Gaps in the Management of Depression Symptoms Following Cancer Diagnosis: A Population-Based Analysis of Prospective Patient-Reported Outcomes.
One of the most common psychological morbidities of cancer is depression. Routine depression symptoms screening (DSS) is recommended, but its ability to lead to psychosocial interventions in clinical practice is limited. We examined the use of and factors associated with psychosocial interventions for positive DSS following cancer diagnosis. We conducted a population-based cohort study of patients with diagnoses from 2010 to 2017 who reported ≥1 patient-reported Edmonton Symptom Assessment System (ESAS) score. Positive DSS was defined as ESAS ≥2 out of 10 for the depression item within 6 months of diagnosis. Outcomes were psychosocial interventions around the time of positive DSS: palliative care assessment, psychiatry/psychology assessment, social work referral, and antidepressant therapy (in patients ≥65 years of age with universal drug coverage). We examined reduction in depression symptom score (≥1 point) following intervention. Modified Poisson regression examined factors associated with interventions. Of 142,270 patients, 65,424 (46.0%) reported positive DSS at a median of 66 days (interquartile range: 34-105) after diagnosis. Of those with depression symptoms, 17.1% received palliative assessment, 1.7% psychiatry/psychology assessment, 8.4% social work referral, and 4.3% antidepressant therapy. Depression symptom score decreased in 67.2% who received palliative assessment, 63.7% with psychiatry/psychology assessment, 67.3% with social work referral, and 71.4% with antidepressant therapy. On multivariable analysis, patients with older age, rural residence, lowest income quintile, and genitourinary or oropharyngeal cancer were more likely to not receive intervention other than palliative care. The proportion of patients reporting positive DSS after cancer diagnosis receiving psychosocial intervention is low. We identified patients vulnerable to not receiving interventions, who may benefit from additional support. These data represent a call to action to modify practice and optimize the usefulness of systematic symptom screening. Patient-reported depression symptoms screening should be followed by targeted interventions to improve symptoms and patient-centered management.


Neighbors-based prediction of physical function after total knee arthroplasty.
The purpose of this study was to develop and test personalized predictions for functional recovery after Total Knee Arthroplasty (TKA) surgery, using a novel neighbors-based prediction approach. We used data from 397 patients with TKA to develop the prediction methodology and then tested the predictions in a temporally distinct sample of 202 patients. The Timed Up and Go (TUG) Test was used to assess physical function. Neighbors-based predictions were generated by estimating an index patient's prognosis from the observed recovery data of previous similar patients (a.k.a., the index patient's "matches"). Matches were determined by an adaptation of predictive mean matching. Matching characteristics included preoperative TUG time, age, sex and Body Mass Index. The optimal number of matches was determined to be m = 35, based on low bias (- 0.005 standard deviations), accurate coverage (50% of the realized observations within the 50% prediction interval), and acceptable precision (the average width of the 50% prediction interval was 2.33 s). Predictions were well-calibrated in out-of-sample testing. These predictions have the potential to inform care decisions both prior to and following TKA surgery.


Ensuring Quality and Status: Peer Review Practices in Kriterium, A Portal for Quality-Marked Monographs and Edited Volumes in Swedish SSH.
Although established forms of peer review are often criticized for being slow, secretive, and even unfair, they are repeatedly mentioned by academics as the most important indicator of quality in scholarly publishing. In many countries, the peer review of books is a less codified practice than that of journal articles or conference papers, and the processes and actors involved are far from uniform. In Sweden, the review process of books has seldom been formalized. However, more formal peer review of books has been identified as a response to the increasing importance placed on streamlined peer-reviewed publishing of journal articles in English, which has been described as a direct challenge to more pluralistic publication patterns found particularly in the humanities. In this study, we focus on a novel approach to book review, Kriterium, where an independent portal maintained by academic institutions oversees the reviewing of academic books. The portal administers peer reviews, providing a mark of quality through a process which involves reviewers, an academic coordinator, and an editorial board. The paper studies how this process functions in practice by exploring materials concerning 24 scholarly books reviewed within Kriterium. Our analysis specifically targets tensions identified in the process of reviewing books with a focus on three main themes, namely the intended audience, the edited volume, and the novel role of the academic coordinator. Moreover, we find that the two main aims of the portal-quality enhancement (making research better) and certification (displaying that research is of high quality)-are recurrent in deliberations made in the peer review process. Consequently, we argue that reviewing procedures and criteria of quality are negotiated within a broader discussion where more traditional forms of publishing are challenged by new standards and evaluation practices.


Enhancements of the emission and light extraction of a radiating dipole coupled with localized surface plasmon induced on a surface metal nanoparticle in a light-emitting device.
The radiated power enhancement and more congregated radiation of a radiating dipole within a GaN material when it is coupled with the localized surface plasmon (LSP) resonance modes induced on a surface Ag nanoparticle (NP) are numerically demonstrated. The numerical study is based on an algorithm including the induction of LSP resonance on the Ag NP by the source dipole and the feedback effect of the LSP resonance field on the source dipole behavior. The spectral peaks of radiated power enhancement correspond to the substrate LSP resonance modes with mode fields mainly distributed around the bottom of the Ag NP such that the coupling system radiates mainly into the GaN half-space. By moving the radiating dipole laterally away from the bottom of the Ag NP, the spectral peaks of radiated power enhancement red shift and their levels diminish with increasing lateral distance. The radiation patterns in the GaN half-space show more congregated radiation around the vertical direction, indicating that the light extraction efficiency can be enhanced in an LSP-coupled light-emitting device with surface metal NPs.


Nanoporous gold: a new material for catalytic and sensor applications.
Nanostructured materials are governed by their surface chemical properties. This is strikingly reflected by np-Au. This material can be generated by corrosion of bulk Ag-Au alloys. Based on a self-organisation process, a 3 dimensional sponge like gold structure evolves with ligaments in the range of only a few tens of nanometers. Due to its continuous porosity, the material can be penetrated by gases which then adsorb and interact with the surface. In this perspective we will review potential applications of np-Au resulting from this effect, namely heterogeneous gas phase catalysis, surface chemistry driven actuation, and adsorbate controlled stability of the nanostructure. We will summarize the current knowledge about the low temperature oxidation of CO as well as the highly selective oxidation of methanol. Furthermore, we will address the question how surface chemistry can influence the material properties itself. In particular, we will deal with (a) the actuation of np-Au by the reversible oxidation of its surface using ozone and (b) the adsorbate controlled coarsening of ligaments, using annealing experiments under ozone or inert gas atmosphere.


A Five-Channel Weighted Real-Time Algorithm for High-Density Electrodes Spike Sorting.
With the application of high-density neural probes, a neuron can be detected by multiple adjacent probes, and the traditional single-channel spike sorting is no longer suitable. In this paper, we propose a five-channel weighted real-time spike sorting algorithm based on template-matching to process neural signals recorded by high-density probes. This work uses the signals of the center channel and the adjacent four channels to form a five-channel template by weighting, and employs a modified OSort algorithm with unsupervised learning to update the template. We implemented automatic online spike sorting, and tested it with both ground truth recordings and simulated datasets. The experiments show that our algorithm utilizing the information of adjacent channels has a higher sorting accuracy than traditional single-channel spike sorting. The average sorting accuracy reaches 89%, compared to 78% for single-channel.


Antihypertensive, antidiabetic and lipid-lowering treatment frequencies in France in 2010.
The frequencies of treatment for cardiovascular risk factors are poorly documented in large populations, particularly according to the presence or absence of cardiovascular disease (CVD). To assess frequencies of reimbursements for antihypertensive, lipid-lowering and antidiabetic medications in France among national health insurance beneficiaries in 2010 and their associations according to age, sex, French regions, level deprivation and the presence of certain CVD. Treatment frequencies were calculated among the beneficiaries (58 million people) on the basis of reimbursements for three specific categories of medicinal products in 2010. The presence of CVD was defined by a diagnosis associated with chronic disease status and hospital stays in 2010. Among people aged greater or equal to 20years, treatment frequencies were 22% (men 20% vs. women 23%) for antihypertensives, 15% (14% vs. 16%) for lipid-lowering agents and 6% (6% vs. 5%) for antidiabetic medications. These frequencies were, respectively, 33%, 23% and 8% in patients aged greater or equal to 40years and 55%, 38% and 14% in patients aged greater or equal to 60 years. The frequency of at least one treatment for at least one of the three risk factors was 41% in patients aged greater or equal to 40 years and 66% in patients aged greater or equal to 60 years. Among patients aged greater or equal to 20 years, 22% were treated for at least one risk factor in the absence of CVD and 3% were treated for at least one risk factor in the presence of CVD. Regional differences were observed, with higher frequencies of antihypertensive and antidiabetic use in the North, North-East and Overseas regions. Treatment frequencies increased with level of deprivation, especially for antidiabetics. This national study more clearly defines treatment frequencies and the populations and regions with the highest treatment frequencies.


Regulation of insulin-like growth factor I receptor gene expression by the Wilms' tumor suppressor WT1.
THe insulin-like growth factor I receptor (IGF-I-R) has been implicated in the etiology and/or progression of Wilms' tumor, or nephroblastoma, a pediatric neoplasm of the kidney that is often associated with deletion or mutation of the WT1 tumor suppressor gene. The levels of IGF-I-R mRNA in the tumors were sixfold higher than in normal adjacent kidney tissue and were inversely correlated to the levels of WT1 mRNA, suggesting that the expression of the IGF-I-R gene is under inhibitory control by WT1. Cotransfection of an IGF-I-R promoter-luciferase reporter construct together with a WT1 expression vector resulted in a dose-dependent suppression of promoter activity. Multiple WT1 binding sites were mapped in the 5'-flanking and 5'-untranslated regions of the IGF-I-R gene using gel retardation and DNaseI footprinting assays. Thus, suppression of the IGF-I-R promoter by WT1 involves multiple interactions of its zinc finger domain with sites located both upstream and downstream of the transcription initiation site. Finally, we showed that expression of the endogenous IGF-I-R gene is decreased in G401 cells stably transfected with a WT1 expression vector. Reduction in expression of the IGF-I-R gene is associated with a decrease in a number of IGF-I-mediated biological effects. Thus, deletion or mutation of the WT1 gene in Wilms' tumor and other malignancies can result in overexpression of the receptor, with enhanced autocrine/paracrine activation by locally produced or circulating IGFs.


Voxel-based comparison of preoperative FDG-PET between mesial temporal lobe epilepsy patients with and without postoperative seizure-free outcomes.
This study aims to elucidate differences in preoperative cerebral glucose metabolism between patients who did and did not become seizure free after unilateral mesial temporal lobe epilepsy (mTLE) surgery. We hypothesized that regional glucose metabolism on preoperative fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with seizure-free outcomes differed from that in patients who were not seizure free after appropriate epilepsy surgery for unilateral mTLE. In this study, we compared preoperative FDG-PET findings between these two patient groups by applying a statistical analysis approach, with a voxel-based Asymmetry index (AI), to improve sensitivity for the detection of hypometabolism. FDG-PET scans of 28 patients with medically refractory mTLE, of whom 17 achieved a seizure-free outcome (Engel class 1 a-b) during a postoperative follow-up period of at least 2 years, were analyzed retrospectively. Voxel values were adjusted by the AI method as well as the global normalization (GN) method. Two types of statistical analysis were performed. One was a voxel severity analysis with comparison of voxel values at the same coordinate, and the other was extent analysis with comparison of the number of significant voxels in the anatomical areas predefined with Talairach's atlas. In the voxel severity analysis, significant hypometabolism restricted to the ipsilateral temporal tip and hippocampal area was detected in the postoperative seizure-free outcome group as compared to controls. No significant area was detected in the non-seizure-free group as compared to controls (family-wise error corrected, p < 0.05). With extent analysis using a low threshold, the extents of hypometabolism in the ipsilateral hippocampal, frontal and thalamic areas were larger in the seizure-free than in the non-seizure-free group (p = 0.01, 0.03 and 0.01, respectively.) On the other hand, in the contralateral frontal and thalamic areas, extents of hypometabolism were smaller in the seizure-free than in the non-seizure-free group (p = 0.01 and 0.01). We found the preoperative distribution of hypometabolism to differ between the two patient groups. Severe hypometabolism restricted to the unilateral temporal lobe, with ipsilateral dominant hypometabolism including mild decreases, may support the existence of an epileptogenic focus in the unilateral temporal lobe and a favorable seizure outcome after mTLE surgery.


Boulder ALignment Editor (ALE): a web-based RNA alignment tool.
The explosion of interest in non-coding RNAs, together with improvements in RNA X-ray crystallography, has led to a rapid increase in RNA structures at atomic resolution from 847 in 2005 to 1900 in 2010. The success of whole-genome sequencing has led to an explosive growth of unaligned homologous sequences. Consequently, there is a compelling and urgent need for user-friendly tools for producing structure-informed RNA alignments. Most alignment software considers the primary sequence alone; some specialized alignment software can also include Watson-Crick base pairs, but none adequately addresses the needs introduced by the rapid influx of both sequence and structural data. Therefore, we have developed the Boulder ALignment Editor (ALE), which is a web-based RNA alignment editor, designed for editing and assessing alignments using structural information. Some features of BoulderALE include the annotation and evaluation of an alignment based on isostericity of Watson-Crick and non-Watson-Crick base pairs, along with the collapsing (horizontally and vertically) of the alignment, while maintaining the ability to edit the alignment. http://www.microbio.me/boulderale.


Pyrazole induced oxidative liver injury independent of CYP2E1/2A5 induction due to Nrf2 deficiency.
Pyrazole can induce CYP2E1 and 2A5, which produce reactive oxygen species (ROS). Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates important antioxidant enzymes to remove ROS. In this study, we applied Nrf2 knockout mice to test the hypothesis that pyrazole will cause hepatotoxicity and elevate oxidative stress to a greater extent in Nrf2 knockout mice compared to wild type mice. Pyrazole induced severe oxidative liver damage in Nrf2 knockout mice but not in wild type mice. Activities and levels of CYP2E1 and 2A5 were elevated by pyrazole in the wild type mice but not in the Nrf2 knockout mice. However, expression or activity of Nrf2-regulated antioxidant enzymes, such as gamma-glutamylcysteine synthetase (GCS), heme oxygenase-1 (HO-1) and glutathione-S-transferase (GST), were upregulated in the pyrazole-treated wild type mice, but to a lesser extent or not at all in the pyrazole-treated Nrf2 knockout mice. Treatment with antioxidants such as vitamin C or S-adenosyl-l-methionine (SAM) or an inhibitor of iNOS prevented the pyrazole-induced oxidative liver damage, thus validating the role of oxidative/nitrosative stress in the pyrazole induced liver injury to the Nrf2 knockout mice. In summary, even though ROS-producing CYP2E1/2A5 were not elevated by pyrazole, impaired antioxidant capacity resulting from Nrf2 deficiency appear to be sufficient to promote pyrazole-induced oxidative liver injury.


Mortalin expression in pancreatic cancer and its clinical and prognostic significance.
Mortalin, an essential mitochondrial chaperone protein, is involved in the tumorigenesis of a number of malignancies. This study aimed to investigate the expression of Mortalin in pancreatic ductal adenocarcinoma (PDAC) cells and to determine its clinicopathological and prognostic significance. The localization of Mortalin protein was detected in BXPC-3 PDAC cells using immunofluorescence. Immunohistochemistry was also used to detect Mortalin expression in well-defined tissues obtained from 106 PDAC patients and 46 corresponding nontumor pancreatic tissues. Clinicopathological parameters and overall survival data were collected and compared between different Mortalin statuses. The results of immunohistochemistry and immunofluorescence showed that Mortalin was primarily present in the cytoplasm of PDAC cells. The ratio of strong positive staining for Mortalin was higher in PDAC tissues (55.66%; 59/106) than in normal adjacent tissues (23.91%; 11/46). Positive relationships between Mortalin expression and clinical stage, perineural invasion, lymph node metastasis, and lower overall survival were observed. Multivariate Cox regression analysis identified Mortalin as a significant independent prognostic factor, in addition to location, clinical stage, and perineural invasion, for survival of PDAC patients. Therefore, we present strong evidence that Mortalin may function as a practical marker to predict prognosis and as a potential therapeutic target in PDAC treatment.


Biochemical basis of prolidase deficiency. Polypeptide and RNA phenotypes and the relation to clinical phenotypes.
Cultured skin fibroblasts or lymphoblastoid cells from eight patients with clinical symptoms of prolidase deficiency were analyzed in terms of enzyme activity, presence of material crossreacting with specific antibodies, biosynthesis of the polypeptide, and mRNA corresponding to the enzyme. There are at least two enzymes that hydrolyze imidodipeptides in these cells and these two enzymes could be separated by an immunochemical procedure. The specific assay for prolidase showed that the enzyme activity was virtually absent in six cell strains and was markedly reduced in two (less than 3% of controls). The activities of the labile enzyme that did not immunoprecipitate with the anti-prolidase antibody were decreased in the cells (30-60% of controls). Cell strains with residual activities of prolidase had immunological polypeptides crossreacting with a Mr 56,000, similar to findings in the normal enzyme. The polypeptide biosynthesis in these cells and the controls was similar. Northern blot analyses revealed the presence of mRNA in the polypeptide-positive cells, yet it was absent in the polypeptide-negative cells. The substrate specificities analyzed in the partially purified enzymes from the polypeptide-positive cell strains differed, presumably due to different mutations. Thus, there seems to be a molecular heterogeneity in prolidase deficiency. There was no apparent relation between the clinical symptoms and the biochemical phenotypes, except that mental retardation was present in the polypeptide-negative patients. The activities of the labile enzyme may not be a major factor in modifying the clinical symptoms.


[Pasqualini's syndrome: hypoandrogenism with spermatogenesis].
Pasqualini and Bur published the first case of eunuchoidism with preserved spermatogenesis in 1950 in Revista de la Asociación Médica Argentina. The hypoandrogenism with spermatogenesis syndrome included: (a) eunuchoidism, (b) testis with normal spermatogenesis and full volume, with mature spermatozoa in a high proportion of seminiferous tubes and undifferentiated and immature Leydig cells (c) full functional compensation through the administration of chorionic gonadotropin hormone, while hCG is administered (d) total urinary gonadotrophins within normal limits (e) this definition supposes the normal activity of the pituitary and the absence of congenital malformations in general. A first step in the understanding of the physiopathogeny of Pasqualini syndrome or the so called "fertile eunuch" syndrome was the absence of LH in plasma and urine of patients. The second breakthrough was the functional and genetic studies that validated the hypothesis of a functional deficit of LH in these men: it will then also be described in some women. Different groups including ours demonstrated in these cases a LH with varying degrees of immunological activity but biologically inactive in most of the patients, due to one or more inactivating mutations in the LHB gene. Finally, the full comprehension of Pasqualini syndrome allowed to reverse the hypoandrogenic phenotype and to restore fertility in these patients through the use of chorionic gonadotropin and the modern in-vitro fertility techniques. This article is an historical review and a tribute to the memory of Rodolfo Q. Pasqualini.


In situ growth of α-Fe2O3@Co3O4 core-shell wormlike nanoarrays for a highly efficient photoelectrochemical water oxidation reaction.
Photoelectrochemical (PEC) water splitting represents a promising strategy to convert solar energy into chemical energy in the form of hydrogen, but its performance is severely limited by the sluggish water oxidation reaction. Herein, for the first time, we report the direct assembly of an ultrathin, uniform, and dense layer of Co3O4 on wormlike nanostructured hematite (WN-α-Fe2O3) to form a large-area and high-density WN-α-Fe2O3@Co3O4 core-shell nanoarray via in situ hydrothermal growth followed by calcination, in which the electrostatic force between WN-α-Fe2O3 and the reactants, pH- and temperature-controlled structures of WN-α-Fe2O3, and ultralow nucleation rate of Co3O4 precursors all play critical roles. The obtained heteronanostructure array shows a photocurrent density of 3.48 mA cm-2, which is 4.05 times higher than that of pristine WN-α-Fe2O3 (0.86 mA cm-2), an onset potential of ∼0.62 V, 60 mV lower than that of α-Fe2O3 (∼0.68 V), and a photoconversion efficiency of 0.55%, 3.93 times higher than that of WN-α-Fe2O3 (0.14%). This is among the highest performances reported for Fe2O3-based photoanodes for water splitting. It is discovered that the Co3O4 shells can significantly enhance the charge separation, accelerate the charge transport and transfer, and reduce the charge transfer resistance from the photoelectrode to the electrolyte for a fast water oxidation reaction, thereby greatly promoting the PEC water oxidation performance of pristine WN-α-Fe2O3. This work not only creates a novel low-cost and Earth-abundant WN-α-Fe2O3@Co3O4 photoelectrode with superior PEC water oxidation performance and provides scientific insights into the enhancement mechanism, but also offers a general strategy for the in situ growth of water oxidation catalysts on various photoelectrodes with 3-D complex geometries for PEC water splitting.


When to start antiretroviral therapy: a swinging pendulum?
Although early initiation of antiretroviral treatment has long been associated with some benefit over later initiation, the magnitude of the benefit is becoming better defined with longer follow-up of large numbers of patients in cohort studies. These benefits have become more evident in part because of improvements in efficacy, tolerability, and convenience of antiretroviral treatment regimens. The benefits also reflect growing recognition of the effect of such treatment in reducing risk of both HIV-related and non-HIV-related complications that are not associated with low CD4+ cell count. On balance, currently available information supports using a CD4+ count of 350 cells/microL as a general threshold for initiating treatment, with immediate treatment warranted for selected patients, including those with conditions for which antiretroviral therapy is the best or only treatment. This article summarizes a presentation on when to initiate antiretroviral therapy made by Joel E. Gallant, MD, MPH, at an International AIDS Society-USA Continuing Medical Education course in New York in October 2007.


Neural substrates for sexual preference and motivation in the female and male rat.
Rodents identify a mating partner by using olfactory cues. Female rats in estrus spend a longer time sniffing odors of sexually active males when physical contacts are hampered. Sexually active males are attracted by odors of receptive females. The preference in either sex disappears when the subjects are gonadectomized, an effect reversible by supplement with estrogen or testosterone. Thus, circulating sex steroids determine the odor preference in both sexes. In both sexes, olfactory cues get to the basal forebrain; this area includes the preoptic area (POA), substantia innominata and accumbens, structures with estrogen receptor-positive neurons. In estrous females, neurons in the POA are activated during precopulatory motivational behavior. Lesion in this area practically eliminates sexual preference and diminishes the motivation. An increase in locomotion in females in estrus, which apparently depends on estrogen-sensitive POA projections to the midbrain locomotor region, has been considered to embody enhanced sexual motivation.


GABAergic control of rubral single unit activity during a reaction time task.
The activity of 61 rubral neurones was recorded in association with microinjections of GABA, muscimol, bicuculline-methiodide or saline, in cat Red Nucleus area, during the performance of a reaction time task. The depressing action of GABA and muscimol on the firing of most neurones (17/23) suggests that, in a behavioural situation, an inhibitory GABAergic control can be exerted on rubral neurones discharging with different patterns during the reaction time task. The motor slowing down induced by GABA and muscimol is in agreement with a general reduction of the rubral output. Injections of bicuculline, whose antagonistic effects on GABA transmission are well established in the Red Nucleus, had various consequences on the firing of rubral neurones: 1) the decreases of activity related to the reaction time task were never suppressed, suggesting that these task-related inactivations are probably not mediated by GABA A receptors; 2) an enhancement of the tonic and phasic discharges was found for 1/4 of the neurones (7/29), which were either activated or not modulated in relation to the reaction time task, suggesting that a sustained GABA A-mediated inhibition, blocked by bicuculline, could be exerted on these neurones; 3) a reduction of the tonic and phasic discharges was observed for other neurones (15/29), which were either activated, inactivated or not modulated in relation to the reaction time task, suggesting that the activity of these neurones could be controlled by inhibitory processes not mediated by GABA A receptors, possibly enhanced or released by bicuculline. The delay in motor triggering induced by bicuculline could be related to the disruption of the pattern or rubral output during the reaction time task, as a result of the opposite changes affecting the firing of rubral neurones. A well-balanced GABAergic activity appears to be critical in the control of rubral firing during the performance of the reaction time task.


A new computer enhanced visual learning method to train urology residents in pediatric orchiopexy: a prototype for Accreditation Council for Graduate Medical Education documentation.
Residency programs must continue to restructure teaching and assessment of surgical skills to improve the documentation of Accreditation Council for Graduate Medical Education competencies. To improve teaching and documenting resident performance we developed a computer enhanced visual learning method that includes a curriculum and administrative reports. The curriculum consists of 1) study of a step-by-step surgical tutorial of computer enhanced visuals that show specific surgical skills, 2) a checklist tool to objectively assess resident performance and 3) a log of postoperative feedback that is used to structure deliberate practice. All elements of the method are repeated with each case performed. We used the Accreditation Council for Graduate Medical Education index case of orchiopexy to pilot this project. All urology residents who trained at our institution from January 2006 to October 2007 performed orchiopexy using the computer enhanced visual learning method. The computer enhanced visual learning tutorial for orchiopexy consisted of customized computer visuals that demonstrate 11 steps or skills involved in routine inguinal orchiopexy, eg ligate hernia. The attending urologist rated resident competence with each skill using a 5-point Likert scale and provided specific feedback to the resident suggesting ways to improve performance. These ratings were weighted by case difficulty. The computer enhanced visual learning weighted score at entry into the clinical rotation was compared to the best performance during the rotation in each resident. Seven attending surgeons and 24 urology residents (resident training postgraduate years 1 to 8) performed a total of 166 orchiopexies. Overall the residents at each postgraduate year performed an average of 7 cases each with complexity ratings that were not significantly different among postgraduate year groups (average 2.4, 1-way ANOVA p not significant). The 7 attending surgeons did not differ significantly in assessment of skill performance or case difficulty (1-way ANOVA p not significant). Of the 24 residents 23 (96%) showed improvement in computer enhanced visual learning score/skill performance. In the entire group the average computer enhanced visual learning weighted score increased more than 50% from entry to best performance (137 to 234 orchiopexy units, paired t test p <0.0001). Computer enhanced visual learning is a novel method that enhances resident learning by breaking a core procedure into discrete steps and providing a platform for constructive feedback. Computer enhanced visual learning, which is a checklist tool, complies with Accreditation Council for Graduate Medical Education documentation requirements. Computer enhanced visual learning has wide applicability among surgical specialties.


Cystatin E1 and E2, new members of male reproductive tract subgroup within cystatin type 2 family.
The family of type 2 cystatin proteins is a class of cysteine proteinase inhibitors that function as potent inhibitors of papain-like cysteine proteinases. Recent studies have suggested that cystatins in the male reproductive tract subgroup may perform functions distinct from those of typical cystatins. The objective of the present study was to identify and characterize the expression of new gene members of the cystatin family 2 in mouse male reproductive tissues. Two new members of cystatin family 2, named mouse Cystatin E1 and mouse Cystatin E2 (mCST E1 and mCST E2, respectively), were identified in mice by searching the National Center for Biotechnology Information database for proteins containing homology to known type 2 cystatins. Human CST E1 has recently been reported independently under the name CST 11. The deduced amino acid sequences of these genes have significant homology with the family 2 cystatins, including four conserved cysteine residues at the C-terminus. Similar to other male reproductive subgroup cystatins, the inhibitory motifs are not well conserved in these genes. Northern blot analyses showed that both genes were highly expressed only in the epididymis. In situ hybridization demonstrated that both genes were restricted in their expression to the epithelial cells of the caput and that the highest expression was localized to the initial segment of caput epididymis. Northern blot analyses and in situ hybridization showed that both mCST E1 and E2 mRNA decreased after castration, and treatment with testosterone propionate (T) did not maintain expression of these genes. In fact, T treatment further repressed the expression of these genes in the epididymis following castration. Efferent ductule ligation resulted in a dramatic decrease of epididymal expression of mCST E1 and E2. The expression of mCST E1 mRNA was up-regulated by 17 beta-estradiol (E) administration for 7 days postcastration, whereas no recovery of mCST E1 mRNA level was detected after 14 days of E treatment. Combined E and T (E+T) treatment for 1 and 2 wk reduced the mCST E1 transcripts. The expression of mCST E2 mRNA was maintained by E administration for both 7 and 14 days after castration, whereas treatment of both T and E repressed the expression of mCST E2. Although both mCST E1 and E2 share significant homology with family 2 cystatins, including similar distribution in tissues and localization in epididymis, these genes may have different functions, because their regulation involves different hormones and, probably, other testicular factors.


Accuracy of cone-beam computed tomography at different resolutions assessed on the bony covering of the mandibular anterior teeth.
The aim of this study was to determine the accuracy of cone-beam computed tomography (CBCT) with different voxel resolutions. Measurements were made of the bony covering of the mandibular anterior teeth because this region is crucial in orthodontic treatment planning. CBCT data at 2 resolutions (0.125-mm and 0.4-mm voxels) were collected from 8 intact cadaver heads. The vertical position of the mucogingival junction was clinically assessed. After removal of the gingiva, vertical and horizontal bony measurements were taken, and the buccal alveolar bone margin was determined. Anatomic bony measures were compared with the CBCT measures, and the correlation of the mucogingival junction measures to the buccal alveolar bone margin measures was evaluated. Bony measures obtained with CBCT were accurate and differed only slightly from the physical findings. The mean differences, ranging from -0.13 to +0.13 mm, were statistically not significant, but the limits of agreement showed discrepancies in the measurements as large as 2.10 mm, depending on measurement and resolution. Buccal alveolar bone margin measurements correlated with the mucogingival junction measurements (P <0.001). On average, the mucogingival junction was 1.67 mm more apical than the buccal alveolar bone margin (CI 95%, 1.35-1.98 mm). CBCT renders anatomic measures reliably and is an appropriate tool for linear measurements. Presence of soft tissue as well as different voxel size affect the precision of the data. A customized resolution protocol must be chosen according to the accuracy needed. However, even the 0.125-mm voxel protocol does not depict the thin buccal alveolar bone covering reliably, and there is a risk of overestimating fenestrations and dehiscences. The mucogingival junction appears to follow the buccal alveolar bone margin in a parallel line.


The limit fold change model: a practical approach for selecting differentially expressed genes from microarray data.
The biomedical community is developing new methods of data analysis to more efficiently process the massive data sets produced by microarray experiments. Systematic and global mathematical approaches that can be readily applied to a large number of experimental designs become fundamental to correctly handle the otherwise overwhelming data sets. The gene selection model presented herein is based on the observation that: (1) variance of gene expression is a function of absolute expression; (2) one can model this relationship in order to set an appropriate lower fold change limit of significance; and (3) this relationship defines a function that can be used to select differentially expressed genes. The model first evaluates fold change (FC) across the entire range of absolute expression levels for any number of experimental conditions. Genes are systematically binned, and those genes within the top X% of highest FCs for each bin are evaluated both with and without the use of replicates. A function is fitted through the top X% of each bin, thereby defining a limit fold change. All genes selected by the 5% FC model lie above measurement variability using a within standard deviation (SDwithin) confidence level of 99.9%. Real time-PCR (RT-PCR) analysis demonstrated 85.7% concordance with microarray data selected by the limit function. The FC model can confidently select differentially expressed genes as corroborated by variance data and RT-PCR. The simplicity of the overall process permits selecting model limits that best describe experimental data by extracting information on gene expression patterns across the range of expression levels. Genes selected by this process can be consistently compared between experiments and enables the user to globally extract information with a high degree of confidence.


Distribution of C-reactive protein and its association with cardiovascular risk factors in a population-based sample of Chinese.
C-reactive protein (CRP) levels vary remarkably with ethnic status. Its distribution and correlates should be investigated across diverse populations, and these were limited in a representative Chinese population. We investigated 3133 participants aged 18-80 years in Shanghai, which were sampled using a randomized, stratified, multi-stage sampling method. The distribution of CRP was highly skewed toward a lower level. The median CRP was 0.55 mg/L (0.61 mg/L in males, 0.51 mg/L in females). Participants living in urban region had higher CRP levels than those in rural region (0.67 vs. 0.46 mg/L). CRP levels showed significant correlation with traditional cardiovascular risk factors, and it was most strongly correlated with body mass index. Multivariate logistic regression analyses indicated that elevated CRP (being in the top 15 percentile of CRP; CRP > or =2.09 mg/L) was significantly associated with obesity, hypertension, diabetes, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol, high triglycerides and cardiovascular disease history. In conclusion, the distribution of CRP in adult Chinese was comparable with that of many other Asian populations but different from that of Western populations. Metabolic impairment was associated with elevated CRP, and CRP levels should be interpreted in conjunction with the lipid profile.


Differential survival of Ichthyophonus isolates indicates parasite adaptation to its host environment.
In vitro viability of Ichthyophonus spp. spores in seawater and freshwater corresponded with the water type of the host from which the spores were isolated. Among Ichthyophonus spp. spores from both marine and freshwater fish hosts (Pacific herring, Clupea pallasii, and rainbow trout, Oncorhynchus mykiss, respectively), viability was significantly greater (P < 0.05) after incubation in seawater than in freshwater at all time points from 1 to 60 min after immersion; however, magnitude of the spore tolerances to water type differed with host origin. Ichthyophonus sp. adaptation to its host environment was indicated by greater seawater tolerance of spores from the marine host and greater freshwater tolerance of spores from the freshwater host. Prolonged aqueous survival of Ichthyophonus spp. spores in the absence of a host provides insight into routes of transmission, particularly among planktivorous fishes, and should be considered when designing strategies to dispose of infected fish carcasses and tissues.


Localization of shapes using statistical models and stochastic optimization.
In this paper, we present a new model for deformations of shapes. A pseudo-likelihood is based on the statistical distribution of the gradient vector field of the gray level. The prior distribution is based on the Probabilistic Principal Component Analysis (PPCA). We also propose a new model based on mixtures of PPCA that is useful in the case of greater variability in the shape. A criterion of global or local object specificity based on a preliminary color segmentation of the image, is included into the model. The localization of a shape in an image is then viewed as minimizing the corresponding Gibbs field. We use the Exploration/Selection (E/S) stochastic algorithm in order to find the optimal deformation. This yields a new unsupervised statistical method for localization of shapes. In order to estimate the statistical parameters for the gradient vector field of the gray level, we use an Iterative Conditional Estimation (ICE) procedure. The color segmentation of the image can be computed with an Exploration/Selection/Estimation (ESE) procedure.


Mechanistic aspects of beta-bond-cleavage reactions of aromatic radical cations.
The mesolytic cleavage of a beta-C-X bond (ArCR(2)-X(*+) --> ArCR(2)(*/+) + X(+/*)) is one of the most important reactions of alkylaromatic radical cations. In this Account, our group's results concerning some fundamental aspects of this process (cleavage mode, structural and stereoelectronic effects, competitive breaking of different beta-bonds, nucleophilic assistance, possible stereochemistry, carbon vs oxygen acidity in arylalkanol radical cations) are presented and critically discussed for reactions where X = H, CR(3), SR, and SiR(3). Several examples illustrating how this information was exploited as a tool to detect electron-transfer mechanisms in chemical and enzymatic oxidations are also reported.


Vibrational dynamics in dendridic oligoarylamines by Raman spectroscopy and incoherent inelastic neutron scattering.
Vibrational dynamics in triarylamine dendrimers was studied in a complementary way by Raman and infrared (IR) spectroscopies and incoherent inelastic neutron scattering (IINS). Three molecules were investigated, namely, unsubstituted triarylamine dendrimer of the first generation and two dendrimers of the first and second generation, substituted in the crown with butyl groups. To facilitate the assignment of the observed IR and Raman modes as well as the IINS peaks, vibrational models, based on the general valence force field method (GVFF), were calculated for all three compounds studied. A perfect consistency between the calculated and experimental results was found. Moreover, an important complementarity of the vibrational spectroscopies and IINS was established for the investigated dendrimers. The IINS peaks originating mainly from the C-H motions were not restricted by particular selection rules and only dependent on the IINS cross section. To the contrary, Raman and IR bands were imposed by the selection rules and the local geometry of the dendrimers yielding mainly C-C and C-N deformation modes with those of C-H nature of much lower intensity. Raman spectroscopy was also applied to the studies of the oxidation of dendrimers to their cationic forms. A strong Raman resonance effect was observed, since the spectra of the studied compounds, registered at different levels of their oxidation, strongly depended on the position of the excitation line with respect to their electronic spectrum. In particular, the blue (458 nm) excitation line turned out to be insensitive toward the cationic forms yielding very limited spectral information. To the contrary, the use of the red (647 nm) and infrared (1064 nm) excitation lines allowed for an unambiguous monitoring of the spectral changes in dendrimers oxidized to nominally monocationic and tricationic states. The analysis of oxidation-induced spectral changes in the tricationic state indicated that the charge storage configuration predominantly involved one spinless dication of the quinoid bond sequence and one radical cation. However, small numbers of dications were also found in a nominally monocationic state, where only radical cations should have been present. This finding was indicative of some inhomogeneity of the oxidation.


Empathy and feelings of guilt experienced by nurses: A cross-sectional study of their role in burnout and compassion fatigue symptoms.
The main goal of this study was to explore the relationships between empathy, empathy-based pathogenic guilt and professional quality of life (burnout and compassion fatigue). We aim to test a model in which we hypothesize that when empathic feelings are related to pathogenic guilt, burnout and compassion fatigue symptoms may be increased. Empathy is at the core of nursing practice, and has been associated with positive outcomes not only for the healthcare provider but also for the patient. However, empathy is also at the core of guilt feelings that, when excessive and misdirected, can lead to pathogenic guilt beliefs. We focused on two types of empathy-based guilt characterized by excessive responsibility over others' well-being and how these can be related to professional quality of life. This study is a cross-sectional self-report survey. Data were collected during 2014 and 2015. Two hundred ninety-eight nurses from public hospitals in Portugal's north and center region were surveyed. Professional quality of life (burnout and compassion fatigue), empathy, and empathy-based guilt were measured using validated self-report measures. Correlation analyses showed that empathy-based guilt was positively associated with empathy, and with burnout and compassion fatigue. Results from multiple mediation models further indicated when empathy is associated with empathy-based guilt, this leads to greater levels of burnout and compassion fatigue. Given the nature of their work, nurses who experience pathogenic guilt feelings may have compromised well-being, and this should be addressed in training programs aiming at preventing or treating burnout and compassion fatigue.


Suppression of NF-κB signaling by Pseudorabies virus DNA polymerase processivity factor UL42 via recruiting SOCS1 to promote the ubiquitination degradation of p65.
The NF-κB pathway is a critical signaling involved in the regulation of the inflammatory and innate immune responses. Previous studies have shown that Pseudorabies Virus (PRV), a porcine alpha herpesvirus, could lead to the phosphorylation and nucleus translocation of p65 while inhibiting the expression of NF-κB-dependent inflammatory cytokines, which indicated that there may be unknown mechanisms downstream of p65 that downregulate the activation of NF-κB signaling. Here, we found that PRV DNA polymerase factor UL42 inhibited TNFα-, LPS-, IKKα-, IKKβ-, and p65-mediated transactivation of NF-κB signaling, which demonstrated UL42 worked either at or downstream of p65. In addition, it was found that the DNA-binding activity of UL42 was required for inhibition of NF-κB signaling. Importantly, it was revealed that UL42 could induce the ubiquitination degradation of p65 by upregulating the suppressor of cytokine signaling 1 (SOCS1). Additionally, it was found that UL42 could promote the K6/K29-linked ubiquitination of p65. Finally, knockdown of SOCS1 attenuated the replication of PRV and led to a significant increase of the inflammatory cytokines. Taken together, our findings uncovered a novel mechanism that PRV-UL42 could upregulated SOCS1 to promote the ubiquitination degradation of p65 to prevent excessive inflammatory response during PRV infection.


Troglitazone protects human erythrocytes from oxidant damage.
The antidiabetic drug troglitazone contains the active chromanol ring of alpha-tocopherol, which should give it antioxidant properties within cells. In these studies, the antioxidant effects of troglitazone were tested in human erythrocytes and in their ghosts. Troglitazone bound to erythrocyte ghosts in a linear manner and was retained even after centrifugation washes. In response to an oxidant stress generated by a water-soluble free radical initiator, troglitazone that was bound to erythrocyte ghosts was oxidized, but induced a lag-phase in the disappearance of endogenous alpha-tocopherol and in the appearance of lipid hydroperoxides. Troglitazone also delayed loss of endogenous alpha-tocopherol and hemolysis in washed intact erythrocytes in response to free radical-induced extracellular oxidant stress. To mimic exposure of erythrocytes to lipid hydroperoxides in vivo, erythrocytes were incubated with phospholipid liposomes that contained small amounts of preformed lipid hydroperoxides. This induced an oxidant stress in both the liposomes and cells. Troglitazone in concentrations above 4 microM almost completely prevented further appearance of lipid hydroperoxides in the liposomes, and also completely preserved alpha-tocopherol in the erythrocytes. The present results suggest that troglitazone will help to prevent peroxidative damage to erythrocytes in areas of excessive oxidant stress in the vascular bed.


Monte Carlo investigation of the thermodynamic properties of (H2O)n and (H2O)nH2 (n = 2-20) clusters.
The classical thermodynamic properties of water clusters modeled by the TIP4P potential with and without the inclusion of molecular hydrogen are calculated using Monte Carlo methods. The temperature-dependent heat capacity curves of the dimer and the smaller pure water clusters having ring structures show low-temperature anomalies arising from the onset of a transition from librational motion to free rotational motion. Pure water clusters having cage structures display heat capacity anomalies characteristic of "melting" phase changes. The addition of molecular hydrogen to the water clusters has little impact on the structure of the water core, but low-temperature heat capacity anomalies are observed that arise from the onset of hindered to free rotational and translational motion of the hydrogen molecule with respect to the skeletal moieties of the core. The Gibbs free energy changes associated with the growth of pure water clusters and the addition of molecular hydrogen to the water clusters are determined using a combination of state-integration methods and an application of the Gibbs-Helmholtz equation. For the temperature integration of the Gibbs-Helmholtz equation, a quadrature method is introduced that avoids numerical difficulties arising from singularities in the integrand at low temperatures. For the growth of pure water clusters, the fine structure of the enthaply and the low-temperature Gibbs free energy as a function of cluster size is rationalized using an ansatz of molecular dipole orientations. For the addition of molecular hydrogen to water clusters, the Gibbs free energy change is a virtually flat function of cluster size showing no fine structure.


The evolutionary ecology of generalization: among-year variation in host plant use and offspring survival in a butterfly.
The majority of phytophagous insects are relatively specialized in their food habits, and specialization in resource use is expected to be favored by selection in most scenarios. Ecological generalization is less common and less well understood, but it should be selected for by (1) rarity of resources, (2) resource inconstancy, or (3) unreliability of resource quality. Here, we test these predictions by studying egg distribution and offspring survival in the orange tip butterfly, Anthocharis cardamines, on different host plants in Sweden over a five-year period. A total of 3800 eggs were laid on 16 of the 18 crucifers available at the field site during the five years. Three main factors explained host plant generalization: (1) a rarity of food resources in which the female encounter rate of individual crucifer plants was low and within-year phenological succession of flowering periods of the different crucifers meant that individual species were suitable for oviposition only within a short time window, which translates to a low effective abundance of individual crucifer species as experienced by females searching for host plants, making specialization on a single crucifer species unprofitable; (2) variation in food resources in which among-year variation in availability of any one host plant species was high; and (3) larval survivorship varied unpredictably among years on all host plants, thereby necessitating a bet-hedging strategy and use of several different host plants. Unpredictable larval survival was caused by variation in plant stand habitat characteristics, which meant that drowning and death from starvation affected different crucifers differently, and by parasitism, which varied by host plant and year. Hence, our findings are in agreement with the theoretical explanation of ecological generalization above, helping to explain why A. cardamines is a generalist throughout its range with respect to genera within the Cruciferae.


Individual nurse and organizational context considerations for better Knowledge Use in Pain Care.
Nurses are involved in many of the painful procedures performed on hospitalized children. In collaboration with physicians, nurses have an exceptional responsibility to have knowledge to manage the pain; however, the evidence indicates this is not being done. Issues may be twofold: (a) opportunities to improve knowledge of better pain care practices and/or (b) ability to use knowledge. Empirical evidence is available that if used by health care providers can reduce pain in hospitalized children. Theory-guided interventions are necessary to focus resources designated for learning and knowledge translation initiatives in the area of pain care. This article presents the Knowledge Use in Pain Care (KUPC) conceptual model that blends concepts from the fields of knowledge utilization and work life context, which are believed to influence the translation of knowledge to practice. The four main components in the KUPC model include those related to the organization, the individual nurse, the individual patient, and the sociopolitical context. The KUPC model was conceptualized to account for the complex circumstances surrounding nurse's knowledge uptake and use in the context of pain care. The model provides a framework for health care administrators, clinical leaders, and researchers to consider as they decide how to intervene to increase knowledge use to reduce painful experiences of children in the hospital.


Silent myelin-weighted magnetic resonance imaging.
Background: Inhomogeneous Magnetization Transfer (ihMT) is an emerging, uniquely myelin-specific magnetic resonance imaging (MRI) contrast. Current ihMT acquisitions utilise fast Gradient Echo sequences which are among the most acoustically noisy MRI sequences, reducing patient comfort during acquisition. We sought to address this by modifying a near silent MRI sequence to include ihMT contrast. Methods: A Magnetization Transfer preparation module was incorporated into a radial Zero Echo-Time sequence. Repeatability of the ihMT ratio and inverse ihMT ratio were assessed in a cohort of healthy subjects. We also investigated how head orientation affects ihMT across subjects, as a previous study in a single subject suggests this as a potential confound. Results: We demonstrated that ihMT ratios comparable to existing, acoustically loud, implementations could be obtained with the silent sequence. We observed that the ihMT ratio varied with the orientation of the head. Conclusions: Silent ihMT imaging is a comparable alternative to conventional, noisy, alternatives. For all future ihMT studies we recommend careful attention should be paid to subject positioning within the scanner.


FLIP is frequently expressed in endometrial carcinoma and has a role in resistance to TRAIL-induced apoptosis.
The FLICE-inhibitory protein (FLIP) plays a key role in the regulation of apoptosis triggered by death ligands. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in some types of tumor but not in others. To assess the possible role of FLIP in apoptosis resistance in endometrial carcinoma, we performed an immunohistochemical study on a tissue microarray composed of 95 endometrial carcinomas. We found positive signals in 43% of the cases, as well as a significant difference in FLIP expression between stage I and II tumors. Moreover, we observed that endometrial carcinoma cell lines Ishikawa and KLE did not undergo apoptosis after TRAIL treatment. Cotreatment of these cells with the inhibitor of transcription actinomycin D resulted in a dramatic decrease in cell viability and induced activation of caspase-8. These events coincided with downregulation of FLIP mRNA and protein. Inhibitors of caspase-8 or overexpression of FLIP completely blocked apoptosis induced by actinomycin D plus TRAIL cotreatment. More importantly, downregulation of endogenous FLIP expression by specific siRNAs sensitized endometrial carcinoma cells to TRAIL-induced apoptosis in the absence of actinomycin D. Taken together, our results suggest for the first time a critical role for FLIP in the regulation apoptosis triggered by TRAIL in endometrial carcinoma cells.


Virus-induced gene silencing of WRKY53 and an inducible phenylalanine ammonia-lyase in wheat reduces aphid resistance.
Although several wheat genes differentially expressed during the Russian wheat aphid resistance response have recently been identified, their requirement for and specific role in resistance remain unclear. Progress in wheat-aphid interaction research is hampered by inadequate collections of mutant germplasm and difficulty in transforming hexaploid wheat. Virus-induced gene silencing (VIGS) technology is emerging as a viable reverse genetics approach in cereal crops. However, the potential of VIGS for determining aphid defence gene function in wheat has not been evaluated. We report on the use of recombinant barley stripe mosaic virus (BSMV) to target and silence a WRKY53 transcription factor and an inducible phenylalanine ammonia-lyase (PAL) gene, both predicted to contribute to aphid defence in a genetically resistant wheat line. After inoculating resistant wheat with the VIGS constructs, transcript abundance was reduced to levels similar to that observed in susceptible wheat. Notably, the level of PAL expression was also suppressed by the WKRY53 construct, suggesting that these genes operate in the same defence response network. Both knockdowns exhibited a susceptible phenotype upon aphid infestation, and aphids feeding on silenced plants exhibited a significant increase in fitness compared to aphids feeding on control plants. Altered plant phenotype and changes in aphid behaviour after silencing imply that WKRY53 and PAL play key roles in generating a successful resistance response. This study is the first report on the successful use of VIGS to investigate genes involved in wheat-insect interactions.


Clinical education in the ambulatory care setting.
New training initiatives in ambulatory medicine are being developed in medical schools and residency training programs due to the need to expand education in ambulatory medicine. Most diagnostic and management decisions are being made in outpatient settings. In this context the perception of what constitutes effective teaching in the ambulatory setting needs to be addressed. The skills of questioning, role modeling, emphasizing general principles, and concept comprehension are similar in both inpatient teaching and outpatient teaching. The approach to problem solving, site of teaching, and provision of feedback may differ from inpatient teaching.


The aqueous degradation of butylated hydroxyanisole by UV/S2O8(2-): study of reaction mechanisms via dimerization and mineralization.
Three distinctive phases of BHA reactivity toward UV/ S2O8(2-) at acidic, neutral, and basic pH range were examined, where 80-100% mineralization has been observed within an hour of irradiation under 254 nm. A reduction in solution pH during the reaction was observed mainly due to the complete conversion of S2O8(2-) to sulfate ion together with proton generation. Seven measurable intermediates were found via an oxidation and dimerization process at all tested pH levels. The BHA decay mechanisms are quite different in acidic condition and at other pH levels. There are three unique intermediates that are only detectable at pH 3 via two additional pathways. This is due to the generation of weaker oxidants or radicals which results in a slower degradation of the BHA, and therefore, the accumulation of these intermediates to detectable levels. The rate of BHA decay generally increases from low to high pH levels; however, the corresponding mineralization at higher pH is retarded due to the futile process of recombining radicals and involvement of intermediates. Therefore, neutral pH was suggested to be the optimum condition in terms of mineralization and moderate efficiency in removing BHA.


Voice disorders in teachers. The role of family physicians.
To look at the prevalence and impact of voice problems on teachers and assessing the teachers knowledge on vocal hygiene and habits, as well as which parameters mostly triggered the seeking of medical attention and how family doctors could intervene in this spectrum. A survey that consists of 16 questions was used to look at the prevalence and impact of voice problems on teachers and to identify the associated risk factors at the American University of Beirut, Lebanon, during the year 2005. A considerable proportion (46%) perceived their voice as fair or worse, and 79% had never consulted a throat specialist. Voice disorders affected most of teachers particularly on their job. The mean number of vocal habits per person was estimated at 2.4 with smoking being the most common (38.7%). Two thirds of teachers were unaware of more than half the factors that can negatively affect their voice. Symptoms exceeding 6 months significantly increased the probability of consulting a physician by 2.5 folds. Family physicians can reduce the prevalence of vocal dysfunction in teachers through education and by pointing the various symptoms necessitating a specialist's early consultation especially when history of smoking is present.


Association between diabetes mellitus and poor patient outcomes after out-of-hospital cardiac arrest: A systematic review and meta-analysis.
Diabetes mellitus (DM) serves as an important prognostic indicator in patients with cardiac-related illness. Our objective is to compare survival and neurological outcomes among diabetic and non-diabetic patients who were admitted to the hospital after an out-of-hospital cardiac arrest (OHCA). We searched MEDLINE and EMBASE for relevant articles from database inception to July 2018 without any language restriction. Studies were included if they evaluated patients who presented with OHCA, included mortality and neurological outcome data separately for DM patients and Non-DM patients and reported crude data, odds ratio (OR), relative risk (RR) or hazard ratio (HR). Two investigators independently reviewed the retrieved citations and assessed eligibility. The quality of included studies was evaluated using Newcastle-Ottawa quality assessment scale for cohort studies. Random-effect models using the generic variance method were used to create pooled odds ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using the I2 value. Survival and neurological outcomes (using modified rankin scale and cerebral performance category scale) after OHCA in hospitalized patients with DM compared with patients without DM. Out of 57 studies identified, six cohort studies met the inclusion criteria. In an analysis of unadjusted data, patients with DM had lower odds of survival, pooled OR 0.64; 95% CI, 0.52-0.78, [I2 = 90%]. When adjusted ORs were pooled, the association between DM and survival after OHCA was still significantly reduced, pooled OR 0.78, 95% CI, 0.68-0.89 [I2 = 55%]. Unadjusted pooled OR revealed poor neurological outcomes in patients with DM, pooled OR 0.55, 95% CI, 0.38-0.80 [I2 = 90%]. The result demonstrates significant poor outcomes of in-hospital survival and neurological outcomes among DM patients after OHCA.


[Isolation and properties of specific trypsin inhibitor from human seminal plasma].
Gel filtration of human seminal plasma on Sephadex G-100 revealed four zones displaying the activity of trypsin inhibitors. The inhibitor from the zone corresponding to the molecular mass of 30-40 kDa was obtained in an electrophoretically homogeneous form. The purification procedure included gel filtration on Sephadex G-100, anion-exchange chromatography on DEAE-Sephadex A-50, ammonium sulfate precipitation and hydrophobic chromatography on phenyl-Sepharose 4B. The inhibitor thus obtained has a specific activity of 1.29 IU/mg protein in a caseinolytic test, molecular mass of about 36 kDA and pI of 7.2. The glycosidase and lectin analysis of the carbohydrate component of the protein revealed the presence of neuraminic (sialic) acid and galactose (galactosamine). The amino acid composition of the protein was determined. Antibodies to this protein were obtained; the high specificity of the protein for human sperm was demonstrated The inhibitor was found to be immunochemically identical to previously described prostatic beta-globulin.


[Functional effects of pentagastrin and diagnostic possibilities of the pentagastrin test].
The effect on gastric secretion of a single pentagastrin dose (6 micrograms/kg) against submaximal doses of histamine, euphylline and limontar was studied in 100 healthy subjects aged 20-30. It is shown that pentagastrin test corresponds to maximal histamine test allowing rough measurement of lining cells mass. Normal secretory values and mass of the lining cells have been established as well as normal secretory response of the stomach to submaximal histamine (0.008 mg/kg) and euphylline (7 mg/kg) tests. Diagnostic significance of the pentagastrin test in peptic ulcer and chronic gastritis with secretory insufficiency has been supported. There were some cases of secretory response to euphylline and limontar in pentagastrin-refractory forms of gastric secretion due to mobilization of functional cellular component of the gastric glands. Pentagastrin inhibited initially enhanced gastric evacuation though motor function of the stomach showed no response.


Reduction in overweight and obesity from a 3-year community-based intervention in Australia: the 'It's Your Move!' project.
'It's Your Move!' was a 3-year intervention study implemented in secondary schools in Australia as part of the Pacific Obesity Prevention In Communities Project. This paper reports the outcome results of anthropometric indices and relevant obesity-related behaviours. The interventions focused on building the capacity of families, schools and communities to promote healthy eating and physical activity. Baseline response rates and follow-up rates were 53% and 69% respectively for the intervention group (n=5 schools) and 47% and 66% respectively for the comparison group (n=7 schools). Statistically significant relative reductions in the intervention versus comparison group were observed: weight (-0.74 kg, P < 0.04), and standardized body mass index (-0.07, P<0.03), and non-significant reductions in prevalence of overweight and obesity (0.75 odds ratio, P=0.12) and body mass index (-0.22, P=0.06). Obesity-related behavioural variables showed mixed results with no pattern of positive intervention outcomes. In conclusion, this is the first study to show that long-term, community-based interventions using a capacity-building approach can prevent unhealthy weight gain in adolescents. Obesity prevention efforts in this important transitional stage of life can be successful and these findings need to be translated to scale for a national effort to reverse the epidemic in children and adolescents.


A versatile nano display platform from bacterial spore coat proteins.
Dormant bacterial spores are encased in a thick protein shell, the 'coat', which contains ∼70 different proteins. The coat protects the spore from environmental insults, and is among the most durable static structures in biology. Owing to extensive cross-linking among coat proteins, this structure has been recalcitrant to detailed biochemical analysis, so molecular details of how it assembles are largely unknown. Here, we reconstitute the basement layer of the coat atop spherical membranes supported by silica beads to create artificial spore-like particles. We report that these synthetic spore husk-encased lipid bilayers (SSHELs) assemble and polymerize into a static structure, mimicking in vivo basement layer assembly during sporulation in Bacillus subtilis. In addition, we demonstrate that SSHELs may be easily covalently modified with small molecules and proteins. We propose that SSHELs may be versatile display platforms for drugs and vaccines in clinical settings, or for enzymes that neutralize pollutants for environmental remediation.


Working memory in schizophrenia: an EEG study using power spectrum and coherence analysis to estimate cortical activation and network behavior.
This study examined regional cortical activations and cortico-cortical connectivity in a group of 20 high-functioning patients with schizophrenia and 20 healthy controls matched for age and sex during a 0- and a 2-back working memory (WM) task. An earlier study comparing schizophrenia patients with education level-matched healthy controls revealed less "optimally" organized network during the 2-back task, whereas a second study with healthy volunteers had suggested that the degree of cortical organization may be inversely proportional to educational level (less optimal functional connectivity in better educated individuals interpreted as the result of higher efficiency). In the present study, both groups succeeded in the 2-back WM task although healthy individuals had generally attained a higher level of education. First absolute power spectrum of the different frequency bands corresponding to the electrodes of each lobe was calculated. Then the mean values of coherence were calculated as an index of the average synchronization to construct graphs in order to characterize local and large scale topological patterns of cortico-cortical connectivity. The power spectra analyses showed signs of hypofrontality in schizophrenics with an asymmetry. Additionally, differences between the groups with greater changes during WM in healthy individuals were visible in all lobes more on the left side. The graph parameter results indicated decreased small-world architecture i.e. less optimal cortico-cortical functional organization in patients as compared to controls. These findings are consistent with the notion of aberrant neural organization in schizophrenics which is nevertheless sufficient in supporting adequate task performance.


Using Technology to Enhance Discharge Teaching and Improve Coping for Patients After Stroke.
A diagnosis of stroke is a life-changing event. Effective discharge teaching after a stroke is crucial for recovery, but the overload of information can be overwhelming for patients and caregivers. The purpose of this study was to examine differences in discharge readiness and postdischarge coping in patients admitted for stroke after the use of individualized postdischarge information/education provided via a technology package (including patient online portal access, e-mail/secure messaging) compared with current standard discharge teaching methods (verbal/written instructions). This study used a descriptive comparative design to evaluate the difference between the nonintervention group A and the intervention group B. Patients in group B received additional discharge information via secured e-mail messaging at postdischarge days 2, 6, and 10. Two validated tools, Readiness for Hospital Discharge Form and Post-Discharge Coping Difficulty Scale, were used. One hundred patients were recruited for the study, but the final number of complete data sets collected was 86-42 in group A and 44 in group B. There was no statistically significant difference between the groups in discharge readiness. There was a significant difference in coping scores between the 2 groups, with the technology group exhibiting higher coping. New technology affords new options to improve discharge readiness and contribute to positive patient coping after stroke. The researchers hope that this study will contribute to the growing body of evidence showing success using aspects of technology to enhance discharge teaching and follow-up after discharge.


[New class of drugs for treatment of eye vascular diseases].
Hemolytic ocular film (HOF) represents a polymer-based "puff pastry" whose external layers contain antioxidant emoxipine and the internal layer contains an immobilized thrombolytic enzyme; such a structure ensures a successive multifunctional effect on the main components of pathogenesis: lipid peroxidation, local hemostasis, fibrinolysis, and immune system of patients with vascular abnormalities of the eyes. The drug was used in the treatment of 248 patients with intraocular hemorrhages of traumatic origin. Control group (150 patients with the same condition) was treated traditionally. Application of HOF resulted in complete or almost complete lysis of the blood in 95% of patients; in 5% the effect was null. Traditional therapy helped attain complete lysis of the blood in 9% and partial in 43% of patient; in 48% of patients the effect was null.


Challenges for meeting the global food and nutrient needs in the new millennium.
Major advances have occurred in food production during the last 30 years as a result of the adoption of green revolution technology. The price of rice and wheat is 40 % lower than it was in the 1950s. This lower price has helped the poorer sections of society, who spend 50-60% of their income on food. The proportion of the population in the developing world that is malnourished fell from 46.5% in the early 1960s to 31% in 1995. However, there are still 1.3 billion of the population who go to bed hungry every day. Deficiencies of micronutrients such as Fe, Zn and vitamin A affect millions of the population in the developing world. The world population is increasing at the rate of 1.4%, or an increase of eighty million per year. It is estimated that we will have to produce 50% more food grains by 2025. Various strategies for meeting this challenge exist, including the development of cereal varieties with a higher yield potential and yield stability, and farmer-friendly public policies. In order to tackle hidden hunger, efforts are underway to develop crop varieties with higher concentrations of Fe and Zn. Recently, a breakthrough has occurred in the introduction of the genes for the pathway leading to the biosynthesis of beta-carotene, a precursor of vitamin A, in rice. Various conventional approaches and modem tools of biotechnology are being employed in the development of crop varieties with higher yields and higher levels of micronutrients.


Combinatorial design of ionizable lipid nanoparticles for muscle-selective mRNA delivery with minimized off-target effects.
Ionizable lipid nanoparticles (LNPs) pivotal to the success of COVID-19 mRNA (messenger RNA) vaccines hold substantial promise for expanding the landscape of mRNA-based therapies. Nevertheless, the risk of mRNA delivery to off-target tissues highlights the necessity for LNPs with enhanced tissue selectivity. The intricate nature of biological systems and inadequate knowledge of lipid structure-activity relationships emphasize the significance of high-throughput methods to produce chemically diverse lipid libraries for mRNA delivery screening. Here, we introduce a streamlined approach for the rapid design and synthesis of combinatorial libraries of biodegradable ionizable lipids. This led to the identification of iso-A11B5C1, an ionizable lipid uniquely apt for muscle-specific mRNA delivery. It manifested high transfection efficiencies in muscle tissues, while significantly diminishing off-targeting in organs like the liver and spleen. Moreover, iso-A11B5C1 also exhibited reduced mRNA transfection potency in lymph nodes and antigen-presenting cells, prompting investigation into the influence of direct immune cell transfection via LNPs on mRNA vaccine effectiveness. In comparison with SM-102, while iso-A11B5C1's limited immune transfection attenuated its ability to elicit humoral immunity, it remained highly effective in triggering cellular immune responses after intramuscular administration, which is further corroborated by its strong therapeutic performance as cancer vaccine in a melanoma model. Collectively, our study not only enriches the high-throughput toolkit for generating tissue-specific ionizable lipids but also encourages a reassessment of prevailing paradigms in mRNA vaccine design. This study encourages rethinking of mRNA vaccine design principles, suggesting that achieving high immune cell transfection might not be the sole criterion for developing effective mRNA vaccines.


Chemically Diverse S. mansoni HDAC8 Inhibitors Reduce Viability in Worm Larval and Adult Stages.
Schistosoma mansoni HDAC8 is a reliable target to fight schistosomiasis, and several inhibitors have been reported in the literature up to now. Nevertheless, only a few displayed selectivity over the human deacetylases and some exhibited very low or no activity against parasite larvae and/or adult worms. We report here the in vitro enzyme and biological activity of a small library of HDAC inhibitors from our lab, in many cases exhibiting submicromolar/nanomolar potency against smHDAC8 and diverse degrees of selectivity over hHDAC1 and/or hHDAC6. Such compounds were tested against schistosomula, and a selection of them against the adult forms of S. mansoni, to detect their effect on viability. Some of them showed the highest viability reduction for the larval stage with IC50 values around 1 μM and/or displayed ∼40-50 % activity in adult worms at 10 μM, joined to moderate to no toxicity in human fibroblast MRC-5 cells.


Exploring non-linear transition pathways in social-ecological systems.
Tipping point dynamics are fundamental drivers for sustainable transition pathways of social-ecological systems (SES). Current research predominantly analyzes how crossing tipping points causes regime shifts, however, the analysis of potential transition pathways from these social and ecological tipping points is often overlooked. In this paper, we analyze transition pathways and the potential outcomes that these may lead to via a stylized model of a system composed of interacting agents exploiting resources and, by extension, the overall ecosystem. Interactions between the social and the ecological system are based on a perception-exploitation framework. We show that the presence of tipping points in SES may yield counter-intuitive social-ecological transition pathways. For example, the high perception of an alarming ecological state among agents can provide short-term ecological benefits, but can be less effective in the long term, compared to a low-perception condition. This work also highlights how understanding non-linear interactions is critical for defining suitable transition pathways of any SES.


Single-molecule visualization of twin-supercoiled domains generated during transcription.
Transcription-coupled supercoiling of DNA is a key factor in chromosome compaction and the regulation of genetic processes in all domains of life. It has become common knowledge that, during transcription, the DNA-dependent RNA polymerase (RNAP) induces positive supercoiling ahead of it (downstream) and negative supercoils in its wake (upstream), as rotation of RNAP around the DNA axis upon tracking its helical groove gets constrained due to drag on its RNA transcript. Here, we experimentally validate this so-called twin-supercoiled-domain model with in vitro real-time visualization at the single-molecule scale. Upon binding to the promoter site on a supercoiled DNA molecule, RNAP merges all DNA supercoils into one large pinned plectoneme with RNAP residing at its apex. Transcription by RNAP in real time demonstrates that up- and downstream supercoils are generated simultaneously and in equal portions, in agreement with the twin-supercoiled-domain model. Experiments carried out in the presence of RNases A and H, revealed that an additional viscous drag of the RNA transcript is not necessary for the RNAP to induce supercoils. The latter results contrast the current consensus and simulations on the origin of the twin-supercoiled domains, pointing at an additional mechanistic cause underlying supercoil generation by RNAP in transcription.


Branching pattern of the extraosseous mental nerve in a kenyan population.
Knowledge of the branching pattern of the mental nerve is an important consideration during placement of tooth implants and reconstructive plates. It is known to display population variations and data for the same is scarce form the sub-Saharan region. With the recent increase in surgical interventions in the mandibular region in Kenya, a detailed description of mental nerve is warranted. A total of 64 mental nerves were dissected and branching pattern was noted. Single mental nerve was present in 60 (93.7%) cadavers while double mental nerves occurred in 3 (4.7%) and accessory in 1(1.6%). Most common pattern was bifurcation (39%) followed by trifurcation (34%), single (19%), and quadrification (8%). The double and triple branches were seen to further divide into two to three subbranches with diverse patterns. Side symmetry in branching was seen in four (6.25%). These are important anatomical considerations during placement of reconstructive plates for mandibular trauma and administration of mental nerve blocks.


Factors influencing community participation in control and related operational research for urogenital schistosomiasis and soil-transmitted helminths in rural villages of Kwale County, coastal Kenya.
helminthic infections caused by soil-transmitted helminths (STH) and schistosomes are among the most prevalent afflictions of humans who live in areas of poverty. An operational research was undertaken in 5 villages of Kwale County during a pilot control programme which included both the adults and school going children. Willingness of community members to participate in the treatment as well as in the research is critical. A cross sectional study sought to determine factors influencing community participation in control and related operational research and assess the treatment coverage for urogenital schistosomiasis and hookworms in rural villages of Kwale County. cross-sectional survey utilized quantitative and qualitative methods of data collection. A total of 220 households were recruited and household heads interviewed. Bivariate analysis was used to test association between different independent and dependent factors. Multivariate analysis was done using binary logistic regression to control for confounders and effect modification. Qualitative data was transcribed, coded and analyzed thematically. religion and levels of income were significantly (P =0.04 and P = 0.026 respectively) associated with participation in the research and control programme, history of ever suffering from schistosomiasis and intestinal worms was found to be significantly (P = 0.008) associated with participation in the research. The study established that 82% (178) of the respondents received treatment for urogenital schistosomiasis and hookworms and 67% (146) of the respondents had participated in the research. this information will be useful in promoting health, enhancing learning and behaviour changes which will lead to increased community participation in similar disease control.


Resting state functional connectivity associated with trait emotional intelligence.
Previous neuroimaging studies have suggested that trait emotional intelligence (TEI) is associated with components of the neural network involved in social cognition (SCN) and somatic marker circuitry (SMC). Our study is the first to investigate the association of TEI with resting-state functional connectivity (RSFC) between the key nodes of SCN and SMC [medial prefromtal cortex (mPFC) and bilateral anterior insula (AI), respectively] and other brain regions. We found that (a) the intrapersonal factor of TEI was negatively correlated with RSFC between mPFC and the anterior part of the right dorsolateral prefrontal cortex (DLPFC), (b) the TEI interpersonal factor score was positively correlated with RSFC between mPFC and the lingual gyrus, and (c) total TEI was positively correlated with RSFC between mPFC and the precuneus as well as (d) between the left AI and the middle part of the right DLPFC. Taken together with previous study findings, our findings can be comprehensively understood as neural mechanisms of SCN and SMC components are associated with TEI. In particular, the fluent interaction between SCN's two key nodes (mPFC and precuneus/PCC) [as well as between DMN's two key nodes] is suggested to be crucial for total TEI. Our study also indicated that (a) a clear functional separation between the two key nodes of the two major intrinsic networks, DMN and the task-positive network (mPFC and DLPFC), is important for higher intrapersonal TEI, (b) brain interactions involving vision-related areas (lingual gyrus) and the key node of SCN (mPFC) are important for interpersonal TEI, and (c) control of DLPFC over the key node of SMC (AI) is important for total TEI.


Regulation and translocation of ATP-dependent apical membrane proteins in rat liver.
The bile canalicular membrane contains four specific ATP-dependent transport processes that are involved in secretion of bile acids, non-bile acid organic anions (mrp1), phospholipids (mdr2), and organic cations (mdr3). The aim of this study was to determine how the canalicular presence of these transport proteins is regulated. Canalicular membrane vesicles (CMV) were prepared from livers of rats treated with taurocholate (TC) and/or dibutyryl-adenosine 3',5'-cycle monophosphate (DBcAMP) with and without pretreatment with colchicine. Transport studies were performed with radiolabeled substrates. Changes in the relative amounts of transport proteins were determined by Western blots. Compared with controls, the specific activity of each of the transport processes was enhanced 1.5- and 3-fold with TC and DBcAMP treatments, respectively. Western blots revealed the same increases with mdr2 and mdr3. Pretreatment of rats with colchicine prevented these responses fully with TC treatment, whereas only partial prevention was obtained with DBcAMP treatment. Besides the ATP-dependent transporters, the relative specific activities of the canalicular membrane ectoenzyme markers, leucine aminopeptidase and gamma-glutamyltranspeptidase, were also affected the same way. These results suggest that TC and DBcAMP increase the specific activity of the canalicular ATP-dependent transport proteins and some canalicular membrane ectoenzymes by stimulating an increase in the relative amounts of these proteins in the membrane.


Platelet Analysis in the Thrombus Plus Serum BNP for Detecting Clot-Related Atrial Fibrillation. Results From the ITACAT Multicentric Registry.
Occult atrial fibrillation (AF) is a common cause of cryptogenic stroke. This study aimed to investigate the utility of surrogate markers within the clot (clot markers), in combination with serum biomarkers, to identify AF-associated clots in patients who underwent mechanical thrombectomy. Each retrieved thrombus was analyzed to identify fibrin, red blood cells, platelets - CD61 staining (PLT) and T-CD4 lymphocyte/macrophage/monocyte (CD4) profile. Serum biomarkers such as D-dimer, lipoprotein (A), and brain natriuretic peptide (BNP) were also assessed in the acute phase of the stroke. Patients with stroke-related AF and large artery atherosclerosis (LAA) stroke were compared by matched case-control design to identify markers associated with AF clot profile. The predictive abilities of clot markers and serum biomarkers to detect AF clot were tested in patients with cryptogenic stroke. In patients with AF clot, the PLT percentage was higher (66.64% vs. 55.43%, OR = 1.03); CD4 percentage was lower (3.84% vs. 7.95%, OR = 0.95); and BNP marker was higher (2114 pg/ml vs. 276 pg/ml, OR = 1.04) compared to LAA clot. PLT was independently associated to AF-clot (OR, 1.04) but demonstrated moderate ability to identify AF-clot cases (C-test 0.668, p = 0.018). The combination of PLT with BNP significantly improved AF-clot prediction (C-test 0.847, p < 0.001). The clot composition of patients with cryptogenic stroke and AF detection showed four-fold higher PLT and BNP pattern of risk than patients with cryptogenic stroke without AF detection (38.5% vs. 8.7%) (OR = 1.40). Integrating intra-thrombus platelet with serum BNP offers a promising approach for detecting AF-associated clots in patients with cryptogenic stroke.


Vasculogenesis drives pulmonary vascular growth in the developing chick embryo.
Formation of the pulmonary vasculature has been described as occurring by outgrowth of existing vessels (angiogenesis), de novo formation of new vessels (vasculogenesis), or a combination of both processes. Uncertainty about the contribution of angiogenesis and vasculogenesis to pulmonary vascular formation is partly due to methodologic approaches. Evidence in favor of angiogenesis stems from studies that used vascular-filling methods. Such methods identify only directly continuous lumina. Evidence for vasculogenesis has been provided by the use of molecular markers of blood vessel endothelium. Use of both methods has not been combined in the same species, however. We hypothesized, based on published evidence from quail and mouse, that chick pulmonary vascular formation occurs by vasculogenesis. To test that hypothesis, we used vascular filling, serial section, and immunohistochemical methods to analyze the developing lungs of chick embryos from Hamburger and Hamilton stages 20 to 43. Vascular filling suggested that the lumen of the pulmonary arteries sprouted from the sixth pharyngeal arch arteries. However, serial sections and immunohistochemical localization of fetal liver kinase-1 protein, the receptor for vascular endothelial growth factor, showed that the pulmonary arterial tree formed from endothelial cell precursors and coalescence of isolated blood vessels in the mediastinal splanchnic mesenchyme centrally to the developing lung tissue distally. Pulmonary veins grew from the left atrium to the developing lungs. Pulmonary blood vessel formation occurred continuously throughout the embryonic period studied. Our results show that vasculogenesis is the main process by which the pulmonary vasculature forms in the developing chick embryo.


The Role of fibroblast growth factor receptor substrate 2 (FRS2) in the regulation of two activity levels of the components of the extracellular signal-regulated kinase (ERK) pathway in the mouse epididymis.
The components of the extracellular signal-regulated kinase (ERK) pathway are involved in the regulation of epididymal cellular processes. Interestingly, our previous studies showed that there are two different activity levels of the ERK pathway components in the epididymal epithelium: a basal level in most regions and a higher level in the differentiated initial segment (IS). In this study we analyzed the role of fibroblast growth factor receptor substrate 2 (FRS2) in the regulation of these two levels. Two mouse models were generated. In the first model, Frs2 was deleted from epithelial cells of most epididymal regions except for the IS from the embryonic period onward. Loss of Frs2 dampened the basal activity level of the ERK pathway components, which resulted in an increase in apoptosis along the epididymal duct. This was observed during the period when FRS2 expression level was highest in wild-type epididymides. In the second model, Frs2 was deleted from the proximal epididymal epithelium from Postnatal Day 17 onward. Most of the epididymides in this model exhibited normal morphology. Loss of Frs2 in these epididymides did not affect the high activity level of the ERK pathway components in the IS. However, a subgroup of epididymides in the second model showed increased apoptosis which resulted in an abnormally shaped proximal region or development of granulomas. Therefore, data from these two models showed that FRS2 played different roles in the regulation of two activity levels of the ERK pathway components in the epididymis.


Diagnosis of iron deficiency anemia in a rural population of children. Relative usefulness of serum ferritin, red cell protoporphyrin, red cell indices, and transferrin saturation determinations.
The diagnostic usefulness in iron deficiency anemia of serum ferritin, red cell protoporphyrin (Epp), mean corpuscular volume, mean corpuscular hemoglobin (MCH), and transferrin saturation measurements has been studied in a population of 294 children aged 1 to 6 yr. Of the children studied 19% had hemoglobin below 11 g/dl. Iron deficiency, diagnosed by at least two abnormal independent laboratory parameters, was the cause of anemia in all except two cases. The Pearson correlation coefficient for hemoglobin was highest with MCH, followed in decreasing order of magnitude by MCV, Epp, transferrin saturation, and finally by ferritin. Sensitivity and specificity were highest for MCH and lowest for ferritin. Of anemic, iron deficient individuals 97 to 100% could be identified by low MCH, 88 to 100% by transferrin saturation, 66 to 83% by ferritin, and 61 to 74% by Epp. In contrast, only 0 to 6% of normal, nonanemic individuals had low MCH, 0 to 4% had high Epp, but 21 to 39% had low transferrin saturation and 25 to 39% had low ferritin. Although reduced serum ferritin in anemic individuals is good evidence of iron deficiency, a significant proportion of anemic iron-deficient patients is missed by this procedure rendering it less useful than other, less expensive laboratory methods.


[Clinical pharmacology and therapeutic aspects in certain degenerative neurological diseases].
The knowledge in the pathophysiology of neurodegenerative disorders, and their classification has been dramatically improved by the progresses in genetics and molecular biology. Such a progress has not yet been observed in therapeutics but sustained symptomatic results may occur in the treatment of Parkinson's disease and to a lesser extent in Alzheimer's disease. More recently, other therapeutic approaches were used in trials with neuroprotective drugs with some encouraging results.


Relationship between albuminuria and cardiovascular disease in Type 2 diabetes.
Impaired renal function and albuminuria, common among people with type 2 diabetes, are strong predictors of atherosclerotic cardiovascular events. However, the relationships among albuminuria and measures of calcified atherosclerotic plaque are unknown. Coronary and carotid artery calcified plaque were measured using fast-gated helical computed tomography, and B-mode ultrasonography measured common carotid artery intima-medial thickness (IMT) in 588 white participants with type 2 diabetes from 325 families ascertained for the presence of multiple siblings with type 2 diabetes. Measured risk factors included age, gender, BP, body mass index, GFR, glycosylated hemoglobin, LDL cholesterol, HDL cholesterol, smoking, and medications that affect urine albumin:creatinine ratio (ACR). Generalized estimating equations with exchangeable correlation and the sandwich estimator of the variance were used to test for an association among coronary artery calcified plaque, carotid artery calcified plaque, carotid IMT, and ACR while adjusting for measured risk factors. Participants had a mean +/- SD (median) age of 61.2 +/- 9.2 yr (61.0 yr), ACR of 106.2 +/- 590 mg/g (12.9 mg/g), GFR of 93.3 +/- 33.2 ml/min (87.4 ml/min), coronary artery calcium mass score of 1394 +/- 2685 (323), carotid artery calcium mass score of 295 +/- 652 (51), and IMT of 0.66 +/- 0.12 mm (0.65 mm). Adjusting for the measured covariates, ACR was strongly and positively associated with coronary artery calcium (P = 0.004) and carotid artery calcium (P = 0.0004). Albuminuria is strongly associated with calcified plaque in the coronary and carotid arteries in white individuals with type 2 diabetes and relatively preserved renal function.