Using network analysis to examine links between individual depressive symptoms, inflammatory markers, and covariates.
Studies investigating the link between depressive symptoms and inflammation have yielded inconsistent results, which may be due to two factors. First, studies differed regarding the specific inflammatory markers studied and covariates accounted for. Second, specific depressive symptoms may be differentially related to inflammation. We address both challenges using network psychometrics. We estimated seven regularized Mixed Graphical Models in the Netherlands Study of Depression and Anxiety (NESDA) data (N = 2321) to explore shared variances among (1) depression severity, modeled via depression sum-score, nine DSM-5 symptoms, or 28 individual depressive symptoms; (2) inflammatory markers C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α); (3) before and after adjusting for sex, age, body mass index (BMI), exercise, smoking, alcohol, and chronic diseases. The depression sum-score was related to both IL-6 and CRP before, and only to IL-6 after covariate adjustment. When modeling the DSM-5 symptoms and CRP in a conceptual replication of Jokela et al., CRP was associated with 'sleep problems', 'energy level', and 'weight/appetite changes'; only the first two links survived covariate adjustment. In a conservative model with all 38 variables, symptoms and markers were unrelated. Following recent psychometric work, we re-estimated the full model without regularization: the depressive symptoms 'insomnia', 'hypersomnia', and 'aches and pain' showed unique positive relations to all inflammatory markers. We found evidence for differential relations between markers, depressive symptoms, and covariates. Associations between symptoms and markers were attenuated after covariate adjustment; BMI and sex consistently showed strong relations with inflammatory markers.


Hematopoietic stem cells from the marrow of mice treated with Flt3 ligand are significantly expanded but exhibit reduced engraftment potential.
Hematopoietic stem cells (HSC) can be significantly expanded by hematopoietic growth factors. Flt3 ligand (FL) is a hematopoietic growth factor that induces proliferation and mobilization of HSC into the peripheral blood. We previously reported that FL-mobilized HSC exhibit superior engraftment potential. The engraftment potential of FL-expanded HSC in the bone marrow compartment has not been evaluated. In this study, we investigated the effect of in vivo administration of FL on the engraftment potential of HSC expanded in the marrow. B10.BR (H-2k) donor mice were treated for 10 days with 10 microg of FL per day. Partially conditioned allogeneic B10 (H-2b) recipients received whole bone marrow. Purified HSC (c-Kit+/Sca1+/lin-) from the marrow were also transplanted in ablated syngeneic B10.BR recipients. FL treatment significantly expanded HSC in the marrow compartment. The absolute number of T cells and granulocytes were unchanged whereas dendritic cells, facilitating cells, and HSC were significantly increased in the bone marrow of donor mice treated with FL compared with untreated mice. Mice conditioned with 700 cGy and transplanted with FL-treated allogeneic bone marrow showed a significantly lower rate of engraftment (14%) compared with recipients of bone marrow from untreated mice (100%). Syngeneic recipients transplanted with 500, 1000, 2000, or 3000 purified HSC from FL-treated donors also showed reduced long-term survival compared with mice transplanted with HSC from untreated donors. Cell cycle analysis revealed that significantly more bone marrow HSC were in cycle after FL treatment compared with unmanipulated controls. These data show that FL treatment for 10 days induces proliferation of HSC but reduces the engraftment potential of HSC harvested from the marrow. The reduced syngeneic engraftment of HSC indicates that FL treatment induces intrinsic changes in HSC, resulting in failure of long-term engraftment or self-renewal despite no change in characteristic phenotype of HSC.


Synthesis of High Molecular Weight Cyclic Poly(ε-caprolactone)s of Variable Ring Size Based on a Light-Induced Ring-Closure Approach.
High molecular weight cyclic poly(ε-caprolactone)s (cPCLs) with variable ring size are synthesized via light-induced ring closure of α,ω-anthracene-terminated PCL (An-PCL-An). The ring size of cPCL is tunable simply by adjusting the polymer concentration from 10 to 100 mg mL(-1) in THF. The cyclo-addition via the bimolecular cyclization of An-PC-An is well characterized by a variety of analyses such as (1) H NMR and UV-vis spectroscopies, gel-permeation chromatography, and differential scanning calorimetry. The reversible dimerization of An induced by heating enables the cyclic PCL to have a switchable "on-off" capability. This novel light-induced ring-closure technique can be one of the most powerful candidates for producing various well-defined cyclic polymers in highly concentrated polymer solution.


Developing co-funded multi-sectoral partnerships for chronic disease prevention: a qualitative inquiry into federal governmental public health staff experience.
Multi-sectoral partnerships (MSPs) are frequently cited as a means by which governments can improve population health while leveraging the resources and expertise of the private and non-profit sectors. As part of their efforts in this area, the Public Health Agency of Canada (the Agency) introduced a novel funding programme requiring applicants to procure matched resources from private sources to support large-scale interventions for chronic disease prevention. The current literature on MSPs is limited in its applicability to this model of multi-sectoral engagement. The purpose of this study was to explore the experiences of Agency staff working with potential partners to develop programme applications, such that we might identify lessons from adopting this type of partnership approach. Semi-structured interviews were conducted with the 12 staff working in the MSP programme. Interviews were recorded, transcribed and analysed using thematic analysis. Preliminary themes were used to inform follow up focus-groups sessions. A second round of analysis was conducted guided by a coding paradigm focused on understanding process. We identified "experiencing uncertainty" to be a central concept in participants' accounts of the MSP process, related specifically to the MSP programme's novel conditions, shifts that occurred in sectoral roles and demands for new capacities. In response, Agency staff employed strategies to clarify partner interests, build trust in inter-sectoral relationships, and support internal and partner capacity. Outcomes associated with this process include impacts on trust between the Agency and potential partners, a deeper understanding of other sectors, and programme adaptations and refinements to address challenges related to the programme model. The co-funding model employed by the Agency is a potentially popular one for government bodies wanting to leverage funding from private sector sources. Our study identifies the potential challenges that can occur under this model. Some challenges are related to addressing material conditions related to partner capacity, whereas other challenges speak to deeper and more difficult to address concerns regarding trust and alignment of motivations and interests between partners. Future research exploring the challenges associated with specific models of MSP engagement is necessary to inform approaches to addressing complex problems through collaborative efforts.


Monte Carlo calculations of electron beam output factors for a medical linear accelerator.
The purpose of this study was to investigate the application of the Monte Carlo technique to the calculation and analysis of output factors for electron beams used in radiotherapy. The code EGS4/BEAM was used to obtain phase-space files for 6, 12 and 20 MeV clinical electron beams from a scattering-foil linac (Varian Clinac 2100C) for a clinically representative range of applicator and square or rectangular insert combinations. The source-to-surface distance used was 100 cm. The field sizes ranged from 1 x 1 cm2 to 20 x 20 cm2. These phase-space files were analysed to study the intrinsic beam characteristics and used as source input for relative dose and output factor computations in homogeneous water phantoms using the code EGS4/DOSXYZ. The calculated relative central-axis depth-dose and transverse dose profiles at various depths of clinical interest agreed with the corresponding measured dose profiles to within 2% of the maximum dose. Calculated output factors for the fields studied agreed with measured output factors to about 2%. This demonstrated that for the Varian Clinac 2100C linear accelerator, electron beam dose calculations in homogeneous water phantoms can be performed accurately at the 2% level using Monte Carlo simulations.


Prophylactic antibiotics for tube thoracostomy may not be appropriate in the developing world setting.
Prophylactic antibiotics for tube thoracostomy (TT) for the prevention of post-traumatic empyema (PTE) remain controversial. Literature specifically focusing on the developing world setting is limited. A retrospective study was conducted over a four-year period on patients managed with TT alone in which prophylactic antibiotics was not utilised. We documented the actual incidence of PTE in a high volume trauma service in South Africa. A total of 1002 patients who had TT in the trauma room were eligible for inclusion. Ninety-one percent (912/1002) were males and the mean age for all patients was 26 years (SD 7). Seventy-five percent (755/1002) sustained penetrating trauma (PT), while the remaining 25% (247/1002) sustained blunt trauma (BT). Six hundred and twenty patients (62%) sustained HTXs and the remaining 382 patients (38%) had PTXs. Of the 1002 patients who underwent TT, 15 (1.5%, 95% CI: 0.8-2.5%) developed PTE. The incidence of empyema in those with PT was 1.9% (14/755) and 0.4% (1/247) for BT. This difference was not statistically significant (p=0.166). All 15 patients who developed PTE were males, with a mean age of 31 years (SD 6). All 15 patients had HTX as the initial thoracic pathology. This difference was highly statistically significant when compared to PTX (p=0.002). The mean length of hospital stay was 11 days (SD 7). There were no mortalities in these patients. In our setting where prophylactic antibiotics are not routinely used, the actual incidence of PTE in our population is extremely low. In the absence of further definitive evidence to support its use, routine prophylactic antibiotics for TT is difficult to justify in a developing world setting at present.


Absolute Quantitation of Oxidizable Peptides by Coulometric Mass Spectrometry.
Quantitation methods for peptides using mass spectrometry have advanced rapidly. These methods rely on using standard and/or isotope-labeled peptides, which might be difficult or expensive to synthesize. To tackle this challenge, we present a new approach for absolute quantitation without the use of standards or calibration curves based on coulometry combined with mass spectrometry (MS). In this approach, which we call coulometric mass spectrometry (CMS), the mass spectrum of a target peptide containing one or more tyrosine residues is recorded before and after undergoing electrochemical oxidation. We record the total integrated oxidation current from the electrochemical measurement, which according to the Faraday's Law of coulometry, provides the number of moles of oxidized peptide. The ion intensity ratio of the target peptide before and after oxidation provides an excellent estimate of the fraction of the peptide that has been oxidized, from which the total amount of peptide is calculated. The striking strength of CMS is that it needs no standard peptide, but CMS does require the peptide to contain a known number of oxidizable groups. To illustrate the power of this method, we analyzed various tyrosine-containing peptides such as GGYR, DRVY, oxytocin, [Arg8]-vasotocin and angiotensinogen 1-14 with a quantification error ranging from - 7.5 to + 2.4%. This approach is also applicable to quantifying phosphopeptides and could be useful in proteomics research.


Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface.
To evaluate whether experimentally induced dry eye in mice activates mitogen-activated protein kinase (MAPK) signaling pathways, c-Jun N-terminal kinases (JNK), extracellular-regulated kinases (ERK), and p38 and stimulates ocular surface inflammation. 129SvEv/CD-1 mixed mice aged 6 to 8 weeks were treated with systemic scopolamine and exposure to an air draft for different lengths of time, from 4 hours to 10 days. Untreated mice were used as the control. The concentrations of IL-1beta and TNF-alpha in tear fluid washings and in corneal and conjunctival epithelia were measured by ELISA. MMP-9 in tear washings was evaluated by zymography, and gelatinase activity in the cornea and conjunctiva was determined by in situ zymography. Corneal and conjunctival epithelia were lysed in RIPA buffer for Western blot with MAPK antibodies, or they were lysed in 4 M guanidium thiocyanate solution for extraction of total RNA, which was used to determine gene expression by semiquantitative RT-PCR, real-time PCR, and gene array. Compared with those in age-matched control subjects, the concentrations of IL-1beta and MMP-9 in tear fluid washings and the concentrations of IL-1beta and TNF-alpha and gelatinolytic activity in the corneal and conjunctival epithelia were significantly increased in mice receiving treatments to induce dry eye after 5 or 10 days. The expression of IL-1beta, TNF-alpha, and MMP-9 mRNA by the corneal and conjunctival epithelia was also stimulated in mice treated for 5 or 10 days. The levels of phosphorylated JNK1/2, ERK1/2, and p38 MAPKs in the corneal and conjunctival epithelia were markedly increased as early as 4 hours after treatment, and they remained elevated up to 5 days. Experimental dry eye stimulates expression and production of IL-1beta, TNF-alpha, and MMP-9 and activates MAPK signaling pathways on the ocular surface. MAPKs are known to stimulate the production of inflammatory cytokines and MMPs, and they could play an important role in the induction of these factors that have been implicated in the pathogenesis of dry eye disease.


On the symmetry of siblings: automated single-cell tracking to quantify the behavior of hematopoietic stem cells in a biomimetic setup.
The interplay between hematopoietic stem and progenitor cells (HSPC) and their local microenvironment is a key mechanism for the organization of hematopoiesis. To quantitatively study this process, a time-resolved analysis of cellular dynamics at the single-cell level is an essential prerequisite. One way to generate sufficient amounts of appropriate data is automatic single-cell tracking using time-lapse video microscopy. We describe and apply newly developed computational algorithms that allow for an automated generation of high-content data of single-cell characteristics at high temporal and spatial resolution, together with the reconstruction and statistical evaluation of complete genealogical histories. This methodology has been applied to the particular example of purified primary human HSPCs in bioengineered culture conditions. The combination of genealogical information and dynamic profiles of cellular properties identified a marked symmetry between sibling HSPCs regarding cell cycle time, but also migration speed and growth kinetics. Furthermore, we demonstrate that this symmetry of HSPC siblings can be altered by exogenous cues of the local biomimetic microenvironment. Using the example of HSPC growth in biomimetic culture systems, we show that our approach provides a valuable tool for the quantitative analysis of dynamic single-cell features under defined in vitro conditions, allowing for integration of functional and genealogical data. The efficiency and accuracy of our approach pave the way for new and intriguing insights into the organizational principles of developmental patterns and the respective influence of exogenous cues not limited to the study of primary HSPCs.


[Vestibular disorders in the minimal cerebral dysfunсtion in adults].
Vestibular dysfunction is the most frequent symptom of minimal cerebral dysfunction in adults. Objective of the research was to study the etiopathogenesis of minimal cerebral dysfunction based on the analysis of the latency of different types of induced nystagmus. Threshold stimulation by physiological stimuli was used to study vestibular function (functional load tests) for the evaluation of neurodynamical plasticity of all parts of vestibular analyzer. Sixty males with manifestations of posterior cervical sympathetic syndrome, consequences of traumatic brain injury and neuroinfection, history of syncopes were examined. Spontaneous and different types of induced nystagmus were chosen as markers of vestibular dysfunction. Results of the study demonstrated that induced nystagmus had multineuronal arc, the latency of induced nystagmus was higher than that of spontaneous nystagmus and depended on the nature of stimulus applied to the vestibular system. In 3 patients, induced nystagmus was revealed in all tests with significant latency shortening compared to induced nystagmus in other patients. Functional load tests allowed to find a significant role of autonomic dysfunction, changes in the venous outflow and CSF flow in the cranial cavity and cervical proprioception in the etiopathogenesis of latent vestibular dysfunction in patients with minimal cerebral dysfunction.


[Osseous orbitotomies using a coronal flap: a retrospective study of 87 intraorbital lesions].
To present our experience in 80 patients with intraorbital tumours and lesions who underwent 87 osseous orbitotomies with coronal incision during a 12 year period. Hemangioma was the most frequent histologic diagnosis, being the intraconical retrobulbar compartment the most common location. Bilateral presentation of lesions occurred in 7 patients. Lateral and supero-lateral orbitotomies were preferably applied (87.35%). In 90.80% of cases some kind of osteosynthesis was employed, 51.75% with bio-resorbable plates. Intraoperative exposure or dura mater breakage occurred in 10 patients. 45 transitory and 21 permanent postoperative complications were seen, being the nervous ones (diplopia and ptosis) the most frequent. Most of these were spontaneously solved in a short time period. 15 patients required multi-disciplinary collaboration with neurosurgery. Coronal incision allows any bone orbitotomy, with security, guarantee and good aesthetic and functional results. Lateral and supero-lateral orbitotomies provide an ideal extradural approach to the retrobulbar compartment. An approach to the apex, orbital channel and medial compartment to the optic nerve, usually requires a combined neurosurgical approach through anterior cranial fossa. Orbitotomy fixation with bio-resorbable ostheosynthesis is an alternative to titanium plates. They can even be a first choice in paediatric age. The morbidity of this surgical technique is low.


Binding of RNA by APOBEC3G controls deamination-independent restriction of retroviruses.
APOBEC3G (A3G) is a host-encoded protein that potently restricts the infectivity of a broad range of retroviruses. This can occur by mechanisms dependent on catalytic activity, resulting in the mutagenic deamination of nascent viral cDNA, and/or by other means that are independent of its catalytic activity. It is not yet known to what extent deamination-independent processes contribute to the overall restriction, how they exactly work or how they are regulated. Here, we show that alanine substitution of either tryptophan 94 (W94A) or 127 (W127A) in the non-catalytic N-terminal domain of A3G severely impedes RNA binding and alleviates deamination-independent restriction while still maintaining DNA mutator activity. Substitution of both tryptophans (W94A/W127A) produces a more severe phenotype in which RNA binding and RNA-dependent protein oligomerization are completely abrogated. We further demonstrate that RNA binding is specifically required for crippling late reverse transcript accumulation, preventing proviral DNA integration and, consequently, restricting viral particle release. We did not find that deaminase activity made a significant contribution to the restriction of any of these processes. In summary, this work reveals that there is a direct correlation between A3G's capacity to bind RNA and its ability to inhibit retroviral infectivity in a deamination-independent manner.


An Assembled Detector Based on Geometrical Constraint for Power Component Recognition.
The intelligent inspection of power lines and other difficult-to-access structures and facilities has been greatly enhanced by the use of Unmanned Aerial Vehicles (UAVs), which allow inspection in a safe, efficient, and high-quality fashion. This paper analyzes the characteristics of a scene containing power equipment and the operation mode of UAVs. A low-cost virtual scene is created, and a training sample for the power-line components is generated quickly. Taking a vibration-damper as the main object, an assembled detector based on geometrical constraint (ADGC) is proposed and is used to analyze the virtual dataset. The geometric positional relationship is used as the constraint, and the Faster R-CNN, Deformable Part Model (DPM), and Haar cascade classifiers are combined, which allows the features of different classifiers, such as contour, shape, and texture to be fully used. By combining the characteristics of virtual data and real data using UAV images, the power components are detected by the ADGC. The result produced by the detector with relatively good performance can help expand the training set and achieve a better detection model. Moreover, this method can be smoothly transferred to other power-line facilities and other power-line scenarios.


High-frequency oscillatory ventilation as a rescue for severe asthma crisis in a child.
Mechanical ventilation in the asthmatic child may be complicated by dynamic air trapping leading to hemodynamic compromise and cardiac arrest. High-frequency oscillatory ventilation is relatively contraindicated because it may cause hyperinflation compared to conventional mechanical ventilation. A 2-year-old girl (weight, 11 kg) with a history of asthma was admitted because of status asthmaticus. Despite treatment with intravenous methylprednisolone, continuous albuterol, terbutaline, aminophylline, and magnesium sulfate, she had persistent respiratory distress. She required endotracheal intubation and mechanical ventilation because of worsening respiratory fatigue and hypercarbia ((PCO2), 96 mm Hg). Severe airflow obstruction persisted, and the hypercarbia worsened despite conventional mechanical ventilation (PCO2 > 134 mm Hg). It was judged that the patient was at risk for dynamic air trapping leading to hemodynamic compromise and cardiac arrest. High-frequency oscillatory ventilation was started to overcome airflow obstruction, and a decrease in arterial PCO2 to 87 mm Hg was observed within 2 h. High-frequency oscillatory ventilation was discontinued after 5 h, and conventional mechanical ventilation resumed. The patient was extubated after 5 days without further complications. In summary, this case shows that high-frequency oscillatory ventilation may be considered as a rescue treatment in children who have severe status asthmaticus with persistent airflow obstruction and hypercarbia unresponsive to pharmacological therapy and conventional mechanical ventilation.


The effects of co-morbidity in defining major depression subtypes associated with long-term course and severity.
Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods. However, it is not known whether these distinctions can be refined by added information about co-morbid conditions. The current report presents results on this question. Data came from 8261 respondents with lifetime DSM-IV MDD in the World Health Organization (WHO) World Mental Health (WMH) Surveys. Outcomes included four retrospectively reported measures of persistence/severity of course (years in episode; years in chronic episodes; hospitalization for MDD; disability due to MDD). Machine learning methods (regression tree analysis; lasso, ridge and elastic net penalized regression) followed by k-means cluster analysis were used to augment previously detected subtypes with information about prior co-morbidity to predict these outcomes. Predicted values were strongly correlated across outcomes. Cluster analysis of predicted values found three clusters with consistently high, intermediate or low values. The high-risk cluster (32.4% of cases) accounted for 56.6-72.9% of high persistence, high chronicity, hospitalization and disability. This high-risk cluster had both higher sensitivity and likelihood ratio positive (LR+; relative proportions of cases in the high-risk cluster versus other clusters having the adverse outcomes) than in a parallel analysis that excluded measures of co-morbidity as predictors. Although the results using the retrospective data reported here suggest that useful MDD subtyping distinctions can be made with machine learning and clustering across multiple indicators of illness persistence/severity, replication with prospective data is needed to confirm this preliminary conclusion.


Absorption and fluorescence spectra of light-harvesting bacteriochlorophyll-protein complexes from Rhodopseudomonas palustris in the near-infrared region.
Bacteriochlorophyll (Bchl)-protein complexes were isolated from Rhodopseudomonas palustris. Detergent treatment and polyacrylamide gel electrophoresis under rather mild conditions resulted in clear separation of light-harvesting Bchls into B870 Bhls and B800-850 Bchls as two distinctly different protein complexes. It was shown that almost all the Bchl contained in intracytoplasmic membranes was recovered as either B870-reaction center complexes or B800-850 complexes without loss of Bchls as free pigments. Furthermore, it was shown that the spectral form of each type of Bchl was not altered by this procedure for isolation, as judged by the calculated absorption spectrum which was the sum of the absorption spectra of the isolated complexes. Fluorescence measurement of the isolated complexes and intracytoplasmic membranes not only supported these ideas, but also indicated that the excited state was actually transferred from B800-850 Bchls to B870 Bchls. The isolation and measurements of absorption and fluorescence were carried out on spectrally different types of intracytoplasmic membrane from cells cultured under different culture conditions. The B870-reaction center complexes from different types of intracytoplasmic membrane were spectrally identical. The B800-850 complexes were widely different in absorption spectra, especially in the ratios of peaks at 800 and 850 nm, but exhibited similar fluorescence spectra.


Chemical weed control in triticale (x Triticosecale Wittmack): review of five years of field experiments.
During five subsequent growing seasons field experiments were carried out at the experimental farm of the University College Ghent (Belgium) to evaluate the selectivity and efficacy of herbicides for chemical weed control in triticale (x Triticosecale Wittmack). The experiments were set up on a sandy loam soil, according to a completely randomised block design with four replicates. Several herbicides and combinations of herbicides were applied pre- and post-emergence, at different rates. The influence of the different treatments on weed diversity, weed density, growth inhibition and chlorosis of the crop and grain yield was studied. Results obtained from these field trials indicated differences between the different treatments.


Sperm recovery and ICSI outcomes in Klinefelter syndrome: a systematic review and meta-analysis.
Specific factors underlying successful surgical sperm retrieval rates (SRR) or pregnancy rates (PR) after testicular sperm extraction (TESE) in adult patients with Klinefelter syndrome (KS) have not been completely clarified. The aim of this review was to meta-analyse the currently available data from subjects with KS regarding SRRs as the primary outcome. In addition, when available, PRs and live birth rates (LBRs) after the ICSI technique were also investigated as secondary outcomes. An extensive Medline, Embase and Cochrane search was performed. All trials reporting SRR for conventional-TESE (cTESE) or micro-TESE (mTESE) and its specific determinants without any arbitrary restriction were included. Out of 139 studies, 37 trials were included in the study, enrolling a total of 1248 patients with a mean age of 30.9 ± 5.6 years. The majority of the studies (n = 18) applied mTESE, 13 applied cTESE and in one case testicular sperm aspiration (TESA) was used. Additionally, four studies used a mixed approach and in one study, the method applied for sperm retrieval was not specified. Overall, a SRR per TESE cycle of 44[39;48]% was detected. Similar results were observed when mTESE was compared to cTESE (SRR 43[35;50]% vs 45[38;52]% for cTESE vs micro-TESE, respectively; Q = 0.20, P = 0.65). Meta-regression analysis showed that none of the parameters tested, including age, testis volume and FSH, LH and testosterone (T) levels at enrollment, affected the final SRR. Similarly, no difference was observed when a bilateral procedure was compared to a unilateral approach. No sufficient data were available to evaluate the effect of previous T treatment on SRR. Information on fertility outcome after ICSI was available for 29 studies. Overall a total of 218 biochemical pregnancies after 410 ICSI cycles were observed (PR = 43[36;50]%). Similar results were observed when LBR was analyzed (LBR = 43[34;53]%). Similar to what was observed for SRR, no influence of KS age, mean testis volume, LH, FSH or total T levels on either PR and LBR was observed. No sufficient data were available to test the effect of the women's age or other female fertility problems on PR and LBR. Finally, no difference in PR or LBR was observed when the use of fresh sperm was compared to the utilization of cryopreserved sperm. The present data suggest that performing TESE/micro-TESE in subjects with KS results in SRRs of close to 50%, and then PRs and LBRs of close to 50%, with the results being independent of any clinical or biochemical parameters tested.


Translational illusion of acoustic sources by transformation acoustics.
An acoustic illusion of creating a translated acoustic source is designed by utilizing transformation acoustics. An acoustic source shifter (ASS) composed of layered acoustic metamaterials is designed to achieve such an illusion. A practical example where the ASS is made with naturally available materials is also given. Numerical simulations verify the performance of the proposed device. The designed ASS may have some applications in, e.g., anti-sonar detection.


Surgeon and Radiation Oncologist Views on Omission of Adjuvant Radiotherapy for Older Women with Early-Stage Breast Cancer.
Although clinical trials have shown no survival advantage and only a modest improvement in local control from adjuvant radiotherapy after lumpectomy in older women with stage I, estrogen receptor-positive (ER+) breast cancer, radiotherapy is commonly administered, raising concerns about overtreatment. Therefore, we sought to evaluate physician views on omission of radiotherapy in older women with favorable prognosis breast cancer. We surveyed a national sample of 713 radiation oncologists and 879 surgeons. Of these, 1504 were eligible and 825 responded (55%). We assessed responses to clinical scenarios, knowledge of pertinent risk information, and correlates of views on radiotherapy omission. Omission of radiotherapy in patients age ≥70 years with stage I, ER+ breast cancer, treated with lumpectomy and endocrine therapy, was felt to be unreasonable by 40% of surgeons and 20% of radiation oncologists. Many surgeons (29%) and radiation oncologists (10%) erroneously associated radiotherapy in older women with improvement in survival. Similarly, 32% of surgeons and 19% of radiation oncologists tended to substantially overestimate the risk of locoregional recurrence in older women with omission of RT. In a scenario with an 81-year-old with multiple comorbidities, 31% of surgeons and 35% of radiation oncologists would still recommend radiotherapy. Many radiation oncologists and surgeons continue to consider omission of radiotherapy as substandard therapy and overestimate the benefits of radiotherapy. Surgeons, in addition to radiation oncologists, may have an opportunity to play a pivotal role in reducing overuse of aggressive care in this setting.


Seroepidemiology of Toxoplasma gondii infection in a Mennonite community in Durango State, Mexico.
There is a lack of information concerning the epidemiology of Toxoplasma gondii infection in Mennonites (an ethnic group of Mexican citizens of German descent living in rural communities). The prevalence of anti- T. gondii immunoglobulin (Ig) G and IgM antibodies was examined in 152 Mennonites in Durango State, Mexico, using enzyme-linked immunoassays. In total, 46 (30.3%) of 152 participants (mean age 38.4 ± 15.5 yr) had IgG T. gondii antibodies; 5 (3.3%) also had IgM T. gondii antibodies. Toxoplasma gondii infection was significantly associated with the presence of cats at home (adjusted OR = 3.93; 95% CI: 1.40-11.05), raising cattle (adjusted OR = 3.88; 95% CI: 1.24-12.11), consumption of pigeon meat (adjusted OR = 3.0; 95% CI: 1.36-6.63), and consumption of untreated water (adjusted OR = 2.42; 95% CI: 1.09-5.40). This is the first report of seroprevalence and contributing factors for T. gondii infection in Mennonites and of an association of the consumption of pigeon meat with T. gondii infection. Results of this study should be useful in the design of optimal preventive measures against T. gondii infection.


Early increases in breast tumor xenograft water mobility in response to paclitaxel therapy detected by non-invasive diffusion magnetic resonance imaging.
An important goal in cancer chemotherapy is to sensitively and quantitatively monitor the response of individual patients' tumors to successful, or unsuccessful, therapy so that regimens can be altered iteratively. Currently, tumor response is monitored by frank changes in tumor morphology, yet these markers take long to manifest and are not quantitative. Recent studies suggest that the apparent diffusion coefficient of water (ADCw), measured noninvasively with magnetic resonance imaging, is sensitively and reliably increased in response to successful CTx. In the present study, we investigate the combination chemotherapy response of human breast cancer tumor xenografts sensitive or resistant to Paclitaxel by monitoring changes in the ADCw. Our results indicate that there is a clear, substantial, and early increase in the ADCw after successful therapy in drug sensitive tumors and that there is no change in the ADCw in p-glycoprotein-positive tumors, which are resistant to Paclitaxel. The mechanism underlying these changes is unknown yet is consistent with apoptotic cell shrinkage and a concomitant increase in the extracellular water fraction.


[Serologic response against hepatitis C virus as a predictive factor to the treatment with interferon].
Serologic response of patients with chronic hepatitis C (CHC) was studied as a predictor of response to IFN therapy and we evaluated the correlation between such response with gender, risk factor, serum ferritin, GGT, Knodell's index and fibrosis. A study was carried out in 40 patients with CHC who were treated with interferon-alpha 3 MU 3 times weekly 48 weeks. The diagnosis of hepatitis C was made based upon Inmuno-Blot (core, NS3, NS4 y NS5) and confirmed by detection of HCV-RNA in serum. Responses were evaluated (normal ALT and undetectable HCV-RNA in serum) at three months, at the end of treatment and six months after treatment. No significant differences were observed in responses at three months with regard to gender (47% males responded versus 55% females, n.s.), source of infection (50% intravenous drug users versus 50% non intravenous drug users; n.s.) and GGT level (50% with high levels versus 50% with normal levels, n.s.); however 25% of patients with high level of serum iron responded versus 59% with normal values (p = 0.04) and 28% of patients with fibrosis at liver histopathology responded versus 82% without fibrosis (p = 0.0006). No differences were observed at the response rates with regard to levels of core (20.1 SD:4 versus 19.5 SD:2.2, n.s.), NS3 (18.6 SD:7 versus 17.1 SD:7.3, n.s.) and NS4 (14.3 SD:7.7 versus 10.5 SD:9.2, n.s.). However NS5 levels in responders were 2.5 (0-16) versus 5.2 (0-16.5) in nonresponders (p < 0.05) and score in Knodell's index was 6.1 SD:2.6 in responders versus 9.2 SD:2.4 in nonresponders (p = 0.006). 47% of responders relapsed 6 months after the end of treatment with IFN. Titers of anti-NS5 showed predictive value of response as opposed to anti-core, anti-NS3 and anti-NS4 and it may justify its determination in the assessment of a patient with CHC at centers without capacity for measuring genotype and viral load. Low level of serum iron and Knodell's index like absence of fibrosis at liver histopathology were also variables with predictive value of response, as opposed to gender, GGT level and source of infection.


Factor H-related protein 1 (CFHR-1) inhibits complement C5 convertase activity and terminal complex formation.
Homozygous deletion of a 84-kb genomic fragment in human chromosome 1 that encompasses the CFHR1 and CFHR3 genes represents a risk factor for hemolytic uremic syndrome (HUS) but has a protective effect in age-related macular degeneration (AMD). Here we identify CFHR1 as a novel inhibitor of the complement pathway that blocks C5 convertase activity and interferes with C5b surface deposition and MAC formation. This activity is distinct from complement factor H, and apparently factor H and CFHR1 control complement activation in a sequential manner. As both proteins bind to the same or similar sites at the cellular surfaces, the gain of CFHR1 activity presumably is at the expense of CFH-mediated function (inhibition of the C3 convertase). In HUS, the absence of CFHR1 may result in reduced inhibition of terminal complex formation and in reduced protection of endothelial cells upon complement attack. These findings provide new insights into complement regulation on the cell surface and biosurfaces and likely define the role of CFHR1 in human diseases.


Did I Do That? Expectancy Effects of Brain Stimulation on Error-related Negativity and Sense of Agency.
This study examines the effects of expected transcranial stimulation on the error(-related) negativity (Ne or ERN) and the sense of agency in participants who perform a cognitive control task. Placebo transcranial direct current stimulation was used to elicit expectations of transcranially induced cognitive improvement or impairment. The improvement/impairment manipulation affected both the Ne/ERN and the sense of agency (i.e., whether participants attributed errors to oneself or the brain stimulation device): Expected improvement increased the ERN in response to errors compared with both impairment and control conditions. Expected impairment made participants falsely attribute errors to the transcranial stimulation. This decrease in sense of agency was correlated with a reduced ERN amplitude. These results show that expectations about transcranial stimulation impact users' neural response to self-generated errors and the attribution of responsibility-especially when actions lead to negative outcomes. We discuss our findings in relation to predictive processing theory according to which the effect of prior expectations on the ERN reflects the brain's attempt to generate predictive models of incoming information. By demonstrating that induced expectations about transcranial stimulation can have effects at a neural level, that is, beyond mere demand characteristics, our findings highlight the potential for placebo brain stimulation as a promising tool for research.


Creating change agents: a national substance abuse education project.
This study evaluated the effects of a national interdisciplinary faculty development program, Project MAINSTREAM, on creating curriculum enhancement in health professional education. Thirty-nine faculty completed a two-year, part-time fellowship program featuring interdisciplinary collaboration, mentoring, training meetings, and Internet-based instructional materials. The main vehicle for curricular change was a required collaborative education project to develop trainees' core competencies in substance abuse prevention services. Fellows used a variety of approaches to implement 123 curricula and provide 66,995 hours of training to 10,170 trainees. Ninety percent of the training hours occurred in required courses, a potential indication of sustainability. Fellows indicated that a majority of the offerings would be sustained beyond the fellowship. Project MAINSTREAM shows promise as a model for achieving durable curriculum change in response to the public health crisis associated with a workforce untrained to deliver substance abuse services.


Current challenges for the advancement of neural stem cell biology and transplantation research.
Transplantation of neural stem cells (NSC) is hoped to become a promising primary or secondary therapy for the treatment of various neurodegenerative disorders of the central nervous system (CNS), as demonstrated by multiple pre-clinical animal studies in which functional recovery has already been demonstrated. However, for NSC therapy to be successful, the first challenge will be to define a transplantable cell population. In the first part of this review, we will briefly discuss the main features of ex vivo culture and characterisation of NSC. Next, NSC grafting itself may not only result in the regeneration of lost tissue, but more importantly has the potential to improve functional outcome through many bystander mechanisms. In the second part of this review, we will briefly discuss several pre-clinical studies that contributed to a better understanding of the therapeutic potential of NSC grafts in vivo. However, while many pre-clinical animal studies mainly report on the clinical benefit of NSC grafting, little is known about the actual in vivo fate of grafted NSC. Therefore, the third part of this review will focus on non-invasive imaging techniques for monitoring cellular grafts in the brain under in vivo conditions. Finally, as NSC transplantation research has evolved during the past decade, it has become clear that the host micro-environment itself, either in healthy or injured condition, is an important player in defining success of NSC grafting. The final part of this review will focus on the host environmental influence on survival, migration and differentiation of grafted NSC.


Relationship type, condom use and HIV/AIDS risks among men who have sex with men in six Chinese cities.
This study is the first to examine the role of partner type in sexual practices of men who have sex with men (MSM) in China. Using cross-sectional self-administered questionnaires (N=692) with MSM in six Chinese cities (Shanghai, Guangzhou, Shenzhen, Xi'an, Dalian and Beijing) in 2008, this paper examines MSM's sexual practices, particularly condom use with different male and female partner types. We categorise sexual partner relationships into five types: partner/spouse, boyfriend/girlfriend, acquaintance, stranger and sex worker and hypothesise that the greater the affective distance between the partners, the greater the likelihood of engaging with intimate act and the lesser likelihood condom use. Results show that respondents had more MSM than heterosexual experiences. Relationships tended to be short-term, multiple (more than two) and concurrent (simultaneously two or more) principally with other men and to a lesser degree with women. Findings reveal that affective distance varied with partner types. Respondents performed more intimate acts (e.g., kissing, caressing) with intimate or stable partners (partner/spouse, boyfriend/girlfriend) than casual or unknown partners (acquaintance, stranger, sex worker). Condom use decreased when the affective distance with a partner increased. We conclude that partner type is a key factor of HIV infection among MSM in China; short-term, multiple and concurrent relationships are clear risk factors. Future research should focus on the subjective varied meanings of relationships, the idea of trust and the dynamics with different relationships to understand HIV infection of MSM in China.


The Influence of Lifestyle Factors on the Occurrence and Severity of Premature Ventricular Contractions: A Comprehensive Review.
Premature ventricular contractions (PVC) are a type of ventricular arrhythmias, occurring as a result of formation or reentry of an abnormal impulse in the ventricular myocardium or in the Purkinje system. PVC occurs commonly in healthy individuals and is observed in 1%-4% of the population. Several lifestyle factors like stress levels, caffeine, drugs, alcohol, nicotine, sleep, and physical exercise have been implicated in increasing the risk. Caffeine and drugs precipitate heightened cardiac stimulation, precipitating PVCs. Excessive alcohol and nicotine disturb the electrical pathways resulting in PVCs. Higher rates of PVCs have been associated with obesity. Individuals with insomnia and increased stress levels are also at an increased risk due to an imbalance in the autonomic system. Exercise is known to induce PVCs, including in healthy, asymptomatic individuals. Modification of these factors can decrease PVC risk. This article aims to provide a comprehensive review of the effects of lifestyle factors on PVC.


An online study of Australian Enrolled Nurse conversion.
This paper reports the findings of a study exploring the reasons why rural Enrolled Nurses have chosen to convert to level 1 of the nursing register. Whilst the Project 2000: A New Preparation for Practice report resulted in the cessation of second level or Enrolled Nurse training in the United Kingdom, Australia has continued to educate enrolled nurses. Currently Australia is facing critical shortages of level 1 nurses and nowhere is this more acute than in rural areas. There are indications that there are large numbers of rural Enrolled Nurses who are interested in 'converting' from level 2 to level 1 of the nursing register. Using a computer program that facilitates engagement and interaction, an 'online' focus group was conducted with 38 Enrolled Nurses undertaking a conversion programme at a rural university in Victoria, Australia. During a period of 2 months the Enrolled Nurses participated in a discussion focusing on their reasons for undertaking a conversion programme. Their responses were categorized into five interrelated broad themes. These Enrolled Nurses suggested that disillusionment with their role and role ambiguity were the primary reasons for their decision to undertake a conversion programme. All participants suggested that their scope of practice as an Enrolled Nurse is significantly broadened in rural areas. They argued that, following conversion, they are in an ideal position to manage the diversity of rural nursing practice. In Australia, Enrolled Nurse conversion has the potential to ease some of the workforce shortages, particularly in rural areas. By supporting Enrolled Nurses to undertake conversion programmes, rural areas may benefit from having nurses with the knowledge and skills to deal with the rural environment.


Specificity of synergistic coronary flow enhancement by adenosine and pulsatile perfusion in the dog.
1. Coronary flow elevation from enhanced perfusion pulsatility is synergistically amplified by adenosine. This study determined the specificity of this interaction and its potential mechanisms. 2. Mean and phasic coronary flow responses to increasing pulsatile perfusion were assessed in anaesthetized dogs, with the anterior descending coronary artery servoperfused to regulate real-time physiological flow pulsatility at constant mean pressure. Pulsatility was varied between 40 and 100 mmHg. Hearts ejected into the native aorta whilst maintaining stable loading. 3. Increasing pulsatility elevated mean coronary flow +11.5 +/- 1.7 % under basal conditions. Co-infusion of adenosine sufficient to raise baseline flow 66 % markedly amplified this pulsatile perfusion response (+82. 6 +/- 14.3 % increase in mean flow above adenosine baseline), due to a leftward shift of the adenosine-coronary flow response curve at higher pulsatility. Flow augmentation with pulsatility was not linked to higher regional oxygen consumption, supporting direct rather than metabolically driven mechanisms. 4. Neither bradykinin, acetylcholine nor verapamil reproduced the synergistic amplification of mean flow by adenosine and higher pulsatility, despite being administered at doses matching basal flow change with adenosine. 5. ATP-sensitive potassium (KATP) activation (pinacidil) amplified the pulse-flow response 3-fold, although this remained significantly less than with adenosine. Co-administration of the phospholipase A2 inhibitor quinacrine virtually eliminated adenosine-induced vasodilatation, yet synergistic interaction between adenosine and pulse perfusion persisted, albeit at a reduced level. 6. Thus, adenosine and perfusion pulsatility specifically interact to enhance coronary flow. This synergy is partially explained by KATP agonist action and additional non-flow-dependent mechanisms, and may be important for modulating flow reserve during exercise or other high output states where increased flow demand and higher perfusion pulsatility typically co-exist.


Prognostic value of duration of untreated psychosis in long-term outcome of schizophrenia.
The goal of this prognostic study was to investigate whether the duration of untreated psychosis (DUP) may have a prognostic value with regard to the further course of the illness. Fifty-eight patients (77% of the original study group) diagnosed with DSM III schizophrenia and later re-diagnosed with DSM IV T-R were assessed at 4 time points. Number of relapses, average time of inpatient treatment, number of inpatient readmissions, and severity of psychopathological symptoms were assessed at 1-, 3-, 7- and 12-year follow-ups. DUP information was obtained by clinical interview with patients and their families. The severity of symptoms was assessed using BPRS-SA, UCLA version. Increases in the number of relapses at follow-ups were more prominent in the group with a longer DUP (p<0.001). Decreases in the results of BPRS (symptom improvement) were more prominent in patients with a shorter DUP. The latter had significantly lower results than patients with a long DUP at each assessment except the index hospitalization (p equalled, respectively: 0.449; 0.002; 0.012; 0.034 and 0.014). Decreases in positive symptoms were greater in patients with a short DUP--significant at all except the 7-year follow-up (p equalled respectively: 0.230; <0.001; 0.011; 0.214; <0.001). 1) A positive correlation was found between DUP and the dynamics of general and positive symptoms and the number of relapses. 2) There was no significant relationship between DUP and the dynamics of negative symptoms, whereas the relationship between the time and number of re-hospitalizations was marginally significant.


[Ultrasonic diagnosis of complications after bypass operations in lower extremities arteries].
After reconstructive vascular operations the patients need dynamic control and non-invasive monitoring. The purpose of the study was to reveal the potential of duplex scanning (DS) in assessment of bypasses function and diagnosis of postoperative complications. 148 patients after aorto-femoral and femoro-popliteal bypass, including patients with late postoperative complications (shunt thrombosis, stenosis or spurious aneurysm of anastomosis) were examined. Energy colored DS was performed in scans "Toshiba" SSH-140 and "Acuson" Sequoia-512. In ultrasonic diagnosis the vascular graft was imaged as a tube structure with hyperechogenic walls and distinct pulse; it was easy to detect the material of vascular graft. In examination of distal anastomosis the initial portions of efferent arteries were usually imaged distinctly. In satisfactory distal vascular bed, the shunt's blood flow did not differ from normal blood flow. In patients with multifocal lesions the spectrum of shunt's blood flow was similar to main-changed blood flow. Substantial change of blood velocity was revealed in complications (aneurysm or stenosis of anastomosis). Spurious aneurysm was imaged as a hypoechogenic pulsating formation. Thrombotic masses in aneurysm's cavity were distinctly detected at DS, unlike at angiography. In case of anastomosis insufficiency, the suture's disrupted filaments and free branch's ends could be imaged. Stenosis of anastomosis was characterized by visible lumen's stenosis, local thickening and unevenness of wall, spectrum's change and blood velocity increase. In shunt's thrombosis the DS permitted to follow the thrombed graft's path, to reveal the cause of thrombosis and to detect the condition of outflow tract. The authors regard DS as a method of choice in dynamic control for state of bypasses and arteries in patients after reconstructive operations in lower extremities arteries.


A survey of the beliefs regarding international emergency medicine among fourth-year medical students planning on matching in emergency medicine.
With the recent growth of fellowships in international emergency medicine, the authors sought to evaluate medical students' attitudes toward international emergency medicine and to determine the effects these attitudes have on their residency selection. Cross-sectional survey. An anonymous, eight-question online survey was distributed to all members of the American Academy of Emergency Medicine Resident and Student section. This survey was also distributed to fourth-year medical students rotating through the Emergency Department at Los Angeles County and the University of Southern California. Ninety-eight surveys were collected, 61 from rotating students and 37 from the AAEM mailing. There were no statistically significant differences in responses between the two groups. Of the respondents, 49.4% of have been exposed to IEM, and 46.9% have participated in international health projects. Ninety-four percent agree that IEM is an exciting career option. Seventy-nine percent said programs with IEM opportunities are more appealing than those without, and 45% said the presence of IEM opportunities would be an important factor in rank list; 53% believe that IEM requires formal public health training, and 63% believe it requires tropical medicine training; 68.3%of respondents speak a language in addition to English. This subset was more likely to have participated in IEM projects previously (p = 0.026) but not more likely to make match choices based on IEM. Half of medical students surveyed had prior experience in international health, and most agree that international emergency medicine is an exciting career option. Over two thirds believe that the presence of IEM opportunities will be a factor in their match list decision.


Rapid and Scalable Plant-Based Production of a Potent Plasmin Inhibitor Peptide.
The backbone cyclic and disulfide bridged sunflower trypsin inhibitor-1 (SFTI-1) peptide is a proven effective scaffold for a range of peptide therapeutics. For production at laboratory scale, solid phase peptide synthesis techniques are widely used, but these synthetic approaches are costly and environmentally taxing at large scale. Here, we developed a plant-based approach for the recombinant production of SFTI-1-based peptide drugs. We show that transient expression in Nicotiana benthamiana allows for rapid peptide production, provided that asparaginyl endopeptidase enzymes with peptide-ligase functionality are co-expressed with the substrate peptide gene. Without co-expression, no target cyclic peptides are detected, reflecting rapid in planta degradation of non-cyclized substrate. We test this recombinant production system by expressing a SFTI-1-based therapeutic candidate that displays potent and selective inhibition of human plasmin. By using an innovative multi-unit peptide expression cassette, we show that in planta yields reach ~60 μg/g dry weight at 6 days post leaf infiltration. Using nuclear magnetic resonance structural analysis and functional in vitro assays, we demonstrate the equivalence of plant and synthetically derived plasmin inhibitor peptide. The methods and insights gained in this study provide opportunities for the large scale, cost effective production of SFTI-1-based therapeutics.


Identification and characterization of a novel infectious bursal disease virus from outbreaks in Maharashtra Province of India.
The study was undertaken to isolate infectious bursal disease virus (IBDV) from clinical cases in broiler and cockerel flocks of Maharashtra state, India, and its molecular epidemiological investigation. The morbid bursal tissues were collected from flocks suspected for IBD. The samples were subjected for virus adaptation in primary chicken embryo fibroblast (CEF) cells followed by confirmation by reverse transcription polymerase chain reaction (RT-PCR) for partial VP2 sequence and phylogenetic analysis. The isolation of IBDV from field samples took seven blind passages for adaptation in CEF. The cytopathic effects included rounding, aggregation, vacuolation, and detachment of the cells. The RT-PCR showed amplification of 627 bp amplicon specific to the primers for VP2 gene fragment which confirmed successful adaptation and isolation of IBDV using CEF. The nucleotide and deduced amino acids based on phylogeny clustered the current isolate in a distinct clade with classical virulent and antigenic variants. It showed divergence from very virulent (vv) and vaccine strains of Indian origin. The isolate showed unique amino acid substitution at A329V as compared to all other IBDVs. The variation in key amino acids was reported at A222, I242, Q249, Q253, A256, T270, N279, T284, I286, L294, N299, and V329. It shared conserved amino acids at position A222, I242, and Q253 as reported in vvIBDV isolates. However, the amino acids reported at position T270, N279, T284, L294, and N299 are conserved in classic, antigenic variant and attenuated strains of IBDV. The amino acids at positions N279 and T284 indicated that the isolate has key amino acids for cell culture replication. The IBDV field isolate does not reveal the full nucleotide sequence signature of vvIBDV as well as vaccine strains. Hence, we can conclude that it might not belong to vvIBDVs of Indian origin and the vaccine strain used in the region. This may be suggestive of the evolution of the IBDV in the field due to the coexistence of circulating field strains and live attenuated hot strains, resulting into morbidity and mortality, warranting the need for safer protective vaccines, and implementation of stringent biosecurity measures to minimize loss to farmers.


Diagnosis and management of 365 ureteric injuries following obstetric and gynecologic surgery in resource-limited settings.
Ureteric injuries are among the most serious complications of pelvic surgery. The incidence in low-resource settings is not well documented. This retrospective review analyzes a cohort of 365 ureteric injuries with ureterovaginal fistulas in 353 women following obstetric and gynecologic operations in 11 countries in Africa and Asia, all low-resource settings. The patients with ureteric injury were stratified into three groups according to the initial surgery: (a) obstetric operations, (b) gynecologic operations, and (c) vesicovaginal fistula (VVF) repairs. The 365 ureteric injuries in this series comprise 246 (67.4%) after obstetric procedures, 65 (17.8%) after gynecologic procedures, and 54 (14.8%) after repair of obstetric fistulas. Demographic characteristics show clear differences between women with iatrogenic injuries and women with obstetric fistulas. The study describes abdominal ureter reimplantation and other treatment procedures. Overall surgical results were good: 92.9% of women were cured (326/351), 5.4% were healed with some residual incontinence (19/351), and six failed (1.7%). Ureteric injuries after obstetric and gynecologic operations are not uncommon. Unlike in high-resource contexts, in low-resource settings obstetric procedures are most often associated with urogenital fistula. Despite resource limitations, diagnosis and treatment of ureteric injuries is possible, with good success rates. Training must emphasize optimal surgical techniques and different approaches to assisted vaginal delivery.


Effect of light bias on male mating signal and female mate choice in a sexually dimorphic Amazon fish.
Colourful signals are usually honest indicators of mate quality since they are energetically costly. However, how colours are perceived by choosers is highly affected by the environmental light condition. Amazon black waters are strongly red-biased while clear waters show no apparent colour bias. The sailfin tetra Crenuchus spilurus is a sexually dimorphic Amazon fish species; males have hyperallometric dorsal and anal fins conspicuously ornamented with red and yellow markings. The species has two main lineages, which inhabit black and clear waters. A comparison of the red colouration of the ornaments of males from different lineages indicates that red bias increases the perceived intensity of red colouration but decreases the perceived among-individual variation in red colour. In mate choice experiments, females from all lineages preferred males with larger ornaments. Clear water lineage females were more likely to accept males under red-biased lighting, which increases the apparent red colouration, suggesting the importance of the red colouration in their mate choice. On the other hand, male acceptance by females from black waters did not change under different light conditions, suggesting that signals other than the red colouration (e.g. size of ornaments) were more important in their mate choice.


Cytochrome P450 inhibition profile in liver of veal calves administered a combination of 17beta-estradiol, clenbuterol, and dexamethasone for growth-promoting purposes.
The effects of the administration of a combination of 17beta-estradiol (10mg i.m. for three times at 17 days intervals), dexamethasone (4 mg/day for 6 days and 5mg/day for further 6 days, dissolved in milk), and clenbuterol (20 microg/kg b.w./day, dissolved in milk, for the last 40 days before slaughtering) for growth-promoting (GP) purposes on liver drug metabolising capacity were studied in crossbred Friesian male calves. Compared to controls, liver preparations from GP-treated calves showed an overall reduction in the extent of the in vitro ability to metabolize testosterone and a number of substrates, most notably those associated with CYP 2C or CYP 3A, which also displayed a reduced expression on western blotting. By contrast, the tested hydrolytic and conjugative pathways were not significantly affected. As measured by northern blot, the lack of significant differences in CYP mRNA abundance point to a post-transcriptional effect of the GP combination. The remarkable involvement of the affected hepatic CYPs in the biotransformation of both steroid hormones and a large array of commonly used drugs may result in the further accumulation of undesirable residues in meat and offals of illegally treated calves.


Quantitative phosphoproteomic analysis of soybean root hairs inoculated with Bradyrhizobium japonicum.
Root hairs are single hair-forming cells on roots that function to increase root surface area, enhancing water and nutrient uptake. In leguminous plants, root hairs also play a critical role as the site of infection by symbiotic nitrogen fixing rhizobia, leading to the formation of a novel organ, the nodule. The initial steps in the rhizobia-root hair infection process are known to involve specific receptor kinases and subsequent kinase cascades. Here, we characterize the phosphoproteome of the root hairs and the corresponding stripped roots (i.e. roots from which root hairs were removed) during rhizobial colonization and infection to gain insight into the molecular mechanism of root hair cell biology. We chose soybean (Glycine max L.), one of the most important crop plants in the legume family, for this study because of its larger root size, which permits isolation of sufficient root hair material for phosphoproteomic analysis. Phosphopeptides derived from root hairs and stripped roots, mock inoculated or inoculated with the soybean-specific rhizobium Bradyrhizobium japonicum, were labeled with the isobaric tag eight-plex iTRAQ, enriched using Ni-NTA magnetic beads and subjected to nanoRPLC-MS/MS1 analysis using HCD and decision tree guided CID/ETD strategy. A total of 1625 unique phosphopeptides, spanning 1659 nonredundant phosphorylation sites, were detected from 1126 soybean phosphoproteins. Among them, 273 phosphopeptides corresponding to 240 phosphoproteins were found to be significantly regulated (>1.5-fold abundance change) in response to inoculation with B. japonicum. The data reveal unique features of the soybean root hair phosphoproteome, including root hair and stripped root-specific phosphorylation suggesting a complex network of kinase-substrate and phosphatase-substrate interactions in response to rhizobial inoculation.


Integration of the yeast retrotransposon Ty1 is targeted to regions upstream of genes transcribed by RNA polymerase III.
Retroviruses and their relatives, the LTR-containing retrotransposons, integrate newly replicated cDNA copies of their genomes into the genomes of their hosts using element-encoded integrases. Although target site selection is not well understood for this general class of elements, it is becoming clear that some elements target their integration events to very specific regions of their host genomes. Evidence is accumulating that the yeast retrotransposon Ty1 behaves in this manner. Ty1 is found frequently adjacent to tRNA genes in the yeast genome and experimental evidence implicates these regions as preferred integration sites. To determine the basis for Ty1 targeting, we developed an in vivo integration assay using a Ty1 donor plasmid and a second target plasmid that could be used to measure the relative frequency of Ty1 integration into sequences cloned from various regions of the yeast genome. Targets containing genes transcribed by RNA polymerase III (Pol III) were up to several hundredfold more active as integration targets than "cold" sequences lacking such genes. High-frequency targeting was dependent on Pol III transcription, and integration was "region specific," occurring exclusively upstream of the transcription start sites of these genes. Thus, Ty1 has evolved a powerful targeting mechanism, requiring Pol III transcription to integrate its DNA at very specific locations within the yeast genome.


Alpha 1-adrenoceptor mediation of urinary bicarbonate excretion.
The adrenoceptor mechanism that mediates the reduction of urinary sodium (UNa V) and bicarbonate (UHCO3 V) excretion during 1.0-Hz renal nerve stimulation (RNS) was evaluated in 21 anesthetized dogs. In each animal RNS decreased UNa V and UHCO3 V without changing mean arterial pressure, renal blood flow, or glomerular filtration rate. After these initial responses, dogs were administered phentolamine [2.0 micrograms.kg-1.min-1 intrarenal artery (ira); n = 7], prazosin (0.7 micrograms.kg-1.min-1 ira; n = 5), (+/- )-propranolol (2.0 micrograms.kg-1.min-1 ira; n = 4), or atenolol (50 mg/kg iv; n = 5) and the renal responses to RNS were again tested. Both the antinatriuretic response and reduction of UHCO3 V during RNS were abolished by alpha 1/alpha 2-adrenoceptor blockade with phentolamine and by alpha 1-adrenoceptor antagonism with prazosin. beta-Adrenoceptor blockade with (+/- )-propranolol (beta 1/beta 2) or atenolol (beta 1) did not alter either the decrease in UNa V or UHCO3 V after RNS. These results provide further evidence that, during low-frequency RNS, reduction of UNa V is mediated in part by carbonic anhydrase-dependent bicarbonate reabsorption. These antinatriuretic responses and decreases in UHCO3 V during 1.0-Hz RNS are mediated by adrenergic neurotransmitter stimulation of alpha 1-adrenoceptors.


Greater Minority Stress is Associated with Lower Intentions to Disclose Suicidal Thoughts among LGBTQ + Youth.
The current study examined suicide-related disclosure intentions in LGBTQ + youth, and the associations between reporting of lifetime experiences of minority stress and intentions to disclose suicidal thoughts. A sample of 592 LGBTQ + youth ages 12-24 (22.3% cisgender men, 33.1% cisgender women, 44.6% gender diverse, 75.3% white) who contacted an LGBTQ-specific crisis service, completed a survey. Youth reported highest intentions to disclose future suicidal ideation to LGBTQ-specific crisis services, a mental health professional, and someone they know who also identifies as LGBTQ. They reported lowest suicide-related disclosure intentions to family, spiritual counselors, and emergency room personnel. Greater lifetime minority stress was significantly associated with lower suicide-related disclosure intentions. When specific domains of minority stress were examined separately, five domains were significantly associated with lower suicide-related disclosure intentions: identity management, family rejection, homonegative communication, negative expectancies, and internalized homonegativity. However, only internalized homonegativity remained significant when they were examined simultaneously. In addition, greater lifetime minority stress was significantly associated with lower suicide-related disclosure intentions to some groups (e.g., family, friends), but not others (e.g., others who have thought about or attempted suicide, others who identify as LGBT). Minority stress may play an important role in LGBTQ + youth's suicide-related disclosure intentions. As such, reducing minority stress and its effects may be an important target to promote disclosure of suicidal thoughts and access to treatment among LGBTQ + youth.HIGHLIGHTSMinority stress was associated with lower suicide-related disclosure intentions.Internalized homonegativity was uniquely associated with disclosure intentions.Reducing minority stress may promote disclosure of suicidal thoughts.


Mortality following acute pancreatitis: social deprivation, hospital size and time of admission: record linkage study.
Very little is known about whether mortality following acute pancreatitis may be influenced by the following five factors: social deprivation, week day of admission, recruitment of junior doctors in August each year, European Working Time Directives (EWTDs) for junior doctors' working hours and hospital size. The aim of this study was to establish how mortality following acute pancreatitis may be influenced by these five factors in a large cohort study. Systematic record linkage of inpatient, mortality and primary care data for 10 589 cases of acute pancreatitis in Wales, UK (population 3.0 million), from 1999 to 2010. The main study outcome measure was mortality at 60 days following the date of admission. Mortality was 6.4% at 60 days. There was no significant variation in mortality according to social deprivation or the week day of admission. There was also no significant variation according to calendar month for acute pancreatitis overall or for gallstone aetiology, but for alcoholic acute pancreatitis, mortality was increased significantly by 93% for admissions during the months of August and September and 102% from August to October when compared with all other calendar months. Mortality was increased significantly for alcoholic aetiology in August 2004, the official month that the first EWTD was implemented, but there were no other increases following the first or second EWTDs. There were also indications of increased mortality in large hospitals when compared with small hospitals, for acute pancreatitis overall and for gallstone aetiology but not for alcoholic acute pancreatitis, although these increases in mortality were of quite marginal significance. Although we found some evidence of increased mortality for patients admitted with alcoholic acute pancreatitis during August to October, in August 2004, and in large hospitals for acute pancreatitis overall and for gallstone aetiology, the study factors had limited impact on mortality following acute pancreatitis and no significant impact when adjusted for multiple comparisons.


A community experience with entericovesical fistulas.
A community experience with entericovesical fistulas is presented as well as a review of the literature. The series of 16 cases illustrates that this complication continues to present challenges in diagnosis and treatment. Diverticulitis is by far the most common primary disease process leading to the formation of entericovesical fistulas and the controversy involved in the surgical management of diverticulitis carries over to the management of this rare complication of the disease. It is felt that a one-stage procedure can often be accomplished and should be the procedure of choice in well-prepared, electively operated patients. When multiple stages are required, the two-stage approach is recommended. Familiarity with the proper treatment and a greater index of suspicion for this complication will lead to more acceptable management of patients with entericovesical fistulas.


Role of acetylcholine and dopamine in dorsal hippocampus on hoarding behavior in rats.
The probable roles of Acetylcholine (Ach) and Dopamine (DA) in the modulation of instinctual behaviors of feeding and hoarding (HS), as also the body weight and vaginal cyclicity (EI), were studied by instillation of Atropine (Ach antagonist), Haloperidol (DA antagonist) and Apomorphine (DA agonist) in the dorsal hippocampus of nonpregnant female rats. It was observed that the HS was significantly decreased with both Atropine and haloperidol and increased with Apomorphine, although the food intake was decreased with the three chemicals. It appears that action of both Ach and DA on the dorsal hippocampus has a positive influence on hoarding behavior.


Bone mineral density and the risk of incident dementia: A meta-analysis.
It is not known whether bone mineral density (BMD) measured at baseline or as the rate of decline prior to baseline (prior bone loss) is a stronger predictor of incident dementia or Alzheimer's disease (AD). We performed a meta-analysis of three longitudinal studies, the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Rush Memory and Aging Project (MAP), modeling the time to diagnosis of dementia as a function of BMD measures accounting for covariates. We included individuals with one or two BMD assessments, aged ≥60 years, and free of dementia at baseline with follow-up available. BMD was measured at the hip femoral neck using dual-energy X-ray absorptiometry (DXA), or at the heel calcaneus using quantitative ultrasound to calculate estimated BMD (eBMD). BMD at study baseline ("baseline BMD") and annualized percentage change in BMD prior to baseline ("prior bone loss") were included as continuous measures. The primary outcome was incident dementia diagnosis within 10 years of baseline, and incident AD was a secondary outcome. Baseline covariates included age, sex, body mass index, ApoE4 genotype, and education. The combined sample size across all three studies was 4431 with 606 incident dementia diagnoses, 498 of which were AD. A meta-analysis of baseline BMD across three studies showed higher BMD to have a significant protective association with incident dementia with a hazard ratio of 0.47 (95% CI: 0.23-0.96; p = 0.038) per increase in g/cm2 , or 0.91 (95% CI: 0.84-0.995) per standard deviation increase. We observed a significant association between prior bone loss and incident dementia with a hazard ratio of 1.30 (95% CI: 1.12-1.51; p < 0.001) per percent increase in prior bone loss only in the FHS cohort. Baseline BMD but not prior bone loss was associated with incident dementia in a meta-analysis across three studies.


Association of adenovirus with the microtubule organizing center.
Adenoviruses (Ad) must deliver their genomes to the nucleus of the target cell to initiate an infection. Following entry into the cell and escape from the endosome, Ad traffics along the microtubule cytoskeleton toward the nucleus. In the final step in Ad trafficking, Ad must leave the microtubule and establish an association with the nuclear envelope. We hypothesized that in cells lacking a nucleus, the capsid moves to and associates with the microtubule organizing center (MTOC). To test this hypothesis, we established an experimental system to examine Ad trafficking in enucleated cells compared to Ad trafficking in intact, mock-enucleated cells. Enucleation of a monolayer of A549 human lung epithelial cells was accomplished by depolymerization of the actin cytoskeleton followed by centrifugation. Upon infection of enucleated cells with Cy3-labeled Ad, the majority of Ad capsid trafficked to a discrete, centrally located site which colocalized with pericentrin, a component of the MTOC. MTOC-associated Ad had escaped from endosomes and thus had direct access to MTOC components. Ad localization at this site was sensitive to the microtubule-depolymerizing agent nocodazole, but not to the microfilament-depolymerizing agent cytochalasin B, indicating that intact microtubules were required to maintain the localization with the MTOC. Ad localization to the MTOC in the enucleated cells was stable, as demonstrated by continuing Ad localization with pericentrin for more than 5 h after infection, a strong preference for Ad arrival at rather than Ad departure from the MTOC, and minimal redistribution of Ad between MTOCs within a single cell. In summary, the data demonstrate that the Ad capsid establishes a stable interaction with the MTOC when a nucleus is not present, suggesting that dissociation of Ad from microtubules likely requires nuclear factors.


The Potential Effect of Lowering the Threshold of Statistical Significance From P < .05 to P < .005 in Orthopaedic Sports Medicine.
To determine how changing the P value threshold of statistical significance from .05 to .005 could affect the statistical significance of findings in previously published orthopaedic sports medicine randomized controlled trials (RCTs). The authors searched PubMed from January 1, 2016, to December 31, 2017, for RCTs published in the American Journal of Sports Medicine, Arthroscopy, and Knee Surgery, Sports Traumatology, Arthroscopy. Data were extracted blinded and in duplicate fashion by 2 of us. The authors then extracted P value data for primary end points, since RCTs are most often powered for these end points. Discrepancies were resolved by consensus. Google Forms were used for data extraction and STATA 15.1 for the data analysis. In total, 275 primary end points were identified from 132 trials. Analysis of primary end points found 45.8% (126/275) had a P value less than .05 and were classified as statistically significant under the current threshold, whereas 54.2% (149/275) had a P value greater than .05 and were not classified as suggestive. Of those end points that were previously considered statistically significant, 38.9% (49/126) were less than .005, whereas 61.1% (77/126) were between .005 and .05 and thereby would be reclassified as suggestive rather than statistically significant under the proposed threshold. Overall, when analyzing the 275 primary end points, we found only 49 (17.8%) of the end points were less than .005 and would hold statistical significance with the proposed threshold. The results suggest that if the threshold of statistical significance were to change to .005, the significance of orthopaedic sports medicine RCTs would be heavily altered. The authors also acknowledge the many issues research faces in regard to P value reliability and therefore interpretation of study results. Because P values from RCTs can often influence the ways physicians choose interventions, it is important to implement methodology that decreases incidence of bias and misrepresentation of these results. However, the authors also understand that lowering the P value could increase the needed sample size and by consequence increase study costs as well, while not directly correlating to clinical significance. Thus, the authors recommend that this proposed threshold should be further evaluated and cautiously interpreted. If the statistical significance threshold is changed, clinical practice guideline recommendations also may be affected.


Recognizing sleep disorders in a primary care setting.
As many as one third of the general population suffers from some form of sleep disorder. Although sleep disorders are widespread in society, few patients present with overt sleep complaints; they instead present with symptoms of fatigue, excessive sleepiness, and impaired waking function. Untreated sleep disorders, particularly insomnia, can lead to potentially life-threatening automobile crashes and industrial accidents. In addition, poor motor, mental, and cognitive function at home, work, and school can negatively impact a patient's quality of life. Therefore, physicians must maintain a high index of suspicion for sleep disorders whenever they see patients, and they must ask sleep-related questions during office visits for acute conditions, chronic conditions, and annual physical examinations. Today's "24/7" society experiences sleep disorders in ever-increasing numbers, and people who work shifts are at risk for developing circadian rhythm sleep disorder, particularly shift work sleep disorder. Physicians must engage their patients in a discussion of their occupations and sleeping habits in order to detect and treat sleep disorders.


The original hole-in-one guide for atlantoaxial transarticular screw fixation.
Atlantoaxial fusion by transarticular screw fixation provides firm fixation, and good results have been reported. However, there are also problems, such as injury of the vertebral artery at the time of screw insertion. For accurate facet fusion, we developed a new hole-in-one guide for screw fixation and obtained good results with its use. In 60 adult subjects. we measured the antero-posterior and transverse axes and determined the center of the atlantoaxial surface and the insertion point of the screw in three dimensions on computed tomography scans. Based on these values, we measured the optimum screw insertion angle on sagittal and coronal planes, and the distance between the center and the posterior margin of the joint surface; our new hole-in-one guide was produced with these data. When the guide tip is determined to be located at the center posterior margin of the axial joint surface, and the guidewire insertion point is determined to be located at the center of the axial inferior facet immediately above the C2/3 joint, the guidewire is passed through the axial pedicle and the center of the atlantoaxial joint. Since April 1997, we have used this hole-in-one guide technique in eight patients with atlantoaxial instability. The screws passed the pars interarticularis and the center of the atlantoaxial joint in all patients with safety and accuracy. No complications associated with this technique occurred.


POLQ plays a key role in the repair of CRISPR/Cas9-induced double-stranded breaks in the moss Physcomitrella patens.
Double-stranded breaks can be repaired by different mechanisms such as homologous recombination (HR), classical nonhomologous end joining (C-NHEJ) and alternative end joining (Alt-EJ). Polymerase Q (POLQ) has been proposed to be the main factor involved in Alt-EJ-mediated DNA repair. Here we describe the role of POLQ in DNA repair and gene targeting in Physcomitrella patens. The disruption of the POLQ gene does not influence the genetic stability of P. patens nor its development. The polq mutant shows the same sensitivity as wild-type towards most of the genotoxic agents tested (ultraviolet (UV), methyl methanesulfonate (MMS) and cisplatin) with the notable exception of bleomycin for which it shows less sensitivity than the wild-type. Furthermore, we show that POLQ is involved in the repair of CRISPR-Cas9-induced double-stranded breaks in P. patens. We also demonstrate that POLQ is a potential competitor and/or inhibitor of the HR repair pathway. This finding has a consequence in terms of genetic engineering, as in the absence of POLQ the frequency of gene targeting is significantly increased and the number of clean two-sided HR-mediated insertions is enhanced. Therefore, the control of POLQ activity in plants could be a useful strategy to optimize the tools of genome engineering for plant breeding.


Accuracy of cardiovascular magnetic resonance in myocarditis: comparison of MR and histological findings in an animal model.
Because endomyocardial biopsy has low sensitivity of about 20%, it can be performed near to myocardium that presented as late gadolinium enhancement (LGE) in cardiovascular magnetic resonance (CMR). However the important issue of comparing topography of CMR and histological findings has not yet been investigated. Thus the current study was performed using an animal model of myocarditis. In 10 male Lewis rats experimental autoimmune myocarditis was induced, 10 rats served as control. On day 21 animals were examined by CMR to compare topographic distribution of LGE to histological inflammation. Sensitivity, specificity, positive and negative predictive values for LGE in diagnosing myocarditis were determined for each segment of myocardium. Latter diagnostic values varied widely depending on topographic distribution of LGE and inflammation as well as on the used CMR sequence. Sensitivity of LGE was up to 76% (left lateral myocardium) and positive predictive values were up to 85% (left lateral myocardium), whereas sensitivity and positive predictive value dropped to 0-33% (left inferior myocardium). Topographic distribution of LGE and histological inflammation seem to influence sensitivity, specificity, positive and negative predictive values. Nevertheless, positive predictive value for LGE of up to 85% indicates that endomyocardial biopsy should be performed "MR-guided". LGE seems to have greater sensitivity than endomyocardial biopsy for the diagnosis of myocarditis.


Escherichia coli K-12 mutants altered in the transport of branched-chain amino acids.
Two mutants of Escherichia coli K-12 are described which are resistant to the inhibition that valine exerts on the growth of E. coli. These mutants have lesions at two different loci on the chromosome. One of them, brnP, is linked to leu (87% cotransduction) and is located between leu and azi represented on the map at 1 min; the other, brnQ, is linked to phoA (96% cotransduction), probably between proC and phoA and represented at 10 min. These mutants are resistant to valine inhibition but are sensitive to dipeptides containing valine. Since it is known that dipeptides are taken up by E. coli through a transport system(s) different from those used by amino acids, this sensitivity to the peptides suggests an alteration in the active transport of valine. The mutants are resistant to valine only if leucine is present in the growth medium; the uptake of valine is less in both mutants than it is in wild-type E. coli, and it is reduced even further if leucine is present. Under these conditions the total uptake of valine is almost completely abolished in the brnQ mutant. The brnP mutant takes up about 60% as much valine as does the wild type, but no exogenous valine is incorporated into proteins. The apparent K(m) and V(max) of isoleucine, leucine, and valine for the transport system are reported; the brnP mutant, when compared to the wild type, has a sevenfold higher K(m) for isoleucine and a 17-fold lower K(m) for leucine; the V(max) for the three amino acids is reduced in the brnQ mutant, up to 20-fold for valine. The transport of arginine, aspartic acid, glycine, histidine, and threonine is not altered in the brnQ mutant under conditions in which that of the branched amino acids is. Evidence is reported that O-methyl-threonine enters E. coli through the transport system for branched amino acids, and that thiaisoleucine does not.


Low glycogen and branched-chain amino acid ingestion do not impair anaplerosis during exercise in humans.
We examined the hypothesis that increasing the rate of branched-chain amino acid (BCAA) oxidation, during conditions of low glycogen availability, reduces the level of muscle tricarboxylic acid cycle intermediates (TCAI) by placing a carbon "drain" on the cycle at the level of 2-oxoglutarate. Six men cycled at approximately 70% of maximal oxygen uptake for 15 min under two conditions: 1) low preexercise muscle glycogen (placebo) and 2) low glycogen combined with BCAA ingestion. We have previously shown that BCAA ingestion increased the activity of branched-chain oxoacid dehydrogenase, the rate-limiting enzyme for BCAA oxidation in muscle, compared with low glycogen alone [M. L. Jackman, M. J. Gibala, E. Hultman, and T. E. Graham. Am. J. Physiol. 272 (Endocrinol. Metab. 35): E233-E238, 1997]. Muscle glycogen concentration was 185 +/- 22 and 206 +/- 22 mmol/kg dry wt at rest for the placebo and BCAA-supplemented trials, respectively, and decreased to 109 +/- 18 and 96 +/- 10 mmol/kg dry wt after exercise. The net increase in the total concentration of six measured TCAI ( approximately 95% of TCAI pool) during exercise was not different between trials (3.97 +/- 0. 34 vs. 3.88 +/- 0.34 mmol/kg dry wt for the placebo and BCAA trials, respectively). Muscle 2-oxoglutarate concentration decreased from approximately 0.05 at rest to approximately 0.03 mmol/kg dry wt after exercise in both trials. The magnitude of TCAI pool expansion in both trials was similar to that seen previously in subjects who performed an identical exercise bout after a normal mixed diet [M. J. Gibala, M. A. Tarnopolsky, and T. E. Graham. Am. J. Physiol. 272 (Endocrinol. Metab. 35): E239-E244, 1997]. These data suggest that increasing the rate of BCAA oxidation has no measurable effect on muscle TCAI during exercise with low glycogen in humans. Moreover, it appears that low resting glycogen per se does not impair the increase in TCAI during moderate exercise.


Aging-induced IL27Ra signaling impairs hematopoietic stem cells.
Hematopoietic stem cell (HSC) aging correlates with an increasing risk of myeloproliferative disease and immunosenescence. In this study, we show that aging-related inflammation promotes HSC aging through tumor necrosis factor-α (TNF-α)→ERK→ETS1→interleukin27Ra (IL27Ra) pathway. TNF-α, a well-known biomarker of inflammation, increases during aging and induces the expression of IL27Ra on HSCs via ERK-ETS1 signaling. Deletion of IL27Ra rescues the functional decline and myeloid bias of HSCs and also reverses the inhibitory effect of TNF-α on HSCs. Aged IL27Ra-/- mice had a reduced proportion of myeloid-biased HSCs and did not display the biased myeloid differentiation that occurs in aged wild-type mice. IL27Ra+ HSCs exhibit impaired reconstitution capacity and myeloid-bias compared with IL27Ra- HSCs and serve as a myeloid-recovery pool upon inflammatory insult. Inflammation-related genes were enriched in IL27Ra+ HSCs and this enrichment increases with aging. Our study demonstrates that age-induced IL27Ra signaling impairs HSCs and raises the possibility that interfering with IL27Ra signaling can counter the physiologically deleterious effect of aging on hematopoietic capacity.


Rural/urban and socioeconomic differentials in quality of antenatal care in Ghana.
Approximately 800 women die of pregnancy-related complications every day. Over half of these deaths occur in sub-Saharan Africa (SSA). Most maternal deaths can be prevented with high quality maternal health services. It is well established that use of maternal health services vary by place of residence and socioeconomic status (SES), but few studies have examined the determinants of quality of maternal health services in SSA. The purpose of this study is to examine the determinants of antenatal care (ANC) quality in Ghana-focusing on the role of place of residence and SES (education and wealth). The analysis also examines the interactions of these variables and the mediating role of ANC timing, frequency, facility type, and provider type. The data are from the Ghana Maternal Health Survey (N = 4,868). Analytic techniques include multilevel linear regression with mediation and moderation analysis. Urban residence and higher SES are positively associated with higher ANC quality, but the urban effect is completely explained by sociodemographic factors. Specifically, about half of the urban effect is explained by education and wealth alone, with other variables accounting for the remainder. The effects of education are conditional on wealth and are strongest for poor women. Starting ANC visits early and attending the recommended four visits as well as receiving ANC from a higher level facility and from a skilled provider are associated with higher quality ANC. These factors partially explain the SES differentials. Ghanaian women experience significant disparities in quality of ANC, with poor illiterate women receiving the worst care. Targeted efforts to increase quality of ANC may significantly reduce maternal health disparities in Ghana and SSA. A particularly crucial step is to improve ANC quality in the lower level health facilities, where the most vulnerable women are more likely to seek ANC.


Prioritising, Ranking and Resource Implementation - A Normative Analysis.
Priority setting in publicly financed healthcare systems should be guided by ethical norms and other considerations viewed as socially valuable, and we find several different approaches for how such norms and considerations guide priorities in healthcare decision-making. Common to many of these approaches is that interventions are ranked in relation to each other, following the application of these norms and considerations, and that this ranking list is then translated into a coverage scheme. In the literature we find at least two different views on how a ranking list should be translated into coverage schemes: (1) rationing from the bottom where everything below a certain ranking order is rationed; or (2) a relative degree of coverage, where higher ranked interventions are given a relatively larger share of resources than lower ranked interventions according to some "curve of coverage." The aim of this article is to provide a normative analysis of how the background set of ethical norms and other considerations support these two views. The result of the analysis shows that rationing from the bottom generally gets stronger support if taking background ethical norms seriously, and with regard to the extent the ranking succeeds in realising these norms. However, in non-ideal rankings and to handle variations at individual patient level, there is support for relative coverage at the borderline of what could be covered. A more general relative coverage curve could also be supported if there is a need to generate resources for the healthcare system, by getting patients back into production and getting acceptance for priority setting decisions. Hence, different types of reasons support different deviations from rationing from the bottom. And it should be noted that the two latter reasons will imply a cost in terms of not living up to the background set of ethical norms.


The micromorphological investigation of pollen grains of some important allergenic plants in Kermanshah (West of Iran).
Allergenic pollens are found in gardens, fields and green spaces around cities. In Kermanshah, located in the west of Iran, seven allergen pollen samples were collected directly from nature and studied according to the Erdtman acetolysis method by using Light Microscope (LM) and Scanning Electron Microscope (SEM). In this study, atmospheric pollens were also examined by the Durham method. The results showed that the pollen grains were small, medium, and large in terms of size, and Triporate, Pantoporate, Colpate and Tricolporate in terms of aperture. In addition, they were Striate, Perforate, Macroechinate, Microechinate, and Psilate with regard to exine ornamentation; however, the echinate type was more common. In general, Prolate to a spherical shape, medium-sized, perforate, and echinate pollen characteristics are popular in the important allergenic plants. Therefore, due to the human's manipulations in nature and also the extensive size of gardens and fields, there are many types of weeds in Kermanshah Province which are significant in terms of being allergenic.


Identification of orally available naphthyridine protein kinase D inhibitors.
A novel 2,6-naphthyridine was identified by high throughput screen (HTS) as a dual protein kinase C/D (PKC/PKD) inhibitor. PKD inhibition in the heart was proposed as a potential antihypertrophic mechanism with application as a heart failure therapy. As PKC was previously identified as the immediate upstream activator of PKD, PKD vs PKC selectivity was essential to understand the effect of PKD inhibition in models of cardiac hypertrophy and heart failure. The present study describes the modification of the HTS hit to a series of prototype pan-PKD inhibitors with routine 1000-fold PKD vs PKC selectivity. Example compounds inhibited PKD activity in vitro, in cells, and in vivo following oral administration. Their effects on heart morphology and function are discussed herein.