Increasing the species diversity in the Aspergillus section Nidulantes: Six novel species mainly from the indoor environment.
Aspergillus section Nidulantes encompasses almost 80 homothallic and anamorphic species, mostly isolated from soil, plant material, or the indoor environment. Some species are clinically relevant or produce mycotoxins. This study reevaluated the species boundaries within several clades of section Nidulantes. Five data sets were assembled, each containing presumptive new species and their closest relatives, and phylogenetic and phenotypic analyses were performed. We tested the hypotheses that the newly isolated or reexamined strains constitute separate species (splitting approach) or should be treated as part of broadly defined species (lumping approach). Four DNA sequence loci were amplified, internal transcribed spacer (ITS) and large subunit (LSU) regions of the rDNA and partial sequences of the β-tubulin (benA), calmodulin (CaM), and RNA polymerase II second largest subunit (RPB2) genes. The latter three loci were used for the phylogenetic analysis and served as input for single-locus (GMYC, bGMYC, PTP, and bPTP) and multilocus (STACEY and BP&P) species delimitation analyses. The phenotypic analysis comprised macro- and micromorphology (including scanning electron microscopy) and comparison of cardinal growth temperatures. The phylogenetic analysis supported the splitting hypothesis in all cases, and based on the combined approach, we propose six new species, four that are homothallic and two anamorphic. Four new species were isolated from the indoor environment (Jamaica, Trinidad and Tobago, USA), one originated from soil (Australia), and one from a kangaroo rat cheek pouch (USA).


A source of adenosine involved in cardiovascular responses to defense area stimulation.
We have investigated the source of central adenosine important in modulating the cardiovascular response to hypothalamic defense area (HDA) stimulation in alpha-chloralose-anesthetized rats. Microinjections of an ecto-5'-nucleotidase inhibitor, alpha,beta-methylene ADP (alpha,beta-meADP), were made into caudal nucleus of the solitary tract (cNTS) and rostral ventrolateral medulla (RVLM), and its effects on HDA-evoked responses were observed. Stimulation of HDA evoked an increase in arterial pressure and a secondary rise in arterial pressure after stimulation ceased. There was also an increase in heart rate and hindlimb blood flow. alpha,beta-meADP had no effect on resting levels of arterial pressure, heart rate, and hindlimb blood flow when injected into the cNTS or RVLM. alpha,beta-meADP also had no effect on the HDA-evoked tachycardia and increase in muscle blood flow. However, alpha,beta-meADP reduced the primary increase in arterial pressure evoked by HDA stimulation when microinjected into the cNTS. In contrast, alpha,beta-meADP reduced the secondary increase in arterial pressure when microinjected into the RVLM. From these results, we suggest that at least part of the adenosine released centrally during HDA stimulation is derived extracellularly from ATP metabolism.


Living at the threshold: where does the neotropical phytoseiid mite Typhlodromalus aripo survive the dry season?
The establishment of the neotropical predatory mite Typhlodromalus aripo in sub-Saharan Africa has resulted in broadly successful biological control of the cassava green mite Mononychellus tanajoa throughout the cassava belt of Africa. In some mid-altitude areas and drier lowland savannahs of sub-Saharan Africa, which are characterized by cool or hot long (> or =5 months) dry seasons, the predator disappears from its habitat in the cassava apex during the dry season and reappears after the onset of rains. It is not known, however, where the predator remains during this time period. In this study, we conducted a field enclosure experiment of cassava plants with the objectives to determine if (a) T. aripo survives at very low densities in the apex, if (b) it survives in the soil or leaf litter below the cassava plant, and if (c) it recolonizes the cassava plant from the surrounding vegetation. Towards the end of the dry season, when the predators had disappeared from all cassava plants included in the experiment, five treatments were applied: (1) plants without enclosure; (2) plants with enclosure; (3) plants with enclosure, apices removed; (4) plants with enclosure, glue barrier around stem; and (5) plants kept free of T. aripo, without enclosure. Predator (re)appearance on cassava apices was monitored non-destructively at weekly intervals and was expressed as the proportion of plants with at least one apex with T. aripo per total number of plants of the treatment. The predators reappeared first on the plants of the treatments (1), (2), and (4). With a time lag of 7-8 weeks, the predators appeared also on the plants of the treatments (3) and (5). The time pattern of the predator's (re)appearance in the cassava apex of the different treatments suggests that (a) T. aripo survives the dry season in very low densities in the cassava apex; this result is supported by an assessment of the efficiency of non-destructive visual in-field apex inspections which proved that about 10% of the cassava apices that had T. aripo were not recognized as such; (b) T. aripo does not survive in the soil or leaf litter, but we did document cases in a screenhouse experiment, where few individuals migrated down to the ground and walked over exposed soil until they reached the apex bouquet traps; additionally, microclimate measurements in various cassava plant strata proved that the cassava apex and the cassava stem base are the locations with the highest relative humidity during the dry season--which makes the stem base a potentially interesting refuge; (c) T. aripo does not survive in the surrounding vegetation, which is supported by a vegetation survey, where T. aripo was not found on any other plant species than cassava.


Co-payments and the use of emergency department services in the children's health insurance program.
Research suggests that more than half of all emergency department (ED) visits in the United States are for nonurgent conditions, leading to billions of dollars in potentially avoidable spending annually. In this study, we examine the effects of co-payment changes on ED utilization among children enrolled in ALL Kids, Alabama's Children's Health Insurance Program We separately model the effect of the 2003 co-payment increases on the monthly probability of any ED visit, and visits within three severity categories, using linear probability models that control for beneficiary characteristics and time trends that are allowed to vary in the pre- and postperiods. We observe a small decline in the probability of ED visits 1 year after the co-payment increase. However, low-severity visits, which we hypothesize to be more price sensitive, show no significant evidence of a decline. Our study suggests that the modest co-payment changes were not effective in improving the efficiency of ED utilization.


[The need for a law concerning human body rights].
This new "turn of the century", at least in France, is marked by an increasing discrepancy between laws and new medical discoveries. Medical practitioners, scientists and researchers have had such a fantastic power and, as a consequence, the patients have never run such an important risk of loosing human dimensions. The basic question is the legal status of the human body. Until now, common law considers human being as a citizen whose liberty should be limited under certain conditions. However, this point of view poorly prepares to rule man as a creature of flesh and sentiment. There is an almost complete deficit of the legal statute of man in his globality, especially concerning the juridical status of the human body which is totally lacking as a whole in the french civil code. Human body represents a double legal problem: is its integrity a private or a public privilege? Are his dignity and identity really warranted for everyone?


HemR is an OmpR/PhoB-like response regulator from Leptospira, which simultaneously effects transcriptional activation and repression of key haem metabolism genes.
Several Leptospira species cause leptospirosis, the most extended zoonosis worldwide. In bacteria, two-component systems constitute key signalling pathways, some of which are involved in pathogenesis. The physiological roles of two-component systems in Leptospira are largely unknown, despite identifying several dozens within their genomes. Biochemical confirmation of an operative phosphorelaying two-component system has been obtained so far only for the Hklep/Rrlep pair. It is known that hklep/rrlep knockout strains of Leptospira biflexa result in haem auxotrophy, although their de novo biosynthesis machinery remains fully functional. Haem is essential for Leptospira, but information about Hklep/Rrlep effector function(s) and target(s) is still lacking. We are now reporting a thorough molecular characterization of this system, which we rename HemK/HemR. The DNA HemR-binding motif was determined, and found within the genomes of saprophyte and pathogenic Leptospira. In this way, putative HemR-regulated genes were pinpointed, including haem catabolism-related (hmuO - haem oxygenase) and biosynthesis-related (the hemA/C/D/B/L/E/N/G operon). Specific HemR binding to these two promoters was quantified, and a dual function was observed in vivo, inversely repressing the hmuO, while activating the hemA operon transcription. The crystal structure of HemR receiver domain was determined, leading to a mechanistic model for its dual regulatory role.


Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma.
Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma (MM) is lacking in the current literature. We evaluated 258 patients with relapsed MM, diagnosed from 2008 to 2015, to investigate the prognostic impact of deep immunoparesis on post-relapse survival. On qualitative immunoparesis assessment, no, partial and full immunoparesis was present in 9%, 30% and 61% of patients, respectively. Quantitative immunoparesis was assessed by computing the average relative difference (ARD) between polyclonal immunoglobulin(s) and corresponding lower normal limit(s), with greater negative values indicating deeper immunoparesis. The median ARD was -39%, with an optimal cut-off of -50% for overall survival (OS) by recursive partitioning analysis. Deep immunoparesis (ARD ≤-50%) was associated with a higher tumour burden at first relapse compared to none/shallow [ARD >-50%] immunoparesis. The OS (P = 0·007) and progression-free survival (PFS; P < 0·001) differed significantly between the deep and none/shallow immunoparesis groups. Kaplan-Meier estimates for 3-year OS were 36% and 46%, and for 2-year PFS were 17% and 27%, respectively. On multivariable analysis (MVA) for PFS, both qualitative and quantitative immunoparesis retained negative prognostic impact independently. However, only quantitative immunoparesis was independently prognostic for OS on MVA. Depth of immunoparesis in relapsed MM is an important prognostic factor for post-relapse survival in the era of novel agents and continuous therapy.


Electronic counting in growth studies of Mycobacterium avium.
Metabolically uniform cells of Mycobacterium avium were obtained by selective filtration. The life cycle of these cells was followed by photomicrographs, electronic enumeration, and sizing and by viability and protein determinations. The cells elongate to form filaments several times their initial length; the increase in mass is reflected by a five- to sixfold increase of total protein in the culture. The filaments then fragment causing the production of viable coccobacilli. The techniques employed to obtain this form of growth are described and comparisons with nocardial growth are noted.


Reduced risk of sudden death from chest wall blows (commotio cordis) with safety baseballs.
In an experimental model of sudden death from baseball chest wall impact (commotio cordis), we sought to determine if sudden death by baseball impact could be reduced with safety baseballs. Sudden cardiac death can occur after chest wall impact with a baseball (commotio cordis). Whether softer-than-standard (safety) baseballs reduce the risk of sudden death is unresolved from the available human data. In a juvenile swine model, ventricular fibrillation (VF) has been shown to be induced reproducibly by precordial impact with a 30-mph baseball 10 to 30 ms before the T-wave peak, and this likelihood was reduced with the softest safety baseballs (T-balls). To further test whether safety baseballs would reduce the risk of sudden death at velocities more relevant to youth sports competition, we used our swine model of commotio cordis to test baseballs propelled at the 40-mph velocity commonly attained in that sport. Forty animals received up to 3 chest wall impacts at 40 mph during the vulnerable period of repolarization for VF with 1 of 3 different safety baseballs of varying hardness, and also by a standard baseball. Safety baseballs propelled at 40 mph significantly reduced the risk for VF. The softest safety baseballs triggered VF in only 11% of impacts, compared with 19% and 22% with safety baseballs of intermediate hardness, and 69% with standard baseballs. In this experimental model of low-energy chest wall impact, safety baseballs reduced (but did not abolish) the risk of sudden cardiac death. More universal use of these safety baseballs may decrease the risk of sudden death on the playing field for young athletes.


Mutator factors and genetic variance components of viability in Drosophila melanogaster.
In the process of testing whether or not the independent-locus selection model holds true with previously estimated genetic parameters (cf. MUKAI and MARUYAMA 1971) in D. melanogaster collected near Raleigh, North Carolina, we found an abnormal phenomenon: an unusually large increase in dominance variance for viability in comparison with additive variance with the accumulation of mutations on 140 randomyl sampled, inversion-free second chromosomes. Mutations were accumulated only through males heterozygous for the Pm-carrying chromosome [In(2LR)bwV1] and the extracted second chromosomes, and the genetic variance components were estimated by using a partial diallel cross method.--Further investigations clarified that chromosome abberations occurred at a frequency of 0.0114 per second chromosome per generation (inversions: 0.0098; transpositions: 0.0011; translocation: 0.0004), and recessive lethal mutations occurred at an average rate of 0.031 per second chromosome per generation.--From these results and from the amount of change in the homozygous load, it was speculated that about 60--70% of the second chromosomes used had a kind of mutator which induced chromosome and/or chromatid breaks at a minimum rate of 0.18 per second chromosome per generation. These breaks resulted in recessive lethal mutations at a rate more than ten times higher than the normal rate. Also these breaks were most probably the cause of male recombination.--The above unusual increase in dominance variance can be explained by assuming that chromosome segments, introduced into the extracted "wild" chromosomes by male recombinations (double crossover) from the marker chromosomes [In(2LR)bwV1], showed heterosis and linkage disequilibria with deleterious mutations and possibly with other introduced segments.--Finally, the nature and possible significance of mutator factors are discussed.


Linking short tandem repeat polymorphisms with cytosine modifications in human lymphoblastoid cell lines.
Inter-individual variation in cytosine modifications has been linked to complex traits in humans. Cytosine modification variation is partially controlled by single nucleotide polymorphisms (SNPs), known as modified cytosine quantitative trait loci (mQTL). However, little is known about the role of short tandem repeat polymorphisms (STRPs), a class of structural genetic variants, in regulating cytosine modifications. Utilizing the published data on the International HapMap Project lymphoblastoid cell lines (LCLs), we assessed the relationships between 721 STRPs and the modification levels of 283,540 autosomal CpG sites. Our findings suggest that, in contrast to the predominant cis-acting mode for SNP-based mQTL, STRPs are associated with cytosine modification levels in both cis-acting (local) and trans-acting (distant) modes. In local scans within the ±1 Mb windows of target CpGs, 21, 9, and 21 cis-acting STRP-based mQTL were detected in CEU (Caucasian residents from Utah, USA), YRI (Yoruba people from Ibadan, Nigeria), and the combined samples, respectively. In contrast, 139,420, 76,817, and 121,866 trans-acting STRP-based mQTL were identified in CEU, YRI, and the combined samples, respectively. A substantial proportion of CpG sites detected with local STRP-based mQTL were not associated with SNP-based mQTL, suggesting that STRPs represent an independent class of mQTL. Functionally, genetic variants neighboring CpG-associated STRPs are enriched with genome-wide association study (GWAS) loci for a variety of complex traits and diseases, including cancers, based on the National Human Genome Research Institute (NHGRI) GWAS Catalog. Therefore, elucidating these STRP-based mQTL in addition to SNP-based mQTL can provide novel insights into the genetic architectures of complex traits.


Platelet-Rich Plasma Versus Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis: Results at 5 Years of a Double-Blind, Randomized Controlled Trial.
Platelet-rich plasma (PRP) injections have been proposed as a new conservative option for knee degeneration to provide symptomatic relief and delay surgical intervention. Although the current literature provides some evidence on the benefits of this technique compared with viscosupplementation, no studies have been performed to compare their long-term effects. To compare the long-term clinical outcomes provided by intra-articular injections of either PRP or hyaluronic acid (HA) to treat knee degenerative disease. Randomized controlled trial; Level of evidence, 1. Patients with a history of chronic symptomatic knee degenerative changes and osteoarthritis (Kellgren-Lawrence grade 0-3) were enrolled: 192 patients were randomized to undergo 3 blinded weekly intra-articular injections of either PRP or HA. Patients were prospectively evaluated before the injection and then at 2, 6, 12, and 24 months and a mean of 64.3 months (SD, 7.8 months) of follow-up. Evaluation was based on International Knee Documentation Committee (IKDC) subjective (main outcome), EuroQol visual analog scale, and Tegner scores; 167 patients reached the final evaluation. Both treatments were effective in improving knee functional status and symptoms over time: Mean ± SD IKDC subjective score improved significantly for both PRP and HA groups ( P < .0005) and remained stable over time up to 24 months (from 53.3 ± 14.3 to 67.3 ± 18.1 and from 50.3 ± 13.2 to 62.1 ± 20.8 for PRP and HA groups, respectively). At final evaluation, a significant IKDC reduction was observed in both treatment groups, with the PRP group still presenting significantly higher values compared with baseline: PRP 60.5 ± 19.0 ( P < .001 vs baseline), HA 55.7 ± 18.8 (not significant vs baseline). A comparative analysis showed no significant intergroup difference in any of the clinical scores at any follow-up point. The median duration of patient subjective perception of symptomatic relief was 9 months for HA and 12 months for PRP (not significant). The only significant difference was observed in the rate of reintervention at 24 months, which was significantly lower in the PRP group (22.6% vs 37.1%, P = .036). Both treatments were effective in improving knee functional status and symptoms over time. PRP did not provide an overall superior clinical improvement compared with HA in terms of either symptomatic-functional improvement at different follow-up points or effect duration. NCT01670578 (ClinicalTrials.gov identifier).


A predictive model of response to erythropoietin stimulating agents in myelodysplastic syndrome: from the Canadian MDS patient registry.
Prediction of response to erythropoietin stimulating agents (ESAs) in anemic MDS patients is often based on the Nordic score. We wished to validate the Nordic score (IWG 2006 response criteria) in a larger cohort and determine if other variables such as IPSS/IPSS-R, ferritin, LDH, and a novel European ESA response score (Santini 2013) were of prognostic importance. We analyzed 208 ESA-treated MDS patients (WHO 2008 criteria) from a prospective registry. Ninety-four and 93% had lower risk scores by IPSS (low/int - 1) and IPSS-R (low/very low), respectively. Erythroid response was achieved in 94 patients (47%); responses were similar with erythropoietin (50%) and darbepoetin (39%; p = 0.2). The Nordic and European scores were both validated on univariate analysis. Variables independently predictive of response in multivariate analysis were low-risk IPSS score (OR 0.1, p = 0.0016) and serum EPO level < 100 mIU/mL (OR 8.7, p < 0.0001). We propose a new ESA response score, consisting of (a) IPSS low score (1 point) and (b) serum EPO levels < 100 mIU/ml (2 points), yielding scores ranging from 0 to 3, with response rates varying from 17 to 81%. The Nordic score has validity but we observed lower than the expected response rates in the best risk group. Our proposed scoring system appears more discriminating but needs validation.


A complicated case of recurrent Cowper's gland abscess.
A Caucasian man 64 years old was admitted to our department for fever, strangury, frequency and pain in the perineum secondary to the relapse of Cowper's gland abscess previously treated by antibiotic therapy and trans-perineal ultrasound-guided aspiration. At admission, the clinical parameters were suggestive of sepsis; moreover, the trans-perineal ultrasound detected an hypoechoic mass suspicious for the recurrence of Cowper's gland abscess. A suprapubic catheter was positioned and a targeted antibiotic therapy (Colistin 9000.000 U intravenously every day for 8 days plus meropenem 500 mg intravenously every 8 hours for 10 days) was administered. The patient during the follow up presented long fibers of mucus in the urine and recurrent positive urine culture, therefore two months later underwent trans-perineal surgical asportation of the left Cowper's gland. One month after surgery the patient was readmitted for the presence of a urinary fistula between bulbar urethra and perineum. A new suprapubic catheter was positioned and after three months was removed because a complete restitutio ad integrum was shown by retrograde cystourethrogram and uroflowmetry. In conclusion, the abscess of Cowper's gland could represent a very rare but severe clinical event that need aggressive therapy and close follow up for its potentially high rate of early and late clinical complications; in the presence of recurrence the surgical asportation of the Cowper's gland should be considered.


Loss of metallothionein predisposes mice to diethylnitrosamine-induced hepatocarcinogenesis by activating NF-kappaB target genes.
Metallothioneins (MT) are potent scavengers of free radicals that are silenced in primary hepatocellular carcinomas (HCC) of human and rodent origin. To examine whether loss of MT promotes hepatocarcinogenesis, male Mt-1 and Mt-2 double knockout (MTKO) and wild-type (WT) mice were exposed to diethylnitrosamine (DEN) and induction of HCC was monitored at 23 and 33 weeks. The size and number of liver tumors, the ratio between liver and body weight, and liver damage were markedly elevated in the MTKO mice at both time points compared with the WT mice. At 23 weeks, MTKO mice developed HCC whereas WT mice developed only preneoplastic nodules suggesting that loss of MT accelerates hepatocarcinogenesis. MTKO tumors also exhibited higher superoxide anion levels. Although NF-κB activity increased in the liver nuclear extracts of both genotypes after DEN exposure, the complex formed in MTKO mice was predominantly p50/65 heterodimer (transcriptional activator) as opposed to p50 homodimer (transcriptional repressor) in WT mice. Phosphorylation of p65 at Ser276 causing its activation was also significantly augmented in DEN-exposed MTKO livers. NF-κB targets that include early growth response genes and proinflammatory cytokines were significantly upregulated in MTKO mice. Concurrently, there was a remarkable increase (∼100-fold) in Pai-1 expression; significant increase in c-Jun, c-Fos, c-Myc, Ets2, and ATF3 expressions; and growth factor signaling that probably contributed to the increased tumor growth in MTKO mice. Taken together, these results demonstrate that MTs protect mice from hepatocarcinogen-induced liver damage and carcinogenesis, underscoring their potential therapeutic application against hepatocellular cancer.


A microcomputer-based averager.
A disadvantage of commercially available averagers is the time needed for the output routine. This paper describes a microcomputer, programmed as an averager, with additional features to obtain an examination time as short as possible, which indeed is important for clinical application. Through this apparatus, the time needed for a standard ERG and VECP examination could be reduced from 50 to 25 min.


A noncovalent backbone planarization strategy increases the NIR-II extinction coefficients for gas/phototheranostic applications.
We propose a noncovalent backbone planarization strategy to fabricate a gas/phototheranostic nanocomposite (B-E-NO NPs) in the near-infrared-II (NIR-II, 1000-1700 nm) window by incorporating noncovalent conformational locks. B-E-NO NPs display a giant NIR-II extinction coefficient, realizing multimodal imaging-guided high-efficiency NIR-II photothermal therapy (η = 45.4%) and thermal-initiated nitric oxide combination therapy.


Playing with fire: effects of negative mood induction and working memory on vocabulary acquisition.
We investigated the impact of emotions on learning vocabulary in an unfamiliar language to better understand affective influences in foreign language acquisition. Seventy native English speakers learned new vocabulary in either a negative or a neutral emotional state. Participants also completed two sets of working memory tasks to examine the potential mediating role of working memory. Results revealed that participants exposed to negative stimuli exhibited difficulty in retrieving and correctly pairing English words with Indonesian words, as reflected in a lower performance on the prompted recall tests and the free recall measure. Emotional induction did not change working memory scores from pre to post manipulation. This suggests working memory could not explain the reduced vocabulary learning in the negative group. We argue that negative mood can adversely affect language learning by suppressing aspects of native-language processing and impeding form-meaning mapping with second language words.


Evolution of Attenuation and Risk of Reversal in Peste des Petits Ruminants Vaccine Strain Nigeria 75/1.
Peste des Petits Ruminants (PPR) is a highly infectious disease caused by a virus of the Morbillivirus genus. The current PPR eradication effort relies mainly on the implementation of massive vaccination campaigns. One of the most widely used PPR vaccines is the Nigeria 75/1 strain obtained after attenuation by 75 serial passages of the wild type isolate in cell cultures. Here we use high throughput deep sequencing of the historical passages that led to the Nigeria 75/1 attenuated strain to understand the evolution of PPRV attenuation and to assess the risk of reversal in different cell types. Comparison of the consensus sequences of the wild type and vaccine strains showed that only 18 fixed mutations separate the two strains. At the earliest attenuation passage at our disposal (passage 47), 12 out of the 18 mutations were already present at a frequency of 100%. Low-frequency variants were identified along the genome in all passages. Sequencing of passages after the vaccine strain showed evidence of genetic drift during cell passages, especially in cells expressing the SLAM receptor targeted by PPRV. However, 15 out of the 18 mutations related to attenuation remained fixed in the population. In vitro experiments suggest that one mutation in the leader region of the PPRV genome affects virus replication. Our results suggest that only a few mutations can have a serious impact on the pathogenicity of PPRV. Risk of reversion to virulence of the attenuated PPRV strain Nigeria 75/1 during serial passages in cell cultures seems low but limiting the number of passages during vaccine production is recommended.


Blended Training for Frontline Health Functionaries: Is this the Way Ahead?
To test the change in the knowledge of the study participants following a Blended Training and Learning Approach (BTLA). Secondly, the paper also tries to discuss the use of this method over the classical classroom based trainings. Frontline health functionaries are the backbone of almost all health goals. It is therefore essential to ensure proper training of this cadre of workers for optimum service delivery. The present paper tries to discuss the use of an effective new training pedagogy over the classical classroom based trainings. A cross-sectional study was conducted from August 2013 to April 2014 in all districts in the state of Odisha. The study participants comprised of two groups. Group 1: Integrated Child Development Services supervisors, Child Development Project Officers received training on reduction of stunting. Group 2: Nutrition Counselors and Auxiliary Nurses and Midwifes received training on management of severe acute malnutrition (SAM). Selection of participants was done following complete enumeration technique. The training effectiveness was measured using paired t-test. Out of approximately 2400 participants identified across the state of Odisha, 2350 participants provided consent to participate in the study. The change in knowledge was determined by using paired t-test. The results of the paired t-test for the training on reduction of stunting were significant, P < 0.001, indicates that there was a significant increase in the score from (mean = 11.4; standard deviation [SD] = 2.34) to the post-test (mean = 13.8; SD = 2.34). The mean increase was 2.4 with 95% confidence interval [CI] for the difference between means of 11.4 and 13.8. Similar test was conducted to evaluate the training on SAM. The results of the paired t-test were significant, P < 0.001, indicates that there was a significant increase in the score from (mean = 14.7; SD = 2.8) to the post-test (mean = 15.8; SD = 2.3). The mean increase was 1.12 with 95% CI for the difference between means of mean = 14.7 to mean = 15.8. There are different approaches that can be adapted during any training ranging from the traditional form of classroom teaching to the new technologically advanced forms of training such as e-learning. Understanding the merits and demerits, there was the felt need to try a newer approach of training. Thus, the method of BTLA was tried in the study and was proved to be effective. The newly tried and tested pedagogy of training would provide the necessary evidence for future policy decisions.


Origin of polytype formation in VLS-grown Ge nanowires through defect generation and nanowire kinking.
We propose layer-by-layer growth mechanisms to account for planar defect generation leading to kinked polytype nanowires. Cs-corrected scanning transmission electron microscopy enabled identification of stacking sequences of distinct polytype bands found in kinked nanowires, and Raman spectroscopy was used to distinguish polytype nanowires from twinned nanowires containing only the 3C diamond cubic phase. The faceting and atomic-scale defect structures of twinned 3C are compared with those of polytype nanowires to develop a common model linking nucleation pinning to nanowire morphology and phase.


Metabolic changes induced by the biliopancreatic diversion in diet-induced obesity in male rats: the contributions of sleeve gastrectomy and duodenal switch.
The mechanisms underlying the body weight and fat loss after the biliopancreatic diversion with duodenal switch (BPD/DS) remain to be fully delineated. The aim of this study was to examine the contributions of the two main components of BPD/DS, namely sleeve gastrectomy (SG) and duodenal switch (DS), on energy balance changes in rats rendered obese with a high-fat (HF) diet. Three different bariatric procedures (BPD/DS, SG, and DS) and three sham surgeries were performed in male Wistar rats. Sham-operated animals fed HF were either fed ad libitum (Sham HF) or pair weighed (Sham HF PW) by food restriction to the BPD/DS rats. A group of sham-operated rats was kept on standard chow and served as normal diet control (Sham Chow). All three bariatric surgeries resulted in a transient reduction in food intake. SG per se induced a delay in body weight gain. BPD/DS and DS led to a noticeable gut malabsorption and a reduction in body weight and fat gains along with significant elevations in plasma levels of glucagon-like peptide-1(7-36) and peptide YY. BPD/DS and DS elevated energy expenditure above that of Sham HF PW during the dark phase. However, they reduced the volume, oxidative metabolism, and expression of thermogenic genes in interscapular brown adipose tissue. Altogether the results of this study suggest that the DS component of the BPD/DS, which led to a reduction in digestible energy intake while sustaining energy expenditure, plays a key role in the improvement in the metabolic profile led by BPD/DS in rats fed a HF diet.


Patchwork: alignment-based retrieval and concatenation of phylogenetic markers from genomic data.
Low-coverage whole-genome sequencing (LC-WGS; also known as "genome skimming") is becoming an increasingly affordable approach to large-scale phylogenetic analyses. While already routinely used to recover organellar genomes, genome skimming is rather rarely utilized for recovering single-copy nuclear markers. One reason might be that only few tools exist to work with this data type within a phylogenomic context, especially to deal with fragmented genome assemblies. We here present a new software tool called Patchwork for mining phylogenetic markers from highly fragmented short-read assemblies as well as directly from sequence reads. Patchwork is an alignment-based tool that utilizes the sequence aligner DIAMOND and is written in the programming language Julia. Homologous regions are obtained via a sequence similarity search, followed by a "hit-stitching" phase, in which adjacent or overlapping regions are merged into a single unit. The novel sliding window algorithm trims away any non-coding regions from the resulting sequence. We demonstrate the utility of Patchwork by recovering near-universal single-copy orthologs (USCOs) within a benchmarking study, and we additionally assess the performance of Patchwork in comparison with other programs. We find that Patchwork allows for accurate retrieval of (putatively) single-copy genes from genome skimming datasets at different sequencing depths with high computational speed, outperforming existing software targeting similar tasks. Patchwork is released under the GNU General Public License version 3. Installation instructions, additional documentation, and the source code itself are all available via GitHub at https://github.com/fethalen/Patchwork.


Utility of red-light ultrafast optogenetic stimulation of the auditory pathway.
Optogenetic stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in current cochlear implants. Here, we employed fast and very fast variants of the red-light-activated channelrhodopsin (ChR) Chrimson (f-Chrimson and vf-Chrimson) to study their utility for optogenetic stimulation of SGNs in mice. The light requirements were higher for vf-Chrimson than for f-Chrimson, even when optimizing membrane expression of vf-Chrimson by adding potassium channel trafficking sequences. Optogenetic time and intensity coding by single putative SGNs were compared with coding of acoustic clicks. vf-Chrimson enabled putative SGNs to fire at near-physiological rates with good temporal precision up to 250 Hz of stimulation. The dynamic range of SGN spike rate coding upon optogenetic stimulation was narrower than for acoustic clicks but larger than reported for electrical stimulation. The dynamic range of spike timing, on the other hand, was more comparable for optogenetic and acoustic stimulation. In conclusion, f-Chrimson and vf-Chrimson are promising candidates for optogenetic stimulation of SGNs in auditory research and future cochlear implants.


Marked reduction of cerebral vasospasm with lumbar drainage of cerebrospinal fluid after subarachnoid hemorrhage.
Cerebral vasospasm after subarachnoid hemorrhage (SAH) continues to be a major source of morbidity in patients despite significant clinical and basic science research. Efforts to prevent vasospasm by removing spasmogens from the subarachnoid space have produced mixed results. The authors hypothesize that lumbar cisternal drainage can remove blood from the basal subarachnoid spaces more effectively than an external ventricular drain (EVD). This non-randomized, controlled-cohort study was undertaken to evaluate the effectiveness of a lumbar drain in patients with SAH compared with those in whom an EVD or no form of cerebrospinal fluid (CSF) drainage was used to prevent the development of clinical vasospasm and its sequelae. The authors collected data on 266 patients with nontraumatic SAH who were admitted to the University of Utah Health Sciences Center between January 1994 and January 2003. Of these, 167 met the study entry criteria. The treatment group consisted of 81 patients in whom a lumbar drain had been placed for CSF shunting, whereas the control group was composed of 86 patients who received no form of CSF drainage or who were treated solely with an EVD. Primary outcome measures were as follows: 1) clinically evident vasospasm; 2) the need for endovascular intervention; 3) vasospasm-induced infarction; 4) disposition at time of discharge; and 5) Glasgow Outcome Scale (GOS) score at 1 to 3 months postdischarge. Secondary outcomes included length of stay and the need for CSF shunting. The presence of a lumbar drain conferred a statistically significant protective and beneficial effect across all outcome measures, reducing the incidence of clinical vasospasm from 51 to 17%, the need for angioplasty from 45 to 17%, and the occurrence of vasospastic infarction from 27 to 7% (all p < or = 0.001-0.008). Patients in the treatment group were more likely to be discharged home (54% compared with 25%, p = 0.002) and to have a GOS score of 5 at follow up (71% compared with 35%, p < 0.001). The mean number of days spent in the intensive care unit and in the hospital overall was also fewer in the treatment group. A similar degree of benefit was found in patients with different Fisher grades and regardless of whether an EVD was needed on presentation, both by subgroup analysis and multivariate logistic regression modeling. There was no statistical difference between the groups in terms of patients requiring a shunt. Complications with lumbar drains were rare and yielded no permanent sequelae. Shunting of CSF through a lumbar drain after an SAH markedly reduces the risk of clinically evident vasospasm and its sequelae, shortens hospital stay, and improves outcome. Its beneficial effects are probably mediated through the removal of spasmogens that exist in the CSF. The results of this study warrant a randomized clinical trial, which is currently under way.


Marriage and family therapy: examining the impact of licensure on an evolving profession.
Regulatory responsibilities for the profession of marriage and family therapy have shifted from the American Association of Marriage and Family Therapy (AAMFT) to state regulatory boards. The impact of these changes has not been adequately addressed. The purpose of this article is to highlight many of these changes and explore their implications. The educational, experience, and supervision requirements of states regulating the profession of marriage and family therapy in 2007 are examined using descriptive data from 47 regulatory entities and then compared with the current (2012) regulatory standards from 51 regulatory entities. In turn, these are compared with AAMFT prelicensure clinical membership requirements. Results indicate a marked difference between AAMFT prelicensure and state licensure requirements in both 2007 and 2012, but that state requirements continue to evolve. Additionally, the changing roles of the AAMFT and the Association of Marital and Family Therapy Regulatory Boards (AMFTRB) within the profession are explored.


Decision-making under risk of loss in children.
In human adults, judgment errors are known to often lead to irrational decision-making in risky contexts. While these errors can affect the accuracy of profit evaluation, they may have once enhanced survival in dangerous contexts following a "better be safe than sorry" rule of thumb. Such a rule can be critical for children, and it could develop early on. Here, we investigated the rationality of choices and the possible occurrence of judgment errors in children aged 3 to 9 years when exposed to a risky trade. Children were allocated with a piece of cookie that they could either keep or risk in exchange of the content of one cup among 6, visible in front of them. In the cups, cookies could be of larger, equal or smaller sizes than the initial allocation. Chances of losing or winning were manipulated by presenting different combinations of cookie sizes in the cups (for example 3 large, 2 equal and 1 small cookie). We investigated the rationality of children's response using the theoretical models of Expected Utility Theory (EUT) and Cumulative Prospect Theory. Children aged 3 to 4 years old were unable to discriminate the profitability of exchanging in the different combinations. From 5 years, children were better at maximizing their benefit in each combination, their decisions were negatively induced by the probability of losing, and they exhibited a framing effect, a judgment error found in adults. Confronting data to the EUT indicated that children aged over 5 were risk-seekers but also revealed inconsistencies in their choices. According to a complementary model, the Cumulative Prospect Theory (CPT), they exhibited loss aversion, a pattern also found in adults. These findings confirm that adult-like judgment errors occur in children, which suggests that they possess a survival value.


Real-time fluorescence image-guided oncologic surgery.
Medical imaging plays a critical role in cancer diagnosis and planning. Many of these patients rely on surgical intervention for curative outcomes. This requires a careful identification of the primary and microscopic tumors, and the complete removal of cancer. Although there have been efforts to adapt traditional-imaging modalities for intraoperative image guidance, they suffer from several constraints such as large hardware footprint, high-operation cost, and disruption of the surgical workflow. Because of the ease of image acquisition, relatively low-cost devices and intuitive operation, optical imaging methods have received tremendous interests for use in real-time image-guided surgery. To improve imaging depth under low interference by tissue autofluorescence, many of these applications utilize light in the near-infrared (NIR) wavelengths, which is invisible to human eyes. With the availability of a wide selection of tumor-avid contrast agents, advancements in imaging sensors, electronic and optical designs, surgeons are able to combine different attributes of NIR optical imaging techniques to improve treatment outcomes. The emergence of diverse commercial and experimental image guidance systems, which are in various stages of clinical translation, attests to the potential high impact of intraoperative optical imaging methods to improve speed of oncologic surgery with high accuracy and minimal margin positivity.


Predictors of nosocomial bloodstream infections in older adults.
To identify predictors and construct a prediction model for nosocomial bloodstream infection (BSI) in older adults. Retrospective case-control study. Hospitals belonging to the Duke Infection Control Outreach Network. Patients age 65 and older with a nosocomial BSI and matched uninfected controls. Multiple variables were captured and compared between groups. Independent predictors were identified using conditional logistic regression. A prediction model and score was constructed. Eight hundred thirty cases were compared with 830 controls. Eighty-one percent of nosocomial BSIs were catheter related (CRBSI). Methicillin-resistant Staphylococcus aureus (MRSA) was the most common pathogen isolated (23%). Independent predictors of nosocomial BSI in older adults were male sex, obesity, low McCabe score on admission, presence of a central line at admission, gastrostomy at admission, recent surgery, and urinary incontinence. A prediction model score greater than 11 (total possible score 23) was predictive of infection. MRSA is a common cause of CRBSI in older adults. Male sex, obesity, the presence of a central line, a gastrostomy tube, and urinary incontinence at the time of admission were independent predictors of BSI in hospitalized older adults. The prediction model constructed in this study should be validated prospectively in a different cohort.


A Systematic Review of Athletes' and Coaches' Nutrition Knowledge and Reflections on the Quality of Current Nutrition Knowledge Measures.
Nutrition knowledge can influence dietary choices and impact on athletic performance. Valid and reliable measures are needed to assess the nutrition knowledge of athletes and coaches. (1) To systematically review the published literature on nutrition knowledge of adult athletes and coaches and (2) to assess the quality of measures used to assess nutrition knowledge. MEDLINE, CINAHL, SPORTDiscuss, Web of Science, and SCOPUS. 36 studies that provided a quantitative measure of nutrition knowledge and described the measurement tool that was used were included. Participant description, questionnaire description, results (mean correct and responses to individual items), study quality, and questionnaire quality. All studies were of neutral quality. Tools used to measure knowledge did not consider health literacy, were outdated with regards to consensus recommendations, and lacked appropriate and adequate validation. The current status of nutrition knowledge in athletes and coaches is difficult to ascertain. Gaps in knowledge also remain unclear, but it is likely that energy density, the need for supplementation, and the role of protein are frequently misunderstood. Previous reports of nutrition knowledge need to be interpreted with caution. A new, universal, up-to-date, validated measure of general and sports nutrition knowledge is required to allow for assessment of nutrition knowledge.


The cardiac sarcolemmal protein kinase reaction. Kinetic characteristics and sensitivity to cyclic AMP.
Isolated and carefully purified preparations of the sarcolemmal membrane from rat cardiac muscle were used to study the membrane-bound protein kinase (PrK) reaction. Contamination of the membrane preparation by mitochondria and sarcoplasmic reticulum was practically absent, and the sarcolemmal membrane vesicles were mostly oriented inside out. These membrane vesicles contained protein kinase tightly bound to the membrane and able to phosphorylate both the endogenous membrane protein with molecular mass of 11,500 daltons and the exogenous added protein (histone, type II). Endogenous protein phosphorylation was completely independent of cAMP which only stimulated the phosphorylation of histone in the membrane-bound PrK reaction. The kinetics of the membrane-bound PrK reaction with MgATP and histone as substrates was studied, and the kinetic mechanism was found to be of sequential Bi-Bi type. Kinetic characteristics of the enzyme were very close to those found earlier for the soluble muscle enzyme. On the basis of data obtained, it is suggested that membrane-bound PrK may be of the same origin as the soluble enzyme and that cAMP may influence the binding of PrK to the surface membrane of cardiac cells.


Presenilin 1 controls gamma-secretase processing of amyloid precursor protein in pre-golgi compartments of hippocampal neurons.
Mutations of presenilin 1 (PS1) causing Alzheimer's disease selectively increase the secretion of the amyloidogenic betaA4(1-42), whereas knocking out the gene results in decreased production of both betaA4(1-40) and (1-42) amyloid peptides (De Strooper et al. 1998). Therefore, PS1 function is closely linked to the gamma-secretase processing of the amyloid precursor protein (APP). Given the ongoing controversy on the subcellular localization of PS1, it remains unclear at what level of the secretory and endocytic pathways PS1 exerts its activity on APP and on the APP carboxy-terminal fragments that are the direct substrates for gamma-secretase. Therefore, we have reinvestigated the subcellular localization of endogenously expressed PS1 in neurons in vitro and in vivo using confocal microscopy and fine-tuned subcellular fractionation. We show that uncleaved PS1 holoprotein is recovered in the nuclear envelope fraction, whereas the cleaved PS fragments are found mainly in post-ER membranes including the intermediate compartment (IC). PS1 is concentrated in discrete sec23p- and p58/ERGIC-53-positive patches, suggesting its localization in subdomains involved in ER export. PS1 is not found to significant amounts beyond the cis-Golgi. Surprisingly, we found that APP carboxy-terminal fragments also coenrich in the pre-Golgi membrane fractions, consistent with the idea that these fragments are the real substrates for gamma-secretase. Functional evidence that PS1 exerts its effects on gamma-secretase processing of APP in the ER/IC was obtained using a series of APP trafficking mutants. These mutants were investigated in hippocampal neurons derived from transgenic mice expressing PS1wt or PS1 containing clinical mutations (PS1(M146L) and PS1(L286V)) at physiologically relevant levels. We demonstrate that the APP-London and PS1 mutations have additive effects on the increased secretion of betaA4(1-42) relative to betaA4(1-40), indicating that both mutations operate independently. Overall, our data clearly establish that PS1 controls gamma(42)-secretase activity in pre-Golgi compartments. We discuss models that reconcile this conclusion with the effects of PS1 deficiency on the generation of betaA4(1-40) peptide in the late biosynthetic and endocytic pathways.


Comprehensive systems biology analysis of a 7-month cigarette smoke inhalation study in C57BL/6 mice.
Smoking of combustible cigarettes has a major impact on human health. Using a systems toxicology approach in a model of chronic obstructive pulmonary disease (C57BL/6 mice), we assessed the health consequences in mice of an aerosol derived from a prototype modified risk tobacco product (pMRTP) as compared to conventional cigarettes. We investigated physiological and histological endpoints in parallel with transcriptomics, lipidomics, and proteomics profiles in mice exposed to a reference cigarette (3R4F) smoke or a pMRTP aerosol for up to 7 months. We also included a cessation group and a switching-to-pMRTP group (after 2 months of 3R4F exposure) in addition to the control (fresh air-exposed) group, to understand the potential risk reduction of switching to pMRTP compared with continuous 3R4F exposure and cessation. The present manuscript describes the study design, setup, and implementation, as well as the generation, processing, and quality control analysis of the toxicology and 'omics' datasets that are accessible in public repositories for further analyses.


Violet-Blue Light Arrays at 405 Nanometers Exert Enhanced Antimicrobial Activity for Photodisinfection of Monomicrobial Nosocomial Biofilms.
Light-emitting diodes (LEDs) demonstrate therapeutic effects for a range of biomedical applications, including photodisinfection. Bands of specific wavelengths (centered at 405 nm) are reported to be the most antimicrobial; however, there remains no consensus on the most effective irradiation parameters for optimal photodisinfection. The aim of this study was to assess decontamination efficiency by direct photodisinfection of monomicrobial biofilms using a violet-blue light (VBL) single-wavelength array (SWA) and multiwavelength array (MWA). Mature biofilms of nosocomial bacteria (Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus) were grown on 96-well polypropylene PCR plates. The biofilms were then exposed to VBL for 2,700 s (SWA) and 1,170 s (MWA) to deliver 0 to 670 J/cm2, and the antibacterial activity of VBL was assessed by comparing the seeding of the irradiated and the nonirradiated biofilms. Nonirradiated groups were used as controls. The VBL arrays were characterized optically (spectral irradiance and beam profile) and thermally. The SWA delivered 401-nm VBL and the MWA delivered between 379-nm and 452-nm VBL, albeit at different irradiances and with different beam profiles. In both arrays, the irradiated groups were exposed to increased temperatures compared to the nonirradiated controls. All bacterial isolates were susceptible to VBL and demonstrated reductions in the seeding of exposed biofilms compared with the nonirradiated controls. VBL at 405 nm exerted the most antimicrobial activity, exhibiting reductions in seeding of up to 94%. Decontamination efficiency is dependent on the irradiation parameters, bacterial species and strain, and experimental conditions. Controlled experiments that ameliorate the heating effects and improve the optical properties are required to optimize the dosing parameters to advance the successful clinical translation of this technology.IMPORTANCE This study reports the efficacy of VBL and blue light (BL) and their antimicrobial activity against mature biofilms of a range of important nosocomial pathogens. While this study investigated the antibacterial activity of a range of wavelengths of between 375 and 450 nm and identified a specific wavelength region (∼405 nm) with increased antibacterial activity, decontamination was dependent on the bacterial species, strain, irradiation parameters, and experimental conditions. Further research with controlled experiments that ameliorate the heating effects and improve the optical properties are required to optimize the dosing parameters to advance the successful clinical translation of this technology.


Midwifery education in Canada.
This article is part of a special series on midwifery education and describes the approach to midwifery education in Canada We begin with an overview of the model of midwifery practice introduced in Canada in the 1990s. We describe the model of midwifery education developed and report how it is implemented, with particular attention to the two longest established programs. Midwifery education programs in Ontario and British Columbia. Midwifery education programs in Canada are offered at the undergraduate baccalaureate level at universities and are typically four years in length. Programs are competence-based and follow a spiral curriculum. The first semesters focus on on core sciences, social sciences and introduction to midwifery concepts. Students spend fifty percent of the program in clinical practices with community-based midwives. Innovative education models enable students to be placed in distant placements and help to align theoretical and practice components. Clinically active faculty adds to the credibility of teaching but bring its own challenges for midwifery educators. The Canadian model of midwifery education has been very effective with low attrition rates and high demand for the number of places available. Further program expansion is warranted but is contingent on the growth of clinical placements.


The 'Digital Twin' to enable the vision of precision cardiology.
Providing therapies tailored to each patient is the vision of precision medicine, enabled by the increasing ability to capture extensive data about individual patients. In this position paper, we argue that the second enabling pillar towards this vision is the increasing power of computers and algorithms to learn, reason, and build the 'digital twin' of a patient. Computational models are boosting the capacity to draw diagnosis and prognosis, and future treatments will be tailored not only to current health status and data, but also to an accurate projection of the pathways to restore health by model predictions. The early steps of the digital twin in the area of cardiovascular medicine are reviewed in this article, together with a discussion of the challenges and opportunities ahead. We emphasize the synergies between mechanistic and statistical models in accelerating cardiovascular research and enabling the vision of precision medicine.


Pharmacophores for ligand recognition and activation/inactivation of the cannabinoid receptors.
The cannabinoid CB(1) and CB(2) receptors belong to the Class A, rhodopsin-like family of G protein-coupled receptors. Antagonists for each receptor sub-type, as well as four structural classes of agonists that bind to both receptors, have been identified. An extensive amount of SAR has been developed for agonists and antagonists that bind at CB1, while the SAR of CB2 ligands is only now emerging in the literature. Cannabinoid agonists have been suggested to have potential therapeutic uses as appetite stimulants, analgesics, anti-emetics, anti-diarrheals, anti-spasmodics, tumor anti-proliferative agents, anti-glaucoma agents and as agents for the treatment of diseases associated with inappropriate retention of aversive memories such as post-traumatic stress disorders and phobias. Cannabinoid CB1 antagonists have been suggested to have potential therapeutic uses as appetite suppressants and as agents that improve memory. This review focuses first on recent CB1 and CB2 SAR and on the pharmacophores that have been developed for ligand recognition at the CB1 receptor. Emerging ideas about how the cannabinoid receptors are activated by agonists or inactivated by inverse agonists are then presented. Challenges for future SAR and pharmacophore development are also identified.


[Responses of neurons in isolated strips of cat auditory cortex to intracortical stimulation].
Neuron responses in an isolated slab of the auditory cortex (A1 zone) to intracortical electric stimulation of its layer IV have been investigated extracellularly in acute experiments on cats immobilized with d-tubocurarin. Responding neurons have been found in all layers of the slab. Their distribution in the slab depth depended on the distances between the recording and stimulating electrodes. The latent periods of responses of different neurons varied between 0.8 and 25 ms. Most of neurons were involved in the reaction mono- or disynaptically within the employed limits of distances between the electrodes (0.5-2 mm). However, many neurons responded polysynaptically. This indicates a complex character of interneuron interactions even in a limited section of the brain cortex. No after-discharges with latent periods above 40 ms have been recorded in the isolated auditory cortex slab in response to intracortical stimulation.


[Morphometric analysis of the structure of tear and aqueous humor in senile cataract].
The parameters of the wedge dehydrated samples of aqueous humor and tear taken from patients with senile cataract were compared by a morphometric assay. Computer-aided processing of the images of the test biological fluids was made on a Morphotest-1 hardware-software complex. The study has provided evidence for the uniformity of distribution of major structural components in the dehydrated samples of tear and aqueous humor in each specific examinee. This fact opens up possibilities for studying the signs of different intraocular pathological conditions from the morphological pattern of tear.


Rationing healthcare: Should life-style be used as a criterion?
Health is considered as important due to its impacts on individuals' lives. Although individual health level is determined partly by the accessibility of the services and their quality, there are many other factors that may influence an individual's health condition, which are mainly social determinants. Since there are many factors that determine health conditions of the individuals, it would be wrong to hold someone totally responsible for her health condition on the basis of her life-style; such as prudency. Indeed, before deciding about whether the patient was prudent or not; first, we have to look at those determinants of health, and investigate whether there is an effective intervention to avoid those determinants. Furthermore, life-styles of the individuals, which are thought to be the personal choices, are just one of the relatively less effective factors that may influence a person's health and also the autonomy of those choices is controversial. In our paper, we will endeavor to develop an argument showing that since health is one of our primary goods that needs to be protected as one of our basic human rights, and since the health status of individuals are not determined only by their personal choices, we claim that it would be unfair to consider accessing healthcare as something removable or limitable based on conditions other than medical criteria.


Dissection of cis-regulatory elements in the C. elegans Hox gene egl-5 promoter.
Hox genes are highly conserved segmental identity genes well known for their complex expression patterns and divergent targets. Here we present an analysis of cis-regulatory elements in the Caenorhabditis elegans Hox gene egl-5, which is expressed in multiple tissues in the posterior region of the nematode. We have utilized phylogenetic footprinting to efficiently identify cis-regulatory elements and have characterized these with gfp reporters and tissue-specific rescue experiments. We have found that the complex expression pattern of egl-5 is the cumulative result of the activities of multiple tissue or local region-specific activator sequences that are conserved both in sequence and near-perfect order in the related nematode Caenorhabditis briggsae. Two conserved regulatory blocks analyzed in detail contain multiple sites for both positively and negatively acting factors. One of these regions may promote activation of egl-5 in certain cells via the Wnt pathway. Positively acting regions are repressed in inappropriate tissues by additional negative pathways acting at other sites within the promoter. Our analysis has allowed us to implicate several new regulatory factors significant to the control of egl-5 expression.


Free radical scavenging actions of three Trifolium species in the protection of blood plasma antioxidant capacity in vitro.
Three clover [Trifolium L. (Leguminosae)] species were selected on the basis of data from traditional medicine, phytochemical profiles, and agricultural significance. The in vitro evaluations of free radical scavenging properties, ferric reducing abilities, and antioxidant effects of extracts from T. pratense L. (crude extract and phenolic fraction), T. pallidum L., and T. scabrum L. (phenolic fractions) were performed. Activities of the Trifolium extracts were determined at their final concentrations of 1.5-50 µg/ml. Free radical scavenging properties of methanol extract solutions were estimated by the reduction of DPPH(•) and ABTS(•) radicals. Measurements of the total antioxidant capacity (TAC) were carried out to assess the antioxidant activities of the extracts in human blood plasma under conditions of oxidative stress, induced by 200 μM peroxynitrite. The phenolic fraction of T. pratense displayed the strongest ABTS(•) and DPPH(•) radical scavenging effects (EC50 value of 21.69 and 12.27 µg/ml, respectively). The EC50 value for T. pallidum extract attained 29.77 and 30.06 µg/ml. The two remaining extracts were less potent scavengers (EC50 value higher than 50 µg/ml). Similar differences were obtained during evaluation of the ferric reducing abilities. Analysis of antioxidant properties of the extracts in blood plasma did not provide such evident differences in their actions, however, it indicated that the T. pratense phenolic fraction displayed the strongest effect. The examined Trifolium extracts partly protected blood plasma and enhanced its non-enzymatic antioxidant defense against harmful action of peroxynitrite in vitro.


Src and Cas are essentially but differentially involved in angiotensin II-stimulated migration of vascular smooth muscle cells via extracellular signal-regulated kinase 1/2 and c-Jun NH2-terminal kinase activation.
Angiotensin II (Ang II) plays an important role in several cardiovascular diseases associated with vascular smooth muscle cell (VSMC) growth and migration. Src activity is known to be required for the migration of a number of cell types. p130Cas was reported to be essential for cell migration and actin filament reorganization. Mitogen-activated protein (MAP) kinases were also reported to be critical regulatory factors for growth and migration of VSMC. However, precise intracellular mechanisms involving c-Src, p130Cas, and MAP kinases in Ang II-stimulated migration of VSMC have not been well elucidated. Here we demonstrated that Ang II rapidly and significantly stimulated tyrosine phosphorylation of Src and Cas and their association in rat aortic smooth muscle cells (RASMC). Ang II-stimulated tyrosine phosphorylation of Src and Cas and activation of ERK1/2 and JNK, but not p38, were potently inhibited by Src family tyrosine kinase inhibitors, herbimycin A (HA) and PP2. Ang II-stimulated Src and Cas association, tyrosine phosphorylation of Cas, and activation of ERK1/2 and JNK were suppressed in kinase-inactive Src (KI Src)-overexpressed RASMC. Ang II-stimulated JNK activation but not ERK1/2 activation was blocked in substrate domain-deleted Cas (DeltaSD Cas)-overexpressed RASMC. In addition, HA, PP2, ERK1/2 inhibitor, 2'-amino-3'-methoxyflavone (PD98059) and JNK inhibitor, and anthra[1,9-cd]pyrazol-6(2H)-one (SP600125) significantly inhibited Ang II-stimulated migration of RASMC. Ang II-induced colocalization of Src and Cas and migration were inhibited in both KI Src- and DeltaSD Cas-overexpressed RASMC. These findings suggest that Src and Cas are essentially but differentially involved in Ang II-stimulated migration of VSMC through the activation of ERK1/2 and JNK.


Insular thyroid carcinoma in a Filipino woman.
A 30-year-old Filipino woman presented with goitre of 4 years' duration. The right thyroid lobe was enlarged with no palpable lymph nodes. She had no thyrotoxic signs and symptoms. Free thyroxine and thyrotropin were normal. Ultrasound revealed a cystic nodule on the right lobe. Fine needle aspiration biopsy was consistent with colloid nodule. She underwent right lobectomy with extended isthmusectomy. Microscopic examination of the 6.5 cm mass showed well-defined, round, nests of tumour cells surrounded by a rim of collagen. Mitotic figures and necrosis were absent. There was capsular invasion. Immunohistochemical staining was positive for thyroglobulin and negative for calcitonin. These findings gave the diagnosis of insular thyroid carcinoma. She underwent complete thyroidectomy with central node dissection. Five weeks after, she received 3700 MBq of radioactive iodine 131. Post-treatment, whole body scan revealed functioning thyroid tissue limited to the thyroid bed. The patient is on regular follow-up 2 years after diagnosis with no evidence of disease.


A pilot bioretention system with commercial activated carbon and river sediment-derived biochar for enhanced nutrient removal from stormwater.
Bioretention is an effective technology for urban stormwater management, but the nutrient removal in conventional bioretention systems is highly variable. Thus, a pilot bioretention column experiment was performed to evaluate the nutrient control of systems with commercial activated carbon and river sediment-derived biochar. Significant chemical oxygen demand (COD) and total phosphorus (TP) leaching were found with the addition of activated carbon and biochar, but total nitrogen (TN) leaching was significantly improved when activated carbon was used as the medium. During a semi-synthetic runoff experiment, the bioretention systems containing two types of fluvial biochar showed relatively better COD and TN control (average mass removal efficiencies and cumulative removal efficiencies) than commercial activated carbon. However, the average TP mass removal efficiency with commercial activated carbon (95% ± 3%) was significantly higher than biochar (48% ± 20% and 56 ± 14%). The addition of biochar in the media increased the nitrogen removal efficiency, and the addition of activated carbon significantly increased the phosphorous removal efficiency. Therefore, both biochar and activated carbon are effective materials for bioretention, and fluvial biochar provides an alternative approach to comprehensively utilize river sediment.


Metallopolymer precursors to L10-CoPt nanoparticles: synthesis, characterization, nanopatterning and potential application.
Ferromagnetic (L10 phase) CoPt alloy nanoparticles (NPs) with extremely high magnetocrystalline anisotropy are promising candidates for the next generation of ultrahigh-density data storage systems. It is a challenge to generate L10 CoPt NPs with high coercivity, controllable size, and a narrow size distribution. We report here the fabrication of L10 CoPt NPs by employing a heterobimetallic CoPt-containing polymer as a single-source precursor. The average size of the resulting L10 CoPt NPs is 3.4 nm with a reasonably narrow size standard deviation of 0.58 nm. The coercivity of L10 CoPt NPs is 0.54 T which is suitable for practical application. We also fabricated the L10 CoPt NP-based nanoline and nanodot arrays through nanoimprinting the polymer blend of CoPt-containing metallopolymer and polystyrene followed by pyrolysis. The successful transfer of the pre-defined patterns of the stamps onto the surface of the polymer blend implies that this material holds great application potential as a data storage medium.


Relative performance of hybrid nestlings in Ficedula flycatchers: a translocation experiment.
Ecological speciation predicts that hybrids should experience relatively low fitness in the local environments of their parental species. In this study, we performed a translocation experiment of nestling hybrids between collared and pied flycatchers into the nests of conspecific pairs of their parental species. Our aim was to compare the performance of hybrids with purebred nestlings. Nestling collared flycatchers are known to beg and grow faster than nestling pied flycatchers under favorable conditions, but to experience higher mortality than nestling pied flycatchers under food limitation. The experiment was performed relatively late in the breeding season when food is limited. If hybrid nestlings have an intermediate growth potential and begging intensity, we expected them to beg and grow faster, but also to experience lower survival than pied flycatchers. In comparison with nestling collared flycatchers, we expected them to beg and grow slower, but to survive better. We found that nestling collared flycatchers indeed begged significantly faster and experienced higher mortality than nestling hybrids. Moreover, nestling hybrids had higher weight and tended to beg faster than nestling pied flycatchers, but we did not detect a difference in survival between the latter two groups of nestlings. We conclude that hybrid Ficedula nestlings appear to have a better intrinsic adaptation to food limitation late in the breeding season compared with nestling collared flycatchers. We discuss possible implications for gene flow between the two species.


Ionic basis of electrical activity in cardiac tissues.
Cardiac electrical events are described in terms of membrane physiology. The concept that cardiac membranes possess specific ionic channels controlled by gates bearing electrical charges is discussed. When open, these channels permit ions to cross the membrane, giving rise to passive inward (depolarizing) and outward (repolarizing) currents. Two different inward and four or five different outward currents appear to be responsible for the development of cardiac electrical activity; both inward currents appear to be controlled by activation and inactivation variables, whereas outward currents are essentially controlled by activation variables and/or inward-going rectifiers. The potential range in which the different currents activate and inactivate (or are limited by inward-going rectification), and the kinetics of activation and inactivation processes explain the development of electrical activity in normal cardiac tissues and in partially depolarized fibers. In addition to passive ionic currents, electrogenic active transport participates in the development of electrical phenomena. The conductance of the membrane for potassium ions and the electrical coupling between cardiac cells depend on the intracellular concentration of calcium ions.


Utp8p is a nucleolar tRNA-binding protein that forms a complex with components of the nuclear tRNA export machinery in Saccharomyces cerevisiae.
Utp8p is an essential nucleolar component of the nuclear tRNA export machinery in Saccharomyces cerevisiae. It is thought to act at a step between tRNA maturation/aminoacylation and translocation of the tRNA across the nuclear pore complex. To understand the function of Utp8p in nuclear tRNA export, a comprehensive affinity purification analysis was conducted to identify proteins that interact with Utp8p in vivo. In addition to finding proteins that have been shown previously to copurify with Utp8p, a number of new interactions were identified. These interactions include aminoacyl-tRNA synthetases, the RanGTPase Gsp1p, and nuclear tRNA export receptors such as Los1p and Msn5p. Characterization of the interaction of Utp8p with a subset of the newly identified proteins suggests that Utp8p most likely transfer tRNAs to the nuclear tRNA export receptors by using a channeling mechanism.


Toxicity of L19-Interleukin 2 Combined with Stereotactic Body Radiation Therapy: A Phase 1 Study.
The immunocytokine L19-IL2 delivers interleukin-2 to the tumor by exploiting the selective L19-dependent binding of extradomain B of fibronectin on tumor blood vessels. In preclinical models, L19-IL2 has been shown to enhance the local and abscopal effects of radiation therapy. The clinical safety of L19-IL2 monotherapy has been established previously. In this study, the safety and tolerability of L19-IL2 after stereotactic body radiation therapy (SBRT) was assessed. Patients with oligometastatic solid tumors received radical SBRT to all visible metastases. Within 1 week after SBRT, intravenous L19-IL2 using a 3 + 3 dose escalation design was administered. Safety and tolerability were analyzed as the primary endpoint using the Common Terminology Criteria for Adverse Events 4.03 scoring system, with progression-free and overall survival as secondary endpoints. A total of 6 patients in 2 L19-IL2 dose levels were included. The 15 million International Units (Mio IU) dose level was well tolerated with no dose-limiting toxicity. The most frequently reported adverse events were chills, noninfectious fever, fatigue, edema, erythema, pruritus, nausea/vomiting, and cough and dyspnea. Blood analysis revealed abnormalities in liver function tests, anemia, hypoalbuminemia, and hypokalemia. At the second dose level (ie, 22.5 Mio IU), which is the recommended dose for L19-IL2 monotherapy, all 3 included patients experienced dose-limiting toxicity but recovered without sequelae. We documented 2 long-term progression-free responders, both having non-small cell lung cancer as primary tumor. Based on the results of this phase 1 clinical trial, the recommended phase 2 dose for SBRT combined with L19-IL2 is 15 Mio IU. The therapeutic efficacy of this combination is currently being evaluated in the multicentric EU-funded phase 2 clinical trial, ImmunoSABR.


Water chemistry in 179 randomly selected Swedish headwater streams related to forest production, clear-felling and climate.
From a policy perspective, it is important to understand forestry effects on surface waters from a landscape perspective. The EU Water Framework Directive demands remedial actions if not achieving good ecological status. In Sweden, 44 % of the surface water bodies have moderate ecological status or worse. Many of these drain catchments with a mosaic of managed forests. It is important for the forestry sector and water authorities to be able to identify where, in the forested landscape, special precautions are necessary. The aim of this study was to quantify the relations between forestry parameters and headwater stream concentrations of nutrients, organic matter and acid-base chemistry. The results are put into the context of regional climate, sulphur and nitrogen deposition, as well as marine influences. Water chemistry was measured in 179 randomly selected headwater streams from two regions in southwest and central Sweden, corresponding to 10 % of the Swedish land area. Forest status was determined from satellite images and Swedish National Forest Inventory data using the probabilistic classifier method, which was used to model stream water chemistry with Bayesian model averaging. The results indicate that concentrations of e.g. nitrogen, phosphorus and organic matter are related to factors associated with forest production but that it is not forestry per se that causes the excess losses. Instead, factors simultaneously affecting forest production and stream water chemistry, such as climate, extensive soil pools and nitrogen deposition, are the most likely candidates The relationships with clear-felled and wetland areas are likely to be direct effects.


Historically Underrepresented Graduate Students' Experiences During the COVID-19 Pandemic.
The purpose of this study was to understand the experiences of historically underrepresented graduate students, more than half of whom were enrolled in science, technology, engineering, and mathematics (STEM) disciplines, during the COVID-19 pandemic. This focus group study represents an initial stage in developing an intervention for historically underrepresented graduate students and their families. Underrepresentation of graduate students of color in STEM has been attributed to a myriad of factors, including a lack of support systems. Familial support is an endorsed reason for persisting in graduate school. It is unclear what historically underrepresented graduate students' experiences are during uncertain times, such as a pandemic. Focus groups were conducted online using a videoconferencing platform during the COVID-19 pandemic. Five focus groups included: historically underrepresented doctoral students (n = 5), historically underrepresented master's students (n = 6), academic faculty (n = 7), administrator, administrative faculty, and academic faculty (n = 6), and families of historically underrepresented doctoral students (n = 6). Data were analyzed using thematic analysis. Historically underrepresented graduate students experienced difficulties in accessing resources, adjustments to home and family life, amplification of existing nonfinancial issues, and expressed both fears of and hopes for the future. The COVID-19 pandemic exacerbated existing inequalities in access to resources as well as nonfinancial family support. This study may help normalize historically underrepresented graduate students' experiences during the COVID-19 pandemic. The findings include ideas for informing families about graduate school that can enlighten family support efforts for historically underrepresented graduate students and their families.


Evolution of brain tissue injury after evacuation of acute traumatic subdural hematomas.
Acute traumatic subdural hematoma complicated by brain parenchymal injury is associated with a 60 to 90% mortality rate. Early surgical evacuation of the mass lesion is essential for a favorable outcome, but the severity of the underlying brain injury determines the outcome, even when surgery has been prompt. The purpose of this study was to analyze tissue biochemical patterns in the brain underlying an evacuated acute subdural hematoma to identify a characteristic pattern of changes that might indicate evolving brain injury. Prospectively collected data from 33 patients after surgical evacuation of acute subdural hematoma were analyzed. Both a brain tissue oxygen tension probe and an intracerebral microdialysis probe were placed in brain tissue exposed at surgery. On the basis of the postoperative clinical course, the patients were divided into three groups: patients with early intractable intracranial hypertension, patients with evolution of delayed traumatic injury (DTI), and patients with an uncomplicated course (the no-DTI group). The overall mortality rate was 46%, with 100% mortality in the intracranial hypertension group (five patients). Mortality in the DTI group was 53% compared with only 9% in the no-DTI group (P = 0.002). There were no significant differences in the initial computed tomographic scan characteristics, such as thickness of the subdural hematoma or amount of midline shift, among the three groups. Physiological variables, as well as the microdialysate measures of brain biochemistry, were markedly different in the intracranial hypertension group compared with the other groups. Differences between the other two groups were more subtle but were significant. Significantly lower values of brain tissue oxygen tension (14 +/- 8 mm Hg versus 27 +/- 14 mm Hg) and higher dialysate values of lactate and pyruvate were documented in patients who developed a delayed injury compared with patients with uncomplicated courses (4.1 +/- 2.3 mmol/L versus 1.7 +/- 0.7 mmol/L for lactate, and 104 +/- 47 micromol/L versus 73 +/- 54 micromol/L for pyruvate at 24 h after injury). Evolution of DTI in the area of brain underlying an evacuated subdural hematoma is associated with a significant increase in mortality. Postoperatively decreasing brain tissue oxygen tension and increasing dialysate concentrations of lactate and pyruvate in this area may warn of evolving brain injury and evoke further diagnostic and therapeutic activity.


Assessment of protein model structure accuracy estimation in CASP13: Challenges in the era of deep learning.
Scoring model structure is an essential component of protein structure prediction that can affect the prediction accuracy tremendously. Users of protein structure prediction results also need to score models to select the best models for their application studies. In Critical Assessment of techniques for protein Structure Prediction (CASP), model accuracy estimation methods have been tested in a blind fashion by providing models submitted by the tertiary structure prediction servers for scoring. In CASP13, model accuracy estimation results were evaluated in terms of both global and local structure accuracy. Global structure accuracy estimation was evaluated by the quality of the models selected by the global structure scores and by the absolute estimates of the global scores. Residue-wise, local structure accuracy estimations were evaluated by three different measures. A new measure introduced in CASP13 evaluates the ability to predict inaccurately modeled regions that may be improved by refinement. An intensive comparative analysis on CASP13 and the previous CASPs revealed that the tertiary structure models generated by the CASP13 servers show very distinct features. Higher consensus toward models of higher global accuracy appeared even for free modeling targets, and many models of high global accuracy were not well optimized at the atomic level. This is related to the new technology in CASP13, deep learning for tertiary contact prediction. The tertiary model structures generated by deep learning pose a new challenge for EMA (estimation of model accuracy) method developers. Model accuracy estimation itself is also an area where deep learning can potentially have an impact, although current EMA methods have not fully explored that direction.


The relation of serum cholesterol to risk of coronary heart disease: implications for the elderly.
Elevated cholesterol is a known risk factor for coronary heart disease (CHD) in young and middle-aged persons. Because of the high prevalence of CHD in a growing elderly population, physicians must decide whether to devote clinical attention to this condition in older patients. Longitudinal cohort studies show that while the association between serum cholesterol and CHD decreases after age 55 years, it still persists. Primary prevention trials performed mostly on middle-aged men have reduced the incidence rate of CHD through cholesterol lowering but they have yet to show a reduction in overall mortality. Secondary prevention studies of lipid alteration have reported decreased mortality and slowed progression of coronary stenoses, again in predominantly male subjects aged less than 60 years. Implications of these findings for care of older patients are discussed along with recommendations for clinical management and future research.


Operative parameters that predict the outcomes of hepatic transplantation.
A growing discrepancy between the number of patients awaiting liver transplantation and the number of organs available mandates the use of even marginal organ donors in whom there is major risk of suboptimal graft function. A comprehensive analysis of operative parameters on the outcomes of liver transplantation has not been reported. We analyzed the impact of 24 operative variables on the survival of 942 consecutive primary liver allografts performed at a single center from June 1992 through December 1997. Univariate and Cox proportional hazards analysis was used to identify those variables with independent prognostic significance in graft survival. Resource utilization for variables with multivariate significance was also analyzed. Of 12 intraoperative variables found to have significance in univariate analysis, three were significant by Cox multivariate analysis: 1) lack of immediate bile production by the graft intraoperatively, 2) platelet transfusion > or = 20 U, and 3) recipient urine output < or =2.0 mL/kg/h intraoperatively. Each of the three variables was associated with marked increases in hospital and Intensive Care Unit length of stay and hospital charges accrued during the admission for transplantation. We identified three operative parameters that predict a poor outcome after liver transplantation. The presence of these indicators suggests that early retransplantation should be considered. Early identification of grafts likely to have poor function might also provide an opportunity for therapeutic intervention to salvage graft function.


[Osteoprotegerin and adynamic bone disease].
"The skeletal resistance to PTH" which is receiving much attentions especially after the break through in the field of osteoclastogenesis/activation research, is a practical pathogenesis of adynamic bone diseases. Serum osteoprotegerin (OPG) levels increase along with the deteriorations of glomerular filtration rate, and that in dialysis patients would be high enough to demonstrate a osteoclastogenesis inhibitory action in vitro. In fact, the parameters for bone resorption in biopsied iliac bone from dialysis patients showed a negative correlation with serum OPG levels. Moreover, serum OPG concentration increases with aging even among dialysis patients. Therefore "the skeletal resistance to PTH" in aged dialysis patients should be greater than that in younger ones, that possibly explains why adynamic bone disease is more common in aged patients. Thus, circulating OPG in uremic patients may promote the development of adynamic bone disease through the osteoclastogenesis inhibitory action.


Going where traditional markers have not gone before: utility of and promise for RAD sequencing in marine invertebrate phylogeography and population genomics.
Characterization of large numbers of single-nucleotide polymorphisms (SNPs) throughout a genome has the power to refine the understanding of population demographic history and to identify genomic regions under selection in natural populations. To this end, population genomic approaches that harness the power of next-generation sequencing to understand the ecology and evolution of marine invertebrates represent a boon to test long-standing questions in marine biology and conservation. We employed restriction-site-associated DNA sequencing (RAD-seq) to identify SNPs in natural populations of the sea anemone Nematostella vectensis, an emerging cnidarian model with a broad geographic range in estuarine habitats in North and South America, and portions of England. We identified hundreds of SNP-containing tags in thousands of RAD loci from 30 barcoded individuals inhabiting four locations from Nova Scotia to South Carolina. Population genomic analyses using high-confidence SNPs resulted in a highly-resolved phylogeography, a result not achieved in previous studies using traditional markers. Plots of locus-specific FST against heterozygosity suggest that a majority of polymorphic sites are neutral, with a smaller proportion suggesting evidence for balancing selection. Loci inferred to be under balancing selection were mapped to the genome, where 90% were located in gene bodies, indicating potential targets of selection. The results from analyses with and without a reference genome supported similar conclusions, further highlighting RAD-seq as a method that can be efficiently applied to species lacking existing genomic resources. We discuss the utility of RAD-seq approaches in burgeoning Nematostella research as well as in other cnidarian species, particularly corals and jellyfishes, to determine phylogeographic relationships of populations and identify regions of the genome undergoing selection.


[Biochemical studies on functional proteins in the brain nervous system. Neurobiochemical studies on nerve growth factor].
Nerve growth factor (NGF) is a polypeptide that is necessary for the survival and growth of developing sympathetic and sensory neurons as well as basal forebrain cholinergic neurons in the brain. The effects of NGF are mediated by the binding of the factor to its specific receptor present on the surface of NGF-responsive cells. Since NGF-responsive basal forebrain cholinergic neurons are lost in Alzheimer's disease, treatment with NGF may be therapeutically beneficial for the patients with this disease. Our studies were focused on the purification, amino acid sequence, enzyme immunoassay (EIA), NGF-biosynthesizing cells, regulation of the biosynthesis, compounds stimulating NGF-biosynthesis/secretion, etc. The major results obtained are summarized as follows: 1) We purified NGFs from snake venoms and determined their amino acid sequences. Among them, Crotalus adamanteus-and Vipera russelli-NGFs were glycoproteins. 2) We developed highly sensitive (0.03-0.05 pg/tube or bead), simple, and reliable EIA systems for NGFs and NT-3. 3) Catecholamine, its derivatives, p-quinone derivatives, nicotine, nicotine derivatives, coenzymes, etc. enhanced the NGF-biosynthesis/secretion of fibroblasts and astrocytes by increasing their cellular content of NGF mRNA. 4) Basal forebrain-lesioned rats (an animal model of amnesia) administered 6-(4-hydroxybutyl)-2,3,5-trimethyl-1,4-benzoquinone (TMQ) orally showed improvement not only their NGF level and choline acetyltransferase (CAT) activity in the brain but also their memory and learning. 5) Interleukins (IL)-4 and -5 significantly increased the amounts of NGF secreted by mouse astrocytes; whereas IL-2, -3, and -6 had no significant effect. 6) Interferons-beta and -lambda inhibited the DNA- and NGF-synthesis in growing astrocytes cultured from neonatal mouse brain but they had no effect on the NGF-synthesis/secretion in quiescent astrocytes. 7) Alkylcatechols regulated the NGF gene expression in astrocytes via both protein kinase C- and cAMP-independent mechanisms.


High shear stress induces a strain increase in human coronary plaques over a 6-month period.
Atherosclerotic plaques develop in low shear stress regions. In the more advanced phase of the disease, plaques are exposed to altered shear stress levels, which could influence plaque composition. We investigated changes in plaque composition in human coronary arteries over a 6-month period and how these changes are related to shear stress. We took images of eight coronary arteries to obtain the 3D shape of the arteries. Lumen data were combined with computational fluid dynamics to obtain shear stress. Palpography was applied to measure strain at baseline and at 6-month follow-up. The change in strain from baseline to follow-up served as a marker for the change in plaque composition. We identified 17 plaques, and each plaque was divided into four regions: the upstream, throat, shoulder and downstream region. Shear stress and strain in the downstream region was significantly lower than in the other regions. There was no significant change in strain for the four different plaque regions. However, we observed that those plaque regions exposed to high shear stress showed a significant increase in strain. Plaque regions exposed to high shear stress showed an increase in strain over time. This indicates that shear stress may modulate plaque composition in human coronary arteries.


Suppressive Effects of Rosmarinic Acid Rich Fraction from Perilla on Oxidative Stress, Inflammation and Metastasis Ability in A549 Cells Exposed to PM via C-Jun, P-65-Nf-Κb and Akt Signaling Pathways.
Particulate matter from forest fires (PMFF) is an environmental pollutant causing oxidative stress, inflammation, and cancer cell metastasis due to the presence of polycyclic aromatic hydrocarbons (PAHs). Perilla seed meal contains high levels of polyphenols, including rosmarinic acid (RA). The aim of this study is to determine the anti-oxidative stress, anti-inflammation, and anti-metastasis actions of rosmarinic acid rich fraction (RA-RF) from perilla seed meal and its underlying molecular mechanisms in A549 cells exposed to PMFF. PMFF samples were collected via the air sampler at the University of Phayao, Thailand, and their PAH content were analyzed using GC-MS. Fifteen PAH compounds were detected in PMFF. The PMFF significantly induced intracellular reactive oxygen species (ROS) production, the mRNA expression of pro-inflammatory cytokines, MMP-9 activity, invasion, migration, the overexpression of c-Jun and p-65-NF-κB, and Akt phosphorylation. Additionally, the RA-RF significantly reduced ROS production, IL-6, IL-8, TNF-α, and COX-2. RA-RF could also suppress MMP-9 activity, migration, invasion, and the phosphorylation activity of c-Jun, p-65-NF-κB, and Akt. Our findings revealed that RA-RF has antioxidant, anti-inflammatory, and anti-metastasis properties via c-Jun, p-65-NF-κB, and Akt signaling pathways. RA-RF may be further developed as an inhalation agent for the prevention of lung inflammation and cancer metastasis induced by PM exposure.


The Generic Conspiracist Beliefs Scale-5: further psychometric evaluation using a United Kingdom-based sample.
The 5-item Generic Conspiracist Beliefs Scale (GCB-5) is an abridged version of the 15-item GCBS. It was developed as a global measure of the tendency to engage in non-event-based, conspiracy-related ideation. The GCB-5 is appealing to researchers because of its brevity, which facilitates the measurement of belief in conspiracies alongside multiple constructs and/or in situations where resources are limited (time, etc.). Noting that several studies failed to find an adequate unidimensional fit in the parent GCBS measures across different contexts, the present study further assessed the psychometric properties of the GCB-5. This was necessary since the GCB-5 was validated using North American samples. Thus, to ensure that the GCB-5 was satisfactory for use with samples in the United Kingdom (UK), GCBS/GCB-5 items were administered to a large, representative UK-based sample (N = 1,331), alongside a range of validated conspiracy scales. Confirmatory factor analysis found that a one-factor GCB-5 model produced a good model fit. This specified that the GCB-5 was underpinned by a single dimension. Furthermore, the performance of the GCB-5 was equivalent to the longer GCBS. Both instruments produced similar mean item scores and standard deviations and were comparably positively correlated with concurrent measures. Although the GCB-5 internal reliability was lower than the GCBS, it was good. The GCB-5 also demonstrated configural, metric, and scalar invariance (among gender and age subgroups). This indicated that the GCB-5 was interpreted similarly by men and women and different age groups. Overall, results supported the assertion that the GCB-5 is a psychometrically satisfactory global measure of non-event-based, conspiratorial ideation.