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Congenital hypopituitarism is a rare disease. It can be caused by isolated inborn defects of the pituitary, gene mutations (PROP1, PIT1), and chromosomal abnormalities.Deletions of chromosome 18 (De Grouchy syndrome types 1 and 2) are a group of rare genetic diseases with a frequency of 1:50,000. Hypopituitarism in these syndromes is detected in from 13 to 56% of cases and depends on the size and location of the deleted segment.We have described a series of clinical cases of patients with congenital hypopituitarism due to deletions in chromosome 18. All children had a characteristic dysmorphic features and delayed mental and speech development. Within first months of life, patients developed muscular hypotension, dysphagia, and respiratory disorders. The patients had various congenital malformations in combination with hypopituitarism (isolated growth hormone deficiency and multiple pituitaryhormone deficiencies). In the neonatal period, there were the presence of hypoglycemia in combination with cholestasis.Hormone replacement therapy led to rapid relief of symptoms.capital ES, Cyrillichromosomal microarray analysis in 2 patients allowed us to identify exact location of deleted area and deleted genes and optimize further management for them. | Chromosomes, Human, Pair 18 |
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder of unknown aetiology for which there is no effective treatment. Although IBS does not increase mortality, it reduces the quality of life and is an economic burden to both the patients themselves and society as a whole. Peptide YY (PYY) is localized in endocrine cells located in the ileum, colon and rectum. The concentration of PYY and the density of PYY cells are decreased in both the colon and rectum but unchanged in the ileum of patients with IBS. The low density of PYY cells in the large intestine may be caused by a decreased number of stem cells and their progeny toward endocrine cells. PYY regulates the intestinal motility, secretion and absorption as well as visceral sensitivity via modulating serotonin release. An abnormality in PYY may therefore contribute to the intestinal dysmotility and visceral hypersensitivity seen in IBS patients. Diet management involving consuming a low-FODMAP diet restores the density of PYY cells in the large intestine and improves abdominal symptoms in patients with IBS. This review shows that diet management appears to be a valuable tool for correcting the PYY abnormalities in the large intestine of IBS patients in the clinic. | Peptide YY |
A large number of intra-RNA and RNA-protein cross-link sites have been localized within the 23S RNA from E. coli 50 S ribosomal subunits. These sites, together with other data, are sufficient to constrain the secondary structure of the 23 S molecule into a compact three-dimensional shape. Some of the features of this structure are discussed, in particular, those relating to the orientation of tRNA on the 50 S subunit as studied by site-directed cross-linking techniques. A corresponding model for the 16S RNA within the 30 S subunit has already been described, and here a site-directed cross-linking approach is being used to determine the path followed through the subunit by messenger RNA. | RNA, Ribosomal, 23S |
The acinar salivary glands of the cockroach, Periplaneta americana, are innervated by dopaminergic and serotonergic nerve fibers. Serotonin stimulates the secretion of protein-rich saliva, whereas dopamine causes the production of protein-free saliva. This suggests that dopamine acts selectively on ion-transporting peripheral cells within the acini and the duct cells, and that serotonin acts on the protein-producing central cells of the acini. We have investigated the pharmacology of the dopamine-induced secretory activity of the salivary gland of Periplaneta americana by testing several dopamine receptor agonists and antagonists. The effects of dopamine can be mimicked by the non-selective dopamine receptor agonist 6,7-ADTN and, less effectively, by the vertebrate D1 receptor-selective agonist chloro-APB. The vertebrate D1 receptor-selective agonist SKF 38393 and vertebrate D2 receptor-selective agonist R(-)-TNPA were ineffective. R(+)-Lisuride induces a secretory response with a slower onset and a lower maximal response compared with dopamine-induced secretion. However, lisuride-stimulated glands continue secreting saliva, even after lisuride-washout. Dopamine-induced secretions can be blocked by the vertebrate dopamine receptor antagonists cis(Z)-flupenthixol, chlorpromazine, and S(+)-butaclamol. Our pharmacological data do not unequivocally indicate whether the dopamine receptors on the Periplaneta salivary glands belong to the D1 or D2 subfamily of dopamine receptors, but we can confirm that the pharmacology of invertebrate dopamine receptors is remarkably different from that of their vertebrate counterparts. | Butaclamol |
The third-generation aromatase inhibitors suppress whole-body estrogen production in postmenopausal women with high specificity and potency. In women with hormone-sensitive breast cancer, three of these agents, letrozole, anastrozole, and exemestane, provide an important alternative endocrine therapy to the antiestrogen tamoxifen, which blocks estrogen activation of the estrogen receptor. For treatment of advanced or metastatic breast cancer that has progressed on first-line tamoxifen, all three agents are active. On that basis, they have each been compared with tamoxifen as first-line therapy of advanced breast cancer, in phase III trials. Letrozole was significantly superior to tamoxifen in the primary end point, median time to progression, as well as in response rate and clinical benefit rate, and treatment was well tolerated. Although there was no significant difference in median overall survival, an advantage seen with letrozole for the first 2 years may have been lost because of crossover to the alternate agent at disease progression. Anastrozole was evaluated in two separate trials designed for combined analysis. Overall, anastrozole was at least equivalent to tamoxifen in activity, but clearly superior only for median time to progression in the subgroup of patients with hormone receptor-positive disease. Treatment was generally as well tolerated as tamoxifen. In an early report, exemestane was significantly better than tamoxifen in response rate and median time to progression, with overall survival data not yet available. To date, letrozole appears to be the most effective aromatase inhibitor in the first-line advanced breast cancer setting. | Anastrozole |
The existing information supports the use of this material as described in this safety assessment. Isobutyl propionate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog isobutyl acetate (CAS # 110-19-0) show that isobutyl propionate is not expected to be genotoxic. Data from read-across analog isoamyl acetate (CAS # 123-92-2) show that there are no safety concerns for isobutyl propionate for skin sensitization under the current declared levels of use. The repeated dose and reproductive endpoints were evaluated using the TTC for a Cramer Class I material, and the exposure to isobutyl propionate is below the TTC (0.03â¯mg/kg/day and 0.03â¯mg/kg/day, respectively). For the local respiratory endpoint, a calculated MOE >100 was provided by read-across analog butyl acetate (CAS # 123-86-4). The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; isobutyl propionate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; isobutyl propionate is not PBT as per the IFRA Environmental Standards. For the risk assessment, isobutyl propionate was not able to be risk screened as there were no reported volumes of use for North America or Europe in the 2015 IFRA Survey. | Propionates |
Climate-driven biodiversity erosion is escalating at an alarming rate. The pressure imposed by climate change is exceptionally high in tropical ecosystems, where species adapted to narrow environmental ranges exhibit strong physiological constraints. Despite the observed detrimental effect of climate change on ecosystems at a global scale, our understanding of the extent to which multiple climatic drivers affect population dynamics is limited. Here, we disentangle the impact of different climatic stressors on 47 rainforest birds inhabiting the mountains of the Australian Wet Tropics using hierarchical population models. We estimate the effect of spatiotemporal changes in temperature, precipitation, heatwaves, droughts and cyclones on the population dynamics of rainforest birds between 2000 and 2016. We find a strong effect of warming and changes in rainfall patterns across the elevational-segregated bird communities, with lowland populations benefiting from increasing temperature and precipitation, while upland species show an inverse strong negative response to the same drivers. Additionally, we find a negative effect of heatwaves on lowland populations, a pattern associated with the observed distribution of these extreme events across elevations. In contrast, cyclones and droughts have a marginal effect on spatiotemporal changes in rainforest bird communities, suggesting a species-specific response unrelated to the elevational gradient. This study demonstrated the importance of unravelling the drivers of climate change impacts on population changes, providing significant insight into the mechanisms accelerating climate-induced biodiversity degradation. | Rainforest |
PURPOSE: Many pediatric patients with severe scoliosis requiring surgery have baseline anemia. Pediatric scoliosis fusion surgery is associated with perioperative blood loss requiring transfusion. As such, many patients in this surgical population could benefit from a perioperative blood conservation program. METHODS: Here we present a narrative review of perioperative blood conservation strategies for pediatric scoliosis surgery involving nurses, transfusion medicine physicians, anesthesiologists, surgeons, dieticians, perfusionists and neurophysiologists spanning the pre-, intra- and postoperative phases of care. RESULTS: The review highlights how perioperative blood conservation strategies, have the potential to minimize exposures to exogenous blood products. Further, we describe a relevant example of blood conservation related to the care of a Jehovah's Witness patient undergoing staged scoliosis repair. Lastly, we outline areas which would benefit from clinical studies to further elucidate perioperative blood conservation interventions and their outcomes relevant to pediatric scoliosis surgery patients. CONCLUSION: Interdisciplinary communication and meticulous blood conservation strategies are proving to be a means of reducing if not eliminating the need for allogeneic blood products for surgical correction of pediatric scoliosis." | Bloodless Medical and Surgical Procedures |
OBJECTIVE/HYPOTHESIS: To determine if angiogenic growth factors including vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) are expressed in human paragangliomas. STUDY DESIGN: A histopathologic and molecular examination of paraganglioma specimens obtained from surgical cases or retrieved from the Pathology Department of the Massachusetts Eye and Ear Infirmary. METHODS: Fresh tumor or archival, paraffin-embedded paraganglioma specimens were analyzed by immunohistochemistry, Western blotting, and ELISA. RESULTS: Positive immunohistochemical staining for VEGF was observed in five of nine surgical specimens and in six of eight archival specimens (11/17, or 65%). PD-ECGF immunoreactivity was detected in four of five surgical specimens and six of eight archival specimens (10/13, or 77%). The presence of PD-ECGF was confirmed by Western blot assay and ELISA confirmed the presence of VEGF in tumor extract. CONCLUSIONS: Both VEGF and PD-ECGF are expressed in paragangliomas and may contribute to the extreme vascularity of these tumors. Key Words. Vascular endothelial growth factor, platelet-derived, endothelial cell growth factor, hypoxia, tumor vasculature. | Aortic Bodies |
Glyphosate is the leading herbicide worldwide, but it also affects prokaryotes because it targets the central enzyme (5-enolpyruvylshikimate-3-phosphate, EPSP) of the shikimate pathway in the synthesis of the three essential aromatic amino acids in bacteria, fungi and plants. Our results reveal that bacteria may easily become resistant to glyphosate through changes in the 5-enolpyruvylshikimate-3-phosphate synthase active site. This indicates the importance of examining how glyphosate affects microbe-mediated ecosystem functions and human microbiomes." | 3-Phosphoshikimate 1-Carboxyvinyltransferase |
Division of labor, where subpopulations perform complementary tasks simultaneously within an assembly, characterizes major evolutionary transitions of cooperation in certain cases. Currently, the mechanism and significance of mediating the interaction between different cell types during the division of labor, remain largely unknown. Here, we investigated the molecular mechanism and ecological function of a policing system for optimizing the division of labor in Bacillus velezensis SQR9. During biofilm formation, cells differentiated into the extracellular matrix (ECM)-producers and cheater-like nonproducers. ECM-producers were also active in the biosynthesis of genomic island-governed toxic bacillunoic acids (BAs) and self-resistance; while the nonproducers were sensitive to this antibiotic and could be partially eliminated. Spo0A was identified to be the co-regulator for triggering both ECM production and BAs synthesis/immunity. Besides its well-known regulation of ECM secretion, Spo0A activates acetyl-CoA carboxylase to produce malonyl-CoA, which is essential for BAs biosynthesis, thereby stimulating BAs production and self-immunity. Finally, the policing system not only excluded ECM-nonproducing cheater-like individuals but also improved the production of other public goods such as protease and siderophore, consequently, enhancing the population stability and ecological fitness under stress conditions and in the rhizosphere. This study provides insights into our understanding of the maintenance and evolution of microbial cooperation. | Bacillus |
It has been demonstrated clinically and experimentally that administration of nonachlazine enhances myocardial contractility because of the stimulation of beta-adrenostructures and that the initial status of the latter ones determines in many respects the drug action intensity. | Nonachlazine |
Adipocyte differentiation can be regulated by the combined activity of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). In particular, PTPs act as key regulators in differentiation-associated signaling pathways. We recently found that receptor-type PTPmu (RPTPmu) expression is markedly increased during the adipogenic differentiation of 3T3-L1 preadipocytes and mesenchymal stem cells. Here, we investigate the functional roles of RPTPmu and the mechanism of its involvement in the regulation of signal transduction during adipogenesis of 3T3-L1 cells. Depletion of endogenous RPTPmu by RNA interference significantly inhibited adipogenic differentiation, whereas RPTPmu overexpression led to an increase in adipogenic differentiation. Ectopic expression of p120 catenin suppressed adipocyte differentiation, and the decrease in adipogenesis by p120 catenin was recovered by introducing RPTPmu. Moreover, RPTPmu induced a decrease in the cytoplasmic p120 catenin expression by reducing its tyrosine phosphorylation level, consequently leading to enhanced translocation of Glut-4 to the plasma membrane. On the basis of these results, we propose that RPTPmu acts as a positive regulator of adipogenesis by modulating the cytoplasmic p120 catenin level. Our data conclusively demonstrate that differentiation into adipocytes is controlled by RPTPmu, supporting the utility of RPTPmu and p120 catenin as novel target proteins for the treatment of obesity." | Receptor-Like Protein Tyrosine Phosphatases, Class 2 |
PURPOSE: Given the anatomical relationship between the ACom complex and the optic nerve, small aneurysms of the ACom can present with visual symptoms. CASE REPORTS: We summarize and illustrate the clinical course of three patients with symptomatic small ACom aneurysms and collect similar other cases reported. RESULTS: Ten patients with small unruptured visually symptomatic anterior communicating artery aneurysms were found in the literature. Including three patients herein reported, the mean age at presentation was 56. The most common visual symptoms were bitemporal vision loss and/or a decrease in visual acuity. CONCLUSION: Unruptured aneurysms of the anterior communicating artery can present with visual symptoms due to compression of optic pathways, even at a small size. Prompt recognition and treatment of such a condition are paramount as new onset of visual symptoms can signify impending rupture akin to small PCom aneurysms compressing the third nerve. We discuss a few pitfalls of clipping small ACom aneurysms compressing the optic nerve. | Anterior Cerebral Artery |
BACKGROUND: Hosta plantaginea (Lam.) Aschers flower is a famous Mongolian folk medicine in China and has a therapeutic effect on acute pharyngitis (AP). However, the effect and potential mechanism of H. plantaginea flower on AP have not been fully elucidated. AIM OF THE STUDY: The present work aimed to evaluate the effects and mechanisms of the crude extract of H. plantaginea flowers (HP) and its four fractions of petroleum ether fraction (HPA), ethyl acetate fraction (HPB), n-butanol fraction (HPC), and water residue (HPD) against AP in rats. MATERIALS AND METHODS: A 15% ammonia-induced AP rat model in rats was established. Therapeutic effects of HP and HPA approximately D in model rats were evaluated based on body weight, histopathological analysis, and inflammatory parameters, including tumor necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2), interleukin 1beta (IL-1beta), and IL-6. The protein expression of nuclear factor kappa-B p65 (NF-kappaB p65), inhibitor of NF-kappaB alpha (IkappaBalpha), c-Jun N-terminal kinases (JNK), mitogen-activated protein kinase (MAPK) p38, extracellular signal-regulated kinase (Erk), just another kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) were detected by a Western blotting assay. RESULTS: HP, HPB, and HPC treatments markedly alleviated AP in rats by increasing body weight and improving pathological damages in pharyngeal tissues. In addition, HP, HPB, and HPC treatments significantly inhibited inflammation, including decreasing the levels of TNF-alpha, PGE2, IL-1beta, and IL-6, and suppressing phosphorylated protein expression of p65, IkappaBalpha, JNK, p38, Erk, JAK1, STAT3, PI3K, and Akt in pharyngeal tissues of rats. CONCLUSION: Collectively, HP, HPB, and HPC can attenuate pharynx injury in rats by suppressing inflammation via inhibition of NF-kappaB, MAPKs, JAK-STAT, and PI3K-Akt pathways, which supports the traditional use of H. plantaginea flowers. | Hosta |
Neonates are at risk for 3 major forms of leukemia in the first year of life: acute leukemia, juvenile myelomonocytic leukemia, and transient abnormal myelopoiesis associated with Down syndrome. These disorders are rare but generate interest due to aggressive clinical presentation, suboptimal response to current therapies, and fascinating biology. Each can arise as a result of unique constitutional and acquired genetic events. Genetic insights are pointing the way toward novel therapeutic approaches. This article reviews key epidemiologic, clinical, and molecular features of neonatal leukemias, focusing on risk stratification, treatment, and strategies for developing novel molecularly targeted approaches to improve future outcomes." | Leukemia, Myelomonocytic, Juvenile |
Considering the increase in the consumption of yeasts as human probiotics, the aim of this study was to broadly investigate the beneficial properties of the lactic yeast Kluyveromyces marxianus (formerly Kluyveromyces fragilis) B0399. Several potential probiotic traits of K. marxianus B0399 were investigated by using in vitro assays, including adhesion and immune modulation, and the effect of the administration of 10(7) CFU/day of K. marxianus B0399 on the composition and metabolic activity of the human intestinal microbiota was investigated in a 3-stage continuous-culture system simulating the human colon. We demonstrated that this strain was highly adhesive to human enterocyte-like Caco-2 cells and modulated the immune response, inducing proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs). In the presence of inflammatory stimulation with lipopolysaccharide (LPS), K. marxianus B0399 provoked decreases in the levels of production of proinflammatory cytokines in PBMCs and Caco-2 cells, thus ameliorating the inflammatory response. Furthermore, K. marxianus B0399 impacted the colonic microbiota, increasing the bifidobacterial concentration in the stages of the colonic model system simulating the proximal and transverse colon. The amounts of the short-chain fatty acids acetate and propionate also increased following yeast supplementation. Finally, K. marxianus B0399 was found to induce a decrease of the cytotoxic potential of the culture supernatant from the first stage of the colonic model system. The effects of K. marxianus B0399 on adhesion, immune function, and colonic microbiota demonstrate that this strain possesses a number of beneficial and strain-specific properties desirable for a microorganism considered for application as a probiotic. | Kluyveromyces |
While constitutive CCCTC-binding factor (CTCF)-binding sites are needed to maintain relatively invariant chromatin structures, such as topologically associating domains, the precise roles of CTCF to control cell-type-specific transcriptional regulation remain poorly explored. We examined CTCF occupancy in different types of primary blood cells derived from the same donor to elucidate a new role for CTCF in gene regulation during blood cell development. We identified dynamic, cell-type-specific binding sites for CTCF that colocalize with lineage-specific transcription factors. These dynamic sites are enriched for single-nucleotide polymorphisms that are associated with blood cell traits in different linages, and they coincide with the key regulatory elements governing hematopoiesis. CRISPR-Cas9-based perturbation experiments demonstrated that these dynamic CTCF-binding sites play a critical role in red blood cell development. Furthermore, precise deletion of CTCF-binding motifs in dynamic sites abolished interactions of erythroid genes, such as RBM38, with their associated enhancers and led to abnormal erythropoiesis. These results suggest a novel, cell-type-specific function for CTCF in which it may serve to facilitate interaction of distal regulatory emblements with target promoters. Our study of the dynamic, cell-type-specific binding and function of CTCF provides new insights into transcriptional regulation during hematopoiesis." | Regulatory Elements, Transcriptional |
BACKGROUND: Arteriovenous malformations (AVM) of the urinary tract are extremely rare. To the best of our knowledge, only three case of AVM of the ureter have been described in the literature so far. CASE PRESENTATION: We present an additional, fourth case of an AVM of the ureter, clinically presented as asymptomatic haematuria and an obstructive process in the left ureter. Ureteroscopic evaluation revealed a fibroepithelial polypoid-like lesion in the proximal ureter. After biopsy showed a benign lesion, the lesion was treated with the 2-mum continuous wave (cw) thulium laser. Histopathological examination revealed a polypoid laesion caused by a circumscribed arteriovenous malformation. Almost four years after operation the patient remains asymptomatic and free of recurrence. CONCLUSION: Arteriovenous malformations of the urinary tract are extremely rare. We presented a fourth case of a arteriovenous malformation of the ureter. | Neoplasms, Fibroepithelial |
An extracellular glucoamylase produced by Paecilomyces variotii was purified using DEAE-cellulose ion exchange chromatography and Sephadex G-100 gel filtration. The purified protein migrated as a single band in 7% PAGE and 8% SDS-PAGE. The estimated molecular mass was 86.5 kDa (SDS-PAGE). Optima of temperature and pH were 55 degrees C and 5.0, respectively. In the absence of substrate the purified glucoamylase was stable for 1 h at 50 and 55 degrees C, with a t (50) of 45 min at 60 degrees C. The substrate contributed to protect the enzyme against thermal denaturation. The enzyme was mainly activated by manganese metal ions. The glucoamylase produced by P. variotii preferentially hydrolyzed amylopectin, glycogen and starch, and to a lesser extent malto-oligossacarides and amylose. Sucrose, p-nitrophenyl alpha-D-maltoside, methyl-alpha-D-glucopyranoside, pullulan, alpha- and beta-cyclodextrin, and trehalose were not hydrolyzed. After 24 h, the products of starch hydrolysis, analyzed by thin layer chromatography, showed only glucose. The circular dichroism spectrum showed a protein rich in alpha-helix. The sequence of amino acids of the purified enzyme VVTDSFR appears similar to glucoamylases purified from Talaromyces emersonii and with the precursor of the glucoamylase from Aspergillus oryzae. These results suggested the character of the enzyme studied as a glucoamylase (1,4-alpha-D-glucan glucohydrolase). | Glucan 1,4-alpha-Glucosidase |
A problem that has limited orthodontic treatment is lack of buccal-lingual alveolar width into which teeth can be moved. Causes may range from surgical obliteration to physiologic constriction after tooth removal. Lack of buccal-lingual alveolar width does not have to be an orthodontic limitation anymore. A technique used routinely to graft alveolar clefts can remedy this problem. Autogenous cancellous bone is placed subperiosteally on the buccal aspect of the constricted edentulous space. The flap is closed over the bone. The adjacent teeth may be orthodontically moved into the grafted edentulous area in approximately 6 weeks. Long-term follow-up has revealed excellent orthodontic stability, periodontal health, and dental vitality. A case report of one patient with loss of buccal-lingual alveolar space is presented. It is concluded that loss or lack of sufficient buccal-lingual alveolar width no longer must be an orthodontic limiting factor. | Alveoloplasty |
High temperature (HT) causes male sterility and decreases crop yields. Our previous works have demonstrated that sugar and auxin signaling pathways, Gossypium hirsutum Casein kinase I (GhCKI), and DNA methylation are all involved in HT-induced male sterility in cotton. However, the signaling mechanisms leading to distinct GhCKI expression patterns induced by HT between HT-tolerant and HT-sensitive cotton anthers remain largely unknown. Here, we identified a GhCKI promoter (ProGhCKI) region that functions in response to HT in anthers and found the transcription factor GhMYB4 binds to this region to act as an upstream positive regulator of GhCKI. In the tapetum of early-stage cotton anthers, upregulated expression of GhMYB4 under HT and overexpressed GhMYB4 under normal temperature both led to severe male sterility phenotypes, coupled with enhanced expression of GhCKI. We also found that GhMYB4 interacts with GhMYB66 to form a heterodimer to enhance its binding to ProGhCKI. However, GhMYB66 showed an expression pattern similar to GhMYB4 under HT but did not directly bind to ProGhCKI. Furthermore, HT reduced siRNA-mediated CHH DNA methylations in the GhMYB4 promoter, which enhanced the expression of GhMYB4 in tetrad stage anthers and promoted the formation of the GhMYB4/GhMYB66 heterodimer, which in turn elevated the transcription of GhCKI in the tapetum, leading to male sterility. Overall, we shed light on the GhMYB66-GhMYB4-GhCKI regulatory pathway in response to HT in cotton anthers. | Casein Kinases |
Due to a number of unpleasant considerations, marketed drugs have steadily lost their importance in the treatment of cancer. In order to find a viable cancer cell diagnostic agent, we therefore focused on metal complexes that displayed target adequacy, permeability to cancer cells, high standard water solubility, cytoselectivity, and luminescent behavior. In this aspect, luminescent 11-naphthalen-1-yl dipyrido [3,2-a:2',3'-c] phenazine based Ru(II)/Ir(III)/Re(I) complexes have been prepared for HCT-116 colorectal cancer stem cell therapy. Our study successfully established the possible cytotoxicity of IrL complex at different doses on HCT-116 colorectal cancer stem cells (CRCSCs). Additionally, an immunochemistry analysis of the complex IrL showed that the molecule was subcellularly localized in the nucleus and other regions of the cytoplasm, where it caused nuclear DNA damage and mitochondrial dysfunction. The level of BAX and Bcl-2 was further quantified by qRT-PCR. The expression of proapoptotic BAX showed increased expression in the complex IrL-treated cell compared to the control, indicating the potential of complex IrL for apoptotic induction. Upon further validation, complex IrL was developed as an inhibitor of autophagy for the eradication of cancer stem cells. | Phenazines |
Mycoplasma synoviae is responsible for respiratory tract disease and synovitis in chickens and turkeys. In an attempt to identify the most prominent proteins expressed by this microorganism, a proteome map of M. synoviae was developed by using two-dimensional gel electrophoresis in combination with mass spectrometry. Based on the genome sequence of M. synoviae, a total of 30 different coding DNA sequences, including one hypothetical and one conserved-hypothetical protein, were experimentally verified with the identification of the corresponding protein products by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF). The identified proteins were assigned according to the Clusters of Orthologous Groups of proteins functional classification. M. synoviae has 694 predicted CDSs. Overall, in this work 416 proteins spots were resolved in Coomassie Blue stained 2DE gels and were analyzed by mass spectrometry (MS). Altogether, we have achieved by MS the identification of 78 protein spots, corresponding to 30 different proteins. This is the first proteome map to be described in M. synoviae, and it is expected to be useful as a reference for comparative analysis. | Mycoplasma synoviae |
The levels of cooperation and conflict in the relationships of 40 sibling pairs, 11 to 14 years old, were explored from several different perspectives. Ratings of levels of cooperation and conflict in the sibling relationship were obtained from the participants, siblings, and mothers. Amounts of cooperation and conflict were also coded from responses to a projective story test that elicited perceptions of the relationship from each child, and from their conjoint performance on three interactive tasks. Either child's perspective on the sibling relationship evidenced more conflict and less cooperation relative to maternal evaluations. Interactive tasks revealed more cooperation, whereas projective stories revealed more conflict for these siblings. In addition, levels of cooperation varied by sex, birth order, and dyad type, whereas conflict levels differed only by dyad type. | Sibling Relations |
As hospitals examine their infection control procedures in the light of the COSHH regulations, they have the perfect opportunity to replace unnecessary ritual with sound, cost effective, efficient and environmentally responsible practices. | Asepsis |
87 either cylindroid or laminar trabeculae, isolated from the perpendicular or inferior bundles of the human calcaneus, were embedded in methylmatecrylate and serially cut along longitudinal and transversal planes with a rotatory-blade saw. The microscopical study of the sections showed that in 83% of the samples secondary osteons run along the longitudinal axis of the trabeculae and their lumina either form a continuous channel network throughout each trabecula (37% of cases) or are restricted to discrete segments (46% of cases). The trabeculae entirely devoid of osteons (17%) are the thinnest, never exceeding 400 microns in thickness. This value is not even exceeded by the segments devoid of osteons in the trabeculae in which the Haversian canals occur only intermittently; conversely, the segments containing Haversian canals can reach and exceed 600 microns in thickness. The maximum distance of the osteocytic lacunae from filtering surfaces--i.e. outer surface of the trabeculae or inner surface of the Haversian canals--was found to be almost the same in the segments of the trabeculae that enclose or not osteons, even though the average trabecular thickness is greater in the former than in the latter regions. On the basis of these findings the formation of endotrabecular osteons may be viewed as a device that indirectly favours the metabolic exchange of deep-seated osteocytes while increasing the free surface area available for bone tissue reconstruction. It remains doubtful whether the Haversian systems may also contribute to improve the mechanical properties of the trabeculae. The arrangement of the collagen fibrils, which differs between cylindroid and laminar trabeculae, is apparently well suited to ensure the resistance of the trabeculae to mechanical loading through the use of the least amount of building material, in accordance with Wolff's law. | Calcaneus |
Periodontal disease is common in dogs and cats. Prevention and treatment is important for general health and well-being of our pets. Both prevention and treatment of periodontal disease have two components, namely maintenance of oral hygiene and professional periodontal therapy. Maintenance of oral hygiene is performed by the owner and is, therefore, also called home care. The preventions and long-term control of periodontal disease requires adequate home care. This chapter details home care techniques and available products. | Dental Devices, Home Care |
Fifteen monoclonal antibodies (MAbs) made to coxsackievirus B-3 were tested against a panel of enteroviruses by indirect immunofluorescence. The MAbs included seven which reacted with coxsackievirus B-3 only, five which reacted with more than one enterovirus included in the panel, one which reacted with broad enteroviral specificity and did not react with any heterologous virus (group specific), and two which reacted with all enteroviruses tested and at least one heterologous virus. The group-specific MAb identified 44 of 45 clinical isolates as enteroviruses, while the two broadly reactive MAbs reacted with all 45 of the clinical isolates. These MAbs are potentially important diagnostic reagents for grouping and typing enteroviruses by indirect immunofluorescence. | Enterovirus B, Human |
Medical case reports suggest that cannabinoids extracted from Cannabis sativa have therapeutic effects; however, the therapeutic employment is limited due to the psychotropic effect of its major component, Delta9-tetrahydrocannabinol (THC). The new scientific discoveries related to the endocannabinoid system, including new receptors, ligands, and mediators, allowed the development of new therapeutic targets for the treatment of several pathological disorders minimizing the undesirable psychotropic effects of some constituents of this plant. Today, FDA-approved drugs, such as nabiximols (a mixture of THC and non-psychoactive cannabidiol (CBD)), are employed in alleviating pain and spasticity in multiple sclerosis. Dronabinol and nabilone are used for the treatment of chemotherapy-induced nausea and vomiting in cancer patients. Dronabinol was approved for the treatment of anorexia in patients with AIDS (acquired immune deficiency syndrome). In this review, we highlighted the potential therapeutic efficacy of natural and synthetic cannabinoids and their clinical relevance in cancer, neurodegenerative and dermatological diseases, and viral infections. | Cannabinoids |
Brachyspira species have been implicated as a potential cause of gastroenteritis in humans; this is, however, controversial. In 733 gastroenteritis cases and 464 controls, we found 29 samples positive for Brachyspira species (2.3% of cases and 2.6% of controls; P = 0.77). Brachyspira species were not associated with gastroenteritis in humans. | Brachyspira |
Electrical activity in the heart depends critically on the interactions of multiple ion channels to coordinate the timing of excitation and contraction of the ventricles. Voltage-gated sodium channels underlie the rapid spread of impulses through the atria and ventricles, but the importance of sodium (Na(+)) channels to the control of the ventricular action potential has only most recently become apparent through the investigation of the relationship between mutation-induced clinical phenotypes and the altered function of mutant Na(+) channels linked to inherited arrhythmias. Investigation into the structural basis of disease-associated mutations of the cardiac Na(+) channel has led to the discovery of novel role of the Na(+) channel carboxy-terminal (CT) domain in controlling channel inactivation. Intramolecular interactions between the carboxy-terminal domain and an intracellular peptide loop that forms the inactivation gate are required to minimize channel reopening during prolonged depolarization. Disruption of this interaction leads to persistent sodium channel current, action potential prolongation, and elevated risk of cardiac arrhythmia. | Sodium Channels |
Setleis syndrome (SS), or focal facial dermal dysplasia type III (FFDD3, MIM #227260), is an autosomal recessive condition caused by biallelic loss-of-function variants in TWIST2. It is characterized by bitemporal atrophic skin lesions and distinctive facial features. Individuals with de novo or inherited duplication or triplication of the chromosomal region 1p36.22p36.21 have also been reported to have the SS phenotype with additional neurodevelopmental challenges (rarely seen in individuals with TWIST2 mutations) and variable expressivity and penetrance. Triplication of this region is also associated with more severe manifestations compared to a duplication. We report a 2-year-old female patient with features of SS associated with a de novo 3.603 Mb triplication at 1p36.23p36.22 identified on postnatal microarray analysis. Her triplication shares a 281.263 kb overlap with gains at 1p36.22, reported by previous groups, delineating the shortest region of overlap (SRO) to date. This SRO involves 10 RefSeq and 4 OMIM morbid map genes and highlights the candidate dosage-sensitive element(s) underlying the cardinal features of SS phenotype in individuals with gains at 1p36." | Focal Facial Dermal Dysplasias |
In the cutaneous nerves, unmyelinated nerve fibers outnumber the myelinated ones but are scarcely analyzed, especially at autopsy. This indifference toward the pathology of unmyelinated nerve fibers may be due to the necessity of electron microscopic analyses and, more importantly, the obscurity of pathological alteration of unmyelinated nerve fibers in aging as well as in peripheral nerve disorders. The aim of this article is to review (1) the normal appearance including postmortem changes, (2) the age-related changes, and (3) the pathological alteration in various neuropathic and non-neuropathic conditions, of unmyelinated nerve fibers in the sural nerve. For the complete analyses of sural nerve, qualitative and quantitative estimation of unmyelinated nerve fibers in all specimens should be recommended and it sometimes has an important diagnostic value. | Nerve Fibers |
Acebutolol (400 mg once daily), atenolol (100 mg once daily) and placebo were self administered to 12 healthy male volunteers in a double-blind crossover study. Each drug treatment was administered for 4 days so that subjects' plasma levels of the drug were at steady state. Subjects were tested on the 4th day. On each of the 3 test days subjects underwent an anxiety induction procedure involving both easy and difficult versions of the Stroop test and syntactic reasoning. Measures of state anxiety were taken during the difficult task, an easy version of the task and after a period of quiet relaxation. High, medium and low levels of anxiety corresponded to the three levels of task difficulty. Highly significant differences were exhibited in state anxiety between high, medium and low anxiety induction procedures with both Stroop test and syntactic reasoning. This was shown by highly significant main effects for task difficulty with both tasks. There was no significant anxiolytic action of either acebutolol or atenolol when compared to placebo (there were no drug effects or any interaction of drugs with task difficulty). There were no significant drug effects upon any of the cognitive test measures. Overall, there was no evidence of either anxiolysis or sedation with either of these two relatively hydrophilic drugs. | Acebutolol |
BACKGROUND: Tembusu virus (TMUV), a newly emerging pathogenic flavivirus, spreads rapidly between ducks, causing massive economic losses in the Chinese duck industry. Vaccination is the most effective method to prevent TMUV. Therefore, it is urgent to look for an effective vaccine strategy against TMUV. Heterologous prime-boost regimens priming with vaccines and boosting with recombinant adenovirus vaccines have been proven to be successful strategies for protecting against viruses in experimental animal models. METHODS: In this study, heterologous and homologous prime-boost strategies using an attenuated salmonella vaccine and a recombinant adenovirus vaccine expressing prM-E or the E gene of TMUV were evaluated to protect ducks against TMUV infection for the first time, including priming and boosting with the attenuated salmonella vaccine, priming and boosting with the recombinant adenovirus vaccine, and priming with the attenuated salmonella vaccine and boosting with the recombinant adenovirus vaccine. Humoral and cellular immune responses were detected and evaluated. We then challenged the ducks with TMUV at 12 days after boosting to assay for clinical symptoms, mortality, viral loads and histopathological lesions after these different strategies. RESULTS: Compared with the homologous prime-boost strategies, the heterologous prime-boost regimen produced higher levels of neutralizing antibodies and IgG antibodies against TMUV. Additionally, it could induce higher levels of IFN-gamma than homologous prime-boost strategies in the later stage. Interestingly, the heterologous prime-boost strategy induced higher levels of IL-4 in the early stage, but the IL-4 levels gradually decreased and were even lower than those induced by the homologous prime-boost strategy in the later stage. Moreover, the heterologous prime-boost strategy could efficiently protect ducks, with low viral titres, no clinical symptoms and histopathological lesions in this experiment after challenge with TMUV, while slight clinical symptoms and histopathological lesions were observed with the homologous prime-boost strategies. CONCLUSIONS: Our results indicated that the heterologous prime-boost strategy induced higher levels of humoral and cellular immune responses and better protection against TMUV infection in ducks than the homologous prime-boost strategies, suggesting that the heterologous prime-boost strategy is an important candidate for the design of a novel vaccine strategy against TMUV. | Immunization, Secondary |
Bioactive equivalent combinatorial components play a critical role in herbal medicines. However, how to discover and enrich them efficiently is a question for herbal pharmaceuticals researchers. In our work, a novel two-dimensional reversed-phase/hydrophilic interaction high-performance liquid chromatography method was established to perform real-time components trapping and combining for preparation and isolation of coeluting components. Arenaria kansuensis was taken as an example, and solid-phase extraction coupled with liquid-liquid extraction as a simple and efficient method for enriching trace components, reversed phase column coupled with hydrophilic interaction liquid chromatography XAmide column as two-dimensional chromatography technology for isolation and preparation of coeluting constituents, enzyme-linked immune-sorbent assay as bio-guided assay, and anti-inflammatory bioactivity evaluation for bioactive constituents. A combination of 12 beta-carboline alkaloids was identified as anti-inflammatory bioactive equivalent combinatorial components from A. kansuensis, which accounts for 1.9% w/w of original A. kansuensis. This work answers the key question of which are real anti-inflammatory components from A. kansuensis and provides a fast and efficient approach for discovering and enriching trace beta-carboline alkaloids from herbal medicines for the first time. More importantly, the discovery of bioactive equivalent combinatorial components could improve the quality control of herbal products and inspire a herbal medicine based on combinatorial therapeutics. | Arenaria Plant |
PURPOSE: To determine whether caspase or cathepsin pathways are activated in human retinal pigment epithelial cells (ARPE-19) after exposure to 7-ketocholesterol (7kCh). METHODS: ARPE-19 cells were exposed to 7kCh with or without z-VAD-fmk, a pan-caspase inhibitor. Caspase-3, -8, and -9 activities were measured by a fluorochrome inhibitor of caspase (FLICA) assay. Caspase-12 activity was detected by Western blotting. RT-PCR was performed for 18s, mortalin-2, cathepsins B, D, and L/V2. RESULTS: At 24 hours, 7kCh-treated cultures had increased caspase-8 (P < 0.001) and caspase-3 (P < 0.001) activities compared with vehicle-treated cultures. 7kCh-induced caspase-3 activation was blocked by z-VAD-fmk (P < 0.001). Caspase-9 was not activated by 7kCh treatment (P > 0.05). Procaspase-12 was cleaved into its active form after treatment with 7kCh for 24 hours. At 6 hours, the RNA level for mortalin-2, a pro-survival gene, was upregulated. ARPE-19 cells did not express RNA for cathepsins B, D, or L/V2 under any conditions. CONCLUSIONS: In ARPE-19 cells, 7kCh-induced apoptosis uses the receptor-mediated caspase-8 pathway and the endoplasmic reticulum stress-induced caspase-12 pathway but not the mitochondrial caspase-9 pathway. The cathepsin pathways are not involved in 7kCh-induced cell death. These data demonstrate that 7kCh causes a loss of cell viability through caspase-dependent apoptosis and can act as an oxidative stressor leading to retinal pigment epithelial cell atrophy. Elucidating the specific apoptotic pathways involved may have therapeutic potential for AMD and other retinal diseases. | Caspase 12 |
The cellulose-binding domain (CBD) is the second important and the most wide-spread element of cellulase structure involved in cellulose transformation with a great structural diversity and a range of adsorption behavior toward different types of cellulosic materials. The effect of the CBD from Clostridium cellulovorans on the supramolecular structure of three different sources of cellulose (cotton cellulose, spruce dissolving pulp, and cellulose linters) was studied. Fourier-transform infrared spectroscopy (FTIR) was used to record amides I and II absorption bands of cotton cellulose treated with CBD. Structural changes as weakening and splitting of the hydrogen bonds within the cellulose chains after CBD adsorption were observed. The decrease of relative crystallinity index of the treated celluloses was confirmed by FTIR spectroscopy and X-ray diffraction (XRD). X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) were used to confirm the binding of the CBD on the cellulose surface and the changing of the cellulose morphology. | Clostridium cellulovorans |
The digestive physiology of ruminants is sufficiently different (e.g., with respect to mean retention time of digesta, digestibility of the feed offered, digestion, and fermentation characteristics) that caution is needed before extrapolating results from one type of ruminant to another. The objectives of the present study were (1) to provide an overview of some essential differences in rumen physiology between dairy cattle, beef cattle, and sheep that are related to methane (CH(4)) emission; and (2) to evaluate whether dietary strategies to mitigate CH(4) emission with various modes of action are equally effective in dairy cattle, beef cattle, and sheep. A literature search was performed using Web of Science and Scopus, and 94 studies were selected from the literature. Per study, the effect size of the dietary strategies was expressed as a proportion (%) of the control level of CH(4) emission, as this enabled a comparison across ruminant types. Evaluation of the literature indicated that the effectiveness of forage-related CH(4) mitigation strategies, including feeding more highly digestible grass (herbage or silage) or replacing different forage types with corn silage, differs across ruminant types. These strategies are most effective for dairy cattle, are effective for beef cattle to a certain extent, but seem to have minor or no effects in sheep. In general, the effectiveness of other dietary mitigation strategies, including increased concentrate feeding and feed additives (e.g., nitrate), appeared to be similar for dairy cattle, beef cattle, and sheep. We concluded that if the mode of action of a dietary CH(4) mitigation strategy is related to ruminant-specific factors, such as feed intake or rumen physiology, the effectiveness of the strategy differs across ruminant types, whereas if the mode of action is associated with methanogenesis-related fermentation pathways, the strategy is effective across ruminant types. Hence, caution is needed when translating effectiveness of dietary CH(4) mitigation strategies across different ruminant types or production systems. | Rumination, Digestive |
Time-space synesthesia is a variant of sequence-space synesthesia and involves the involuntary association of months of the year with 2D and 3D spatial forms, such as arcs, circles, and ellipses. Previous studies have revealed conflicting results regarding the association between time-space synesthesia and enhanced spatial processing ability. Here, we tested 15 time-space synesthetes, and 15 non-synesthetic controls matched for age, education, and gender on standard tests of mental rotation ability, spatial working memory, and verbal working memory. Synesthetes performed better than controls on our test of mental rotation, but similarly to controls on tests of spatial and verbal working memory. Results support a dissociation between visuo-spatial imagery and spatial working memory capacity, and suggest time-space synesthesia is associated only with enhanced visuo-spatial imagery. These data are consistent with the time-space connectivity thesis that time-space synesthesia results from enhanced connectivity in the parietal lobe between regions supporting the representation of temporal sequences and those underlying visuo-spatial imagery. | Synesthesia |
Toll-like receptor 2 (TLR2) plays an essential role in innate immunity by the recognition of a large variety of pathogen-associated molecular patterns. It induces its recruitment to lipid rafts induces the formation of a membranous activation cluster necessary to enhance, amplify, and control downstream signaling. However, the exact composition of the TLR2-mediated molecular complex is unknown. We performed a proteomic analysis in lipopeptide-stimulated THP1 and found IMPDHII protein rapidly recruited to lipid raft. Whereas IMPDHII is essential for lymphocyte proliferation, its biologic function within innate immune signal pathways has not been established yet. We report here that IMPDHII plays an important role in the negative regulation of TLR2 signaling by modulating PI3K activity. Indeed, IMPDHII increases the phosphatase activity of SHP1, which participates to the inactivation of PI3K." | Protein Tyrosine Phosphatase, Non-Receptor Type 6 |
The default-mode network (DMN) has been implicated in the neurobiology of major depressive disorder (MDD), and the cerebellum is suggested to be involved in high-order cognitive network such as the DMN. However, the specific contribution of the cerebellum to the DMN alterations remains equivocal. This study was conducted to examine the cerebellar-DMN connectivity in drug-naive MDD directly by using the cerebellum Crus I as seeds.Forty-four drug-naive MDD patients and 44 healthy controls participated in the resting-state scan. Functional connectivity (FC) was applied to analyze the images.Significantly increased FCs were observed between the right Crus I and the right inferior frontal cortex (orbital part)/superior temporal pole, bilateral MPFC (orbital part), and left middle temporal gyrus in the patients compared with the controls. There was a significantly positive correlation between the z values of the right Crus I-bilateral MPFC (orbital part) connectivity and the scores of Automatic Thoughts Questionnaire in the patients (r = 0.329, P = 0.029).The findings reveal that depressed patients have increased cerebellar-DMN connectivity with clinical significance, and thus highlight the contribution of the cerebellum to the DMN alterations in neurobiology of MDD. | Cerebral Crus |
In this paper, we present a cultural evolutionary model in which norms for cooperation and punishment are acquired via two cognitive mechanisms: (1) payoff-biased transmission-a tendency to copy the most successful individual; and (2) conformist transmission-a tendency to copy the most frequent behavior in the population. We first show that if a finite number of punishment stages is permitted (e.g. two stages of punishment occur if some individuals punish people who fail to punish non-cooperators), then an arbitrarily small amount of conformist transmission will stabilize cooperative behavior by stabilizing punishment at some n -th stage. We then explain how, once cooperation is stabilized in one group, it may spread through a multi-group population via cultural group selection. Finally, once cooperation is prevalent, we show how prosocial genes favoring cooperation and punishment may invade in the wake of cultural group selection. | Social Conformity |
OBJECTIVE: Pedicled flaps (PFs) have historically served as the preferred option for reconstruction of large chest wall defects. More recently, the indications for microvascular-free flaps (MVFFs) have increased, particularly for defects in which PFs are inadequate or unavailable. We sought to compare oncologic and surgical outcomes between MVFFs and PFs in reconstructions of full-thickness chest wall defects. METHODS: We retrospectively identified all patients who underwent chest wall resection at our institution from 2000 to 2022. Patients were stratified by flap reconstruction. End points were defect size, rate of complete resection, rate of local recurrence, and postoperative outcomes. Multivariable analysis was performed to identify factors associated with complications at 30 days. RESULTS: In total, 536 patients underwent chest wall resection, of whom 133 had flap reconstruction (MVFF, n = 28; PF, n = 105). The median (interquartile range) covered defect size was 172 cm(2) (100-216 cm(2)) for patients receiving MVFF versus 109 cm(2) (75-148 cm(2)) for patients receiving PF (P = .004). The rate of R0 resection was high in both groups (MVFF, 93% [n = 26]; PF, 86% [n = 90]; P = .5). The rate of local recurrence was 4% in MVFF patients (n = 1) versus 12% in PF patients (n = 13, P = .3). Postoperative complications were not statistically different between groups (odds ratio for PF, 1.37; 95% confidence interval, 0.39-5.14]; P = .6). Operative time >400 minutes was associated with 30-day complications (odds ratio, 3.22; 95% confidence interval, 1.10-9.93; P = .033). CONCLUSIONS: Patients with MVFFs had larger defects, a high rate of complete resection, and a low rate of local recurrence. MVFFs are a valid option for chest wall reconstructions. | Free Tissue Flaps |
Injuries to the articular cartilage surface are challenging to repair because cartilage possesses a limited capacity for self-repair. The outcomes of current clinical procedures aimed to address these injuries are inconsistent and unsatisfactory. We have developed a novel method for generating hyaline articular cartilage to improve the outcome of joint surface repair. A suspension of 10(7) swine chondrocytes was cultured under reciprocating motion for 14 days. The resulting dynamic self-regenerating cartilage (dSRC) was placed in a cartilage ring and capped with fibrin and collagen gel. A control group consisted of chondrocytes encapsulated in fibrin gel. Constructs were implanted subcutaneously in nude mice and harvested after 6 weeks. Gross, histological, immunohistochemical, biochemical, and biomechanical analyses were performed. In swine patellar groove, dSRC was implanted into osteochondral defects capped with collagen gel and compared to defects filled with osteochondral plugs, collagen gel, or left empty after 6 weeks. In mice, the fibrin- and collagen-capped dSRC constructs showed enhanced contiguous cartilage matrix formation over the control of cells encapsulated in fibrin gel. Biochemically, the fibrin and collagen gel dSRC groups were statistically improved in glycosaminoglycan and hydroxyproline content compared to the control. There was no statistical difference in the biomechanical data between the dSRC groups and the control. The swine model also showed contiguous cartilage matrix in the dSRC group but not in the collagen gel and empty defects. These data demonstrate the survivability and successful matrix formation of dSRC under the mechanical forces experienced by normal hyaline cartilage in the knee joint. The results from this study demonstrate that dSRC capped with hydrogels successfully engineers contiguous articular cartilage matrix in both nonload-bearing and load-bearing environments. | Hyalin |
BACKGROUND: Code status discussions are important in cancer care, but the best modality for such discussions has not been established. The objective of this study was to determine the impact of a physician ending a code status discussion with a question (autonomy approach) versus a recommendation (beneficence approach) on patients' do-not-resuscitate (DNR) preference. METHODS: Patients in a supportive care clinic watched 2 videos showing a physician-patient discussion regarding code status. Both videos were identical except for the ending: one ended with the physician asking for the patient's code status preference and the other with the physician recommending DNR. Patients were randomly assigned to watch the videos in different sequences. The main outcome was the proportion of patients choosing DNR for the video patient. RESULTS: A total of 78 patients completed the study, and 74% chose DNR after the question video, whereas 73% chose DNR after the recommendation video. Median physician compassion score was very high and not different for both videos. All 30 of 30 patients who had chosen DNR for themselves and 30 of 48 patients who had not chosen DNR for themselves chose DNR for the video patient (100% versus 62%). Age (odds ratio = 1.1/year) and white ethnicity (odds ratio = 9.43) predicted DNR choice for the video patient. CONCLUSIONS: Ending DNR discussions with a question or a recommendation did not impact DNR choice or perception of physician compassion. Therefore, both approaches are clinically appropriate. All patients who chose DNR for themselves and most patients who did not choose DNR for themselves chose DNR for the video patient. Age and race predicted DNR choice. | Resuscitation Orders |
A brief overview of the evidence for omega-3 fatty acids and, in particular, of docosahexaenoic acid (DHA), involvement in cognition and in dementia is given. Two studies are presented in this regard in which the key intervention is a DHA supplement. The fist, the MIDAS Study demonstrated that DHA can be of benefit for episodic memory in healthy adults with a mild memory complaint. The second, the ADCS AD trial found no benefit of DHA in the primary outcomes but found an intriguing benefit for cognitive score in ApoE4 negative allele patients. This leads to a consideration of the mechanisms of action and role of ApoE and its modulation by DHA. Given the fundamental role of ApoE in cellular lipid transport and metabolism in the brain and periphery, it is no surprise that ApoE affects n-3 PUFA brain function as well. It remains to be seen to what extent ApoE4 deleterious effect in AD is associated with n-3 PUFA-related cellular mechanisms in the brain and, more specifically, whether ApoE4 directly impairs the transport of DHA into the brain, as has been suggested. | Docosahexaenoic Acids |
PURPOSE: This paper recounts the history and experiences of one academic medical center that sought to improve the care of elderly patients by adopting and adapting the Geriatric Resource Nurse (GRN) model recommended by the Nurses Improving the Care of Healthsystem Elderly (NICHE) program. A formal evaluation examined the perceptions, opinions and attitudes of non-GRN nursing peers, Nurse Managers (NMs) and members of the Inter-Professional Advisory Board (IAB) regarding GRN practices and the institution's NICHE program. DESIGN: A qualitative research design with purposive sampling was utilized. METHODS: Semi-structured interviews and focus groups conducted in the fall/winter 2017 were analyzed using standard content analysis methods of isolating and grouping contextual themes without a predefined framework. FINDINGS: The institution's GRN training program, a hybrid of the national NICHE program and organization-developed components, has strong support among NMs, members of the IAB and other RNs. However, there exist many misconceptions, erroneous information and misunderstandings about the program and the roles and expectations of GRNs that have hindered the likelihood of producing desired outcomes. CONCLUSIONS: Training GRNs was insufficient in disseminating and implementing evidenced-based geriatric practices in this hospital. Future work in this area would benefit from integrating concepts and methods from dissemination and implementation science when developing, launching, and sustaining NICHE programs. CLINICAL RELEVANCE: Integrating principles and models of dissemination and implementation science can increase consistent use of evidence based practices and the likelihood of improved geriatric patient outcomes in NICHE hospitals." | Nurses Improving Care for Health System Elders |
The body's ability to produce prostacyclin and thromboxane by blood vessels and platelets may be important in hemostatic and thrombotic disorders and in blood pressure regulation. There are limitations to the information that can be derived from measurement of the active substances or metabolites in plasma and urine. Assays for thromboxane and prostacyclin in bleeding time blood reflect production in response to a single standardized vascular injury, and show considerable promise in furthering our understanding of the production of these chemicals in vivo. These assays may improve the assessment of risk of developing thrombotic disorders and improve the ability to monitor treatment. Studies to date have focused largely on the influences of various doses of aspirin on the production of prostacyclin and thromboxane in bleeding time blood, but also suggest that smokers are high thromboxane producers. In addition, individuals who exhibit type A behavior, a behavior pattern characterized by a relatively high level of ambitiousness, hostility, and competitive drive and a chronic sense of urgency appear to be low prostacyclin producers. Diets enriched in sunflower oil were found to diminish thromboxane production, while diets high in canola oil enhanced prostacyclin formation. | 6-Ketoprostaglandin F1 alpha |
Eukaryotic poly(A)-binding protein (PABP) commonly binds to the 3'-UTR poly(A) tail of every mRNA, but it also binds to the 5'-UTR of PABP mRNA for autoregulation of its expression. In the sequence of the latter binding site, the contiguous A residues are segmented discretely by the insertion of short pyrimidine oligonucleotides as linkers, so that (A)(6-8) segments are repeated six times. This differs from the poly(A)-tail sequence, which has a higher binding affinity for PABP. In order to examine whether the A-rich repeats have a functional structure, several RNA/DNA analogues were subjected to crystallization. It was found that some of them could be crystallized. Single crystals thus obtained diffracted to 4.1 A resolution. The fact that the repeated sequences can be crystallized suggests the possibility that the autoregulatory sequence in PABP mRNA has a specific structure which impedes the binding of PABP. When PABP is excessively produced, it could bind to this sequence by releasing the structure in order to interfere with initiation-complex formation for suppression of PABP translation. Otherwise, PABP at low concentration preferentially binds to the poly(A) tail of PABP mRNA. | Poly(A)-Binding Proteins |
Cytochrome c (cyt c) is widely used as a model protein to study (i) folding and stability aspects of the protein folding problem and (ii) structure-function relationship from the evolutionary point of view. Databases of cyts c now contain 285 cyt c sequences from different organisms. A sequence alignment of all these proteins with respect to horse cyt c led to several important conclusions. One of them is that Leu94 is always conserved in all 30 mammalian cyts c. It is known that mutation L94G of the wild type (WT) horse cyt c is destabilizing and mutant exists as molten globule under the native condition (buffer pH 6 and 25 degrees C). We have expressed and purified uniformly labeled ((13)C and (15)N) and unlabeled WT horse cyt c and its L94G mutant. We report that labeling does not affect the thermodynamic stability of proteins. To support this conclusion, the secondary and tertiary structure of each protein in labeled and unlabeled forms was determined by conventional techniques (UV-Vis absorption and circular dichroism spectroscopy). | Cytochromes c' |
The type 1 equilibrative nucleoside transporter (ENT1) is implicated in regulating levels of extracellular adenosine ([AD]ex). In the basal forebrain (BF) levels of [AD]ex increase during wakefulness and closely correspond to the increases in the electroencephalogram (EEG) delta (0.75-4.5Hz) activity (NRdelta) during subsequent non-rapid eye movement sleep (NREMS). Thus in the BF, [AD]ex serves as a biochemical marker of sleep homeostasis. Waking EEG activity in theta range (5-9Hz, Wtheta) is also described as a marker of sleep homeostasis. An hour-by-hour temporal relationship between the Wtheta and NRdelta is unclear. In this study we examined the relationship between these EEG markers of sleep homeostasis during spontaneous sleep-wakefulness and during sleep deprivation (SD) and recovery sleep in the ENT1 gene knockout (ENT1KO) mouse. We observed that baseline NREMS amount was decreased during the light period in ENT1KO mice, accompanied by a weak correlation between Wtheta of each hour and NRdelta of its subsequent hour when compared to their wild-type (WT) littermates. Perfusion of low dose of adenosine into BF not only strengthened the Wtheta-NRdelta relationship, but also increased NREMS to match with the WT littermates suggesting decreased [AD]ex in ENT1KO mice. However, the SD-induced [AD]ex increase in the BF and the linear correlation between the EEG markers of sleep homeostasis were unaffected in ENT1KO mice suggesting that during SD, sources other than ENT1 contribute to increase in [AD]ex. Our data provide evidence for a differential regulation of wakefulness-associated [AD]ex during spontaneous vs prolonged waking." | Equilibrative Nucleoside Transporter 1 |
Functional impairment of the vagotomized stomach used as a substitute oesophagus seriously deteriorates the quality of life of patients following oesophageal cancer surgery. We speculated that if the enteric neurons of the reconstructed gastric tube survived functionally, the motility of the gastric tube could be facilitated and the recovery process after operation would improve as a consequence. In the present study we investigated whether direct electrical stimulation was effective for facilitating the motility of the canine vagotomized stomach. Dogs underwent truncal vagotomy by transabdominal approach and, in some cases, arteries to the upper stomach and the oesophagus were also ligated and resected to resemble the blood supply and surgical invasion of the reconstructed gastric tube. Electrical stimulation, a few minutes of positive rectangular current pulses, amplitude 20 V (or 15 mA), duration 0.5 ms and frequency between 0.2 and 7 Hz, was delivered on the greater curvature of the mid corpus. Changes in mechanical contractions were recorded using strain gauge force transducers. Electrical stimulation successfully enhanced the mechanical force of the phasic ring contractions of the vagotomized stomach in a frequency dependent manner. Aboral propagation and periodicity of the contractions, impaired by surgical procedures, were restored during stimulation. These excitatory effects were inhibited by atropine, hexamethonium and tetrodotoxin, suggesting that electrical stimulation acts on intramural cholinergic nerves that have survived functionally. These results suggest that electrical stimulation could be an effective method for improving the motility of the vagotomized stomach. | Stomach |
The human gene MafF (hMafF) is a member of bZip transcription factor Maf family, but it alone cannot activate its target genes. In 2006, a novel hMafF interacting protein (MIP) was identified. Transient transfection assay in Hela cells suggested that co-expression of MIP and hMafF could activate US2-driven transcription. In this work, we constructed a series of plasmids and transformed YM4271 yeast strain to establish a recombinant yeast detection system. In this system, MIP's expression level could be regulated using glucose incubation or galactose-induced incubation. The expression level of reporter gene LacZ in obtained recombinant yeast strains was measured using quantitative liquid assay. By comparing and analyzing the beta-galactosidase activities of different yeast strains or the same yeast strain in different culture media, the effect of MIP on transactivation driven by nUS2-hMafF was finally determined. Only in the presence of both MIP and hMafF could the nUS2-pLacZi reporter in yeast genome be activated. More importantly, this work established a novel recombinant yeast detection system, which may serve as a powerful tool to study the regulatory mechanisms of transcription complex in the future. | MafF Transcription Factor |
Commercial gambling is expanding rapidly across the globe. However, the field of gambling research has not kept pace with this expansion, and continues to focus on prevalence studies and individuated treatment regimes, with little attention to the political, economic or technological underpinnings of commercial gambling. The implications of this lack of sophistication in the research agenda are that society is ill-equipped to understand the nature and underlying causes of gambling harms, and how these might best be avoided, minimized or ameliorated. Around the world, various levels of government benefit from gambling revenue, with consequences for the independent regulation of gambling. Further, there is considerable industry influence on the research agenda, often involving similar techniques to those employed previously by the tobacco and alcohol industries to engage researchers. This influence is compounded by a failure of many gambling researchers and journals to adopt traditional academic safeguards, such as the disclosure of conflicts of interest, and by many arguing for a 'partnership model' with industry to advance the research agenda. This paper identifies five basic principles to restore reasonable standards of integrity in gambling studies: (1) research should not be funded by the proceeds of gambling; (2) research priorities should not be influenced by the beneficiaries of gambling; (3) conferences and other research fora should not be influenced by industry; (4) funding sources should be disclosed in journals and at conferences; and (5) meaningful access to gambling products and environments must be part of licensing. We also propose a range of actions to promote greater transparency and independence in the gambling research field. | Disclosure |
Analysis of a randomized study of preoperative skin preparation techniques in thoracic and general surgical patients revealed that the use of a one minute alcohol cleansing and application of an antimicrobial film provides equivalent bactericidal activity to a five minute iodophor scrub and paint. Initial bacterial kill is greater with a one minute alcohol cleansing than a five minute iodophor scrub. There were fewer patients with high bacterial counts at the time of closure in the groups treated with the antimicrobial film than in the traditional iodophor scrub group. Saving in preoperative operating room time can be achieved using a one minute alcohol cleansing plus application of an antimicrobial film with equal antibacterial efficacy to that of conventional methods. | Iodophors |
CONTEXT: Micropapillary variant of urothelial carcinoma (MPUC) is a rare but well-recognized tumor of the urinary bladder. Tumors with micropapillary areas accompanying conventional urothelial carcinoma are more aggressive compared to conventional urothelial carcinoma and show variable keratin 7, keratin 20 and human epidermal growth factor receptor 2 (Her 2)neu expression. AIM: The aim of the study was to analyze the clinical, morphological and immunohistochemical profile of MPUC. MATERIALS AND METHODS: Transurethral resection of bladder tumor (TURBT) chips of seven cases of invasive MPUC with subsequent cystoprostatectomy specimens of five patients was reviewed. Epithelial membrane antigen (EMA), Keratin 7, Keratin 20, and Her 2 immunohistochemistry were performed in all cases. Follow-up information was available for all patients (2-36 months). RESULTS: All seven patients were male, and their ages ranged from 50 to 62 years. All cases presented with hematuria. The micropapillary pattern was seen in 20-95% of the tumor. All cases showed extensive lymphatic emboli with detrusor muscle invasion. Lymph node metastasis was present in all cases undergoing cystoprostatectomy except one. Keratin 7 and abluminal pattern of EMA positivity were seen in all cases. Keratin 20 was positive in five cases (71%), and Her 2neu positivity was seen in four cases. Three patients died 2, 3, and 6 months after initial diagnosis, among which two were Her 2 positive and one was Her 2 negative. There was no clear prognostic significance of Her 2 positivity. CONCLUSION: (1) MPUC is a rare but highly aggressive tumor. (2) Micropapillary is usually the predominant pattern. (3) Keratin 7 is expressed universally, whereas Keratin 20 expression is variable. (4) Her 2 expression has no clear influence on the survival. | Keratin-7 |
This article is an overview of our studies of childhood-onset schizophrenia. Data are presented demonstrating that (1) the majority of the sample showed continuing schizophrenia as they progressed through adolescence; (2) there was considerable variability in outcome, defined by global adjustment scores, with 56 percent of the sample showing improvement in functioning during a 2- to 7-year followup period and the other 44 percent showing minimal improvement or a deteriorating course; (3) schizophrenia in childhood could be diagnosed by the same criteria used for adults and was associated with severe dysfunction; and (4) some intrafamilial attributes found to be associated with schizophrenia in adults were also associated with schizophrenia in children, but there were some differences in the family environmental correlates of childhood- and later-onset schizophrenia. These data are consistent with the hypothesis that childhood- and later-onset schizophrenia represent the same illness or illnesses. Additional research is needed, however, to clarify the etiologic and clinical significance of the atypical early onset in childhood cases. | Schizophrenia, Childhood |
Rose-scented geranium, Pelargonium graveolens L'Herit. (Geraniaceae), is an economically important plant. GC-MS analysis of the essential oil, prepared by hydro-distillation from this plant species, showed the presence of iso-menthone (15.71%), epi-alpha-cadinol (15.49%), iso-menthol (6.46%), geranyl formate (6.22%), geraniol (6.16%) and citronellol (5.53%). The composition of the absolute prepared by solvent extraction was compared to that of the essential oil. Change in citronellol to geraniol ratio in the absolute was monitored during leaf development. Estimation of the ratio of the two compounds was carried out using (1)H NMR spectroscopy. Geraniol content was highest in young leaves and citronellol content increased with increase in leaf age. Meta-analysis of the essential oil constituents reported from different countries was carried out. Menthone and isomenthone as well as citronellol and geraniol were negatively correlated. A significantly positive correlation was found between geraniol and linalool. | Viridiplantae |
Selenium compounds have emerged as promising chemotherapeutic agents with proposed epigenetic effects, however the mechanisms and downstream effects are yet to be studied. Here we assessed the effects of the inorganic selenium compound selenite and the organic form methylseleninic acid (MSA) in a leukemic cell line K562, on active (histone H3 lysine 9 acetylation, H3K9ac and histone H3 lysine 4 tri-methylation, H3K4me3) and repressive (histone H3 lysine 9 tri-methylation, H3K9me3) histone marks by Chromatin immunoprecipitation followed by DNA sequencing (ChIP-Seq). Both selenite and MSA had major effects on histone marks but the effects of MSA were more pronounced. Gene ontology analysis revealed that selenite affected genes involved in response to oxygen and hypoxia, whereas MSA affected distinct gene sets associated with cell adhesion and glucocorticoid receptors, also apparent by global gene expression analysis using RNA sequencing. The correlation to adhesion was functionally confirmed by a significantly weakened ability of MSA treated cells to attach to fibronectin and linked to decreased expression of integrin beta 1. A striking loss of cellular adhesion was also confirmed in primary patient AML cells. Recent strategies to enhance the cytotoxicity of chemotherapeutic drugs by disrupting the interaction between leukemic and stromal cells in the bone marrow are of increasing interest; and organic selenium compounds like MSA might be promising candidates. In conclusion, these results provide new insight on the mechanism of action of selenium compounds, and will be of value for the understanding, usage, and development of new selenium compounds as anticancer agents. | Selenious Acid |
INTRODUCTION: To search for a new radiographic view/projection of the acetabular anterior column to provide a safe guide for percutaneous screw placement for acetabular fractures. MATERIALS AND METHODS: Eight pelvic specimens taken from normal adult cadavers were positioned in a supine position on the operating table. First, the ipsilateral ilium-oblique view of the observed side was obtained on C-arm fluoroscopy by tilting the C-arm approximately 35 degrees toward the contralateral hip joint. Then, the tilting angle of the C-arm was changed gradually until an oval track image (acetabular anterior column axial view) appeared. The oval shadow was clear only in one position as the angle of the C-arm was changed toward the caudal side of the operating table. A guide pin was put on the skin of the cadaver, and the location and tilting direction of the guide pin were adjusted under C-arm fluoroscopy until the pin's shadow became a point in the center of the oval track. Then, the guide pin was inserted into the bone using a battery-powered drill. The degree of inclination of the guide pin in the cadaver in the frontal and sagittal planes was measured using computed tomography (CT). RESULTS: Axial views of the anterior column were found successfully in all of the pelvic specimens, and the guide pins were inserted accurately into the acetabular anterior column under C-arm fluoroscopic guidance. On the CT-reconstructed image, the average degree of angle between the guide pin and the sagittal plane was 33.6 degrees (range 29.6 degrees -36.5 degrees ). The average angle between the guide pin and the transverse plane was 59.1 degrees (range 56.4 degrees -63.2 degrees ). CONCLUSION: This axial view of the acetabular anterior column is a novel X-ray projection which provides an optimal method for guiding percutaneous insertion of anterior column screws for acetabular fractures. | Acetabulum |
Considering the large yield of viable cells comparable to human liver, primary porcine hepatocytes offer a valuable resource for constructing a bioartificial liver device. In this study, the ability of cultured primary porcine hepatocytes to detoxify xenobiotics has been examined using various known substrates of cytochrome P450 isoenzymes and UDP-glucuronosyltransferases. Present investigation demonstrated the stability of the isoenzymes responsible for the metabolism of diazepam in native state and stabilization of other isoenzymes, as judged by ethoxycoumarin o-dealkylase (ECOD), ethoxyresorufin o-dealkylase (EROD), benzyloxyresorufin o-dealkylase (BROD), and pentoxyresorufin o-dealkylase (PROD) activities following induction in culture environment, for a period of 8 days. Resorufin O-dealkylase activities were found to be the most unstable and deteriorated within first 5 days in culture. These activities were restored following induction with 3-methylcholanthrene (3-MC) or sodium phenobarbital (PB) to 20-fold of 1 activity for EROD, and 60 and 174% of day 1 activity for PROD and BROD on day 8, respectively. Metabolism of methoxyresorufin was most strikingly increased following induction with 3-MC to approximately 60-fold of day 1 activity, on day 8. UDP-glucuronosyltransferase-dependent glucuronidation of phenol red, however, stayed intact during the course of our study without induction. Our study indicated that porcine hepatocytes in vitro maintain many important liver-specific functions including detoxification (steady state and inducibility). | 7-Alkoxycoumarin O-Dealkylase |
BACKGROUND: Prussian Blue (PB), ferric hexacyanoferrate is indicated for (oral) treatment of internal contamination with radioisotopes of cesium or thallium. Cyanide is 35-40% of PB's molecular composition, thus cyanide may be released during transit through the digestive tract under physiological pH. The U.S. Food and Drug Administration investigated the issue of cyanide release prior to drug approval to ensure the drug's benefits exceeded risks. OBJECTIVES: To determine cyanide released from PB under pH conditions that bracket human physiological exposure. METHODS: PB was incubated in situ at pH 1.0-12, 37 degrees C for 1-48 hours. Cyanide was measured using a validated colorimetric method by UV-VIS spectroscopy. RESULTS: PB had the highest cyanide release at pH 1 (135 ug/g) and lowest release at pH 5.0-7.0 from the highest daily dose of PB (17.5 g) (21 ug/g). Considering the minimal lethal dose of cyanide is approximately 50 mg, the maximal cyanide released (1.6 mg) does not present a safety concern. | Ferrocyanides |
OBJECTIVE: To study whether the timing of puberty in adolescents who reported gender incongruence (incongruence between birth-assigned sex and self-identified gender) was different from those adolescents who reported gender congruence. DESIGN: Population-based cohort study using data from the Danish National Birth Cohort. SETTING: Not applicable. PATIENT(S): Birth-assigned boys and girls born between 2000 and 2003, who self-reported gender incongruence at 11 years (N = 10,046) and their pubertal developmental stages from age 11 years to every 6 months throughout puberty were included. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE: Mean age differences in months at reaching Tanner stages 2-5 for breast or genital development and pubic hair, voice break, first ejaculation, menarche, axillary hair, acne, and the average difference at attaining all pubertal milestones (primary outcome). RESULT(S): In total, 549 (5.5% ) adolescents reported part or full gender incongruence at 11 years. Tendencies toward earlier timing of puberty were observed in adolescents who reported part gender incongruence (average difference, birth-assigned boys: -3.2 months [95% confidence interval CI: -6.7; 0.3]; birth-assigned girls: -2.0 months [95% CI: -3.9; -0.1]). Tendencies toward earlier timing of puberty were observed in adolescents who reported full gender incongruence (average difference, birth-assigned boys: -2.4 months [95% CI: -5.0; 0.4]; birth-assigned girls: -1.9 months [95% CI: -5.1; 1.2]). CONCLUSIONS: The results from this study indicated that birth-assigned boys and girls who reported either part or full gender incongruence tended to reach puberty slightly earlier than those adolescents who reported gender congruence at 11 years of age. Knowledge on the timing of puberty among adolescents who experience gender incongruence is essential to inform mutual decision-making in clinical settings. | Puberty |
1. Activation of vascular smooth muscle by angiotensin II results in the generation of two second messengers, inositol trisphosphate (IP3) and diacylglycerol (DG). 2. IP3 is responsible for mobilizing calcium from endoplasmic reticulum. This signal is transient, most likely serving to initiate calcium events leading to contraction, and is attenuated by activation of protein kinase C. 3. DG stimulates protein kinase C and ultimately Na+/H+ exchange, leading to intracellular alkalinization. Accumulation of DG/activation of protein kinase C is sustained, and may be enhanced by concurrent intracellular alkalinization. The delay in induction of the sustained response appears to be related to cellular processing of the angiotensin II-receptor complex. 4. Angiotensin II-stimulated, phospholipase C-mediated IP3 formation is also modulated by a pertussis toxin-insensitive guanine nucleotide regulatory protein. 5. The GTP binding protein, movement of the receptor-ligand complex, and the signals generated by the two second messengers, IP3 and DG, interact in a complex manner to cause an integrated response of vascular smooth muscle cells to angiotensin II stimulation. | Tunica Media |
Marijuana use has increased significantly among adolescents and young adults. It is important for prevention scientists to understand youth motivations for marijuana use in order to refine and/or create intervention to limit harm. The current study surveyed 114 marijuana using college students (67% women; 78% White) on their motivations for using marijuana, frequency of use and associated negative consequences, and theoretical and empirical influences on motivations and use. Results indicated that students most frequently endorsed enjoyment, sleep, and low-risk motivations for use. Variables associated with the Theory of Planned Behavior and Strain Theory were associated with a variety of motivations for use. Motivations, perceived behavioral control regarding marijuana, and parental active tracking were associated with frequency of use, while negative consequences were predicted by frequency of use and attitudes regarding marijuana. Researchers seeking to develop programs to prevent marijuana-related harm may benefit from focusing on the differential motivations for use observed. | Smoking, Non-Tobacco Products |
Diagnosis of pruritic skin disease can be a time-consuming process. Careful attention must be paid to history, clinical examination, laboratory and clinical testing, methodical elimination of the differential diagnoses, and client communication in order to achieve success. | Skin Manifestations |
Based on the premise that aqueous anions of hexavalent chromium (Cr(VI)) are capable of electrostatic interaction with cationic and polar active sites, acid-washed Madacamia nutshell biomass was sequentially treated with diethylenetriamine (DETA) and maleic anhydride (MA) to graft poly(diethylenetriamine-co-maleic anhydride). By displaying a new peak at 1685 cm(-1) ascribed to amide CO stretching vibrations, Fourier transform infrared spectroscopy highlighted the formation of amide groups through reaction of DETA with carboxyl groups on the biomass surface. Scanning electron microscopic images of the MA-modified biomass displayed polymeric growths attributed to copolymerization of DETA with MA. The polar and ionizable amide and amine groups of the grafted copolymer endowed the adsorbent with Cr(VI) removal capabilities over a wide pH range demonstrated by removal efficiencies between 70.9% and 81.7% in the pH 1.6 to pH 10.0 range for the treatment of 20 mL solutions containing 100 mg L(-1) Cr(VI) with 200 mg of adsorbent. Conformity of the adsorption isotherm data to the Freundlich model revealed the heterogeneous nature of the adsorbent surface, which comprised a variety of functional groups capable of interaction with Cr(VI) species in solution. The Sips isotherm model provided the best fit to the equilibrium experimental data, and the adsorption capacity was 779.1 mg g(-1) at pH 1.6, room temperature and an adsorbent dosage of 5.0 g L(-1). The findings indicate that Cr(VI) adsorption onto diethylenetriamine and maleic anhydride modified Madacamia nutshell biomass is a promising option for Cr(VI) removal from aqueous solutions. | Macadamia |
In order to obtain functional images of brain perfusion, we exploited a new concept, which is to take advantage of the short half-life of a radioactive tracer. Under continuous intracarotid infusion of a solution of Kr-81m (T1/2 = 13 sec; produced from its parent, 4.6-hr Rb-81), this tracer will never reach equilibrium within the brain because of the rapid radioactive decay. Its distribution will therefore reflect regional arrival of the nuclide, indicating regional cerebral blood flow rather than volume. During continuous infusion of Kr-81m, perfusion images can be obtained by simply collecting counts with a gamma camera and recording on Polaroid film. The procedure is readily repeatable in order to get images in multiple veiws or to follow minute-by-minute changes of cerebral perfusion. | Krypton |
Steroid refractory acute graft-versus-host disease (SR aGvHD) is a major limitation of successful allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photopheresis (ECP) has been used to treat SR aGvHD effectively and with low treatment related toxicity. In this study, we retrospectively analyzed the outcomes of 103 Steroid Refractory aGvHD (SR aGvHD) patients to identify factors associated with improved outcomes including the use of ECP. A total of 79 patients received ECP as part of their SR aGVHD treatment compared to 24 patients who did not. Both groups had similar aGVHD grade and maximum organ stage at onset of aGVHD and treatment initiation. Patients in the group that received ECP had better OS (p = 0.01), DFS (p = 0.008), lower relapse (p = 0.05) and similar NRM compared to the group that did not receive ECP. Patients that received ECP treatment also had shorter hospital stays in the first 180 days after onset of SR aGvHD (20 vs. 38 days, p = 0.03). Multivariable analysis for OS indicated patient CMV status (CMV+ versus CMV-, HR 2.34, CI 1.16-4.69), regimen intensity (Myelo vs. non-Myeloablative, HR 0.39, CI 0.20-0.75), and the use of ECP (ECP vs. no ECP, HR 0.39, CI 0.20-0.75) were associated with OS. In summary, the use of ECP in the treatment of SR aGvHD results in improved overall survival secondary to lower relapse rates compared to other therapeutic modalities that do not incorporate ECP. | Photopheresis |
Previous evidence suggested that transfer RNAs (tRNAs) cross the nuclear envelope to the cytosol only once after maturing in the nucleus. We now present evidence for nuclear import of tRNAs in yeast. Several export mutants accumulate mature tRNAs in the nucleus even in the absence of transcription. Import requires energy but not the Ran cycle. These results indicate that tRNAs shuttle between the nucleus and cytosol. | RNA, Transfer, Ile |
OBJECTIVE: The Mental Health Parity and Addiction Equity Act (MHPAEA) of 2008 mandates equivalent insurance coverage for mental health (MH) and substance use disorders (SUD) to other medical and surgical services covered by group insurance plans, Medicaid, and Children's Health Insurance Programs (CHIP). We explored the impact of MHPAEA on enrollees in ALL Kids, the Alabama CHIP. METHODS: We use ALL Kids claims data for October 2008 to December 2014. October 2008 through September 2009 marks the period before MHPAEA implementation. We evaluated changes in MH/SUD-related utilization and program costs and changes in racial/ethnic disparities in the use of MH/SUD services for ALL Kids enrollees using 2-part models. This allowed analyses of changes from no use to any use, as well as in intensity of use. RESULTS: No significant effect was found on overall MH service-use. There were statistically significant increases in inpatient visits and length of stay and some increase in overall MH costs. These increases may not be clinically important and were concentrated in 2009 to 2011. Disparities in utilization between African-American and non-Hispanic white enrollees were somewhat exacerbated, whereas disparities between other minorities and non-Hispanic whites were reduced. CONCLUSIONS: Findings indicate that MHPAEA led to a 14.3% increase in inpatient visits, a 12.5% increase in length of inpatient stay, and a 7.8% increase in MH costs. The increases appear limited to 2009 to 2011, suggesting existing pent-up "needs" among enrollees for added MH/SUD services that resulted in a temporary spike in service use and cost immediately after MHPAEA, which subsequently subsided." | Children's Health Insurance Program |
Liposomes are spherical phospholipid bilayer vesicles. In the present study, we found that cationic liposomes made by (2,3-dioleoyloxy-propyl)-trimethylammonium (DOTAP) could enhance the luminol-H(2)O(2) chemiluminescence (CL) reaction. Mechanism studies showed that the positive charge on the surface of liposomes plays an important role in the CL process. We speculated that the cationic liposomes with quaternary ammonium groups on the surface may be capable of catalyzing the decomposition of H(2)O(2) leading to the formation of oxygen-related free radicals including OH, (1)O(2), and O(2) (-). The luminol anions tend to move close to the surface of the cationic liposomes and then to be oxidized by the oxidizing radical species which may be around the surface of cationic liposomes forming excited-state 3-aminophthalate* (3-APA*). When the 3-APA* returns to the ground state, an enhanced CL is observed. In addition, the single-strand DNA (ssDNA) showed a significant inhibition effect on the proposed CL reaction. The CL intensity decreased linearly with an increasing amount of DNA from 0.05 to 2 pmol. We assumed that the binding of ssDNA with cationic liposomes would neutralize the positive charge on the surface of liposomes and inhibit the catalytic activity of DOTAP cationic liposomes. Based on the ssDNA-inhibited luminol-H(2)O(2)-cationic liposome CL reaction, simple label-free CL sensing platforms were developed for the detection of sequence-specific DNA related to the hepatitis B virus (HBV) gene and for the detection of ATP (as a model analyte) using an anti-ATP aptamer as the recognition element. | Immobilized Nucleic Acids |
The unregulated use of acetaminophen (APAP), an antipyretic and analgesic drug, harms hepatocytes and kidney cells, leading to liver failure and acute kidney injury. Herein, we investigate whether APAP damages macrophages in the immune system by observing its effects on macrophage proliferation and apoptosis. Using proteomics, we analyzed the effects of APAP on macrophage protein expression profiles and evaluated whether polydatin, the active ingredient in grapes and wine, can repair the damaged cells. The results showed that APAP alters the morphology and physiological processes of macrophages, inhibits macrophage proliferation, and promotes apoptosis. We observed 528 differentially expressed proteins when 500 microg/mL APAP was administered to the cells. These proteins are involved in biological processes including cell division, apoptosis, and acute phase response. Overall, our findings demonstrate that APAP harms the immune system by damaging macrophages and that polydatin can repair this damage. | Reynoutria |
The effect of simultaneous injections of ACTH and methylandrostenediol (MAD), a synthetic androgen, has been studied in the rat. ACTH accelerated the production of cytoplasmic vacuoles by MAD in as much as no such structures were observed in MAD-treated animals at 4 weeks. Adrenal weight was decreased in MAD-treated animals but restored to that of controls by ACTH (MAD plus ACTH group). ACTH by itself did not, however, cause the production of any vacuolar structures nor did it cause any reparation in the number of mitochondrial cristae which were considerably reduced in numbers after MAD plus ACTH. | Methandriol |
Campylobacter jejuni 81116 is able to switch flagellum formation on and off. To study the expression of flagellin, the main component of flagella, an expression library of C. jejuni DNA was constructed in lambda gt11. Screening of this library with a flagellin-specific antiserum resulted in a clone producing a beta-galactosidase-flagellin fusion protein; it contained a DNA insert of 850 base pairs and coded for about 15 kilodaltons of the flagellin, corresponding to 410 base pairs of the flagellin gene. To study the regulation of the on-and-off switch of flagellum production, a nonmotile variant was isolated from semisolid medium. Western blots (immunoblots) showed the absence of flagellin in the nonmotile form. Southern blots of digested DNA of both motile, flagellate bacteria and nonmotile, aflagellate bacteria were identical, while Northern (RNA) blot analysis showed the absence of flagellin mRNA in the aflagellate form. Thus, it is concluded that reversible flagellin expression is regulated at the transcriptional level. Southern blots suggest that more than one flagellin gene is present. The structure and function of campylobacter flagellin can now be further investigated at the DNA level. | Flagellin |
Symbiosis with arbuscular mycorrhizal fungi (AMF) improves plant nutrition in most land plants, and its contribution to the colonization of land by plants has been hypothesized. Here, we identify a conserved transcriptomic response to AMF among land plants, including the activation of lipid metabolism. Using gain of function, we show the transfer of lipids from the liverwort Marchantia paleacea to AMF and its direct regulation by the transcription factor WRINKLED (WRI). Arbuscules, the nutrient-exchange structures, were not formed in loss-of-function wri mutants in M. paleacea, leading to aborted mutualism. Our results show the orthology of the symbiotic transfer of lipids across land plants and demonstrate that mutualism with arbuscular mycorrhizal fungi was present in the most recent ancestor of land plants 450 million years ago. | Hepatophyta |
Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4(+)CCR6(+)IL-7R(+)T cells from human tonsils produced IL-10 following stimulation by naive B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6(+)B helper T cells were phenotypically distinct from follicular helper T (T(FH)) cells and lacked BCL6 expression. In peripheral blood, a CCR6(+)T cell population with similar characteristics was identified, which lacked Th17- and T(FH)-associated gene signatures and differentiation-associated surface markers. CD4(+)CCR6(+)T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4(+)CCR6(+)IL-7R(+)T cells were associated with the presence of pathogenic anti-dsDNA (double-stranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6(+)T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE. | Receptors, CCR6 |
Lyme disease is a long-term infection whose most severe pathology is characterized by inflammatory arthritis of the lower bearing joints, carditis, and neuropathy. The inflammatory cascades are initiated through the early recognition of invading Borrelia burgdorferi spirochetes by cells of the innate immune response, such as neutrophils and macrophage. B. burgdorferi does not have an intracellular niche and thus much research has focused on immune pathways activated by pathogen recognition molecules at the cell surface, such as the Toll-like receptors (TLRs). However, in recent years, studies have shown that internalization of the bacterium by host cells is an important component of the defense machinery in response to B. burgdorferi. Upon internalization, B. burgdorferi is trafficked through an endo/lysosomal pathway resulting in the activation of a number of intracellular pathogen recognition receptors including TLRs and Nod-like receptors (NLRs). Here we will review the innate immune molecules that participate in both cell surface and intracellular immune activation by B. burgdorferi. | Borrelia burgdorferi |
A precocious line (PrEmag) of Eimeria magna in rabbits was obtained by selecting for early development of oocysts. The prepatent period was shortened by 46 h. The pathogenicity of PrEmag was substantially reduced and its reproductive potential was much lower (500 times) than that of the parent strain. Rabbits given 2500 oocysts of PrEmag were almost totally protected against a challenge with the parent strain. As in other precocious lines of coccidia from the rabbit, PrEmag showed morphological anomalies of the sporulated oocysts. Each sporocyst harboured one large refractile body instead of the two smaller ones in the parent strain. | Eimeriidae |
The emergence of nontoxic, eco-friendly, and biocompatible polymers derived from natural sources has added a new and exciting dimension to the development of low-cost and scalable biomaterials for tissue engineering applications. Here, we have developed a mechanically strong and durable hydrogel composed of an eco-friendly biopolymer that exists within the cell walls of fruits and plants. Its trade name is pectin, and it bears many similarities with natural polysaccharides in the native extracellular matrix. Specifically, we have employed a new pathway to transform pectin into a ultraviolet (UV)-cross-linkable pectin methacrylate (PEMA) polymer. To endow this hydrogel matrix with cell differentiation and cell spreading properties, we have also incorporated thiolated gelatin into the system. Notably, we were able to fine-tune the compressive modulus of this hydrogel in the range approximately 0.5 to approximately 24 kPa: advantageously, our results demonstrated that the hydrogels can support growth and viability for a wide range of three-dimensionally (3D) encapsulated cells that include muscle progenitor (C2C12), neural progenitor (PC12), and human mesenchymal stem cells (hMSCs). Our results also indicate that PEMA-gelatin-encapsulated hMSCs can facilitate the formation of bonelike apatite after 5 weeks in culture. Finally, we have demonstrated that PEMA-gelatin can yield micropatterned cell-laden 3D constructs through UV light-assisted lithography. The simplicity, scalability, processability, tunability, bioactivity, and low-cost features of this new hydrogel system highlight its potential as a stem cell carrier that is capable of bridging the gap between clinic and laboratory. | Cells, Immobilized |
Xenogenic extracellular matrix (xECM)-based organ transplantation will be a promising approach to address the problem of donor shortage for allotransplantation, which has achieved great success in organ regeneration. However, current approaches to utilize xECM-based organ have limited capacity to yield the host a biofriendly microenvironment for long-term immunity homeostasis, compromising the application of these xenografts for repairing and replacing damaged tissues. As the key innate immune cells, macrophages directly determine the prognosis of xenografts in long term. However, it has not been fully elucidated that how to modulate their biological behavior for microenvironment homeostasis in tissue reconstruction. In this study, we report a robust strategy to impart an immunosuppressive surface to naturally sponge-like porous xECM scaffolds by loading rosiglitazone (RSG) to activate peroxisome proliferators receptors-gamma (PPAR-gamma). The resultant xECM-RSG complex, enabling RSG to be delivered sequentially and continuously to cells without obvious systemic side effects, is recognized as self" to escape immune monitoring in local immunoregulation by downregulating the expression of proinflammatory NOS2+ M1 macrophages and oxygen species (ROS) through suppressing NF-kappaB expression, greatly facilitating the regeneration of enthesis anchoring between the transplanted xenograft and host in both heterotopic and orthotopic models. The newly formed bio-root is morphologically and biomechanically equivalent to native tooth root with a significant expression of odontogenic differentiation-related critical proteins. Therefore, the PPAR-gamma-NF-kappaB axis activated by the xECM-RSG complex enables the xenografts to converse towards M2 macrophages with a modest immunosuppressive capacity for facilitating in xECM-based tissue or organ regeneration." | Immune Evasion |
Eggshell membrane, an eco-compatible, safe and cheap by-product was employed as carrier for the laccase from Trametes versicolor immobilization. In order to evaluate the best protocol to apply for the syringic acid degradation, two different types of laccase loading on eggshell membrane were used by incubation in solution or by enzyme-dropping. Chemicals (covalent) and physicals (adsorption) immobilizations were tested for both procedure using native or periodate-oxidized laccase. It is shown that immobilization of periodate-oxidized laccase on NiCl(2)-pretreated eggshell membrane was the best method for the first procedure (immobilized activity 1300 U/Kg, a residual activity of 30 % for 6 reuse). For the enzyme-dropping protocol a covalent method with the bifunctional cross linker (glutaraldehyde) was the best method (immobilized activity 3500 U/Kg, a residual activity of 45 % for 6 reuse). | Trametes |
Unlike the most well-characterized prokaryotic polymerase, E. coli DNA pol l, none of the eukaryotic polymerases have their own 5' to 3' exonuclease domain for nick translation and Okazaki fragment processing. In eukaryotes, FEN-1 is an endo- and exonuclease that carries out this function independently of the polymerase molecules. Only seven nucleases have been cloned from multicellular eukaryotic cells. Among these, FEN-1 is intriguing because it has complex structural preferences; specifically, it cleaves at branched DNA structures. The cloning of FEN-1 permitted establishment of the first eukaryotic nuclease family, predicting that S. cerevisiae RAD2 (S. pombe Rad13) and its mammalian homolog, XPG, would have similar structural specificity. The FEN-1 nuclease family includes several similar enzymes encoded by bacteriophages. The crystal structures of two enzymes in the FEN-1 nuclease family have been solved and they provide a structural basis for the interesting steric requirements of FEN-1 substrates. Because of their unique structural specificities, FEN-1 and its family members have important roles in DNA replication, repair and, potentially, recombination. Recently, FEN-1 was found to specifically associate with PCNA, explaining some aspects of FEN-1 function during DNA replication and potentially in DNA repair. | Exodeoxyribonuclease V |
Chagas disease is major public health problem, affecting nearly 10 million people, characterized by cardiac alterations leading to congestive heart failure and death of 20-40% of the patients infected with Trypanosoma cruzi, the protozoan parasite responsible for the disease. A vaccine would be key to improve disease control and we review here the recent advances and challenges of a T. cruzi vaccine. There is a growing consensus that a protective immune response requires the activation of a Th1 immune profile, with the stimulation of CD8 (+) T cells. Several vacines types, including recombinant proteins, DNA and viral vectors, as well as heterologous prime-boost combinations, have been found immunogenic and protective in mouse models, providing proof-of-concept data on the feasibility of a preventive or therapeutic vaccine to control a T. cruzi infection. However, several challenges such as better end-points, safety issues and trial design need to be addressed for further vaccine development to proceed. | Protozoan Vaccines |
Many pharmacologic and nonpharmacologic strategies are available to treat sleep disorders successfully. Conventional stimulants and the new stimulant modafinil have roles to play in the management of narcolepsy and idiopathic hypersomnia. Knowledge of the properties and clinical effects of these drugs allows adequate doses of medications to be used with the goal of attaining as maximal alertness as possible. A range of dopaminergic agents is available to treat restless legs syndrome; other medications such as opiates, benzodiazepines, and anticonvulsants can also be used. Successful use of the dopaminergic agents depends on an understanding of the phenomena of augmentation, rebound, and tolerance. Arousal parasomnias can be treated with behavioral methods such as hypnosis and drug therapy. Clonazepam provides relief of the symptoms in most patients with REM sleep behavior disorder. | Sleep Wake Disorders |
Trachoma causes one-quarter of the world's blindness and, although it has disappeared from many developed areas, it remains a major problem, especially in underprivileged rural areas in developing countries. Recent advances in the understanding of the molecular biology of chlamydia offer encouragement for the eventual development for an effective trachoma vaccine. Advances in the understanding of the epidemiology of trachoma, particularly of the importance of reinfection and the intrafamily transmission of infection, have led to the identification of the key importance of simple hygiene measures such as facial cleanliness in preventing the transmission of trachoma. Community-based health education intervention programs are being developed to assess the efficacy of a public health approach to the control of trachomatous blindness. | Conjunctivitis, Bacterial |
When a protein derived from the immunoglobulin G (IgG)-binding domains of staphylococcal protein A was expressed in Escherichia coli and recovered from cell extract by IgG affinity chromatography, the 69-kilodalton heat shock protein DnaK was found to be copurified. DnaK could be selectively eluted from the IgG column by ATP or by lowering the pH to 4.7. Protein A could subsequently be eluted by lowering the pH to 3.2. Thus, this procedure allows a one-step purification of both DnaK and protein A from cell extract. In vitro experiments with pure DnaK and protein A revealed that DnaK did not interfere with the IgG-binding properties of protein A but associated with its unfolded C-terminal in a salt-resistant manner. In addition, a specific interaction between DnaK and denaturated casein was found. | Staphylococcal Protein A |
In marine invertebrates, waterborne chemical stimuli mediate responses including prey detection and predator avoidance. Alarm and flight, in response to damaged conspecifics, have been reported in echinoderms, but the nature of the stimuli involved is not known. The responses of Asterias rubens Linnaeus, Psammechinus miliaris (Gmelin), and Echinus esculentus Linnaeus to conspecifics were tested in a choice chamber against a control of clean seawater (no stimulus). All three species showed statistically significant movement toward water conditioned by whole animals or homogenate of test epithelium. P. miliaris and E. esculentus displayed a statistically significant avoidance reaction, moving away from conspecific coelomic fluid, gut homogenate, and gonad homogenate. A. rubens was indifferent to conspecific coelomic fluid, pyloric cecum homogenate, and gonad homogenate but moved away from cardiac gut homogenate. P. miliaris was indifferent to gametes, but the other two species were significantly attracted to them. No species showed preference for one particular side of the chamber during trials to balance water flow. These echinoderms can distinguish between homogenates of conspecific tissues that might be exposed when a predator damages the test, and those that may emanate from the exterior surface during normal activities. | Behavior, Animal |
Glucose is freely filtered in the glomeruli before being almost entirely reabsorbed into circulation from the proximal renal tubules. The sodium-glucose cotransporter 2 (SGLT2), present in the S1 segment of the proximal tubule, is responsible for the majority of glucose reabsorption. SGLT2 inhibitors reduce glucose reabsorption and increase urinary glucose excretion. In animal models and humans with type 2 diabetes, this effect is associated with reduced fasting and postprandial blood glucose levels, and reduced hemoglobin A1c. Animal studies suggest that reduction of hyperglycemia with SGLT2 inhibitors may also improve insulin sensitivity and preserve beta-cell function. Urinary excretion of excess calories with SGLT2 inhibitors is also associated with reduction in body weight. Modest reductions in blood pressure have been noted with SGLT2 inhibitors, consistent with a mild diuretic action. Some C-glucoside SGLT2 inhibitors, such as dapagliflozin, have pharmacokinetic properties that make them amenable to once-daily dosing. | Hypoglycemic Agents |
BACKGROUND: Leber's hereditary optic neuropathy (LHON) mostly affects young males. In patients carrying one of the primary mutations the risk to develop LHON is 50% for males and 10% for females. We report a family with predominantly young girls affected. METHODS: In a family with 14 known maternal relatives (11 females, 3 males) 9 patients in 4 generations developed LHON. Eight of the 9 patients were females. Three affected females could be examined and followed. RESULTS: The only affected male showed the typical course of LHON with acute visual loss in both eyes (20/400-20/800) within 6 weeks at 20 years of age. Eight of 9 females developed signs of LHON. In these females acute visual loss occurred at about 10 years of age. Final visual acuity was about 20/200. Central or paracentral scotomata, color vision defects and delayed P100 latencies in the VEP were seen. Ophthalmoscopy showed hyperemic discs in the acute stage and optic atrophy in later stages. Molecular genetic analysis revealed the presence of the mtDNA ND4/np11778 mutation in this family. Specific clinical or additional molecular genetic risk factors could not be detected. CONCLUSION: Families with LHON may show considerable variations of the clinical course and the gender- or age-specific risk. We present a family with a high disease penetrance of 64% and a 2 times higher risk for young females than for males. Furthermore, early visual loss in this family is permanent. | Optic Atrophies, Hereditary |
Venezuelan equine encephalitis virus (VEEV) is an alphavirus in the family Togaviridae. VEEV is highly infectious in aerosol form and a known bio-warfare agent that can cause severe encephalitis in humans. Periodic outbreaks of VEEV occur predominantly in Central and South America. Increased interest in VEEV has resulted in a more thorough understanding of the pathogenesis of this disease. Inflammation plays a paradoxical role of antiviral response as well as development of lethal encephalitis through an interplay between the host and viral factors that dictate virus replication. VEEV has efficient replication machinery that adapts to overcome deleterious mutations in the viral genome or improve interactions with host factors. In the last few decades there has been ongoing development of various VEEV vaccine candidates addressing the shortcomings of the current investigational new drugs or approved vaccines. We review the current understanding of the molecular basis of VEEV pathogenesis and discuss various types of vaccine candidates." | Encephalomyelitis, Venezuelan Equine |
Gold nanoparticles (AuNP) have been extensively developed as contrast agents, theranostic platforms, and probes for molecular imaging. This popularity has yielded a large number of AuNP designs that vary in size, shape, surface functionalization, and assembly, to match very closely the requirements for various imaging applications. Hence, AuNP based probes for molecular imaging allow the use of computed tomography (CT), fluorescence, and other forms of optical imaging, photoacoustic imaging (PAI), and magnetic resonance imaging (MRI), and other newer techniques. The unique physicochemical properties, biocompatibility, and highly developed chemistry of AuNP have facilitated breakthroughs in molecular imaging that allow the detection and imaging of physiological processes with high sensitivity and spatial resolution. In this Review, we summarize the recent advances in molecular imaging achieved using novel AuNP structures, cell tracking using AuNP, targeted AuNP for cancer imaging, and activatable AuNP probes. Finally, the perspectives and current limitations for the clinical translation of AuNP based probes are discussed. | Molecular Imaging |
Parasites have been engineered to express fluorescent reporter proteins, yet the impact of red fluorescent proteins on Leishmania infections remains largely unknown. We analysed the infection outcome of Leishmania mexicana parasites engineered for the constitutive expression of mKate protein and evaluated their immunogenicity in BALB/c mice. Infection of BALB/c mice with mKate transfected L. mexicana (Lmex(mKate) ) parasites caused enlarged lesion sizes, leading to ulceration, and containing more parasites, as compared to Lmex(WT) . The mKate protein showed immunogenic properties inducing antibody production against the mKate protein, as well as enhancing antibody production against the parasite. The augmented lesion sizes and ulcers, together with the more elevated antibody production, were related to an enhanced number of TNF-alpha and IL-1beta producing cells in the infected tissues. We conclude that mKate red fluorescent protein is an immunogenic protein, capable of modifying disease evolution of L. mexicana. | Leishmania mexicana |
To achieve the main goal of net zero carbon emission, the shift from conventional fossil-based energy/products to renewable and low carbon-based energy/products is necessary. Biomass has been perceived as a carbon-neutral source from which energy and value-added products can be derived, while sludge is a slurry waste that inherently contains high amount of minerals and organic matters. Hence, thermochemical co-processing of biomass wastes and sludge could create positive synergistic effects, resulting in enhanced performance of the process (higher conversion or yield) and improved qualities or characteristics of the products as compared to that of mono-processing. This review presents the current progress and development for various thermochemical techniques of biomass-sludge co-conversion to energy and high-value products, and the potential applications of these products from circular economy's point of view. Also, these technologies are discussed from economic and environmental standpoints, and the outlook towards technology maturation and successful commercialization is laid out. | Biomass |
PURPOSE: The inhibition of activated Ras combined with radiotherapy was identified as a potential method for radiosensitization. MATERIALS AND METHODS: Immunoblotting was used to control for prenylation inhibition of the respective Ras isoforms and for changes in activity of downstream proteins. Clonogenic assays with human and rodent tumour cell lines and transfected cell lines served for the testing of radiosensitivity. Xenograft tumours were treated with farnesyl transferase inhibitors and radiation and assayed for ex vivo plating efficiency, regrowth of tumours and EF5 staining for detection of hypoxia. Concurrent treatment with L-778,123 and radiotherapy was performed in non-small cell lung cancer (NSCLC) and head and neck cancer (HNC) patients. RESULTS: Blocking the prenylation of Ras proteins in cell lines with Ras activated by mutations or receptor signalling resulted in radiation sensitization in in vitro and in vivo. The PI3 kinase downstream pathway was identified as a contributor to Ras-mediated radiation resistance. Additionally, increased oxygenation of xenograft tumours was observed after FTI treatment. Combined treatment in a phase I study was safe and effective in NSCLC and HNC. CONCLUSIONS: Tumour cells with activated Ras were sensitized to radiation. Unravelling the underlying mechanisms promises to lead to even more specific drugs with higher potency and safety. | Genes, ras |
BACKGROUND: Detection of normal and variant glycophorin electrophoretic bands with T- and Tn-specific lectins is based on the possibility of glycophorin transformation into T or Tn antigens by simple chemical modifications in the blot. STUDY DESIGN AND METHODS: Human red cell membrane proteins were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and blotted onto nitrocellulose. The blots were submitted to mild acid hydrolysis (desialylation of glycophorins exposing T antigens) and then to Smith degradation (degalactosylation of asialo-glycophorins exposing Tn antigens). The modified glycophorin bands were detected with biotinylated lectins and horseradish peroxidase-conjugated avidin. RESULTS: The lectins from Artocarpus integrifolia (jacalin, anti-T/Tn), Amaranthus hybridus (anti-T), Salvia sclarea (anti-Tn), and Vicia villosa (anti-Tn) were used. The lectins detected normal glycophorin bands in control and variant red cells and characteristic additional bands in Mi.III (GP.Mur) red cells. The sensitivity of the method is comparable to that obtained by immunoblotting with glycophorin monoclonal antibodies. Comparison of the electrophoretic mobility of normal and variant bands is helpful in the classification of glycophorin variants. CONCLUSION: Lectinoblotting, based on carbohydrate recognition, enables the detection in a red cell sample, with high sensitivity, of all normal and variant glycophorin bands. The method can be also applied to other purposes, such as the identification of poly-O-glycosylated glycoproteins in other cells or the characterization of glycosylation of glycophorins and other poly-O-glycosylated proteins. | Glycophorins |
The composition of pollenkitt and its role in the progamic phase of reproduction are poorly understood. With the aim of extending knowledge on these topics, we chose to study two monocotyledons rich in pollenkitt, with bi-celled and long-lived pollen and dry-type stigma: Crocus vernus Hill subsp. vernus and Narcissus poeticus L. Fatty acids of pollenkitt were assayed with gas chromatography. Germination tests were performed in vivo by pollinating the stigmas with a beard hair under a stereomicroscope, and in vitro in liquid culture medium using pollen, either treated or not, with carbon disulphide to remove pollenkitt. The pollen tube percentages were evaluated using fluorescence microscopy techniques. Scanning electron microscopy was used to examine pollen and to follow the early post-pollination stages. Pollenkitt forms bridges between pollen grains but not between grains and stigma papillae. It consists of a mixture of 25 fatty acids, most with long and unsaturated chains, among which are some omega acids. The same acids with different percentages persist on the peritapetal membrane. After its removal, the pollen loses adhesiveness and dries quickly, but retains full capacity for germination on the papillae and can even trigger germination in contiguous pollen grains that do not touch the papillae. The results, while confirming the key role of pollenkitt in protecting pollen and favouring pollination, suggest secondary roles in the progamic phase, and highlight the interactive ability of the pollen regardless of lipid shell. The predominance of fatty acids with 18:3 and 16:0, as already noted in Brassica napus pollenkitt, suggests their hierarchy independent of plant species. | Narcissus |
The value of simulation-based education can be lost without a structured and purposeful guided debrief where nursing students and health care professionals are able to think critically and reflect on the experiential learning. Debriefing enhances peer-to-peer learning and aids the nursing student in formulating best practice for the next time when this encounter may occur in the clinical setting. Debriefing should be led by a trained facilitator using evidence-based methods to ensure a safe learning environment for nursing students. Debriefing is an essential learning tool that should be considered for application in the classroom, clinical, and laboratory settings. | Evidence-Based Nursing |
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