cessation treatment with existing clinical guidelines for smoking cessation. Latino caregivers who smoked (N = 133; 72.9% female; mean age = 36.8 years) and had a child with asthma were randomly assigned to receive 1 of 2 smoking cessation counseling interventions during a home-based asthma program: (a) behavioral action model (BAM; modeled on clinical guidelines for smoking cessation) or (b) precaution adoption model (PAM; feedback on the caregiver's carbon monoxide level and child's secondhand smoke exposure using Motivational Interviewing). Counseling was delivered by a bilingual Latina health educator, and the content was tailored to Latino values and culture. It was not necessary for smokers to want to quit smoking to participate. Smoking cessation was biochemically verified and secondhand smoke exposure was objectively measured through passive nicotine monitors. Intent-to-treat analyses showed that 20.5% of participants in the PAM condition and 9.1% of those in the BAM condition were continuously abstinent at 2 months posttreatment (OR = 2.54; 95% CI = 0.91-7.10), whereas 19.1% of participants in the PAM condition and 12.3% of those in BAM condition were continuously abstinent at 3 months posttreatment (OR = 1.68; 95% CI = 0.64-4.37). Secondhand smoke exposure decreased only in the BAM condition (p < .001), an effect due to less smoking around the child among nonquitters in this condition. Asthma morbidity showed significant decreases in the posttreatment period for the PAM group only (p < .001). Results provide support for targeting specific populations with theory-based interventions.


The Influence of Larval Stage and Density on Oviposition Site-Selection Behavior of the Afrotropical Malaria Mosquito Anopheles coluzzii (Diptera: Culicidae).
In the selection of oviposition sites female mosquitoes use various cues to assess site quality to optimize survival of progeny. The presence of conspecific larvae influences this process. Interactive effects of oviposition site selection were studied in the malaria mosquito Anopheles coluzzii Coetzee & Wilkerson in dual- and no-choice assays, by exposing single gravid mosquitoes to oviposition cups containing 1) larvae of different developmental stages, 2) larvae-conditioned water (LCW), and 3) cups where visual cues of conspecific larvae were absent. Early-stage conspecific larvae had a positive effect on the oviposition response. By contrast, late stages of conspecific larvae had a negative effect. Oviposition choice was dependent on larval density. Moreover, in oviposition cups where larvae were hidden from view, late-stage larvae had a significant negative effect on oviposition suggesting the involvement of olfactory cues. LCW had no effect on oviposition response, indicating involvement of chemicals produced by larvae in vivo. It is concluded that the presence of larvae in a breeding site affects the oviposition response depending on the development stage of the larvae. These responses appear to be mediated by olfactory cues emitted by the larval habitat containing live larvae, resulting in the enhanced reproductive fitness of the females.


[Alloimmune neonatal neutropenia in homozygotic female twins].
Female homozygous twins presented with alloimmune neonatal neutropenia due to a maternal neutrophil-specific anti-NA2 antibody. The disease is usually benign, but when accompanied by severe infection it may require exchange transfusion and transfusion of granulocytes free of the antigen involved in the immunological conflict. Owing to the risk of relapse in subsequent pregnancies, the haemogram of the following infants must be supervised.


Surface depression with double-angle geometry during the discharge of grains from a silo.
When rough grains in loose packing conditions are discharged from a silo, a conical depression with a single slope is formed at the surface. We observed that the increase of volume fraction generates a more complex depression, characterized by two angles of discharge: one at the bottom similar to the angle of repose and a considerably larger upper angle. The change in slope appears at the boundary between a dense stagnant region at the periphery and the central flowing channel formed over the aperture. Since the material in the latter zone is always fluidized, the flow rate is unaffected by the initial packing of the bed. On the other hand, the contrast between both angles is markedly smaller when smooth particles of the same size and density are used, which reveals that high packing fraction and friction must combine to produce the observed geometry. Our results show that the surface profile helps to identify by simple visual inspection the packing conditions of a granular bed, being useful to prevent undesirable collapses during silo discharge in industry.


Computed tomography of deep cerebral venous thrombosis.
We present three cases of deep cerebral venous thrombosis. The CT features and their evolution are discussed with review of the literature. New direct and indirect CT signs are described.


Gene expression profiling during the transition to failure in TNF-alpha over-expressing mice demonstrates the development of autoimmune myocarditis.
Transgenic mice with cardiac-specific over-expression of tumor necrosis factor-alpha (TNF1.6) progress to dilated heart failure. A significant inflammatory response precedes functional deterioration, and may contribute to cardiac damage in this model. To evaluate the underlying molecular mechanisms, we assessed the gene expression in six groups of mouse hearts defined by age, gender, and phenotype (n = 3/group) using Affymetrix microarray analysis. Phenotype was defined as compensated (in young TNF1.6) or decompensated (in older TNF1.6) via echocardiogram. Of the >1000 transcripts altered in the compensated hearts (fold change > 2, P < 0.05 vs. wild-type (WT)), 102 were identified as immune response genes, 20 of which function in antigen presentation and processing. When comparing the compensated and decompensated hearts, >50 genes were differentially regulated, including seven immunoglobulin genes. Real-time reverse transcriptase-polymerase chain reaction and cDNA microarray confirmed the Affymetrix data. Mac3+ macrophages, CD4+ T and CD45/B220+ B-cells were identified in both compensated and decompensated hearts. However, a large amount of IgG was found deposited in areas devoid of B-lymphocytes in the myocardium of decompensated TNF1.6 mice; no such accumulation was seen in the compensated or age-matched controls. Furthermore, nuclei density analyses showed a two-fold increase in the myocardium of both compensated and decompensated TNF1.6 mice (vs. WT). This study suggests that TNF-alpha over-expression activates not only the inflammatory response, but also humoral immune responses within the transgenic hearts. The autoimmune response occurs concomitantly with cardiac decompensation and may participate in triggering the transition to failure in TNF1.6 mice.


Nonvisual motor learning improves visual motion perception: evidence from violating the two-thirds power law.
Few studies have reported direct effects of motor learning on visual perception, especially when using novel movements for the motor system. Atypical motor behaviors that violate movement constraints provide an excellent opportunity to study action-to-perception transfer. In our study, we passively trained blindfolded participants on movements violating the 2/3 power law. Before and after motor training, participants performed a visual discrimination task in which they decided whether two consecutive movements were same or different. For motor training, we randomly assigned the participants to two motor training groups or a control group. The motor training group experienced either a weak or a strong elliptic velocity profile on a circular trajectory that matched one of the visual test stimuli. The control group was presented with linear trajectories unrelated to the viewed movements. After each training session, participants actively reproduced the movement to assess motor learning. The group trained on the strong elliptic velocity profile reproduced movements with increasing elliptic velocity profiles while circular geometry remained constant. Furthermore, both training groups improved in visual discrimination ability for the learned movement as well as for highly similar movements. Participants in the control group, however, did not show any improvements in the visual discrimination task nor did participants who did not acquire the trained movement. The present results provide evidence for a transfer from action to perception which generalizes to highly related movements and depends on the success of motor learning. Moreover, under specific conditions, it seems to be possible to acquire movements deviating from the 2/3 power law.


Rodents as potential hosts and reservoirs of parasites along the edge of a Central African forest: Bwindi impenetrable national park, South Western Uganda.
Rodents which constitute 42% of the world's mammalian population are major reservoirs of pathogens that cause zoonoses. Currently we know little about rodents' potential zoonotic transfer from human settlements into protected areas and how any such threats might be reduced. To investigate the role of rodents as reservoirs of zoonotic pathogens along the boundary of Bwindi. A rodent inventory in three villages along the edge of Bwindi, was carried using live trapping techniques and the local rodents' ecto and endoparasite fauna investigated. Two hundred eighty eight rodents captured belonged to 24 species, 17 genera and 4 families with Lophuromys aquilus being most abundant (30.2%). 240 ectoparasites which included mites, fleas and ticks were collected from 88 rodents out of 249. Proamys jacksoni rodents were most infested. Although the mites represented the largest proportion (84.6%), the highest species diversity was shown among the fleas (9 species). Some 36.9% of the rodents were infected with endoparasites of which L. aquilus haboured most. Endoparasitic genera identified included Nippostrongylus, Ascaris, Strongyloides, Trichuris, Hymenolepis, Taenia and Cryptosporidium. Rodents have a zoonotic potentiality. There is need for developing effective integrated rodent management programs against rodent to reduce chances of parasite transmission within the protected areas.


Total body irradiation plus fludarabine versus thiotepa, busulfan plus fludarabine as a myeloablative conditioning for adults with acute lymphoblastic leukemia treated with haploidentical hematopoietic cell transplantation. A study by the Acute Leukemia Working Party of the EBMT.
Optimal conditioning for adults with acute lymphoblastic leukemia (ALL) treated with haploidentical hematopoietic cell transplantation (haplo-HCT) and post-transplant cyclophosphamide has not been established so far. We retrospectively compared outcomes for two myeloablative regimens: fludarabine + total body irradiation (Flu-TBI, n = 117) and thiotepa + iv. busulfan + fludarabine (TBF, n = 119). Patients transplanted either in complete remission (CR) or with active disease were included in the analysis. The characteristics of both groups were comparable except for patients treated with TBF were older. In univariate analysis the incidence of non-relapse mortality (NRM) at 2 years was increased for TBF compared to Flu-TBI (31% vs. 19.5%, p = 0.03). There was a tendency towards reduced incidence of relapse after TBF (p = 0.11). Results of multivariate analysis confirmed a reduced risk of NRM using Flu-TBI (HR = 0.49, p = 0.03). In the analysis restricted to patients treated in CR1 or CR2, the use of Flu-TBI was associated with a decreased risk of NRM (HR = 0.34, p = 0.009) but an increased risk of relapse (HR = 2.59, p = 0.01) without significant effect on survival and graft-versus-host disease. We conclude that for haplo-HCT recipients with ALL, Flu-TBI may be preferable for individuals at high risk of NRM while TBF should be considered in cases at high risk of relapse.


Medicus Deus: a review of factors affecting hospital library services to patients between 1790-1950.
What are some of the historical societal, medical, and public health trends leading to today's provision of hospital library services to patients? Literature from the archives of the Bulletin of the Medical Library Association and other library sources, medical journals, primary historical documents, and texts from the history of medicine form the core of this review. The period of review extends from about 1790 through 1950 and focuses solely on trends in the United States. Of primary concern are explicitly documented examples that appear to illustrate the patient-physician relationship and those between librarians and their patient-patrons during the earliest years of the profession's development. An historical timeline was created to allow the identification of major trends that may have affected library services. Multiple literature searches were conducted using library, medical, and health anthropology resources. When possible, primary sources were preferred over reviews. Juxtapositioning historical events allows the reader to obtain an overview of the roots of consumer health services in medical libraries and to consider their potential legacy in today's health care libraries. This review article highlights early developments in hospital library service to patients. Further research is needed to verify a preliminary conclusion that in some medical library settings, services to the general public are shaped by the broader health care environment as it has evolved.


Successive Stages of Amyloid-β Self-Assembly Characterized by Solid-State Nuclear Magnetic Resonance with Dynamic Nuclear Polarization.
Self-assembly of amyloid-β (Aβ) peptides in human brain tissue leads to neurodegeneration in Alzheimer's disease (AD). Amyloid fibrils, whose structures have been extensively characterized by solid state nuclear magnetic resonance (ssNMR) and other methods, are the thermodynamic end point of Aβ self-assembly. Oligomeric and protofibrillar assemblies, whose structures are less well-understood, are also observed as intermediates in the assembly process in vitro and have been implicated as important neurotoxic species in AD. We report experiments in which the structural evolution of 40-residue Aβ (Aβ40) is monitored by ssNMR measurements on frozen solutions prepared at four successive stages of the self-assembly process. Measurements on transient intermediates are enabled by ssNMR signal enhancements from dynamic nuclear polarization (DNP) at temperatures below 30 K. DNP-enhanced ssNMR data reveal a monotonic increase in conformational order from an initial state comprised primarily of monomers and small oligomers in solution at high pH, to larger oligomers near neutral pH, to metastable protofibrils, and finally to fibrils. Surprisingly, the predominant molecular conformation, indicated by (13)C NMR chemical shifts and by side chain contacts between F19 and L34 residues, is qualitatively similar at all stages. However, the in-register parallel β-sheet supramolecular structure, indicated by intermolecular (13)C spin polarization transfers, does not develop before the fibril stage. This work represents the first application of DNP-enhanced ssNMR to the characterization of peptide or protein self-assembly intermediates.


What is a cohort effect? Comparison of three statistical methods for modeling cohort effects in obesity prevalence in the United States, 1971-2006.
Analysts often use different conceptual definitions of a cohort effect, and therefore different statistical methods, which lead to differing empirical results. A definition often used in sociology assumes that cohorts have unique characteristics confounded by age and period effects, whereas epidemiologists often conceive that period and age effects interact to produce cohort effects. The present study aims to illustrate these differences by estimating age, period, and cohort (APC) effects on obesity prevalence in the U.S. from 1971 to 2006 using both conceptual approaches. Data were drawn from seven cross-sectional waves of the National Health and Nutrition Examination Survey. Obesity was defined as BMI >or=30 for adults and >or=95th percentile for children under the age of 20. APC effects were estimated using the classic constraint-based method (first-order effects estimated and interpreted), the Holford method (first-order effects estimated but second-order effects interpreted), and median polish method (second-order effects are estimated and interpreted). Results indicated that all methods report significant age and period effects, with lower obesity prevalence in early life as well as increasing prevalence in successive surveys. Positive cohort effects for more recently born cohorts emerged based on the constraint-based model; when cohort effects were considered second-order estimates, no significant effects emerged. First-order estimates of age-period-cohort effects are often criticized because of their reliance on arbitrary constraints, but may be conceptually meaningful for sociological research questions. Second-order estimates are statistically estimable and produce conceptually meaningful results for epidemiological research questions. Age-period-cohort analysts should explicitly state the definition of a cohort effect under consideration. Our analyses suggest that the prevalence of obesity in the U.S. in the latter part of the 20th century rose across all birth cohorts, in the manner expected based on estimated age and period effects. As such, the absence or presence of cohort effects depends on the conceptual definition and therefore statistical method used.