The intracellular localization and stability of the dihydrofolate synthetase in pea seedlings.
The amount of folate compounds rapidly increased during germination of the pea. An especially high increase was observed 2 days after sowing, with a continouously increasing content during germination. Dihydrofolate synthetase [EC 18.104.22.168] activity also increased with the increase in the amount of folate compounds, and the maximum activity was observed at 6 days after sowing in the dark and at 8 days after sowing in the light. The dihydrofolate synthetase was localized mostly in the mitochondrial fraction and it was easily extracted from the cell particles by osmotic shock. A similar localization was also observed in spinach leaves. The enzyme which was extracted from the isolated mitochondria was relatively stable im comparison with that extracted from whole cells.


Evaporation dynamics of tarsal liquid footprints in flies (Calliphora vicina)and beetles (Coccinella septempunctata).
Insect tarsal adhesive structures secrete a thin layer of fluid into the contact area. It was previously reported that the presence of this fluid significantly increases adhesion on various substrata. Previous data obtained from representatives of different insect groups suggest a difference not only in the chemical composition of the fluid, but also in its physical properties. In the present study, we have measured for the first time changes in the droplet geometry over time and the evaporation rate of the fluid in flies (Calliphora vicina) and beetles (Coccinella septempunctata) by the use of atomic force microscopy. Flattened droplets of the beetle had lower evaporation rates than hemispherical footprints of the fly. Within 1 h, the droplet volume reduced to 21% of the initial volume for the fly, and to 65% for the beetle, suggesting a larger fraction of volatile compounds in the fly fluid. It was revealed that drop geometry changes significantly during evaporation and shows pinning effects for the fly footprints due to an assumed self-organizing oil layer on top of the water fraction of the micro-emulsion. The data obtained suggest that the adhesion strength in capillarity-based switchable adhesive systems must be time-dependent because of the specific evaporation rate of the adhesive fluid. These results are important for our understanding of the functional mechanism of insect adhesive systems and also for biomimetics of artificial capillarity-based adhesive systems.


Expecting the unexpected: the effects of deviance on novelty processing.
Novelty is often prioritized and detected automatically. It attracts attention-eliciting the orienting response. However, novelty is not a unitary concept, and the extent to which the orienting response is elicited depends on several factors. In the present study we investigated how stimulus novelty, deviance from the context, and complexity of the stimulus context contribute to the anterior N2 and novelty P3 event-related potential components, using the visual novelty oddball paradigm. In the first experiment the novelty P3 was drastically reduced when the stimulus context was complex compared with simple, and in a second experiment when novels were frequent rather than deviant. No such effect was found for the anterior N2, suggesting it is a function of stimulus characteristics, not deviance. In contrast, the novelty P3 depended on deviance and contextual complexity.


Fungal species identification from avian lung specimens by single hypha laser microdissection and PCR product sequencing.
Accurate species diagnosis in cases of fungal pneumonia may be hampered by environmental contamination and colonization resulting in false-positive results. Our novel approach for fungal species diagnostics combines fluorescent staining of mounted cryosections with the optical brightener Blankophor, laser capture microdissection and PCR amplification with subsequent sequencing of the first internal transcribed spacer region (ITS-1). Using clinical specimens from infected birds, we show that the procedure is suitable for species identification from single hyphae of intralesional filamentous fungi. Our data also suggest that multiple Aspergillus fumigatus strain infections may occur frequently in pulmonary aspergillosis of birds.


Synthetic orocutaneous stimulation entrains preterm infants with feeding difficulties to suck.
Prematurity can disrupt the development of a specialized neural circuit known as suck central pattern generator (sCPG), which often leads to poor feeding skills. The extent to which suck can be entrained using a synthetically patterned orocutaneous input to promote its development in preterm infants who lack a functional suck is unknown. To evaluate the effects of a new motorized 'pulsating' pacifier capable of entraining the sCPG in tube-fed premature infants who lack a functional suck and exhibit feeding disorders. Prospective cohort study of 31 preterm infants assigned to either the oral patterned entrainment intervention (study) or non-treated (controls) group, matched by gestational age, birth weight, oxygen supplementation history and oral feed status. Study infants received a daily regimen of orocutaneous pulse trains through a pneumatically controlled silicone pacifier concurrent with gavage feeds. The patterned orocutaneous stimulus was highly effective in accelerating the development of non-nutritive suck (NNS) in preterm infants. A repeated-measure multivariate analysis of covariance revealed significant increases in minute rates for total oral compressions, NNS bursts, and NNS cycles, suck cycles per burst, and the ratiometric measure of NNS cycles as a percentage of total ororhythmic output. Moreover, study infants also manifest significantly greater success at achieving oral feeds, surpassing their control counterparts by a factor of 3.1 x (72.8% daily oral feed versus 23.3% daily oral feed, respectively). Functional expression of the sCPG among preterm infants who lack an organized suck can be induced through the delivery of synthetically patterned orocutaneous pulse trains. The rapid emergence of NNS in treated infants is accompanied by a significant increase in the proportion of nutrient taken orally.


Cancer-associated fibroblast-derived Gremlin 1 promotes breast cancer progression.
Bone morphogenetic proteins (BMPs) have been reported to maintain epithelial integrity and to antagonize the transforming growth factor β (TGFβ)-induced epithelial to mesenchymal transition. The expression of soluble BMP antagonists is dysregulated in cancers and interrupts proper BMP signaling in breast cancer. In this study, we mined the prognostic role of BMP antagonists GREMLIN 1 (GREM1) in primary breast cancer tissues using in-house and publicly available datasets. We determined which cells express GREM1 RNA using in situ hybridization (ISH) on a breast cancer tissue microarray. The effects of Grem1 on the properties of breast cancer cells were assessed by measuring the mesenchymal/stem cell marker expression and functional cell-based assays for stemness and invasion. The role of Grem1 in breast cancer-associated fibroblast (CAF) activation was measured by analyzing the expression of fibroblast markers, phalloidin staining, and collagen contraction assays. The role of Grem1 in CAF-induced breast cancer cell intravasation and extravasation was studied by utilizing xenograft zebrafish breast cancer (co-) injection models. Expression analysis of clinical breast cancer datasets revealed that high expression of GREM1 in breast cancer stroma is correlated with a poor prognosis regardless of the molecular subtype. The large majority of human breast cancer cell lines did not express GREM1 in vitro, but breast CAFs did express GREM1 both in vitro and in vivo. Transforming growth factor β (TGFβ) secreted by breast cancer cells, and also inflammatory cytokines, stimulated GREM1 expression in CAFs. Grem1 abrogated bone morphogenetic protein (BMP)/SMAD signaling in breast cancer cells and promoted their mesenchymal phenotype, stemness, and invasion. Moreover, Grem1 production by CAFs strongly promoted the fibrogenic activation of CAFs and promoted breast cancer cell intravasation and extravasation in co-injection xenograft zebrafish models. Our results demonstrated that Grem1 is a pivotal factor in the reciprocal interplay between breast cancer cells and CAFs, which promotes cancer cell invasion. Targeting Grem1 could be beneficial in the treatment of breast cancer patients with high Grem1 expression.


Preserved motor skill learning in acute stroke patients.
Recovery is dynamic during acute stroke, but whether new motor skills can be acquired with the paretic upper limb (UL) during this recovery period is unknown. Clarifying this unknown is important, because neurorehabilitation largely relies on motor learning. The aim was to investigate whether, during acute stroke, patients achieved motor skill learning and retention with the paretic UL. Over 3 consecutive days (D1-D3), 14 patients practiced with their paretic UL the CIRCUIT, a motor skill learning task with a speed/accuracy trade-off (SAT). A Learning Index (LI) was used to quantify normalised SAT changes in comparison with baseline. Spontaneous motor recovery was quantified by another task without SAT constraint (EASY), by grip force (GF), and the Box and Blocks test (BBT). In patients, CIRCUIT LI improved 98% ± 66.2 (mean ± SD). This improvement was similar to that of young healthy individuals (n = 30) who trained with a slightly different protocol for 3 consecutive days (83.8% ± 58.8%). Generalisation of SAT gains to an untrained circuit was observed in both groups. From D1 to D3, stroke patients improved their performance on EASY, while changes in GF and BBT were heterogeneous. During acute stroke, patients retained SAT gains for a motor skill learned with the paretic UL in a manner similar to that of healthy individuals. These results demonstrate acute stroke patients achieved motor skill learning and retention that exceeded paretic UL improvements explained by spontaneous recovery.


Medical service use in children with cerebral palsy: The role of child and family factors characteristics.
The aim of the study was to investigate the patterns of medical service use in children with cerebral palsy (CP), taking into account child and family characteristics. Nine hundred and one parents and carers of children registered with the Victorian CP Register were invited to complete a survey. Participants were asked about their child's appointments with general practitioners and public and private paediatric medical specialists over the preceding 12 months. Information on family characteristics and finances was also collected. Data on CP severity and complexity were extracted from the CP Register. Three hundred and fifty parents and carers (39%) participated. Of these, 83% reported that their child had ≥1 appointment with a general practitioner over the preceding 12 months, while 84% had ≥1 appointment with a public or private paediatric medical specialist. Overall, 58% of children saw 2-5 different paediatric medical specialists, while 9% had appointments with ≥6 clinicians. Children with severe and complex CP were more likely to have had ≥1 appointment with a publically funded paediatric medical specialist and had seen a greater number of different clinicians over the study period. Family characteristics were not associated with service use. Children with CP are managed by a number of paediatric medical specialists, and they continue to see a range of specialists throughout adolescence. In Victoria, differences in service use are not based on family characteristics; instead the highest service users are those with severe and complex CP. For this group, care co-ordination and information sharing between treating clinicians are important, if gaps in care are to be avoided.


Prophage map of converting corynebacteriophage beta.
A prophage map for corynebacteriophage beta consisting of seven markers has been constructed and compared with the vegetative map. The mapping system utilizes heteroimmune double lysogens and capitalizes on the fact that these double lysogens are very unstable and throw off monolysogenic segregants. The prophage map, produced by characterizing the recombinant phage in these monolysogenic segregants, appears to be a cyclic permutation of the vegetative map with the gene for toxin at one end of the prophage map and the gene for phage immunity at the other. This permutation is in accord with the Campbell model for insertion of lambda phage if a site between the toxin and immunity genes in the vegetative map is designated as the phage attachment site. The position of the gene for toxin in the prophage map suggests that converting phages may have originated as specialized transducing phages for this gene.


[Suppression of HCT116 growth of cells by Gadd45].
To study the mechanism of suppression of growth of HCT116 human colon carcinoma cells by Gadd45 gene. HCT116 human colon carcinoma cells were transfected with pTRE-Gadd45 vector so as to establish Gadd45-inducible cell line that was cultured in medium with tetracycline. Then tetracycline was withdrawn. The number of cell clones was counted. Flow cytometry was used to detect the percentages of cells at the G1, S, and G2-M phases. TUNEL technique was used to detect the apoptosis of cells. Western blotting was used to analyze the expression of Gadd45 protein, and apoptosis-related proteins: poly-ADP-ribose polymerase (PARP), and caspase 3 protein. Gadd45 protein was not expressed in the HCT116 cells cultured in the medium with tetracycline, however, it was expressed with a gradually increased level in the cells cultured in the medium from which tetracycline was withdrawn, The clone formation rate of HCT116 cells was 100% in the medium with tetracycline, however, was only 14.2% in the medium with tetracycline withdrawal, with a suppression rate of more than 85%. The percentage of cells in G(2)-M phase was significantly increased in the cells cultured in the medium with tetracycline withdrawal. 24-36 hours after the withdrawal of tetracycline, PARP and caspase 3 protein were activated remarkably. High expression of Gadd45 inhibits the growth of HCT116 cells, through inducing G2-M arrest and activating apoptotic pathway.


Prognostic impact of the expression of Wnt-signaling proteins in cervical carcinoma FIGO stage I-IV treated with radiotherapy or chemoradiotherapy.
Wnt signaling proteins were assessed in patients with primary cervical carcinomas who received chemoradiation. The associations between three Wnt signaling proteins and prognosis were assessed. Specimens from 122 patients with cervical carcinomas (FIGO stage I-IV) were immunohistochemically (IHC) analyzed for β-catenin, APC and axin protein expression. Associations between these Wnt-protein expressions, clinicopathological factors, and clinical outcome data were examined.Positive IHC staining for the β-catenin protein (cell-membranes, cytoplasm and nuclei) was recorded in 88%, 58% and 5%, respectively. There was a strong association between β-catenin staining of the cell-membranes and prediction of recurrences and prognosis (p = 0. 002). Tumors with > 5% of nuclear β-catenin staining were associated with inferior cancer-specific survival (p = 0.048) compared with no staining. The overall recurrence rate was significantly higher in the group with increased nuclear staining (67%) compared with the group with no staining (33%). Nuclear APC staining of high intensity was associated with a significantly worse cancer-specific survival and increased overall recurrence rate compared to tumors with weak staining. Distant recurrences were recorded in 29% of cases with intense staining and in 14% of cases with low staining.The Wnt signaling pathway seems to be of importance in the process of cervical oncogenesis. A predictive and prognostic value was found for β-catenin, where strong cell-membrane staining was favorable, and > 5% positive nuclear staining was associated with poorer cancer-specific survival and overall recurrence rate. Nuclear APC staining intensity was also associated with a less favorable prognosis.


Physiology of Batrachochytrium dendrobatidis, a chytrid pathogen of amphibians.
Batrachochytrium dendrobatidis is a pathogen of amphibians that has been implicated in severe population declines on several continents. We investigated the zoospore activity, physiology and protease production of B. dendrobatidis to help understand the epidemiology of this pathogen. More than 95% of zoospores stopped moving within 24 h and swam less than 2 cm before encysting. Isolates of B. dendrobatidis grew and reproduced at temperatures of 4-25 C and at pH 4-8. Growth was maximal at 17-25 C and at pH 6-7. Exposure of cultures to 30 C for 8 d killed 50% of the replicates. B. dendrobatidis cultures grew on autoclaved snakeskin and 1% keratin agar, but they grew best in tryptone or peptonized milk and did not require additional sugars when grown in tryptone. B. dendrobatidis produced extracellular proteases that degraded casein and gelatin but had no measurable activity against keratin azure. The proteases were active against azocasein at temperatures of 6-37 C and in a pH range of 6-8, with the highest activity at temperatures of 23-30 C and at pH 8. The implications of these observations on disease transmission and development are discussed.


Teratocarcinoma formation in embryonic stem cell-derived neural progenitor hippocampal transplants.
Embryonic stem cells (ESCs) hold great therapeutic potential due to their ability to differentiate into cells of the three primary germ layers, which can be used to repopulate disease-damaged tissues. In fact, two cell therapies using ESC derivatives are currently in phase I clinical trials. A main concern in using ESCs and their derivatives for cell transplantation is the ability of undifferentiated ESCs to generate tumors in the host. Positive selection steps are often included in protocols designed to generate particular cell types from ESCs; however, the transition from ESC to progenitor cell or terminally differentiated cell is not synchronous, and residual undifferentiated cells often remain. In our transplants of ESC-derived neural progenitors (ESNPs) into the adult mouse hippocampus, we have observed the formation of teratocarcinomas. We set out to reduce teratocarcinoma formation by enrichment of ESNPs using fluorescence-activated cell sorting (FACS) and have found that, although enrichment prior to transplant reduces the overall rate of teratocarcinoma formation, the tumorigenicity of cell batches can vary widely, even after FACS enrichment to as much as 95% ESNPs. Our data suggest that this variability may be due to the percentage of residual ESCs remaining in the transplant cell population and to the presence of pluripotent epiblast-like cells, not previously identified in transplant batches. Our data emphasize the need for stringent characterization of transplant cell populations that will be used for cell replacement therapies in order to reduce the risk of tumor formation.


Environmental magnetic fields inhibit the antiproliferative action of tamoxifen and melatonin in a human breast cancer cell line.
We have previously reported that environmental-level magnetic fields (1.2 microT [12 milligauss], 60 Hz) block the growth inhibition of the hormone melatonin (10(-9) M) on MCF-7 human breast cancer cells in vitro. We now report that the same 1.2 microT, 60 Hz magnetic fields significantly block the growth inhibitory action of pharmacological levels of tamoxifen (10(-7) M). In biophysical studies we have taken advantage of Faraday's Law of Current Induction and tested whether the 1.2 microT magnetic field or the associated induced electric field is responsible for this field effect on melatonin and tamoxifen. We observe that the magnetic field component is associated with the field blocking effect on melatonin and tamoxifen function. To our knowledge the tamoxifen studies represent the first experimental evidence for an environmental-level magnetic field modification of drug interaction with human breast cancer cells. Together, these findings provide support to the theory that environmental-level magnetic fields can act to modify the action of a drug or hormone on regulation of cell proliferation. Melatonin and tamoxifen may act through different biological pathways to down-regulate cell growth, and further studies are required to identify a specific biological site of interaction for the 1.2 microT magnetic field.


Relationship between circulating tumor cells, blood coagulation, and urokinase-plasminogen-activator system in early breast cancer patients.
Cancer is a risk factor for venous thromboembolism (VTE) and plasma d-dimer (DD) and tissue factor (TF) are established VTE associated markers. Circulating tumor cells (CTCs) are associated with the risk of VTE in metastatic breast cancer. This study aimed to correlate CTCs, blood coagulation and the urokinase plasminogen activator (uPA) system in primary breast cancer (PBC) patients. This prospective study included 116 PBC patients treated by primary surgery. CTCs were detected by quantitative RT-PCR assay for expression of epithelial (CK19) or epithelial-mesenchymal transition (EMT) genes (TWIST1, SNAIL1, SLUG, ZEB1, FOXC2). Plasma DD, TF, uPA system proteins were detected by enzyme-linked immunosorbent assays, while expressions of uPA system in surgical specimens were evaluated by immunohistochemistry. CTCs were detected in 27.6% patients. Patients with CTCs had a significantly higher mean plasma DD (ng/mL) than those of patients without CTCs (632.4 versus 365.4, p = 0.000004). There was no association between plasma TF and CTCs. Epithelial CTCs exhibit higher expression of uPA system genes compared to EMT_CTCs. Patients with CTCs had higher plasma uPA proteins than those of patients without CTCs; there was no correlation between tissue expression of uPA system, CTCs, DD or TF levels. In multivariate analysis CTCs and patients age were independent factors associated with plasma DD. We found association between plasma DD and CTCs indicating a potential role for activation of the coagulation cascade in the early metastatic process. CTCs could be directly involved in coagulation activation or increased CTCs could be marker of aggressive disease and increased VTE risk.


Lack of antinociceptive cross-tolerance between [D-Pen2, D-Pen5]enkephalin and [D-Ala2]deltorphin II in mice: evidence for delta receptor subtypes.
This study has investigated the development of antinociceptive tolerance to, and cross-tolerance between, two highly selective delta agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2] deltorphin II as well as to [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO), a highly selective mu agonist, in mice. Intracerebroventricular administration of DPDPE, [D-Ala2]deltorphin II and DAMGO each produced an antinociceptive effect. Pretreatment with i.c.v. DPDPE twice daily for 3 days resulted in tolerance to DPDPE as shown by a 4.8-fold rightward shift in the dose-response curve. In contrast, in DPDPE pretreated mice, the dose-response lines for [D-Ala2]deltorphin II and DAMGO were not altered when compared to those obtained in naive animals. The development of tolerance was also shown by pretreating mice with i.c.v. [D-Ala2]deltorphin II; following this pretreatment, the [D-Ala2]deltorphin II dose-response line was displaced to the right by more than 37-fold. In contrast, in [D-Ala2]deltorphin II-pretreated mice, the dose-response lines for DPDPE and DAMGO were not altered compared to those obtained in naive animals. Finally, pretreatment with i.c.v. DAMGO produced a rightward displacement of the DAMGO dose-response line of 47-fold, indicating the development of antinociceptive tolerance. In DAMGO-pretreated mice, however, the dose-response lines for DPDPE and [D-Ala2]deltorphin II were not altered compared to those obtained in naive mice. Thus, the data indicate that antinociceptive tolerance develops to DPDPE, [D-Ala2]deltorphin II and DAMGO but that there is no cross-tolerance between these compounds.(ABSTRACT TRUNCATED AT 250 WORDS)


Influenza A viruses target type II pneumocytes in the human lung.
Highly pathogenic avian H5N1 influenza viruses preferentially infect alveolar type II pneumocytes in human lung. However, it is unknown whether this cellular tropism contributes to high viral virulence because the primary target cells of other influenza viruses have not been systematically studied. We provide the first comparison of the replication, tropism, and cytokine induction of human, highly pathogenic avian influenza A virus subtype H5N1 and other animal influenza A viruses in primary human lung organ cultures. Subytpe H5N1 and human-adapted subtype H1N1 and H3N2 viruses replicated efficiently in the lung tissue, whereas classic swine and low-pathogenicity avian viruses propagated only poorly. Nevertheless, all viruses examined were detected almost exclusively in type II pneumocytes, with a minor involvement of alveolar macrophages. Infection with avian viruses that have a low and high pathogenicity provoked a pronounced induction of cytokines and chemokines, while human and pandemic H1N1-2009 viruses triggered only weak responses. These findings show that differences in the pathogenic potential of influenza A viruses in the human lung cannot be attributed to a distinct cellular tropism. Rather, high or low viral pathogenicity is associated with a strain-specific capacity to productively replicate in type II pneumocytes and to cope with the induced cytokine response.


Growth rate of small lung cancers detected on mass CT screening.
CT has recently been used in mass screening for lung cancer. Small cancers have been identified but the growth characteristics of these lesions are not fully understood. We identified 82 primary cancers in our 3-year mass CT screening programme, of which 61 were examined in the present study. The volume doubling time (VDT) was calculated based on the exponential model using successive annual CT images or follow-up CT images. All cases were also examined in the hospital by high resolution CT (HRCT). Lesions were divided into three types based on HRCT characteristics: type G (n = 19), ground glass opacity (GGO); type GS (n = 19), focal GGO with a solid central component; and type S (n = 23), solid nodule. 18 (95%) lesions of type G, 18 (95%) of type GS and 7 (30%) of type S were invisible on conventional chest radiographs. The mean size of the tumour was 10 mm, 11 mm and 16 mm for type G, type GS and type S, respectively. Most tumours (80%) were adenocarcinomas; 78% of these were GGO (type G and GS). Mean VDT values were 813 days, 457 days and 149 days for type G, type GS and type S, respectively; these are significantly different from each other (p < 0.05). Our results show that annual mass screening CT for 3 successive years resulted in the identification of a large number of slowly growing adenocarcinomas that were not visible on chest radiographs.


Different steps of sexual development are differentially regulated by the Sec8p and Exo70p exocyst subunits.
In this paper we show that in Schizosaccharomyces pombe, mating-specific cell adhesion is dependent on the exocyst subunit Sec8p, but independent of the exocyst subunit Exo70p. In the absence of Exo70p, the forespore membrane does not develop properly and the leading edge protein Meu14p is abnormally distributed. Additionally, the spindle pole body is aberrant in a significant number of exo70Delta asci. In both the sec8-1 and the exo70Delta mutants, the development of the spore cell wall is impaired. These results show that different steps of sexual development are differentially regulated by the exocyst and suggest the existence of exocyst subcomplexes with distinct roles in mating.


Household Exposure to Livestock and Health in the CHILILAB HDSS Cohort, Vietnam.
In Vietnam, pigs and poultry are predominantly produced by small-scale farmers, creating challenges for zoonotic disease management. The objective of this study was to characterize practices related to livestock and manure management and to measure association with 3 self-reported health symptoms (coughing, fever, and diarrhea/nausea/vomiting) in a region currently undergoing health transitions. We analyzed cross-sectional survey data collected from a subset (N = 5520) of the Chi Linh Health and Demographic Surveillance System cohort in Chi Linh district, Vietnam. Bivariate analyses indicated that female gender was a significant risk factor for all 3 health symptoms, whereas age (≥60 years), suburban living, low education level, and household wealth were risk factors for 2 symptoms. Overall, we found no indication that biogas production or exposure to livestock and manure adversely affected human health. Efforts to control zoonotic disease transmission should prioritize utilization of veterinarians, enhanced farm biosecurity, and improvements to commune drinking water/wastewater infrastructure.


Pilot study of a condensed communication skills workshop for gynecologic oncology fellows.
In gynecologic oncology (GO) fellowship, devoting sufficient time to learning communication skills can be challenging due to required time and logistics. A two day workshop was previously piloted at a single institution with GOs and found to be beneficial. We sought to implement that curriculum in a condensed form. We conducted two four-hour sessions with 4 GO fellows at a single institution over 4 months. Sessions consisted of a didactic in communication skills led by faculty with VitalTalk™ training, followed by application with a simulated patient. Cases were developed and previously used in a two-day workshop at another institution. Fellows were surveyed prior to both sessions and after the second session. Perceived confidence was assessed on a Likert scale (1 to 5). An improvement was defined by an increase of ≥1 in Likert score. All fellows reported that the educational quality of the sessions was "excellent," that the time in between sessions was "just right," allowing them to apply skills learned in the first session prior to the second. After both sessions, at least three of the four fellows reported an improvement in confidence in nearly 50% (10/21) of the communication topics assessed. GO fellows perceived improvements in communication skills with condensed half-day training seminars.


Multi-functionalization of cotton fabrics with excellent flame retardant, antibacterial and superhydrophobic properties.
Cotton fabric is widely used in many fields for its excellent comfortability, breathability and hygroscopicity. However, the development of multifunctional cotton fabrics to meet the requirements of different scenarios is a top priority. In this study, multifunctional coating was constructed through facile layer-by-layer assembly phytic acid and chitosan, and spraying divalent copper ion and polydimethylsiloxane (PDMS) on cotton fabrics, anticipating to endow them with flame retardancy, antibacterial and superhydrophobic properties simultaneously. The treated cotton fabric achieved a limiting oxygen index (LOI) value of 32 %, with the char length reducing to 10.7 cm revealing excellent flame retardancy. The water contact angle of multifunctional treated cotton fabric was above 150°, demonstrating it had superhydrophobicity. The antibacterial rates of multifunctional cotton fabrics against E. coli and S. aureus reached to higher than 99 %, indicating that the excellent antibacterial properties. Combined with the thermal stability of cotton fabrics and their char residues analysis, these results demonstrated that the multifunctional coating could act through intumescent flame retardant mechanism to flame retardant cotton fabrics. This research provides a facile way to prepare multifunctional cotton fabrics to broaden the application prospect.


Liposuction-Augmentation Mammaplasty.
The female breast loses superior fullness and becomes more ptotic over time. Women often present to their plastic surgeon requesting reversal of this evolution. While liposuction alone has been proven to lift the breast, no solution combining augmentation and liposuction has been reported. Herein, we introduce a technique called liposuction-augmentation mammaplasty (LAM) that can achieve "scarless" lifting or simply volume equalization prior to inserting same-sized implants. We then compare its safety and efficacy to two gold-standard techniques with similar aims, mastopexy-augmentation mammaplasty (MAM) and reduction-augmentation mammaplasty (RAM). A retrospective 3-year chart review was conducted on 359 patients (652 breasts) undergoing LAM (n = 125), MAM (n = 188), and RAM (n = 46). Patient demographics, operative details, and revisions were documented. Degree of lift was measured on pre- and postoperative photographs using sternal notch-to-nipple distances (SN-N). Statistical differences were assessed between the groups. The LAM group's mean age and OR time (37 years, 46 minutes) were significantly lower than those of MAM (43 years, 90 minutes) and RAM (42 years, 106 minutes). Mean BMIs and revision rates were uniform between the LAM and MAM groups (24, 2.5%), but significantly higher for RAM (28, 4.6%). Aspirate volumes and resection weights averaged 151 cc and 307 g (left breast) and 173 cc and 298 g (right breast). Minimum follow up was 12 months. The LAM group's mean SN-N reduction (~6%) was statistically significant, albeit much lower than MAM (~16%) and RAM (~22%). LAM is a safe, facile, reliable solution for the ptotic, fatty breast. Patients can direct their volumetric outcome and enjoy lower costs and shorter downtime.


Epigenetic control of Ccr7 expression in distinct lineages of lung dendritic cells.
Adaptive immune responses to inhaled allergens are induced following CCR7-dependent migration of precursor of dendritic cell (pre-DC)-derived conventional DCs (cDCs) from the lung to regional lymph nodes. However, monocyte-derived (moDCs) in the lung express very low levels of Ccr7 and consequently do not migrate efficiently to LN. To investigate the molecular mechanisms that underlie this dichotomy, we studied epigenetic modifications at the Ccr7 locus of murine cDCs and moDCs. When expanded from bone marrow precursors, moDCs were enriched at the Ccr7 locus for trimethylation of histone 3 lysine 27 (H3K27me3), a modification associated with transcriptional repression. Similarly, moDCs prepared from the lung also displayed increased levels of H3K27me3 at the Ccr7 promoter compared with migratory cDCs from that organ. Analysis of DC progenitors revealed that epigenetic modification of Ccr7 does not occur early during DC lineage commitment because monocytes and pre-DCs both had low levels of Ccr7-associated H3K27me3. Rather, Ccr7 is gradually silenced during the differentiation of monocytes to moDCs. Thus, epigenetic modifications of the Ccr7 locus control the migration and therefore the function of DCs in vivo. These findings suggest that manipulating epigenetic mechanisms might be a novel approach to control DC migration and thereby improve DC-based vaccines and treat inflammatory diseases of the lung.


Lessons learned from implementation of computerized provider order entry in 5 community hospitals: a qualitative study.
Computerized Provider Order Entry (CPOE) can improve patient safety, quality and efficiency, but hospitals face a host of barriers to adopting CPOE, ranging from resistance among physicians to the cost of the systems. In response to the incentives for meaningful use of health information technology and other market forces, hospitals in the United States are increasingly moving toward the adoption of CPOE. The purpose of this study was to characterize the experiences of hospitals that have successfully implemented CPOE. We used a qualitative approach to observe clinical activities and capture the experiences of physicians, nurses, pharmacists and administrators at five community hospitals in Massachusetts (USA) that adopted CPOE in the past few years. We conducted formal, structured observations of care processes in diverse inpatient settings within each of the hospitals and completed in-depth, semi-structured interviews with clinicians and staff by telephone. After transcribing the audiorecorded interviews, we analyzed the content of the transcripts iteratively, guided by principles of the Immersion and Crystallization analytic approach. Our objective was to identify attitudes, behaviors and experiences that would constitute useful lessons for other hospitals embarking on CPOE implementation. Analysis of observations and interviews resulted in findings about the CPOE implementation process in five domains: governance, preparation, support, perceptions and consequences. Successful institutions implemented clear organizational decision-making mechanisms that involved clinicians (governance). They anticipated the need for education and training of a wide range of users (preparation). These hospitals deployed ample human resources for live, in-person training and support during implementation. Successful implementation hinged on the ability of clinical leaders to address and manage perceptions and the fear of change. Implementation proceeded smoothly when institutions identified and anticipated the consequences of the change. The lessons learned in the five domains identified in this study may be useful for other community hospitals embarking on CPOE adoption.


From Wood to Tetrahydro-2-benzazepines in Three Waste-Free Steps: Modular Synthesis of Biologically Active Lignin-Derived Scaffolds.
Inherently complex, lignin-derived aromatic monomers comprising valuable structural moieties present in many pharmaceuticals would serve as ideal substrates for the construction of biologically active molecules. Here, we describe a strategy that incorporates all intrinsic functional groups present in platform chemicals obtained by lignin depolymerization into value-added amines, using sustainable catalytic methods and benign solvents. Our strikingly efficient protocol provides access to libraries of aminoalkyl-phenol derivatives and seven-membered N-heterocycles directly from wood in two, respectively three, waste-free steps. Several molecules in these libraries have shown promising antibacterial or anticancer activities, emphasizing the advantage of this modular synthetic strategy and the potential for drug discovery. The sustainable catalytic pathways presented here can lead to significant benefits for the pharmaceutical industry where reduction of hazardous waste is a prime concern, and the described strategies that lead to high-value products from non-edible biomass waste streams also markedly increase the economic feasibility of lignocellulosic biorefineries.


Testing the importance of jasmonate signalling in induction of plant defences upon cabbage aphid (Brevicoryne brassicae) attack.
Phloem-feeding aphids deprive plants of assimilates, but mostly manage to avoid causing the mechanical tissue damage inflicted by chewing insects. Nevertheless, jasmonate signalling that is induced by infestation is important in mediating resistance to phloem feeders. Aphid attack induces the jasmonic acid signalling pathway, but very little is known about the specific impact jasmonates have on the expression of genes that respond to aphid attack. We have evaluated the function that jasmonates have in regulating Arabidopsis thaliana responses to cabbage aphid (Brevicoryne brassicae) by conducting a large-scale transcriptional analysis of two mutants: aos, which is defective in jasmonate production, and fou2, which constitutively induces jasmonic acid biosynthesis. This analysis enabled us to determine which genes' expression patterns depend on the jasmonic acid signalling pathway. We identified more than 200 genes whose expression in non-challenged plants depended on jasmonate levels and more than 800 genes that responded differently to infestation in aos and fou2 plants than in wt. Several aphid-induced changes were compromised in the aos mutant, particularly genes connected to regulation of transcription, defence responses and redox changes. Due to jasmonate-triggered pre-activation of fou2, its transcriptional profile in non-challenged plants mimicked the induction of defence responses in wt. Additional activation of fou2 upon aphid attack was therefore limited. Insect fitness experiments revealed that the physiological consequences of fou2 mutation contributed to more effective protection against B. brassicae. However, the observed resistance of the fou2 mutant was based on antibiotic rather than feeding deterrent properties of the mutant as indicated by an analysis of aphid feeding behaviour. Analysis of transcriptional profiles of wt, aos and fou2 plants revealed that the expression of more than 200 genes is dependent on jasmonate status, regardless of external stimuli. Moreover, the aphid-induced response of more than 800 transcripts is regulated by jasmonate signalling. Thus, in plants lacking jasmonates many of the defence-related responses induced by infestation in wt plants are impaired. Constant up-regulation of jasmonate signalling as evident in the fou2 mutant causes reduction in aphid population growth, likely as a result of antibiotic properties of fou2 plants. However, aos mutation does not seem to affect aphid performance when the density of B. brassicae populations on plants is low and aphids are free to move around.


Fat embolism syndrome: traumatic coagulopathy with respiratory distress.
Fractures and other types of trauma can cause severe metabolic, platelet, coagulative, and pulmonary changes. These changes are variable but tend to increase with the severity of the trauma and may result in the clinical findings often referred to as the fat embolism syndrome. The role in pathogenesis of increased liberation of lipids into the bloodstream, either from the marrow at the fracture site or because of physiochemical changes in the blood and mobilization of fat stores, has received a great deal of attention. These changes, however, may not be as important as the platelet activation and intravascular coagulation that occurs simultaneously. All of these phenomena appear to impair pulmonary function and cause hypoxemia. The results of treatment of the fat embolism syndrome should improve if there is a realization that even relatively uncomplicated fractures of the extremities cause significant metabolic, platelet, coagulation and pulmonary changes. These asymptomatic or subclinical forms of fat embolism are far more frequent than generally appreciated. Evidence of increasing platelet, coagulation or blood gas changes should alert the physician to begin aggressive therapy. Particular emphasis must be placed on maintaining optimal ventilation, using ventilatory assistance early if needed. Aspirin or massive steroids may also be quite helpful, particularly if they are given before the fat embolism syndrome has become fully established.


Simultaneous XIAP and cIAP1/2 inhibition by a dimeric SMAC mimetic AZD5582 induces apoptosis in multiple myeloma.
Overexpression of inhibitor of apoptosis (IAP) proteins is associated with poor prognosis. In multiple myeloma (MM), the IAP inhibitors (IAPi), LCL161, have been evaluated in preclinical and clinical settings but are not fully effective. Among IAPs, XIAP has the strongest anti-apoptotic function with direct binding activity to caspases and cIAP1 and cIAP2 are positive regulator of NF-κB signaling. Prior IAPi such as LCL161 has high affinity to cIAP1 and cIAP2 resulting in inferior inhibiting activity against XIAP. A novel dimeric IAPi, AZD5582 (C58H78N8O8), have high binding potency to XIAP with EC50 dose of 15 nM, enabling to simultaneous inhibit XIAP and cIAP1/2. AZD5582 monotherapy showed cell growth inhibition for all MM cell lines, MM1S, RPMI8226, U266 and KMS-5 and induced apoptosis. AZD5582 further showed anti-proliferation effect under the IL-6 additional condition and inhibited JAK-STAT signaling triggered by IL-6. AZD5582 combined with carfilzomib therapy showed a synergistic effect. Enhanced apoptosis was also observed in combination therapy. Synergistic effect was further observed with other conventional therapeutics. Simultaneous XIAP and cIAP1/2 inhibition by the dimeric IAPi AZD5582 is promising. This study provides a rationale of AZD5582 as a new treatment strategy in monotherapy and in combination therapy.


Spontaneous otoacoustic emissions, threshold microstructure, and psychophysical tuning over a wide frequency range in humans.
Hearing thresholds have been shown to exhibit periodic minima and maxima, a pattern known as threshold microstructure. Microstructure has previously been linked to spontaneous otoacoustic emissions (SOAEs) and normal cochlear function. However, SOAEs at high frequencies (>4 kHz) have been associated with hearing loss or cochlear pathology in some reports. Microstructure would not be expected near these high-frequency SOAEs. Psychophysical tuning curves (PTCs), the expression of frequency selectivity, may also be altered by SOAEs. Prior comparisons of tuning between ears with and without SOAEs demonstrated sharper tuning in ears with emissions. Here, threshold microstructure and PTCs were compared at SOAE frequencies ranging between 1.2 and 13.9 kHz using subjects without SOAEs as controls. Results indicate: (1) Threshold microstructure is observable in the vicinity of SOAEs of all frequencies; (2) PTCs are influenced by SOAEs, resulting in shifted tuning curve tips, multiple tips, or inversion. High frequency SOAEs show a greater effect on PTC morphology. The influence of most SOAEs at high frequencies on threshold microstructure and PTCs is consistent with those at lower frequencies, suggesting that high-frequency SOAEs reflect the same cochlear processes that lead to SOAEs at lower frequencies.


A high proliferation rate is required for cell reprogramming and maintenance of human embryonic stem cell identity.
Human embryonic stem (hES) cells show an atypical cell-cycle regulation characterized by a high proliferation rate and a short G1 phase. In fact, a shortened G1 phase might protect ES cells from external signals inducing differentiation, as shown for certain stem cells. It has been suggested that self-renewal and pluripotency are intimately linked to cell-cycle regulation in ES cells, although little is known about the overall importance of the cell-cycle machinery in maintaining ES cell identity. An appealing model to address whether the acquisition of stem cell properties is linked to cell-cycle regulation emerged with the ability to generate induced pluripotent stem (iPS) cells by expression of defined transcription factors. Here, we show that the characteristic cell-cycle signature of hES cells is acquired as an early event in cell reprogramming. We demonstrate that induction of cell proliferation increases reprogramming efficiency, whereas cell-cycle arrest inhibits successful reprogramming. Furthermore, we show that cell-cycle arrest is sufficient to drive hES cells toward irreversible differentiation. Our results establish a link that intertwines the mechanisms of cell-cycle control with the mechanisms underlying the acquisition and maintenance of ES cell identity.


Karyotype studies on different strains of Candida molischiana by pulsed-field gel electrophoresis.
We used pulsed-field gel electrophoresis to compare the electrophoretic karyotype of a Candida molischiana mutant, de-repressed for beta-glucosidase production, with a wild-type strain and a reference strain. The chromosomal organization in this mutant yeast was found to be quite different. Hybridization patterns and the relative fluorescence of all bands indicated eight chromosomes in the mutant strain and seven in the other two. All three strains seemed to be haploid, with an estimated genome size of 12 Mb; the beta-glucosidase gene was on the same chromosome in all of them and the SfiI restriction patterns of this chromosome indicated that it is not affected by the mutation.


Stereotactic Staged Asymmetric Bilateral Radiofrequency Lesioning for Parkinson's Disease.
Parkinson's disease (PD) is one of the most common neurodegenerative progressive disorders. Despite the dominance of neurostimulation technology, stereotactic lesioning operations play a significant role in the treatment of PD. The aim of the study was to evaluate the effectiveness and safety of staged bilateral asymmetric radiofrequency (RF) stereotactic lesioning in a highly selected group of PD patients. A retrospective review of 418 consecutive patients undergoing stereotactic ablation for advanced PD at our institution revealed 28 patients who underwent staged asymmetric bilateral ablation. In this subset, after initial RF thalamotomy, contralateral pallidotomy was performed in 16 (57.1%) patients (group Vim-GPi), and contralateral lesion of the subthalamic nucleus (STN) was performed in 12 (32.9%) patients (group Vim-STN). The mean duration of disease before the first surgery was 9.9 ± 0.8 years. The mean interval between the two operations was 3.5 ± 0.4 years (range, 1-10 years); in the Vim-GPi group, it was 3.1 ± 0.4 years; and in the Vim-STN group, it was 4.3 ± 0.1 years. After the second operation, the long-term follow-up lasted from 1 to 8 years (mean 4.8 ± 0.5 years). All patients were evaluated 1 year after the second operation. One year after staged bilateral lesioning, the mean tremor score improved from baseline, prior to the first operation, from 19.8 to 3.8 (improvement of 81%), the overall mean rigidity score improved from 11.0 to 3.7 (improvement of 66%), and hypokinesia improved from 14.8 to 8.9 (improvement of 40%). One year after staged bilateral lesioning, the total UPDRS score improved in the Vim-GPi group by 47% in the OFF and 45.9% in the ON states. In the Vim-STN group, the total UPDRS score improved from baseline, prior to the first operation, by 44.8% in the OFF and 51.6% in the ON states. Overall, levodopa dose was reduced by 43.4%. Neurological complications were observed in 4 (14.3%) cases; among them, 1 (3.6%) patient had permanent events related to local ischemia after pallidotomy. Staged asymmetric bilateral stereotactic RF lesioning can be a safe and effective method in highly selected patients with advanced PD, particularly where deep brain stimulation is not available or desirable. Careful identification and selection of patients for ablative surgery allow achieving optimal results in the treatment of PD with bilateral symptoms.


The past, present and future of African dust.
African dust emission and transport exhibits variability on diurnal to decadal timescales and is known to influence processes such as Amazon productivity, Atlantic climate modes, regional atmospheric composition and radiative balance and precipitation in the Sahel. To elucidate the role of African dust in the climate system, it is necessary to understand the factors governing its emission and transport. However, African dust is correlated with seemingly disparate atmospheric phenomena, including the El Niño/Southern Oscillation, the North Atlantic Oscillation, the meridional position of the intertropical convergence zone, Sahelian rainfall and surface temperatures over the Sahara Desert, all of which obfuscate the connection between dust and climate. Here we show that the surface wind field responsible for most of the variability in North African dust emission reflects the topography of the Sahara, owing to orographic acceleration of the surface flow. As such, the correlations between dust and various climate phenomena probably arise from the projection of the winds associated with these phenomena onto an orographically controlled pattern of wind variability. A 161-year time series of dust from 1851 to 2011, created by projecting this wind field pattern onto surface winds from a historical reanalysis, suggests that the highest concentrations of dust occurred from the 1910s to the 1940s and the 1970s to the 1980s, and that there have been three periods of persistent anomalously low dust concentrations--in the 1860s, 1950s and 2000s. Projections of the wind pattern onto climate models give a statistically significant downward trend in African dust emission and transport as greenhouse gas concentrations increase over the twenty-first century, potentially associated with a slow-down of the tropical circulation. Such a dust feedback, which is not represented in climate models, may be of benefit to human and ecosystem health in West Africa via improved air quality and increased rainfall. This feedback may also enhance warming of the tropical North Atlantic, which would make the basin more suitable for hurricane formation and growth.


Adnexal masses: development and preliminary validation of an MR imaging scoring system.
To construct and undertake preliminary validation of a magnetic resonance (MR) imaging scoring system designed for use in pelvic MR imaging performed for characterization of adnexal masses that were indeterminate at ultrasonography (US). The institutional ethics committee approved this retrospective study and granted a waiver of informed consent. The study population comprised 394 women who underwent MR imaging between January 1, 2008, and October 30, 2010, for characterization of 497 adnexal masses that were seen at US. Then, masses were chronologically divided into a training set (329 masses) and a validating set (168 masses). Two radiologists who were blinded to the clinical findings retrospectively evaluated MR imaging criteria for characterization of adnexal masses. In the training set, the positive likelihood ratio (PLR) of malignancy and κ values were calculated for each criterion. The reference standard was surgical pathologic findings or findings at imaging follow-up of at least 1 year. On the basis of the PLR and multivariate analysis, a five-category MR scoring system called the ADNEX MR SCORING system was created and was subsequently tested by six readers with the validating set. There was almost perfect agreement (κ > 0.80) for each MR imaging feature except for grouped septa (κ = 0.558) and thickened regular septa (κ = 0.555). The classification was accurate in both the training set (area under the receiver operating characteristic [ROC] curve [AUC] = 0.981 for reader 1 and 0.961 for reader 2) and the validating set (AUC = 0.964 for reader 1 and 0.943 for reader 2). ROC curve analysis demonstrated that the optimal cutoff point was an ADNEX MR score of 3; an ADNEX MR score of 4 or higher was associated with malignancy with a sensitivity of 93.5% (58 of 62) and a specificity of 96.6% (258 of 267). In this study, a reproducible and accurate MR imaging scoring system that has the potential to improve patient care was developed and tested. Multicenter prospective validation of the score is warranted. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13121161/-/DC1.


Usefulness of preoperative extracranial imaging in radiologically suspicious glioblastoma in the West of Scotland and proposal of an imaging diagnostic pathway.
A computed tomography chest, abdomen and pelvis scan (CT CAP) is probably unnecessary if a glioblastoma is detected on the initial CT brain (CTB) before more radiologically definitive magnetic resonance imaging (MRI). We audited its frequency to develop and improve our diagnostic management pathway. Twelve-month retrospective case series from 2018 of patients having an initial CTB suspicious for glioblastoma. We dichotomised patients into two groups: Group 1, tissue proven; and Group 2, non-tissue proven, owing to increased extracranial comorbidity in Group 2, which might influence a medical decision to request a CT CAP despite the radiological diagnosis of a glioblastoma being obvious on an initial CT. We quantified the frequencies of plain and contrast CTBs, CT CAPs and extracranial malignancy. In total, 131 patients had a CTB suspicious for glioblastoma; of these, 72% had a CT CAP and 17% had extracranial malignancy. In Group 1 (n = 84 [mean age 59 years]), 64% had a CT CAP. Plain CTB was undertaken in 24% of patients and contrast CTB in 76%. Extracranial malignancy was present in 8% and 12%. In Group 2 (n = 47 [mean age 73 years]), 85% had a CT CAP. Plain CTB was undertaken in 22% of patients and contrast CTB in 78%. Extracranial malignancy was present in 33% and 23%. Negative CT CAPs were found in ∼88% of CTBs in Group 1 and ∼75% of CTBs in Group 2. Patients having an initial contrast CTB suggestive of glioblastoma, prior to definitive MRI, who are going to be managed surgically, having no history of extracranial malignancy, do not necessarily need a CT CAP unless MRI is non-diagnostic.


Effect of cerium lanthanide on Hela and MCF-7 cancer cell growth in the presence of transferring.
The anti-cancer activity of metal ions in the lanthanide group is being considered recently. It has been reported that cerium salts might stimulate the metabolism and therefore, produce anti-cancer effects. However, little is known about the effects of protein-cerium complex in controlling cancer cell growth. The aim of the present study was to elucidate the possible pathways for the cytotoxic effect of cerium in the presence of apo-transferrin on two cancer cell lines (Hela and MCF-7), that express transferrin receptors 3-4 fold higher than normal cells. The effect of different concentrations of cerium (0.1, 1, 10, 100 μM) in the presence and absence of transferrin for 48 h and 72 h incubation periods (37°C, 5% CO2 and 95% humidity) was studied using the MTT assay. The results showed that cerium has a cell-proliferation inhibitory activity which is significantly increased by transferrin protein. Compared with the direct treatment of cancer cells with cerium, the presence of transferrin assisted inhibition of cell proliferation by 20% and 40% in Hela and MCF-7 cells, respectively. Though apo-transferrin could lightly induce cell growth particularly in MCF-7 cells by itself, this phenomenon could not overcome the cerium-protein cell-proliferation inhibition activity. In conclusion, our results indicate that at a certain concentration, the cerium compounds could be possibly involved in the control of cell proliferation and inhibiting the growth of cancer cells.


Embryonic phenotype of Unc5h3 mutant mice suggests chemorepulsion during the formation of the rostral cerebellar boundary.
Mutation of the Unc5h3 (formally known as rcm) gene has important consequences on neuronal migration during cerebellar development. Unc5h3 transcripts are expressed early (embryonic day 8.5) in the hindbrain region and later in the cerebellar primordia. In Unc5h3 mutant embryos, both the development and initial migration of Purkinje cell progenitors occur as in wild-type controls. The rhombic lip, from which granule cell precursors arise, also appears to form normally in mutants. However, at E13.5, an abnormal subpopulation of granule cell and Purkinje cell precursors becomes detectable in rostral areas of the Unc5h3 mutant brain stem. These ectopic cerebellar cells increase in number and continue moving in a rostral direction throughout the remainder of embryogenesis and early stages of postnatal development invading the lateral regions of the pontine area and eventually the inferior colliculus. Cell proliferation markers demonstrate the mitotic nature of these subpial ectopic granule neurons indicating the displacement of the rostral external germinal layer in mutant animals. Our data suggest that establishment of the rostral cerebellar boundary may rely on chemorepulsive signaling events that require UNC5H3 expressed by cerebellar neurons and extracellular ligands that are functionally related to the UNC5H3-binding, guidance molecule netrin1. Although the phenotype resulting from the Unc5h3 mutation is apparently limited to the formation of the cerebellum, additional sites of Unc5h3 expression are also found during development suggesting the compensatory function of other genes.


Defining the role of histone deacetylases in the inhibition of mammary carcinogenesis by dietary energy restriction (DER): effects of suberoylanilide hydroxamic acid (SAHA) and DER in a rat model.
Dietary energy restriction (DER) inhibits experimentally induced mammary cancer, an effect accompanied by elevated levels of silent information regulator 2 (SIRT1), a class III histone deacetylase (HDAC). However, the effect of DER on targets of other classes of HDACs has not been reported, a highly relevant issue given evidence that HDAC induction favors the development of cancer and tumor growth. Experiments were carried out to determine whether suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor with broad activity, would affect the anti-cancer activity of DER. Female Sprague Dawley rats (n = 30/group) were injected with 1-methyl-1-nitrosourea (50 mg/kg) at 21 days of age and 7 days thereafter were randomized to groups fed: (i) control diet (AIN-93G), (ii) 0.1% SAHA (w/w), (iii) 40% DER, or (iv) 0.1% SAHA + 40% DER. An additional group was fed 0.1% SAHA + 40%DER for 5 weeks and released to control diet for 3 weeks. DER significantly reduced mammary cancer incidence, multiplicity, and cancer burden and prolonged cancer latency (P < 0.01). Cancer inhibition was maintained in SAHA + DER, despite evidence that histone (H2A(Lys9), H2B(Lys5), and H4(Lys5/8/12/16), but not H3(Lys9); P < 0.001) and non-histone protein deacetylation (p53(Lys373) and p53(Lys382); P < 0.001) induced by DER was reversed by SAHA. This indicates that the inhibition of DER of cancer is not dependent on HDAC induction. After releasing rats from DER + SAHA, cancer multiplicity remained lower than control (P < 0.05), consistent with apoptosis-mediated cell deletion. These findings support further investigation of the hypothesis that HDAC induction by DER blunts its anti-carcinogenic impact.


Basic Study for the Purpose of Developing a Quantitative 67Ga-SPECT Measurement Method.
67Ga-single photon emission computed tomography (SPECT) images vary according to the imaging time and image display methods. The calculation of an index, such as the standardized uptake value used in positron emission tomography, from 67Ga-SPECT images would enable the accurate evaluation of the region of accumulation. The purpose of this study was to elucidate the conversion formula, the lower detection limit (LDL), and recovery coefficient (RC) for quantifying the radiation concentration in the 67Ga accumulation site. After chronologically obtaining SPECT/CT images at a radiation concentration of 1.0-442.4 kBq/mL with 27 bottles (diameter: 48 mm, 100 mL), the radiation concentration conversion formula was calculated using the successive approximation reconstruction method. The conversion coefficient was then calculated from the relationship between the count rate and the radiation concentration, and the LDL was determined. To compensate for the partial volume effect, the recovery curve was calculated using the mean SPECT count for six bottles (diameter: 9, 18, 29, 38, 48, and 94 mm). There was a linear relationship between the radiation concentration and the count rate with a good correlation (r=0.99). The LDL was 1.0 kBq/mL. The recovery curve reached a plateau at a diameter of at least 48 mm. The calculation of the absorbed dose index was possible using the radiation concentration conversion formula and the RC.


Efficacy of 3rd generation TKI in patients with EGFR mutation lung adenocarcinoma with bone metastases: A review of 3 case reports and literature.
With the advancement of targeted therapies, epidermal growth factor receptor tyrosine kinase inhibitors have become the preferred initial treatment for patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer. Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is effective against exon 19 and 21 mutations as well as the T790M mutation. It has been approved by both the food and drug administration and European Medicines Agency for the treatment of non-small cell lung cancer patients with locally advanced or metastatic EGFR-mutated tumors, including those who have acquired T790M mutations. To evaluate the effectiveness of osimertinib in treating patients with EGFR-mutated advanced lung adenocarcinoma and bone metastases, we present the treatment outcomes of 3 patients with EGFR 19 deletion-mutated advanced lung adenocarcinoma and bone metastases who received osimertinib treatment in recent years. All 3 cases involved elderly female patients, aged 62, 62, and 54, respectively. All 3 cases exhibited a diagnosis of pulmonary adenocarcinoma accompanied by osseous metastases, with genetic testing revealing the presence of an EGFR 19del mutation. In the first case, following 17 months of gefitinib therapy, disease progression prompted a switch to osimertinib treatment. In the second case, bone metastases were detected after 20 months of pemetrexed-carboplatin chemotherapy, leading to a transition to osimertinib therapy. In the third case, after 11 months of erlotinib treatment, bone metastases were identified. Subsequent interventions, including radiation therapy, pemetrexed-carboplatin chemotherapy, pemetrexed-bevacizumab maintenance therapy, and docetaxel chemotherapy, failed to arrest the progression of bone metastases. As a result, a combination of osimertinib and anlotinib targeted therapy was administered. All 3 patients experienced relatively good and favorable survival outcomes, with a progression-free survival of 22.7 months, 12 months, and 17.7 months, respectively. These cases suggest that osimertinib is a promising treatment option for patients with EGFR 19 deletion-mutated lung adenocarcinoma and bone metastases, although further clinical studies are needed to confirm its efficacy.


Elevated 18 F-AIF-FAPI-04 Uptake in Hepatic Hemangioma.
A 67-year-old woman who was diagnosed with intrahepatic cholangiocellular carcinoma (CCC) by biopsy underwent 18 F-FDG and 18 F-AIF-FAPI-04 PET/CT for initial and treatment assessment. In addition to CCC, she had a history of hepatic hemangioma for 3 years. 18 F-FDG PET/CT images showed increased uptake in CCC, but no uptake in hemangiomas. However, images on 18 F-AIF-FAPI-04 PET/CT indicated negative 18 F-AIF-FAPI-04 uptake in CCC, but intense activity in hemangiomas. Our case illustrates that hepatic hemangioma demonstrated intense 18 F-AIF-FAPI-04 uptake, and final diagnosis should be made with caution.


Ultrasound determination of foetal gender: accuracy and social implications.
Seventy six pregnant women were examined by ultrasound (US) for prenatal determination of foetal gender. Results were compared with those of outcome at delivery. The range of gestational age (GA) at scan was 22-40 weeks (mean 35 +/- 4.0 weeks). Forty seven of the babies at birth were boys, while twenty nine were girls. Incorrect prediction foetal gender occurred in four out of seventy-six (5.3%) comprising two males and two females giving an overall accuracy of seventy two out of seventy six (94.7%). Accuracy of gender assignment was forty five out of forty seven (95.7%) for boys and twenty seven out of twenty nine (93.1%) for girls. It is recommended that discretion should be exercised in disclosing the gender of an unborn baby, especially if it does not correspond to the preferred sex of the mother. Determination of foetal gender should not be performed on demand or as a matter of routine in developing countries because of limited resources and shortage of skilled manpower.


Limitations of using feline coronavirus spike protein gene mutations to diagnose feline infectious peritonitis.
Feline infectious peritonitis (FIP) is a fatal disease of cats, and a sequela of systemic feline coronavirus (FCoV) infection. Mutations in the viral spike (S) gene have been associated with FCoVs found in tissues from cats with FIP, but not FCoVs found in faeces from healthy cats, and are implicated in monocyte/macrophage tropism and systemic spread. This study was designed to determine whether S gene mutation analysis can reliably diagnose FIP. Cats were categorised as with FIP (n = 57) or without FIP (n = 45) based on gross post-mortem and histopathological examination including immunohistochemistry for FCoV antigen. RNA was purified from available tissue, fluid and faeces. Reverse-transcriptase quantitative-PCR (RT-qPCR) was performed on all samples using FCoV-specific primers, followed by sequencing of a section of the S gene on RT-qPCR positive samples. Samples were available from a total of 102 cats. Tissue, fluid, and faecal samples from cats with FIP were more likely to be FCoV RT-qPCR-positive (90.4, 78.4 and 64.6% respectively) than those from cats without FIP (7.8, 2.1 and 20% respectively). Identification of S gene mutated FCoVs as an additional step to the detection of FCoV alone, only moderately increased specificity for tissue samples (from 92.6 to 94.6%) but specificity was unchanged for fluid samples (97.9%) for FIP diagnosis; however, sensitivity was markedly decreased for tissue (from 89.8 to 80.9%) and fluid samples (from 78.4 to 60%) for FIP diagnosis. These findings demonstrate that S gene mutation analysis in FCoVs does not substantially improve the ability to diagnose FIP as compared to detection of FCoV alone.


Pharmacological characterization of orphanin FQ/nociceptin and its fragments.
The cloning of a fourth member of the opioid receptor family has led to the discovery of a new neuropeptide termed orphanin FQ or nociceptin (OFQ/N). Studies in CD-1 mice confirm the ability of OFQ/N to rapidly induce hyperalgesia within 15 min which is insensitive to opioid antagonists. This is followed in the next 30 min by loss of hyperalgesia and the appearance of analgesia in the tailflick assay which is readily reversed by opioid antagonists. However, the very poor affinity of OFQ/N for all the traditional opioid receptors and the insensitivity of OFQ/N analgesia to antisense oligodeoxynucleotides active against MOR-1, DOR-1 or KOR-1 sequences that selectively block mu, delta or kappa1 analgesia, respectively, make it unlikely that OFQ/N analgesia is mediated through typical opioid receptors. Blockade of the antiopioid sigma system by haloperidol enhances the analgesic potency of OFQ/N of more than 100-fold. This effect is pronounced in BALB-C and Swiss-Webster mice. Although OFQ/N alone has little analgesic activity in these mice, the blockade of sigma systems with haloperidol uncovers a robust analgesic response in both strains. Two shorter OFQ/N fragments, OFQ/N(1-7) and OFQ/N(1-11), also are analgesic in CD-1 mice and their actions are reversed by the opioid antagonist diprenorphine despite very poor affinities of both peptides against [125I]OFQ/N binding and all the opioid receptors. In antisense studies, a probe targeting the first coding exon of KOR-3 eliminates OFQ/N hyperalgesia, but not OFQ/N analgesia. Conversely, antisense probes based on the second and third coding exons are inactive against OFQ/N hyperalgesia but readily reverse kappa3 opioid analgesia. These results suggest that OFQ/N elicits both analgesia and hyperalgesia through pharmacologically distinct receptors that do not correspond to traditional opioid receptors.


Treatment of atrophic cholecystitis by regulating the function of the spleen--a report of 50 cases.
Fifty cases of atrophic cholecystitis were treated mainly by regulation of the function of the spleen. Of them, 21 cases were cured, 18 markedly effective, and 7 effective. The total effective rate was 92.0%. By comparison of results of ultrasonography B performed before and after treatment, it was shown that both the longitudinal and transverse inner diameters of gallbladder cross section increased evidently, and the condition of atrophy was improved remarkably after treatment.


The osmoprotectant glycine betaine inhibits salt-induced cross-tolerance towards lethal treatment in Enterococcus faecalis.
The response of Enterococcus faecalis ATCC 19433 to salt stress has been characterized previously in complex media. In this report, it has been demonstrated that this bacterium actively accumulates the osmoprotectant glycine betaine (GB) from salt-enriched complex medium BHI. To further understand the specific effects of GB and other osmoprotective compounds in salt adaptation and salt-induced cross-tolerance to lethal challenges, a chemically defined medium lacking putative osmoprotectants was used. In this medium, bacterial growth was significantly reduced by increasing concentrations of NaCl. At 0.75 M NaCl, 90% inhibition of the growth rate was observed; GB and its structural analogues restored growth to the non-salt-stressed level. In contrast, proline, pipecolate and ectoine did not allow growth recovery of stressed cells. Kinetic studies showed that the uptake of betaines shows strong structural specificity and occurs through a salt-stress-inducible high-affinity porter [Km = 3.3 microM; Vmax = 130 nmol min(-1) (mg protein)(-1); the uptake activity increased 400-fold in the presence of 0.5 M NaCl]. Moreover, GB and its analogues were accumulated as non-metabolizable cytosolic osmolytes and reached intracellular levels ranging from 1-3 to 1.5 micromol (mg protein)(-1). In contrast to the beneficial effect of GB on the growth of salt-stressed cultures of E. faecalis, its accumulation inhibits the salt-induced cross-tolerance to a heterologous lethal challenge. Indeed, pretreatment of bacterial cells with 0.5 M NaCl induced resistance to 0.3% bile salts (survival of adapted cells increased by a factor of 6800). The presence of GB in the adaptation medium reduced the acquisition of bile salts resistance 680-fold. The synthesis of 11 of the 13 proteins induced during salt adaptation was significantly reduced in the presence of GB. These results raise questions about the actual beneficial effect of GB in natural environments where bacteria are often subjected to various stresses.


Factors critical to implementation success of cleaner cooking interventions in low-income and middle-income countries: protocol for an umbrella review.
Over a third of the world's population relies on solid fuels as their primary energy source. These fuels have damaging effects on health, air quality and forest resources. Interventions to promote access to cleaner solid fuel cookstoves and clean fuels have existed for decades. However, the adoption by local communities has largely failed, which led to a waste of resources and suboptimal outcomes. Therefore, the objective of this umbrella review is to identify factors that determine implementation success for cleaner cooking interventions in low-resource settings and weigh their level of confidence in the evidence. We identified systematic and narrative reviews examining factors that influence the acquisition, initial adoption or sustained use of cleaner solid fuel cookstoves and clean fuels at any scale by a literature search in PubMed, Embase, Global Health Database, Cochrane, PsycINFO, Emcare, Web of Science and CINAHL, without date or language restrictions. The search was conducted on 23 October 2017 and updated on 10 July 2019. Reviews based on qualitative, quantitative or mixed-methods studies were included and will be appraised using the Meta Quality Appraisal Tool combined with the Assessment of Multiple Systematic Reviews. Data will be extracted and factors affecting implementation will be coded using the Consolidated Framework for Implementation Research. The Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative Research tool will be used to determine the level of confidence in the coded factors. Two researchers will independently conduct these steps. This umbrella review does not require the approval of an ethical review board. Study results will be published in an international peer-reviewed journal. The outcomes will be converted into two practical tools: one for cleaner solid fuel cookstoves and one for clean fuels. These tools can guide the development of evidence-based implementation strategies for cleaner cooking interventions in low-income and middle-income countries to improve implementation success. These tools should be pilot-tested and promoted among regional and global initiatives. CRD42018088687.


Use of augmented reality for image-guided spine procedures.
Because of its ability to superimpose imaging data on a patient, while anchoring the user's view to the immediate surroundings, augmented reality (AR) has the potential to dramatically improve the accuracy and reduce the time required for preoperative planning and performance of minimally invasive spine surgeries and procedures. Described and reported herein is the direct clinical application of AR navigation on a series of common percutaneous image-guided spine procedures. AR, including a "virtual needle" (VN) asset, was used to guide and navigate a total of 18 procedures performed on 10 patients. Comparative control data were generated using a phantom model (n = 32). These data are used to determine the accuracy of AR for federal drug administration submissions. Optical codes were implemented to allow automatic and real-time registration. A manual process was used when the use of optical codes was not available. Target error, distance to the target and target size were measured for both phantom and clinical groups. Mean errors between the two groups were compared. Target error between the control and clinical data sets showed no significant difference. Moreover, the distance to the target site and the target size had no effect on target acquisition. This data set suggests that AR navigation, utilizing a VN, is an emerging, accurate, valuable additive method for surgical and procedural planning for percutaneous image-guided spinal procedures and has potential to be applied to a broad range of clinical and surgical applications.


Role of stereotaxis in the treatment of cerebral palsy.
There is a renewed interest in basal ganglia surgery for improvement of motor symptoms in cerebral palsy. Rigidity, choreoathetosis, and tremor can be improved or abolished by a well-placed radiofrequency lesion, either in the ventrolateral nucleus of the thalamus or ventroposterior pallidum. The target is chosen based on the predominance of the symptoms in a given patient. A review of the main reports on surgery of the basal ganglia for cerebral palsy, as well as the author's data, shows that the surgery can have a remarkable impact on patients' quality of life when motor dysfunction is improved. An update of the physiopathology of cerebral palsy motor symptoms related to anatomic findings on experimental work, magnetic resonance imaging, and autopsy is used to rationalize surgery of the basal ganglia. Modern stereotactic technique based on exquisite demonstration of the basal ganglia anatomy by magnetic resonance imaging is described and supported by intraoperative electricophysiologic studies. The author stresses the importance of a multidisciplinary approach to provide the cerebral palsy patient with a comprehensive treatment plan before stereotactic surgery.


Investigation of structural models for O-Y and O-Y-Ti clusters in bcc Fe: a density functional theory study.
Six different structural models for atomic clusters in bcc Fe are investigated by density functional theory (DFT) calculations. Results for clusters with identical numbers of constituents (O, Y, Ti, and vacancies) are compared. It is found that the data on the stability or energetics of the relaxed clusters are comparable although their atomic configurations are often different. This contradicts the prevailing opinion in the related theoretical literature that favors the so-called structure matching model. In all studied cases, the absolute value of the total binding energy per cluster constituent becomes lower if Y is partially replaced by Ti. Therefore the driving force for the growth of O-Y clusters should be higher than that of O-Y-Ti clusters. This may be correlated with the experimental observation that the presence of Ti leads to a reduction of the size of the oxide clusters in nanostructured ferritic alloys and to a higher dispersion. Not only cage-like clusters but also clusters with oxygen in the center (cage) are investigated. In the absence of Ti, clusters with oxygen in the center attain more stability that cage-like clusters and the opposite holds for clusters with Ti. It is also shown that adding O atoms to cage-like clusters leads to structures with O in the center. In the present comprehensive DFT study only clusters with dimensions below 1 nm could be treated. This is still below or close to the limit of the experimental resolution of methods allowing for a simultaneous determination of atomic structure and composition of the clusters. These small clusters may be considered as nuclei for further structural evolution and growth during which a selection of the most favored cluster structures could occur.


Skeleton phylogeny reconstructed with transcriptomes for the tribe Drosophilini (Diptera: Drosophilidae).
The family Drosophilidae is one of the most important model systems in evolutionary biology. Thanks to advances in high-throughput sequencing technology, a number of molecular phylogenetic analyses have been undertaken by using large data sets of many genes and many species sampled across this family. Especially, recent analyses using genome sequences have depicted the family-wide skeleton phylogeny with high confidence. However, the taxon sampling is still insufficient for minor lineages and non-Drosophila genera. In this study, we carried out phylogenetic analyses using a large number of transcriptome-based nucleotide sequences, focusing on the largest, core tribe Drosophilini in the Drosophilidae. In our analyses, some noise factors against phylogenetic reconstruction were taken into account by removing putative paralogy from the datasets and examining the effects of missing data, i.e. gene occupancy and site coverage, and incomplete lineage sorting. The inferred phylogeny has newly resolved the following phylogenetic positions/relationships at the genomic scale: (i) the monophyly of the subgenus Siphlodora including Zaprionus flavofasciatus to be transferred therein; (ii) the paraphyly of the robusta and melanica species groups within a clade comprised of the robusta, melanica and quadrisetata groups and Z. flavofasciatus; (iii) Drosophila curviceps (representing the curviceps group), D. annulipes (the quadrilineata subgroup of the immigrans group) and D. maculinotata clustered into a clade sister to the Idiomyia + Scaptomyza clade, forming together the expanded Hawaiian drosophilid lineage; (iv) Dichaetophora tenuicauda (representing the lineage comprised of the Zygothrica genus group and Dichaetophora) placed as the sister to the clade of the expanded Hawaiian drosophilid lineage and Siphlodora; and (v) relationships of the subgenus Drosophila and the genus Zaprionus as follows: (Zaprionus, (the quadrilineata subgroup, ((D. sternopleuralis, the immigrans group proper), (the quinaria radiation, the tripunctata radiation)))). These results are to be incorporated into the so-far published phylogenomic tree as a backbone (constraint) tree for grafting much more species based on sequences of a limited number of genes. Such a comprehensive, highly confident phylogenetic tree with extensive and dense taxon sampling will provide an essential framework for comparative studies of the Drosophilidae.


Strong terahertz emission enhancement via femtosecond laser filament concatenation in air.
We investigate the emission of terahertz (THz) radiation from two laser filaments in air. An increase by 1 order of magnitude of the overall THz power is found when the two filaments are coherently linked on-axis, leading to a single longer concatenated filament. The observed enhancement is found to be the same for the cases of single-color and two-color filamentation approaches.


Saccadic eye movement changes in Parkinson's disease dementia and dementia with Lewy bodies.
Neurodegeneration in Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) affect cortical and subcortical networks involved in saccade generation. We therefore expected impairments in saccade performance in both disorders. In order to improve the pathophysiological understanding and to investigate the usefulness of saccades for differential diagnosis, saccades were tested in age- and education-matched patients with PDD (n = 20) and DLB (n = 20), Alzheimer's disease (n = 22) and Parkinson's disease (n = 24), and controls (n = 24). Reflexive (gap, overlap) and complex saccades (prediction, decision and antisaccade) were tested with electro-oculography. PDD and DLB patients had similar impairment in all tasks (P > 0.05, not significant). Compared with controls, they were impaired in both reflexive saccade execution (gap and overlap latencies, P < 0.0001; gains, P < 0.004) and complex saccade performance (target prediction, P < 0.0001; error decisions, P < 0.003; error antisaccades: P < 0.0001). Patients with Alzheimer's disease were only impaired in complex saccade performance (Alzheimer's disease versus controls, target prediction P < 0.001, error decisions P < 0.0001, error antisaccades P < 0.0001), but not reflexive saccade execution (for all, P > 0.05). Patients with Parkinson's disease had, compared with controls, similar complex saccade performance (for all, P > 0.05) and only minimal impairment in reflexive tasks, i.e. hypometric gain in the gap task (P = 0.04). Impaired saccade execution in reflexive tasks allowed discrimination between DLB versus Alzheimer's disease (sensitivity > or =60%, specificity > or =77%) and between PDD versus Parkinson's disease (sensitivity > or =60%, specificity > or =88%) when +/-1.5 standard deviations was used for group discrimination. We conclude that impairments in reflexive saccades may be helpful for differential diagnosis and are minimal when either cortical (Alzheimer's disease) or nigrostriatal neurodegeneration (Parkinson's disease) exists solely; however, they become prominent with combined cortical and subcortical neurodegeneration in PDD and DLB. The similarities in saccade performance in PDD and DLB underline the overlap between these conditions and underscore differences from Alzheimer's disease and Parkinson's disease.


Cannabinoid receptors as novel therapeutic targets for the management of non-alcoholic steatohepatitis.
Prevalence of non-alcoholic steatohepatitis (NASH) rises steadily in Western countries with the obesity epidemic. NASH is associated with activation of liver fibrogenesis and predisposes to cirrhosis and associated morbi-mortality. The cannabinoid system is increasingly emerging as a crucial mediator of acute and chronic liver injury. Recent experimental and clinical data indicate that peripheral activation of cannabinoid CB1 receptors promotes insulin resistance and liver steatogenesis, two key steps in the pathogenesis of non-alcoholic fatty liver disease. Moreover, CB1 receptors enhance progression of liver fibrogenesis. These findings provide a strong rationale for the use of CB1 antagonists in the management of NASH.


Positive Psychosocial Outcomes and Fanship in K-Pop Fans: A Social Identity Theory Perspective.
Korean pop culture (K-Pop) has spread its influence outside of Korea to a worldwide fan audience. The present study investigated the self-categorised K-Pop fandom characteristics that predicted higher levels of K-Pop fanship, and subsequent psychosocial outcomes. Social identity theory was applied as a theoretical framework. In total, 1477 K-Pop fans from 92 predominantly Western countries fully completed an extensive online survey measuring fanship, fandom and psychosocial outcomes (happiness, self-esteem and social connectedness). Results of this study indicated that K-Pop fanship was significantly predicted by a several K-Pop demographic and fandom characteristics. K-Pop fanship was a significant predictor of increased happiness, self-esteem and social connectedness. The study findings advance the application of social identity theory in a K-Pop fan context and the psychological fanship research more broadly.


Effects of maternal or paternal bisphenol A exposure on offspring behavior.
Bisphenol A (BPA) is an endocrine disrupting chemical used in the production of polycarbonate plastics and resins. Exposure to BPA during gestation has been proposed as a risk factor for the development of neurobehavioral disorders, such as autism spectrum disorder. To address the behavioral impact of developmental exposure to BPA, we tested offspring of mice exposed to a daily low dose of BPA during pregnancy. We also asked if preconception exposure of the sire affected behaviors in offspring. Sires that consumed BPA for 50days prior to mating weighed less than controls, but no effects on any reproductive measures were noted. Juvenile offspring exposed to BPA maternally, but not paternally, spent less time in the open arms of the elevated plus maze than controls, indicating increased anxiety-like behavior. However, neither parental exposure group differed significantly from controls in the social recognition task. We also assessed the behaviors of maternally exposed offspring in two novel tasks: ultrasonic vocalizations (USVs) in pups and operant reversal learning in adults. Maternal BPA exposure increased the duration and median frequency of USVs emitted by pups during maternal separation. In the reversal learning task, females responded more accurately and earned more rewards than males. Additionally, control females received more rewards than BPA females during the acquisition phase of the task. These are among the first studies conducted to ask if BPA exposure via the sire affects offspring behavior and the first study to report effects of gestational BPA exposure on pup USVs and adult operant responding.


The prevalence, risk factors and outcomes of anaemia in South African pregnant women: a systematic review and meta-analysis.
BackgroundAnaemia is associated with maternal and perinatal morbidity and mortality. The pooled prevalence of anaemia in the South African (SA) pregnant population was ascertained by systematically reviewing available literature. Severity, risk factors (HIV, tuberculosis, race, province, year of study), maternal morbidity and mortality (hypertensive disorders of pregnancy), birth outcomes (including low birth weight) and supplementation during pregnancy were also described.MethodsEligible studies reported on haemoglobin concentration or prevalence of anaemia in a SA pregnant population and were available in full text. Case-control and estimation studies were excluded with no restriction on the date of publication. PubMed, CINAHL, EMBASE, EBSCO, Ovid maternity and infant care databases, Cochrane Database of Systematic Reviews, Web of Science and SCOPUS were searched, using the keywords 'anaemia', 'haemoglobin', 'pregnancy', 'South Africa'. Risk of bias was conducted using the Hoy tool and the Doi plot and LFK ratio. Overall study quality was assessed using the GRADE tool. Due to heterogeneity amongst studies subgroup analyses were performed (random effects and quality effects model) using MetaXL addon tool for Microsoft Excel.ResultsThe initial search yielded 7010 articles and 26 were selected for inclusion. Twenty studies were cross-sectional, three were longitudinal and one a randomised control trial. Studies ranged in publication year from 1969 to 2020. The pooled prevalence of anaemia in pregnant women in SA was determined to be 31% (95% CI, 23-40%). Hypertensive disorders of pregnancy and low birth weight were associated with anaemia. While iron deficiency was reported as the main cause, other risk factors included HIV and other infections.DiscussionLimitationsThere was limited data reporting on prevalence of anaemia and direct maternal and foetal outcomes. Heterogeneity amongst studies was not explained by subgroup analysis. Majority of cross-sectional study designs reduced the ability to infer causality.InterpretationWhile the prevalence of anaemia remains high and of concern, risk factors are varied. Iron deficiency is still common but the presence of comorbidities also contributes to anaemia and should not be ignored. More longitudinal research into associations between anaemia and birth outcomes is needed due to a lack of available evidence.Systematic review registrationPROSPERO 2020: CRD42020157191.


Modeling Dynamic Contrast-Enhanced MRI Data with a Constrained Local AIF.
This study aims to develop a constrained local arterial input function (cL-AIF) to improve quantitative analysis of dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) data by accounting for the contrast-agent bolus amplitude error in the voxel-specific AIF. Bayesian probability theory-based parameter estimation and model selection were used to compare tracer kinetic modeling employing either the measured remote-AIF (R-AIF, i.e., the traditional approach) or an inferred cL-AIF against both in silico DCE-MRI data and clinical, cervical cancer DCE-MRI data. When the data model included the cL-AIF, tracer kinetic parameters were correctly estimated from in silico data under contrast-to-noise conditions typical of clinical DCE-MRI experiments. Considering the clinical cervical cancer data, Bayesian model selection was performed for all tumor voxels of the 16 patients (35,602 voxels in total). Among those voxels, a tracer kinetic model that employed the voxel-specific cL-AIF was preferred (i.e., had a higher posterior probability) in 80 % of the voxels compared to the direct use of a single R-AIF. Maps of spatial variation in voxel-specific AIF bolus amplitude and arrival time for heterogeneous tissues, such as cervical cancer, are accessible with the cL-AIF approach. The cL-AIF method, which estimates unique local-AIF amplitude and arrival time for each voxel within the tissue of interest, provides better modeling of DCE-MRI data than the use of a single, measured R-AIF. The Bayesian-based data analysis described herein affords estimates of uncertainties for each model parameter, via posterior probability density functions, and voxel-wise comparison across methods/models, via model selection in data modeling.


The importance of animal welfare and Veterinary Services in a changing world.
Animal welfare is an essential component of the future of sustainable agriculture and the United Nations Sustainable Development Goals. There is growing global recognition of the importance of animal welfare, which must always be considered as part of the decision-making around food and nutrition security. Veterinary Services, encompassing public and private veterinarians and para-veterinarians, are custodians of animal welfare and key players in future actions to improve it. The welfare of animals is everyone's responsibility, from the individual farmer and practitioner to policymakers at the national and intergovernmental level. In this paper, after providing background information about current animal welfare issues and identifying animal welfare risks, the authors make a number of recommendations for action at the institutional and individual level. They do so because while the former is essential to generate change at scale and effective resourcing, the latter can create immediate action at a local level and drive change from the ground up. Without coordinated action from Veterinary Services, opportunities to improve animal welfare, alongside human and environmental health and well-being, may very well be lost, and animal welfare may fail to improve or even be at risk of decline.


Proteins in ecotoxicology - how, why and why not?
The growing interest in the application of proteomic technologies to solve toxicology issues and its relevance in ecotoxicology research has resulted in the emergence of "ecotoxicoproteomics". There is a general consensus that ecotoxicoproteomics is a powerful tool to spot early molecular events involved in toxicant responses, which are responsible for the adverse effects observed at higher levels of biological organization, thus contributing to elucidate the mode of action of stressors and to identify specific biomarkers. Ultimately, early-warning indicators can then be developed and deployed in "in situ" bioassays and in environmental risk assessment. The number of field experiments or laboratory trials using ecologically relevant test-species and involving proteomics has been, until recently, insufficient to allow a critical analysis of the real benefits of the application of this approach to ecotoxicology. This article intends to present an overview on the applications of proteomics in the context of ecotoxicology, focusing mainly on the prospective research to be done in invertebrates. Although these represent around 95% of all animal species and in spite of the key structural and functional roles they play in ecosystems, proteomic research in invertebrates is still in an incipient stage. We will review applications of ecotoxicoproteomics by evaluating the technical methods employed, the organisms and the contexts studied, the advances achieved until now and lastly the limitations yet to overcome will be discussed.