[Benefits of mothers' permanence and participation in the care for their hospitalized child].
The purpose of the present study was to identify, according to the mothers' perspective, the benefits related to her permanence and participation in the care for her child hospitalized at a Pediatric Intensive Care Unit (PICU). The theoretical framework was Cross-cultural Nursing Theory, and the methodological framework was the assistant convergent research approach. Data was collected from six mothers of children hospitalized at a PICU of a University Hospital, in the period from January to May 2007, through interviews and active observation. Analysis was conducted following four generic processes: collection, synthesis, theorization and application. The results evidenced that the mothers' presence and care increased the attachment between mother and child, increased mothers' confidence, and made the child calmer. This produced positive feelings such as joy and satisfaction for being able to care for their child. Nurses should review their behavior toward the mothers accompanying their child at the hospital, and adopt attitudes that support her participation in the care for her hospitalized child.


Anterior and posterior commissures in agenesis of the corpus callosum: Alternative pathways for attention processes?
Developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation resulting from disruption of corpus callosum formation, a structure that is crucial for the transfer and integration of information, including attention processes, across the brain. This study aimed to investigate previously proposed candidates for alternative inter-hemispheric pathways in AgCC by examining (1) white matter volume and microstructure of the anterior and posterior commissures in children with AgCC compared to typically developing controls (TDC), and (2) in children with AgCC, examine the associations of white matter volume and microstructure of the anterior and posterior commissures and any remaining corpus callosum with attention processes. Participants were 21 children with AgCC (13 complete, 8 partial) recruited from The Royal Children's Hospital, Melbourne, and 30 TDC aged 8-17 years. T1-and diffusion-weighted MR sequences were used to calculate volume and microstructural parameters. Neuropsychological testing assessed attention processes. We found the anterior commissure was significantly larger in volume in children with AgCC than TDC (p = .027), with reduced mean FA (p = .001) associated with increased mean RD (p < .001). In children with AgCC, we found microstructural properties of the anterior commissure associated with attentional processes, specifically, mean FA of the anterior commissure was associated with better divided attention (p = .03), and the association between alerting attention and mean AD and RD was found to be moderated by age (p = .027, p = .008) and the degree of corpus callosum agenesis (p = .025, p = .016). Furthermore, in partial AgCC, larger posterior commissure volume was associated with better orienting attention (p = .035). In conclusion, we provide evidence that the volume and microstructure of the anterior commissure are altered in children with AgCC, and this neuroplastic response might have an influence on attention processes.


Erythrina abyssinica prevents meningoencephalitis in chronic Trypanosoma brucei brucei mouse model.
Human African trypanosomiasis is prevalent in Sub-sahara African countries that lie between 14° North and 29° south of the equator. Sixty million people are at risk of infection. Trypanosoma brucei gambesience occurs in West and Central Africa while Trypanosoma brucei rhodesience occurs in East and Southern Africa. The neurological stage of the disease is characterized by neuroinflammation. About 10% of patients treated with the recommended drug, melarsoprol develop post treatment reactive encephalopathy, which is fatal in 50% of these patients, thus melarsoprol is fatal in 5% of all treated patients. This study was aimed at establishing the potential activity of Erythrina abyssinica in reducing neuroinflammation following infection with Trypanosoma brucei brucei. Swiss white mice were divided into ten groups, two control groups and eight infected groups. Infected mice received either methanol or water extract of Erythrina abyssinica at 12.5, 25, 50 or 100 mg/kg body weight. Parasite counts were monitored in peripheral circulation from the third day post infection up to the end of the study. Brains were processed for histology, immunohistochemistry scanning and transmission electron microscopy. Following infection, trypanosomes were observed in circulation 3 days post-infection, with the parasitaemia occurring in waves. In the cerebrum, typical brain pathology of chronic trypanosomiasis was reproduced. This was exhibited as astrocytosis, perivascular cuffing and infiltration of inflammatory cells into the neuropil. However, mice treated with Erythrina abyssinica water extract exhibited significant reduction in perivascular cuffing, lymphocytic infiltration and astrocytosis in the cerebrum. The methanol extract did not have a significant difference compared to the non-treated group. This study provides evidence of anti-inflammatory properties of Erythrina abyssinica and may support its wide use as a medicinal plant by various communities in Kenya.


Perceptions of the South African 24-Hour Movement Guidelines for Birth to 5 Years: A Qualitative Study.
South Africa launched 24-hour movement guidelines for birth to 5 years in 2018. Perceptions of these guidelines were assessed as part of the dissemination process with community-based organizations in 2019. Fifteen dissemination workshops were held with community-based organization representatives and a range of stakeholders. Discussions were held with workshop attendees (n = 281) to obtain qualitative feedback on the guidelines and workshop. Six follow-up focus groups (n = 28) were conducted to obtain additional feedback on the guidelines and their dissemination. Discussions and focus groups were thematically analyzed. Participants recognized the importance of the guidelines for the health and development of young South African children. Participants' perceptions of the guidelines were consistently positive. The participants acknowledged the alignment of the guidelines with other South African programs and initiatives, and that they addressed gaps. Screen time and sleep were identified as the behaviors needing particular attention among young South African children. The negative impact of COVID-19 on young children's movement behaviors was acknowledged, especially regarding screen time. These findings provide evidence of stakeholders' positive perceptions of the South African guidelines and support the dissemination and implementation of these guidelines for the promotion of early childhood health and development in South Africa.


GATA factors participate in tissue-specific immune responses in Drosophila larvae.
Drosophila responds to infection by producing a broad range of antimicrobial agents in the fat body and more restricted responses in tissues such as the gut, trachea, and malpighian tubules. The regulation of antimicrobial genes in larval fat depends on linked Rel/NF-kappaB and GATA binding sites. Serpent functions as the major GATA transcription factor in the larval fat body. However, the transcriptional regulation of other tissue-specific responses is less well understood. Here, we present evidence that dGATAe regulates antimicrobial gene expression in the midgut. Regulatory regions for antimicrobial genes Diptericin and Metchnikowin require GATA sites for activation in the midgut, where Grain (dGATAc), dGATAd, and dGATAe are expressed in overlapping domains. Ectopic expression of dGATAe in the larval fat body, where it is normally absent, causes dramatic up-regulation of numerous innate immunity and gut genes, as judged by microarray analysis and in situ hybridization. Ectopic dGATAe also causes a host of symptoms reminiscent of hyperactive Toll (Toll(10b)) mutants, but without apparent activation of Toll signaling. Based on this evidence we propose that dGATAe mediates a Toll-independent immune response in the midgut, providing a window into the first and perhaps most ancient line of animal defense.


Assistive devices, hip precautions, environmental modifications and training to prevent dislocation and improve function after hip arthroplasty.
Total hip arthroplasty (THA) is one of the most common orthopaedic operations performed worldwide. Painful osteoarthritis of the hip is the primary indication for THA. Following THA, people have conventionally been provided with equipment, such as raised toilet seats and chairs, and educated to avoid activities that could cause the hip joint to be in a position of flexion over 90 degrees, or adduction or rotation past the midline. These aspects of occupational therapy have been advocated to reduce the risks of prosthesis dislocation. However, the appropriateness of these recommendations has been questioned. To assess the effects of provision of assistive devices, education on hip precautions, environmental modifications and training in activities of daily living (ADL) and extended ADL (EADL) for people undergoing THA. We searched MEDLINE (1946 to April 2016), EMBASE (1947 to April 2016), the Cochrane Library including CENTRAL (Issue 4 of 12, 2016), Database of Reviews of Effects (DARE), Health Technology Assessment (HTA), Economic Evaluations Database (EED), CINAHL, PEDro and CIRRIE from inception to April 2016. In addition we checked Controlled Clinical Trials, Clinicaltrials.gov, the National Institutes of Health Trial Registry, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and the OpenGrey database from inception to April 2016. We included randomised controlled trials (RCTs), quasi-RCTs and cluster-RCTs that evaluated the effectiveness of the provision of assistive devices, education on hip precautions, environmental modifications, or training in ADL and EADL for people undergoing THA. The main outcomes of interest were pain, function, health-related quality of life (HRQOL), global assessment of treatment success, reoperation rate, hip dislocation and adverse events. We used standard methodological procedures recognised by Cochrane. We conducted a systematic literature search using several databases and contacted corresponding authors, appraised the evidence using the Cochrane risk of bias tool, analysed the data using a narrative analysis approach (as it was not possible to conduct a meta-analysis due to heterogeneity in interventions), and interpreted all outcomes using the GRADE approach. We included three trials with a total of 492 participants who had received 530 THA. The evidence presented with a high risk of performance, detection and reporting bias.One study (81 participants) compared outcomes for participants randomised to the provision of hip precautions, equipment and functional restrictions versus no provision of hip precautions, equipment or functional restrictions. Due to the quality of evidence being very low, we are uncertain if the provision of hip precautions, equipment and functional restrictions improved function measured using the Harris Hip Score at 12 month follow-up, or health-related quality of life (HRQOL) measured by the Short Form-12 at four week follow-up, compared to not providing this. There were no incidences of hip dislocation or adverse events in either group during the initial 12 postoperative months. The study did not measure pain score, global assessment of treatment success or total adverse events.One study (265 participants; 303 THAs) evaluated the provision of hip precautions with versus without the prescription of postoperative equipment and restrictions to functional activities. Due to the quality of evidence being very low, we are uncertain if perceived satisfaction in the rate of recovery differed in people who were not prescribed postoperative equipment and restrictions (135/151 satisfied) compared to those prescribed equipment and restrictions (113/152) (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.93; 265 participants, one trial; number needed to treat for an additional beneficial outcome (NNTB) = 7). Due to the low quality evidence, we are uncertain if the incidence of hip dislocation differed between participants provided with hip precautions with (1/152) compared to without providing equipment or restrictions post-THA (0/151) (RR 2.98, 95% CI 0.12 to 72.59). The study did not measure pain, function, HRQOL, re-operation rates or total adverse events.One study (146 participants) investigated the provision of an enhanced postoperative education and rehabilitation service on hospital discharge to promote functional ADL versus a conventional rehabilitation intervention in the community. This study was of very low quality evidence. We were uncertain if the provision of enhanced postoperative education and rehabilitation improved function at six months follow-up, when assessed using the Objective and Subjective Functional Capability Index (146 participants, one trial; P > 0.05; no numerical results provided) compared to conventional rehabilitation. The study did not measure pain score, HRQOL, global assessment of treatment success, hip dislocation, re-operation rate or total adverse events. Very low quality evidence is available from single trials, thus we are uncertain if hip precautions with or without the addition of equipment and functional restrictions are effective in preventing dislocation and improving outcomes after THA. There is also insufficient evidence to support or refute the adoption of a postoperative community rehabilitation programme consisting of functional reintegration and education compared to conventional rehabilitation strategies based on functional outcomes.Further high-quality trials are warranted to assess the outcomes of different occupational therapy interventions both in the short and longer-term for those who undergo THA. An assessment of the impact of such interventions on pain and restriction on personal ADL, EADL and instrumental ADL is needed, and also of functional integration-type interventions rather than just hip precautions, equipment and restrictions.


The Kv1.1 null mouse, a model of sudden unexpected death in epilepsy (SUDEP).
Kv1.1 potassium channel null mouse (NULL) exhibits spontaneous seizure-related bradycardia, dies following seizure, and has been proposed as a model for vagus-mediated SUDEP. We characterized the cardiac events surrounding sudden unexpected death in epilepsy (SUDEP) in NULL during terminal asystole for comparison to patients with epilepsy who exhibit bradycardia and terminal or nonterminal asystole during/following seizure and explored the contribution of vagal-mediated bradycardia to SUDEP. Electrocardiography (ECG) studies of 27 freely moving telemetered NULL mice was evaluated surrounding seizure-associated death. Chronic unilateral vagal section and, in a separate set of experiments, electrical stimulation of the cervical vagi in NULL and wild-type (WT) littermates assessed the role of the vagus nerve in seizure-related death. Seizure activity indicated by intense myogenic activity on the ECG recording correlated with visual and video recording. All NULL died following seizures, which were preceded by normal rhythm. Bradycardia followed seizure and led to slow ventricular escape rhythm (70-150 bpm) and asystole. The sequence from seizure to asystole was complete within approximately 3 min and was similar to that reported in individuals exhibiting ictal and postictal bradycardia/asystole. To address the singular role of vagus nerves in seizure-related asystole, cervical vagus nerves were stimulated in the absence of seizure. Heart rate was reduced 3 min to values similar to that following seizure but never produced asystole, suggesting activation of the vagi alone is insufficient for SUDEP. Nevertheless, unilateral chronic section of the vagus nerve increased survival time compared to nonsectioned NULL animals, supporting a role for the vagus nerve in seizure-associated death. The Kv1.1 null mouse is a potential model for SUDEP in patients who experience ictal and postictal bradycardia. It offers the opportunity for evaluation of the combination of factors, in addition to vagal activation, necessary to produce a terminal asystole following seizure. It is notable that long-term studies that evaluate electroencephalography (EEG) and cardiorespiratory events surrounding nonfatal seizures may provide indices predictive of terminal seizure.


Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy.
Experimental diabetic peripheral neuropathy (DPN) is marked by impaired nerve conduction velocity (NCV), reduced nerve blood flow (NBF), and a variety of metabolic abnormalities in peripheral nerve that have been variously ascribed to hyperglycemia, abnormal fatty acid metabolism, ischemic hypoxia, and/or oxidative stress. Some investigators propose that NCV slowing in experimental DPN can be explained entirely on the basis of nerve energy depletion secondary to reduced NBF. This article reports highly selective effects of administration of the antioxidant DL-alpha-lipoic acid (LA) to streptozotocin-injected diabetic rats. LA improved digital sensory but not sciatic-tibial motor NCV, corrected endoneurial nutritive but not composite NBF, increased the mitochondrial oxidative state without correcting nerve energy depletion, and enhanced the accumulation of polyol pathway intermediates without worsening myo-inositol or taurine depletion. These studies implicate oxidative stress as an important pathophysiological factor in experimental DPN. They reveal complex interrelationships among nerve perfusion, energy metabolism, osmolyte content, conduction velocity, and oxidative stress that may reflect the heterogeneous and compartmentalized composition of peripheral nerve.


Should job applicants be excited or calm? The role of culture and ideal affect in employment settings.
Do cultural differences in emotion play a role in employment settings? We predicted that cultural differences in ideal affect-the states that people value and ideally want to feel-are reflected in: (a) how individuals present themselves when applying for a job, and (b) what individuals look for when hiring someone for a job. In Studies 1-2 (NS1 = 236, NS2 = 174), European Americans wanted to convey high arousal positive states (HAP; excitement) more and low arousal positive states (LAP; calm) less than did Hong Kong Chinese when applying for a job. European Americans also used more HAP words in their applications and showed more "high intensity" smiles in their video introductions than did Hong Kong Chinese. In Study 3 (N = 185), European American working adults rated their ideal job applicant as being more HAP and less LAP than did Hong Kong Chinese, and in Study 4a (N = 125), European American Masters of Business Administration (MBAs) were more likely to hire an excited (vs. calm) applicant for a hypothetical internship than were Hong Kong Chinese MBAs. Finally, in Study 4b (N = 300), employees in a U.S. company were more likely to hire an excited (vs. calm) applicant for a hypothetical internship. In Studies 1-4a, observed differences were partly related to European Americans valuing HAP more than Hong Kong Chinese. These findings support our predictions that culture and ideal affect shape behavior in employment settings, and have important implications for promoting cultural diversity in the workplace. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Rational Design of Photosynthesis-Inspired Nanomedicines.
The sun is the most abundant source of energy on earth. Phototrophs have discovered clever strategies to harvest this light energy and convert it to chemical energy for biomass production. This is achieved in light-harvesting complexes, or antennas, that funnel the exciton energy into the reaction centers. Antennas contain an array of chlorophylls, linear tetrapyrroles, and carotenoid pigments spatially controlled by neighboring proteins. This fine-tuned regulation of protein-pigment arrangements is crucial for survival in the conditions of both excess and extreme light deficit. Photomedicine and photodiagnosis have long been utilizing naturally derived and synthetic monomer dyes for imaging, photodynamic and photothermal therapy; however, the precise regulation of damage inflicted by these therapies requires more complex architectures. In this Account, we discuss how two mechanisms found in photosynthetic systems, photoprotection and light harvesting, have inspired scientists to create nanomedicines for more effective and precise phototherapies. Researchers have been recapitulating natural photoprotection mechanisms by utilizing carotenoids and other quencher molecules toward the design of photodynamic molecular beacons (PDT beacons) for disease-specific photoactivation. We highlight the seminal studies describing peptide-linked porphyrin-carotenoid PDT beacons, which are locally activated by a disease-specific enzyme. Examples of more advanced constructs include tumor-specific mRNA-activatable and polyionic cell-penetrating PDT beacons. An alternative approach toward harnessing photosynthetic processes for biomedical applications includes the design of various nanostructures. This Account will primarily focus on organic lipid-based micro- and nanoparticles. The phenomenon of nonphotochemical quenching, or excess energy release in the form of heat, has been widely explored in the context of porphyrin-containing nanomedicines. These quenched nanostructures can be implemented toward photoacoustic imaging and photothermal therapy. Upon nanostructure disruption, as a result of tissue accumulation and subsequent cell uptake, activatable fluorescence imaging and photodynamic therapy can be achieved. Alternatively, processes found in nature for light harvesting under dim conditions, such as in the deep sea, can be harnessed to maximize light absorption within the tissue. Specifically, high-ordered dye aggregation that results in a bathochromic shift and increased absorption has been exploited for the collection of more light with longer wavelengths, characterized by maximum tissue penetration. Overall, the profound understanding of photosynthetic systems combined with rapid development of nanotechnology has yielded a unique field of nature-inspired photomedicine, which holds promise toward more precise and effective phototherapies.


Plant response to fungal root endophytes varies by host genotype in the foundation species Spartina alterniflora.
Root-associated fungi provide a wide range of functions for their host plants, including nutrient provisioning, pathogen protection, and stress alleviation. In so doing, they can markedly influence host-plant structural and physiological traits, although the degree to which these effects vary within particular plant host species is not well understood. We conducted a 7-month common-garden inoculation experiment to test the potential effects of a marine fungus (Lulwoana sp.) on the phenotypic traits of different genotypes of the host, the salt marsh plant species Spartina alterniflora. Lulwoana belongs to the dark septate endophytes (DSE), a polyphyletic group of fungi that are commonly found colonizing healthy plant roots, though their ecological role remains unclear. We documented significant impacts of Lulwoana on S. alterniflora morphology, biomass, and biomass allocation. For most traits in our study, these impacts varied significantly in direction and/or magnitude across S. alterniflora genotypes. Effects that were consistent across genotype were generally negative. Plant response was not predicted by the percentage of roots colonized, consistent with findings that dark septate endophytes do not necessarily influence plant growth responses through direct contact with roots. The observed changes in stem height, biomass, and biomass allocation have important effects on plant competitive ability, growth, and fitness, suggesting that plant-fungal interactions have community and ecosystem level effects in salt marshes.


First Report of Banana mild mosaic virus Infecting Plantain in Ivory Coast.
Plantain (Musa sp., genomic group AAB) is an important crop for millions of the world's poorest people. In Ivory Coast, it is the second most consumed food and an important source of income for farmers. Between 2010 and 2011, a survey for viruses infecting plantain (AAB) was conducted in 10 major plantain-growing regions located in eastern (Abengourou), middle-western (Bouaflé, Daloa, Issia, Oumé, Sinfra, Zuenoula), central (Yamoussoukro), and southern (Aboisso, Gagnoa) Ivory Coast. Leaf samples showing yellow streaks or mild chlorotic streaks were collected and dried on CaCl2 for storage. A representative sample from each location was selected and tested for the presence of Cucumber mosaic virus (CMV, genus Cucumovirus), Banana streak virus (BSV, genus Badnavirus), Banana mild mosaic virus (BanMMV, family Flexiviridae), and Banana bract mosaic virus (BBrMV, genus Potyvirus). Immunocapture (IC)-PCR was used for the detection of BSV while reverse transcription (RT)-PCR was used for the detection of CMV, BanMMV, and BBrMV. The following primers sets were used: BSV cl1 and BSV cl2 (1), CMV 3' and CMV 5' (3), BanMMV BanCP1 and BanCP2 (4), BBrMV Bract N2 and Bract NR (2). BanMMV was detected as mixed infections with BSV in the 10 tested samples, one of which also contained CMV. To confirm the identity of the amplification products from the BanMMV primers, one cDNA fragment was directly sequenced in the forward direction (Macrogen Inc., Seoul, South Korea). BLAST search in GenBank revealed that the partial coat protein (CP) sequence of the Ivorian isolate shared 80 to 88% nucleotides and 81 to 92% deduced amino acid similarities with BanMMV isolates. In contrast, partial CP sequence of the Ivorian isolate had less than 40% deduced amino acid sequence identity with other Flexiviridae CP sequence. The partial CP sequence of the Ivorian BanMMV isolate was deposited in GenBank under Accession No. JX014304. To further confirm the identification, all the samples were tested by plate trapped antigen (PTA)-ELISA with rabbit polyclonal antiserum specific to BanMMV (obtained from B. E. Lockhart, University of Minnesota, U.S.A.) and anti-rabbit IgG (Sigma-Aldrich, Belgium/A3687). The 10 samples reacted positive for BanMMV by ELISA. CMV and BSV have been reported in Ivory Coast, but to our knowledge, this is the first report of BanMMV in the country. The detection of BanMMV in association with BSV or CMV in mixed infection in 10 locations which are important plantain growing areas is a first step in the evaluation of the impact of virus diseases on plantain production in this country. References: (1) S. Dallot et al. Arch. Virol. 146:2182, 2001. (2) M.-L. Iskra-Caruana et al. J. Virol. Methods 153:224, 2008. (3) M. Sharman et al. J. Virol. Methods 89:77, 2000. (4) P.-Y. Teycheney et al. J. Gen. Virol. 86:3181, 2005.


Postoperative tetralogy of fallot with concomitant atrial fibrillation and ventricular tachycardia.
Postoperative tetralogy of Fallot patients, since the first corrective surgical correction in the 1960s, have borne a burden of postoperation arrhythmias and sudden death. This is confirmed to be secondary to supraventricular arrhythmias and predominantly ventricular arrhythmias. It is rare to have both types of arrhythmias in the same patient, which the index case developed. Attempts to stratify patients in groups to predict which patients are susceptible to sudden death and arrhythmias have not been unanimous, despite multiple retrospective and prospective analysis of this group of patients.


Genetic variation and relationships of eighteen Chinese indigenous pig breeds.
Chinese indigenous pig breeds are recognized as an invaluable component of the world's pig genetic resources and are divided traditionally into six types. Twenty-six microsatellite markers recommended by the FAO (Food and Agriculture Organization) and ISAG (International Society of Animal Genetics) were employed to analyze the genetic diversity of 18 Chinese indigenous pig breeds with 1001 individuals representing five types, and three commercial breeds with 184 individuals. The observed heterozygosity, unbiased expected heterozygosity and the observed and effective number of alleles were used to estimate the genetic variation of each indigenous breed. The unbiased expected heterozygosity ranged between 0.700 (Mashen) and 0.876 (Guanling), which implies that there is an abundant genetic variation stored in Chinese indigenous pig breeds. Breed differentiation was shown by fixation indices (FIT, FIS, and FST). The FST per locus varied from 0.019 (S0090) to 0.170 (SW951), and the average FST of all loci was 0.077, which means that most of the genetic variation was kept within breeds and only a little of the genetic variation exists between populations. The Neighbor-Joining tree was constructed based on the Nei DA (1978) distances and one large cluster with all local breeds but the Mashen breed, was obtained. Four smaller sub-clusters were also found, which included two to four breeds each. These results, however, did not completely agree with the traditional type of classification. A Neighbor-Joining dendrogram of individuals was established from the distance of -ln(proportions of shared alleles); 92.14% of the individuals were clustered with their own breeds, which implies that this method is useful for breed demarcation. This extensive research on pig genetic diversity in China indicates that these 18 Chinese indigenous breeds may have one common ancestor, helps us to better understand the relative distinctiveness of pig genetic resources, and will assist in developing a national plan for the conservation and utilization of Chinese indigenous pig breeds.


Use of helium-oxygen mixture in adult patients presenting with exacerbations of asthma and chronic obstructive pulmonary disease: a systematic review.
We examined systematically all controlled and cross-over randomised trials in patients with acute exacerbations of asthma and chronic obstructive pulmonary disease comparing Heliox against air-oxygen mixtures. Fourteen studies were identified. In asthma studies, peak expiratory flow rate (PEFR) was increased by an average of 29.6% (95% CI 16.6-42.6) by Heliox-driven nebulisers, or by 13.3 l.min(-1) (95% CI 3.71-22.81) absolute. In studies of patients with chronic obstructive pulmonary disease receiving non-invasive ventilation the arterial carbon dioxide tension (P(a)co(2)) and respiratory rate were unchanged: weighted mean difference for P(a)co(2)-0.29kPa (95% CI - 0.64-0.07) favoured Heliox, and for respiratory rate 1.6 breaths.min(-1) (95% CI - 0.93, 4.14) favoured control. Heliox minimally reduced the work of breathing in intubated patients, and reduced intrinsic positive end expiratory pressure (iPEEP). The use of Heliox to drive nebulisers in patients with acute asthma slightly improves airflow measures. We were unable to determine whether this improved recovery.


In-Hospital Outcomes of Patients on Maintenance Dialysis With Frailty: 10-year Results From the US National Inpatient Sample Database.
The in-hospital mortality rate of patients with end-stage renal disease (ESRD) is 6-8 times greater than that of the general population. A large fraction of patients with ESRD are frail, which further exacerbates this poor outcome. This study aimed to determine the impact of frailty on in-hospital outcomes of patients with ESRD. This population-based, retrospective study used data from the Nationwide Inpatient Sample (NIS), the largest all-payer US inpatient care database. Data of 1,424,026 hospitalized patients on maintenance dialysis between 2005 and 2014 were included. Patients were classified with respect to frailty status. Primary endpoints were all-cause in-hospital mortality, discharge disposition, length of hospital stay, and hospital costs. Patient characteristics included age, sex, race, income, insurance status, and Charlson's comorbidity index. Logistic regression and linear regression analyses were conducted to evaluate the associations between frailty and clinical outcomes. After adjustment for the confounders, hospitalized patients with frailty on maintenance dialysis were at double the risk of in-hospital mortality, 3 times the risk of discharge to long-term facilities, had hospital stays 5 days longer, and incurred $40,000 more in-hospital costs than those without frailty. The impact of frailty on all these in-hospital outcomes was greater among patients aged <65 years than among older adults. For hospitalized patients on maintenance dialysis, frailty independently predicts worse in-hospital outcomes, with stronger effects on younger patients. The development of adequate interventions for frailty in patients with ESRD and vigilance in treating this subgroup during hospitalization are highly warranted.


Proline racemases are conserved mitogens: characterization of a Trypanosoma vivax proline racemase.
Trypanosoma cruzi proline racemases (TcPRAC) are the only eukaryotic proline racemases described so far. Except their role in the interconversion of free L- and D-proline enantiomers, parasite TcPRACs are involved in major T. cruzi biological pathways. These essential enzymes are implicated in the process of parasite differentiation and the acquisition of virulence during metacyclogenesis and are currently considered as key targets for drug development against Chagas' disease. In this study, we searched for the presence of TcPRAC gene homologues among other trypanosomatid genomes. Despite the high degree of gene synteny observed in Kinetoplastidae genomes, PRAC genes are missing in Trypanosoma brucei, Trypanosoma congolense and Leishmania spp. genomes. Interestingly, we identified a hypothetical PRAC gene in Trypanosoma vivax that is the major hemoparasite responsible for livestock trypanosomiasis, a serious economical impact for most of African and South American countries. We report here that the product of this T. vivax gene is bona fide a proline racemase with an activity comparable to the one we described previously for TcPRAC. Inhibition studies using the pyrrole-2-carboxylic acid confirmed that this compound is a competitive inhibitor for both TcPRAC and TvPRAC enzymes. Similarly to TcPRAC and all members of the racemase family studied so far in other pathogenic and nosocomial bacteria, our results show that TvPRAC is a T-cell-independent B-cell mitogen. Therefore the product of the novel TvPRAC gene identified in T. vivax and reported herein has the potential to be used as a drug target for this parasite-based trypanosomiasis.


Chronic transmural bronchiolitis: a non-specific lesion of small airways.
To investigate nine patients with histological changes at open lung biopsy compatible with so-called "small airways disease"; to define these changes and distinguish them from other types of bronchiolitis; and to correlate them with clinical features, respiratory physiology, and other laboratory investigations. The open biopsy sections and the clinical records were reviewed. There was chronic inflammation of the walls of centri-acinar respiratory bronchioles and peribronchiolar alveoli. Peripheral alveoli of affected acini were spared. Although lumens were narrowed and distorted, obstruction by granulation tissue plugs was not a feature. Clinical backgrounds included Hodgkin's disease, yellow nail syndrome, sicca syndrome, asthma and psoriasis. The main presenting symptoms were cough, dyspnoea and wheeze, often associated with basal crackles and basal shadowing. There was no consistent immunological or haematological abnormality. Sputum culture was negative in six patients, and a variety of organisms were cultured from three others. In most cases respiratory function tests revealed an irreversible obstructive defect (combined in some cases with a restrictive defect), gas trapping, and well preserved gas transfer. Lung volumes were normal. Bronchodilators, with steroids and azathioprine in more seriously affected patients, stabilised the disease process. The histological changes may be distinguished from bronchiolitis obliterans and bronchiolitis obliterans organising pneumonia by the absence of intraluminal granulation tissue plugs, and from the obliterative bronchiolitis of rheumatoid disease and diffuse peribronchiolitis on clinical grounds. Although often striking, this lesion does not represent a clinico-pathological entity, and may occur in the distal lung in association with a number of different diseases. "Small airways disease" is often used by clinicians in a functional context, and may lead to confusion. It is suggested that "chronic transmural bronchiolitis" is a more appropriate term.


Avenanthramides inhibit proliferation of human colon cancer cell lines in vitro.
A high intake of whole grain foods is associated with reduced risk of colon cancer, but the mechanism underlying this protection has yet to be elucidated. Chronic inflammation and associated cyclooxygenase-2 (COX-2) expression in the colon epithelium are causally related to epithelial carcinogenesis, proliferation, and tumor growth. We examined the effect of avenanthramides (Avns), unique polyphenols from oats with anti-inflammatory properties, on COX-2 expression in macrophages, colon cancer cell lines, and on proliferation of human colon cancer cell lines. We found that Avns-enriched extract of oats (AvExO) had no effect on COX-2 expression, but it did inhibit COX enzyme activity and prostaglandin E(2) (PGE(2)) production in lipopolysaccharide-stimulated mouse peritoneal macrophages. Avns (AvExO, Avn-C, and the methylated form of Avn-C (CH3-Avn-C)) significantly inhibited cell proliferation of both COX-2-positive HT29, Caco-2, and LS174T, and COX-2-negative HCT116 human colon cancer cell lines, CH3-Avn-C being the most potent. However, Avns had no effect on COX-2 expression and PGE(2) production in Caco-2 and HT29 colon cancer cells. These results indicate that the inhibitory effect of Avns on colon cancer cell proliferation may be independent of COX-2 expression and PGE(2) production. Thus, Avns might reduce colon cancer risk through inhibition of macrophage PGE(2) production and non-COX-related antiproliferative effects in colon cancer cells. Interestingly, Avns had no effect on cell viability of confluence-induced differentiated Caco-2 cells, which display the characteristics of normal colonic epithelial cells. Our results suggest that the consumption of oats and oat bran may reduce the risk of colon cancer not only because of their high fiber content but also due to Avns, which attenuate proliferation of colonic cancer cells.


Detection, characterization and functional assessment of reperfused Q-wave acute myocardial infarction by cine magnetic resonance imaging.
The capability of dynamic gradient-refocused magnetic resonance imaging (cine MRI) to detect, localize and functionally assess acute myocardial infarction (AMI) in 25 patients at a mean time interval of 7 days after AMI was evaluated. Fifteen asymptomatic volunteers were also examined to determine the specificity of the observations. Upon presentation, each patient received intravenous thrombolytic therapy, underwent immediate cardiac catheterization and had percutaneous transluminal coronary angioplasty performed when coronary reperfusion was absent. Twenty-four of the patients had documented coronary reperfusion at a mean interval of 259 +/- 129 minutes. Global ejection fraction and regional wall motion abnormalities were evaluated at 7 days by cine MRI, left ventriculography and radionuclide angiography. Twenty patients with both an absolute decrease in myocardial signal and a matched regional wall motion abnormality had AMI properly identified by cine MRI. In contrast, the finding of both decreased signal intensity and a matched regional wall motion abnormality was absent in the group of asymptomatic volunteers. The ejection fraction by cine MRI correlated better with the ejection fraction by left ventriculography (r = 0.94, standard error of the estimate = 3.6) than did the ejection fraction by radionuclide angiography (r = 0.82, standard error of the estimate = 5.8). The regional wall motion concordance rate in comparison to left ventriculography was similar for both cine MRI (69%) and radionuclide angiography (65%). These findings suggest that cine MRI may play an important role in the future detection and functional characterization of AMI.


PSP toxin release from the cyanobacterium Raphidiopsis brookii D9 (Nostocales) can be induced by sodium and potassium ions.
Paralytic shellfish poisoning (PSP) toxins are a group of naturally occurring neurotoxic alkaloids produced among several genera of primarily freshwater cyanobacteria and marine dinoflagellates. Although saxitoxin (STX) and analogs are all potent Na(+) channel blockers in vertebrate cells, the functional role of these compounds for the toxigenic microorganisms is unknown. Based upon the known importance of monovalent cations (such as sodium) in the maintenance of cellular homeostasis and ion channel function, we examined the effect of high extracellular concentrations of these ions on growth, cellular integrity, toxin production and release to the external medium in the filamentous freshwater cyanobacterium, Raphidiopsis brookii D9; a gonyautoxins (GTX2/3) and STX producing toxigenic strain. We observed a toxin export in response to high (17 mM) NaCl and KCl concentrations in the growth medium that was not primarily related to osmotic stress effects, compared to the osmolyte mannitol. Addition of exogenous PSP toxins with the same compositional profile as the one produced by R. brookii D9 was able to partially mitigate this effect of high Na⁺ (17 mM). The PSP toxin biosynthetic gene cluster (sxt) in D9 has two genes (sxtF and sxtM) that encode for a MATE (multidrug and toxic compound extrusion) transporter. This protein family, represented by NorM in the bacterium Vibrio parahaemolyticus, confers resistance to multiple cationic toxic agents through Na⁺/drug antiporters. Conserved domains for Na⁺ and drug recognition have been described in NorM. For the D9 sxt cluster, the Na⁺ recognition domain is conserved in both SxtF and SxtM, but the drug recognition domain differs between them. These results suggest that PSP toxins are exported directly in response to the presence of monovalent cations (Na⁺, K⁺) at least at elevated concentrations. Thus, the presence of both genes in the sxt cluster from strain D9 can be explained as a selective recognition mechanism by the SxtF/M transporters for GTX2/3 and STX. We propose that these toxins in cyanobacteria could act extracellularly as a protective mechanism to ensure homeostasis against extreme salt variation in the environment.


Staphylococcal protein A, Panton-Valentine leukocidin and coagulase aggravate the bone loss and bone destruction in osteomyelitis.
Osteomyelitis is a debilitating infectious disease of the bone which is predominantly caused by Staphylococcus aureus (S. aureus). The purpose of this study was to investigate the role of the S. aureus virulence factors, i.e. protein A (SpA), Panton-Valentine leukocidin (PVL) and coagulase (Coa) on osteomyelitis. The effect of SpA, PVL and Coa on osteoblasts was studied through the following aspects including osteoblast proliferation, apoptosis, bone formation, bone mineralization and RANK-L expression. S. aureus overexpressing PVL, SpA or Coa was constructed and used to study the role of PVL, SpA and Coa, respectively. S. aureus silencing PVL, SpA or Coa was also constructed and used for reversing verification. Osteoblast proliferation was detected by MTT tetrazolium dye reduction assay. Apoptosis was determined by Annexin V-FITC staining. The levels of pro-caspase 3, cleaved-caspase 3, pro-caspase 9 and cleaved-caspase 9 were detected by western blot. Bone formation markers including collagen I, osteopontin and osteocalcin were detected by real time RT-PCR. Alkaline phosphatase activity was measured by adding p-nitrophenyl phosphate as a phosphatase substrate. Von kossa stain and alizarin red stain were applied for determining phosphate and calcium deposition, respectively. The RANK-L expression was tested by ELISA. PVL, SpA and Coa inhibited osteoblast proliferation, induced osteoblast apotosis, prohibited bone formation and mineralization and upregulated RANK-L expression. PVL, SpA and Coa play a critical role on bone loss and bone destruction of osteomyelitis.


Sulfonamide antibiotic removal and nitrogen recovery from synthetic urine by the combination of rotating advanced oxidation contactor and methylene urea synthesis process.
The combination of nitrogen recovery and pharmaceutical removal processes for livestock urine treatment were investigated to suppress the discharge of pollutants and recover nitrogen as resources. We combined methylene urea synthesis from urea and adsorption and photocatalytic decomposition of sulfonamide antibiotic using rotating advanced oxidation contactor (RAOC) contained for obtaining both safe fertilizer and reclaimed water. The methylene urea synthesis could recover urea in synthetic urine, however, almost all sulfonamide antibiotic was also incorporated, which is unfavorable from a safety aspect if the methylene urea is to be used as fertilizer. Conversely, RAOC could remove sulfonamide antibiotic without consuming urea. It was also confirmed that the methylene urea could be synthesized from synthetic urine treated by RAOC. Thus, we concluded that RAOC should be inserted prior to the nitrogen recovery process for effective treatment of urine and safe use of methylene urea as fertilizer.


Directional control of infrared antenna-coupled tunnel diodes.
Directional control of received infrared radiation is demonstrated with a phased-array antenna connected by a coplanar strip transmission line to a metal-oxide-metal (MOM) tunnel diode. We implement a MOM diode to ensure that the measured response originates from the interference of infrared antenna currents at specific locations in the array. The reception angle of the antenna is altered by shifting the diode position along the transmission line connecting the antenna elements. By fabricating the devices on a quarter wave dielectric layer above a ground plane, narrow beam widths of 35° FWHM in power and reception angles of ± 50° are achieved with minimal side lobe contributions. Measured radiation patterns at 10.6 μm are substantiated by electromagnetic simulations as well as an analytic interference model.


Low engagement in HIV services and progress through the treatment cascade among key populations living with HIV in Mozambique: alarming gaps in knowledge of status.
Mozambique has a generalized HIV epidemic of 13.5% among the general population. Early modeling exercises in Mozambique estimate that key populations (KP), defined as men who have sex with men (MSM), female sex workers (FSW), and people who inject drugs (PWID), along with their partners account for about one third of all new infections. There is limited data describing the engagement of KP living with HIV in testing, care and treatment services. We conducted a secondary data analysis of HIV-positive participants in the first Bio-behavioral Surveillance (BBS) surveys in Mozambique conducted 2011-2014 in order to assess service uptake and progress though the HIV treatment cascade among MSM, FSW, and PWID. Unweighted pooled estimates were calculated for each key population group. Among HIV-positive MSM, 63.2% of participants had ever received an HIV test, 8.8% were aware of their status, 6.1% reported having been linked to care, while 3.5% initiated ART and were currently on treatment. Of the HIV-infected FSW participants, 76.5% reported a previous HIV test and 22.4% were previously aware of their status. Linkage to care was reported by 20.1%, while 12.7% reported having initiated ART and 11.8% reported being on treatment at the time of the survey. Among HIV-infected PWID participants, 79.9% had previously received an HIV test, 63.2% were aware of their HIV status, and 49.0% reported being linked to care for their HIV infection. ART initiation was reported by 42.7% of participants, while 29.4% were on ART at the time of the survey. Among the three high risk populations in Mozambique, losses occurred throughout critical areas of service uptake with the most alarming breakpoint occurring at knowledge of HIV status. Special attention should be given to increasing HIV testing and linkage to ART treatment. Future surveys will provide the opportunity to monitor improvements across the cascade in line with global targets and should include viral load testing to guarantee a more complete picture of the treatment cascade.


Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic transplantation: influence of Campath dose on lymphoid recovery, mixed chimerism and survival.
Sixty-nine consecutive patients (median age 54 years) were prospectively enrolled in a single-institution protocol for allogeneic transplantation with adjusted non-myeloablative fludarabine-melfalan-based conditioning including cyclosporin A and MMF, and one of three modes of serotherapy. Thirty-one donors (45%) were unrelated. The first cohort of 29 had ATG (Thymoglobulin 2 mg/kg x 3 days), the subsequent 26 had Campath 30 mg x 3 days subcutaneously, and the final cohort of 14 had 30 mg Campath once. The groups were similar as regards age, diagnosis and risk factors. Campath-patients had no acute toxicity, fewer days with fever and antibiotics, and required fewer transfusions than ATG-treated patients. 3-d-Campath patients showed lower lymphocyte counts from day +4, and CD4+, CD8+, CD19+ and NK cells recovered slower than in ATG-treated patients. More Campath patients developed mixed chimerism that required DLI. 3-d-Campath induced more serious and opportunistic infections than ATG, which resulted in a greater non-relapse mortality and an impaired overall survival despite a low tumor-related mortality. The change of the Campath dosing schedule to one dose abrogated the deleterious effect of 3-d-Campath on immune recovery, severe infections and survival. Subcutaneous Campath is simple and provides strong immune suppression with no early toxicity, but dose limitation to 30 mg once is recommended.


Functional characterization of cinnamyl alcohol dehydrogenase and caffeic acid O-methyltransferase in Brachypodium distachyon.
Lignin is a significant barrier in the conversion of plant biomass to bioethanol. Cinnamyl alcohol dehydrogenase (CAD) and caffeic acid O-methyltransferase (COMT) catalyze key steps in the pathway of lignin monomer biosynthesis. Brown midrib mutants in Zea mays and Sorghum bicolor with impaired CAD or COMT activity have attracted considerable agronomic interest for their altered lignin composition and improved digestibility. Here, we identified and functionally characterized candidate genes encoding CAD and COMT enzymes in the grass model species Brachypodium distachyon with the aim of improving crops for efficient biofuel production. We developed transgenic plants overexpressing artificial microRNA designed to silence BdCAD1 or BdCOMT4. Both transgenes caused altered flowering time and increased stem count and weight. Downregulation of BdCAD1 caused a leaf brown midrib phenotype, the first time this phenotype has been observed in a C3 plant. While acetyl bromide soluble lignin measurements were equivalent in BdCAD1 downregulated and control plants, histochemical staining and thioacidolysis indicated a decrease in lignin syringyl units and reduced syringyl/guaiacyl ratio in the transgenic plants. BdCOMT4 downregulated plants exhibited a reduction in total lignin content and decreased Maule staining of syringyl units in stem. Ethanol yield by microbial fermentation was enhanced in amiR-cad1-8 plants. These results have elucidated two key genes in the lignin biosynthetic pathway in B. distachyon that, when perturbed, may result in greater stem biomass yield and bioconversion efficiency.


The searchlight effect in hyperbolic materials.
The quasistatic field around a circular hole in a two-dimensional hyperbolic medium is studied. As the loss parameter goes to zero, it is found that the electric field diverges along four lines each tangent to the hole. In this limit, the power dissipated by the field in the vicinity of these lines, per unit length of the line, goes to zero but extends further and further out so that the net power dissipated remains finite. Additionally the interaction between polarizable dipoles in a hyperbolic medium is studied. It is shown that a dipole with small polarizability can dramatically influence the dipole moment of a distant polarizable dipole, if it is appropriately placed. We call this the searchlight effect, as the enhancement depends on the orientation of the line joining the polarizable dipoles and can be varied by changing the frequency. For some particular polarizabilities the enhancement can actually increase the further the polarizable dipoles are apart.


HIV infection and cardiovascular disease.
With the success of antiretroviral therapy (ART), non-human immunodeficiency virus (HIV)-related comorbidities like cardiovascular diseases (CVDs) are of increasing concern. We describe important recent research developments on the epidemiology of CVD in HIV infection, ART-related metabolic changes, and cardioprotective anti-inflammatory mechanisms, and summarize management strategies for CVD risk reduction. We systematically identified and analysed systematic reviews and most cited literature published in the last 3 years and supplemented findings with selected evidence based on clinical expertise. Among HIV-infected individuals, the prevalence of CVD risk factors and the risk for CVD is higher compared with HIV negatives. Antiretroviral drugs may induce dyslipidaemia, reduce insulin sensitivity, and promote body fat redistribution that additionally contributes to CVD risk. Some antiretroviral drugs may increase risk for CVD events, but the absolute risk increase is moderate and has to be put into perspective with the massive HIV-related benefits. Sustained HIV suppression reduces systemic inflammatory markers and is associated with a moderate reduction in CVD events. Regular CVD risk assessment and counselling to stop smoking must be regularly done in all HIV-infected individuals. Statins are effective for the treatment of dyslipidaemia in HIV infection, but drug interactions with ART need to be considered. Human immunodeficiency virus-infected individuals are at increased risk for CVD. Timely initiation of ART with consequent viral suppression is likely to reduce CVD events and to offset potential side effects from ART-induced metabolic changes. Reduction in smoking in HIV-infected individuals is a public health priority.


High surface area of porous silicon drives desorption of intact molecules.
The surface structure of porous silicon used in desorption/ionization on porous silicon (DIOS) mass analysis is known to play a primary role in the desorption/ionization (D/I) process. In this study, mass spectrometry and scanning electron microscopy (SEM) are used to examine the correlation between intact ion generation with surface ablation and surface morphology. The DIOS process is found to be highly laser energy dependent and correlates directly with the appearance of surface ions (Si(n)(+) and OSiH(+)). A threshold laser energy for DIOS is observed (10 mJ/cm(2)), which supports that DIOS is driven by surface restructuring and is not a strictly thermal process. In addition, three DIOS regimes are observed that correspond to surface restructuring and melting. These results suggest that higher surface area silicon substrates may enhance DIOS performance. A recent example that fits into this mechanism is the surface of silicon nanowires, which has a high surface energy and concomitantly requires lower laser energy for analyte desorption.


Pancreatic ductal adenocarcinoma: From genetics to biology to radiobiology to oncoimmunology and all the way back to the clinic.
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death. Despite improvements in the clinical management, the prognosis of PDAC remains dismal. In the present comprehensive review, we will examine the knowledge of PDAC genetics and the new insights into human genome sequencing and clonal evolution. Additionally, the biology and the role of the stroma in tumour progression and response to treatment will be presented. Furthermore, we will describe the evidence on tumour chemoresistance and radioresistance and will provide an overview on the recent advances in PDAC metabolism and circulating tumour cells. Next, we will explore the characteristics and merits of the different mouse models of PDAC. The inflammatory milieu and the immunosuppressive microenvironment mediate tumour initiation and treatment failure. Hence, we will also review the inflammatory and immune escaping mechanisms and the new immunotherapies tested in PDAC. A better understanding of the different mechanisms of tumour formation and progression will help us to identify the best targets for testing in future clinical studies of PDAC.


MK4MDD: a multi-level knowledge base and analysis platform for major depressive disorder.
Major depressive disorder (MDD) is a complex neuropsychiatric syndrome with high heterogeneity. There are different levels of biological components that underlie MDD and interact with each other. To uncover the disease mechanism, large numbers of studies at different levels have been conducted. There is a growing need to integrate data from multiple levels of research into a database to provide a systematic review of current research results. The cross level integration will also help bridge gaps of different research levels for further understanding on MDD. So far, there has been no such effort for MDD. We offer researchers a Multi-level Knowledge base for MDD (MK4MDD) to study the interesting interplay of components in the pathophysiological cascade of MDD from genetic variations to diagnostic syndrome. MK4MDD contains 2,341 components and 5,206 relationships between components based on reported experimental results obtained by diligent literature reading with manual curation. All components were well classified with careful curation and supplementary annotation. The powerful search and visualization tools make all data in MK4MDD form a cross-linked network to be applied to a broad range of both basic and applied research. MK4MDD aims to provide researchers with a central knowledge base and analysis platform for MDD etiological and pathophysiological mechanisms research. MK4MDD is freely available at http://mdd.psych.ac.cn.


[Evaluation of The Medical Board Exam in Portugal].
There is a high heterogeneity in the structure of postgraduate medical training evaluation worldwide. However, in contrast to other countries, there have been no scientific studies of the final medical board examination, in Portugal. The present study aimed to evaluate the adequacy of the medical board examination including its validity as measured by its association with medical school grade average and national seriation examination. Cross-sectional, observational study. We analyzed the final results on the medical board examination of 2439 physicians, across 47 specialties, who completed their training in 2016 and 2017, using measures of central tendency and variability. We assessed the association between these grades and the national exam to initiate residency, and the grade average in Medical School. Measures of central tendency and variability, and consequent shape measures, revealed that the distribution of the scores of the final medical board exam is extremely negatively asymmetric and leptokurtic. A positive association was also found between the results in this exam and the score on national exam to initiate residency, and the grade average in Medical School. Although the medical board examination was, in general, positively associated with scores on the national exam to initiate residency, and the mean final Medical School grades, thus indicating its potential validity, our results demonstrate that this exam presents no satisfactory discriminative capacity. Therefore, there is room to improve the actual postgraduate medical examination model, including changes in its classification system and potentially consider other assessment models.


First Report of Curvularia gladioli Causing a Leaf Spot on Gladiolus grandiflorus in Brazil.
Gladiolus (Iridaceae) is a popular bulbous plant grown worldwide as an ornamental garden plant or cut flower due to its attractive color, size, and flower shape. In April 2012, leaf spots were observed on plants of Gladiolus grandiflorus varieties T-704 and Amsterdam growing in a production area of cut flowers located in the city of Viçosa, Minas Gerais. The oval to round leaf spots were brown with a dark border surrounded by a halo of yellow tissue. Infected leaf samples were deposited in the herbarium at the Universidade Federal de Viçosa (VIC31897). A fungus was isolated from the leaf spots and a single-spore pure culture was initiated and grown on corn meal carrot agar (CCA) medium in petri dishes incubated at 25°C under a 12-h photoperiod for 4 weeks. A sporulating single-spore culture was deposited at the Coleção de Culturas de fungos fitopatogênicos "Prof. Maria Menezes" (UFRPE, Brazil) code CMM 4055. On CCA medium, the fungal isolate initially appeared white, becoming dark after 14 days. Thirty conidia and conidiophores were measured for identification to species. The septate, smooth to pale brown conidiophores were present singly or in groups. The simple, straight or flexuous conidiophores were 42.5 to 82.5 × 3.5 to 7.5 μm and some had a geniculate growth pattern. The majority of conidia were curved at the third (central) cell from the base, which was usually enlarged compared to the end cells. The cells at each end of the 3-distoseptate conidia were pale brown, the intermediate cell brown or dark brown, and the third (central) cell was often the darkest. The basal cell had a protuberant hilum. Conidia were smooth and 20.0 to 33.5 × 10 to 17.5 μm. These characteristics matched well with the description of Curvularia gladioli (1). To confirm this identification, DNA was extracted using a Wizard Genomic DNA Purification Kit and the internal transcribed spacer region (ITS) of rDNA was amplified using ITS1 and ITS4 primers and the partial 28S rDNA region using primers LR0R and LR5. The sequences were deposited in GenBank as accession nos. JX995106 and JX995107, respectively. The ITS sequence matched sequence AF071337, C. gladioli, with 100% identity. This pathogen was first identified as C. lunata, but based on the characteristic of the hilum, spore size, and pathogenicity testing, the fungus was renamed C. trifolii f. sp. gladioli (3). Due to the explicit curvature of the conidia at the third cell and molecular data, the fungus was reclassified as C. gladioli (1,2). To confirm Koch's postulates, 1-month-old healthy plants of G. grandiflorus var. T-704 and Amsterdam (five plants each) were inoculated with a conidial suspension (2 × 104 conidia mL-1) by spraying the foliage and then placed on a growth chamber at 25°C. The control plants were sprayed with distilled water. Symptoms were consistent with those initially observed and all plants developed leaf spots by 4 days post-inoculation. C. gladioli was consistently recovered from the symptomatic tissue and control plants remained symptomless. To our knowledge, this is the first report of C. gladioli causing leaf spot on G. grandiflorus in Brazil. Due to a lack of chemical fungicides for management of this pathogen, further studies to evaluate the susceptibility of the main varieties of gladiolus grown in Brazil to C. gladioli may be necessary. References: (1) G. H. Boerema and M. E. C. Hamers. Neth. J. Plant Pathol. 95:1, 1989. (2) D. S. Manamgoda et al. Fungal Divers. 56:131, 2012. (3) J. A. Parmelee. Mycologia 48:558, 1956.


Mesenchymal stem cell characteristics of human anterior cruciate ligament outgrowth cells.
When ruptured, the anterior cruciate ligament (ACL) of the human knee has limited regenerative potential. However, the goal of this report was to show that the cells that migrate out of the human ACL constitute a rich population of progenitor cells and we hypothesize that they display mesenchymal stem cell (MSC) characteristics when compared with adherent cells derived from bone marrow or collagenase digests from ACL. We show that ACL outgrowth cells are adherent, fibroblastic cells with a surface immunophenotype strongly positive for cluster of differentiation (CD)29, CD44, CD49c, CD73, CD90, CD97, CD105, CD146, and CD166, weakly positive for CD106 and CD14, but negative for CD11c, CD31, CD34, CD40, CD45, CD53, CD74, CD133, CD144, and CD163. Staining for STRO-1 was seen by immunohistochemistry but not flow cytometry. Under suitable culture conditions, the ACL outgrowth-derived MSCs differentiated into chondrocytes, osteoblasts, and adipocytes and showed capacity to self-renew in an in vitro assay of ligamentogenesis. MSCs derived from collagenase digests of ACL tissue and human bone marrow were analyzed in parallel and displayed similar, but not identical, properties. In situ staining of the ACL suggests that the MSCs reside both aligned with the collagenous matrix of the ligament and adjacent to small blood vessels. We conclude that the cells that emigrate from damaged ACLs are MSCs and that they have the potential to provide the basis for a superior, biological repair of this ligament.


Redefining genera of cereal pathogens: Oculimacula, Rhynchosporium and Spermospora.
The taxonomy of Oculimacula, Rhynchosporium and Spermospora is re-evaluated, along with that of phylogenetically related genera. Isolates are identified using comparisons of DNA sequences of the internal transcribed spacer ribosomal RNA locus (ITS), partial translation elongation factor 1-alpha (tef1), actin (act), DNA-directed RNA polymerase II largest (rpb1) and second largest subunit (rpb2) genes, and the nuclear ribosomal large subunit (LSU), combined with their morphological characteristics. Oculimacula is restricted to two species, O. acuformis and O. yallundae, with O. aestiva placed in Cyphellophora, and O. anguioides accommodated in a new genus, Helgardiomyces. Rhynchosporium s. str. is restricted to species with 1-septate conidia and hooked apical beaks, while Rhynchobrunnera is introduced for species with 1-3-septate, straight conidia, lacking any apical beak. Rhynchosporium graminicola is proposed to replace the name R. commune applied to the barley scald pathogen based on nomenclatural priority. Spermospora is shown to be paraphyletic, representing Spermospora (type: S. subulata), with three new species, S. arrhenatheri, S. loliiphila and S. zeae, and Neospermospora gen. nov. (type: N. avenae). Ypsilina (type: Y. graminea), is shown to be monophyletic, but appears to be of minor importance on cereals. Finally, Vanderaaea gen. nov. (type: V. ammophilae), is introduced as a new coelomycetous fungus occurring on dead leaves of Ammophila arenaria. Citation: Crous PW, Braun U, McDonald BA, Lennox CL, Edwards J, Mann RC, Zaveri A, Linde CC, Dyer PS, Groenewald JZ (2020). Redefining genera of cereal pathogens: Oculimacula, Rhynchosporium and Spermospora. Fungal Systematics and Evolution 7: 67-98. doi: 10.3114/fuse.2021.07.04.


A dangerous method? The German discourse on hypnotic suggestion therapy around 1900.
In the late nineteenth century, German-speaking physicians and psychiatrists intensely debated the benefits and risks of treatment by hypnotic suggestion. While practitioners of the method sought to provide convincing evidence for its therapeutic efficacy in many medical conditions, especially nervous disorders, critics pointed to dangerous side effects, including the triggering of hysterical attacks or deterioration of nervous symptoms. Other critics claimed that patients merely simulated hypnotic phenomena in order to appease their therapist. A widespread concern was the potential for abuses of hypnosis, either by giving criminal suggestions or in the form of sexual assaults on hypnotized patients. Official inquiries by the Prussian Minister for Religious, Educational and Medical Affairs in 1902 and 1906 indicated that relatively few doctors practised hypnotherapy, whereas the method was increasingly used by lay healers. Although the Ministry found no evidence for serious harm caused by hypnotic treatments, whether performed by doctors or by lay healers, many German doctors seem to have regarded hypnotic suggestion therapy as a problematic method and abstained from using it.


Increasing role of angiography and segmental artery embolization in the management of renal stab wounds.
During a 5-year period 93 patients with stab wounds involving the upper urinary tract were treated. Of these patients 79 were treated initially at our department (group 1) and 14 were referred with complications after initial treatment elsewhere (group 2). In group 1, 26 patients (33%) were selected for surgery on the basis of signs of severe blood loss or associated intra-abdominal injury, or major abnormality on the excretory urogram. At operation a major renal injury and/or associated intra-abdominal laceration was found in 23 patients (88%) and nephrectomy was required in 7 (27%) of them. Nonoperative management was selected in 53 patients (67%) in group 1 and secondary hemorrhage occurred in 8 (15%). Of the patients in group 2, 4 had undergone an operation elsewhere and 10 had been managed nonoperatively. Renal arteriography was performed in 14 patients who had been managed nonoperatively (6 from group 1 and 8 from group 2) and demonstrated a traumatic pseudoaneurysm in 6, an arteriovenous fistula in 5 and no large vessel injury in 3. Selective embolization of the involved segmental artery was successful in 9 of 11 patients (82%) when angiography showed a vascular lesion. This study demonstrates the increasingly important role of renal angiography and selective embolization in the selective nonoperative management of patients with stab wounds of the kidney.


Aspergillus fumigatus and related species.
The genus Aspergillus contains etiologic agents of aspergillosis. The clinical manifestations of the disease range from allergic reaction to invasive pulmonary infection. Among the pathogenic aspergilli, Aspergillus fumigatus is most ubiquitous in the environment and is the major cause of the disease, followed by Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Aspergillus nidulans, and several species in the section Fumigati that morphologically resemble A. fumigatus. Patients that are at risk for acquiring aspergillosis are those with an altered immune system. Early diagnosis, species identification, and adequate antifungal therapy are key elements for treatment of the disease, especially in cases of pulmonary invasive aspergillosis that often advance very rapidly. Incorporating knowledge of the basic biology of Aspergillus species to that of the diseases that they cause is fundamental for further progress in the field.


A nation-wide multicenter 10-year (1999-2008) retrospective clinical study of endocrine therapy for Chinese females with breast cancer.
Endocrine therapy (ET) is one of the main systemic treatments for patients with breast cancer. To our knowledge, few studies have addressed the performance of ET or relevant influencing factors in cancer treatment in China. By retrospectively analyzing the clinicopathological data on breast cancer collected from representative hospitals of 7 traditional areas in China in one random month from each year between year 1999 and 2008, we found that: 1) The rate of the use of hormone receptor (HR) testing was 83.8% (3529/4211), with the estrogen receptor-positive (ER+) rate and/or the progesterone receptor-positive (PR+) rate being 67.9% (2395/3529), and the ER-PR rate being 32.1% (1134/3529). 2) Of the 1599 patients who had received ET, 999 patients (58.3%) were premenopausal while 600 (41.7%) were postmenopausal; 1598 patients received adjuvant hormonal therapy (AHT), whereas only 1 patient received palliative therapy. The medications mainly administered to patients were anti-estrogen agents (80.3% [1283/1598]), followed by AIs (15.5% [248/1598]). Of the 1598 patients receiving AHT, 1416 patients (88.6%) were positive for ER and/or PR, while 75 (4.7%) were negative for both and 108 patients (6.7%) had unknown HR status. The ratio of the use of endocrine therapy for breast cancer patients with ER+ and/or PR+ status was 60.0% (1416/2395). 3) Results from the logistic regression analysis revealed that geography, occupations, and history of chemotherapy and surgery were dependent factors affecting the application of ET in breast cancer treatment in China (P<0.001). In conclusion, the use of ET on Chinese women with breast cancer is increasingly and gradually accounted into the standardized process. Economic status, occupations, and history of chemotherapy and surgery were key factors affecting the application of ET. People residing in developed areas, engaging in mental labour, having history of chemotherapy and surgery are susceptible to accept ET.


Flexible and scalable genotyping-by-sequencing strategies for population studies.
Many areas critical to agricultural production and research, such as the breeding and trait mapping in plants and livestock, require robust and scalable genotyping platforms. Genotyping-by-sequencing (GBS) is a one such method highly suited to non-human organisms. In the GBS protocol, genomic DNA is fractionated via restriction digest, then reduced representation is achieved through size selection. Since many restriction sites are conserved across a species, the sequenced portion of the genome is highly consistent within a population. This makes the GBS protocol highly suited for experiments that require surveying large numbers of markers within a population, such as those involving genetic mapping, breeding, and population genomics. We have modified the GBS technology in a number of ways. Custom, enzyme specific adaptors have been replaced with standard Illumina adaptors compatible with blunt-end restriction enzymes. Multiplexing is achieved through a dual barcoding system, and bead-based library preparation protocols allows for in-solution size selection and eliminates the need for columns and gels. A panel of eight restriction enzymes was selected for testing on B73 maize and Nipponbare rice genomic DNA. Quality of the data was demonstrated by identifying that the vast majority of reads from each enzyme aligned to restriction sites predicted in silico. The link between enzyme parameters and experimental outcome was demonstrated by showing that the sequenced portion of the genome was adaptable by selecting enzymes based on motif length, complexity, and methylation sensitivity. The utility of the new GBS protocol was demonstrated by correctly mapping several in a maize F2 population resulting from a B73×Country Gentleman test cross. This technology is readily adaptable to different genomes, highly amenable to multiplexing and compatible with over forty commercially available restriction enzymes. These advancements represent a major improvement in genotyping technology by providing a highly flexible and scalable GBS that is readily implemented for studies on genome-wide variation.


Accelerated echo-planar J-resolved spectroscopic imaging in the human brain using compressed sensing: a pilot validation in obstructive sleep apnea.
Echo-planar J-resolved spectroscopic imaging is a fast spectroscopic technique to record the biochemical information in multiple regions of the brain, but for clinical applications, time is still a constraint. Investigations of neural injury in obstructive sleep apnea have revealed structural changes in the brain, but determining the neurochemical changes requires more detailed measurements across multiple brain regions, demonstrating a need for faster echo-planar J-resolved spectroscopic imaging. Hence, we have extended the compressed sensing reconstruction of prospectively undersampled 4D echo-planar J-resolved spectroscopic imaging to investigate metabolic changes in multiple brain locations of patients with obstructive sleep apnea and healthy controls. Nonuniform undersampling was imposed along 1 spatial and 1 spectral dimension of 4D echo-planar J-resolved spectroscopic imaging, and test-retest reliability of the compressed sensing reconstruction of the nonuniform undersampling data was tested by using a brain phantom. In addition, 9 patients with obstructive sleep apnea and 11 healthy controls were investigated by using a 3T MR imaging/MR spectroscopy scanner. Significantly reduced metabolite differences were observed between patients with obstructive sleep apnea and healthy controls in multiple brain regions: NAA/Cr in the left hippocampus; total Cho/Cr and Glx/Cr in the right hippocampus; total NAA/Cr, taurine/Cr, scyllo-Inositol/Cr, phosphocholine/Cr, and total Cho/Cr in the occipital gray matter; total NAA/Cr and NAA/Cr in the medial frontal white matter; and taurine/Cr and total Cho/Cr in the left frontal white matter regions. The 4D echo-planar J-resolved spectroscopic imaging technique using the nonuniform undersampling-based acquisition and compressed sensing reconstruction in patients with obstructive sleep apnea and healthy brain is feasible in a clinically suitable time. In addition to brain metabolite changes previously reported by 1D MR spectroscopy, our results show changes of additional metabolites in patients with obstructive sleep apnea compared with healthy controls.


Effects of a gonadotropin-releasing hormone analog on rabbit ovarian function.
This study was undertaken to elucidate the effects of a GnRH analog (GnRH-a) on rabbit ovulation, oocyte maturation, and steroidogenesis, and to verify whether treatment with a GnRH-a interferes with ovarian response to exogenous gonadotropin (hCG), both in vivo and in vitro. Three approaches were used. In the first, adult New Zealand White (NZW) rabbits were divided into two groups. Both received PMSG and hCG administered 72 h after PMSG. In the test group a GnRH-a, leuprolide acetate (LA; 20 microg/kg) was administered s.c. every 24 h. Treated rabbits showed a significant decrease in ovulatory efficiency (control = 88%; treated = 72%), and an increase in degeneration rate of preimplantation embryos (control = 30% vs. treated = 40%). For the second approach, in vitro perfusion experiments were designed to compare the direct effects of LA (10.000 ng/ml) and hCG (50 IU) on ovarian function and to verify whether the presence of a GnRH-a in the perfusate modifies the actions of hCG. LA reduced the ovulatory efficiency of hCG-treated ovaries perfused in vitro (hCG-treated = 87%; hCG-treated LA-perfused = 70%), reduced the potential for preimplantation development (morula stage: hCG-treated = 53%; hCG-treated LA-perfused = 31%; LA-perfused = 12%), and increased the degeneration rate of early embryos (21%, 48%, and 56% respectively). In the third approach, the direct effect of LA (Group I: control, Group II:1.000 ng/ml, and Group III:10.000 ng/ml) on the in vitro maturation of denuded rabbit oocytes was evaluated. LA induced meiotic maturation, but increased oocyte degeneration rate. The potential for preimplantation development was reduced (Morula stage: control = 16%, Group II = 8%, and Group III = 6%), and degeneration rate was increased (38%, 65%, 63% respectively). This study suggests that pharmacological doses of LA may exert a negative effect on oocyte function by direct action on the oocyte, indirectly via alteration of the intrafollicular environment and/or through interference with gonadotropin-induced biological effects within the ovary.


Acute postoperative neurological deterioration associated with surgery for ruptured intracranial aneurysm: incidence, predictors, and outcomes.
Subarachnoid hemorrhage (SAH) results in significant morbidity and mortality, even among patients who reach medical attention in good neurological condition. Many patients have neurological decline in the perioperative period, which contributes to long-term outcomes. The focus of this study is to characterize the incidence of, characteristics predictive of, and outcomes associated with acute postoperative neurological deterioration in patients undergoing surgery for ruptured intracranial aneurysm. The Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) was a multicenter randomized clinical trial that enrolled 1001 patients and assesssed the efficacy of hypothermia as neuroprotection during surgery to secure a ruptured intracranial aneurysm. All patients had a radiographically confirmed SAH, were classified as World Federation of Neurosurgical Societies (WFNS) Grade I-III immediately prior to surgery, and underwent surgery to secure the ruptured aneurysm within 14 days of SAH. Neurological assessment with the National Institutes of Health Stroke Scale (NIHSS) was performed preoperatively, at 24 and 72 hours postoperatively, and at time of discharge. The primary outcome variable was a dichotomized scoring based on an IHAST version of the Glasgow Outcome Scale (GOS) in which a score of 1 represents a good outcome and a score > 1 a poor outcome, as assessed at 90-days' follow-up. Data from IHAST were analyzed for occurrence of a postoperative neurological deterioration. Preoperative and intraoperative variables were assessed for associations with occurrence of postoperative neurological deterioration. Differences in baseline, intraoperative, and postoperative variables and in outcomes between patients with and without postoperative neurological deterioration were compared with Fisher exact tests. The Wilcoxon rank-sum test was used to compare variables reported as means. Multiple logistic regression was used to adjust for covariates associated with occurrence of postoperative deficit. Acute postoperative neurological deterioration was observed in 42.6% of the patients. New focal motor deficit accounted for 65% of postoperative neurological deterioration, while 60% was accounted for using the NIHSS total score change and 51% by Glasgow Coma Scale score change. Factors significantly associated with occurrence of postoperative neurological deterioration included: age, Fisher grade on admission, occurrence of a procedure prior to aneurysm surgery (ventriculostomy), timing of surgery, systolic blood pressure during surgery, ST segment depression during surgery, history of abnormality in cardiac valve function, use of intentional hypotension during surgery, duration of anterior cerebral artery occlusion, intraoperative blood loss, and difficulty of aneurysm exposure. Of the 426 patients with postoperative neurological deterioration at 24 hours after surgery, only 46.2% had a good outcome (GOS score of 1) at 3 months, while 77.7% of those without postoperative neurological deterioration at 24 hours had a good outcome (p < 0.05). Neurological injury incurred perioperatively or in the acute postoperative period accounts for a large percentage of poor outcomes in patients with good admission WFNS grades undergoing surgery for aneurysmal SAH. Avoiding surgical factors associated with postoperative neurological deterioration and directing investigative efforts at developing improved neuroprotection for use in aneurysm surgery may significantly improve long-term neurological outcomes in patients with SAH.


Expression of a Soybean Hydroxyproline-Rich Glycoprotein Gene Is Correlated with Maturation of Roots
A novel extensin gene has been identified in soybean (Glycine max L.) that encodes a hydroxyproline-rich glycoprotein (SbHRGP3) with two different domains. In this study expression of SbHRGP3 was investigated during soybean root development. SbHRGP was expressed in roots of mature plants, as well as seedlings, and showed a distinct pattern of expression during root development. The expression of SbHRGP3 increased gradually during root development of seedlings and reached a maximum while the secondary roots were maturing. The maximum expression level was contributed mainly by the secondary roots rather than by the primary root. Furthermore, expression of SbHRGP3 was preferentially detected in the regions undergoing maturation of the primary and secondary roots. These results imply that the expression of SbHRGP3 is regulated in an organ- and development-specific manner and that in soybean SbHRGP3 expression may be required for root maturation, presumably for the cessation of root elongation. Wounding and sucrose in combination enhanced expression of SbHRGP3 in roots, whereas both wounding and sucrose were required for the expression of SbHRGP3 in leaves.


LRIG1-Mediated Inhibition of EGF Receptor Signaling Regulates Neural Precursor Cell Proliferation in the Neocortex.
Here, we ask how neural stem cells (NSCs) transition in the developing neocortex from a rapidly to a slowly proliferating state, a process required to maintain lifelong stem cell pools. We identify LRIG1, known to regulate receptor tyrosine kinase signaling in other cell types, as a negative regulator of cortical NSC proliferation. LRIG1 is expressed in murine cortical NSCs as they start to proliferate more slowly during embryogenesis and then peaks postnatally when they transition to give rise to a portion of adult NSCs. Constitutive or acute loss of Lrig1 in NSCs over this developmental time frame causes stem cell expansion due to increased proliferation. LRIG1 controls NSC proliferation by associating with and negatively regulating the epidermal growth factor receptor (EGFR). These data support a model in which LRIG1 dampens the stem cell response to EGFR ligands within the cortical environment to slow their proliferation as they transition to postnatal adult NSCs.


The role of the district nurse in bereavement support.
District nurses are frequently involved in the care of patients immediately prior to death and could therefore provide support to bereaved relatives. However, little is known about nurses' views on bereavement support or their actual involvement. To survey a representative sample of district nurses to ascertain their current practice and perceived role in supporting bereaved people and to identify factors that influence their practice. A self-completed postal questionnaire was distributed anonymously to 522 district nurses in the central southern coastal area of Britain. It comprised five sections: interest in and education about bereavement; a Likert scale to measure nurses' views about bereavement care; information about the practice with which the nurse had links; bereavement care provided by the practice; and demographics. A 62% response rate was achieved following two reminders. Sixty-nine per cent reported having an interest in bereavement support. Logistic regression modelling identified older age of the nurse and district of employment as the best predictors of interest in bereavement, and older age of the nurse, district of employment and higher level of academic qualification (having a diploma or degree) as the best predictors of active follow-up bereavement visiting. Ninety five percent of district nurses believed their role should involve visiting bereaved relatives/carers of patients they have nursed, but only 19% believed they should visit bereaved people when the deceased was not their patient. Older age, higher qualifications and district of employment among district nurses were associated with greater interest in bereavement and more proactive care of bereaved people. The findings of this survey have important implications for the training, continued education and the extended role of the nurse in bereavement support.


Lithium clearance in chronic nephropathy.
1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function. 2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption of lithium or influence of osmotic diuresis. 3. Fractional reabsorption of lithium was reduced in most patients with glomerular filtration rates below 25 ml/min. 4. Calculated fractional distal reabsorption of sodium was reduced in most patients with glomerular filtration rates below 50 ml/min. 5. Lithium clearance data were independent of whether renal disease was of primarily glomerular or tubular origin and, further, were not influenced by long-term conventional antihypertensive treatment. 6. It is concluded that, even with a reduced kidney function, the data are compatible with the suggestion that lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct). With more severe impairment the proximal tubule also becomes involved in the adjustment.


RET-mediated gene expression pattern is affected by isoform but not oncogenic mutation.
The inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN 2) is caused by mutations of the RET receptor tyrosine kinase and is characterized by medullary thyroid carcinoma. MEN 2 subtypes have distinct mutational spectrums and vary in severity. The most severe disease subtype, MEN 2B, is associated with a specific RET mutation (M918T) that has been predicted to alter downstream signaling and target gene expression patterns. We used gene expression microarray analysis to identify target genes modulated by RET. We compared two oncogenic RET mutants, associated with MEN 2A (2ARET) or MEN 2B (2BRET) disease subtypes, that are predicted to have distinct downstream target genes. We showed that overall, 2ARET and 2BRET modulated genes with similar functional ontologies. Further, when we validated our microarray data by quantitative real time PCR, we did not detect major differences in gene expression associated with these mutants when differences in receptor activity levels were considered. We did, however, detect differences in gene expression induced by two RET COOH-terminal isoforms, RET9 and RET51, irrespective of the RET form present (wildtype, 2ARET, or 2BRET). Our data suggest that similar transcriptional programs contribute to all forms of MEN 2 but that differences in target gene expression may contribute to developmental pattern differences observed between RET isoforms.


Use of topical lidocaine for cosmetic dermatologic procedures.
Topical anesthetic agents are frequently used by dermatologists to decrease the pain associated with a variety of cutaneous procedures, including laser surgery, soft tissue augmentation, and other cosmetic surgical treatments. These lidocaine-containing creams play an integral role in the cosmetic dermatology office by providing patient comfort with minimal side effects. This review of topical lidocaine preparations should aid practitioners in the selection of an appropriate topical anesthetic, taking into consideration its onset and duration of action and potential side effects.


Hierarchical line integration.
This paper presents an acceleration scheme for the numerical computation of sets of trajectories in vector fields or iterated solutions in maps, possibly with simultaneous evaluation of quantities along the curves such as integrals or extrema. It addresses cases with a dense evaluation on the domain, where straightforward approaches are subject to redundant calculations. These are avoided by first calculating short solutions for the whole domain. From these, longer solutions are then constructed in a hierarchical manner until the designated length is achieved. While the computational complexity of the straightforward approach depends linearly on the length of the solutions, the computational cost with the proposed scheme grows only logarithmically with increasing length. Due to independence of subtasks and memory locality, our algorithm is suitable for parallel execution on many-core architectures like GPUs. The trade-offs of the method--lower accuracy and increased memory consumption--are analyzed, including error order as well as numerical error for discrete computation grids. The usefulness and flexibility of the scheme are demonstrated with two example applications: line integral convolution and the computation of the finite-time Lyapunov exponent. Finally, results and performance measurements of our GPU implementation are presented for both synthetic and simulated vector fields from computational fluid dynamics.


Diagnosing pneumonia in patients with acute cough: clinical judgment compared to chest radiography.
Pneumonia is often diagnosed and treated empirically. We set out to determine the diagnostic accuracy of clinical judgment based on signs and symptoms to detect radiographic pneumonia in patients presenting with acute cough in primary care. In 2810 European patients with acute cough, general practitioners (GPs) recorded whether they considered pneumonia to be present ("yes" or "no") immediately after history and physical examination. Chest radiography was performed within 1 week by local radiologists blind to other patient characteristics. 140 patients had radiographic pneumonia (5%), of whom 41 (29%) had been diagnosed as such. 31 (1%) patients had a clinical diagnosis that was not confirmed by radiography (n=2670). In clinically suspected pneumonia, 57% of subjects were subsequently diagnosed with radiographic pneumonia. Negative predictive value (NPV), sensitivity and specificity of GPs' clinical judgment were 96%, 29% and 99%, respectively. Compared to patients with a clinical diagnosis of pneumonia, less severe symptoms were found in radiographic pneumonia cases not suspected clinically (p<0.05). The predictive values of GPs' clinical judgment, particularly the high NPVs, are helpful in routine care. Nonetheless, the majority of diagnoses of radiographic pneumonias was not suspected on clinical grounds. There is a need to further support the detection of clinically relevant pneumonia in primary care.


Stimulation of muscle anabolism by resistance exercise and ingestion of leucine plus protein.
Leucine is known to stimulate muscle protein synthesis and anabolism. However, evidence for the efficacy of additional leucine to enhance the response of muscle anabolism to resistance exercise and protein ingestion is unclear. Thus, we investigated the response of net muscle protein balance to ingestion of additional leucine with protein in association with resistance exercise. Two groups of untrained subjects performed an intense bout of leg resistance exercise following ingestion of 1 of 2 drinks: flavored water (PL); or 16.6 g of whey protein + 3.4 g of leucine (W+L). Arteriovenous amino acid balance across the leg was measured to assess the anabolic response of muscle in each group. Arterial amino acid concentrations increased in response to ingestion of W+L. Amino acid concentrations peaked between 60 and 120 min after ingestion, and then declined to baseline values. Valine concentration decreased to levels significantly lower than baseline. Net balance of leucine, threonine, and phenylalanine did not change following PL ingestion, but increased and remained elevated above baseline for 90-120 min following W+L ingestion. Leucine (138 +/- 37 and -23 +/- 23 mg), phenylalanine (58 +/- 28 and -38 +/- 14 mg), and threonine (138 +/- 37 and -23 +/- 23 mg) uptake was greater for W+L than for PL over the 5.5 h following drink ingestion. Our results indicate that the whey protein plus leucine in healthy young volunteers results in an anabolic response in muscle that is not greater than the previously reported response to whey protein alone.


Differences in bulk and microscale yttrium speciation in coal combustion fly ash.
Coal combustion ash is a promising alternative source of rare earth elements (REE; herein defined as the 14 stable lanthanides, yttrium, and scandium). Efforts to extract REE from coal ash will depend heavily on the location and speciation of these elements in the ash. This study sought to identify the major chemical forms of yttrium (Y), as a representative REE in coal fly ash samples selected from major coal sources in the United States. Y speciation was evaluated using both bulk scale analyses (sequential extractions, Y K-edge X-ray absorption near-edge spectroscopy - XANES) and complementary analyses at the micron scale (micro-focus X-ray fluorescence and micro-XANES). Sequential selective extractions revealed that the REE were primarily in the residual (unextracted fraction) of coal fly ash samples. Extraction patterns for yttrium resembled those of the lanthanides, indicating that these elements were collectively dispersed throughout the aluminosilicate glass in fly ash. Bulk XANES analysis indicated that Y coordination states resembled a combination of Y-oxides, Y-carbonate, and Y-doped glass, regardless of ash origin. However, in the microprobe analysis, we observed "hotspots" of Y (∼10-50 μm) in some samples that included different Y forms (e.g., Y-phosphate) not observed in bulk measurements. Overall, this study demonstrated that yttrium (and potentially other REEs) are entrained in the glass phase of fly ash and that microscale investigations of individual high-REE regions in fly ash samples do not necessarily capture the dominant speciation.